Toxic/Metabolic/Nutritional Disease

Question 1

Acute effects of alcohol of CNS

Answer 1

• can be life-threatening
• can lead to cerebral edema

Question 2

Chronic effects of alcohol on CNS

Answer 2

• cerebellar degeneration
  
  • crests of folia most affected
  • granule cell neurons lost > Purkinje cell neurons lost
• neuronal loss
• global cerebral atrophy
  
  • damage to white matter
• menigeal fibrosis
• changres are reversible in early phases

Question 3

Clinical features of Wernicke’s encephalopathy

Answer 3

• Thiamine deficiency (vitamin B1)
• Wernicke’s encephalopathy - full triad of ataxia, nystagmus (or ophthalmoplegia) and confusion
  
  • these signs not always present
• Korsakoff’s psychosis
• Peripheral neuropathy

Question 4

Pathologic findings in Wernicke’s encephalopathy

Answer 4

• Selective vulnerability: mammillary bodies
  
  • also walls of third ventricle, medial thalamus, inferior colliculi, brainstem tegmentum
• acute: macroscopic and microscopic hemorrhage + dilation of capillaries (= disruption of BBB)
  
  • myelin damage
  • reversible neuronal damage
• chronic: neuronal loss, hemosiderin accumulation, mamillary body atrophy

Question 5

Etiology of Wernicke’s encephalopathy

Answer 5

• Vitamin B1 (Thiamine) deficiency
• Alcoholism = common cause
  
  • ==> poor food intake + reduced absorption
• Patients w/GI or absorbing problems are also at risk

Question 6

Radiographic finding in Wernicke’s encephalopathy

Answer 6

• 50% of cases detectable by MRI
• damage to affected structures (mammillary body, ventricles, etc.)
• disruption of BBB

Question 7

Characteristics of Korsakoff’s Psychosis

Answer 7

• Memory loss associated with Wernicke’s encephalopathy
• Thiamine deficiency ==> damage to dorsomedial nucleus

Question 8

Disorders of electrochemical neurotransmission (w/out morphological correlates)

Answer 8

• Endocrinological disorders
• Acid/base imbalances
• Electrolyte imbalances
• Renal failure
• Heavy metal toxicities
• Exposure to environmental toxins
• Other neurotoxins

Question 9

Characteristics of Fetal Alcohol Syndrome

Answer 9

• Affects ~40,000 babies annually in the US
• hyperactivity
• poor motor skills
• learning difficulties
• developmental delay

Question 10

Etiology of Hepatic Encephalopthy

Answer 10

• often: Alcoholism ==> cirrhosis ==> reduced liver fxn ==> increased toxins
• Increased ammonia (from catabolism of proteins) ==> disturbance of amino acid balance ==> disturbance of inhibitory and excitatory NTs @ brain

Question 11

Pathogenesis of Hepatic Encephalopthy

Answer 11

• Normally: Ammonia ==> BBB ==> astrocytes
  
  • glutamine synthetase converts glutamate + ammonia ==> glutamine
  • ==> neuronal axon ==> converted to glutamate and then GABA
• Excess ammonia: “stressed astrocyte” ==> Alzheimer Type II astrocytes = swollen nuclei, little cytoplasm
  
  • atrocytes lose ability to fxn ==> pH imbalance + NT imbalance

Question 12

Presentation of Hepatic Encephalopathy

Answer 12

• Episodes of confusion, forgetfulness ==>
• drowsiness, stupor ==>
• coma

Question 13

Etiology of Wilson’s Disease

Answer 13

• Autosomal recessive
• Chromosome 13 gene
• disorder of copper metabolism
• mean age of presentation = 12 years
  
  • may present w/signs of liver disease + motor/neuro signs

Question 14

Pathogenesis of Wilson’s disease

Answer 14

• Accumulation of copper @ lentiform nucleus ==> neuronal damage via free radicals/oxidation of membrane lipids
• • basal ganglia degeneration ==> movement disorders
• microscopic:
  
  • neuronal loss
  • astrocytosis + Alzheimer type II astrocytes
• copper acculation @ liver ==> cirrhosis ==> hepatic encephalopathy

Question 15

Etiology of Cobalamin deficiency

Answer 15

• Vitamin B12 deficiency
• causes:
  
  • reduced dietary intake (e.g. of meat/dairy)
  • pernicious anemia
    
    • inability to absorb B12
  • gastric neoplasms, gastrectromy

Question 16

Mechanism of CNS damage caused by Cobalamin deficiency

Answer 16

• Vitamin B needed for methionine synthetase
• methionine synthetase = helps methylate myelin basic protein
• VitB deficiency ==> demyelination @ CNS

Question 17

Clinical presentation of Cobalamin deficiency

Answer 17

• Megaloblastic anemia (~70% of cases)
• disorder of dorsal column + lateral corticospinal tract ==>
  
  • diminished vibration + proprioception of lower limbs
  • abnormal reflexes
  • spacsticity
  • incontinence
  • orthostatic hypotension
• damage to cerebral hemispheric white matter ==>
  
  • psychoses
  • dementia
• damage to optic nerve (rare)
  
  • visual changes

Question 18

Pathologic findings in Cobalmin deficiency

Answer 18

• spongy cavuolization of spinal cord white matter of “combined posterior system”
• ==> myelin breakdon + macrophage influx ==> axonal degeneration

Question 19

Treatment of Colbamin deficiency

Answer 19

• parenteral administration of vitamin B12

Question 20

Etiology/Presentation of Central Pontine Myelinolysis (CPM)

Answer 20

• electrolyte imbalance resulting from rapid correction/overrcorrection of hyponatremia
  
  • low serum sodium ==> water into cells ==> cytotoxic edema
  • fluid restriction + hypertonic saline ==> overcorrection ==> high blood osmolarity ==> flow across BBB
• Sx: confusion, delirium, balance issues, speech problems, difficulty swallowing

Question 21

Pathogenesis of CPM

Answer 21

• Edema-mediated myelin damage, resulting from osmotic opening of the blood brain barrier
• Selective vulnerability for areas where gray matter and white matter are closely apposed
  
  • e.g. Pons

Question 22

Pathologic findings in CPM

Answer 22

• focal demyelinating lesions of ventral pons
• sparing of axons and neurons

Question 23

Treatment of CPM

Answer 23

• Slow correction of hyponatremia
• Steroids – tighten up the BBB