当前期刊: Parkinsonism & Related Disorders Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Gait characterization for patients with orthostatic tremor
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2020-01-17
    Enrico Opri; Wei Hu; Zakia Jabarkheel; Christopher Hess; Abigail C. Schmitt; Aysegul Gunduz; Chris J. Hass; Michael S. Okun; Aparna Wagle Shukla

    Introduction Orthostatic tremor (OT) patients frequently report gait unsteadiness with the advancement of disease; however, there is little understanding of its physiology. We sought to examine in OT, the spatial and temporal characteristics of gait, and the relationship with tremor physiology. Methods Gait parameters for OT (n = 16) were recorded with an instrumented Zeno walkway system. All participants complained of gait unsteadiness, especially during slow walking. In a subset of OT, recordings were synchronized with a wireless EMG system for tremor assessment and feet pressure recording. Gait assessments were performed at self-selected habitual, fast, and slow speeds. Results Compared to data available for an age- and sex-matched healthy controls, OT patients had a significantly reduced step length, increased step width, and increased gait variability (p < 0.0001). Tremor discharges related to OT were consistently recorded across three different speeds of walking. These discharges persisted through all phases of the gait cycle, including the swing phase when the limb was not weight-bearing. The highest tremor amplitude was recorded in the single support phase, followed by double support, and least during the swing phase. Conclusion OT patients have distinct gait abnormalities similar to cerebellar disorders. Tremor discharges from the non-weight bearing leg in the swing phase suggests that muscle contractions, even when occurring without resistance, contribute to OT generation.

    更新日期:2020-01-17
  • Cortical thickness in visuo-motor areas is related to motor outcomes after STN DBS for Parkinson's disease
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2020-01-17
    Leonardo A. Frizon; Raghavan Gopalakrishnan; Olivia Hogue; Darlene Floden; Sean J. Nagel; Kenneth B. Baker; Gustavo R. Isolan; Marco A. Stefani; Andre G. Machado

    Introduction Deep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome. Methods Using freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons. Results Based on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis. Conclusions Our data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers.

    更新日期:2020-01-17
  • Does acute peripheral trauma contribute to idiopathic adult-onset dystonia?
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2020-01-13
    Giovanni Defazio; Giovanni Fabbrini; Roberto Erro; Alberto Albanese; Maurizio Zibetti; Marcello Esposito; Roberta Pellicciari; Laura Avanzino; Francesco Bono; Roberto Eleopra; Laura Bertolasi; Maria Concetta Altavista; Maria Sofia Cotelli; Roberto Ceravolo; Cesa Scaglione; Anna Rita Bentivoglio; Giovanni Cossu; Mario Coletti Moja; Nicola Modugno

    Background Acute peripheral trauma is a controversial risk factor for idiopathic dystonia. Materials and methods We retrospectively analyzed data from the Italian Dystonia Registry regarding the occurrence of acute peripheral trauma severe enough to require medical attention in 1382 patients with adult-onset idiopathic dystonia and 200 patients with acquired adult-onset dystonia. Results Patients with idiopathic and acquired dystonia showed a similar burden of peripheral trauma in terms of the number of patients who experienced trauma (115/1382 vs. 12/200, p = 0.3) and the overall number of injuries (145 for the 1382 idiopathic patients and 14 for the 200 patients with secondary dystonia, p = 0.2). Most traumas occurred before the onset of idiopathic or secondary dystonia but only a minority of such injuries (14 in the idiopathic group, 2 in the acquired group, p = 0.6) affected the same body part as that affected by dystonia. In the idiopathic group, the elapsed time between trauma and dystonia onset was 8.1 ± 9.2 years; only six of the 145 traumas (4.1%) experienced by 5/1382 idiopathic patients (0.36%) occurred one year or less before dystonia onset; in the acquired dystonia group, the two patients experienced prior trauma to the dystonic body part 5 and 6 years before dystonia development. Discussion and conclusion Our data suggest that the contribution of peripheral acute trauma to idiopathic dystonia is negligible, if anything, and likely involves only a small subset of patients.

    更新日期:2020-01-13
  • Upper camptocormia in Parkinson's disease: Neurophysiological and imaging findings of both central and peripheral pathophysiological mechanisms
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2020-01-11
    Francesca Magrinelli; Christian Geroin; Giovanna Squintani; Marialuisa Gandolfi; Giulio Rizzo; Marco Barillari; Gaetano Vattemi; Francesca Morgante; Michele Tinazzi

    Background Camptocormia is a disabling complication of Parkinson's disease (PD), but its pathophysiology is poorly elucidated. Depending on the fulcrum of forward trunk flexion, two subtypes have been defined, upper (UCC) and lower camptocormia, the former being much more frequent. The aim of the study was to explore possible pathophysiological mechanisms of PD-related UCC. Methods Ten PD patients with UCC (UCC-PD) and ten PD patients without camptocormia (NoUCC-PD) underwent simultaneous electromyography (EMG) of thoracic paraspinal (TPS), obliquus externus abdominis (OEA), rectus abdominis (RA), and iliopsoas (IP) muscles during relaxed standing (both groups) and trunk realignment (UCC-PD group). Quantitative EMG and magnetic resonance imaging (MRI) of TPS muscles were also performed. Results UCC-PD patients showed hyperactivity of TPS and OEA muscles in quiet stance. During voluntary trunk extension, hyperactivity of OEA muscles persisted, thus revealing a co-contraction of flexor and extensor trunk muscles. Motor unit potentials (MUP) of TPS muscles showed shorter duration (p = 0.005) and lower amplitude (p = 0.004) in UCC-PD than in NoUCC-PD patients. MRI did not detect significant between-group differences in the cross-sectional area and fat fraction of TPS muscles, although the latter was higher in the UCC-PD than in the NoUCC-PD group at all thoracic levels. Conclusion Our findings suggest that hyperactivity of OEA might sustain UCC in PD. Concurrent mild myopathic changes in TPS muscles in PD with UCC may be secondary to muscle disuse but nevertheless may contribute to abnormal trunk posture.

    更新日期:2020-01-13
  • Real world use of a neurophysiology service for the differential diagnosis of hyperkinetic movement disorders
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2020-01-11
    Sacha E. Gandhi; Monty A. Silverdale; Deborah Mercer; Andrew G. Marshall; Christopher Kobylecki

    Introduction Clinical neurophysiology constitutes a potentially useful aid in differentiating hyperkinetic movement disorders (HMD). Parameters including presence of a Bereitschaftspotential on back-averaged electroencephalography (EEG) have been demonstrated to help distinguish between these disorders. In 2008, a Movement Disorder neurophysiology service was established in Greater Manchester to aid in the diagnostic process. Methods We retrospectively reviewed records of 39 patients with HMD who underwent EEG back-averaging through this service from January 2009 until January 2018. The aim was (i) to characterise the clinical characteristics of our patient cohort and (ii) to determine how frequently neurophysiological testing altered the final diagnosis. Results A total of 39 patients (23 females, 16 males), with a mean age at onset of 42.6 years and mean disease duration of 2.0 years underwent neurophysiological examination. The clinical diagnosis was changed in 16 cases (41%) and refined in a further seven. Distractibility (P = 0.001), variability (P = 0.002), the presence of a Bereitschaftspotential (P < 0.0001), and electromyography burst duration > 300 ms (P = 0.012) were more frequent in those with an eventual diagnosis of functional movement disorder (n = 24) compared to other HMDs (n = 15). Conclusion Neurophysiology is an invaluable adjunct in complex HMD, altering the diagnosis and treatment options for a significant proportion of patients. Our data also demonstrate, consistent with previous studies, that the majority of patients referred for jerky HMDs to a tertiary movement disorder service have a functional movement disorder.

