cns vasculitis

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Interesting caseBy Dr Kishore.K .KFellow in Pediatric Neurology

Case senario6 months male baby, 4 th issue of NCM brought with h/o fever since 3 days Convulsions since 1 day (GTC of Lt UL & LL)Birth, developmental and family history normal.

Course in hospital

Child was put on ventilator for 10 daysHad raised ICT with conus (treated)Methyl prednisolone course givenLater was consious and irritable, vitals stable.Cranial nerves normal.Moves all limbs (power is 3-4/5)Tone increased (UL>LL), brisk reflexes.

MRI shows non enhancing focal areas showing restricted diffusion in the temporal and frontal lobes B/L.Subtle enhancement in basal cisternsB/L narrowing of ICA, MCA and ACAS/O basal meningitis with vasculitis


DWI - image

MR - angio

Differential diagnosisMoya moya disease (stroke)CNS vasculitisViral encephalitis

CNS VasculitisBy Dr Kishore.K .KFellow in Pediatric Neurology

Introduction CNS vasculitis refers to a spectrum of heterogeneous disorders characterized by inflammation of the blood vessels, including arteries and veins of all calibers.Which results in a variety of clinical neurologic manifestations related to ischemic and/or hemorrhagic parenchymal damage

IntroductionIf unrecognized and consequently untreated CNS vasculitis leads to permanent neurologic injury and disability.Thus it is important for accurate diagnosis and management of each one of the variant in this group of disorders.CNS vasculitis in children can occur as a primary disease that is isolated to the CNS or as a secondary manifestation of an underlying systemic condition

Classification1. Primary Referring to those patients with vasculitis isolated primarily to the brain, cord and their leptomeninges occurring in the absence of recognizable triggers or conditions2. Secondary Referring to where such associated conditions or co-factors are apparent. occurring as a result of an underlying systemic infectious, noninfectious immunologic, neoplastic, or other etiologyIt can be broadly classified into two major categories

Classification Primary Angiitis of the Central Nervous System (PACNS) (Unknown Immunopathogenesis)Granulomatous angiitis of the CNS (GACNS) Benign angiopathy of the CNS (BACNS)

Secondary CNS Vasculitis in Children

Secondary CNS VasculitisInfective (either direct infection or autoimmune mechanisms )Bacterial (eg-N.mening)Mycobacterial (TB)Spirochetal (Lymes, syphilis)Rickettsial (Rocky Mount spot fev)Fungal (aspergillosis, mucormycosis)Viral (HZV/VZV, HIV, hepatitis C)Parasitic (Toxoplasma gondii)Primarily immunologicSystemic vasculitis(ANCA) mediatedWegener granulomatosisMicroscopic polyarteritisChurg-Strauss syndromeDirect antibody attack mediatedKawasaki disease (antiendothelial antibodies)

Secondary CNS VasculitisImmune complex mediatedHS purpuraCryoglobulinemiaSerum sicknessUnknown immunopathogenesisTemporal arteritisTakayasu arteritisPolyarteritis nodosaCollagen vascular diseasesSLE, JRABehacets, SjorgensVascular injuryDissectionIrradiationDrugsAmphetaminesContraceptives

Pathophysiology CNS vasculitis is characterized by transmural inflammation of cerebral blood vessels of all types and sizes involving the endothelial lining and/or the cellular components of the vascular wall. The inflammatory responses may be triggered by microbial pathogens (antigen) or by altered host proteins (molecular mimicry)

Pathophysiology Vascular inflammation causes local hemodynamic derangements leading to luminal compromise, vasospasm, distal embolization arising from necrotic vascular endothelium.Perifocal tissue injury attributed to proinflammatory factors like NO, cytokines, cytotoxic lymphocytes, endothelins and proteases produced by the infiltrating inflammatory cells or by the injured brain vascular endothelial cells

Pathophysiology This results in damage of cerebral blood vessels and disruption of the BBB and local hemodynamic derangements.The main pathologic correlate of vasculitis-related neurologic dysfunction is hypoxic-ischemic injury of the CNS parenchyma.

Primary Angiitis of the CNSPrimary angiitis of the CNS is a rare disease characterized by vasculitis of small and medium arteries in the brain and spinal cord. Presentations are highly variable, but the triad of headache, organic brain syndrome and multifocal neurologic deficits is most suggestive.

