Toxic/Metabolic Disorders

Question 1

Neuropathological effects of alcohol - acute vs. chronic

Answer 1

Acute - cerebral edema

Chronic - global cerebral atrophy via damage to white matter (loss of executive function, poor memory, dementia); meningeal fibrosis; selective degeneration of the superior cerebellar vermis

Question 2

Clinical presentation of fetal alcohol syndrome

Answer 2

Hyperactivity
Poor motor skills
Learning difficulties
Developmental delay

Question 3

Characteristic pathological finding of methanol toxicity

Answer 3

Bilateral hemorrhaging necrosis of the putamen

Question 4

Hepatic Encephalopathy - Etiology

Answer 4

Caused by accumulation of toxins (primarily ammonia) in the blood due to liver damage, mainly 2/2 alcoholic cirrhosis

Question 5

Hepatic Encephalopathy - Pathogenesis

Answer 5

Ammonia crosses the BBB and is taken up by astrocytes; excess ammonia within the astrocytes stresses the astrocytes, which become “Alzheimer Type II astrocytes,” with swollen nuclei - these cells are primarily seen in the deep cerebral cortex, globus pallidus, and dentate nucleus of the cerebellum

Question 6

Hepatic Encephalopathy - Clinical Presentation

Answer 6

Episodes of confusion, forgetfulness, drowsiness, stupor, and eventually coma

Flapping tremor of the extended wrist (asterixis) is common

Question 7

Wilson’s Disease

Answer 7

Autosomal recessive disorder of copper metabolism; presents with liver disease, motor dysfunction due to degeneration of the lentiform nucleus and basal ganglia, and encephalopathy due to liver cirrhosis

Treated with iron chelating agents

Question 8

Wernicke’s Encephalopathy

Answer 8

Thiamine (Vitamin B1) deficiency - often seen in alcoholics but may be seen in a subset of GI patients

Question 9

What is the classical triad of Wernicke’s Encephalopathy?

Answer 9

Confusion
Opthalmoplegia (weakness/paralysis of extraocular muscles)
Ataxia

Each of these signs presents in only 1/3 of cases; IV infusion of glucose precipitates the encephalopathy by consuming thiamine, which is utilized as a cofactor in glucose metabolism

Question 10

Wernicke’s Encephalopathy - Pathology

Answer 10

Acutely - macroscopic and microscopic hemorrhage of affected structures, primarily the Mamillary Body; myelin damage results in microglial and macrophage response

Chronic - neuronal loss, mammillary body atrophy

Question 11

Korsakoff Syndrome

Answer 11

Memory loss associated with Wernicke’s encephalopathy

Caused by damage to the dorsomedial nucleus of the thalamus, secondary to thiamine deficiency

Question 12

Causes of cobalmin (B12) deficiency

Answer 12

Reduced dietary intake 
Pernicious anemia - loss of gastric parietal cells which secrete intrinsic factor 
Gastric neoplasms
Gastritis
Gastrectomy

Question 13

Pathogenesis of cobalmin deficiency

Answer 13

Vitamin B12 is required for the function of methionine synthetase, which is involved in methylation of myelin basic protein; abnormalities of this enzymatic function result in demyelination within the CNS

Question 14

Clinical presentation of cobalmin deficiency

Answer 14

Megaloblastic anemia - seen in 70%

Dysfunction of the combined posterior system (dorsal column and lateral corticospinal tracts)

Question 15

Cobalmin deficiency - Pathology

Answer 15

Spongy vacuolization of the spinal cord white matter of the combined posterior system, leading to myelin breakdown, macrophage influx, and axonal degeneration

Question 16

Central Pontine Myelinolysis

Answer 16

Caused by rapid over-correction of hyponatremia; high blood osmolarity opens the BBB causing edema-mediated myelin damage with selective vulnerabilities in areas of gray/white matter apposition (i.e. pons)

Question 17

Central Pontine Myelinolysis - Pathology

Answer 17

Focal demyelinating lesions of the ventral pons

Question 18

Central Pontine Myelinolysis - Treatment

Answer 18

Slow correction of hyponatremia

Steroids - tighten up the BBB