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Afeerah Mumtaz MD, Junaid Kalia MD
IntroductionClassificationClinical FeaturesSome general features of CNS vasculitis are as followsPrimary angiitis of CNSOverviewClinical manifestationsTable 1: Subtypes of PACNSDiagnostic criteriaSystemic vasculitis involving CNSTable 2: Classification and features of systemic vasculitis involving CNSSecondary CNS vasculitisTable 3: Causes of secondary CNS vasculitisDiagnosisTable 4: Diagnostic workup in patients with suspected CNS vasculitisDifferential diagnosisTreatmentAcute therapyMaintenance therapyTable 5: Agents used in treatment of CNS vasculitisFurther readingBibliography
- Vasculitides are a heterogenous group of disorders characterized by inflammation of blood vessels restricting blood flow to the vital organs and tissues and thus,causing severe damage.
- CNS vasculitis particularly refers to the inflammation and resultant blockage of the blood vessels supplying brain and spinal cord.
- CNS vasculitis is classified as follows;
- Primary angiitis of CNS
- Systemic vasculitis involving CNS
- Secondary (Secondary CNS vasculitis)
- Primary Angiitis of CNS:
It is confined to brain and spinal cord and not associated with any other systemic disease
- Systemic vasculitis involving CNS
It may be of large calibre arteries, medium calibre arteries or small calibre arteries
- Secondary CNS vasculitis:
It occurs in the presence of other autoimmune disorders like SLE (systemic lupus erythematosus), dermatomyositis, rheumatoid arthritis and bacterial and viral infections
- New, severe headache
- Strokes or mini strokes (transient ischemic attacks)
- Visual impairment (diplopia,blurred vision,papilledema)
- Confusion or forgetfulness
- Hemiparesis or may be quadriparesis
- Loss of balance and gait disturbance
- Sensation abnormalities (numbness and tingling particularly on one side of body)
- Seizures or convulsions
Presence of above features make CNS vasculitis a probable diagnosis. However, confirmation can be done by taking into account the clinical manifestations associated with different types of CNS vasculitis.
- It can occur at any age but is very uncommon in children. Most of the patients at the time of diagnosis are between the ages of 40 and 60 years.
- Women are slightly more frequently affected than men.
- Onset could be abrupt but is usually gradual and progressive in course.
- These are diverse and non-specific. However, the most common features include
- Altered cognition
- Persistent neurologic deficit or stroke
- These are also the initial manifestations in about 75% of cases. In children,however, seizures are commonly observed.
Table 1: Subtypes of PACNS
• Cognitive impairment • Greater CSF abnormalities • Good response to treatment
Meningeal and parenchymal enhancing lesions
• Older age • Predominantly male • Cognitive impairment
Contrast enhanced meningeal lesions
Granulomatous pattern βamyloid deposits in vessel wall
• Spinal cord symptoms • Cerebral manifestations usually present
Enhanced spinal lesions in thoracic region
• Predominant in women • Good response to treatment
Intracerebral or subarachnoid hemorrhage
• Aggressive disease course • Worsening cognition • Less responsive to treatment • Often fatal
Bilateral multiple vessel lesions
Granulomatous or necrotizing pattern
Derived from [Beuker C, Schmidt A, Strunk D, et al. Primary angiitis of the central nervous system: diagnosis and treatment. Ther Adv Neurol Disord. 2018;11:1756286418785071. Published 2018 Jul 9. doi:10.1177/1756286418785071]
Calabrese and Mallek proposed a criteria for PACNS which is as follows
- A history of clinical findings of an acquired otherwise unexplained neurologic deficit
- Presence of classic histologic or angiographic features of angiitis within the CNS.
- No evidence of systemic vasculitis or of any disorder that could cause or mimic the angiographic or pathologic features
Birnbaum and colleagues modified these criteria in 2009 to differentiate PACNS from its very challenging mimic reversible cerebral vasoconstriction syndrome (RCVS).
- The level of certainty of diagnosis was classified as;
Definite: when tissue biopsy confirms presence of vasculitis
Probable: when there are high probability findings on angiograms with abnormal findings on MRI and CSF analysis consistent with PACNS.
- General clinical features of CNS vasculitis are seen along with the specific manifestations of systemic disease.
- Laboratory findings suggestive of systemic vasculitis include
- Elevated ESR and C-reactive protein
- Elevated liver enzymes
- Low complement
Table 2: Classification and features of systemic vasculitis involving CNS
Type of vasculitis
Giant cell or temporal arteritis
Churg strauss syndrome
Derived From: Giannini C, Salvarani C, Hunder G, Brown RD. Primary central nervous system vasculitis: pathology and mechanisms. Acta Neuropathol. 2012 Jun;123(6):759-72. doi: 10.1007/s00401-012-0973-9. Epub 2012 Mar 16. PMID: 22421812
- It occurs in the setting of some underlying autoimmune disease or some infection.
Table 3: Causes of secondary CNS vasculitis
Derived From: Hajj-Ali, R., 2021. CNS Vasculitis. [online] Rheumatology Advisor
Patients suspected of CNS vasculitis need to undergo a diagnostic workup that includes proper history, clinical examination, laboratory tests, specialized imaging studies and tissue biopsy.
