Inflammatory and thrombotic processes of CNS vessels — vasculitides and cerebral venous sinus thrombosis (CVST) — produce distinctive pathology that often requires biopsy or specialized vascular imaging to recognize. CNS vasculitis is rare but treatable; missing it can be devastating. CVST is a major treatable cause of stroke in younger patients, with characteristic clinical and imaging features. This page covers the pathology of primary and secondary CNS vasculitides and the spectrum of CVST.

Classification of CNS Vasculitis

Primary CNS Vasculitis

• Primary angiitis of the CNS (PACNS) / Primary CNS vasculitis: idiopathic, restricted to CNS vessels.
• Granulomatous angiitis of the CNS (GACNS): subset with granulomatous features; classical and most severe.

Secondary CNS Vasculitis

• Systemic vasculitides involving CNS: GPA (granulomatosis with polyangiitis), MPA (microscopic polyangiitis), eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss), Behçet, polyarteritis nodosa.
• Connective tissue diseases: SLE, Sjögren, rheumatoid arthritis.
• Infectious vasculitis: bacterial (TB, syphilis), viral (VZV, HIV), fungal (mucormycosis, aspergillosis).
• Drug-induced: cocaine, amphetamines, ephedrine.
• Neoplastic: lymphomatoid granulomatosis, intravascular lymphoma.
• Amyloid-β-related angiitis (ABRA): granulomatous reaction to CAA.
• Radiation-induced vasculopathy: late.

Primary Angiitis of the CNS (PACNS)

Clinical Features

• Subacute onset of multifocal neurologic deficits.
• Headache (often the most consistent feature).
• Cognitive decline or encephalopathy.
• Stroke (often multiple, small).
• Seizures.
• Cranial neuropathies.
• Often few systemic features.

Imaging

• Multiple small infarcts in different territories.
• White matter T2 hyperintensities.
• Sometimes hemorrhages.
• Conventional angiography: “beading” of vessels (alternating stenoses and dilations); may be normal in small vessel forms.
• High-resolution vessel wall MRI: concentric vessel wall enhancement (helpful but not specific).

Diagnosis

The Calabrese criteria require:

• Clinical history compatible.
• Angiographic OR histologic evidence.
• Exclusion of alternative causes.

Brain biopsy is the gold standard. Sensitivity is around 50-75% (sampling error common; involvement is patchy). The “negative biopsy” does not exclude PACNS.

Pathology

• Vessel wall inflammation: small and medium arteries; lymphocytic, granulomatous, or necrotizing.
• Fibrinoid necrosis: in severe cases.
• Granulomas: GACNS subtype.
• Vessel wall destruction: smooth muscle loss, intimal thickening.
• Thrombosis: secondary to wall damage.
• Perivascular inflammation: lymphocytic predominance.
• Distribution: leptomeningeal and cortical vessels; small intracerebral arteries.

Treatment

• Corticosteroids (high-dose).
• Cyclophosphamide for induction.
• Azathioprine, methotrexate, or mycophenolate for maintenance.
• Rituximab in refractory cases.

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

The most important mimic of PACNS. Features:

• Thunderclap headache (often recurrent).
• Reversible segmental vasoconstriction of cerebral arteries (resolves within 12 weeks).
• Sometimes complicated by SAH (convexity), ICH, or infarction.
• Triggers: postpartum, sympathomimetics, SSRIs, cannabis, ergot derivatives, exertion.
• Predominantly young women.

Imaging

Conventional angiography or MRA: smooth segmental narrowing of large arteries. The vasoconstriction RESOLVES on follow-up (key distinction from PACNS).

Treatment

Calcium channel blockers (nimodipine), removal of triggers, supportive care.

Distinguishing RCVS from PACNS

Systemic Vasculitides Involving CNS

Granulomatosis with Polyangiitis (GPA, Wegener)

• ANCA-positive (PR3-ANCA).
• Necrotizing granulomatous vasculitis.
• CNS: cranial neuropathies, meningitis, ICH, infarct.
• Systemic: upper airway, lung, kidney.

