Add new markdown files for various documents and implement document conversion script
- Created markdown files for CDC Diagnostic Criteria for Creutzfeldt-Jakob Disease and multiple media documents. - Added a script to convert JSON documents containing HTML into markdown format. - Implemented functions to extract titles and HTML content from JSON files. - Enhanced markdown generation with support for various HTML elements including tables, lists, and images. - Included error handling and logging for file processing.
This commit is contained in:
Ross
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# Alzheimer Disease
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# KEY FACTS
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- ## Terminology
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- Alzheimer disease (AD)
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- Progressive neurodegenerative brain disease related to build up of (Aβ) neuritic plaques and subsequent tau neurofibrillary tangles (NFTs)
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- ## Imaging
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- Amyloid PET
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- Cortical amyloid deposition on PET is early biomarker in AD and appears prior to clinical symptoms
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- Absence of amyloid plaque rules out AD in patients with dementia
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- ↓ gray-white matter differentiation in at least 2 regions or single area of focally ↑ gray matter uptake are signs of positive florbetapir study
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- F-18 FDG PET
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- Glucose hypometabolism in parietotemporal, posterior cingulate, and precuneus regions; usually symmetric
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- Glucose hypometabolism continues to worsen with disease progression
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- Atypical AD variants can show hypometabolism in occipital lobes, frontal lobes, or with marked bilateral asymmetry
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- SPECT
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- 2nd-line study if PET is not available/reimbursed
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- Tau PET
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- Cortical deposition of tau NFTs in posterolateral temporal lobes, parietal lobes, occipital lobes, and cingulate gyrus can stage disease severity
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- Negative to early disease stage by tau PET can predict better response to amyloid targeting therapies (ATTs) with 50% of patients showing improved memory function at 3 years of treatment
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# TERMINOLOGY
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- ## Definitions
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- Alzheimer disease (AD)
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- Progressive neurodegenerative brain disease generally characterized by impairments in episodic memory and other cognitive domains
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- Likely related to β-amyloid (Aβ) neuritic plaques and tau neurofibrillary tangles (NFTs) leading to synaptic dysfunction, neuronal/glial cell death
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- ATN(C) classification defines patient status according to amyloid (A), tau (T), neurodegeneration (N), and clinical (C) status
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- Amyloid determined by PET &/or certain cerebrospinal fluid (CSF) biomarkers with plasma biomarkers on horizon
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- Tau determined by PET &/or CSF markers with plasma biomarkers on horizon
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- Neurodegeneration typical for AD via MR, FDG PET, or CSF biomarkers
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- Clinical status by formal neurocognitive evaluation/screening with MMSE or MoCA
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- Role of imaging
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- Early detection of AD neuropathologic changes (ADNCs) prior to symptom onset
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- Diagnosis of AD with clinical presentation and other biomarkers
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- Differential diagnosis between AD and other causes of dementia
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- Preclinical AD or asymptomatic ADNC
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- Stage of disease process where pathologic Aβ plaque or tau NFT deposition has occurred but prior to onset of significant clinically detectable symptoms
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- Amyloid PET positive; positive CSF Aβ42 or p-tau181/217
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- Mild cognitive impairment (MCI)
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- Clinical symptoms of memory &/or other cognitive problems greater than normal for age and education
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- ↑ risk of conversion to AD but not all progress to full dementia
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- Annual conversion rate from MCI to dementia ~ 5-10%
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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- ADNC (A+T+/-N+/-C-)
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- Amyloid PET positive (or CSF biomarker positive)
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- May or may not show changes on tau PET or FDG PET/MR
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- ↑ risk of developing AD symptoms
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- MCI and early AD (A+T+/-N+/-C+) clinically meeting criteria for MCI
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- Amyloid PET positive
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- F-18 FDG PET, tau PET, and MR abnormalities become more evident and can help stage disease severity, risk for symptomatic conversion of ADNC, and help assess likelihood that symptoms are related to AD
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- Mild clinical symptoms
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- Late AD (A+T+/-N+/-C+) clinically meeting criteria for dementia
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- Amyloid and F-18 FDG PET grossly positive
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- FDG PET hypometabolism and cortical tau PET accumulation can become more extensive or involve atypical areas
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- More extensive atrophy present (CT/MR)
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- ## Nuclear Medicine Findings
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- Amyloid PET imaging
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- F-18 florbetapir, flutemetamol, and florbetaben tracers are FDA approved
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- ↑ brain amyloid in gray matter on PET, normal off-target white matter binding to myelin proteins
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- Earliest imaging biomarker in AD
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- Absence of amyloid plaque rules out AD in patients with dementia
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- Interpretation of amyloid PET images
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- View in black-on-white background at high contrast levels (flutemetamol can be read in color)
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- View axial images 1st
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- Coronal and sagittal views for confirmation
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- Cerebellum gray-white differentiation is baseline for discerning normal gray matter from physiologic tracer retained in white matter
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- Positive scan (moderate or frequent Aβ deposition in cerebral cortex)
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- Blurring of gray/white matter junction due to radiotracer uptake in gray matter
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- ↑ gray matter uptake in temporal, parietal, and frontal cortices
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- Uptake in posterior cingulate gyrus and precuneus (may be early deposition sign)
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- F-18 florbetapir: ↓ gray-white matter differentiation in at least 2 regions or single area of focally ↑ gray matter uptake ≥ adjacent white matter = positive
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- Extent of amyloid deposition does not correlate with severity of AD
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- Negative scan (no evidence of significant Aβ deposition)
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- Symptoms unlikely due to AD
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- Does not exclude non-AD dementia
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- Artifacts and pitfalls
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- Severely diminished gray matter volume in AD patients may make abnormal exam appear normal due to contoured cortex
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- View fused PET/CT or PET/MR images as supplement to evaluate uptake relative to white and gray matter
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- Highest transaxial images above orbits often have diminished gray-white matter differentiation, even in normal patients
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- F-18 FDG PET
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- General F-18 FDG uptake patterns
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- MCI: Medial temporal lobe hypometabolism
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- Early AD
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- Relative reduction in activity in parietal, temporal lobes and posterior cingulate gyri and precuneus, usually symmetric
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- Advanced AD
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- Progression of findings present in early AD
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- Usually symmetric
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- Frontal lobe hypometabolism can develop later in disease course
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- Moderate to severe atrophy
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- Atypical AD patterns
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- Posterior cortical atrophy: Similar hypometabolism to typical AD + asymmetric occipital hypometabolism
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- Logopenic variant primary progressive aphasia (lvPPA): Similar to typical AD though with strong left-sided predominance (language dominant hemisphere)
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- Behavioral or dysexecutive AD: 50% similar to typical AD + extensive frontal hypometabolism; 50% indistinguishable from frontotemporal dementia (FTD) without parietal involvement
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- F-18 FDG PET most accurate when read in conjunction with quantitative software that compares F-18 FDG uptake to age-matched normal database
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- Surface projections also ↑ sensitivity for AD detection
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- SPECT perfusion with Tc-99m HMPAO or Tc-99m ethyl cystine dimer (ECD) has similar appearance as PET but ↓ resolution and sensitivity
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- Tau PET
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- Flortaucipir: Only FDA-approved tau PET tracer
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- Compare uptake to reference region [1.65 x mean standardized uptake value ratio (SUV) cerebellum], which acts as internal negative control during interpretation
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- Negative if cortical binding is limited to mesial and anteromedial temporal lobes or isolated frontal lobes, off-target binding to choroid plexus
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- Mild/early AD may be indistinguishable from normal study
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- Moderate AD if cortical binding extends to posterolateral temporal lobes and temporooccipital regions
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- Advanced AD if cortical binding extends beyond to parietal, occipital, and cingulate regions
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- Negative to early disease stage by tau PET can predict better response to amyloid targeting therapies (ATTs) with 50% of patients showing improved memory function at 3 years of treatment
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- ## MR Findings
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- T1WI, T2WI
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- Atrophy of medial temporal lobe structures (entorhinal cortex, hippocampus); visible as early as MCI and posterior structures (precuneus and parietal convexities)
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- Rates of whole-brain and hippocampal atrophy may be used to monitor progression of neurodegeneration and help stage AD severity
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- Can use volumetrix to quantitatively assess volume loss
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- ## Imaging Recommendations
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- ### Best imaging tool
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- Amyloid PET best for ruling out AD
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- Appropriate Use Criteria (AUC) for amyloid PET (SNMMI and AA joint task force)
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- Objectively confirmed persistent or progressive unexplained cognitive impairment
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- May satisfy core clinical criteria for AD but unclear presentation, such as atypical or mixed
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- Progressive dementia and atypically early age of onset (< 65 years)
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- Candidacy for ATTs
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- If considering amyloid PET, knowledge of Aβ pathology should ↑ diagnostic certainty &/or patient management
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- Amyloid and F-18 FDG PET can help to differentiate between AD and other causes of dementia (FTD, Lewy body dementia)
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- PET may be used in early diagnosis of ADNC
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- Correlate imaging results with clinical picture and other biomarkers of AD
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- ### Protocol advice
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- Amyloid PET
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- Patient preparation
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- Patient needs to lie still for 20-30 min; thus, immobilization techniques may be necessary
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- Radiopharmaceutical, dose, and time of scan post injection
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- F-18 florbetapir (Amyvid), 10 mCi, 30-50 min
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- F-18 flutemetamol (Vizamyl), 5 mCi, 90 min
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- F-18 florbetaben (Neuraceq), 8 mCi, 45-130 min
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- Dosimetry: Gallbladder wall receives highest dose, followed by intestines
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- Image acquisition
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- Depends largely on available PET scanner
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- CT typically used for attenuation correction; older PET scanners may use separate source (e.g., Ge-68/68-Ga) for transmission scan
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- Imaging begins 30-130 min after injection
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- 20-min acquisition
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- Matrix: Transaxial 128 x 128 or 256 x 256
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- Pixel size: 2-3 mm
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- Slice thickness: 2-4 mm
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- Filtered back projection or iterative reconstruction
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- F-18 FDG PET
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- Patient preparation
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- Patient should fast, stop IV fluids containing dextrose, and stop parenteral feeding for 4-6 hours
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- Blood sugar should be < 150-200 mg/dL
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- Patient should be placed in quiet, dimly lit room prior to and after injection for 30 min
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- Radiopharmaceutical: F-18 FDG
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- Dose: 5-20 mCi (185-740 MBq)
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- Dosimetry: Urinary bladder receives largest dose
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- Image acquisition: 30-60 min after injection
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- Perfusion SPECT
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- 2nd-line study if PET is not available
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- Patient preparation
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- Place patient in quiet, dimly lit room prior to and after injection for 30 min
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- Radiopharmaceutical
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- Tc-99m exametazime (HMPAO)
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- Tc-99m bicisate (ECD)
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- Dose: 15-30 mCi (555 MBq to 1.1 GBq)
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- Dosimetry
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- Tc-99m HMPAO: Kidneys receive highest dose
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- Tc-99m ECD: Bladder wall receives highest dose
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- Image acquisition
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- Optimal imaging time for Tc-99m HMPAO: 90 min post injection
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- Optimal imaging time for Tc-99m ECD: 45 min post injection
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- Tau PET
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- Dose: 10 mCi flortaucipir
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- Image acquisition: ~ 80 min after injection, 20-min acquisition
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- Dosimetry: Intestines and liver are critical organs
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# DIFFERENTIAL DIAGNOSIS
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- ## Vascular Dementia (Multiinfarct Dementia)
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- Impaired blood supply to brain regions
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- 2nd most common cause of dementia
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- Global atrophy with diffuse white matter lesions/infarcts that generally correlate with cognitive symptoms
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- ## Alzheimer Disease Mixed Dementia
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- AD and other dementia
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- ## Dementia With Lewy Bodies
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- Commonly presents with hallucinations, sleep disturbances, and parkinsonian motor features
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- F-18 FDG PET hypometabolism in occipital cortex distinguishes from typical amnestic AD
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- Consider DaT SPECT or FDOPA PET to help exclude posterior cortical atrophy if clinically uncertain
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- Can consider cardiac MIBG scan (reduced cardiac sympathetic activity in dementia with Lewy bodies, see on MIBG)
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- Skin biopsy for α-synuclein
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- ## Frontotemporal Dementia
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- Commonly presents with personality and behavioral changes, which can also be seen with behavioral/dysexecutive AD variants
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- Atrophy of frontal and anterior temporal lobes
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- Language variant FTDs (semantic and nonfluent agrammatic PPA) can mimic lvPPA
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- F-18 FDG PET hypometabolism primarily in frontal and anterior temporal lobes
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- Negative amyloid PET; helps exclude AD in favor of FTD
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- ## Creutzfeldt-Jakob Disease
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- Rapidly fatal, prion-related disease with impairments in cognition and behavioral changes
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- MR DWI: Hyperintensity in striatum, cingulum, neocortex
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- ## Causes of Reversible Dementia
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- [Normal-pressure hydrocephalus](/document/normal-pressure-hydrocephalus/834ccc3e-2116-4295-8408-0ac9a06bd2ff)
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- Hypothyroidism
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- Infections: Neurosyphilis, HIV
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- Trauma (e.g., chronic subdural hematoma)
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- Tumor, other mass lesions
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- Depression
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- Vitamin B12 deficiency
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- ## Other Neurodegenerative Disease
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- Parkinson disease
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- Huntington disease
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- ## Cerebral Amyloid Angiopathy
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- Abnormal accumulation of amyloid in leptomeningeal and cortical vessels, leading to intracranial hemorrhage
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- Can present with cognitive decline concerning for AD
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- Amyloid positive scan
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- MR is most helpful for finding lobar predominant microhemorrhages and superficial siderosis
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- Can have inflammatory variants and even amyloidomas (mimicking intracranial mass)
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- ## Primary Age-Related Tauopathy (A-T+N+/-C+)
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- Tau-related NFTs limited to temporal lobes without amyloid deposition on PET
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- Patients are typically much older than AD, and cognitive decline rate is typically slower
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- ## Limbic-Predominant Age-Related TDP-43 Encephalopathy
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- Amyloid negative (unless associated with AD copathology)
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- Typically in older patients (> 80 years)
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- Extensive temporal lobe FDG hypometabolism with less involvement of parietal structures
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- MR may show marked hippocampal sclerosis
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# PATHOLOGY
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- ## General Features
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- ### Etiology
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- Most likely combination of genetic, lifestyle, and environmental factors
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- Pathologic deposition of Aβ neuritic plaques and subsequent tau NFTs in pathogenesis
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- Accumulation of extracellular amyloid plaques contribute to disrupted synaptic communication and neuronal death
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- Accumulation of intracellular tau NFTs contribute to disruption of nutrient and molecular transfer and neuronal death
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- ### Genetics
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- Early-onset, familial AD
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- Single-gene mutation
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- βA precursor protein (*APP*) gene on chromosome 21
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- Presenilin 1 (*PSEN1*) gene on chromosome 14
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- Presenilin 2 (*PSEN2*) gene on chromosome 1
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- Results in formation of abnormal proteins involved in APP
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- May contribute to production of harmful forms of βA and βA-related pathology
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- Late-onset, sporadic AD
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- Significant risk is related to apolipoprotein E (*APOE*) gene on chromosome 19
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- ApoE plays role in cholesterol transport and βA maintenance
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- ApoE exists as 3 alleles (e2, e3, e4) with each individual carrying 2 copies
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- ApoE-e4 allele is present in 20-30% of USA population and confers ↑ risk for AD development
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- 40-65% of individuals with AD carry at least 1 copy of e4 allele
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- Significant impairment in memory and cognition with typical AD
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- Mood and personality changes with behavioral/dysexecutive AD variant
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- Language impairment, including sentence repetition, preserved single-word meaning with lvPPA
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- Visuospatial and visuoperceptual impairment with posterior cortical atrophy
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- ### Clinical profile
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- Preclinical AD
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- Amyloid PET turns positive during this period
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- No noticeable symptoms of AD with early AD brain changes (up to 20 years before symptoms)
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- MCI
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- Change in cognition within ≥ 1 cognitive domains with functional independence intact
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- Possible AD
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- Significant cognitive/behavioral symptoms
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- Must represent change from prior status
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- Must interfere with functional ability
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- In presence of sudden onset &/or another disorder that could cause similar symptoms, e.g., cerebrovascular disease
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- Probable AD
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- Insidious change of cognitive/behavioral symptoms that interferes with functional ability
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- Not in presence of another disorder that could cause similar symptoms
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- ## Demographics
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- ### Epidemiology
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- ~ 5.2 million in USA affected by AD
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- Most common cause of dementia (60-80% of cases)
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- Prevalence
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- ~ 11% of adults ≥ 65 years
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- ~ 32% of adults ≥ 85 years
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- ## Treatment
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- Novel amyloid-targeting antibody therapies slow decline and may improve mental status if started early
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- Requires initial baseline MR to exclude cerebral amyloid and preexisting risk for hemorrhage
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- Requires surveillance for development of amyloid-related imaging abnormalities (ARIA)
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- Cholinesterase inhibitors may delay worsening of cognitive symptoms for 6-12 months
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- NMDA inhibitors may temporarily delay worsening of symptoms
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# DIAGNOSTIC CHECKLIST
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- ## Key Imaging Findings
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- AD neuropathic change
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- Amyloid PET positive or positive key CSF biomarkers
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- AD
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- FDG hypometabolism develops in parietal lobes, precuneus, posterior cingulate gyrus, posterior temporal lobes, and frontal lobes in advanced cases
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- Tau PET shows NFTs in posterolateral temporal neocortex, temporooccipital regions, and, eventually, parietal and cingulate regions
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47897414-6c3f-419d-8061-50a189ef4e1f
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+316
@@ -0,0 +1,316 @@
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# Alzheimer Disease
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# KEY FACTS
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- ## Terminology
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|
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- Alzheimer disease (AD)
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- Slowly progressive neurodegenerative disease
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- ## Imaging
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- Current role of imaging in AD
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- Exclude other causes of dementia
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- Identify region-specific patterns of brain volume loss
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- Identify imaging markers of coexistent disease, such as amyloid angiopathy
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- Identify early AD for possible innovative therapy
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- Best imaging = volumetric MR, F-18 FDG PET
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- Thinned gyri, widened sulci, and enlarged ventricles
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- Medial temporal lobe particularly hippocampus and entorhinal cortex disproportionately affected
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- F-18 FDG PET
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- Early-stage AD: ↓ metabolism in parietotemporal association cortices, posterior cingulate, and precuneus regions
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- Moderate to severe AD: Additional frontal lobe involvement
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- Amyloid PET imaging: High sensitivity in detecting amyloid plaques and vascular amyloid in vivo
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- ## Top Differential Diagnoses
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- Normal aging
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- Vascular dementia
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- Normal-pressure hydrocephalus
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- Frontotemporal lobar degeneration
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- Dementia with Lewy bodies
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- ## Clinical Issues
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- Most common cause of dementia > age 65
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- Age is biggest risk factor
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- 1-2% prevalence at age 65
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- Incidence doubles every 5 years after age of 60
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- ## Diagnostic Checklist
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- Look for reversible causes of dementia
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# TERMINOLOGY
|
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- ## Abbreviations
|
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|
