1、Cerebro-vascular diseases,Categories of cerebro-vascular diseases,Thrombosis Embolus HemorrhageStroke,Pathophysiology and anatomical pathology of stroke,Two processesHypoxia, ischemia and infarct secondary to a deficit in blood supply and oxygenation of nervous tissuesHemorrhage secondary to a ruptu
2、re of a CNS blood vessel,Hypoxia versus Ischemia,Important to know the characteristics of hypoxia and ischemia before tackling the major causes of stroke,Hypoxia-Anoxia,Delivery of oxygen is impaired or abolished- low partial pressure of O2- impairment of the bloods oxygen-carrying capacity- inhibit
3、ion of oxygen use in tissue Delivery of glucose continues Waste products are removed Morphological consequences: synaptic damage and regeneration may correct the damage in days or weeks,Ischemia,No delivery of oxygen or glucose by interruption of the normal circulatory flowNo removal of waste produc
4、tsConsequences: Spectrum: Selective neuronal necrosis infarct,Early infarct: The two neurons in the center show the earliest visible changes in an infarct or selective neuronal necrosis. There is shrinkage, cytoplasmic hypereosinophilia, and nuclear pyknosis.,Factors influencing selective necrosis-i
5、nfarct,Duration of ischemiaCompleteness or degree of ischemia- collateral circulation- magnitude and importance of the reduction of flowTemperature of the brainLevel of glucose,Types of acute ischemic injury,Global cerebral ischemia (diffuse hypoxic/ischemic encephalopathy): cardiac arrest, shock, s
6、evere hypotensionFocal cerebral ischemia: embolic or thrombotic arterial occlusion; or small vessel disease: vasculitis or hypertensive changes,Distribution of brain damage: hypoxia and ischemia,Cerebral cortex: layer III, Vwatershed zonesHippocampus: CA1, Cerebellum: Purkinje cellswatershed zonesNo
7、tion of selective vulnerability,Global cerebral ischemia: The cerebral cortex shows dusky Discolouration. Notice the bilateral infarcts involving the CA1 Sector of the hippocampus (Somers sector; arrows).,Causes of infarcts,Thrombosis/occlusion, atherosclerosis being the most frequent cause Decrease
8、d blood flow:- hypotension- vascular stenosis- increase in vascular permeability Emboli- artery to artery ( arterial territory )- cardioembolic ( all territories ),Recent infarct: An infarct involving the left MCA territory has caused massive sweeling of the left hemisphere with a rightward shift of
9、 midline structures and marked distortion of the brain.,Some infarcts may show a hemorrhagic component. Hemorrhagic Infarcts are more commonly embolic or due to venous obstruction. Note the anemic portion above the hemorrhagic one.,“Remote” or “old” infarct in the territory of the right middle cereb
10、ral artery. This patient survived for many years following his stroke. Compare this picture with the one showing recent infarction. How do they differ?,Small infarcts in the brainstem can have stereotyped locations and produce well-known constellations of signs and symptoms. This infarct would cause
11、 a “medial medullary syndrome”.,Myelin stained transverse section of the cervical spinal cord. Where is the lesion? Can you link the pathology in this spinal cord to that in the previous photo?,Sequence of histological changes in cerebral infarts,1 hour: microvacuoles within neurons followed by peri
12、neuronal vacuolation4-12 hours: increasing eosinophilia of cytoplasm, Nissl substance disappears, nucleus becomes pycnotic.Blood-brain barrier begins to leak,Early infarct: Perineuronal and neuropil vacuolation,15-24 hours: neutrophilic infiltration begins2-3 days: Macrophages appear5 days: neutroph
13、ilic infiltration ceases7 days: early astrocytic reaction around the infarct8-10 days: vascular proliferation begins,Old infarct (months). The infarcted tissue is removed by invading macrophages leaving a cavity (arrowhead) surrounded by gliotic tissue. In most cortical infarcts, there is preservati
14、on of layer I (the molecular layer; arrow); which forms a “roof” over the cavity.,Causes of infarcts,Thrombosis/occlusion Decreased blood flow:- hypotension- vascular stenosis- increase in vascular permeability Emboli- artery to artery ( arterial territory )- cardioembolic ( all territories ),Intrac
