CNS VASCULAR DISEASE. Reid R. Heffner, M.D. Department of Pathology/Anatomy UB Jacobs School of Medicine January 15, 2019

Size: px

Start display at page:

Download "CNS VASCULAR DISEASE. Reid R. Heffner, M.D. Department of Pathology/Anatomy UB Jacobs School of Medicine January 15, 2019"

Irma Warren
5 years ago
Views:

1 CNS VASCULAR DISEASE Reid R. Heffner, M.D. Department of Pathology/Anatomy UB Jacobs School of Medicine January 15, 2019

2 I HAVE NO CONFLICTS OF INTEREST OR ANY DISCLOSURES TO DECLARE. I HAVE NO FINANCIAL INTEREST IN, I RECEIVE NO FINANCIAL SUPPORT FROM AND I HAVE NO CONTRACTS WITH OR GRANTS FROM ANY PHARMACEUTICAL COMPANY OR ANY INDUSTRY

3 CNS VASCULAR DISEASE General Facts Third leading cause of death in the United States Accounts for at least 50% of all CNS disease Often referred to as stroke

4 CNS VASCULAR DISEASE Stroke Nonspecific term Derived from middle English word meaning (struck down) Implies sudden onset

5 INCIDENCE OF CLINICAL STROKE NIH Stroke Data Bank Infarcts-almost 80% of stroke cases** 40% of those are embolic 25% are lacunar 15-20% are atherothrombotic Hemorrhage-10% cases Aneurysm- 5-10% cases Vascular malformations-less common ** Does not include many lacunar and most watershed infarcts

6 Prototypes of Vascular Disease

7 CNS INFARCTION GENERAL CONCEPTS Infarct is ischemic tissue necrosis Neurons, glia, vessels involved Pathology depends on vessel size Large artery: thrombosis or embolus Intermediate size artery: embolus Small artery(arteriole): lacunar infarct Generalized low flow: watershed infarction

8 CNS INFARCTION Gross Pathology Day 1: Tissue pale in ischemic infarct Day 2:Blurring of grey-white junction Edema which peaks at day 5-7 Infarct soft to palpation Day 10: Margins well defined; liquifaction beginning Day 21:Cyst formation begins

9 CNS INFARCTION-DAY 2 Edema forming My pipe sprung a leak

10 CNS INFARCTION-DAY 10 Liquifaction beginning

11 CNS INFARCTION-DAY 21 Cavitation

12 CNS INFARCTION-REMOTE

13 Day 1-2 Day 3 Day 4-5 Cellular events in acute brain infarction

14 CNS INFARCTION Early Microscopic Appearance Day 1: Eosinophilic necrosis of neurons May remain for days, then disappear Day 1-2: Neutrophils appear Usually gone 2-3 days later Day 3: Macrophages appear Remain for weeks to months Day 4-5: Reactive astrocytes appear

15 CNS INFARCTION-DAY 1 Eosinophilic necrosis Normal neurons

16 CNS INFARCTION-DAY 1-2 Neutrophils are messy eaters

17 CNS INFARCTION-DAY 3 Macrophages (Pac-man) phagocytize the debris

18 CNS INFARCTION-DAY 4-5 Reactive astrocytes Intracellular edema

19 CNS INFARCTION Later Microscopic Appearance Day 7:Reactive gliosis is apparent Seen in surrounding preserved tissue Remains for months, but slowly diminishes Day 5-10:Neovascularity apparent Capillaries invade the infarct as conduit for macrophages (gitter cells) Day 21:Cavitation begins Proceeds until infarct is totally cystic

20 CNS INFARCTION DAY 5-10 Neovascularity-infarct may show increased density on CT scan

21 CNS INFARCTION-CYST FORMING Macrophages are the polite eaters

22 Mechanisms of ischemic injury Necrosis and apoptosis 02 energy (ATP) depolarization Glutamate release=acts as neurotoxin Binding to NMDA receptors depolarization Calcium influx tissue damage

23 Mechanisms of ischemic injury

24 LARGE VESSEL INFARCTION Occlusion in circle of Willis or one of its branches Due to atherothrombosis or embolus Infarcts are large Size influenced by collateral circulation Result in typical clinical syndromes Example, middle cerebral artery syndrome Mortality depends on size, location