Clinical featuresA broad spectrum of clinical presentation ranging fromInsidious onset of headacheFocal neurological deficitCognitive decline or behavior changesAcute stroke like Seizures or status epilepticus.Optic neuritis(B/L) and cranial nerve palsies

Differential diagnosisPatients with CNS Vasculitis are often misdiagnosed initially.StrokeViral encephalitisTuberculosisSevere migraine headachesMultiple sclerosisTumor

Because many diseases may mimic CNSV and because the treatments for CNSV are potentially dangerous, it is essential to confirm the diagnosis before starting treatment. Nearly all patients therefore require either an angiogram or biopsy of the brain. Tests such as magnetic resonance imaging (MRI) studies and lumbar punctures (spinal taps) are also helpful in the workup of a patient with possible CNSV

Vasculitides Affecting the Nervous SystemDiseaseSystemic ManifestationsCharacteristic Laboratory FeaturesNeurologic SymptomsChurg-Strauss syndromeLungs primarilyPeripheral hypereosinophiliaPeripheral neuropathyCogan syndromeInterstitial keratitis, aortic valvulitisCerebrospinal fluid pleocytosisProgressive deafness, vestibular abnormalities, encephalopathyTakayasu diseaseAortic arch affected predominantly, female individuals affected mainlyElevated erythrocyte sedimentation rateVascular accidents, vision lossTemporal arteritisIn pediatric population affects temporal arteries and external carotidsElevated serum levels of elastin peptideHeadaches, painful nodule of superficial temporal artery, vision lossWegener granulomatosisSmall vessels of respiratory tract and kidneysElevated erythrocyte sedimentation rate, thrombocytosisPeripheral neuropathyMixed connective tissue diseaseSkin lesions of dermatomyositis, sclerodermaAntibodies directed at the ribonuclease-sensitive component of extractable nuclear antigenHeadache, seizures, aseptic meningitis

How to diagnose CNS vasculitisCSF analysis not diagnostic but helps in confirming CNS inflammation/infectionPatients may have mildly elevated ESR, CRP, WBC counts and C3 complement and IgG levels.Neuroimaging MRI, MRAAngiographyBrain biopsy

Neuroimaging MRI brain classically reveals areas of acute ischemia in a vascular distribution in large-medium vessel disease.These lesions are typically multifocal in progressive disease and unilateral in non-progressive disease involving gray and white matter. MRI in small vessel disease shows lesions that may be bilateral or unilateral, multifocal and involve both gray and white matter

This is T2-weighted MRI showing involvement of bilateral basal ganglia nuclei, thalami, subcortical and deep white matter, greater on the right.

The distribution of abnormality is consistent with both anterior and posterior circulation involvement.

MRSAMagnetic resonance angiography and conventional angiography provide detailed assessment of the vasculature.The classic angiographic findings in CNSV include beading (alternating dilatations and narrowings of blood vessels)And other irregularities within blood vessels like tortuosity, stenosis, and occlusion of the vessels.

MRA (A) demonstrates bilateral proximal vessel stenoses of the middle carotid artery (arrows).The corresponding conventional angiography of the right middle cerebral artery (B) demonstrates proximal (arrow) and distal (open circle) vessel stenoses

Brain biopsyBiopsy of the brain and leptomeninges.The presence of an inflammatory process and fibrinoid necrosis in the walls of small veins and arterioles remains the gold standard for the diagnosis of primary angitis of CNS.But brain biopsy also has pitfalls and should therefore be strongly considered in a child with typical clinical features and suggestive MRI lesions but normal angiography.

Many diseases may mimic CNS vasculitis and because the treatments for CNS vasculitis are potentially dangerous.It is essential to confirm the diagnosis before starting treatment.Nearly all patients therefore require either an angiogram or biopsy of the brain.

Treatment Immunosuppressive through methyl prednisolone and/or cyclophosphamideLMWH/warfarin Low dose aspirin in pts with no complications


Moyamoya diseaseMoyamoya disease was first described in Japan in 1957 (Suzuki)Moyamoya is a Japanese word meaning puff of smokeIt is a chronic progressive non-atherosclerotic, non-inflammatory occlusive arteriopathy of unknown cause

EpidemiologyThe annual incidence of MM is 0.35 to 0.94 per 100.000 population.The prevalence of MM is 3.2 to 10.5 per 100.000 population (Japan)Asian: 0.28 per 100.000 population Age distribution in child: 10 14 yr oldMale/Female: 1/1.8 to 1/2.2Etiology unknownFamilial occurrence of appr 10% of casesFamilial MM has been linked to chromosomes 3P24,2-P26, 6Q25,12P12, and 17Q25

PathophysiologyCharacterized by progressive bilateral stenosis of distal ICA extending to proximal ACA and MCA With involvement of circle of Willis and development of extensive collateral network (parenchymal, leptomeningeal or transdural) at the base of the brain like a puff of smoke. Intracranial aneurysms are seen, especially in posterior circulation.

CLINICAL FEATURESTransient ischemic attack (TIA)Cerebral infarctionRepeated ischemic or hemorrhagic strokeSeizures Headache, movement disorders, mental deteriorationIn children, symptomatic episode