STROKE IN THE YOUNG

1. STROKE IN THE YOUNG Chair : Prof. Dr. B. Jayakumar

2. INTRODUCTION • Young stroke is stroke occurring between 15 and 45 years of age • Differential diagnosis for potential etiologies is broader • Even after extensive investigations, the cause may remain elusive in 20-50% cases • Prognosis depends on the underlying factor

3. Responsible for about 5% of all cases of stroke • Incidence is much higher in developing countries like India. • Above the age of 30 years stroke is more common in males whereas below that female predominance is seen.

4. Etiology of young stroke ISCHEMIC • Large artery disease • Premature atherosclerosis • Dissection (spontaneous or traumatic) • Inherited metabolic diseases (homocysteinuria, Fabry’s disease, pseudoxanthoma elasticum, MELAS syndrome) • Fibromuscular dysplasia • Vasculitis • Moyamoya disease • Radiation • Toxic (drug induced)

5. Small vessel disease • Vasculopathy (infectious, non infectious, microangiopathy) • Cardioembolic disease • Rheumatic heart disease • Congenital heart disease • Arrhythmias • Bacterial and non-bacterial endocarditis • Mitral valve prolapse • Patent foramen ovale • Atrial myxoma • Cardiac surgeries and procedures

6. Hematologic disease • Sickle cell disease • Leukemia • Hypercoagulable states (antiphospholipid antibody syndromes, deficiency of antithrombin III or protein S or C, resistance to activated protein C, increased factor VIII) • Disseminated intravascular coagulation • Thrombocytosis • Polycythemia vera • Thrombotic thrombocytopenic purpura • Venous occlusion • Migraine

7. HEMORRHAGIC • Subarachnoid hemorrhage • Cerebral aneurysm • Intraparenchymal hemorrhage • Arteriovenous malformation • Neoplasm (primary central nervous system, metastatic, leukemia) • Hematological disorders (sickle cell disease, neoplasm, thrombocytopenia) • Moyamoya disease • Drug use (warfarin, amphetamines, cocaine, phenylpropanolamine) • Iatrogenic (peri-procedural)

8. Premature atherosclerosis • Premature atherosclerosis is the single most important cause of stroke as age advances • Incidence is 7-30% below the age of 50 years. • It is presumed in all undiagnosed cases with more than two risk factors.

9. Risk factors for atherosclerosis • Male sex • Systemic hypertension • Diabetes mellitus • Dyslipidemia (low HDL cholesterol, hypertriglyceridemia) • Cigarette smoking • Alcohol abuse • Ischemic heart disease • Recent infection • Oestrogen related stroke including oral contraceptives

10. NON ATHEROSCLEROTIC VASCULOPATHIES • Cervicocephalic arterial dissections • Traumatic cerebrovascular disease • Radiation-induced vasculopathy • Moyamoya disease • Fibromuscular dysplasia • Vasculitis • Migrainous infarction

11. Cerviocephalic arterial dissections • Subintimal penetration of blood with subsequent longitudinal extension of the hematoma between its layers • Common sites • Extracranial segment of internal carotid artery • Extracranial vertebral arteries • Recurrence rate is 1%, more in young and in those with positive family history

12. Causes • Spontaneous • Secondary • Blunt or penetrating trauma • Fibromuscualar dysplasia • Ehlers’ Danlos syndrome type IV • Marfan’s syndrome • Pseudoxanthoma elasticum • Coarctation of aorta • Menke’s disease • α1-antitrypsin deficiency • Cystic medial degeneration • Osteogenesis imperfecta • Adult polycystic kidney disease • Homocystinuria • Luteic arteritis

13. Dissection results in ischemic symptoms due to arterial occlusion or secondary embolism • Diagnosis • Arteriography – Elongated, irregular, narrow column of dye, ‘string sign’ • High resolution MRI • MR angiography • CT angiography • Doppler ultrasound of the neck especially for carotid diseection