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|
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- Alzheimer disease (AD)
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- ## Synonyms
|
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- Senile/presenile dementia of Alzheimer type
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- ## Definitions
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- AD dementia is progressive neurodegenerative condition characterized by progressive cognitive decline, memory impairment, and adverse impact on activities of daily living
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- National Institute on Aging and Alzheimer's Association (NIA-AA) 2011 workgroup recommendations
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- Phases of AD pathophysiological processes
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- Preclinical AD
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- Mild cognitive impairment (MCI) in AD
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- AD dementia
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- AD is pathologic process reflected in specific postmortem histopathologic criteria, which is frequently but not necessarily associated with characteristic dementia syndrome
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- Probable AD dementia: Clinical syndrome meeting core clinical criteria specified in NIA-AA workgroup report
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- Possible AD dementia: Clinical syndrome meeting core clinical criteria for AD dementia in terms of nature of cognitive deficits for AD dementia, but either 1) has sudden onset of impairment or demonstrates insufficient historical detail or objective documentation of progression, or 2) has mixed etiological presentation due to evidence of vascular or Lewy body pathology
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- MCI: Clinical syndrome meeting published core clinical criteria for MCI; generally agreed core features include 1) concern for change in cognition, 2) impairment in one or more cognitive domains, and 3) preservation of independence in functional activities, but 4) not demented
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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||||
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- MR: Temporal/parietal cortical atrophy
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- Disproportionate hippocampal volume loss
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- FDG PET: Regional ↓ glucose metabolism
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- Temporoparietal lobes, posterior cingulum
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- **Current role of imaging in AD**
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- Exclude other structural abnormalities
|
||||
- Evaluate degree and location of atrophic changes
|
||||
- Evaluate for metabolic abnormalities
|
||||
- When structural abnormalities absent/uncharacteristic (i.e., early in disease course)
|
||||
- Identify preclinical and MCI in AD for possible innovative therapy
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- ### NECT
|
||||
|
||||
|
||||
- Screening to exclude potentially reversible or treatable causes of dementia
|
||||
- Medial temporal lobe atrophy in early disease and generalized atrophy in late stages
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- Current role of MR
|
||||
- Exclude other causes of dementia
|
||||
- Identify region-specific patterns of brain volume loss
|
||||
- Identify imaging markers of coexistent disease, such as amyloid angiopathy
|
||||
- T1 to assess medial temporal atrophy score and atrophy patterns
|
||||
- High resolution (MPRAGE/SPGR) for volumetric analysis
|
||||
- Thinned gyri, widened sulci, and enlarged ventricles
|
||||
- Medial temporal lobe disproportionately affected
|
||||
- May help distinguish patients with MCI from normal elderly
|
||||
- Average hippocampal volume reduction 20-25% in AD and 10-15% in MCI
|
||||
- T2* GRE/SWI for microhemorrhages, amyloid angiopathy
|
||||
- MRS
|
||||
- ↓ NAA and ↑ mI in AD, even in early stage
|
||||
- NAA:mI ratio relatively sensitive and highly specific in differentiating AD from normal elderly
|
||||
- NAA:Cr ratio in posterior cingulate gyri and left occipital cortex predicts conversion of MCI to probable AD
|
||||
- DTI: ↓ FA in multiple regions, especially superior longitudinal fasciculus and splenium
|
||||
- Perfusion MR: ↓ rCBV in temporal, parietal regions
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- F-18 FDG PET
|
||||
- Early-stage AD
|
||||
- ↓ metabolism in parietotemporal association cortices, posterior cingulate, and precuneus regions
|
||||
- Most reliable early changes in posterior cingulate
|
||||
- Moderate to severe AD
|
||||
- Additional frontal lobe involvement
|
||||
- MCI in AD
|
||||
- Same pattern of ↓ metabolism as AD
|
||||
- Higher accuracy than MR for diagnosing early AD
|
||||
- Amyloid (Aβ) PET imaging
|
||||
- Specifically bind to Aβ plaques and retention of tracer is specific for Aβ neuritic plaque pathology
|
||||
- F-18 florbetapir, F-18 florbetaben, and F-18 flutemetamol FDA approved for clinical use
|
||||
- Positive scan shows loss of gray/white matter distinction due to tracer uptake in neocortex
|
||||
- Negative scan retains gray/white matter distinction
|
||||
- Criteria for appropriate use (AUC) of amyloid PET
|
||||
- Persistent/progressive unexplained MCI
|
||||
- Possible AD with unclear presentation
|
||||
- Atypical early-onset progressive dementia
|
||||
- In patients with MCI fulfilling clinical AUC, Aβ-PET is associated with
|
||||
- Significant improvement in diagnostic confidence
|
||||
- High impact on therapeutic management
|
||||
- Tau PET imaging
|
||||
- Currently under development
|
||||
- Signal matches anatomic distribution of neurofibrillary tangles
|
||||
- Earliest detection in entorhinal cortex and hippocampus, later inferior and lateral temporal, followed by parietal and occipital, and finally frontal cortices
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- Volumetric MR (MPRAGE/SPGR sequences)
|
||||
- F-18 FDG PET
|
||||
- Aβ PET for patients who meet AUC
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- MPRAGE or SPGR for volumetric measurement
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- ## Causes of Reversible Dementia
|
||||
|
||||
|
||||
- [Thiamine deficiency, vitamin B12 deficiency, hypothyroidism](/document/alcoholic-encephalopathy/88021852-b73d-4cdf-a719-dd4ae3231e45)
|
||||
- Depression ("pseudodementia")
|
||||
- [Normal-pressure hydrocephalus](/document/normal-pressure-hydrocephalus/ba3f857d-58de-4f21-8463-1631b4cb9972)
|
||||
- [Mass lesions (chronic subdural hematoma, tumor, etc.)](/document/chronic-subdural-hematoma/cc7b52b4-c6a0-4b4e-ae8c-f05bfc5c5cb2)
|
||||
- [Vascular Dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
|
||||
- 2nd most common dementia (15-30%)
|
||||
- Parenchymal hyperintensities, focal atrophy (infarcts)
|
||||
- [Frontotemporal Lobar Degeneration](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
|
||||
- Frontal &/or anterior temporal atrophy
|
||||
- [Dementia With Lewy Bodies](/document/dementia-with-lewy-bodies/e8e46d1d-46d2-4e5a-880f-f025a84c5871)
|
||||
- Hypometabolism of entire brain
|
||||
- [Corticobasal Degeneration](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
|
||||
- Prominent extrapyramidal, cortical symptoms
|
||||
- Asymmetric severe frontoparietal atrophy
|
||||
- [Creutzfeldt-Jakob Disease](/document/creutzfeldt-jakob-disease-cjd/e1b27954-6591-4bb0-a659-b13790492620)
|
||||
- Dementia with myoclonus, EEG abnormalities
|
||||
- Hyperintensity in anterior basal ganglia, cortex
|
||||
- [Cerebral Amyloid Angiopathy](/document/cerebral-amyloid-disease/48e9458e-102f-40bd-8eec-bc0bc97101c6)
|
||||
- Often coexists with AD
|
||||
- Microhemorrhages on T2* GRE/SWI
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Extracellular β-amyloid plaques
|
||||
- Located in cerebral cortex
|
||||
- Intracellular accumulation of neurofibrillary tangles (NTs)
|
||||
- Initially around hippocampus, later spread to other cortical areas
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Most cases late-onset sporadic AD
|
||||
- Deterministic genetic mutation not found
|
||||
- Apolipoprotein E (*ApoE*) ε4 allele is major genetic risk factor
|
||||
- Rare early-onset AD
|
||||
- Mutations in 1 of 3 genes
|
||||
- Amyloid precursor protein gene on chromosome 21
|
||||
- Presenilin-1 (*PSEN1*) gene on chromosome 14
|
||||
- Presenilin-2 (*PSEN2*) gene on chromosome 1
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- Consortium to Establish a Registry for Alzheimer Disease (CERAD)
|
||||
- Semiquantitative approach counting plaques/tangles
|
||||
- Frequent, moderate, or infrequent
|
||||
- Braak and Braak (B&B)
|
||||
- 6 levels of staging
|
||||
- Transentorhinal stage (1-2): NTs develop in parahippocampal gyrus (clinically asymptomatic)
|
||||
- Limbic stage (3-4): NTs dramatically increase in parahippocampal gyrus, begin to develop in hippocampus (mild cognitive impairment)
|
||||
- Neocortical stage (5-6): NTs develop in temporal and parietal cortex, eventually spread to entire neocortex (severe dementia)
|
||||
- NIA-Reagan
|
||||
- Likelihood high
|
||||
- CERAD frequent, B&B 5/6
|
||||
- Likelihood intermediate
|
||||
- CERAD moderate, B&B 3/4
|
||||
- Likelihood low
|
||||
- CERAD infrequent, B&B 1/2
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Shrunken gyri, widened sulci
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- 2 abnormal protein aggregates characterize AD pathologically
|
||||
- Neurofibrillary tangles
|
||||
- Intracellular aggregates in neurons due to hyperphosphorylation of tau protein
|
||||
- Begins in entorhinal cortex, progresses to hippocampus, paralimbic system, and adjacent medial-basal temporal lobe
|
||||
- Aβ deposition
|
||||
- Hallmark of Aβ peptide deposit in AD is neuritic plaque
|
||||
- Dense Aβ core with inflammatory cells and dystrophic neurites in its periphery
|
||||
- Neurodegeneration: Synapse and neuron loss
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Slowly progressive neurodegenerative disease
|
||||
- Initially affects episodic memory
|
||||
- Then, at least 1 other area of cognition
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- Clinical subtypes
|
||||
- MCI: Early, mild memory impairment; no deficits in cognitive domains other than memory, not impairing daily function
|
||||
- Possible AD: Dementia features in presence of 2nd disease that could cause memory deficit but is not likely cause
|
||||
- Probable AD: Memory deficits on neuropsychological testing, progressive worsening of memory and ≥ 2 cognitive functions
|
||||
- Definite AD: Pathologic diagnosis
|
||||
- 5 major biomarkers for AD
|
||||
- Amyloid accumulation: CSF Aβ 42, Aβ-PET imaging
|
||||
- Neurogeneration or neuronal injury: CSF tau (total and phosphorylated), structural MR, and FDG PET
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Biggest risk factor
|
||||
- 1-2% prevalence at age 65
|
||||
- Incidence doubles every 5 years after age of 60
|
||||
- ### Sex
|
||||
|
||||
|
||||
- Women more commonly affected
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- AD most common neurodegenerative dementia
|
||||
- 5-7 million new AD dementia cases every year
|
||||
- Currently ~ 5.3 million in USA
|
||||
- 13% of individuals > 65 years and > 50% of individuals > 85 years
|
||||
- Other risk factors
|
||||
- Family history (20%)
|
||||
- Head trauma, metabolic syndrome
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Chronic, progressive
|
||||
- Patients live average 8-10 years after diagnosis
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- No established treatments
|
||||
- May transiently improve cognitive function
|
||||
- Cholinesterase inhibitors, NMDA receptor antagonists
|
||||
- Many current disease-modifying drugs to reduce Aβ
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- Look for
|
||||
- Reversible causes of dementia
|
||||
- Ventricular enlargement, sulcal widening proportionate
|
||||
- ↑ temporal horns of lateral ventricle
|
||||
- Hippocampal, entorhinal cortex volume loss
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- MR volumetric analysis helps distinguish MCI in AD from normal elderly subjects, measure change hippocampus/parahippocampal gyri over time
|
||||
- F-18 FDG PET
|
||||
- Helps distinguish AD from frontotemporal dementia
|
||||
- May identify early AD when MR normal
|
||||
|
||||
5dea6eed-cbf2-4d32-8c2b-43f74913fca6
|
||||
+78
@@ -0,0 +1,78 @@
|
||||
# Attention Control Network
|
||||
|
||||
# IMAGING ANATOMY
|
||||
|
||||
- ## Overview
|
||||
|
||||
|
||||
- Attention control network is a constellation of distributed brain networks processing attention to external stimuli and symbols
|
||||
- Many aliases: Task-positive network, frontoparietal network, executive control network, and central executive network, each referring to subsets of the attention control network
|
||||
- Terminology is not standard in the literature, and different authors use many of these terms interchangeably or to refer to different subsets of a broader attentional network
|
||||
- ## Dorsal Attention Network
|
||||
|
||||
|
||||
- Function: Voluntary control of attentional focus and goal-directed behavior
|
||||
- Regions: Intraparietal sulcus, frontal eye fields, middle temporal, dorsolateral prefrontal cortex
|
||||
- Intraparietal sulcus
|
||||
- Weighting of sensory inputs: Direct control of relative "value" or "attention" to sensory stimuli
|
||||
- Topographically organized by stimulus modality and spatial location
|
||||
- Frontal eye fields and supplementary eye fields
|
||||
- Control of direction of gaze to attentionally relevant stimuli
|
||||
- Middle temporal (MT)
|
||||
- Motion perception, dynamic features of attention
|
||||
- Dorsolateral prefrontal cortex (DLPFC)
|
||||
- Shared with ventral attention network, representations of objects and symbols, working memory
|
||||
- ## Ventral Attention Network
|
||||
|
||||
|
||||
- Function: Control of reorienting to relevant stimuli, working memory
|
||||
- Aliases: Frontoparietal control network, executive control network
|
||||
- Regions: Supramarginal and angular gyri, inferior frontal gyrus, dorsolateral prefrontal cortex, ventral anterior cingulate cortex
|
||||
- Inferior parietal lobule (supramarginal and angular gyri)
|
||||
- Inferior frontal gyrus
|
||||
- DLPFC
|
||||
- Ventral anterior cingulate cortex
|
||||
- ## Salience Network
|
||||
|
||||
|
||||
- Function: Detection of novel or salient stimuli
|
||||
- Aliases: Novelty detection network, cingulo-opercular network
|
||||
- Regions: Frontoinsula, dorsal anterior cingulate cortex
|
||||
- Frontoinsula
|
||||
- "Sensory" arm of salience network
|
||||
- Mid superior insula: Detection of stimulus salience
|
||||
- Mid inferior insula: Detection of emotive salience
|
||||
- Anterior insula: Control of attention
|
||||
- Dorsal anterior cingulate cortex
|
||||
- "Motor" arm of salience network
|
||||
- More anterior (pregenual) cingulate more associated with emotive salience, merges with ventral attention network
|
||||
|
||||
# ANATOMY IMAGING ISSUES
|
||||
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- Specific subnetworks may be activated by specific tasks (e.g., oddball task for salience network, n-back task for dorsal attention network)
|
||||
- ## Imaging Pitfalls
|
||||
|
||||
|
||||
- Many fMRI tasks have differential stimulus attention between active and control conditions
|
||||
- Activation in attentional regions may not be task specific, but a general consequence of differential attention between conditions
|
||||
- ## Network Relationships
|
||||
|
||||
|
||||
- Attention control network is anticorrelated to default mode network: When one is active, the other tends to be less active
|
||||
- Allows focus of attention to shift between external and internal stimuli
|
||||
- Gradients of anticorrelation across the attention control network are seen with specific subregions of each network hub showing greatest anticorrelation
|
||||
- Attentional regions typically located in association cortex in regions spatially "equidistant" from primary sensory areas
|
||||
- Flow of information from primary sensory to unimodal sensory association cortex to polymodal association cortex
|
||||
|
||||
# CLINICAL IMPLICATIONS
|
||||
|
||||
- ## Clinical Importance
|
||||
|
||||
|
||||
- Right-dominant network for attention in most individuals
|
||||
- Lesions of right ventral attention network may produce hemispatial neglect
|
||||
|
||||
8145fc24-f946-49ef-9ae0-c4315a58d768
|
||||
+78
@@ -0,0 +1,78 @@
|
||||
# Attention Control Network
|
||||
|
||||
# IMAGING ANATOMY
|
||||
|
||||
- ## Overview
|
||||
|
||||
|
||||
- Attention control network is a constellation of distributed brain networks processing attention to external stimuli and symbols
|
||||
- Many aliases: Task-positive network, frontoparietal network, executive control network, and central executive network, each referring to subsets of the attention control network
|
||||
- Terminology is not standard in the literature, and different authors use many of these terms interchangeably or to refer to different subsets of a broader attentional network
|
||||
- ## Dorsal Attention Network
|
||||
|
||||
|
||||
- Function: Voluntary control of attentional focus and goal-directed behavior
|
||||
- Regions: Intraparietal sulcus, frontal eye fields, middle temporal, dorsolateral prefrontal cortex
|
||||
- Intraparietal sulcus
|
||||
- Weighting of sensory inputs: Direct control of relative "value" or "attention" to sensory stimuli
|
||||
- Topographically organized by stimulus modality and spatial location
|
||||
- Frontal eye fields and supplementary eye fields
|
||||
- Control of direction of gaze to attentionally relevant stimuli
|
||||
- Middle temporal (MT)
|
||||
- Motion perception, dynamic features of attention
|
||||
- Dorsolateral prefrontal cortex (DLPFC)
|
||||
- Shared with ventral attention network, representations of objects and symbols, working memory
|
||||
- ## Ventral Attention Network
|
||||
|
||||
|
||||
- Function: Control of reorienting to relevant stimuli, working memory
|
||||
- Aliases: Frontoparietal control network, executive control network
|
||||
- Regions: Supramarginal and angular gyri, inferior frontal gyrus, dorsolateral prefrontal cortex, ventral anterior cingulate cortex
|
||||
- Inferior parietal lobule (supramarginal and angular gyri)
|
||||
- Inferior frontal gyrus
|
||||
- DLPFC
|
||||
- Ventral anterior cingulate cortex
|
||||
- ## Salience Network
|
||||
|
||||
|
||||
- Function: Detection of novel or salient stimuli
|
||||
- Aliases: Novelty detection network, cingulo-opercular network
|
||||
- Regions: Frontoinsula, dorsal anterior cingulate cortex
|
||||
- Frontoinsula
|
||||
- "Sensory" arm of salience network
|
||||
- Mid superior insula: Detection of stimulus salience
|
||||
- Mid inferior insula: Detection of emotive salience
|
||||
- Anterior insula: Control of attention
|
||||
- Dorsal anterior cingulate cortex
|
||||
- "Motor" arm of salience network
|
||||
- More anterior (pregenual) cingulate more associated with emotive salience, merges with ventral attention network
|
||||
|
||||
# ANATOMY IMAGING ISSUES
|
||||
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- Specific subnetworks may be activated by specific tasks (e.g., oddball task for salience network, n-back task for dorsal attention network)
|
||||
- ## Imaging Pitfalls
|
||||
|
||||
|
||||
- Many fMRI tasks have differential stimulus attention between active and control conditions
|
||||
- Activation in attentional regions may not be task specific, but a general consequence of differential attention between conditions
|
||||
- ## Network Relationships
|
||||
|
||||
|
||||
- Attention control network is anticorrelated to default mode network: When one is active, the other tends to be less active
|
||||
- Allows focus of attention to shift between external and internal stimuli
|
||||
- Gradients of anticorrelation across the attention control network are seen with specific subregions of each network hub showing greatest anticorrelation
|
||||
- Attentional regions typically located in association cortex in regions spatially "equidistant" from primary sensory areas
|
||||
- Flow of information from primary sensory to unimodal sensory association cortex to polymodal association cortex
|
||||
|
||||
# CLINICAL IMPLICATIONS
|
||||
|
||||
- ## Clinical Importance
|
||||
|
||||
|
||||
- Right-dominant network for attention in most individuals
|
||||
- Lesions of right ventral attention network may produce hemispatial neglect
|
||||
|
||||
6e3d29ca-3af0-4a42-b125-7ec5fad53f3f
|
||||
+78
@@ -0,0 +1,78 @@
|
||||
# Attention Control Network
|
||||
|
||||
# IMAGING ANATOMY
|
||||
|
||||
- ## Overview
|
||||
|
||||
|
||||
- Attention control network is a constellation of distributed brain networks processing attention to external stimuli and symbols
|
||||
- Many aliases: Task-positive network, frontoparietal network, executive control network, and central executive network, each referring to subsets of the attention control network
|
||||
- Terminology is not standard in the literature, and different authors use many of these terms interchangeably or to refer to different subsets of a broader attentional network
|
||||
- ## Dorsal Attention Network
|
||||
|
||||
|
||||
- Function: Voluntary control of attentional focus and goal-directed behavior
|
||||
- Regions: Intraparietal sulcus, frontal eye fields, middle temporal, dorsolateral prefrontal cortex
|
||||
- Intraparietal sulcus
|
||||
- Weighting of sensory inputs: Direct control of relative "value" or "attention" to sensory stimuli
|
||||
- Topographically organized by stimulus modality and spatial location
|
||||
- Frontal eye fields and supplementary eye fields
|
||||
- Control of direction of gaze to attentionally relevant stimuli
|
||||
- Middle temporal (MT)
|
||||
- Motion perception, dynamic features of attention
|
||||
- Dorsolateral prefrontal cortex (DLPFC)
|
||||
- Shared with ventral attention network, representations of objects and symbols, working memory
|
||||
- ## Ventral Attention Network
|
||||
|
||||
|
||||
- Function: Control of reorienting to relevant stimuli, working memory
|
||||
- Aliases: Frontoparietal control network, executive control network
|
||||
- Regions: Supramarginal and angular gyri, inferior frontal gyrus, dorsolateral prefrontal cortex, ventral anterior cingulate cortex
|
||||
- Inferior parietal lobule (supramarginal and angular gyri)
|
||||
- Inferior frontal gyrus
|
||||
- DLPFC
|
||||
- Ventral anterior cingulate cortex
|
||||
- ## Salience Network
|
||||
|
||||
|
||||
- Function: Detection of novel or salient stimuli
|
||||
- Aliases: Novelty detection network, cingulo-opercular network
|
||||
- Regions: Frontoinsula, dorsal anterior cingulate cortex
|
||||
- Frontoinsula
|
||||
- "Sensory" arm of salience network
|
||||
- Mid superior insula: Detection of stimulus salience
|
||||
- Mid inferior insula: Detection of emotive salience
|
||||
- Anterior insula: Control of attention
|
||||
- Dorsal anterior cingulate cortex
|
||||
- "Motor" arm of salience network
|
||||
- More anterior (pregenual) cingulate more associated with emotive salience, merges with ventral attention network
|
||||
|
||||
# ANATOMY IMAGING ISSUES
|
||||
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- Specific subnetworks may be activated by specific tasks (e.g., oddball task for salience network, n-back task for dorsal attention network)
|
||||
- ## Imaging Pitfalls
|
||||
|
||||
|
||||
- Many fMRI tasks have differential stimulus attention between active and control conditions
|
||||
- Activation in attentional regions may not be task specific, but a general consequence of differential attention between conditions
|
||||
- ## Network Relationships
|
||||
|
||||
|
||||
- Attention control network is anticorrelated to default mode network: When one is active, the other tends to be less active
|
||||
- Allows focus of attention to shift between external and internal stimuli
|
||||
- Gradients of anticorrelation across the attention control network are seen with specific subregions of each network hub showing greatest anticorrelation
|
||||
- Attentional regions typically located in association cortex in regions spatially "equidistant" from primary sensory areas
|
||||
- Flow of information from primary sensory to unimodal sensory association cortex to polymodal association cortex
|
||||
|
||||
# CLINICAL IMPLICATIONS
|
||||
|
||||
- ## Clinical Importance
|
||||
|
||||
|
||||
- Right-dominant network for attention in most individuals
|
||||
- Lesions of right ventral attention network may produce hemispatial neglect
|
||||
|
||||
6e3d29ca-3af0-4a42-b125-7ec5fad53f3f
|
||||
+320
@@ -0,0 +1,320 @@
|
||||
# Creutzfeldt-Jakob Disease (CJD)
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Creutzfeldt-Jakob disease (CJD): Rapidly progressing, fatal, potentially transmissible dementia caused by prion
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Best imaging clue: Progressive DWI/FLAIR hyperintensity of basal ganglia (BG), thalamus, and cerebral cortex
|
||||
- Predominantly gray matter (GM): Caudate and putamen > globus pallidus (GP)
|
||||
- Thalamus: Common in variant CJD (vCJD)
|
||||
- Cerebral cortex: Frontal, parietal, and temporal
|
||||
- Heidenhain variant: Occipital lobe
|
||||
- 2 signs seen in 90% of vCJD but can also occur in sporadic CJD (sCJD)
|
||||
- Pulvinar sign: Symmetric T2 hyperintensity of pulvinar of thalamus
|
||||
- Hockey stick sign: Symmetric pulvinar and dorsomedial thalamic nuclear hyperintensity
|
||||
- Best imaging tool: MR with DWI
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Hypoxic-ischemic injury
|
||||
- Osmotic demyelination syndrome
|
||||
- Other causes of dementia
|
||||
- Alzheimer, frontotemporal, and multiinfarct dementia; dementia in motor neuron disease
|
||||
- Leigh syndrome
|
||||
- Corticobasal degeneration
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Definite CJD diagnosed by neuropathology
|
||||
- Progressive dementia associated with myoclonic jerks and akinetic mutism; variable constellation of pyramidal, extrapyramidal, and cerebellar signs
|
||||
- CSF protein biomarkers: 14-3-3 protein, total tau (t-tau), S100 and neuron-specific enolase (NSE)
|
||||
- DWI MR has higher diagnostic accuracy, 97% more than any or all of these CSF biomarkers
|
||||
- Incidence 1 per 1,000,000 (USA and internationally)
|
||||
- sCJD (85%), familial (15%), infectious/iatrogenic (< 1%) (includes vCJD)
|
||||
- Death usually ensues within months of onset
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Creutzfeldt-Jakob disease (CJD)
|
||||
- Sporadic Creutzfeldt-Jakob disease (sCJD)
|
||||
- Variant Creutzfeldt-Jakob disease (vCJD)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Rapidly progressing, fatal, neurodegenerative disorder caused by prion (proteinaceous infectious particle devoid of DNA and RNA)
|
||||
- Transmissible spongiform encephalopathy
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Progressive T2 hyperintensity of basal ganglia (BG), thalamus, and cerebral cortex
|
||||
- ### Location
|
||||
|
||||
|
||||
- Predominantly gray matter (GM)
|
||||
- BG: Caudate and putamen > globus pallidus (GP)
|
||||
- Thalamus (common in vCJD)
|
||||
- Cerebral cortex (most commonly frontal, parietal, and temporal lobes)
|
||||
- Cortical involvement often asymmetric
|
||||
- Heidenhain variant: Occipital lobe
|
||||
- Brownell-Oppenheimer: Cerebellum
|
||||
- May involve only peripheral cortex
|
||||
- Cortical involvement often asymmetric
|
||||
- Primary sensorimotor cortex relatively spared
|
||||
- White matter (WM) usually not involved
|
||||
- Size: Slight decrease (atrophy)
|
||||
- Morphology: Hyperintense T2 signal conforms to outline of BG and gyriform pattern in cortex
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- NECT: Usually normal
|
||||
- May show rapidly progressive atrophy and ventricular dilatation on serial CT
|
||||
- Serial CT illustrates atrophy progression
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Normal
|
||||
- GP hyperintensity reported in sCJD
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Hyperintense signal in BG, thalami, cortex
|
||||
- Cerebral atrophy
|
||||
- With time, hyperintense foci may develop in WM
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- 2 signs seen in 90% of vCJD but can also occur in sCJD
|
||||
- **Pulvinar**sign: Bilateral symmetrical hyperintensity of **pulvinar** (posterior) nuclei of **thalamus**
|
||||
- **Hockey stick** sign: Symmetrical **pulvinar and dorsomedial thalamic** nuclear hyperintensity
|
||||
- Periaqueductal GM hyperintensity
|
||||
- Cortical hyperintensity (common in sCJD)
|
||||
- ### DWI
|
||||
|
||||
|
||||
- Progressive hyperintensity in striatum and cortex
|
||||
- Gyriform hyperintense areas in cerebral cortex (cortical ribbon sign*)*
|
||||
- Correspond to localization of periodic sharp wave complexes on EEG
|
||||
- DWI hyperintensity may disappear late in disease
|
||||
- T1WI C+: No abnormal enhancement
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- F-18 FDG PET: Regional glucose hypometabolism correlates with sites of neuropathologic lesions
|
||||
- SPECT with N-isopropyl-p-(I-123) iodoamphetamine (DaTSCAN)
|
||||
- ↓ uptake of tracer in BG reported
|
||||
- Sometimes in asymmetrical pattern
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- Best imaging tool: MR with DWI and FLAIR
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Hypoxic-Ischemic Injury](/document/adult-hypoxic-ischemic-injury/dfb41c7a-2914-4a29-b05b-3a45c241f4a1)
|
||||
- BG and parasagittal cortical areas involved
|
||||
- Hyperintense BG lesions on T1WI and T2WI
|
||||
- DWI + symmetric GM involvement
|
||||
- [Osmotic Demyelination Syndrome](/document/osmotic-demyelination-syndrome/e061cc1f-61b4-4c4c-8b91-f53bf170180e)
|
||||
- Extrapontine: T2-hyperintense putamen and caudate
|
||||
- DWI positive acutely
|
||||
- ## Leigh Syndrome
|
||||
|
||||
|
||||
- Primarily seen in pediatric patients
|
||||
- T2 hyperintensity in putamen and GP
|
||||
- [Other Causes of Dementia](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
|
||||
- [Alzheimer disease](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
|
||||
- [Dementia in motor neuron disease](/document/amyotrophic-lateral-sclerosis-als/23de52b7-d9bd-441c-a18c-95c8afccb470)
|
||||
- [Frontotemporal dementia](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
|
||||
- [Multiinfarct dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
|
||||
- [Corticobasal Degeneration](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
|
||||
- Neuronal loss in substantia nigra, frontoparietal cortex, and striatum (BG atrophy may be subtle)
|
||||
- MR: Symmetric/asymmetric atrophy of pre- and postcentral gyri; prominent parasagittal involvement
|
||||
- Subcortical gliosis: High intensity on T2WI
|
||||
- [Wilson Disease](/document/wilson-disease/3d4d4876-4ce4-4af0-9e75-1a419bdd813c)
|
||||
- WM and deep GM lesions (BG, dentate nucleus, brainstem); variably T2 hyperintense
|
||||
- T1-hypointense (rarely hyperintense) lesions
|
||||
- [Arteriolosclerosis](/document/arteriolosclerosis/ce5a75ed-3a88-42a4-a0e8-4f339375c062)
|
||||
- BG involvement: Typically asymmetric and multifocal (rather than diffuse as in CJD)
|
||||
- Focal hyperintensities in deep WM
|
||||
- DWI negative, unless acute
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Prion protein is misfolded isoform (PrPSc) of normal host-encoded protein (PrPc)
|
||||
- PrPSc = conformationally isomer of PrPc
|
||||
- PrPSc introduced into healthy cells → initiates self-perpetuating vicious cycle: PrPc → PrPSc → neurotoxicity
|
||||
- sCJD: Spontaneous PrPc → PrPSc or somatic mutation
|
||||
- Familial CJD (fCJD): Mutations in *PRNP*gene
|
||||
- Iatrogenic CJD: Infection from prion-containing material
|
||||
- Surgical instruments, dura mater grafts, stereotactic electrodes
|
||||
- Cadaveric corneal transplants, human pituitary hormones (growth hormone and gonadotropins)
|
||||
- vCJD: Bovine spongiform encephalopathy in cattle is transmitted to humans through infected beef
|
||||
- Primarily present in UK
|
||||
- a.k.a. new variant CJD (nvCJD)
|
||||
- Risk for health care workers
|
||||
- Physical contact with patients is no risk for transmission
|
||||
- Special precautions in handling brain tissue
|
||||
- All used materials and instruments decontaminated as per established protocols
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Can be inherited, sporadic, or acquired (infectious)
|
||||
- 10-15% of human prion disease cases associated with dominant mutations in autosomal prion protein (PrPc) gene (*PRNP*) on chromosome 20
|
||||
- PrPc is normal host protein on surface of many cells, particularly neurons
|
||||
- ### Associated abnormalities
|
||||
|
||||
|
||||
- EEG: Periodic (high-voltage) sharp wave complexes (PSWCs) on background of low-voltage activity
|
||||
- 67-95% patients with sCJD show PSWCs at some point during course of illness
|
||||
- False-positive EEG findings in Alzheimer dementia and vascular dementia patients
|
||||
- PSWCs helpful in differentiating sCJD from other prion disease
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- Sporadic CJD
|
||||
- Definite
|
||||
- Characteristic neuropathology (biopsy or autopsy)
|
||||
- Protease-resistant PrPSc (PrPres) by Western blot
|
||||
- Probable
|
||||
- Neuropsychiatric disorder with positive RT-QuIC in CSF or other tissues
|
||||
- OR
|
||||
- Rapidly progressive dementia and at least 2 out of 4 clinical features listed in table 1
|
||||
- AND positive result on at least 1 of 3 lab tests listed in table 1
|
||||
- AND without routine investigations indicating alternative diagnosis
|
||||
- Possible
|
||||
- Progressive dementia and at least 2 out of 4 clinical features listed in table 1
|
||||
