Copolymer-1 (Copaxone or COP) inhibits experimental allergic encephalomyelitis and has beneficial effects in multiple sclerosis. There is presently no practical in vitro assay for monitoring the immunological effects of COP. We used an automated, computer-assisted enzyme-linked immunoadsorbent spot assay for detecting COP-induced interferon-gamma (IFN-gamma)- and interleukin-4 (IL-4)-producing cells and a standard proliferation assay to assess the immunological response to COP in peripheral blood mononuclear cells from 20 healthy donors, 20 untreated multiple sclerosis patients and 20 COP-treated multiple sclerosis patients. Compared with untreated and healthy controls, COP-treated patients showed (i) a significant reduction of COP-induced proliferation; (ii) a positive IL-4 Elispot response mediated predominantly by CD4 cells after stimulation with a wide range of COP concentrations; and (iii) an elevated IFN-gamma response partially mediated by CD8 cells after stimulation with high COP concentrations. All three effects were COP-specific as they were not observed with the control antigens, tuberculin-purified protein or tetanus toxoid. The COP-induced changes were consistent over time and allowed correct identification of COP-treated and untreated donors in most cases. We propose that these criteria may be helpful to monitor the immunological response to COP in future clinical trials.

Acquired pendular nystagmus (APN) is regularly accompanied by oscillopsia and impairment of static visual acuity. Therapeutic approaches to APN remain controversial, and there is no generally accepted therapeutic approach. We tested 14 patients who had suffered from APN caused by multiple sclerosis for several years; 12 patients presented with fixational pendular nystagmus (increasing during fixation) and 2 with spontaneous pendular nystagmus. All 11 patients with fixational pendular nystagmus who were given memantine, a glutamate antagonist, experienced complete cessation of the nystagmus. In contrast, scopolamine caused no (6 of 8) or only a minor (10-50%) reduction of the nystagmus (2 of 8). It was concluded that memantine is a safe treatment option for APN.

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Objective: To investigate the effect of peripheral sustained cooling on intention tremor in patients with multiple sclerosis (MS). MS induced upper limb intention tremor affects many functional activities and is extremely difficult to treat. Materials/Methods: Deep (18˚C) and moderate (25˚C) cooling interventions were applied for 15 minutes to 23 and 11 tremor arms of patients with MS, respectively. Deep and moderate cooling reduced skin temperature at the elbow by 13.5˚C and 7˚C, respectively. Evaluations of physiological variables, the finger tapping test, and a wrist step tracking task were performed before and up to 30 minutes after cooling. Results: The heart rate and the central body temperature remained unchanged throughout. Both cooling interventions reduced overall tremor amplitude and frequency proportional to cooling intensity. Tremor reduction persisted during the 30 minute post cooling evaluation period. Nerve conduction velocity was decreased after deep cooling, but this does not fully explain the reduction in tremor amplitude or the effects of moderate cooling. Cooling did not substantially hamper voluntary movement control required for accurate performance of the step tracking task. However, changes in the mechanical properties of muscles may have contributed to the tremor amplitude reduction. Conclusions: Cooling induced tremor reduction is probably caused by a combination of decreased nerve conduction velocity, changed muscle properties, and reduced muscle spindle activity. Tremor reduction is thought to relate to decreased long loop stretch reflexes, because muscle spindle discharge is temperature dependent. These findings are clinically important because applying peripheral cooling might enable patients to perform functional activities more efficiently.

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A prospective examiner-blind, cross-over study was conducted to compare the efficacy of memantine (40 or 60 mg/day) and gabapentin (1,200 mg/day) as therapy for acquired fixational pendular nystagmus (APN) in 11 patients with multiple sclerosis. APN was documented in 20 eyes by electrooculography (EOG). The primary objective of the study was an at least 50% reduction in amplitude and/or frequency of APN compared with baseline values in EOG. This aim was reached for 17 of 20 APN-affected eyes with memantine 40-60 mg and for 11 eyes with gabapentin up to 1,200 mg. A complete cessation of APN was achieved in eight eyes (four patients) with memantine 40 mg and in a further four eyes (two patients) with memantine 60 mg. One patient achieved the same benefit with memantine 40 mg and gabapentin. In two other eyes APN completely subsided with gabapentin 1,200 mg only, but not with memantine. Near visual acuity, a secondary outcome parameter, improved by at least 0.1 in 11 of 17 eyes treated with memantine and in 8 out of 16 eyes treated with gabapentin. In summary, memantine and gabapentin are safe and effective treatment options for APN.

In this preliminary study we measured maximum walking distance and walking time on four consecutive days in 29 patients with clinically stable multiple sclerosis (MS). Patients were included in the study if they could achieve a maximum unaided walking distance of 100 up to 500 m. Our results showed a certain day-to-day variability of maximum walking distance, in some cases meaning changes up to 1.5 points in the expanded disability status scale (EDSS), which could be misinterpreted as a progression of the disease. Simultaneous measurements of maximum walking time showed a similar variability, unlike the mean walking speed which turned out to be more stable. Our results therefore suggest that scoring of MS patients should not be based on one single measurement of the maximum walking distance. The more reliable parameter appears to be the mean walking speed.