Faculty Bibliography

BACKGROUND: Amantadine hydrochloride and pemoline, both frequently used to treat the fatigue of multiple sclerosis (MS), may also improve attention and other cognitive functions in MS. To our knowledge, these agents have never been compared in a placebo-controlled trial of patients with MS. OBJECTIVE: To evaluate the effects of amantadine and pemoline on cognitive functioning in MS. METHODS: A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine, pemoline, or placebo using a parallel group design. They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning. Primary outcome measures were tests of attention (Digit Span, Trail Making Test, and Symbol Digit Modalities Test), verbal memory (Selective Reminding Test), nonverbal memory (Benton Visual Retention Test), and motor speed (Finger Tapping Test). RESULTS: Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment. All three treatment groups improved on tests of attention (P < .003), verbal memory (P < .001), and motor speed (P < .002). There were no significant differences between amantadine, pemoline, and placebo. CONCLUSIONS: Cognitive functioning in MS is independent of fatigue. Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo.

Multiple sclerosis (MS) patients often report that heat makes their symptoms worse. There is anecdotal evidence that the opposite, body cooling, may make MS symptoms better. The goal of this study was to determine whether core body temperature cooling compared to placebo treatment produced objective changes on the neurologic examination, and affected immune parameters, in MS patients. Eleven relapsing-remitting patients who reported heat sensitivity underwent cooling or sham cooling using a commercially available active liquid flow cooling garment. Clinical parameters of visual acuity, timed walk, muscle strength, and coordination, and immune parameters of cytokine production were examined one hour before and after treatment. Cooling produced a significant improvement in acuity, timed walk, and muscle strength compared to sham cooling. Cooling, but not sham cooling, also decreased cytokine production by MS peripheral blood cells. These results suggest that cooling can result in objective clinical improvements in several functional systems of heat sensitive MS patients. In addition to a clinical effect, cooling may also have an immune effect on MS.

The effects of cooling on sensory and cognitive processes were investigated in heat-sensitive multiple sclerosis (MS) patients and healthy control (HC) subjects. The Life-Support cooling jacket was used to lower core body temperature by one degree or more. Auditory event-related potentials and neuropsychological test performance were examined in both the cooled and the normal states. Eight MS patients and eight HC subjects underwent two hours of cooling on one day and two hours of sham cooling on another day (order counterbalanced across subjects). Cooling significantly slowed conduction speed in the auditory brainstem pathway of both groups. Cooling also delayed a longer latency sensory ERP (N100) in the MS patients, but not in the healthy controls. A cognitive evoked related potential measure (P300) was delayed in the MS patients but was not affected by cooling in either group. The MS patients had significantly poorer neuropsychological performance than HC subjects but performance on most of these tests was not affected by cooling. Since the electrophysiological and neuropsychological measures tapped a broad range of CNS functions and brain areas, the data suggest that the marked clinical improvement seen with cooling in heat-sensitive MS patients is not accounted for by facilitation of the sensory and cognitive processes of the CNS.