Metabolic disorders of the nervous system

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jknell
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194789
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Metabolic disorders of the nervous system
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2013-01-25 02:12:44
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MBB II
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metabolic disorders of the nervous system
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  1. Metabolic disorders
    general principlese
    • Diffuse - selective vulnerabilities can make them appear very specific
    • Subacute dysfunction - min to months. rapid subacute (i.e. ischemia) to gradual deposition or accumulation of toxic substances
    • Inherited and acquired

    often seen as part of multi-organ dysfunction
  2. Hypoxia
    causes
    • oxygen deficiency at a tissue level
    • 1. Hypoxic hypoxia - PO2 of arterial blood is reduced (high altitude, anesthetic accident, pulm disease)
    • 2. Anemic hypoxia - oxygen carrying capacity of blood is reduced; decreased Hgb (anemia, CO poisoning)
    • 3. Ischemic hypoxia - decreased blood flow (almost all clinically relevant hypoxia is ischemic hypoxia)
    • 4. Histotoxic hypoxia - toxin prevents cells from making use of O2 (cyanide poisoning)
  3. Hypoxia
    sx
    slow onset (COPD): inattentive and uncoordinated, decreased executive function

    profound: stuporous, comatose... brain injury will probably ensue within minutes

    gradual improvement with time

    • *Adults: cardiac arrest (leading cause of hypoxemia and ischemia)
    • *Children: pulmonary events
  4. Pathology of cerebral ischemia
    over time
    12-24 hours - red dead neurons

    24 hrs - 2 weeks - necrosis of tissue, infiltration by neutrophils, macrophages

    several weeks - gliosis
  5. Pathology of cerebral ischemia
    location
    selective vulnerability too...

    • 1. Hypoxic-ischemic injury
    •    A. Pyramidal cells in the areas CA1 of the hippocampus
    •    B. Purkinje cells in the cerebellum
    •    C. Cortical pyramidal neurons in the layers 3 and 5

    • 2. Watershed - in the setting of global hypoperfusion
    •    A. Border zone between ACA and MCA
    •    B. Border zone between MCA and PCA
    •    C. border zone in the mid to low thoracic spinal cord (anterior spinal artery [from the vertebral arteries and some radicular arteries] and the inferior supply [from the great spinal artery and other radicular arteries of the aorta])
  6. hypoxic cell death
    • Severe deprivation - immediate cell death, massive cytotoxic edema
    • Apoptosis, due to:
    • 1. excitotoxicity from neurotransmitter release (glutamate). Calcium influx --> kinases --> cell death. --> also from free radical generation
  7. Hypoxic ischemic brain injury
    evaluation and treatment
    • Evaluation:
    • -rule out other pathologies

    • Tx:
    • -limit further damage (vital signs and cerebral perfusion
    • -prognosis based on mile stones and available resources
    • -CPR
    • -Hypothermia; core temp reduced ~10% within 2-3 hours of injury. Cool for ~48hrs
  8. Hypercarbia
    hypercapnia

    Sx and causes; treatment
    Increased CO2

    • Clinical:
    • -Headache - CO2 causes increased blood flow/volume in the skull
    • -Papilledema - bilaterally
    • -Drowsiness and confusion (stupor and coma)
    • -Asterixis - irregular lapse of sustained posture (hands/wrist); often seen in hepatic encephalopathy, but not specific
    • -Essential-like tremor
    • -Bilateral hyperreflexia and babinski 

    • Causes:
    • - COPD (or similar obstructive lung disease)
    • - Central drive (non-pulmonary; often medullary lesion)

    • - treat the underlying etiology
    • - positive pressure ventilation
  9. Hypoglycemia
    dx
    selective vulnerability
    Hypoglycemia doesn't produce symptoms until glucose < 30 mg/dL.

