HYPERTENSIVE ENCEPHALOPATHY - Inova Presentations and...HYPERTENSIVE ENCEPHALOPATHY •Reversible posterior leukoencephalopathy syndrome •Cause Renal disease ... ENCEPHALOPATHY Gross

HYPERTENSIVE ENCEPHALOPATHY

• Reversible posterior leukoencephalopathy syndrome • Cause Renal disease Pheochromocytoma Disseminated vasculitis Eclampsia Acute toxemia Medications & illicit drugs (cocaine) Discontinuation of hypertensive medications • Disruption of BBB vasogenic edema • Vascular fibrinoid necrosis hemorrhages

Adams & Victor’s Principles of

Neurology, 9th edition, 2009

CHRONIC HYPERTENSION

• Atherosclerosis & microatheroma

Lacunar infarcts

• Arteriolarsclerosis

Subcortical ischemic vascular dementia

• Fibrinoid necrosis

Bleeding

• ?Microaneurysms (Charcot Bouchard aneurysms)

Bleeding

Ferrer I, et al: Vascular Diseases. In: Greenfield’s Neuropathology, 8th edition, 2008

Lacunar Infarct

• Less than 15 mm in diameter

• Occlusion of terminal arteries

• Arteriolarsclerosis

• Embolism

• Narrowing of ostium at site of origin

Trichrome

AMYLOID ANGIOPATHIES

• Sporadic or AD-associated

• Familial AD

• HCHWA-D

• HCHWA-I

• Meningovascular amyloidosis

• Familial amyloidosis, Finnish type

• Familial British dementia

• Familial Danish dementia

• Prion disease

• Amyloid beta

• Amyloid beta

• Amyloid beta

• Cystain C

• Transthyretin

• Gelsolin

• ABri

• ADan

• APrion protein

Ellison D, et al. Neuropathology, 3rd edition. 2013

Congo red

Beta amyloid Beta amyloid

CADASIL • Cerebral autosomal dominant artheriopathy with

subcortical infarcts and leukoencephalopathy

• Clinically associated with migraine, recurrent strokes, psychiatric symptoms & dementia

• Linked to mutations in the NOCHT 3 gene on chromosome 19

• Related to deposits of PAS positive granular material in the tunica media of arteries of the CNS, skin, skeletal muscle and peripheral nerve

• Demyelination of centrum semiovale

• Lacunar infarcts in white matter, basal ganglia, thalamus and brain stem

PAS

PAS

Courtesy Dr. D. Louis, Boston, MA

Brain Ischemia • Arterial cerebral blood flow is insufficient to

maintain cellular functions

• Normal CBF:

55 ml/100g/min – Moderate ischemia:

CBF 15-20ml/100g/min

Short duration <30 min

Reversible cell injury

– Severe ischemia:

CBF 10 ml/100g/min

Irreversible cell injury

• Regional ischemia:

Pancellular necrosis

Anemic infarct

Hemorrhagic infarct

Lacunar infarct

Microscopic infarct

Incomplete infarct

Global ischemia

Selective neuronal necrosis

Brain Ischemia

Brain Infarct Gross Findings

• Recent (acute) Infarct

8-38 hours Blurring of gray/white matter junction

Dusky gray discoloration of neural tissue

Tissue softening on palpation

2-4 days Edema

• Organizing (subacute) infarct 5-30 days

Liquefactive necrosis

• Organized (chronic) infarct >1 month

Cystic cavity

Modified from Ellison D, et al. Neuropathology, 3rd edition. 2013

Hemorrhagic Infarct

• Result from hemorrhagic transformation of ischemic lesion

• Mechanism

Reperfusion of ischemic territory

Episodes of hypertension

Partial occlusion of arterial lumen

• Pathologic features

Cortical petechial hemorrhages

Hematoma

BRAIN INFARCT MICROSCOPIC FINDINGS

• Recent (acute) infarct 1-4 days Neuronal eosinophilia Edema Acute inflammation • Organizing (subacute) infarct 5-30 days Necrosis Macrophages Neovascularization • Organized (chronic) infarct >1 month Gliosis at periphery of cavity Few macrophages Mineralized neurons Spheroids Preservation of cortical molecular layer Modified from Ellison D, et al. Neuropathology, 3rd edition. 2013

NISSL

GLOBAL ISCHEMIA • Terminology

Diffuse anoxic/hypoxic -ischemic encephalopathy

Anoxic/hypoxic brain injury

Respirator brain

Non-perfused brain

Liquefied brain

• Transient: If blood flow to the brain is restored. Associated with selective neuronal necrosis

• Permanent: If blood flow to the brain is not restored. Associated with total brain necrosis

TRANSIENT GLOBAL ISCHEMIA

Modifying factors

• Duration of ischemic episode

• Severity of ischemia

• Body temperature

Hypothermia is protective

• Blood glucose level

Hyperglycemia worsens outcome

GLOBAL BRAIN ISCHEMIA CAUSES

• Cardiac pathology • Cardiac arrest • Hypotension • Shock • Seizures including status epilepticus • Intoxications (drug abuse) • Increased intracranial pressure Traumatic brain injury Intracranial space occupying lesion

SELECTIVE VULNERABILITY

Refers to differential susceptibility of CNS regions to

a hypoxic-ischemic event

Hippocampus: CA1 field (Summer sector)

• Cerebral cortex: Neurons in laminae 3 & 5

• Cerebellum: Purkinje cells

• In premature and term infants, neuronal susceptibility differs from that in adults

GLOBAL ANOXIC-ISCHEMIC ENCEPHALOPATHY

Gross acute/ subacute changes • Generalized dusky discoloration, edema and softening • Patchy gray discoloration of cortex with blurring of white and gray matter junction • Watershed infarcts • Cortical laminar or pancortical necrosis • Bilateral hemorrhagic/ischemic necrosis of basal ganglia/thalamus • Liquefaction necrosis • Normal brain

24-year-old female Drug use Found unresponsive in bathroom Dx: Anoxic brain injury Survived 6 days

GLOBAL ANOXIC-ISCHEMIC BRAIN INJURY

Macroscopic chronic changes • Diffuse or focal brain atrophy • Watershed infarcts • Cystic, bilateral, and symmetric necrosis of basal ganglia/

thalamus • Hippocampal atrophy due to sclerosis • Granular cerebral cortical atrophy related to watershed infarct • Leukoencephalopathy • Normal brain

32-year-old male Schizophrenia Seizures Died in hospital

Otto Binswanger, M.D. (1852-1928) Sir Thomas Willis (1621-1675)

C. Miller Fisher, M. D. (1913-2012)