Surgical therapy for multiple sclerosis tremor: a 12‐year follow‐up study

Background and purpose: Severe multiple sclerosis (MS) tremor causes disability poorly responsive to medication. Deep brain stimulation (DBS) or thalamotomy can suppress tremor, but long‐term outcomes are unclear. Methods: Nine patients with MS tremor underwent disability measures at baseline and 12 months post‐surgery (six thalamotomy, three DBS) in 1997–1998 (previously reported, Matsumoto et al., Neurology 2001;57:1876–82). We report the prospective 12‐year follow‐up of this cohort for tremor, disability, and death. Results: Surgery was initially successful in all. Tremor recurred in all patients within median 3 months, although two DBS patients were tremor‐free for 5 years. Median tremor‐free survival (tremor‐free time/survival time) was 4.3%. At 12‐year follow‐up, four survivors (two thalamotomy, two DBS) (Expanded Disability Status Scale scores 8–8.5) were severely disabled. Five patients were dead (four thalamotomy, one DBS) median 5.8 years post‐operative. Conclusions: Surgery benefit for severe tremor was overall short‐lived (median 3 months), with long‐term poor prognosis. Although two DBS patients had sustained 5‐year tremor‐suppression, the observed progressive disability and death in this cohort bear importance for long‐term success in future MS tremor surgery trials.     

Validity and test-retest reliability of a disability questionnaire for essential tremor.

BACKGROUND: One important outcome in clinical trials is patients' own opinions about whether the medication alleviates their symptoms and improves their ability to function. A valid and reliable method with which to assess this subjective information is important. OBJECTIVE: To determine the validity and test-retest reliability of the Columbia University Disability Questionnaire for Essential Tremor (ET). METHODS: Patients with ET underwent a 2.5-hour evaluation, including a 36-item tremor disability questionnaire, to assess the functional impact of tremor, a 26-item videotaped tremor examination rated by a neurologist, a 15-item performance-based test, and quantitative computerized tremor analysis. We determined the validity and test-retest reliability of the tremor disability questionnaire. Correlations between variables were assessed using Pearson's correlation coefficients and test-retest reliability with the weighted kappa statistic. RESULTS: Ninety-five patients with ET participated. The score on tremor disability questionnaire correlated with the neurologist's clinical ratings (r = 0.57, p <0.001) and the total score on the performance-based test (r = 0.69, p < 0.001). Correlations with quantitative computerized tremor analysis results were less robust, but each remained significant, including mean amplitude of dominant arm tremor while arms were extended (r = 0.56, p <0.001), while drawing a spiral (r = 0.42, p = 0.01), and while pouring (r = 0.34, p = 0.04). The questionnaire was readministered to 32 subjects, and the test-retest reliability was substantial (weighted kappa = 0.67). CONCLUSIONS: This Tremor Disability Questionnaire demonstrated substantial reliability, and it correlated with multiple measures of tremor severity, including a neurologist's clinical ratings, a performance-based test of function, and quantitative computerized tremor analysis results. The questionnaire would be useful in clinical trials in which it could be used as a reliable and valid tool to assess disability in ET.     

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.     

Validity of clinical and patient ratings of tremor disability among older adults

OBJECTIVE: To evaluate the validity of the clinical tremor disability interview using a performance-based measure, patient ratings of tremor disability, and bedside tremor severity ratings of upper extremity (UE) action/intention (A/I) and postural (P) tremor. METHOD: Sixteen older adult essential tremor patients (mean age=75.4 years, sd=5.7 years) took part in a study evaluating the validity of clinical and self-rating scales of tremor disability. A neurologist obtained bedside clinical ratings of UE A/I and P tremor of each limb and completed a clinical tremor disability rating. A second investigator, blind to neurological exam results obtained a clinical disability rating using the same measure, patient rated tremor disability ratings and conducted a performance-based disability assessment. RESULTS: Clinical tremor disability ratings were not significantly related to functional performance-based or patient ratings of tremor disability. Bedside clinical ratings of tremor severity also were not associated with clinical or patient-rated tremor disability. Patient ratings were significantly correlated with performance-based ratings. CONCLUSIONS: Further research is needed to validate a brief, sensitive clinical rating scale of tremor disability among older adults. Use of bedside ratings of tremor severity may be problematic and possibly estimate tremor disability. Empirical evaluation of differences in rating methods needs to be directly addressed.     

