Transcranial magnetic stimulation for upper motor neuron involvement in amyotrophic lateral sclerosis (ALS).
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Amyotrophic Lateral Sclerosis↗
Biomedical subjects
S L Pullman
Publications and source records attributed to S L Pullman.
Operative techniques and morbidity with subthalamic nucleus deep brain stimulation in 100 consecutive patients with advanced Parkinson's disease.
OBJECTIVE: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. METHODS: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation. RESULTS: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. CONCLUSION: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.
Adult↗
Objective tests for upper motor neuron involvement in amyotrophic lateral sclerosis (ALS).
OBJECTIVE: To develop objective markers for upper motor neuron (UMN) involvement in ALS, the value of single-voxel MR spectroscopy (MRS) and transcranial magnetic stimulation (TMS) was studied. METHODS: Test results of 164 ALS patients who had MRS only (n = 91), TMS only (n = 13), or both (n = 60) were analyzed; also, 11 autopsy examinations were evaluated. RESULTS: Abnormal test results consistent with UMN involvement were found in 134 patients with clinical UMN signs: 86% on MRS, 77% on TMS, and 70% on MRS and TMS together. Among 30 patients with solely LMN signs (progressive muscular atrophy), UMN results were found in 63% on MRS, 63% on TMS, and 46% on both tests together. There was a significant association of the degree of abnormal N-acetyl aspartate/creatine ratios with UMN signs (p = 0.01). The sensitivity to detect UMN involvement was 0.86 for MRS (specificity 0.37) and 0.77 for TMS (specificity 0.38). At autopsy, all 11 patients had pathologic UMN abnormalities, including 4 with normal MRS and 1 with normal TMS in life. CONCLUSIONS: MRS is highly sensitive, somewhat more than TMS, and shows good correlation with clinical UMN signs. Combining MRS and TMS results in the same patient with further refinement may help in the early diagnosis of ALS.
Amyotrophic Lateral Sclerosis↗
Subthalamic nucleus stimulation in advanced Parkinson's disease: blinded assessments at one year follow up.
OBJECTIVE: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease. DESIGN: Open label follow up using blinded ratings of videotaped neurological examinations. PATIENTS: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. MAIN OUTCOME MEASURES: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. RESULTS: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. CONCLUSIONS: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.
Activities of Daily Living↗
Mirtazapine in Parkinsonian tremor.
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Adult↗
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.
Aged↗
Comparison of clinical vs. electrophysiological methods of diagnosing of essential tremor.
Essential tremor (ET) may be differentiated from normal or enhanced physiological tremor based on a clinical examination or electrophysiological tests such as quantitative computerized tremor analysis. There have been few head to head comparisons of the two methods. Our objective was to estimate diagnostic agreement between these two methods. Cases and controls underwent a clinical evaluation (interview and videotaped examination) and an electrophysiological evaluation (quantitative computerized tremor analysis using accelerometry and electromyography) on the same day, and diagnoses were independently assigned using clinical vs. electrophysiological criteria. Agreement between diagnoses was assessed with a concordance rate and kappa statistic (kappa).Thirty-two (59.3%) of 54 subjects were diagnosed clinically as ET (possible, probable, or definite), compared with 35 (64.8%) of 54 based on tremor analysis. The concordance rate between the two methods of diagnosis was 94.4% (51 of 54). Kappa was 0.88, indicating a level of agreement between diagnoses that was in the "near perfect" range. All of the subjects who received electrophysiological diagnoses of definite ET also received clinical diagnoses of ET. Conversely, all of the subjects who received clinical diagnoses of definite ET also received electrophysiological diagnoses of ET. The agreement between the clinical and electrophysiological diagnosis of ET was substantial, suggesting that study protocols that were to utilize either technique would arrive at similar diagnostic conclusions. In addition, physiological testing can quantify potentially valuable subclinical measurements as well as detect possible additional cases of ET not diagnosed as such during clinical assessments.
Adult↗
Correlates of functional disability in essential tremor.
