“The true measure of a man is how he treats someone who does him absolutely no good.” – Ann Landers

Pathology of Cerebro-vascular Disease (Stroke) Dr. Venkatesh M. Shashidhar Associate Professor of Pathology Fiji School of Medicine

Shashi-Apr-15 Introduction: Stroke is the third most common cause of death and the second most common cause of neurologic disability after Alzheimer's disease. Its incidence has decreased in recent decades, but the decrease appears now to have leveled off, and it remains the leading cause of institutionalization for loss of independence.

Shashi-Apr-15 Introduction: “Stroke” Cerebro Vascular accident (CVA) Acute neurological deficit ↓ blood supply. Third leading cause of death. (2/1000/y) Varying severity, location & types Global / Focal Transient Ischemia evolving & completed. Low O2 (hypoxia) / Low blood supply.

Shashi-Apr-15 Brain Blood Supply Features: High oxygen requirement. Brain 2% of body weight - 15% of cardiac output 20% of total body oxygen. Continuous oxygen requirement Few minutes of ischemia - irreversible injury. Neurons - Predominantly aerobic. Sensitive areas: Adults -Hippocampus, 3,5 th & 6 th layer of cortex, Purkinje cells. Border zone (watershed areas) Brain stem nuclei in infants.

Shashi-Apr-15 Stroke Types: Clinical Transient Ischemic Attack –TIA <24h Evolving stroke Completed stroke Recurrent / multiple stroke. Pathological Focal / Global Ischemic (white/pale) & hemorrhagic (red) Lacunar infarcts (pale chronic cystic)

Shashi-Apr-15 Common Types and Incidence: Infarction: Incidence 80% - mortality 40% 50% - Thrombotic – atherosclerosis Large-vessel 30% (carotid, middle cerebral) Small vessel 20% (lacunar stroke) 30% Embolic (heart dis / atherosclerosis) Young, rapid, extensive. Hemorrhage: Incidence 20% - mortality 80% Intracerebral or subarachnoid. aneurysm, hypertension/congenital.

Shashi-Apr-15 Etiology: Complication of several disorders Atherosclerosis – most common. Hypertension, smoking, diabetes. Heart disease – Atrial fibrillation. Other: Trauma – fat embolism Tumor, Infection Caissons disease – Bends *Pacific.

Shashi-Apr-15 Risk factors: Non modifiable Age Male sex Race Heredity Modifiable Hypertension Diabetes Smoking Hyperlipidemia Excess Alcohol* Heart disease (AF) Oral contraceptives Hypercoagulability.

Shashi-Apr-15 Clinical Categories: Global Ischemia. Hypoxemic encephalopathy Hypotension, hypoxemia, anemia. Focal Ischemia. Obstruction to blood supply to focal area. Thrombosis, embolism or hemorrhage.

Shashi-Apr-15 Global Ischemia: Etiology: Impaired blood supply - Lung & Heart disorders. Impaired O2 carrying – Anemia/Blood dis. Morphology: Laminar necrosis, Hippocampus, Purkinje cells. Border zone infarcts – “Watershed” Sickle shaped band of necrosis on cortex. Clinical Features: Mild transient confusion state to Severe irreversible brain death. Flat EEG, Vegetative state. Coma.

Shashi-Apr-15 Causes of hypotension Myocardial infarction Septic shock Internal hemorrhage Massive GI bleed ruptured varices bleeding ulcer, carcinoma Ruptured aortic aneurysm. Shock, Others

Shashi-Apr-15 Watershed/Boundary zone infarcts:

Shashi-Apr-15

Focal Ischemia: Thrombosis: Progressive, recurrent, Pale or ischemic infarct. Eg. Lacunar infarct Embolism / Hemorrhage: Sudden. Red or hemorrhagic infarct. Atherosclerosis – rupture/embolism

Shashi-Apr-15 Embolism formation:

Shashi-Apr-15 Local infarction: Cell death ~ 6min central infarct area or umbra, surrounded by a penumbra of ischemic tissue that may recover

Shashi-Apr-15 Haemorrhagic - Arterial embolus

Shashi-Apr-15 Infarct Pathogenesis: Reduced blood supply – hypoxia/anoxia. Altered metabolism  Na/K pump block. Glutamate receptor act.  calcium influx. 1-6 min – ischemic injury – vacuolation. >6 min – cell death.

Shashi-Apr-15 Infarct Stages: Immediate – 6 hours No Change both gross & micro Acute stage – 2 days Oedema, loss of grey/white matter border. Inflammation, Red neurons, neutrophils Intermediate stage – 2 weeks. Demarcation, soft friable tissue, cysts Macrophages, liquifactive necrosis Late stage – After 4 weeks. Fluid filled cysts with dark grey margin (gliosis) Removal of tissue by macrophages Gliosis – proliferation of glia, loss of architecture.

