Johan C. Koetsier

Intensity of leg and arm training after primary middle-cerebral-artery stroke: a randomised trial

BACKGROUND We investigated the effects of different intensities of arm and leg rehabilitation training on the functional recovery of activities of daily living (ADL), walking ability, and dexterity of the paretic arm, in a single-blind randomised controlled trial. METHODS Within 14 days after stroke onset, 101 severely disabled patients with a primary middle-cerebral-artery stroke were randomly assigned to: a rehabilitation programme with emphasis on arm training; a rehabilitation programme with emphasis on leg training; or a control programme in which the arm and leg were immobilised with an inflatable pressure splint. Each treatment regimen was applied for 30 min, 5 days a week during the first 20 weeks after stroke. In addition, all patients underwent a basic rehabilitation programme. The main outcome measures were ability in ADL (Barthel index), walking ability (functional ambulation categories), and dexterity of the paretic arm (Action Research arm test) at 6, 12, 20, and 26 weeks. Analyses were by intention to treat. FINDINGS At week 20, the leg-training group (n=31) had higher scores than the control group (n=37) for ADL ability (median 19 [IQR 16-20] vs 16 [10-19], p<0.05), walking ability (4 [3-5] vs 3 [1-4], p<0.05), and dexterity (2 [0-56] vs 0 [0-2], p<0.01). The arm-training group (n=33) differed significantly from the control group only in dexterity (9 [0-39] vs 0 [0-2], p<0.01). There were no significant differences in these endpoints at 20 weeks between the arm-training and leg-training groups. INTERPRETATION Greater intensity of leg rehabilitation improves functional recovery and health-related functional status, whereas greater intensity of arm rehabilitation results in small improvements in dexterity, providing further evidence that exercise therapy primarily induces treatment effects on the abilities at which training is specifically aimed.

Effects of Intensity of Rehabilitation After Stroke A Research Synthesis

BACKGROUND AND PURPOSE A research synthesis was performed to (1) critically review controlled studies evaluating effects of different intensities of stroke rehabilitation in terms of disabilities and impairments and (2) quantify patterns by calculating summary effect sizes. The influences of organizational setting of rehabilitation management, blind recording, and amount of rehabilitation on the summary effect sizes were calculated. METHODS A Medline literature search was performed for a critical review of the literature. The internal and external validity of the studies was evaluated. In addition, a meta-analysis was performed by applying the fixed (Hedgess g) effects model. RESULTS The effects of different intensities of rehabilitation were studied in nine controlled studies involving 1051 patients. Analysis of the methodological quality revealed scores varying from 14% to 47% of the maximum feasible score. Meta-analysis demonstrated a statistically significant summary effect size for activities of daily living (0.28 +/- 0.12). Lower summary effect sizes (0.19 +/- 0.17) were found for studies in which experimental and control groups were treated in the same setting compared with studies in which the two groups of patients were treated in different settings (0.40 +/- 0.19). Variables defined on a neuromuscular level (0.37 +/- 0.24) showed larger summary effect sizes than variables defined on a functional level (0.10 +/- 0.21). Weighting individual effect sizes for the difference in amount of rehabilitation between experimental and control groups resulted in larger summary effect sizes for activities of daily living and functional outcome parameters for studies that were not confounded by organizational setting. CONCLUSIONS A small but statistically significant intensity-effect relationship in the rehabilitation of stroke patients was found. Insufficient contrast in the amount of rehabilitation between experimental and control conditions, organizational setting of rehabilitation management, lack of blinding procedures, and heterogeneity of patient characteristics were major confounding factors.

Randomised double blind controlled trial of cyclosporin in multiple sclerosis.

In a 2 year double blind controlled trial of cyclosporin against placebo in multiple sclerosis conducted at two centres there was a beneficial effect of the therapy upon the progression of the disease, relapse rate and relapse severity at one of the centres where the patients received a mean dose of 7.2 mg/kg/day. This beneficial effect was not seen in the other centre where a lower dose (mean 5 mg/kg/day) was given. Reduction in clinical progression was accompanied by decreased IgG synthesis in the central nervous system. Side effects included hypertension, renal insufficiency and anaemia and were of such severity to preclude the use of cyclosporin in a high enough dose to alter the course of the disease.

4-aminopyridine in Patients with Multiple Sclerosis: Dosage and Serum Level Related to Efficacy and Safety

In a recent randomized, double-blind, placebo-controlled crossover trial, we demonstrated efficacy of 4-aminopyridine (4-AP) in improving disability of patients with multiple sclerosis (MS). Here we describe the relationship between dosage, serum level, efficacy, and safety of intravenously and orally administered 4-AP in the same group of 70 MS patients. After both intravenous and oral administration there was a significant relationship between serum levels and 4-AP doses used (p < 0.001 and p < 0.01, respectively). The use of 4-AP in oral doses three times a day showed a large variation and fluctuation in serum levels. After 12 weeks of oral treatment (maximum daily dosage 0.5 mg/kg body weight), a statistically significant improvement was found for the smooth pursuit gain of the eye movements (estimated effect 0.14, 95% confidence interval 0.06-0.23, p < 0.001). The amount of improvement was significantly related to 4-AP serum levels (p = 0.0013). Side effects after intravenous 4-AP occurred frequently and were very troublesome (pain in infusion arm, dizziness). Side effects during oral treatment (dizziness, paresthesias) were very mild and occurred 30-45 min after intake of the medication and could be related to high serum levels.

Evaluation of the visual system in multiple sclerosis: a comparative study of diagnostic tests

In 22 patients with clinically definite multiple sclerosis (MS) who were without visual symptoms and had a visual acuity of at least 1.0 in both eyes at the time of measurement, the following tests were performed to detect subclinical lesions in the visual system: visual evoked potential (VEP), contrast sensitivity test (CS), flight of colours test (FOC), colour vision test (Ishihara plates) (CV) and the pupillary light reflex (PLR). VEP was abnormal in 81.8%, CS in 72.7%, FOC in 36.4%, CV in 31.8%, and PLR in 52.3% of the patients. VEP and CS together were most sensitive: combining these techniques subclinical lesions of the visual system were detected in 90.9% (20/22) of these asymptomatic patients.