ORCID Profile
0000-0003-3869-0564
Current Organisations
Université de Nantes
,
CHU Nantes
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Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.PARKRELDIS.2019.05.023
Abstract: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. At 1/5/12/24 months follow up, mean litude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Ω) and TEED (33.7/69.0/84.4/93.0 V2*μs*Hz/Ω) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 μs), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between typical (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. In the first 5 months an increase in litude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study.
Publisher: Oxford University Press (OUP)
Date: 2023
Publisher: Wiley
Date: 05-06-2023
DOI: 10.1002/MDC3.13795
Abstract: Monoallelic pathogenic variants of PRRT2 often result in paroxysmal kinesigenic dyskinesia (PKD). Little is known about health‐related quality of life (HrQoL), non‐motor manifestations, self‐esteem, and stigma in patients with PKD. We investigated non‐motor symptoms and how they related to HrQoL in a genetically homogeneous group of PRRT2 ‐PKD patients. We paid special attention to perceived stigmatization and self‐esteem. We prospectively enrolled 21 consecutive PKD patients with a pathogenic variant of PRRT2 , and 21 healthy controls matched for age and sex. They were evaluated with dedicated standardized tests for non‐motor symptoms, HrQoL, anxiety, depression, stigma, self‐esteem, sleep, fatigue, pain, and psychological well‐being. Patients reported an alteration of the physical aspects of HrQoL, regardless of the presence of residual paroxysmal episodes. Non‐motor manifestations were frequent, and were an important determinant of the alteration of HrQoL. In addition, patients perceived a higher level of stigmatization which positively correlated with a delay in diagnosis ( ρ = 0.615, P = 0.003 ) and the fear of being judged ( ρ = 0.452, P = 0.04 ), but not with the presence of paroxysmal episodes ( ρ = 0.203, P = 0.379 ). Our findings have important implications for care givers concerning patient management and medical education about paroxysmal dyskinesia. PRRT2 ‐PKD patients should be screened for non‐motor disorders in routine care. A long history of misdiagnosis may play a role in the high level of perceived stigmatization. Improving knowledge about diagnostic clues suggestive of PKD is mandatory.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.NBD.2018.07.016
Abstract: Slowly progressive, levodopa-responsive multiple system atrophy (MSA) may be misdiagnosed as Parkinson's disease (PD). Deep brain stimulation (DBS) is mostly ineffective in these patients and may even worsen the clinical course. Here we assessed whether neuropathological differences between patients with MSA who were treated with DBS of the subthalamic nucleus because of a misleading clinical presentation and typical disease cases may explain the more benign disease course of the former, and also the rapid clinical decline after surgery. The post-mortem assessment included the subthalamic nucleus, the globus pallidus, the thalamus and the putamen in five patients with MSA who received DBS and nine typical disease cases. There was no evidence for distinct neuroinflammatory profiles between both groups that could be related to the surgical procedure or that could explain the rapid clinical progression during DBS. Patients who received deep brain stimulation displayed a higher proportion of α-synuclein bearing neuronal cytoplasmic inclusions in the putamen compared with typical cases, while the number of surviving neurons was not different between groups. Our findings suggest that DBS does not induce neuroinflammatory changes in patients with MSA, at least several years after the surgery. We further hypothesize that the peculiar pattern of α-synuclein pathology may contribute to differences in the clinical phenotype, with a greater proportion of neuronal inclusions in the putamen being associated to a milder, "PD-like" phenotype with sustained levodopa response and slower disease progression.
Publisher: Wiley
Date: 02-2022
DOI: 10.1002/MDS.28952
Abstract: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) ~3.8 mm. The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to in idual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Publisher: Wiley
Date: 05-04-2022
DOI: 10.1002/MDS.29006
Abstract: ADCY5-related dyskinesia is characterized by early-onset movement disorders. There is currently no validated treatment, but anecdotal clinical reports and biological hypotheses suggest efficacy of caffeine. The aim is to obtain further insight into the efficacy and safety of caffeine in patients with ADCY5-related dyskinesia. A retrospective study was conducted worldwide in 30 patients with a proven ADCY5 mutation who had tried or were taking caffeine for dyskinesia. Disease characteristics and treatment responses were assessed through a questionnaire. Caffeine was overall well tolerated, even in children, and 87% of patients reported a clear improvement. Caffeine reduced the frequency and duration of paroxysmal movement disorders but also improved baseline movement disorders and some other motor and nonmotor features, with consistent quality-of-life improvement. Three patients reported worsening. Our findings suggest that caffeine should be considered as a first-line therapeutic option in ADCY5-related dyskinesia. © 2022 International Parkinson and Movement Disorder Society.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.PARKRELDIS.2022.08.025
Abstract: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.
