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Excessive body fat at birth is a risk factor for the development of childhood obesity. The aim of the present systematic review with meta-analysis was to evaluate the effect of lifestyle interventions in pregnant women with overweight or obesity on neonatal adiposity. The PubMed, Embase, Web of Science, Scopus, and LILACS databases were used as information sources. Original articles from randomized clinical trials of lifestyle intervention studies on pregnant women with excessive body weight and the effect on neonatal adiposity were considered eligible. The risk of bias was assessed using Cochrane criteria. The meta-analysis was calculated using the inverse variance for continuous data expressed as mean difference (MD), using the random effect model with a 95% confidence interval (CI). The outcomes were submitted to the GRADE evaluation. Of 2877 studies, four were included in the qualitative and quantitative synthesis (n = 1494). All studies were conducted in developed countries, with three including pregnant women with overweight or obesity, and one only pregnant women with obesity. The interventions had no effect on neonatal adiposity [Heterogeneity = 56%, MD = −0.21, CI = (−0.92, 0.50)] with low confidence in the evidence, according to GRADE. Studies are needed in low- and medium-developed countries with different ethnic-racial populations. PROSPERO (CRD42020152489).

Bibliographic systematic reviews emerged in the health area and were later adopted by other scientific fields, based on adaptations to better attend to their study objects. As the socio-environmental field is relatively new, it is hard to find a guide to orient bibliographic systematic reviews about emergent problems in the knowledge area. Therefore, aiming to include qualitative studies, more common to the social and human sciences, as well as quantitative studies, more common to the natural science, this article proposes an integrative review protocol adapted to the specifications of socio-environmental studies. Hence, the literature was verified regarding systematic bibliographic reviews and a documentary survey was carried out, which included forms, templates and support systems to search specific elements, tools and procedures that can be used in the socio-environmental area. The proposal of a specific method has the potential to contribute more rigor to the systematic reviews that take place in the socio-environmental field and to collaborate to the disclosing of its research studies, in addition to the possibility of being used as a tool for interdisciplinarity practice among researchers of the diverse scientific fields in the area.

Objective: To assess the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on standard cardiovascular risk markers among women with thrombophilia and/or previous venous thromboembolism (VTE).Methods: A prospective cohort study enrolled women aged 18-45 years with thrombophilia and/or a history of VTE who received the 52-mg LNG-IUS (20 μg/d initial release) at the University of Ribeirão Preto Medical School, Brazil, from January 2006 to December 2015. Before and 12 months after LNG-IUS placement, the following cardiovascular risk markers were assessed: lipid profile, body mass index (BMI), blood glucose, systolic blood pressure, diastolic blood pressure, and waist circumference. The primary outcome was changes in cardiovascular risk markers. A subanalysis of anticoagulant users versus non-users was also conducted.Results: In total, 45 women were enrolled. BMI increased by 2.3% after 12 months of LNG-IUS placement (P < 0.01), but the other risk factors did not change. Cardiovascular risk markers were similar between anticoagulant users and non-users after 12 months of LNG-IUS use.Conclusion: Among women with thrombophilia and/or previous VTE, cardiovascular risk markers were not found to change significantly after 12 months of LNG-IUS use. The study adds safety information regarding use of the LNG-IUS for women at risk of thromboembolism. [ABSTRACT FROM AUTHOR]

BACKGROUND Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease. METHODS In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period. The primary end point was the change from baseline in scores on the Movement Disorder Society--Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability), which was assessed in patients in the on-medication state at 12 months. Secondary end points included other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent. RESULTS A total of 156 persons were enrolled, with 78 assigned to each group. MDS-UPDRS part III scores at baseline were approximately 15 in both groups. At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P=0.007). At 14 months, after a 2-month washout period, the mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) with lixisenatide and 20.6 (95% CI, 18.5 to 22.8) with placebo. Other results relative to the secondary end points did not differ substantially between the groups. Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%. CONCLUSIONS In participants with early Parkinson's disease, lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months in a phase 2 trial but was associated with gastrointestinal side effects. Longer and larger trials are needed to determine the effects and safety of lixisenatide in persons with Parkinson's disease. (Funded by the French Ministry of Health and others; LIXIPARK ClinicalTrials.gov number, NCT03439943.) [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) are among the most common public health problems worldwide, especially among adolescents and young adults, who account for almost 50% of all STI patients. Studies on the subject in the western Amazon are limited. This study aimed to evaluate the prevalence of STIs (chlamydia, gonorrhea, trichomoniasis, herpes simplex virus, syphilis, human immunodeficiency virus [HIV], hepatitis B, and hepatitis C) in adolescents treated at a family planning outpatient clinic in the western Amazon: Porto Velho, Rondônia, Brazil. A total of 196 adolescents were enrolled. During the gynecological examination, endocervical samples were collected to test for four STIs (chlamydia, gonorrhea, trichomoniasis, and herpes simplex virus), and blood samples were collected for the detection of HIV, syphilis, and hepatitis B and C. The mean age was 17.3 ± 1.5 years, the age at sexarche was 14.4 ± 1.6 years, and 54.6% of participants had their first sexual intercourse at 14 years or younger. Only 1.0% of the adolescents used condoms in all sexual relations, and 19.9% had casual partner(s) in the last year. In the evaluation of prevalence, we found that 32% of the adolescents had at least one STI, with the most prevalent being chlamydia (23%), followed by trichomoniasis (5.6%), herpes simplex (4.6%), and gonorrhea (3.1%). No positive cases of hepatitis B, hepatitis C, or HIV were detected, but 1% of the adolescents tested positive for syphilis. These indicators will support more effective health care strategies aimed at improving the quality of life of populations in this region of the western Amazon. In conclusion, our findings demonstrated high rates of STIs in the studied patients, reinforcing the need to expand epidemiological studies to implement more appropriate public policies and intervention strategies to prevent STIs in adolescents and other vulnerable populations in the western Amazon.

