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Economic evaluation (Italian NHS perspective) modeling (123)I-FP-CIT SPECT (DaTSCAN) compared to clinical judgment alone for differentiating essential tremor (ET) from Parkinson's Disease (PD). A 5-year Markov model was constructed to assess the cost-effectiveness of (123)I-FP-CIT SPECT to differentiate ET from PD in patients referred to a movement disorder specialist in Italy. Published data and a double-round, Delphi panel of 12 specialists populated the model. Effectiveness was expressed as the projected Years on potentially beneficial therapy (PBTYs). Costs were expressed in Euros (2005 values). The model suggests that over 5 years, the "current" diagnostic pathway generated an average of 2.3 PBTYs/patient at an estimated cost of 8,864 euros. (123)I-FP-CIT SPECT generated an average of 4.1 PBTYs/patient at an estimated cost of 8,422 euros, which represented an additional 1.8 PBTYs at a cost saving of 442 euros/patient (341 euros when discounted at 5%). The estimated cost-effectiveness of (123)I-FP-CIT SPECT is under 1,000 euros per PBTY gained when the underlying disease prevalence is high (55-70%), and cost-saving at prevalence under 55%. (123)I-FP-CIT SPECT is likely to be regarded as economically advantageous to differentiate ET from PD, increasing time on potentially beneficial therapy at a lower overall cost to the healthcare system.

We investigated gender-differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinson's disease (PD). Thirty-eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa-induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender-related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN-DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN-DBS treatment.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's 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 Parkinson's 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.

Numerous factors need to be taken into account when managing a patient with Parkinson's 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 Parkinson's 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.

Deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. It also provides an opportunity to record neural activity from the human basal ganglia. In this study, to investigate the involvement of the human STN in sensory functions, we recorded somatosensory evoked potentials (SEPs) elicited by contralateral median-nerve stimulation, from STN electrodes implanted for DBS in patients with Parkinson's disease. We suggest that the STN N18 component of SEPs in Parkinson's disease is a mainly local field potential elicited by muscle afferent input to the nucleus.

Cabergoline is a long-acting D2 dopamine (DA) agonist. We conducted an open study to investigate the effectiveness and tolerability of cabergoline, administered once a day orally, in 50 consecutive patients with Parkinson's disease complicated by motor fluctuations and dyskinesias. In 15 patients cabergoline replaced another direct DA agonist. Evaluation after 6 months of treatment (also including patients who dropped out during this period), showed an improvement in off or on hours, or both, in excess of 50% in 27 patients, comprising 20 of the 35 patients (57%) previously untreated with DA agonists and seven of the 15 patients (47%) already on DA agonists when the study began. Of the 22 patients who received the treatment for 1 year, the improvement was maintained up to final evaluation in the patients not on DA agonists at admission (n = 16), whereas a slight deterioration in clinical condition was observed in the patients already on DA agonists at admission (n = 6). Only six patients showed a detectable increase in dyskinesias. The most common side effects were gastric upset (n = 12), orthostatic hypotension (n = 3), and ankle edema (n = 3), all mild; also observed were two cases of pleural effusion/pulmonary fibrosis. Twenty patients (40%) failed to complete the treatment; of these, five (10% of total) dropped out because of adverse effects. It is concluded that once-daily administrations of cabergoline are useful for treating patients with Parkinson's disease with motor fluctuations and may advantageously substitute other DA agonists. The side effects of the drug are generally mild, although two cases involving pleuropulmonary complications did emerge.

A multicenter study has been conducted to determine the interobserver reproducibility of four of the most frequently used rating scales for Parkinson's disease: the Columbia University Rating Scale (CURS) and the Webster Rating Scale (WRS), both for assessing clinical signs; the Northwestern University Disability Scale (NUDS); and the Hoehn and Yahr staging. Four resident neurologists, inexperienced in the use of the four scales, independently examined 48 parkinsonian patients. The extent to which their assessments agreed was determined by calculating the Cohen k index after the scores had been recodified. The physicians' scores agreed substantially for the CURS and the Hoehn and Yahr scale, while those for the NUDS and the WRS agreed only moderately. Analysis of individual item scores within the scales suggests improvements that would offer greater interobserver consistency.