25 LARGE VESSEL INFARCTION

26 Distribution of anterior, middle and posterior cerebral arteries seen from lateral aspect. Note border zones.

27 Collateral circulation variants

28 LARGE VESSEL INFARCTION Atherosclerosis

29 LARGE VESSEL INFARCTION

30 Distribution of Middle Cerebral Artery with respect to function.

31 Correlated patterns of MCA occlusion and cerebral infarction. Proximal Occlusion; Poor Collateral Circulation Distal Occlusion; Poor Collateral Circulation

32 Correlated patterns of MCA occlusion and cerebral infarction. Proximal Occlusion; Good Collateral Circulation Distal Occlusion; Good Collateral Circulation

33 EMBOLIC INFARCTION Occlude large or intermediate arteries Most are thromboemboli Originate in heart, carotid system An important risk factor is atrial fibrillation- >30% of strokes in some studies Preceded by transient attacks (TIAs) Symptoms usually last min Clot is lysed Often multiple episodes

34 INFARCTION DUE TO SMALL EMBOLI More frequent in anterior part of the circle Infarcts small, often one or two gyri May be undiagnosed clinically Sometimes hemorrhagic or dusky Reperfusion after lysis of embolus Tend to be multiple, differing ages Released repetitively over time

35 Sources of emboli to cerebral arteries

36 Thrombus in left atrium of patient with atrial fibrillation

37 EMBOLIC INFARCTION Infarcts are hemorrhagic, often multiple

38 LACUNAR INFARCTION Most common type at autopsy Disease of parenchymal arterioles Infarcts small, < 1 cm dimension Very frequently clinically silent Tend to be multiple Favorite locations are deep structures Basal ganglia, cerebral white matter, pons

39 Lacuna means gap or empty space

40 LACUNAR INFARCTION

41 LACUNAR INFARCTION Arteriolosclerosis in small arterioles

42 CORTICAL/SUBCORTICAL INFARCTS Due to arteriolar disease May be associated with dementia Multi-infarct dementia and Binswanger s CADASIL-chromosome 19q12 NOTCH3 gene mutations Encodes transmembrane receptor (EGFR like) Located in vascular smooth muscle

43 Binswanger s Disease Many tiny infarcts

44 Infarction the of white matter; associated with hypertension, cerebrovascular disease, cognitive impairment

45 CADASIL Cerebral Autosomal dominant Arteriopathy Subcortical ischemia Leukoencephalopathy Age onset years Seizures, strokes, headache, dementia

46 CADASIL

47 CADASIL PAS + vascular staining Granular material replaces normal smooth muscle

48 WATERSHED INFARCTION Develop during global ischemia Shock, cardiac arrhythmias In territories of shared blood supply Ex: Border zone between ACA and MCA CNS circulation may be normal More severe when vessels are narrowed Classic finding is pseudolaminar necrosis

49 Watershed concept of infarction is actually backward

50 Watershed and blood flow Shared territory Artery pumps blood up the mountain Mountain

51 Poiseuille s (pwaswee) Law 50% drop in blood pressure will cause a proportional reduction in blood flow

52 Distribution of anterior, middle and posterior cerebral arteries seen from lateral aspect. Note border zones.

53 Watershed territory

54 WATERSHED INFARCTION Pseudolaminar necrosis Some layers are more vulnerable to ischemia Band-like pseudolaminar necrosis

55 Causes of Brain Hemorrhage Primary (spontaneous) hemorrhage Ruptured berry aneurysm Vascular malformation Trauma Vascular injury Bleeding/clotting disorders Hemorrhage into a tumor

56 PRIMARY BRAIN HEMORRHAGE History of hypertension Development of microaneurysms Damage to small arterioles Favorite sites Basal ganglia, pons, cerebellum Blood acts as mass lesion Mortality 30-40%

57 Primary Brain Hemorrhage Microaneurysm injected with a dye

58 High magnification of the angiogram reveals the tiny aneurysms, which can occasionally be seen under the microscope.

59 Primary Brain Hemorrhage Basal ganglia most common location

60 Primary Brain Hemorrhage

61 Clinical Features of Infarcts vs. Hemorrhage Infarct History of TIA Onset at rest Minimal discomfort Sudden onset of focal deficit without change in consciousness or mentation Moderate hypertension (occasionally normotensive) Clear CSF Hemorrhage No TIA Onset during activity Headache (often severe) Rapidly evolving neurological deficit including state of consciousness Severe hypertension (Occasionally moderate) Bloody CSF

