Therapeutic Approaches in Movement Disorders: A Narrative Review

Mental and Behavioral Dysfunction in Movement Disorders

<strong>Background:</strong> Non-motor symptoms, quality of life, service needs, and barriers to care of individuals with movement disorders are not well explored. This study assessed these domains within a sample of individuals with essential tremor (ET) and Parkinson’s disease (PD). <strong>Methods:</strong> A survey exploring symptoms, needs, and barriers to care was disseminated to a convenience sample (<em>N</em>=96) of individuals with a primary diagnosis of ET (<em>N</em>=19) or PD (<em>N</em>=77). <strong>Results:</strong> Similarities in overall quality of life and impact on daily functioning were found across individuals with ET and PD. Noteworthy differences included endorsement of different types of service needs and utilization patterns and fewer non-motor symptoms reported among those with ET (M=6.1, SD=2.4) than those with PD (<em>M</em>=10.4, SD=3.4). Non-motor symptoms significantly impacted movement disorder-related quality of life for both diagnostic groups, but this relationship was stronger for individuals with ET, <em>t</em>(12)=3.69, <em>p</em>=0.003, <em>β</em>=0.73 than with PD, <em>t</em>(56)=4.00, <em>p</em>&lt;0.001, <em>β</em>=0.47. Individuals with ET also reported higher rates of stigma (31.6% vs. 7.8%) and greater impact of non-motor symptoms on emotional well-being, <em>R</em>²=0.37, <em>F</em>(1, 13)=7.17, <em>p</em>=0.020. <strong>Discussion:</strong> This is the first study to describe and compare the needs, barriers to care, and impact on quality of life of two distinct movement disorder groups. Our results support the recent efforts of the field to identify interventions to address the non-motor symptoms of movement disorders and indicate need for greater appreciation of the specific differences in symptoms and quality of life experienced across movement disorder diagnoses.

To explore the incidence of depression in movement disorders and associated factors. A total of 121 Parkinson's disease (PD) patients from August 2010 to June 2011 and 62 ET patients from July 2009 to June 2010 were recruited. All of them were outpatients of our hospital. PD patients received the unified Parkinson's disease rating scale (UPDRS) -motor examination and a modified Hoehn and Yahr scale to stage the severity of their disorders while 62 essential tremor (ET) patients were evaluated with tremor rating scale for tremor-motor examination (items 1 - 15 of rating scale). All participants completed Hamilton depression rating scale (24 items) to measure the presence and degree of symptoms of depression. It was found that 56.2% of PD patients and 53.2% of ET patients were depressed (HAMD score of 8 or higher). Among them, the rates of mild depression were 38.9% and 35.5%, moderate depression 15.7% and 17.7% and severe depression 1.7% and 0% in PD and ET patients respectively. No significant differences existed between each group. The factor scores of cognitive impairment were 1.81 ± 1.86 and 1.04 ± 1.07 in PD and ET patients while those of sense of despair were 2.95 ± 1.97 and 4.09 ± 2.08 in each group. The differences had statistical significance in two factor scores of two groups (P < 0.05). No differences in anxiety/somatization, lose weight, day-and-night changes, block and sleep disorders between two groups. For PD patients, the motor score of UPDRS-III was positively correlated with total HAMD score (r = 0.511, P < 0.01). Similarly, for ET patients, tremor rating scale for tremor-motor subscale score and HAMD score were positively correlated (r = 0.828, P < 0.01). As two common movement disorders, PD and ET have a high incidence of depression. The severity of depression is similar in two groups. There is no significant intra-group difference in severity and frequency of depression. The most common symptoms are anxiety somatization, anhedonia, working difficulty, slowness and sleep disturbance. The depression and motor symptoms are positively correlated. Like the non-motor symptoms in PD, we should also pay attention to the non-motor symptoms in ET.

