Movement Disorders最新文献

{"title":"Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy","authors":"Shawna R. Cook PhD,&nbsp;Cleo Schwarz MedVet,&nbsp;Julien Guevar DVM, MVM, DECVN, MRCVS,&nbsp;Charles-Antoine Assenmacher DVM, Msc, DACVP,&nbsp;Maeve Sheehy BS,&nbsp;Nathan Fanzone VMD,&nbsp;Molly E. Church MS, VMD, PhD,&nbsp;Leonardo Murgiano PhD,&nbsp;Margret L. Casal DVM, PhD,&nbsp;Vidhya Jagannathan PhD,&nbsp;Rodrigo Gutierrez-Quintana MVZ, MVM,&nbsp;Mark Lowrie MA, VetMB, MVM, DECVN, MRCVS,&nbsp;Frank Steffen DECVN,&nbsp;Tosso Leeb PhD,&nbsp;Kari J. Ekenstedt DVM, PhD","doi":"10.1002/mds.29977","DOIUrl":"10.1002/mds.29977","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in <i>RNF170</i> encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine <i>RNF170</i> variant was estimated at ~30 years, before the reproductive isolation of the MAS breed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>RNF170</i> variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2049-2057"},"PeriodicalIF":7.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Sleep Detection in Movement Disorders Using Deep Brain Stimulation and Machine Learning","authors":"Arjun Balachandar MD,&nbsp;Yosra Hashim,&nbsp;Okeanis Vaou MD,&nbsp;Alfonso Fasano MD, PhD, FAAN","doi":"10.1002/mds.29987","DOIUrl":"10.1002/mds.29987","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Automated sleep detection in movement disorders may allow monitoring sleep, potentially guiding adaptive deep brain stimulation (DBS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aims were to compare wake-versus-sleep status (WSS) local field potentials (LFP) in a home environment and develop biomarkers of WSS in Parkinson's disease (PD), essential tremor (ET), and Tourette's syndrome (TS) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five PD, 2 ET, and 1 TS patient were implanted with Medtronic Percept (3 STN [subthalamic nucleus], 3 GPi [globus pallidus interna], and 2 ventral intermediate nucleus). Over five to seven nights, β-band (12.5–30 Hz) and/or α-band (7–12 Hz) LFP power spectral densities were recorded. Wearable actigraphs tracked sleep.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From sleep to wake, PD LFP β-power increased in STN and decreased in GPi, and α-power increased in both. Machine learning classifiers were trained. For PD, the highest WSS accuracy was 93% (F1 = 0.93), 86% across all patients (F1 = 0.86). The maximum accuracy was 86% for ET and 89% for TS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Chronic intracranial narrowband recordings can accurately identify sleep in various movement disorders and targets in this proof-of-concept study. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2097-2102"},"PeriodicalIF":7.4,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha tACS Improves Cognition and Modulates Neurotransmission in Dementia with Lewy Bodies","authors":"Alberto Benussi MD,&nbsp;Valentina Cantoni PhD,&nbsp;Jasmine Rivolta MSc,&nbsp;Nicola Zoppi MD,&nbsp;Maria Sofia Cotelli MD,&nbsp;Marta Bianchi MD,&nbsp;Maria Cotelli PhD,&nbsp;Barbara Borroni MD","doi":"10.1002/mds.29969","DOIUrl":"10.1002/mds.29969","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dementia with Lewy bodies (DLB) is characterized by a marked shift of electroencephalographic (EEG) power and dominant rhythm, from the α toward the θ frequency range. Transcranial alternate current stimulation (tACS) is a non-invasive brain stimulation technique that allows entrainment of cerebral oscillations at desired frequencies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our goal is to evaluate the effects of occipital α-tACS on cognitive functions and neurophysiological measures in patients with DLB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a double-blind, randomized, sham-controlled, cross-over clinical trial in 14 participants with DLB. Participants were randomized to receive either α-tACS (60 minutes of 3 mA peak-to-peak stimulation at 12 Hz) or sham stimulation applied over the occipital cortex. Clinical evaluations were performed to assess visuospatial and executive functions, as well as