Neurodegenerative disorders Flashcards
hypothyroidism, vitamin B12 deficiency, neurosyphilis, normal pressure hydrocephalus
are all what?
Reversible causes of Dementia
Loss of dopaminergic neurons (depigmentation)
of substantia nigra pars compacta
Parkinson
Lewy bodies are found in what disease?
Parkinson
Lewy body dementia
MPTP, a contaminant in illegal drugs, is metabolized to MPP+, which is toxic and can cause
Parkinson
damage to Substania Nigra
Atrophy of caudate and putamen with ex vacuo ventriculomegaly.
Huntington’s
Tremor (pill-rolling tremor at rest)
Rigidity (cogwheel)
Akinesia (or bradykinesia)
Postural instability
Shuffling gait
Small handwriting (micrographia)
Parkinson
Autosomal dominant trinucleotide (CAG)n repeat expansion
Huntington’s
gene on chromosome 4
Neurodegenerative disease
HTT gene
Huntington’s
chorea, athetosis, aggression, depression, dementia (sometimes initially mistaken for substance abuse).
Huntington’s
Anticipation results from Tri nucleotide expansion in what codon and gene
seen in what disease?
Huntington’s
CAG –> HTT gene
Neuronal death via NMDA-R binding and glutamate excitotoxicity.
Huntington’s
High dopamine
Low GABA & ACh
in brain
Huntington’s
Most common cause of dementia in elderly
Alzheimer’s
Down syndrome patients haveincreased risk because APP is located on chromosome 21
Alzheimer’s
Associated with the following altered proteins:
ApoE-2:______ risk of sporadic form
ApoE-4:______ risk of sporadic form
Alzheimer’s
2: decreased
4: increased
APP, presenilin-1, presenilin 2: familial forms (10%) with risk of ________
earlier onset Alzheimer’s
Wide spread cortical atrophy, especially hippocampus
Narrowing of gyri and widening of sulci
Alzheimer’s
_______ are composed of extra cellular β amyloid core; found in gray matter
Amyloid β (Aβ) synthesized by cleaving amyloid precursor protein (APP)
In what disease?
Senile (Alzheimer) plaques
(looks like black dot aggregates)
Alzheimer’s
Intracellular, hyper phosphorylated tau protein are insoluble cytoskeletal elements called?
Number of these correlates with degree of which dementia?
Neurofibrillary Tangles in Alzheimer’s
(Poppy’s Troll hair)
*Tangles consist Tau protein, which forms part of the microtubule.
intracellular eosinophilic proteinaceous rods in hippocampus are called? In what’s disease?
Hirano bodies
Alzheimer’s
Early changes in personality and behavior
(gambling, shopping, hypersexual, aggressive, etc.),
or aphasia (primary progressive aphasia).
May have associated movement disorders
Fronto-temporal lobe dementia (Pick’s disease)
due to Fronto-temporal lobe degeneration
Round inclusions of hyper phosphorylated tau are called what and seen in what dementia?
Pick bodies (Brownish/black spots on histo) seen in Fronto-temporal lobe dementia (Pick's disease)
Aggregates of ubiquitinated TDP-43
a DNA/mRNA binding protein
Fronto-temporal lobe dementia (Pick’s disease)
look brown
Visual hallucinations
Lewy Body Dementia
dementia with fluctuating cognition/alertness
Lewy Body Dementia
REM sleep behavior disorder, and parkinsonism
Lewy Body Dementia
Called _______ dementia if cognitive and motor symptom on set <1 year apart
Lewy body dementia
*otherwise considered dementia 2° to Parkinson disease
Intracellular Lewy bodies located primarily in the ____
cortex
Result of multiple arterial infarcts and/or chronic ischemia.
Vascular Dementia
Step-wise decline in cognitive ability with late-onset memory impairment
Vascular Dementia
2nd most common cause of dementia in elderly
Vascular Dementia
MRI or CT shows multiple cortical and/or subcortical infarcts.
Vascular Dementia
Rapidly progressive (weeks to months) dementia with myoclonus (“startle myoclonus”) seizures and/or ataxia
Creutzfeldt -Jakob disease
Commonly see periodic sharp waves on EEG
Creutzfeldt -Jakob disease
Increased 14-3-3 protein in CSF
Creutzfeldt -Jakob disease
Spongiform cortex (vacuolization without inflammation).
Creutzfeldt -Jakob disease
Prions PrPcalpha sheets are converted to
PrPsc β pleated sheet resistant to ______.
Creutzfeldt -Jakob disease
proteases
*(look like purple specks with some white halos)
α synuclein (eosinophilic inclusion) +
(Lewy bodies)
Lewy body demetia
and
parkinson’s
Parkinsonism degeneration of midbrain and frontal subcortical white matter
Progressive supranuclear palsy
Gait disturbances, vertical gaze palsy, abnormally phosphorylated Tau protein, loss of executive functions
Progressive supranuclear palsy
composed of α synuclein
intracellular eosinophilic inclusions
Lewy Bodies (pink smooth dots, may have brown smudges near them)
may cause amyloid angiopathy and/or intracranial hemorrhage
in what disease?
