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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... 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 -
Tremor and Other Hyperkinetic Movements... 2023Functional movement disorders (FMD) are a diagnostic and therapeutic challenge, both to the neurologist and psychiatrists. The phenomenology is varied and can present as... (Review)
Review
BACKGROUND
Functional movement disorders (FMD) are a diagnostic and therapeutic challenge, both to the neurologist and psychiatrists. The phenomenology is varied and can present as tremors, dystonia, jerks/myoclonus, gait disorder, other abnormal movements or a combination. There has been an increase in the use of electrophysiological studies that are an important tool in the evaluation of FMDs.
METHODS
We searched the database platforms of MEDLINE, Google scholar, Web of Sciences, Scopus using the Medical Subject Heading terms (MeSH) for all the articles from 1st January 1970 till November 2022. A total of 658 articles were obtained by the search mechanism. A total of 79 relevant articles were reviewed thoroughly, of which 26 articles that had electrophysiological data were included in the present review.
RESULTS
Variability, distractibility and entertainability can be demonstrated in functional tremors by using multichannel surface electromyography. Voluntary ballistic movements tend to decrease the tremor, while loading the tremulous limb with weight causes the tremor amplitude to increase in functional tremor. Presence of Bereitschaftspotential demonstrates the functional nature of palatal tremor and myoclonus. Co-contraction testing may be helpful in differentiating functional from organic dystonia. The R2 blink reflex recovery cycle has been found to be abnormally enhanced in organic blepharospasm, whereas it is normal in presumed functional blepharospasm. Plasticity is found to be abnormally high in organic dystonia and normal in functional dystonia, in addition to enhanced facilitation in patients with organic dystonia.
CONCLUSIONS
Electrophysiological tests supplement clinical examination and helps in differentiating FMD from organic movement disorders.
Topics: Humans; Tremor; Myoclonus; Dystonia; Blepharospasm; Movement Disorders; Dystonic Disorders; Electrophysiology; Conversion Disorder
PubMed: 38162980
DOI: 10.5334/tohm.793 -
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 -
Medicine Jul 2023Clinical use of onabotulinumtoxinA evolved based on strategic, hypothesis-driven applications, as well as serendipitous observations by physicians and patients. The... (Review)
Review
Clinical use of onabotulinumtoxinA evolved based on strategic, hypothesis-driven applications, as well as serendipitous observations by physicians and patients. The success of onabotulinumtoxinA in blepharospasm and strabismus led to its study in other head and neck dystonias, followed by limb dystonia, tremor, and spasticity. The aesthetic use of onabotulinumtoxinA followed initial reports from patients of improved facial lines after injections for facial dystonias and hemifacial spasm. Although patients with dystonias and spasticity regularly reported that their local pain improved after injections, onabotulinumtoxinA was not systematically explored for chronic migraine until patients began reporting headache improvements following aesthetic injections. Clinicians began assessing onabotulinumtoxinA for facial sweating and hyperhidrosis based on its inhibition of acetylcholine from sympathetic cholinergic nerves. Yet another line of research grew out of injections for laryngeal dystonia, whereby clinicians began to explore other sphincters in the gastrointestinal tract and eventually to treatment of pelvic sphincters; many of these sphincters are innervated by autonomic nerves. Additional investigations in other autonomically mediated conditions were conducted, including overactive bladder and neurogenic detrusor overactivity, achalasia, obesity, and postoperative atrial fibrillation. The study of onabotulinumtoxinA for depression also grew out of the cosmetic experience and the observation that relaxing facial muscle contractions associated with negative emotions may improve mood. For approved indications, the safety profile of onabotulinumtoxinA has been demonstrated in the formal development programs and post-marketing reports. Over time, evidence has accumulated suggesting clinical manifestations of systemic effects, albeit uncommon, particularly with high doses and in vulnerable populations. Although onabotulinumtoxinA is approved for approximately 26 indications across multiple local regions, there are 15 primary indication uses that have been approved in most regions, including the United States, Europe, South America, and Asia. This review describes many uses for which AbbVie has not sought and/or received regulatory approval and are mentioned for historical context only.
Topics: Humans; Botulinum Toxins, Type A; Treatment Outcome; Urinary Bladder, Overactive; Blepharospasm; Headache; Dystonia
PubMed: 37499079
DOI: 10.1097/MD.0000000000032373 -
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 -
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... Mar 2021
Topics: Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Pallidotomy
PubMed: 33749921
DOI: 10.1002/mds.28409 -
Indian Pediatrics Jan 2021
Topics: Dystonia; Dystonic Disorders; Group VI Phospholipases A2; Humans; Mutation; Parkinsonian Disorders
PubMed: 33452780
DOI: No ID Found -
Current Opinion in Neurology Aug 2023The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia. (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia.
RECENT FINDINGS
Accurate phenotyping of focal dystonia is essential in the process of finding an underlying cause, including acquired, genetic, and idiopathic causes. Motor symptoms as well as the associated nonmotor symptoms and their detrimental impact on quality of life have received increased interest over the last years. The diagnostic process is complicated by the steadily increasing numbers of newly discovered genes associated with dystonia. Recent efforts have been aimed at further developing recommendations and algorithms to aid in diagnosis and in navigating the use of diagnostic tools. In terms of treatment, research on DBS is advancing towards a better understanding of the most effective stimulation locations within the globus pallidus. Moreover, with the introduction of the LFP-recording devices, the search continues for an accurate electrophysiological biomarker for dystonia.
SUMMARY
Accurate phenotyping and (sub)classification of patients with dystonia is important for improving diagnosis, subsequent treatment effect and population-based study outcomes in research. Medical practitioners should be attentive to the presence of nonmotor symptoms in dystonia.
Topics: Humans; Adult; Dystonia; Quality of Life; Deep Brain Stimulation; Treatment Outcome; Dystonic Disorders; Globus Pallidus
PubMed: 37381892
DOI: 10.1097/WCO.0000000000001165