-
Toxins Jan 2023This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed... (Review)
Review
This review provides an up-to-date literature account on the efficacy of Botulinum toxin treatment for common motor disorders of Parkinson Disease. The reviewed disorders include the common motor disorders in PD such as tremor, focal foot dystonia, rigidity and freezing of gait (FOG). In the area of Parkinson tremor, two newly described evaluation/injection techniques (Yale method in USA and Western University method in Canada) offer efficacy with low incidence of hand and finger weakness as side effects. Blinded studies conducted on foot dystonia of PD indicate that botulinum toxin injections into toe flexors are efficacious in alleviating this form of dystonia. Small, blinded studies suggest improvement of Parkinson rigidity after botulinum toxin injection; proof of this claim, however, requires information from larger, blinded clinical trials. In FOG, the improvement reported in open label studies could not be substantiated in blinded investigations. However, there is room for further controlled studies that include the proximal lower limb muscles in the injection plan and/or use higher doses of the injected toxin for this indication.
Topics: Humans; Botulinum Toxins; Parkinson Disease; Dystonia; Tremor; Motor Disorders; Gait Disorders, Neurologic; Dystonic Disorders; Botulinum Toxins, Type A; Treatment Outcome
PubMed: 36828396
DOI: 10.3390/toxins15020081 -
Tremor and Other Hyperkinetic Movements... 2020Telemedicine is the use of electronic communication technology to facilitate healthcare between distant providers and patients. In addition to synchronous video... (Review)
Review
Telemedicine is the use of electronic communication technology to facilitate healthcare between distant providers and patients. In addition to synchronous video conferencing, asynchronous video transfer has been used to support care for neurology patients. There is a growing literature on using telemedicine in movement disorders, with the most common focus on Parkinson's disease. There is accumulating evidence for videoconferencing to diagnose and treat patients with hyperkinetic movement disorders and to support providers in remote underserviced areas. Cognitive testing has been shown to be feasible remotely. Genetic counseling and other counseling-based therapeutic interventions have also successfully performed in hyperkinetic movement disorders. We use a problem-based approach to review the current evidence for the use of telemedicine in various hyperkinetic movement disorders. This Viewpoint attempts to identify possible telemedicine solutions as well as discussing unmet needs and future directions.
Topics: Dystonic Disorders; Genetic Counseling; Humans; Huntington Disease; Hyperkinesis; Medically Underserved Area; Movement Disorders; Myoclonus; Neuropsychological Tests; Parkinson Disease; Remote Consultation; Telemedicine; Tic Disorders; Tremor; Videoconferencing
PubMed: 32195039
DOI: 10.7916/tohm.v0.698 -
Tremor and Other Hyperkinetic Movements... 2023Genetic factors have been implicated in the pathogenesis of blepharospasm (BSP), a dystonia characterized by excessive blinking and involuntary eyelid closure. Previous...
BACKGROUND
Genetic factors have been implicated in the pathogenesis of blepharospasm (BSP), a dystonia characterized by excessive blinking and involuntary eyelid closure. Previous research identified a co-segregating deleterious variant (GRCh38/hg38, NC_000009.12: g.127733410G>A, NM_001085347.3:c.568C>T, p. Arg190Cys) in three subjects with BSP and three carriers within a multi-generation pedigree. Other variants have been reported in patients with dystonia.
METHODS
Sanger sequencing was used to screen a cohort of 307 subjects with isolated BSP or BSP-plus dystonia affecting additional anatomical segments (BSP+). We also utilized computational tools to uniformly assess the deleteriousness and potential pathogenicity of previously reported variants.
RESULTS
There were no highly deleterious variants in the coding or contiguous splice site regions of within our cohort of 307 subjects.
DISCUSSION
Highly deleterious variants in are rare in patients with BSP/BSP+ phenotypes.
HIGHLIGHTS
Over 300 patients with BSP were screened for variants in , a (DYT1) homologue. No highly deleterious variants were identified in our cohort. The role of in BSP and other forms of dystonia remains indeterminant.
