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1.
Stereotactic medial posteroventral pallidotomy for treatment of Parkinson's disease attracts increasing attention. We report on the preliminary results of 12 patients at 1 year after microelectrode-guided unilateral pallidotomy. The primary indications were severe bradykinesia and levodopa-induced dyskinesias. After radiofrequency lesioning all patients had immediate improvement of contralateral parkinsonian signs. Postoperative magnetic resonance imaging confirmed the localization of the lesions. At the 1-year follow-up, all patients had sustained benefit. The global improvement was rated as moderate in six cases, and as marked in six other cases. The mean values of various subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) showed highly significant changes in the "off" state (pre/postoperatively): UPDRS Motor score (60.3/31). UPDRS Activities of Daily Living (ADL) score (33.2/18.3), gait/postural stability score (13.8/7.0), and subscores for contralateral rigidity (4.9/2.1), tremor (7.1/1.4) and bradykinesia (11.6/5.3). There was also significant improvement of ipsilateral bradykinesia and rigidity. Furthermore, we found significant changes of the mean values of the UPDRS ADL and motor "on" scores, an increase of the percentage of "on" time with reduced on-off fluctuations, and a decrease of the percentage of levodopa-induced dyskinesias, with marked improvement or complete abolition of contralateral dyskinesias in particular. The preoperative levodopa regimen was maintained, in general, or only slightly modified, if necessary. Two patients had transient complications: one patient suffered postoperative pneumonia and altered mental status; another patient displayed mild Broca's aphasia secondary to a small stroke involving the dorsal thalamus and the adjacent white matter. There were no persistent side effects at the 1-year follow-up. Contemporary unilateral pallidotomy is an effective and promising therapeutical option for surgical treatment of advanced Parkinson's disease.  相似文献   

2.
The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.  相似文献   

3.
OBJECTIVE: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD). BACKGROUND: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties. METHODS: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews. RESULTS: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries. CONCLUSIONS: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.  相似文献   

4.
BACKGROUND/OBJECTIVE: Studies in animal models of Parkinson's disease (PD) suggest that GM1 ganglioside treatment can restore neurologic and dopaminergic function. In view of positive preclinical findings and the results of a previous open-label study demonstrating efficacy of GM1 in PD patients, this study compared effects of GM1 ganglioside and placebo on motor functions in PD patients. METHODS: Forty-five patients with mild to moderate PD were studied. The primary efficacy measure was change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. After three independent baseline assessments, patients received IV infusion of the test drug (1,000 mg GM1 or placebo) and then self-administered either GM1 or placebo twice daily (200 mg/day, subcutaneously) for 16 weeks. Patients were examined during monthly follow-up visits. RESULTS: There was a significant difference between groups in UPDRS motor scores at 16 weeks (p=0.0001). The activities of daily living portion of the UPDRS (off-period assessment) also showed a significant effect in favor of the GM1-treated patients (p=0.04). GM1-treated patients also had significantly greater mean improvements than placebo-treated patients in performance of timed motor tests including tests of arm, hand, and foot movements, and walking. GM1 was well tolerated and no serious adverse events were reported. CONCLUSIONS: This study demonstrates that GM1 ganglioside treatment enhances neurologic function significantly in PD patients. Further study is warranted to evaluate long-term effects of GM1 in PD patients and to elucidate further the mechanisms underlying patient improvements.  相似文献   

5.
The multiaxial system (MAS) of ICD-10, chapter V (F) consists of three axes: axis I, clinical syndromes (psychiatric disorders including personality disorders and somatic diseases); axis II, disabilities; axis III, environmental/circumstantial and personal life-style/life management factors. Results of a multicentric field trial evaluating a preliminary draft of the MAS are presented. 45 raters in seven German centers made 488 ratings on 12 written case histories. With a mean kappa of 0.50 for 3-character diagnoses interrater reliability for axis I was moderate although lower than expected from previous field trials. On axis II the WHO Disability Diagnostic Scale (WHO-DDS) was compared to the Global Assessment of Functioning (GAF) used in DSM-III-R and DSM-IV. For both scales the intraclass correlation coefficient showed a moderate interrater reliability (WHO-DDS = 0.62; GAF = 0.65). On axis III the number of relevant psychosocial circumstances coded by the different raters varied greatly. Interrater reliability was very poor with kappa values ranging from 0.03 to 0.55 for the different categories and an overall kappa of 0.16.  相似文献   