BackgroundNon-motor symptoms, quality of life, service needs, and barriers to care of individuals with movement disorders are not well explored. This study assessed these domains within a sample of individuals with essential tremor (ET) and Parkinson's disease (PD).MethodsA survey exploring symptoms, needs, and barriers to care was disseminated to a convenience sample (N = 96) of individuals with a primary diagnosis of ET (N = 19) or PD (N = 77).ResultsSimilarities in overall quality of life and impact on daily functioning were found across individuals with ET and PD. Noteworthy differences included endorsement of different types of service needs and utilization patterns and fewer non-motor symptoms reported among those with ET (M = 6.1, SD = 2.4) than those with PD (M = 10.4, SD = 3.4). Non-motor symptoms significantly impacted movement disorder-related quality of life for both diagnostic groups, but this relationship was stronger for individuals with ET, t(12) = 3.69, p = 0.003, β = 0.73 than with PD, t(56) = 4.00, p<0.001, β = 0.47. Individuals with ET also reported higher rates of stigma (31.6% vs. 7.8%) and greater impact of non-motor symptoms on emotional well-being, R2 = 0.37, F(1, 13) = 7.17, p = 0.020.DiscussionThis is the first study to describe and compare the needs, barriers to care, and impact on quality of life of two distinct movement disorder groups. Our results support the recent efforts of the field to identify interventions to address the non-motor symptoms of movement disorders and indicate need for greater appreciation of the specific differences in symptoms and quality of life experienced across movement disorder diagnoses.

Movement disorder surgery Part I: historical background and principle of surgery

The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP). As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine. COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Successful treatment of the Meige's syndrome with navigated repetitive transcranial magnetic stimulation: A case report

Introduction: We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to modulate the expression of one or more genes to achieve a therapeutic benefit.Methods: We systematically reviewed movement disorders gene therapy clinical trials from PubMed and ClinicalTrials.gov using a searching strategy that included Parkinson disease (PD), Huntington disease (HD), amino acid decarboxylase (AADC) deficiency, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dystonia, tremor, ataxia, and other movement disorders. Data extracted included study characteristics, investigational product, route of administration, safety/tolerability, motor endpoints, and secondary outcomes (i.e., neuroimaging, biomarkers).Results: We identified a total of 46 studies focusing on PD (21 published and nine ongoing), HD (2 published and 5 ongoing), AADC deficiency (4 published and 2 ongoing), MSA (2 ongoing), and PSP (1 ongoing). In PD, intraparenchymal infusion of viral vector-mediated gene therapies demonstrated to be safe and showed promising preliminary data in trials aiming at restoring the synthesis of dopamine, enhancing the production of neurotrophic factors, or modifying the functional interaction between different nodes of the basal ganglia. In HD, monthly intrathecal delivery of an antisense oligonucleotide (ASO) targeting the huntingtin protein (HTT) mRNA proved to be safe and tolerable, and demonstrated a dose-dependent reduction of the cerebrospinal fluid levels of mutated HTT, while a small phase-I study testing implantable capsules of cells engineered to synthesize ciliary neurotrophic factor failed to show consistent drug delivery. In AADC deficiency, gene replacement studies demonstrated to be relatively safe in restoring catecholamine and serotonin synthesis, with promising outcomes. Ongoing movement disorders clinical trials are focusing on a variety of gene therapy approaches including alternative viral vector serotypes, novel recombinant genes, novel delivery techniques, and ASOs for the treatment of HD, MSA, and distinct subtypes of PD (LRRK2 mutation or GBA1 mutation carriers).Conclusion: Initial phase-I and -II studies tested the safety and feasibility of gene therapy in PD, HD, and AADC deficiency. The ongoing generation of clinical trials aims to test the efficacy of these approaches and explore additional applications for gene therapy in movement disorders.

Editorial: Neurotherapeutics of movement disorders.

Deep brain stimulation with short versus conventional pulse width in Parkinson's disease and essential tremor: A systematic review and meta-analysis

