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Biomedical subjects

G T Stebbins

Publications and source records attributed to G T Stebbins.

At least 37 records · Page 2Linked to original sources

Teaching tape for the motor section of the Toronto Western Spasmodic Torticollis Scale.

The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) assesses the character and severity of cervical dystonia (CD). We developed a teaching tape of the TWSTRS scoring for the motor symptoms of CD. The tape provides investigators with visual representations of each component of the motor section of the TWSTRS as agreed upon by three independently scoring raters. The rate of agreement for the nondichotomous components was always significant, with a Kendall's coefficient of concordance W ranging between 0.98 and 0.76 (p < 0.01 for all measures). For the two dichotomous components, a weighted kappa coefficient was also significant at 0.86 for lateral shift and 0.89 for sagittal shift (p < 0.01 for both measures). Scale deficiencies identified by the raters were an explicit definition of midline for assessment of range of motion, the absence of a separate scoring category assessing dystonic tremor, and the specification of duration for the effect of sensory tricks. These observations should be taken into account in future revisions of the TWSTRS and in refinements of other rating scales for CD.

Dystonia↗

Efficacy of a patient-training videotape on motor fluctuations for on-off diaries in Parkinson's disease.

Patient on-off diaries are used in clinical trials, but a method to assure agreement between patient and examiner has never been developed. We tested whether a patient-teaching tape increased the rate of agreement between patient diary ratings and simultaneous neurologic assessment by a trained professional. A total of 32 consecutive patients who had Parkinson's disease with motor fluctuations independently completed a 4-h on-off diary (nine ratings) at the same time as an examiner. Those with < 80% agreement with the examiner (n = 20) were randomized to view either a training tape that showed motor fluctuations (experimental group) or-another videotape of general patient educational material (control group). All patients then underwent the same 4-h assessment of motor fluctuations. To test for long-term retention, they returned 1 month later and, without reviewing the videotape, underwent a final 4-h correlation assessment. After the training tape, the experimental group showed significant improvement, whereas the control group showed no improvement. Furthermore, another month later, the improvement in the experimental group was retained. Based on these findings, we suggest that future clinical trials assessing motor fluctuations incorporate this tape into their basic methodology.

Activities of Daily Living↗

Effect of stereotaxic intrastriatal cografts of autologous adrenal medulla and peripheral nerve in Parkinson's disease: two-year follow-up study.

Studies in nonhuman primates with experimental parkinsonism have shown that intrastriatal cografts of autologous adrenal medulla and peripheral nerve yield greater behavioral improvement and graft survival than do adrenal medulla grafts alone. To test these observations, five patients with advanced Parkinson's disease were selected to receive unilateral intrastriatal adrenal medulla-intercostal nerve cografts. They were evaluated using the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol. Three of these patients also underwent quantitative motor testing for the measurement of upper limb bradykinesia (movement time; MT). Following right flank adrenalectomy, cografts consisting of small fragments of adrenal medullary tissue and minced intercostal nerve were stereotaxically implanted into three targets in the right striatum using computerized tomography guidance. Surgery was uneventful and postoperative magnetic resonance imaging revealed accurate placement of the grafts. No morbidity was encountered. Results of 24 months of clinical and quantitative motor assessments postoperatively are reported. Total UPDRS motor scores in the "off" state improved from a mean preoperative score of 39.5 to 32.1 at 3, 29.7 at 6, 27.6 at 9, 28.5 at 12, 31.4 at 18, and 26.5 at 24 months after surgery. Total timed motor test scores during the "off" state improved 17.9% at 6, 23.3% at 9, 18.2% at 12, 38.2% at 18, and 34.9% at 24 months postoperatively compared to baseline. Movement time showed statistically significant improvement (repeated measures ANOVA, P < 0.05) in the left arm (contralateral to surgery) in all three patients tested. These results indicate that stereotaxic intrastriatal implantation of autologous adrenal medulla-peripheral nerve cografts can be performed safely and clinical improvement from this procedure is sustained for a period of 24 months. The clinical improvement was paralleled by improvement in objective, quantitative motor testing.

