Pathology of Stroke & CVA

1. Pathology of Stroke & CVA “The true measure of a man is how he treats someone whodoes him absolutely no good...” – Ann Landers True beauty lies in the Heart….!

2. CPC 4.3.5 – Robert• Robert is a 62 year old recently retired from QLD railways.• He lives in Cairns with his wife Rose and their son Aiden who is 40 yrs old with Downs syndrome.• He has fallen from a ladder whilst picking mangoes.• His wife found him unconscious in the back yard.• On arrival at the A&E department he is conscious but appears confused. He is complaining of a pain in his L arm. CPC 4.3.5 – Robert• Robert is a 62 year old recently retired from QLD railways.• He lives in Cairns with his wife Rose and their son Aiden who is 40 yrs old with Downs syndrome.• He has fallen from a ladder whilst picking mangoes.• His wife found him unconscious in the back yard.• On arrival at the A&E department he is conscious but appears confused. He is complaining of a pain in his L arm.

3. CPC 4.3.5 – Robert• What happened:Patient is unable to talk• Collateral History: wife,son, neighbours, paramedics.• What happened? Neighbour saw him at top of ladder veer to the left and fall 2.5 m landing on his head. She called out to his wife who attended the scene. Wife says that he did not seem to hear her and his left arm was shaking. The shaking lasted for about 2minutes. He did not seem to regain consciousness until he was administered oxygen by the paramedics about 10 minutes later. He then seemed to come around but appeared confused . He was unable to move his Left arm, R arm and Right leg. Wife says he was well prior to going out to pick mangoes. CPC 4.3.5 – Robert• What happened:Patient is unable to talk• Collateral History: wife,son, neighbours, paramedics.• What happened? Neighbour saw him at top of ladder veer to the left and fall 2.5 m landing on his head. She called out to his wife who attended the scene. Wife says that he did not seem to hear her and his left arm was shaking. The shaking lasted for about 2minutes. He did not seem to regain consciousness until he was administered oxygen by the paramedics about 10 minutes later. He then seemed to come around but appeared confused . He was unable to move his Left arm, R arm and Right leg. Wife says he was well prior to going out to pick mangoes.

4. CPC 4.3.5 – Robert• PMH: Hypertension diagnosed in 2000. a bit forgetful taking medication.• PSH: 1968 appendicectomy.• SH married for 40 years to Rose, they had 2 children. Their oldest Aiden was born with downs syndrome and has lived with them all his life; alcohol 2 beers x2/week, non smoker.• FH mother: breast ca age 72 years; well age 85yr• Father died CVA aged 71• Brother has hypertension and type 2 DM• Allergies: aspirin• Immunisation Fluvax 4.06, Pneumovax 2004• Medication Ramipril 2.5mg OD [when remembers it] CPC 4.3.5 – Robert• PMH: Hypertension diagnosed in 2000. a bit forgetful taking medication.• PSH: 1968 appendicectomy.• SH married for 40 years to Rose, they had 2 children. Their oldest Aiden was born with downs syndrome and has lived with them all his life; alcohol 2 beers x2/week, non smoker.• FH mother: breast ca age 72 years; well age 85yr• Father died CVA aged 71• Brother has hypertension and type 2 DM• Allergies: aspirin• Immunisation Fluvax 4.06, Pneumovax 2004• Medication Ramipril 2.5mg OD [when remembers it]

5. CPC 4.3.5 – Robert• T 36.4 C rr 16/min BP 168/98 mmHg pulse 110 bpm irregular, O2 sats RA 92% (on mask O2 4l/min) BMI 31 BGL 16m/mol• General appearance : confused to place and time; no memory of fall or period preceding fall; drooping R side face and R side of body• EMST cervical collar ABCDE• Peripheries : no clubbing. CRT<2 secs• CVS Irregular HR no murmurs, no carotid Bruits• CNS GCS 13 Pupils R>L sluggish response[AVPU]; CPC 4.3.5 – Robert• T 36.4 C rr 16/min BP 168/98 mmHg pulse 110 bpm irregular, O2 sats RA 92% (on mask O2 4l/min) BMI 31 BGL 16m/mol• General appearance : confused to place and time; no memory of fall or period preceding fall; drooping R side face and R side of body• EMST cervical collar ABCDE• Peripheries : no clubbing. CRT<2 secs• CVS Irregular HR no murmurs, no carotid Bruits• CNS GCS 13 Pupils R>L sluggish response[AVPU];

