Young Stroke Etiology and Clinical Approach

Dr Prakash Harischandra Moderated by Dr B.P Shelley MD.DM Prof and H D !eurology" Yenepoya #ni$ersity

 %ndia is silently &itnessing a stroke epide'ic. (here is an urgent need to de$elop a national progra' to&ards )*ighting Stroke+. (his progra' should be specific to our national needs. %n order to reco''end on &ho should lead an %ndian fight, stroke progra'

 Stroke in young adults is surprisingly common. Young stroke is stroke occurring bet&een -. and /. years of age E$en after e0tensi$e in$estigations" the cause 'ay re'ain elusi$e in 12,.23 cases Prognosis depends on the underlying factor The differential diagnosis for potential etiologies is broader than that for older adults.

Etiology
subarachnoid hae'orrhage and intracranial hae'orrhage in young adults 4/25..36 atherosclerosis re'ains an i'portant risk factor cardioe'bolic stroke is 'ore co''on a'ong younger patients 4-.57.3 of cases6 e0tracranial artery dissection 4151.3 of cases6 'igraine 4up to 123 ral contracepti$e use has been i'plicated in up to 83 of cases of young stroke in so'e populations

antiphospholipid antibody syndro'e 4.5-23 of cases6 Sickle cell disease" in &hich 9 to -23 of affected indi$iduals e0perience strokes before the age of 12 rheu'atic $al$ular heart disease are i'portant 7.3 of cases" the underlying etiology re'ains unclear

 Causes of %sche'ic Stroke in Young Adults Eur !eurol 1229:.9;1-151-8

%ndian stroke studies perspecti$es

(able 7; Pro<ection of nu'ber of cases of stroke in %ndia Place Age group No. of patients Aim of the study !ayak et al -==9>.? (ri$andru' -.5/. years -99 Clinical features and risk factors @ipska et al 1229>A? (ri$andru' -.5/. years 1-/ Bisk factors BaCdan et al -=8=>9? Bural Dash'ir E-. years" subgroup -.57=" /25/= years =- Pre$alence study Abraha' et al -=92>8? Fellore All age groups -/9 Pre$alence study Das et al 1229>=? Dolkata All age groups" subgroup G/2 years" and E/2 years 1/9 Pre$alence and incidence study Dalal et al 1228>-2? Mu'bai E1. years" subgroups 1.57/ and 7.5 // years /.A %ncidence study

Ischemic stroke

Common Cardioe'bolic Bheu'atic heart disease Bacterial endocarditis Prosthetic $al$es Cortical $enous thro'bosis Pregnancy Post partu' Dehydration Arterial dissection He'atological causes %nfections Atherosclerotic $ascular Disease

Fasculitis Polyarterits nodosa (akayasuHs arteritis @upus erythe'atosus Iiant cell arteritis Pri'ary angitis of central ner$ous syste' JegnerHs granulo'atosis Miscellaneous ME@AS syndro'e CADAS%@

Hemorrhagic stroke Venous thrombosis

Arterio $enous 'alfor'ations 4AFM6 Saccular aneurys's Moya Moya syndro'e Arteritis 4Septic arteritis and 'ycotic aneurys's6 Bleeding disorders Anticoagulants thers Cocaine and other substance abuse Fasculitis %ntracerebral tu'ors
Pregnancy Post partu' period Dehydration ral contracepti$e use Prothro'botic states Bed blood cell disorders %ntracranial infections BechetHs disease Connecti$e tissue Diseases AP@AS

Haemorrhagic Stroke
(his issue has not been &ell e0a'ined a'ong young Asians" apart fro' a study in !orth %ndia that did not find an increased proportion of hae'orrhagic to total strokes 4i.e." only -/3 of cases &ere hae'orrhagic6 >-1-? co'pared to Jestern countries 4&ith reported proportions in the range of /25..3 of all young strokes (here is no& a con$incing body of e$idence to suggest a high pre$alence of underlying cerebro$ascular abnor'alities a'ong patients e0periencing %CH or SAH in association &ith cocaine and other drug abuse

%!(BACEBEBBA@ HEM BBHAIE

Fascular 'alfor'ations %ntracranial tu'ours Bleeding disorders" anticoagulant and fibrinolytic treat'ent Cerebral a'yloid angiopathy Iranulo'atous angitis of the central ner$ous syste' He'orrhagic infarction (rau'a

