Neurodegenerative Disorders Flashcards
Pathogenesis of Multiple Sclerosis
chronic degenerative demyelination of white matter in the CNS by TH1 and TH17 lymphocytes
Diagnostics of Multiple sclerosis
oligoclonal IgG bands in CSF electrophoresis
Acute Morphology of MS
periventricular inflammatory infiltrates
chronic morphology of MS
loss of oligodendrocytes
astrocyte proliferation
gliosis
Associations of MS
HLA-DR2
Vitamin D Insufficiency
EBV
Most common sites for MS
Periventricular areas
Brain Stem
Optic Nerve
Cerebellum
Spinal Cord
Morphology of PML
demyelination of axons and intranuclear inclusions
Diagnostics of PML
PCR shows JC Virus in CSF
MRI: non-enhancing white matter lesions
without mass effect
What causes central pontine myelinosis
Rapid correction of chronic hyponatremia causes cell lysis
behavior changes
cognitive disorder
impaired vigilance
seizure
Presentation of PML
autonomic dysfunction
charcot triad
abnormal reflexes/ sensation
Lhermitte sign
Internuclear opthalmoplegia
Optic neuritis
Presentation of MS
Locked in syndrome
AMS
pseudo bulbar signs
Presentation of central pontine myelinosis
what are pseudobulbar signs
dysarthria
dysphagia
dysphonia
Pathogenesis of Alzheimer Disease
Extracellular senile plaques and intracellular neurofibrillary tangles cause damage to the hippocampus and cause degeneration of cholinergic neurons in the nucleus basalis of Meynert
what ar Alzheimer plaques made of
AB protein
What are Alzheimer tangles made of
hyperphosphorylated tau proteins
Diagnostics of Alzheimer Disease
CT/MRI: widened sulci with narrowed gyri
Morphology of Alzheimer Disease
intracellular neurofibrillary tangles and extracellular neuritic plaques
Abnormal amyloid gene expression on chromosome 1 is due to
presenilin 2 mutation
Abnormal amyloid gene expression on chromosome 14 is due to
Presenilin 1 mutation
Abnormal amyloid gene expression on chromosome 21 is due to
APP mutation
Associations of Alzheimer Disease
Hydrocephalus ex vacuo
Down Syndrome
HTN
DM type 2
HLD
Traumatic brain injury
family history
ACh deficiency
Morphology of Frontotemporal dementia
spherical intracellular hyperphosphorylated tau inclusion bodies
Hyperphosphorylated TDP-43
What are pick bodies
spherical intracellular hyperphosphorylated tau inclusion bodies
Contrast CSF of FTD and Alzheimer Disease
FTD: increased AB protein
AD: decreased B amyloid, but increased phosphorylated tau
Pathogenesis of FTD
mutations in microtubule associated tau proteins or progranulin gene
Diagnostic findings of someone with HIV-associated dementia
CD4 <200
Morphology of HIV associated dementia
Microglial nodules: macrophage-derived multinucleated giant cells and foci of tissue necrosis with reactive gliosis
What are lewy bodies
intranuclear eosinophilic inclusions of misfolded alpha synuclein
Pathogenesis of Lewy bodies dementia
Lewy bodies in glial cells cause myelin and glial dysfunction with subsequent neuronal degeneration
Diagnostics of Lewy Body Dementia
cerebral atrophy of the frontal lobe with relative sparing of the hippocampus
Paranoia
frequent falls
cognitive fluctuations
impaired executive function and attention
Late onset dementia
Parkinsonism
Features of Lewy Body Dementia
Behavior changes
Personality Changes
Dementia
Features of FTD
Subcortical dementia
Attention/ Working Memory/ Executive function Deficit
Slow information processing
Features of HIV associated dementia
Memory loss
anomic aphasia
apraxia
visual-spatial deficits
behavior/ mood changes
hallucinations
paranoia
incontinence
seizure
Features of Alzheimer Disease
Pathogenesis of Parkinson disease
nigrostriatal degeneration leads to excessive excitation of GPI by the subthalamic nucleus causing excessive inhibition of the thalamus
Inheritance of Huntington Disease
Autosomal Dominant
pathogenesis of Huntington Disease
CAG repeats on chromosome 4 causes neuronal loss and gliosis in the caudate nucleus, decreasing GABA and ACh
caudate atrophy with enlargement of lateral ventricles
CT/MRI of Huntington Disease
Lewy bodies in Basal ganglia
Parkinson Disease
Lewy Bodies in Cortex
Lewy Body Dementia
features of Huntington disease
chorea
aggressiveness
depression
progressive dementia
features of Parkinson disease
bradykinesia/ akinesia
resting tremor
pill-rolling tremor
cogwheel rigidity
postural instability
shuffling gait
features of Freidrich Ataxia aside from ataxia
frequent falls
intention tremor
scoliosis
Features of Ataxia-telangiectasia aside from ataxia and telangiectasia
recurrent infection
Athetosis
Mode of inheritance of Friedrich Ataxia and Ataxia-telangiectasia
Autosomal Recessive
PAthogenesis of Friedrich Ataxia
GAA trinucleotide repeats on the frataxin gene of chromosome 9 cause mitochondrial accumulation of iron, leading to free radical damage and degeneration
Pathogenesis of Ataxia-Telangiectasia
mutation of ATM gene, causing inability to repair dsDNA breaks
Diagnostics of Friedrich Ataxia
absent/ reduced nerve action potential
normal motor conduction until late stages
Associations of Friedrich Ataxia
hypertrophic cardiomyopathy
first decade of life
Associations of Ataxia-Telangiectasia
increased risk for carcinomas, gliomas and lymphomas
What is ALS
Asymmetric UMN and LMN impairment due to mutation of SOD1 gene
Signs of ALS
asymmetric limb weakness
UMN and LMN signs
dysarthria
dysphagia
cognitive impairment
respiratory failure
Diagnostics of ALS
Normal nerve conduction
Elevated Creatine Kinase
Morphology of ALS
thin ventral roots
atrophy of precentral gyrus
UMN and LMN degeneration at corticospinal tracts
muscle atrophy
gliosis
bunina bodies
loss of LMN at anterior horn
what are Bunina bodies
eosinophilic inclusions located in nerve cell cytoplasm, as seen in ALS
