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Most-read articles are from the articles published in 2020 during the last three month.

Original Article
Increased Mortality in Young-Onset Parkinson’s Disease
Eldbjørg Hustad, Tor Åge Myklebust, Sasha Gulati, Jan O. Aasly
J Mov Disord. 2021;14(3):214-220.   Published online July 29, 2021
DOI: https://doi.org/10.14802/jmd.21029
  • 9,712 View
  • 163 Download
  • 2 Citations
AbstractAbstract PDF
Objective
Few studies have followed Parkinson’s disease (PD) patients from the time of diagnosis to the date of death. This study compared mortality in the Trondheim PD cohort to the general population, investigated causes of death and analyzed the associations between mortality and age at disease onset (AAO) and cognitive decline defined as Montreal Cognitive Assessment (MoCA) score below 26.
Methods
The cohort was followed longitudinally from 1997. By the end of January 2020, 587 patients had died. Comparisons to the Norwegian population were performed by calculating standardized mortality ratios (SMRs). Survival curves were estimated using the standard Kaplan-Meier estimator, and multivariable Cox proportional hazard models were estimated to investigate associations.
Results
SMR was 2.28 [95% confidence interval (CI): 2.13–2.44] for the whole cohort. For participants with AAO 20–39 years, the SMR was 5.55 (95% CI: 3.38–8.61). Median survival was 15 years (95% CI: 14.2–15.5) for the whole cohort. Early-onset PD (EOPD) patients (AAO < 50 years) had the longest median survival time. For all groups, there was a significant shortening in median survival time and an almost 3-fold higher age- and sex-adjusted hazard ratio for death when the MoCA score decreased below 26.
Conclusion
PD patients with an AAO before 40 years had a more than fivefold higher mortality rate compared to a similar general population. EOPD patients had the longest median survival; however, their life expectancy was reduced to a greater degree than that of late-onset PD patients. Cognitive impairment was strongly associated with mortality in PD.
Review Articles
Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders
Pei-Chen Hsieh, Yih-Ru Wu
J Mov Disord. 2022;15(2):95-105.   Published online May 26, 2022
DOI: https://doi.org/10.14802/jmd.21077
  • 1,427 View
  • 255 Download
AbstractAbstract PDFSupplementary Material
Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection or neoplasm. Certain phenotypes correlate with specific autoantibody-related neurological disorders, such as orofacial-lingual dyskinesia with N-methyl-D-aspartate receptor encephalitis and faciobrachial dystonic seizures with leucine-rich glioma-inactivated protein 1 encephalitis. Early diagnosis and treatment, especially for autoantibodies targeting neuronal surface antigens, can improve prognosis. In contrast, the presence of autoantibodies against intracellular neuronal agents warrants screening for underlying malignancy. However, early clinical diagnosis is challenging because these diseases can be misdiagnosed. In this article, we review the distinctive clinical phenotypes, magnetic resonance imaging findings, and current treatment options for autoimmune-mediated encephalitis.
Diagnostic Criteria for Dementia with Lewy Bodies: Updates and Future Directions
Masahito Yamada, Junji Komatsu, Keiko Nakamura, Kenji Sakai, Miharu Samuraki-Yokohama, Kenichi Nakajima, Mitsuhiro Yoshita
J Mov Disord. 2020;13(1):1-10.   Published online November 8, 2019
DOI: https://doi.org/10.14802/jmd.19052
  • 19,711 View
  • 1,428 Download
  • 15 Citations
AbstractAbstract PDF
The aim of this article is to describe the 2017 revised consensus criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) with future directions for the diagnostic criteria. The criteria for the clinical diagnosis of probable and possible DLB were first published as the first consensus report in 1996 and were revised in the third consensus report in 2005. After discussion at the International DLB Conference in Fort Lauderdale, Florida, USA, in 2015, the International DLB Consortium published the fourth consensus report including the revised consensus criteria in 2017. The 2017 revised criteria clearly distinguish between clinical features and diagnostic biomarkers. Significant new information about previously reported aspects of DLB has been incorporated, with increased diagnostic weighting given to rapid eye movement (REM) sleep behavior disorder (RBD) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. Future directions include the development of the criteria for early diagnosis (prodromal DLB) and the establishment of new biomarkers that directly indicate Lewy-related pathology, including α-synuclein imaging, biopsies of peripheral tissues (skin, etc.) for the demonstration of α-synuclein deposition, and biochemical markers (cerebrospinal fluid/blood), as well as the pathological evaluation of the sensitivity and specificity of the 2017 revised diagnostic criteria. In conclusion, the revised consensus criteria for the clinical diagnosis of DLB were reported with the incorporation of new information about DLB in 2017. Future directions include the development of the criteria for early diagnosis and the establishment of biomarkers directly indicative of Lewy-related pathology.