Publisher: Hindawi Limited
Date: 03-12-2022
DOI: 10.1155/2022/1800567
Abstract: Introduction. In Parkinson’s disease (PD), the quality of life of both patients and caregivers is affected. While key issues relating to quality of life may not emerge in conversations with healthcare professionals (HCPs), unguarded social media conversations can provide insight into how people with Parkinson’s disease (PwPD) and their caregivers are affected. We conducted a qualitative and quantitative netnographic study of PD conversations posted on social media sites over a 12-month period. Objective. To identify key themes and issues for PwPD. Methods. Using predefined and piloted search terms, we identified 392,962 social media posts (between March 31, 2020, and March 31, 2021, for the UK and France, and between September 30, 2019, and March 31, 2021, for Italy, Spain, and Germany). A random s le of these posts was then analyzed using natural language processing (NLP), and quantitative, qualitative,in-depth contextual analysis was also performed. Results. Key themes that emerged in the PD conversation related to the changing experience of symptoms over time are the physical, emotional, and cognitive impact of symptoms, the management and treatment of PD, disease awareness among the general public, and the caregiver burden. The emotional impact of motor symptoms on PwPD is significant, particularly when symptoms increase and PwPD lose their independence, which may exacerbate existing anxiety and depression. Nonmotor symptoms can also compound the difficulties with managing the physical impact of motor symptoms. The burden of nonmotor symptoms is felt by both PwPD and their caregivers, with the impact of nonmotor symptoms on cognitive processes particularly frustrating for caregivers. The experience of off-time was also featured in the online conversation. Some PwPD believe there is a lack of adequate management from healthcare professionals, who may not appreciate their concerns or take sufficient time to discuss their needs. Conclusion. This study identified key themes that PwPD and their caregivers discuss online. These findings help signpost issues of importance to PwPD and areas in which their care may be improved.
Publisher: Wiley
Date: 03-12-2022
DOI: 10.1002/MDS.29282
Abstract: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN‐DBS) and best medical treatment (BMT) was superior to BMT alone. This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN‐DBS and BMT over 2 years, and secondary outcomes included non‐speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician‐ and patient‐reported assessments. STN‐DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation—for STN‐DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN‐DBS and BMT groups from baseline to 24 months. Over the 2‐year period, changes in speech intelligibility and MPT, as well as patient‐reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN‐DBS and BMT groups, on medication and OFF STN‐DBS, with patients in the STN‐DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN‐DBS was found for the in idual speech item of the Unified Parkinson's Disease Rating Scale, Part III. At this early stage of the patients' disease, STN‐DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient‐reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Publisher: Oxford University Press (OUP)
Date: 02-11-2022
DOI: 10.1093/BRAINCOMMS/FCAC319
Abstract: Idiopathic normal pressure hydrocephalus has a complex multifactorial pathogenesis and is associated with Alzheimer’s disease in many patients. To date, it is not well known if a similar association exists with behavioural variant of frontotemporal lobar degeneration. In a first step, we compare the prevalence of idiopathic normal pressure hydrocephalus in two groups of patients, one with behavioural variant of frontotemporal lobar degeneration (n = 69) and the other with Alzheimer’s disease (n = 178). In the second step, we describe more precisely the phenotype of patients with the association of idiopathic normal pressure hydrocephalus and behavioural variant of frontotemporal lobar degeneration. Firstly, we report that the prevalence of idiopathic normal pressure hydrocephalus was far higher in the group of patients with behavioural variant of frontotemporal lobar degeneration than in the group of patients with Alzheimer’s disease (7.25% and 1.1%, respectively, P = 0.02). Secondly, we show that patients with the double diagnosis share common clinical and para-clinical features of both idiopathic normal pressure hydrocephalus and behavioural variant of frontotemporal lobar degeneration patients, including CSF shunting efficacy in real-life experience. Overall, our results suggest a link between these two conditions and should encourage neurologists to look for idiopathic normal pressure hydrocephalus in their behavioural variant of frontotemporal lobar degeneration patients in the event of gait disturbances the benefit/risk balance could indeed be in favour of shunt surgery for selected patients with this newly described entity.
Location: France
No related grants have been discovered for Philippe DAMIER.