Lecture 27: diseases of motor units

Question 1

Frequent symptoms/neurological terms?

Answer 1

Paralysis - inable to conduct voluntary movements in a certain part

Paresis - weakness in a certain part but not full paralysis

Muscle tone abnormalities - (Hypertonia)

= spasicity(stroke, ALS, MS) or rigidity (PD)

Ataxia - (Incoordination)

= decomposition of movement or dysmetria

Involuntary movements

= Spasm, epileptic fit, tremor (at rest in PD or intention tremour in cerebellar ataxia), dyskinesia (PD after prolonged L-DOPA)

Question 2

Acute v chronic

focal v diffuse?

Answer 2

Question 3

A motor unit consists of?

Answer 3

Cell body and axon with a varying number of branches off the axon towards the endplates/neuromuscular junction and all the striated muscle fibres innervated by these braches.

Question 4

Most common form of myopathy?

in Children?

Answer 4

Muscular dystrophy -(a familiar form of myopathy)

A group of inherited disorders characterised by deficits in muscle proteins and progressive muscle wasting and weakness (without primary structural abnormality in motorneurons)

In children most common is DMD - Duchenne MD where protein dystrophin has a mutation on its gene.

Question 5

Most common MD in adults?

Answer 5

• MMD - Myotonic MD
• Onset usually in the 30s
• Is a wasting and weakness of muscles (inc. the heart)
• Myotonia: Delayed relaxation of a muscle after a strong contraction
• Inherited (dominant): up to 2000 triple (CTG) repeats in chromosome 19 coding for protein kinase (Myotonin)

Question 6

Myasthenia Gravis features?

Answer 6

• Muscle weakness (without wasting)
• Autoimmune disease
• Fewer ACh receptors > dec end plate potential > dec transmission
• Junctional folds become a lot smaller
• May be generalised and/or ocular form

Question 7

Diagnosis of Mysthenia Gravis?

Answer 7

Face appears droopy and then after an injection of endophonium (a blocker of ACh esterase) their face become a lot more normal looking for about 30sec-1min.

-Often pre-treated atropine to reduce gastro-intestinal and other side-effects.

detection of antibodies against ACh receptors in the serum (found in ≈ 85%)

Question 8

Botilism features?

Mechanism of action?

Muscles affected and effects of this?

Answer 8

Food poisoning (by Clostridium botulinum)

Botulinum toxins produced under anaerobic conditions: 1 microgram can kill a human if injected

Muscle paralysis due to decreased ACh release by:

1. Toxins bind to nerve terminals and are internalised by endocytosis
2. Toxins cause proteolysis of several membrane proteins involved in neurotransmitter release (eg. SNAP-25 and Syntaxin)

Striated and Smooth muscle affected:

• Disruptions also in the ANS (dry mouth, postural hypotension)
• Infant botulism = constipation, lethargy, weakness, difficulty feeding, can progress to flaccid paralysis and resp arrest!

Question 9

Other applications of botulinum toxins? (botox)

Answer 9

• Severe neck spasms
• Cross eyes
• upper and lower limb spasticity
• Dystonias
• Hyperhydrosis
• Gastrointestinal and urinary disorders
• migrane
• depression

Question 10

Wallerian degeneration in peripheral nervous system?

Answer 10

Changes in distal part of the axon:

• Loss of synaptic transmission (on electrical stimulation of the axon) within ≈24h
• Progressie degeneration within days (due to the loss of the ‘axon survival factor’ NMAT2)
• changes in the motorneuron cell body: Chromatolysis
• Axon regeneration: 1-2mm /day facillitated by schwann cells > re-innervation of muscles > Re-myelination of axons (partial) > sometimes functional recovery to varied extent.

Question 11

Wallerian degeneration in the CNS?

Answer 11

This will occur the same in the CNS but it is not followed by regeneration.

Question 12

First symptoms patients present with when suffering from mysthenia gravis?

Answer 12

Muscle weakness that gets worse when they try and do simple tasks

Issues with day to day tasks like washing their hair and prolonged chewing.