- In CSF analysis cell count >250 cells/μl are indicative of infectious cause. IL-17 producing CD41 cells in CSF discriminate CNS vasculitis from ischemic stroke.
- Brain MRI is significant as it is normal in RCVS (reversible cerebral vasoconstriction syndrome) and helps differentiate vasculitis from RCVS.
- Biopsy must be done in patients with chronic meningitis picture or with suspected malignancy.
Table 4: Diagnostic workup in patients with suspected CNS vasculitis
• Usually normal in PACNS • Elevated ESR and CRP in systemic vasculitis • Associated antibodies in autoimmune disorders
• Mild lympho-monocytic pleocytosis • Elevated protein level • Occasional presence of oligoclonal band
• Ischemic infarctions • Signs of microangiopathy • Contrast enhancement • Tumor like lesions
• Vessel beading (segmental arterial wall narrowing followed by post stenotic dilatation
• Granulomatous • Lymphocytic or acute necrotizing pattern
Derived from: Beuker C, Schmidt A, Strunk D, et al. Primary angiitis of the central nervous system: diagnosis and treatment. Ther Adv Neurol Disord. 2018;11:1756286418785071. Published 2018 Jul 9. doi:10.1177/1756286418785071]
Consideration of possible differential diagnoses is crucial in a diagnostic approach as to avoid unnecessary immunosuppressive therapy. This includes;
- Noninflammatory vasculopathies like atherosclerosis
- CADASIL(Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
- Radiation vasculopathy
- Ischemic stroke
- Moyamoya disease
- Treatment is aggressive for the first 6-8 months and then tapered depending upon the resolution of symptoms.
- Monitoring of treatment is necessary. MRI should be done after 4-6 weeks of initiation of therapy and afterwards done every 3-4 months in first year of treatment.
- In patients with worsening neurological symptoms, conventional angiography might be necessary.
- CNS vasculitis is typically treated with high dose corticosteroids. Oral prednisone is recommended therapy at the time of diagnosis. However IV corticosteroid is preferred in severe and rapidly progressive course to induce remission.
- For more severe cases, prednisone is used in combination with immunosuppressive agents. Cyclophosphamide either as oral dose or IV pulse is recommended for use in combination with corticosteroid.
- Biological agents are also used in severe and rapidly progressive disease or in cases not responding to immunosuppressive therapy
- It is initiated 4-6 months after the initiation of induction therapy
- It reduces the risk of relapses and prevents long term disabilities.
- During immunosuppressive therapy,administration of calcium and vitamin D for osteoporosis, gastric ulcer and pneumocystis prophylaxis is recommended
Derived from Beuker C, Schmidt A, Strunk D, et al. Primary angiitis of the central nervous system: diagnosis and treatment. Ther Adv Neurol Disord. 2018;11:1756286418785071. Published 2018 Jul 9. doi:10.1177/1756286418785071]
- Patzig M, Forbrig R, Küpper C, et al. Diagnosis and follow-up evaluation of central nervous system vasculitis: an evaluation of vessel-wall MRI findings [published online ahead of print, 2021 Jul 8]. J Neurol. 2021;1-15. doi:10.1007/s00415-021-10683-7
- Arif S, Arif S, Liaqat J, Slehria AU, Palwa AR. Central Nervous System Vasculitis Secondary to Sarcoidosis: A Rare Case of Lupus Pernio With Complete Occlusion of Right Internal Carotid Artery. Cureus. 2020;12(9):e10274. Published 2020 Sep 6. doi:10.7759/cureus.10274
- Vasculitis Foundation. 2021. Central Nervous System Vasculitis - Vasculitis Foundation. [online] Available at <https://www.vasculitisfoundation.org/education/forms/central-nervous-system/>
- Uofmhealth.org. 2021. Central Nervous System (CNS) Vasculitis | Michigan Medicine. [online] Available at: <https://www.uofmhealth.org/conditions-treatments/brain-neurological-conditions/central-nervous-system-cns-vasculitis>
- Giannini C, Salvarani C, Hunder G, Brown RD. Primary central nervous system vasculitis: pathology and mechanisms. Acta Neuropathol. 2012 Jun;123(6):759-72. doi: 10.1007/s00401-012-0973-9. Epub 2012 Mar 16. PMID: 22421812.
- Beuker C, Schmidt A, Strunk D, et al. Primary angiitis of the central nervous system: diagnosis and treatment. Ther Adv Neurol Disord. 2018;11:1756286418785071. Published 2018 Jul 9. doi:10.1177/1756286418785071
- Berlit P. Diagnosis and treatment of cerebral vasculitis. Ther Adv Neurol Disord. 2010;3(1):29-42. doi:10.1177/1756285609347123
- Hajj-Ali, R., 2021. CNS Vasculitis. [online] Rheumatology Advisor. Available at: <https://www.rheumatologyadvisor.com/home/decision-support-in-medicine/rheumatology/cns-vasculitis/>