CNS VASCULITIS

Dr Sankalp MohanSenior Resident

Neurology GMC, Kota

VASCULITIS The vasculitides are defined by the presence

of inflammatory leukocytes in vessel walls with reactive damage to mural structures. 

Compromise of the lumen leads to downstream tissue ischemia and necrosis

Pathogenetic mechanisms – immune complex deposition , invasion of endothelial cells by microorganisms , autoantibodies ,granuloma formation

CLASSIFICATION OF VASCULITIS

•Takayasu•Giant Cell ArteritisLarge vessel

•PAN•Kawasaki s disease•Primary CNS vasculitis

Medium vessel

•Microscopic Polyangiitis•Churg Strauss Syndrome•Wegner s Granulomatosis

Small Vessel

CNS VASCULITIS

CLASSIFICATION

Primary angiitis of the CNS (PACNS) when it is confined to the CNS.

Secondary when associated with various other disorders.

Reversible cerebral vasoconstriction syndromes

PRIMARY CENTRAL NERVOUS SYSTEM VASCULITIS (PACNS)

.  Defined as inflammation of the cerebral vasculature without angiitis in other organs

 affects small- and medium-sized arteries of the brain parenchyma, spinal cord, and leptomeninges

1. Granulomatous angiitis of the CNS (GACNS)

2. Atypical PACNS

GRANULOMATOUS ANGIITIS OF THE CENTRAL NERVOUS SYSTEM

20% of all patients with PACNS male-predominant (2:1) at any age mean age at diagnosis is

42 years, long prodromal period insidious onset

of symptoms

PATHOLOGY  Langerhans or foreign body giant cells,

necrotizing vasculitis, or lymphocytic vasculitis

Atypical PACNS –biopsy is not granulomatous , only lymphocytic infiltrate

vessels to become narrowed, occluded and thrombosed – ischemia

In contrast to systemic vasculitides, the finding of aneurysms in the cerebral arteries is rare

PATHOGENESIS The cause of PACNS is unknown Infection  — Infectious agents,

particularly mycoplasma and viruses varicella zoster virus, West Nile virus HIV infection can cause both a CNS

vasculitis and a CNS vasculopathy that is associated with aneurysm formation

Amyloid angiopathy 

CLINICAL MANIFESTATIONS  characterized by a long prodromal

period Signs and symptoms of systemic

vasculitis, such as, fever, weight loss, or rash, are usually lacking.

 highly variable and nonspecific PACNS should be suspected when

strokes, more often recurrent, occur in young patients

& unexplained diffuse neurologic dysfunction

Decreased cognition — 83 percent Headache — 56 percent Seizure — 30 percent Stroke — 14 percent Cerebral hemorrhage — 12 percent Angiitis affecting the spinal cord usually

presents as a myelopathy /spinal cord infarction

PROPOSED THE CRITERIA FOR THE DIAGNOSIS OF PACNS.

The presence of an acquired and otherwise unexplained neurologic deficit and with (a) the presence of either classic

angiographic or histopathologic features of angiitis within the CNS, and

(b) no evidence of systemic vasculitis or any condition that could elicit the angiographic or pathologic features

DIAGNOSTIC TESTS erythrocyte sedimentation rate (ESR) and C-

reactive protein (CRP) are usually normal  Serologic evaluation  Antinuclear antibodies Rheumatoid factor Antibodies to the Ro/SSA, La/SSB, Sm, and RNP antigens Antibodies to double-stranded DNA Antineutrophil cytoplasmic antibodies (ANCA) Serum C3 and C4 Serum cryoglobulins

Testing for infections appropriate to the clinical circumstances 

Lumbar puncture – CSF is abnormal in 80 to 90 percent of

patients with pathologically documented disease. There are no specific abnormalities of the CSF in PACNS.

excluding any infectious or malignant process  RCVS – CSF normal

NEUROIMAGING MR imaging  = single or multiple, may include infarcts (both

white and gray matter) and hemorrhage, and may be tumor-like 

Nonspecific high-intensity T2WI/FLAIR lesions in white matter present in 42 percent of Secondary vasculitis (low specificity )

MR angiography  — The resolution of MR angiography (MRA) remains inadequate for the demonstration of vasculitic changes 

NEUROIMAGING Angiography  positive findings if focal or diffuse areas of

arterial stenosis, occlusion, dilatation, or beading were detected 

findings of ectasia and stenosis referred to as "beading", usually in the small arteries

sensitivity of angiography in biopsy proven PACNS cases was only 60 percent

Thus, a negative angiogram cannot be used to exclude the diagnosis of PACNS.

Brain and leptomeningeal biopsy 

REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROMES 

 group of disorders linked by prolonged but reversible vasoconstriction of the cerebral arteries 

severe, acute-onset headaches Ischemic stroke and/or hemorrhage associated

with reperfusion may occur in the setting of RCVS. pheochromocytoma and poorly-controlled

hypertension can also be associated with cerebral vasospasm and clinical presentations that mimic PACNS.

RCVS AND PACNS Symptom onset Clinical setting  Reversibility of angiographic findings  Cerebral spinal fluid (CSF)

SYSTEMIC VASCULITIS INVOLVING THE BRAIN  

systemic vasculitides, connective tissue disease (CTD),

sarcoidosis, infections, and lymphoproliferative diseases.