Abstract Objective To evaluate the assistance provided to women victims of sexual violence and their participation in the follow-up treatment after the traumatic event, presenting a sociodemographic profile, gynecological background, and circumstances of the event, and reporting the results, acceptance, and side effects of prophylaxis for sexually transmitted infections (STIs) and pregnancy. Methods A retrospective cohort study comprising the period between 2007 and 2016. All women receiving medical care and clinical follow-up after a severe episode of sexual violence were included. Records of domestic violence, male victims, children, and adolescents who reported consensual sexual activity were excluded. The present study included descriptive statistics as frequencies and percentages. Results A total of 867medical records were reviewed and 444 cases of sexual violence were included. The age of the victims ranged from10 to 77 years old, most of them selfdeclared white, with between 4 and 8 years of education, and denying having a sexual partner. Sexual violence occurred predominantly at night, on public thoroughfare, being committed by an unknown offender. Most victims were assisted at the referral service center within 72 hours after the violence, enabling the recommended prophylaxis. There was high acceptance of antiretroviral therapy (ART), although half of the users reported side effects. Seroconversion to human immunodeficiency virus (HIV) or to hepatitis B virus (HBV) was not detected in women undergoing prophylaxis. Conclusion In the present cohort, the profile of victims of sexual violence was loweducated, young, white women. The traumatic event occurred predominantly at night, on public thoroughfare, being committed by an unknown offender. Assistance within the first 72 hours after sexual violence enables the healthcare center to provide prophylactic interventions against STIs and unwanted pregnancies.

Este estudo investigou os fatores associados à morbidade materna grave entre mulheres atendidas em maternidades públicas do Município de Ribeirão Preto, São Paulo, Brasil. Trata-se de um estudo quantitativo, analítico, transversal. Participaram 1.098 puérperas com parto em uma das quatro maternidades públicas do município. A coleta de dados ocorreu entre 3 de agosto de 2015 e 2 de fevereiro de 2016, a partir de entrevistas face a face, obtenção de informações dos prontuários e dos cartões da gestante. Para a análise de dados, considerou-se como variável dependente a ocorrência de morbidade materna grave, ou seja, quando a mulher era classificada como near miss materno ou condição potencialmente ameaçadora à vida a partir dos critérios de elegibilidade da Organização Mundial de Saúde. Calculou-se a razão do near miss materno, odds ratio (OR), intervalo de 95% de confiança (IC95%) e regressão logística múltipla. A razão do near miss materno foi de 3,6 casos por mil nascidos vivos. As complicações ocorreram principalmente na gravidez (53,8%) e os distúrbios hipertensivos foram os mais frequentes (49,4%). A análise de regressão múltipla mostrou associação entre morbidade materna grave e gestação de risco (OR = 4,5; IC95%: 2,7-7,7) e com trabalho de parto induzido (OR = 2,1; IC95%: 1,2-3,9). A ocorrência de morbidade materna grave, principalmente na gestação, com destaque para as síndromes hipertensivas, aponta para a necessidade de melhor rastreamento e manejo da elevação dos níveis pressóricos no pré-natal. A associação entre morbidade materna grave e gestação de risco também remonta ao pré-natal, para a demanda de uma maior atenção às mulheres classificadas como risco gestacional. A qualidade da assistência é ponto chave para o enfretamento da morbimortalidade materna no país.

