High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study.

BACKGROUND AND PURPOSE: Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. METHODS: Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (UPDRS) motor score measured on video recordings by raters blinded to the medication status of the patients. RESULTS: There was no significant difference in OFF-DOPA UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4 ± 9.3 vs. 21.5 ± 14.2) nor considering W39 differences from baseline (-1.5 ± 12.1 vs. +0.9 ± 12.1). The 39-item Parkinson's disease questionnaire scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage. CONCLUSIONS: High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of l-DOPA equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies.

Assessing health-related quality of life with the SCOPA-PS in French individuals with Parkinson's disease having undergone DBS-STN: A validation study.

INTRODUCTION: The aims of this study were to validate the French version of the SCales for Outcomes in Parkinson's Disease-PsychoSocial (SCOPA-PS) in individuals with Parkinson's disease (PD) who underwent deep brain stimulation of the subthalamic nucleus (DBS-STN), to confirm the unifactorial structure of this questionnaire, and to establish its psychometric properties. METHODS: Routinely used psychological questionnaires (BDI-II, STAI-Y, PDQ-39, UPDRS III) and the SCOPA-PS were used for a cross-sectional observational study of 154 PD patients. SCOPA-PS acceptability, scaling assumption, reliability, ordinal confirmatory factor analysis and validity were assessed. RESULTS: The ICC for two-week test-retest reliability was 0.88. SEM was 8.42. In confirmatory factor analysis, the one-factor model showed an acceptable fit to the data (Chi(2)/df=2.130; CFI=0.976; RMSEA=0.086). No floor or ceiling effects were observed. Skewness was 0.33. Item-total correlation coefficients ranged from 0.47 to 0.71. Cronbach's alpha was 0.86. SCOPA-PS SI correlated with PDQ-39 SI (rs=0.83) and with state-anxiety and depression (rs=0.56 and 0.69 respectively). The SCOPA-PS SI was higher in more depressed patients and in those with the most severe PD motor symptoms. CONCLUSION AND DISCUSSION: SCOPA-PS French version is a one-factor scale with satisfactory psychometric properties consistent with other language versions. This short scale can be used to evaluate the psychosocial component of QoL in PD patients treated with DBS-STN.

Changes in quality of life, burden and mood among spouses of Parkinson's disease patients receiving neurostimulation.

BACKGROUND: Deep brain stimulation improves motor function and quality of life in patients with Parkinson's disease. The impact of these changes on patients' spouses is largely unknown. METHODS: Twenty-six spouses of patients undergoing surgery were evaluated before and 12 months after surgery, using the 36-Item Short Form Health Survey for quality of life, the Beck Depression Inventory, and the Zarit Burden Inventory. RESULTS: The spouses' mean mood and quality of life scores changed little, while burden improved in younger spouses. There was no significant change in the spouses' overall status. However, at the individual level the effect of surgery was more frequently negative than positive. Changes in psychological status and quality of life in the spouses did not correlate with changes in the patients' motor status or quality of life. CONCLUSIONS: Spouses' experience of neurostimulation for Parkinson's disease is variable and complex. The improvement in burden experienced by younger spouses may reflect a greater capacity to cope with new situations.

Attempted and completed suicides after subthalamic nucleus stimulation for Parkinson's disease.

A higher than expected frequency of suicide has been reported among patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) for advanced Parkinson's disease (PD). We conducted a retrospective survey of 200 patients with PD who underwent STN DBS. Two patients (1%) committed suicide and four (2%) attempted suicide, despite clear motor improvements. Suicidal patients did not differ from non-suicidal patients with respect to age, disease duration or preoperative depressive and cognitive status. Suicidal behaviour was associated with postoperative depression and/or altered impulse regulation. Suicidal behaviour is a potential hazard of STN DBS, calling for careful preoperative assessment and close postoperative psychiatric and behavioural follow-up.

Subthalamic nucleus stimulation in Parkinson's disease: postoperative CT-MRI fusion images confirm accuracy of electrode placement using intraoperative multi-unit recording.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is increasingly used to treat advanced Parkinson's disease (PD). The optimal method for targeting the STN before implanting the definitive DBS electrode is still a matter of debates. Beside methods of direct visualization of the nucleus based on stereotactic magnetic resonance imaging (MRI), the most often used technique for targeting STN consists in recording single-cell activity along exploratory tracks of 10-15mm in length, centered on the theoretical or MRI-defined target coordinates. Single-unit recordings with a microelectrode present various drawbacks. They are time-consuming if correctly performed and a single-cell precision is probably superfluous, taking into account the size of the implanted electrode. In this study, we present an original method of recording and quantification of a multi-unit signal recorded intraoperatively with a semi-microelectrode for targeting the STN. Twelve patients with advanced PD have been included and assessed clinically before and one year after bilateral STN-DBS electrode implantation guided by multi-unit electrophysiological recordings. After one year of chronic stimulation, all patients showed a marked clinical improvement. The motor score of the unified Parkinson's disease rating scale decreased by more than 57% and the required levodopa-equivalent daily dose by 59.5% in on-stimulation off-medication condition compared to off-stimulation off-medication condition. The accuracy of STN-DBS lead placement was confirmed on postoperative computed tomography (CT) scans, which were fused to preoperative T2-weighted MRI. The boundaries of the STN were easily determined by an increase in multi-unit signal amplitude, which was observed on average from 0.492mm below the rostral border of the STN down to 0.325mm above its caudal border. Signal amplitude significantly increased at the both rostral and caudal STN margins (P<0.05) and the level of neuronal activity easily distinguished inside from outside the nucleus. This study showed that STN boundaries could be adequately determined on the basis of intraoperative multi-unit recording with a semi-microelectrode. The accuracy of our method used for positioning DBS electrodes into the STN was confirmed both on CT-MRI fusion images and on the rate of therapeutic efficacy.

Hernia de spiegel. Diagnóstico y epidemiología / Spigelian hernia. Diagnosis and epidemiology

En la experiencia de los cirujanos, las hernias de la pared abdominal constituyen una enfermedad cuyo diagnóstico es básicamente clínico. Sin embargo, la hernia de Spiegel, por su infrecuente presentación (0,2 por ciento), sintomatología inespecífica y exploración anodina, pasa fácilmente desapercibida. Presentamos nuestra experiencia en 7 pacientes (2 por ciento) con hernia de Spiegel, analizando las dificultades diagnósticas que aconsejan con frecuencia el empleo de pruebas diagnósticas complementarias (AU)

[Platelets and migraine]. / Plaquettes et migraine.

Platelet function studies in migraine patients have evidenced a number of anomalies (hyperreactivity and serotonin metabolism disorders) that have been suggested as causative factors in migraine attacks. However, a review of the literature shows that these disorders are inconsistent and are probably consequences rather than causes of the headache, although they may contribute to the pathophysiology of the attack. From a broader perspective, the demonstration of platelet dysfunction in migraine raises questions as to the source of these disorders (secondary to plasma factors or due to platelet anomalies) and their significance (do they have any link with transient ischemic attacks or central serotonin neurotransmission dysfunction?).