    更新日期:2020-01-11
  • Co-Existence of tau and α-synuclein pathology in fetal graft tissue at autopsy: A case report
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2020-01-11
    Abbie S. Ornelas; Charles H. Adler; Geidy E. Serrano; Jasmine R. Curry; Holly A. Shill; Oleg Kopyov; Thomas G. Beach

    Introduction Transplant of fetal ventral mesencephalic tissue into the striatum of Parkinson's disease (PD) patients has been performed to increase dopamine production and stimulate neuronal regeneration. Analysis of fetal graft tissue at autopsy has demonstrated 6 cases of α-synuclein pathology in PD patients, one case with both α-synuclein and tau pathology in a PD patient, and two cases of tau pathology within a Huntington's Disease patient. Methods A 49 year old man with PD underwent bilateral fetal ventral mesencephalic cell transplants into the striatum. Autopsy at age 70 included immunohistochemical staining of host and graft tissue with antibodies to phosphorylated α-synuclein and phosphorylated tau protein. Results Autopsy confirmed the diagnosis of PD. Immunohistochemical staining of graft tissue demonstrated frequent neuronal perikaryal inclusions of phosphorylated α -synuclein and tau in the left graft only. Conclusion Speculations on the formation of pathology include: 1) α-synuclein and tau pathology spread from host to the graft in a neuron-neuron manner. 2) The nature of the fetal cells themselves, or transplantation process, may render fetal tissue more susceptible to the spontaneous generation of pathology. 3) Factors within host environment caused native tau and α-synuclein in fetal tissue graft to become phosphorylated.

    更新日期:2020-01-11
  • Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12-month pulmonary safety study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-23
    Donald G. Grosset; Rohit Dhall; Tanya Gurevich; Jan Kassubek; Werner H. Poewe; Olivier Rascol; Monika Rudzinska; Jennifer Cormier; Alexander Sedkov; Charles Oh

    Introduction CVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's disease patients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg). Methods Patients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care. Pulmonary safety was assessed using spirometry and carbon monoxide diffusion capacity (DLCO). Exploratory efficacy endpoints, assessed only for CVT-301, included change in Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), patients achieving ON within 60 min and remaining ON at 60 min, Patient Global Impression of Change (PGIC) scale, and total daily OFF time. Results Of 408 patients randomized, 310 completed the study (204 in CVT-301 and 106 in OC). Mean 12-month changes from baseline for CVT-301 were −0.105 L (FEV1) and −0.378 mL/min/mm Hg (DLCO), and for OC were −0.117 L and −0.722 mL/min/mm Hg, respectively. Between-group comparisons were not statistically significant. For FEV1/FVC the 12-month change was −0.3 and −1.6, respectively, which was a significant between group difference. However, between-group differences were not significant at 3 and 9 months and all changes from baseline were small (<2.0%). UPDRS-III scores improved from predose to 60 min postdose at all assessments; 80%–85% of patients switched ON within 60 min and remained ON; and >75% reported improvement in PGIC. OFF time decreased by 1.32–1.42 h/day. Conclusion CVT-301 84 mg induced no clinically significant differences in pulmonary function compared with the OC. Improvements in motor scores, OFF time, and patient-reported outcomes support clinical efficacy for up to 12 months.

    更新日期:2019-12-23
  • Acute readmission following deep brain stimulation surgery for Parkinson's disease: A nationwide analysis
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-19
    Ruth B. Schneider; Joohi Jimenez-Shahed; Danielle S. Abraham; Dylan P. Thibault; Sneha Mantri; Michelle Fullard; Michelle A. Burack; Kelvin L. Chou; Meredith Spindler; Walter J. Jermakowicz; Pierre-François D'Haese; Michele K. York; James C. Kirk; Jason M. Schwalb; Alberto J. Espay; Ludy C. Shih; David K. Simon; Christine Hunter; Allison W. Willis

    Introduction Deep brain stimulation (DBS) surgery is an efficacious, underutilized treatment for Parkinson's disease (PD). Studies of DBS post-operative outcomes are often restricted to data from a single center and consider DBS in isolation. National estimates of DBS readmission and post-operative outcomes are needed, as are comparisons to commonly performed surgeries. Methods This study used datasets from the 2013 and 2014 Nationwide Readmissions Database (NRD). Our sample was restricted to PD patients discharged alive after hospitalization for DBS surgery. Descriptive analyses examined patient, clinical, hospital and index hospitalization characteristics. The all-cause, non-elective 30-day readmission rate after DBS was calculated, and logistic regression models were built to examine factors associated with readmission. Readmission rates for the most common surgical procedures were calculated and compared to DBS. Results There were 6058 DBS surgeries for PD in our sample, most often involving a male aged 65 and older, who lived in a high socioeconomic status zip code. DBS patients had an average of four comorbidities. With respect to outcomes, the majority of patients were discharged home (95.3%). Non-elective readmission was rare (4.9%), and was associated with socioeconomic status, comorbidity burden, and teaching hospital status. Much higher acute, non-elective readmission rates were observed for common procedures such as upper gastrointestinal endoscopy (16.2%), colonoscopy (14.0%), and cardiac defibrillator and pacemaker procedures (11.1%). Conclusion Short-term hospitalization outcomes after DBS are generally favorable. Socioeconomic disparities in DBS use persist. Additional efforts may be needed to improve provider referrals for and patient access to DBS.

    更新日期:2019-12-19
  • Evolution of neuropsychological profile in motor subtypes of multiple system atrophy
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-19
    Gabriella Santangelo; Sofia Cuoco; Marina Picillo; Roberto Erro; Massimo Squillante; Giampiero Volpe; Autilia Cozzolino; Giulio Cicarelli; Paolo Barone; Maria Teresa Pellecchia

    Introduction Cognitive deficits and neuropsychiatric symptoms occur in parkinsonian and cerebellar subtypes of Multiple System Atrophy (MSA-P and MSA-C), These symptoms have been investigated mainly in cross-sectional studies. The present 1-year follow-up study aimed at evaluating the evolution of cognitive and neuropsychiatric profile in patients with MSA-C and MSA-P. Methods Twenty-nine patients with MSA-P, 21 with MSA-C and 30 healthy subjects (HCs) underwent a neuropsychological battery and questionnaires assessing depression and apathy (T0). After 1 year (T1), patients with MSA-C and MSA-P underwent the same neuropsychological and neuropsychiatric tools employed at T0. Results At T0, MSA-P and MSA-C groups were more depressed and apathetic and performed worse on tests assessing repetition abilities, executive and attentive functions than HCs. MSA-P and MSA-C groups did not differ on cognitive variables and neuropsychiatric scales. At T1, a significant worsening in spatial planning and psychomotor speed in MSA-C group and a significant worsening in memory, spatial planning, repetition abilities and functional autonomy in MSA-P group were found. The prevalence of apathy increased in both subtypes, whereas the prevalence of depression was reduced in MSA-C and relatively consistent in MSA-P. Conclusions The finding revealed a wide-ranging worsening of cognitive functions in MSA-P and a significant decline in processing speed in MSA-C. These results underline the relevance of evaluating cognitive and psychiatric features of MSA over the course of the disease in the daily clinical practice.