Original Article
Comparison of Spontaneous Motor Tempo during Finger Tapping, Toe Tapping and Stepping on the Spot in People with and without Parkinson’s Disease
Dawn Rose, Daniel J. Cameron, Peter J. Lovatt, Jessica A. Grahn, Lucy E. Annett
J Mov Disord. 2020;13(1):47-56.   Published online January 31, 2020
DOI: https://doi.org/10.14802/jmd.19043
  • 10,776 View
  • 135 Download
  • 7 Citations
AbstractAbstract PDFSupplementary Material
Objective
Spontaneous motor tempo (SMT), observed in walking, tapping and clapping, tends to occur around 2 Hz. Initiating and controlling movement can be difficult for people with Parkinson’s (PWP), but studies have not identified whether PWP differ from controls in SMT. For community-based interventions, e.g. dancing, it would be helpful to know a baseline SMT to optimize the tempi of cued activities. Therefore, this study compared finger tapping (FT), toe tapping (TT) and stepping ‘on the spot’ (SS) in PWP and two groups of healthy controls [age-matched controls (AMC) and young healthy controls (YHC)], as SMT is known to change with age.
Methods
Participants (PWP; n = 30, AMC; n = 23, YHC; n = 35) were asked to tap or step on the spot at a natural pace for two trials lasting 40 seconds. The central 30 seconds were averaged for analyses using mean inter-onset intervals (IOI) and coefficient of variation (CoV) to measure rate and variability respectively.
Results
PWP had faster SMT than both control groups, depending on the movement modality: FT, F(2, 87) = 7.92, p < 0.01 (PWP faster than YHC); TT, F(2, 87) = 4.89, p = 0.01 (PWP faster than AMC); and SS, F(2, 77) = 3.26, p = 0.04 (PWP faster than AMC). PWP had higher CoV (more variable tapping) than AMC in FT only, F(2, 87) = 4.10, p = 0.02.
Conclusion
This study provides the first direct comparison of SMT between PWP and two control groups for different types of movements. Results suggest SMT is generally faster in PWP than control groups, and more variable when measured with finger tapping compared to stepping on the spot.
Review Articles
Update on Current Technologies for Deep Brain Stimulation in Parkinson’s Disease
Michelle Paff, Aaron Loh, Can Sarica, Andres M. Lozano, Alfonso Fasano
J Mov Disord. 2020;13(3):185-198.   Published online August 31, 2020
DOI: https://doi.org/10.14802/jmd.20052
  • 11,896 View
  • 545 Download
  • 30 Citations
AbstractAbstract PDF
Deep brain stimulation (DBS) is becoming increasingly central in the treatment of patients with Parkinson’s disease and other movement disorders. Recent developments in DBS lead and implantable pulse generator design provide increased flexibility for programming, potentially improving the therapeutic benefit of stimulation. Directional DBS leads may increase the therapeutic window of stimulation by providing a means of avoiding current spread to structures that might give rise to stimulation-related side effects. Similarly, control of current to individual contacts on a DBS lead allows for shaping of the electric field produced between multiple active contacts. The following review aims to describe the recent developments in DBS system technology and the features of each commercially available DBS system. The advantages of each system are reviewed, and general considerations for choosing the most appropriate system are discussed.