Adrenal Medulla↗

Intact mirror-tracing and impaired rotary-pursuit skill learning in patients with Huntington's disease: evidence for dissociable memory systems in skill learning.

Skill learning in early-stage Huntington's disease (HD) patients was compared with that of normal controls on 2 perceptual-motor tasks, rotary pursuit and mirror tracing. HD patients demonstrated a dissociation between impaired rotary-pursuit and intact mirror-tracing skill learning. These results suggest that different forms of perceptual-motor skill learning are mediated by separable neural circuits. A striatal memory system may be essential for sequence or open-loop skill learning but not for skills that involve the closed-loop learning of novel visual-response mappings. It is hypothesized that working memory deficits in HD resulting from frontostriatal damage may account broadly for intact and impaired long-term learning and memory in HD patients.

Adult↗

Levodopa stability in solution: time course, environmental effects, and practical recommendations for clinical use.

We defined the temporal stability characteristics of levodopa/carbidopa (LD/CD) solution, and determined the effects of temperature, ascorbate, and light on LD stability over 7 days. At room temperature and without ascorbate, LD levels significantly declined by 48 h. Ascorbate prolonged stability to 72 h. Refrigeration and freezing prevented a significant decline in LD levels for the full 7 days. Light or darkness had no effect on stability. LD/CD solution, if made daily, requires no special handling and longer stability is maintained with ascorbate, refrigeration, or freezing.

Antiparkinson Agents↗

Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients: dose-response study and correlations with plasma levels.

OBJECTIVE: To determine if ventricular cerebrospinal fluid (vCSF) alpha-tocopherol levels in Parkinson's disease (PD) patients can be increased by oral alpha-tocopherol supplementation and whether vCSF levels are linearly related to plasma alpha-tocopherol levels. BACKGROUND: In spite of its putative neuroprotective properties, alpha-tocopherol has failed to alter PD clinical progression. However, the ability of supplemental alpha-tocopherol to affect brain or vCSF levels has never been assessed in humans nor has a dose response curve for alpha-tocopherol in vCSF been established. METHODS: Five PD patients with Ommaya catheters received oral dl-alpha-tocopherol over 5 months. Each patient ingested alpha-tocopherol daily with monthly dosage increases (400, 800, 1,600, 3,200, 4,000 IU/day). Plasma and vCSF samples were obtained at baseline and at the end of each month. Alpha-tocopherol levels were determined in triplicate by high-pressure liquid chromatography with fluorometric and electrochemical detection. RESULTS: At baseline, endogenous alpha-tocopherol was detected in plasma and vCSF, with a greater than one-hundred-fold difference between the fluid compartments (mean plasma level 18.76 microM/l (SD +/- 4.69) versus mean CSF level 0.114 microM/l (SD +/- 0.084). A clear dose-response curve occurred in plasma, with statistically significant increases over baseline developing even with 400 IU/d. With higher doses, a significant increase continued without evidence of saturation. However, there was no significant increase in vCSF alpha-tocopherol levels at any dose, including the supraclinical (4,000 IU/d). There was no correlation between plasma and vCSF alpha-tocopherol levels. CONCLUSION: Oral alpha-tocopherol supplementation, even at supraclinical doses, fails to increase vCSF alpha-tocopherol levels. This lack of change may be due to limited passage across the blood-brain barrier or very rapid alpha-tocopherol metabolism. All prior negative studies on efficacy of alpha-tocopherol in PD may need reevaluation in light of these pharmacologic data.

Dose-Response Relationship, Drug↗

Liquid levodopa/carbidopa produces significant improvement in motor function without dyskinesia exacerbation.

