Primary Vasculitis of the Central Nervous System

You’ve been diagnosed with CNS vasculitis—what does this mean for you?

A diagnosis of CNS vasculitis means there is inflammation affecting blood vessels in your brain. This can produce minor to more significant brain injury—ranging from small MRI “spots” to true stroke events.

For you and your family, this typically means:

• a specialized workup is required to exclude secondary causes (infection, systemic vasculitis, RCVS, etc.),
• treatment is often long-term (months to years) and may involve immunosuppression,
• an accurate, timely diagnosis can help prevent new injury and lasting disability.

What exactly is CNS vasculitis?

CNS vasculitis refers to inflammation of the vessel wall—typically arteries (and sometimes veins)—within the brain and spinal cord. Broadly, we distinguish:

• Primary Angiitis of the CNS (PACNS): inflammation is confined to the brain/spinal cord, with no evidence of systemic vasculitis or organ involvement (kidneys, lungs, etc.).
• Secondary CNS vasculitis: vascular inflammation occurs as a consequence of another condition—such as systemic vasculitis (e.g., granulomatosis with polyangiitis, PAN, EGPA), autoimmune disease, infection, medication, or substance exposure.

In PACNS, small and medium vessels become inflamed; the wall thickens, the lumen narrows, and—less commonly—vessels may dissect or weaken, leading to:

• small ischemic infarcts,
• thrombosis,
• microhemorrhages.

Causes and risk factors—primary vs secondary vasculitis

In PACNS, the exact cause is not fully understood. The prevailing hypothesis is that:

• an immune-mediated trigger activates inflammatory pathways (T cells, macrophages),
• inflammation develops within the vessel wall (often with a granulomatous pattern),
• for reasons not entirely clear, the process remains confined to the brain/spinal cord.

In secondary CNS vasculitis, cerebral vessels become inflamed as part of:

• systemic vasculitis (GPA, PAN, EGPA, giant cell arteritis, and others),
• infections (viral, bacterial, fungal—e.g., HIV, syphilis),
• autoimmune disease (SLE, Sjögren’s syndrome, etc.),
• medications or substances (certain chemotherapies, immunotherapies, illicit drugs),
• malignancy (e.g., lymphoma, angiocentric lymphoproliferative disorders).

The goal of a comprehensive evaluation is to answer: “Is this true primary PACNS, or secondary CNS vasculitis?” because that distinction directly shapes treatment.

What are the symptoms, and how does it evolve?

PACNS most often has an insidious, subacute onset. Common symptoms include:

• a persistent or new headache that feels unlike “usual” headaches,
• fatigue, impaired concentration, “brain fog,” memory difficulties,
• personality change, irritability, depression, apathy,
• focal deficits (arm/leg weakness, speech difficulty, visual symptoms),
• seizures,
• gait or balance disturbance, depending on lesion distribution on MRI.

Without treatment, the course may be:

• gradually progressive (new small strokes and worsening cognition),
• or relapsing–remitting, with episodic deterioration followed by partial improvement.

A frequent “mimic” is reversible cerebral vasoconstriction syndrome (RCVS), which typically presents with sudden, thunderclap headaches (often in younger women), normal CSF inflammatory markers, and reversible vasoconstriction. Distinguishing PACNS from RCVS is essential because management is fundamentally different.

How is the diagnosis made?

PACNS is a diagnosis of exclusion. There is no single blood test that confirms it. Diagnosis requires an integrated assessment that typically includes:

1. Blood testing

• CBC, ESR, CRP.
• Autoimmune serologies: ANA, RF, p-ANCA, c-ANCA, anti-SSA/SSB, complement levels, cryoglobulins.
• Targeted infectious evaluation where appropriate.

In “pure” PACNS, these tests are often normal.

2. Cerebrospinal fluid (CSF) analysis

• Mild lymphocytic pleocytosis and modest protein elevation.
• Occasional oligoclonal bands (which may mimic multiple sclerosis).
• Parallel testing to exclude infectious meningitis/encephalitis (PCR, cultures, targeted studies).

3. Brain MRI

• Multiple bilateral lesions, often ischemic, involving both white and gray matter.
• Contrast enhancement around vessels or meninges may be seen.
• MRI is typically abnormal in PACNS; a normal MRI makes the diagnosis substantially less likely.

4. Cerebrovascular imaging (DSA / MRA / CTA)

• Assessment for “beading” — alternating stenoses and dilations across multiple vessels.
• Multifocal segmental narrowing in different vascular territories.