Topics: Humans; Blepharospasm; Dystonia; Dystonic Disorders; Molecular Chaperones; Pedigree
PubMed: 38076033
DOI: 10.5334/tohm.825 -
Current Neuropharmacology 2023Dystonia, the third most common movement disorder, refers to a heterogeneous group of neurological diseases characterized by involuntary, sustained or intermittent... (Review)
Review
Dystonia, the third most common movement disorder, refers to a heterogeneous group of neurological diseases characterized by involuntary, sustained or intermittent muscle contractions resulting in repetitive twisting movements and abnormal postures. In the last few years, several studies on animal models helped expand our knowledge of the molecular mechanisms underlying dystonia. These findings have reinforced the notion that the synaptic alterations found mainly in the basal ganglia and cerebellum, including the abnormal neurotransmitters signalling, receptor trafficking and synaptic plasticity, are a common hallmark of different forms of dystonia. In this review, we focus on the major contribution provided by rodent models of DYT-, DYT-, DYT-, DYT/ PARK-, DYT/PARK- and DYT- dystonia, which reveal that an abnormal motor network and synaptic dysfunction represent key elements in the pathophysiology of dystonia.
Topics: Animals; Dystonia; Dystonic Disorders; Basal Ganglia; Cerebellum; Disease Models, Animal
PubMed: 37464831
DOI: 10.2174/1570159X21666230718100156 -
Scientific Reports Mar 2022Smoothness (i.e. non-intermittency) of movement is a clinically important property of the voluntary movement with accuracy and proper speed. Resting head position and...
Smoothness (i.e. non-intermittency) of movement is a clinically important property of the voluntary movement with accuracy and proper speed. Resting head position and head voluntary movements are impaired in cervical dystonia. The current work aims to evaluate if the smoothness of voluntary head rotations is reduced in this disease. Twenty-six cervical dystonia patients and 26 controls completed rightward and leftward head rotations. Patients' movements were differentiated into "towards-dystonia" (rotation accentuated the torticollis) and "away-dystonia". Smoothness was quantified by the angular jerk and arc length of the spectrum of angular speed (i.e. SPARC, arbitrary units). Movement amplitude (mean, 95% CI) on the horizontal plane was larger in controls (63.8°, 58.3°-69.2°) than patients when moving towards-dystonia (52.8°, 46.3°-59.4°; P = 0.006). Controls' movements (49.4°/s, 41.9-56.9°/s) were faster than movements towards-dystonia (31.6°/s, 25.2-37.9°/s; P < 0.001) and away-dystonia (29.2°/s, 22.9-35.5°/s; P < 0.001). After taking into account the different amplitude and speed, SPARC-derived (but not jerk-derived) indices showed reduced smoothness in patients rotating away-dystonia (1.48, 1.35-1.61) compared to controls (1.88, 1.72-2.03; P < 0.001). Poor smoothness is a motor disturbance independent of movement amplitude and speed in cervical dystonia. Therefore, it should be assessed when evaluating this disease, its progression, and treatments.
Topics: Dystonic Disorders; Head Movements; Humans; Torticollis
PubMed: 35332258
DOI: 10.1038/s41598-022-09149-1 -
Movement Disorders : Official Journal... Mar 2021Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned... (Review)
Review
Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2-180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Movement Disorders; Pallidotomy; Treatment Outcome
PubMed: 33215750
DOI: 10.1002/mds.28384 -
Neurobiology of Disease Jan 2021Focal dystonias are the most common forms of isolated dystonia; however, the etiopathophysiological signatures of disorder penetrance and clinical manifestation remain...
Focal dystonias are the most common forms of isolated dystonia; however, the etiopathophysiological signatures of disorder penetrance and clinical manifestation remain unclear. Using an imaging genetics approach, we investigated functional and structural representations of neural endophenotypes underlying the penetrance and manifestation of laryngeal dystonia in families, including 21 probands and 21 unaffected relatives, compared to 32 unrelated healthy controls. We further used a supervised machine-learning algorithm to predict the risk for dystonia development in susceptible individuals based on neural features of identified endophenotypes. We found that abnormalities in prefrontal-parietal cortex, thalamus, and caudate nucleus were commonly shared between patients and their unaffected relatives, representing an intermediate endophenotype of laryngeal dystonia. Machine learning classified 95.2% of unaffected relatives as patients rather than healthy controls, substantiating that these neural alterations represent the endophenotypic marker of dystonia penetrance, independent of its symptomatology. Additional abnormalities in premotor-parietal-temporal cortical regions, caudate nucleus, and cerebellum were present only in patients but not their unaffected relatives, likely representing a secondary endophenotype of dystonia manifestation. Based on alterations in the parietal cortex and caudate nucleus, the machine learning categorized 28.6% of unaffected relative as patients, indicating their increased lifetime risk for developing clinical manifestation of dystonia. The identified endophenotypic neural markers may be implemented for screening of at-risk individuals for dystonia development, selection of families for genetic studies of novel variants based on their risk for disease penetrance, or stratification of patients who would respond differently to a particular treatment in clinical trials.
