Term
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Definition
muscle
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NMJ
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nerves
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plexus
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nerve roots
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anterior horn cell
lesions at each PNS level result in different pathology |
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Term
| anterior horn cell lesions |
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Definition
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Definition
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Term
| purely motor PNS diseases |
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Definition
motor neuron disease
NMJ disease
myopathies |
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Term
| sensorimotor PNS diseases |
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Definition
radiculopathy
plexopathy
neuropathy |
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Term
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Definition
| a single anterior horn cell, its axon, and the individual muscle fibers it innervates |
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Term
| clinical patterns of PNS lesions |
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Definition
geographic distribution:
-proximal predominance
-distal predominance
-patchy |
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Definition
myopathy
NMJ disease
--pure motor |
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Definition
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Definition
pure motor: motor neuron disease (lesion at anterior horn cell)
sensorimotor: plexopathy, mononeuropathy multiplex |
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Term
motor neuron disease
def and examples |
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Definition
(anterior horn lesion)
a degenerative disorder characterized by loss of motor neurons, involving UMN, LMN, or both
-ALS
-PLS
-PMA |
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Term
amyotrophic lateral sclerosis (ALS)
clinical features |
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Definition
usually begins with focal weakness (typ one arm)
gradually spread to contiguous muscles in limb
usually NOT in the distribution of individual nerves or roots (and no sensory involvement)
25% intially show bulbar muscles weakness (CNs)
typical symptoms depend on area affected: arm, leg, bulbar, "other" |
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Term
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Definition
problems:
-turning key
-opening jars, bottles
-using screw driver
-turning door knob
-buttoning |
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Term
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Definition
-unstable gait
-falling
-fatigue when walking
-foot drop |
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Term
typical ALS symptoms
bulbar |
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Definition
-dysarthria
-dysphagia
-hoarseness |
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Term
typical ALS symptoms
"other" |
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Definition
-emotional incontinence
-cognitive impairment (FTD)
-excessive forced yawning |
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Term
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Definition
stiffness
spasticity
cramps
muscle spasms
HYPERreflexia |
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Term
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Definition
fasciculations
atrophy
generalized cachexia |
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Term
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Definition
relentless progression, can be in any pattern; most common:
UE --> contralat UE --> ipsilat LE --> contralat LE --> bulbar muscles
(--> UEs --> thoracic region --> LEs; when the initial symptoms are bulbar)
>90% of patients will eventually have bulbar muscle involvement
-mortality from weak resp muscles; inadequate airway protection leading to aspiration |
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Term
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Definition
progresses rapidly
mean survival of 27-43 months from onset
respiratory failure or pneumonia are the usual cause of death |
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Term
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Definition
*loss of nerve cells in the anterior horns of the spinal cord and motor nuclei of the brainstem*
lost neurons replaced by astrocytes
surviving neurons shrunken, lipofuscin-filled
thin anterior roots, disproportional loss of large myelinated fibers
degeneration throughout corticospinal tracts
muscles are atrophic and show typical findings of denervation |
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Term
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Definition
free radical injury
protein aggregation
glutamate excitotoxicity
immunologic abnormalities
neurofilament dysfunction |
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Term
ALS pathophysiology:
free radical injury |
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Definition
mutation in superoxide dismutase (SOD) seen in up to 20% of familial ALS
SOD scavenges free radicals; prevents cytotoxicity
not the only player - enzyme activity does NOT correlate well with disease severity; SOD-KO mice don't get motor neuron disease |
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Term
ALS pathophysiology:
protein aggregation |
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Definition
SOD mutations lead to misfolded protein aggregation
nonSOD pts have TDP-43 inclusions in some motor neurons (same as in FTD!)
familial and sporadic ALS show TDP-43 mutations
FUS mutations in familial ALS
--much FTD/ALS overlap! |
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Term
ALS pathophysiology:
glutamate excitotoxicity |
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Definition
increased glutamate in serum, plasma, CSF
decreased glutamate in CNS tissue
toxic levels of glutamate receptor agonists can mimic ALS somewhat |
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Term
ALS pathophysiology:
immunologic abnormalities |
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Definition
immune complexes found in intestine and renal tissue
increased inflammatory cytokine levels and expression of cyclo-oxygenase 2 |
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Term
ALS pathophysiology:
neurofilament dysfunction |
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Definition
suggested by abnormal axonal spheroids identified in tissue of some ALS patients
axonal transport appears to be slow |
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Term
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Definition
based primarily on the clinical exam, supplemented by EMG if needed
UMN findings occurring ABOVE LMN findings |
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Term
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Definition
riluzole - anti-glutamate, extends survival ~6 months
symptom management
advance directives
BiPAP - alternate (+)/(-) pressure to help rest respiratory muscles
stem cells? |
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Term
| spinal muscular atrophy (SMA) |
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Definition
hereditary
LMN
childhood onset
three typse |
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Term
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Definition
onset before birth or within first 6 months
severe hypotonia, weak cry, respiratory distress, no head control, areflexia
severe, generalized limb weakness, worse proximally
usually die by age 2 from respiratory failure/pneumonia |
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Term
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Definition
onset 6-8 months
milder, slower progressing that type 1
most kids are eventually able to roll over and sit unsupported, but rarely achieve independent walking
survive to 30-40's, or may die ealier secondary to respiratory disease |
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Term
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Definition
onset 5-15 years
gait becomes waddling, with trouble climbing stairs; exaggerated lumbar lordosis
LEs weaker than UEs
slower progression than types 1 and 2, may remain ambulatory for up to 30 years from onset; eventual degree of disability is difficult to predict |
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Term
| SMA - *commonalities among types 1, 2, 3* |
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Definition
areflexia in all 3 types
tremor (postural or kinetic) common types 2 and 3, rare in type 1 |
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Term
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Definition
resemble LMN aspects of ALS:
reduction of nerve cells in anterior horns or spinal cord and motor nuclei of brainstem, replaced by astrocytes
surviving neurons shrunken, lipofuscin-filled
thin anterior roots, decreased large myelinated fibers
muscle devernation changes |
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Term
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Definition
all 3 types caused by mutations in "survival motor neuron 1" SMN1 gene
specific phenotype depends on mutations in nearby genes, including SMN2
mechanisms unknown |
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Term
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Definition
protein function of these genes unknown
ubiquitously expressed gene that is important in the processing of other genes
associated with both nuclear and cytoplasmic complexes involved in mRNA splicing |
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Term
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Definition
bases on history and physical
supplemented by EMG (often tricky to do in kids)
confirmed by genetic testign |
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Term
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Definition
no disease-specific treatment
supportive, manage symptoms, maximize mobility and independence
PT and stretching exercises |
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Term
| primary lateral sclerosis (PLS) |
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Definition
rare; onset usually after age 50
very slowly progressive spastic paraparesis
gradually spreads to involve UEs, then bulbar; atrophy occurs only late in the course
spasticity and clumliness most limiting (not so much the weakness)
purely UMN |
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Term
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Definition
indentical to UMN findings in ALS
corticospinal tract degeneration |
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Term
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Definition
based on history and exam
exclusion of all other potential causes of generalized UMN dysfunction
(spinal cord compression, multiple sclerosis, vit B12 def, copper def, thyroid disease, neuropsyphilis, HIV, sarcoidosis...) |
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Term
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Definition
no disease-specific treatment
symptomatic management
major emphasis on treatment of spasticity |
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