    更新日期:2019-12-19
  • Drug-induced parkinsonism: Revisiting the epidemiology using the WHO pharmacovigilance database
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-17
    Sibylle de Germay; François Montastruc; Alfonso Carvajal; Maryse Lapeyre-Mestre; Jean-Louis Montastruc

    Introduction Drug-Induced Parkinsonism (DIP) is the second most common cause of parkinsonism after idiopathic Parkinson's disease. Little is known about DIP epidemiology. Using VigiBase®, the objective of this study was to assess the main characteristics of DIP reporting around the world. Methods We described reports recorded in the WHO pharmacovigilance database, Vigibase® and classified as “Parkinsonism” between 2000 and 2017. Differences of reporting between geographical locations and characteristics of reports were investigated using disproportionality analysis with calculation of Reporting Odds Ratios (ROR) and its 95% confidence interval. Results Among the 9,009,107 reports recorded in VigiBase®, 4,565 (0.05%) were DIP. Co reported terms were mainly “tremor” (n = 408, 8.9%), “gait disturbance” (n = 209, 4.6%) and “extrapyramidal disorders” (n = 180, 3.9%). DIP reports were significantly more frequent in men (ROR = 1.4; 95% CI 1.3–1.5) and in patients aged 75 and over (ROR = 2.12; 95% CI 1.98–2.26). Compared to all other continents, risk of reporting drug-induced parkinsonism was higher in Europe (ROR = 2.89; 95% CI 2.73–3.07), Africa (ROR = 1.81; 95% CI 1.46–2.25) and Oceania (ROR = 1.50; 95% CI 1.27–1.77). The risk was lower in Asia (ROR = 0.55; 95% CI 0.51–0.59) and America (ROR = 0.55 95% CI 0.51–0.59). The highest risk of DIP reporting was found with sulpiride and haloperidol followed by risperidone, aripiprazole, paliperidone, metoclopramide, olanzapine, quetiapine and clozapine. Conclusion Risk of DIP reports was higher in men, in people aged 75 and over and in Europe. Main drugs involved are antipsychotics not only drugs from the first generation but also those from the second one.

    更新日期:2019-12-18
  • Disrupted salience network dynamics in Parkinson's disease patients with impulse control disorders
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-16
    Irene Navalpotro-Gomez; Jinhee Kim; Pedro M. Paz-Alonso; M. Delgado-Alvarado; A. Quiroga-Varela; H. Jimenez-Urbieta; Carreiras M; Antonio P. Strafella; Maria Cruz Rodriguez-Oroz

    Background 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 within-network 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.

    更新日期:2019-12-17
  • Sex differences in smoking, alcohol consumption, and risk of Parkinson's disease: A nationwide cohort study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-13
    Ryul Kim; Dallah Yoo; Yu Jin Jung; Kyungdo Han; Jee-Young Lee

    Objective We assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD). Methods This population-based cohort study examined data of 6,795,816 Koreans aged ≥40 years from the Korea National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years’ observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI). Results 3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,153 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P < 0.0001 for interaction) and duration (P < 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P < 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014). Conclusion Our data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.

    更新日期:2019-12-13
  • Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: A phase 3 randomized clinical trial
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-12
    Miho Murata; Toshinari Odawara; Kazuko Hasegawa; Ritsuko Kajiwara; Hisao Takeuchi; Masaaki Tagawa; Kenji Kosaka

    Introduction Zonisamide is approved in Japan for treating motor dysfunction in Parkinson's disease, and might also be effective for parkinsonism in patients with dementia with Lewy bodies (DLB). Our study evaluated the safety and efficacy of zonisamide for treating parkinsonism in patients with DLB. Methods This multicenter, randomized, double-blind, phase 3 trial was conducted in Japan between April 2015 and November 2017. Following a 4-week run-in period, outpatients diagnosed with probable DLB who had developed parkinsonism were randomized to receive oral zonisamide (25 or 50 mg/day) or placebo for 12 weeks, followed by a 40-week open-label extension. The primary endpoint was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part III total score at Week 12. Results Of 351 patients randomized, 346 (mean age, 77.2 years; 188 males) were included in the modified intention-to-treat population. At Week 12, the group difference (least squares mean ± SEM) for changes from baseline (vs placebo) in UPDRS part III total score was −2.7 ± 0.9 (95% confidence interval [CI]: −4.4, −0.9, P = 0.005) in the zonisamide 25-mg group and −2.6 ± 0.9 (95% CI: −4.4, −0.8, P = 0.005) in the zonisamide 50-mg group. Adverse events were reported in 47.1%, 48.7%, and 54.5% of patients in the placebo and zonisamide 25- and 50-mg groups, and led to treatment discontinuation in 5.0%, 4.3%, and 9.8% of patients, respectively. Conclusion Daily administration of 25- or 50-mg zonisamide significantly improved motor function compared with placebo; both doses were safe and well tolerated in patients with DLB.

    更新日期:2019-12-13
  • Midbrain hyperechogenicity, hyposmia, mild parkinsonian signs and risk for incident PD over 10 years: A prospective population-based study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-11
    Philipp Mahlknecht, Heike Stockner, Kathrin Marini, Arno Gasperi, Atbin Djamshidian, Peter Willeit, Stefan Kiechl, Johann Willeit, Gregorio Rungger, Werner Poewe, Klaus Seppi

    Introduction Associations of substantia nigra (SN) hyperechogenicity on transcranial sonography, olfactory dysfunction, and mild parkinsonian signs (MPS) with incident Parkinson's disease (PD) have only been studied over limited periods of follow-up and their long-term predictive properties are unclear. We aimed to prospectively assess the risk for incident PD over 10 years in community-dwelling elderly individuals with these risk markers. Methods SN-hyperechogenicity, olfactory function and MPS were assessed in the prospective population-based Bruneck Study (2005 assessment; n = 574, aged 55–94 years). Cases of incident PD were identified at 5-year and 10-year follow-up visits. We estimated relative risks of baseline markers for incident cases. Results After excluding 35 cases with PD or secondary parkinsonism at baseline, a total of 20 cases of incident PD were identified from the remaining 539 participants (11 at 5 years and 9 at 10 years). Relative risks for incident PD over the 10-year follow-up period were 7.43 (2.71–20.39), 3.60 (1.48–8.78), and 5.52 (2.43–12.57) for baseline SN-hyperechogenicity, hyposmia, and mild parkinsonian signs, respectively. While risk of hyposmia for incident PD was similar for the two sequential 5-year periods studied, relative risks of SN-hyperechogenicity and MPS were higher for the first five years as compared to later. Conclusion Our findings extend the established risk relationship of SN-hyperechogenicity, hyposmia and MPS with incident PD beyond 5 years.

    更新日期:2019-12-11
  • Decline in drawing ability and cerebral perfusion in Parkinson's disease patients after subthalamic nucleus deep brain stimulation surgery
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-03
    Shogo Furukawa, Shigeki Hirano, Tatsuya Yamamoto, Masato Asahina, Tomoyuki Uchiyama, Yoshitaka Yamanaka, Yoshikazu Nakano, Ai Ishikawa, Kazuho Kojima, Midori Abe, Yuriko Uji, Yoshinori Higuchi, Takuro Horikoshi, Takashi Uno, Satoshi Kuwabara

    Background Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery. Methods Western aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[123I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients , before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected. Results Although motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery. Conclusion Present results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.

