Onset of dyskinesia with adjunct ropinirole prolonged‐release or additional levodopa in early Parkinson's disease

Levodopa‐induced dyskinesia can result in significant functional disability and reduced quality of life in patients with Parkinson's disease (PD). The goal of this study was to determine if the addition of once‐daily ropinirole 24‐hour prolonged‐release (n = 104) in PD patients not optimally controlled with levodopa after up to 3 years of therapy with less than 600 mg/d delays the onset of dyskinesia compared with increasing doses of levodopa (n = 104). During the study, 3% of the ropinirole prolonged‐release group (mean dose 10 mg/d) and 17% of the levodopa group (mean additional dose 284 mg/d) developed dyskinesia (P < 0.001). There were no significant differences in change in Unified Parkinson's Disease Rating Scale activities of daily living or motor scores, suggesting comparable efficacy between the two treatments. Adverse events were comparable in the two groups with nausea, dizziness, insomnia, back pain, arthralgia, somnolence, fatigue, and pain most commonly reported. Ropinirole prolonged‐release delayed the onset of dyskinesia with comparable efficacy to increased doses of levodopa in early PD patients not optimally controlled with levodopa. © 2010 Movement Disorder Society     

Seizure risk associated with neuroactive drugs: Data from the WHO adverse drug reactions database

PurposeTo explore the association between the use of neuroactive drugs and reports of epileptic seizures.MaterialUsing the WHO adverse drug reactions (ADR) database, VigiBase, we surveyed reports of suspected seizures from 1968 until February 2006. Case reports of ADRs, that were classified as convulsions were collected and compared to the total number of ADRs reported.ResultsThe total number of ADRs was 7,375,325. The number of convulsive events was 71,471. The ratio of convulsive ADRs to the total number of ADRs reported for each drug was evaluated and expressed as a percentage. The 10 drugs most frequently associated with convulsive ADRs were maprotilene (14.42%), escitaloprame (9.78%), buproprione (9.49%), clozapine (9.0%), chlorprothiexene (8.89%), amoxapine (8.74%), donepezil (8.40%), rivastigmine (6.41%), quetiapine (5.90%) and trimipramine (5.69%).ConclusionsBased on the reports in VigiBase, ADR reports relating to antidepressants, antipsychotic and cholinomimetic drugs included seizures more often than other neuroactive drugs.     

The assessment of light intensity preference in psychiatric patients: a questionnaire

The assessment of abnormal light-related behaviour is important for methodological reasons, and has a prophylactic and heuristic value. Since no operationalization of these behaviour patterns has been published until now, we constructed a questionnaire to identify abnormal light intensity preference based on a systematic study and previous case reports. We administered the questionnaire to patients with schizophrenia (n=46) or major depression (n=55), and to healthy control subjects (n=70). Photophilia was more frequently diagnosed in schizophrenia than in depression (P<0.001). Photophobia was more frequently observed in depression than in schizophrenia; however, this difference was not statistically significant. None of the healthy subjects showed these phenomena. The kappa value was 0.66 for photophilia and 0.65 for photophobia. Patients with schizophrenia had a higher mean photophilia score than depressive patients (P<0.001) and healthy subjects (P<0.05). Depressed patients had higher photophobia scores than schizophrenics (P<0.05) and healthy subjects (P<0.001). The photophilia score was positively correlated and the photophobia score was negatively correlated with the light intensity preference (measured by means of a photometer) (P<0.001). A significant positive correlation between the photophilia score and the percentage of time spent in bright and very bright areas was observed (P<0.05). Scores were not related to age or gender. These results represent initial data in support of the validity and reliability of our questionnaire for distinguishing between patients with and without abnormal light-exposure behaviour patterns.     

Rotigotine vs ropinirole in advanced stage Parkinson's disease: A double-blind study

ObjectiveTo confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy.MethodsThis trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period.ResultsThe difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was −6.4 ± 1.2 (95% CI: −8.7 to −4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was −1.4 ± 1.0 (95% CI: −3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted.ConclusionsRotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.     

Ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease: a 16-week bromocriptine controlled study

Background: and objectives Ropinirole is a non-ergoline, selective dopamine D₂ agonist. The aim of this study was to evaluate the efficacy and safety of ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease (PD) complicated by motor fluctuations. Methods: A total of 76 patients with PD (Hoehn and Yahr stage II to IV) were included in this trial. Each patient was randomly allocated to receive either ropinirole (n = 37) or bromocriptine (n = 39) as an adjunct to levodopa over a 16-week period. Ropinirole and bromocriptine were titrated for optimal efficacy and tolerability. This optimal dose was then maintained for the rest of the study. Response rate was defined as the percentage of patients who achieved at least a 20 % reduction in levodopa dose. Clinical status was also assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression (CGI), and reduction in time spent ‘off’. Results: Ropinirole produced a significantly greater response rate than bromocriptine (odds ratio 2.995, 95 % C. I. (1.157, 7.751) p < 0.05). There was also a statistically significant difference between the groups in the proportion of patients who were ‘improved’ on the CGI improvement scale (91.9 % for ropinirole, 74.3 % for bromocriptine, p = 0.046). Other measures, including at least a 20 % improvement in the UPDRS motor score (70 % for ropinirole and 63.3 % for bromocriptine), and a 20 % reduction in ‘off’ duration (81 % for ropinirole and 52.4 % for bromocriptine) showed a trend in favour of ropinirole. There was no significant difference between the two groups in the overall incidence of adverse effects (ropinirole, 59.5 %; bromocriptine, 59 %). In each group, the most common side-effects were dizziness, dyskinesia and nausea/vomiting. No patients were withdrawn from the study because of side-effects. Conclusion: Ropinirole was found to be safe and well-tolerated. Ropinirole as an adjunct to levodopa in the treatment of PD with motor fluctuation was associated with more significant reduction of levodopa dose and, on one form of analysis, with significantly greater improvement in CGI ratings than bromocriptine. On the other efficacy measures the two drugs were comparable. Received: 4 September 2001, Received in revised form: 8 May 2002, Accepted: 31 July 2002 This study was supported by SmithKline Beecham Korea and presented at the XIII International Congress on Parkinson's Disease, Vancouver, Canada, July 24–28, 1999. Correspondence to Joo-Hyuk Im, MD     

A six-month multicentre,double-blind,bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by <Emphasis Type="SmallCaps">l</Emphasis>-dopa

Summary. Objectives: To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. Methods: A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry. Patient response was defined as at least a 20% reduction in daily L-dopa dose plus: for patients with no prior treatment and no motor fluctuations, a 20% reduction in UPDRS motor score; for patients with motor fluctuations, a 20% reduction in time spent "off"; and for patients already taking an agonist, an improvement on the CGI scale. Results: Safety assessments showed no significant differences in the two treatment groups for patients without prior dopamine-agonist therapy. In the group of patients with prior dopamine-agonist therapy, more patients reported adverse events in the ropinirole group (90% versus 79%, p < 0.001). The proportions of responders tended to be higher in ropinirole groups compared with bromocriptine groups and, in the subgroup with motor fluc-tuations, this difference was statistically significant (9.1% versus 0.0%, respectively; p < 0.05). Conclusions: Both drugs were well tolerated. In patients receiving a relatively high dose of L-dopa and requiring the addition of a dopamine agonist to control motor fluctuations or dyskinesias, ropinirole was significantly more effective than bromocriptine. Received January 31, 2001; accepted October 23, 2001     

Ropinirole as a treatment of restless legs syndrome in patients on chronic hemodialysis: an open randomized crossover trial versus levodopa sustained release

OBJECTIVE: Restless legs syndrome (RLS) is a common neurologic condition characterized by uncomfortable and unpleasant sensations in the legs, occurring primarily at rest, which are usually worse in the evening and are alleviated by movement. RLS is present in 20-40% of patients with renal failure. This study was a 14-week open, randomized, crossover trial of ropinirole vs. levodopa sustained release (SR) in 11 patients with RLS on chronic hemodialysis. METHODS: Eleven patients (7 men, 4 women) were enrolled in the study. They received either levodopa SR or ropinirole for 6 weeks, followed by a washout week, then the alternate treatment for 6 weeks. Patients rated the severity of RLS by means of a 6-item questionnaire developed by the International Restless Legs Study Group (6-item IRLS), by the Clinical Global Impression (CGI) scale, and by sleep diaries. RESULTS: Under treatment with levodopa SR, 1 patient presented severe vomiting, leading to study discontinuation. The 10 patients who completed the study reported a 33.5% improvement (from 16.7 +/- 3.2 to 11.1 +/- 4; P < 0.001) of the 6-item IRLS scores during levodopa SR treatment and a 73.5% improvement (from 16.6 +/- 2.8 to 4.4 +/- 3.8; P < 0.001) during ropinirole treatment. By the end of the study the mean levodopa SR dosage was 190 mg/d and the mean ropinirole dosage was 1.45 mg/d. Ropinirole was superior to levodopa SR in reducing 6-item IRLS scores (P < 0.001) and in increasing sleep time (P < 0.001). The patient CGI scale showed a significant difference favoring ropinirole (P < 0.01). There was no significant carryover or period effect for any outcome measure. Four patients reported a complete reversion of RLS symptoms during ropinirole treatment at doses ranging from 0.25-2 mg/d. CONCLUSIONS: These results suggest that ropinirole is more effective than levodopa SR in the treatment of RLS in patients on chronic hemodialysis.     