RESUMO Introdução O parceiro tem um papel importante quando ele acompanha o pré-natal, parto e pós-parto de sua companheira como mostram os resultados positivos em relação à saúde materna, infantil e também relacionados à saúde do homem. É uma importante estratégia de aproximar os futuros pais dos serviços de saúde e melhorar o vínculo destes com a paternidade. Objetivo Avaliar se a implementação da tecnologia SMS através do programa PRENACEL para o parceiro como um programa de educação em saúde é um suplemento útil ao acompanhamento pré-natal padrão. Método Ensaio aleatorizado controlado por conglomerados representados por unidades de saúde de atenção primária. Selecionamos as 20 unidades de saúde com maior número de gestantes acompanhadas em 2013. Segundo critérios de tamanho da população adscrita e pela situação de vulnerabilidade houve um balanço e as unidades de saúde foram aleatoriamente alocadas em unidades intervenção e controle. Os parceiros das gestantes que iniciaram o pré-natal antes da 20ª semana de gestação foram a população do grupo intervenção. Os parceiros inscritos no PRENACEL receberam periodicamente mensagens curtas de texto via celular com informações sobre gestação e parto. Nas unidades do grupo controle os parceiros receberam, junto com suas companheiras, o pré-natal padrão. Resultados 186 parceiros foram entrevistados, 62 do grupo PRENACEL, 73 do grupo intervenção, mas que não optaram pelo PRENACEL e 51 do grupo controle. Encontramos um perfil com idade média de 30 anos e a maioria dos entrevistados (51%) se declarou como raça/cor parda. Os entrevistados tinham em média de 9,3 anos de estudo. A maioria dos homens (95,2%) coabita com a companheira e foi classificada como classe C (63,7%). A adesão ao programa PRENACEL foi de 53,4%. Em relação aos resultados individuais, houve uma maior participação dos parceiros do grupo PRENACEL nas consultas de pré-natal, assim como foi observada uma maior presença destes no momento do parto como acompanhante quando comparado aos demais grupos. Conclusão O estudo mostrou que uma estratégia de educação em saúde utilizando as tecnologias de comunicação parece ser um suplemento útil para o cuidado pré-natal, teve uma boa aceitabilidade e um papel promissor no engajamento de homens aos cuidados pré-natal, parto e pós-parto de suas companheiras.

Risposta ai commenti su Ernesto De Martino, La fine del mondo. Contributo all’analisi delle apocalissi culturali, nuova edizione a cura di Giordana Charuty, Daniel Fabre e Marcello Massenzio, 2019 [ed. fr. La fin du monde. Essai sur les apocalypses culturelles, Éditions EHESS, 2016].

Resumo: Este estudo objetivou investigar a ocorrência de morbidade materna grave, os critérios diagnósticos mais frequentes e a qualidade da assistência obstétrica nos hospitais públicos de Ribeirão Preto, São Paulo, Brasil. Trata-se de uma pesquisa quantitativa de vigilância das morbidades maternas graves, utilizando os critérios da Organização Mundial da Saúde (OMS) para condições potencialmente ameaçadoras à vida e near miss materno. Os casos foram identificados entre 1º de agosto de 2015 e 2 de fevereiro de 2016. Participaram 259 mulheres com morbidade materna grave (condições potencialmente ameaçadoras à vida/near miss materno) durante o ciclo gravídico-puerperal, internadas para o parto nas quatro instituições públicas com assistência obstétrica no município. Realizou-se análise descritiva a partir das frequências absolutas e relativas dos critérios diagnósticos para condições potencialmente ameaçadoras à vida e near miss materno, além da descrição das mulheres pesquisadas (caracterização sociodemográfica, antecedentes obstétricos, assistência pré-natal e ao parto). Indicadores de qualidade da assistência estabelecidos pela OMS a partir da morbimortalidade também foram calculados. Ocorreram 3.497 partos, 3.502 nascidos vivos em todos os hospitais do município, 2 mortes maternas e 19 near miss materno. A razão do near miss materno foi de 5,4 casos por 1.000 nascidos vivos, e a razão de mortalidade materna foi de 57,1 óbitos por 100 mil nascidos vivos. A taxa de mortalidade entre os casos com desfecho materno grave (somados os casos de near miss materno e morte materna) foi de 9,5%. Observou-se importante frequência de casos de condições potencialmente ameaçadoras à vida e near miss materno no presente estudo. A ocorrência de óbitos por causas hemorrágicas mostra a necessidade de melhoria da qualidade da assistência prestada. Os resultados poderão contribuir para o aprimoramento da política local de assistência obstétrica.

Abstract Background The aim of this study was to determine whether PRENACEL (a bi-directional, mobile-phone based, short text message service (SMS)) increases the coverage of recommended antenatal care (ANC) practices. Methods A parallel, cluster-randomized trial in which 20 public primary Health Care Units (PHCUs) were randomly allocated to the intervention (10 PHCUs) or control (10 PHCUs) group. The study population included pregnant women aged 18 or above with a gestational age of 20 weeks or less. Pregnant women receiving ANC in intervention PHCUs were invited through leaflets and posters to register in PRENACEL. Women who registered in PRENACEL received a weekly set of short text messages with health education and health promotion content related to pregnancy and childbirth and were also able to clarify ANC queries through SMS. All women received routine ANC. The primary outcome was the proportion of women with high ANC Score, a composite measure of coverage of recommended ANC practices. Chi-square or Fisher’s exact tests and multivariate log-binomial regression were used to analyze the outcomes. Results A total of 1210 eligible women received ANC in the participating PHCUs and took part of this study (770 in the intervention group and 440 in the control group). 20.4% (157/770) of intervention-group women registered in PRENACEL, but only 116 read all messages (73.9% of women who registered in PRENACEL, 116/157). The adjusted intention-to-treat analysis suggested no difference between intervention and control groups in the primary outcome (Adjusted Relative Risk (AdjRR): 1.05 (95% Confidence Interval (CI): 1.00–1.09). Both crude and adjusted per-protocol analysis suggested a positive effect of PRENACEL (Crude RR (95% CI): 1.14 (1.06–1.22), AdjRR (95% CI): 1.12 (1.05–1.21). The multivariate analysis also suggests that the PRENACEL group (women who read all SMS) had higher mean ANC score [48.5 (±4.2) vs 45.2 (±8.7), p