- AND absence of positive lab tests that would classify case as "probable"
|
||||
- AND duration of illness < 2 years
|
||||
- AND without routine investigations indicating alternative diagnosis
|
||||
- Iatrogenic CJD: Progressive cerebellar syndrome in recipient of human cadaveric-derived pituitary hormone; or sporadic CJD with recognized exposure risk, e.g., antecedent neurosurgery with dura mater implantation
|
||||
- Familial CJD: Definite or probable CJD **with** definite or probable CJD in 1st-degree relative; &/or neuropsychiatric disorder **with** disease-specific PrP gene mutation
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Mild cortical atrophy
|
||||
- Diffuse or confined to affected structures
|
||||
- Ventricular enlargement
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Spongiform encephalopathy: GM most affected
|
||||
- Marked neuronal loss with reactive astrocytosis
|
||||
- Replacement gliosis
|
||||
- Neuronal vacuolation with spongiform changes
|
||||
- Spongiform panencephalopathy (very rare)
|
||||
- Primary extensive involvement of WM
|
||||
- Loss of myelin and axons associated with generalized spongiform change in WM
|
||||
- ± diffuse cerebral atrophy, loss of neurons, and proliferation of astrocytes in cerebral cortex
|
||||
- 10% of patients with CJD have amyloid plaques in cerebellum or cerebral hemispheres
|
||||
- Apple-green birefringence using Congo red staining when viewed under polarized light
|
||||
- Variable accumulation of PrPSc in brain tissue
|
||||
- PrPSc = abnormal, insoluble, protease-resistant amyloid form of PrPc
|
||||
- Diffuse (common in sCJD) or discrete plaques
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Rapidly progressive dementia associated with myoclonic jerks and akinetic mutism
|
||||
- Variable constellation of pyramidal, extrapyramidal, and cerebellar signs
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- **sCJD**: Cerebellar dysfunction, rapidly progressive cognitive impairment, both
|
||||
- 6 molecular subtypes: MM1, MM2 (thalamic and cortical), MV1, MV2, VV1, and VV2
|
||||
- Vary with respect to age at onset, disease duration, early symptoms, and neuropathology
|
||||
- **vCJD**: Psychiatric and sensory symptoms
|
||||
- **Heidenhain variant** of CJD
|
||||
- Isolated visual signs/symptoms (initially)
|
||||
- Predominantly occipital lobe degeneration
|
||||
- Normal conventional T1 and T2WI of brain
|
||||
- DWI/FLAIR may detect early cortical abnormalities
|
||||
- **Brownell-Oppenheimer**: Cerebellar signs/symptoms
|
||||
- Extrapyramidal type of CJD
|
||||
- May show ↑ signal intensity in BG
|
||||
- Pyramidal involvement with disease progression
|
||||
- BG dysfunction
|
||||
- Spinal cord involvement → muscle atrophy and fasciculations
|
||||
- **CSF studies**
|
||||
- CSF protein biomarkers: 14-3-3 protein, total tau (t-tau), S100, neuron-specific enolase (NSE), and thymosin β4
|
||||
- 14-3-3 protein detection is adjunctive rather than diagnostic for prior disease
|
||||
- t-tau > 1,150 picogram/mL has superior accuracy and specificity than 14-3-3 protein for CJD
|
||||
- Significant false-positives and negatives with 14-3-3 and t-tau protein test results
|
||||
- DWI MR has higher diagnostic accuracy than any or all CSF biomarkers
|
||||
- Real-time quaking-induced conversion (RT-QUIC) testing of CSF to detected PrPsc
|
||||
- More sensitive using olfactory epithelium (nasal brushing) than CSF
|
||||
- Nasal brushing not performed in USA
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Younger in vCJD, older in sCJD (6th-7th decades)
|
||||
- ### Sex
|
||||
|
||||
|
||||
- No sex preponderance
|
||||
- ### Ethnicity
|
||||
|
||||
|
||||
- sCJD occurs throughout world, in all races
|
||||
- In USA, CJD ↓ in Blacks, American Indians, and Alaskan natives than White population
|
||||
- vCJD limited to Europe (nearly all cases in UK)
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- Incidence 1.0-1.5 per million in USA
|
||||
- sCJD (85-95%), familial (5-15%), infectious/iatrogenic (< 1%)
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Long incubation period but rapidly progressive once clinical symptoms begin
|
||||
- Rapidly progressing dementia with death usually ensuing within months of onset
|
||||
- Median survival from time of onset of symptoms to death is 4.5 months
|
||||
- 90% live < 1 year
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- No effective treatment
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- Heidenhain variant of CJD in patients with visual disorders of unclear origin and dementia
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Lack of BG findings does not rule out CJD
|
||||
|
||||
94600a52-3136-46e8-a827-05e281f28d7e
|
||||
+266
@@ -0,0 +1,266 @@
|
||||
# Dementia With Lewy Bodies
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Progressive neurodegenerative dementia
|
||||
- Parkinsonism, visual hallucinations prominent
|
||||
- Caused by abnormal accumulation of α-synuclein protein
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- MR may differentiate Alzheimer disease (AD) from dementia with Lewy bodies (DLB)
|
||||
- PET, SPECT most useful for DLB diagnosis
|
||||
- Voxel-based morphometry
|
||||
- Relatively preserved hippocampal/medial temporal lobe volume in DLB vs. AD
|
||||
- ↓ volume of hypothalamus, substantia innominata, & putamen in DLB vs. AD
|
||||
- FDG PET
|
||||
- ↓ in glucose metabolism in occipital cortex, especially primary visual cortex
|
||||
- F-18 fluorodopa-PET: ↓ striatal dopamine uptake in DLB vs. AD
|
||||
- SPECT: Occipital lobe hypoperfusion, especially visual cortex
|
||||
- 123 FP-CIT SPECT: ↓ uptake in striatum in DLB vs. AD
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Parkinson disease-associated dementia (PDD)
|
||||
- Similar clinical, pathological, imaging features with DLB
|
||||
- AD
|
||||
- Frontotemporal lobar degeneration (FTLD)
|
||||
- Vascular dementia
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Pathologic aggregation of α-synuclein protein in neurites (LB)
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Unlike AD, medial temporal lobe atrophy not prominent feature
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Dementia with Lewy bodies (DLB)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Neurodegenerative dementia characterized by cognitive fluctuations, visual hallucinations, & motor parkinsonism
|
||||
- Caused by pathologic aggregation of α-synuclein protein in neurites (LB)
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- MR may differentiate Alzheimer disease (AD) from DLB
|
||||
- PET, SPECT most useful for DLB diagnosis
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- PET or SPECT
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Mild generalized atrophy
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Nonspecific white matter (WM) hyperintensities
|
||||
- ### MRS
|
||||
|
||||
|
||||
- ↓ WM NAA/Cr in DLB vs. healthy controls (HC)
|
||||
- ↑ Cho/Cr ratios in DLB vs. HC
|
||||
- Normal levels of NAA/Cr & myoinositol in DLB vs. AD
|
||||
- Voxel-based morphometry
|
||||
- Relatively preserved hippocampal/medial temporal lobe volume in DLB vs. AD
|
||||
- ↓ volume of hypothalamus, substantia innominata, & putamen in DLB vs. AD
|
||||
- ↓ gray matter in temporal, parietal, & occipital regions vs. HC
|
||||
- DTI
|
||||
- ↑ mean diffusivity in amygdala
|
||||
- ↓ fractional anisotropy in pons & left thalamus vs. AD
|
||||
- ↓ fractional anisotropy in inferior longitudinal fasciculus & inferior occipitofrontal fasciculi vs. HC
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- ### PET
|
||||
|
||||
|
||||
- FDG PET: ↓ glucose metabolism in occipital cortex & visual association cortex with relative preservation of posterior cingulate
|
||||
- F-18 fluorodopa-PET: ↓ striatal dopamine uptake in DLB vs. AD
|
||||
- ### MIBG scintigraphy
|
||||
|
||||
|
||||
- ↓ myocardial uptake in DLB due to ↓ postganglionic sympathetic cardiac innervation
|
||||
- SPECT
|
||||
- Occipital lobe hypoperfusion, especially visual cortex
|
||||
- 123 FP-CIT SPECT: Visualize DAT (dopamine transporter) loss
|
||||
- ↓ uptake in striatum in DLB
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Parkinson Disease-Associated Dementia](/document/parkinson-disease/0bc3188a-935b-416d-b1a0-25b2d52c6399)
|
||||
- Dementia typically develops at least 12 months after onset of initial parkinsonian symptoms
|
||||
- Similar clinical, pathologic, imaging features to DLB
|
||||
- Less pronounced atrophy in temporal, occipital, & parietal lobes vs. DLB
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
|
||||
- Parietal/temporal cortical atrophy
|
||||
- Disproportionate hippocampal volume loss
|
||||
- Amyloid uptake of cerebral cortex in PiB-PET
|
||||
- More severe, faster rate of progression than DLB
|
||||
- [Frontotemporal Lobar Degeneration](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
|
||||
- Asymmetric frontal, anterior temporal lobar atrophy
|
||||
- Behavioral variant: Both frontal lobes atrophic
|
||||
- Semantic variant: Asymmetric anterior temporal lobe atrophy
|
||||
- [Vascular Dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
|
||||
- 2nd most common dementia (15-30%)
|
||||
- WM & deep gray lacunae
|
||||
- Infarcts of different ages
|
||||
- Hyperintense lesions on T2WI, hypodense areas on CT, & focal atrophy suggestive of chronic infarcts
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Accumulation of α-synuclein protein (LB)
|
||||
- LB, neuronal loss in substantia nigra → dopamine depletion
|
||||
- Loss of cholinergic neurons in nucleus basalis of Meynert
|
||||
- → cognitive impairment, visual hallucinations
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Majority of DLB is sporadic; some are familial
|
||||
- α-synuclein gene mutation on chromosome 4 (*A53T*, *E46K* mutation)
|
||||
- Similar inheritance, similar genetic risk for PD
|
||||
- Other genes associated with DLB include *SNCA*, *APP*, *PSEN1*/*PSEN2*, *MAPT*, *GBA*, & *APOE*
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- 3 major forms: Brainstem dominant, limbic/transitional, diffuse neocortical
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Nonspecific & overlap with other neurodegenerative dementias
|
||||
- Cortical atrophy is less than AD
|
||||
- Atrophy affects frontal, temporal, & parietal lobes, relative sparing of occipital lobes
|
||||
- Amygdala & cingulate gyri can show severe atrophy
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- LB in substantia nigra, neocortex, limbic system
|
||||
- α-synuclein protein aggregates: Pale eosinophilic inclusions
|
||||
- α-synuclein
|
||||
- Physiologic function: Synaptic transmission, neuroprotective effect
|
||||
- Predominantly expressed in neurons
|
||||
- Lewy neurites in hippocampus, amygdala, brainstem nuclei
|
||||
- Neuronal loss in substantia nigra, locus ceruleus, nucleus basalis of Meynert, dorsal raphe nuclei
|
||||
- Relative preservation of cortical neurons
|
||||
- Superficial microvacuolation of cerebral cortex, especially temporal cortex in severe cases
|
||||
- 80% have associated AD-like pathology
|
||||
- Neuritic/diffuse plaques or neurofibrillary tangles
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Cognitive fluctuations, visual hallucinations, parkinsonism
|
||||
- Dysautonomia & sleep disorders
|
||||
- Clinical criteria for DLB diagnosis
|
||||
- Core clinical features
|
||||
- Fluctuating cognition with pronounced variations in attention & alertness
|
||||
- Recurrent visual hallucinations (typically well formed & detailed)
|
||||
- REM sleep behavior disorder (May precede cognitive decline)
|
||||
- 1 or more spontaneous cardinal features of parkinsonism (bradykinesia, rest tremor, rigidity)
|
||||
- Supportive clinical features
|
||||
- Severe sensitivity to antipsychotic agents
|
||||
- Postural instability, repeated falls
|
||||
- Syncope or other transient episodes of unresponsiveness
|
||||
- Severe autonomic dysfunction (constipation, orthostatic hypotension, urinary incontinence)
|
||||
- Hypersomnia, hyposmia, hallucinations in other modalities, systematized delusions
|
||||
- Apathy, anxiety, & depression
|
||||
- Indicative biomarkers
|
||||
- ↓ dopamine transporter uptake in basal ganglia by SPECT or PET
|
||||
- Abnormal (low-uptake) I-123-MIBG myocardial scintigraphy
|
||||
- Polysomnographic confirmation of REM sleep without atonia
|
||||
- Supportive biomarkers
|
||||
- Relative preservation of medial temporal lobe structures on CT/MR
|
||||
- Generalized low uptake on SPECT/PET perfusion/metabolism scan with ↓ occipital activity ± cingulate island sign on FDG PET imaging
|
||||
- Prominent posterior slow-wave activity on EEG with periodic fluctuations in pre-alpha/theta range
|
||||
- Probable DLB
|
||||
- ≥ 2 core clinical features of DLB with or without indicative biomarkers; **or**
|
||||
- Only 1 core clinical feature but with ≥ 1 indicative biomarkers
|
||||
- Probable DLB should not be diagnosed on basis of biomarkers alone
|
||||
- Possible DLB
|
||||
- Only 1 core clinical feature of DLB with no indicative biomarker evidence; **or**
|
||||
- ≥ 1 indicative biomarkers but no core clinical features
|
||||
- DLB is less likely
|
||||
- Presence of any other physical illness or brain disorder, including cerebrovascular disease, sufficient to account in part or in total for clinical picture
|
||||
- If parkinsonian features are only core clinical feature & appear for 1st time at stage of severe dementia
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- 55-85 years; age is only risk factor
|
||||
- Average at presentation is 75 years
|
||||
- ### Ethnicity
|
||||
|
||||
|
||||
- LB formation more common in African Americans than Caucasians, but clinical diagnosis of DLB is not significantly different
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M:F = 4:1
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- 5% of general population & 30% of dementia cases
|
||||
- 2nd most common neurodegenerative dementia (after AD)
|
||||
- Incidence rate of 0.1% per year in general population & 3.2% for new dementia cases
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Average survival after diagnosis < 8 years
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- ### Options, risks, complications
|
||||
|
||||
|
||||
- No disease-modifying treatments for DLB
|
||||
- Symptomatic, targeted toward specific disease manifestations
|
||||
- Cholinesterase inhibitor for cognitive features
|
||||
- DLB responds better to cholinesterase inhibitor than AD
|
||||
- Treatment against hallucination should be conservative due to neuroleptic hypersensitivity of DLB
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- No characteristic features on standard MR
|
||||
- Clinical dementia + no/relatively mild medial temporal lobe atrophy
|
||||
- Unlike AD, medial temporal lobe atrophy is not prominent
|
||||
|
||||
2eb83d9f-537e-4b39-96ac-8099cafa2337
|
||||
+266
@@ -0,0 +1,266 @@
|
||||
# Dementia With Lewy Bodies
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Progressive neurodegenerative dementia
|
||||
- Parkinsonism, visual hallucinations prominent
|
||||
- Caused by abnormal accumulation of α-synuclein protein
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- MR may differentiate Alzheimer disease (AD) from dementia with Lewy bodies (DLB)
|
||||
- PET, SPECT most useful for DLB diagnosis
|
||||
- Voxel-based morphometry
|
||||
- Relatively preserved hippocampal/medial temporal lobe volume in DLB vs. AD
|
||||
- ↓ volume of hypothalamus, substantia innominata, & putamen in DLB vs. AD
|
||||
- FDG PET
|
||||
- ↓ in glucose metabolism in occipital cortex, especially primary visual cortex
|
||||
- F-18 fluorodopa-PET: ↓ striatal dopamine uptake in DLB vs. AD
|
||||
- SPECT: Occipital lobe hypoperfusion, especially visual cortex
|
||||
- 123 FP-CIT SPECT: ↓ uptake in striatum in DLB vs. AD
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Parkinson disease-associated dementia (PDD)
|
||||
- Similar clinical, pathological, imaging features with DLB
|
||||
- AD
|
||||
- Frontotemporal lobar degeneration (FTLD)
|
||||
- Vascular dementia
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Pathologic aggregation of α-synuclein protein in neurites (LB)
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Unlike AD, medial temporal lobe atrophy not prominent feature
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Dementia with Lewy bodies (DLB)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Neurodegenerative dementia characterized by cognitive fluctuations, visual hallucinations, & motor parkinsonism
|
||||
- Caused by pathologic aggregation of α-synuclein protein in neurites (LB)
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- MR may differentiate Alzheimer disease (AD) from DLB
|
||||
- PET, SPECT most useful for DLB diagnosis
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- PET or SPECT
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Mild generalized atrophy
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Nonspecific white matter (WM) hyperintensities
|
||||
- ### MRS
|
||||
|
||||
|
||||
- ↓ WM NAA/Cr in DLB vs. healthy controls (HC)
|
||||
- ↑ Cho/Cr ratios in DLB vs. HC
|
||||
- Normal levels of NAA/Cr & myoinositol in DLB vs. AD
|
||||
- Voxel-based morphometry
|
||||
- Relatively preserved hippocampal/medial temporal lobe volume in DLB vs. AD
|
||||
- ↓ volume of hypothalamus, substantia innominata, & putamen in DLB vs. AD
|
||||
- ↓ gray matter in temporal, parietal, & occipital regions vs. HC
|
||||
- DTI
|
||||
- ↑ mean diffusivity in amygdala
|
||||
- ↓ fractional anisotropy in pons & left thalamus vs. AD
|
||||
- ↓ fractional anisotropy in inferior longitudinal fasciculus & inferior occipitofrontal fasciculi vs. HC
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- ### PET
|
||||
|
||||
|
||||
- FDG PET: ↓ glucose metabolism in occipital cortex & visual association cortex with relative preservation of posterior cingulate
|
||||
- F-18 fluorodopa-PET: ↓ striatal dopamine uptake in DLB vs. AD
|
||||
- ### MIBG scintigraphy
|
||||
|
||||
|
||||
- ↓ myocardial uptake in DLB due to ↓ postganglionic sympathetic cardiac innervation
|
||||
- SPECT
|
||||
- Occipital lobe hypoperfusion, especially visual cortex
|
||||
- 123 FP-CIT SPECT: Visualize DAT (dopamine transporter) loss
|
||||
- ↓ uptake in striatum in DLB
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Parkinson Disease-Associated Dementia](/document/parkinson-disease/0bc3188a-935b-416d-b1a0-25b2d52c6399)
|
||||
- Dementia typically develops at least 12 months after onset of initial parkinsonian symptoms
|
||||
- Similar clinical, pathologic, imaging features to DLB
|
||||
- Less pronounced atrophy in temporal, occipital, & parietal lobes vs. DLB
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
|
||||
- Parietal/temporal cortical atrophy
|
||||
- Disproportionate hippocampal volume loss
|
||||
- Amyloid uptake of cerebral cortex in PiB-PET
|
||||
- More severe, faster rate of progression than DLB
|
||||
- [Frontotemporal Lobar Degeneration](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
|
||||
- Asymmetric frontal, anterior temporal lobar atrophy
|
||||
- Behavioral variant: Both frontal lobes atrophic
|
||||
- Semantic variant: Asymmetric anterior temporal lobe atrophy
|
||||
- [Vascular Dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
|
||||
- 2nd most common dementia (15-30%)
|
||||
- WM & deep gray lacunae
|
||||
- Infarcts of different ages
|
||||
- Hyperintense lesions on T2WI, hypodense areas on CT, & focal atrophy suggestive of chronic infarcts
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Accumulation of α-synuclein protein (LB)
|
||||
- LB, neuronal loss in substantia nigra → dopamine depletion
|
||||
- Loss of cholinergic neurons in nucleus basalis of Meynert
|
||||
- → cognitive impairment, visual hallucinations
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Majority of DLB is sporadic; some are familial
|
||||
- α-synuclein gene mutation on chromosome 4 (*A53T*, *E46K* mutation)
|
||||
- Similar inheritance, similar genetic risk for PD
|
||||
- Other genes associated with DLB include *SNCA*, *APP*, *PSEN1*/*PSEN2*, *MAPT*, *GBA*, & *APOE*
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- 3 major forms: Brainstem dominant, limbic/transitional, diffuse neocortical
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Nonspecific & overlap with other neurodegenerative dementias
|
||||
- Cortical atrophy is less than AD
|
||||
- Atrophy affects frontal, temporal, & parietal lobes, relative sparing of occipital lobes
|
||||
- Amygdala & cingulate gyri can show severe atrophy
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- LB in substantia nigra, neocortex, limbic system
|
||||
- α-synuclein protein aggregates: Pale eosinophilic inclusions
|
||||
- α-synuclein
|
||||
- Physiologic function: Synaptic transmission, neuroprotective effect
|
||||
- Predominantly expressed in neurons
|
||||
- Lewy neurites in hippocampus, amygdala, brainstem nuclei
|
||||
- Neuronal loss in substantia nigra, locus ceruleus, nucleus basalis of Meynert, dorsal raphe nuclei
|
||||
- Relative preservation of cortical neurons
|
||||
- Superficial microvacuolation of cerebral cortex, especially temporal cortex in severe cases
|
||||
- 80% have associated AD-like pathology
|
||||
- Neuritic/diffuse plaques or neurofibrillary tangles
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Cognitive fluctuations, visual hallucinations, parkinsonism
|
||||
- Dysautonomia & sleep disorders
|
||||
- Clinical criteria for DLB diagnosis
|
||||
- Core clinical features
|
||||
- Fluctuating cognition with pronounced variations in attention & alertness
|
||||
- Recurrent visual hallucinations (typically well formed & detailed)
|
||||
- REM sleep behavior disorder (May precede cognitive decline)
|
||||
- 1 or more spontaneous cardinal features of parkinsonism (bradykinesia, rest tremor, rigidity)
|
||||
- Supportive clinical features
|
||||
- Severe sensitivity to antipsychotic agents
|
||||
- Postural instability, repeated falls
|
||||
- Syncope or other transient episodes of unresponsiveness
|
||||
- Severe autonomic dysfunction (constipation, orthostatic hypotension, urinary incontinence)
|
||||
- Hypersomnia, hyposmia, hallucinations in other modalities, systematized delusions
|
||||
- Apathy, anxiety, & depression
|
||||
- Indicative biomarkers
|
||||
- ↓ dopamine transporter uptake in basal ganglia by SPECT or PET
|
||||
- Abnormal (low-uptake) I-123-MIBG myocardial scintigraphy
|
||||
- Polysomnographic confirmation of REM sleep without atonia
|
||||
- Supportive biomarkers
|
||||
- Relative preservation of medial temporal lobe structures on CT/MR
|
||||
- Generalized low uptake on SPECT/PET perfusion/metabolism scan with ↓ occipital activity ± cingulate island sign on FDG PET imaging
|
||||
- Prominent posterior slow-wave activity on EEG with periodic fluctuations in pre-alpha/theta range
|
||||
- Probable DLB
|
||||
- ≥ 2 core clinical features of DLB with or without indicative biomarkers; **or**
|
||||
- Only 1 core clinical feature but with ≥ 1 indicative biomarkers
|
||||
- Probable DLB should not be diagnosed on basis of biomarkers alone
|
||||
- Possible DLB
|
||||
- Only 1 core clinical feature of DLB with no indicative biomarker evidence; **or**
|
||||
- ≥ 1 indicative biomarkers but no core clinical features
|
||||
- DLB is less likely
|
||||
- Presence of any other physical illness or brain disorder, including cerebrovascular disease, sufficient to account in part or in total for clinical picture
|
||||
- If parkinsonian features are only core clinical feature & appear for 1st time at stage of severe dementia
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- 55-85 years; age is only risk factor
|
||||
- Average at presentation is 75 years
|
||||
- ### Ethnicity
|
||||
|
||||
|
||||
- LB formation more common in African Americans than Caucasians, but clinical diagnosis of DLB is not significantly different
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M:F = 4:1
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- 5% of general population & 30% of dementia cases
|
||||
- 2nd most common neurodegenerative dementia (after AD)
|
||||
- Incidence rate of 0.1% per year in general population & 3.2% for new dementia cases
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Average survival after diagnosis < 8 years
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- ### Options, risks, complications
|
||||
|
||||
|
||||
- No disease-modifying treatments for DLB
|
||||
- Symptomatic, targeted toward specific disease manifestations
|
||||
- Cholinesterase inhibitor for cognitive features
|
||||
- DLB responds better to cholinesterase inhibitor than AD
|
||||
- Treatment against hallucination should be conservative due to neuroleptic hypersensitivity of DLB
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- No characteristic features on standard MR
|
||||
- Clinical dementia + no/relatively mild medial temporal lobe atrophy
|
||||
- Unlike AD, medial temporal lobe atrophy is not prominent
|
||||
|
||||
f336b865-74c1-456e-9130-6db7efb9e7b3
|
||||
+147
@@ -0,0 +1,147 @@
|
||||
# Enlarged Perivascular Spaces
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Key imaging questions
|
||||
- Does lesion follow CSF on all modalities/sequences?
|
||||
- Is there any associated mass effect?
|
||||
- Does lesion enhance?
|
||||
- Included
|
||||
- CSF-like cystic mass(es), e.g., enlarged perivascular spaces (PVS), neuroglial cysts
|
||||
- Excluded
|
||||
- Cystic neoplasms, abscess, resolving hematoma (rarely exactly like CSF)
|
||||
- Developmental cysts that do not behave exactly like CSF (e.g., epidermoid, neurenteric cysts)
|
||||
- ## Helpful Clues for Common Diagnoses
|
||||
|
||||
|
||||
- **Enlarged Perivascular Spaces**
|
||||
- PVS
|
||||
- Can be seen at all ages but ↑ with age
|
||||
- Filled with interstitial fluid but follow CSF on all sequences
|
||||
- Most have no abnormality in surrounding parenchyma on FLAIR
|
||||
- ~ 25% have thin, hyperintense rim
|
||||
- Bilateral > unilateral
|
||||
- Multiple > solitary
|
||||
- "Clusters" of variably sized, CSF-like cysts characteristic
|
||||
- Can occur anywhere but most common locations = basal ganglia (BG), hemispheric white matter (WM), midbrain, dentate nuclei
|
||||
- Variant (mostly in older adults) = "état criblé" ("cribriform state") with multiple tiny cysts in BG
|
||||
- Classification
|
||||
- Type I: BG
|
||||
- Type II: High convexity WM
|
||||
- Type III: Midbrain
|
||||
- Large PVS cause mass effect, assume bizarre configurations, and can mimic cystic neoplasm
|
||||
- **Encephalomalacia**
|
||||
- Etiology varies (trauma, infarction, etc.)
|
||||
- Can be solitary, multifocal, multicystic
|
||||
- CSF-like ± adjacent FLAIR hyperintensity
|
||||
- **Lacunar Infarction**
|
||||
- Solitary or multiple
|
||||
- Typically along single long, unpaired penetrating arteries &/or vascular watershed zones
|
||||
- BG, thalamus, WM common
|
||||
- Multifocal BG infarcts + surrounding gliosis = "état lacunaire" or "lacunar state"
|
||||
- **Neurocysticercosis**
|
||||
- Most neurocysticercosis (NCC) cysts are actually in sulci
|
||||
- Cysts in vesicular stage smooth, thin walled, with scolex generally visible as "dot" within cyst
|
||||
- Multiple lesions in mixed stages common
|
||||
- Some enhance, some do not
|
||||
- Ca⁺⁺ (multiple = starry-sky pattern)
|
||||
- ## Helpful Clues for Less Common Diagnoses
|
||||
|
||||
|
||||
- **Porencephalic Cyst**
|
||||
- CSF-filled parenchymal cavity
|
||||
- Communicates with ventricle &/or pial surface
|
||||
- Lined by reactive gliosis/astrocytic proliferation
|
||||
- Does not enhance
|
||||
- Etiology varies (trauma, infarction, etc.)
|
||||
- **Multiple Sclerosis**
|
||||
- Chronic "burned-out" lesions
|
||||
- Appear as CSF foci with hyperintense rinds on FLAIR
|
||||
- Look for faint T1 hyperintensity surrounding lesions ("lesion within lesion")
|
||||
- Obtain sagittal FLAIR to look for other lesions along callososeptal interface
|
||||
- **Hippocampal Sulcus Remnants**
|
||||
- "String of beads" cysts medial to temporal horns of lateral ventricles
|
||||
- Developmental variant, incidental
|
||||
- Remnants of vestigial primary embryonic hippocampal sulcus
|
||||
- Imaging
|
||||
- Between hippocampus, dentate gyrus
|
||||
- Follow CSF on all sequences
|
||||
- No surrounding gliosis
|
||||
- **Connatal Cysts**
|
||||
- Single or multiple
|
||||
- Location
|
||||
- Intra- or periventricular (may actually be cysts of anterior choroid plexus)
|
||||
- Small cyst adjacent to tip of frontal horn may be normal anatomic variant
|
||||
- Lined with ependyma
|
||||
- Present at birth
|
||||
- Usually transient
|
||||
- Occasionally seen in older patients
|
||||
- No septations, no hemosiderin
|
||||
- Generally isolated without associated abnormalities
|
||||
- ## Helpful Clues for Rare Diagnoses
|
||||
|
||||
|
||||
- **Neuroglial Cyst**
|
||||
- Benign, glial-lined, nonenhancing CSF-like cyst
|
||||
- No surrounding signal abnormality
|
||||
- Does not communicate with ventricle
|
||||
- Subcortical WM, choroidal fissure common sites
|
||||
- Does not restrict on DWI
|
||||
- No enhancement
|
||||
- **Cryptococcosis**
|
||||
- Opportunistic fungal infection
|
||||
- Nonenhancing, gelatinous pseudocysts in PVS
|
||||
- BG, thalamus, brainstem, cerebellum, dentate nucleus, periventricular WM
|
||||
- Multifocal > > solitary lesions
|
||||
- Most patients have HIV/AIDS
|
||||
- **Parasites, Miscellaneous**
|
||||
- Other than NCC, parasitic brain cysts uncommon
|
||||
- Hydatid cyst
|
||||
- Unilocular cyst, isointense to CSF
|
||||
- T2-hypointense rim, no enhancement
|
||||
- **Mucopolysaccharidoses**
|
||||
- Group of lysosomal storage disorders
|
||||
- PVS dilated by accumulated glycosaminoglycans
|
||||
- Corpus callosum, peritrigonal WM
|
||||
- Multiple, bilateral
|
||||
- Dilated PVS in deep periventricular WM
|
||||
- FLAIR-hyperintense rim surrounding dilated PVS
|
||||
- **Germinolytic Cysts**
|
||||
- Periventricular/subependymal cysts
|
||||
- Cyst(s) along caudothalamic groove probably resulting from germinolysis
|
||||
- Glial (not ependymal)-lined cysts/pseudocysts
|
||||
- Distinguish from "connatal" cysts (intraventricular anterior choroid plexus cysts)
|
||||
- Many etiologies, including inherited metabolic disorders (e.g., Zellweger, infantile Refsum), congenital infections (CMV)
|
||||
- CSF-like; ± septations, hemosiderin; do not enhance
|
||||
- Look for associated abnormalities
|
||||
- Leukoencephalopathy
|
||||
- Delayed myelination
|
||||
- Polymicrogyria, pachygyria, heterotopias
|
||||
- **Miscellaneous Congenital Malformations**
|
||||
- Several have parenchymal CSF-like cysts as part of syndrome
|
||||
- van der Knaap leukoencephalopathies (megaloencephalic leukoencephalopathy with subcortical cysts, anterior temporal lobe cavitations)
|
||||
- Congenital muscular dystrophy (cerebellar cysts common, may represent dilated PVS)
|
||||
- Dorsal interhemispheric CSF cyst
|
||||
- Corpus callosal dysgenesis
|
||||
- Holoprosencephaly
|
||||
- ## Alternative Differential Approaches
|
||||
|
||||
|
||||
- **Based on location**
|
||||
- Deep gray nuclei
|
||||
- Enlarged PVS
|
||||
- Lacunar infarction
|
||||
- Cryptococcosis
|
||||
- Periventricular WM
|
||||
- Multiple sclerosis
|
||||
- Connatal cysts
|
||||
- Germinolytic cysts
|
||||
- Lobar
|
||||
- Encephalomalacia
|
||||
- NCC
|
||||
- Porencephalic cyst
|
||||
- Neuroglial cyst
|
||||
- Hydatid cyst
|
||||
+147
@@ -0,0 +1,147 @@
|
||||
# Enlarged Perivascular Spaces
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Key imaging questions
|
||||
- Does lesion follow CSF on all modalities/sequences?
|
||||
- Is there any associated mass effect?
|
||||
- Does lesion enhance?
|
||||
- Included
|
||||
- CSF-like cystic mass(es), e.g., enlarged perivascular spaces (PVS), neuroglial cysts
|
||||
- Excluded
|
||||
- Cystic neoplasms, abscess, resolving hematoma (rarely exactly like CSF)
|
||||
- Developmental cysts that do not behave exactly like CSF (e.g., epidermoid, neurenteric cysts)
|
||||
- ## Helpful Clues for Common Diagnoses
|
||||
|
||||
|
||||
- **Enlarged Perivascular Spaces**
|
||||
- PVS
|
||||
- Can be seen at all ages but ↑ with age
|
||||
- Filled with interstitial fluid but follow CSF on all sequences
|
||||
- Most have no abnormality in surrounding parenchyma on FLAIR
|
||||
- ~ 25% have thin, hyperintense rim
|
||||
- Bilateral > unilateral
|
||||
- Multiple > solitary
|
||||
- "Clusters" of variably sized, CSF-like cysts characteristic
|
||||
- Can occur anywhere but most common locations = basal ganglia (BG), hemispheric white matter (WM), midbrain, dentate nuclei
|
||||
- Variant (mostly in older adults) = "état criblé" ("cribriform state") with multiple tiny cysts in BG
|
||||
- Classification
|
||||
- Type I: BG
|
||||
- Type II: High convexity WM
|
||||
- Type III: Midbrain
|
||||
- Large PVS cause mass effect, assume bizarre configurations, and can mimic cystic neoplasm
|
||||
- **Encephalomalacia**
|
||||
- Etiology varies (trauma, infarction, etc.)
|
||||
- Can be solitary, multifocal, multicystic
|
||||
- CSF-like ± adjacent FLAIR hyperintensity
|
||||
- **Lacunar Infarction**
|
||||
- Solitary or multiple
|
||||
- Typically along single long, unpaired penetrating arteries &/or vascular watershed zones
|
||||
- BG, thalamus, WM common
|
||||
- Multifocal BG infarcts + surrounding gliosis = "état lacunaire" or "lacunar state"
|
||||
- **Neurocysticercosis**
|
||||
- Most neurocysticercosis (NCC) cysts are actually in sulci
|
||||
- Cysts in vesicular stage smooth, thin walled, with scolex generally visible as "dot" within cyst
|
||||
- Multiple lesions in mixed stages common
|
||||
- Some enhance, some do not
|
||||
- Ca⁺⁺ (multiple = starry-sky pattern)
|
||||
- ## Helpful Clues for Less Common Diagnoses
|
||||
|
||||
|
||||
- **Porencephalic Cyst**
|
||||
- CSF-filled parenchymal cavity
|
||||
- Communicates with ventricle &/or pial surface
|
||||
- Lined by reactive gliosis/astrocytic proliferation
|
||||
- Does not enhance
|
||||
- Etiology varies (trauma, infarction, etc.)
