Add comprehensive articles on Vascular Dementia and Wallerian Degeneration

- Created a detailed article for Vascular Dementia covering key facts, terminology, imaging findings, differential diagnoses, pathology, clinical issues, and diagnostic checklist. - Developed an extensive article on Wallerian Degeneration including key facts, terminology, imaging features, differential diagnoses, pathology, clinical issues, and diagnostic checklist.
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+---
+title: "Wallerian Degeneration"
+docid: "e4bb682d-6534-4176-9d39-34c1a42f3771"
+breadcrumbs:
+  - "Brain"
+  - "Diagnosis"
+  - "Pathology-Based Diagnoses"
+  - "Acquired Toxic/Metabolic/Degenerative Disorders"
+  - "Dementias and Degenerative Disorders"
+  - "Wallerian Degeneration"
+---
+# KEY FACTS
+
+- ## Terminology
+  
+  
+    - Wallerian degeneration (WaD)
+    - Progressive secondary anterograde degeneration of axons and their myelin sheaths caused by interruption of axonal integrity or damage to neuron
+- ## Imaging
+  
+  
+    - Primary lesion is cortical or subcortical with WaD in descending white matter (WM) tracts ipsilateral to neuronal injury
+          - WaD can be seen in fibers crossing corpus callosum, fibers of optic radiations, fornices, and cerebellar peduncles
+    - CT is not sensitive for WaD in acute-subacute stages
+          - Detects atrophy of corticospinal tracts (CSTs) in chronic stage
+    - Time-dependent changes in CSTs on MR
+          - Strong correlation between WaD detected on T2WI and DWI and long-term morbidity
+          - DWI findings precede development of WaD assessed by conventional MR
+    - DTI may distinguish between primary lesion and associated WaD
+          - Reduced fractional anisotropy (FA) with ↑ mean diffusivity (MD) in infarct
+          - Reduced FA with preserved MD in CST
+- ## Top Differential Diagnoses
+  
+  
+    - Normal CST can appear T2/FLAIR hyperintense on high-field-strength MR
+    - Neurodegenerative diseases
+    - Brainstem glioma
+    - Demyelinating and inflammatory diseases
+    - Hypertrophic olivary degeneration
+    - Metabolic diseases
+    - Intoxication (heroin inhalation)
+
+# TERMINOLOGY
+
+- ## Abbreviations
+  
+  
+    - Wallerian degeneration (WaD)
+- ## Definitions
+  
+  
+    - Progressive secondary anterograde degeneration of axons and their myelin sheaths caused by interruption of axonal integrity or damage to neuron
+
+# IMAGING
+
+- ## General Features
+  
+  
+    - ### Best diagnostic clue
+      
+      
+          - Contiguous T2 hyperintensity along topographic distribution of corticospinal tract (CST) in internal capsule (IC) and brainstem in patients with various cerebral pathologies
+    - ### Location
+      
+      
+          - Primary lesion: Cortical or subcortical
+          - WaD: Descending white matter (WM) tracts ipsilateral to neuronal injury
+                  - CST, corticobulbar, corticopontocerebellar tracts
+                  - Corpus callosum, posterior column of spinal cord, limbic circuit, and optic pathway
+          - Center of cerebral peduncle may reveal WaD of CST
+          - Lateral side of cerebral peduncle may show WaD of corticopontine tract
+          - WaD can be seen in corpus callosum, optic radiations, fornices, and cerebellar peduncles
+                  - WaD in distal optic radiations after infarction at their root
+                  - Pontine infarct can cause WaD in middle cerebellar peduncle
+          - Corpus callosum has been shown to be susceptible to atrophy in Alzheimer disease mainly as correlate of WaD of commissural nerve fibers of neocortex
+                  - Callosal atrophy is present predominantly in latest stage of Alzheimer disease
+          - Seizure-induced damage may cause secondary WM degeneration along tapetum and through splenium of corpus callosum
+    - ### Size
+      
+      
+          - Acute stage: Normal size
+          - Chronic stage: ↓ (atrophy)
+    - ### Morphology
+      
+      
+          - Signal changes conforming to WM tract shape
+                  - Oval regions in posterior limb of IC and cerebral peduncle; thin curvilinear regions in pons
+- ## CT Findings
+  
+  
+    - ### NECT
+      
+      
+          - Not sensitive for WaD in acute-subacute stages
+          - Detects atrophy of CSTs in chronic stage
+                  - ↓ size of corresponding aspect of brainstem
+- ## MR Findings
+  
+  
+    - ### T1WI
+      
+      
+          - Time-dependent changes in descending WM tracts
+                  - Stage 1: No changes
+                  - Stage 2: T1 hyperintense
+                  - Stage 3: T1 hypointense
+                  - Stage 4: Ipsilateral brainstem atrophy ± hypointensity
