Neuro - CNS - Metabolic DIsease Flashcards
1
Q
Central Pontine Myelinolysis
A
- represents a non-inflammatory demyelination of the pons secondary to the rapid correction of a hyponatremic state or production of a hypernatremic state.
2
Q
Central Pontine Myelinolysis - Epidemeology
A
- Incidence unknown
- CPM was present in 29% of postmortum exams of liver transplant patients; 2/3 of these patients had serum sodium fluctuations of only plus/minus 15-20mEq/L
- In consecutive series of autopsies, CPM was found in 9 cases or 0.25%
3
Q
Central Pontine Myelinolysis - Etiology
A
- More than half of the cases have appeared in association with severe alcoholism
- Other associated diseases include renal dialysis and hepatic failure and other severe terminal diseases
- ** Rapid correction of hyponatremia to normal hypernatremic levels is the causal factor (also assoc. with severe electrolyte /osmolar imbalance.
4
Q
Central Pontine Myelinolysis - Pathology
A
- Lesion involves severe demyelination beginning in the geometric center of the pons (basis pontis, pontine tegmentum) sparing eriventricular and subpial regions.
- Reactive phagocytes and glial cells are present but no signs of inflammation.
- Lesions can also appear in the thalamus, supratentorium but rarely below pontomedullary junction
5
Q
Central Pontine Myelinolysis - Presentation
A
- Acute to subacute
- Rapidly evolving flaccid quadriplegia
- ++Inability to chew, swallow or speak
- Eye movements and facial expressions are often spared.
- Survival is followed by the development of spasticity
- ** Locked-in Syndrome can present (patient is aware and awake, but cannot move or communicate verbally due to paralysis of nearly all voluntary muscles in body except for eyes)
6
Q
Central Pontine Myelinolysis - Prevention
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- Prevent rapid correction/over-correction of sodium levels
7
Q
Ethanol Toxicity
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- The presence of ethanol in the body fluids at levels that are toxic to neurons
8
Q
Ethanol Toxicity - Etiology
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- Alcoholism
9
Q
Ethanol Toxicity - Pathogenesis - Direct Effects
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- Cerebellar (vermal) atrophy - particularly anterior lobe
- Truncal ataxia, unsteady gait, nystagmus
- Loss of purkinje and granule cells and Bergmann gliosis
10
Q
Ethanol Toxicity - Pathogenesis - Indirect Effects
A
- Vitamin deficiency with Wernicke-Korsakoff or subacute combined degeneration
- Cerebral traumatic injury
Liver cirrhosis with hyperammonemia and hepatic encephalopathy
11
Q
Ethanol Toxicity - Presentation
A
- Peripheral neuropathy; bilateral limb numbness, tingling, paresthesias
12
Q
Ethanol Toxicity - Diagnosis
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MRI, CT Scan
* Brain atropgy: ventricular enlargement, widended cortical sulci
13
Q
Ethanol Toxicity - Management with Complication
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- Development of Wernicke-Korsakoff Syndrome
* Liver Cirrhosis, failure and hepatic encephalopathy
14
Q
Hepatic Encephalopathy
A
a metabolic toxification of the brain due to portosystemic shunting of blood secondary to hepatic resistance such as seen in cirrhosis.
15
Q
Hepatic Encephalopathy - History
A
- Associated with liver disease (or any situation where portal blood is shunted around the liver ot the systemic circulation
- Subtle signs of hepatic encephalopathy are present in approximately 70% of the patients with cirrhosis
- Ammonia Theory
- normally 90% of ammonia is removed by the liver
- normally, astrocytes remove brain NH3 by conversion to glutamine
- HE pathology includes the presence of abnormal astrocytes n the cerebral cortical tissue
- elevated blood NH3 concentration detected in HE
- High NH3 damages the astrocyte’s ability to remove NH3 from the neuron, and impairs neuron function
- GABA-benzodiazepine theory
- increased production of endogenous benzodiazepines
- Increase in GABA content of the brain
16
Q
Hepatic Encephalopathy - Presentation
A
- Initially:
- derangement of consciousness
- mental confusion
- increased psychomotor activity
- Eventually
- drowsiness
- stupor
- coma
- Asterixis (intermittent muscle contraction when attempting a postural fixation; non-rhythmic rapid extension-flexion movements of the head and extremities
- grimacing, suck and grasp reflexes
- exaggerated or asymmetric tendon reflexes, babinski sign
- focal or generalized seizures
17
Q
Subacute Combined Degeneration
A
Degeneration fo the posterior and lateral columns of the spinal cord secondary to a deficiency in vitamin B12 (cobalamin) (vitamin B12 deficiency)
18
Q
Subacute Combined Degeneration - History
A
- Failure to transfer minute amounts of B12 across the intestinal wall
- Can be precipitated by exposure to nitrous oxide gas
19
Q
Subacute Combined Degeneration - Pathology
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- Deficiency leads to spongy vacuolation, intramyelinic and interstitial edena of myelin sheaths and their eventual destruction and astrocytosis.