    Glucose 10-30mg/dL will present with: nervousness, flushing, sweats, trembles, palpitations... can progress to drowsiness and rarely seizures and focal neurological signs

    Glucose <10mg/dL leads to coma, dilation of pupils, shallow respiration, hypotonia and bradycardia

    • Sensitive cells: (same as hypoxia)
    • -CA1 of hippocampus
    • -Purkinge cells
    • -large cortical pyramidal neurons

    Mechanism: unclear, excitotoxicity similar to ischemic injury
  10. Hyperglycemias
    Ketotic hyperglycemia (aka diabetic ketoacidosis)

    • - evolves over days, involves dehydration, headache, fatigue, weakness, abdominal pain, xerostomia, stupor/coma
    • - glucose is typically over 400mg/dL, pH is <7.2, ketone bodies are elevated in blood and urine
    • -Reversible with treatment

    Hyperosmolar nonketotic hyperglycemia

    • -slower process
    • -fatigue and confusion --> stupor coma
    • -glucose > 600mg/dL, no or minimal ketosis, osmolality is >330mOsm/L
    • -focal symptoms and signs (hemiparesis, hemisensory deficit, homonymous visual field defect, focal seizures)
    • -most often seen in elderly diabetics, often in setting of infection, enteritis, dehydration, meds that interfere with diabetic control.

    Correction of severe hyperglycemia can cause cerebral edema in a small number of patients
  11. Renal failure
    uremia
    Clinical phenotype depends on rapidity of failure:

    1. Rapid onset --> apathy, fatigue, confusion, progression to asterixis, dysarthria, stupor and coma. Multifocal myoclonus is usually present; may have abnormal chorea-like movements and tremors. very sick, right away.

    2. Slow onset --> more indolent presentation: inattention, visual hallucinations (but don't interact with patient), motor findings that are mild

    BOTH lead to coma, disordered breathing, and death

    Pathology: CNS changes are minimal, hyperplasia of protoplasmic astrocytes in the brain and spinal cord

    Pathophys: not known
  12. Hyponatremia
    Sx: seizures, delirium, stupor and coma, and rare focal neurological deficits in the absence of focal brain lesions

    sudden lowering of sodium causes more pronounced symptoms

    Levels must be < 115-125mEq/L

    • Causes:
    • -SIADH (syndrome of inappropriate antidiuretic hormone secretion): complication in a trauma, stroke, bacterial meningitis, cerebral infarction, Guillain-Barre syndrome, and meds.
    •      -produces hypotonic isovolemic hyponatremia; most common cause of this type of hyponatremia

    -
    Other

    *Caution with the speed of correction --> brain damage
  13. Hypernatremia
    • sx: impaired consciousness, asterixis, myoclonus, seizures
    • degree of sx corresponds with the rapidity of change
    • Na > 170mEq/L

    Severe hypernatremia can cause brain shrinkage --> subdural hematoma (tearing of bridging veins)
  14. Central pontine myelinolysis
    aka osmotic demyelination syndrome
    • (correcting hyponatremia)
    • Rapid increase in serum osmolality causes a syndrome of rapid subacute onset flaccid paralysis "from the face down".

    = Locked-in syndrome: vertical eye movements, alertness, sleep wake cycles, cognition are preserved

    Pathology: symmetrical severe demyelination with preserved cell bodies and axons involving basis pontis and sometimes the anterior pontine tegmentum

    *prevent: correct by no more than 10mEq/L in the first 24hrs; no more than 21mEq/L in the first 48hrs
  15. Hypokalemia and hyperkalemia
    Weakness of skeletal muscles (can look like myopathy); most notably large proximal muscles.

    Often iatrogenic, or due to renal dysfunction

    Weakness corresponds to rapidity of change (increase or decrease)

    • <2mEq/L
    • >7mEq/L -->cardiac rhythm disorders may also be present

    No pathology
  16. Hypocalcemia
    ...eventually progress to delirium and stupor

    • subacute onset:
    • - parasthesia
    • - tetany - involuntary cramp-like spasms; any muscle except the extraocular muscle
    • - seizures (less commonly) 

    Risk factors: hypoparathyroidism

    Serum Ca <7mg/dL; ionized calcium determines clinical effect. Recall Ca is bound to albumin

    Correct by IV calcium gluconate
  17. Hypercalcemia
    ...eventually progress to delirium and stupor

    Subacute onset of thirst, polyuria, constipation, nausea, nephrolithiasis, fatigue and headaches

    • Risk factors:
    • - hyperparathyroidism in young pts
    • - osteolytic bone tumors in older patients

    Serum Ca > 12mg/dL (in pts with normal albumin)

    Tx: isotonic saline hydration
  18. Hypomagnesia
    Subacute onset of diffuse tremor, muscle weakness, tetanic muscle spasm, and seizures

    RARE; tx with magnesium supplementation
  19. hypermagnesemia
    Muscle weakness and CNS depression

    Rare;  ouside accidental or intentional magnesium overdose, or as iatrogenic complication of magnesium infusion for the tx of eclampsia in pregnancy.

