NS66: Toxic or Metabolic Nervous System Disease

  1. What are the symptoms of Central Pontine Myelinolysis?
    Progressive spastic quadriplaresis and lower cranial nerve palsies
  2. What are the histological findings of Central Pontine Myelinolysis?
    Discolored area in central basis pons, which is because there is a demyelinated area in the basis pons with preserved axons and pontine neurons.
  3. What causes Central Pontine Myelinolysis?
    • too rapid correction of hyponatremia (not enough salt) or serum hypo-osmolality
    • often found in alcoholics who are hydrated too quickly in ICU or syndromes of inappropriate ADH levels
  4. What are the symptoms of methanol ingestion?
    • intial drukennes
    • headache
    • abdominal pain
    • visual loss
    • delirium
    • coma
  5. How is methanol injestion treated?
    infusion with water and ethanol (to compete with methanol molecules at hepatic alcohol dehdrogenase sites). methanol then gets secreted instead of being filtered in the kidney
  6. Why do people who drink methanol have extrapyramidal movement disorders?
    because they have injury to the putamen
  7. What happens at the molecular level when methanol is ingested?
    • methanol is converted to formic acid and formaldehyde by hepatic alcohol dehydrogenase
    • this causes severe metabolic acidosis
  8. What injuries does the brain suffer from methanol ingestion?
    • 1.) blindness: formic acid disrupts axoplasmic flow in optic nerve, resulting in optic disc swelling, axonal destruction, and permanent blindness
    • 2.) the putamen is injured causing extrapyramidal movement disorders
  9. What is the major constituent of antifreeze?
    ethylene glycol
  10. What are the symptoms of ethylene glycol ingestion?
    • initial drunkenness
    • generalized convulsions
    • coma
  11. What are the molecular mechanisms of ethylene glycol poisining?
    • the ethylene glycol gets converted to glycolic acid and oxalic acid
    • this produces severe acidosis
  12. What are one of the most common causes of kidney stones?
    • oxalate crystals from the break down of ethylene glycol
    • these stones cause uremia and eventually kidney failure
  13. What organs does ethylene glycol poisining affect?
    • Brain: chemical meningitis
    • Kidneys: uremia
    • both are affected by oxalate crystal deposition
  14. Wernicke-Korsakoff Syndrome is really what?
    • 2 diseases: Wernicke disease (an encephalopathy) is an acute disorder
    • Korsakoff's pyschosis is the chronic disorder that follows Wernicke disease
  15. What are the symptoms of Wernicke's disease?
    • Abrupt onset of nystagmus and lateral rectus palsy progressing to external ophthalmoplegia
    • truncal and gait ataxia
    • global confusion state
  16. What areas of the brain does the petechial hemorrages, edema, gliosis, and demyelination of Wernicke's disease affect?
    • confusion:
    • mammillary bodies
    • hypothalamus
    • periventricular thalamus
    • truncal gait and ataxia:
    • periaqueductal gray
    • gray beneath 4th ventricle
  17. What are the symptoms of Korsakoff's psychosis?
    • anterograde amnesia- inability to form new memories despite intact immediate recall and remote memory
    • confabulation- falsifying memories by filling in gaps in memory with information that sounds plausable but has little basis in reality
  18. What is the cause of Korsakoff's Psychosis?
    • Bilateral neuronal loss and gliosis of dorsomedial thalamus and mammillary bodies
    • for pictures, this means enlarged 3rd ventricle
  19. Why should we always be careful in administering parenteral glucose to alcoholics who have just been admitted?
    • b/c they may have low thiamine levels
    • thiamine is a cofactor in Kreb's cycle enzymes, which are heavily utilized when metabolizing glucose
    • neuronal death is caused by this problem
  20. What are the two enzymes in the Kreb's cycle that utilize thiamine as a co-factor?
    • pyruvate dehydrogenase complex
    • alpha-ketoglutarate dehydrogenase
  21. What treatment, if administered early in the on-set of Wernicke-Korsakoff Syndrome, can produce rapid improvement?
    high-dose parenteral thiamine
  22. What are the symptoms of alcholic cerebellar degeneration?
    truncal and gait ataxia; this means that they have a wide-based gait and difficulty ascending stairs
  23. What are the brain findings in an alcoholic cerebellar degeneration?
    shrinkage of folia of superior (rostral) vermis and adjacent anterior lobe
  24. What are four classical symptoms seen in adults who have mercury poisining?
    • personality disturbance and dementia "mad as a hatter"