|
||||
- **Multiple Sclerosis**
|
||||
- Chronic "burned-out" lesions
|
||||
- Appear as CSF foci with hyperintense rinds on FLAIR
|
||||
- Look for faint T1 hyperintensity surrounding lesions ("lesion within lesion")
|
||||
- Obtain sagittal FLAIR to look for other lesions along callososeptal interface
|
||||
- **Hippocampal Sulcus Remnants**
|
||||
- "String of beads" cysts medial to temporal horns of lateral ventricles
|
||||
- Developmental variant, incidental
|
||||
- Remnants of vestigial primary embryonic hippocampal sulcus
|
||||
- Imaging
|
||||
- Between hippocampus, dentate gyrus
|
||||
- Follow CSF on all sequences
|
||||
- No surrounding gliosis
|
||||
- **Connatal Cysts**
|
||||
- Single or multiple
|
||||
- Location
|
||||
- Intra- or periventricular (may actually be cysts of anterior choroid plexus)
|
||||
- Small cyst adjacent to tip of frontal horn may be normal anatomic variant
|
||||
- Lined with ependyma
|
||||
- Present at birth
|
||||
- Usually transient
|
||||
- Occasionally seen in older patients
|
||||
- No septations, no hemosiderin
|
||||
- Generally isolated without associated abnormalities
|
||||
- ## Helpful Clues for Rare Diagnoses
|
||||
|
||||
|
||||
- **Neuroglial Cyst**
|
||||
- Benign, glial-lined, nonenhancing CSF-like cyst
|
||||
- No surrounding signal abnormality
|
||||
- Does not communicate with ventricle
|
||||
- Subcortical WM, choroidal fissure common sites
|
||||
- Does not restrict on DWI
|
||||
- No enhancement
|
||||
- **Cryptococcosis**
|
||||
- Opportunistic fungal infection
|
||||
- Nonenhancing, gelatinous pseudocysts in PVS
|
||||
- BG, thalamus, brainstem, cerebellum, dentate nucleus, periventricular WM
|
||||
- Multifocal > > solitary lesions
|
||||
- Most patients have HIV/AIDS
|
||||
- **Parasites, Miscellaneous**
|
||||
- Other than NCC, parasitic brain cysts uncommon
|
||||
- Hydatid cyst
|
||||
- Unilocular cyst, isointense to CSF
|
||||
- T2-hypointense rim, no enhancement
|
||||
- **Mucopolysaccharidoses**
|
||||
- Group of lysosomal storage disorders
|
||||
- PVS dilated by accumulated glycosaminoglycans
|
||||
- Corpus callosum, peritrigonal WM
|
||||
- Multiple, bilateral
|
||||
- Dilated PVS in deep periventricular WM
|
||||
- FLAIR-hyperintense rim surrounding dilated PVS
|
||||
- **Germinolytic Cysts**
|
||||
- Periventricular/subependymal cysts
|
||||
- Cyst(s) along caudothalamic groove probably resulting from germinolysis
|
||||
- Glial (not ependymal)-lined cysts/pseudocysts
|
||||
- Distinguish from "connatal" cysts (intraventricular anterior choroid plexus cysts)
|
||||
- Many etiologies, including inherited metabolic disorders (e.g., Zellweger, infantile Refsum), congenital infections (CMV)
|
||||
- CSF-like; ± septations, hemosiderin; do not enhance
|
||||
- Look for associated abnormalities
|
||||
- Leukoencephalopathy
|
||||
- Delayed myelination
|
||||
- Polymicrogyria, pachygyria, heterotopias
|
||||
- **Miscellaneous Congenital Malformations**
|
||||
- Several have parenchymal CSF-like cysts as part of syndrome
|
||||
- van der Knaap leukoencephalopathies (megaloencephalic leukoencephalopathy with subcortical cysts, anterior temporal lobe cavitations)
|
||||
- Congenital muscular dystrophy (cerebellar cysts common, may represent dilated PVS)
|
||||
- Dorsal interhemispheric CSF cyst
|
||||
- Corpus callosal dysgenesis
|
||||
- Holoprosencephaly
|
||||
- ## Alternative Differential Approaches
|
||||
|
||||
|
||||
- **Based on location**
|
||||
- Deep gray nuclei
|
||||
- Enlarged PVS
|
||||
- Lacunar infarction
|
||||
- Cryptococcosis
|
||||
- Periventricular WM
|
||||
- Multiple sclerosis
|
||||
- Connatal cysts
|
||||
- Germinolytic cysts
|
||||
- Lobar
|
||||
- Encephalomalacia
|
||||
- NCC
|
||||
- Porencephalic cyst
|
||||
- Neuroglial cyst
|
||||
- Hydatid cyst
|
||||
+147
@@ -0,0 +1,147 @@
|
||||
# Enlarged Perivascular Spaces
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Key imaging questions
|
||||
- Does lesion follow CSF on all modalities/sequences?
|
||||
- Is there any associated mass effect?
|
||||
- Does lesion enhance?
|
||||
- Included
|
||||
- CSF-like cystic mass(es), e.g., enlarged perivascular spaces (PVS), neuroglial cysts
|
||||
- Excluded
|
||||
- Cystic neoplasms, abscess, resolving hematoma (rarely exactly like CSF)
|
||||
- Developmental cysts that do not behave exactly like CSF (e.g., epidermoid, neurenteric cysts)
|
||||
- ## Helpful Clues for Common Diagnoses
|
||||
|
||||
|
||||
- **Enlarged Perivascular Spaces**
|
||||
- PVS
|
||||
- Can be seen at all ages but ↑ with age
|
||||
- Filled with interstitial fluid but follow CSF on all sequences
|
||||
- Most have no abnormality in surrounding parenchyma on FLAIR
|
||||
- ~ 25% have thin, hyperintense rim
|
||||
- Bilateral > unilateral
|
||||
- Multiple > solitary
|
||||
- "Clusters" of variably sized, CSF-like cysts characteristic
|
||||
- Can occur anywhere but most common locations = basal ganglia (BG), hemispheric white matter (WM), midbrain, dentate nuclei
|
||||
- Variant (mostly in older adults) = "état criblé" ("cribriform state") with multiple tiny cysts in BG
|
||||
- Classification
|
||||
- Type I: BG
|
||||
- Type II: High convexity WM
|
||||
- Type III: Midbrain
|
||||
- Large PVS cause mass effect, assume bizarre configurations, and can mimic cystic neoplasm
|
||||
- **Encephalomalacia**
|
||||
- Etiology varies (trauma, infarction, etc.)
|
||||
- Can be solitary, multifocal, multicystic
|
||||
- CSF-like ± adjacent FLAIR hyperintensity
|
||||
- **Lacunar Infarction**
|
||||
- Solitary or multiple
|
||||
- Typically along single long, unpaired penetrating arteries &/or vascular watershed zones
|
||||
- BG, thalamus, WM common
|
||||
- Multifocal BG infarcts + surrounding gliosis = "état lacunaire" or "lacunar state"
|
||||
- **Neurocysticercosis**
|
||||
- Most neurocysticercosis (NCC) cysts are actually in sulci
|
||||
- Cysts in vesicular stage smooth, thin walled, with scolex generally visible as "dot" within cyst
|
||||
- Multiple lesions in mixed stages common
|
||||
- Some enhance, some do not
|
||||
- Ca⁺⁺ (multiple = starry-sky pattern)
|
||||
- ## Helpful Clues for Less Common Diagnoses
|
||||
|
||||
|
||||
- **Porencephalic Cyst**
|
||||
- CSF-filled parenchymal cavity
|
||||
- Communicates with ventricle &/or pial surface
|
||||
- Lined by reactive gliosis/astrocytic proliferation
|
||||
- Does not enhance
|
||||
- Etiology varies (trauma, infarction, etc.)
|
||||
- **Multiple Sclerosis**
|
||||
- Chronic "burned-out" lesions
|
||||
- Appear as CSF foci with hyperintense rinds on FLAIR
|
||||
- Look for faint T1 hyperintensity surrounding lesions ("lesion within lesion")
|
||||
- Obtain sagittal FLAIR to look for other lesions along callososeptal interface
|
||||
- **Hippocampal Sulcus Remnants**
|
||||
- "String of beads" cysts medial to temporal horns of lateral ventricles
|
||||
- Developmental variant, incidental
|
||||
- Remnants of vestigial primary embryonic hippocampal sulcus
|
||||
- Imaging
|
||||
- Between hippocampus, dentate gyrus
|
||||
- Follow CSF on all sequences
|
||||
- No surrounding gliosis
|
||||
- **Connatal Cysts**
|
||||
- Single or multiple
|
||||
- Location
|
||||
- Intra- or periventricular (may actually be cysts of anterior choroid plexus)
|
||||
- Small cyst adjacent to tip of frontal horn may be normal anatomic variant
|
||||
- Lined with ependyma
|
||||
- Present at birth
|
||||
- Usually transient
|
||||
- Occasionally seen in older patients
|
||||
- No septations, no hemosiderin
|
||||
- Generally isolated without associated abnormalities
|
||||
- ## Helpful Clues for Rare Diagnoses
|
||||
|
||||
|
||||
- **Neuroglial Cyst**
|
||||
- Benign, glial-lined, nonenhancing CSF-like cyst
|
||||
- No surrounding signal abnormality
|
||||
- Does not communicate with ventricle
|
||||
- Subcortical WM, choroidal fissure common sites
|
||||
- Does not restrict on DWI
|
||||
- No enhancement
|
||||
- **Cryptococcosis**
|
||||
- Opportunistic fungal infection
|
||||
- Nonenhancing, gelatinous pseudocysts in PVS
|
||||
- BG, thalamus, brainstem, cerebellum, dentate nucleus, periventricular WM
|
||||
- Multifocal > > solitary lesions
|
||||
- Most patients have HIV/AIDS
|
||||
- **Parasites, Miscellaneous**
|
||||
- Other than NCC, parasitic brain cysts uncommon
|
||||
- Hydatid cyst
|
||||
- Unilocular cyst, isointense to CSF
|
||||
- T2-hypointense rim, no enhancement
|
||||
- **Mucopolysaccharidoses**
|
||||
- Group of lysosomal storage disorders
|
||||
- PVS dilated by accumulated glycosaminoglycans
|
||||
- Corpus callosum, peritrigonal WM
|
||||
- Multiple, bilateral
|
||||
- Dilated PVS in deep periventricular WM
|
||||
- FLAIR-hyperintense rim surrounding dilated PVS
|
||||
- **Germinolytic Cysts**
|
||||
- Periventricular/subependymal cysts
|
||||
- Cyst(s) along caudothalamic groove probably resulting from germinolysis
|
||||
- Glial (not ependymal)-lined cysts/pseudocysts
|
||||
- Distinguish from "connatal" cysts (intraventricular anterior choroid plexus cysts)
|
||||
- Many etiologies, including inherited metabolic disorders (e.g., Zellweger, infantile Refsum), congenital infections (CMV)
|
||||
- CSF-like; ± septations, hemosiderin; do not enhance
|
||||
- Look for associated abnormalities
|
||||
- Leukoencephalopathy
|
||||
- Delayed myelination
|
||||
- Polymicrogyria, pachygyria, heterotopias
|
||||
- **Miscellaneous Congenital Malformations**
|
||||
- Several have parenchymal CSF-like cysts as part of syndrome
|
||||
- van der Knaap leukoencephalopathies (megaloencephalic leukoencephalopathy with subcortical cysts, anterior temporal lobe cavitations)
|
||||
- Congenital muscular dystrophy (cerebellar cysts common, may represent dilated PVS)
|
||||
- Dorsal interhemispheric CSF cyst
|
||||
- Corpus callosal dysgenesis
|
||||
- Holoprosencephaly
|
||||
- ## Alternative Differential Approaches
|
||||
|
||||
|
||||
- **Based on location**
|
||||
- Deep gray nuclei
|
||||
- Enlarged PVS
|
||||
- Lacunar infarction
|
||||
- Cryptococcosis
|
||||
- Periventricular WM
|
||||
- Multiple sclerosis
|
||||
- Connatal cysts
|
||||
- Germinolytic cysts
|
||||
- Lobar
|
||||
- Encephalomalacia
|
||||
- NCC
|
||||
- Porencephalic cyst
|
||||
- Neuroglial cyst
|
||||
- Hydatid cyst
|
||||
+258
@@ -0,0 +1,258 @@
|
||||
# Frontotemporal Dementia
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Frontotemporal dementia (FTD): Progressive neurodegenerative disorder of frontal/anterior temporal lobes
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- F-18 FDG PET
|
||||
- Helps differentiate between FTD and other causes of dementia
|
||||
- Glucose hypometabolism
|
||||
- Initially in frontal lobes progressing to temporal lobes
|
||||
- Anterior cingulate also commonly hypometabolic
|
||||
- Left-sided asymmetry could suggest underlying primary progressive aphasia (PPA)
|
||||
- Hypometabolism within motor strip (precentral gyrus) could suggest motor neuron disease FTD (FTD-MND)
|
||||
- Perfusion SPECT
|
||||
- Similar pattern of frontal hypoperfusion as F-18 FDG PET
|
||||
- Potentially less sensitive than F-18 FDG PET
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Progressive changes in behavior, language, or motor function depending upon subtype
|
||||
- Memory is less dominant clinical feature in FTDs
|
||||
- No current disease-modifying treatment for FTD, only symptomatic therapy
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Clinical therapy decisions depend on proper diagnosis
|
||||
- FTD important to distinguish from Alzheimer disease (AD) because AD medications do not slow progression of FTD and can worsen symptoms
|
||||
- Amyloid-targeting therapies (ATTs) have no role in treating FTDs
|
||||
- Image analysis
|
||||
- If hypometabolism is anterior-predominant (e.g., frontal, anterior temporal, anterior cingulate), this favors FTD
|
||||
- Amyloid PET can also help exclude AD pathology
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Frontotemporal dementia (FTD)
|
||||
- Alzheimer disease (AD)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Progressive neurodegenerative disorder of frontal/anterior temporal lobes
|
||||
- Typically subdivided into categories based on underlying molecular aggregates [TDP-43 (50%), tauopathy without amyloid (40%), and FET protein family (10%)] and main functional deficit (cognitive and behavior, language, or motor)
|
||||
- Behavioral variant FTD (bvFTD) (formerly Pick disease)
|
||||
- Commonly characterized by behavioral disinhibition, apathy, loss of sympathy, hyperorality, executive deficits
|
||||
- Most commonly seen with TDP-43 aggregation, initially described with intracellular τ inclusions (Pick bodies)
|
||||
- Prosopagnosia (inability to recognize familiar faces) has been described with right temporal variant FTD
|
||||
- Language variant FTD [FTD-primary progressive aphasia (PPA)]
|
||||
- Includes 2/3 subtypes of PPA, semantic variant PPA (svPPA) and nonfluent agrammatic variant PPA (nfvPPA)
|
||||
- svPPA is predominantly seen with TDP-43 pathology and nfvPPA with τ pathology
|
||||
- Other PPA variant, logopenic variant (lvPPA), is atypical AD variant (amyloid and τ positive)
|
||||
- Motor neuron disease FTD (FTD-MND)
|
||||
- Includes amyotrophic lateral sclerosis (FTD-ALS; 95% TDP-43) as well as atypical parkinsonian syndromes of progressive supranuclear palsy (PSP; tauopathy) and corticobasal degeneration (CBD; tauopathy)
|
||||
- ALS classically presents with both upper motor neuron signs (spasticity, rigidity, hyperreflexia), lower motor neuron signs (muscle fasciculations, muscle atrophy), and nonmotor signs (behavioral disturbances), as seen with bvFTD (30% of cases)
|
||||
- PSP usually presents with bradykinesia, rigidity, **vertical gaze palsy**, dysphagia, dysarthria
|
||||
- CBD presents with parkinsonism, dystonia, apraxia, executive dysfunction, aphasia, "alien limb" phenomenon
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- F-18 FDG PET/CT
|
||||
- Glucose hypometabolism initially in frontal lobes with progression to include regions of temporal/parietal lobes
|
||||
- Anterior cingulate cortex, frontal insula, caudate nuclei, thalamus may also have hypometabolism bilaterally
|
||||
- Relative sparing of motor cortex, except in FTD-MNDs, specifically ALS and CBD, which can show hypometabolism
|
||||
- Hemispheric metabolic asymmetry may be present
|
||||
- Hypometabolism occurs before atrophy visually evident on CT/MR
|
||||
- Most sensitive diagnostic tool currently available
|
||||
- Glucose hypometabolism worsens with disease progression
|
||||
- May be used to distinguish between FTD and AD
|
||||
- AD often shows hypometabolism in posterior cingulate/temporoparietal regions, spared with FTD
|
||||
- 50% of patients with behavioral or dysexecutive AD variant do not show typical parietal and posterior cingulate hypometabolism
|
||||
- Amyloid PET can be helpful in this situation if considering amyloid-targeting therapies (ATTs)
|
||||
- Attenuation correction CT can show
|
||||
- Preferential atrophy of frontal/temporal lobes
|
||||
- Increased CSF space surrounding medial temporal lobes
|
||||
- Enlargement of lateral ventricles
|
||||
- Perfusion SPECT
|
||||
- Pattern is similar to F-18 FDG PET with decreased radiotracer activity in frontal/temporal lobes
|
||||
- SPECT generally has less sensitivity and quantitative potential compared to PET
|
||||
- More sensitive than structural MR in detecting early changes
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- F-18 FDG PET helps to differentiate between FTD and other causes of dementia, e.g., AD and Lewy body dementia (LBD)
|
||||
- Correlates with disease progression
|
||||
- Amyloid PET can help exclude AD variants that can mimic FTDs, such as lvPPA
|
||||
- I-123 ioflupane scan can help in cases of suspected PSP or CBD, which will show decreased/abnormal uptake
|
||||
- CT/MR documents atrophy of mainly frontal/temporal lobe structures
|
||||
- Look for reversible causes of dementia, e.g., normal-pressure hydrocephalus
|
||||
- Motor band sign with T2* hypointensity of precentral gyri or T2/FLAIR hyperintensity of corticospinal tracts in ALS
|
||||
- F-18 FDG PET
|
||||
- Patient preparation
|
||||
- Patient should fast, stop IV fluids containing dextrose, and stop parenteral feeding for 4-6 hours
|
||||
- Blood sugar should be < 150-200 (mg/dL)
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection (30 min)
|
||||
- Radiopharmaceutical: F-18 FDG
|
||||
- Dose: 5-20 mCi (185-740 MBq)
|
||||
- Dosimetry: Urinary bladder receives largest dose
|
||||
- Image acquisition: Image 30-60 min after injection
|
||||
- SPECT
|
||||
- 2nd-line study if F-18 FDG PET is not available/reimbursed
|
||||
- Patient preparation
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection (30 min)
|
||||
- Radiopharmaceutical
|
||||
- Tc-99m exametazime (HMPAO)
|
||||
- Tc-99m ethyl cysteinate dimer (ECD)
|
||||
- Dose: 15-30 mCi (555 MBq to 1.1 GBq)
|
||||
- Dosimetry
|
||||
- Tc-99m HMPAO: Kidneys receive highest dose
|
||||
- Tc-99m ECD: Bladder wall receives highest dose
|
||||
- Image acquisition
|
||||
- Optimal imaging time for Tc-99m HMPAO: 90 min post injection
|
||||
- Optimal imaging time for Tc-99m ECD: 45 min post injection
|
||||
- ## Artifacts and Quality Control
|
||||
|
||||
|
||||
- Immobilize patient's head to decrease motion, attenuation correction artifacts
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Most common cause of dementia generally leading to impairments in episodic memory and other cognitive domains
|
||||
- Related to aggregation of amyloid-β and τ proteins; therefore, positive on amyloid PET
|
||||
- Behavioral and dysexecutive variants of AD
|
||||
- Clinical presentation with less memory impairment and more behavioral disinhibition/loss of executive function
|
||||
- Can be clinically indistinguishable from bvFTD
|
||||
- 50% of cases show F-18 FDG hypometabolism in precuneus and posterior cingulate gyrus (similar to classic AD); 50% show frontal hypometabolism with parietal sparing similar to FTD
|
||||
- Must consider amyloid PET in these cases; prerequisite for ATTs
|
||||
- lvPPA
|
||||
- Predominant language loss with spared memory that can mimic other PPAs
|
||||
- Sentence repetition and single-word meaning usually preserved
|
||||
- Often have mild cognitive impairments outside of language (more than seen with svPPA or nfvPPA)
|
||||
- F-18 FDG hypometabolism shows more parietal involvement than other PPAs; amyloid PET can be helpful if considering ATTs
|
||||
- ## Limbic-Predominant Age-Related TDP-43 Encephalopathy
|
||||
|
||||
|
||||
- Newly recognized neurodegenerative disease with predominant memory deficits related to hippocampal dysfunction
|
||||
- Typically in patients > 80 years
|
||||
- Often slower decline than AD, though can commonly be comorbid with AD, accelerating disease progression
|
||||
- F-18 FDG PET shows marked hippocampal hypometabolism with less severe involvement of precuneus and posterior cingulate
|
||||
- MR often shows marked hippocampal sclerosis
|
||||
- ## Vascular Dementia
|
||||
|
||||
|
||||
- 2nd most common cause of dementia
|
||||
- Caused by impaired blood supply to brain regions
|
||||
- Global atrophy with diffuse white matter lesions (infarcts)
|
||||
- Lesions generally correlate with cognitive symptoms
|
||||
- ## Lewy Body Dementia
|
||||
|
||||
|
||||
- Commonly presents with hallucinations, sleep disturbances, and parkinsonian motor features
|
||||
- F-18 FDG PET hypometabolism in occipital cortex
|
||||
- Cardiac MIBG demonstrates sympathetic denervation (CBD and PSP do not demonstrate denervation)
|
||||
- Positive α-synuclein skin test (CBD and PSP are tauopathies)
|
||||
- ## Psychiatric Illness
|
||||
|
||||
|
||||
- Bipolar disorder, schizophrenia, obsessive compulsive disorder
|
||||
- ## Reversible Dementias
|
||||
|
||||
|
||||
- Mass lesions (brain tumor), head trauma, normal-pressure hydrocephalus, vitamin B12 deficiency, hypothyroidism, infections (neurosyphilis, Lyme disease)
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Heterogeneous pathologic and clinical subtypes
|
||||
- Resulted from disease naming related to clinical presentation, before etiology/pathology was well understood
|
||||
- Pathologic subtypes of FTD are classified based upon pattern of protein accumulation in groups encompassing disorders of frontotemporal lobar degeneration
|
||||
- Etiology uncertain but associated with 3 major protein aggregates
|
||||
- τ (microtubule-associated protein)
|
||||
- TDP-43 (transactive response DNA binding protein of 43kD)
|
||||
- FET protein family, including FUS (tumor-associated protein; fused in sarcoma)
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Autosomal dominant inheritance in 10-25% of FTD cases
|
||||
- c9orf72 most common genetic mutation in familial FTD and familial ALS
|
||||
- *SOD1*(superoxide dismutase) gene mutation in 10% of familial ALS with specific treatment, intrathecal tofersen
|
||||
- Positive family history of FTD is only known risk factor
|
||||
- 30-50% of individuals with bvFTD have positive family history
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Progressive changes in behavior, personality, language, &/or motor function, depending upon clinical subtype
|
||||
- Disinhibition, apathy, loss of sympathy, hyperorality, dysexecutive behaviors
|
||||
- Bradykinesia, rigidity, tremor, spasticity, hyperreflexia, fasciculations, muscle atrophy in motor subtypes
|
||||
- Loss of language comprehension, including word meaning or agrammatism in language subtypes
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- FTD is composed of 3 main clinical subtypes
|
||||
- bvFTD
|
||||
- Most common, accounting for ~ 1/2 of cases
|
||||
- Progressive decline in social function with personality changes, often with disinhibition
|
||||
- Language presentation (PPA)
|
||||
- Including variants svPPA and nfvPPA
|
||||
- Motor presentation
|
||||
- ALS, PSP, CBD
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Mean of onset: 50-60 years
|
||||
- ~ 10% > 70 years
|
||||
- Younger onset than AD, which is generally > 65 years
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Insidious onset of behavioral and cognitive dysfunction
|
||||
- More significant behavioral, language, executive functioning impairment than memory
|
||||
- Slowly progressive with eventual functional impairment
|
||||
- Median survival ~ 8-10 years after diagnosis; varies widely based upon underlying pathology
|
||||
- Median survival in ALS is 2-5 years
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- No current disease-modifying treatment for FTD
|
||||
- ALS with *SOD1*mutation can be treated with intrathecal tofersen (6.5-month increase in median survival at 3 years)
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- FTD important to distinguish from AD because AD medications do not slow progression of FTD and can worsen symptoms
|
||||
- FTDs are not amenable to ATTs due to lack of underlying amyloid pathology
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- When analyzing images, use surface projections and normative dataset comparison to increase sensitivity
|
||||
|
||||
c96633b0-f435-4b0a-9f06-702857dfe4c4
|
||||
+258
@@ -0,0 +1,258 @@
|
||||
# Frontotemporal Dementia
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Frontotemporal dementia (FTD): Progressive neurodegenerative disorder of frontal/anterior temporal lobes
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- F-18 FDG PET
|
||||
- Helps differentiate between FTD and other causes of dementia
|
||||
- Glucose hypometabolism
|
||||
- Initially in frontal lobes progressing to temporal lobes
|
||||
- Anterior cingulate also commonly hypometabolic
|
||||
- Left-sided asymmetry could suggest underlying primary progressive aphasia (PPA)
|
||||
- Hypometabolism within motor strip (precentral gyrus) could suggest motor neuron disease FTD (FTD-MND)
|
||||
- Perfusion SPECT
|
||||
- Similar pattern of frontal hypoperfusion as F-18 FDG PET
|
||||
- Potentially less sensitive than F-18 FDG PET
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Progressive changes in behavior, language, or motor function depending upon subtype
|
||||
- Memory is less dominant clinical feature in FTDs
|
||||
- No current disease-modifying treatment for FTD, only symptomatic therapy
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Clinical therapy decisions depend on proper diagnosis
|
||||
- FTD important to distinguish from Alzheimer disease (AD) because AD medications do not slow progression of FTD and can worsen symptoms
|
||||
- Amyloid-targeting therapies (ATTs) have no role in treating FTDs
|
||||
- Image analysis
|
||||
- If hypometabolism is anterior-predominant (e.g., frontal, anterior temporal, anterior cingulate), this favors FTD
|
||||
- Amyloid PET can also help exclude AD pathology
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Frontotemporal dementia (FTD)
|
||||
- Alzheimer disease (AD)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Progressive neurodegenerative disorder of frontal/anterior temporal lobes
|
||||
- Typically subdivided into categories based on underlying molecular aggregates [TDP-43 (50%), tauopathy without amyloid (40%), and FET protein family (10%)] and main functional deficit (cognitive and behavior, language, or motor)
|
||||
- Behavioral variant FTD (bvFTD) (formerly Pick disease)
|
||||
- Commonly characterized by behavioral disinhibition, apathy, loss of sympathy, hyperorality, executive deficits
|
||||
- Most commonly seen with TDP-43 aggregation, initially described with intracellular τ inclusions (Pick bodies)
|
||||
- Prosopagnosia (inability to recognize familiar faces) has been described with right temporal variant FTD
|
||||
- Language variant FTD [FTD-primary progressive aphasia (PPA)]
|
||||
- Includes 2/3 subtypes of PPA, semantic variant PPA (svPPA) and nonfluent agrammatic variant PPA (nfvPPA)
|
||||
- svPPA is predominantly seen with TDP-43 pathology and nfvPPA with τ pathology
|
||||
- Other PPA variant, logopenic variant (lvPPA), is atypical AD variant (amyloid and τ positive)
|
||||
- Motor neuron disease FTD (FTD-MND)
|
||||
- Includes amyotrophic lateral sclerosis (FTD-ALS; 95% TDP-43) as well as atypical parkinsonian syndromes of progressive supranuclear palsy (PSP; tauopathy) and corticobasal degeneration (CBD; tauopathy)
|
||||
- ALS classically presents with both upper motor neuron signs (spasticity, rigidity, hyperreflexia), lower motor neuron signs (muscle fasciculations, muscle atrophy), and nonmotor signs (behavioral disturbances), as seen with bvFTD (30% of cases)
|
||||
- PSP usually presents with bradykinesia, rigidity, **vertical gaze palsy**, dysphagia, dysarthria
|
||||
- CBD presents with parkinsonism, dystonia, apraxia, executive dysfunction, aphasia, "alien limb" phenomenon
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- F-18 FDG PET/CT
|
||||