Microscopic Polyangiitis (MPA)

• ANCA-positive (MPO-ANCA).
• Small vessel vasculitis.
• CNS: stroke, encephalopathy, peripheral neuropathy.

Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss)

• Eosinophilic vasculitis + asthma + eosinophilia.
• CNS: stroke, peripheral neuropathy (mononeuritis multiplex).

Polyarteritis Nodosa (PAN)

• Necrotizing arteritis of medium vessels.
• CNS: stroke, mononeuritis multiplex.
• Hepatitis B-associated form common.

Behçet Disease

• Recurrent oral ulcers + genital ulcers + uveitis.
• CNS: cerebral venous thrombosis (classic), brainstem encephalitis, focal lesions.
• Specific pattern: brainstem T2 lesions often diencephalic-pontine.

SLE-Related CNS Disease

• Strokes (often APLA-related), cognitive impairment, seizures, psychiatric symptoms.
• Pathology often shows lupus vasculopathy (non-inflammatory thickening) more than true vasculitis.

Infectious Vasculitis

VZV Vasculopathy

• VZV reactivation produces vasculitis weeks to months after zoster (especially ophthalmic zoster).
• Strokes in vessels supplying affected dermatome distribution.
• CSF: VZV PCR positive in some, VZV antibody index elevated.
• Treat with IV acyclovir + steroids.

Tuberculous Vasculitis

TB meningitis preferentially involves basal cisterns, with vasculitis of vessels traversing the meningitis (lenticulostriate, perforators). Causes deep infarcts. Treat TB.

Neurosyphilis

Meningovascular syphilis produces a vasculitis of cortical and meningeal vessels. Heubner arteritis. Treat with penicillin.

Fungal Vasculitis

Aspergillus and mucormycosis can invade vessel walls causing hemorrhagic infarction. Immunocompromised host. Devastating.

Cerebral Venous Sinus Thrombosis (CVST)

Pathology

Thrombosis of dural venous sinuses (most often superior sagittal, transverse, sigmoid) or cortical veins. Pathology:

• Clot occluding lumen of affected sinus or vein.
• Venous infarction in territory drained: often hemorrhagic.
• Edema (mixed vasogenic and cytotoxic).
• Eventual recanalization in many.

Risk Factors

• Procoagulant: OCPs, pregnancy/postpartum, factor V Leiden, prothrombin G20210A, antiphospholipid syndrome.
• Infection: sinusitis, mastoiditis, meningitis, otitis.
• Trauma: head, neck.
• Dehydration.
• Malignancy.
• Chemotherapy.
• VITT (vaccine-induced immune thrombotic thrombocytopenia): rare; adenoviral vector COVID vaccines.
• Idiopathic: 15-20%.

Clinical Presentations

• Headache (most common).
• Isolated intracranial hypertension picture (papilledema, sometimes visual loss).
• Focal deficits ± seizures (from venous infarction).
• Encephalopathy (extensive sinus thrombosis or deep venous thrombosis).
• Cavernous sinus thrombosis: painful ophthalmoplegia + chemosis + V1/V2 sensory loss; often septic.
• Deep cerebral vein thrombosis (internal cerebral veins, vein of Galen, straight sinus): bilateral thalamic infarcts + severely altered consciousness.

Specific Sinus Patterns

• Superior sagittal sinus thrombosis: bilateral parasagittal infarcts (often hemorrhagic), often with motor or cognitive findings.
• Transverse / sigmoid sinus thrombosis: temporal lobe infarct (vein of Labbé), sometimes pulsatile tinnitus before clot.
• Cavernous sinus thrombosis: emergency picture from facial infection; septic.
• Straight sinus / deep cerebral veins: bilateral thalamic infarcts; profound encephalopathy.