Neuropathy and levodopa in Parkinson's disease: Evidence from a multicenter study

The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037‐1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130‐5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical‐neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa. © 2013 International Parkinson and Movement Disorder Society     

Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study

Comorbid depressive symptoms in restless legs syndrome (RLS) remain a treatment challenge, as some antidepressants aggravate RLS symptoms. Preliminary data in depressive patients suggest antidepressant properties of ropinirole. The present study investigates the effects of ropinirole immediate release (IR) on depressive symptoms and RLS severity. A multicenter, placebo-controlled, double-blind randomized (3:1) study was performed including patients with moderate to severe idiopathic RLS and at least mild depressive symptoms. Ropinirole IR (in flexible doses up to 4 mg/day) or placebo was given for 12 weeks including an uptitration phase of 7 weeks. Visits were scheduled at screening, baseline, and weeks 1, 4, and 12 with additional telephone contacts for dosing decisions. The modified intent to treat population comprised 231 patients (171 ropinirole, 60 placebo). The MADRS (Montgomery–Asberg Depression Rating Scale) scores decreased from baseline to week 12 from 18.8 to 8.7 in the ropinirole group and from 18.4 to 12.1 in the placebo group (primary endpoint, adjusted mean treatment difference −3.6 (95% CI: −5.6 to −1.6, significance in favor of ropinirole: P < 0.001). The superiority of ropinirole compared to placebo was confirmed by the Hamilton Scale for Depression and Beck Depression Inventory-II scores. RLS severity scores (IRLS) decreased by 14.7 (ropinirole) and by 9.9 (placebo, P < 0.001) points. Three out of four subdomains of the Medical Outcomes Study Sleep Scale improved significantly. The findings indicate that mild to moderate depressive symptoms should not be treated before sufficient therapy for RLS. Antidepressant medication can be necessary if depression symptoms still persist even if RLS symptoms are ameliorated.     

Conversion from dopamine agonists to pramipexole

Abstract.Background: Pramipexole is a nonergoline dopamine agonist with D2 and preferential D3 dopamine receptor activity. This selective activity may result in clinically different effects. Small clinical trials indicate that overnight switching from one agonist to another can be performed safely. Objective To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinsons disease (PD).Objective: To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinsons disease (PD).Methods: Patients with advanced PD and motor complications not optimally controlled by levodopa and a stable dose of bromocriptine, pergolide or ropinirole were converted to pramipexole overnight. Clinical assessments were performed just prior to conversion and after 2, 6 and 12 weeks of treatment, when an optimal dose of pramipexole was achieved.Results: Two hundred and seventeen patients were included in the trial. One hundred and twenty five were converted from pergolide to pramipexole, 58 from bromocriptine and 34 from ropinirole. After 12 weeks, the average dose of pramipexole was 2.8, 2.9 and 3.4 mg/d in patients converted from bromocriptine, pergolide, and ropinirole, respectively. UPDRS II, III and IV scores were reduced by 26–30 % in all patients (p < 0.0001). Mean levodopa dose was slightly reduced in all groups (p: NS). No serious or unexpected side effects were reported. The dose equivalences calculated from this trial were: bromocriptine: pramipexole 6.9:1, pergolide: pramipexole 0.9:1, ropinirole: pramipexole 1.5:1.Conclusion: Switching from bromocriptine, pergolide or ropinirole to pramipexole in an overnight schedule is safe. The observed clinical improvement may be related to a placebo effect, to the use of low doses of dopamine agonists or to a direct effect of pramipexole.     

Development of dyskinesias in a 5-year trial of ropinirole and L-dopa.