- Glucose hypometabolism initially in frontal lobes with progression to include regions of temporal/parietal lobes
|
||||
- Anterior cingulate cortex, frontal insula, caudate nuclei, thalamus may also have hypometabolism bilaterally
|
||||
- Relative sparing of motor cortex, except in FTD-MNDs, specifically ALS and CBD, which can show hypometabolism
|
||||
- Hemispheric metabolic asymmetry may be present
|
||||
- Hypometabolism occurs before atrophy visually evident on CT/MR
|
||||
- Most sensitive diagnostic tool currently available
|
||||
- Glucose hypometabolism worsens with disease progression
|
||||
- May be used to distinguish between FTD and AD
|
||||
- AD often shows hypometabolism in posterior cingulate/temporoparietal regions, spared with FTD
|
||||
- 50% of patients with behavioral or dysexecutive AD variant do not show typical parietal and posterior cingulate hypometabolism
|
||||
- Amyloid PET can be helpful in this situation if considering amyloid-targeting therapies (ATTs)
|
||||
- Attenuation correction CT can show
|
||||
- Preferential atrophy of frontal/temporal lobes
|
||||
- Increased CSF space surrounding medial temporal lobes
|
||||
- Enlargement of lateral ventricles
|
||||
- Perfusion SPECT
|
||||
- Pattern is similar to F-18 FDG PET with decreased radiotracer activity in frontal/temporal lobes
|
||||
- SPECT generally has less sensitivity and quantitative potential compared to PET
|
||||
- More sensitive than structural MR in detecting early changes
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- F-18 FDG PET helps to differentiate between FTD and other causes of dementia, e.g., AD and Lewy body dementia (LBD)
|
||||
- Correlates with disease progression
|
||||
- Amyloid PET can help exclude AD variants that can mimic FTDs, such as lvPPA
|
||||
- I-123 ioflupane scan can help in cases of suspected PSP or CBD, which will show decreased/abnormal uptake
|
||||
- CT/MR documents atrophy of mainly frontal/temporal lobe structures
|
||||
- Look for reversible causes of dementia, e.g., normal-pressure hydrocephalus
|
||||
- Motor band sign with T2* hypointensity of precentral gyri or T2/FLAIR hyperintensity of corticospinal tracts in ALS
|
||||
- F-18 FDG PET
|
||||
- Patient preparation
|
||||
- Patient should fast, stop IV fluids containing dextrose, and stop parenteral feeding for 4-6 hours
|
||||
- Blood sugar should be < 150-200 (mg/dL)
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection (30 min)
|
||||
- Radiopharmaceutical: F-18 FDG
|
||||
- Dose: 5-20 mCi (185-740 MBq)
|
||||
- Dosimetry: Urinary bladder receives largest dose
|
||||
- Image acquisition: Image 30-60 min after injection
|
||||
- SPECT
|
||||
- 2nd-line study if F-18 FDG PET is not available/reimbursed
|
||||
- Patient preparation
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection (30 min)
|
||||
- Radiopharmaceutical
|
||||
- Tc-99m exametazime (HMPAO)
|
||||
- Tc-99m ethyl cysteinate dimer (ECD)
|
||||
- Dose: 15-30 mCi (555 MBq to 1.1 GBq)
|
||||
- Dosimetry
|
||||
- Tc-99m HMPAO: Kidneys receive highest dose
|
||||
- Tc-99m ECD: Bladder wall receives highest dose
|
||||
- Image acquisition
|
||||
- Optimal imaging time for Tc-99m HMPAO: 90 min post injection
|
||||
- Optimal imaging time for Tc-99m ECD: 45 min post injection
|
||||
- ## Artifacts and Quality Control
|
||||
|
||||
|
||||
- Immobilize patient's head to decrease motion, attenuation correction artifacts
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Most common cause of dementia generally leading to impairments in episodic memory and other cognitive domains
|
||||
- Related to aggregation of amyloid-β and τ proteins; therefore, positive on amyloid PET
|
||||
- Behavioral and dysexecutive variants of AD
|
||||
- Clinical presentation with less memory impairment and more behavioral disinhibition/loss of executive function
|
||||
- Can be clinically indistinguishable from bvFTD
|
||||
- 50% of cases show F-18 FDG hypometabolism in precuneus and posterior cingulate gyrus (similar to classic AD); 50% show frontal hypometabolism with parietal sparing similar to FTD
|
||||
- Must consider amyloid PET in these cases; prerequisite for ATTs
|
||||
- lvPPA
|
||||
- Predominant language loss with spared memory that can mimic other PPAs
|
||||
- Sentence repetition and single-word meaning usually preserved
|
||||
- Often have mild cognitive impairments outside of language (more than seen with svPPA or nfvPPA)
|
||||
- F-18 FDG hypometabolism shows more parietal involvement than other PPAs; amyloid PET can be helpful if considering ATTs
|
||||
- ## Limbic-Predominant Age-Related TDP-43 Encephalopathy
|
||||
|
||||
|
||||
- Newly recognized neurodegenerative disease with predominant memory deficits related to hippocampal dysfunction
|
||||
- Typically in patients > 80 years
|
||||
- Often slower decline than AD, though can commonly be comorbid with AD, accelerating disease progression
|
||||
- F-18 FDG PET shows marked hippocampal hypometabolism with less severe involvement of precuneus and posterior cingulate
|
||||
- MR often shows marked hippocampal sclerosis
|
||||
- ## Vascular Dementia
|
||||
|
||||
|
||||
- 2nd most common cause of dementia
|
||||
- Caused by impaired blood supply to brain regions
|
||||
- Global atrophy with diffuse white matter lesions (infarcts)
|
||||
- Lesions generally correlate with cognitive symptoms
|
||||
- ## Lewy Body Dementia
|
||||
|
||||
|
||||
- Commonly presents with hallucinations, sleep disturbances, and parkinsonian motor features
|
||||
- F-18 FDG PET hypometabolism in occipital cortex
|
||||
- Cardiac MIBG demonstrates sympathetic denervation (CBD and PSP do not demonstrate denervation)
|
||||
- Positive α-synuclein skin test (CBD and PSP are tauopathies)
|
||||
- ## Psychiatric Illness
|
||||
|
||||
|
||||
- Bipolar disorder, schizophrenia, obsessive compulsive disorder
|
||||
- ## Reversible Dementias
|
||||
|
||||
|
||||
- Mass lesions (brain tumor), head trauma, normal-pressure hydrocephalus, vitamin B12 deficiency, hypothyroidism, infections (neurosyphilis, Lyme disease)
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Heterogeneous pathologic and clinical subtypes
|
||||
- Resulted from disease naming related to clinical presentation, before etiology/pathology was well understood
|
||||
- Pathologic subtypes of FTD are classified based upon pattern of protein accumulation in groups encompassing disorders of frontotemporal lobar degeneration
|
||||
- Etiology uncertain but associated with 3 major protein aggregates
|
||||
- τ (microtubule-associated protein)
|
||||
- TDP-43 (transactive response DNA binding protein of 43kD)
|
||||
- FET protein family, including FUS (tumor-associated protein; fused in sarcoma)
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Autosomal dominant inheritance in 10-25% of FTD cases
|
||||
- c9orf72 most common genetic mutation in familial FTD and familial ALS
|
||||
- *SOD1*(superoxide dismutase) gene mutation in 10% of familial ALS with specific treatment, intrathecal tofersen
|
||||
- Positive family history of FTD is only known risk factor
|
||||
- 30-50% of individuals with bvFTD have positive family history
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Progressive changes in behavior, personality, language, &/or motor function, depending upon clinical subtype
|
||||
- Disinhibition, apathy, loss of sympathy, hyperorality, dysexecutive behaviors
|
||||
- Bradykinesia, rigidity, tremor, spasticity, hyperreflexia, fasciculations, muscle atrophy in motor subtypes
|
||||
- Loss of language comprehension, including word meaning or agrammatism in language subtypes
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- FTD is composed of 3 main clinical subtypes
|
||||
- bvFTD
|
||||
- Most common, accounting for ~ 1/2 of cases
|
||||
- Progressive decline in social function with personality changes, often with disinhibition
|
||||
- Language presentation (PPA)
|
||||
- Including variants svPPA and nfvPPA
|
||||
- Motor presentation
|
||||
- ALS, PSP, CBD
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Mean of onset: 50-60 years
|
||||
- ~ 10% > 70 years
|
||||
- Younger onset than AD, which is generally > 65 years
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Insidious onset of behavioral and cognitive dysfunction
|
||||
- More significant behavioral, language, executive functioning impairment than memory
|
||||
- Slowly progressive with eventual functional impairment
|
||||
- Median survival ~ 8-10 years after diagnosis; varies widely based upon underlying pathology
|
||||
- Median survival in ALS is 2-5 years
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- No current disease-modifying treatment for FTD
|
||||
- ALS with *SOD1*mutation can be treated with intrathecal tofersen (6.5-month increase in median survival at 3 years)
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- FTD important to distinguish from AD because AD medications do not slow progression of FTD and can worsen symptoms
|
||||
- FTDs are not amenable to ATTs due to lack of underlying amyloid pathology
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- When analyzing images, use surface projections and normative dataset comparison to increase sensitivity
|
||||
|
||||
c96633b0-f435-4b0a-9f06-702857dfe4c4
|
||||
+304
@@ -0,0 +1,304 @@
|
||||
# Frontotemporal Lobar Degeneration
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Clinical subtypes
|
||||
- Behavioral variant frontotemporal dementia **(bvFTD)**
|
||||
- Primary progressive aphasia syndromes **(PPA)**
|
||||
- Semantic variant **(sv-PPA)**: Previously known as semantic dementia
|
||||
- Nonfluent/agrammatic variant **(nfv-PPA)**: Previously known as progressive nonfluent aphasia
|
||||
- Logopenic variant **(lv-PPA)**
|
||||
- Frontotemporal dementia with motor symptoms
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Early
|
||||
- PET shows frontotemporal ↓ glucose metabolism
|
||||
- Late: Frontotemporal atrophy with knife-like gyri on MR
|
||||
- Subtypes have characteristic cortical atrophy patterns
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Alzheimer dementia (AD)
|
||||
- Vascular dementia
|
||||
- Corticobasal ganglionic degeneration (CBD)
|
||||
- Dementia with Lewy bodies (DLB)
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Clinical syndromes (some overlap)
|
||||
- **bvFTD**: Disinhibition, apathy & loss of empathy, hyperorality, & compulsive behavior
|
||||
- **sv-PPA**: Impaired single-word comprehension & object naming with preserved fluency, repetition, & grammar
|
||||
- **nfv-PPA**: Effortful speech production of phonemes (linguistic units of sound) & orofacial apraxia
|
||||
- **lv-PPA**: Impaired word finding & repetition with errors in speech & naming
|
||||
- Younger age group than AD
|
||||
- FTLD most common cause of early-onset (< 65 years) dementia
|
||||
- Median survival: 6-11 years from symptom onset & 3-4 years from diagnosis
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Frontotemporal lobar degeneration (FTLD)
|
||||
- Clinical subtypes
|
||||
- Behavioral variant frontotemporal dementia **(bvFTD)**
|
||||
- Primary progressive aphasia syndromes **(PPA)**
|
||||
- Semantic variant **(sv-PPA)**: Previously known as semantic dementia
|
||||
- Nonfluent/agrammatic variant **(nfv-PPA)**: Previously known as progressive nonfluent aphasia
|
||||
- Logopenic variant**(lv-PPA)**: Has Alzheimer pathology & is not included as 1 of 3 clinical FTD syndromes
|
||||
- Frontotemporal dementia (FTD) with motor symptoms
|
||||
- Corticobasal degeneration (CBD)
|
||||
- Progressive supranuclear palsy (PSP)
|
||||
- FTD with motor neuron disease
|
||||
- FTD with amyotrophic lateral sclerosis (ALS)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Pick disease no longer used
|
||||
- Referred to pathologic variant with Pick bodies
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Heterogeneous family of neurodegenerative disorders characterized by focal lobar degeneration of frontal &/or temporal lobes
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Structural & functional imaging are supportive but not diagnostic of FTD
|
||||
- PET showing frontotemporal ↓ glucose metabolism
|
||||
- Anterior frontotemporal atrophy with knife-like gyri
|
||||
- ### Location
|
||||
|
||||
|
||||
- Anterior temporal/frontal lobes, orbitofrontal cortex, medial temporal region
|
||||
- Relative sparing of parietooccipital lobes
|
||||
- ### Morphology
|
||||
|
||||
|
||||
- Knife blade appearance of atrophic gyri
|
||||
- ± marked asymmetry
|
||||
- May have worst atrophy in dominant hemisphere
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- ### NECT
|
||||
|
||||
|
||||
- Frontal lobe atrophy often most prominent feature
|
||||
- ↑ size of frontal horns (larger than rest of lateral ventricles)
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Atrophy of frontal & temporal lobes, often asymmetric
|
||||
- Knife-like gyri with normal signal
|
||||
- Dilated frontal sulci reflecting atrophy
|
||||
- Relative sparing of parietooccipital lobes
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- ± hyperintensity in frontotemporal white matter (WM)
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- ± hyperintensity in frontotemporal WM
|
||||
- ### MRS
|
||||
|
||||
|
||||
- ↓ NAA glutamate + glutamine (neuronal loss), ↑ myoinositol (↑ glial content) in frontal lobes
|
||||
- ↓ NAA in posterior cingulate gyri
|
||||
- Reflects ↓ neuronal population, viability
|
||||
- ± lactate peak in frontal lobes
|
||||
- MR voxel-based morphometry
|
||||
- Subtypes have characteristic cortical atrophy patterns
|
||||
- Frontal vs. temporal, left vs. right help discriminate
|
||||
- **bvFTD**: Atrophy of frontal & temporal lobes
|
||||
- Anterior insula, anterior cingulate, orbitofrontal cortex, & amygdala (early changes occur in right hemisphere)
|
||||
- **sv-PPA**: Typically anterior temporal lobe atrophy (asymmetric to left)
|
||||
- Entire temporal lobe can be involved
|
||||
- Ventromedial & superior frontal lobes
|
||||
- Right temporal atrophy as disease progresses
|
||||
- **nfv-PPA**: Selective left posterior frontoinsular region
|
||||
- **lv-PPA**: Predominant atrophy of left posterior temporal cortex & parietal lobe
|
||||
- DTI
|
||||
- Widespread damage to WM tracts reported
|
||||
- **bvFTD**: Uncinate fasciculus, inferior longitudinal fasciculus, & anterior commissural fibers
|
||||
- **sv-PPA**: Inferior longitudinal & uncinate fasciculi
|
||||
- **nfv-FTD**: Left superior longitudinal fasciculus
|
||||
- **lv-PPA**: Widespread dorsal & ventral WM tracts
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- ### PET
|
||||
|
||||
|
||||
- Functional imaging more sensitive than MR in early-stage disease
|
||||
- FDG PET: ↓ metabolic activity in frontotemporal cortex
|
||||
- Amyloid PET helps differentiate FTLD from Alzheimer disease (AD)
|
||||
- HMPAO-SPECT
|
||||
- Sensitive technique for early detection of FTD
|
||||
- Occurs before atrophy is evident
|
||||
- **bvFTD**: ↓ perfusion frontal & anterior temporal lobes
|
||||
- Asymmetric, left or right dominant
|
||||
- **sv-PPA**: Prominent anterior temporal hypoperfusion, left > right
|
||||
- **nfv-PPA**: Asymmetric frontal hypoperfusion often involving insular cortex
|
||||
- **lv-PPA**: ↓ perfusion in left parietal inferior lobule & posterolateral temporal lobe
|
||||
- SPECT perfusion deficits predominantly in frontal & anterior temporal lobes with preserved perfusion posteriorly
|
||||
- Helps distinguish FTD from AD
|
||||
- Reduced frontal perfusion is not specific to FTD but also occurs in some cases of schizophrenia, depression, HIV encephalopathy, Creutzfeldt-Jakob disease, AD
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- PET/SPECT; MR voxel-based morphometry
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- Routine T1WI, T2WI, coronal T2WI MR
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
|
||||
- Parietal & temporal cortical atrophy with disproportionate hippocampal volume loss
|
||||
- Increased rate of atrophy in FTD compared to AD
|
||||
- Often coexisting microvascular disease, WM hyperintensities, microhemorrhages
|
||||
- Amyloid imaging (11C-labeled Pittsburgh Compound-B) helps to differentiate AD from other dementias
|
||||
- [Vascular Dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
|
||||
- 2nd most common dementia (15-30%)
|
||||
- WM & deep gray lacunae
|
||||
- Hyperintense lesions on T2WI & focal atrophy is suggestive of chronic infarcts
|
||||
- [Corticobasal Degeneration](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
|
||||
- Prominent extrapyramidal, cortical symptoms
|
||||
- Severe frontoparietal atrophy contralateral to more severely affected clinically
|
||||
- Atrophy of paracentral structures
|
||||
- [Dementia With Lewy Bodies](/document/dementia-with-lewy-bodies/e8e46d1d-46d2-4e5a-880f-f025a84c5871)
|
||||
- Hypometabolism of entire brain, especially visual cortex
|
||||
- Visual & auditory hallucinations, paranoid delusions
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Tau protein (hyperphosphorylated microtubular protein) or TDP-43 (TAR DNA-binding protein-43)
|
||||
- Rare cases change on fused-in-sarcoma (FUS) protein
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- FTD is highly heritable without clear inheritance pattern
|
||||
- 25-40% of FTD is familial, > 50% of bvFTD is autosomal dominant
|
||||
- Mutations in following 3 genes together constitute 15% of FTD cases
|
||||
- Most common: Hexanucleotide expansion in chromosome 9 open reading frame 72 (*C9orf72*) gene
|
||||
- Microtubule-associated protein tau (*MAPT*) gene
|
||||
- Granulin precursor (*GRN*) gene
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- Histopathologic classification of FTLD based on abnormal inclusions
|
||||
- FTLD-tau: Tau inclusion (hyperphosphorylated tau protein)/Pick bodies
|
||||
- FTLD-TDP: Tau-negative & TDP-43-positive inclusions (subtypes: Type A, B, C, & D)
|
||||
- FTLD-FUS: Tau-/TDP-negative & FUS-positive inclusions
|
||||
- FTLD-ALS/dipeptide repeats (DPR): TDP-negative DPR protein aggregates
|
||||
- FTLD-ni: No inclusions
|
||||
- FTD clinical syndromes correlate with brain atrophy patterns & not with pathologic subtypes
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Gross atrophy of frontal &/or anterior temporal lobes
|
||||
- Firm cortical gray matter (gliosis) &/or basal ganglia atrophy
|
||||
- Soft, retracted subcortical WM
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Loss of pyramidal neurons & microvacuolar degeneration in layer II & III of frontal & temporal cortex
|
||||
- Subjacent WM shows axonal & myelin loss
|
||||
- FTLD-related tauopathies
|
||||
- Pick disease: Prototypical tauopathy of FTLD
|
||||
- Characterized by Pick bodies: Solitary, round or oval, argyrophilic inclusions in cytoplasm of neurons
|
||||
- Commonly found in dentate gyrus of hippocampus, amygdala, frontal & temporal neocortex
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Personality, behavior, & language changes
|
||||
- Memory loss, confusion, cognitive & speech dysfunction, apathy, & abulia
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- **bvFTD**: Disinhibition, apathy & loss of empathy, hyperorality, & compulsive behavior
|
||||
- 15-20% may develop concomitant motor neuron disease (MND)
|
||||
- **sv-PPA**: Impaired single-word comprehension & object naming with preserved fluency, repetition, & grammar
|
||||
- **nfv-PPA**: Effortful speech production of phonemes (linguistic units of sound) & orofacial apraxia
|
||||
- **lv-PPA**: Impaired word finding & repetition with errors in speech & naming
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- More common cause of early-onset (midlife) dementia
|
||||
- Mean age of onset is 58 years; rare < 40 & > 75 years
|
||||
- Peak incidence 45-65 years
|
||||
- ### Sex
|
||||
|
||||
|
||||
- bvFTD & sv-FTD: Male preponderance
|
||||
- nfv-PPA: Female predominance
|
||||
- ### Ethnicity
|
||||
|
||||
|
||||
- Familial forms of Pick complex dementias particularly common in people of Scandinavian origin
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- FTLD more common cause of early-onset (< 65 years) dementia
|
||||
- Age > 65 years account for 20-25% of cases of FTLD
|
||||
- Prevalence: 3.5-15/100,000 person-years
|
||||
- FTLD accounts for ~ 5% of all pathologic diagnoses in patients with dementia
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Insidious onset of behavioral & cognitive dysfunction
|
||||
- Speech & language disturbance are often more profound than memory disorder
|
||||
- Median survival 6-11 years from symptom onset & 3-4 years from diagnosis
|
||||
- Currently no FDA-approved disease-modifying drugs available for treatment of FTD
|
||||
- Some patients develop artistic talents during course of dementia (disinhibition of "creative" brain areas)
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- Other common forms of dementia (AD, dementia with Lewy bodies)
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Bilateral frontal lobe atrophy should make one consider diagnosis of FTD
|
||||
- Bilateral asymmetric anterior temporal lobe atrophy: sv-PPA
|
||||
- ## Reporting Tips
|
||||
|
||||
|
||||
- Report pattern of cortical volume loss
|
||||
|
||||
69c47a04-dd7a-4a23-a55b-21542ccce82a
|
||||
+241
@@ -0,0 +1,241 @@
|
||||
# Lewy Body Dementia
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Progressive neurodegenerative disease characterized by parkinsonism, visual hallucinations, fluctuations in cognition (alertness/attention), and other cognitive impairments leading to functional decline
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Low dopamine transporter uptake in basal ganglia on I-123 FP-CIT SPECT similar to parkinsonian syndromes
|
||||
- Decreased tracer binding may be more symmetric and diffuse when compared to typical cases of Parkinson disease (PD)
|
||||
- Cardiac sympathetic denervation on MIBG
|
||||
- Significant occipital lobe glucose hypometabolism relative to Alzheimer disease (AD) with preservation of posterior cingulate gyrus
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- PD and PD dementia (PDD)
|
||||
- AD, including posterior cortical atrophy
|
||||
- Frontotemporal dementia (FTD)
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Intraneuronal aggregates of α-synuclein result in neurodegeneration
|
||||
- Significant amount of Lewy body dementia (LBD) cases involve comorbid Alzheimer pathology, which can complicate decisions about amyloid-targeting therapies (ATTs)
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Parkinsonism
|
||||
- Fluctuating cognition, especially in attention/alertness
|
||||
- Recurrent visual hallucinations
|
||||
- Progressive impairment of cognition with motor complications leading to loss of functional independence
|
||||
- REM sleep behavioral disorders
|
||||
- No current disease-modifying treatment for LBD
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Lewy body dementia (LBD)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Dementia with Lewy bodies
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Progressive neurodegenerative disease of brain characterized by
|
||||
- Visual hallucinations
|
||||
- Parkinsonism (bradykinesia, rigidity, tremor)
|
||||
- Fluctuations in cognition (alertness/attention)
|
||||
- REM sleep behavioral disorder
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Indicative imaging criteria
|
||||
- Abnormally low dopamine transporter (DaT) binding in basal ganglia on DaT SPECT study
|
||||
- Absent myocardial uptake on MIBG [sympathetic denervation can also be seen with primary heart disease and diabetic neuropathy as well as Parkinson disease (PD) dementia (PDD)]
|
||||
- Supportive imaging criteria
|
||||
- Medial temporal lobe hypometabolism less severe than Alzheimer disease (AD) on FDG PET
|
||||
- Significant occipital lobe glucose hypometabolism relative to AD on FDG PET
|
||||
- Preservation of posterior cingulate gyrus on FDG PET (cingulate island sign)
|
||||
- ### Location
|
||||
|
||||
|
||||
- Cortical, subcortical, and brainstem structures; midbrain, basal ganglia, occipital lobe
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- DaT SPECT with I-123 ioflupane (FP-CIT)
|
||||
- Binds to DaT predominantly in presynaptic striata
|
||||
- Normal uptake in caudate and putamen
|
||||
- Abnormal DaT imaging indicative feature for LBD diagnosis
|
||||
- Compared to PD, DaT findings in LBD can be more uniformly decreased between caudate and putamen and less likely asymmetric
|
||||
- DaT imaging differentiates between LBD (abnormal DaT) and AD (normal DaT)
|
||||
- Cannot reliably distinguish between other disorders with parkinsonism
|
||||
- I-123 MIBG cardiac exam
|
||||
- Norepinephrine analogue taken up by sympathetic cardiac nerves
|
||||
- Cardiac sympathetic denervation seen with PD, PDD, and LBD
|
||||
- Usually preserved with atypical parkinsonian syndromes, AD, and frontotemporal dementia (FTD)
|
||||
- F-18 FDG PET
|
||||
- Generalized glucose hypometabolism with significant occipital lobe hypometabolism
|
||||
- Occipital lobe involvement may help distinguish from classic AD-like pattern of hypometabolism
|
||||
- Similar hypometabolic pattern seen in PD and PDD
|
||||
- Medial temporal lobe hypometabolism less severe than in AD
|
||||
- F-18 amyloid PET
|
||||
- Can be positive in 50% or more of LBD patients, possibly reflecting AD-LBD copathology
|
||||
- Important to consider DaT scan in patients with positive amyloid and any clinical concern for LBD before starting amyloid-targeting therapy (ATTs)
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- I-123 ioflupane
|
||||
- Patient preparation
|
||||
- Patient should be off all interfering dopaminergic medications
|
||||
- Pretreat with thyroid blocker (oral potassium solution, Lugol) 1 hour before tracer injection
|
||||
- Pregnancy category C: Unknown whether I-123 ioflupane can cause fetal damage or early termination of pregnancy
|
||||
- Radiopharmaceutical: I-123 ioflupane
|
||||
- Dose: 3-5 mCi (111-185 MBq)
|
||||
- Dosimetry: Striata receives highest radiation exposure, followed by bladder, bowel, and lungs (assuming thyroid is blocked)
|
||||
- Image acquisition: 3-6 hours after injection
|
||||
- I-123 MIBG
|
||||
- Patient preparation
|
||||
- Patient should be off all interfering medications
|
||||
- Pretreatment with Lugol (KI) solution
|
||||
- Dose: 3-10 mCi (111-370 MBq)
|
||||
- Dosimetry: Bladder (assuming thyroid is blocked)
|
||||
- Image acquisition: Anterior planar imaging early (15 min) after injection and delayed (4 hours) after injection; can perform SPECT as well
|
||||
- Heart:mediastinum ratio calculated on delayed anterior planar image (< 1.8 concerning for denervation)
|
||||
- F-18 FDG PET
|
||||
- Patient preparation
|
||||
- Patient should fast, stop IV fluids containing dextrose, stop parenteral feeding for 4-6 hours
|
