Faculty Bibliography

OBJECTIVE: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known. METHODS: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response. RESULTS: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo. CONCLUSION: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.

OBJECTIVE: To determine the potential of detection in CSF of specific Borrelia burgdorferi antigen, OspA, as a marker of infection in neurologic Lyme disease and compare this with the detection of antibody. DESIGN: CSF from 83 neurologic patients in an area highly endemic for Lyme disease was examined prospectively for (1) OspA by antigen capture ELISA and Western blot employing monoclonal antibodies, and for (2) B burgdorferi antibodies by ELISA. RESULTS: Of the 35 of 83 (42%) patients who were positive for OspA antigen in their CSF, 15 (43%) were antigen positive despite being antibody-negative in CSF. Seven of these 15 (47%) had otherwise normal routine CSF analyses. Six of these 15 (40%) patients met strict CDC surveillance criteria for Lyme disease; four (27%) patients had seroconversion coincident with new neurologic problems; and three (20%) with characteristic syndromes for Lyme disease were seronegative, but had complexed antibody to B burgdorferi. The final two patients (13%) were seropositive and had unexplained neurologic problems not characteristic of Lyme disease. CONCLUSIONS: B burgdorferi antigen can be detected in CSF that is otherwise normal by conventional methodology, and can be present without positive CSF antibody. Since CSF antigen implies intrathecal seeding of the infection, the diagnosis of neurologic infection by B burgdorferi should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.

The similarity of eosinophilia-myalgia syndrome (EMS) and toxic-oil syndrome (TOS) to systemic sclerosis and diffuse fasciitis with eosinophilia (DFE) highlights the potential for environmental agents to induce autoimmune disease. Further, a candidate etiologic agent for EMS, 3-(phenylamino)alanine, is chemically similar to the aniline derivative identified in samples of oil implicated in TOS, 3-(N-phenylamino)-1,2-propanediol, suggesting pathogenic overlap. The late-stage manifestations of EMS and TOS are muscle cramping, arthralgia, severe fatigue, and cognitive impairment. This review focuses on the divergent and parallel findings in EMS, TOS, and DFE. The formation of the Environmentally Associated Connective Tissue Disease Study Group within the American College of Rheumatology will provide a forum for the development of registries to study suspected toxin-induced disorders.

OBJECTIVE: To describe the development of tremor, myoclonus, and myokymia as chronic sequelae of eosinophilia-myalgia syndrome (EMS). METHODS: Four patients among a cohort of 57 individuals with EMS followed prospectively were identified to have objective movement disorders. Electrophysiologic findings were assessed by recording of electromyographic activity from pairs of upper extremity antagonist muscles using 2 input channels. RESULTS: Clinical and electrophysiologic studies documented the presence of tremor (4 patients), myoclonus (3 patients), and myokymia (1 patient) as late sequelae of EMS. CONCLUSION: The recognition of these movement disorders extends the spectrum of chronic neurologic disease in EMS.