+    - ### T2WI
+      
+      
+          - Time-dependent changes in descending WM tracts
+                  - Stage 1: No changes in adult CNS
+                  - Stage 2: T2 hypointense
+                  - Stage 3: T2 hyperintense
+                  - Stage 4: Atrophy, best seen in brainstem
+                            - Sometimes, T2 hyperintense signal may persist
+          - Neonates and infants: Identification of WaD by T2WI complicated by high water content and lack of myelination in immature WM
+          - Adults: Strong correlation between T2WI-detected WaD and long-term morbidity
+    - ### FLAIR
+      
+      
+          - Same as T2WI
+    - ### DWI
+      
+      
+          - Can demonstrate acute injury to descending WM tracts < 10 days after primary injury such as infarction
+          - Neonates and infants: Indicates acute WM injury
+                  - DWI findings precede development of WaD assessed by conventional MR
+                  - May portend poor clinical outcome
+          - Adults: Correlation of DW changes in descending motor pathways at presentation with long-term neurologic disability
+          - ↑ signal intensity in descending WM tract ipsilateral to territorial infarct at level of IC or cerebral peduncle or both
+          - ↓ ADC values in involved WM tract compared with normal WM
+          - Extent and severity of territorial ischemia is related to development of descending WM tract injury detectable by DWI
+          - Hyperintense DW signal intensity and ↓ ADC values within territorial infarct and ipsilateral CST
+                  - DW and ADC time courses in region of territorial injury and CST injury may be different
+                            - Relatively delayed development of diffusion abnormality in descending WM tracts
+          - Subacute period after territorial infarction in adults
+                  - Within infarct, WM ADC reduction > that in GM
+          - DW signal intensity abnormality in descending WM tracts may persist, even as DW hyperintensity in ipsilateral cerebral hemisphere fades
+          - WaD of inferior cerebellar peduncle (after lateral medullary infarction) depicted by thin slice DWI has been reported
+    - ### T1WI C+
+      
+      
+          - No contrast enhancement of degenerated tracts
+    - ### MRS
+      
+      
+          - ¹H-MRS enables in vivo assessment of axonal injury based on signal intensity of N-acetyl aspartate (NAA)
+          - ↓ NAA concentration in normal-appearing WM in pons and cerebellar peduncles in early stages of relapsing-remitting multiple sclerosis (MS)
+                  - Evidence of early WaD outside MS plaques
+                  - Correlates best with disability, MS duration, and relapse rate
+    - DTI
+          - Myelin breakdown leads to ↓ diffusion anisotropy
+          - DTI may distinguish between primary lesion and associated WaD
+                  - Difference in diffusion properties between primary lesion and degenerated tract
+                            - Fractional anisotropy (FA) = measure of directionality of water diffusion
+                            - Mean diffusivity (MD) = measure of amount of water diffusion
+          - Reduced FA with ↑ MD in infarct
+          - Reduced FA with preserved MD in CST
+          - In patients with motor pathway infarction, diffusion indices in degenerated CST stabilize within 3 months and early changes in CST FA may predict long-term clinical outcomes
+- ## Imaging Recommendations
+  
+  
+    - ### Best imaging tool
+      
+      
+          - MR
+    - ### Protocol advice
+      
+      
+          - DWI allows early detection (stage 1)
+          - T2WI detects changes after 4 weeks
+
+# DIFFERENTIAL DIAGNOSIS
+
+- ## Normal CST
+  
+  
+    - CST can appear T2/FLAIR hyperintense on 3T MR (normal fully myelinated brain)
+- ## Neurodegenerative Diseases
+  
+  
+    - [Amyotrophic lateral sclerosis (upper &/or lower motor neuron involvement)](/document/amyotrophic-lateral-sclerosis-als/23de52b7-d9bd-441c-a18c-95c8afccb470)
+          - Bilateral hyperintensities along CST extending from corona radiata to brainstem on T2WI/PD/FLAIR
+    - Primary lateral sclerosis and infantile-onset hereditary spastic paraplegia
+          - Upper motor neuron degeneration only
+- [Brainstem Glioma](/document/brainstem-tumors/657b37eb-c286-42bf-b8e6-55b5c20e5e50)
+    - T2 hyperintense mass ± enhancement
+- ## Demyelinating and Inflammatory Diseases
+  
+  
+    - [MS: Periventricular T2 hyperintensity](/document/multiple-sclerosis/7892b2a2-f52a-4d7f-9858-a326f2b7ab04)
+    - [ADEM: Asymmetric T2 hyperintensity in WM and gray matter (GM) after viral prodrome](/document/adem/a3fafeb7-5861-4364-beb8-c0e30220564e)
