ALS Flashcards
when is the average age of onset
mid 50s
what is the pathogenesis of ALS and what makes it unique among neuro conditions
progressive degenerative motor neuron dz
has features of both LMN and UMN conditions
what is the pathophys that leads to features of both UMNs and LMNs
LMN: loss of ant horn cells and CN motor nuclei w degeneration of axons -> denervated skeletal ms and atrophy (AMMYOTROPHIC)
UMN: degeneration of Betz cells in motor cortex w demyelination and gliosis of corticospinal (LATERAL SCLEROSIS) and corticobulbar tracts
- tracts fill w plaque and scar
- tracts run laterally = lateral sclerosis
- corticobulbar = impact CNs
what CNs are typically spared
III, IV, and VI
- eye mvmts preserved
what tract and function is often spared
spinocerebellar tracts and sensory function
what other physiological changes also happen in the CNS and is this considered primary or secondary to ALS pathogenesis
mitochondrial dysfunction, collection of cytoskeleton proteins, high levels of glutamate (excitatory neurotransmitter in CNS), free radical release (garbage in CNS), excitotoxicity, inflammation and apoptosis
not sure if secondary to dz process or causing it
what are the two patterns of onset
bulbar onset
limb onset
describe a bulbar pattern of onset
difficulty speaking, swallowing, respiratory w onset (CNs)
describe a limb pattern of onset
asymmetrical weakness in UE, LE, or both
will eventually have impairments in both as dz progresses
who do you see a slower progression in
younger pts
limb onset
what is the prognosis but what about this is slightly misleading
poor, death w/i 2-5 years after dx
dz process has been likely occurring for several years before dx bc of the damage seen when finally dx
what is the most common cause of death in ALS
respiratory complications
- respiratory ms so weak can’t breathe -> respiratory failure
what are some etiologies
not well understood
cell abnormalities triggered by genetic predisposition and/or environmental insults
5-10% have genetic link
mutation of chromosome 21
theories: viral infection, environmental toxins, autoimmune reaction
how could a gene mutation of chromosome 21 be a possible etiology and what does the research say
dec action of superoxide dismutase 1
- enzyme/protein that helps to breakdown garbage and byproducts of O2 metabolism
leads to free radical accumulation -> start cytotoxicity process
carriers of mutation don’t always develop ALS
how is ALS dx
no definitive dx test
dx made by recognition of clinical pattern (both UMN and LMN signs) and a synthesis of test results
- neuroimaging (MRI), SPECT/PET
how may neuroimaging (ie MRI) help w dx
may show signs of atrophy of precentral and postcentral gyri, frontal lobe
may see scarring in descending corticospinal tracts
may be normal especially in early stages
how may SPECT/PET help w dx
evidence of glucose hypometabolism c/w neuronal loss in motor cortex & corticospinal tract
- more sensitive in detection
what may PET and fMRI show in dx and why would this be the case
shift of motor cortical activation and extra-motor activation during limb task
- neuroplasticity able to reshape cortex and take over new functions as Betz cells degenerate
how might EMGs help in dx
spontaneous fibrillations and fasciculations w giant or large unit spikes upon volitional activity
how might NCV help in dx
usually WNL
- if nerve hasn’t degenerated yet, conduction isn’t impaired
how might a CSF sample help in dx
inflammatory markers, elevated proteins may be present
- no specific biomarkers determined yet
what has been a major limitation in trying to develop effective meds
short lifespan after dx
what are limitations in medical management (4)
poorly understood etiology
different phenotypes
difficult to dx early
lack of translation b/w mouse and human models
what are properties of Riluzole and what were outcomes
glutamate inhibitor
- dec amt of glutamate in CNS
neuroprotective agent
- dec hyperexcitability of neurons and damage from accumulation of glutamate
inc survival by ~3mo
Radicava: form, MOA, SE, and outcomes
IV infusions
unknown MOA, but antioxidant
may cause allergic reaction
slows decline in physical functioning
pts may take meds for symptom management such as:
pain
spasticity
sialorrhea
anxiety
depression
what are 2 medical management treatments under investigation
stem cell therapy
gene therapy
Relyvrio: efficacy, MOA, ADE
better survival than in other meds
supports survival of motor neurons by supporting mitochondria and sarchoplasmic reticulum
main ADE are GI sx
- diarrhea, abdominal pain, nausea
- upper respiratory tract infections