Topics: Adult; Aged; Brain; Case-Control Studies; Caudate Nucleus; Cerebellum; Dystonic Disorders; Endophenotypes; Family; Female; Functional Neuroimaging; Humans; Laryngeal Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Motor Cortex; Parietal Lobe; Penetrance; Prefrontal Cortex; Risk Assessment; Supervised Machine Learning; Temporal Lobe; Thalamus
PubMed: 33316367
DOI: 10.1016/j.nbd.2020.105223 -
Movement Disorders : Official Journal... Dec 2022
Topics: Humans; Dystonia; Disruptive, Impulse Control, and Conduct Disorders; Dystonic Disorders
PubMed: 36168795
DOI: 10.1002/mds.29230 -
Neurobiology of Disease Dec 2022During the last decades deep brain stimulation (DBS) has become an important treatment option for a variety of neurological disorders such as drug-intractable dystonia.... (Review)
Review
During the last decades deep brain stimulation (DBS) has become an important treatment option for a variety of neurological disorders such as drug-intractable dystonia. Yet, the mechanisms of action of DBS are still largely unknown. Dystonia is a heterogenous movement disorder characterized by involuntary muscle contractions causing abnormal movements, postures, or both. The underlying pathophysiological processes remain unclear, but a dysfunction of the basal ganglia circuit is critically involved as supported by the effectiveness of DBS of the globus pallidus internus (GPi) in various types of dystonia. However, the degree of clinical improvement differs among the types of dystonia, as well as from patient to patient, and the delayed response to GPi-DBS in dystonia patients hampers the adjustment and optimization of stimulation parameters. Preclinical studies in suitable animal models can contribute decisively to detect the underlying mechanisms of DBS and biomarkers, to identify new possible stimulation targets and to optimize stimulation patterns. In this review, we give an overview of previous research on DBS in animal models of dystonia. With regard to the aims of research we discuss the opportunities and limitations concerning different available animal models of dystonia and technical challenges.
Topics: Animals; Dystonia; Deep Brain Stimulation; Globus Pallidus; Dystonic Disorders; Models, Animal; Treatment Outcome
PubMed: 36307031
DOI: 10.1016/j.nbd.2022.105912 -
Neurologia 2022A growing body of evidence highlights the importance of understanding both the sensory and the motor pathophysiology of focal dystonia in order to improve its treatment....
INTRODUCTION
A growing body of evidence highlights the importance of understanding both the sensory and the motor pathophysiology of focal dystonia in order to improve its treatment. This study aims to evaluate somatosensory afferences in patients with focal or segmental dystonia affecting the upper limbs, to analyse whether the dominant limb is more frequently affected, to analyse pain tolerance, and to examine the potential association with pain perception in patients with hand dystonia.
METHODS
We recruited 24 participants: 12 patients with focal hand dystonia and 12 individuals without dystonia. All participants were evaluated with a digital algometer (Somedic SenseLab AB®, Farsta, Sweden), a Semmes-Weinstein monofilament test, and the visual analogue scale for pain.
RESULTS
According to our data, patients showed greater impairment in surface sensitivity than controls, both in the dominant and the non-dominant hands, as well as greater presence of pain (P > .001). Furthermore, the dystonia group showed a negative correlation between perceived pain and pressure pain tolerance threshold (rho = -0.83; P < .001).
CONCLUSIONS
Patients with focal hand dystonia presented alterations in sensitivity and more severe perceived pain than individuals without dystonia. Future studies with larger samples should aim to analyse the clinical implications and everyday impact of both objective and subjective pain.
Topics: Humans; Dystonia; Dystonic Disorders; Hand; Pain
PubMed: 34801480
DOI: 10.1016/j.nrleng.2019.12.005