Fascular 'alfor'ations
(he $ascular 'alfor'ation 'ay be
Saccular or 'ycotic aneurys's Arterio$enous 'alfor'ations Ca$ernous angio'as

%ntracerebral he'orrhages caused by s'all lesions are characteriCed by

@ocated in the subcortical &hite 'atter He'ato'a is s'aller Sy'pto's de$elop slo&ly #sually subarachnoid he'orrhage seen Younger patients &ith fe'ale preponderance

MB% or histological e0a'ination needed for diagnosis

 Aneurys's
n the basis of 'orphology" aneurys's are classified as saccular" fusifor' or dissecting.

Saccular aneurys's are 'ore often acKuired than congenital (hey tend to occur at the branching points in the circle of Jillis and pro0i'al cerebral arteries 4/23 in anterior co''unicating artery6. #sually presents as SAH: less co''only as %CH" space occupying lesion producing co'pression" seiCures" e'bolis' fro' thro'bus" hydorocephalus

 Associations of intracranial saccular aneurys's

Polycystic kidney disease *ibro'uscular dysplasia Cer$ical artery dissection Coarctation of the aorta %ntracranial $ascular 'alfor'ations MarfanHs syndro'e Ehler,Danlos syndro'e Pseudo0antho'a elasticu' Hereditary he'orrhagic telangiectasia Moya'oya syndro'e DlinefelterHs syndro'e Progeria

(ypes of aneurys's

Click to edit Master te0t styles Second le$el (hird le$el *ourth le$el *ifth le$el

 Arterio$enous 'alfor'ations
Abnor'al fistulous connections bet&een one or 'ore hypertrophied feeding arteries and dilated draining $eins Diagnosis suspected in Ct scan. !on, enhanced scan sho&s calcification and non,specific hypo, or hyperdensity. Contrast C( scan sho&s dilated $eins of large 'alfor'ations. MB% or angiogra' 'ay be needed to confir' diagnosis.

Click to edit Master te0t styles Second le$el (hird le$el *ourth le$el *ifth le$el

 Ca$ernous he'angio'a
Detected using MB% Sho&s a central nidus of irregular bright signal intensity 'i0ed &ith 'ottled hypointensity" surrounded by a peripheral hypointense ring He'osiderin deposits in periphery due to prior bleeding #sually single lesions Predo'inantly supratentorial" presents as seiCures

rare causes of nonatherosclerotic arteriopathies

Cerebral $enous thro'bosis is an unco''on cause of young stroke 4i.e." G-3 of cases SneddonHs syndro'e: Moya'oya disease 'itochondrial 'yopathy" encephalopathy" lactic acidosis" and stroke,like episodes 4ME@AS6: cerebral autoso'al do'inant arteriopathy &ith subcortical infarcts and leukoencephalopathy 4CADAS%@6: $asculitis: prior che'oradiotherapy: H%F infection

HYPEBC AI#@AB@E D%S BDEBS

Pri'ary hypercoagulable states AP@AS
Antithro'bin %%% deficiency Protein C deficiency Protein S deficiency Acti$ated protein C resistance Prothro'bin I121-2 'utation Afibrinogene'ia Hypofibrinogene'ia Hypoplas'inogene'ia Plas'inogen acti$ators deficiency @upus anticoagulant and anticardiolipin antibodies

 Secondary hypercoagulable states

Malignancy PregnancyLPuerperiu' ral contracepti$e useL ther hor'onal treat'ents $arian hypersti'ulation syndro'e

!ephrotic syndro'e Polycythe'ia $era Essential thro'bocythe'ia Paro0ys'al nocturnal he'oglobinuria Diabetes 'ellitus Heparin induced thro'bocytopenia Ho'ocysteinuria Sickle cell disease (hro'botic thro'bocytopenic purpura Che'otherapeutic agents

 %nherited thro'bophilias suspected if

Becurrent episodes of deep $enous thro'bosis Becurrent pul'onary e'boli *a'ily history of thro'botic e$ents #nusual sites of $enous 4'esenteric" portal or cerebral6 or arterial thro'bosis (hro'botic e$ents in childhood" adolescence or early adulthood

More than half of the e$ents occur spontaneously Bisk is increased &ith additional risk factors like pregnancy" surgery" trau'a or CP