verbal episodic memory. Neurophysiological assessments and EEG recordings were conducted at baseline and following both α-tACS and sham stimulations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Occipital α-tACS was safe and well-tolerated. We observed a significant enhancement in visuospatial abilities and executive functions, but no improvement in verbal episodic memory. We observed an increase in short latency afferent inhibition, a neurophysiological marker indirectly and partially dependent on cholinergic transmission, coinciding with an increase in α power and a decrease in Δ power following α-tACS stimulation, effects not seen with sham stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that occipital α-tACS is safe and enhances visuospatial and executive functions in patients with DLB. Improvements in indirect markers of cholinergic transmission and EEG changes indicate significant neurophysiological engagement. These findings justify further exploration of α-tACS as a therapeutic option for DLB patients. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"1993-2003"},"PeriodicalIF":7.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is SH3GL2 p.G276V the Causal Functional Variant Underlying Parkinson's Disease Risk at this Locus?","authors":"Alejandra Lázaro-Figueroa BSc,&nbsp;Ana Jimena Hernández-Medrano MSc,&nbsp;Diana Berenice Ramírez-Pineda BSc,&nbsp;Andrés Navarro Cadavid PhD,&nbsp;Mary Makarious BSc,&nbsp;Jia Nee Foo PhD,&nbsp;Chelsea X. Alvarado MSc,&nbsp;Sara Bandres-Ciga PhD,&nbsp;Maria Teresa Periñan PhD,&nbsp;the Global Parkinson's Genetics Program (GP2)","doi":"10.1002/mds.29719","DOIUrl":"10.1002/mds.29719","url":null,"abstract":"&lt;p&gt;We read with great interest the article by Bademosi and colleagues,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; where they investigated the role of &lt;i&gt;SH3GL2&lt;/i&gt; p.G276V on neuron dysfunction in Parkinson's disease (PD).&lt;/p&gt;&lt;p&gt;The &lt;i&gt;SH3GL2&lt;/i&gt; gene encodes the endophilin-A1 (EndoA1) protein, crucial for synaptic vesicle endocytosis and blood–brain barrier permeability regulation.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Two &lt;i&gt;SH3GL2&lt;/i&gt; independent signals have been identified to potentially increase PD risk in the latest European genome-wide association studies (GWAS) meta-analysis: rs13294100 and rs10756907.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Exome sequencing on a German cohort suggested the p.G276V variant as an independent PD risk factor. Bademosi et al&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; recently demonstrated that p.G276V impairs Ca2+ influx-induced synaptic autophagy without destabilizing EndoA1. The authors found that the human p.G276V protein was stable but showed a significant decrease in the number of autophagosomes compared with control neurons.&lt;/p&gt;&lt;p&gt;To clarify the association between &lt;i&gt;SH3GL2&lt;/i&gt; and PD, we leveraged whole-genome sequencing (WGS) data from the Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD; https://amp-pd.org/) release 3.0, consisting of 3,105 cases and 3,670 controls from European descent, and large-scale genotyping imputed data from the Global Parkinson's Genetics Program (GP2; https://gp2.org/) release 5.0, consisting of 12,728 cases and 10,533 controls from 10 different ancestries. Quality control analyses are described elsewhere (https://github.com/vitale199/GenoTools/). Variants were annotated using ANNOVAR, and Fisher's exact test was applied using PLINK 1.9. Summary statistics from the latest PD risk GWAS meta-analyses were assessed.&lt;span&gt;&lt;sup&gt;2-5&lt;/sup&gt;&lt;/span&gt; We leveraged data from the omicSynth data resource looking at quantitative trait loci (QTL). Gene-based burden analyses were performed by using RVTESTS.&lt;/p&gt;&lt;p&gt;We identified 14,590 &lt;i&gt;SH3GL2&lt;/i&gt; variants in AMP-PD (Supplementary Table S1). Likewise, 30,719 variants were identified in GP2 (Supplementary Table S1). The p.G276V variant was found in Europeans in both AMP-PD (one case, two controls) and GP2 (three cases, one control); however, no association was found with PD risk (AMP-PD: &lt;i&gt;P&lt;/i&gt; = 0.394, odds ratio [OR] = 1.296; GP2: &lt;i&gt;P&lt;/i&gt; = 0.869, OR = 1.034) (Table 1). This variant was also identified in GP2 in three African American (AAC) controls and one Ashkenazi Jew (AJ) PD patient.