Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

Box 5

Primary and secondary factors in multiple sclerosis fatigue.(Adapted from: MacAllister and Krupp [48]).

Primary factors

(i) Immune dysregulation—changes in neuroendocrine function.

(ii) Central nervous system mechanisms—neuronal dysfunction due to immune injury, demyelination and inflammation,

impaired innervation, and activation of muscle groups leading to compensatory increase in central motor drive exertion and

more energy depletion.

(iii) Endocrine factors—abnormalities in hypothalamic/pituitary/adrenal axis.

(iv) Neurotransmitter dysregulation—dopaminergic, histaminergic, and serotonergic pathways may contribute to fatigue.

Secondary factors

(i) Physical deconditioning from failure to get adequate exercise.

(ii) Sleep dysfunction—may also be due to nocturnal spasms, pain, incontinence, and depression.

(iii) Pain—sensory disturbances, neuralgia, dysesthesia, and spasms.

(iv) Depression—in closely related to poor sleep, pain, and fatigue.

(v) Medications—can worsen fatigue (antispasticity agents, e.g., Baclofen).