Shashi-Apr-15 Cerebral edema

Shashi-Apr-15 Edema, loss of demarcation:

Shashi-Apr-15 Acute Infarction: Oedema

Shashi-Apr-15 Cerebral Infarct : Red Neurons

Shashi-Apr-15 Cerebral Infarct - 1 Week

Shashi-Apr-15 Cerebral Infarct - 2 Weeks

Shashi-Apr-15 Cerebral Infarction: Macrophages

Shashi-Apr-15 Cerebral Infarct - Cyst formation

Shashi-Apr-15 Infarct with Punctate hemorrhage

Shashi-Apr-15 Cerebral Infarction - Late

Shashi-Apr-15 C. Infarct - Cyst formation

’Smile’ at each other, smile at your friends, smile at your partner, smile at strangers - it doesn't matter who it is – This will help you to grow up in greater love for each other. ’Smile’ at each other, smile at your friends, smile at your partner, smile at strangers - it doesn't matter who it is – This will help you to grow up in greater love for each other. Mother Teresa , Roman Catholic Missionary

Shashi-Apr-15 Intracranial Hemorrhage:  TRAUMA:  Epidural  Subdural  VASCULAR & TRAUMA  Intracerebral  Subarachnoid  Mixed cerebral-subarachnoid Intracerebral - Hypertension Subarachnoid - Berry aneurysm + Hptn. Mixed cerebral – Vascular malformations.

Shashi-Apr-15

Hypertensive CVD Massive Intracerebral Hemorrhage Ganglionic & Lobar hemorrhages Putamen(60%), thalamus, ventricles. Slit hemorrhages. Microhemorrhages heal as slit spaces. Lacunar infarcts Brain stem pale infarcts – arteriolar sclerosis Hypertensive encephalopathy Headache, confusion, vomiting – raised ICP.

Shashi-Apr-15 Subarachnoid Hemorrhage:

Shashi-Apr-15 Ruptured Berry Aneurism

Shashi-Apr-15 Intraventricular Hemorrhage:

Shashi-Apr-15 Cerebral Infarction  hemorrhage

Shashi-Apr-15 Cerebral Infarction  hemorrhage

Shashi-Apr-15 Lacunar Infarct in pons

Shashi-Apr-15 Summary: Stroke: Acute neurological deficit - Clinical Cerebrovascular Accident – pathology. Ischemic/Hemorrhagic Thrombosis, Embolism/Hemorrhage Atherosclerosis, Hypertension, Heart Disease. Global – Systemic Hypoxia – Watershed infarct Focal – Thrombosis, Embolism or Hemorrhage Liquifaction necrosis  Cyst formation, gliosis. Hypertension – Pale, Lacunar infarcts, slit hem.

Shashi-Apr-15 Ischemic penumbra:

“The ultimate measure of a man is not where he stands in moments of comfort, but where he stands in time of challenge and controversy” “The ultimate measure of a man is not where he stands in moments of comfort, but where he stands in time of challenge and controversy” – Martin Luther King Jr.

Anatomy – Stroke.

Shashi-Apr-15 Left (Dominant) Hemisphere Stroke: Common Pattern Aphasia Right hemiparesis Right-sided sensory loss Right visual field defect Poor right conjugate gaze Dysarthria Difficulty reading, writing, or calculating

Shashi-Apr-15 Right (Non-dominant) Hemisphere Stroke: Common Pattern Defect of left visual field Extinction of left-sided stimuli Left hemiparesis Left-sided sensory loss Left visual field defect Poor left conjugate gaze Dysarthria Spatial disorientation

Shashi-Apr-15 Brain Stem Stroke: Common Pattern Pure Motor - Weakness of face and limbs on one side of the body without abnormalities of higher brain function, sensation, or vision (MCA/ACA) Pure Sensory - Decreased sensation of face and limbs on one side of the body without abnormalities of higher brain function, motor function, or vision (PCA).

Shashi-Apr-15 Brain Stem / Cerebellum / Post Hemisp. Patterns. Motor or sensory loss in all four limbs Crossed signs Limb or gait ataxia Dysarthria Dysconjugate gaze Nystagmus Amnesia Bilateral visual field defects

Shashi-Apr-15 Investigations: CT of the brain without contrast – location/ext. Electrocardiogram - heart Chest x-ray - heart complete blood count, platelet count – hemat. PT, aPTT – coagulation. Serum electrolytes – complications. Blood glucose - DM Renal and hepatic chemical analyses – status. National Institutes of Health Scale (NIHSS) score – clinical/prognosis ?

Shashi-Apr-15 “We must all suffer from one of two pains: the pain of discipline or the pain of regret” The difference is Discipline weighs ounces.. while regret weighs ton’s..! Jim Rohn

Shashi-Apr-15 Hypertensive Intracerebral Hem: Sites 1. Putamen-Claustrum 2. Cerebral white matter 3. Thalamus 4. Pons 5. Cerebellum 55% 15 10

Shashi-Apr-15 Stroke types and incidence:

Shashi-Apr-15 Anatomy – Stroke.