    更新日期:2019-12-03
  • Obstructive sleep apnea, CPAP therapy and Parkinson's disease motor function: A longitudinal study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-02
    Lingrui Meng, Andrea Benedetti, Anne-Louise Lafontaine, Victoria Mery, Ann Ross Robinson, John Kimoff, Priti Gros, Marta Kaminska

    Introduction We aimed to assess, in patients with Parkinson's disease (PD), the association between obstructive sleep apnea (OSA), progression of motor dysfunction and the effect of OSA treatment. Methods Data were analysed from a prospective cohort study of idiopathic PD patients from a movement disorders clinic. Patients found to have OSA on polysomnography (apnea-hypopnea index [AHI] ≥15 events/h, OSA+) were offered treatment using continuous positive airway pressure (CPAP). CPAP+ was defined as an average ≥ 2 h/night use at each follow-up. Motor symptoms were assessed using the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (mUPDRS) and the Timed-Up-And-Go (TUG). Follow-up times were 3, 6 and 12 months. Mixed models were constructed, adjusting for age, sex, body mass index, levodopa equivalent dose and comorbidities. Results We studied 67 individuals (61.2% male) of mean age 64.7 years (SD = 10.1). Baseline mUPDRS was higher in OSA + compared to OSA- (24.5 [13.6] vs. 16.2 [7.2], p < 0.001). Motor dysfunction increased at comparable rates in OSA- and OSA + CPAP-. However, in OSA + CPAP+, mUPDRS change was significantly lower compared to OSA- (β = −0.01 vs. 0.61, p = 0.03; p = 0.12 vs. OSA + CPAP- [β = 0.39]) and TUG change was lower compared to OSA + CPAP- (β = −0.01 vs. 0.13, p = 0.002; p = 0.05 vs. OSA- [β = 0.02]). Conclusions In this PD cohort, OSA was associated with higher baseline mUPDRS. In those with OSA, CPAP use was associated with stabilization of motor function (mUPDRS and TUG) over 12 months. These observations support further research to clarify the role of OSA in PD pathophysiology and motor dysfunction.

    更新日期:2019-12-02
  • Nanopore sequencing of the glucocerebrosidase (GBA) gene in a New Zealand Parkinson's disease cohort
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-29
    O.E.E. Graham, T.L. Pitcher, Y. Liau, A.L. Miller, J.C. Dalrymple-Alford, T.J. Anderson, M.A. Kennedy

    Introduction Bi-allelic mutations in the gene for glucocerebrosidase (GBA) cause Gaucher disease, an autosomal recessive lysosomal storage disorder. Gaucher disease causing GBA mutations in the heterozygous state are also high risk factors for Parkinson's disease (PD). GBA analysis is challenging due to a related pseudogene and structural variations (SVs) that can occur at this locus. We have applied and refined a recently developed nanopore DNA sequencing method to analyze GBA variants in a clinically assessed New Zealand longitudinal cohort of PD. Method We examined amplicons encompassing the coding region of GBA (8.9 kb) from 229 PD cases and 50 healthy controls using the GridION nanopore sequencing platform, and Sanger validation. Results We detected 23 variants in 21 PD cases (9.2% of patients). We detected modest PD risk variant p.N409S (rs76763715) in one case, p.E365K (rs2230288) in 12 cases, and p.T408 M (rs75548401) in seven cases, one of whom also had p.E365K. We additionally detected the possible risk variants p.R78C (rs146774384) in one case, p.D179H (rs147138516) in one case which occurred on the same haplotype as p.E365K, and one novel variant c.335C > T or p.(L335 = ), that potentially impacts splicing of GBA transcripts. Additionally, we found a higher prevalence of dementia among patients with GBA variants. Conclusion This work confirmed the utility of nanopore sequencing as a high-throughput method to identify known and novel GBA variants, and to assign precise haplotypes. Our observations may contribute to improved understanding of the effects of variants on disease pathogenesis, and to the development of more targeted treatments.

    更新日期:2019-11-30
  • Vocal cord electromyographic correlates of stridor in multiple system atrophy phenotypes
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-27
    Massimiliano Todisco, Enrico Alfonsi, Ioannis Ugo Isaias, Roberta Zangaglia, Brigida Minafra, Giuseppe Cosentino, Michele Terzaghi, Nicoló Gabriele Pozzi, Raffaele Manni, Claudio Pacchetti

    Introduction Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by dysautonomia in combination with parkinsonian and cerebellar signs. Stridor may also occur and it is associated with life-threatening events and poor prognosis. The pathophysiology of stridor in MSA is still debated. Objective To define correlations between diurnal electromyographic (EMG) abnormalities of vocal cord muscles and stridor in MSA phenotypes. Methods We recruited 60 patients with “probable” MSA (45 with parkinsonian [MSA-P] and 15 with cerebellar phenotype [MSA-C]). Nocturnal stridor was detected with video-polysomnography, whereas diurnal stridor was clinically noted when present. A diurnal kinesiologic EMG study of the adductor thyroarytenoid and the abductor posterior cricoarytenoid muscles was also performed. Results Among subjects with nocturnal stridor, MSA-P patients predominantly showed a paradoxical burst-like activation of the adductor thyroarytenoid muscle during inspiration. This dystonic pattern was associated with nocturnal stridor in MSA-P (odds ratio [OR] = 23.64, 95% confidence interval [CI] 3.42–70.77, p < 0.001). Conversely, MSA-C patients with nocturnal stridor mainly had additional neurogenic findings of vocal cord muscles. This dystonic-plus pattern correlated with nocturnal stridor in MSA-C (OR = 17.21, 95% CI 4.17–74.92, p < 0.01). The findings of diurnal stridor paralleled the observations for nocturnal stridor. Conclusions The pathophysiology of stridor may differ between MSA phenotypes, possibly related to dysfunctional supranuclear mechanisms in MSA-P (dystonic pattern) and to additional nuclear damage in MSA-C (dystonic-plus pattern).

    更新日期:2019-11-28
  • Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-26
    Wolfgang H. Jost, Andrzej Friedman, Olaf Michel, Christian Oehlwein, Jaroslaw Slawek, Andrzej Bogucki, Stanislaw Ochudlo, Marta Banach, Fernando Pagan, Birgit Flatau-Baqué, Ulrike Dorsch, János Csikós, Andrew Blitzer

    Background Botulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks. Methods Adults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs). Results In total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by −0.16 and −0.17, respectively, at the end-of-study visit. Subjects’ GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%). Conclusions Data support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.

    更新日期:2019-11-27
  • Shared demographics and comorbidities in different functional motor disorders
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-23
    J.M. Gelauff, J.G.M. Rosmalen, J. Gardien, J. Stone, M.A.J. Tijssen

    Introduction Functional motor disorders are often delineated according to the dominant motor symptom. In a large cohort, we aimed to find if there were differences in demographics, mode of onset, pain, fatigue, depression and anxiety and levels of physical functioning, quality of life and social adjustment between patients with different dominant motor symptoms. Methods Baseline data from the Self-Help and Education on the Internet for Functional Motor Disorders Trial was used. Patients were divided into dominant motor symptom groups based on the diagnosis of the referring neurologist. Data on the above topics were collected by means of an online questionnaire and compared between groups using parametric and nonparametric statistics. Results In 160 patients a dominant motor symptom could be determined, 31 had tremor, 45 myoclonus, 23 dystonia, 30 paresis, 31 gait disorder. No statistical differences between groups were detected for demographics, mode of onset and severity of pain, fatigue, depression and anxiety. Physical functioning was worse in the gait disorder group (median 20, IQR 25) compared to tremor (50 (55), p = 0.002) and myoclonus (50 (52), p = 0.001). Work and social adjustment was less impaired in the myoclonus group (median 20, IQR 18) compared to gait disorder (median 30, IQR18, p < 0.001) and paresis (28, IQR 10, p = 0.001). Self-report showed large overlap in motor symptoms. Conclusion No differences were detected between groups of functional motor symptoms, regarding demographics, mode of onset, depression, anxiety, pain and fatigue. The large overlap in symptoms contributes to the hypothesis of shared underlying mechanisms of functional motor disorders.

