Study and Treatment of Visual Dysfunction and Motor Fatigue in Multiple Sclerosis
Condition: Multiple Sclerosis; Internuclear Ophthalmoplegia; Fatigue
MeSH terms: Multiple Sclerosis; Ophthalmoplegia; Vision Disorders; Ocular Motility Disorders; Sclerosis; Fatigue
Intervention: Dalfampridine; Placebo
Intervention description: 10-week randomized, placebo controlled, double-blind, crossover trial, which includes a period of wash out of two weeks between treatment with dalfampridine and placebo.; 10-week randomized, placebo controlled, double-blind, crossover trial, which includes a period of wash out of two weeks between treatment with dalfampridine and placebo.
Intervention MeSH terms: 4-Aminopyridine
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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