    • cerebellar ataxia
    • intention tremor
    • motor neuropathy
  25. What are the symptoms of mercury poisining in children?
    • acrodynia: pink disease
    • children have swollen, red, cold, moist hands and feet, irritability and insomnia, and anorexia
    • if recieved mercury in the womb, then child will have mental retardation and cerebral palsy
  26. Mercury poisining would seem uncommon, yet there are plenty of cases of it. What were some we discussed?
    • seed sent to middle east coated with mercury as a fungicide
    • minamata disease: term used for mercury disease b/c of seaside town in Japan who dumped mercury in the ocean and people suffered effects
  27. What disorder does Vitamin E (Alpha-tocopherol) often present as?
    Friederich's Ataxia
  28. What is Vitamin E (alpha-tocopherol) deficiency often associated with?
    chronic malabsorption syndromes such as cystic fibrosis in kids
  29. What are four symptoms seen in Vitamin E (alpha-tocopherol) defiency?
    • peripheral polyneuropathy (damage to peripheral nerves)
    • ataxia
    • opthalmoplegia (extra-occular muscle weakness)
    • pigmentary retinopathy
  30. What is the pathogenesis of Vitamin E (alpha-tocopherol) deficiency?
    • demyelination of spinal cord posterior columns
    • axonal enlargements containing filaments, membranes, abnormal mitochondria, and granular materal
    • excessive lipofuscion pigmentation of neurons, astrocytes, and muscle cells
  31. What are the symptoms of Vitamin B12 deficiency?
    • loss of posterior column sensation (proprioception: vibratory and position sense) this leads to a positive Romberg Test
    • spasticity with bilateral extensor planter responses and loss of tendon reflexes
    • depression
    • memory disturbance
    • dementia
  32. What three diseases can Vitamin B12 deficiency cause?
    • Pernicious anemia
    • Subacute combined degeneration of spinal cord
    • Combined systems disease
  33. What are some indications of Vitamin B12 deficiency?
    • Elevated levels of methylmalonic acid in serum or urine
    • Low serum vitamin B12 levels (not a very reliable determinant)
    • Anemia (megaloblastic anemia), macrocytosis, or hypersegmented neutrophils
  34. Since this is Neuroscience, what does Vitamin B12 defiency do to the CNS?
    • Vacuolation (small cavity found in cytoplasm) and fragmentation of myelin followed by axonal degeneration
    • It involves the anterior, posterior, and lateral columns, centered in mid-thoracic spinal cord
  35. What is Sandhoff's Disease?
    • It is a GM2 Gangliosidosis
    • Deficiency of hexosaminidase A and B
  36. What are the symptoms of Tay-Sachs Disease?
    • Initially normal infant
    • By 3 months presents: hyperacusis (hypersensitivity to sound), hyperexcitability, psychomotor retardation, hypotonia, macular cherry-red spot
    • Progressive decerebrate posturing and opisthotonus
    • Macrocrania and seizures
    • Die by age 2
  37. What is the pathology of Tay-Sachs Disease?
    • Initial brain enlargement followed later by marked cerebral atrophy
    • Ballooned neurons containing enlarged lysosomes with granular and lamellar storage material: constipated lysosomes
  38. What are the characteristics of neuronal ceroid lipofuscinosis?
    • Autosomal Recessive Inheritance
    • Progressive Cognitive Deterioration
    • Seizures
    • Retinal Abnormalities (pigmentary retinopathy because destruction of sensory retinas)
  39. What are typical findings in Neuronal Ceroid Lipofuscinosis?
    • Markedly atrophic brain
    • Ceroid lipofuscin in neurons
    • Curvilinear bodies
    • Autofluorescent material (the actual ceroid lipofuscin) stored in lysosomes of multiple organs
  40. Where is the ceroid lipofuscin stored in Neuronal Ceroid Lipofuscinosis?
    • Lysosomes of : Macrophages in spleen, liver, and lymph nodes
    • smooth muscle cells of GI tract, arterioles, and arteries
    • skeletal and cardiac muscle
    • renal glomeruli and tubules
    • neurons of brain and retina
  41. What causes Metachromatic Leukodystrophy?
    • Accumulation of sulfatide (galactocerebroside sulfate)
    • Deficiency of enzyme arylsulfatase A which normally cleaves sulfate from sulfatide
  42. Is metachromatic leukodystrophy more severe as a child or an adult?
  43. What is the affect of Metchromatic Leukodystrophy on adults?
    insidious onset in late adolescence or early adulthood of slowly progressive gait disturbance, behavioral problems, spasiticity, and peripheral neuropathy