6. CPC 4.3.5 – Robert• Boggy Haematoma L temporo parietal area.• Gross dysphasia, drooping R side of face,• Flaccidity R side of body, brisk reflexes with equivocal plantar reflex• Painful swelling with bruising lower L arm just distal to elbow, unable to test L power, tone or reflexes due to pain when moving L arm• Power/reflexes/tone normal L leg• Sensation : responds to pain• Resp., GI, Renal: all normal CPC 4.3.5 – Robert• Boggy Haematoma L temporo parietal area.• Gross dysphasia, drooping R side of face,• Flaccidity R side of body, brisk reflexes with equivocal plantar reflex• Painful swelling with bruising lower L arm just distal to elbow, unable to test L power, tone or reflexes due to pain when moving L arm• Power/reflexes/tone normal L leg• Sensation : responds to pain• Resp., GI, Renal: all normal

7. CPC 4.3.5 – Robert• Head injury – Contusion, Concussion – Epidural hematoma – Subdural hematoma• Cerebrovascular accident (stroke) – CVA: embolic – CVA: haemorrhagic – Metabolic cause – Seizure ? cause• Trauma to L arm ?# radius / ulna CPC 4.3.5 – Robert• Head injury – Contusion, Concussion – Epidural hematoma – Subdural hematoma• Cerebrovascular accident (stroke) – CVA: embolic – CVA: haemorrhagic – Metabolic cause – Seizure ? cause• Trauma to L arm ?# radius / ulna

8. Education must award self-confidence, the courage to depend on one’s own strength. - Baba Education must award self-confidence, the courage to depend on one’s own strength. - Baba

9. Pathology ofCerebro-Vascular Disease (Stroke) Dr. Shashidhar Venkatesh Murthy Associate Professor & Head of Pathology Pathology ofCerebro-Vascular Disease (Stroke) Dr. Shashidhar Venkatesh Murthy Associate Professor & Head of Pathology

10. . Introduction:• “Stroke” Acute neurological deficit – clinical.• Cerebro Vascular accident (CVA) – Pathology.• Low O2 (hypoxia) / Low blood supply.• Varying severity, location & types• Transient, evolving & completed.• Global / Focal, arterial / venous• Ischemic / hemorrhagic.

11. . Introduction:• Stroke is the third most common cause of death and the second most common cause of neurologic disability after Alzheimers 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.

12. . Brain Blood Supply Features:• High oxygen requirement. – Brain 2% of body weight - 15% of cardiac output – 20% of total body oxygen – Continuous oxygen requirement – no change with BP – Few minutes of ischemia - irreversible injury.• Neurons - Predominantly aerobic.• Sensitive areas: – Adults - Hippocampus, 3,5th & 6th layer of cortex, Purkinje cells - cerebellum Border zone (watershed areas) – Brain stem nuclei in infants.

13. . Anatomy – Stroke.

14. . Brodman’s Cortical Map:

15. . Stroke Types:• Clinical – Transient Ischemic Attack –TIA - resolve <24h – Evolving stroke – increasing >24h. – Thromb. • Recurrent / multiple stroke – sec. factors. – Completed stroke – no change… embolic.• Pathological – Focal / Global – Ischemic (Embolic/Thrombotic), Hemorrhagic. – Venous infarcts. (young, infections)

16. . 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. – Venous thromboembolism (rare)• Hemorrhage: Incidence 20% - mortality 80% – Berry aneurysm, Microaneurysm, Atheroma. – Intracerebral or subarachnoid.

17. . Stroke location and incidence: Clinical 30dayCause % presentation mort(%) PathogenesisCerebral 85 Slowly / sudden 15-45 Cerebralinfarction evolving signs and hypoperfusion symptoms Embolism ThrombosisIntracerebral 10 Sudden onset of 80 Rupture of micro-hem. stroke with raised aneurysm or arteriole intracranial pressureSubarachnoid 5 Sudden headache 45 Rupture of saccularhaemorrhage with meningism aneurysm on circle of Willis

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

19. . 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.

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

21. . Clinical Categories:• Global Ischemia. – Hypoxemic encephalopathy – Hypotension, hypoxemia, anemia.• Focal Ischemia. – Obstruction to blood supply to focal area. – Thrombosis, embolism or hemorrhage.

22. . Global Ischemia:• Etiology: – Impaired blood supply - Lung & Heart disorders. – Impaired O2 carrying – Anemia/Blood dis. – Impaired O2 utilization – Cyanide poisoning.• Morphology: – 3rd, 5th and 6th layers of the cortex, CA1 sector of the hippocampus and in the Purkinje cells in the cerebellum – 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.

23. . Morphology in Global Ischemia1. Watershed zone (Acute - ACA-MCA)2. Laminar necrosis - (chronic- short penetrating arteries)3. Sommer sector of hippocampus.4. Purkinje cells of cerebellum.

24. . Watershed/Boundary zone infarcts: Carotid thrombosis

25. . Lamellar necrosis in global ischemia. Chronic

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

27. . Infarct Pathogenesis: • Reduced blood supply – hypoxia/anoxia.Hours • Altered metabolism  Na/K pump block. • Glutamate receptor act.  calcium influx. • ischemic injury – Red neuron, vacuolation. • cell death, karyorrhexis.1-day3-day • Inflammation – edema.1 wk. • Macrophages - > 5d. • Liquifaction cavity – >1wk>4wk • Glial proliferation – >1wk. (astrocytes)

28. . Infarct Stages:• Immediate – <24 hours – No Change gross, micro  Na/K loss, Ca+ influx.• Acute stage – < 1week – Oedema, loss of grey/white matter border. – Inflammation, Red neurons, necrosis, neutrophils• Intermediate stage – 1- 4 weeks. – Clear demarcation, soft friable tissue, cysts – Macrophages, liquifactive necrosis• Late stage – > 4 weeks. – Removal of tissue by macrophages – Fluid filled cysts with dark grey margin (gliosis) – Gliosis – proliferation of glia at periphery.

29. . Cerebral Edema: narrow sulci, flat gyri. Edema -  Normal - 

30. . Cerebral edema • Congestion • Flat gyri • Narrow sulci

31. . Edema, loss of demarcation:

32. . Cerebral Infarct - 2 Weeks

33. . Cerebral Infarct – 1-4 Week

34. . Cerebral Infarction - Late Cyst + hemosiderin

35. . Normal Cerebral cortex:

36. . Normal Cerebral cortex: gray matter. Yellow  oligodendrocytes Orange  astrocytes, Blue  neurons.

37. . Normal Cerebral cortex: white matter. Yellow  oligodendrocytes Orange  astrocytes

38. . Cerebral Edema:Normal Edema

39. . Axonal Injury:A, Hypoxic/ischemic injury in cerebral cortex - "red neurons." shrunken cellB, Axonal spheroids at points of axonal disruptionC, Swollen cell body and peripheral dispersion of Nissl substance (chromatolysis)H&E Stain.

40. . Acute Infarction: Oedema Edema - Normal

41. . Cerebral Infarction: Macrophages

42. . Infarct : Microscopy 3 days 1 week >3 week 1 Day DA- 3 days: neutrophils. B-10 days: plenty of macrophagesC-old: tissue loss + gliosis. D-1day: Red neurons & axon bulbs

43. . Infarct 4wk - Cyst formation

44. . “Where there is love ofMedicine, there is love ofhumankind” -- Hippocrates

45. . Specific focal InfarctsMCAACAPCA

46. . MCA ACA PCASpecificfocalInfarcts

47. . MCA Features: • Paralysis of the contralateral face, arm and leg • Sensory impairment over the contralateral face, arm and leg • Homonymous hemi or quadrantonopia • Paralysis of gaze to the opposite side • Aphasia (dominant) and dysarthria • Penetrating - contralateral hemiplegia/paresis, slurred speech.

48. . MCA stroke.

49. . MCA stroke. Wikipedia: GNU Free Documentation license

50. . MCA stroke. Wikipedia: GNU Free Documentation license