INFECTIOUS CAUSES 1. VZV -associated cerebral angiitis affects older age groups disease tends to be more localized Cerebral angiographic findings of segmental,

unilateral involvement of the vessels in the distribution of the middle cerebral artery/ICA

Diagnosis -higher antibodies levels of VZV in the CSF than in the serum

positive VZV PCR in the CSF

(35%) of pathologic findings of AIDS-associated CNS disease demonstrate encephalitis, leptomeningitis, and/or vasculitis,

Treponema pallidum – neurosyphilis most common in patients with HIV infections Meningitis and meningovascular disease are

the usual manifestation. May present as stroke

CNS vasculitis associated with hepatitis C virus (HCV) without underlying cryoglobulinemia

SYSTEMIC VASCULITIDES AFFECTING CNS Temporal Arteritis Takayasu s Arteritis Wegener Granulomatosis Henoch Scholein Purpura Polyarteritis Nodosa

TEMPORAL ARTERITIS >50 years age .Women >men Transmural inflammation of arteries .intimal

hyperplasia Branches of ECA – sup temporal most common ICA ,Subclavian ,coronary and intracranial Systemic features fatigue, weight loss , anorexia - Headche (new onset )unilateral localised to

areas of scalp ,Jaw claudication,scalp tenderness -Neuropathy – Median nerve ,TIA and stroke

Cranial neuropathies – AION .23 % of cases Temporary or permanent blindness Posterior ciliary arteritis Diagnosis – anemia ,High Esr ,CRP Angiography – stenotic segments or complet

occlusions Biopsy – Transmural inflammation,occlusion Sensitivity – 70 % Treatment – Prednisolone -40 -80 mg /day >high dose

for a month then taper .50% by one month.1mg/month

POLYARTERITIS NODOSA Medium vessel vasculitis 40 -60 yrs . Asso - Hep B,C ,cryoglobulinemia Inflammation of PMN, Monocytes – Fibrinoid necrosis Most common neurologic manifestation –

Mononeuritis multiplex CNS- 20 % - 40 %.diffuse

encephalopathy ,focal ..infarcts in spinal cord ,brainstem.Rarely ICH,

Optic neuropathy (AION) CNS abnormalities are late -after systemic signs and

PN

Diagnosis – Clinical Multisystem involvement –Skin ,PN,

Renal ,GIT Fever ,weight loss ,anemia raised ESR Angiography – may show saccular or

fusiform aneurysms Treatment – Systemic steroids with

cytotoxic agents – cyclophosphamide azthioprine

TAKAYASU S ARTERITIS 10 -30 yrs of age .women more commonr ,fatigue ,anoreixa Aorta and its branches innominate,common

carotid ,subclavian ,abdominal aorta ,celiac ,mesentric Symptoms – Acute stage – low grade fever Stage of acute inflammation – Vascular Bruits ,diminished

pulses,hypertension Chronic phase- Claudication ,ischemic ulcers Neurologic – Headche ,syncope blurred vision . DIAGNOSIS –Arteriography – occlusion or dilatation/Stenosis

aneurysm of entire aorta or its primary branches TREATMENT – Prednisolone 1mg/kg /d for 3 months –taper In unsuccesful cases cyclophosphamide ,MTX

WEGNER S GRANULOMATOSIS More in men 40 yrs Small and medium sized vessels Necrotizing granulomatous lesion in upper ,lower

respiratory tract , Kidneys 50 % develop neurologic involvement Most have recurrent

mononeuropathies,mononeuritis multiplex, Cranial neuropathies II,VI,VII

Ischemic stroke ,encephalopathy ,granulomatous basilar meningitis , pachnymenigitis – less frequently

Diagnosis –Clinical picture with c-ANCA Radiographically confirmed vasculitis of

the CNS in Wegener’s granulomatosis is rare, because the small vessel

MR findings – Dural thickening and enhancement hyperintense brainstem signals

Treatment – corticosteroids plus cyclophosphamide/azathioprine

BEHCET S DISEASE Oral ulcers ,Genital ulcers and

Uveitis,Skin finding ,(folliculitis and erythema nodosum ),Thrombophlebitis

Neurologic involvement occurs in 6-10 %

CONNECTIVE TISSUE DISORDERS CTDs that can involve the CNS include Sjogren’s syndrome, rheumatoid

arthritis, mixed CTDs, and dermatomyositis

NEUROLOGIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS

seen in 10 to 80 percent of patients  Direct involvement of CNS Secondary to complications of

disease /Treatment

PATHOPHYSIOLOGY initially thought to be due to vasculitis. vasculopathy is characterized by a small

to moderate perivascular accumulation of mononuclear cells, without destruction

Accelerated atherosclerosis may contribute to the risk of stroke

Autoantibodies  — The demonstration of a number of autoantibodies including APLA

Secondary factors  — Prospective studies suggest that from 50 to 78 percent of neurologic episodes are caused by secondary factors [ 2,35 ], including:

Infections associated with immunosuppressive therapy

Metabolic complications of other organ system failure, such as uremia

Hypertension Toxic effects of therapy (particularly corticosteroids)

COMMON CLINICAL SYNDROMES

REFERENCES CNS Vasculitis in Autoimmune Disease: MR Imaging

Findings and Correlation with Angiography -- AJNR 1999 20: 75-85

Central nervous system vasculitis - Rula A. Hajj-Alia and Leonard H. Calabreseb -, Cleveland Clinic, Cleveland, Ohio, USA ; Current Opinion in Rheumatology 2009, 21:10–18

Neurology Clinics –Neurology and systemic Disease . Feb 2010,vol28

Caplan’s – Stroke –A clinical approach 4th edition ,Chapter 11-Non atherosclerotic vasculopathies

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