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      Sex Disparities in the Self-Evaluation of Subthalamic Deep Brain Stimulation Effects on Mood and Personality in Parkinson's Disease Patients

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          Abstract

          Changes in personality are one of the main concerns Parkinson's disease (PD) patients raise when facing the decision to undergo neurosurgery for deep brain stimulation (DBS) of the subthalamic nucleus (STN). While clinical instruments for monitoring functional changes following DBS surgery are well-established in the daily therapeutic routine, personality issues are far less systematically encompassed. Moreover, while sex disparities in the outcomes of STN-DBS therapy have been reported, little is known about the different effects that DBS treatment may have on mood and personality traits in female and male patients. To this aim, the effect of STN-DBS on personality traits was assessed in 46 PD patients (12 women and 34 men) by means of the Freiburg Personality Inventory. The Becks Depression Inventory (BDI-I) and the Parkinson's Disease Questionnaire were used to evaluate patients' level of depression and quality of life (QoL). Patients completed the questionnaires a few days before, within the first year, and 2 years after surgery. The 12 personality traits defined by the FPI-R questionnaire did not change significantly after STN-DBS surgery ( p = 0.198). Women declared higher depression scores through all study stages ( p = 0.009), but also showed a stronger QoL amelioration after surgery than male patients ( p = 0.022). The BDI-I scores of female patients clearly correlated with their levodopa equivalent daily dose (LEDD; r = 0.621, p = 0.008). Remarkably, in both male and female patients, higher pre-operative LEDDs were related to worse post-operative QoL scores ( p = 0.034). These results mitigate the concerns about systematic personality changes due to STN-DBS treatment in PD patients and encourage an early DBS approach, before severe levodopa-induced sequelae may irreparably compromise the patients' QoL. In the future, more focus should lie on sex-related effects, since female patients seem to profit more than male patients from STN-DBS, in terms of reduced depressive symptoms associated with a reduction of the LEDD and amelioration of QoL. These aspects may help to redress the sex imbalance in PD patients treated with DBS, given that women are still strongly under-represented.

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          Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism.

          Deep brain stimulation (DBS) of the subthalamic nucleus markedly improves the motor symptoms of Parkinson's disease, but causes cognitive side effects such as impulsivity. We showed that DBS selectively interferes with the normal ability to slow down when faced with decision conflict. While on DBS, patients actually sped up their decisions under high-conflict conditions. This form of impulsivity was not affected by dopaminergic medication status. Instead, medication impaired patients' ability to learn from negative decision outcomes. These findings implicate independent mechanisms leading to impulsivity in treated Parkinson's patients and were predicted by a single neurocomputational model of the basal ganglia.
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            Neurosurgery in Parkinson disease: a distressed mind in a repaired body?

            To prospectively evaluate the impact of subthalamic nucleus (STN) stimulation on social adjustment in patients with Parkinson disease (PD). Before and 18 to 24 months after bilateral STN stimulation, the authors assessed 29 patients with PD for motor disability, cognition (Mattis dementia rating scale, frontal score), psychiatric morbidity (Mini-5.0.0, MADRS, BAS), quality of life (PDQ-39), social adjustment (Social Adjustment Scale), and psychological status using unstructured in-depth interviews. Despite marked improvement in parkinsonian motor disability, the absence of significant changes in cognitive status, and improvement of activities of daily living and quality of life by the end of the study, social adjustment did not improve. Several kinds of problems with social adjustment were observed, affecting the patients' perception of themselves and their body, marital situation, and professional life. Marital conflicts occurred in 17/24 couples. Only 9 out of 16 patients who had a professional activity before the operation went back to work after surgery. After STN stimulation, patients experienced difficulties in their relations with themselves, their spouses, their families, and their socio-professional environment. The authors suggest a multidisciplinary psychosocial preparation and follow-up to help patients and their entourage cope with the sudden changes in their existence following successful neurosurgery.
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              The relevance of gender in Parkinson's disease: a review.

              Since the official and systematic inclusion of sex and gender in biomedical research, gender differences have been acknowledged as important determinants of both the susceptibility to develop neurodegenerative diseases in general population and the clinical and therapeutic management of neurodegenerative patients. In this review, we gathered the available evidence on gender differences in Parkinson's disease (PD) regarding clinical phenotype (including motor and non-motor symptoms), biomarkers, genetics and therapeutic management (including pharmacological and surgical treatment). Finally, we will briefly discuss the role of estrogens in determining such differences. Several data demonstrate that PD in women starts with a more benign phenotype, likely due to the effect of estrogens. However, as the disease progresses, women are at higher risk of developing highly disabling treatment-related complications, such as motor and non-motor fluctuations as well as dyskinesia, compared with men. In addition, women have lower chances of receiving effective treatment for PD as deep brain stimulation. Taken together these findings challenge the definition of a more benign phenotype in women. Still, much work needs to be done to better understand the interaction between gender, genetics and environmental factors in determining the PD risk and clinical features. Improving our understanding in this field may result in implementation of strategies to identify prodromal PD and speed efforts to discern new directions for disease tailored treatment and management.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                31 July 2020
                2020
                : 11
                : 776
                Affiliations
                [1] 1Department of Neurosurgery, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [2] 2Department of Neurology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [3] 3Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [4] 4Neurological Outpatient Clinic for Parkinson's Disease and Deep Brain Stimulation , Gera, Germany
                [5] 5Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                Author notes

                Edited by: Maria Fiorella Contarino, Leiden University Medical Center, Netherlands

                Reviewed by: Juan Carlos Martinez Castrillo, Ramón y Cajal University Hospital, Spain; Erwin Montgomery, McMaster University, Canada; Antonella Macerollo, University College London, United Kingdom

                *Correspondence: Alessandro Gulberti a.gulberti@ 123456uke.de

                This article was submitted to Movement Disorders, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2020.00776
                7412792
                32849228
                ec61cef8-aafc-4648-8438-f7238f4841e5
                Copyright © 2020 Dietrich, Koeppen, Buhmann, Pötter-Nerger, Pinnschmidt, Oehlwein, Oehlwein, Mittmann, Gerloff, Engel, Westphal, Schaper, Hamel, Moll and Gulberti.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 February 2020
                : 24 June 2020
                Page count
                Figures: 7, Tables: 4, Equations: 0, References: 96, Pages: 15, Words: 11843
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Categories
                Neurology
                Original Research

                Neurology
                parkinson's disease,deep brain stimulation,subthalamic nucleus,personality traits,depression,non-motor symptoms,quality of life,sex differences

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