The decision to treat patients with essential tremor (ET) is based primarily on the functional impact of the tremor. Correlates of functional disability, apart from the severity of the tremor itself, have not been studied. The objective of this work was to study correlates of functional disability in ET, and to present data on the extent of functional disability in community-dwelling ET cases. ET cases and age-matched control subjects were ascertained from a tertiary referral center at Columbia-Presbyterian Medical Center and a community in northern Manhattan, N.Y. Subjects underwent a 2.5-hour evaluation, including a tremor disability questionnaire, a videotaped tremor examination rated by a neurologist, a performance-based test of function, quantitative computerized tremor analysis, the Hamilton Anxiety Rating Scale, and the depression module of the Structured Clinical Interview for DSM-IV. Seventy-six (85.4%) of 89 cases reported disability on > or =1 item on the disability questionnaire. In multivariate linear regression analyses, current major depression, Hamilton Anxiety Rating Scale score, age, and tremor severity were independently correlated with performance-based test scores. Twenty-seven (73.0%) of 37 community cases reported disability on > or =1 (mean = 8.4) item on the questionnaire, and 25 (67.6%) demonstrated moderate or greater difficulty on > or =1 (mean = 4.2) task in a performance-based test. Depression, anxiety, and age, independent of the severity of tremor, were associated with greater functional disability in ET, so that these factors must be considered when assessing the impact of new treatments in ET. Among a group of community-dwelling cases, approximately three-quarters reported disability, suggesting that the number of individuals who might receive some benefit from advances in the treatment of ET is probably a great deal larger than previously thought.
Activities of Daily Living↗
Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson's disease.
OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed.
Aged↗
Clinical utility of surface EMG [RETIRED]: report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology.
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Electromyography↗
Ethnic differences in essential tremor.
BACKGROUND: Ethnic differences in the clinical characteristics (severity and distribution) of essential tumor (ET) have not been studied. The presence of these differences suggests that ET is not a homogeneous disease and that there is variability in disease expression under different circumstances. As part of a community-based study, we evaluated a multiethnic group of cases. OBJECTIVE: To assess whether there are ethnic differences in the clinical characteristics of ET. METHODS: Elderly residents of Washington Heights-Inwood, New York, were enrolled in a community-based health study (N = 2117). Participants underwent a medical interview and a neurological examination conducted by a neurologist, and subjects with ET were identified. These subjects with ET were then enrolled in a community-based study of ET and underwent a tremor interview, a videotaped tremor examination, and in some cases, a performance-based test of function and quantitative computerized tremor analysis. A total tremor score (range, 0-36, with 0 indicating no tremor and 36 indicating maximum tremor) was assigned to each subject based on 2 neurologists' ratings of the tremor examination. RESULTS: Among 62 subjects with ET (white [n = 16], African American [n = 18], and Hispanic [n = 28]), there were ethnic differences in the total tremor score (F = 3.68, P = .03). In a multiple regression model adjusting for age, white subjects had a mean total tremor score that was 5.3 points lower than that of nonwhite subjects (P = .008). We divided the nonwhite group into African American and Hispanic subgroups. In a regression model adjusting for age and duration, the white group had a mean total tremor score that was 6.1 points lower than that of the Hispanic group (P = .07) and 7.2 points lower than that of the African American group (P = .05). The mean performance-based test score was 1.7 times higher in the African American group and 2.1 times higher in the Hispanic group compared with the white group (P = .38). No subjects in the African American group had head tremor, while 4 subjects in the white group (25%) and 8 subjects in the Hispanic group (29%) did have head tremor (chi2 = 6.17, P = .05). CONCLUSIONS: There are ethnic differences in the expression of ET, suggesting that ET is not a homogeneous disorder. These differences may reflect phenotypic variability caused by genotypic differences or differences in exposure to environmental factors that influence tremor.
Black or African American↗
Validation of a portable instrument for assessing tremor severity in epidemiologic field studies.
