What is the diagnostic approach for cerebral vasculitis?

Diagnostic Approach for Cerebral Vasculitis

The diagnosis of cerebral vasculitis requires a comprehensive, stepwise approach including clinical assessment, laboratory testing, neuroimaging, and often brain biopsy, as it is a challenging condition to diagnose with confidence due to nonspecific presentations and findings.

Clinical Presentation

• Cerebral vasculitis should be considered in patients with ischemic or hemorrhagic stroke, recurrent stroke, stroke with encephalopathic changes, or stroke accompanied by fever, multifocal neurological events, unexplained skin lesions, glomerulopathy, or elevated sedimentation rate 1
• Primary CNS vasculitis typically presents with headache, followed by encephalopathy and behavioral changes, with focal neurological deficits occurring in 20-30% of patients 1
• Seizures and intracranial hemorrhage may also occur as presenting symptoms 1
• Small-vessel strokes may develop over weeks to many months 1

Initial Laboratory Evaluation

• Anti-neutrophilic cytoplasmic antibody (ANCA) testing should be performed using both indirect immunofluorescence and ELISA in the appropriate clinical context (Level of evidence 1A, Grade of recommendation A) 1
• Erythrocyte sedimentation rate is usually normal or only minimally elevated in primary CNS vasculitis, and other acute-phase reactants are characteristically normal 1
• Cerebrospinal fluid analysis may reveal increased opening pressure, elevated protein values, or lymphocytic pleocytosis (rarely exceeding 250 cells/mm³) 1
• A structured clinical assessment, urine analysis, and other basic laboratory tests should be performed at each clinical visit (Level of evidence 3, Grade of recommendation C) 1

Neuroimaging

• MRI head is the preferred initial imaging modality for suspected CNS vasculitis, with abnormal findings in >90% of cases 1
• Multiple infarcts of variable ages are identified on MRI in up to 50% of patients with CNS vasculitis 1
• Other MRI findings may include mass lesions (5%), meningeal enhancement (8%), and hemorrhage (9%) 1
• MRA head offers noninvasive examination of intracranial vessels but has limited specificity and sensitivity compared to conventional angiography 1
• Time-of-flight MRA was abnormal in 81% of patients with angiographic findings of vasculitis in comparative studies 1

Advanced Vascular Imaging

• Cerebral arteriography (DSA) has long been the standard in imaging diagnosis of CNS vasculitis due to its submillimeter resolution 1
• Characteristic angiographic findings include arterial beading and alternating areas of constriction and dilatation, though these findings are nonspecific 1
• DSA may show segmental arterial narrowing, vascular occlusions, peripheral aneurysms, vascular shifts, or avascular areas, but may also be entirely unremarkable 1
• CTA head can characterize intracranial vessel luminal characteristics but has limited resolution for distal small arteries 1

Diagnostic Criteria

• Diagnostic criteria for CNS vasculitis proposed by Calabrese and Mallek in 1988 required diagnosis via histopathology or characteristic findings on DSA 1
• Some experts now propose diagnostic criteria that require histology from biopsy or autopsy rather than relying solely on angiography 1
• With strong clinical suspicion, brain imaging is important for supporting the diagnostic process and directing biopsy 1

Tissue Biopsy

• A positive biopsy is strongly supportive of vasculitis and is recommended to assist diagnosis and further evaluation (Level of evidence 3, Grade of recommendation C) 1
• For diffuse or multifocal CNS vasculitis, cortical-leptomeningeal biopsy is the most specific diagnostic test 1
• Due to the focal nature of primary cerebral arteritis, a negative biopsy result does not preclude the diagnosis 1
• The yield of biopsy increases if performed in an area that is demonstrably abnormal on imaging studies, including MRI and cerebral angiography 1

Management Considerations

• Patients with primary small and medium vessel vasculitis should be managed in collaboration with, or at centers of expertise (Level of evidence 3, Grade of recommendation D) 1
• Treatment for primary CNS vasculitis typically involves corticosteroids and cytotoxic agents, particularly cyclophosphamide 1
• It is important to distinguish between transient/nonprogressive and progressive arteriopathies, as some children with arteritis stabilize or improve without specific treatment 1

Pitfalls and Challenges

• Cerebral angiography has low specificity for vasculitis given significant overlap of findings with other cerebrovascular diseases such as atherosclerosis or reversible cerebral vasoconstriction syndrome 1
• Vascular imaging has limited sensitivity as the degree of vascular involvement can be below angiography resolution 1
• Distinguishing primary CNS vasculitis from its mimics is crucial to avoid unnecessary immunosuppressive therapy 2
• Not all individuals with cerebral vasculitis have clinical or laboratory signs of inflammation 1

Diagnostic Algorithm

1. Evaluate for clinical features suggestive of vasculitis (headache, encephalopathy, focal deficits, seizures)
2. Perform laboratory testing (ANCA, ESR, CSF analysis)
3. Obtain MRI brain with and without contrast
4. Proceed to MRA/CTA for vascular evaluation
5. Consider conventional cerebral angiography if noninvasive imaging is inconclusive
6. Perform brain biopsy (preferably targeting abnormal areas on imaging) if diagnosis remains uncertain
7. Integrate all findings to establish diagnosis and guide treatment decisions