cns vasculitis

Interesting case

By Dr Kishore.K .K

Fellow in Pediatric Neurology

Case senario 6 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 days Had raised ICT with conus (treated) Methyl prednisolone course given Later 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 cisterns

B/L narrowing of ICA, MCA and ACA

S/O basal meningitis with vasculitis

MRI T1 MRI T 2

DWI - image

MR - angio

Differential diagnosis Moya moya disease (stroke) CNS vasculitis Viral encephalitis

CNS Vasculitis

By 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

Introduction If 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

Classification

1. Primary Referring to those patients with vasculitis isolated

primarily to the brain, cord and their leptomeninges occurring in the absence of recognizable triggers or conditions

2. 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 etiology

It can be broadly classified into two major categories

Classification

Primary Angiitis of the Central Nervous System (PACNS) (Unknown Immunopathogenesis)

1. Granulomatous angiitis of the CNS (GACNS)

2. Benign angiopathy of the CNS (BACNS)

Secondary CNS Vasculitis in Children               

Secondary CNS Vasculitis Infective (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) mediated Wegener

granulomatosis Microscopic polyarteritis Churg-Strauss

syndrome Direct antibody

attack mediated Kawasaki disease

(antiendothelial antibodies)

Secondary CNS Vasculitis Immune complex

mediated HS purpura Cryoglobulinemia Serum sickness

Unknown immunopathogenesis Temporal arteritis Takayasu arteritis Polyarteritis nodosa

Collagen vascular diseases SLE, JRA Behacets,

Sjorgens Vascular injury

Dissection Irradiation

Drugs Amphetamines Contraceptives

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 CNS Primary 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 features A broad spectrum of clinical

presentation ranging from Insidious onset of headache Focal neurological deficit Cognitive decline or behavior changes Acute stroke like Seizures or status epilepticus. Optic neuritis(B/L) and cranial nerve

palsies

Differential diagnosis Patients with CNS Vasculitis are often

misdiagnosed initially. Stroke Viral encephalitis Tuberculosis Severe migraine headaches Multiple sclerosis Tumor

How to diagnose CNS vasculitis

CSF analysis – not diagnostic but helps in confirming CNS inflammation/infection

Patients may have mildly elevated ESR, CRP, WBC counts and C3 complement and IgG levels.

Neuroimaging – MRI, MRA Angiography Brain 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.

MRSA Magnetic 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.

1. MRA (A) demonstrates bilateral proximal vessel stenoses of the middle carotid artery (arrows).

2. The corresponding conventional angiography of the right middle cerebral artery (B) demonstrates proximal (arrow) and distal (open circle) vessel stenoses

Brain biopsy Biopsy 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 cyclophosphamide

LMWH/warfarin Low dose aspirin in pts with no

complications

THANK YOU

Moyamoya disease

Moyamoya disease was first described in Japan in 1957 (Suzuki)

Moyamoya is a Japanese word meaning ‘puff of smoke’

It 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 episodes of ischemia

may be triggered by exercise, crying, coughing, straining, fever or hyperventilation

NEUROIMAGINGCT scan: infarction may involve cortical and

subcortical regions. In the patients with parenchymal

hemorrhage, cranial CT usually show a high density area indicating blood in the basal ganglia, thalamus and/or ventricular system

CTA: can also demonstrate the abnormal vessels of MM.D, including the collateral MM vessels in the basal ganglia

MRI: acute ischemic brain lesions, in some cases, dilated collateral vessels

MRA,

The diagnosis of MM.D is based upon the characteristic angiographic appearance of bilateral stenoses affecting the distal internal carotid arteries & proximal circle of willis vessels, along with the presence of prominent basal collateral vessels

MCA block with multiple collateral moyamoya vessels

(c) MRI Diffusion-weighted image shows bright signal of left insular and temporal cortex indicating cytotoxic edema. (d) MR-angiogram shows poor representation of distal branches of left middle cerebral artery .

MANAGEMENTAcute management is mainly symtomatic and

directed towards reducing elevated intracranial pressure, improving cerebral blood flow, and controlling seizures.

In patients with intracerebral hemorrhage, ventricular drainage, and/or hematoma, removal is often required.

There is no curative treatment for MM.DSecondary prevention for patients with

symptomatic MM syndrome is largely centered on surgical revascularization techniques(EDAS) and

Aspirin after surgery and in asymptomatic children

Thank You