Transcranial magnetic stimulation: role in the evaluation of disability in multiple sclerosis

BACKGROUND: In patients with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) has shown significant prolongation of central motor conduction time (CMCT). Abnormal CMCT may reflect sub-clinical involvement of motor pathways and correlate with clinical motor disability. OBJECTIVE: To determine the diagnostic yield of TMS in MS and the possible correlation of TMS abnormalities with clinical disability. MATERIALS AND METHODS: Thirty patients with clinically definite MS presenting in acute relapse or with progressive disease course and 30 healthy controls were evaluated. TMS parameters evaluated included threshold intensity, motor evoked potentials (MEP) amplitudes and latencies and CMCT. Reassessment studies were done after three months. STATISTICAL ANALYSIS: Student t-test, Mann-Whitney U test and Spearman's rank correlation test were used to assess the relationships. RESULTS: Patients with MS had significantly higher threshold intensities, prolonged CMCT and reduced MEP amplitudes as compared to controls. Abnormalities in at least one parameter were observed in 86.7% of patients. When inter-side asymmetries in MEP latency and/or in CMCT were considered, the diagnostic yield increased to 96.7%. The diagnostic yield was 74.7% for visual evoked potentials, 13.3% for brainstem auditory evoked response and 10% for cerebrospinal fluid oligoclonal band. One MS patient without pyramidal or cerebellar dysfunction had prolonged CMCT. CMCT abnormalities correlated significantly with the degree of pyramidal signs, limb ataxia, intention tremor, dysdiadokokinesia and overall cerebellar score. In patients who had clinical improvement, follow-up studies showed improvement in CMCT parameters. CONCLUSION: TMS is a highly sensitive technique to evaluate cortico-spinal conduction abnormalities in MS that may have no clinical correlate and in monitoring the course of the disease. The effects of cerebellar dysfunction on TMS results need further evaluation.     

Evaluation of three different ways of assessing tremor in multiple sclerosis

OBJECTIVES: To examine the comparative reliability and validity of three simple ways of rating upper limb tremor in patients with multiple sclerosis. METHODS: Three examiners independently rated severity of upper limb tremor in patients with multiple sclerosis on a 0-10 scale by studying videotape recordings of patients' examinations, spiral drawings, and handwriting samples. The correlations of the tremor severity scores with scores from arm dexterity tests and a tremor related disability scale were also assessed. RESULTS: Rating tremor on posture had a good intrarater and interrater reliability. However, these reliabilities decreased when kinetic tremor was assessed, in part because dysmetria was a confounding factor. The intrarater reliabilities of rating tremor from spirals and handwriting were also good but the interrater reliabilities were only fair to moderate. Tremor severity scored by all three methods correlated highly with scores obtained from the nine hole peg test, finger tapping test, and a tremor related activities of daily living (ADL) questionnaire, indicating that all three methods were valid ways of assessing tremor in multiple sclerosis. CONCLUSION: Multiple sclerosis tremors in posture can be scored using a clinical rating scale in a valid and reliable way, and from spirals and handwriting samples if the ratings are carried out by the same examiner. However, scoring kinetic tremor was less reliable. In addition, the nine hole peg and finger tapping tests provide useful objective assessments of upper limb function in tremulous patients with multiple sclerosis.     

Objective changes in motor function during placebo treatment in PD

OBJECTIVE: To examine the frequency, temporal development, and stability of objectively derived motor changes during placebo treatment in PD and to define the clinical domains and demographic groups most affected. BACKGROUND: Placebo effects are documented in neurology, but the timing and specific disabilities most susceptible to changes during placebo treatment in PD have not been examined. METHODS: The authors examined the placebo-treated group from a randomized, multicenter, placebo-controlled clinical trial of monotherapy ropinerole in PD patients without motor fluctuations. In 105 patients, they evaluated placebo-associated effects on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), dividing the motor examination into four categories: tremor, bradykinesia, rigidity, and gait/balance/midline functions. The motor UPDRS and its subscales were compared over time (at baseline and at 4, 12, and 24 weeks) using Wilcoxon's signed rank test. They applied a rigorous definition of placebo-associated improvement as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by > or =2 points. RESULTS: During the 6-month study, 16% of subjects improved on placebo treatment. The prevalence of response was steady (8 to 9%) at any one visit without a predominance of an early effect. No patient showed a placebo-associated improvement on all visits. All domains of parkinsonian disability were subject to placebo-associated improvement, with a trend toward more response in bradykinesia and rigidity than in tremor or gait/balance/midline function. Gender, age, disease duration, and baseline disability score did not influence the likelihood of improvement in association with placebo treatment. CONCLUSION: Based on a rigorous definition of placebo-associated improvement, prominent improvements in objective measures of PD disability occur during clinical trials. Because placebo-associated improvements occur throughout a 6-month trial, placebo-controlled studies in PD should be at least 6 months to capture early as well as late improvements.     

