A controlled trial of isoniazid therapy for action tremor in multiple sclerosis. Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Topiramate in medically intractable partial epilepsies: double-blind placebo-controlled randomized parallel group trial. Korean Topiramate Study Group. Efficacy of a neuropsychological training programme for patients with multiple sclerosis -- a randomised controlled trial. Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis.
Ten patients with clinically definite multiple sclerosis (MS) and action tremor were treated with isoniazid (INH) in a double-blind single crossover trial. The daily dose of INH administered during the 4-week treatment phase of the trial was determined by acetylator phenotype with slow acetylators receiving 12 mg/kg per day and rapid acetylators 20 mg/kg per day. Six of eight patients who completed the trial showed clinical improvement in the postural (alternating) tremor while on INH but the degree was minimal in all cases. Results of tremograms indicated that improvement also occurred in the intentional (synchronous) component of three patients while on INH, but this did not achieve statistical significance. Cerebrospinal fluid (CSF) levels of gamma-aminobutyric acid (GABA) homocarnosine and ornithine were markedly elevated with INH therapy (providing evidence for substantial inhibition of GABA aminotransferase activity and increase in GABA in the CNS), but no correlation was found between the degree of GABA elevation in the CSF and the clinical response. Side effects were minimal and well tolerated. Although INH appears to have a limited therapeutic role, a trial is warranted in MS patients with postural tremor. To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy.
                A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. Following a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin 600 mg/day administered twice daily (BID) or three times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing > or =50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population.
                Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID (p < or = 0.0001) and 44% for pregabalin BID (p < or = 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo (p < or = 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia.
                Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice daily or three times daily schedule with similar efficacy and tolerability results. This study was planned to investigate the efficacy of neuromuscular rehabilitation and Johnstone Pressure Splints in the patients who had ataxic multiple sclerosis.
                Twenty-six outpatients with multiple sclerosis were the subjects of the study. The control group (n = 13) was given neuromuscular rehabilitation, whereas the study group (n = 13) was treated with Johnstone Pressure Splints in addition.
                In pre- and posttreatment data, significant differences were found in sensation, anterior balance, gait parameters, and Expanded Disability Status Scale (p < 0.05). An important difference was observed in walking-on-two-lines data within the groups (p < 0.05). There also was a statistically significant difference in pendular movements and dysdiadakokinesia (p < 0.05). When the posttreatment values were compared, there was no significant difference between sensation, anterior balance, gait parameters, equilibrium and nonequilibrium coordination tests, Expanded Disability Status Scale, cortical onset latency, and central conduction time of somatosensory evoked potentials and motor evoked potentials (p > 0.05). Comparison of values revealed an important difference in cortical onset-P37 peak amplitude of somatosensory evoked potentials (right limbs) in favor of the study group (p < 0.05).
                According to our study, it was determined that physiotherapy approaches were effective to decrease the ataxia. We conclude that the combination of suitable physiotherapy techniques is effective multiple sclerosis rehabilitation. To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients.
                In vitro, 4AP improves conduction through demyelinated axons. A previous multicenter trial of 4AP SR using the Expanded Disability Status Scale (EDSS) as the primary outcome was unable to establish clinical efficacy.
                Ten MS patients with stable motor deficits (EDSS 6.0-7.5) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind, placebo-controlled, crossover trial. Time to walk 8 meters, time to climb four stairs, maximum voluntary isometric contraction measured quantitatively (MVICT), manual muscle testing (MMT), grip strength, EDSS, and the patient's global impression were measured.
                Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects (p = 0.02). Timed stair climbing, MVICT, MMT, grip strength, and EDSS showed nonsignificant improvements on 4AP SR. Based on their global impressions, seven subjects preferred 4AP SR over placebo; only one preferred placebo. There were no serious side effects.
                4AP SR improved motor function in MS patients. The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS. Deep-brain stimulation through an electrode implanted in the thalamus was developed as an alternative to thalamotomy for the treatment of drug-resistant tremor. Stimulation is thought to be as effective as thalamotomy but to have fewer complications. We examined the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis.
                Sixty-eight patients (45 with Parkinson's disease, 13 with essential tremor, and 10 with multiple sclerosis) were randomly assigned to undergo thalamotomy or thalamic stimulation. The primary outcome measure was the change in functional abilities six months after surgery, as measured by the Frenchay Activities Index. Scores for this index can range from 0 to 60, with higher scores indicating better function. Secondary outcome measures were the severity of tremor, the number of adverse effects, and patients' assessment of the outcome.
