Short and long term outcome of bilateral pallidal stimulation in chorea-acanthocytosis

BACKGROUND: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. METHODS: Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). RESULTS: Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥ 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. CONCLUSION: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc

Erratum : Pagonabarraga, J.; et al. A Spanish Consensus on the Use of Safinamide for Parkinson's Disease in Clinical Practice. Brain Sci. 2020, 10, 176

We would like to submit the following erratum to our recently published paper [1] due to the errors in the abstract. We request (1) the removal of the word “motor” from the first line of the abstract, so that the sentence reads: “Safinamide is an approved drug for the treatment of fluctuations in Parkinson’s disease (PD)”, and (2) that the word “OFF” is changed to “ON” in line 6 of the abstract, so that the sentence reads: “Safinamide significantly improves the mean daily ON time without troublesome dyskinesias.

Disrupted salience network dynamics in Parkinson's disease patients with impulse control disorders

Available online 16 December2019Background: Dynamic functional network analysis may add relevant information about the temporal nature of the neurocognitive alterations in PD patients with impulse control disorders (PD-ICD). Our aim was to investigate changes in dynamic functional network connectivity (dFNC) in PD-ICD patients, and topological properties of such networks. Methods: Resting state fMRI was performed on 16 PD PD-ICD patients, 20 PD patients without ICD and 17 healthy controls, whose demographic, clinical and behavioral scores were assessed. We conducted a group spatial independent component analysis, sliding window and graph-theory analyses. Results: PD-ICD patients, in contrast to PD-noICD and HC subjects, were engaged across time in a brain configuration pattern characterized by a lack of between-network connections at the expense of strong withinnetwork connections (State III) in temporal, frontoinsular and cingulate cortices, all key nodes of the salience network. Moreover, this increased maintenance of State III in PD-ICD patients was positively correlated with the severity of impulsivity and novelty seeking as measured by specific scales. While in State III, these patients also exhibited increased local efficiency in all the aforementioned areas. Conclusions: Our findings show for the first time that PD-ICD patients have a dynamic functional engagement of local connectivity involving the limbic circuit, leading to the inefficient modulation in emotional processing and reward-related decision-making. These results provide new insights into the pathophysiology of ICD in PD patients and indicate that the dFC study of fMRI could be a useful biomarker to identify patients at risk to develop ICD.This work was supported by the Carlos III Institute of Health [PI11/ 02109] and by the ERA-NET Neuron program [PIM2010ERN-00733]. I.N-G. held a Mobility of Research Staff 2017 grant [MV17/00015] from the Carlos III Institute of Health under the framework of a Rio Hortega 2016 grant [CM16/00033]. J.K. has no disclosures to declare. P.M.P-A was supported by grants from the Spanish Ministry of Economy and Competitiveness [MINECO, RYC-2014-15440 and PGC2018- 093408-B-I00], and Neuroscience Research Projects programme from the Fundación Tatiana Pérez de Guzmán el Bueno. BCBL acknowledges funding from the Basque Government through the BERC 2018–2021 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation [SEV-2015-0490]. A.P.S. is supported by the Canadian Institute of Health Research and Canada Research Chair program. M.C.R–O. received financial support for her research from national and local government institutions in Spain (Carlos III Institute of Health, Basque Country Government, Diputacion Foral Guipuzcoa and the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED))

Regression analysis between preoperative (PREOP) severity of motor impairment, as assessed by the Unified Huntington’s Disease Rating Scale-Motor Score (UHDRS-MS), and motor severity improvement at early and late post-operative time points (EPOP, panel A,

<p>For each patient, motor and functional improvements correspond to the difference between appropriate UHDRS scores at PREOP and EPOP or LOR time points.</p

Effect of deep brain stimulation on independence and functional impairment as assessed by the Unified Huntington’s Disease Rating Scale-Independence Score (UHDRS-IS) and UHDRS-Functional Capacity Score (UHDRS-FCS), respectively.

<p>Bar histograms (panels <b>A</b>, <b>D</b>) represent means ± SEM (n= 11 patients). Line plots (panels <b>B</b>, <b>C</b>, <b>E</b>, <b>F</b>) show individual values per patient plotted at each of three time points: 2-6 months preoperatively (PREOP), 1-5 months postoperatively (early post-operative: EPOP), and 6 months or more after surgery (last outcome reporting: LOR). Individual data curves are shown in panels <b>B</b> and <b>E</b>, whereas panels <b>C</b> and <b>F</b> depict percentage changes at EPOP and LOR with PREOP values set to 100% to make improvements and deteriorations easier to distinguish. *p&lt;0.05 <i>versus</i> the corresponding PREOP time point (Bonferroni test after ANOVA: F_{(2, 20)}= 4.72, p&lt; 0.05, n= 11, and F_{(2, 20)}= 5.94, p&lt; 0.01, n= 11, for UHDRS-IS and UHDRS-FCS, respectively).</p

Short and long term outcome of bilateral pallidal stimulation in chorea-acanthocytosis

BACKGROUND: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. METHODS: Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). RESULTS: Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥ 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. CONCLUSION: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc

Effect of deep brain stimulation on motor impairment as assessed by the Unified Huntington’s Disease Rating Scale-Motor Score (UHDRS-MS).

<p>Bar histograms (panel <b>A</b>) represent means ± SEM (n= 11 patients). Line plots (panels <b>B</b>, <b>C</b>) show individual values per patient plotted at each of three time points: 2-6 months preoperatively (PREOP), 1-5 months postoperatively (early post-operative: EPOP), and 6 months or more after surgery (last outcome reporting: LOR). Individual data curves are shown in panel <b>B</b>, whereas panel <b>C</b> depicts percentage changes at EPOP and LOR with PREOP values set to 100% to make improvements and deteriorations easier to distinguish. Scores of patient 7 correspond to the Burke-Fahn-Marsden Dystonia Rating Scale-Motor part (BFMDRS-M) [16]. **p&lt;0.01, ***p&lt;0.001 <i>versus</i> PREOP time point (Bonferroni test after ANOVA: F_{(2, 20)}= 15.11, p&lt; 0.001, n= 11).</p

Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson’s disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptom