Motor neuron diseases Flashcards
What is the name of a disease that affects the muscle fibres but not the motor neuron or synapse?
Myopathies, e.g, muscular dystrophy
Describe muscular dystrophy?
Inherited disorders characterised by muscle wasting and weakness without primary structural abnormalities in motorneurons.
Children - duchenne muscular dystrophy
Adults - myotonic muscular dystrophy, increased muscle tone, starts in 30s, wasting and weakness of muscles including heart.
Myotonia - delayed relaxation after a contraction,
triplet repeats of CTG
What are the pathology and features of myasthenia gravis and how do you diagnose it?
Caused by problems in the neuromuscular junction. Abs target acetchyoline receptors. This reduces the end-plate potential. Thus reducing the action potential in muscle fibre.
Muscle weakness but not wasting.
Many forms of the disease.
Inject a small amount of a blocker of acetylcholine esterase. If this causes a reduction of symptions for a short period of time. Need to give this drug in combintion with atropine because ofthe unwanted side-effects of increased Acetylcholine in the ANS. These are usually gastrointestinal.
Can also detect the antibodies.
What are the features of botulism?
Also affects the neuromuscular junction.
Food poisoning.
Cause muscle paralysis due to reduceded Ach release. toxins bind to the nerve terminals, are endocytosed and cause proteolysis of proteins involved in neurotransmitter release.
Striated and smooth muscles affected. Also causes dry mouth and postural hypertension
Infant botulism: respiratory arrest (respiratory muscles and diaphragm)
What is wallerian degeneration?
When a peripheral neuron axon has a lesion. The upper part is largely normal but the lower part of the axon degenerates because it cannot survive without the cell body.
chromatolysis of cell bodies
Peripheral axons can regenerate though.
What happens to a damaged peripheral nerve injury?
24 hours - loss of synaptic transmission
Days - degeneration due to axon survival factor
Changes in motor neuron cell body - chromatolysis
Axon regeneration 1-2 mm/day facilitated by schwan cells leading to reinnervation of musles
Remyelination of axons. (Functional recovery)?
Does not recovery in the CNS
What causes and happens in polio?
A virus causes an acute and focal degeneration of motor neurons.
Does amylotrophic lateral scleosis have a genetic component?
Only in 5% of patients. Caused by mutation of superoxide dismutase or TDP-43/FUS
When does AML start and what are the symptoms
5th decade
Progressive weakening and atrophy of muscles leading to paralysis.
Weakness of legs arms and hands.
Difficulty with speech and swallowing.
Impairment of respiration - intercostal muscles and diaphragm. This makes lungs prone to infection, which is what kills most patients.
Stretch reflexes - increased
Muscle tone - increased (painfully stiff)
Death within 2-5 years
What are the signs of ALS?
Muscle denervation - Muscle fasiculations (twitches of motor units that survived atrophy.
Muscle fibrillations - shown on an EMG, spontaneous action potentials generaed by individual muscle fibres.
Occular muscles are not affected (CN3, 4, 6)
Anal and bladder sphincters not affected.
No sensory or intellectual defects.
What is the pathology of ALS?
Progressive weakening and atrophy of muscles leading to paralysis.
Affects motor neurons in the spinal cord - excluding those controlling the sphincets.
Affects motor neurons in the brainstem, excluding CN3, 4, 6
UMNs - corticospinal tract degenerates
What is the pathogenesis of AML
Oxidative stress when the production exceeds the removal of free radicals because of enzyme impairments, such as sueroxide dismutase.
Excitotoxic hypothesis - excessive activation of AMPA and/or NMDA by glutamate.
Reduced GLuR2 in the AMPA receptor allows Cs2+ to enter.
TDP-43/FUS - proteins involved in RNA processing, usually in nucleus, but when in the cytoplasm they aggregate and affect neuronal function.
What are the treatments for AML?
Riluzole - adds 3 months $7000 per year.
Baclophen to reduce muscle spasticity
Control of saliva because of difficulty swallowing.