5. Brain biopsy (gold standard)

When the overall picture suggests PACNS but diagnostic uncertainty remains—or before initiating aggressive immunosuppression—a surgical biopsy may be recommended.

When is it dangerous and requires urgent action?

CNS vasculitis is considered urgent and potentially life-threatening when:

• there are recurrent or extensive stroke events,
• there is rapid decline in memory, level of alertness, or behavior,
• seizures are frequent or difficult to control,
• MRI shows multiple new lesions over a short time period.

In such settings, patients often require:

• admission to a specialized neurology service with neurosurgical coverage,
• rapid completion of the diagnostic pathway,
• initiation of high-dose corticosteroids with or without additional immunosuppression.

What treatments are used? (corticosteroids & immunosuppressive therapy)

The goal of therapy is to halt and reverse vascular inflammation to prevent new brain injury. Treatment is commonly structured in two phases:

1. Induction of remission

• High-dose corticosteroids—often IV methylprednisolone 1 g/day for 3 days followed by oral prednisone with a gradual taper.
• Cyclophosphamide (oral or IV) or rituximab in more severe or extensive cases to achieve stronger immunosuppression.

2. Maintenance of remission

• Once remission is achieved, more intensive agents (cyclophosphamide/rituximab) are typically stopped to reduce toxicity (myelosuppression, cystitis, etc.).
• Transition to less toxic maintenance agents such as mycophenolate mofetil for approximately 18 months after remission.
• Ongoing corticosteroid taper under close supervision.

Throughout treatment:

• patients undergo regular blood and metabolic monitoring, with bone health surveillance,
• repeat MRI/angiographic follow-up is performed when indicated,
• infection prevention strategies are implemented (vaccination planning and prophylaxis when appropriate).

Role of angiography and brain biopsy—when might “surgery” be needed?

Cerebral angiography (digital subtraction angiography—DSA) is an invasive test. It is used to:

• identify characteristic multifocal narrowing/dilation (“beading”),
• exclude alternative diagnoses (aneurysms, AVMs, vascular malformations, etc.).

A brain biopsy is a minimally invasive neurosurgical procedure that:

• is typically performed in the non-dominant hemisphere (often right frontal or temporal),
• involves a small craniotomy and sampling of dura/meninges plus cortical tissue (~1 cm²),
• is sent for specialized neuropathology.

When do we seriously consider it?

• when diagnostic uncertainty persists despite comprehensive evaluation,
• when aggressive immunosuppression is contemplated and maximal diagnostic confidence is needed,
• when an alternative diagnosis is suspected (e.g., lymphoma or infection) that would completely change management.

Prognosis and long-term course

Historically, PACNS carried a poor prognosis. With modern immunosuppressive therapy:

• a substantial proportion of patients (~80%) can achieve a good functional outcome when treated early,
• mortality has declined significantly in experienced centers,
• some patients may have persistent cognitive or neurological deficits due to prior injury.

Factors associated with worse outcomes include:

• large established strokes at first presentation,
• severe cognitive impairment or major focal deficits prior to treatment,
• large-vessel involvement,
• delayed diagnosis and delayed initiation of therapy.

Long-term follow-up is essential—to monitor for relapse, adjust therapy, and manage the potential adverse effects of immunosuppression.

Daily life, work, and practical guidance

Living with CNS vasculitis—key considerations:

• Treatment coordination and follow-up: scheduled visits with neurology/rheumatology, blood monitoring, and MRI when indicated.
• Work and activity: many patients can continue working, often with adjustments to schedule and stress load—this is individualized.
• Cognitive recovery: memory exercises, cognitive rehabilitation strategies, and neuropsychological support may help.
• Infection prevention: vaccination planning (per your treating team), avoidance of exposure to contagious illness, and prompt evaluation of fever.
• Lifestyle optimization: avoid smoking; optimize blood pressure and glucose; maintain gentle, regular activity; and follow a Mediterranean-style diet.

When is it an emergency, and when should I go to the hospital immediately?

Call emergency services or go directly to the Emergency Department if you experience:

• sudden weakness in an arm/leg or facial droop,
• sudden difficulty speaking or understanding speech,
• a new major seizure, especially if it lasts longer than 5 minutes,
• sudden confusion, loss of awareness, or loss of consciousness,
• a “thunderclap” headache—the worst headache of your life.