- Initially, the heavily myelinated posterior and lateral columns of the spinal cord are prime targets
- With time, both the ascending sensory tracts and the descending motor tracts become demyelinated (hence name subacute combined degeneration)
20
Q
Subacute Combined Degeneration - Presentation
A
- Subacute and progressive development of ataxia, numbness and tingling in the LE. Progresses to weakness and spasticity and increased DTR
- Loss of 2PV
- Pernicious anemia (decreased RBC)
- Spinal cord myelopathy (injury relating to spinal cord)
- Diffuse and symmetric presentation
- Paresthesias in hands and feet
- peripheral neuropathy: swelling of myelin layers
Dementia
21
Q
Subacute Combined Degeneration - Treatment
A
- Prompt B12 supplements may be reversible
* Irreversible with complete paraplegia has developed
22
Q
Thiamine Deficiency
A
- Thiamine is a water soluble vitamin and must be acquired from the diet. A deficiency state (in famine-affected parts of the world, alcoholics, or medical patients with dietary problems) can result in cardiac problems and peripheral neuropathy (beriberi)
23
Q
Thiamine Deficiency - Etiology
A
Deficiency can cause:
- Wernicke’s encephalopathy - gaze palsies, ataxia, confusion
- Korsakoff’s Syndrome : memory difficulties and confabulation
- In alcoholics, the two often occur together
24
Q
Thiamine Deficiency - Pathology
A
- Characterized by foci of hemorrhage and necrosis in structures around the third ventricle
- classically the mamillary bodies
- also the colliculi, DM thalamus, hypothalamus
- Lesions eventually infiltrated by macrophages > cystic
25
Thiamine Deficiency - Presentation
* Cardiomyopathy: peripheral vasodilation, high output cardiac failure, peripheral edema
* Peripheral neuropathy (dry beriberi); toe drop > foot drop > wrist drop, hyporeflexia, muscle weakness
* Encephalopathy: Wernicke-Korsakoff
26
Thiamine Deficiency - Diagnosis
High resolution MRI may show mammillary body atrophy
27
Wernicke-Korsakoff Syndrome (alcoholic encephalopathy)
* This syndrome is actually two processes: Wernicke's syndrome and Korsakoff's syndrome.
* However, they often present together particularly in alcoholics where they tend to associate with a thiamine deficiency
28
Wernicke-Korsakoff Syndrome - Epidemiology
* Incidence of 10/1000 per year in the US
| * ** Alcoholism is the most common cause
29
Wernicke-Korsakoff Syndrome - Etiology
* Appears in approximately 3% of the alcoholic population in the US
* Other causes: malnutrition due to hyperemesis, starvation, renal dialysis, cancer, AIDS or extreme diets
* Syndrome is associated with thiamine deficiency
30
Wernicke-Korsakoff Syndrome - Pathogenesis
* Lesions in the paraventricular regions of the third ventricle (mamillary bodies) and cerebral aqueduct such as the thalamus, hypothalamus and midbrain
31
Wernicke-Korsakoff Syndrome - Presentation
Wernicke Syndrome - Abrupt onset
* Nystagmus
* Abducens or horizontal gaze palsy
* Gait ataxia
* Mental confusion
Korsakoff Psychosis (prolonged and irreversible)
* Learning and retentive memory defect out of proportion with all other mental status changes
* Confabulation
32
Wernicke-Korsakoff Syndrome - Diagnostic Testing
* Diagnosis on clinical findings
* MRI can be helpful
* Vestibular testing in impaired
* CAGE screen for alcoholism
33
Wernicke-Korsakoff Syndrome - Treatment
* Medical emergency
* Administration of thiamine
- only within first days of symptom onset because Korsakoff psychosis produces irreversible damage to the mamillary bodies.
34
Wernicke-Korsakoff Syndrome - Management with Complications
* Recovery with thiamine treatment canbe dramatic
* Sequelae of ethanol toxicity
* Complications include such thing as:
* Signs and symptoms of alcohol withdrawl
* Liver failure
* Systemic infection
35
Wernicke-Korsakoff Syndrome - Prevention
* Life style changes
* Improved Diet
* Avoidance of Alcohol
36
Wilson's Diseases ( hepatolenticular degeneration)
* autosomal recessive disorder resulting in defective metabolism of copper and copper toxicity
* Sequale primarily involve the liver and brain
37
Wilson's Diseases - Epidemiology
* Worldwide incidence is 10-30 million cases, with increased rates in areas of consanguinity
- 9,000 patients in the US
- manifests between 6-40 years of age
* The heterozygote carrier rate is 1 case per 100 persons, corresponding to a gene frequency varying between 0.3% - 0.7%
* The frequency ranges worldwide from 1 case per 30,000 in Japan to 1 case per 100,000 in Australia.
38
Wilson's Diseases - Pathology
* Mutation on the ATP7B gene (Chromosome 13), a copper-transporting ATPase > failure of biliary copper execretion > copper accumulation in liver > toxic injury through copper catalyzed formation of reactive oxygen species.
* Low blood levels of ceruloplasmin > low blood levels of copper > copper built up in body tissue (liver brain eye) > copper toxicity
39
Wilson's Diseases - Presentation
* Latent period for accumulation followed by onset of critical systemic illness
* Hepatic: Hepatitis, cirrhosis and or hepatic failure (most common)
* Neurologic:
- dystonia, incoordination and tremor
- autonomic dysfunctions include orthostatic hypotension, sweating, bladder and bowel
- memory loss, migraines and seizures
- parkinson disease-like syndromes (tremors)
* Psychiatric
- behavioral disturbances, frank psychosis, can precede the clinical manifestations
* increased copper output in urine