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

The symposium will consist of two keynote speakers and peer‐reviewed platform and poster presentations designed to communicate recent research advances, including new pharmacological and non‐pharmacological treatment options, in the field of Parkinson's disease, Huntington disease, ataxia, dystonia, myoclonus, Tourette's syndrome, Essential Tremor and other movement disorders thereby enhancing patient care. Professionals in neurology and related disciplines as well as practitioners, psychologists, educators, and researchers are invited to attend. The gaps in clinical practice we wish to address are the unmet needs pertaining to the translational and clinical evaluation, along with the care and treatment of patients and families affected by Parkinson's disease and other movement disorders.At the conclusion of this session, participants should be able to: 1) Identify and describe by scholarly review, oral presentation and group discussion the current research into the diagnosis, prevention and treatment of Parkinson's disease (PD) and Essential Tremor (ET) which may be relevant to current treatment or which may lead to the development of further research protocols; 2) Distinguish and assess the important advances in research and clinical treatments relating to Parkinson's disease and Essential Tremor in terms of available treatment options or new methodologies for clinical research; 3) Explain new pharmacological and non‐pharmacological treatment options available for Parkinson's disease and other movement disorders in connection with their clinical practice or with regard to further clinical research methods; 4) Interpret the mechanisms (genetic, environmental, pathophysiology, neurobiology) linked to Parkinson's disease and other movement disorders when assessing Parkinson's disease or other movement disorder patients or when developing new research protocols; and 5) Employ diagnostic approaches and tools available for assessing Parkinson's disease and Essential Tremor when diagnosing new patients or when conducting clinical research.

ObjectivesTo compare non-motor symptoms (NMSs) among patients with essential tremor (ET), Parkinson’s disease (PD) subtypes (akinetic-rigid type (ART) and tremor-dominant type (TDT)), and healthy controls.Patients and methodsThis retrospective study included 129 participants, 72 PD (33 PD-ART, 33 PD-TDT, and 6 Mixed), 29 ET patients, and 28 controls. PD patients were assessed by the unified Parkinson’s disease rating scale (UPDRS), Hoehn, and Yahr scale (H&Y), while ET patients were evaluated by the Fahn Tolosa Marin Tremor Rating Scale. All subjects were evaluated by non-motor symptoms scale (NMSS) for NMSs and Beck depression inventory (BDI) for depression.ResultsPD subtypes groups, ET, and controls were age and gender-matched. Compared to controls, all PD, PD subtypes, and ET showed significantly worse most of NMSs (p<0.001) and depression. Compared to ET, all PD and PD-ART had significantly worse gastrointestinal (p = 0.002), urinary symptoms (p = 0.001, p = 0.003) and depression (p = 0.002) and PD-TDT worse depression, while ET patients showed worse memory/attention than PD subtypes. Total NMSS of ET is highly correlated to depression and moderately to tremor severity and age of onset, while total of NMSS is highly correlated to depression, disease severity, and disability.ConclusionThe current study demonstrated several comparable domains of NMSs of PD subtypes and ET, except worse gastrointestinal and urinary symptoms among PD-ART. Identifying different NMSs profiles is important for predicting, better assessing, and tailoring management of ET and PD subtypes.

Recent electrocorticography data have demonstrated excessive coupling of beta-phase to gamma-amplitude in primary motor cortex and that deep brain stimulation facilitates motor improvement by decreasing baseline phase-amplitude coupling. However, both the dynamic modulation of phase-amplitude coupling during movement and the general cortical neurophysiology of other movement disorders, such as essential tremor, are relatively unexplored. To clarify the relationship of these interactions in cortical oscillatory activity to movement and disease state, we recorded local field potentials from hand sensorimotor cortex using subdural electrocorticography during a visually cued, incentivized handgrip task in subjects with Parkinson's disease (n = 11), with essential tremor (n = 9) and without a movement disorder (n = 6). We demonstrate that abnormal coupling of the phase of low frequency oscillations to the amplitude of gamma oscillations is not specific to Parkinson's disease, but also occurs in essential tremor, most prominently for the coupling of alpha to gamma oscillations. Movement kinematics were not significantly different between these groups, allowing us to show for the first time that robust alpha and beta desynchronization is a shared feature of sensorimotor cortical activity in Parkinson's disease and essential tremor, with the greatest high-beta desynchronization occurring in Parkinson's disease and the greatest alpha desynchronization occurring in essential tremor. We also show that the spatial extent of cortical phase-amplitude decoupling during movement is much greater in subjects with Parkinson's disease and essential tremor than in subjects without a movement disorder. These findings suggest that subjects with Parkinson's disease and essential tremor can produce movements that are kinematically similar to those of subjects without a movement disorder by reducing excess sensorimotor cortical phase-amplitude coupling that is characteristic of these diseases.