Principles of Electrophysiological Assessments for Movement Disorders
Kai-Hsiang Stanley Chen, Robert Chen
J Mov Disord. 2020;13(1):27-38.   Published online January 31, 2020
DOI: https://doi.org/10.14802/jmd.19064
  • 9,194 View
  • 813 Download
  • 21 Citations
AbstractAbstract PDFSupplementary Material
Electrophysiological studies can provide objective and quantifiable assessments of movement disorders. They are useful in the diagnosis of hyperkinetic movement disorders, particularly tremors and myoclonus. The most commonly used measures are surface electromyography (sEMG), electroencephalography (EEG) and accelerometry. Frequency and coherence analyses of sEMG signals may reveal the nature of tremors and the source of the tremors. The effects of voluntary tapping, ballistic movements and weighting of the limbs can help to distinguish between organic and functional tremors. The presence of Bereitschafts-potentials and beta-band desynchronization recorded by EEG before movement onset provide strong evidence for functional movement disorders. EMG burst durations, distributions and muscle recruitment orders may identify and classify myoclonus to cortical, subcortical or spinal origins and help in the diagnosis of functional myoclonus. Organic and functional cervical dystonia can potentially be distinguished by EMG power spectral analysis. Several reflex circuits, such as the long latency reflex, blink reflex and startle reflex, can be elicited with different types of external stimuli and are useful in the assessment of myoclonus, excessive startle and stiff person syndrome. However, limitations of the tests should be recognized, and the results should be interpreted together with clinical observations.
Immune-Mediated Cerebellar Ataxias: Clinical Diagnosis and Treatment Based on Immunological and Physiological Mechanisms
Hiroshi Mitoma, Mario Manto, Marios Hadjivassiliou
J Mov Disord. 2021;14(1):10-28.   Published online January 12, 2021
DOI: https://doi.org/10.14802/jmd.20040
  • 6,314 View
  • 489 Download
  • 15 Citations
AbstractAbstract PDF
Since the first description of immune-mediated cerebellar ataxias (IMCAs) by Charcot in 1868, several milestones have been reached in our understanding of this group of neurological disorders. IMCAs have diverse etiologies, such as gluten ataxia, postinfectious cerebellitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacities (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, good prognosis is expected when immune-mediated therapeutic interventions are delivered during early stages when the cerebellar reserve can be preserved. However, some types of IMCAs show poor responses to immunotherapies, even if such therapies are introduced at an early stage. Thus, further research is needed to enhance our understanding of the autoimmune mechanisms underlying IMCAs, as such research could potentially lead to the development of more effective immunotherapies. We underscore the need to pursue the identification of robust biomarkers.
COVID-19: An Early Review of Its Global Impact and Considerations for Parkinson’s Disease Patient Care
Roongroj Bhidayasiri, Sasivimol Virameteekul, Jong-Min Kim, Pramod Kr. Pal, Sun-Ju Chung
J Mov Disord. 2020;13(2):105-114.   Published online April 30, 2020
DOI: https://doi.org/10.14802/jmd.20042
  • 11,814 View
  • 727 Download
  • 41 Citations
AbstractAbstract PDF
While many infectious disorders are unknown to most neurologists, COVID-19 is very different. It has impacted neurologists and other health care workers, not only in our professional lives but also through the fear and panic within our own families, colleagues, patients and their families, and even in the wider public. COVID-19 affects all sorts of individuals, but the elderly with underlying chronic conditions are particularly at risk of severe disease, or even death. Parkinson’s disease (PD) shares a common profile as an age-dependent degenerative disorder, frequently associated with comorbidities, particularly cardiovascular diseases, so PD patients will almost certainly fall into the high-risk group. Therefore, the aim of this review is to explore the risk of COVID-19 in PD based on the susceptibility to severe disease, its impact on PD disease severity, potential long-term sequelae, and difficulties of PD management during this outbreak, where neurologists face various challenges on how we can maintain effective care for PD patients without exposing them, or ourselves, to the risk of infection. It is less than six months since the identification of the original COVID-19 case on New Year’s Eve 2019, so it is still too early to fully understand the natural history of COVID-19 and the evidence on COVID-19-related PD is scant. Though the possibilities presented are speculative, they are theory-based, and supported by prior evidence from other neurotrophic viruses closely related to SARS-CoV-2. Neurologists should be on high alert and vigilant for potential acute and chronic complications when encountering PD patients who are suspected of having COVID-19.
