Slowed nerve conduction: fatigue and heat sensitivity

As a follow-up to my post yesterday.

"Roshni was correct; well done!"

The main consequence to slowed conduction is fatigue. The commonest example is exercise-induced fatigue. For example you may find that as you walk or exercise it becomes more difficult; your leg begins to drag, your vision may blur or your thought processes seem to slow. The reason for this is that those demyelinated segments in the nerve stop conducting due to conduction block. Why this happens is complex, but could be related to an energy deficit, a rise in body temperature, or both. The molecules that transmit the electrical signal down a nerve fibre, are little pumps (ion pumps) and require energy to work. In addition, these ion pumps are optimised to function at a certain temperature, this is why some MS'ers are heat sensitive.

"Have you heard of Uhthoff's phenomenon?"

Wilhelm Uhthoff (1853-1927) was a famous German Professor of ophthalmology who described temporary visual loss associated with optic neuritis linked to physical exercise. This was later found to be caused by a rise in body temperature. This phenomenon is now known to affect other neurological systems as well, for example the motor system when walking, balance and sensory pathways and even the cognitive centres. 

Up until recently, apart from cooling, we have not had a treatment for Uhthoff's phenomenon. More recently the drug Fampridine has been licensed to improve walking speed in MS'ers; I suspect that MS'ers with heat sensitivity or fatigue-related conduction block will be more likely to be fampridine responders (see figure below).

Goodman et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009 Feb 28;373(9665):732-8.

"Symptomatic treatments remain the mainstay of MS therapies; having drugs to treat fatigue due to conduction block are welcomed. However, I remain sceptical about their long-term effectiveness which is why we need effective remyelination therapies." 

"Remyelination therapies, should be neuroprotective preventing or slowing down the degeneration of nerve fibres that have been left vulnerable by demyelination."

CoI: Multiple