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Understanding Cerebrovascular Diseases: Pathology and Treatment Modern Insights

Explore the complexities of cerebrovascular diseases including ischemic and hemorrhagic conditions, vascular anatomy, neuropathological changes, and therapeutic strategies to salvage brain tissue. Learn about the clinical course of strokes and insights from experimental systems. This resource provides a comprehensive overview for students, researchers, and healthcare professionals.

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Understanding Cerebrovascular Diseases: Pathology and Treatment Modern Insights

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  1. Vascular NeuropathologyFebruary 2002 Charleen T. Chu, M.D., Ph.D. Dept. of Pathology, Division of Neuropathology University of Pittsburgh School of Medicine Pittsburgh Institute for Neurodegenerative Disease http://path.upmc.edu/people/faculty/chu.html

  2. Cerebrovascular Disease • Ischemic • Atherosclerosis • Embolism • Hypotensive episode • Hemorrhagic • Trauma • Berry aneurysm • Hypertension, vascular malformations, amyloid • Superior sagittal sinus thrombosis • Inflammatory - vasculitis, primary vs. secondary • Neoplastic - lymphoma, angiosarcoma, hemangiopericytoma, hemangioblastoma

  3. Systemic hypertension Cerebrovascular Disease • Third leading cause of death in the US • Most prevalent neurologic disorder • Hypoxia, ischemia, infarction • Intracranial hemorrhage • Herniation • Small vessel disease

  4. Cerebrovascular Disease • Hypoxia, ischemia, infarction • Anatomy • Atherosclerosis and emboli • Hypotensive episode • Acute, subacute, chronic infarcts • Intracranial hemorrhage • Herniation • Vasculitis, small vessel disease

  5. Vascular Supply to the Brain Modified from Watson 1995 Basic Human Neuro-anatomy, 5th Edition, p. 103. Little, Brown & Co.

  6. PCA ACA MCA Modified from Poirier et al.1990 Manual of Basic Neuropathology, 3rd Edition, Fig. 117, p. 88. W.B. Saunders

  7. Anatomic Considerations • Vascular anatomy • Circle of Willis and anastomoses (Figs. 109-110 - Poirier) • Internal carotid-middle cerebral artery • Watershed zone • Rigid brain case and herniation (Robbins p. 1298) • Falx • Tentorium • Foramen Magnum

  8. Oil red O stain showing sites of AS Courtesy of Dr. Julio Martinez

  9. Plaque rupture Atheromatous carotid stenosis Modified from Poirier et al. 1990 Manual of Basic Neuropathology, 3rd Edition, p. 85. WB Saunders

  10. Pathology of Cerebral Infarcts • Distribution • Fits within vascular territory (atherosclerotic) • Multiple, grey-white jxn (embolic) • Vulnerable areas (hypotensive/hypoxic) • Centered at depths of sulci, sometimes with sparing of subpial cortex (in contrast to contusion at tips of gyri) • Age • Acute • Subacute • Remote

  11. Recent infarct with gyral edema, softening, discoloration Courtesy of Dr. Julio Martinez

  12. Subacute infarcts Courtesy of Dr. Julio Martinez

  13. Remote infarcts Courtesy of Dr. Christine Hulette

  14. Infarct Age - Gross Acute6-48 h Pale, soft, swollen, blurred gray-white jxn Subacute2 d - 3 wks 2-10 d Gelatinous, friable, distinct infarct boundary Then, gradual removal of tissue Remotemonths-years Cystic +/- hemosiderin staining Secondary degeneration of axon tracts

  15. Infarct Age - Microscopic > 1 h Neuronal and perineuronalvacuolation, Dark neurons 4-12 h Red neurons, Pallor (BBB leaky) 15-24 h - 5 d Neutrophils 2-3 d - wks MØ, myelin phagocytosis 1-2 wks Astrocyte & vascular prolif. mo-yrs Cyst, residual MØ, gliotic wall

  16. Acute infarcts

  17. Subacute infarct, H&E/LFB stain

  18. Remote cystic infarct

  19. Multiple embolic infarcts Courtesy of Dr. Christine Hulette

  20. Diffuse hypoxia-ischemia Vulnerable areas • “Watershed” or “borderzone” • CA1 region of hippocampus • Cerebellar Purkinje cells • Mid- to deeper layers of cortex (pyramidal) - laminar necrosis

  21. Watershed infarcts Courtesy of Dr. Christine Hulette

  22. CA2 CA1

  23. Vulnerability of the Brain • High consumption of oxygen and glucose • Dependence on oxidative phosphorylation • Maintain membrane polarization • Relatively low levels of antioxidant protection • Growing evidence for physiologic role for free radicals in neurotransmission (•NO, •O2-)

  24. Clinical Course • “Stroke” • Acute onset of focal neurologic syndrome due to vascular event • Acute change to pre-existing AS plaque • Symptoms tend to improve during 1st week after stroke • Believed to reflect acute neuronal death followed by resolution of edema