    更新日期:2019-11-26
  • Subjective memory decline in Parkinson's disease patients with and without fatigue
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-21
    Mattia Siciliano, Luigi Trojano, Rosa De Micco, Antonio Russo, Gioacchino Tedeschi, Alessandro Tessitore

    Introduction Previous studies on Parkinson's disease (PD) have shown that memory complaints and fatigue co-occur since premotor stages of disease, but whether Subjective Memory Decline (SMD, defined as memory complaints with normal objective cognitive performance) and fatigue were associated in PD has not been explored yet. Methods One-hundred PD patients underwent measures of memory complaints (Multifactorial Memory Questionnaire, MMQ), neuropsychological test (Parkinson's Disease-Cognitive Rating Scale), and assessment of behavioural symptoms. Fatigue was diagnosed according to current diagnostic criteria. Mann-Whitney test or Pearson chi-square test were used to compare fatigued and nonfatigued patients for prevalence of SMD and for demographic, clinical, and behavioural features, memory complaint, and objective cognitive measures. The confounding effect of features on results was controlled by logistic regression and Quade's rank analysis. Results Twenty-three patients were diagnosed as fatigued whereas 15 patients met SMD criteria. Fatigued patients showed higher levodopa equivalent daily dose and more marked behavioural symptoms than nonfatigued patients (ps < 0.01). The prevalence of SMD was higher in fatigued patients than in those nonfatigued (35% vs 9%, p < 0.01). After controlling for confounds, the patients with fatigue had an odds ratio for SMD 5.97 [CI 95%, 1.18–30.03] times higher and presented significantly lower scores on Contentment subscales of MMQ (p < 0.01) than those without fatigue. Conclusion Fatigue in PD is associated with SMD mainly characterized by less contentment with one's own memory ability. These findings suggest possible shared pathogenic mechanisms underlying these two nonmotor manifestations and foster to identify potential phenotypes of patients requiring multistrategic therapeutic approaches.

    更新日期:2019-11-21
  • Quality of life outcomes after deep brain stimulation in dystonia: A systematic review
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-18
    Takashi Tsuboi, Joshua K. Wong, Michael S. Okun, Adolfo Ramirez-Zamora

    Dystonia is an incurable movement disorder which can cause not only physical but also mental problems, leading to impaired health-related quality of life (HRQoL). For patients with dystonia refractory to medical treatment, deep brain stimulation (DBS) is a well-established surgical treatment. The objective of this systematic review is to provide a better understanding of HRQoL outcomes after DBS for dystonia. A search of the literature was conducted using Medline (PubMed), Embase, and Cochrane Library databases in May 2019. HRQoL outcomes after DBS along with motor outcomes were reported in a total of 36 articles involving 610 patients: 21 articles on inherited or idiopathic isolated dystonia, 5 on tardive dystonia, 3 on cerebral palsy, 2 on myoclonus-dystonia, 1 on X-linked dystonia-parkinsonism, and 3 on mixed cohorts of different dystonia subtypes. DBS improved motor symptoms in various subtypes of dystonia. Most studies on patients with inherited or idiopathic isolated dystonia showed significant improvement in physical QoL, whereas gains in mental QoL were less robust and likely related to the complexity of associated neuropsychiatric problems. HRQoL outcomes beyond 5 years remain scarce. Although the studies on patients with other subtypes of dystonia also demonstrated improvement in HRQoL after DBS, the interpretation is difficult because of a limited number of articles with small cohorts. Most articles employed generic measures (e.g. Short Form Health Survey-36) and this highlights the critical need to develop and to utilize sensitive and disease-specific HRQoL measures. Finally, long-term HRQoL outcomes and predictors of HRQoL should also be clarified.

    更新日期:2019-11-19
  • Autophagy lysosomal pathway dysfunction in Parkinson's disease; evidence from human genetics
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-17
    Konstantin Senkevich, Ziv Gan-Or

    In recent years, multiple lines of evidence from human genetic and molecular studies have highlighted the importance of the autophagy lysosomal pathway (ALP) in Parkinson's disease (PD). Genes such as GBA and LRRK2, which harbor some of the most common mutations associated with PD, have essential roles in the ALP. α-synuclein, encoded by the SNCA gene, is degraded mainly by the ALP, and mutations/multiplications in SNCA may lead to impairment of chaperone mediated autophagy or other ALP functions. Numerous other PD-related genes, such as PARK2, PINK1, TMEM175, SMPD1, CTSD, CTSB and many more, have also been reported to have important roles in the ALP. Understanding the relationship between ALP impairment and PD pathogenesis may be crucial for uncovering the mechanisms underlying PD, and for the development of long-awaited neuroprotective therapies. In this review, we will discuss the data linking the ALP to PD (other, atypical forms of Parkinsonism, will not be discussed in this review). We will focus on evidence from studies on specific genes and proteins, their roles in the ALP, and the potential mechanisms underlying the involvement of these genes in PD.

    更新日期:2019-11-18
  • Cognitive associations with comprehensive gait and static balance measures in Parkinson's disease
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-07-04
    Rosie Morris, Douglas N. Martini, Katrijn Smulders, Valerie E. Kelly, Cyrus P. Zabetian, Kathleen Poston, Amie Hiller, Kathryn A. Chung, Laurice Yang, Shu-Ching Hu, Karen L. Edwards, Brenna Cholerton, Thomas J. Grabowski, Thomas J. Montine, Joseph F. Quinn, Fay Horak

    Introduction Gait and balance impairments are cardinal features of Parkinson's disease (PD) that require cognitive input. However, the extent to which specific gait and balance characteristics relate to cognition in PD is unclear. In addition, independent models of gait and balance have not been developed from the same cohort. We aimed to i) develop models of gait and balance in a large PD cohort and ii) determine which gait and balance characteristics best related to cognition. Methods One hundred and ninety-eight people with PD were recruited to the Pacific Udall Center. Using six inertial sensors (APDM, Inc.), comprehensive gait measurements were collected over a 2-min continuous walk and comprehensive static balance measures were collected during a 60-second standing task. Six domains of cognition were assessed: global cognition, attention, executive function, language, memory, and visuospatial function. Correlations and hierarchical linear regression determined independent associations. Results Principal components analysis identified a gait model containing four domains accounting for 80.1% of total variance: pace/turning, rhythm, variability, and trunk. The balance model contained four independent domains accounting for 84.5% of total variance: sway area/jerkiness, sway velocity, sway frequency anteroposterior, and sway frequency mediolateral. Gait domains of pace/turning and variability were strongly associated with attention and executive function. Sway area and jerkiness of balance associated with attention and visuospatial function. Conclusions Gait and balance characteristics were associated with specific types of cognition. The specific relationships between gait or balance with cognitive functions suggests shared cerebral cortical circuitry for mobility and cognitive functions.

    更新日期:2019-11-18
  • The efficacy of the Strength, Hope and Resourcefulness Program for people with Parkinson's disease (SHARP-PWP): A mixed methods study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-16
    Kenneth Murdoch, Denise Larsen, Wendy Edey, Chelsea Arsenault, Andrew Howell, Anthony Joyce, Tricia Sandham, Janis Miyasaki

    Introduction Treatment of PD focuses on improving symptoms and quality of life, yet research has not examined interventions aimed at promoting hope in patients. This study examined the effects of a Strength, Hope, and Resources Program for People with PD (SHARP-PWP), based on the principles of positive psychology. Methods A mixed method design examined the effects of a randomized, waitlist-controlled trial of SHARP-PWP. 31 PD patients diagnosed in the last 5 years (average age = 66; 13 men, 18 women) participated in a 6-session program. All participants completed self-report measures at pre-treatment, post-treatment, and 6-week follow-up. Data were analyzed using ANOVA. After the program, 15 participants completed a semi-structured interview. Qualitative interview data were analyzed using Interpretive Description. Results No significant differences in improvement were found between the Immediate and Delayed intervention groups. However, significant effects for time (i.e., pre-treatment to post-treatment) were found for health-related quality of life and well-being in both Immediate and Delayed conditions. Additional quantitative analysis revealed significant improvement in both groups on hope from pre-treatment to follow-up. Qualitative findings revealed that clients identified social, emotional, behavioral and cognitive changes experienced in the group. Conclusions Participating in positive psychology research improved health-related quality of life (HrQoL) and mental health and patients identified additional benefits at 6-week follow-up. Our results provide insight about the placebo effect and Hawthorne pre-placebo effects in the context of PD research. The findings can inform trial design and clinical care of patients with PD.

