Pub Date : 2025-02-10DOI: 10.1016/j.parkreldis.2025.107326
Lazzaro di Biase, Pasquale Maria Pecoraro, Vincenzo Di Lazzaro
Our pathology-validated study on Parkinson's disease aligns with recently reported findings in dementia with Lewy bodies regarding an inverse association with smoking. Understanding this epidemiological relationship is crucial for uncovering potential pathogenic mechanisms in α-synucleinopathies, emphasizing the need for rigorous studies that integrate neuropathological validation and address diagnostic uncertainty.
{"title":"Correspondence to \"The association between cigarette smoking and dementia with Lewy bodies\".","authors":"Lazzaro di Biase, Pasquale Maria Pecoraro, Vincenzo Di Lazzaro","doi":"10.1016/j.parkreldis.2025.107326","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107326","url":null,"abstract":"<p><p>Our pathology-validated study on Parkinson's disease aligns with recently reported findings in dementia with Lewy bodies regarding an inverse association with smoking. Understanding this epidemiological relationship is crucial for uncovering potential pathogenic mechanisms in α-synucleinopathies, emphasizing the need for rigorous studies that integrate neuropathological validation and address diagnostic uncertainty.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107326"},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-09DOI: 10.1016/j.parkreldis.2025.107313
Riya Sharma, C V Sai Teja, Aditya Nayan, Manoj K Goyal, Karthik V Mahesh, Ritu Shree, Chirag K Ahuja, Manish Modi
Adrenoleukodystrophy is the most common peroxisomal disorder of beta oxidation with highly complex clinical presentation across different ages of life challenging the diagnostic skills of neurologists. We report a 35-year-male with orbitofrontal lobar dysfunction, spastic paraparesis, cerebellar ataxia and characteristic perioral and palatal tremor with dentate nuclei calcification in imaging.
{"title":"Dentate calcifications with palatal tremor and facial myorhythmia in adult-onset cerebral X-linked adrenoleukodystrophy.","authors":"Riya Sharma, C V Sai Teja, Aditya Nayan, Manoj K Goyal, Karthik V Mahesh, Ritu Shree, Chirag K Ahuja, Manish Modi","doi":"10.1016/j.parkreldis.2025.107313","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107313","url":null,"abstract":"<p><p>Adrenoleukodystrophy is the most common peroxisomal disorder of beta oxidation with highly complex clinical presentation across different ages of life challenging the diagnostic skills of neurologists. We report a 35-year-male with orbitofrontal lobar dysfunction, spastic paraparesis, cerebellar ataxia and characteristic perioral and palatal tremor with dentate nuclei calcification in imaging.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107313"},"PeriodicalIF":3.1,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-08DOI: 10.1016/j.parkreldis.2025.107305
Wen Zhou, Qingqing Xia, Duan Liu, Jun ying Li, Liang Gong
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting quality of life. The onset of PD is thought to result from a multifaceted convergence of aging, genetic predisposition, and environmental exposure. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a specific measure of inflammation and nutrition, has been identified in the literature. No study has determined whether there are differences in inflammation and nutrition between sporadic and familial forms of PD.
Methods
A cross-sectional study was conducted involving 1036 participants from Parkinson's Progression Markers Initiative (PPMI), including sporadic PD (sPD) and familial PD (fPD). Data on demographics (age, sex, race, years of education, BMI, age of onset), clinical characteristics (Hoehn and Yahr Scale, Movement Disorder Society-Unified Parkinson's Disease Rating Scale(MDS-UPDRS) Part III Score, MDS-UPDRS Total Score, Montreal Cognitive Assessment, Epworth Sleepiness Scale Score, Geriatric Depression Scale Score, Rapid Eye Movement(REM) Sleep Behavior Disorder Questionnaire Score, caudate nucleus uptake value on dopamine transporter scan, putamen uptake value on dopamine transporter scan, striatum uptake value on dopamine transporter scan), and laboratory parameters (hemoglobin, lymphocytes, monocytes, neutrophils, platelets, blood glucose, uric acid, total protein, urea nitrogen, and albumin) were collected from all participants. Logistic regression and smooth curve fitting analyses were used to support the research objective.