6.
BACKGROUND AND PURPOSE: Ensuring the reliability and validity of outcome measures used in clinical trials is essential to the success of the trial. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) is a multicenter clinical trial that is recruiting patients with acute ischemic stroke seen at medical centers across the United States. METHODS: This paper describes an approach to train physicians to use three clinical measures: the National Institutes of Health (NIH) Stroke Scale, a supplemental motor examination, and the Glasgow Outcome Scale. The program included education, certification, remediation when needed, monitoring, and reliability assessment. The goal was to ensure that interrater assessments were as equivalent to one another as possible. RESULTS: Of the first 95 clinicians who began the certification process, 75 passed during the first evaluation. Eighteen of the other physicians were able to complete the process after remediation. The intraclass correlations of both the NIH Stroke Scale and supplemental motor examination exceeded 0.95. The kappa values for the Glasgow Outcome Scale were 0.61 and 0.62 for the first and second ratings of the videotape, respectively. CONCLUSIONS: Our experience suggests that a program that includes educational and certification processes can be performed as part of the design of a multicenter clinical trial. The method of providing educational and testing videotapes to each site so that physicians can be trained and certified is an effective, inexpensive, and practical approach for enhancing and certifying the expertise of the large number of physicians involved in a multicenter study.  相似文献   

7.
Depression has been shown to be more common in Parkinson's disease (PD) than in other chronic and disabling disorders. Neurochemical and functional disturbances are important etiopathogenic factors. The prevalence and clinical features associated with depression in PD remain controversial. The purpose of this study is to estimate the prevalence of depressive symptoms in our patients, as related to other clinical data, and to assess clinical outcomes of these symptoms. A series of PD patients were evaluated over a 9-year period, using the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage (HY), Schwab and England Scale (SE), Mini-Mental State Examination (MMSE), and Yesavage Geriatric Depression Scale (GDS). Presence of depressive symptoms was considered if GDS score was higher than 10: mild-moderate (MD) for GDS scores between 11 and 20 and moderate-severe (SD) for GDS scores greater than 20. Three hundred and fifty-three patients were included in this study and additional follow up information was obtained for 184 patients. MD and SD were found in 40.2 and 16.7% of PD patients, respectively. Female gender, high HY, high UPDRS total and subtotal, and low MMSE and SE scores were significantly associated with depressive symptoms. According to changes in GDS score, 34% of patients remained stable, 35% showed an improvement, and 30.9% worsened in the follow up study. Gender, age, age of onset, HY, UPDRS, and PD duration are not related to depression outcome.  相似文献   

8.
A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125). The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid). Primary efficacy endpoint was the percentage improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Ropinirole-treated patients had a significantly greater percentage improvement in UPDRS motor score than patients who received placebo (+24% vs -3%; p < 0.001). Ropinirole was well tolerated and patient withdrawals were infrequent. Most adverse experiences were related to peripheral dopaminergic activity. Ropinirole monotherapy is an effective and well-tolerated therapeutic option for treatment of early Parkinson's disease.  相似文献   

9.
The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum concentration) was also decreased by 80%d after the administration (p = 0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.  相似文献   

10.
Twenty de novo patients with Parkinson's disease (Hoehn-Yahr stages I, II, III) were studied in a double blind trial after introducing (--)-deprenyl monotherapy. The parkinsonian symptoms were assessed by a novel graded clinical rating scale, by UPDRS and by the North Western self-rating scale. A significant change was observed in motor behaviour and daily activity (UPDRS) after 3 weeks of treatment with (--)-deprenyl at 10 mg/day. The total scores using UPDRS and the North Western ratings were changed significantly after 4 weeks. The greatest changes observed were in walking and in hypokinesia. Rigidity was not modified by (--)-deprenyl.  相似文献   

11.
OBJECT: The goal of this study was to investigate the impact of mild or moderate degrees of degenerative or ischemic encephalopathy on predicting clinical outcome following unilateral posteroventral medial pallidotomy for treatment of advanced Parkinson's disease (PD). METHODS: Thirty-five patients with PD were studied prospectively. The presence and degree of cortical atrophy, ventriculomegaly, deep white matter lesions (DWML), periventricular lucencies (PVL), and the presence of lacunes and status cribriformis (multiple and bilateral enlarged Virchow-Robin spaces) were determined by magnetic resonance (MR) imaging before the patients underwent stereotactic pallidotomy performed according to a standard protocol. Clinical outcome was measured using a standard battery of tests including application of the Unified Parkinson's Disease Rating Scale (UPDRS). The preoperative MR imaging features were correlated with UPDRS subscores such as motor "off' score, the activities of daily living (ADL) off score, the off subscore for bradykinesia, the percentage of "on" time dyskinesias, and a global outcome rating. The MR findings were also correlated with the occurrence of side effects. Global outcome was rated as markedly improved in 22 patients (63%) and as moderately improved in 12 patients (34%) 6 months postoperatively. At the 1-year follow-up examination, global outcome in 31 patients was rated as markedly improved in 14 patients (45%), as moderately improved in another 14 (45%), as slightly improved in two (6%), and as worse in one patient (3%). The mean UPDRS motor off score changed from 58.7 preoperatively to 33.2 at 6 months and 33.4 at 1 year (p < 0.0001), the ADL off score from 31.8 to 18.2 at 6 months and 18.6 at 1 year (p < 0.0001), the off score from contralateral bradykinesia from 11.6 to 5.6 at 6 months and 4.1 at 1 year (p < 0.0001), and the percentage of awake time with dyskinesias from 37.4 to 17.4% at 6 months and 21.1% at 1 year (p < 0.0001). The presence of mild or moderate degrees of cortical atrophy, PVL, and DWML had no effect on clinical outcome. Patients with status cribriformis and those with lacunes tended to show comparatively less improvement in the UPDRS ADL off score (p = 0.014 and p = 0.016, respectively) at 6 months. This tendency was also present in patients with status cribriformis 1 year postoperatively (p = 0.046). Patients with both status cribriformis and lacunes had a higher incidence of transient altered mental status immediately postoperatively (p = 0.05). CONCLUSIONS: Mild-to-moderate degrees of cortical atrophy, ventriculomegaly, and ischemic encephalopathy do not predispose patients to less favorable outcomes following unilateral pallidotomy. Patients with both status cribriformis and lacunes have a higher risk of transient side effects; however, with regard to clinical outcome, these patients should not be denied surgical treatment.  相似文献   