||||
- Blood sugar should be 150-200 mg/dL
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection for 30 min
|
||||
- Radiopharmaceutical: F-18 FDG
|
||||
- Dose: 5-20 mCi (185-740 MBq)
|
||||
- Dosimetry: Urinary bladder receives largest dose
|
||||
- Image acquisition: 30-60 min after injection
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Parkinson Disease and Parkinson Disease Dementia](/document/parkinsonian-syndromes/2b99b31a-ec1a-4dce-bb63-2a101fe9f044)
|
||||
- Neurodegenerative disease that often presents with cogwheel rigidity, shuffled gate, pill-rolling tremor at rest, bradykinesia
|
||||
- Shares similar Lewy body-related neuropathology with LBD
|
||||
- Dementia may develop but generally 10 years after onset of motor symptoms
|
||||
- PDD: PD cases where dementia is diagnosed 1 year after onset of motor symptoms
|
||||
- ## Posterior Cortical Atrophy (Visual Alzheimer Disease Variant)
|
||||
|
||||
|
||||
- Most commonly resulting from amyloid-β and τ protein aggregates, similar to classic AD
|
||||
- Visuospatial and visuoperception deficits most common, simultanagnosia
|
||||
- FDG PET often shows hypometabolism in classic areas (precuneus, posterior cingulate, posterior temporal lobes) with atypical occipital involvement
|
||||
- Unlike LBD, tends to involve posterior cingulate, typically more occipital asymmetric hypometabolism than LBD, negative DaT and MIBG
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Most common cause of dementia
|
||||
- Impairments in episodic memory and other cognitive domains
|
||||
- Preservation of motor functions
|
||||
- Early F-18 FDG hypometabolism in parietotemporal and posterior cingulate cortices
|
||||
- F-18 FDG PET hypometabolism spares occipital visual cortex
|
||||
- Related to aggregation of amyloid-β and τ proteins
|
||||
- Positive on amyloid PET
|
||||
- [Frontotemporal Dementia](/document/frontotemporal-dementia/9f9eda8c-7e3c-4292-9861-4b8abc2c6474)
|
||||
- Commonly presents with personality and behavioral changes
|
||||
- Atrophy of frontal and anterior temporal lobes
|
||||
- F-18 FDG PET hypometabolism primarily in frontal/anterior temporal lobes
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Abnormal aggregates of α-synuclein protein within neurons
|
||||
- More diffusely seen than in PD
|
||||
- ### Associated abnormalities
|
||||
|
||||
|
||||
- Significant amount of LBD cases involve comorbid Alzheimer pathology, which can complicate decisions about ATTs
|
||||
- LBD is diagnosed when dementia is present before or concurrently with parkinsonian features
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Relative preservation of total brain volume relative to other dementias
|
||||
- Increased volume of lateral ventricles relative to healthy controls
|
||||
- Decreased pigmentation within substantia nigra (midbrain) and loci cerulei (pons)
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Parkinsonism
|
||||
- Fluctuating cognition, especially in attention/alertness
|
||||
- Recurrent visual hallucinations
|
||||
- REM sleep behavioral disorder
|
||||
- ### Other signs/symptoms
|
||||
|
||||
|
||||
- Severe neuroleptic sensitivity
|
||||
- Hallucinations (other than visual)
|
||||
- Depression
|
||||
- Severe autonomic dysfunction
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- 3 main types of dementia related to continuum of Lewy body clinicopathology
|
||||
- Diffuse LBD (isolated)
|
||||
- Dementia with diffuse cortical LB pathology
|
||||
- No other significant pathology (minimal plaques/tangles)
|
||||
- PDD
|
||||
- PD patients diagnosed with dementia 1 year after onset of motor symptoms
|
||||
- Onset of dementia in PD is generally 10 years after onset of motor symptoms
|
||||
- LBD-AD copathology
|
||||
- Pathology consistent with cortical LB (α-synuclein) and AD-like pathologic changes (amyloid plaques/neurofibrillary tangles)
|
||||
- Most common presentation, occurring in ~ 70% of LBD cases
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Progressive impairment of cognition with motor complications leading to loss of functional independence
|
||||
- Core features include fluctuating cognition with impact on alertness/attention, visual hallucinations, and features of parkinsonism
|
||||
- Memory loss is less prominent early symptom in LBD but may develop with progression of disease
|
||||
- Significant distinction from AD, where memory is common early symptom
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- No current disease-modifying treatment for LBD
|
||||
- Several therapies may help alleviate common symptoms
|
||||
- Levodopa can be used for some motor symptoms
|
||||
- Cholinesterase inhibitors may be used for some cognitive symptoms
|
||||
- Can have neuroleptic malignant syndrome if given some antipsychotic medications that interact with dopamine
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- I-123 ioflupane
|
||||
- Abnormally low DaT binding in basal ganglia on DaT SPECT study
|
||||
- I-123 MIBG
|
||||
- Sympathetic cardiac denervation
|
||||
- F-18 FDG PET/CT
|
||||
- Occipital lobe hypometabolism and normal posterior cingulate gyrus (cingulate island sign) to distinguish LBD from AD
|
||||
- F-18 amyloid PET
|
||||
- Consider recommending DaT scan in patients with positive amyloid biomarkers and any clinical concern for LBD before starting ATTs
|
||||
|
||||
363e0379-1464-405c-a8e1-ad3a47aac7e8
|
||||
+193
@@ -0,0 +1,193 @@
|
||||
# Multiinfarct Dementia
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Impairments in cognition and behavior affecting functional status due to pathologic changes resulting from various vascular insults throughout brain
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- F-18 FDG PET may be used in differential diagnosis between vascular dementia and Alzheimer disease
|
||||
- Glucose hypometabolism in multifocal (scattered) pattern of cortical with subcortical regions is indicative of vascular dementia
|
||||
- Multifocal or unifocal hypometabolism involving cortical gray matter, subcortical white matter, and other structures
|
||||
- Generally involves cerebral hemispheres, thalamus, basal ganglia, hippocampi
|
||||
- Amyloid PET imaging does not demonstrate gray matter amyloid deposition in vascular dementia
|
||||
- SPECT with Tc-99m HMPAO or Tc-99m ECD shows similar asymmetrically decreased perfusion
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Vascular-related lesions leading to loss of brain function
|
||||
- Chronic small vessel insults > large vessel infarcts
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Significant heterogeneity in clinical presentation depending on location, type, and size of vascular lesion
|
||||
- Overt disease: Cognitive impairment due to clinically evident vascular event (i.e., stroke)
|
||||
- Covert disease: Insidious process of vascular insults (clinically silent strokes)
|
||||
- 2nd most common cause of dementia after Alzheimer disease
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Impairments in cognition and behavior affecting functional status due to pathologic changes resulting from various vascular insults throughout brain
|
||||
- Vascular cognitive impairment (VCI) is more comprehensive term incorporating vascular dementia (VaD) as well as other vascular-related cognitive impairment, including mild cognitive impairment due to vascular disease
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Multifocal or unifocal infarcts involving cortical gray matter, subcortical white matter, and other structures
|
||||
- Especially when correlates with other clinical findings
|
||||
- Generally involve cerebral hemispheres, thalamus, basal ganglia, hippocampi
|
||||
- Generally significant white matter involvement
|
||||
- Bilateral > unilateral
|
||||
- Size: Decreased due to atrophy
|
||||
- Morphology: Multiple small &/or large vessel with lacunar infarcts
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- F-18 FDG PET/CT
|
||||
- Glucose hypometabolism in multifocal (scattered) pattern of cortical with subcortical regions
|
||||
- Altered pattern depending on subtype (i.e., multifocal small vessel infarcts vs. large territory infarcts)
|
||||
- Hypometabolism often in clinically affected areas: Correlates with other clinical findings
|
||||
- May be used in differential diagnosis between VaD and Alzheimer disease (AD)
|
||||
- AD pattern: Hypometabolism in bilateral parietotemporal with posterior cingulate cortices: Extension to frontal/occipital
|
||||
- VaD may have hypometabolism in subcortical areas, which are spared in AD
|
||||
- Amyloid PET without gray matter amyloid deposition
|
||||
- May be used in differential diagnosis between VaD and AD
|
||||
- SPECT with Tc-99m HMPAO or Tc-99m ECD shows similar asymmetric decreased perfusion
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- F-18 FDG PET may aid in differential diagnosis
|
||||
- MR to see vascular insults and look for potential reversible causes of dementia
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- F-18 FDG PET
|
||||
- Patient preparation
|
||||
- Patient should fast, stop IV fluids containing dextrose, stop parenteral feeding for 4-6 hours
|
||||
- Blood sugar should be < 150-200 mg/dL
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection for 30 min
|
||||
- Radiopharmaceutical: 5-15 mCi F-18 FDG
|
||||
- Dosimetry: Urinary bladder receives largest dose
|
||||
- Image acquisition: 30-60 min after injection
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Early F-18 FDG hypometabolism in parietotemporal and posterior cingulate cortices
|
||||
- Later changes include frontal lobe
|
||||
- Positive amyloid PET
|
||||
- Atrophy of medial temporal lobe structures on MR/CT
|
||||
- ## Dementia With Lewy Bodies
|
||||
|
||||
|
||||
- Commonly presents with hallucinations, sleep disturbances, and parkinsonian motor features
|
||||
- F-18 FDG PET hypometabolism in occipital cortex or striatal loss of dopamine transport
|
||||
- [Normal-Pressure Hydrocephalus](/document/normal-pressure-hydrocephalus/834ccc3e-2116-4295-8408-0ac9a06bd2ff)
|
||||
- Dilated ventricles on CT or MR
|
||||
- Metabolic or perfusion reductions in lateral cortex (frontal and parietal), separation of caudate heads
|
||||
- Reduced activity in periventricular WM and ventricular regions > expected for age
|
||||
- ## Mixed Dementia
|
||||
|
||||
|
||||
- Characteristic features of > 1 type of dementia
|
||||
- Commonly includes AD and another pathology (such as VaD)
|
||||
- ## Frontotemporal Dementia
|
||||
|
||||
|
||||
- Commonly presents with personality and behavioral changes
|
||||
- Atroph of frontal and anterior temporal lobes
|
||||
- F-18 FDG PET hypometabolism primarily in frontal and anterior temporal lobes
|
||||
- [Huntington Disease](/document/huntington-disease/4abd9bb7-7d47-4308-a71f-9985fdb23c2c)
|
||||
- Major reduction in basal ganglia metabolism and perfusion (worse in caudate)
|
||||
- Cortical reductions (late)
|
||||
- ## Posttraumatic Dementia
|
||||
|
||||
|
||||
- Pattern of abnormality on functional imaging variable: Depends on severity, directional forces at injury
|
||||
- Chronic subdural may cause significant asymmetry
|
||||
- Deceleration injury may cause anterior frontal and temporal tip reductions
|
||||
- Atrophic pattern may occur; worse with increasing severity of injury
|
||||
- Focal reduction correlates with encephalomalacia and other cortical abnormalities on CT or MR
|
||||
- Basal ganglia, thalamic abnormalities may be present
|
||||
- ## Drug-Related Dementia
|
||||
|
||||
|
||||
- Cocaine and amphetamine abuse: Random small focal defects throughout brain
|
||||
- Swiss cheese pattern on FDG PET and SPECT
|
||||
- Alcohol abuse: May demonstrate frontal lobe decrease
|
||||
- ## Autoimmune Dementia
|
||||
|
||||
|
||||
- Vasculitis pattern in systemic lupus; frontal watershed abnormalities
|
||||
- Small cortical defects mainly frontal lobe
|
||||
- [Creutzfeldt-Jakob Disease](/document/creutzfeldt-jakob-disease-cjd/e1b27954-6591-4bb0-a659-b13790492620)
|
||||
- Rapidly fatal, prion-related disease with impairments in cognition and behavioral changes
|
||||
- Diffusion-weighted imaging hyperintensity in striatum, cingulum, and neocortex
|
||||
- ## Causes of Reversible Dementia
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus, vitamin B12 deficiency, hypothyroidism, depression, mass lesions, infections (neurosyphilis, HIV), trauma (chronic subdurals)
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- Vascular-related lesions leading to loss of brain function
|
||||
- Chronic small vessel insults > large vessel infarcts
|
||||
- Areas of infarction (focal or multifocal) with associated atrophy
|
||||
- ## Risk Factors
|
||||
|
||||
|
||||
- History of myocardial infarction/coronary artery disease, stroke/transient ischemic attack (TIA)
|
||||
- Atherosclerosis, hypertension, hyperlipidemia, atrial fibrillation
|
||||
- Diabetes, obesity, smoking, advanced age
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- Significant heterogeneity in clinical presentation depending on location, type, and size of vascular lesion
|
||||
- Impairment in at least 1 cognitive domain leading to decline in functional status
|
||||
- Executive function and attention more commonly initially affected than in AD
|
||||
- Slow motor/information processing
|
||||
- Language difficulties
|
||||
- Changes in behavior and personality
|
||||
- Depression and anxiety
|
||||
- Other: Seizures, bladder incontinence, gait disturbance, and additional focal abnormalities
|
||||
- Overt disease: Cognitive impairment due to clinically evident vascular event [large territory infarct(s)]
|
||||
- > 60% of stroke patients (dementia in ~ 30% of cases)
|
||||
- Covert disease: Insidious process of vascular insults (clinically silent with extensive lacunar infarcts)
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- 2nd most common cause of dementia after AD
|
||||
- > 10% of dementia cases
|
||||
- Age: Incidence increases with age
|
||||
- Sex: M > F
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Heterogeneous F-18 FDG activity without any specific pattern suggests VaD
|
||||
- Lesions can include basal ganglia and other areas typically spared in other diseases
|
||||
- MR correlation helpful
|
||||
|
||||
7855ad33-290d-4bb0-81a6-63126fea7e4f
|
||||
+129
@@ -0,0 +1,129 @@
|
||||
# Neurocysticercosis
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Cystic lesions with solid nodular components can be divided into 2 categories
|
||||
- Lesions that typically demonstrate cyst with nodule morphology
|
||||
- Neurocysticercosis (NCC), pilocytic astrocytoma, ganglioglioma, hemangioblastoma, pleomorphic xanthoastrocytoma (PXA), desmoplastic infantile ganglioglioma (DIG), intraparenchymal schwannoma
|
||||
- Lesions that may demonstrate cyst with nodule morphology
|
||||
- Metastases, glioblastoma (GBM), abscess, toxoplasmosis, parasites, dysplastic neuroepithelial tumor (DNET), thrombosed arteriovenous malformation (AVM), supratentorial ependymoma
|
||||
- Although metastases, abscesses, & GBMs do not classically present as "cysts with nodules," they are included because of their overall prevalence
|
||||
- Statistically, atypical form of these common diseases may be more likely than some of other "classic" cysts with nodule lesions
|
||||
- ## Helpful Clues for Common Diagnoses
|
||||
|
||||
|
||||
- **Neurocysticercosis**
|
||||
- Intracranial parasitic infection caused by pork tapeworm *Taenia solium*
|
||||
- Cyst with "dot" inside representing scolex
|
||||
- Imaging appearance varies with stage; increased enhancement & edema when organism dies (inflammatory host response)
|
||||
- Location: Convexity subarachnoid space > > cisterns > parenchyma > ventricles
|
||||
- Lesions may be at different stages in same patient
|
||||
- **Pilocytic Astrocytoma**
|
||||
- Cerebellar cystic mass with mural nodule in child; rarely supratentorial
|
||||
- T1 C+ MR: Nodule shows intense but heterogeneous enhancement
|
||||
- Cyst wall may show enhancement
|
||||
- T1 & T2 MR: Cyst content iso- to hyperintense to CSF
|
||||
- Most common brain tumor in children
|
||||
- **Ganglioglioma**
|
||||
- Cortically based, slow-growing, enhancing mass in older child or young adult
|
||||
- Circumscribed cyst with mural nodule most common
|
||||
- May be solid and appear well circumscribed
|
||||
- Often expands cortex; calcification common
|
||||
- Most common tumor to cause temporal lobe epilepsy
|
||||
- Cortical dysplasia is commonly associated
|
||||
- **Hemangioblastoma**
|
||||
- Vascular neoplasm of uncertain etiology
|
||||
- Parenchymal posterior fossa cyst with nodule mass in adult
|
||||
- T1 C+ MR: Nodule abuts pial surface & shows intense, homogeneous enhancement
|
||||
- Prominent flow voids may be seen
|
||||
- Multiple in von Hippel-Lindau syndrome (VHL) (25-40% of hemangioblastomas)
|
||||
- ## Helpful Clues for Less Common Diagnoses
|
||||
|
||||
|
||||
- **Metastases, Parenchymal**
|
||||
- Discrete, gray-white interface mass(es) with adjacent vasogenic edema
|
||||
- Multiplicity, history of primary malignancy helpful if present
|
||||
- Solitary metastasis may mimic GBM
|
||||
- Often known history of primary neoplasm
|
||||
- **Glioblastoma, IDH-Wildtype**
|
||||
- Malignant white matter mass with central necrosis
|
||||
- Predilection to spread across midline along corpus callosum; "butterfly glioma"
|
||||
- T1 C+ MR: Thick, irregular, nodular, enhancing margins
|
||||
- T2/FLAIR MR: Surrounding hyperintensity & mass effect reflect edema + infiltrative tumor
|
||||
- **Pleomorphic Xanthoastrocytoma**
|
||||
- Cortically based cyst + nodule ± involvement of adjacent meninges
|
||||
- T1 C+ MR
|
||||
- Enhancing nodule
|
||||
- Thickening, enhancement of adjacent meninges
|
||||
- 70% have dural tail
|
||||
- Temporal lobe predominance; young adult
|
||||
- Maybe associated with cortical dysplasia
|
||||
- **Abscess**
|
||||
- T2 MR: Hypointense rim with surrounding edema classic
|
||||
- T1 C+ MR: Enhancing capsule thinnest at ventricular side
|
||||
- DWI MR: Cystic component bright (diffusion restriction)
|
||||
- SWI MR: Dual rim sign (hypointense outside, hyperintense inside )
|
||||
- **Opportunistic Infection, AIDS, Toxoplasmosis**
|
||||
- Caused by parasite *Toxoplasma gondii*
|
||||
- Toxoplasmosis: Ring-enhancing lesion containing eccentric nodule = eccentric target sign specific but not sensitive
|
||||
- Location: Basal ganglia > hemispheres
|
||||
- Clinical: Immunocompromised patient
|
||||
- **Parasites, Miscellaneous**
|
||||
- Multiple enhancing lesions typical
|
||||
- May mimic brain tumor
|
||||
- Travel history critical
|
||||
- **Dysplastic Neuroepithelial Tumor**
|
||||
- Bubbly, wedge-shaped, cortically based mass "points" toward lateral ventricle
|
||||
- T2 MR: Very hyperintense; nodular, septate; no surrounding edema
|
||||
- FLAIR MR: Hyperintense ring sign
|
||||
- Thin rim of well-defined peritumoral hyperintensity separating it from surrounding normal brain
|
||||
- T1 C+ MR: No to minimal enhancement; may be nodular
|
||||
- Temporal lobe predominance
|
||||
- ## Helpful Clues for Rare Diagnoses
|
||||
|
||||
|
||||
- **Desmoplastic Infantile Ganglioglioma**
|
||||
- Supratentorial cystic/nodular mass with dominance of cyst
|
||||
- Cortically based nodule with intense enhancement & dural tail
|
||||
- May be massive
|
||||
- Peak age: 3-6 months
|
||||
- **Schwannoma, Intraparenchymal**
|
||||
- Only 1-2% of schwannomas are parenchymal
|
||||
- Cyst with strongly enhancing nodule
|
||||
- **Arteriovenous Malformation**
|
||||
- When hemorrhagic with partial or complete thrombosis, may present as cyst with nodule
|
||||
- Blood breakdown products of various ages; fluid-fluid levels
|
||||
- **Ependymoma, Supratentorial**
|
||||
- 40% of supratentorial ependymomas are extraventricular
|
||||
- Large, complex, mixed solid/cystic mass
|
||||
- Calcification, intratumoral hemorrhage common
|
||||
- Moderate but inhomogeneous enhancement
|
||||
- **Meningioma (Cystic)**
|
||||
- Meningioma with intraparenchymal cyst may mimic cyst + nodule mass
|
||||
- **Rosette-Forming Glioneuronal Tumor**
|
||||
- Rare, slowly growing benign tumor of young adults
|
||||
- 4th ventricle most common site > cerebellum
|
||||
- Mixed solid-cystic appearance, variable Ca⁺⁺, hemorrhage
|
||||
- May show cyst with nodule configuration
|
||||
- **Papillary Glioneuronal Tumor**
|
||||
- Temporal lobe predilection
|
||||
- Parenchymal mass with solid, cystic, or cyst/mural nodule architecture
|
||||
- May show calcification
|
||||
- Imaging may be indistinguishable from ganglioglioma
|
||||
- ## Alternative Differential Approaches
|
||||
|
||||
|
||||
- By location
|
||||
- Posterior fossa: Pilocytic astrocytoma, hemangioblastoma, metastasis, Rosette-forming glioneuronal tumor
|
||||
- Temporal lobe: Ganglioglioma, PXA, DNET, papillary glioneuronal tumor
|
||||
- Gray-white junction: Metastases, abscess
|
||||
- Hemispheric: NCC, metastases, GBM, infections, DIG, AVM, supratentorial ependymoma
|
||||
- Patient age
|
||||
- Child & young adult: Pilocytic astrocytoma, ganglioglioma, PXA, DNET
|
||||
- Adult: Hemangioblastoma, GBM, metastases
|
||||
- Any age: NCC, abscess, other infections
|
||||
- Multiple lesions
|
||||
- Metastases (50-55%), NCC (50-70%), hemangioblastoma (VHL), abscesses (septic emboli), toxoplasmosis, parasites
|
||||
+256
@@ -0,0 +1,256 @@
|
||||
# Normal-Pressure Hydrocephalus
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus (NPH): Ventriculomegaly out of proportion to sulcal enlargement in setting of normal cerebrospinal fluid (CSF) pressure
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- In-111 DTPA radionuclide cisternography
|
||||
- Used in patients in whom MR is contraindicated and CT is equivocal
|
||||
- Protocol
|
||||
- Intrathecal injection of In-111 DTPA
|
||||
- Obtain planar images with gamma camera immediately after injection and at 4, 24, and 48 hours
|
||||
- Normal study
|
||||
- 1 hour: Radiotracer reaches basal cisterns
|
||||
- 2-6 hours: Radiotracer reaches sylvian fissures
|
||||
- 12 hours: Radiotracer reaches cerebral convexities
|
||||
- 24 hours: Radiotracer reaches superior sagittal sinus and is absorbed by arachnoid villi
|
||||
- Normally no radiotracer enters ventricles, although transient activity in ventricles at 4 hours is still considered normal
|
||||
- NPH
|
||||
- Radiotracer activity in ventricles at ≥ 24 hours
|
||||
- Absence of radiotracer activity in cerebral convexities by 24-72 hours
|
||||
- SPECT/CT can help confirm ventricular activity
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Symptoms: Gait disturbance, urinary incontinence, dementia
|
||||
- Treatment: Ventriculoperitoneal shunt
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Ventricular dilation on anatomic imaging may related to cerebral atrophy or underlying neurodegenerative disease
|
||||
- Classic finding of NPH on radionuclide cisternography
|
||||
- Prominent ventricular activity at 24-72 hours with absent activity over convexities
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus (NPH): Ventriculomegaly out of proportion to sulcal enlargement in setting of normal cerebrospinal fluid (CSF) pressure
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- In-111 DTPA radionuclide cisternography
|
||||
- Advantages
|
||||
- Provides physiologic information about CSF flow
|
||||
- Useful in patients who cannot receive MR or in whom CT is nondiagnostic (equivocal findings)
|
||||
- May help determine who may benefit from ventriculoperitoneal (VP) shunt (controversial)
|
||||
- Disadvantages
|
||||
- Radiation
|
||||
- Time consuming
|
||||
- Normal study
|
||||
- 1 hour: Radiotracer reaches basal cisterns
|
||||
- 2-6 hours: Radiotracer reaches sylvian fissures
|
||||
- Trident sign: Activity in anterior interhemispheric fissure and sylvian fissures
|
||||
- 12 hours: Radiotracer reaches cerebral convexities
|
||||
- 24 hours: Radiotracer reaches superior sagittal sinus and is absorbed by arachnoid villi
|
||||
- No radiotracer activity should be seen in ventricles, although transient activity in ventricles at 4 hours is still considered normal
|
||||
- NPH
|
||||
- 24-48 hours: Ventricular activity is present, and no activity is seen in cerebral convexities
|
||||
- Heart configuration: Appearance of radiotracer activity in lateral ventricles on anterior view
|
||||
- Comma (also C-shaped) configuration: Appearance of radiotracer activity in lateral ventricles on lateral views
|
||||
- Butterfly configuration: Appearance of radiotracer activity in lateral ventricles on posterior view
|
||||
- Radiotracer activity in lateral ventricles at 24 hours or later is abnormal and consistent with diagnosis of NPH
|
||||
- Radiotracer activity not present in cerebral convexities by 24-72 hours is abnormal and suggestive of NPH
|
||||
- CSF movement patterns on cisternography
|
||||
- Type I: Radiotracer activity in cerebral convexities at 24 hours
|
||||
- Normal or noncommunicating hydrocephalus
|
||||
- Type II: Delayed activity in cerebral convexities at 24 hours without ventricular activity
|
||||
- Cerebral atrophy or aging
|
||||
- Type IIIa: Radiotracer activity in cerebral convexities at 24 hours with early transient ventricular activity
|
||||
- Indeterminate (can be seen with noncommunicating hydrocephalus, developing or resolving communicating hydrocephalus, or cerebral atrophy)
|
||||
- Type IIIb: No radiotracer activity in cerebral convexities at 24 hours with early transient ventricular activity
|
||||
- Suggestive of NPH (communicating hydrocephalus)
|
||||
- Type IV: No radiotracer activity in cerebral convexities at 24 hours with persistent ventricular activity
|
||||
- Suggestive of NPH (communicating hydrocephalus)
|
||||
- ## Other Modality Findings
|
||||
|
||||
|
||||
- MR
|
||||
- 1st-line imaging to diagnose NPH
|
||||
- Findings include ventriculomegaly out of proportion to sulcal enlargement, crowding of vertex sulci, acute callosal angle, enlarged sylvian fissures, hyperintense lesions in deep and periventricular white matter, flow void in cerebral aqueduct
|
||||
- Contraindications include hardware incompatible with MR and claustrophobia
|
||||
- CT
|
||||
- Shows ventriculomegaly out of proportion to sulcal enlargement and potentially additional MR findings
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR
|
||||
- Findings
|
||||
- Ventriculomegaly out of proportion to sulcal enlargement
|
||||
- Hyperintense lesions in deep and periventricular white matter
|
||||
- Flow void in cerebral aqueduct
|
||||
- 1st-line imaging to diagnose NPH
|
||||
- Advantages
|
||||
- No radiation to patient
|
||||
- Provides both anatomic and physiologic (CSF flow dynamics) information
|
||||
- Contraindications
|
||||
- Hardware incompatible with MR (cardiac pacemaker, aneurysm/embolization clips, prosthetic heart valves, etc.)