15、ranial Hemorrhage,Giant (2 cm) saccular anerysm arising at the trifurcation of the left internal carotid, middle cerebral, and anterior cerebral arteries.,Saccular aneurysm: microscopic appearance. There is abrupt termination or the internal elastic lamina (arrow) and media (muscularis; arrowheads)
16、where the parent artery becomes aneurysmal.,Common locations of saccular aneurysms: the “90:10 rule”. 90% occur in the anterior circulation; 10% in the posterior circulation.From: Poirier J., Gray F., Escourolle R. Manual of BasicNeuropathology. W.B. Saunders, 1990,Intracerebral Hemorrhage,Causes of
17、 non-traumatic intracerebral hemorhages,Hypertension 50% Cerebral amyloid angiopathy 12% Anticoagulants 10% Tumors 8% Illicit and licit drugs 6% AV malformations, aneurysms 5% Miscellaneous 9%,Intracerebral hemorrhage: secondary to hypertension. Hypertensive intracerebral hematomas tend to be locate
18、d in “deep” structures. One common location is shown here; ie in the basal ganglia with the epicenter in the external capsule. Notice extension of the hemorrhage Iinto the lateral ventricle.,Another common location for hypertensive intracerebral hemorrhage; the pons. Other areas of predilection incl
19、ude the cerebellum and the thalamus.,Hypertensive arteriopathy or hypertensive “small vessel disease”. There is marked thickening of the wall od this small penetrating arteriole with invasion by macrophages (lipohyalinosis). This occurs as a consequence of hypertension and predisposes the artery to
20、rupture with consequent hemorrhage.,These hypertensive vascular changes can lead to the development of “Charcot-Bouchard” aneurysms (arrow). These can rupture and lead to intracerebral hematoma.,In contrast to the “deep” location of hypertensive bleeds, intracerebral hemorrhages secondary to congoph
21、ilic or amyloid angiopathy tend to be located in subcortical white matter and are called “lobar” hemorrhages.,Intracerebral hemorrhages can be considered an “expanding ball of blood”. As such, they push adjacent brain tissue away. When they resorb, the brain tissue closes back in and a slit-like cav
22、ity remains (arrowheads). Contrast this with the pictures of an old infarct where the infarcted tissue is destroyed, leaving a large cavity behind.,TUMOURS OF THE CENTRAL NERVOUS SYSTEM,CEREBRAL TUMOURS Incidence,8-10% of all human tumours 1-2% of all deaths In children, second only to leukemia/lymp
23、homa,CEREBRAL TUMOURS Etiology,Unknown in most cases Association of lymphomas and Epstein-Barr virus in immunosuppression Hereditary dysgenetic syndromes in which tumours are frequent P53 and epidermal growth factor important in astrocytic tumours,Marumoto et al., Nature Medicine 2009;15(1):110-116,
24、DYSGENETIC SYNDROMES,Neurofibromatosis 1 (Von Recklinghausen) Neurofibromatosis 2 Tuberous Sclerosis (Bournevilles Disease) Von-Hippel-Lindau Disease Neurocutaneous Melanosis Cowden Syndrome Li-Fraumeni Syndrome Nevoid Basal Cell Carcinoma Syndrome,CLINICAL MANIFESTATIONS,Very variable in view of mu
25、ltiple possible sites, variable growth patterns and biological characteristics Space-occupying lesion Edema may also play a role,GENERAL SYMPTOMS,Intracranial hypertension Alterations of mental function,LOCAL EFFECTS,Seizures: first symptom in approximately 1/3 of cerebral tumours Hemiparesis Ataxia
26、 Weakness Hydrocephalus: Especially with tumours of the IIIrd ventricle or posterior fossa,From: Ironside J.W., Moss T.H., Louis D.N., Lowe J.S., Weller R.O. (Eds.) Diagnostic pathology of nervous system tumours. Churchill-Livingston. 2002,From: Ironside J.W., Moss T.H., Louis D.N., Lowe J.S., Welle
27、r R.O. (Eds.) Diagnostic pathology of nervous system tumours. Churchill-Livingston. 2002,BIOLOGICAL PROPERTIES,Biological Malignancy (Malignant by Location) Vs Histological Malignancy,From: Louis D.N., Oghaki H., Wiestler O.D., Cavenee W.K. (Eds.): WHO Classification of Tumours of the Nervous System
28、. IARC: Lyon 2007,TUMOURS OF NEUROEPITHELIAL TISSUE,Astrocytic Tumours Oligodendroglial Tumours Ependymal Tumours Choroid Plexus Tumours Glial Tumours of Uncertain Origin Neuronal and Mixed Neuronal-Glial Tumours Pineal Parenchymal Tumours Embryonal Tumours,DIFFUSE ASTROCYTOMAS: 3 TUMOURS:1 DISEASE,Diffuse AstrocytomaWHO Grade II,Anaplastic AstrocytomaWHO Grade III,GlioblastomaWHO Grade IV,Nuclear pleomorphism,Mitotic figures,Microvascular proliferation Or Necrosis,+,+,Cell Density: Normal White Matter,Oligodendroglioma genetic signature,Loss of heterozygosity 1p/19q,
