Impulse conduction in multiple sclerosis: a theoretical basis for modification by temperature and pharmacological agents.
The simplest model for explaining conduction defects in multiple sclerosis (MS) and other demyelinating diseases assumes that the only abnormality present is loss of myelin. The consequences of such an assumption have been investigated by numerical solution of a well-known set of differential equations describing conduction in a model demyelinated axon. In agreement with clinical findings, we show that this model predicts that the temperature at which conduction block occurs is a steep function of the extent of demyelination, so that small temperature increases may block large numbers of conducting fibres. Decreasing calcium concentration (or increasing pH) is calculated markedly to improve the conduction velocity of conducting demyelinated fibres and will, in addition, restore conduction in blocked fibres. The effects of other pharmacological agents have also been computed. The presence of a demyelinating lesion in a nerve fibre is shown greatly to impair the ability of the fibre to conduct repetitive impulses, conduction failing at much lower frequencies than in normal fibres. These calculations provide some insight into the nature of conduction defects in demyelinated nerve, demonstrate that many clinical features of MS are the expected consequence of loss of myelin and do not require the presence of other defects for their explanation, and provide a useful approach to the search for a symptomatic therapy.
D001369:Axons / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D003711:Demyelinating Diseases / Q000503:physiopathology; D004558:Electric Stimulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008433:Mathematics; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009186:Myelin Sheath; D009431:Neural Conduction / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological; D009435:Synaptic Transmission; D013696:Temperature
D011188:Potassium; D002118:Calcium