NS66: Toxic or Metabolic Nervous System Disease

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-osmolalityoften found in alcoholics who are hydrated too quickly in ICU or syndromes of inappropriate ADH levels

What are the symptoms of methanol ingestion?

intial drukennesheadacheabdominal painvisual lossdeliriumcoma

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 dehydrogenasethis 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 blindness2.) the putamen is injured causing extrapyramidal movement disorders

What is the major constituent of antifreeze?

ethylene glycol

What are the symptoms of ethylene glycol ingestion?

initial drunkennessgeneralized convulsionscoma

What are the molecular mechanisms of ethylene glycol poisining?

the ethylene glycol gets converted to glycolic acid and oxalic acidthis produces severe acidosis

What are one of the most common causes of kidney stones?

oxalate crystals from the break down of ethylene glycolthese stones cause uremia and eventually kidney failure

What organs does ethylene glycol poisining affect?

Brain: chemical meningitisKidneys: uremiaboth are affected by oxalate crystal deposition

Wernicke-Korsakoff Syndrome is really what?

2 diseases: Wernicke disease (an encephalopathy) is an acute disorderKorsakoff'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 ophthalmoplegiatruncal and gait ataxiaglobal confusion state

What areas of the brain does the petechial hemorrages, edema, gliosis, and demyelination of Wernicke's disease affect?

confusion:mammillary bodieshypothalamusperiventricular thalamustruncal gait and ataxia:periaqueductal graygray 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 bodiesfor 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 levelsthiamine is a cofactor in Kreb's cycle enzymes, which are heavily utilized when metabolizing glucoseneuronal 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 complexalpha-ketoglutarate dehydrogenase

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"cerebellar ataxiaintention tremormotor neuropathy

What are the symptoms of mercury poisining in children?

acrodynia: pink diseasechildren have swollen, red, cold, moist hands and feet, irritability and insomnia, and anorexiaif 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 fungicideminamata 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?

Friederich's Ataxia

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)ataxiaopthalmoplegia (extra-occular muscle weakness)pigmentary retinopathy

What is the pathogenesis of Vitamin E (alpha-tocopherol) deficiency?

demyelination of spinal cord posterior columnsaxonal enlargements containing filaments, membranes, abnormal mitochondria, and granular materalexcessive 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 reflexesdepressionmemory disturbancedementia

What three diseases can Vitamin B12 deficiency cause?

Pernicious anemiaSubacute combined degeneration of spinal cordCombined systems disease

What are some indications of Vitamin B12 deficiency?

Elevated levels of methylmalonic acid in serum or urineLow 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 degenerationIt involves the anterior, posterior, and lateral columns, centered in mid-thoracic spinal cord

What is Sandhoff's Disease?

It is a GM2 GangliosidosisDeficiency of hexosaminidase A and B

What are the symptoms of Tay-Sachs Disease?

Initially normal infantBy 3 months presents: hyperacusis (hypersensitivity to sound), hyperexcitability, psychomotor retardation, hypotonia, macular cherry-red spotProgressive decerebrate posturing and opisthotonusMacrocrania and seizuresDie by age 2

What is the pathology of Tay-Sachs Disease?

Initial brain enlargement followed later by marked cerebral atrophyBallooned neurons containing enlarged lysosomes with granular and lamellar storage material: constipated lysosomes

What are the characteristics of neuronal ceroid lipofuscinosis?

Autosomal Recessive InheritanceProgressive Cognitive DeteriorationSeizuresRetinal Abnormalities (pigmentary retinopathy because destruction of sensory retinas)

What are typical findings in Neuronal Ceroid Lipofuscinosis?

Markedly atrophic brainCeroid lipofuscin in neuronsCurvilinear bodiesAutofluorescent 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 nodessmooth muscle cells of GI tract, arterioles, and arteriesskeletal and cardiac musclerenal glomeruli and tubulesneurons 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?

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 myelinGranular 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?

Adrenoleukodystrophy/adrenomyeloneuropathyZellweger's Syndrome

What are the characteristics of adrenoleukodystrophy/adrenomyeloneuropathy?

x-linked inheritancesingle enzyme deficiency

What are the characteristics of Zellweger's Syndrome?

Autosomal RecessiveDefective peroxisomal biogenesis resultant multiple enzyme deficiencies

What are the 6 symptoms of Andrenoleukodystrophy/Adrenomyeloneuropathy?

Spastic paraparesis and sensory lossimpaired bladder functionadrenal insufficiencylow serum testosterone levelsperipheral neuropathybronzing of the skin

What would you expect to find on a brain with Adrenoleukodystrophy / Adrenomyeloneuropathy?

symmetrical demyelination of cerebral white matter, most severe in occipital regions

What is phenylketonuria?

Accumulation of phenylalanine due to lack of phenylalanine hydroxylase which converts phenylalanine to tyrosine

How is phenylketonuria treated?

involves restricting phenylalanine intake in diet

Why is phenylketonuria not really a problem anymore?

because of newborn screening using the Guthrie test

What do infants present with phenylketonuria?

seizuresrestlessnessrigiditymicrocephalysevere mental retardationdefective pigment formation: fair skin, hair, and eyes

What did this man have? What caused it?

Central Pontine Myelinolysistoo rapid correction of hyponatremia/serum hypo-osmolarity

What do these brain sections of an autoposied patient suggest was the cause of death?Which two areas are injured?

Methanol Ingestionputamen and optic nerve

What syndrome is associated with this picture?What structures are damaged?How are they damaged?

Wernicke Diseasemammillary bodies, hypothalamus, periventricular thalamus, ophthalmoplegia, ataxia, periaqueductal gray, gray beneath the floor of the 4th ventriclepetechial hemorrhages,edema, gliosis, and demyelination

What is lost here?What is the resulting syndrome?

dorsomedial thalamus and mammillary bodiesKorsakoff's Pyschosis

What is this cerebellum showing us?What shrank on this?

Alcoholic Cerebellar DegenerationFolia

What is this presentation called?What is the Dx?

AcrodyniaMercury Poisining

Look at this LFP-PAS stain of this spinal cord section, what is wrong?What is the cause?

loss of myelin in the anterior, posterior, and lateral columns in the thoracic spinal cordVitamin B12 deficiency

What are the figures in this EM image of a neuron?What is the diagnosis for this?

the onion looking things are ballooned lysosomes with granular and lamellar storage materialTay-Sachs Disease

This brain is markedly atrophic. What metabolic disorder would do this?

Neuronal Ceroid Lipofuscinosis

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?

Ceroid LipofuscinNeuronal Ceroid LipofuscinosisMacrophages (spleen, liver, lymph nodes), smooth muscle cells (arteries, arterioles, GI tract), cardiac muscle, skeletal muscle, renal glomeruli, renal tubules

What is this stain indicative of?What is it called when a color changes in a dye due to binding to certain compounds?

Metachromatic LeukodystrophyMetachromasia

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?

Adrenoleukodystrophy/Adrenomyelinoneuropathy