The aim of this research is to study the impact of religious coping, social support and subjective severity on Posttraumatic Growth (PTG) in people who lost their homes after the earthquake in Chile in 2010 and who now live in transitional shelters. One hundred sixteen adult men and women were evaluated using a subjective severity scale, the Posttraumatic Growth Inventory (PTGI), the Multidimensional Scale of Perceived Social Support (MSPSS) scale of social support and the Brief RCOPE scale of religious coping. The multiple linear regression analysis shows that social support and positive religious coping have an impact on PTG. On using a bootstrap estimate, it was found that positive religious coping fully mediates the relationship between subjective severity and PTG.

Resumo: O PRENACEL é uma pesquisa que incorpora duas abordagens inovadoras para a saúde materna e perinatal: a necessidade de melhorar os níveis de satisfação das mulheres com a experiência do parto; e, a avaliação de impactos do uso de tecnologias de informação e comunicação em saúde. Trata-se de um programa de comunicação via mensagens curtas de textos no celular desenvolvido para gestantes brasileiras atendidas no pré-natal do Sistema Único de Saúde. Nesta análise, pretende-se determinar se o programa contribui positivamente para a percepção das mulheres de sentirem-se melhor preparadas para o parto. Um ensaio aleatorizado por conglomerados foi realizado em 20 unidades de saúde da atenção primária de Ribeirão Preto, São Paulo, entre 2015 e 2016. Dados de entrevista e revisão de prontuários foram coletados de 1210 mulheres. Estes foram submetidos a dois modelos de análise, por protocolo e intenção de tratamento. Receber informações do programa PRENACEL durante a gestação foi associado a um aumento na percepção das mulheres de se sentirem melhor preparadas para o parto, e na percepção de que o pré-natal colabora para que se sintam mais preparadas. Também foram observados impactos positivos no estabelecimento do contato pele a pele e aleitamento materno em sala de parto e no conhecimento sobre intervenções obstétricas. Não foram encontradas diferenças nos demais desfechos maternos e perinatais avaliados, incluindo a satisfação das mulheres com o atendimento ao parto. O PRENACEL pode contribuir com a ampliação do acesso das mulheres a informações que lhes sejam estratégicas para que se sintam mais bem preparadas para a experiência do parto.

Background: NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson's disease (PD)., Methods: Patients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations., Results: 310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa., Conclusions: This is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL)., Methods: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions., Results: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores., Conclusions: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Acting on the main target of dopaminergic cells, the striatal γ-aminobutyric acid (GABA)-ergic cells, might be a new way to treat persons with Parkinson's disease (PD)., Objective: The objective of this study was to assess the efficacy of bumetanide, an Na-K-Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD., Methods: This was a 4-month double-blind, randomized, parallel-group, placebo-controlled trial of 1.75 to 3 mg/day bumetanide as an adjunct to levodopa in 44 participants with PD and motor fluctuations., Results: Compared to the baseline, the mean change in OFF Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score after 4 months of treatment (primary endpoint) did not improve significantly compared with placebo. No changes between participants treated with bumetanide and those treated with placebo were observed for most other outcome measures. Despite no relevant safety signals, bumetanide was poorly tolerated., Conclusions: There was no evidence in this study that bumetanide has efficacy in improving motor symptoms of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: First, to investigate the patterns of [ 18 F]-FDOPA positron emission tomography imaging in corticobasal syndrome using visual and semi-quantitative analysis and to compare them with patterns found in Parkinson's disease and progressive supranuclear palsy. Then, to search for correlations with clinical features and [ 18 F]-FDG positron emission tomography imaging., Methods: 27 corticobasal syndrome patients who underwent [ 18 F]-FDOPA positron emission tomography imaging were retrospectively studied. They were compared to 27 matched Parkinson's disease patients, 12 progressive supranuclear palsy patients and 53 normal controls. Scans were visually assigned to one of the following patterns: normal; unilateral homogeneous striatal uptake reduction; putamen uptake reduction with putamen-caudate gradient. A semi-quantitative analysis of striatal regional uptake and asymmetry was performed and correlated to clinical features and [ 18 F]-FDG positron emission tomography patterns., Results: [ 18 F]-FDOPA positron emission tomography appeared visually abnormal in only 33.5% of corticobasal syndrome patients. However, semi-quantitative analysis found putaminal asymmetry in 63%. Striatal uptake was homogeneously reduced in both putamen and caudate nucleus in corticobasal syndrome patients unlike in Parkinson's disease and progressive supranuclear palsy. No correlation was found between [ 18 F]-FDOPA positron emission tomography and clinical features. Half of corticobasal syndrome patients presented a corticobasal degeneration pattern on [ 18 F]-FDG positron emission tomography.  CONCLUSION: [ 18 F]-FDOPA positron emission tomography can often be normal in corticobasal syndrome patients. Semi-quantitative analysis is useful to unmask a significant asymmetry in many of them. Homogeneous striatal uptake reduction contralateral to the clinical signs is highly suggestive of corticobasal syndrome. This finding can be helpful to better characterize this syndrome with respect to Parkinson's disease and progressive supranuclear palsy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. The Author(s).)