A 5-year trial of ropinirole and levodopa in early Parkinson's disease showed that ropinirole is associated with reduced incidence of dyskinesias. This post hoc analysis investigated whether the dyskinesia-sparing benefit of ropinirole is lost when levodopa is added to the regimen and evaluated other risk factors for developing dyskinesias. Patients receiving levodopa had a significantly higher risk of dyskinesias than those taking ropinirole monotherapy (hazard ratio [HR], 6.67; 95% confidence interval [CI], 3.23-14.29; P < 0.001). When patients randomized to ropinirole were treated with supplementary levodopa, the development of dyskinesias was not significantly different from that in those receiving levodopa from the start (HR, 0.80; 95% CI, 0.48-1.33; P = 0.39). However, the onset of dyskinesias was delayed by around 3 years compared with levodopa monotherapy. Adjusted analyses taking into account baseline and on-treatment factors that influenced use of supplementary levodopa or the development of dyskinesias produced similar results. In conclusion, the risk of developing dyskinesias during maintained initial ropinirole monotherapy is very low. Only once levodopa is added does the risk substantially change. Early use of ropinirole postpones the onset of dyskinesias, but these benefits decline when levodopa therapy is started, with no evidence of a subsequent rapid "catch-up" or a persisting preventive effect.     

Adverse drug reactions to selegiline: a review of the French pharmacovigilance database

The present pharmacoepidemiologic study was performed to characterize the profile of adverse drug reactions (ADRs) reported with selegiline, a monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease and previously reported to induce an excess of mortality. The analysis was performed with use of the French Pharmacovigilance Database between 1989 and 1997.This database includes all ADRs reported by French practitioners (and especially "serious" and "unexpected" ADRs). Three different analyses were performed: identification of ADRs reported with selegiline, comparison with the ADR profile observed with other antiparkinsonian drugs, and a case/non-case study investigating the occurrence of cardiovascular ADRs with selegiline in comparison with other drugs in general and other antiparkinsonian drugs (e.g., levodopa [L-Dopa], dopamine agonists) in particular. The most often reported ADRs with selegiline were psychiatric (delirium, hallucinations, agitations), cardiovascular (orthostatic hypotension, arterial hypertension, etc.) and neurologic (sedation, abnormal movements, etc.). Psychiatric and cardiovascular ADRs were more frequently reported with selegiline than with L-Dopa or dopamine agonists. The case/ non-case study found an increased risk of cardiovascular ADRs (OR = 1.72; 95% Cl = 1.16-2.55)when selegiline was associated with L-Dopa. These data show that the profile of selegiline-induced ADRs differs from that of other antiparkinsonian drugs (L-Dopa, dopamine agonists) with more psychiatric and cardiovascular ADRs. We suggest that the higher frequency of cardiovascular ADRs could explain, at least partially, the previously reported increase in mortality rate.     

Early treatment benefits of ropinirole prolonged release in Parkinson's disease patients with motor fluctuations

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE‐PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2–24 mg/day) versus placebo in patients with moderate‐to‐advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in “off” time (adjusted mean treatment difference [AMTD] – 0.7 hours; 95% confidence interval [CI], –1.1, –0.2; P = 0.0029), and “on” time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, –3.1; 95%CI, –4.4, –1.8; P < 0.0001), activities of daily living score (AMTD, –1.1; 95%CI, –1.7, –0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once‐daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation. © 2010 Movement Disorder Society     

Improvements in nocturnal symptoms with ropinirole prolonged release in patients with advanced Parkinson’s disease

Background: The 24‐week, double‐blind Efficacy and Safety Evaluation in PD–Adjunct (EASE‐PD Adjunct) study randomized patients with advanced Parkinson’s disease (PD) suboptimally controlled with levodopa to once‐daily placebo or adjunctive ropinirole prolonged release (2–24 mg/day). We investigated the effect of ropinirole prolonged release on nocturnal symptoms in these patients. Methods: Total and grouped item PD Sleep Scale (PDSS) scores were analyzed post hoc in patients with baseline PDSS total scores ≤ 100 (troublesome nocturnal symptoms) and >100. Results: Baseline PDSS total score was ≤ 100 in 93 of 198 (47%) and 89 of 189 (47%) patients receiving ropinirole prolonged release and placebo, respectively; this subgroup displayed evidence at baseline of greater daily awake ‘off’ time, reduced night‐time sleep and worse quality of life, than the PDSS >100 subgroup. Significant improvements with ropinirole prolonged release versus placebo in PDSS score from baseline to Week 24 last observation carried forward were observed for those with baseline PDSS ≤ 100 [adjusted mean treatment difference 9.0 (95% CI: 2.76, 15.33; P = 0.0051)], but not >100. The PDSS ≤ 100 subgroup demonstrated treatment benefits for PDSS groupings of motor symptoms on waking and global quality of sleep. Changes in daytime sleepiness were similar between treatment groups. The PDSS >100 subgroup demonstrated significant treatment benefit for global quality of sleep. The unadjusted odds ratio for a positive response with ropinirole prolonged release relative to placebo, for the PDSS ≤ 100 subgroup, was 2.90 (95% CI: 1.42, 5.95, P = 0.004). Conclusions: Once‐daily ropinirole prolonged release improves nocturnal symptoms in patients with advanced PD not optimally controlled with levodopa who suffer troublesome nocturnal disturbance.     

