What are the symptoms of Central Pontine Myelinolysis?
Progressive spastic quadriplaresis and lower cranial nerve palsies
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.
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
What are the symptoms of methanol ingestion?
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
Why do people who drink methanol have extrapyramidal movement disorders?
because they have injury to the putamen
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
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
What is the major constituent of antifreeze?
What are the symptoms of ethylene glycol ingestion?
What are the molecular mechanisms of ethylene glycol poisining?
the ethylene glycol gets converted to glycolic acid and oxalic acid
this produces severe acidosis
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
What organs does ethylene glycol poisining affect?
Brain: chemical meningitis
both are affected by oxalate crystal deposition
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
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
What areas of the brain does the petechial hemorrages, edema, gliosis, and demyelination of Wernicke's disease affect?
truncal gait and ataxia:
gray beneath 4th ventricle
What are the symptoms of Korsakoff's psychosis?
anterograde amnesia- inability to form new memories despite intact immediate recall and remote memoryconfabulation- falsifying memories by filling in gaps in memory with information that sounds plausable but has little basis in reality
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
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
What are the two enzymes in the Kreb's cycle that utilize thiamine as a co-factor?
pyruvate dehydrogenase complex
What treatment, if administered early in the on-set of Wernicke-Korsakoff Syndrome, can produce rapid improvement?
high-dose parenteral thiamine
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
What are the brain findings in an alcoholic cerebellar degeneration?
shrinkage of folia of superior (rostral) vermis and adjacent anterior lobe
What are four classical symptoms seen in adults who have mercury poisining?
personality disturbance and dementia "mad as a hatter"
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
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
What disorder does Vitamin E (Alpha-tocopherol) often present as?
What is Vitamin E (alpha-tocopherol) deficiency often associated with?
chronic malabsorption syndromes such as cystic fibrosis in kids
What are four symptoms seen in Vitamin E (alpha-tocopherol) defiency?
peripheral polyneuropathy (damage to peripheral nerves)
opthalmoplegia (extra-occular muscle weakness)
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
What are the symptoms of Vitamin B12 deficiency?
loss of posterior column sensation (proprioception: vibratory and position sense) this leads to a positive Romberg Testspasticity with bilateral extensor planter responses and loss of tendon reflexes
What three diseases can Vitamin B12 deficiency cause?
Subacute combined degeneration of spinal cord
Combined systems disease
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
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
What is Sandhoff's Disease?
It is a GM2 Gangliosidosis
Deficiency of hexosaminidase A and B
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
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
What are the characteristics of neuronal ceroid lipofuscinosis?
Autosomal Recessive Inheritance
Progressive Cognitive Deterioration
Retinal Abnormalities (pigmentary retinopathy because destruction of sensory retinas)
What are typical findings in Neuronal Ceroid Lipofuscinosis?
Markedly atrophic brain
Ceroid lipofuscin in neurons
Autofluorescent material (the actual ceroid lipofuscin) stored in lysosomes of multiple organs
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
What causes Metachromatic Leukodystrophy?
Accumulation of sulfatide (galactocerebroside sulfate)
Deficiency of enzyme arylsulfatase A which normally cleaves sulfate from sulfatide
Is metachromatic leukodystrophy more severe as a child or an adult?
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
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
What is the ultimate result of child-onset metachromatic leukodystrophy?
quadrapelises and death
What are the two peroxisomal disorders we learned about?
What are the characteristics of adrenoleukodystrophy/adrenomyeloneuropathy?
single enzyme deficiency
What are the characteristics of Zellweger's Syndrome?