                Functional status improved more in the thalamic-stimulation group than in the thalamotomy group, as indicated by increases in the score for the Frenchay Activities Index (from 31.4 to 36.3 and from 32.0 to 32.5, respectively; difference between groups, 4.4 points; 95 percent confidence interval, 2.0 to 6.9). After adjustment for base-line characteristics, multivariate analysis also showed that the thalamic-stimulation group had greater improvement (difference between groups, 5.1 points; 95 percent confidence interval, 2.3 to 7.9). Tremor was suppressed completely or almost completely in 27 of 34 patients in the thalamotomy group and in 30 of 33 patients in the thalamic-stimulation group. One patient in the thalamic-stimulation group died perioperatively after an intracerebral hemorrhage. With the exception of this incident, thalamic stimulation was associated with significantly fewer adverse effects than thalamotomy. Functional status was reported as improved by 8 patients in the thalamotomy group, as compared with 18 patients in the thalamic-stimulation group (P=0.01).
                Thalamic stimulation and thalamotomy are equally effective for the suppression of drug-resistant tremor, but thalamic stimulation has fewer adverse effects and results in a greater improvement in function. The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression. To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies.
                We used a multicenter double-blind placebo-controlled randomized parallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of titration phase, and 8 weeks of stabilization phase. The primary efficacy variable was the median seizure frequency reduction rate (MSFRR), and the other efficacy variables included responder rate, seizure-free rate, and global evaluations by the patient and the physician. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 50 mg/day and gradually increased to the target dose over a 10-week period.
                A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who were randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were available for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001). Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation greatly favored TPM (p = 0.001). The incidence of adverse events (AEs) was higher in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, anorexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) patients taking TPM and three (3.5%) patients taking PLC. No serious systemic AEs were observed.
                TPM was highly effective and safe as add-on therapy in medically intractable partial epilepsies. Slower titration of TPM might be responsible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites. One aim of this project was to investigate the efficacy of a specific training programme for MS patients which also contained compensation strategies and relaxation exercises relevant to everyday life. The other aim was to check the programme's relevance to everyday life.
                19 patients, randomised into two groups, took part in the study. The participants in the treated group completed a specific neurological training programme which began immediately after the basic testing (visit 1) and lasted 4 weeks, with a total of 12 sessions. The monitoring test was done immediately after the training programme (at visit 2) and the follow-up was 3 months later (visit 3). Both study groups were fully comparable as regards clinical and socio-demographic data and baseline intelligence level.
                The results of the cognitive training programme were especially evident in the significant improvements in executive functions (CKV) and spatial-constructional abilities (HAWIE-R). Comparison between the treated and the control group showed no significant difference in the fatigue values (MFIS). However, when the treated group was examined over the three times of measurements, the symptoms of fatigue had diminished significantly. Regarding memory, comparison of the groups showed no changes; within the treated group; however, the verbal (VLT) and nonverbal learning and memory (NVLT) improved significantly. The results for sustained attention improved in both groups over time. It must be assumed that a learning effect had occurred here. The depression values (BDI) also improved in both study groups. The follow-up questionnaire showed that 60% (6) attributed an average to above-average benefit to the training.
                To summarise, it is apparent that MS patients with mild to moderate cognitive impairment are able to profit from even a fairly brief neuropsychological training programme and to integrate much of it into their everyday lives. In view of this, it would seem appropriate to offer such a programme as standard, associated with medication. Six patients with severe postural cerebellar tremor were studied in a double-blind, placebo-controlled, crossover trial with isoniazid. Each phase of the study lasted 4 weeks, and in the isoniazid phase patients received an increasing dose up to 1200 mg/d. Patients were studied with self-rating scales, quantitative tremor recording, and blinded ratings of videotapes. All patients improved by at least one method, three improved by all methods, and four improved sufficiently to want to continue with the drug after the trial was finished. There is a definite, but limited, therapeutic role for isoniazid.
The absolute and comparative efficacy and tolerability of pharmacotherapies to treat ataxia in MS are poorly documented and no recommendations can be made to guide prescribing. Although studies on neurosurgery and neurorehabilitation showed promising results, the absolute indications for treating with those methods cannot be developed. Standardised, well validated measures of ataxia and tremor need to be developed and employed in larger randomised controlled trials with careful blinding.