Head tremor secondary to MS resolved with rituximab

We describe the case of a 33-year-old woman who presented with a 2-month history of worsening head tremor. The medical evaluation led to the new diagnosis of MS and the MRI of brain demonstrated prominently active disease. Intravenous rituximab was started according to the HERMES trial, and significant improvement was noted. She has received additional rituximab dosing approximately every 6 months, and at the 2-year follow-up the tremor has not recurred. The resolution of head tremor likely resulted from the complete suppression of MS disease activity, which must have allowed restoration of normal neural circuitry. In agreement with a growing body of evidence that supports early control of MS disease activity to prevent accumulation of fixed disability, this case advocates for aggressive immunological therapy at the onset of tremor in MS patients.     

Personality in essential tremor: further evidence of non-motor manifestations of the disease

OBJECTIVE: To ascertain whether patients with essential tremor have distinct definable personality traits. METHODS: A case-control study of patients with essential tremor was carried out to look for differences in personality characteristics. The controls were derived from the same source population. Using the tridimensional personality questionnaire (TPQ), personality traits were assessed in three dimensions: harm avoidance (HA), novelty seeking (NS), and reward dependence (RD). Additional analyses were conducted to address the possibility of selection bias among the patients with essential tremor. RESULTS: There were 55 patients and 61 controls. There was a difference between patients and controls in HA subscale scores (p = 0.005) but not in NS or RD scores. The difference remained significant in analyses that adjusted for age, sex, race, and education (p = 0.005). HA subscale scores did not correlate with subjective or objective measures of disability or with indices of severity of tremor. CONCLUSIONS: Patients with essential tremor scored higher on the harm avoidance subscale scores than control subjects. HA subscale scores did not correlate with the severity of tremor or with subjective and objective scales of disability, suggesting that the personality profile observed was not entirely related to functional disability caused by the tremor. Longitudinal studies of personality in essential tremor are needed to characterise the stability and evolution of these personality traits within the natural history of the disease process.     

Multiple sclerosis tremor and the Stewart-Holmes manoeuvre.

The objective of this study is to define tremor and cerebellar dysfunction and determine whether kinetic and postural tremor correlate with cerebellar dysfunction in patients with multiple sclerosis (MS). Cerebellar symptoms such as dysmetria often interfere with tremor evaluation in MS. The Stewart-Holmes (SH) manoeuvre, which has been recently quantified, may offer a selective evaluation of cerebellar dysfunction in such patients. Thirty-two patients with definite MS and arm tremor were evaluated (simplified Fahn tremor scale for kinetic and postural tremor, finger-to-nose test, clinical SH manoeuvre, quantitative study of the SH manoeuvre). Median severity of kinetic and postural tremor on the most disabled side was, respectively, 2 (range 0-4) and 1.5 (range 0-4). Clinical SH scores were moderately correlated to quantified SH measures (r = 0.36, P < 0.05). Kinetic and postural tremors were strongly correlated (r = 0.73, P < 0.0001) but did not correlate with clinical or quantified SH scores. Patients with bilateral tremor had higher scores for quantified SH, and a trend to higher clinical SH and finger-to-nose scores than patients with unilateral tremor. Although clinically associated, cerebellar dysfunction and tremor may be partly independent symptoms, suggesting they may relate to dysfunction of different neuronal systems. The SH manoeuvre should be part of the evaluation of MS patients considered for surgery of tremor.     

Three-dimensional measurement of essential tremor.

A mechanical linkage device was used to measure the three-dimensional position of the fingertip during a postural task. Thirty patients with essential tremor were tested simultaneously with the device, uniaxial accelerometry, and clinical tremor measures. Eighteen patients were tested again 16+/-4 days later. The device accurately recorded the three-dimensional behavior of essential tremor. Measures from the device included mean three-dimensional velocity, mean three-dimensional dispersion, and power of the three-dimensional acceleration. The logarithms of these measures were strongly correlated (r = .841-.984) with all clinical measures including self-reported tremor disability. The device measures were reliable within and between testing sessions (intraclass correlation coefficients = .971-.977). The performance of the device was superior to uniaxial accelerometry, most likely as a result of the three-dimensional nature of the measurements. We conclude that essential tremor can be validly and reliably quantified during a postural task providing the recording device records movement in three dimensions and the measurements are logarithmically transformed.     