    更新日期:2019-11-18
  • A physical therapy programme for functional motor symptoms: A telemedicine pilot study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-05-03
    Benedetta Demartini, Federica Bombieri, Diana Goeta, Orsola Gambini, Lucia Ricciardi, Michele Tinazzi

    Introduction for a proportion of patients with functional motor symptoms (FMS), specific physiotherapy has recently emerged as a promising treatment. Aim of the present study was to assess in a sample of patients with FMS the efficacy of a physical therapy-based telemedicine programme on the motor symptoms themselves and on some psychological variables such as anxiety, depression, alexithymia and quality of life. Materials and methods eighteen patients were recruited. The programme consisted of 24 sessions: three face-to-face sessions (at week 0 (T0), 12 (T1) and 24 (T2)) and 21 tele-sessions. Each session included education, movement retraining exercises and development of a management plan. All patients underwent the following assessment at T0, T1 and T2: Psychogenic movement disorders rating scale (PMDRS), assessment of depression, anxiety, alexithymia and quality of life. Self-assessment of outcome (CGI) was recorded at T1 and T2. Results On the CGI improvement was reported by 66,7% of patients at T1 and 77,8% at T2. A significant improvement over the three time points was shown for PMDRS and for the following domains of the SF-36: general health, vitality, social functioning and mental health. Conclusion the use of two innovative approaches for FMS (physiotherapy and telemedicine), combined together, might have a valuable role in the treatment of this neuropsychiatric condition.

    更新日期:2019-11-18
  • Progressive loss of raphe nuclei serotonin transporter in early Parkinson's disease: A longitudinal 123I-FP-CIT SPECT study
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-04-05
    Jacopo Pasquini, Roberto Ceravolo, David James Brooks, Ubaldo Bonuccelli, Nicola Pavese

    Background Serotonergic raphe nuclei dysfunction has been documented in Parkinson's disease, both in pathological and neuroimaging studies, and has been associated with scores of tremor and non-motor symptoms. However, no in vivo longitudinal investigations have been conducted to assess the rate of decline of raphe serotonin transporter availability in the early stages of the disease. Objective To measure the rate of decline of raphe serotonin transporter availability over a two-year interval in patients with recently diagnosed disease and its association with non-motor symptoms over time. Methods Baseline and two-year follow-up 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodo-phenyltropane (123I-FP-CIT) SPECT scans of 173 early Parkinson's disease patients enrolled in the Parkinson's Progressive Markers Initiative were analysed and non-motor symptoms scores recorded. Results A 16.6 ± 20.9% (mean ± SD) reduction in raphe serotonin transporter availability was found from baseline to two-year follow-up in the entire cohort. No differences in progression were found between tremor dominant and postural instability/gait difficulty phenotypes. At follow-up 34.1% of patients showed a moderate-to-severe reduction of raphe serotonin transporter availability with respect to the controls’ mean. We did not find any significant correlation between raphe serotonin transporter availability and scores of depression, excessive daytime sleepiness and REM sleep behaviour disorder. Conclusion 123I-FP-CIT SPECT was able to measure longitudinal reductions in raphe serotonin transporter availability in the early phases of Parkinson's disease. About four years after diagnosis, raphe serotonin transporter availability was significantly reduced in more than one third of the population, but does not appear to be correlated to non-motor symptoms at this stage.

    更新日期:2019-11-18
  • Complex dyskinesias in Parkinson patients on levodopa/carbidopa intestinal gel
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-14
    Massimo Marano, Taline Naranian, Lazzaro di Biase, Alessandro Di Santo, Yu-Yan Poon, Roberta Arca, Giovanni Cossu, Pietro Marano, Vincenzo Di Lazzaro, Alfonso Fasano

    Background Levodopa-carbidopa intestinal infusion is an effective treatment for motor fluctuations of Parkinson's disease. However, it has been recently associated with emergent complex/atypical dyskinesias. We sought to characterize patients who developed these dyskinesias after levodopa infusion initiation, and to compare these patients to a control population with conventional motor fluctuations. Methods 208 Parkinson's disease patients, treated with levodopa intestinal infusion due to motor fluctuations, were screened for onset and/or worsening of dyskinesias after initiation of levodopa infusion, resistant to the routine titration, and presenting with atypical or unexpected patterns. Patients with extensive follow-up data were enrolled for a longitudinal analysis. Cases were compared to a control sample with conventional motor fluctuations in order to investigate predisposing factors, difference in dyskinesia phenotype, management strategies and dropouts. Results Thirty patients out of 208 (14.4%) reported atypical (i.e. long-lasting) biphasic, biphasic-like (i.e. continuous) or mixed (peak-dose and continuous biphasic) dyskinesias after levodopa infusion. They were compared at baseline and follow-up to a sample of 49 patients with conventional motor fluctuations on levodopa infusion. Both groups had similar demographic and clinical features, except the former having higher prevalence of biphasic dyskinesias while on oral therapy. Biphasic-like dyskinesias in nearly half the number of cases improved with increasing the dopaminergic load, while mixed dyskinesias had the worst outcome and highest dropout rate (58%). Conclusions Atypical biphasic, biphasic-like and complex dyskinesias could hinder the course of patients treated with levodopa infusion. This study further informs the selection process of advanced therapies, particularly in dyskinetic patients.

    更新日期:2019-11-14
  • Reporting and methodological quality of clinical trials on exercise therapy for Parkinson's disease
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-13
    Cláudia M. Silva, André M. Travessa, Raquel Bouça-Machado, Daniel Caldeira, Joaquim J. Ferreira

    Background Exercise therapy is becoming extremely relevant as a new efficacious intervention in multiple medical fields. Although several clinical trials have reported benefits of exercise therapy for Parkinson's disease (PD), recommendations and prescriptions for its use in clinical practice remain limited. Objectives To evaluate the methodological quality and publication rate of clinical trials on exercise therapy for PD. Methods We analyzed all clinical trials assessing exercise therapy for PD registered in the WHO International Clinical Trials Registry Platform and the ClinicalTrials.gov registries, from 2000 to 2017. We evaluated the methodological quality of trials using the Cochrane Risk of Bias criteria. Results A total of 236 clinical trials were identified. Only 70 (29.7%) trials reported their findings, and 61 (25.8%) had results published in scientific journals. Most trials had an unclear risk of bias concerning incomplete and selective outcome reporting and lacked data on the randomization process, allocation concealment, blinding of participants and personnel, and outcomes assessors. Aerobic capacity was the most frequent type of exercise intervention. Conclusions Although a large number of trials on exercise are registered in international portals, the quality of reporting remains suboptimal and only a quarter of trials have their results published in scientific journals. These two factors, in addition to the heterogeneity of the interventions tested and the unsatisfactory reported methodological quality of most trials, compromise the interpretation of study results. Therefore, higher quality clinical trials reports are needed to establish exercise as part of the PD armamentarium.

    更新日期:2019-11-13
  • Pimavanserin versus quetiapine for the treatment of psychosis in Parkinson's disease and dementia with Lewy bodies
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-11
    Sarah Horn, Hayley Richardson, Sharon X. Xie, Daniel Weintraub, Nabila Dahodwala

    Introduction Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies. Methods Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available. Results Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001). Conclusion Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.

