Toxic/Metabolic/Nutritional Disease Flashcards
Acute effects of alcohol of CNS
- can be life-threatening
- can lead to cerebral edema
Chronic effects of alcohol on CNS
- 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
Clinical features of Wernicke’s encephalopathy
- 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
Pathologic findings in Wernicke’s encephalopathy
- 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
Etiology of Wernicke’s encephalopathy
- Vitamin B1 (Thiamine) deficiency
- Alcoholism = common cause
- ==> poor food intake + reduced absorption
- Patients w/GI or absorbing problems are also at risk
Radiographic finding in Wernicke’s encephalopathy
- 50% of cases detectable by MRI
- damage to affected structures (mammillary body, ventricles, etc.)
- disruption of BBB
Characteristics of Korsakoff’s Psychosis
- Memory loss associated with Wernicke’s encephalopathy
- Thiamine deficiency ==> damage to dorsomedial nucleus
Disorders of electrochemical neurotransmission (w/out morphological correlates)
- Endocrinological disorders
- Acid/base imbalances
- Electrolyte imbalances
- Renal failure
- Heavy metal toxicities
- Exposure to environmental toxins
- Other neurotoxins
Characteristics of Fetal Alcohol Syndrome
- Affects ~40,000 babies annually in the US
- hyperactivity
- poor motor skills
- learning difficulties
- developmental delay
Etiology of Hepatic Encephalopthy
- 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
Pathogenesis of Hepatic Encephalopthy
- 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
Presentation of Hepatic Encephalopathy
- Episodes of confusion, forgetfulness ==>
- drowsiness, stupor ==>
- coma
Etiology of Wilson’s Disease
- 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
Pathogenesis of Wilson’s disease
- 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
Etiology of Cobalamin deficiency
- Vitamin B12 deficiency
- causes:
- reduced dietary intake (e.g. of meat/dairy)
- pernicious anemia
- inability to absorb B12
- gastric neoplasms, gastrectromy
Mechanism of CNS damage caused by Cobalamin deficiency
- Vitamin B needed for methionine synthetase
- methionine synthetase = helps methylate myelin basic protein
- VitB deficiency ==> demyelination @ CNS
Clinical presentation of Cobalamin deficiency
- 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
Pathologic findings in Cobalmin deficiency
- spongy cavuolization of spinal cord white matter of “combined posterior system”
- ==> myelin breakdon + macrophage influx ==> axonal degeneration
Treatment of Colbamin deficiency
- parenteral administration of vitamin B12
Etiology/Presentation of Central Pontine Myelinolysis (CPM)
- 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
Pathogenesis of CPM
- 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
Pathologic findings in CPM
- focal demyelinating lesions of ventral pons
- sparing of axons and neurons
Treatment of CPM
- Slow correction of hyponatremia
- Steroids – tighten up the BBB