12.
OBJECT: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that becomes refractory to medication as the disease progresses. Although in the past 5 years increasing numbers of patients have undergone stereotactically guided posteroventral pallidotomy for advanced PD, the safety and efficacy of surgery remains to be documented. The goal in this study was to determine the potential operative morbidity and types of functional outcomes by using validated PD rating scales and a patient survey. METHODS: In a prospective analysis of a consecutive surgical series the authors evaluated 58 patients with advanced PD who ranged in age from 40 to 79 years (mean 67 years) and who had undergone surgery between 1994 and 1997. They used a patient survey and the Unified Parkinson's Disease Rating Scale (UPDRS) to study patients during periods of medication administration ("on") and withdrawal ("off"; mean off score before surgery = 96). Temporary surgical morbidity was found in four patients (6.9%), three of whom developed transient dysarthria and one of whom exhibited transient confusion (1.7%). One patient had persistent dysarthria (1.7%). No patient developed a visual field deficit or sustained a brain hemorrhage. All patients were discharged from the hospital within 24 hours. Significant postsurgical improvements were noted in the UPDRS off-period total and motor scores, as well as in tremor, rigidity, bradykinesia, and contralateral dyskinesia (p < 0.005). Improvements persisted in dyskinesia and tremor for the 21 patients who were evaluated past 1 year. The authors found no improvement in any on-period symptoms except dyskinesia. Thirty-one (61 %) of 51 patients surveyed reported functional gains and/or dramatic improvement in symptoms, 17 (33%) reported symptomatic improvement without functional gains, and three (6%) had minimal or no change in symptoms. No change in the mini mental state examination score was noted during follow up. There were no significant postoperative changes in the use of medication. CONCLUSIONS: In advanced PD associated with either a medically refractory state with significant off periods or levodopa-induced dyskinesias, magnetic resonance imaging-guided pallidotomy with macrostimulation was associated with minimal morbidity and yet significantly reduced dyskinesia and off-period disability. These improvements were of value to the patient and persisted beyond the 1st year.  相似文献   

13.
OBJECTIVE: Construction and validation of a new instrument, the Brain Injury Community Rehabilitation Outcome scales, to assess problems experienced by brain-injured patients living in the community. DESIGN: Seventy-six items describing aspects of personal and social functioning were generated. Two hundred thirty-five patients and/or their carers (separately) rated the items on 6-point scales, and patients retrospectively rated their functioning before injury. Seven scales were derived from factor analysis; one was included a priori. Thirty-nine items with high factor loadings were retained. Test-retest reliability, interrater reliability, and construct validity were examined in subsamples. SETTING: Patients were recruited from four centers: two community-based teams, a day-patient clinic, and an outpatient clinic. PATIENTS: Of the patients, 127 had traumatic brain injury, 72 had cerebrovascular accidents, 15 had multiple sclerosis, and 21 had acquired brain injury of other origins. Mean time since brain injury was 2.6 years; mean age was 43 years; 164 were men and 71 were women. RESULTS: All scales showed good test-retest reliability, and agreement between patient and carer ratings was moderate to high. They showed predicted moderate correlations with other relevant scales. Postinjury scores differed significantly from preinjury scores, and 6 of the 8 scales showed change over a period of recovery/rehabilitation. CONCLUSIONS: The scales appear reliable and easy to complete. They may have utility as quantitative measures of outcome for clinical and treatment evaluations.  相似文献   