    Tx: calcium salt or dialasis
  20. Hepatic failure
    (Hepatic encephalopathy)

    Time course: variable

    • Sx: mental slowing and confusion, progression to stupor and coma. Motor signs: asterixis, myoclonus, rigidity, seizures
    • Sx often occur in response to an increased protein load (after meal or GI bleed).

    • Causes:
    • 1. Cirrhosis - alcohol, viral, other
    • 2. Infectious hepatitis
    • 3. Intoxications - acetaminophen
    • 4. Genetics, other

    Pathology: increase number and size of protoplasmic astrocytes throughout the brain regions. "Alzheimer type II astrocytes"; contain glycogen inclusions. On EM, astrocytes have swollen terminal processes, cytoplasmic vacuolation, increased mitochondria

    Pathophysiology: failure of liver to metabolize ammonia --> toxic level reaches the brain; direct toxicity; ammonia inhibits metabolism of GABA by the astrocytes (enhances gabaergic neurotransmission
  21. Hepatic failure
    evaluation and treatment
    dependent on the rapidity of onset of the encephalopathy and pt's level of consciousness

    - EEG patterns are strongly suggestive of hepatic encephalopathy

    • Tx:
    • -indolent: restriction of dietary protein and lactulose

    -Lactulose (PO, rectal), inert sugar that acts as osmotic laxative, leads to diarrhea. Metabolism by colonic bacteria produces lactic acid, and small amounts of formic and acetic acid.

    The acidic environment ionizes ammonia in the colon to ammonium, which cannot diffuse across the colonic membrane --> excreted. This reduces the blood ammonia levels by 25 to 50%
  22. Hypertensive encephalopathy
    including posterior reversible leukoencephalopathy
    rapid subacute onset (1-2 days) headache, nausea, vomiting, visual disturbances, confusion, and potentially stupor and coma. Seizures frequently occur and are often focal

    Exam: HTN (BP >200/100), retinal hemorrhages, exudates, papilledema

    • Predilection for inducing changes in occipital white matter... PRES
    • Posterior reversible leukoencephalopathy syndrome 
    • -characteristic MR with hyperintensities bilat occipital and parietal

    Epidemiology: pts with longstanding and worsening essential HTN, stimulant drug abuse, renal dysfunction, eclampsia in pregnant women

    Complications: worry about hemorrhages, lacunar infarctions

    • Tx: lower BP, but not too quickly (worry about watershed ischemia
    • -nitroprusside
    • -nicardipine
    • -esmolol
  23. Metabolic/respiratory acidosis and alkalosis
    • Metabolic acidosis (severe) - may be associated with delirium or lethargy
    • Metabolic alkalosis (severe) - may cause tetany, encephalopathy (rare)

    • Respiratory acidosis - hypercarbia (increased CO2)
    • Respiratory alkalosis - lightheadedness, confusion (low PCO2 --> vasoconstriction, decreases cerebral blood flow)
  24. Wilson's disease
    hepatolenticular degeneration
    abnormal deposition of copper in wide variety of organs; most notably the liver, brain, and eye

    • Liver - hepatocyte necrosis, moderate inflammation, vacuolated hepatocellular nuclei... eventually proceed to cirrhosis
    • Brain - atrophy, cavitation in the basal ganglia, especially the putamen
    • Eye - Kayser-Fleischer rings - golden or rusty brown deposits of copper around the outer margins of the cornea

    • Cause: autosomal recessive; both coppies of ATP7B genes, which encode for membrane bound copper-binding ATPase
    • --> decreased biliary copper excretion. increased copper urinary excretion

    • Presentation: liver disease or neurologic disease; often presents during 2nd or third decade of life.
    • -extra-pyramidal motor dysfunction, with slowness and rigidity particularly in the oropharyngeal musculature.
    • -balisthmus like movements, "wing-beating" tremor

    • Tx: reduction of dietary intake of copper and copper chelation (with D-penicillamine)
    • -Liver transplant

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