Ten years of adverse drug reaction reports for the multiple sclerosis immunomodulatory therapies: a Canadian perspective

Adverse drug reaction (ADR) reporting is essential in the post-marketing surveillance of drugs, detection of serious adverse reactions, and has been the basis for drug withdrawals. The study aimed to examine ADR reporting patterns to the multiple sclerosis (MS) immunomodulatory drugs (IMD) in Canada. All ADRs reported to the Canadian ADR Monitoring Program (CADRMP) from 1965 to March 2006 (n=193 208) were accessed and ADRs in which an IMD for MS (beta-interferon or glatiramer acetate) was the suspected drug extracted (n=888 reports were dated March/96-March/06). Almost half of all IMD ADRs reports (438/888) were sourced through the patient compared to 14.9% (10 649/71 373) of all ADRs reported to CADRMP over the same period. Of IMD ADR reports, 88.7% (788/888) were directed through the manufacturer compared to 57.7% (41197/71373) of all ADRs. Encouragement to others involved in patient care, such as pharmacists, nurses and physicians might enhance reporting of MS ADRs. Despite the limitations of ADR reporting data, previously unpublished case reports in several understudied MS populations were detailed: paediatrics (or= 65 years, n=23) and during pregnancy (n=12). In addition, 46 deaths suspected by the reporter as being related to IMD treatment were detailed as well as three possible drug interactions.     

Impulsivity in overweight children

Objective This study investigates whether or not obese children have a stronger tendency to act on impulse than normal weight children, taking into account the multidimensionality and complexity of the impulsivity construct. Method A performance based test (Matching Familiar Figure Test, MFFT), a child interview and questionnaire, and parental reports were obtained from 56 overweight children and 53 normal weight children aged 10–18 years. Results Overweight children responded in a more impulsive way on the MFFT (P < .01). On the child questionnaire, overweight boys reported more problems with focussing attention (P < .05) and both overweight boys and girls reported being worse at shifting their attention compared with normal weight children (P < .05). In particular, overweight boys showed more impulsivity (P < .05), hyperactivity (P < .01), and inattention symptoms (P < .001) as measured via the clinical interview. Parents of overweight children reported an equal amount of impulsivity and hyperactivity symptoms as parents of normal weight children, but scored their children lower on the Conscientiousness personality dimension (P < .01). Conclusion A subgroup of overweight children appears to have a stronger tendency to act on impulse than normal weight children, and demonstrated an impulsivity prone personality. Hence, overweight children should be screened for impulse control deficiencies. More research is needed to clear out the robustness of gender differences, the existence of a specific personality profile and possibly common underlying mechanisms of childhood obesity and Attention Deficit Hyperactivity Disorder.     

Levodopa response in early Parkinson's disease

To further characterize the short‐term levodopa response in early PD, we performed a retrospective analysis of the ELLDOPA study which randomized 361 early PD subjects to placebo, levodopa 150, 300, or 600 mg/day. We evaluated change in UPDRS motor scores (UPDRSm) from baseline to weeks 9 and 24, and identified changes in UPDRSm that best discriminated treatment with levodopa from placebo. Linear regressions were used to determine associations between baseline characteristics and changes in UPDRSm. Mean percent improvement in UPDRSm in levodopa‐treated subjects was greater than that for placebo‐treated subjects (27.4% vs. 5.8% at 9 weeks, P < 0.001 and 26.2% vs. 4.0% at 24 weeks, P < 0.001). UPDRSm change at 9 weeks ranged from –92.9% (improvement) to 85.7% (worsening) for levodopa and –86.7% to 160% for placebo, and at 24 weeks ranged from –100.0% to 242.9% for levodopa and –87.5% to 112.5% for placebo. UPDRSm improvements of 22.0% at 9 weeks and 23.8% at 24 weeks best discriminated treatment with levodopa 300 mg/day (a common initial maintenance dosage in clinical practice) from placebo. Significant associations were not observed between baseline subject characteristics and magnitude of response from baseline to week 24. We conclude that although levodopa treatment significantly improved PD signs when compared with placebo, there was a wide range and considerable overlap in clinical responses to levodopa and placebo. A substantial proportion of subjects with early PD did not experience a robust response to levodopa. An improvement in UPDRSm of ～22% best discriminated levodopa treatment from placebo. © 2009 Movement Disorder Society     

