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When 251 relapsing-remitting patients with multiple sclerosis were randomized to receive daily subcutaneous injections of glatiramer acetate, previously called copolymer 1 (Copaxone; n = 125) or placebo (n = 126) for 24 months, there were no laboratory abnormalities associated with glatiramer acetate treatment and it was well tolerated with few side effects. Patients receiving glatiramer acetate had significantly fewer relapses and were more likely to be neurologically improved, whereas those receiving placebo were more likely to worsen. This study was extended for 1 to 11 months (mean of 5.2 months for the glatiramer acetate group and 5.9 months for the placebo group). The blinding and study conditions used during the core 24-month study were unchanged throughout the extension. The results of this extension study confirm the excellent tolerance and safety profile of glatiramer acetate for injection. The clinical benefit of glatiramer acetate for both the relapse rate and for neurologic disability was sustained at the end of the extension trial.

We studied copolymer 1 (Copaxone) in a multicenter (11-university) phase III trial of patients with relapsing-remitting multiple sclerosis (MS). Two hundred fifty-one patients were randomized to receive copolymer 1 (n = 125) or placebo (n = 126) at a dosage of 20 mg by daily subcutaneous injection for 2 years. The primary end point was a difference in the MS relapse rate. The final 2-year relapse rate was 1.19 +/- 0.13 for patients receiving copolymer 1 and 1.68 +/- 0.13 for those receiving placebo, a 29% reduction in favor of copolymer 1 (p = 0.007) (annualized rates = 0.59 for copolymer 1 and 0.84 for placebo). Trends in the proportion of relapse-free patients and median time to first relapse favored copolymer 1. Disability was measured by the Expanded Disability Status Scale (EDSS), using a two-neurologist (examining and treating) protocol. When the proportion of patients who improved, were unchanged, or worsened by > or = 1 EDSS step from baseline to conclusion (2 years) was evaluated, significantly more patients receiving copolymer 1 were found to have improved and more receiving placebo worsened (p = 0.037). Patient withdrawals were 19 (15.2%) from the copolymer 1 group and 17 (13.5%) from the placebo group at approximately the same intervals. The treatment was well tolerated. The most common adverse experience was an injection-site reaction. Rarely, a transient self-limited systemic reaction followed the injection in 15.2% of those receiving copolymer 1 and 3.2% of those receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Spatiotemporal contrast sensitivity at three orientations, vertical, horizontal and oblique, was studied in 18 patients with clinically definite and laboratory-confirmed definite multiple sclerosis (MS). Nineteen age-matched control subjects were also studied under identical experimental conditions. Contrast thresholds for detecting steady and counterphase modulated (5 Hz) gratings ranging in spatial frequency from 0.5 to 12 c/deg were measured by a modified psychophysical method of limits. With the exception of two patients (three eyes) whose Snellen acuity scores were 20/70, all observers had acuity scores of 20/30 or better. All subjects were corrected for astigmatism. Orientation, spatial frequency and temporal frequency interacted differently in determining contrast sensitivity in the two groups of observers. For the controls, an oblique effect was present for both the steady and counterphase modulated gratings of high spatial frequencies, and there was no orientation-dependent loss of sensitivity for low spatial frequencies. For the observers with MS, there was no oblique effect, but sensitivity was dependent on orientation for the low spatial frequencies. Most patients with MS had reduced contrast sensitivity, compared to the controls, at one or more orientations. Counterphase modulation increased sensitivity to the low spatial frequencies and decreased sensitivity to the high spatial frequencies for both normal controls and patients with MS. In patients with MS this effect of temporal modulation on contrast sensitivity was markedly enhanced.

A specific subpopulation of mononuclear cells bearing a surface receptor for the Fc portion of IgG was considerably reduced in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during exacerbation, but returned toward normal levels as the patient entered remission. Low concentrations of immune complexes were found in the CSF in nearly 50% of MS patients during exacerbations but immune complexes were not found in patients with stable MS.

Retention of information concerning steroid medication dosage, side effects, and course of action to follow when certain danger signs or side effects occur was tested prospectively in multiple sclerosis patients about to be treated with alternate-day steroid medication. Each patient received identical oral instruction from both a physician and a clinical nurse specialist, followed by a written pretest of the orally imparted information. Alternate patients then received a written instruction booklet to reinforce the information concerning steroid medications. After one month, a written posttest was given. Patients who received the written instructional booklet showed a significant increase in retained knowledge concerning steroids.

The prevalence and nature of emotional disturbance in patients with multiple sclerosis (MS) was studied prospectively in 64 MS patients and 23 spinal cord-injured (SCI) control patients by administration of the 28-item subscale General Health Questionnaire (GHQ). MS patients in remission had a mean GHQ score of 4.4, and patients with acute exacerbation or progressive nonremitting MS had a mean score of 15.7, a significant difference (p less than 0.001). The prevalence of emotional disturbance was 90% in exacerbating or progressing patients, 39% in stable patients, and 12% in SCI control patients. The presence of emotional disturbance was not related to age, sex, or other demographic variables, to duration or severity of disease, or to the degree of disability. In the group of MS patients in remission, somatic complaints, anxiety, and social dysfunction were more prevalent than symptoms of depression.

Eighty-seven patients with definite multiple sclerosis (MS) were examined neurologically and administered the Mini-mental State examination (MMS) to assess cognitive disability at the beginning and end of a one-year study. A CT scan was performed in 37. A group of 16 patients with stable spinal cord injuries (SCI) were studied in a similar manner. Of the MS patients, 47% had a mean General Health Questionnaire (GHQ) score in the abnormal range. This was a higher rate than in SCI patients (P = 0.004). Mean depression scores were similar in MS and SCI patients, but MS patients with brain involvement were more depressed than those with cord lesions only (P = 0.05). Depression score was unrelated to functional disability but was correlated with the degree of neurological impairment (P = 0.03). Euphoric patients were more likely to have brain involvement (P = 0.006), to have progressive MS (P less than 0.0001), and to have enlarged ventricles (P = 0.04) and were more impaired cognitively (P = 0.04) than noneuphoric patients. These results suggest that depression in MS patients is partly determined by the presence of brain involvement, but that it is also an emotional reaction to the disorder. Euphoria and cognitive disorder are reflections of brain involvement.