Motor Neuron Diseases & Disorders of the NMJ Flashcards
Disorders that cause degeneration of the anterior horn cells in the spinal cord with or without similar lesions in the lower brainstem motor nuclei and/or Betz cells of the brain and associated tracts
Motor neuron diseases
Motor neuron diseases are characterized clinically by progressive _____ and _____ of the affected muscles without accompanying sensory, cerebellar, or mental changes
Wasting; weakness
4 main types of adult motor neuron disease
Amyotrophic lateral sclerosis (most common)
Progressive bulbar palsy
Progressive (spinal) muscular atrophy
Primary lateral sclerosis
T/F: Aside from the 4 main types of adult motor neuron disease (ALS, progressive bulbar palsy, progressive SMA, and primary lateral sclerosis), there are rarer, more benign, and limited forms of adult motor neuron diseases that exist
True
[these include brachial amyotrophic diplegia, leg amyotrophic diplegia, isolated bulbar ALS, monomelic amyotrophy (Hirayama’s disease), etc]
Clinical features of ALS in terms of gender distribution, upper vs lower motor neuron disease, and risk factors
Slightly more common in males
Mixed upper and lower motor neuron signs, especially in same limb [upper = spasticity, hyperreflexia, babinski sign; lower = atrophy, fasciculations]
May also be bulbar involvement of the upper or lower motor neuron type
No definite risk factors related to occupation, trauma, diet, SES, etc.!
The pathophysiology of ALS involves degeneration of _____ cells, ______ ____ nuclei, descending _________ tracts, and ______ horn cells
Betz; lower brainstem; corticospinal; anterior
The clinical presentation of ALS is highly variable, but what are some commonalities in terms of age of onset and presenting signs/symptoms?
Age 20-60, most common after age 50
First sign is often hand clumsiness or impaired dexterity with mild wasting/weakness of hand intrinsics
Eventually other hand/arm becomes involved and weakness/atrophy spreads proximally in arms
Later the legs become involved, followed by atrophic weakness in tongue, pharynx, and muscles of respiration
Accompanying symptoms include fasciculations, cramps, drooling, and weight loss
Prognosis of ALS
Relentlessly progressive without remissions, relapses, or stable plateaus
Death from respiratory failure, aspiration PNA, or PE
Mean duration of symptoms = 4 years, death within 2-5 years
[treatment is supportive — feeding tubes, ventilatory support, various assistive devices, symptomatic meds, riluzol (glutamate inhibitor)]
Adult motor neuron disease characterized by selective involvement of the motor nuclei of the lower cranial nerves; clinical presentation includes dysarthria, dysphagia, dysphonia, chewing difficulty, drooling, and respiratory difficulty
Progressive bulbar palsy
Progressive bulbar palsy rarely runs its course as an isolated syndrome, and it almost always progresses to generalized disease (i.e., ______).
The earlier the onset of ______ symptoms in ALS, the shorter the course of the disease
ALS
Bulbar
Adult motor neuron disease affecting M>F, mean age at onset 64, and lower motor neuron deficits predominate due to degeneration of anterior horn cells. There is NO upper motor neuron involvement
Progressive spinal muscular atrophy
Clinical features of progressive spinal muscular atrophy
Often begins with symmetric upper extremity involvement
Weakness, atrophy, respiratory difficulty
Can progress to ALS but usually does not
Survival rate >15 yrs — better with earlier age of onset
Adult motor neuron disease typically affecting pts 50-55 y/o, and upper motor neuron (corticospinal) deficits prevail — causing weakness, spasticity, hyperreflexia, Babinski signs with a slow progression that can evolve into ALS, but with a better survival rate
Primary lateral sclerosis
Acquired motor neuron disease associated with asthma
Hopkins syndrome
Describe the anatomy and physiology of the NMJ
A nerve AP arrives at the motor nerve terminal and depolarizes the nerve terminal membrane
This initiates influx of calcium into the motor axon, leading to fusion of vesicles containing ACh with the presynaptic membrane and release of ACh which diffuses across the synaptic cleft, binds post-synaptic receptors on the muscle membrane, and generates a localized endplate potential (EPP)
If the EPP reaches threshold, the muscle membrane undergoes an increase in sodium conductance and a muscle AP is generated. Propagation of the AP through the muscle fiber ultimately results in muscle contraction.
Neuromuscular transmission is terminated by diffusion of ACh from the synapse and its rapid cleavage by AChE
