neurodegenerative diseases Flashcards
cortical degenerative diseases
alzheimers frontotemporal dementias picks diffuse lewy body disease corticobasal degneration
midbrain degenerative diseases
parkinsons and parkinsonian diseases
caudate nucleus degenerative diseases
huntingtons
spinocerebellar degenerations
CAG repeat syndromes
spoinocerebellar ataxias
friedreich’s ataxia
motor system degenerative diseases
ALS
beta amyloid diseases
alzheimers (AD)
cerebral amyloid angiopahty
Tau diseases
AD frontotemporal lobar degeneration (FTLD) Picks progressive supranuclear palsy corticobasal degeneration
TDP43
FTLS
some forms of ALS
synuclein
parkinsons
dementia w/lewy bodies
multiple system atrophy
huntingtin
hungtington disease
AD
most common cause of dementia >85 onset >65 most are sporadic can be familial common at early age in Down syndrome
AD and beta amyloid
abnormal cleave of protein leads to insoluble monomors which aggregate in neuropile -> plaques
AD and tau
normal tau associated with microtubules intracellularly to stabilize them
abnormal dissociates and aggregates to form tangles
familial AD
-beta amyloid precursor protein (21q21) -this is in the same region
as down syndrome mutations
-apolipoprotein E gene (19q13.2)
-tau (17q21.1)
early onset AD
presenilin 1 (14q24.3) presenilin 2 (1q31-q42)
cerebral amyloid angiopathy
not AD, but all AD pts have amyloid deposition (however it is a different type of amyloid then non-AD associated)
can cause ischemic or hemorrhagic lesions
AD CSF
decreased B-amyloid
increased Tau
frontotemporal lobar degenerations (FTLD)
common cause of early onset dementia
two categories:
tau associated
TDP43 associated
tau associated FTLD
Picks
PSP
CD
picks
tau aggregates in neuronal cytoplasm are circular and smooth - called pick bodies
presents 45-65 w/confusion a
advances stages clinically identical to AD
progressive supranuclear palsy
progressive truncal rigidity, disequillibrium w/frequent falls and difficulty w/voluntary eye mvmts
onset 5-6 decades
M>F
fatal in 2-7 years
parkinsons disease (PD)
hypokinetic disorder d/t loss of dopaminergic neurons of substantia nigra
progresses to global lewy body disease
lewy bodies
fibrils of insoluble polymers of alpha synuclein deposited in neuronal body form eosinophilic cytoplamic inclusions
also deposited in glial cells
diffuse lewy body disease
sporadic neurodegenerative disease thought to be second most common cause of dementia after AD
combines manifestations of dementia and parkinosonism
present with fluctuating attention, cognition, and visual hallucinations
multiple system atrophy
severe white matter atrophy of pons and putamen involving:
- basal ganglia -> parkinsonism
- olivopontocerebellar circuit -> ataxia
- autonomic nervous system -> orthostatic hypotension
differentiating MSA and PD
no lewy bodies in MSA
in MSA there are immunoreactive cytoplasmic inclusions in oligodendrocytes
huntingtons disease
fatal autosomal dominant disease with onset in 4-5th decades loss of caudate and putamen with gliosis huntingtin intranuclear inclusions huntingtin may be passed like a prion d/t CAG repeats >36 =HD
amyotrophic lateral sclerosis (ALS)
fatal degenerative disorder of UMN and LMN
dementia may appear at onset or develop later
usually die in 2-3 yrs d/t respiratory paralysis
progressive bulbar palsy
variant of ALS that begins with brainstem symptoms and is much more aggressive
proteins that may be involved with ALS
SOD-1
TDP-43
pathophys of ALS
95% sporadic
motor neurons die by wallerian degeneration w/secondary gliosis
friedreichs ataxia
autosomal recessive
GAA repeats on frataxin gene
1st decade- hand clumsiness, ataxia, pes cavus, DM
death usually d/t CHF or arrythimias
spinocerebellar ataxias
group of autosomal dominant ataxias d/t CAG repeats at multiple loci
autosomal dominant spinocerebellar ataxias (ADSCA)
very diverse group of conditions
all have CAG expansion
shows anticipation
core neuropath is cerebellar degeneration
post viral demyelination
in kids
autoimmune molecular mimicry response
usually recover spontaneously
rare hemorrhagic form that is usually fatal
neuromyelitis optica (NMO)
aka Devics disease
b/l painful optic neuritis and spinal cord demyelination
intense vomiting
W>M
poor recovery
autoAbs against aquaporin-4 of astrocytes
Tx- plasmaphoresis and anti CD20
MS
autoimmune demyelinating disease w/relapsing and remitting episodes of neurologic loss strong geographic link to northern latitudes before age 5
pathophys of MS
TH1 and TH17 lymphocytes react to meylin Ags (type IV hypersensitivity)
humoral immunity w/production of IgG oligoclonal bands in CSF
MS histology
active plaque- lymphocytes and lipid laden macros
inactive plaque- loss of oligodendroctyes, astrocyte proliferation, and gliosis -> sclerosis
MS clinical
F>M
young adult
sesnroy loss, motor loss, cramping, autonomics affected (incontinence)
optic neuritis w/loss of vision or pain on mvmt
fatigue, depression
UMN signs
Dx MS
clinical- more then one attack
MRI
CSF- IgG oligoclonal bands
CSF in bacterial infections
low glucose
neutrophils
increased protein
CSF in viral infections
normal glucose
lymphocytes
increased protein
CSF in TB
decreased glucose
lymphocytes
increased protein
CSF in GB
decreased glucose
no immune cells
increased protein
CSF in MS
normal glucose
no immune cells
normal protein w/oligoclonal bands
central pontine myelinosis
ostomic demyelination syndrome
occurs after rapid correction of sever hyponatremia
