Amyotrophic Lateral Sclerosis Flashcards
Polio
Causes poliomyelitis, degeneration of motoneurons. Caused by acute viral infection and usually focal to one area.
Incidence of ALS
note ALS effects motoneuron cell bodies
Very low, 5/100000
90-95% have no family history, sporadic form
5% have familial autosomal dominant form, a mutation in the superoxide dismutase.
Onset usually 5th decade.
Symptoms of ALS
- PROGRESSIVE wasting, weakness and atrophy of muscles leading to paralysis.
- Difficulty with speech and swallowing ( progressive bulbar palsy)
- impairment of respiration (can lead to infections)
- Muscle stretch reflexes exaggerated, and tone increased leading to spasticity
Some other signs of ALS
- Signs of muscle denervation: fasciculations and fibrillations (spontaneous AP’s EMG)
- no signs of extraocular muscles (CN 3,4,6)
- no sphincter involvement
Causes of ALS
Progressive degeneration of motoneurons (alpha and gamma) in the:
Spinal cord (sphincters ok)
Brainstem (not 3,4,6)
UMN’s in corticopsinal tract to cause spasticity and babinksi reflex
Oxidative stress hypothesis
Damage of neurons by free radicals, when free radical production exceeds the detoxification process by enzymes such as superoxide dismutase (like in the familial form) and catalase.
Excitotoxic hypothesis
Excessive activation of NMDA and AMPA receptors by glutmate.
- Due to decrease of GLT1 transporter in astrocytes which takes up glutamate.
- Or reduced GluR2 expression of AMPA, meaning likely to transport Ca2+ not Na+, calcium toxicity.
TDP-43/FUS mutation hypothesis
These proteins are involved in RNA processing, normally found in nucleus.
Mutation has them in the cytoplasm forming aggregates affecting function.
Treatment for ALS
Very limited, no effective drugs
- Riluzole has a small beneficial effect by blocking glutamate release. Slow disease by a few months.
- Baclophen agonist of GABA-B to reduce spasticity, a symptomatic treatment, so can do these to improve quality of life.