Imaging

• CT venography: empty delta sign (post-contrast filling defect in SSS).
• MR venography: absent flow void in affected sinus; signal abnormality of clot.
• Non-contrast CT: hyperdense thrombus in sinus (especially fresh).
• SWI: low signal in venous infarcts (deoxyhemoglobin).
• Conventional venography: gold standard if uncertain.

Treatment

• Anticoagulation (heparin acutely → oral anticoagulant) for several months. Indicated even with hemorrhagic venous infarction (this is one of the few situations where anticoagulation is indicated despite ICH).
• Treat underlying cause (infection, remove OCPs, etc.).
• Mechanical thrombectomy for severe cases (research; not standard).
• Decompression for malignant edema.

🔍 Did You Know?

The classical vein of Labbé thrombosis is one of the most distinctive — and most often missed — patterns of cerebral venous sinus thrombosis. The vein of Labbé (the inferior anastomotic vein) drains the temporal lobe into the transverse sinus. When the transverse sinus thromboses, the vein of Labbé may also clot, producing hemorrhagic infarction of the lateral temporal lobe. The patient presents with headache and often seizures (the temporal lobe being highly epileptogenic), sometimes with neglect, aphasia, or visual field defects depending on lateralization. The classic radiographic finding is a hemorrhagic infarct in a non-arterial distribution — the lesion crosses arterial boundaries because venous drainage territories don’t match arterial supply. Missing the diagnosis and treating only with anti-epileptics will miss the underlying CVST that is still propagating. The lesson: any hemorrhagic infarct that does not respect arterial territory deserves venous imaging. The clinical phenotype — young or middle-aged patient (often woman on OCPs or postpartum), headache, seizures, temporal lobe hemorrhagic infarct — is recognizable once you know the pattern. Anticoagulation, even in the presence of the hemorrhage, is the indicated treatment, and patients typically do well if recognized early. The recognition of CVST has improved dramatically with widespread MR venography, but vein of Labbé thrombosis specifically requires thinking about it.

Pitfalls and Pearls

• PACNS: subacute multifocal CNS disease, headache, ± seizures; angiographic beading or biopsy proof; treat with steroids + cyclophosphamide.
• RCVS: thunderclap headache + reversible vasoconstriction + young woman ± triggers; calcium channel blocker; mimics PACNS but is treatable differently.
• Brain biopsy for PACNS: sensitivity ~50-75%; negative biopsy does not exclude.
• VZV vasculopathy: stroke weeks-months after zoster; IV acyclovir + steroids.
• TB vasculitis: basal cistern preference, deep infarcts.
• Cocaine, amphetamine vasculitis: mimic PACNS; history is key.
• Amyloid-β-related angiitis (ABRA): subtype of CAA with granulomatous vasculitis; responds to steroids.
• Behçet: oral + genital ulcers + uveitis; CVST common; brainstem disease.
• CVST: headache + papilledema + sometimes seizures + focal deficits.
• Anticoagulation indicated in CVST even with hemorrhagic infarction.
• Cavernous sinus thrombosis: facial infection source; painful ophthalmoplegia + chemosis + V1/V2 sensory loss; emergency.
• Deep cerebral vein thrombosis: bilateral thalamic infarcts; coma.
• Vein of Labbé thrombosis: temporal lobe hemorrhagic infarct + seizures.
• VITT: rare; adenoviral COVID vaccine context; severe with thrombocytopenia.
• Hemorrhagic infarct not respecting arterial territory → suspect CVST.

References

1. Calabrese LH, Mallek JA. Primary angiitis of the central nervous system. Report of 8 new cases, review of the literature, and proposal for diagnostic criteria. Medicine. 1988;67(1):20-39.
2. Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62(5):442-451.
3. Singhal AB, Hajj-Ali RA, Topcuoglu MA, et al. Reversible cerebral vasoconstriction syndromes: analysis of 139 cases. Arch Neurol. 2011;68(8):1005-1012.
4. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the AHA/ASA. Stroke. 2011;42(4):1158-1192.
5. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005;352(17):1791-1798.
6. Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol. 2007;6(2):162-170.