A controlled trial of isoniazid therapy for action tremor in multiple sclerosis

Summary 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 -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.     

Effects of mannitol and glycerol on cerebral energy metabolism in gerbils

Objectives - To test new electronic equipment, TREMOR, for quantitative registration of rest tremor and kinetic tremor of the extremities. Patients and methods - The tremor intensity of rest tremor and kinetic tremor was studied in 14 multiple sclerosis (MS) patients. Clonazepam was used in an open study in 11 MS patients to evaluate the sensitivity of TREMOR, compared to the clinical observations. Results - We found no diurnal variations in tremor. Five patients discontinued the trial because of side effects due to clonazepam. Clonazepam significantly reduced clinically rest tremor in all 6 patients and clinically kinetic tremor in 5 patients. Tested by TREMOR all patients showed significant reduction in rest tremor and kinetic tremor. Correlation between electronic assessment of kinetic tremor, clinical score and Peg board test were good. Conclusion - TREMOR was found useful for assessment of the severity of tremor in patients with kinetic tremor and thereby avoid intra- and interobserver variation.     

Systematic evaluation of rating scales for impairment and disability in Parkinson's disease.

We assessed the clinometric characteristics of rating scales used for the evaluation of motor impairment and disability of patients with Parkinson's disease (PD), conducting a systematic review of PD rating scales published from 1960 to the present. Thirty studies describing clinometrics of 11 rating scales used for PD were identified. Outcome measures included validity (including factor structure), reliability (internal consistency, inter-rater, and intrarater) and responsiveness. We traced three impairment scales (Webster, Columbia University Rating Scale [CURS] and Parkinson's Disease Impairment Scale), four disability scales (Schwab and England, Northwestern University Disability Scale [NUDS], Intermediate Scale for Assessment of PD, and Extensive Disability Scale), and four scales evaluating both impairment and disability (New York University, University of California Los Angeles, Unified Parkinson's Disease Rating Scale [UPDRS], and Short Parkinson Evaluation Scale). The scales showed large differences in the extent of representation of items related to signs considered responsive to dopaminergic treatment or to those signs that appear late in the disease course and lack responsiveness to treatment. Regardless of the scale, there was a conspicuous lack of consistency concerning inter-rater reliability of bradykinesia, tremor, and rigidity. Overall disability items displayed moderate to good inter-rater reliability. The available evidence shows that CURS, NUDS, and UPDRS have moderate to good reliability and validity. In contrast to their widespread clinical use for assessment of impairment and disability in PD, the majority of the rating scales have either not been subjected to an extensive clinometric evaluation or have demonstrated clinometric shortcomings. The CURS, NUDS, and UPDRS are the most evaluated, valid, and reliable scales currently available.     

Use of the Multiple Sclerosis Functional Composite to predict disability in relapsing MS

OBJECTIVE: To determine whether the MS Functional Composite (MSFC) can predict future disease progression in patients with relapsing remitting MS (RR-MS). BACKGROUND: The MSFC was recommended by the Clinical Outcomes Assessment Task Force of the National MS Society as a new clinical outcome measure for clinical trials. The MSFC, which contains a test of walking speed, arm dexterity, and cognitive function, is expressed as a single score on a continuous scale. It was thought to offer improved reliability and responsiveness compared with traditional clinical MS outcome measures. The predictive value of MSFC scores in RR-MS has not been determined. METHODS: The authors conducted a follow-up study of patients with RR-MS who participated in a phase III study of interferon beta-1a (AVONEX) to determine the predictive value of MSFC scores. MSFC scores were constructed from data obtained during the phase III trial. Patients were evaluated by neurologic and MRI examinations after an average interval of 8.1 years from the start of the clinical trial. The relationships between MSFC scores during the clinical trial and follow-up status were determined. RESULTS: MSFC scores from the phase III clinical trial strongly predicted clinical and MRI status at the follow-up visit. Baseline MSFC scores, and change in MSFC score over 2 years correlated with both disability status and the severity of whole brain atrophy at follow-up. There were also significant correlations between MSFC scores during the clinical trial and patient-reported quality of life at follow-up. The correlation with whole brain atrophy at follow-up was stronger for baseline MSFC than for baseline EDSS. CONCLUSION: MSFC scores in patients with RR-MS predict the level of disability and extent of brain atrophy 6 to 8 years later. MSFC scores may prove useful to assign prognosis, monitor patients during early stages of MS, and to assess treatment effects.     

