Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions.

In contrast to other diseases that go along with spasticity (e.g. spinal cord injury), spasticity in chronic autoimmune diseases involving the CNS is complicated by the ongoing damage of neuronal networks that leads to permanent changes in the clinical picture of spasticity. Multiple sclerosis (MS) is the most frequent autoimmune disease of the central nervous system (CNS) and spasticity is one of the most disabling symptoms. It occurs in more than 80% MS patients at some point of the disease and is associated with impaired ambulation, pain and the development of contractures. Besides causing cumulative structural damage, neuroinflammation occurring in MS leads to dynamic changes in motor circuit function and muscle tone that are caused by cytokines, prostaglandins, reactive oxygen species and stress hormones that affect neuronal circuits and thereby spasticity. The situation is complicated further by the fact that therapeutics used for the immunotherapy of MS may worsen spasticity and drugs used for the symptomatic treatment of spasticity have been shown to have the potential to alter immune cell function and CNS autoimmunity itself. This review summarizes the current knowledge on the immunologic pathways that are involved in the development, maintenance, dynamic changes and pharmacological modulation of spasticity in MS.