Path XII Flashcards
synucleinopathy
parkinsons
lewy bodies
fibrils of insoluble polymers of alpha synuclein deposited in neuronal body and form lamellated eosinophilic cytoplasmic inclusions (lewy bodies)
lewy bodies are also found in what cells
astrocytes and oligodendrocytes
aggregates in parkinsons
alpha synuclein
lewy bodies cause what
neuronal degeneration and death
lewy bodies are found where in brain
all throughout
black color of substantia nigra can come from what
melanin in catecholaminergic cells
melanin granule color in lewy body
red brown
what stain would be + in substantia nigra neurons
GFAP for gliosis
second most common cause of dementia (not AD)
diffuse lewy body disease
diffuse lewy body disease combines what
dementia and parkinsonism
diffuse lewy body disease presentation
fluctuating attention and cognition and visual hallucinations
depression, sleep disorder and autonomic dysfunction
motor manifestations in diffuse lewy body disease
bradykinesia, rigidity, and less frequently tremor… may appear later
brain in diffuse lewy body disease
not atrophic
small inconspicuous lewy bodies in neocortex, limbic system and brainstem
circuits involved in multiple system atrophy MSA
1: striatonigral circuit (parkinsonism)
2: olivopontocerebellar circuit (ataxia)
3: autonomic nervous system including central elements (orthostatic hypotension as prominent component)
steele gray color of putamen
multiple system atrophy
are there lewy bodies in substantia nigra in multiple system atrophy
no
huntingtons
fatal autosomal dominant condition beings in 4th-5th decade of life
characterization of huntingtons
behavioral changes, chorea, dementia
Sx begin before age 20
areas affected by huntington
caudate and putamen
IHC stain for huntingonts
huntington protein or ubiquitin
aggregations in huntingtons
abnormal huntington protein (with ubiquitin)
aggregated huntington can cause what
taken up by neurons and suggests prion like spread from one neuron to another
trineucleotide repeat disorder in huntingtons
CAG
increased glutamine
gene for huntington
4p16.3 encodes protein huntingtin
more than 35 CAG copies assoc with disease
type of transmission of CAG in huntingtons
paternal transmission
“anticipation” inc risk earlier onset in upcoming generations
polyglutamine or polyQ
HD
because inc CAG which encodes glutamine or “Q”
3 mechanisms of unstable repeats cause disease
loss of function from transcription silencing
toxic gain of function from alterations of protein structure
toxic gain of function mediated by mRNA like fragile X tremor ataxia syndrome
gross image of HD brain
large ventricles and atrophy of caudate nuclei
Tx HD
dopamine antagonists
genetic screening
structure implicated in HD
degeneration GABA neurons of striatum-caudate nucleus
hemibalismus affects what structure
subthalamic nucleus
contralateral hemorrhagic damage
characteristics hemiballismus
violent, flinging movements usually involving an entire arm on one side
chorea, dance like gait, athetosis, personality changes
HD
pill rolling tremor at rest bradykinesia masked facies small movements cogwheel rigidity
PD
ALS affects what motor neurons
UMN and LMN
LMN loss causes what
mm weakness, atrophy and fasciculations
UMN involvement causes what
spasticity, clonus, hyperactive DTR and babinski sign
when does dementia occur in ALS
onset or later
what type ALS has worse prognosis
progressive bulbar palsy
ALS patients die from
respiratory paralysis usually within 2-3 years Sx
Dx ALS based on
clinical and electrodiagnositc findings and muscle biopsy
Where does the degeneration in ALS occur
anterior horns and motor nuclei of brain stem
what nuclei are specifically affected in ALS
hypoglossal nuclei, oculomotor, trochlear and abducens
medulla
open space at top where 4th ventricle is
etiology of ALS
prion like spread misfolded proteins SOD-1 and TDP-43
how do motor neurons die in ALS
wallerian degeneration with secondary gliosis
Dx ALS
clinical: progression of weakness over mo
needle electromyography and nerve conduction studies
3 groups ataxia
friedreichs ataxia
spinocerebellar ataxia
cerebellar ataxia
friedreichs ataxia
autosomal recessive
GAA repeats on frataxin gene
spasticity weakness, sensory neurpathy, cardiomyopathy
friedrichs ataxia seen in what age group
young kids <10
death in friedrichs ataxia
CHF and arrhythmias
spinocerebellar ataxias
autosomal dominant ataxias caused by CAG repeats on multiple chromosomal loci
cerebellar ataxias
diverse group of sporadic diseases that cause cerebellar degeneration and degeneration of other anatomical systems
friedreichs ataxia is what type disease
degenerative. not demyelinating
what causes cerebellar ataxia in friedreichs
loss of sensory ganaglion cells and degeneration of axons in peripheral nerves, dorsal roots and posterior columns deprives cerebellum of sensory input