  44. What are the molecular findings in metachromatic leukodystrophy?
    • cavitated white matter (with sparing of U-Fibers)
    • loss of oligodendrocytes and Schwann cells and myelin
    • Granular masses of accumulated sulfatide in macrophages this accumulated sulfatide stains metachromatically with toluidine blue or cresyl violet
  45. What is the ultimate result of child-onset metachromatic leukodystrophy?
    quadrapelises and death
  46. What are the two peroxisomal disorders we learned about?
    • Adrenoleukodystrophy/adrenomyeloneuropathy
    • Zellweger's Syndrome
  47. What are the characteristics of adrenoleukodystrophy/adrenomyeloneuropathy?
    • x-linked inheritance
    • single enzyme deficiency
  48. What are the characteristics of Zellweger's Syndrome?
    • Autosomal Recessive
    • Defective peroxisomal biogenesis resultant multiple enzyme deficiencies
  49. What are the 6 symptoms of Andrenoleukodystrophy/Adrenomyeloneuropathy?
    • Spastic paraparesis and sensory loss
    • impaired bladder function
    • adrenal insufficiency
    • low serum testosterone levels
    • peripheral neuropathy
    • bronzing of the skin
  50. What would you expect to find on a brain with Adrenoleukodystrophy / Adrenomyeloneuropathy?
    symmetrical demyelination of cerebral white matter, most severe in occipital regions
  51. What is phenylketonuria?
    Accumulation of phenylalanine due to lack of phenylalanine hydroxylase which converts phenylalanine to tyrosine
  52. How is phenylketonuria treated?
    involves restricting phenylalanine intake in diet
  53. Why is phenylketonuria not really a problem anymore?
    because of newborn screening using the Guthrie test
  54. What do infants present with phenylketonuria?
    • seizures
    • restlessness
    • rigidity
    • microcephaly
    • severe mental retardation
    • defective pigment formation: fair skin, hair, and eyes
  55. Image Upload 2
    What did this man have? What caused it?
    • Central Pontine Myelinolysis
    • too rapid correction of hyponatremia/serum hypo-osmolarity
  56. What do these brain sections of an autoposied patient suggest was the cause of death?
    Which two areas are injured?
    Image Upload 4
    • Methanol Ingestion
    • putamen and optic nerve
  57. What syndrome is associated with this picture?
    What structures are damaged?
    How are they damaged?
    Image Upload 6
    • Wernicke Disease
    • mammillary bodies, hypothalamus, periventricular thalamus, ophthalmoplegia, ataxia, periaqueductal gray, gray beneath the floor of the 4th ventricle
    • petechial hemorrhages,edema, gliosis, and demyelination
  58. What is lost here?
    What is the resulting syndrome?
    Image Upload 8
    • dorsomedial thalamus and mammillary bodies
    • Korsakoff's Pyschosis
  59. What is this cerebellum showing us?
    What shrank on this?
    Image Upload 10
    • Alcoholic Cerebellar Degeneration
    • Folia
  60. What is this presentation called?
    What is the Dx?
    Image Upload 12
    • Acrodynia
    • Mercury Poisining
  61. Look at this LFP-PAS stain of this spinal cord section, what is wrong?
    What is the cause?
    Image Upload 14
    • loss of myelin in the anterior, posterior, and lateral columns in the thoracic spinal cord
    • Vitamin B12 deficiency
  62. What are the figures in this EM image of a neuron?
    What is the diagnosis for this?
    Image Upload 16
    • the onion looking things are ballooned lysosomes with granular and lamellar storage material
    • Tay-Sachs Disease
  63. This brain is markedly atrophic. What metabolic disorder would do this?
    Image Upload 18
    Neuronal Ceroid Lipofuscinosis
  64. This unstained brain is glow'n out of control! What material in the neurons is causing this?
    What is the disease?
    What else would you find this glow'n material?
    Image Upload 20
    • Ceroid Lipofuscin
    • Neuronal Ceroid Lipofuscinosis
    • Macrophages (spleen, liver, lymph nodes), smooth muscle cells (arteries, arterioles, GI tract), cardiac muscle, skeletal muscle, renal glomeruli, renal tubules
  65. What is this stain indicative of?
    What is it called when a color changes in a dye due to binding to certain compounds?
    Image Upload 22
    • Metachromatic Leukodystrophy
    • Metachromasia
  66. When you see symmetrical demyelination of cerebral white matter, which high severity in the occipital regions like this, what do you suspect could be a diagnosis?
    Image Upload 24
Card Set
NS66: Toxic or Metabolic Nervous System Disease
Neuroscience Week 7