Results
A total of 1036 patients aged between 29.26 and 85.88 years were included in the analysis. A high HALP level was associated with an increased risk of fPD (per 10 units: OR = 1.18, 95 % CI = 1.07–1.29, P = 0.001), after adjustment for potential confounders. In multivariable logistic regression analyses, the risk of fPD occurring in Q3 was 1.8 times that in the Q1 group (OR = 1.8, 95 % CI = 1.16–2.78, P = 0.009). In addition, the results of the subgroup and sensitivity analysis were robust.
Conclusion
This study highlights that HALP levels are associated with an increased risk of fPD, independent of confounders.
{"title":"The HALP score differs among sporadic and familial Parkinson's disease","authors":"Wen Zhou, Qingqing Xia, Duan Liu, Jun ying Li, Liang Gong","doi":"10.1016/j.parkreldis.2025.107305","DOIUrl":"10.1016/j.parkreldis.2025.107305","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting quality of life. The onset of PD is thought to result from a multifaceted convergence of aging, genetic predisposition, and environmental exposure. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a specific measure of inflammation and nutrition, has been identified in the literature. No study has determined whether there are differences in inflammation and nutrition between sporadic and familial forms of PD.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted involving 1036 participants from Parkinson's Progression Markers Initiative (PPMI), including sporadic PD (sPD) and familial PD (fPD). Data on demographics (age, sex, race, years of education, BMI, age of onset), clinical characteristics (Hoehn and Yahr Scale, Movement Disorder Society-Unified Parkinson's Disease Rating Scale(MDS-UPDRS) Part III Score, MDS-UPDRS Total Score, Montreal Cognitive Assessment, Epworth Sleepiness Scale Score, Geriatric Depression Scale Score, Rapid Eye Movement(REM) Sleep Behavior Disorder Questionnaire Score, caudate nucleus uptake value on dopamine transporter scan, putamen uptake value on dopamine transporter scan, striatum uptake value on dopamine transporter scan), and laboratory parameters (hemoglobin, lymphocytes, monocytes, neutrophils, platelets, blood glucose, uric acid, total protein, urea nitrogen, and albumin) were collected from all participants. Logistic regression and smooth curve fitting analyses were used to support the research objective.</div></div><div><h3>Results</h3><div>A total of 1036 patients aged between 29.26 and 85.88 years were included in the analysis. A high HALP level was associated with an increased risk of fPD (per 10 units: OR = 1.18, 95 % CI = 1.07–1.29, P = 0.001), after adjustment for potential confounders. In multivariable logistic regression analyses, the risk of fPD occurring in Q3 was 1.8 times that in the Q1 group (OR = 1.8, 95 % CI = 1.16–2.78, P = 0.009). In addition, the results of the subgroup and sensitivity analysis were robust.</div></div><div><h3>Conclusion</h3><div>This study highlights that HALP levels are associated with an increased risk of fPD, independent of confounders.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107305"},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-08DOI: 10.1016/j.parkreldis.2025.107314
Evridiki Asimakidou , Christos Sidiropoulos
Accumulating evidence points to a critical role of the immune system in the neurodegenerative process in Parkinson's disease (PD). This late knowledge has revolutionised our understanding of the pathogenetic mechanisms underlying PD and has opened new avenues toward disease-modifying rather than dopamine-replacement therapeutic approaches. When pharmacological treatments fail to adequately alleviate clinical symptoms, brain stimulation techniques are taken into consideration. Deep brain stimulation (DBS) constitutes the most common method for invasive brain stimulation, while the non-invasive brain stimulation paradigms comprise among others repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). How each brain stimulation paradigm interferes with disease pathogenesis still remains elusive. In light of recent evidence supporting the involvement of the immune system in PD, a question that arises is whether brain stimulation techniques have an immunomodulatory potential. Here, we summarize the existing knowledge and provide mechanistic insights that should foster future research. Overall, it appears that DBS and rTMS can modulate both the central and the peripheral component of the immune system and can lead to clinical improvement through immunosuppressive/anti-inflammatory mechanisms. The paucity of evidence for tDCS and tACS precludes any conclusions and highlights the necessity of more mechanistic studies focusing on their immunomodulatory potential, if any. Any pre-clinical findings warrant further clinical validation using human in vivo markers and post-mortem human brain tissue. Unravelling the mechanisms that underpin the beneficial therapeutic effects of brain stimulation in PD patients can contribute substantially to the fine-tuning of the current stimulation protocols and pave the way for more efficient and clinically meaningful neuromodulation paradigms.
{"title":"Immunomodulatory effects of invasive and non-invasive brain stimulation in Parkinson's disease","authors":"Evridiki Asimakidou , Christos Sidiropoulos","doi":"10.1016/j.parkreldis.2025.107314","DOIUrl":"10.1016/j.parkreldis.2025.107314","url":null,"abstract":"<div><div>Accumulating evidence points to a critical role of the immune system in the neurodegenerative process in Parkinson's disease (PD). This late knowledge has revolutionised our understanding of the pathogenetic mechanisms underlying PD and has opened new avenues toward disease-modifying rather than dopamine-replacement therapeutic approaches. When pharmacological treatments fail to adequately alleviate clinical symptoms, brain stimulation techniques are taken into consideration. Deep brain stimulation (DBS) constitutes the most common method for invasive brain stimulation, while the non-invasive brain stimulation paradigms comprise among others repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). How each brain stimulation paradigm interferes with disease pathogenesis still remains elusive. In light of recent evidence supporting the involvement of the immune system in PD, a question that arises is whether brain stimulation techniques have an immunomodulatory potential. Here, we summarize the existing knowledge and provide mechanistic insights that should foster future research. Overall, it appears that DBS and rTMS can modulate both the central and the peripheral component of the immune system and can lead to clinical improvement through immunosuppressive/anti-inflammatory mechanisms. The paucity of evidence for tDCS and tACS precludes any conclusions and highlights the necessity of more mechanistic studies focusing on their immunomodulatory potential, if any. Any pre-clinical findings warrant further clinical validation using human <em>in vivo</em> markers and post-mortem human brain tissue. Unravelling the mechanisms that underpin the beneficial therapeutic effects of brain stimulation in PD patients can contribute substantially to the fine-tuning of the current stimulation protocols and pave the way for more efficient and clinically meaningful neuromodulation paradigms.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107314"},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myoclonus, dystonia and parkinsonism due to a de novo novel variant in the NUS1 gene: Furthering the epilepsy-dyskinesia spectrum.","authors":"Divyani Garg, Sampurna Chowdhury, Sreeja Samineni, Ayush Agarwal, Achal Kumar Srivastava","doi":"10.1016/j.parkreldis.2025.107320","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107320","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107320"},"PeriodicalIF":3.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.parkreldis.2025.107322
Joohi Jimenez-Shahed , Irene A. Malaty , Michael Soileau , Connie H. Yan , Lakshmi Kandukuri , Jill Schinkel , Christie Teigland , Megha B. Shah , Pavnit Kukreja , Aaron Hambrick , Hubert H. Fernandez
Introduction
Surgical device-aided therapies (DATs), including carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS), are efficacious treatment options for people with advanced Parkinson's disease (aPD). While provider and patient preference influence treatment choices, DAT use remains low and social drivers of health (SDOH) may present barriers to access. This study aimed to evaluate the relationship of patient characteristics and SDOH—including geographic distance to facilities that provide DATs—with likelihood of receiving DAT.
Methods
Adults diagnosed with PD and meeting aPD clinical indicators were identified among 100 % Medicare Fee-for-Service beneficiaries linked to Inovalon's SDOH data warehouse between 01/01/2018-12/31/2020. Multivariate logistic regression models determined factors associated with DAT vs no-DAT initiation.
Results
Of 503,245 Medicare beneficiaries with PD, 22 % met proxy criteria for aPD, with 2 % (2450) receiving DAT (CLES 24 %; DBS 76 %). Nationwide aPD prevalence was 309 per 100,000 Medicare beneficiaries. There were 413 DAT facilities nationwide (average 8 facilities/state), and aPD patients traveled 98 miles on average to a facility (range 11–255 miles). aPD patients under age 75 were 2-3x more likely to receive DAT, while those identifying as female, Black race, have moderate to severe comorbidity, and lower household incomes were less likely to receive DAT.
Conclusions
Findings suggest low utilization of DATs among US Medicare beneficiaries with aPD. Even states with more DAT facilities often require patients to travel long distances. Identifying and minimizing access disparities, particularly for women, racial minorities, and people with low socioeconomic status may improve DAT utilization and outcomes for patients with aPD.
{"title":"Association of patient characteristics, social drivers of health, and geographic location on access to device-aided therapies among medicare beneficiaries with advanced Parkinson's disease","authors":"Joohi Jimenez-Shahed , Irene A. Malaty , Michael Soileau , Connie H. Yan , Lakshmi Kandukuri , Jill Schinkel , Christie Teigland , Megha B. Shah , Pavnit Kukreja , Aaron Hambrick , Hubert H. Fernandez","doi":"10.1016/j.parkreldis.2025.107322","DOIUrl":"10.1016/j.parkreldis.2025.107322","url":null,"abstract":"<div><h3>Introduction</h3><div>Surgical device-aided therapies (DATs), including carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS), are efficacious treatment options for people with advanced Parkinson's disease (aPD). While provider and patient preference influence treatment choices, DAT use remains low and social drivers of health (SDOH) may present barriers to access. This study aimed to evaluate the relationship of patient characteristics and SDOH—including geographic distance to facilities that provide DATs—with likelihood of receiving DAT.</div></div><div><h3>Methods</h3><div>Adults diagnosed with PD and meeting aPD clinical indicators were identified among 100 % Medicare Fee-for-Service beneficiaries linked to Inovalon's SDOH data warehouse between 01/01/2018-12/31/2020. Multivariate logistic regression models determined factors associated with DAT vs no-DAT initiation.</div></div><div><h3>Results</h3><div>Of 503,245 Medicare beneficiaries with PD, 22 % met proxy criteria for aPD, with 2 % (2450) receiving DAT (CLES 24 %; DBS 76 %). Nationwide aPD prevalence was 309 per 100,000 Medicare beneficiaries. There were 413 DAT facilities nationwide (average 8 facilities/state), and aPD patients traveled 98 miles on average to a facility (range 11–255 miles). aPD patients under age 75 were 2-3x more likely to receive DAT, while those identifying as female, Black race, have moderate to severe comorbidity, and lower household incomes were less likely to receive DAT.</div></div><div><h3>Conclusions</h3><div>Findings suggest low utilization of DATs among US Medicare beneficiaries with aPD. Even states with more DAT facilities often require patients to travel long distances. Identifying and minimizing access disparities, particularly for women, racial minorities, and people with low socioeconomic status may improve DAT utilization and outcomes for patients with aPD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107322"},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mostly known for its implication in synucleinopathies, including Parkinson's disease (PD), α-synuclein is predominantly expressed in the nervous system. Most of the peripheral α-synuclein is found in erythrocytes, and several studies have examined a possible association between erythrocytic α-synuclein and PD.
Methods
We have used a recently developed ELISA that selectively detects fibrillar and oligomeric α-synuclein to measure aggregated α-synuclein in red blood cells (RBCs) collected from PD patients and age/sex-matched control individuals (n = 35). The PD group included patients without any common mutation (genetically undetermined group, GU-PD, n = 56) as well as mutation carriers in the α-synuclein gene (A53T-PD, n = 28) and glucocerebrosidase gene (GBA-PD, n = 24).
Results
We found that the concentration of aggregated α-synuclein in erythrocytes was significantly increased in GU-PD patients compared to controls. A53T-PD and GBA-PD patients exhibited similar levels of erythrocytic aggregated α-synuclein as the control group. The levels of fibrillar/oligomeric α-synuclein in RBCs were reduced in respect to the age of control individuals suggesting that the observed increase in the GU-PD cohort was not due to normal aging. Parallel assessment of monomeric α-synuclein revealed that aggregated, but not total, α-synuclein could discriminate PD patients from control individuals.
Conclusions
The elevation of aggregated α-synuclein in GU-PD erythrocytes, which is not related to aging, suggests that these forms may be indicative of PD pathology and possibly accumulate upon disease establishment. As such, aggregated α-synuclein in RBCs could be a potential biomarker for PD diagnosis.
{"title":"Aggregated α-synuclein in erythrocytes as a potential biomarker for idiopathic Parkinson's Disease","authors":"Konstantina Dimoula , Nikolaos Papagiannakis , Matina Maniati , Leonidas Stefanis , Evangelia Emmanouilidou","doi":"10.1016/j.parkreldis.2025.107321","DOIUrl":"10.1016/j.parkreldis.2025.107321","url":null,"abstract":"<div><h3>Background</h3><div>Mostly known for its implication in synucleinopathies, including Parkinson's disease (PD), α-synuclein is predominantly expressed in the nervous system. Most of the peripheral α-synuclein is found in erythrocytes, and several studies have examined a possible association between erythrocytic α-synuclein and PD.</div></div><div><h3>Methods</h3><div>We have used a recently developed ELISA that selectively detects fibrillar and oligomeric α-synuclein to measure aggregated α-synuclein in red blood cells (RBCs) collected from PD patients and age/sex-matched control individuals (n = 35). The PD group included patients without any common mutation (genetically undetermined group, GU-PD, n = 56) as well as mutation carriers in the α-synuclein gene (A53T-PD, n = 28) and glucocerebrosidase gene (GBA-PD, n = 24).</div></div><div><h3>Results</h3><div>We found that the concentration of aggregated α-synuclein in erythrocytes was significantly increased in GU-PD patients compared to controls. A53T-PD and GBA-PD patients exhibited similar levels of erythrocytic aggregated α-synuclein as the control group. The levels of fibrillar/oligomeric α-synuclein in RBCs were reduced in respect to the age of control individuals suggesting that the observed increase in the GU-PD cohort was not due to normal aging. Parallel assessment of monomeric α-synuclein revealed that aggregated, but not total, α-synuclein could discriminate PD patients from control individuals.</div></div><div><h3>Conclusions</h3><div>The elevation of aggregated α-synuclein in GU-PD erythrocytes, which is not related to aging, suggests that these forms may be indicative of PD pathology and possibly accumulate upon disease establishment. As such, aggregated α-synuclein in RBCs could be a potential biomarker for PD diagnosis.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107321"},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05DOI: 10.1016/j.parkreldis.2025.107319
Antonia M. Stehr , Jan Fischer , Nazanin Mirza-Schreiber , Katerina Bernardi , Joseph Porrmann , Philip Harrer , Frank Kaiser , Rami Abou Jamra , Juliane Winkelmann , Robert Jech , Anne Koy , Konrad Oexle , Michael Zech
Introduction
Variable expressivity is an emerging characteristic of KMT2B-related dystonia. However, it remains poorly understood whether variants reoccurring at specific sites of lysine-specific methlytransferase-2B (KMT2B) can drive intra- and interfamilial clinical heterogeneity. Our goal was to ascertain independent families with variants affecting residue Arg2565 of KMT2B.
Methods
Whole-exome/genome sequencing, multi-site recruitment, genotype-phenotype correlations, and DNA methylation episignature analysis were performed.
Results
We report four individuals from two families harboring the variant c.7693C > G, p.Arg2565Gly. In an additional patient, a de-novo c.7693C > T, p.Arg2565Cys variant was identified. The observed phenotypic spectrum ranged from childhood-onset dystonia (N = 2) over unspecific intellectual disability syndromes (N = 2) to undiagnosed behavioral symptoms in adulthood (N = 1). Samples bearing p.Arg2565Gly had a KMT2B-typical episignature, although the effect on methylation was less pronounced than in carriers of loss-of-function KMT2B variants.
Conclusions
We established the existence of a KMT2B missense-mutation hotspot associated with varying degrees of disease severity and expression, providing information for patient counseling and elucidation of pathomechanisms.
{"title":"Variable expressivity of KMT2B variants at codon 2565 in patients with dystonia and developmental disorders","authors":"Antonia M. Stehr , Jan Fischer , Nazanin Mirza-Schreiber , Katerina Bernardi , Joseph Porrmann , Philip Harrer , Frank Kaiser , Rami Abou Jamra , Juliane Winkelmann , Robert Jech , Anne Koy , Konrad Oexle , Michael Zech","doi":"10.1016/j.parkreldis.2025.107319","DOIUrl":"10.1016/j.parkreldis.2025.107319","url":null,"abstract":"<div><h3>Introduction</h3><div>Variable expressivity is an emerging characteristic of <em>KMT2B</em>-related dystonia. However, it remains poorly understood whether variants reoccurring at specific sites of lysine-specific methlytransferase-2B (KMT2B) can drive intra- and interfamilial clinical heterogeneity. Our goal was to ascertain independent families with variants affecting residue Arg2565 of KMT2B.</div></div><div><h3>Methods</h3><div>Whole-exome/genome sequencing, multi-site recruitment, genotype-phenotype correlations, and DNA methylation episignature analysis were performed.</div></div><div><h3>Results</h3><div>We report four individuals from two families harboring the variant c.7693C > G, p.Arg2565Gly. In an additional patient, a <em>de-novo</em> c.7693C > T, p.Arg2565Cys variant was identified. The observed phenotypic spectrum ranged from childhood-onset dystonia (N = 2) over unspecific intellectual disability syndromes (N = 2) to undiagnosed behavioral symptoms in adulthood (N = 1). Samples bearing p.Arg2565Gly had a <em>KMT2B</em>-typical episignature, although the effect on methylation was less pronounced than in carriers of loss-of-function <em>KMT2B</em> variants.</div></div><div><h3>Conclusions</h3><div>We established the existence of a KMT2B missense-mutation hotspot associated with varying degrees of disease severity and expression, providing information for patient counseling and elucidation of pathomechanisms.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107319"},"PeriodicalIF":3.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.parkreldis.2025.107316
Meng-Lin Lee , Gong-Hong Lin , Yi-Ching Wang , Shih-Chieh Lee , Ching-Lin Hsieh
Introduction
The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a well-known measure to assess disability in persons with Parkinson's disease (PD). The purpose of this study was to develop a short form of the WHODAS 2.0 for persons with PD using a machine learning-based methodology (ML-WHODAS) and to examine the efficiency (i.e., number of items needed to be administered) and validity of the ML-WHODAS.
Methods
A secondary data analysis was performed. Data were randomly assigned to training datasets (80 %) and validation datasets (20 %). For developing the ML-WHODAS, the eXtreme Gradient Boosting (XGBoost) regressor was used to select the most informative items from the training datasets, and then the final XGBoost model was generated. The efficiency, concurrent validity, and convergent validity of the ML-WHODAS were then examined using the validation dataset.
Results
Data from 1633 patients were randomly assigned into the training dataset (1306) and the validation dataset (327). Eighteen items were selected for the ML-WHODAS to reproduce 6 domain scores and one global score of the original WHODAS 2.0. In the validation dataset, the Pearson's coefficients r between the scores of the ML-WHODAS and WHODAS 2.0 were 0.97–0.99, indicating very high concurrent validity. Significant correlations were found regarding convergent validity of the domain and global scores.
Conclusions
The ML-WHODAS showed good efficiency and validity compared to the WHODAS 2.0 in persons with PD. The ML-WHODAS demonstrates its potential as an alternative to the WHODAS 2.0, though further validations (e.g., test-retest reliability and responsiveness) are warranted.
{"title":"Machine Learning-based World Health Organization Disability Assessment Schedule for persons with Parkinson's disease","authors":"Meng-Lin Lee , Gong-Hong Lin , Yi-Ching Wang , Shih-Chieh Lee , Ching-Lin Hsieh","doi":"10.1016/j.parkreldis.2025.107316","DOIUrl":"10.1016/j.parkreldis.2025.107316","url":null,"abstract":"<div><h3>Introduction</h3><div>The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a well-known measure to assess disability in persons with Parkinson's disease (PD). The purpose of this study was to develop a short form of the WHODAS 2.0 for persons with PD using a machine learning-based methodology (ML-WHODAS) and to examine the efficiency (i.e., number of items needed to be administered) and validity of the ML-WHODAS.</div></div><div><h3>Methods</h3><div>A secondary data analysis was performed. Data were randomly assigned to training datasets (80 %) and validation datasets (20 %). For developing the ML-WHODAS, the eXtreme Gradient Boosting (XGBoost) regressor was used to select the most informative items from the training datasets, and then the final XGBoost model was generated. The efficiency, concurrent validity, and convergent validity of the ML-WHODAS were then examined using the validation dataset.</div></div><div><h3>Results</h3><div>Data from 1633 patients were randomly assigned into the training dataset (1306) and the validation dataset (327). Eighteen items were selected for the ML-WHODAS to reproduce 6 domain scores and one global score of the original WHODAS 2.0. In the validation dataset, the Pearson's coefficients r between the scores of the ML-WHODAS and WHODAS 2.0 were 0.97–0.99, indicating very high concurrent validity. Significant correlations were found regarding convergent validity of the domain and global scores.</div></div><div><h3>Conclusions</h3><div>The ML-WHODAS showed good efficiency and validity compared to the WHODAS 2.0 in persons with PD. The ML-WHODAS demonstrates its potential as an alternative to the WHODAS 2.0, though further validations (e.g., test-retest reliability and responsiveness) are warranted.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107316"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143376622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rehabilitation becomes increasingly important in the more advanced stages of Parkinson's Disease. As the disease reaches its more debilitating stages and pharmacological or surgical treatment becomes less relevant, non-pharmacological interventions including rehabilitation become key. Existing systematic interventions typically focus on individuals in the early to mid-stages of the disease. The objective of this scoping review was to identify and map the available evidence on non-pharmacological rehabilitation interventions for people living with advanced Parkinson's disease.
Methods
This scoping review was conducted following the methodology for scoping reviews developed by the Joanna Briggs Institute. A systematic search was conducted in PubMed, EMBASE, CINAHL, and Cochrane. Studies published in English from 2000 to May 2024 were considered eligible and screened for relevance.
Results
Thirteen studies were included. The majority of the interventions were experimental; one had a focus on feasibility and one had a mixed focus on effect and feasibility. Most interventions were referred to as either rehabilitation, training, or therapy, with the two feasibility interventions focusing on comprehensive assessment and referrals. The majority used modalities concerned with levels of functioning. Studies focusing on stage 4 (H&Y) Parkinson's disease were prominent.
Conclusions
This scoping review provides a foundational overview of existing non-pharmacological rehabilitation interventions for advanced Parkinson's disease, revealing a small yet diverse range of approaches, from single-disciplinary to multidisciplinary interventions. It offers initial insights that can point to areas where further research can solidify and expand effective, targeted care strategies for people living with advanced Parkinson's disease.
{"title":"Non-pharmacological rehabilitation for people living with advanced Parkinson's disease: A scoping review of interventions","authors":"Johanne Andersen Elbek , Birgitte Nørgaard , Tina Pedersen , Jette Thuesen","doi":"10.1016/j.parkreldis.2025.107317","DOIUrl":"10.1016/j.parkreldis.2025.107317","url":null,"abstract":"<div><h3>Background</h3><div>Rehabilitation becomes increasingly important in the more advanced stages of Parkinson's Disease. As the disease reaches its more debilitating stages and pharmacological or surgical treatment becomes less relevant, non-pharmacological interventions including rehabilitation become key. Existing systematic interventions typically focus on individuals in the early to mid-stages of the disease. The objective of this scoping review was to identify and map the available evidence on non-pharmacological rehabilitation interventions for people living with advanced Parkinson's disease.</div></div><div><h3>Methods</h3><div>This scoping review was conducted following the methodology for scoping reviews developed by the Joanna Briggs Institute. A systematic search was conducted in PubMed, EMBASE, CINAHL, and Cochrane. Studies published in English from 2000 to May 2024 were considered eligible and screened for relevance.</div></div><div><h3>Results</h3><div>Thirteen studies were included. The majority of the interventions were experimental; one had a focus on feasibility and one had a mixed focus on effect and feasibility. Most interventions were referred to as either rehabilitation, training, or therapy, with the two feasibility interventions focusing on comprehensive assessment and referrals. The majority used modalities concerned with levels of functioning. Studies focusing on stage 4 (H&Y) Parkinson's disease were prominent.</div></div><div><h3>Conclusions</h3><div>This scoping review provides a foundational overview of existing non-pharmacological rehabilitation interventions for advanced Parkinson's disease, revealing a small yet diverse range of approaches, from single-disciplinary to multidisciplinary interventions. It offers initial insights that can point to areas where further research can solidify and expand effective, targeted care strategies for people living with advanced Parkinson's disease.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"133 ","pages":"Article 107317"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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