Stroke: An Acute and Treatable Condition

1. Stroke:An Acute and Treatable Condition Thomas G. Bowers, Ph.D.

2. An Overview • Used to be referred to as a cerebral vascular accident (CVA) • Better referred to as a “brain attack” • Sudden onset, apoplexy

3. Basic Information • Third leading cause of mortality • 2.9 prevalence in 1991 • Heart disease 33.2% • Cancer 23.7% • CVD 6.6% • Leading cause of disability • Cost ~$30 billion year in 1990s • These estimates are probably low, as “silent strokes” can also occur

4. Risk Factors • Age • Gender • Obesity • Lack of exercise • Hypertension • Tobacco smoking • ETOH intake

5. Risk Factors • Cortisol • Stress • Males>Females • Until women are older (>85) • Blacks>Whites • Age adjusted x 103 • White 22.5, Black 48.4

6. Ischemic cell damage occurs Brain is especially sensitive to anoxia Cells are stimulated to death Glutamate neurotoxicity Progression from hypoxia to hypoglycemia and ischemia What happens at the cellular level?

7. Glutamate Toxicity Cell Death

8. Glutamate Toxicity • Glutamate leads to cell death, cellular swelling • Rapid – cell death to Glu excitation can occur in less than five minutes • Also allows high rates of Ca+ entry into the neuron.

9. Glutamate Toxicity • Additional processes occur • Ischemia is fundamentally depolarizing for the cell NMDA AMPA Metabotoxins Leads to an infusion of Ca+ and Na+

10. AMPA Toxicity • Occurs after about 3+ hours of ischemic exposure • Yields 70% cell death • 24 hours yields 100% cell death

11. Summary • Process of Ischemic Attack Induction Amplification Expression

12. Cellular Effects of Hypoxic Injury • Bulbous swelling on the dendrites • Swelling of the cell body • Treatment with Ca+ blockers

13. Some Trials on Ca+ blockers

14. Penumbra Effect Core <O2 Ph 6.4 <<ATP Penumbra

15. Histopathology of Ischemia • With a heart attack, the entire brain becomes ischemic • After 2-3 minutes, cellular energy pumps fail

16. Histopathology of Ischemia Blood Vessel Cell

17. Histopathology of Ischemia Blood Vessel CO2 o2 Lactate Glucose Cell

18. Decreasing Order of Vulnerability to Ischemia • Neurons • Oligondendroglial • Astrocytes • Endothelial cells

19. Decreasing Order of Sensitivity in Vulnerable Regions • Hippocampus • Cerebellum • Striatum • Neocortex

20. Vulnerability • Hippocampal cells may live 24-72 hours

21. Ascending level of clinical severity • Transient Ischemic Attack (TIA) • Resolving Ischemic Neurological Deficits (RIND) • Stroke

22. Clinical Diagnosis • Important in emergency medicine "Time is brain"

23. Clinical Diagnosis • Focal • A “fit” • Migraine • Tumor • “Swoon”

24. Clinical Diagnosis • Non focal • Syncope • Hypoglycemia • Toxicity

25. Clinical Diagnosis • If CVA • Hemorrhage • Subararchoid • Intracerebral • Ischemia • Thrombosis • Embolism • Cardiac? • Intra cerebral? • Systemic hyper fusion

26. Clinical Diagnosis • Common sources • Middle cerebral artery • Basilar artery