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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
- 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

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References

Selected References

Images

Selected Images

Coronal graphic depicts cerebrospinal fluid (CSF) movement patterns: Type I: Normal clearance of ventricles at 2-6 hours with tracer along the convexities at 24 hours; type II: Normal clearance of ventricles with delayed tracer along the convexities seen in aging; type IIIA: Early transient ventricular tracer with delayed tracer along the ventricles, indeterminate for normal-pressure hydrocephalus (NPH); type IIIB: Early transient ventricular tracer without convexity circulation, suggesting NPH; and type IV: Persistent ventricular tracer at 24 hours without convexity circulation, suggesting NPH.

Posterior radionuclide cisternography shows partial epidural injection of In-111 DTPA. Note the classic Christmas tree appearance of radiotracer in the epidural space surrounding the thecal sac and spinal nerve roots. This may result in indeterminate imaging due to lack of tracer in the CSF space.

Posterior radionuclide cisternography in a normal patient immediately after lumbar puncture and injection of radiotracer confirms intrathecal placement . Basilar cisterns are evident.

Anterior radionuclide cisternography at 4 hours shows the normal trident appearance of radiotracer in the anterior interhemispheric fissure and sylvian fissures .

Anterior radionuclide cisternography at 24 hours demonstrates photopenia in the region of the lateral ventricles , a normal finding. This pattern of tracer distribution with activity only along the convexities is consistent with the type II CSF movement pattern (normal).

Anterior radionuclide cisternography in a patient with NPH at 24 hours demonstrates activity in the lateral ventricles, showing a heart-shaped appearance . This pattern of CSF movement is either IIIB or IV, both of which are suspicious for NPH.

Axial fused radionuclide cisternography SPECT/CT in the same patient with NPH at 24 hours confirms activity in the lateral ventricles: Frontal horns and occipital horns , consistent with NPH.

Additional Images

Normal radionuclide cisternogram immediately following lumbar puncture introduction of tracer shows normal cephalad flow. This was appropriately injected into the intrathecal space.

Four-hour multiplanar images in the same patient show normal flow to basal, sylvian, and suprasellar cisterns with faint ventricular activity .

In the same patient, 24-hour multiplanar images show flow of tracer over convexities and into interhemispheric fissure . There is no definite ventricular activity.

24-hour transaxial SPECT in the same patient confirms no ventricular activity. Mild asymmetry to flow over convexities is present and can be normal.

48-hour multiplanar images in the same patient show homogeneous distribution of tracer over brain.

Multiplanar images 4 hours after lumbar puncture injection of In-111 DTPA in a patient with NPH show normal tracer accumulation in basal, suprasellar, and sylvian fissures. There is normal ventricular penetration.

24-hour multiplanar images in the same patient show tracer in lateral ventricle , confirmed by vertex and SPECT images (not shown).

Planar vertex view (top of head with shielding around shoulders) in the same patient shows clear activity in the lateral ventricles , confirming diagnosis of NPH.

Axial SPECT in the same patient is shown. NPH is confirmed by visualization of significant ventricular activity at 24 hours .

Axial SPECT in the same patient is shown. NPH was confirmed by visualization of significant ventricular activity at 24 hours .

24-hour sagittal SPECT in the same patient clearly demonstrates significant tracer in the lateral ventricle , confirming NPH.

Four-hour multiplanar images in a patient with NPH show normal uptake in the basal, sylvian, and suprasellar cisterns as well as in the lateral ventricles .

Lateral ventricle activity is difficult to identify on multiplanar anterior, posterior, and lateral images in the same patient.

Vertex (top of head) view in the same patient suggests lateral ventricle activity, obscured by overlying tracer.

24-hour sagittal SPECT in the same patient demonstrates marked ventricle activity , confirming the presence of NPH.

24-hour axial SPECT in the same patient demonstrates marked ventricle activity , confirming the presence of NPH.

Axial 24-hour axial SPECT in the same patient demonstrates marked ventricle activity , confirming the presence of NPH.

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KEY FACTS

Terminology

Imaging

Clinical Issues

Diagnostic Checklist

TERMINOLOGY

Definitions

IMAGING

Nuclear Medicine Findings

Other Modality Findings

Imaging Recommendations

Best imaging tool

Protocol advice

DIFFERENTIAL DIAGNOSIS

Parkinson Disease

Normal Aging

Noncommunicating Hydrocephalus