|
||||
- Claustrophobia
|
||||
- CT
|
||||
- Findings
|
||||
- Ventriculomegaly out of proportion to sulcal enlargement
|
||||
- Advantages
|
||||
- NECT can suggest diagnosis of NPH
|
||||
- Disadvantages
|
||||
- Radiation
|
||||
- No physiologic information
|
||||
- May be difficult to differentiate ventriculomegaly due to NPH from cerebral atrophy in setting of Alzheimer dementia or normal aging
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- In-111 diethylenetriaminepentaacetic acid (DTPA) radionuclide cisternography
|
||||
- In-111 DTPA
|
||||
- Half-life (t1/2): 67 hours (2.8 days)
|
||||
- γ energies: 173 and 247 keV
|
||||
- Nonlipophilic
|
||||
- Not metabolized
|
||||
- Absorbed by arachnoid villi
|
||||
- Dosimetry
|
||||
- Spinal cord, brain, kidneys, bladder receive largest radiation dose
|
||||
- Patient preparation: Same as for any lumbar puncture (LP), except need radiotracer prepared ahead of time
|
||||
- Intrathecal injection of 0.5 mCi (18.5 MBq) In-111 DTPA
|
||||
- LP usually performed fluoroscopically by neuroradiologist, and radiotracer injected by nuclear medicine physician
|
||||
- Need appropriate cleanup and disposal of equipment due to radioactivity
|
||||
- Avoid contaminating patient's skin with radiotracer
|
||||
- Image acquisition
|
||||
- Planar &/or SPECT/CT with gamma camera
|
||||
- Low- or medium-energy, parallel hole collimator
|
||||
- Immediate anterior planar imaging to confirm intrathecal placement (bring portable gamma camera to LP suite or transport patient to nuclear medicine department)
|
||||
- 4-, 24-, and 48-hour (up to 72-hour) planar images of head: Anterior, posterior, both laterals
|
||||
- 24-hour SPECT/CT images of head if ventricular activity equivocal on planar imaging
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Dementia](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Ventriculomegaly with sulcal enlargement
|
||||
- Small hippocampi
|
||||
- Type II or IIIa CSF flow pattern on cisternography
|
||||
- Dementia most pronounced clinical symptom
|
||||
- ## Parkinson Disease
|
||||
|
||||
|
||||
- Resting tremor (pill-rolling)
|
||||
- Shuffling gate
|
||||
- Cogwheel rigidity
|
||||
- ## Normal Aging
|
||||
|
||||
|
||||
- Type II CSF flow pattern on cisternography
|
||||
- ## Noncommunicating Hydrocephalus
|
||||
|
||||
|
||||
- Type I CSF flow pattern on cisternography
|
||||
- Usually diagnosed on MR
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Causes
|
||||
- Idiopathic (50%)
|
||||
- Secondary (50%)
|
||||
- Subarachnoid hemorrhage or subdural hematoma
|
||||
- Meningitis or encephalitis
|
||||
- Leptomeningeal carcinomatosis
|
||||
- Head trauma
|
||||
- Brain radiation
|
||||
- Neurosurgery
|
||||
- Pathophysiology
|
||||
- Impaired CSF resorption by arachnoid villi causes communicating hydrocephalus
|
||||
- Traditional theory: Increased resistance to CSF outflow
|
||||
- Newer theory: Increased pulsations in intracranial pressure has been suggested as potential mechanism
|
||||
- Dysfunctional CSF dynamics without increase in intracranial pressure
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Heterogeneous triad: Gait abnormality, urinary incontinence, dementia
|
||||
- All 3 present in only 10% of patients
|
||||
- Gait abnormality may manifest as magnetic gait, frontal ataxia, or gait apraxia (can be difficult to distinguish from shuffling gait or Parkinson disease)
|
||||
- Urinary urgency usually precedes incontinence
|
||||
- Dementia usually manifests with frontal lobe symptoms, such as apathy, lack of concentration and inattention, and psychomotor slowing
|
||||
- Symptom severity is related to CSF levels of neurofilament protein, marker of neuronal degeneration
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- Reversible cause of dementia
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Most common in patients > 60 years
|
||||
- Idiopathic form of NPH tends to present in older adults
|
||||
- Secondary NPH can present at earlier age
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M = F
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Natural course: Continuing cognitive and motor decline, akinetic mutism, and eventual death
|
||||
- Potentially reversible cause of dementia when shunted, although gait symptoms are usually most predominant
|
||||
- Some patients worsen after shunting
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Ventricular shunt (most commonly VP)
|
||||
- Predictors of positive response to shunting
|
||||
- Patient < 75 years
|
||||
- Early symptoms (mild gait abnormality and urinary urgency)
|
||||
- Known history of intracranial infection or bleeding (nonidiopathic NPH)
|
||||
- Gait abnormality as dominant clinical symptom
|
||||
- Absence of central atrophy or ischemia
|
||||
- Prominent CSF flow void
|
||||
- Response to CSF removal trial
|
||||
- Exclusion of comorbidities, such as concomitant Alzheimer dementia or Parkinson disease
|
||||
- After shunt surgery
|
||||
- Variable outcome amongst studies, likely due to differing patient selection criteria
|
||||
- Early research may suggest role for amyloid, FDG, &/or DOPA PET in predicting outcomes to surgery
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- Whether ventricular dilation is solely due to atrophy or another underlying neurodegenerative disease
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Classic finding of NPH on radionuclide cisternography
|
||||
- Prominent ventricular activity at 24 hours with absent activity over convexities
|
||||
|
||||
650e8453-816e-4a1a-a422-ae65a07c95e8
|
||||
+256
@@ -0,0 +1,256 @@
|
||||
# Normal-Pressure Hydrocephalus
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus (NPH): Ventriculomegaly out of proportion to sulcal enlargement in setting of normal cerebrospinal fluid (CSF) pressure
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- In-111 DTPA radionuclide cisternography
|
||||
- Used in patients in whom MR is contraindicated and CT is equivocal
|
||||
- Protocol
|
||||
- Intrathecal injection of In-111 DTPA
|
||||
- Obtain planar images with gamma camera immediately after injection and at 4, 24, and 48 hours
|
||||
- Normal study
|
||||
- 1 hour: Radiotracer reaches basal cisterns
|
||||
- 2-6 hours: Radiotracer reaches sylvian fissures
|
||||
- 12 hours: Radiotracer reaches cerebral convexities
|
||||
- 24 hours: Radiotracer reaches superior sagittal sinus and is absorbed by arachnoid villi
|
||||
- Normally no radiotracer enters ventricles, although transient activity in ventricles at 4 hours is still considered normal
|
||||
- NPH
|
||||
- Radiotracer activity in ventricles at ≥ 24 hours
|
||||
- Absence of radiotracer activity in cerebral convexities by 24-72 hours
|
||||
- SPECT/CT can help confirm ventricular activity
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Symptoms: Gait disturbance, urinary incontinence, dementia
|
||||
- Treatment: Ventriculoperitoneal shunt
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Ventricular dilation on anatomic imaging may related to cerebral atrophy or underlying neurodegenerative disease
|
||||
- Classic finding of NPH on radionuclide cisternography
|
||||
- Prominent ventricular activity at 24-72 hours with absent activity over convexities
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus (NPH): Ventriculomegaly out of proportion to sulcal enlargement in setting of normal cerebrospinal fluid (CSF) pressure
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- In-111 DTPA radionuclide cisternography
|
||||
- Advantages
|
||||
- Provides physiologic information about CSF flow
|
||||
- Useful in patients who cannot receive MR or in whom CT is nondiagnostic (equivocal findings)
|
||||
- May help determine who may benefit from ventriculoperitoneal (VP) shunt (controversial)
|
||||
- Disadvantages
|
||||
- Radiation
|
||||
- Time consuming
|
||||
- Normal study
|
||||
- 1 hour: Radiotracer reaches basal cisterns
|
||||
- 2-6 hours: Radiotracer reaches sylvian fissures
|
||||
- Trident sign: Activity in anterior interhemispheric fissure and sylvian fissures
|
||||
- 12 hours: Radiotracer reaches cerebral convexities
|
||||
- 24 hours: Radiotracer reaches superior sagittal sinus and is absorbed by arachnoid villi
|
||||
- No radiotracer activity should be seen in ventricles, although transient activity in ventricles at 4 hours is still considered normal
|
||||
- NPH
|
||||
- 24-48 hours: Ventricular activity is present, and no activity is seen in cerebral convexities
|
||||
- Heart configuration: Appearance of radiotracer activity in lateral ventricles on anterior view
|
||||
- Comma (also C-shaped) configuration: Appearance of radiotracer activity in lateral ventricles on lateral views
|
||||
- Butterfly configuration: Appearance of radiotracer activity in lateral ventricles on posterior view
|
||||
- Radiotracer activity in lateral ventricles at 24 hours or later is abnormal and consistent with diagnosis of NPH
|
||||
- Radiotracer activity not present in cerebral convexities by 24-72 hours is abnormal and suggestive of NPH
|
||||
- CSF movement patterns on cisternography
|
||||
- Type I: Radiotracer activity in cerebral convexities at 24 hours
|
||||
- Normal or noncommunicating hydrocephalus
|
||||
- Type II: Delayed activity in cerebral convexities at 24 hours without ventricular activity
|
||||
- Cerebral atrophy or aging
|
||||
- Type IIIa: Radiotracer activity in cerebral convexities at 24 hours with early transient ventricular activity
|
||||
- Indeterminate (can be seen with noncommunicating hydrocephalus, developing or resolving communicating hydrocephalus, or cerebral atrophy)
|
||||
- Type IIIb: No radiotracer activity in cerebral convexities at 24 hours with early transient ventricular activity
|
||||
- Suggestive of NPH (communicating hydrocephalus)
|
||||
- Type IV: No radiotracer activity in cerebral convexities at 24 hours with persistent ventricular activity
|
||||
- Suggestive of NPH (communicating hydrocephalus)
|
||||
- ## Other Modality Findings
|
||||
|
||||
|
||||
- MR
|
||||
- 1st-line imaging to diagnose NPH
|
||||
- Findings include ventriculomegaly out of proportion to sulcal enlargement, crowding of vertex sulci, acute callosal angle, enlarged sylvian fissures, hyperintense lesions in deep and periventricular white matter, flow void in cerebral aqueduct
|
||||
- Contraindications include hardware incompatible with MR and claustrophobia
|
||||
- CT
|
||||
- Shows ventriculomegaly out of proportion to sulcal enlargement and potentially additional MR findings
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR
|
||||
- Findings
|
||||
- Ventriculomegaly out of proportion to sulcal enlargement
|
||||
- Hyperintense lesions in deep and periventricular white matter
|
||||
- Flow void in cerebral aqueduct
|
||||
- 1st-line imaging to diagnose NPH
|
||||
- Advantages
|
||||
- No radiation to patient
|
||||
- Provides both anatomic and physiologic (CSF flow dynamics) information
|
||||
- Contraindications
|
||||
- Hardware incompatible with MR (cardiac pacemaker, aneurysm/embolization clips, prosthetic heart valves, etc.)
|
||||
- Claustrophobia
|
||||
- CT
|
||||
- Findings
|
||||
- Ventriculomegaly out of proportion to sulcal enlargement
|
||||
- Advantages
|
||||
- NECT can suggest diagnosis of NPH
|
||||
- Disadvantages
|
||||
- Radiation
|
||||
- No physiologic information
|
||||
- May be difficult to differentiate ventriculomegaly due to NPH from cerebral atrophy in setting of Alzheimer dementia or normal aging
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- In-111 diethylenetriaminepentaacetic acid (DTPA) radionuclide cisternography
|
||||
- In-111 DTPA
|
||||
- Half-life (t1/2): 67 hours (2.8 days)
|
||||
- γ energies: 173 and 247 keV
|
||||
- Nonlipophilic
|
||||
- Not metabolized
|
||||
- Absorbed by arachnoid villi
|
||||
- Dosimetry
|
||||
- Spinal cord, brain, kidneys, bladder receive largest radiation dose
|
||||
- Patient preparation: Same as for any lumbar puncture (LP), except need radiotracer prepared ahead of time
|
||||
- Intrathecal injection of 0.5 mCi (18.5 MBq) In-111 DTPA
|
||||
- LP usually performed fluoroscopically by neuroradiologist, and radiotracer injected by nuclear medicine physician
|
||||
- Need appropriate cleanup and disposal of equipment due to radioactivity
|
||||
- Avoid contaminating patient's skin with radiotracer
|
||||
- Image acquisition
|
||||
- Planar &/or SPECT/CT with gamma camera
|
||||
- Low- or medium-energy, parallel hole collimator
|
||||
- Immediate anterior planar imaging to confirm intrathecal placement (bring portable gamma camera to LP suite or transport patient to nuclear medicine department)
|
||||
- 4-, 24-, and 48-hour (up to 72-hour) planar images of head: Anterior, posterior, both laterals
|
||||
- 24-hour SPECT/CT images of head if ventricular activity equivocal on planar imaging
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Dementia](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Ventriculomegaly with sulcal enlargement
|
||||
- Small hippocampi
|
||||
- Type II or IIIa CSF flow pattern on cisternography
|
||||
- Dementia most pronounced clinical symptom
|
||||
- ## Parkinson Disease
|
||||
|
||||
|
||||
- Resting tremor (pill-rolling)
|
||||
- Shuffling gate
|
||||
- Cogwheel rigidity
|
||||
- ## Normal Aging
|
||||
|
||||
|
||||
- Type II CSF flow pattern on cisternography
|
||||
- ## Noncommunicating Hydrocephalus
|
||||
|
||||
|
||||
- Type I CSF flow pattern on cisternography
|
||||
- Usually diagnosed on MR
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Causes
|
||||
- Idiopathic (50%)
|
||||
- Secondary (50%)
|
||||
- Subarachnoid hemorrhage or subdural hematoma
|
||||
- Meningitis or encephalitis
|
||||
- Leptomeningeal carcinomatosis
|
||||
- Head trauma
|
||||
- Brain radiation
|
||||
- Neurosurgery
|
||||
- Pathophysiology
|
||||
- Impaired CSF resorption by arachnoid villi causes communicating hydrocephalus
|
||||
- Traditional theory: Increased resistance to CSF outflow
|
||||
- Newer theory: Increased pulsations in intracranial pressure has been suggested as potential mechanism
|
||||
- Dysfunctional CSF dynamics without increase in intracranial pressure
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Heterogeneous triad: Gait abnormality, urinary incontinence, dementia
|
||||
- All 3 present in only 10% of patients
|
||||
- Gait abnormality may manifest as magnetic gait, frontal ataxia, or gait apraxia (can be difficult to distinguish from shuffling gait or Parkinson disease)
|
||||
- Urinary urgency usually precedes incontinence
|
||||
- Dementia usually manifests with frontal lobe symptoms, such as apathy, lack of concentration and inattention, and psychomotor slowing
|
||||
- Symptom severity is related to CSF levels of neurofilament protein, marker of neuronal degeneration
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- Reversible cause of dementia
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Most common in patients > 60 years
|
||||
- Idiopathic form of NPH tends to present in older adults
|
||||
- Secondary NPH can present at earlier age
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M = F
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Natural course: Continuing cognitive and motor decline, akinetic mutism, and eventual death
|
||||
- Potentially reversible cause of dementia when shunted, although gait symptoms are usually most predominant
|
||||
- Some patients worsen after shunting
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Ventricular shunt (most commonly VP)
|
||||
- Predictors of positive response to shunting
|
||||
- Patient < 75 years
|
||||
- Early symptoms (mild gait abnormality and urinary urgency)
|
||||
- Known history of intracranial infection or bleeding (nonidiopathic NPH)
|
||||
- Gait abnormality as dominant clinical symptom
|
||||
- Absence of central atrophy or ischemia
|
||||
- Prominent CSF flow void
|
||||
- Response to CSF removal trial
|
||||
- Exclusion of comorbidities, such as concomitant Alzheimer dementia or Parkinson disease
|
||||
- After shunt surgery
|
||||
- Variable outcome amongst studies, likely due to differing patient selection criteria
|
||||
- Early research may suggest role for amyloid, FDG, &/or DOPA PET in predicting outcomes to surgery
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- Whether ventricular dilation is solely due to atrophy or another underlying neurodegenerative disease
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Classic finding of NPH on radionuclide cisternography
|
||||
- Prominent ventricular activity at 24 hours with absent activity over convexities
|
||||
|
||||
d11495d3-e2da-4ebf-86d2-25c60a3ed963
|
||||
+243
@@ -0,0 +1,243 @@
|
||||
# Parkinsonian Syndromes
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Chronic, progressive brain disorder characterized by loss of dopaminergic neurons that leads to tremors at rest, rigidity, slowed movements, and shuffling gait
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Dopamine transporters typically decreased for all Parkinson syndromes [Parkinson disease (PD) and atypical parkinsonism syndromes (APS)]
|
||||
- Loss of dopaminergic neurons visualized on I-123 ioflupane (DaT) SPECT and F-18 fluorodopa (FDOPA) PET
|
||||
- **I-123 ioflupane (DaT, FP-CIT) SPECT**
|
||||
- Molecular imaging agent that binds to dopamine transporters located on presynaptic nigrostriatal axons
|
||||
- **F-18 FDOPA PET**
|
||||
- F-18 FDOPA is decarboxylated by amino acid decarboxylase to F-18 fluorodopamine and stored in presynaptic vesicles in dopaminergic nerve terminals
|
||||
- Sensitivity > 90% for differentiating PD and essential tremor
|
||||
- Normal DaT and FDOPA scans demonstrate comma-shaped uptake on axial images
|
||||
- Abnormal scans demonstrate
|
||||
- Asymmetric putamen activity
|
||||
- Symmetrically decreased or absent putamen activity with preservation of caudate
|
||||
- Decreased or absent putamen activity with significantly decreased/absent caudate uptake
|
||||
- Patient should be off all interfering dopaminergic medications
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- PD
|
||||
- Multiple system atrophy
|
||||
- Progressive supranuclear palsy
|
||||
- Dementia with Lewy bodies
|
||||
- Corticobasal degeneration
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- **Parkinsonian syndrome (PS)**
|
||||
- Clinical syndrome presenting with any combination of bradykinesia, resting tremor, rigidity, and autonomic instability
|
||||
- **Parkinson disease** **(****PD**) **(α-synucleinopathy)**
|
||||
- Chronic progressive disorder caused by degenerative loss of dopaminergic neurons
|
||||
- Classically present with bradykinesia and at least 1 of (i) tremor &/or (ii) rigidity
|
||||
- Normal DaT scan considered essentially exclusionary for diagnosis
|
||||
- **Atypical PS (APS)**
|
||||
- Characterized by more rapid progression and poorer prognosis than PD
|
||||
- Includes progressive supranuclear palsy (PSP; 4R-tauopathy), multiple system atrophy (MSA; α-synucleinopathy), and corticobasal degeneration (CBD; 4R-tauopathy)
|
||||
- **Dementia with Lewy bodies (DLB) (****α****-synucleinopathy)**
|
||||
- Dementia + visual hallucinations, parkinsonism, cognitive fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity
|
||||
- **Drug-induced parkinsonism (DIP**)
|
||||
- Secondary parkinsonism, usually reversible
|
||||
- **Vascular parkinsonism (VP)**
|
||||
- Small vessel disease, multiple lacunar infarcts in basal ganglia
|
||||
- **Essential tremor (ET)**
|
||||
- Most common cause of action tremor in adults
|
||||
- Slow, gradual progression
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- Loss of dopaminergic neurons on I-123 ioflupane (DaT) SPECT or F-18 fluorodopa (FDOPA) PET
|
||||
- Relatively normal F-18 FDG PET/CT
|
||||
- Distinct abnormal patterns in APS
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- **I-123 ioflupane (DaT, FP-CIT) SPECT**
|
||||
- Molecular imaging agent that binds to dopamine (DA) transporters located on presynaptic nigrostriatal axons
|
||||
- DA transporters typically decreased for all Parkinson syndromes (PD and APSs)
|
||||
- DA transporters are located in putamen and caudate nuclei
|
||||
- Demonstrates loss of dopaminergic neurons
|
||||
- Sensitivity > 90% for differentiating PD and ET
|
||||
- May be symmetric or asymmetric
|
||||
- Differentiates PD and APS from ET and DIP
|
||||
- PD and APS demonstrate decreased activity in putamen and caudate
|
||||
- Does **not** differentiate PD from APS or between APSs
|
||||
- Image interpretation
|
||||
- Normal scans demonstrate comma-shaped uptake on axial images
|
||||
- Abnormal scans demonstrate period-shaped uptake on axial images indicating more pronounced loss of uptake in putamen
|
||||
- Abnormal uptake may be initially detected in contralateral putamen relative to clinical symptoms
|
||||
- Abnormal patterns
|
||||
- Asymmetric putamen activity
|
||||
- Symmetrically decreased or absent putamen activity with preservation of caudate
|
||||
- Decreased or absent putamen activity with significantly decreased/absent caudate uptake
|
||||
- **F-18 FDOPA PET**
|
||||
- F-18 FDOPA is decarboxylated by amino acid decarboxylase to F-18 fluorodopamine and stored in presynaptic vesicles in dopaminergic nerve terminals
|
||||
- Accumulation of F-18 fluorodopamine in striatum is visually detected on PET
|
||||
- Similar uptake pattern as I-123 ioflupane in normal and disease states but benefits from better quality of PET
|
||||
- Normal scan: Comma-shaped uptake on axial images visualizing caudate and putamen
|
||||
- Abnormal scan: Asymmetric or decreased putamen activity with normal or decreased caudate activity
|
||||
- **F-18 FDG PET/CT**
|
||||
- Typically normal in PD
|
||||
- Preserved F-18 FDG PET/CT in basal ganglia differentiates PD from PS
|
||||
- **MIBG cardiac SPECT**
|
||||
- Absent myocardial tracer binding in PD and LBD
|
||||
- Typically preserved in APDs, DIP, VP, ET
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- **I-123 ioflupane**
|
||||
- Patient should be off all interfering dopaminergic medications
|
||||
- Cocaine, amphetamines, and methylphenidate severely decrease binding
|
||||
- Ephedrine and phentermine may decrease binding
|
||||
- Bupropion, fentanyl, and some anesthetics may decrease binding
|
||||
- Patient preparation
|
||||
- Pretreat with thyroid blocker (400 mg of oral potassium solution or single dose of Lugol solution) 1 hour before tracer injection
|
||||
- Pregnancy category C: Unknown whether I-123 can cause fetal damage or early termination of pregnancy
|
||||
- Radiopharmaceutical: I-123 ioflupane
|
||||
- Dose: 3-5 mCi (111-185 MBq) intravenously
|
||||
- Dosimetry: Striata receives highest radiation exposure, followed by bladder, bowel, and lungs (assuming thyroid is blocked)
|
||||
- Image acquisition: 3-6 hours after injection
|
||||
- SPECT or SPECT/CT acceptable but attenuation correction is recommended
|
||||
- Photopeak should be set to 159 keV ± 10%
|
||||
- Low-energy, high-resolution collimator
|
||||
- 128 x 128 matrix is recommended
|
||||
- 30-second projection time (120 projections)
|
||||
- **F-18 FDOPA**
|
||||
- Patient preparation
|
||||
- Premedicate with 150 mg of carbidopa orally at least 60 minutes (and no longer than 120 minutes) prior to administration of F-18 FDOPA injection
|
||||
- Carbidopa blocks systemic/peripheral decarboxylation of F-18 FDOPA to increase uptake in brain
|
||||
- Patient should be off all interfering dopaminergic medications for at least 12 hours prior to F-18 FDOPA injection
|
||||
- Aromatic L-amino acid decarboxylase (AADC) inhibitors (e.g., carbidopa, benserazide, etc.)
|
||||
- DA agonists, DA reuptake inhibitors, DA-releasing agents (DRAs), such as psychostimulants of amphetamine class, peripheral catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors
|
||||
- Radiopharmaceutical: F-18 FDOPA
|
||||
- Dose: 5 mCi (185 MBq) intravenously
|
||||
- Image acquisition: 80-100 minutes after injection
|
||||
- PET attenuation correction CT
|
||||
- Dosimetry: Critical organ is bladder wall
|
||||
- F-18 FDG PET/CT
|
||||
- Patient preparation
|
||||
- Patient should fast, stop IV fluids containing dextrose, stop parenteral feeding for 4-6 hours
|
||||
- Blood sugar should be 150-200 mg/dL
|
||||
- Patient should be placed in quiet, dimly lit room prior to and after injection for 30 minutes
|
||||
- Radiopharmaceutical: F-18 FDG
|
||||
- Dose: 5-20 mCi (185-740 MBq)
|
||||
- Dosimetry: Urinary bladder receives largest dose
|
||||
- Image acquisition: 30-60 minutes after injection
|
||||
- ## Artifacts and Quality Control
|
||||
|
||||
|
||||
- Certain medications can significantly alter scan appearance and should be discontinued/documented
|
||||
- Ensure patient is off competing medications if activity is diffusely low
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Parkinson Disease](/document/parkinson-disease/0bc3188a-935b-416d-b1a0-25b2d52c6399)
|
||||
- I-123 ioflupane/F-18 FDOPA positive
|
||||
- Amyloid PET negative
|
||||
- F-18 FDG PET grossly normal, but PD-related metabolic pattern reported as increased pallidal, thalamic, and motor cortical metabolic activity associated with decreased lateral premotor and parietooccipital cortical activity
|
||||
- MR T2* can show loss of swallowtail sign in substantia nigra
|
||||
- ## Atypical Parkinsonian Syndromes
|
||||
|
||||
|
||||
- [MSA](/document/multiple-system-atrophy/4fb9af00-e0bd-4164-8f61-4011ddc8bf9e)
|
||||
- Family of neurodegenerative disorders
|
||||
- Symptoms include parkinsonism, ataxia, and autonomic dysfunction
|
||||
- Cerebellar dominant (MSA-C) and parkinsonian dominant (MSA-P)
|
||||
- F-18 FDG PET
|
||||
- MSA-C shows decreased activity in cerebellum
|
||||
- MSA-P shows decreased putamen activity
|
||||
- Amyloid PET negative
|
||||
- I-123 ioflupane/F-18 FDOPA positive
|
||||
- MR shows volume loss/T2 hyperintensity in cerebellum, middle cerebellar peduncles, and putamen
|
||||
- [PSP](/document/progressive-supranuclear-palsy/840ed321-c0ab-4069-a07e-ad416232f916)
|
||||
- Symptoms include parkinsonism, bradykinesia, rigidity, **vertical gaze palsy**, dysphagia, dysarthria
|
||||
- Amyloid PET negative
|
||||
- Ioflupane SPECT positive
|
||||
- Decreased F-18 FDG activity in basal ganglia, frontal lobes, anterior cingulate, midbrain
|
||||
- Volume loss in midbrain with relatively preserved pons, MR hummingbird sign or Mickey Mouse sign
|
||||
- [DLB](/document/lewy-body-dementia/f6a4382b-f0f7-4582-a703-7f695c65656f)
|
||||
- Symptoms include dementia, visual hallucinations, parkinsonism
|
||||
- I-123 ioflupane/F-18 FDOPA positive
|
||||
- Amyloid PET is positive in > 50% of patients
|
||||
- F-18 FDG PET/CT shows generalized reduced cortical uptake most pronounced in occipital region and sparing posterior cingulate gyrus cingulate island sign
|
||||
- [CBD](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
|
||||
- Cognitive/behavioral symptoms precede movement dysfunction
|
||||
- Symptoms include akinesia, rigidity, dystonia, apraxia, executive dysfunction, aphasia, "alien limb" phenomenon
|
||||
- Patients do not respond to levodopa
|
||||
- I-123 ioflupane/F-18 FDOPA positive, typically asymmetric and decreased contralateral to symptoms
|
||||
- Amyloid PET negative
|
||||
- F-18 FDG PET/CT relative decreased activity in contralateral cortex and basal ganglia
|
||||
- May be caused by increased ipsilateral uptake
|
||||
- ## Benign Essential Tremor
|
||||
|
||||
|
||||
- Negative I-123 ioflupane/F-18 FDOPA
|
||||
- ## Vascular Parkinsonism
|
||||
|
||||
|
||||
- Negative I-123 ioflupane/F-18 FDOPA
|
||||
- ## Drug-Induced Parkinsonism
|
||||
|
||||
|
||||
- Negative I-123 ioflupane/F-18 FDOPA
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- PD accounts for > 70% of parkinsonian patients
|
||||
- α-synuclein skin biopsy shows high sensitivity for PD, MSA, and DLB
|
||||
- Loss of dopaminergic neurons
|
||||
- Affected neurons project from substantia nigra (midbrain) to putamen and caudate
|
||||
- Putamen typically affected earlier and more severely
|
||||
- Symptoms begin to show after ~ 50% of neurons are affected
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Rigidity, tremor, bradykinesia, autonomic instability
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- Prevalence of ~ 1% in adults > 65 years
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- I-123 ioflupane SPECT/F-18 FDOPA each differentiate between diseases related to DA loss (PD and APS) and those that mimic them clinically (benign tremor and VP)
|
||||
- Cardiac MIBG may be helpful in diagnosing PD and DLB, though is typically normal in other PSs
|
||||
- ## Reporting Tips
|
||||
|
||||
|
||||
- Reporting scheme in literature
|
||||
- Normal: 2 comma-shaped areas of uptake
|
||||
- Abnormal grade 1: Asymmetric uptake [normal (comma shape) on one side and abnormal (period shape) on other side]
|
||||
- Abnormal grade 2: Abnormal (period shape) reduced putamen activity bilaterally
|
||||
- Abnormal grade 3: Markedly reduced uptake bilaterally
|
||||
|
||||
cc5405dd-1797-4f98-b1a1-127b9159f5f1
|
||||
+210
@@ -0,0 +1,210 @@
|
||||
# Primary Progressive Aphasia
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Group of heterogeneous neurodegenerative disorders characterized by prominent language and word-finding difficulties
|
||||
- This includes logopenic-variant primary progressive aphasia (lvPPA), semantic-variant primary progressive aphasia (svPPA), and nonfluent/agrammatic-variant primary progressive aphasia (nfvPPA)
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Hypometabolism within critical brain areas on F-18 FDG PET
|
||||
- lvPPA: Left precuneus and temporoparietal region
|
||||
- svPPA: Left anterior temporal lobe
|
||||
- nfvPPA: Left inferior frontal lobe and insula
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Alzheimer disease (AD)
|
||||
- Frontotemporal dementia (FTD) (behavioral variant)
|
||||
- Vascular dementia
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- lvPPA is within AD spectrum
|
||||
- svPPA and nfvPPA are within FTD spectrum
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Progressive language and word-finding difficulties
|
||||
- lvPPA: Impaired single-word retrieval, impaired repetition of sentences/phrases
|
||||
- svPPA: Impaired single-word comprehension/naming, object knowledge
|
||||
- nfvPPA: Agrammatism in language production, apraxia of speech
|
||||
- No cure exists for primary progressive aphasias
|
||||
- Patients with lvPPA may be eligible for amyloid-binding therapies
|
||||
- Engagement of social services and supportive care can aid with patients, families, and caregivers
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Primary progressive aphasia (PPA)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Group of heterogeneous neurodegenerative disorders characterized by prominent language and word-finding difficulties
|
||||
- Classically grouped, given their language-predominant symptoms, though they are separate pathologic processes
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Hypometabolism within critical brain areas on F-18 FDG PET
|
||||
- Classically involves left cerebral hemisphere, given majority of people are left language dominant
|
||||
- MR will demonstrate volume loss in affected areas in late-stage disease
|
||||
- ### Location
|
||||
|
||||
|
||||
- Logopenic-variant PPA (lvPPA): Involves left precuneus and left temporoparietal region
|
||||
- Semantic-variant PPA (svPPA): Involves left anterior temporal lobe
|
||||
- Nonfluent/agrammatic PPA (nfvPPA): Involves left inferior frontal lobe and left insula
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- F-18 FDG PET
|
||||
- Prominent, asymmetric hypometabolism within affected left cerebral hemispheric structures
|
||||
- MR
|
||||
- Initially used to assess for alternative etiologies that could cause symptoms (i.e., neoplasm, infarct, infection, trauma)
|
||||
- Qualitative and quantitative volume assessment can be performed to identify areas of neurodegeneration in late-stage disease
|
||||
- Amyloid PET
|
||||
- Positive in majority of lvPPA cases
|
||||
- Negative in svPPA and nfvPPA
|
||||
- Interpreted as "scant to few" (negative) or "moderate to frequent" (positive) β-amyloid neuritic plaques (Aβs)
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- MR
|
||||
- DWI/ADC, T2/FLAIR, and SWI/GRE performed to assess for alternative etiologies (vascular insults, neoplasms, infection)
|
||||
- 3D T1 MR to assess for subtle volume loss; can perform quantitative volumetric analysis
|
||||
- F-18 FDG PET
|
||||
- Patient preparation
|
||||