62 AMYLOID ANGIOPATHY Amyloid makes vessels more brittle or friable Congo red stain for amyloid

63 LOBAR HEMORRHAGE Think of amyloid as a cause

64 BERRY ANEURYSMS Arise in the circle of Willis Origin is controversial Occur at branch points of vessels Arterial pulsation stress is highest at branches Arterial wall is remodeled, thins, then dilates Role of hypertension? Anterior circulation in 80% cases Multiple in 10-20% cases

65 Aneurysms Berry aneurysm

66 BERRY ANEURYSMS Clinical Features Commonly are silent until rupture 50% aneurysms never rupture Larger aneurysms (>6mm) likely to bleed Hemorrhage into subarachnoid space Severe headache, meningeal signs Lumbar puncture shows blood in CSF Mortality can approach 50% Repeat bleeding, spasm, edema

67 BERRY ANEURYSMS More common in anterior circulation

68 BERRY ANEURYSMS

69 BERRY ANEURYSMS Associated with polycystic kidneys The world s earliest berry aneurysm

70 BERRY ANEURYSMS Subarachnoid hemorrhage Ventricular hemorrhage

71 VASCULAR MALFORMATIONS Developmental in origin Chromosome locus 7q in cavernomas Due to abnormal angiogenesis Failure of primordial vessels to involute? Often asymptomatic Symptoms from mass effect, seizures Bleeding from ruptured vessel Enlargement of lesion (mass effect)

72 Vascular malformations Arteriovenous malformations (AVM) Venous angiomas Cavernomas-veins and capillaries Capillary telangiectasia

73 Arteriovenous Malformations Most common vascular malformation Greatest tendency to bleed 2% annual risk Often located in the cerebrum Have meningeal and parenchymal portions Only one or a few feeding arteries

74 AV MALFORMATIONS

75 People who had a stroke

76 Learning Objectives Classify the CNS vascular diseases Compare and contrast diseases due to infarcts and hemorrhage Explain the role of collaterals in infarction Predict clinical symptoms in MCA, ACA and PCA occlusions Explain why berry aneurysms cause subarachnoid hemorrhage more often than brain hemorrhage Compare berry aneurysms with other types of aneurysms Explain why lacunar infarcts are often clinically silent List causes of brain hemorrhage Describe the mechanism of watershed infarction and pseudolaminar necrosis of the cortex Explain why embolic infarcts are multiple, often bilateral, hemorrhagic initially and of different ages

77 Case 1. Worst headache of my life A 59 year old man in previously good health is brought to the ED by ambulance. As he was getting ready for bed, he told his wife he suddenly had the worst headache of his life. After about 20 minutes he became nauseated and vomited. He complained of the bright lights in the room He then collapsed on the floor and his wife called an ambulance. In the ED, exam revealed a confused patient with blurred vision, light sensitivity and nuchal rigidity. A lumbar puncture was done. What would you expect to find? What is your working diagnosis?

78 Case 2. I can t move my arm or leg A 72 year old man with a history of coronary artery disease and atherosclerotic abdominal aneurysm experienced the onset of symptoms over the course of 10 minutes. He told his wife, I can t move my arm or leg. In the hospital he was noted to have developed a right hemiparesis of the arm and leg, right hemiparesis of the lower face and loss of sensation in the right face, arm and leg. He had a speech impairment with word finding difficulties and understanding verbal commands. He also showed a gaze preference to the left. The occlusion of which artery would account for this man s findings?

79 Case 3. I can t walk A 76 year old woman with a history of atrial fibrillation noticed that her face was suddenly numb on the left side. These symptoms disappeared in ten minutes. A week later while grocery shopping she became dizzy and she thought her left leg was weak. Again the symptoms appeared suddenly and abated in a few minutes. While watching TV a month later, her right leg suddenly became weak. She told her son, I can t walk. She was transported to the stroke center. PE revealed atrial fibrillation as well as a dense right hemiplegia. What is your diagnosis?

80 Answers to cases Case 1. Lumbar puncture would show bloody tap Working diagnosis is ruptured berry aneurysm Case 2. Middle cerebral artery Case 3. Embolic infarcts. First two events were temporary (transient ischemic attacks) Atrial fibrillation was the source of emboli

Cerebrovascular Disorders. Blood, Brain, and Energy. Blood Supply to the Brain 2/14/11

Cerebrovascular Disorders. Blood, Brain, and Energy. Blood Supply to the Brain 2/14/11 Cerebrovascular Disorders Blood, Brain, and Energy 20% of body s oxygen usage No oxygen/glucose reserves Hypoxia - reduced oxygen Anoxia - Absence of oxygen supply Cell death can occur in as little as