Body-worn sensors (BWS) could provide valuable information in the management of Parkinson's disease and support therapeutic decisions based on objective monitoring. To study this pivotal step and better understand how relevant information is extracted from BWS results and translated into treatment adaptation, eight neurologists examined eight virtual cases composed of basic patient profiles and their BWS monitoring results. Sixty-four interpretations of monitoring results and the subsequent therapeutic decisions were collected. Relationship between interrater agreements in the BWS reading and the severity of symptoms were analyzed via correlation studies. Logistic regression was used to identify associations between the BWS parameters and suggested treatment modifications. Interrater agreements were high and significantly associated with the BWS scores. Summarized BWS scores reflecting bradykinesia, dyskinesia, and tremor predicted the direction of treatment modifications. Our results suggest that monitoring information is robustly linked to treatment adaptation and pave the way to loop systems able to automatically propose treatment modifications from BWS recordings information., (© 2023. The Author(s).)

Background: Deep brain stimulation (DBS) has been proposed to treat disabling dystonic tremor (DT), but there is debate about the optimal target. DBS of the globus pallidus interna (GPi) may be insufficient to control tremor, and DBS of the ventral intermediate thalamic nucleus (VIM) may inadequately control dystonic features, raising the question of combining both targets., Objectives: To report the respective effects on DT symptoms of high-frequency stimulation of the VIM, the GPi and both targets simultaneously stimulated., Methods: Three patients with DT treated by bilateral high frequency DBS of 2 targets (VIM and GPi) were assessed 12 months after surgery in 4 conditions (VIM and GPi-DBS; GPi-DBS only; VIM-DBS only; DBS switched Off for both targets) by 3 independent movement disorders specialists blinded to the condition., Results: The Fahn-Tolosa-Marin-tremor-rating-scale (FTM-TRS) and Burke-Fahn-Marsden-dystonia-rating-scale (BFM-DRS) scores were more improved by combined DBS than VIM alone or GPi alone. Compared to Off/Off condition, mean total FTM-TRS score decrease was 34%, 42% and 63% respectively with VIM only, GPi only and combined VIM and GPi stimulation. Mean total BFM-DRS score decrease was 34%, 37% and 60% respectively with VIM only, GPi only and combined VIM and GPi stimulation, compared to Off/Off condition. Improvement concerned both motor, functional and activities of daily living sub-scores. No complications or adverse events were observed., Conclusion: Combined VIM- and GPi-DBS, by modulating the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network, both involved in DT pathophysiology, may be more efficient than single DBS targeting only one of them., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson's disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources., Objective: Our objective was to develop a predictive model combining clinical scores and imaging., Methods: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual valuesResults:Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p < 0.001). The models that added imaging features enhanced the performances: with T1w (R2 = 0.65 and 0.76, p < 0.001) and with R2* (R2 = 0.60 and 0.72, p < 0.001)., Conclusion: These results suggest that modeling is potentially a simple way to estimate dopa-sensitivity, but requires confirmation in a larger population, including patients with dopa-sensitivity < 30.

Background: Parkinson's disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes., Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups., Methods: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels., Results: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes., Conclusion: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.

Background and Objectives: To determine whether patients with Parkinson disease (PD) eligible for subthalamic nucleus deep brain stimulation (STN-DBS) with probable REM sleep behavior disorder (RBD) preoperatively could be more at risk of poorer motor, nonmotor, and quality of life outcomes 12 months after surgery compared to those without RBD., Methods: We analyzed the preoperative clinical profile of 448 patients with PD from a French multicentric prospective study (PREDISTIM) according to the presence or absence of probable RBD based on the RBD Single Question and RBD Screening Questionnaire. Among the 215 patients with PD with 12 months of follow-up after STN-DBS, we compared motor, cognitive, psycho-behavioral profile, and quality of life outcomes in patients with (pre-opRBD+) or without (pre-opRBD-) probable RBD preoperatively., Results: At preoperative evaluation, pre-opRBD+ patients were older (61 ± 7.2 vs 59.5 ± 7.7 years; p = 0.02), had less motor impairment (Movement Disorder Society-sponsored version of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] III "off": 38.7 ± 16.2 vs 43.4 ± 7.1; p = 0.03) but more nonmotor symptoms on daily living activities (MDS-UPDRS I: 12.6 ± 5.5 vs 10.7 ± 5.3; p < 0.001), had more psychobehavioral manifestations (Ardouin Scale of Behavior in Parkinson's Disease total: 7.7 ± 5.1 vs 5.1 ± 0.4; p = 0.003), and had worse quality of life (Parkinson's Disease Questionnaire-39: 33 ± 12 vs 29 ± 12; p = 0.03), as compared to pre-opRBD- patients. Both pre-opRBD+ and pre-opRBD- patients had significant MDS-UPDRS IV score decrease (-37% and -33%, respectively), MDS-UPDRS III "med 'off'/stim 'on'" score decrease (-52% and -54%), and dopaminergic treatment decrease (-52% and -49%) after surgery, with no between-group difference. There was no between-group difference for cognitive and global quality of life outcomes., Conclusions: In patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with a different clinical outcome 1 year after neurosurgery., Trial Registration Information: NCT02360683., Classification of Evidence: This study provides Class II evidence that in patients with PD eligible for STN-DBS, the presence of probable RBD preoperatively is not associated with poorer outcomes 1 year post surgery., (© 2021 American Academy of Neurology.)