- Patient should fast, stop IV fluids containing dextrose, and stop parenteral feeding for 4-6 hours; blood sugar should be < 150 mg/dL
|
||||
- Place patient in quiet, dimly lit room for 30 minutes prior to examination
|
||||
- Radiopharmaceutical: F-18 FDG
|
||||
- Dose: 7-10 mCi (260-370 MBq)
|
||||
- Dosimetry: Bladder is critical organ
|
||||
- Image acquisition: 45-60 minutes post injection
|
||||
- Amyloid PET
|
||||
- No patient preparation necessary
|
||||
- Radiopharmaceutical: F-18 florbetapir (or other amyloid-based tracers)
|
||||
- Dose: ~ 10 mCi (370 MBq) for F-18 florbetapir
|
||||
- Dosimetry: Gallbladder, bowel, intestines are critical organs
|
||||
- Image acquisition: 30-50 minutes post injection for F-18 florbetapir
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Disease (Classic Type)](/document/alzheimer-disease/2aad3ac4-44fd-43e5-8e50-a86987483af3)
|
||||
- Most common dementia
|
||||
- Memory impairment is prominent symptom
|
||||
- Language difficulties typically reserved for advanced disease
|
||||
- F-18 FDG PET demonstrates more symmetric temporoparietal hypometabolism
|
||||
- Positive on amyloid PET
|
||||
- [Frontotemporal Dementia (Behavioral Variant)](/document/frontotemporal-dementia/9f9eda8c-7e3c-4292-9861-4b8abc2c6474)
|
||||
- Classically presents with behavioral and personality changes
|
||||
- F-18 FDG PET demonstrates symmetric anterior frontal and temporal hypometabolism
|
||||
- MR demonstrates corresponding atrophy in frontotemporal lobes
|
||||
- [Vascular Dementia](/document/multiinfarct-dementia/3823c4d4-5e98-46da-a717-892fef54b382)
|
||||
- 2nd most common cause of dementia
|
||||
- MR shows scattered infarcts of varying ages, typically in deep gray nuclei or within vascular territory
|
||||
- Left middle cerebral artery (MCA) territory infarcts can affect areas involved in language and communication
|
||||
- ## Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE)
|
||||
|
||||
|
||||
- Recently described neurodegenerative disease that classically occurs in older adult patients (> 80 years old)
|
||||
- Typically does not present with language difficulties
|
||||
- F-18 FDG PET demonstrates hypometabolism within anterior temporal lobes and insula, usually bilateral
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- Undetermined cause, likely secondary to combination of genetic, lifestyle, and environmental factors
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- Diagnostic criteria
|
||||
- lvPPA
|
||||
- Core criteria: Impaired single-word retrieval, impaired repetition of sentences/phrases
|
||||
- Other features: Speech errors in spontaneous speech, spared single-word comprehension and object knowledge, spared motor speech, absence of frank agrammatism
|
||||
- svPPA
|
||||
- Core criteria: Impaired confrontation naming, impaired single-word comprehension
|
||||
- Other features: Impaired object knowledge, surface dyslexia/dysgraphia, spared repetition, spared speech production
|
||||
- nfvPPA
|
||||
- Core criteria: Agrammatism in language production, effortful/halting speech with speech sound errors and distortions (apraxia)
|
||||
- Other features: Impaired comprehension of syntactically complex sentences, spared single-word comprehension, spared object knowledge
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Late-stage disease demonstrates prominent volume loss within affected regions
|
||||
- Increased sulcal volume within left cerebral hemisphere
|
||||
- lvPPA is believed to be within Alzheimer disease (AD) spectrum
|
||||
- Associated with Aβ and τ neurofibrillary tangles (τ-NFT) (80% of cases)
|
||||
- svPPA and nfvPPA are believed to be within frontotemporal dementia spectrum
|
||||
- svPPA is associated with TDP-43
|
||||
- nfvPPA is associated with 4-repeat τ isoform (4R-τ)
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Progressive word-finding and language difficulties
|
||||
- lvPPA: Impaired single-word retrieval, impaired repetition of sentences/phrases
|
||||
- svPPA: Impaired single-word comprehension/naming, object knowledge
|
||||
- nfvPPA: Agrammatism in language production, apraxia of speech
|
||||
- Delayed diagnosis can occur given lack of apparent memory loss or behavioral symptoms
|
||||
- ### Other signs/symptoms
|
||||
|
||||
|
||||
- Late-stage disease will have memory loss/dementia
|
||||
- Psychiatric issues (i.e., depression, anxiety) may be present
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Progressive language and word-finding difficulties
|
||||
- End-stage disease presents with near-complete inability to communicate
|
||||
- Memory loss is less evident in early disease and can present later in disease course
|
||||
- Significant distinction from AD, where memory loss is primary symptom and language difficulties are seen later in disease course
|
||||
- No prominent behavioral, anger, or dysexecutive symptoms
|
||||
- Distinct from behavioral-variant frontotemporal dementia, where behavioral issues are evident early in disease course
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- No cure exists for PPAs
|
||||
- lvPPA patients may be eligible for amyloid-targeting therapy
|
||||
- No disease-modifying therapies exist for svPPA or nfvPPA
|
||||
- Speech therapy and rehabilitation can aid in improving communication with caregivers/family
|
||||
- Engagement of social services and supportive care can aid with patients, families, and caregivers
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- F-18 FDG PET
|
||||
- Asymmetric hypometabolism within left temporoparietal region (lvPPA), left temporal pole (svPPA), or left inferior frontal lobe and insula (nfvPPA)
|
||||
- MR
|
||||
- Asymmetric left cerebral hemispheric volume loss within affected areas
|
||||
- ## Reporting Tips
|
||||
|
||||
|
||||
- Identify asymmetric hypometabolism if present
|
||||
- Describe key brain areas that are affected to convey specificity of underlying disease process
|
||||
- Exclude alternative etiologies and identify normal areas of metabolism on F-18 FDG PET
|
||||
- Consider additional imaging, such as amyloid PET, for suspected lvPPA, which would be beneficial for assessing candidacy for amyloid-targeting therapies
|
||||
|
||||
92b83333-bc7b-40b2-b629-dd77297359fc
|
||||
+308
@@ -0,0 +1,308 @@
|
||||
# Vascular Dementia
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Vascular dementia (VaD), multiinfarct dementia (MID), vascular cognitive impairment (VCI)
|
||||
- Stepwise progressive ↓ in cognitive function
|
||||
- Heterogeneous group of disorders with varying etiologies, pathologic subtypes
|
||||
- VaD often mixed etiology
|
||||
- Can occur alone or in association with Alzheimer disease
|
||||
- MID secondary to repeated cerebral infarctions
|
||||
- VaD: Dementia caused by cerebrovascular disease or ↓ cerebral blood flow
|
||||
- VCI: Cognitive impairment caused by or associated with vascular factors
|
||||
- Can occur alone or in association with Alzheimer disease (AD)
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- General features
|
||||
- Multifocal infarcts [cortical gray matter (GM), subcortical white matter (WM)]
|
||||
- Basal ganglia (BG), pons
|
||||
- Territorial as well as lacunar lesions
|
||||
- Coexisting microvascular WM disease common
|
||||
- Multiple remote microhemorrhages
|
||||
- CT
|
||||
- Multifocal infarcts
|
||||
- Single or multiple, lacunar to territorial
|
||||
- WM hypointensities (discrete to confluent)
|
||||
- FDG PET
|
||||
- Multifocal regions ↓ metabolism in cortex, WM
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- AD
|
||||
- Frontotemporal lobar degeneration
|
||||
- CADASIL
|
||||
- Dementia with Lewy bodies
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- 2nd most common dementia (after AD)
|
||||
- Mood & behavioral changes more typical than memory loss
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Report strategically placed infarcts
|
||||
- Look for hemorrhage, DWI abnormalities
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Vascular dementia (VaD)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Multiinfarct dementia (MID)
|
||||
- Vascular cognitive disorder (VCD)
|
||||
- Vascular cognitive impairment (VCI)
|
||||
- Subcortical ischemic VaD
|
||||
- Poststroke dementia
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Dementia caused by cerebrovascular disease or ↓ cerebral blood flow (CBF)
|
||||
- VCI: Cognitive impairment caused by or associated with vascular factors
|
||||
- Secondary to repeated cerebral infarctions
|
||||
- Can occur alone or in association with Alzheimer disease (AD)
|
||||
- 2nd most common cause of dementia next to AD
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Multifocal infarcts
|
||||
- Cortical gray matter (GM), subcortical white matter (WM)
|
||||
- Basal ganglia (BG), pons
|
||||
- Territorial as well as lacunar infarcts
|
||||
- Changes of microvascular WM ischemia common
|
||||
- ### Location
|
||||
|
||||
|
||||
- Typically involves cerebral hemispheres & BG
|
||||
- Usually bilateral but may be unilateral
|
||||
- ### Size
|
||||
|
||||
|
||||
- Vary from single to multiple, punctate to large/confluent
|
||||
- ### Morphology
|
||||
|
||||
|
||||
- Small infarcts are rounded or oval; large confluent abnormalities are ill defined
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- ### NECT
|
||||
|
||||
|
||||
- Hypodensity in periventricular WM
|
||||
- Cortical, subcortical, BG infarcts
|
||||
- Generalized atrophy with focal cortical infarcts typical
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Generally have hypointense BG lacunar infarcts
|
||||
- Atrophy with enlargement of ventricles & sulci
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Punctate or confluent regions of hyperintense WM
|
||||
- Central pontine infarcts
|
||||
- Large areas of volume loss with widened sulci
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- Hyperintense foci within BG
|
||||
- Multifocal diffuse & confluent WM hyperintensities
|
||||
- ### T2* GRE
|
||||
|
||||
|
||||
- Multiple blooming hypointensities in cortex & along pial surface
|
||||
- ### DWI
|
||||
|
||||
|
||||
- ↓ fractional anisotropy & ↑ ADC within lesions, normal-appearing WM (NAWM)
|
||||
- ↑ in mean diffusivity of NAWM correlates with disability found on tests of executive function
|
||||
- ### MRA
|
||||
|
||||
|
||||
- Most abnormalities in small arteries, generally not well seen on MRA
|
||||
- ### MRS
|
||||
|
||||
|
||||
- ↓ NAA in both cortical & WM regions
|
||||
- Frontal cortex NAA negatively correlated with volume of WM signal hyperintensity
|
||||
- ## Ultrasonographic Findings
|
||||
|
||||
|
||||
- Transcranial Doppler sonography: Pulsatility indices in large arteries ↑ compared to AD
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- FDG PET
|
||||
- Multiple areas of hypometabolism without specific lobar predominance
|
||||
- Severity of MID neuropsychiatric symptoms correlates with extent of ↓ metabolism in cortex & WM
|
||||
- SPECT
|
||||
- Iodine-123-iodoamphetamine: ↓ frontal & BG CBF, which correlates with low cognitive scores
|
||||
- Tc-99m hexamethyl propyleneamine oxime: CBF heterogeneity more prominent in anterior portion of brain
|
||||
- Unlike pattern in AD, in which posterior abnormalities predominate
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR
|
||||
- PET/SPECT may also provide specificity
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- Axial FLAIR to detect WM infarcts
|
||||
- Axial & coronal T2WI to assess regions of atrophy
|
||||
- T2* GRE/SWI to identify hemorrhage
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Alzheimer Disease](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
|
||||
- Striking hippocampus & amygdala atrophy
|
||||
- PET: Bilateral temporoparietal hypoperfusion/hypometabolism (BG spared)
|
||||
- Often coexists with VaD
|
||||
- [Frontotemporal Lobar Degeneration](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
|
||||
- Characterized by early onset of behavioral changes with intact visual, spatial skills
|
||||
- Frontal, temporal lobe atrophy
|
||||
- Marked atrophy → knife-like gyri
|
||||
- [Alcoholic Encephalopathy](/document/alcoholic-encephalopathy/88021852-b73d-4cdf-a719-dd4ae3231e45)
|
||||
- 3rd most common cause of dementia
|
||||
- Generalized > focal atrophy; superior vermis atrophy
|
||||
- [CADASIL](/document/cadasil/6b5a24c8-afd7-4106-bb4b-11421ed1592c)
|
||||
- Most common heritable cause of stroke, VaD in adults
|
||||
- Earlier age of onset
|
||||
- Imaging looks like small vessel disease
|
||||
- [Dementia With Lewy Bodies](/document/dementia-with-lewy-bodies/e8e46d1d-46d2-4e5a-880f-f025a84c5871)
|
||||
- Hypometabolism of entire brain
|
||||
- Without infarcts or significant atrophy
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- MID is usually due to multiple small infarctions
|
||||
- Infarcts involving entire major vessel territories are usually absent
|
||||
- Minority may be secondary to single or few large infarctions
|
||||
- ~ 75% of all MID patients exhibit small vessel disease rather than thromboembolism
|
||||
- Growing evidence exists for involvement of cholinergic system in VaD
|
||||
- Cholinergic deficits well documented in VaD, independent of concomitant AD pathology
|
||||
- Cholinergic neuron loss in 70% of AD, 40% of VaD
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Apolipoprotein E (*APOE*)
|
||||
- Serum protein involved in lipid metabolism
|
||||
- Encoded at single gene locus on chromosome 19 by 3 alleles: ε2, ε3, ε4
|
||||
- Frequency of ε4 allele significantly higher among patients with AD & VaD compared to controls
|
||||
- Odds of developing AD or VaD are 4.4x & 3.7x higher (respectively) in presence of even single ε4 allele
|
||||
- Paraoxonase (*PON1*)
|
||||
- Component of high-density lipoproteins with antioxidative potential
|
||||
- 2 *PON1* polymorphisms (Gln192Arg associated with enzyme activity & T-107C associated with enzyme concentration) are independent risk factors for VaD, particularly in *APOE* (ε4)
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- 8 subtypes of VaD
|
||||
- MIDs: Due to large cerebral emboli, usually readily identifiable
|
||||
- Strategically placed infarctions causing dementia
|
||||
- Multiple subcortical lacunar lesions: Develop VaD 5-25x more frequently than age-matched controls
|
||||
- Binswanger disease: Small vessel disease → widespread incomplete infarction of WM
|
||||
- Mixtures of 2 or more VaD subtypes
|
||||
- Hemorrhagic lesions causing dementia
|
||||
- Subcortical dementias due to other causes [e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts & leukoencephalopathy (CADASIL)]
|
||||
- Hybrid forms of AD & VaD
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Multifocal infarctions with atrophy
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Arteriosclerosis & amyloid angiopathy major underlying pathologies in small vessel vascular disease
|
||||
- Vessels display atheromata, lipohyalinosis, subintimal thickening, fibrinoid necrosis
|
||||
- Infarcted tissue undergoes necrosis → gliotic wall surrounding CSF cavity
|
||||
- Myelin & axonal loss with astrocytosis
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Infarcts with transient focal neurologic deficits
|
||||
- Most deficits persist
|
||||
- Mood & behavioral changes
|
||||
- Deterioration of executive function & attention, changes in personality (rather than memory loss) predominate
|
||||
- Severe depression is more common in VaD than AD
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- Main risk factors
|
||||
- Advanced age, HTN, diabetes, smoking
|
||||
- Hypercholesterolemia, hypercoagulable states
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Generally earlier age than AD
|
||||
- Incidence ↑ with age
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M > F
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- 10% of dementias
|
||||
- 2nd most common dementia (after AD)
|
||||
- ~ 25% of elderly stroke patients meet VaD criteria
|
||||
- Cerebral small vessel disease accounted for 33% of dementia risk
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Poststroke dementia: Progressive, episodic, stepwise cognitive decline following stroke
|
||||
- VaD without recent stroke: Progressive or stepwise cognitive decline without concurrent history of symptomatic stroke but with imaging evidence of clinically unrecognized cerebrovascular disease
|
||||
- Neuropsychiatric & motor signs: VaD accompanied by neuropsychiatric signs, such as depression, abulia, apathy, & psychosis with delusions or hallucinations
|
||||
- Intervals of clinical stabilization ± limited recovery
|
||||
- 5-year survival with VaD ~ 50% of age-matched controls
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Prevent further vascular insult
|
||||
- Control precipitating factors (e.g., HTN, diabetes)
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Not single entity but large group of conditions with variable clinical & imaging findings
|
||||
- ## Reporting Tips
|
||||
|
||||
|
||||
- Report strategically placed infarcts, hemorrhagic components, DWI abnormalities, pattern of cortical volume loss if present
|
||||
|
||||
6999ad9a-6bd9-47dd-8707-b571f32301e3
|
||||
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"groupId": "415b02cf-df4f-4cef-9c2b-866ef0618ec0",
|
||||
"name": "Selected Images",
|
||||
"images": [
|
||||
{
|
||||
"imageId": "ccf3ab42-d18d-44f4-9b3f-cc9fd9510d11",
|
||||
"caption": "Graphic depicts the classic disproportionate frontal lobe atrophy of late-stage frontotemporal dementia (FTD). The sulci are widened & gyri are knife-like . Parietooccipital lobes are spared. Gyri around the central sulcus are normal.",
|
||||
"title": "",
|
||||
"enhancedTitle": "",
|
||||
"annotated": true,
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"flanked": false,
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"documentUrl": "/document/v2/49510d0e-acf7-45cb-9eb1-53f8193b0b6d",
|
||||
"imageTitle": "",
|
||||
"thumbnailUrl": "/image/thumbnail/ccf3ab42-d18d-44f4-9b3f-
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/49510d0e-acf7-45cb-9eb1-53f8193b0b6d/tables
|
||||
|
||||
[
|
||||
"
|
||||
# Imaging Features for Various Clinical Subtypes of Frontotemporal Dementia
|
||||
|
||||
| Clinical Subtypes | Imaging Features |
|
||||
| --- | --- |
|
||||
| bvFTD | MR: Atrophy of frontal & temporal lobes; asymmetric right frontal &/or temporal lobe atrophy may occur NM: Decreased perfusion & metabolism in frontal &/or te |
|
||||
+17
@@ -0,0 +1,17 @@
|
||||
# https://app.statdx.com/document/6cb71737-f574-4121-a8fb-02eeada9f9f7/media
|
||||
|
||||
[
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"images": [
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{
|
||||
"imageId": "e25e1c8a-0345-4b38-89ff-714d2a60ffcc",
|
||||
"caption": "Axial FLAIR MR demonstrates a neurocysticercosis cyst  with an eccentric nodule (scolex) . Additional lesions have surrounding edema . Edema and enhancement vary with the stage of neurocysticercosis and host response.",
|
||||
"title": "Neurocysticercosis",
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"imageT
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# https://app.statdx.com/document/9f9eda8c-7e3c-4292-9861-4b8abc2c6474/media
|
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|
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[
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{
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"imageId": "01274ce7-fce5-4f42-bd69-b5a99e6a4930",
|
||||
"caption": "Axial F-18 FDG PET shows findings associated with frontotemporal dementia (FTD), predominantly frontal  and temporal lobe hypometabolism. Functional changes may occur prior to CT or MR changes.",
|
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"thumbnailUrl": "/image/thumbnail/01274ce7-fce5-4f42-bd69-b5a99e6a4930?size=168&quality=85"
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},
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+19
@@ -0,0 +1,19 @@
|
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# https://app.statdx.com/document/9f9eda8c-7e3c-4292-9861-4b8abc2c6474/media
|
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[
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"name": "Selected Images",
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"images": [
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{
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"imageId": "01274ce7-fce5-4f42-bd69-b5a99e6a4930",
|
||||
"caption": "Axial F-18 FDG PET shows findings associated with frontotemporal dementia (FTD), predominantly frontal  and temporal lobe hypometabolism. Functional changes may occur prior to CT or MR changes.",
|
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"enhancedTitle": "",
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"annotated": true,
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},
|
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+13
@@ -0,0 +1,13 @@
|
||||
# https://app.statdx.com/document/content/24559f7a-ed5a-4ab6-90ba-769f0b5c1197
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Key imaging questions
|
||||
- Does lesion follow CSF on all modalities/sequences?
|
||||
- Is there any associated mass effect?
|
||||
- Does lesion enhance?
|
||||
|
||||
</l
|
||||
+13
@@ -0,0 +1,13 @@
|
||||
# https://app.statdx.com/document/content/24559f7a-ed5a-4ab6-90ba-769f0b5c1197
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Key imaging questions
|
||||
- Does lesion follow CSF on all modalities/sequences?
|
||||
- Is there any associated mass effect?
|
||||
- Does lesion enhance?
|
||||
|
||||
</l
|
||||
+13
@@ -0,0 +1,13 @@
|
||||
# https://app.statdx.com/document/content/24559f7a-ed5a-4ab6-90ba-769f0b5c1197
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Key imaging questions
|
||||
- Does lesion follow CSF on all modalities/sequences?
|
||||
- Is there any associated mass effect?
|
||||
- Does lesion enhance?
|
||||
|
||||
</l
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/2aad3ac4-44fd-43e5-8e50-a86987483af3
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Alzheimer disease (AD)
|
||||
- Progressive neurodegenerative brain disease related to build up of (Aβ) neuritic plaques and subsequent tau neurofibrillary tangles (NFTs)
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/2b99b31a-ec1a-4dce-bb63-2a101fe9f044
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Chronic, progressive brain disorder characterized by loss of dopaminergic neurons that leads to tremors at rest, rigidity, slowed movements, and shuffling gait
|
||||
- ##
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/3823c4d4-5e98-46da-a717-892fef54b382
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Impairments in cognition and behavior affecting functional status due to pathologic changes resulting from various vascular insults throughout brain
|
||||
- ## Imaging</
|
||||
+10
@@ -0,0 +1,10 @@
|
||||
# https://app.statdx.com/document/content/49510d0e-acf7-45cb-9eb1-53f8193b0b6d
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Clinical subtypes
|
||||
- Behavioral variant frontotemporal dementia **(bvFTD)**
|
||||
- Primary progressive aphasia syndromes **(PPA)**<ul class=\"section-points
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/5dca11fe-b5ee-404c-b22e-4008b7571844
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Group of heterogeneous neurodegenerative disorders characterized by prominent language and word-finding difficulties
|
||||
- This includes logopenic-variant primary progressive aphasia (lvPPA), semantic-variant primary progressive
|
||||
+10
@@ -0,0 +1,10 @@
|
||||
# https://app.statdx.com/document/content/6cb71737-f574-4121-a8fb-02eeada9f9f7
|
||||
|
||||
# ESSENTIAL INFORMATION
|
||||
|
||||
- ## Key Differential Diagnosis Issues
|
||||
|
||||
|
||||
- Cystic lesions with solid nodular components can be divided into 2 categories
|
||||
- Lesions that typically demonstrate cyst with nodule morphology
|
||||
- Ne
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/834ccc3e-2116-4295-8408-0ac9a06bd2ff
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus (NPH): Ventriculomegaly out of proportion to sulcal enlargement in setting of normal cerebrospinal fluid (CSF) pressure
|
||||
- ## Imaging</h
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/834ccc3e-2116-4295-8408-0ac9a06bd2ff
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Normal-pressure hydrocephalus (NPH): Ventriculomegaly out of proportion to sulcal enlargement in setting of normal cerebrospinal fluid (CSF) pressure
|
||||
- ## Imaging</h
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/9f9eda8c-7e3c-4292-9861-4b8abc2c6474
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Frontotemporal dementia (FTD): Progressive neurodegenerative disorder of frontal/anterior temporal lobes
|
||||
- ## Imaging
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/9f9eda8c-7e3c-4292-9861-4b8abc2c6474
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Frontotemporal dementia (FTD): Progressive neurodegenerative disorder of frontal/anterior temporal lobes
|
||||
- ## Imaging
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/a1bedda5-6478-40b2-98e7-6c5f5363b06f
|
||||
|
||||
# IMAGING ANATOMY
|
||||
|
||||
- ## Overview
|
||||
|
||||
|
||||
- Attention control network is a constellation of distributed brain networks processing attention to external stimuli and symbols
|
||||
- Many aliases: Task-positive network, frontoparietal network, executive control network, and central executiv
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/a1bedda5-6478-40b2-98e7-6c5f5363b06f
|
||||
|
||||
# IMAGING ANATOMY
|
||||
|
||||
- ## Overview
|
||||
|
||||
|
||||
- Attention control network is a constellation of distributed brain networks processing attention to external stimuli and symbols
|
||||
- Many aliases: Task-positive network, frontoparietal network, executive control network, and central executiv
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/a1bedda5-6478-40b2-98e7-6c5f5363b06f
|
||||
|
||||
# IMAGING ANATOMY
|
||||
|
||||
- ## Overview
|
||||
|
||||
|
||||
- Attention control network is a constellation of distributed brain networks processing attention to external stimuli and symbols
|
||||
- Many aliases: Task-positive network, frontoparietal network, executive control network, and central executiv
|
||||
+9
@@ -0,0 +1,9 @@
|
||||
# https://app.statdx.com/document/content/e1b27954-6591-4bb0-a659-b13790492620
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Creutzfeldt-Jakob disease (CJD): Rapidly progressing, fatal, potentially transmissible dementia caused by prion
|
||||
- ## Imaging
|
||||
+10
@@ -0,0 +1,10 @@
|
||||
# https://app.statdx.com/document/content/e8e46d1d-46d2-4e5a-880f-f025a84c5871
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Progressive neurodegenerative dementia
|
||||
- Parkinsonism, visual hallucinations prominent
|
||||
- Caused by abnormal accumulation of α-synuclein protein
|
||||
+10
@@ -0,0 +1,10 @@
|
||||
# https://app.statdx.com/document/content/e8e46d1d-46d2-4e5a-880f-f025a84c5871
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Progressive neurodegenerative dementia
|
||||
- Parkinsonism, visual hallucinations prominent
|
||||
- Caused by abnormal accumulation of α-synuclein protein
|
||||
+10
@@ -0,0 +1,10 @@
|
||||
# https://app.statdx.com/document/content/f59dab57-c511-4369-8fcc-592421a4b8d1
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Vascular dementia (VaD), multiinfarct dementia (MID), vascular cognitive impairment (VCI)
|
||||
- Stepwise progressive ↓ in cognitive function
|
||||
- Heterogeneous group of disorders with varying etiologies, p
|
||||
+8
@@ -0,0 +1,8 @@
|
||||
# https://app.statdx.com/document/content/f6a4382b-f0f7-4582-a703-7f695c65656f
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Progressive neurodegenerative disease characterized by parkinsonism, visual hallucinations, fluctuations in cognition (alertness/attention), and other cognitive impairments leading to functional decline
|
||||
+12
@@ -0,0 +1,12 @@
|
||||
# https://app.statdx.com/document/content/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58
|
||||
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Alzheimer disease (AD)
|
||||
- Slowly progressive neurodegenerative disease
|
||||
- ## Imaging
|
||||
|
||||
<ul class=\"sect
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/document/csf-like-parenchymal-lesions/24559f7a-ed5a-4ab6-90ba-769f0b5c1197
|
||||
|
||||
html
|
||||
+16
@@ -0,0 +1,16 @@
|
||||
# https://app.statdx.com/document/e1b27954-6591-4bb0-a659-b13790492620/media
|
||||
|
||||
[
|
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"images": [
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||||
{
|
||||
"imageId": "e4dd9275-5048-4513-8288-980aa8250267",
|
||||
"caption": "A 53-year-old man with rapidly progressing cognitive decline due to sporadic Creutzfeldt-Jakob disease (sCJD) is shown. Axial DWI MR demonstrates symmetric bilateral basal ganglia (BG) diffusion restriction  and asymmetric cortical restricted diffusion (cortical ribbon sign) in bilateral (right > > left) hemispheres .",
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||||
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+11
@@ -0,0 +1,11 @@
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||||
# https://app.statdx.com/document/e1b27954-6591-4bb0-a659-b13790492620/tables
|
||||
|
||||
[
|
||||
"
|
||||
# CDC Diagnostic Criteria for Creutzfeldt-Jakob Disease 2018
|
||||
|
||||
| Clinical Features | Lab Tests |
|
||||
| --- | --- |
|
||||
| Myoclonus | Typical EEG (PSWCs) |
|
||||
| Visual or cerebellar signs | 14-3-3 CSF protein positive |
|
||||
| Pyramidal/extrapyramidal signs |
|
||||
+13
@@ -0,0 +1,13 @@
|
||||
# https://app.statdx.com/document/e8e46d1d-46d2-4e5a-880f-f025a84c5871/media
|
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|
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[
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"images": [
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{
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"imageId": "d2ff700c-f618-401b-94df-595198c45827",
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||||
"caption": "Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex  & precuneus . Note moderate ↓ metabolic activity in right occipital lobe  & precuneus  & relative sparing of bilateral posterior cingulate gyri .",
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[
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"caption": "Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex  & precuneus . Note moderate ↓ metabolic activity in right occipital lobe  & precuneus  & relative sparing of bilateral posterior cingulate gyri .",
|
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# https://app.statdx.com/document/f59dab57-c511-4369-8fcc-592421a4b8d1/media
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"imageId": "add7af59-3e22-4ebd-bda3-585280f734e0",
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||||
"caption": "Axial graphic of vascular dementia (VaD) shows diffuse cerebral atrophy, focal volume loss due to multiple chronic infarcts , an acute left occipital lobe infarct , and small lacunar infarcts in the basal ganglia/thalami .",
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# https://app.statdx.com/document/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58/media
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[
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|
||||
"imageId": "c1584b3b-5358-41b3-92ea-8416c9f03019",
|
||||
"caption": "Clinical examination of a 72-year-old woman with AD shows typical findings for long history of memory deficit. FDG PET raw data and 3D SSP show preservation of the primary sensorimotor cortex . There is hypometabolism involving the bilateral parietotemporal association cortices  and mild hypometabolism within the right greater than left posterior cingulate regions  and, to a lesser extent, the precuneus regions . There is no hypometabolism in the primary visual cortices or fr
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
Vendored
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/main
|
||||
|
||||
html
|
||||
+5
@@ -0,0 +1,5 @@
|
||||
# https://app.statdx.com/timetracking/start/CSF-Like%20Parenchymal%20Lesion(s)/Brain/DDX
|
||||
|
||||
```
|
||||
Forbidden
|
||||
```
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
+3
@@ -0,0 +1,3 @@
|
||||
# https://app.statdx.com/tree/brain/6d8829f1-14d7-45af-8675-255189aa526a
|
||||
|
||||
html
|
||||
Reference in New Issue
Block a user