What are the possible types of vasculitis that can cause non-aneurysmal subarachnoid hemorrhage (SAH) and how can they be evaluated?

Vasculitis Causing Non-Aneurysmal Subarachnoid Hemorrhage

Primary CNS vasculitis is the most important vasculitis to consider for non-aneurysmal SAH, though it remains rare (2.4 cases per 1 million person-years), and several systemic vasculitides including varicella-zoster vasculitis, systemic lupus erythematosus, eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis can also present with SAH. 1, 2, 3, 4, 5

Types of Vasculitis That Can Cause SAH

Primary CNS Vasculitis

• Most relevant vasculitis for isolated CNS hemorrhage, affecting small to medium-sized intracranial vessels without systemic involvement 1, 6
• Intracranial hemorrhage occurs in approximately 9% of primary CNS vasculitis cases 1, 6
• Typically presents with headache, encephalopathy, and behavioral changes; focal neurological deficits occur in 20-30% of patients 1, 6

Systemic Vasculitides With CNS Involvement

Small-to-Medium Vessel Vasculitides:

• Varicella-zoster vasculitis: Can present with SAH affecting small and medium-sized vessels, often with concomitant herpes zoster rash 2
• Eosinophilic granulomatosis with polyangiitis (EGPA): Necrotizing vasculitis of small vessels that can cause SAH, even during remission induction therapy 5
• Microscopic polyangiitis: ANCA-associated vasculitis that rarely causes SAH, typically in patients with known renal involvement 4

Variable Vessel Vasculitides:

• Systemic lupus erythematosus: CNS vasculitis can manifest as cerebral and spinal SAH during disease flare-ups 3
• Behçet disease: Affects variable-sized vessels and can involve CNS vasculature 7

Large Vessel Vasculitides (Less Common for SAH):

• Giant cell arteritis and Takayasu arteritis primarily affect large vessels but can extend to medium-sized vessels 1, 7

Diagnostic Evaluation Algorithm

Initial Laboratory Assessment

Mandatory baseline tests:

• ANCA testing using both indirect immunofluorescence and ELISA (Level 1A evidence) 6
• Erythrocyte sedimentation rate (ESR) - typically normal or minimally elevated in primary CNS vasculitis 6
• Complete blood count with differential (look for eosinophilia in EGPA) 5
• Antinuclear antibody (ANA) and anti-dsDNA for SLE 3
• Complement levels (C3, C4) 6

Cerebrospinal fluid analysis:

• Opening pressure, protein, glucose, cell count 6
• Lymphocytic pleocytosis (rarely >250 cells/mm³) may be present 6
• PCR for varicella-zoster virus if herpes zoster is suspected 2

Neuroimaging Protocol

First-line imaging - MRI brain with and without contrast:

• MRI head is the preferred initial modality, abnormal in >90% of CNS vasculitis cases 6
• Look for multiple infarcts of variable ages (present in up to 50% of cases) 1, 6
• Identify hemorrhage (9%), meningeal enhancement (8%), or mass lesions (5%) 1, 6
• Progressive confluent white matter lesions, cortical/subcortical T2 lesions, and multiple microhemorrhages 1
• A normal MRI has nearly 100% sensitivity for excluding CNS vasculitis 1

Vascular imaging:

• MRA head as initial noninvasive vascular assessment - abnormal in 81% of angiographically confirmed vasculitis 1
• Look for multifocal stenosis and dilatation, though specificity is limited by overlap with atherosclerosis and reversible cerebral vasoconstriction syndrome 1

Advanced vascular imaging:

• Cerebral angiography (DSA) remains the gold standard for vascular detail with submillimeter resolution 1, 6
• Characteristic findings: arterial beading, alternating constriction and dilatation, segmental narrowing 6
• Critical limitation: Low specificity due to overlap with other cerebrovascular diseases and limited sensitivity for small vessel involvement 1, 6

CTA head can be used as alternative to MRA but has similar limitations in resolution for distal small arteries 1

Tissue Diagnosis

Brain biopsy (cortical-leptomeningeal):

• Most specific diagnostic test for primary CNS vasculitis (Level 3C evidence) 6
• Target abnormal areas identified on MRI or angiography to increase yield 6
• Critical caveat: Negative biopsy does not exclude diagnosis due to focal nature of disease 6
• Required by some diagnostic criteria (Calabrese and Mallek criteria accept either histopathology OR characteristic DSA findings) 1, 6

Diagnostic Pitfalls to Avoid

Do not rely solely on angiography:

• Angiographic findings overlap significantly with atherosclerosis, reversible cerebral vasoconstriction syndrome, and other non-inflammatory conditions 1, 6
• Small vessel involvement may be below angiographic resolution 1, 6

Do not expect elevated inflammatory markers:

• ESR and acute-phase reactants are characteristically normal in primary CNS vasculitis 6
• Not all patients have clinical or laboratory signs of systemic inflammation 6

Do not dismiss vasculitis with negative initial imaging:

• Consider repeat imaging if clinical suspicion remains high 6
• Proceed to biopsy when imaging is inconclusive but clinical suspicion persists 6

Specific Clinical Clues

Look for these associated features:

• Recent herpes zoster rash (varicella-zoster vasculitis) 2
• Known SLE with disease flare (lupus vasculitis) 3
• Bronchial asthma with eosinophilia (EGPA) 5
• Renal involvement with positive MPO-ANCA (microscopic polyangiitis) 4
• Recurrent oral/genital ulcers with uveitis (Behçet disease) 7

Management Considerations

Immediate steps:

• Manage SAH complications (hydrocephalus, vasospasm) per standard neurosurgical protocols 3
• Initiate corticosteroids once vasculitis diagnosis is established 6, 3
• Add cyclophosphamide or rituximab for primary CNS vasculitis or severe systemic vasculitis 6, 3, 5

Collaboration requirement:

• Manage in collaboration with or at centers of expertise for vasculitis (Level 3D evidence) 6

1, 6, 2, 3, 7, 4, 5