+    - [Behçet disease: Enlarged T2 hyperintense brainstem ± thalamus](/document/behet-disease/4e447bb6-0f14-40e1-929a-4c1465feec0a)
+- [Hypertrophic Olivary Degeneration](/document/hypertrophic-olivary-degeneration/78257543-6d52-4879-84b1-445f3611d996)
+    - Secondary degeneration of inferior olivary nucleus (ION), usually caused by primary lesions in dentato-rubro-olivary pathway
+    - Time-dependent T2 changes of ION
+          - Hyperintense signal without hypertrophy of ION: Within first 6 months of ictus
+          - Both ↑ signal and hypertrophy of ION: Between 6 months and 3-4 years after ictus
+          - Only ↑ signal in ION: Begins when hypertrophy resolves and can persist indefinitely
+- ## Metabolic Diseases
+  
+  
+    - [X-linked adrenoleukodystrophy: Enhancing peritrigonal demyelination](/document/x-linked-adrenoleukodystrophy/0543abe3-8086-488b-85d2-483ce458f345)
+    - [Wilson disease: WM and GM lesions involving basal ganglia, dentate nucleus, brainstem](/document/wilson-disease/3d4d4876-4ce4-4af0-9e75-1a419bdd813c)
+    - [Hypoglycemic coma: Reversible CST changes](/document/adult-hypoglycemia/38e4de6e-07c4-485e-bac1-f4dd4815b3b8)
+- [Heroin Inhalation](/document/drug-abuse/e4502a67-4b96-4d98-a167-6e90f6b65faf)
+    - Symmetric T2 hyperintensity in posterior WM, including posterior limb of IC
+
+# PATHOLOGY
+
+- ## General Features
+  
+  
+    - ### Etiology
+      
+      
+          - Infarction, hemorrhage, neoplasm, encephalitis
+          - Demyelinating disease, trauma, arteriovenous malformations
+          - Reported also in patients with movement disorder
+    - ### Genetics
+      
+      
+          - Process of axonal degeneration is genetically regulated
+    - ### Associated abnormalities
+      
+      
+          - Primary lesion/disorder that caused secondary WM tract degeneration
+- ## Staging, Grading, & Classification
+  
+  
+    - Stage 1 (0-4 weeks)
+          - Degradation of axon; mild changes in myelin
+    - Stage 2 (4-14 weeks)
+          - Myelin protein breakdown; lipids remain intact
+    - Stage 3 (> 14 weeks)
+          - Myelin lipid breakdown, gliosis, changes in water content and structure
+    - Stage 4 (after months to years)
+          - Atrophy of ipsilateral brainstem
+- ## Gross Pathologic & Surgical Features
+  
+  
+    - Brainstem asymmetry due to atrophy in chronic stage
+- ## Microscopic Features
+  
+  
+    - Stage 1: Beginning of myelin and axon breakdown
+          - Myelin sheaths break up into ellipsoids and spheres but retain myelin-staining properties
+    - Stage 2: ↓ protein:lipid ratio
+    - Stage 3: ↑ edema and further lipid breakdown
+    - Stage 4: Atrophy due to volume loss; removal of axonal debris by microglia continues for 2 years (vs. completed in 3 weeks in peripheral nervous system)
+    - Expression of transcription factors *ATF3* and *JUN* by nonneuronal cells during WaD
+          - *ATF3*/*JUN* heterodimers may play role in regulating changes in gene expression necessary for preparing distal segments of injured peripheral nerves for axonal regeneration
+          - Absence of *ATF3* and *JUN* from CNS glia during WaD may limit their ability to support regeneration
+    - In CNS, astrocyte-dominated matrix fails to accommodate new axonal growth
+
+# CLINICAL ISSUES
+
+- ## Presentation
+  
+  
+    - ### Most common signs/symptoms
+      
+      
+          - WaD in CST is associated with persistent hemiparesis
+- ## Demographics
+  
+  
+    - ### Age
+      
+      
+          - Reported in all ages
+    - ### Sex
+      
+      
+          - No preference
+    - ### Epidemiology
+      
+      
+          - WaD commonly follows CNS lesions
+                  - WaD in pyramidal tract reported in 78.6% of cases of capsular infarct
+- ## Natural History & Prognosis
+  
+  
+    - WaD may begin within 1 week of fiber tract damage
+    - Demyelination can continue during next 6 months
+    - Signifies irreversible loss of neuronal function
+          - Little evidence of axonal regeneration in CNS
+    - Presence or absence of WaD may influence clinical outcome after stroke
+    - Extent of WaD is related to severity of motor deficit
+          - Abnormal DWI signal in CST can be acute predictor of motor outcome in childhood infarction
+          - Contralesional CST abnormal DWI signal predicts severe hemiparesis
+- ## Treatment
+  
+  
+    - No specific therapy
+
+# DIAGNOSTIC CHECKLIST
+
+- ## Image Interpretation Pearls
+  
+  
+    - In ischemic stroke: Important to differentiate DWI abnormality related to WaD from additional infarction
+    - Time-specific signal intensity changes of WaD → able to ascertain age of primary lesion
+
+ b1941e68-6700-4295-b371-61c4b12e78ad