14. Internal carotid artery dissection

16. Treatment • Anticoagulation with heparin should be started followed by warfarin therapy for 3–6 months • Antiplatelet therapy • Surgical therapy indicated in the presence of pseudoaneurysms and if there is no response to medical treatment • Anticoagulation should be withheld in intracranial dissection since there is a risk of subarachnoid haemorrhage

17. Trauma • Blunt or penetrating trauma can produce arterial dissection, rupture, thrombosis, pseudoaneurysm formation and AV fistula. • Can occur during sports, violent coughing, vigorous nose blowing, neck manipulation, anesthesia administration etc. • Cervical rotation or extension compresses cervical carotid artery against transverse processes of upper cervical vertebra • Angiography and surgical repair is the treatment.

18. Radiation vasculopathy • Accelerated atherosclerosis occurs especially in those with dyslipidemia • Radiation results in damage to the endothelial cells producing complications months to years later • Lesions occur at unusual sites • The amount of damage depends on • Radiation dose • Age at the time of therapy

19. Moyamoya disease • Moyamoya is a Japanese word meaning ‘puff of smoke’ • It is a chronic progressive non-amyloid non-atherosclerotic, non-inflammatory occlusive arteriopathy of unknown cause. • Characterized 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.

20. Pathology • Fibrocellular intimal thickening, smooth muscle proliferation and increased elastin accumulation leading to stenosis of suprasellar intracranial ICA • Thinning of media with tortuous and multilayered internal elastic lamina • Clinical features • TIA, seizures, headache, movement disorders, mental deterioration, cerebral infarction , intracranial hemorrhage • TIAs are precipitated by crying, blowing and hyperventilation

21. Bimodal age distribution is seen • First decade – ischemic events more common • Fourth decade – Hemorrhagic commoner • Diagnosis is established by arteriography • Suzuki’s six arteriographic changes • Stenosis of carotid fork • Initial appearance of moyamoya vessels at the base of brain • Intensification of moyamoya vessels • Minimization of moyamoya vessels • Reduction of moyamoya vessels • Disappearance of the vessels

22. MCA block with multiple collateral moyamoya vessels

23. Treatment • Ischemic Moyamoya • Platelet antiaggregants, vasodilators, calcium channel blockers and corticosteroids have been tried. • Anticoagulants are not useful • Surgical revascularization techniques like superficial temporal to MCA anastamosis have produced good results. • Hemorrhagic Moyamoya • No established therapy to prevent rebleed

24. Fibromuscualar dysplasia • Segmental, non-atheromatous, dysplastic, non-inflammatory angiopathy • Commonly affects young and middle aged women • White race more affected • Etiology • Unknown • May be related to immunological mechanisms, estrogenic effects, α1-antitrypsin deficiency • Familial association seen

25. Renal arteries most commonly involved. Cervicocephalic involvement in less than 1% • Most often extracranial carotids involved • Bilateral in two thirds • Four histologic types • Intimal hyperplasia • Medial hyperplasia • Medial fibroplasia: Commonest • Perimedial dysplasia • Most of the patients are asymptomatic

26. Diagnosis • Cervical angiography • ‘String of beads’ appearance in medial fibroplasia • Treatment • Benign natural history • Platelet antiaggregants used • Surgical intervention seldom needed

28. Types of fibromuscular dysplasia

29. Cerebral autosomal dominant arteriopathy with subcortcal infarcts and leucoencephalopathy (CADASIL) • Familial nonarteriosclerotic, nonamyloid microangiopathy • Characteristic features • Migraine with aura (CADASILM) • Recurrent subcortical ischemic strokes from mid-adulthood • Pseudobulbar palsy, cognitive decline, subcortical dementia • Early white matter hyperintensities in MRI

30. Genetics • Missense mutations or small deletions in Notch 3 gene on chromosome 19q12 • Codes for transmembrane receptor Notch 3 • Granular eosinophilic material deposited in arterial walls, including dermal arteries