Background and Objectives: Anti-IgLON5 disease is a recently described neurologic disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are underreported. We describe the frequency and types of movement disorders in a series of consecutive patients with this disease., Methods: In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by 3 experts in movement disorders., Results: Seventy-two patients were included. In 41 (57%), the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases., Discussion: Movement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment., (© 2021 American Academy of Neurology.)

Background: Diastolic function in patients with heart failure is usually impaired, resulting in increased left ventricular (LV) filling pressures, whose gold standard assessment is right heart catheterization (RHC). Hemodynamic force (HDF) analysis is a novel echocardiographic tool, providing an original approach to cardiac function assessment through the speckle-tracking technology. The aim of our study was to evaluate the use of HDFs, both alone and included in a new predictive model, as a potential novel diagnostic tool of the diastolic function. Methods: HDF analysis was retrospectively performed in 67 patients enrolled in the "Right1 study." All patients underwent RHC and echocardiography up to 2 h apart. Increased LV filling pressure (ILFP) was defined as pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg. Results: Out of 67 patients, 33 (49.2%) showed ILFP at RHC. Diastolic longitudinal force (DLF), the mean amplitude of longitudinal forces during diastole, was associated with the presence of ILFP (OR = 0.84 [0.70; 0.99], p = 0.046). The PCWP prediction score we built including DLF, ejection fraction, left atrial enlargement, and e' septal showed an AUC of 0.83 [0.76-0.89], with an optimal internal validation. When applied to our population, the score showed a sensitivity of 72.7% and a specificity of 85.3%, which became 66.7 and 94.4%, respectively, when applied to patients classified with "indeterminate diastolic function" according to the current recommendations. Conclusion: HDF analysis could be an additional useful tool in diastolic function assessment. A scoring system including HDFs might improve echocardiographic accuracy in estimating LV filling pressures. Further carefully designed studies could be useful to clarify the additional value of this new technology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Airale, Vallelonga, Forni, Leone, Magnino, Avenatti, Iannaccone, Astarita, Mingrone, Cesareo, Giordana, Omedè, Moretti, Veglio, Pedrizzetti and Milan.)

In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome, design and validate a clinical score to facilitate the identification of patients that should be tested for Kelch-like protein 11 antibodies, and examine in detail the nature of the immune response in both the brain and the tumour samples for a better characterization of the immunopathogenesis of this condition. The presence of Kelch-like protein 11 antibodies was retrospectively assessed in patients referred to the French Reference Center for paraneoplastic neurological syndrome and autoimmune encephalitis with (i) antibody-negative paraneoplastic neurological syndrome [limbic encephalitis ( n = 105), cerebellar degeneration ( n = 33)] and (ii) antibody-positive paraneoplastic neurological syndrome [Ma2-Ab encephalitis ( n = 34), antibodies targeting N-methyl-D-aspartate receptor encephalitis with teratoma ( n = 49)]. Additionally, since 1 January 2020, patients were prospectively screened for Kelch-like protein 11 antibodies as new usual clinical practice. Overall, Kelch-like protein 11 antibodies were detected in 11 patients [11/11, 100% were male; their median (range) age was 44 (35-79) years], 9 of them from the antibody-negative paraneoplastic neurological syndrome cohort, 1 from the antibody-positive (Ma2-Ab) cohort and 1 additional prospectively detected patient. All patients manifested a cerebellar syndrome, either isolated (4/11, 36%) or part of a multi-system neurological disorder (7/11, 64%). Additional core syndromes were limbic encephalitis (5/11, 45%) and myelitis (2/11, 18%). Severe weight loss (7/11, 64%) and hearing loss/tinnitus (5/11, 45%) were common. Rarer neurologic manifestations included hypersomnia and seizures (2/11, 18%). Two patients presented phenotypes resembling primary neurodegenerative disorders (progressive supranuclear palsy and flail arm syndrome, respectively). An associated cancer was found in 9/11 (82%) patients; it was most commonly (7/9, 78%) a spontaneously regressed ('burned-out') testicular germ cell tumour. A newly designed clinical score (MATCH score: male, ataxia, testicular cancer, hearing alterations) with a cut-off ≥4 successfully identified patients with Kelch-like protein 11 antibodies (sensitivity 78%, specificity 99%). Pathological findings (three testicular tumours, three lymph node metastases of testicular tumours, one brain biopsy) showed the presence of a T-cell inflammation with resulting anti-tumour immunity in the testis and one chronic, exhausted immune response-demonstrated by immune checkpoint expression-in the metastases and the brain. In conclusion, these findings suggest that Kelch-like protein 11 antibody paraneoplastic neurological syndrome is a homogeneous clinical syndrome and its detection can be facilitated using the MATCH score. The pathogenesis is probably T-cell mediated, but the stages of inflammation are different in the testis, metastases and the brain., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Levodopa (L-dopa) remains the basis of pharmacological treatment of Parkinson's disease (PD). However, L-dopa therapy is associated with the development of complications and presents major challenges in the long-term treatment. Thus, other medications may be suggested to delay and/or reduce the doses of L-dopa in order to prevent complications. The interpretation of treatment evolution reported in clinical trials on PD may be tricky, especially due to some variability in medications and dose regimens. Some authors have suggested a conversion factor to generate a total L-dopa equivalent daily dose (LEDD), calculated as a sum of each parkinsonian medication. Therefore, LEDD provides an artificial summary of the total daily medication a patient is receiving, and to date, there is no report focusing on the clinical interpretation of this parameter. Thus, based on a 3-year, multi-center retrospective study assessing the impact of second-line therapy initiation on LEDD in PD patients, the aim of our article was to discuss LEDD as a quantitative outcome to estimate the impact of second-line therapies on medication regimens; and in the second part of the discussion, to provide a narrative review of the clinical outcomes associated with LEDD in the literature., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)