We performed the first double-blind, crossover comparison between levodopa/carbidopa (LD/CD) in optimized liquid versus tablet doses to measure plasma LD levels and relative effects on disabilities (motor function, fluctuations, and dyskinesias) in patients with Parkinson's disease. Twenty-three subjects with motor fluctuations were optimized with open-label LD/CD tablets and liquid. In a double-dummy design, patients randomly received 2 weeks of liquid and 2 weeks of tablet LD/CD. Twice during each arm, we evaluated patients hourly 9 AM to 4 PM with the use of plasma LD levels, the Unified Parkinson's Disease Rating Scale, a dyskinesia rating scale, and "on-off" ratings. Patients receiving liquid LD/CD ingested significantly higher doses and had significantly improved motor function and total "on" time, without an increase in dyskinesia severity. The number of motor fluctuations in the two phases was not significantly different. LD levels and variability were also equivalent with the two formulations. At optimized dosing, liquid LD/CD offers a means to significantly improve motor disability in patients with Parkinson's disease without exacerbating dyskinesia.

Adult↗

Teaching tape for the motor section of the unified Parkinson's disease rating scale.

We developed a teaching tape of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) to provide investigators with a visual document of three raters' interpretations of the scoring system for each item except rigidity. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.97 and 0.62. We also provided full UPDRS ratings on sample patients that may be used for training and for multicenter studies to assure uniformity of rating. The study identified several items of the UPDRS motor examination for which written instructions were vague, including speech, action tremor, finger taps, rapid alternating movements, and postural stability. Future versions of the scale should address these problems and correct ambiguities. This project offers the first attempt to provide a visual analog for the UPDRS.

Audiovisual Aids↗

Mortality and hallucinations in nursing home patients with advanced Parkinson's disease.

We monitored 11 patients with advanced Parkinson's disease (PD) who entered nursing homes over a 5-year period and assessed chronicity of nursing home care, mortality, and hallucinatory status. Two years after the original study's close, none of these patients had ever been discharged from the nursing homes and all were dead. The mortality rate among the nursing home patients was significantly greater than that in 22 community-dwelling subjects with PD who were matched for age, gender, and disease duration. Hallucinatory status was generally stable; 82% of patients had the same hallucinatory status (presence or absence) at the two assessments. Four subjects from the original community-dwelling control group entered nursing homes during the follow-up period. Whereas motor and intellectual impairment scores were similar between these patients and the remaining 18 in the community, the presence of hallucinations was significantly greater among patients transferred to nursing homes. The study demonstrates the permanency of nursing home placement in advanced PD and the high mortality associated with such placement. It also documents the chronicity of hallucinatory behavior in these patients with advanced PD and reinforces our previously reported observations on the relationship between hallucinations and placement in chronic-care facilities.

Aged↗

Talipexole and adult Gilles de la Tourette's syndrome: double-blind, placebo-controlled clinical trial.

Talipexole is a new dopamine autoagonist with putative preferential activity on presynaptic dopamine receptors. In a double-blind, placebo-controlled study, we tested the drug's safety and efficacy in 13 adult men with Gilles de la Tourette's syndrome. The drug was poorly tolerated because of clinically significant sedation and dizziness. Tics did not improve at tolerable doses. These findings suggest that talipexole has no role in the regular management of tic disorders.

Adult↗

Utility of an objective dyskinesia rating scale for Parkinson's disease: inter- and intrarater reliability assessment.

Although dyskinesia is a frequent and important problem in Parkinson's disease (PD), a reliable assessment measure has not been thoroughly developed and tested. We modified the Obeso dyskinesia scale to create an objective rating scale for dyskinesia assessment during activities of daily living. Thirteen physicians and 15 study coordinators involved in a clinical trial independently reviewed videotape segments of PD patients performing three tasks: walking, putting on a coat, and lifting a cup to the lips for drinking. Raters evaluated the severity of worst dyskinesia seen, the types of all dyskinesias seen, and the type of dyskinesia most associated with motoric disability. For all assessments, the total group showed statistically significant inter- and intrarater reliability. Physicians had a higher consistency than did coordinators, but for most measures the difference was not statistically significant. Physicians and coordinators found the scale easy to use and especially practical for rating dyskinesia severity and for identifying the most disabling dyskinesia. Dyskinesias can be assessed in clinical trials and warrant regular documentation.

Activities of Daily Living↗

Physical therapy and Parkinson's disease: a controlled clinical trial.