BACKGROUND: An important part of epidemiologic and genetic studies of essential tremor (ET) is an assessment of tremor severity. Clinical rating scales are semiquantitative and computerized tremor analysis, available at tertiary medical centers, is not transportable into the field. As part of an epidemiologic study, we modified the Klove-Matthews Motor Steadiness Battery, collecting objective quantitative data on tremor severity in patients with ET and control subjects. OBJECTIVE: To describe the modified Klove-Matthews Motor Steadiness Battery, validate this test battery against several other measures of tremor severity, demonstrate test-retest reliability, and provide standard reference values for normal control subjects and patients with ET who undergo this test battery. METHODS: Patients with ET and control subjects, ascertained from both a clinic and a community, underwent a standardized evaluation including a demographic and medical questionnaire, tremor disability questionnaire, videotaped tremor examination, performance-based test, modified Klove-Matthews Motor Steadiness Battery (Groove-Type Steadiness Tester [GTST] and Nine-Hole Steadiness Tester [NHST]), and quantitative computerized tremor analysis. RESULTS: There were 19 patients with ET and 28 control subjects. NHST and GTST total scores were correlated significantly with the tremor disability questionnaire score (r = 0.63, p = 0.001 and r = 0.49, p = 0.016), total tremor score (tremor examination, r = 0.68, p<0.001 and r = 0.41, p = 0.005), performance-based test score (r = 0.81, p<0.001 and r = 0.65, p = 0.001), and quantitative computerized tremor analysis results (for example, spiral drawing, r = 0.62, p = 0.01 and r = 0.58, p = 0.019). Test-retest reliability was generally high (r = 0.79-0.94, p<0.001). CONCLUSION: The modified Klove-Matthews Motor Steadiness Battery provides a reliable and valid means to collect objective quantitative data on tremor severity. Rapidity of administration and ease of transport make it a potentially useful tool in epidemiologic and genetic field studies.
Adult↗
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.
Activities of Daily Living↗
Validity of a performance-based test of function in essential tremor.
BACKGROUND: The central factor influencing therapeutic decisions in essential tremor (ET) is the functional impact of the tremor. Neither the neurological examination nor computerized tremor analysis measures function. Questionnaires may assess function, but data are highly subjective. Performance-based tests of functional impairment provide an alternative means with which to assess the functional impact of ET. OBJECTIVE: To determine the internal consistency and validity of a performance-based measure of functional impairment in ET. METHODS: Subjects with ET from a community in northern Manhattan, NY, and from a clinic and control subjects each underwent a 2 1/2-hour evaluation including 12 screening questions for ET, a 31-item Tremor Disability Questionnaire to assess the functional impact of tremor, a 26-item Videotaped Tremor Examination that was rated by a neurologist, a 15-item, 10-minute Performance-Based Test, and Quantitative Computerized Tremor Analysis. Internal consistency was assessed with Cronbach alpha. The correlation between the Performance-Based Test and these other measures of tremor was assessed by means of correlation coefficients (r). RESULTS: There were 50 ET cases and 51 normal control subjects. The Performance-Based Test was internally consistent (Cronbach alpha = .92). It also demonstrated validity among cases; the total score correlated with the total number of screening questions answered yes (r = 0.44; P = .001), the total score on the Tremor Disability Questionnaire (r=0.55; P<.001), the total score on the Videotaped Tremor Examination (r=0.71; P<.001), and multiple physiological measures recorded during Quantitative Computerized Tremor Analysis. CONCLUSIONS: A valid performance-based test was developed to objectively assess functional capacity in patients with ET. This test would be useful in therapeutic trials, where it would provide an objective means to quantify the functional impact of tremor.
Aged↗
Stereotactic posteroventral pallidotomy: clinical methods and results at 1-year follow up.
Twenty consecutive patients with idiopathic Parkinson's disease underwent stereotactic posteroventral pallidotomy. Schwab and England ADL scores in the "off" state were improved by 18% and in the "on" state the scores declined by 2%. Three patients also reported marked improvement in "off" state dystonia. One-year data are available on 12 patients who underwent evaluations according to the Core Assessment Program for Intracerebral Transplantation protocol preoperatively and at 3, 6, and 12 months after surgery. Significant improvements in Unified Parkinson's Disease Rating Scale sections II and III scores in the "off" state, composite "off" state scores of bradykinesia and rigidity, contralateral tremor in the "off" state, and contralateral dyskinesias were observed. Although there was reduction in the daily levodopa dose, this did not reach statistical significance. Major complications (15%) included hemiparesis (one of 20) and visual field cuts (two of 20); minor complications (45%) included mild cognitive dysfunction (four of 20), reading difficulty not related to visual disturbance (one of 20), and 5-10 lb weight gain (four of 20).
Activities of Daily Living↗
Is essential tremor symmetric? Observational data from a community-based study of essential tremor.