Background: Ascending aorta (ASC) dilatation (AAD) is a common finding in arterial hypertension, affecting about 15% of hypertensive patients. AAD is associated with an increase in cardiac and vascular hypertension-related organ damage, but its prognostic role is unknown. The aim of the study was to evaluate the prognostic value of AAD as predictor of cardiovascular events in essential hypertensive patients., Methods: Recruited patients underwent two-dimensional transthoracic echocardiography from 2007 to 2013 and followed-up for cardiovascular events until November 2018 by phone call and hospital information system check. ASC diameter and AAD were defined using both absolute and scaled definitions. Four hundred and twenty-three hypertensive patients were included in our study., Results: During a median follow-up of 7.4 years (interquartile range 5.6-9.1 years), 52 events were observed. After adjusting for age, sex and BSA, both ASC diameter and AAD definition, according to ARGO-SIIA project, resulted associated with a greater risk of cardiovascular event (both P < 0.010), even after adjusting for major confounders (both P < 0.010). Moreover, we observed that the assessment of ASC improves risk stratification compared with pulse wave velocity alone, and that in absence of AAD, sinus of valsalva dilatation lost any prognostic value (P = 0.262)., Conclusions: ASC diameter and AAD are both associated with a greater risk of cardiovascular events. ASC should be assessed to optimize risk stratification in hypertensive patients and its dilatation may be considered as a surrogate for vascular organ damage., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting 'CVAEs risk score' distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.

Background: Impact of subthalamic deep brain stimulation (DBS) on impulse control disorders (ICD) in Parkinson's disease (PD) remains controversial., Objectives: The objectives of this study were to analyze the natural history of ICD between baseline and 1 year after subthalamic DBS in patients with PD and to identify predictive factors, taking into account the positions of the active contact and stimulation parameters., Methods: We analyzed postoperative modifications of ICD based on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. ICD status and Ardouin Scale of Behaviour in PD were assessed at baseline and 1 year following subthalamic DBS. Location of active contacts within the 3 subthalamic nucleus functional territories was investigated., Results: A total of 217 were patients included. Of the patients, 10.6% had ICD at baseline of which 95.6% improved at 1 year following subthalamic DBS; 3.6% of the patients experienced de novo ICD at 1 year following subthalamic DBS. Dopamine agonist dose reduction (from 309.8 to 109.3 mg) was the main driver of ICD regression (P = 0.05). Higher preoperative dyskinesias were associated with poorer ICD evolution (P = 0.04). Whereas baseline apathy was a risk factor of de novo ICD (P = 0.02), ICD improvement correlated with postoperative apathy (P = 0.004). Stimulation power and position of active contacts-mainly located within the sensorimotor part of the subthalamic nucleus-did not influence ICD., Conclusions: This 1-year, postoperative follow-up study showed ICD regression and dopaminergic drug reduction with optimal position of the active contacts within the subthalamic nucleus. Whereas patients with PD with preoperative ICD were prone to postoperative apathy, we also showed that those with preoperative apathy had a higher risk to experience postoperative de novo ICD, further highlighting the meaningful influence of postoperative management of dopaminergic medication on outcome and the continuum between apathy and ICD. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Objective: Meningeal involvement in Immunoglobulin G (IgG)-4-related disease is rare and only described in case reports and series. Because a review into the disease is lacking, we present 2 cases followed by a literature review of IgG4-related hypertrophic pachymeningitis (IgG4-HP)., Methods: Two IgG4-HP cases were reported, one involving the spinal cord and responding to surgical management and a second involving the brain and responding to Rituximab therapy. We then review clinical cases and case-series of histologically proven IgG4-HP that were published in the PubMed-NCBI database., Results: Forty-two case reports and 5 case-series were studied (60 patients, 20 women). The median age was 53. Eighteen patients had systemic involvement and 24 had single-organ IgG4-HP. Fifty-five percent of patients had an elevated serum IgG4. Treatment was surgical in 20/53 cases. Steroid therapy and immunosuppressors were effective in 85% and more than 90% of the cases, respectively. The rate of disease relapse was 42.1% after steroid therapy was discontinued., Discussion/conclusion: IgG4-HP is characterized by the lack of extra-neurologic organ-involvement and systemic signs. Histopathologic studies should be performed as it is crucial for diagnosis because serum markers are rarely informative. 18F-FDG positon tomography can be useful to characterize systemic forms. There is no specific CSF marker for IgG4-HP and the diagnostic value of CSF IgG4 levels needs to be studied with larger samples. We provide a treatment algorithm for IgG4-HP. Such treatment strategies rely on early surgery, steroids, and early immunosuppressive therapy to prevent neurologic complications.

Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new promising therapy for treatment resistant major depressive disorder (TR-MDD). While different DBS stimulating parameters may have an impact on the efficacy and safety of the therapy, there is no data to support a protocol for optimal stimulation parameters for depression. Here we present a prospective multi-center double-blind randomized crossed-over 13-month study that evaluated the effects of High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR-MDD. Four out of nine patients achieved response criteria (≥40% reduction of symptom score) compared to mean baseline values at the end of the study. The mean percent change of MADRS score showed a similar improvement in the high and low frequency stimulation groups after 6 months of stimulation (-15.4 ± 21.1 and -14.7 ± 21.1 respectively). The mean effect at the end of the second period (6 months after cross-over) was higher than the first period (first 6 months of stimulation) in all patients (-23.4 ± 19.9 (n = 6 periods) and -13.0 ± 22 (n = 9 periods) respectively). At the end of the second period, the mean percent change of the MADRS scores improved more in the high than low frequency groups (-31.3 ± 19.3 (n = 4 patients) and -7.7 ± 10.9 (n = 2 patients) respectively). Given the small numbers, detailed statistical analysis is challenging. Nonetheless the results of this study suggest that long term high frequency stimulation might confer the best results. Larger scale, randomized double blind trials are needed in order to evaluate the most effective stimulation parameters., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies., Methods: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques., Results: Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16., Conclusions: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele., (© 2017 American Academy of Neurology.)

After more than 50 years of treating Parkinson's disease with l-DOPA, there are still no guidelines on setting the optimal dose for a given patient. The dopamine transporter type 1, now known as solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3) is the most powerful determinant of dopamine neurotransmission and might therefore influence the treatment response. We recently demonstrated that methylphenidate (a dopamine transporter inhibitor) is effective in patients with Parkinson's disease with motor and gait disorders. The objective of the present study was to determine whether genetic variants of the dopamine transporter type 1-encoding gene (SLC6A3) are associated with differences in the response to treatment of motor symptoms and gait disorders with l-DOPA and methylphenidate (with respect to the demographic, the disease and the treatment parameters and the other genes involved in the dopaminergic neurotransmission). This analysis was part of a multicentre, parallel-group, double-blind, placebo-controlled, randomized clinical trial of methylphenidate in Parkinson's disease (Protocol ID:2008-005801-20; ClinicalTrials.gov:NCT00914095). We scored the motor Unified Parkinson's Disease Rating Scale and the Stand-Walk-Sit Test before and after a standardized acute l-DOPA challenge before randomization and then after 3 months of methylphenidate treatment. Patients were screened for variants of genes involved in dopamine metabolism: rs28363170 and rs3836790 polymorphisms in the SLC6A3 gene, rs921451 and rs3837091 in the DDC gene (encoding the aromatic L-amino acid decarboxylase involved in the synthesis of dopamine from l-DOPA), rs1799836 in the MAOB gene (coding for monoamine oxidase B) and rs4680 in the COMT gene (coding for catechol-O-methyltransferase). Investigators and patients were blinded to the genotyping data throughout the study. Eighty-one subjects were genotyped and 61 were analysed for their acute motor response to l-DOPA. The SLC6A3 variants were significantly associated with greater efficacy of l-DOPA for motor symptoms. The SLC6A3 variants were also associated with greater efficacy of methylphenidate for motor symptoms and gait disorders in the ON l-DOPA condition. The difference between motor Unified Parkinson's Disease Rating Scale scores for patients with different SLC6A3 genotypes was statistically significant in a multivariate analysis that took account of other disease-related, treatment-related and pharmacogenetic parameters. Our preliminary results suggest that variants of SLC6A3 are genetic modifiers of the treatment response to l-DOPA and methylphenidate in Parkinson's disease. Further studies are required to assess the possible value of these genotypes for (i) guiding l-DOPA dose adaptations over the long term; and (ii) establishing the risk/benefit balance associated with methylphenidate treatment for gait disorders., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)