Gold Standard for Diagnosing Neurovasculitis
Brain biopsy showing histologic evidence of vasculitis is the only definitive gold standard for diagnosing neurovasculitis, particularly for small-vessel disease, though catheter angiography serves as the gold standard for radiologic diagnosis in large-to-medium vessel vasculitis. 1, 2
Diagnostic Approach Based on Vessel Size
The gold standard varies critically depending on whether large-to-medium vessels or small vessels are involved:
Large-to-Medium Vessel Vasculitis
- Catheter angiography (DSA) is the most sensitive imaging method for assessing cerebral vasculitis involving large-to-medium vessels 3
- DSA demonstrates characteristic findings including multifocal stenosis, vessel wall narrowing and dilatation, arterial beading, and alternating areas of constriction 3, 1
- However, DSA has only moderate sensitivity and specificity due to significant overlap with other cerebrovascular diseases such as atherosclerosis and reversible cerebral vasoconstriction syndrome 3, 2
- Angiography can be entirely normal despite active vasculitis, particularly when small vessels are involved 1
Small Vessel Vasculitis
- Brain biopsy is the gold standard for small-vessel vasculitis, as vessel abnormalities are too small to be demonstrated on MRA, CTA, or conventional angiography 3
- Cortical-leptomeningeal biopsy is the most specific diagnostic test for diffuse or multifocal CNS vasculitis 1
- Biopsy yield increases significantly when performed in areas demonstrably abnormal on MRI or cerebral angiography 1
- A negative biopsy does not exclude the diagnosis due to the focal nature of primary cerebral arteritis 1
Diagnostic Criteria Evolution
The diagnostic approach has evolved over time:
- Historical criteria (Calabrese and Mallek, 1988) required diagnosis via histopathology OR characteristic findings on DSA 3, 1
- Contemporary criteria proposed by some experts now require histology from biopsy or autopsy and do not accept diagnosis based solely on angiography 3
- This shift reflects recognition of DSA's limited specificity and the need for tissue confirmation 4, 2
Practical Diagnostic Algorithm
Step 1: Initial Imaging
- MRI brain with and without contrast is the preferred initial study, abnormal in >90% of cases 1
- MRI findings include multiple infarcts of variable ages (50% of patients), mass lesions (5%), meningeal enhancement (8%), and hemorrhage (9%) 1
- Diagnosis is unlikely with a normal MRI 2
Step 2: Vascular Imaging
- MRA head offers noninvasive evaluation but was abnormal in only 81% of patients with angiographic vasculitis 3, 1
- MRA, CTA, and DSA are typically negative in small-vessel vasculitis 3
- Proceed to catheter angiography if large-to-medium vessel disease is suspected and noninvasive imaging is inconclusive 3
Step 3: Tissue Diagnosis
- Brain biopsy is strongly recommended to assist diagnosis, particularly when imaging is nondiagnostic or small-vessel disease is suspected 1, 4
- Target biopsy to areas abnormal on MRI or angiography to maximize yield 1
- Biopsy remains the gold standard despite advances in imaging 4
Critical Pitfalls to Avoid
- Do not rely solely on angiography for diagnosis, as it has low specificity and can miss small-vessel disease entirely 3, 5
- Do not exclude vasculitis based on normal inflammatory markers, as ESR is usually normal or minimally elevated in primary CNS vasculitis 1
- Do not dismiss the diagnosis with a negative biopsy, as the focal nature of the disease can result in sampling error 1
- Do not confuse with vasculitis mimics including reversible cerebral vasoconstriction syndrome, atherosclerosis, and infectious/metabolic conditions 6, 2
Supporting Laboratory Studies
- CSF analysis is abnormal in 80-90% of patients, showing elevated protein, lymphocytic pleocytosis (rarely >250 cells/mm³), or increased opening pressure 1, 2
- ANCA testing should be performed using both indirect immunofluorescence and ELISA 1
- Serological markers of inflammation are characteristically normal in primary CNS vasculitis 1, 2