14.
OBJECTIVE: To examine the interrater reliability and completion time of the Functional Assessment Measure, which is the Functional Independence Measure (FIM) plus additional items (FIM+FAM). DESIGN: Interrater reliability study. SETTING: Inpatient rehabilitation units of a postacute care brain injury rehabilitation program. PATIENTS: A convenience sample of 53 extremely severely impaired adult survivors of traumatic brain injuries (40 men, 13 women, mean age 38yrs). MAIN OUTCOME MEASURES: Treatment team members' ratings of the 30 FIM +FAM items, and time taken to complete the FIM+FAM. RESULTS: Intraclass Correlation Coefficients (ICCs) were within the good to excellent range (ICC > .60) for 29 of 30 items and for all subscales except psychosocial adjustment. Higher mean ICC values were obtained for motor domain items than for cognitive/psychosocial domain items. Treatment teams became progressively faster over a 12-week period in completing the FIM+FAM. The generally good to excellent range interrater reliability found in this study helps support the use of the FIM+FAM in rehabilitation settings. Further support was obtained for the finding that motor items are more reliable than cognitive and psychosocial items. Administration of the FIM+FAM can be done in a timely manner in a rehabilitation setting.  相似文献   

15.
Electroconvulsive therapy (ECT) has demonstrated to be useful in psychiatric patients with parkinsonism as well as patients with Parkinson's disease (PD) without associated psychopathology. We prospectively evaluated three patients with PD and major depression in whom ECT proved to be efficacious. These patients experimented a marked improvement measured by the Unified Parkinson's Rating Scale (UPDRS). In two cases the ECT allowed for a reduction in their drug treatment, and in one case complex fluctuations disappeared. In the two patients who continued with ECT fortnightly, the improvement observed inicially has remained. Since ECT has shown a good tolerance, we conclude that this therapy should be considered as an alternative approach for PD patients with a poor answer to conventional treatment.  相似文献   

16.
Formal studies examining the antiparkinsonian efficacy of levodopa and pergolide monotherapy in de novo Parkinson's disease (PD) are lacking. The authors conducted a preliminary, 6-month, open-label parallel experimental study with de novo consecutive PD patients who were randomly assigned to three daily doses of pergolide (n = 10; mean age, 63.7 years; mean Hohen & Yahr score, 1.5; mean final dose, 2.8 mg daily) or levodopa (n = 10; mean age, 67.3 years; mean Hohen & Yahr score, 1.8; mean final dose, 435 mg daily). Doses were titrated individually according to patients' evaluation of their own functional ability, known side-effects, and a monthly administration of the Unified Parkinson's Disease Rating Scale (UPDRS) by a clinician blind to the treatment regime. All patients completed the study. There were no significant basal differences between groups and no significant treatment ortreatment-by-time effects in UPDRS scores (according to two-way ANOVA). A clear time effect was observed for most of the functional and motor variables (p < 0.001), with significant improvement during the first month that was maintained for the duration of the study in both groups. Side effects were mild, transient, and comparable. In this preliminary study, pergolide and levodopa exhibited similar symptomatic efficacy and incidence of side effects in the short-term treatment of de novo PD patients at their usual age of clinical manifestation.  相似文献   

17.
Indexes of interrater reliability and agreement are reviewed, and suggestions are made regarding their use in counseling psychology research. The distinction between agreement and reliability is clarified, and the relationships between these indexes and the level of measurement and type of replication are discussed. Indexes of interrater reliability appropriate for use with ordinal and interval scales are considered. The intraclass correlation as a measure of interrater reliability is discussed in terms of the treatment of between-raters variance and the appropriateness of reliability estimates based on composite or individual ratings. The advisability of optimal weighting schemes for calculating composite ratings is also considered. Measures of interrater agreement for ordinal and interval scales are described, as are measures of interrater agreement for data at the nominal level of measurement. (54 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

18.
Two scaled formats for summarizing the results of psychosocial evaluations of transplant candidates have been published, the Psychosocial Assessment of Candidates for Transplantation (PACT) and the Transplant Evaluation Rating Scale (TERS). In this study, 40 consecutive candidates for bone marrow transplant were rated on the PACT and TERS. The PACT and TERS were comparable in interrater reliability. Similar conceptual items for each scale correlated fairly highly with one another. The PACT and TERS differ in several scale characteristics. The authors discuss the relationship between scale characteristics and clinical utility.  相似文献   

19.
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.  相似文献   

20.
Pilot data on mood and anxiety changes in 15 Parkinson's disease patients with motor fluctuations are described based on ratings every 30 min for 5 h bracketing a 2-h constant-rate levodopa infusion. Robust mood and anxiety effects slightly preceded but temporally paralleled fluctuations in motor tapping scores. Research nurse ratings blind to patient ratings corroborated the changes. The magnitude of changes in mood and anxiety scores did not correlate with the magnitude of changes in tapping scores. The findings of this uncontrolled study suggest mood and anxiety fluctuations may be a common and potentially important component of levodopa-induced fluctuations.  相似文献   

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