An acute and long-term study with a dispersible formulation of levodopa/benserazide (Madopar®) in Parkinson's disease

The clinical efficacy, tolerability and administration regimens of a dispersible formulation of levodopa/benserazide (DM) were investigated in 30 patients with idiopathic Parkinson's disease, complicated by motor fluctuations. All 30 patients showed delayed- “on” phenomenon after administration of the first morning dose of standard levodopa (SM), and 20 showed delayed- “on” phenomenon after the first afternoon dose. Patients were receiving standard formulations of levodopa as monotherapy or in combination. A double-dose study of the dispersible vs the standard formulation was performed in 30 patients, 24 of whom participated in a 36-month, follow-up clinical study. In the long-term study, SM was replaced with DM by substituting the first morning dose or the first morning and first afternoon doses. In the double-dose study, mean latency to “on” after the first morning dose was significantly shorter with DM than with SM (p < 0.001), whereas the duration of “on” was similar with the two preparations. The post-prandial delayed- “on” in the 14 patients who responded to therapy was significantly shorter for DM than for SM (p < 0.001). In the long-term study, the mean latency to “on” in all patients was significantly shorter than at baseline (p < 0.001). Time spent in “on” during the active day increased significantly, and remained stable during the 36-month study. No changes were apparent in the mean dosage of levodopa/day or the number of doses/day, and no acute or long-term adverse events were reported. In conclusion, these results confirm the long-term safety of the dispersible formulation, and its improved efficacy compared with standard levodopa formulations, as monotherapy and in association with slow-release formulations.     

Identifying fasciculation potentials in motor neuron disease: A matter of probability

Introduction: Fasciculations, the spontaneous activity of single motor units (MUs) are characteristic, but nonspecific for motor neuron disease (MND). We aimed to identify MU discharge properties to optimally differentiate MND patients from healthy controls. Methods: High‐density surface electromyography recordings were performed in the thenar muscles during 10 min of rest. MU discharges were classified as “isolated” when the interspike intervals (ISIs) before and after were > 250 ms, “continual” when both ISIs were ≤ 250 ms, or as “other”. Results: In patients (n = 30) compared with controls (n = 14), more MUs were active (9 vs. 3, P < 0.001) and generated relatively more isolated discharges (35% vs. 10%, P = 0.01). Two or more MUs with isolated discharges occurred more frequently in patients compared with controls (24% vs. <1% of 10‐s windows, P < 0.001). Conclusions: More frequent occurrence of multiple MUs showing isolated discharges may improve identification of patients with MND. Muscle Nerve 53: 227–233, 2016     

Assessment of sleepiness and unintended sleep in Parkinson's disease patients taking dopamine agonists

OBJECTIVE: We sought to determine if patients with Parkinson's disease (PD), taking dopamine agonists (DAs) and reporting unintended sleep episodes (SEs), exhibit physiologically defined daytime sleepiness and can thus be differentiated from those taking DAs but not reporting SEs. METHODS: Twenty-four patients with abnormal Epworth Sleepiness Scale scores of >10 who were taking DAs were enrolled into one of two groups: those with SEs (SE+, n=16) and those without (SE-, n=8). Three consecutive days of testing included two nights of polysomnography followed by the Multiple Sleep Latency Test (MSLT). RESULTS: Overall frequency of pathological sleepiness (MSLT <5 min) was 42% (10/24). Mean levels of sleepiness, frequencies of pathological sleepiness, and naps with stage 2 or REM-sleep were similar between SE+ and SE- groups. Sleep tendency was similar in patients prescribed pergolide, ropinirole, and pramipexole combined with levodopa. Polysomnography testing revealed no significant differences between the groups in total sleep time, sleep efficiency, sleep architecture, or presence of restless legs syndrome or periodic leg movements. There was no relation between degree of nocturnal sleep disturbance and level of daytime sleepiness. CONCLUSIONS: The results of this study suggest SEs in PD patients occur upon a background of excessive daytime sleepiness and are unrelated to nocturnal sleep or use of a specific DA.