cns vasculitis
TRANSCRIPT
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