31. Binswanger disease • Widespread degeneration of cerebral white matter of vascular causation • Associated with hypertension, atherosclerosis of small blood vessels and multiple strokes. • Radiological picture of leucoareosis – less intense appearance of periventricualar tissues in chronically hypertensive patients

32. Mitochondrial myopathy, lactic acidosis and strokes (MELAS) • Mitochondrial disorder which may manifest at any age,usually in childhood • Clinical features • Proximal myopathy, exercise intolerance • Recurrent migraine-type headaches • Hemiparesis, hemianopsia or cortical blindness • Precipitated by exercise or infection • Serum and CSF lactate concentrations are elevated

33. Migrainous infarction • Migraine commonly affects women and starts during childhood or adolescence • Rare association of migraine and ischemic stroke seen in young women particularly below 35 years of age. • Pathogenesis is not completely known • Migrainous infarctions are mostly cortical and involve PCA territory • Usually there is gradual build up of unilateral throbbing headaches with visual phenomena occurring in both visual fields simultaneously, in one of which the visual loss becomes permanent.

34. Diagnostic critreria • Definite diagnosis of migraine with aura in the past • One or more of the migrainous aura symptoms must be present and not fully reversed within 7 days from the onset, with neuroimaging confirmation of ischemic infarction • Clinical manifestations should be those typical of previous attacks • Other causes of infarction should be excluded • Definite migrainous infarction – all criteria satisfied • Possible – only some criteria satisfied • Increases risk for recurrent stroke

35. CEREBRAL VASCULITIDES • Infectious vasculitis • Bacterial, fungal, parasitic, spirochetal, viral, rickettsial, mycobacterial • Necrotising vasculitis • Classic polyateritis nodosa, Wegener’s granulomatosis, allergic angitis and granulomatosis, lymphomatoid granulomatosis • Vasculitis associated with collagen vascular disease • SLE, Rheumatoid arthritis, Scleroderma, Sjogren’s syndrome • Giant cell arteritides • Takayasu’s arteritis, temporal arteritis

36. Vasculitis associated with other systemic diseases • Behcet’s disease, Ulcerative colitis, Sarcoidosis, Relapsing polychondritis, Kohlmeier-Degos disease • Hypersensitivity vasculitis • Henoch-Schonlein’s purpura, Drug-induced vasculitis, Essential mixed cryoglobulinemia • Miscellaneous • Vasculitis associated with neoplasia and radiation, Cogan’s syndrome, Dermatomysoitis polymyositis, X-linked lymphoproliferative syndrome, TAO, Kawasaki’s syndrome, Primary central nervous system vasculitis

37. Inflammatory vasculitis should be considered in • Young patients with stroke • Recurrent strokes • Stroke with encephalopathic features • Stroke with fever • Multifocal neurological events • Mononeuritis multiplex, palpable purpura or abnormal urinary sediment • Diagnosis usually requires confirmation with arteriography or biopsy

38. Meningovascular syphilis • Patients usually have prodromal symptoms • Vasculitis can cause cerebral infarctions, commonly in MCA territory or spinal cord infarction. • May be associated with headache, meningismus, mental status abnormalities or cranial nerve abnormalities.

39. Diagnosis • CSF study reveals lymphocytic pleocytosis, elevated protein control and positive VDRL test • Treatment • Aqueous Penicillin G x 10-14 days • Luteic aneurysms of the ascending aorta can extend to the root of great vessels causing stroke

40. Neurotuberculosis • Usually affects basilar meninges resulting in basilar meningitis which traps 3, 4 and 6 cranial nerves causing their palsy. Basilar arteriolitis commonly involves the penetrating branches of ACA, MCA or PCA • Risk factors include alcoholism, substance abuse, corticosteroid use or HIV • CSF study shows increased protein and decreased glucose levels and lymphocytic and mononuclear pleocytosis. 10-20% of the CSF smears show AFB.

