Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis. The effect of cannabis on tremor in patients with multiple sclerosis. Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis. A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study. Effect of baclofen on gait in spastic MS patients. Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. A controlled trial of isoniazid therapy for action tremor in multiple sclerosis.
To determine whether physiotherapy can improve mobility in chronic multiple sclerosis and whether there is a difference between treatment at home and as a hospital outpatient?
                A randomised controlled crossover trial was undertaken in patients with chronic multiple sclerosis who had difficulty walking and were referred from neurology clinics: allocation was to one of six permutations of three 8 week treatment periods separated by 8 week intervals: treatments consisted of physiotherapy at home, as an outpatient, or "no therapy". The main outcome measures were based on independent assessments at home and included mobility related disability (primary outcome: the Rivermead mobility index), gait impairments, arm function, mood, and subjective patient and carer ratings. Therapy was assessed by recording delivery, achievement of set targets, patient and carer preference, and cost.
                On the Rivermead mobility index (scale 0-15) (primary outcome) there was a highly significant (p<0.001) treatment effect of 1.4-1.5 units favouring hospital or home based therapy over no therapy: this was supported by other measures of mobility, gait, balance, and the assessor's global "mobility change" score: there was no major difference between home and hospital. Carers preferred home treatment but neither they nor patients discerned greater benefit there. Estimated costs of home physiotherapy were 25 pounds/session and those at hospital were 18 pounds (including 7 pounds patient travel costs).
                A course of physiotherapy is associated with improved mobility, subjective wellbeing, and improved mood in chronic multiple sclerosis compared with no treatment but benefit may only last a few weeks: there is little to choose between home and hospital based therapy but the first is more costly, mainly due to skilled staff travelling time. Disabling tremor is common in patients with multiple sclerosis (MS). Data from animal model experiments and subjective and small objective studies involving patients suggest that cannabis may be an effective treatment for tremor associated with MS. To our knowledge, there are no published double-blind randomized controlled trials of cannabis as a treatment for tremor in MS patients.
                The authors conducted a randomized double-blind placebo-controlled crossover trial to examine the effect of oral cannador (cannabis extract) on 14 patients with MS with upper limb tremors. There were eight women and six men, with a mean age of 45 years and mean Expanded Disability Status Scale score of 6.25. Patients were randomly assigned to receive each treatment and the doses escalated over a 2-week period before each assessment. The primary outcome was change on a tremor index, measured using a validated tremor rating scale. The study was powered to detect a functionally significant 50% improvement in the tremor index. Secondary outcomes included accelerometry, an ataxia scale, spiral drawing, finger tapping, and nine-hole pegboard test performance.
                Analysis of the data showed no significant improvement in any of the objective measures of upper limb tremor with cannabis extract compared to placebo. Finger tapping was faster on placebo compared to cannabis extract (p < 0.02). However, there was a nonsignificant trend for patients to experience more subjective relief from their tremors while on cannabis extract compared to placebo.
                Cannabis extract does not produce a functionally significant improvement in MS-associated tremor. 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. To use a pilot study to compare two physiotherapy approaches to improve walking in patients with gait disturbance due to multiple sclerosis (MS).
                Patients were assessed and then randomly assigned to one of two groups using a block randomization technique. They were treated by the research physiotherapist for a minimum of 15 treatments over a 5-7-week period and then reassessed by an independent therapist one week after treatment.
                Both assessment and treatment were undertaken at a specialist rehabilitation centre.
                Outpatients with clinically stable MS (chronic progressive or relapsing-remitting types) who were referred for physiotherapy to improve their mobility.
                Comparison was between a facilitation (impairment-based) approach and a task-oriented (disability-focused) approach.
                Mobility was assessed using four measures: the 10-metre timed walk, the Rivermead Mobility Index, stride length and the Rivermead Visual Gait Assessment. Balance was assessed using the Berg Balance Test.
                Twenty-three patients were entered, and 10 in each group completed the study. The groups were similar on all measured items both before and after treatment. There was no significant difference in improvement between the two approaches. Following treatment, patients in both groups showed a significant overall improvement (p < 0.05) in both impairment and disability measures.
                No significant differences in effectiveness between the two methods were demonstrated. Both a task-oriented approach and a facilitation approach to the treatment of MS outpatients were associated with improved mobility. To measure gait and postural stability by objective methods in spastic MS patients and to evaluate the effect of baclofen on gait and postural stability.
                Fourteen spastic MS patients were examined in a placebo controlled double-blind, cross-over trial of oral baclofen treatment. The gait was measured on a computerized treadmill and postural stability was measured on a computer assisted force-plate.
                Only insignificant improvements in the clinical measurements during baclofen treatment were found. At baseline gait was characterized by low speed, short steps and unsteadiness. Postural stability was severely impaired. During baclofen treatment only vertical unsteadiness of gait diminished significantly.
                We conclude that patients primarily with spasticity, concomitant with hampering or painful spasms and co-contractions should be offered treatment with baclofen. Only some will experience improvement of their gait disorders, when treated with baclofen. 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. The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild. 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. 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.
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.