DEGENERATIVE MUSCLE DISEASES II
Neural diseases affecting the motoneurones (e.g. polio) or their axons (Guillain-Barre syndrome) or the descending central pathways (e.g. tropical spastic paraparesis or TSP) may also cause weakness. (Disorders affecting the descending pathways - upper motor neurone disease - will be dealt with in the CNS course.)
When motoneurones degenerate, the muscle fibres in the motor unit which they supply first show denervation supersensitivity, then undergo atrophy. If the fibres are reinnervated by an adjacent axon, they survive, and become part of a larger motor unit (a megaunit). Because of the extra muscle fibres, the summed AP in these units is abnormally large (Giant unit). If they are not reinnervated, the denervated fibres become fibrotic.
Denervation supersensitivity involves proliferation of foetal ACh receptors over the entire surface of the fibre. This return to the foetal state seems to prompt outgrowths from nearby, intact axons to make synapses on the denervated fibres. The supersensitive state is accompanied by fibrillations (spontaneous bursts of muscle action potentials) due to the hypersensitivity of the fibres to mechanical and chemical stimuli. Fibrillations occur in isolated fibres and so are usually small and only detectable by electrodes placed in the affected muscle.
As the motor neurones degenerate, they also may become abnormally excitable and generate spontaneous action potentials. This will cause activation of all the fibres in the motor unit, causing a visible tic or twitch called a fasciculation. Fasciculations are characteristic of disorders affecting the motor neurones or their axons.
The picture to the left shows a muscle that has undergone partial denervation. The denervated fibres have become reinnervated by adjacent motor axons, and so have changed character under the influence of the new motor neurone innervating them. Note that as a result fibres of the same type are now clumped together instead of being randomly interspersed. In this way a 'megaunit' giving giant motor unit potentials is formed.
To the left (top of the picture) is a group of atrophic fibres denervated as a result of degeneration of the spinal motor neurones innervating them (spinal motor neurone atrophy or SMA). This is a hereditary condition leading to weak, floppy muscles.