41. HIV/AIDS • Cerebral infarction on AIDS can result from • Vasculitis, meningovascular syphilis, varicella-zoster virus vasulitis, opportunistic infections, infective endocarditis, aneurysmal dilatation of major cerebral arteries, nonbacterial thrombotic endocarditis, aPL antibodies, or other hypercoagulable states, hyperlipidemia induced by protease inhibitors, HIV-1 related malignancy, cancer chemotherapy and TTP.

42. Other infectious agents are varicella zoster, coxsackie 9 virus, California encephalitis, mumps paramyxovirus, hepatitis C virus, Mycoplasma pneumoniae, Borrelia burgdorferi, Rickettsia typhi, cat-scratch disease, Trichinella infection, cysticercus of Taenia solium and free living amoeba

43. Takayasu’s arteritis • Chronic inflammatory arteriopathy of aorta, its major branches and pulmonary artery • More common in women • Probable immune mechanism • Slow progression of stenosis, occlusion, aneurysmal dilatation and coarctation of the involved vessels

44. Two phases • Acute or prepulseless phase – non-specific systemic symptoms • Occlusive phase – multiple arterial occlusions • Neurological symptoms usually result from CNS or retinal ischemia due to stenosis or occlusion of the aortic arch and arch vessels, or arterial hypertension resulting from coarctation of aorta or renal artery stenosis

45. Diagnosis • MR angiography • Aortogram • Treatment • In active disease, treatment is with oral glucocorticoids; cyclophosphamide, azathiprine or methotrexate used rarely • Surgical treatment of severely stenotic vessels

46. Drug induced vasculitis • Drugs implicated • Amphetamines, cocaine, phencyclidine, phenylpropanolamine, pentazocine with pyribenzamine, heroin, anabolic steroids and glue sniffing. • Mechanisms • Foreign body embolization, vasculitis, vasospasm, acute onset of arterial hypertension or hypotension, endothelial damage, accelerated atherosclerosis, hyper or hypocoagulability, cardiac arrhythmias, emboism from MI or AIDS.

47. CARDIOGENIC EMBOLISM • High embolic potential • Rheumatic mitral valve • Acute myocardial infarction • Infective endocarditis • Mechanical prosthetic valves • Dilated cardiomyopathy • Cardiac tumours • Cardiac arrhythmias – Atrial fibrillation • Other causes • Mitral valve prolapse • Mitral annulus calcification • Aortic valve calcification

48. Non bacterial thrombotic endocarditis • Filamentous strands of mitral valve • Giant Lambl’s excresences • Aneurysms of Sinus of Valsalva • Intracardiac defects with paradoxical embolism • Patent foramen ovale, atrial septal aneurysm, atrial septal defect • Cyanotic congenital heart disease • Iatrogenic embolism • Cavopulmonary anastamosis, coronary artery bypass grafting, pacing, heart transplantation, artificial hearts, cardioversion for atrial fibrillation, balloon angioplasty, ventricular support devices, extracorporeal membrane oxygenator

49. Cardiac sources account for 15 to 20% of all ischemic strokes. • The emboli usually consist of platelet, fibrin, platelet-fibrin, calcium, microorganisms, or neoplastic fragments. • Cardioembolic cerebral infarcts – large, multiple, bilateral, wedge shaped • Features of cardioembolic stroke • Worse at onset, fast recovery • Presence of Wernicke’s aphasia, homonymous hemianopia, ideomotor apraxia • Involvement of posterior division of MCA, ACA or cerebellar involvement • Involvement of multiple vascular territories • Hemorrhagic component of the infarction

50. Acute myocardial infarction • 1% of patients with acute MI have embolic stroke • LV thrombi are commonly associated with recent anterior wall transmural MI • Usually embolism occurs within first 3 months, 85% within 4 weeks • Decreased ejection fraction – independent predictor of risk of embolism • There is more chance of embolism following thrombolysis with tpA