    更新日期:2019-11-13
  • Whole genome sequencing for the genetic diagnosis of heterogenous dystonia phenotypes
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-07
    Kishore R. Kumar, Ryan L. Davis, Michel C. Tchan, G.M. Wali, Neil Mahant, Karl Ng, Katya Kotschet, Sue-Faye Siow, Jason Gu, Zachary Walls, Ce Kang, Gautam Wali, Stan Levy, Chung Sen Phua, Con Yiannikas, Paul Darveniza, Florence C.F. Chang, Hugo Morales-Briceño, Carolyn M. Sue

    Introduction Dystonia is a clinically and genetically heterogeneous disorder and a genetic cause is often difficult to elucidate. This is the first study to use whole genome sequencing (WGS) to investigate dystonia in a large sample of affected individuals. Methods WGS was performed on 111 probands with heterogenous dystonia phenotypes. We performed analysis for coding and non-coding variants, copy number variants (CNVs), and structural variants (SVs). We assessed for an association between dystonia and 10 known dystonia risk variants. Results A genetic diagnosis was obtained for 11.7% (13/111) of individuals. We found that a genetic diagnosis was more likely in those with an earlier age at onset, younger age at testing, and a combined dystonia phenotype. We identified pathogenic/likely-pathogenic variants in ADCY5 (n = 1), ATM (n = 1), GNAL (n = 2), GLB1 (n = 1), KMT2B (n = 2), PRKN (n = 2), PRRT2 (n = 1), SGCE (n = 2), and THAP1 (n = 1). CNVs were detected in 3 individuals. We found an association between the known risk variant ARSG rs11655081 and dystonia (p = 0.003). Conclusion A genetic diagnosis was found in 11.7% of individuals with dystonia. The diagnostic yield was higher in those with an earlier age of onset, younger age at testing, and a combined dystonia phenotype. WGS may be particularly relevant for dystonia given that it allows for the detection of CNVs, which accounted for 23% of the genetically diagnosed cases.

    更新日期:2019-11-07
  • Novel mutations in the SPAST gene cause hereditary spastic paraplegia
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-06
    Zeyu Zhu, Chao Zhang, Guohua Zhao, Qing Liu, Ping Zhong, Mei Zhang, Weiguo Tang, Feixia Zhan, Wotu Tian, Yan Wang, Kaili Yin, Xiaojun Huang, Jingwen Jiang, Xiaoli Liu, Shihua Liu, Haiyan Zhou, Xinghua Luan, Huidong Tang, Li Cao

    Background Mutations in the SPAST gene are the most frequent cause of hereditary spastic paraplegia (HSP). We aim to extend the mutation spectrum of spastic paraplegia 4 (SPG4) and carried out experiment in vitro to explore the influence of the SPAST gene mutation on the function of corresponding protein. Methods Whole-exome sequencing (WES) combined with multiplex ligation-dependent probe amplification (MLPA) were performed in a cohort of 150 patients clinically diagnosed with HSP. We focus on screening for mutations in SPAST gene and carrying out functional experiments to assess the effects of the novel variants. Results A total of 34 different mutations in the SPAST gene were identified, of which 10 were novel, including 1 missense (c.1479T > A), 1 nonsense (c.766G > T), 3 splicing (c.1413 + 1_1413+4delGTAA, c.1729-1G > A and c.1536+2T > G) and 5 frameshift mutations (c.1094delC, c.885dupA, c.517_518delAG, c.280delG and c.908dupC). For 7 novel non-splicing mutations, functional study showed that accumulated M1 spastin colcocalized with microtubules which was different from a uniformly diffused M87 spastin. While an impairment in severing activity was observed in both mutant M1 and mutant M87, except for c.280delG. All 3 novel splicing variants w ere predicted to affect splicing by using bioinformatic programs. However, only c.1536+2T > G had no influence on splice site in vitro, which conflicts with the in-silico analysis. Conclusion We genetically diagnosed 40 SPG4 patients. All the novel non-splicing mutations except for c.280delG were certified to exert an effect on the microtubule-severing and all the novel splicing mutations other than c.1536+2T > G would cause abnormal splicing of the spastin.

    更新日期:2019-11-06
  • A novel homozygous SYNJ1 mutation in two siblings with typical Parkinson's disease
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-05
    Fei Xie, Si Chen, Zhi dong, You Chen, De-hao Yang, Hao-tian Wang, Bao-rong Zhang, Wei Luo

    Background Mutations in the SYNJ1 have been associated with early onset of atypical Parkinson's disease (PARK20). Patients with PARK20 exhibit a wide phenotypic variability. Here, we report the clinical and genetic findings in two affected siblings with a novel homozygous SYNJ1 mutation. Methods A consanguineous family with two affected siblings with Parkinson's disease was recruited. Both siblings underwent detailed neurological examinations. Whole genome sequencing was performed in the proband. Results Both affected siblings presented with pure parkinsonism with no other atypical symptoms and a slow disease progression. The proband had an excellent response to levodopa. Performing the levodopa challenge test in the proband's older brother resulted in improvements in the parkinsonism signs. Genetic analysis identified a homozygous missense mutation in SYNJ1 (c.2495A > G, p.Y832C) in both of siblings. In silico analyses revealed that the mutation was deleterious. Conclusions Screening for SNYJ1 should be considered in patients with typical levodopa-responsive Parkinson's disease.

    更新日期:2019-11-06
  • Clinical findings of autosomal-dominant striatal degeneration and PDE8B mutation screening in parkinsonism and related disorders
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-05
    Jie Ni, Xiaoping Yi, Zhen Liu, Weining Sun, Yanchun Yuan, Jie Yang, Hong Jiang, Lu Shen, Beisha Tang, Yunhai Liu, Junling Wang

    Background Autosomal-dominant striatal degeneration (ADSD) is a rare neurodegenerative movement disorder caused by mutations in the Phosphodiesterase 8B (PDE8B) gene. Objective To summarize the clinical and imaging features of a Chinese ADSD family and determine whether mutations in PDE8B are associated with Parkinson's disease (PD) or Parkinsonism. Methods Clinical, imaging and genetic findings in a Chinese ADSD family are reported. Rare, potentially pathogenic variants in PDE8B were searched in whole-exome sequencing datasets from 1714 PD or parkinsonism patients and 1039 controls. Results An ADSD diagnosis was confirmed by a nonsense mutation in PDE8B (p.E102X) in a patient and a presymptomatic carrier. Clinically, the patient exhibited progressive parkinsonism without tremor and ataxia phenotype. Neuroimaging showed an inhomogeneous increased signal in the patient's striatum on T1-weighted images but a decreased signal in the presymptomatic carrier. Diffusion tensor imaging (DTI) showed a disturbance in the white matter fiber distribution, especially between the lentiform nucleus and caudate nucleus, which was more prominent in the patient than in the presymptomatic carrier. Within the 1714 patients, three PDE8B missense variants were identified that were unlikely to be the cause of the parkinsonism phenotype according to the functional prediction and mutation types reported in ADSD. Conclusions For the first time, we described the typical ataxia phenotype in ADSD. A loss of white matter fiber integrity was shown on DTI scanning. No causative PDE8B mutation was discovered in our cohort of PD or Parkinsonism patients.