Manganese and Movement Disorders: A Review
Dinkar Kulshreshtha, Jacky Ganguly, Mandar Jog
J Mov Disord. 2021;14(2):93-102.   Published online April 6, 2021
DOI: https://doi.org/10.14802/jmd.20123
  • 4,756 View
  • 319 Download
  • 8 Citations
AbstractAbstract PDF
Scientific and technological advances achieved with industrial expansion have led to an ever-increasing demand for heavy metals. This demand has, in turn, led to increased contamination of soil, water and air with these metals. Chronic exposure to metals may be detrimental not only to occupational workers but also to the nonoccupational population exposed to these metals. Manganese (Mn), a commonly used heavy metal, is an essential cofactor for many enzymatic processes that drive biological functions. However, it is also a potential source of neurotoxicity, particularly in the field of movement disorders. The typical manifestation of Mn overexposure is parkinsonism, which may be difficult to differentiate from the more common idiopathic Parkinson’s disease. In addition to environmental exposure to Mn, other potential etiologies causing hypermanganesemia include systemic health conditions, total parenteral nutrition and genetic mutations causing Mn dyshomeostasis. In this review, we critically analyze Mn and discuss its sources of exposure, pathophysiology and clinical manifestations. We have highlighted the global public health impact of Mn and emphasize that movement disorder specialists should record a detailed social and occupational history to ensure that a toxic etiology is not misdiagnosed as a neurodegenerative disease. In the absence of a definite therapeutic option, early diagnosis and timely institution of preventive measures are the keys to managing its toxic effects.
Case Report
Myoclonus-Ataxia Syndrome Associated with COVID-19
Kuldeep Shetty, Atul Manchakrao Jadhav, Ranjith Jayanthakumar, Seema Jamwal, Tejaswini Shanubhogue, Mallepalli Prabhakar Reddy, Gopal Krishna Dash, Radhika Manohar, Vivek Jacob Philip, Vikram Huded
J Mov Disord. 2021;14(2):153-156.   Published online April 6, 2021
DOI: https://doi.org/10.14802/jmd.20106
  • 4,106 View
  • 148 Download
  • 4 Citations
AbstractAbstract PDFSupplementary Material
Neurological manifestations of coronavirus disease (COVID-19) have increasingly been reported since the onset of the pandemic. Herein, we report a relatively new presentation. A patient in the convalescence period following a febrile illness with lower respiratory tract infection (fever, myalgia, nonproductive cough) presented with generalized disabling myoclonus, which is phenotypically suggestive of brainstem origin, along with additional truncal cerebellar ataxia. His neurology work-ups, such as brain MRI, electroencephalography, serum autoimmune and paraneoplastic antibody testing, were normal. His CT chest scan revealed right lower lung infiltrates, and serological and other laboratory testing did not show evidence of active infection. COVID-19 titers turned out to be strongly positive, suggestive of post-COVID-19 lung sequelae. He responded partially to antimyoclonic drugs and fully to a course of steroids, suggesting a para- or postinfectious immune-mediated pathophysiology. Myoclonusataxia syndrome appears to be a neurological manifestation of COVID-19 infection, and knowledge regarding this phenomenon should be increased among clinicians for better patient care in a pandemic situation.
Review Article
Long-Term Outcomes of Genetic Parkinson’s Disease
Jan O. Aasly
J Mov Disord. 2020;13(2):81-96.   Published online May 29, 2020
DOI: https://doi.org/10.14802/jmd.19080
  • 9,257 View
  • 350 Download
  • 6 Citations
AbstractAbstract PDF
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects 1–2% of people by the age of 70 years. Age is the most important risk factor, and most cases are sporadic without any known environmental or genetic causes. Since the late 1990s, mutations in the genes SNCA, PRKN, LRRK2, PINK1, DJ-1, VPS35, and GBA have been shown to be important risk factors for PD. In addition, common variants with small effect sizes are now recognized to modulate the risk for PD. Most studies in genetic PD have focused on finding new genes, but few have studied the long-term outcome of patients with the specific genetic PD forms. Patients with known genetic PD have now been followed for more than 20 years, and we see that they may have distinct and different prognoses. New therapeutic possibilities are emerging based on the genetic cause underlying the disease. Future medication may be based on the pathophysiology individualized to the patient’s genetic background. The challenge is to find the biological consequences of different genetic variants. In this review, the clinical patterns and long-term prognoses of the most common genetic PD variants are presented.
Original Articles
Therapeutic Effect of Levodopa/Carbidopa/Entacapone on Sleep Disturbance in Patients with Parkinson’s Disease
Kye Won Park, Sungyang Jo, Seung Hyun Lee, Yun Su Hwang, Dagyo Lee, Ho-Sung Ryu, Sun Ju Chung
J Mov Disord. 2020;13(3):205-212.   Published online September 9, 2020
DOI: https://doi.org/10.14802/jmd.20055
  • 4,670 View
  • 232 Download
  • 2 Citations
AbstractAbstract PDF
Objective
To investigate the efficacy of levodopa/carbidopa/entacapone (LCE) at bedtime for treating sleep disturbance in patients with Parkinson’s disease (PD) with motor fluctuations.
Methods
Participants included 128 PD patients with motor fluctuations. All patients were assessed for motor, nonmotor, and sleep-specific symptoms using the United Parkinson’s Disease Rating Scale (UPDRS), the Korean version of the Nonmotor Symptom Scale, the Parkinson’s Disease Sleep Scale (PDSS), the Epworth Sleepiness Scale, and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ). We compared the baseline characteristics of patients with sleep disturbance (PDSS score < 120) and those without sleep disturbance (PDSS score ≥ 120). Thirty-nine patients with sleep disturbance who agreed to take LCE at bedtime completed 3-month follow-ups. We analyzed changes in the scores of motor, nonmotor, and sleep symptom scales over the 3 months.
Results
PD patients with sleep disturbance were at more advanced disease stages and had more severe motor, nonmotor, and sleep symptoms than those without sleep disturbance. Patients who took LCE at night showed improvements in motor (UPDRS part III, p = 0.007) and sleep symptoms (total PDSS, p < 0.001). Sleep features that benefitted from LCE included not only nocturnal motor components but also insomnia (PDSS items 2 and 3, p = 0.005 and p < 0.001) and rapid eye movement behavior disorder (PDSS item 6, p = 0.002; and RBDSQ, p < 0.001).
Conclusion
The use of LCE at bedtime may be a useful treatment for sleep disturbance in advanced PD patients with motor fluctuations.
Fecal Calprotectin in Parkinson’s Disease and Multiple System Atrophy
Jia Wei Hor, Shen-Yang Lim, Eng Soon Khor, Kah Kian Chong, Sze Looi Song, Norlinah Mohamed Ibrahim, Cindy Shuan Ju Teh, Chun Wie Chong, Ida Normiha Hilmi, Ai Huey Tan
J Mov Disord. 2022;15(2):106-114.   Published online December 24, 2021
DOI: https://doi.org/10.14802/jmd.21085
  • 1,691 View
  • 259 Download
  • 2 Citations
AbstractAbstract PDFSupplementary Material
Objective
Converging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson’s disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA.