In a randomized, single-blind, crossover study, we evaluated physical disability in moderately advanced Parkinson's disease (PD) patients after 4 weeks of normal physical activity and 4 weeks of an intensive physical rehabilitation program. We used a timed motor task and a standard assessment of PD severity (the Unified Parkinson's Disease Rating Scale [UPDRS] with subscales for mentation, activities of daily living [ADL], and motor function) completed by an investigator blinded to the physical rehabilitation status of the patient. Following physical rehabilitation, there was significant improvement in the UPDRS ADL and motor scores, but no change in mentation score. During the 6 months following physical rehabilitation, patients did not regularly exercise, and the UPDRS scores returned to baseline. We conclude that physical disability in moderately advanced PD objectively improves with a regular physical rehabilitation program, but this improvement is not sustained when normal activity is resumed.

Aged↗

Quantitative electromyographic analysis of changes in muscle activity following botulinum toxin therapy for cervical dystonia.

Reports of efficacy of botulinum toxin for cervical dystonia have relied on subjective reports of improvement or various clinical rating scales. We studied 19 patients with cervical dystonia using Turns analysis to determine if quantitative EMG measures of muscle activity changed following botulinum toxin injections. Before and after botulinum toxin injections, six muscles were evaluated bilaterally. Quantitative EMG analysis of active muscles injected with botulinum toxin showed a significant decline in muscle activity after botulinum toxin (F = [1,41] 55.0; p < 0.001). Significant reductions in quantitative EMG parameters were also noted in noninjected active muscles after botulinum toxin treatment (F = [1,51] 59.15; p < 0.001). The sum of EMG activity for all active muscles was calculated for each subject and showed a significant reduction after botulinum toxin injection [MANOVA: (F = [1,5] 5.69; p < 0.05]. Quantitative EMG assessment provides an objective measure of response to botulinum toxin. Decreased muscle activity in noninjected muscles may result from toxin diffusion or reflect relaxation of muscles only secondarily involved in cervical dystonia.

Adult↗

Risk factors for nursing home placement in advanced Parkinson's disease.

We evaluated the risk factors for nursing home placement of patients with Parkinson's disease (PD) by matching 11 PD patients permanently admitted to nursing homes with two control PD patients remaining at home. Risk factors assessed were motor severity, presence of hallucinations/delusions, and presence of memory of problems. The only statistically significant risk factor was the presence of hallucinations/delusions. Motor severity and the presence of memory problems did not have an impact on nursing home placement. There was no risk factor synergy for hallucinations, motor disability, and mental impairment. Since all patients in this series who entered nursing homes remained there permanently, these data suggest that vigorous efforts to control hallucinations may be warranted to prevent nursing home placement.

Aged↗

Blood levodopa levels and unified Parkinson's disease rating scale function: with and without exercise.

We studied 10 regular exercising men with Parkinson's disease on levodopa (LD) under two conditions--no exercise and vigorous exercise started 1 hour after LD ingestion. We compared LD levels and motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS). There was a high degree of agreement between plasma LD level and the patients' UPDRS scores 30 minutes later (mean Eta2 = 0.84) in both conditions, with no difference between the two. We conclude that LD levels accurately reflect UPDRS motor function in these patients, and that vigorous exercise started 1 hour after LD ingestion does not influence LD or motor scores.

Aged↗

Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson's disease patients with 'on-off' fluctuations.

Ten patients with Parkinson's disease suffering severe motor fluctuations completed a double-blind, placebo-controlled, crossover trial of duodenal infusion of levodopa/carbidopa to determine if this technique improved the duration of functional time by reducing plasma levodopa level variability. With infusion, seven patients experienced increased functional "on" hours and decreased number of "off" episodes; however, two patients were slightly worse and one patient experienced no benefit. All 10 patients had significantly decreased variability in levodopa levels permitting better titration of levodopa dosage to individual requirements. Five patients continued to use infusion 12 to 20 months after completion of this study. Selected patients with Parkinson's disease who experience severe motor fluctuations may benefit from duodenal infusion with an improved and prolonged response to medication.

Administration, Oral↗