A comparison of health utility measures for the evaluation of multiple sclerosis treatments

OBJECTIVES: To evaluate the practical application and psychometric properties of three health utility measures in a sample of MS patients with a broad range of neurological disability as measured by the Extended Disability Status Scale (EDSS). METHODS: Patients randomly selected from two MS clinic registries were assessed using standard clinical methods and completed three generic measures of health utility (EQ-5D, HUI Mark III, SF-6D). The proportion of missing data, test/retest reliability, and construct validity of each health utility measure were examined. RESULTS: The assessments were completed by 187 patients. Less than 10% of data were missing for the subscales of the SF-6D (< 3.2%), HUI Mark III (<1.6%), and EQ-5D (< or =7.5%). Severely disabled patients were more likely to omit physical function questions for the SF-6D (20%), and EQ-5D (43%). Retest reliability for the SF-6D (ICC = 0.83), EQ-5D (ICC = 0.81), and HUI Mark III (ICC = 0.87) were adequate for population surveys. Correlations between assessment of clinical function and each health utility measure were strongest for the HUI Mark III (HUI Mark III EDSS rho = -0.77, HUI Mark III ambulation index rho = -0.76, HUI Mark III timed 25 foot walk rho = -0.73, HUI Mark III nine hole peg test rho = -0.65). CONCLUSIONS: The health utility measures were generally feasible and reliable but the HUI Mark III demonstrated highest concordance with the EDSS across the full range of neurological disability. Of the three measures studied, the HUI Mark III may be the most appropriate for cost effectiveness evaluations of MS therapies.     

Clinical trials in multiple sclerosis: methodological issues

PURPOSE OF REVIEW: The availability of partially effective immunomodulatory and immunosuppressive treatments for relapsing multiple sclerosis (MS) opens important ethical, methodological and practical issues in the design and conduct of new clinical trials in these patients. RECENT FINDINGS: The recommendation of the National Health Authorities to prioritize phase III clinical trials using placebo arm raises ethical questions. In addition, patients are reluctant to be involved in such trials. Alternative clinical trial designs will be discussed. Relapses and active lesions are accepted measures of disease activity; new/enlarging T2 lesions and/or enhancing lesions are accepted surrogate markers of disease activity in phase II clinical trials. On the contrary, there are no accepted magnetic resonance imaging (MRI) surrogate markers of disease progression and also the clinical measures to monitor the degenerative aspects of the disease are not without important limitations. New scales of impairment, disability and quality of life will be reviewed extensively. We will also focus on the value of modern and quantitative MRI techniques, which hold substantial promise as tools to estimate the extent of MS-related irreversible tissue loss. SUMMARY: The use of an active comparator in a superior clinical-trial design is becoming an attractive option for testing the efficacy of new drugs in relapsing MS. At present there are no fully reliable and sensitive clinical markers of the accumulation of irreversible tissue damage in MS. Although additional extensive application in longitudinal studies is needed, modern MRI techniques are promising tools to monitor the neurodegenerative aspects of MS.     

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.     

Thalamotomy versus thalamic stimulation for multiple sclerosis tremor.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.     

A double-blind, placebo-controlled trial of extracorporeal photopheresis in chronic progressive multiple sclerosis.

Extracorporeal photopheresis is a safe therapy for cutaneous T-cell lymphoma and may have efficacy in certain autoimmune disorders. We performed a randomized, double-blinded, placebo-controlled trial of monthly photopheresis therapy in 16 patients with clinically definite multiple sclerosis (MS). All patients had progressed during the preceding year with entry Expanded Disability Status Scale (EDSS) scores between 3.0 and 7.0. Patients received photopheresis or sham therapy for 1 year and were followed for an additional 6 to 12 months. Patients were clinically evaluated by three disability scales: (1) EDSS; (2) Ambulation index and (3) Scripp's quantitative neurologic assessment. No serious side effects occurred in either group. There were no differences between the photopheresis and sham therapy groups by the disability measures. Additionally, there were no differences in progression of MRI plaque burden or evoked potential latencies. In this limited study, photopheresis was found to be safe but did not significantly alter the course of chronic progressive MS.