APPR ACH ! A " #N$ PA!%IN! &I!H S!R '%

 History
Presentation si'ilar 4BLo 'ultiple sclerosis and 'alignancy6 Presence of risk factors HLo drug intake" he'atologic disorders" cardiac disease" $asculitis" infections" radiation

Physical e0a'ination cular findings

Corneal arcus 4hypercholesterole'ia6 Corneal opacity 4*abryHs disease6 @isch nodules" optic atrophy 4!eurofibro'atosis6 @ens sublu0ation 4MarfanHs" ho'ocystinuria6 Betinal peri$asculitis 4sickle cell disease" syphilis" connecti$e tissue disease" %BD6 Betinal occlusions 4e'boli6 Betinal angio'a 4ca$ernous 'alfor'ation6 Ha'arto'a 4tuberous sclerosis6 Both spots 4infecti$e endocarditis6

 Der'atologic e0a'ination
Splinter he'orrhages" slerHs nodes" Mane&ay lesions 4endocarditis6 Nantho'a 4hyperlipide'ia6 CafO,au,lait spots" neurofibro'as 4neurfibro'atosis6 Purpura 4coagulopathy6 Capillary angio'ata 4ca$ernous 'alfor'ation6

Cardio$ascular e0a'ination

Pre$ention of Stroke
Control high blood pressure Pre$ent heart disease Stop cigarette s'oking BecogniCe signs of (%A Beduce blood cholesterol le$els

Stroke Bisk *actors (hat Can Be (reated

HypertensionLHigh Blood Pressure Heart Disease Cigarette S'oking (ransient %sche'ic Attacks Diabetes Ele$ated Blood CholesterolL@ipids Asy'pto'atic Carotid Bruits

Stroke Bisk *actors @ess Jell, Docu'ented

Ieographical @ocation Socioecono'ic *actors E0cessi$e Alcohol %ntake Certain Dinds of Drug Abuse

Young stroke in Jo'en

@ess co''on causes of stroke that are 'ore co''on in &o'en include syste'ic lupus erythe'atosus 4S@E6" antiphospholipid antibody syndro'e 4AP@AS6" central $enous thro'bosis 4CF(6" re$ersible cerebral $asoconstriction syndro'e 4BCFS6" Susac syndro'e" (akayasuHs arteritis" Moya'oya disease" SneddonHs syndro'e" and fibro'uscular dysplasia. %n addition" &o'en are particularly susceptible to stroke in the puerperiu'

(igraine and Stroke

The weight of evidence from case-control studies suggests that migraine, particularly migraine with aura, is associated with an increased risk of ischaemic stroke in young women under 45 years of age . The pathophysiological mechanism underlying this remains unclear. For one, it is difficult to tease out the relative contribution of cases in which migraine precedes ischaemia (i.e., in which stroke occurs secondary to cerebral hypoperfusion during the aura phase , comprising a migrainous infarct, from cases in which migraine with aura is e!perienced secondary to ischaemia. True migrainous infarcts are probably rare and tend to affect the posterior circulation . "t is also possible that young patients with a history of migraine have an increased incidence of stroke due to a shared underlying etiology which predisposes to both. #igraine as a risk factor for future ischaemic stroke seems to apply mostly to young women, and the relative risk may be as high as $-fold in those who e!perience migraine with aura

Migrainous infarction
Migraine co''only affects &o'en and starts during childhood or adolescence Bare association of 'igraine and ische'ic stroke seen in young &o'en particularly belo& 7. years of age. Pathogenesis is not co'pletely kno&n Migrainous infarctions are 'ostly cortical and in$ol$e PCA territory #sually there is gradual build up of unilateral throbbing headaches &ith $isual pheno'ena occurring in both $isual fields si'ultaneously" in one of &hich the $isual loss beco'es per'anent.