&lt;/p&gt;&lt;p&gt;No linkage disequilibrium (LD) was observed between p.G276V and the European GWAS lead single nucleotide polymorphisms (SNPs). Conditional analyses suggested that these variants were most likely independent signals. No significant association between &lt;i&gt;SH3GL2&lt;/i&gt; common genetic variation and PD risk was identified in the Latino nor Asian populations.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; The analysis of a multi-ancestry population&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; identified the intronic variant rs910316833 ","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2117-2119"},"PeriodicalIF":7.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor","authors":"Cletus Cheyuo MD, PhD,&nbsp;Jürgen Germann PhD,&nbsp;Kazuaki Yamamoto MD,&nbsp;Zion Zibly MD,&nbsp;Vibhor Krishna MD, PhD,&nbsp;Can Sarica MD,&nbsp;Yuri Ferreira Felloni Borges MD,&nbsp;Artur Vetkas MD, PhD,&nbsp;Suneil K. Kalia MD, PhD,&nbsp;Mojgan Hodaie MD,&nbsp;Alfonso Fasano MD, PhD,&nbsp;Michael L. Schwartz MD, MSc,&nbsp;W. Jeffrey Elias MD,&nbsp;Andres M. Lozano MD, PhD","doi":"10.1002/mds.29965","DOIUrl":"10.1002/mds.29965","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The post-MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (<i>p</i>_permute &lt; 0.05), with peak TDPD improvement (87%) at <i>x</i> = −13.5; <i>y</i> = −15.0; <i>z</i> = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder-specific voxel-wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (<i>R</i> = 0.8; <i>R</i>² = 0.64; <i>P</i> &lt; 0.0001). The model was validated using the independent cohort of nine TDPD patients (<i>R</i> = 0.73; <i>R</i>² = 0.53; <i>P</i> = 0.025—voxel analysis).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2004-2013"},"PeriodicalIF":7.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computerized Cognitive Training Increases Gray Matter Volumes in Huntington's Disease: A Pilot Study","authors":"Katharine Huynh BPsych (Hons),&nbsp;Nellie Georgiou-Karistianis PhD,&nbsp;Amit Lampit PhD,&nbsp;M. Navyaan Siddiqui BSc (Hons),&nbsp;Julie C. Stout PhD,&nbsp;Sharna D. Jamadar PhD","doi":"10.1002/mds.29972","DOIUrl":"10.1002/mds.29972","url":null,"abstract":"&lt;p&gt;Computerized cognitive training (CCT) aims to improve cognition through practice on tasks that invoke targeted cognitive domains. CCT improvements to cognition and gray matter structure have been found in healthy older adults and clinical populations.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; However, its effects in Huntington's disease (HD) have not been thoroughly examined.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;We conducted a pilot randomized controlled trial to examine the effects of CCT in pre-manifest and early-stage HD. Participants were randomized to either multidomain CCT (two 1-hour sessions weekly) or lifestyle education (monthly newsletters) over 3 months. A sub-sample of participants (n = 6 CCT, n = 10 lifestyle education) completed structural magnetic resonance imaging and cognitive assessments at baseline and follow up. We predicted increased or preserved gray matter volumes in the CCT group, compared to the lifestyle education group. Methods are provided in Supplementary Data S1.&lt;/p&gt;&lt;p&gt;There were no significant differences between groups on demographic or clinical variables at baseline (Supplementary Table S1). Adherence to CCT ranged from 96% to 100% (5/6 participants had 100% adherence). Voxel-based morphometry analyses showed that change in gray matter volumes between baseline and follow up significantly differed between groups in the left putamen, right Heschl's gyrus, right superior temporal gyrus, right middle cingulate, and right middle frontal gyrus (Fig. 1A). Analyses of simple effects (Fig. 1B; Supplementary Table S2) revealed that in all regions, except left putamen, volumes significantly decreased in the lifestyle education group and significantly increased in the CCT group. In left putamen, volume significantly decreased in the lifestyle education group and was preserved in the CCT group. Examination of individual effects showed consistency in directions of effects across participants in each group.