Cns Vasculitis: Symptoms, Types, Causes and Treatment

Central nervous system (CNS) vasculitis is a rare but serious condition characterized by inflammation of the blood vessels in the brain and spinal cord. Its unpredictable nature and diverse presentations make it a challenging diagnosis for clinicians and a daunting experience for patients. Understanding its symptoms, types, underlying causes, and available treatments is crucial for timely intervention and improved outcomes. This article delves into each of these aspects with evidence-based insights.

Symptoms of Cns Vasculitis

CNS vasculitis can present in a variety of ways, often mimicking other neurological conditions. This complexity makes recognizing the symptoms both critical and challenging. Early detection is essential, as untreated CNS vasculitis can lead to irreversible brain damage or disability.

Symptom	Description	Frequency/Pattern	Source(s)
Headache	Persistent or severe, often a first sign	Common, early symptom	1 2 3 4
Seizures	New-onset seizures or status epilepticus	Up to 70% of cases	2 4 5
Stroke	Sudden weakness, numbness, or paralysis	May be recurrent	1 10
Cognitive Changes	Confusion, memory loss, personality change	Progressive or acute	1 4 6
Focal Deficits	Weakness, numbness, speech trouble	Variable, often sudden	1 3 4
Gait Disturbance	Difficulty walking or imbalance	Varies by vessel involvement	3
Visual Changes	Double vision, visual loss	Less common, but notable	14
Encephalopathy	Altered mental status, drowsiness	Can be prominent	10

Table 1: Key Symptoms

Varied and Overlapping Presentations

CNS vasculitis does not follow a single clinical pattern. Most patients initially report headaches—sometimes severe and resistant to standard therapies 1 2 3. Seizures are another frequent presenting feature, especially in younger adults, and can occasionally be the primary symptom 2 4.

Stroke-like Episodes

Strokes—either ischemic or hemorrhagic—are a hallmark of CNS vasculitis 1 10. These may recur and affect different brain regions at different times, leading to a fluctuating clinical course.

Cognitive and Psychiatric Manifestations

Changes in cognition, including confusion, memory loss, and personality changes, can be subtle or dramatic 1 4 6. In some cases, these symptoms progress rapidly, resembling other neurodegenerative or inflammatory conditions.

Focal Deficits and Other Neurological Signs

Patients may display focal neurological deficits (such as unilateral numbness, weakness, or speech difficulties), gait disturbances, and, less commonly, visual changes or cranial nerve palsies 3 14. Encephalopathy, characterized by altered consciousness or drowsiness, is also observed, particularly in small vessel involvement 4 10.

Types of Cns Vasculitis

CNS vasculitis is not a single disease but a spectrum of disorders that can be classified based on vessel size, pathophysiology, and whether the process is primary or secondary. This classification helps guide diagnosis and treatment.

Type	Vessel Size Affected	Primary/Secondary	Source(s)
Primary CNS Vasculitis (PCNSV)	Small/medium/large	Primary	1 2 7 9
Secondary CNS Vasculitis	Variable	Secondary	3 5 6 9
Large Vessel Vasculitis	Large (e.g. giant cell)	Primary/Secondary	5 7 13
Medium Vessel Vasculitis	Medium (e.g. polyarteritis)	Primary/Secondary	4 5 7
Small Vessel Vasculitis	Small (e.g. lymphocytic)	Primary/Secondary	2 4 6 12
Infectious Vasculitis	Any size	Secondary (infection)	3 5 9
Mimics (e.g., RCVS)	Varies	Neither (mimic)	8

Table 2: Classification of CNS Vasculitis Types

Primary vs. Secondary CNS Vasculitis

• Primary CNS Vasculitis (PCNSV): Isolated to the brain and spinal cord without systemic involvement. It is rare, idiopathic, and potentially severe 1 2 7 9.
• Secondary CNS Vasculitis: Occurs due to systemic vasculitides (like lupus, Behçet’s, granulomatosis), infections, malignancy, or drug use. Secondary causes are actually more common in clinical practice 3 5 6 9.

Classification by Vessel Size

• Large Vessel Vasculitis: Includes conditions like giant cell arteritis, typically affecting large arteries 5 7 13.
• Medium Vessel Vasculitis: Polyarteritis nodosa and Kawasaki disease are classic examples. These often present with focal neurological signs 4 5 7.
• Small Vessel Vasculitis: May be lymphocytic or granulomatous in origin, often causing cognitive changes, seizures, or encephalopathy 2 4 6 12.

Infectious and Other Forms

Infectious vasculitis can be caused by bacteria (e.g., syphilis, borreliosis) or viruses, and may affect any vessel size 3 5 9.

Mimics

Reversible cerebral vasoconstriction syndrome (RCVS) and other mimics must be considered, as they can present with similar symptoms but require different management 8.

Causes of Cns Vasculitis

CNS vasculitis has a diverse range of underlying causes, varying from primary idiopathic forms to secondary processes associated with systemic diseases, infections, malignancies, or drugs.

Cause Category	Specific Examples	Notes/Mechanisms	Source(s)
Idiopathic	Primary angiitis of CNS	No identifiable cause	1 2 9
Systemic Vasculitis	Lupus, Behçet’s, ANCA-associated, sarcoidosis	Autoimmune mechanisms	3 5 7 10
Infection	Syphilis, borreliosis, viral infections	Direct vessel invasion	3 5 9 14
Malignancy	Lymphoproliferative diseases	Paraneoplastic, infiltration	9
Drugs/Substances	Cocaine, amphetamines, others	Direct toxicity, hypersensitivity	6 9
Genetic/Immunodeficiency	DOCK8 deficiency, other syndromes	Immune dysregulation	14

Table 3: Main Causes of CNS Vasculitis

Primary (Idiopathic) CNS Vasculitis

This form arises without any identifiable external cause and is restricted to the CNS 1 2 9. Its pathogenesis is not fully understood, but immune-mediated mechanisms are suspected.

Systemic Autoimmune Diseases

Many systemic vasculitides can involve the CNS:

• Systemic lupus erythematosus (SLE)
• ANCA-associated vasculitis
• Behçet’s disease
• Sarcoidosis These conditions cause CNS vasculitis via immune complex deposition, autoantibody formation, or granulomatous inflammation 3 5 7 10.

Infectious Causes

Certain infections directly invade or trigger inflammation in cerebral vessels. Syphilis, Lyme disease (borreliosis), and various viruses are notable causes 3 5 9 14. Early recognition and antimicrobial therapy are critical in these cases.

Malignancies

Blood cancers, especially lymphoproliferative diseases, can cause paraneoplastic vasculitis or direct vessel infiltration 9.

Drug-Induced and Other Secondary Causes

Illicit drugs (cocaine, amphetamines), immune-modulating medications, and some therapeutics can provoke CNS vasculitis through direct toxicity or hypersensitivity reactions 6 9.

Genetic and Immunodeficiency Syndromes

Rarely, primary immunodeficiencies (such as DOCK8 deficiency) predispose to CNS vasculitis, underscoring the importance of recognizing this in young or atypical patients 14.

Treatment of Cns Vasculitis

Management of CNS vasculitis requires prompt, aggressive intervention tailored to the underlying cause and vessel size affected. The goal is to halt inflammation, preserve neurological function, and prevent relapses.

Treatment Option	Indication/Context	Outcome/Notes	Source(s)
Glucocorticoids	First-line for most cases	High response rate, initial therapy	1 2 4 12
Cyclophosphamide (CYC)	Moderate-severe, refractory, or large-vessel	Used with steroids, induction agent	2 4 12 13
Mycophenolate Mofetil (MMF)	Alternative to CYC	Shown effective, fewer side effects	12 14
Rituximab	Refractory or ANCA-associated cases	Useful in some patients	11 13
Other Immunosuppressants	Maintenance or intolerance to CYC	Azathioprine, methotrexate	12 13
Antimicrobials	Infectious vasculitis	Crucial for infection-driven types	3 14
Aspirin	Adjunctive, especially for large-vessel	May assist long-term remission	12

Table 4: CNS Vasculitis Treatments

Initial and Induction Therapy

• Glucocorticoids (e.g., prednisone) are the foundation of treatment, often started as soon as CNS vasculitis is suspected 1 2 4.
• Cyclophosphamide is commonly added for moderate to severe cases, especially with large or medium vessel involvement, or when there is rapid progression 2 4 12 13.

Alternatives and Maintenance

• Mycophenolate mofetil (MMF) is increasingly recognized as an effective alternative to cyclophosphamide, with better long-term tolerance and outcomes in some patient subsets 12 14.
• Other options: Azathioprine and methotrexate may be used for maintenance or in milder cases 12 13.
• Rituximab is reserved for refractory cases or when cyclophosphamide is contraindicated, and has shown benefit in ANCA-associated and some idiopathic cases 11 13.

Special Considerations for Secondary and Infectious Causes

• Antimicrobial therapy must be started promptly for infectious vasculitis (e.g., syphilis, Lyme disease) 3 14.
• Biologic agents (anti-TNF, tocilizumab) are considered in specific secondary forms such as neuro-Behçet’s disease 13.

Prognosis and Follow-Up

Most patients respond to initial treatment, but relapses are common (up to 30%) 12. Maintenance immunosuppression reduces relapse risk. Early diagnosis, aggressive initial therapy, and careful long-term monitoring are key to improving outcomes. Factors such as large vessel involvement, cerebral infarction, advanced age, and cognitive dysfunction at diagnosis are associated with poorer prognosis 12.

Conclusion

CNS vasculitis is a complex, multifaceted disorder with significant potential for neurological disability. Prompt recognition and a multidisciplinary approach to diagnosis and treatment are vital.

Key takeaways:

• CNS vasculitis presents with varied symptoms such as headache, seizures, stroke, cognitive changes, and focal deficits.
• It can be classified as primary or secondary, and by the size of affected vessels.
• Causes range from idiopathic, autoimmune, infectious, malignant, drug-induced, to genetic/immunodeficiency syndromes.
• Treatment focuses on immunosuppression (mainly glucocorticoids and cyclophosphamide), with alternatives like MMF and rituximab for specific cases or intolerances.
• Early, aggressive therapy and tailored long-term management are crucial for optimal outcomes.

Understanding the nuances of CNS vasculitis can empower both clinicians and patients to navigate this challenging condition with greater confidence and effectiveness.