In this one-year prospective study, Parkinson's disease (PD) patients with or without mania following STN-DBS were compared to investigate risk and etiological factors, clinical management and consequences. Eighteen (16.2%) out of 111 consecutive PD patients developed mania, of whom 17 were males. No preoperative risk factor was identified. Postoperative mania was related to ventral limbic subthalamic stimulation in 15 (83%) patients, and resolved as stimulation was relocated to the sensorimotor STN, besides discontinuation or reduction of dopamine agonists and use of low-dose clozapine in 12 patients, while motor and nonmotor outcomes were similar. These findings underpin the prominent role of limbic subthalamic stimulation in postoperative mania. ANN NEUROL 2022;92:411-417.
Introduction Vitamin C is an essential micronutrient playing crucial roles in human biology. Hypovitaminosis C is defined by a plasmatic ascorbemia below 23 µmol/L and is associated with numerous outcomes such as cardiovascular diseases, cancers or neurocognitive disorders. Numerous risk factors are common among older adults making them particularly susceptible to hypovitaminosis C. These risk factors include reduced vitamin intakes, higher vitamin metabolism related to polypathology, and iatrogeny because of polypharmacy. However, the precise prevalence of hypovitaminosis C and its risk factors are poorly documented within the geriatric population. A better knowledge of hypovitaminosis C prevalence and risk factor may lead to improving the vitamin C status among older people and prevent its consequences. Method and analysis To answer these questions, we designed a monocentric cross-sectional study in a population of older hospitalised patients in Lyon, France. A sample size of 385 patients was needed to estimate hypovitaminosis C prevalence. The study was proposed to all eligible patient aged more than 75 years old entering the participating acute geriatric unit. The plasmatic vitamin C status was systematically assessed for participating patients, and variables part of the medical and geriatric evaluation were collected. For patients with severe vitamin C depletion, an oral supplementation and a follow-up phone call were organised to ensure treatment completion and tolerance. Ethics and dissemination The protocol has been approved by an independent national ethics committee and meets the methodological requirements. Final outcomes will be published in a peer-reviewed journal and disseminated through conferences. Trial registration number NCT05668663 .
Growing evidence supports an association between attention-deficit/hyperactivity disorder (ADHD) in childhood and subsequent psychotic disorders. Both disorders share physiopathological features such as attention deficits, dopaminergic imbalance, and genetic susceptibility. However, the results of epidemiologic studies have been conflicting.
To assess the efficacy and safety of topiramate in treating binge eating disorder (BED), using a systematic review and meta-analysis of the available randomized clinical trials (RCTs).The RCTs assessing topiramate vs placebo with or without adjunctive psychotherapy in BED were reviewed using a systematic search in the PubMed, Web of Science, PsycINFO, Cochrane Database of Systematic Review, and ClinicalTrials.gov search Websites, from inception to November 2019. Main outcomes were the changes in binge frequency, quality of life, and weight, respectively. Effect estimates were pooled using random-effect models and presented as risk ratios (RRs) or mean differences (MDs) and their 95% confidence interval (95% CI). Data extraction was performed by two independent reviewers.Three studies were eligible for inclusion, involving 528 BED patients. Topiramate was found to be significantly more efficacious than placebo in reducing: (a) the number of binge episodes per week (MD = -1.31; 95% CI = -2.58 to -0.03; I2 = 94%); (b) the number of binge days per week (MD = -0.98; 95% CI = -1.80 to -0.16; I2 = 94%); and (c) weight (MD = -4.91 kg; 95% CI = -6.42 to -3.41; I2 = 10%). However, participants in the topiramate groups withdrew significantly more frequently for safety reasons, relative to placebo participants (RR = 1.90; 95% CI = 1.13-3.18, I2 = 0%).Preliminary findings support a possible efficacy of topiramate for the treatment of BED, even if safety concerns could limit the practical use of this treatment in BED subjects.
The authors report their experience with dual-chamber pacing in hypertrophy obstructive cardiomyopathy. 22 patients (14 women and 8 men) mean age 60 +/- 13 years were implanted between 1992 and 1998. The criteria for pace-maker implantation were the presence of severe symptoms related with hypertrophy obstructive cardiomyopathy (dyspnea, angina, syncope) and left ventricular outflow tract gradient at mean 30 mmHg. Before pacing, all patients received a medical therapy which included beta-blockers or calcium inhibitors. This treatment was considered as ineffective or responsible of side effects. Patients were followed-up at mean 35.1 +/- 20.3 months. During this period, symptoms improved (mean NYHA class 2.7 +/- 0.5 before pacing vs 1.4 +/- 0.5 after pacing) and left ventricular outflow tract lowered from 95.4 +/- 40.8 to 39.3 +/- 20.5 at 6 months. 34.3 +/- 23.4 at one year and 26.5 +/- 21 at the end of follow-up. Seven patients had RF ablation of atrio-ventricular junction for paroxysmal atrial fibrillation or for lack of hemodynamic improvement with pacing. This procedure permits a significative lowering of gradient and a better ventricular filling. In conclusion, dual-chamber pacing is effective for treatment of hypertrophy obstructive cardiomyopathy when medical therapy is ineffective or bad tolerated at condition of: perfect pacing with permanent ventricular capture and optimal AV delay; RF ablation of AV junction in one third of cases; medical therapy systematically associated in all patients.
FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics’ intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.
Abstract Background Impulse control disorders (ICDs) are frequently encountered in Parkinson’s disease (PD). Objectives We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs. Methods We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs ( n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 μg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease–Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success. Results Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6). Discussion Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted. Trial Registration The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018.