Methods
We recruited 169 subjects (71 PD, 38 MSA, and 60 age-similar nonneurological controls). Clinico-demographic data were collected. PD and MSA were subtyped and the severity assessed using the MDS-UPDRS and UMSARS, respectively. Fecal calprotectin and blood immune markers were analyzed.
Results
Compared to controls (median: 35.7 [IQR: 114.2] μg/g), fecal calprotectin was significantly elevated in PD (median: 95.6 [IQR: 162.1] μg/g, p = 0.003) and even higher in MSA (median: 129.5 [IQR: 373.8] μg/g, p = 0.002). A significant interaction effect with age was observed; between-group differences were significant only in older subjects (i.e., ≥ 61 years) and became more apparent with increasing age. A total of 28.9% of MSA and 18.3% of PD patients had highly abnormal fecal calprotectin levels (≥ 250 μg/g); however, this difference was only significant for MSA compared to controls. Fecal calprotectin correlated moderately with selected blood immune markers in PD, but not with clinical features of PD or MSA.
Conclusions
Elevated fecal calprotectin suggests a role for intestinal inflammation in PD and MSA. A more complete understanding of gut immune alterations could open up new avenues of research and treatment for these debilitating diseases.
Review Articles
Emerging Concepts of Motor Reserve in Parkinson’s Disease
Seok Jong Chung, Jae Jung Lee, Phil Hyu Lee, Young H. Sohn
J Mov Disord. 2020;13(3):171-184.   Published online August 31, 2020
DOI: https://doi.org/10.14802/jmd.20029
  • 6,426 View
  • 253 Download
  • 10 Citations
AbstractAbstract PDF
The concept of cognitive reserve (CR) in Alzheimer’s disease (AD) explains the differences between individuals in their susceptibility to AD-related pathologies. An enhanced CR may lead to less cognitive deficits despite severe pathological lesions. Parkinson’s disease (PD) is also a common neurodegenerative disease and is mainly characterized by motor dysfunction related to striatal dopaminergic depletion. The degree of motor deficits in PD is closely correlated to the degree of dopamine depletion; however, significant individual variations still exist. Therefore, we hypothesized that the presence of motor reserve (MR) in PD explains the individual differences in motor deficits despite similar levels of striatal dopamine depletion. Since 2015, we have performed a series of studies investigating MR in de novo patients with PD using the data of initial clinical presentation and dopamine transporter PET scan. In this review, we summarized the results of these published studies. In particular, some premorbid experiences (i.e., physical activity and education) and modifiable factors (i.e., body mass index and white matter hyperintensity on brain image studies) could modulate an individual’s capacity to tolerate PD pathology, which can be maintained throughout disease progression.
Nutrition and Lifestyle Interventions for Managing Parkinson’s Disease: A Narrative Review
Tracy Lister
J Mov Disord. 2020;13(2):97-104.   Published online May 29, 2020
DOI: https://doi.org/10.14802/jmd.20006
  • 8,816 View
  • 473 Download
  • 2 Citations
AbstractAbstract PDF
The etiology of Parkinson’s disease (PD) is not fully understood, but environmental toxin overexposure, increased intestinal permeability, and dysbiosis related to nutrition and lifestyle habits are thought to be contributors. Considering these nutrition and lifestyle implications, there is a lack of practice-based programs utilizing interventions for managing symptoms or slowing the progression of the disease. The purpose of this narrative review was to identify relevant research related to nutrition and lifestyle interventions for PD, evaluate the research utilizing the evidence analysis process of the Academy of Nutrition and Dietetics to assess the quality of each research article, and group the research into categories. A grading of recommendations assessment, development and evaluation (GRADE) of either good, fair, limited, or not assignable was allocated to each category of research, including diet patterns, vitamin D, B-complex, omega-3 fatty acids, coenzyme Q10, probiotics, physical activity, stress, and sleep. An intervention based on the research presented in the review may be utilized for coaching people with PD on symptom management.

JMD : Journal of Movement Disorders