&lt;/p&gt;&lt;p&gt;Exploratory correlations between changes in gray matter volumes and cognitive outcomes revealed positive correlations between increased volumes and improvement on various cognitive outcomes (Supplementary Data S2). Increased volumes in all regions correlated with improved performance on a task switching paradigm.&lt;/p&gt;&lt;p&gt;The brain regions showing significant change in volume (putamen, Heschl's gyrus, superior temporal gyrus, middle cingulate, and middle frontal gyrus) may be more responsive to CCT given their atrophy in the pre-manifest stage.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Similarly, deficits in task switching can occur decades prior to diagnosis as it engages a widespread brain network.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Although our results are susceptible to small sample bias and overestimated effect sizes, results are consistent with studies in older adults with similar training doses.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Although significant decline in gray matter volumes in the lifestyle education group over 3 months was unexpected, this may be due to ","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2119-2121"},"PeriodicalIF":7.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Movement Disorder as a Prodromal Symptom of Parkinson's Disease—Clinical and Pathophysiological Insights","authors":"Elie Matar MD, PhD,&nbsp;Michele Tinazzi MD, PhD,&nbsp;Mark J. Edwards MD, PhD,&nbsp;Kailash P. Bhatia MD, DM, FRCP","doi":"10.1002/mds.29958","DOIUrl":"10.1002/mds.29958","url":null,"abstract":"<p>Functional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow-up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"1952-1959"},"PeriodicalIF":7.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29958","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Particles, Big Potential: Polymeric Nanoparticles for Drug Delivery in Parkinson's Disease","authors":"Sasivimol Virameteekul MD, MSc,&nbsp;Andrew J. Lees MD, FRCP, FMedSci,&nbsp;Roongroj Bhidayasiri MD, FRCP","doi":"10.1002/mds.29939","DOIUrl":"10.1002/mds.29939","url":null,"abstract":"<p>Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood–brain barrier. © 2024 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"1922-1937"},"PeriodicalIF":7.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress in Musicians with and Without Focal Dystonia Is Not Reflected in Limbic Circuit Activation","authors":"Stine Alpheis MSc,&nbsp;Christopher Sinke PhD,&nbsp;Julian Burek,&nbsp;Tillmann H.C. Krüger MD,&nbsp;Eckart Altenmüller MD,&nbsp;Daniel S. Scholz PhD","doi":"10.1002/mds.29941","DOIUrl":"10.1002/mds.29941","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Musicians' dystonia (MD) is a movement disorder with several established risk factors, but the exact pathophysiology remains unknown. Recent research suggests dysfunction in sensory-motor, basal ganglia, cerebellar, and limbic loops as potential causes. Adverse childhood experiences are also considered risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate whether MD patients have experienced more childhood trauma, leading to increased stress reactivity and neural vulnerability to movement disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using functional magnetic resonance imaging and the Montreal Imaging Stress Task, 40 MD patients were compared with 39 healthy musicians (HMs). Whole-brain analysis and regions of interest analysis were performed. Parameter estimates and subjective stress levels were compared between groups and correlated with the Childhood Trauma Questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MD patients reported significantly higher childhood trauma scores than healthy control subjects, but they