    更新日期:2019-11-06
  • Validity of the wall goniometer as a screening tool to detect postural abnormalities in Parkinson's disease
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-10-30
    Michele Tinazzi, Marialuisa Gandolfi, Carlo Alberto Artusi, Ruggero Lanzafame, Elisabetta Zanolin, Roberto Ceravolo, Marianna Capecci, Elisa Andrenelli, Maria Gabriella Ceravolo, Laura Bonanni, Marco Onofrj, Roberta Telese, Claudio Bertolotti, Paola Polverino, Paolo Manganotti, Sonia Mazzucchi, Sara Giannoni, Laura Vacca, Christian Geroin

    Introduction Software-based measurements of postural abnormalities in Parkinson's disease (PD) are the gold standard but may be time-consuming and not always feasible in clinical practice. Wall goniometer (WG) is an easier, quicker, and inexpensive instrument for screening patients with postural abnormalities, but no studies have investigated its validity so far. The aim of this study was to investigate the validity of the WG to measure postural abnormalities. Methods A total of 283 consecutive PD outpatients with ≥5° forward trunk, lateral trunk or forward neck bending (FTB, LTB, FNB, respectively) were recruited from seven centers for movement disorders. Postural abnormalities were measured in lateral and posterior view using a freeware program (gold standard) and the WG. Both angles are expressed in degrees (°). Sensitivity and specificity for the diagnosis of camptocormia, Pisa syndrome, and anterocollis were assessed. Results WG showed good to excellent agreement (intraclass correlation coefficient from 0.80 to 0.98) compared to the gold standard. Bland-Altman plots showed a mean difference between the methods from −7.4° to 0.4° with limits of agreements from −17.7° to 9.5°. Sensitivity was 100% for the diagnosis of Pisa syndrome, 95.74% for anterocollis, 76.67% for upper camptocormia, and 63.64% for lower camptocormia. Specificity was 59.57% for Pisa syndrome, 71.43% for anterocollis, 89.80% for upper camptocormia, and 100% for lower camptocormia. Overall, the WG underestimated measurements, especially in lower camptocormia with an average of −8.7° (90% of cases). Conclusion WG is a valid tool for screening Pisa syndrome and anterocollis, but approximately 10° more should be added for camptocormia.

    更新日期:2019-11-01
  • Impact of oral COMT-inhibitors on gut microbiota and short chain fatty acids in Parkinson's disease.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : null
    Daniel Grün,Valerie C Zimmer,Jil Kauffmann,Jörg Spiegel,Ulrich Dillmann,Andreas Schwiertz,Klaus Faßbender,Mathias Fousse,Marcus M Unger

    更新日期:2019-11-01
  • Valbenazine-induced parkinsonism.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-12-01
    Umer Akbar,Duk Soo Kim,Joseph H Friedman

    更新日期:2019-11-01
  • Essential tremor seems to be a risk factor for Parkinson's disease.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2016-03-15
    Elan D Louis,Julian Benito-Leon,Phyllis L Faust

    更新日期:2019-11-01
  • Applicability of the Wall Goniometer in Parkinson's disease.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-24
    Diego Orcioli-Silva,Victor Spiandor Beretta

    更新日期:2019-11-01
  • Movement disorders associated with neurocysticercosis.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2018-03-07
    Shakya Bhattacharjee,Fernando Alarcón,Yury Cedeño,Justo García Yébenes

    更新日期:2019-11-01
  • A novel OPTN variant causing PSP-CBS-like phenotype in familial amyotrophic lateral sclerosis.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-24
    Albert Stezin,S P Chaithra,Vikram V Holla,Nitish Kamble,Ravi Yadav,Pramod Kumar Pal

    更新日期:2019-11-01
  • Severe parkinsonism caused by brexpiprazole: A case report.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-23
    Eric M Jackowiak,Kelvin L Chou

    更新日期:2019-11-01
  • Effects of dentate nucleus stimulation in spinocerebellar ataxia type 3.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-11
    Rubens Gisbert Cury,Carina França,Valquiria Silva,Egberto Reis Barbosa,Tamine T C Capato,Guilherme Lepski,Kleber Paiva Duarte,Manoel Jacobsen Teixeira,Daniel Ciampi de Andrade

    更新日期:2019-11-01
  • Conjugal cerebellar type of multiple system atrophy: Person-to-person transmission?
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-08
    Haitian Nan,Takahiro Natori,Yuta Ichinose,Kishin Koh,Fumikazu Kobayashi,Kazumasa Shindo,Masaki Hashiyada,Noboru Adachi,Zentaro Yamagata,Yoshihisa Takiyama

    更新日期:2019-11-01
  • Vibrating socks to improve gait in Parkinson's disease.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-05
    Carola M Koopman,Eric Lutters,Jorik Nonnekes,Bastiaan R Bloem,Jeroen P P van Vugt,Marleen C Tjepkema-Cloostermans

    更新日期:2019-11-01
  • Studying reproducibility of data-driven Parkinson's disease subtypes.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-01-15
    Stephanie M van Rooden,Dagmar Verbaan,Martine Jeukens-Visser,Jacobus J van Hilten

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Co-morbid demyelinating lesions and atypical clinical features in a patient with Parkinson's disease.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-02-11
    Roberta Rodriguez-Diehl,Dolores Vilas,Nuria Bargalló,Eduardo Tolosa,Ellen Gelpi

    更新日期:2019-11-01
  • Neurodevelopmental disorder associated with IRF2BPL gene mutation: Expanding the phenotype?
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-02-09
    Matej Skorvanek,Petr Dusek,Malgorzata Rydzanicz,Anna Walczak,Joanna Kosinska,Grazyna Kostrzewa,Malgorzata Brzozowska,Vladimir Han,Petra Dosekova,Zuzana Gdovinova,Zdenka Lehotska,Pawel Lisowski,Rafal Ploski

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Novel GNAL mutation in an Indian patient with generalized dystonia and response to deep brain stimulation.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-01-21
    Sanjay Pandey,Charulata Savant Sankhla,Vedam L Ramprasad,Thenral S Geetha

    更新日期:2019-11-01
  • High Frequency Bilateral Globus Pallidus Interna Deep Brain Stimulation Can Improve Both Chorea and Dysarthria in Chorea-acanthocytosis.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-01-20
    Kai-Liang Wang,Christopher W Hess,Dan Xu,Jian-Guo Zhang,Wei Hu,Fan-Gang Meng

    更新日期:2019-11-01
  • Variant ataxia-telangiectasia with prominent camptocormia.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2018-12-24
    Martin Paucar,Gaston Schechtmann,Alexander Mr Taylor,Per Svenningsson

    更新日期:2019-11-01
  • Movement disorders rounds: A case of missing pathology in a patient with LRRK2 Parkinson's disease.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-18
    Julian Agin-Liebes,Etty Cortes,Jean-Paul Vonsattel,Karen Marder,Roy N Alcalay

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Setting in motion physiotherapy for MSAp.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-11-05
    A Pérez-Soriano,A Cámara,Y Compta

    更新日期:2019-11-01
  • Primary familial brain calcification caused by MYORG mutations in an Italian family.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-10-18
    Ilaria Taglia,Demy J S Kuipers,Guido J Breedveld,Andrea Mignarri,Maria Teresa Dotti,Antonio Federico,Vincenzo Bonifati

    更新日期:2019-11-01
  • Neuronal exosomes in saliva of Parkinson's disease patients: A pilot study.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-10-18
    Komal Rani,Ranjan Mukherjee,Ekta Singh,Sanjeev Kumar,Vaibhav Sharma,Poorvi Vishwakarma,Prahalad Singh Bharti,Fredrik Nikolajeff,Ashok Kumar Dinda,Vinay Goyal,Saroj Kumar

    更新日期:2019-11-01
  • Intermittent undulating tongue as an involuntary movement in early amyotrophic lateral sclerosis.
    Parkinsonism Relat. Disord. (IF 4.360) Pub Date : 2019-10-18
    Ari Breiner,Ahmed Basndwah,Jodi Warman-Chardon,Pierre R Bourque,Tiago A Mestre

    更新日期:2019-11-01
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug