Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis

Treatment tested

• Dalfampridine

  Voltage-gated potassium channel blocker

Placebo or sham

• Placebo

Other measures (5)

Inclusion Criteria: * Diagnosis of MS of any course and duration * Evidence of mild to moderate internuclear ophthalmoparesis (INO), that is slowing of the adducting eye on physical examination of saccadic speed, whether INO is unilateral or bilateral, symmetrical or asymmetrical * Medically stable conditions, ability to give informed consent and understand and cooperate with the testing * Dalfampridine-naive as well as history of taking dalfampridine in the past, whether there was benefit in gait impairment or not, after a washout period of at least 2 weeks Exclusion Criteria: * Lack of evidence of INO (slowing of the adducting eye) on physical examination of saccadic speed * Severe INO (i.e., exotropia in primary gaze) on physical examination * Medically unstable conditions, inability to give informed consent and understand and cooperate with the testing * History of side effects from dalfampridine * History of seizures * Moderate or severe renal failure, assessed by clearance of creatinine

Primary fatigue represents a major cause of disability in patients with multiple sclerosis (MS), being reported in about 90% of cases. Fatigue interferes with everyday functioning but, unfortunately, little is known about its mechanisms. The investigators propose a characteristic eye movement abnormality (internuclear ophthalmoparesis, INO), commonly encountered in MS, as a simple model for primary motor fatigue. The investigators described worsening of ocular performance in MS patients with INO following visual tasks (ocular motor fatigue), which is likely due to decreased neural conduction along brain pathways injured by MS. This mechanism could represent a major component of MS-related primary motor fatigue. Relevant to Veterans' care, INO is a significant cause of visual disability, especially when complicated by ocular fatigue, and limits daily activities such as reading and driving. The investigators propose a medical treatment to improve ocular performance/fatigue in INO, which can reduce visual disability and improve quality of life in Veterans with MS.