Senile Plaques (Aß core) Alzheimer's
Giant Cells
Infected Oligodendrocytes (viral)
Cerebral atrophy
Worsening memory
HIV assoc. Dementia
AD is caused by a decrease in the acetylcholine level due to a deficiency of ________.
The decline in acetylcholine is most notable in the nucleus basalis of Meynert, which participates in memory and cognition.
choline acetyltransferase
As PD progresses, the therapeutic window for levodopa narrows, possibly due to natural or levodopa-induced ____ degeneration.
naigrostriatal
Ataxia early in disease
Urinary incontinence
Dilated ventricles w/o sulcal widening on neuroimaging
cognitive dysfunction
Normal Pressure Hydrocephalus
Wet
Wobbly
Wacky
Reversible with LP drainage of CSF
It is thought to be caused by a virus with a mutated or absent matrix protein that prevents mature (enveloped) virion particles from forming. However, the virus continues to replicate intracellularly, leading to a persistent, nonproductive infection
Accumulation of viral nucleocapsids within neurons and oligodendrocytes results in the formation of intranuclear inclusions and eventually leads to inflammation, demyelination, and gliosis.
Patients have high titers of viral antibodies in the serum and cerebrospinal fluid (detectable as oligoclonal bands). The disease causes various neurologic deficits and dementia, and is relentlessly progressive and fatal.
Subacute sclerosing panencephalitis (SSPE)
Measles
In Huntington’s, prominent atrophy is seen bilaterally in the caudate nucleus and putamen, leading to the enlargement of the ____ ventricles.
frontal horns of the lateral ventricles
___ agonist medications used to treat Parkinson disease have been associated with the abrupt onset of impulse control disorders,
Dopamine
Nigrostriatal degeneration in Parkinson disease reduces activity of the ___ and its projections to the cortex, resulting in bradykinesia and rigidity.
thalamus
Refractory symptoms of Parkinson disease may benefit from high-frequency deep brain stimulation of the globus pallidus INTERNUS or ____ nucleus as it promotes thalamo-cortical disinhibition with improved mobility.
subthalamic
Multiple ___ infarcts would be expected in vascular dementia.
lacunar
Negri bodies are round eosinophilic inclusions seen in the cytoplasm of pyramidal HIPPOCAMPAL neurons and ____ cells in patients infected with the rabies virus.
cerebellar Purkinje
MOA: decreases glutamate release
Riluzole
ALS
Thin anterior roots
Mild atrophy of the precentral gyrus
Reccurrent INFECTIONS
Loss of neurons in the anterior horn (LMN lesion)
Degeneration and atrophy of the lateral corticospinal tracts (UMN lesion)
Loss of neurons in the motor nuclei of CN V, IX, X, XII
Muscle: denervation atrophy (small angular fibers)
ALS
Amyotrophic Lateral Sclerosis
Patients with ALS most often die of
respiratory failure
due to inspiratory muscle weakness (causing decreased vital capacity due to weak diaphragm),
expiratory muscle weakness (causing a weak cough),
bulbar dysfunction (causing dysphagia and chronic aspiration).
____ may cause syncope due to enhanced parasympathetic tone that leads to bradycardia and atrioventricular block with reduced cardiac output.
Acetylcholinesterase inhibitors (donepezil, rivastigmine) for AD
a peripheral nervous system autoimmune demyelinating polyneuropathy that typically causes lower motor neuron manifestations (eg, areflexia, weakness) in a symmetric ascending pattern.
Guillain-Barré syndrome
Vitamin B12 and __ deficiency can cause ataxia and loss of propioception (Neurological Symptoms).
E
___ is seen in children more often than adults. It manifests with irritability, loss of developmental milestones (in infants), or learning problems (in older children). Gastrointestinal symptoms (eg, constipation, nausea, abdominal pain) also occur.
Lead intoxication
damages the ventral white commissure, leading to bilateral loss of pain and temperature sensation that is limited to the affected levels (typically the arms and hands)
Syringomyelia
atrophy of intrinsic hand muscles also a feature
Refractory symptoms of Parkinson disease may benefit from high-frequency deep brain stimulation of the ____ or subthalamic nucleus as it promotes thalamo-cortical disinhibition with improved mobility.
globus pallidus INTERNUS
Refractory symptoms of Parkinson disease may benefit from high-frequency deep brain stimulation of the globus pallidus INTERNUS or subthalamic nucleus as it promotes _____ with improved mobility.
thalamo-cortical disinhibition
Dopamine agonist medications used to treat Parkinson disease have been associated with the abrupt onset of ____ disorders
impulse control
*Pramipexole, Ropinorole, Bromocriptine