  25. Lessons from Experimental Systems • Core - rapid neuron death from lipolysis, proteolysis, total bioenergetic failure • Penumbra - Delayed neuronal death continues for days/weeks after insult • Excitotoxicity • Spreading dopolarization • Reactive oxygen and nitrogen species • Apoptosis • Inflammation

  26. Evolution of Ischemic Stroke Modified from Dirnagl et al. 1999. TINS 22:391-397

  27. Therapies to Salvage Penumbra • Hypothermia • NMDA antagonists, block “excitotoxicity” • Short window (1-2 h) • Serious unwanted effects (like “off switch” of tv) • New selective antagonists (“volume control”) • Calcium channel blockers • SOD mimetics - longer window • Potential targets for therapies • iNOS and COX2, anti-apoptotic agents?

  28. skull dura arachnoid pia Cerebrovascular Disease • Hypoxia, ischemia, infarction • Intracranial hemorrhages • Epidural • Subdural • Subarachnoid • Intraparenchymal • Herniation • Vasculitis, small vessel disease

  29. Epidural Hemorrhages • Trauma with skull fx • Arterial • Middle meningeal artery • Can be rapidly expanding >> herniation • Less common in children • Meningeal vessels not yet deeply embedded in grooves of the cranium’ • Dense dark-red clot adherent to dura • Can be venous from infratentorial base of skull fxs with laceration of dural sinus

  30. Subdural Hemorrhage • Bridging veins • Early (Acute and subacute) • Trauma, associated with brain contusion • Mixture of blood and CSF - may not clot • Chronic • Mainly in elderly, may not recall trauma • Slow development, may distort brain • Fibrous organization and rebleeding common - sepia/yellow staining

  31. Subdural membrane with rebleeding

  32. SAH

  33. Subarachnoid Hemorrhage • Saccular (Berry) Aneurysms • 1.8% of autopsies • Congenital defect in media at branch point • 90% in anterior circulation • Repetitive bleeding > loculations > rupture into adjacent parenchymal • Plaques, calcifications, thrombi • Associated with polycystic kidney disease

  34. MCA ACA ICA Ruptured Aneurysms Modified from Poirier et al.1990 Manual of Basic Neuropathology, 3rd Edition, p. 73. W.B. Saunders Co.

  35. Intraparenchymal extension from ruptured anterior communicating artery aneurysm

  36. Intraparenchymal Hemorrhage • 15% mortality • Arterial hypertension - 80% of cases • Vascular malformations • Amyloid angiopathy • Neoplasms

  37. Other intracranial aneurysms • Seldom present as SAH • Fusifirm atherosclerotic aneurysms • Basilar artery • Compression of adjacent structures • Infectious and post-traumatic • Mycotic, traumatic, dissecting • Usually involve anterior circulation

  38. Arterial dissection • Young adults - IC, MCA, vertebral, basilar • Hyperextension injury - may be “trivial” • Spontaneous dissection • Arteritis, AS, HTN, birth control pill, Marfan’s, cystic medial necrosis, fibromuscular dysplasia, Ehlers-Danlos • Focal absence, splitting, fraying of internal elastic membrane • 33% no identifiable pathology

  39. Intraparenchymal Hemorrhage • Massive hemorrhage of the basal ganglia, WM, pons, cerebellum >> Hypertension • Superficial/lobar >> contusion, amyloid, AVM • Parasagittal >> venous thrombosis, SSS • Petechial >> blood dyscrasias, fat emboli • Multiple hemorrhaghic infarcts >> emboli (tumor, infectious, cardiac) • Neoplasms can present as hemorrhage

  40. Hypertensive hemorrhage Courtesy of Dr. Julio Martinez

  41. Hypertensive hemorrhage Courtesy of Dr. Julio Martinez

  42. Surgical Pathology Hemorrhages • Usual dx - clotted blood • May see erythrophagocytosis, fibrovascular organization, subdural membrane > then can call organizing hemorrhage/hematoma • Look for brain tissue and note in report • If present, look for underlying cause • Congophilic angiopathy (b-APP, cystatin C) • Tumor • AVM

  43. Congophilic angiopathy in resected hematoma

  44. CNS Vascular Malformations • Arteriovenous malformation (AVM) • Cavernous hemangioma • Capillary telangiectasia - pons • Venous angioma (varices)

  45. Arteriovenous malformation • Medusa-like lesions with potential for rupture • Most over hemispheric surface of MCA • Multiple lesions occasionally seen with Rendo-Osler-Weber disease or Wyburn-Mason syndrome • Sx: seizures, focal deficits, increased ICP, catastrophic hemorrhage

  46. AVM - Pathology • Vessels vary in caliber • Core may exclude brain parenchyma, but feeding and draining vessels interdigitate with intervening brain • Presence of abnormal arteries possessing internal elastic lamina is diagnostic • “Arterialized” veins from the high pressure • Evidence of prior hemorrhage

  47. Arteriovenous malformation • In children, deep AVMs draining into the great vein of Galen can cause cardiac decompensation from shunting

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