 Diagnostic critreria
Definite diagnosis of 'igraine &ith aura in the past ne or 'ore of the 'igrainous aura sy'pto's 'ust be present and not fully re$ersed &ithin 9 days fro' the onset" &ith neuroi'aging confir'ation of ische'ic infarction

Clinical 'anifestations should be those typical of pre$ious attacks ther causes of infarction should be e0cluded

Definite 'igrainous infarction 5 all criteria satisfied Possible 5 only so'e criteria satisfied %ncreases risk for recurrent stroke

-st @ine in$estigations

Co'puted to'ographyLMagnetic resonance i'aging of brain Co'plete blood count &ith differential and platelet count Prothro'bin ti'e" %!B" acti$ated partial thro'boplastin ti'e Blood glucose" seru' electrolytes" blood che'istries @ipid profile Erythrocyte sedi'entation rate Pregnancy test 4in fe'ales6 Chest roentgenogra' Electrocardiogra' (ransthoracic echocardiography Duple0 scanning of the cer$icocephalic $essels

1nd @ine %n$estigations

(ransesophageal echocardiography Magnetic resonance angiography and $enography Cerebral angiography Anticardiolipin antibody Antinuclear and other autoantibodies 4A!CA" Anti,SSA" Anti, SSB" Bheu'atoid factor6 Protein C and S" antithro'bin %%%" acti$ated protein C resistance He'oglobin electrophoresis and sickle cell testing Seru' ho'ocysteine H%F serology Serologic tests for syphilis BloodLcerebrospinal fluid lactate *actor F @eiden 'utation

7rd @ine of %n$estigations

ther in$estigations 4depending on clinical findings or abo$e test results6

Holter 'onitoring %n$estigations for coronary artery disease *ibrin degradation products D,di'er assay Seru' angiotensin con$erting enCy'e assay Plas'a lactate and pyru$ate le$el

(reat'ent
(he 'anage'ent in the acute stage of stroke is si'ilar to that of usual atherosclerotic CFD *urther 'anage'ent depends upon the underlying cause Prognosis is usually 'uch better than strokes in older indi$iduals Chance of recurrence high if the pri'ary cause is not corrected

Diagnosis, Management, and Prognosis of ICH

(anagement depends on si)e and location
%n acute phase" 'ass effect far greater than in large cerebral infarction" so greater risk of herniation and death %n chronic phase" prognosis for sur$i$ing patients 'uch better than &ith ische'ic stroke

(rau'a
Blunt or penetrating trau'a can produce arterial dissection" rupture" thro'bosis" pseudoaneurys' for'ation and AF fistula. Can occur during sports" $iolent coughing" $igorous nose blo&ing" neck 'anipulation" anesthesia ad'inistration etc. Cer$ical rotation or e0tension co'presses cer$ical carotid artery against trans$erse processes of upper cer$ical $ertebra Angiography and surgical repair is the treat'ent.

 (reat'ent
Anticoagulation &ith heparin should be started follo&ed by &arfarin therapy for 75 A 'onths Antiplatelet therapy Surgical therapy indicated in the presence of pseudoaneurys's and if there is no response to 'edical treat'ent Anticoagulation should be &ithheld in intracranial dissection since there is a risk of subarachnoid hae'orrhage

Conclusion
stroke in the young re%uires a different approach to investigation and management than stroke in the elderly given differences in the relative fre%uencies of possible underlying causes. &aemorrhagic stroke is common, and vascular imaging is recommended given a high fre%uency of underlying vascular anomalies. "t is also important to e!plore the possibility of illicit drug use in these cases. 'ith regard to ischaemic stroke, the increased fre%uency of dissection mandates a high inde! of suspicion for imaging the e!tracranial and intracranial vessels. 'hilst the commonest cause of cardioembolic stroke in the elderly is atrial fibrillation, in a young patient transoesophageal echocardiography looking for the presence of a patent foramen ovale ( an atrial septal aneurysm will have a higher yield. )ne must not forget, however, that atherosclerosis still contributes to a large proportion of stroke in young patients and likely e!plains at least some of the ethnic differences noted in the incidence of stroke, emphasi*ing the need for aggressive risk factor management. This, as well as differences in the prevalence of other causative etiologies, such as rheumatic fever and infection, combined with a younger background population age distribution, may contribute to an increased

Beferences
Ann %ndian Acad !eurol. 12-2 Man,Mar: -74-6; 18571. Stroke program for India !ishant D. Mishra and Satish F. Dhadilkar !eurol %ndia. 12-2 May,Mun:.8476;7/7,.2. doi; -2./-27L2218,788A.A..7-.Stroke in young* an Indian perspecti+e.Prasad D" Singhal DD. Principles of neurology 5 Ada's