BACKGROUND: Essential tremor (ET) has been variably portrayed in the literature both as a symmetric arm tremor and as an asymmetric arm tremor. Few quantitative clinical or neurophysiological data specifically address the issue of tremor asymmetry in ET. OBJECTIVES: To examine a community-dwelling cohort of subjects with ET to (1) estimate the prevalence of tremor asymmetry and (2) quantify the magnitude of tremor asymmetry. METHODS: Fifty-four subjects with ET, identified in a community-based study of ET in New York City, underwent a Tremor Interview and a videotaped Tremor Examination. The examination included 6 tasks: sustained arm extension, pouring water, drinking water, using a spoon, finger-to-nose movements, and drawing spirals with each arm. Two neurologists rated the severity of tremor using a 0 to 3 clinical rating scale and a total tremor score was calculated (range, 0-36). Fourteen (25%) of 54 subjects also underwent quantitative computerized tremor analysis. RESULTS: The prevalence of asymmetry depended on the definition of asymmetry; small to moderate differences between sides were common. The mean side-to-side difference in clinical ratings for each of the 6 tasks was 0.54 of 3 points, which represented a 1.32-fold difference between sides. Clinical rating scores were higher in the nondominant arm in 39 subjects (72%), higher in the dominant arm in 9 (17%), and equal in 6 (11%). The 2 left-handed subjects had higher clinical ratings on the right. During quantitative computerized tremor analysis, there was a 1.71-fold mean difference between tremor amplitudes in the dominant and nondominant sides, and in 12 subjects (86%), the maximum tremor amplitude was in the nondominant arm. CONCLUSIONS: Small to moderate differences between sides were common in ET. In most community-dwelling subjects, tremor amplitude was greatest in the nondominant arm. In contrast, clinic-based studies have reported greater tremor in the dominant arm; those with ET who seek medical attention are more likely to exhibit severe tremor in their dominant arms. This study documents that mild asymmetry is a fundamental property of ET and that tremor is more severe in the nondominant arm.
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Spiral analysis: a new technique for measuring tremor with a digitizing tablet.
A new computational method for quantification of tremor and other aspects of motor dysfunction is described. By using a digitizing tablet connected to a microcomputer, this analysis is derived from the handwritten Archimedean spiral. This technique extends the standard clinical neurologic test of spiral drawing into an objective and accurate measure that can automatically detect, characterize, and quantify motor dysfunction in patients with movement disorders. Further, it is safe, inexpensive, fast, portable, noninvasive, and can be administered to a large cohort of patients without the need for wires or other attachments. Spiral data are collected in the X, Y, and pressure axes, providing virtual "triaxial" recordings. Spiral analysis is shown to be capable of assessing subtle motor abnormalities potentially indicative of clinical problems in their earliest stages, and thus allow the most rational forms of genetic testing, treatment, or prevention. Spiral analysis may be useful as an initial marker of clinical involvement or serve as an objective gauge of change after therapeutic intervention.
Diagnosis, Computer-Assisted↗
Prevalence of asymptomatic tremor in relatives of patients with essential tremor.
BACKGROUND: The extent to which essential tremor (ET) clusters within families (ie, the familial aggregation of ET) is not precisely known. In part, this is because studies assign disease status in relatives of patients with ET based solely on interviews without conducting physical examinations. This may lead to underascertainment of affected relatives with mild asymptomatic ET. OBJECTIVE: To determine the prevalence of asymptomatic ET among relatives of patients with ET. METHODS: Interview and examination of 25 patients with ET and 58 of their relatives. The interview included 12 questions that screened the patients for ET. Two neurologists who specialize in movement disorders reviewed the videotaped examinations. Based on standardized criteria, diagnoses included ET (definite, probable, or possible) on normal. RESULTS: Of the 8 relatives who received diagnoses of ET, 5 (62.5%) had asymptomatic ET. Hence, 5 (8.6%) of the 58 relatives (95% confidence interval 1.4%-15.8%) had asymptomatic ET. In those with asymptomatic ET, there was a preponderance of young individuals with mild tremor in the nondominant hand. CONCLUSIONS: The prevalence of asymptomatic ET in relatives of patients with ET was similar to that of symptomatic ET. Family studies that do not perform both an interview and a physical examination will underascertain the number of affected relatives. Therefore, future family studies should evaluate relatives of patients with ET with an interview supplemented by a physical examination.
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