Long fiber pathways or tracts of the CNS are more likely to be involved in the process of demyelination. For example, it is very common for patients to have posterior column signs, such as loss of vibration sense, and pyramidal signs early in the course of the disease when the disease is virtually asymptomatic. A common feature of MS is profound fatigue often with a diurnal (varying throughout the day) pattern. This is characterized as malaise or a lack of motivation for the performance of any physical activity, as well as motor fatigue, which develops with continued physical activity. Another extremely interesting phenomenon is a marked decrease in heat tolerance in some individuals. A limited amount of research has demonstrated the development of neurological signs when an individual is passively heated, or during physical exercise. However, this does not occur in all individuals with MS and often the symptoms are transient, disappearing within hours. The underlying mechanism believed responsible for these clinical signs is that demyelination reduces the efficiency of axonal conduction; thus less current is available for depolarization at nodes of Ranvier. With demyelination and reduction of current density, the safety factor for conduction can be exceeded.

There are numerous signs and symptoms experienced by persons with MS in a variety of combinations. As such, its presentation in each individual is unique. Several of these symptoms are summarized in Table 1.

There are several different clinical courses for MS. The disease usually begins as a relapsing-remitting (RR) form of disease, with exacerbations occurring 2 to 3 times per year at the beginning of the disease. Gradually, the exacerbations decrease to less than 1 per year, approximately, beyond year five. As the disease progresses, neurological deficits accumulate. The disease can be characterized as secondary progressive or progressive relapsing disease with periods of accelerated progression or exacerbation with the development of new deficits superimposed on those that are pre-existing. Finally, the illness may be primary progressive. In this form of MS, the disease does not manifest any ability to remit, but progresses immediately from the outset. This form of MS has been characterized as being more benign than the usual expression of the illness. However, in some cases, particularly when male patients are involved, this form of the illness may be extremely severe, as well as progressive.