Demyelinating/Degenerative/Genetic/Toxic diseases- PART 1 (Martin) Flashcards
What is the most common demyelinating disease?
Multiple sclerosis
What is MS characterized by?
Distinct episodes of neurologic deficits separated in time due to white matter lesions that are separated in space
Why is severe cognitive impairment not a usual feature of MS?
Because gray matter is relatively spared
What is frequently the initial symptom seen with MS?
Unilateral visual impairment
What is a genetic linkage of MS that increases susceptibility?
DR2
What CSF examination finding for MS is indicative of the presence of a small number of activated B cell clones?
Oligoclonal IgG bands
What is Neuromyelitis optica?
Bilateral optic neuritis and spinal cord demyelination at the same time
Neuromyelitis optica is characterized by antibodies against?
Aquaporin-4
Signs and symptoms of acute disseminated encephalomyelitis develop 1-2 weeks after?
Previous viral infection
In terms of symptomology, how does acute disseminated encephalomyelitis differ from MS?
MS has focal neuro deficits while ADEM has diffuse neuro symptoms
Acute necrotizing hemorrhagic encephalomyelitis almost invariably preceded by a recent episode of?
Upper respiratory infection
Central pontine myelinolysis (aka osmotic demyelination disorder) occurs 2-6 days after?
Rapid correction of hyponatremia
What cells are damaged during central pontine myelinolysis?
Oligodendrocytes
What are the plaques in the neuropil aggregates of in regards to Alzheimer Disease?
The neurofibrillary tangles are aggregates of?
1) Aβ (APP protein)
2) tau protein
Between the Aβ aggregates and the tau protein, which needs to come first in order for Alzheimer to occur?
Aβ plaques then tau aggregates
In regards to Alzheimer, what is hydrocephalus ex vacuo?
What causes it?
1) Compensatory ventricular widening
2) Cortical atrophy with widening of the sulci
What AD plaques contain both Aβ40 and Aβ42?
Which contain predominantly Aβ42?
1) Neuritic (senile) plaques
2) Diffuse plaques
In regards to the morphology of the neurofibrillary tangles, they often have what shape in pyramidal cells?
Elongated flame shape
Because the neurofibrillary tangles are soluble and resistant to clearance in vivo, how are they described as long after the death of the parent neuron?
“ghost” or “tombstone” tangles
Between the tangles and the plaques, which correlate better with the degree of dementia in AD?
The number of tangles correlates better with the degree of dementia than does the number of neuritic (senile) plaques
What do frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration all have in common in terms of tau and Aβ plaques?
tau deposits appear without Aβ plaque in
With Cerebral amyloid angiopathy, what protein is present?
Aβ40 protein
How does frontotemporal lobar degenerations differ from AD?
Changes in personality, behavior, and language come about before changes in memory
What disease is the best known frontotemporal lobar degenerations with tau-containing inclusions?
Pick disease
What occurs morphologically in Pick disease?
Asymmetric atrophy of the frontal and temporal lobes that spares the posterior 2/3 of the superior temporal gyrus
How is the gyral atrophy of frontal and temporal lobes described in Pick disease?
Knife-like thin gyri
What is the pathologic hallmark of progressive supranuclear palsy?
Presence of tau-containing inclusions in neurons and glia
What are the clinical features of Parkinson disease?
1) Diminished facial expression
2) Festinating gait (progressively shortened and accelerated steps)
3) Pill rolling tremor
4) Slow voluntary movement
What system is damaged in Parkinson disease?
Nigrostriatal Dopaminergic system
The diagnosis of PD is made by looking at the characteristic features and the symptomatic response to?
L-DOPA (response decreases over time)
The diagnostic hallmark of PD is?
What is a major component of this?
There is an autosomal dominant PD when?
1) The Lewy body
2) α-synuclein
3) α-synuclein is mutated
What occurs in the substantia nigra and locus coeruleus with Parkinson’s?
Loss of pigmentation (pallor)
Cytoplasmic, eosinophilic, round to elongated, dense core and pale halo describes?
Lewy Bodies
Multiple system atrophy is characterized by?
Cytoplasmic inclusions of α-synuclein in oligodendrocytes
What is the main sign seen with loss of ANS function due to Multiple System Atrophy?
Orthostatic hypotension
How does Huntington Disease clinically present?
Jerky, hyperkinetic, movements involving all parts of the body (chorea)
What is characteristic of Huntington’s?
Increased CAG repeats
What is “anticipation” in terms of HD?
Repeat expansions during spermatogenesis leads to earlier onset
The pathologic hallmark of HD is?
Intranuclear inclusions of the mutated protein huntingtin
Atrophy of what part of the brain is characteristic of HD?
Caudate nucleus
There is a severe loss of what neurons especially in the caudate nucleus with HD?
Striatal neurons
What presents as progressive ataxia, spasticity, weakness, sensory neuropathy, and cardiomyopathy?
Friedreich Ataxia
What do most patients with Friedreich Ataxia die from?
Cardiomyopathy complications such arrhythmias and CHF
What trinucleotide repeat is associated with Friedreich Ataxia?
In what protein?
1) GAA
2) FRATAXIN
What gene is mutated in Chr (11q22-q23) in Ataxia-telangiectasia?
ATM gene
Development of immunodeficiency due to Ataxia-telangiectasia causes what recurrent infections?
Sinopulmonary infections
What does Amyotrophic lateral sclerosis (ALS) cause in the spinal cord and brainstem?
In the cerebral cortex?
1) Loss of lower motor neurons
2) Loss of upper motor neurons
What is most commonly mutated that leads to ALS?
SOD1
In the morphology of ALS, the loss of LMN fibers, loss of anterior horn neurons and reactive gliosis causes?
Anterior roots of spinal cord to be thin
In the morphology of ALS, what structure may be atrophic especially in severe cases?
Precentral gyrus (primary motor cortex)
In the morphology of ALS, what leads to the loss of the corticospinal tracts?
Loss of UMNs
In the morphology of ALS, what do skeletal muscles show?
Neurogenic atrophy
What early symptom of ALS is seen?
Asymmetric weakness of the hands (dropping objects)
In regards to ALS, what motor neuron involvement is associated with primary lateral sclerosis?
With progressive muscular atrophy?
1) UMN
2) LMN
