Kelly E. Lyons

Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results

We present a clinimetric assessment of the Movement Disorder Society (MDS)‐sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS‐UPDRS). The MDS‐UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS‐UPDRS has four parts, namely, I: Non‐motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item‐specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS‐UPDRS (65 items) to 877 English speaking (78% non‐Latino Caucasian) patients with Parkinsons disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS‐UPDRS showed high internal consistency (Cronbachs alpha = 0.79–0.93 across parts) and correlated with the original UPDRS (ρ = 0.96). MDS‐UPDRS across‐part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS‐UPDRS for rating PD.

Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinsons disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta‐analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinsons Disease Rating Scale (UPDRS) scores after surgery were generated using random‐effects models. Sources of heterogeneity were explored with meta‐regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty‐seven cohorts were included in the review. Twenty‐two studies with estimates of standard errors were included in the meta‐analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85–15.85; 50%) and 27.55 (95% CI: 24.23–30.87; 52%), respectively. Average reduction in L‐dopa equivalents following surgery was 55.9% (95% CI: 50%–61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%–76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%–78.9%). Average improvement in quality of life using PDQ‐39 was 34.5% ± 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L‐dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L‐dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow‐up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.

Practice parameter: Risk of driving and Alzheimer’s disease (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology

Article abstract Studies of automobile accident frequency among drivers with AD have yielded conflicting results about the risk of accidents. To develop a practice parameter regarding driving and AD the authors performed a systematic review of the literature. The authors identified well-designed, controlled studies of driving and AD using the National Library of Medicine’s MEDLINE database. The authors also compared the relative rates of crashes and other performance measurements of driving ability in the populations studied. Driving was found to be mildly impaired in those drivers with probable AD at a severity of Clinical Dementia Rating (CDR) 0.5. This impairment was no greater than that tolerated in other segments of the driving population (e.g., drivers age 16 to 21 and those driving under the influence of alcohol at a blood alcohol concentration [BAC] < 0.08%). Drivers with AD at a severity of CDR 1 were found to pose a significant traffic safety problem both from crashes and from driving performance measurements.

Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease.

As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinsons disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self‐administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive‐Compulsive Disorders in Parkinsons Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP‐S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP‐S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP‐S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self‐assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.

Surgical and hardware complications of subthalamic stimulation A series of 160 procedures

Objective: To assess the surgical and hardware complications in a series of 81 consecutive patients undergoing subthalamic (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Methods: The authors prospectively documented surgical and hardware complications occurring at the time of surgery and at subsequent neurologic and surgical evaluations for an average of 17 months, ranging from 1 to 54 months. Results: No patient had a serious surgical complication resulting in death or permanent neurologic deficit. One patient had an intracranial hemorrhage but with no permanent deficit. In follow-up, 2.5% had infections requiring system removal, 3.7% had infections requiring implantable pulse generator (IPG) removal, 12.5% had misplaced leads, and 26.2% had hardware complications including lead migration, lead fracture, extension erosion, extension fracture, and IPG malfunction. Conclusion: Serious complications leading to permanent neurologic deficit are rare after STN DBS for advanced PD. However, long-term follow-up demonstrated that hardware complications are relatively common, having occurred in approximately 26% of these patients.

Deep brain stimulation: postoperative issues.

Numerous factors need to be taken into account when managing a patient with Parkinsons disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow‐up care should be determined, including patient adjustments of stimulation, timing of follow‐up visits and telephone contact with the patient, and stimulation and medication conditions during the follow‐up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long‐term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job‐related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinsons Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision‐making with a systematic overview of the literature (until mid‐2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

Ropinirole 24-hour prolonged release Randomized, controlled study in advanced Parkinson disease

Objective: To evaluate the efficacy of ropinirole 24-hour prolonged release (ropinirole 24-hour) as an adjunct to levodopa in patients with Parkinson disease (PD) and motor fluctuations. Methods: In a double-blind, placebo-controlled, 24-week study, 393 subjects with PD were randomized to ropinirole 24-hour (n = 202) or placebo (n = 191). The primary outcome measure was reduction in hours of daily “off” time. Results: At week 24, the mean dose of ropinirole 24-hour was 18.8 mg/day with a mean reduction in daily levodopa of 278 mg. There was a mean reduction in daily “off” time of 2.1 hours in the ropinirole 24-hour group and 0.3 hours with placebo. Secondary outcome measures including change in hours and percent of daily “on” time and “on” time without troublesome dyskinesia, Unified PD Rating Scale motor and activities of daily living subscales, Beck Depression Inventory-II, PDQ-39 subscales of mobility, activities of daily living, emotional well-being, stigma and communication, and PD Sleep Scale were significantly improved at week 24 with ropinirole 24-hour. The most common adverse events (AE) with ropinirole 24-hour were dyskinesia, nausea, dizziness, somnolence, hallucinations, and orthostatic hypotension and AEs led to study withdrawal in 5% of both the active and placebo groups. Conclusion: Ropinirole 24-hour was effective and well tolerated as adjunct therapy in patients with Parkinson disease (PD) not optimally controlled with levodopa. Ropinirole 24-hour demonstrated an improvement in both motor and non-motor PD symptoms, while permitting a reduction in adjunctive levodopa dose.

Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study

Background: In patients experiencing motor fluctuations, a major treatment challenge is the reduction of “off” time, particularly upon awakening. Rotigotine (Neupro) is a novel dopaminergic agonist with 24-hour transdermal delivery. Methods: A randomized, double-blind, placebo-controlled trial (PREFER Study) was performed to assess efficacy and safety with two targeted transdermal doses of rotigotine in subjects with advanced Parkinson disease with ≥2.5 hours of daily “off” time. Subjects were randomized to receive placebo patches (n = 120) or rotigotine up to either 8 mg/24 hours (n = 120) or 12 mg/24 hours (n = 111). The primary efficacy measures compared changes from baseline to the end of week 24 in the number of daily hours “off” and responder rates for subjects achieving ≥30% reduction in “off” time. Results: Compared to placebo, there were significant decreases in mean “off” time of 1.8 hours/day for the rotigotine 8 mg/24 hours group and 1.2 hours/day for the 12 mg/24 hours group. For rotigotine 8 and 12 mg/24 hours groups, ≥30% responder rates were 56.6% and 55.1% compared to the 34.5% placebo response. “On” time without dyskinesia after awakening was more than doubled in both rotigotine treatment groups vs placebo. Drug-related adverse effects included typical dopaminergic side effects, which were generally mild/moderate in intensity. Patch application site reactions including erythema and pruritus were mild to moderate and transient in the majority of instances. Conclusions: Transdermal rotigotine significantly improved “off” time in subjects with Parkinson disease not optimally controlled with levodopa and was safe and well tolerated, with typical dopaminergic side effects and occasional application site reactions.

Deep brain stimulation: preoperative issues.

Numerous factors need to be taken into account in deciding whether a patient with Parkinsons disease (PD) is a candidate for deep brain stimulation. Patient‐related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinsons Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision‐making.

Occupation and Risk of Parkinsonism: A Multicenter Case-Control Study

BACKGROUND We examined risk of parkinsonism in occupations (agriculture, education, health care, welding, and mining) and toxicant exposures (solvents and pesticides) putatively associated with parkinsonism. OBJECTIVE To investigate occupations, specific job tasks, or exposures and risk of parkinsonism and clinical subtypes. DESIGN Case-control. SETTING Eight movement disorders centers in North America. PARTICIPANTS Inclusion criteria were parkinsonism (>or=2 cardinal signs), diagnosis within 8 years of recruitment (to minimize survival bias), and ability to participate in detailed telephone interviews. Control subjects were primarily nonblood relatives or acquaintances of patients. MAIN OUTCOME MEASURES This multicenter case-control study compared lifelong occupational and job task histories to determine associations with parkinsonism and certain clinical subtypes (postural instability and gait difficulty and age at diagnosis <or=50 years). RESULTS Findings in 519 cases and 511 controls were analyzed. Work in agriculture, education, health care, or welding was not associated with increased risk of parkinsonism. Unexpected increased risks associated with legal, construction and extraction, or religious occupations were not maintained after adjustment for duration. Risk of parkinsonism increased with pesticide use (odds ratio, 1.90; 95% confidence interval, 1.12-3.21), use of any of 8 pesticides mechanistically associated with experimental parkinsonism (2.20; 1.02-4.75), and use of 2,4-dichlorophenoxyacetic acid (2.59; 1.03-6.48). None of the specific occupations, job tasks, or task-related exposures were associated with younger age at diagnosis (<or=50 years). Ever working in business and finance, legal occupations, construction and extraction, or transportation and material moving was associated with postural instability and gait difficulty subtype of parkinsonism. Tobacco use was inversely associated with parkinsonism risk. CONCLUSION The association of disease risk with pesticides support a toxicant-induced cause of parkinsonism.