did not differ in their subjective stress experiences. Stress-related activity of limbic areas was neither found in the whole sample nor between the two groups. Instead, increased activity of visual association and temporal areas was observed, but this activation did not differ between patients and HMs. However, patients showed a tendency toward reduced precuneus activity under stress. Adverse childhood experiences were negatively correlated with precuneus, thalamus, and substantia nigra activity across all participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, MD patients and HMs had similar subjective and neurological reactions to stress but differed in childhood trauma experiences and precuneus activity under stress. Further research about the functional connectivity between precuneus, cerebellum, thalamus, and basal ganglia in musicians is needed. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2075-2086"},"PeriodicalIF":7.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: A Randomized Trial","authors":"Lukas L. Goede MD,&nbsp;Simon Oxenford,&nbsp;Daniel Kroneberg MD,&nbsp;Garance M. Meyer PhD,&nbsp;Nanditha Rajamani,&nbsp;Clemens Neudorfer MD,&nbsp;Patricia Krause MD,&nbsp;Roxanne Lofredi MD,&nbsp;Michael D. Fox MD, PhD,&nbsp;Andrea A. Kühn MD,&nbsp;Andreas Horn MD, PhD","doi":"10.1002/mds.29940","DOIUrl":"10.1002/mds.29940","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Recent imaging studies identified a brain network associated with clinical improvement following deep brain stimulation (DBS) in Parkinson's disease (PD), the PD response network.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to assess the impact of neuromodulation on PD motor symptoms by targeting this network noninvasively using multifocal transcranial direct current stimulation (tDCS).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In a prospective, randomized, double-blinded, crossover trial, 21 PD patients (mean age 59.7 years, mean Hoehn &amp; Yahr [H&amp;Y] 2.4) received multifocal tDCS targeting the a-priori network. Twenty-minute sessions of tDCS and sham were administered on 2 days in randomized order. Movement Disorder Society-Unified Parkinson's Disease Rating Scale—Part III (MDS-UPDRS-III) scores were assessed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Before intervention, MDS-UPDRS-III scores were comparable in both conditions (stimulation days: 37.38 (standard deviation [SD] = 12.50, confidence interval [CI] = 32.04, 42.73) vs. sham days: 36.95 (SD = 13.94, CI = 30.99, 42.91), &lt;i&gt;P&lt;/i&gt; = 0.63). Active stimulation resulted in a reduction by 3.6 points (9.7%) to 33.76 (SD = 11.19, CI = 28.98, 38.55) points, whereas no relevant change was observed after sham stimulation (36.43 [SD = 14.15, CI = 30.38, 42.48], average improvement: 0.5 [1.4%]). Repeated-measures analysis of variance (ANOVA) confirmed significance (main effect of time: F&lt;sub&gt;(1,20)&lt;/sub&gt;=4.35, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). Tukey's post hoc tests indicated MDS-UPDRS-III improvement after active stimulation (&lt;i&gt;t&lt;/i&gt; [20] = 2.9, &lt;i&gt;P&lt;/i&gt; = 0.03) but not after sham (&lt;i&gt;t&lt;/i&gt; [20] = 0.42, &lt;i&gt;P&lt;/i&gt; &gt; 0.05). In a subset of patients that underwent DBS surgery later, their DBS response correlated with tDCS effects (&lt;i&gt;R&lt;/i&gt; = 0.55, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;(1)&lt;/sub&gt; = 0.04).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Noninvasive, multifocal tDCS targeting a DBS-derived network significantly improved PD motor symptoms. Despite a small effect size, this study provides proof of principle for the successful noninvasive neuromodulation of an invasively identified network. Future studies should investigate repeated tDCS sessions and their utility for screening before DBS surgery. © 2024 The Author(s). &lt;i&gt;Movement Disorders&lt;/i&gt; published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.&lt;/p&gt;\u0000 ","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"1971-1981"},"PeriodicalIF":7.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}