Classification Of Dystonia Research Articles

A video-based methodology for automated classification of dystonia and choreoathetosis in dyskinetic cerebral palsy during a lower extremity task

A video-based methodology for automated classification of dystonia and choreoathetosis in dyskinetic cerebral palsy during a lower extremity task

A Novel Video-Based Methodology for Automated Classification of Dystonia and Choreoathetosis in Dyskinetic Cerebral Palsy During a Lower Extremity Task.

Movement disorders in children and adolescents with dyskinetic cerebral palsy (CP) are commonly assessed from video recordings, however scoring is time-consuming and expert knowledge is required for an appropriate assessment. To explore a machine learning approach for automated classification of amplitude and duration of distal leg dystonia and choreoathetosis within short video sequences. Available videos of a heel-toe tapping task were preprocessed to optimize key point extraction using markerless motion analysis. Postprocessed key point data were passed to a time series classification ensemble algorithm to classify dystonia and choreoathetosis duration and amplitude classes (scores 0, 1, 2, 3, and 4), respectively. As ground truth clinical scoring of dystonia and choreoathetosis by the Dyskinesia Impairment Scale was used. Multiclass performance metrics as well as metrics for summarized scores: absence (score 0) and presence (score 1-4) were determined. Thirty-three participants were included: 29 with dyskinetic CP and 4 typically developing, age 14 years:6 months ± 5 years:15 months. The multiclass accuracy results for dystonia were 77% for duration and 68% for amplitude; for choreoathetosis 30% for duration and 38% for amplitude. The metrics for score 0 versus score 1 to 4 revealed an accuracy of 81% for dystonia duration, 77% for dystonia amplitude, 53% for choreoathetosis duration and amplitude. This methodology study yielded encouraging results in distinguishing between presence and absence of dystonia, but not for choreoathetosis. A larger dataset is required for models to accurately represent distinct classes/scores. This study presents a novel methodology of automated assessment of movement disorders solely from video data.

Whole exome sequencing and clinical investigation of young onset dystonia: What can we learn?

BackgroundDystonia is a heterogeneous movement disorder involving various genetic backgrounds, and the implication of whole exome sequencing (WES) has yet to be clearly elucidated. In this study, we performed WES in Korean patients with young-onset dystonia. MethodsWe recruited patients with young-onset dystonia based on the new MDS dystonia classification at Samsung Medical Centre from 2015 to 2019. We excluded subjects diagnosed by single gene tests (GCH1, TOR1A, PANK2, PRRT2, and SGCE) or levodopa trials and subjects with focal or possible secondary dystonia. We performed WES in all enrolled subjects and confirmed the results with Sanger sequencing. ResultsOf the 43 patients, we detected 11 disease-causing variants, classified as either pathogenic or likely pathogenic, in 9 patients (20.9%). Generalized dystonia, infancy-childhood-onset dystonia, and other combined neurologic manifestations were related with PV/LPV. When we retrospectively reviewed the patients with PV/LPV, brain imaging was diagnostic in 3 subjects (HTRA1, SCL20A, and WDR45), clinical characteristics of paroxysmal presentation were observed in 2 (ADCY5 and ATP1A3), and microcephaly was noted in 1 patient (KMT2B). ConclusionClinical exome sequencing is helpful for the diagnosis of dystonia, especially for that with infancy-childhood onset, and generalized dystonia with other neurologic manifestations. Additionally, careful evaluations and examinations could provide information for selecting candidates for genetic testing.

Dystonias: Clinical Recognition and the Role of Additional Diagnostic Testing.

Dystonia is the third most common movement disorder, characterized by abnormal, frequently twisting postures related to co-contraction of agonist and antagonist muscles. Diagnosis is challenging. We provide a comprehensive appraisal of the epidemiology and an approach to the phenomenology and classification of dystonia, based on the clinical characteristics and underlying etiology of dystonia syndromes. We discuss the features of common idiopathic and genetic forms of dystonia, diagnostic challenges, and dystonia mimics. Appropriate workup is based on the age of symptom onset, rate of progression, whether dystonia is isolated or combined with another movement disorder or complex neurological and other organ system features. Based on these features, we discuss when imaging and genetic should be considered. We discuss the multidisciplinary treatment of dystonia, including rehabilitation and treatment principles according to the etiology, including when pathogenesis-direct treatment is available, oral pharmacological therapy, chemodenervation with botulinum toxin injections, deep brain stimulation and other surgical therapies, and future directions.

Deep brain stimulation in dystonia: factors contributing to variability in outcome in short and long term follow-up.

Deep brain stimulation (DBS) is currently the most effective treatment for medically refractory dystonia with globus pallidus internus (GPi) usually the preferred target. Despite the overall success of DBS in dystonia, there remains variability in treatment outcome in both short and long-term follow-up, due to various factors. Factors contributing to variability in outcome comprise 'Dystonia Related' including dystonia classification, semiology, duration, body distribution, orthopaedic deformity, aetiology and genetic cause. The majority of these factors are identifiable from clinical assessment, brain MRI and genetic testing, and therefore merit careful preoperative consideration. 'DBS related' factors include brain target, accuracy of lead placement, stimulation parameters, time allowed for response, neurostimulation technology employed and DBS induced side-effects. In this review, factors contributing to variability in short and long-term dystonia DBS outcome are reviewed and discussed. The recognition of differential DBS benefit in monogenic dystonia, increasing experience with subthalamic nucleus (STN) DBS and in DBS for Meige syndrome, elucidation of DBS side effects and novel neurophysiological and imaging techniques to assist in predicting clinical outcome. Improved understanding of factors contributing to variability of DBS outcome in dystonia may assist in patient selection and predicting surgical outcomes.

The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes.

We describe here how such mechanisms shared by different genetic forms can give rise to motor performance dysfunctions with a clinical aspect of dystonia. The continuing discoveries of genetic causes for dystonia syndromes are transforming our view of these disorders. They share unexpectedly common underlying mechanisms, including dysregulation in neurotransmitter signaling, gene transcription, and quality control machinery. The field has further expanded to include forms recently associated with endolysosomal dysfunction. The discovery of biological pathways shared between different monogenic dystonias is an important conceptual advance in the understanding of the underlying mechanisms, with a significant impact on the pathophysiological understanding of clinical phenomenology. The functional relationship between dystonia genes could revolutionize current dystonia classification systems, classifying patients with different monogenic forms based on common pathways. The most promising effect of these advances is on future mechanism-based therapeutic approaches.

Classification of Dystonia.

Dystonia is a hyperkinetic movement disorder characterized by abnormal movement or posture caused by excessive muscle contraction. Because of its wide clinical spectrum, dystonia is often underdiagnosed or misdiagnosed. In clinical practice, dystonia could often present in association with other movement disorders. An accurate physical examination is essential to describe the correct phenomenology. To help clinicians reaching the proper diagnosis, several classifications of dystonia have been proposed. The current classification consists of axis I, clinical characteristics, and axis II, etiology. Through the application of this classification system, movement disorder specialists could attempt to correctly characterize dystonia and guide patients to the most effective treatment. The aim of this article is to describe the phenomenological spectrum of dystonia, the last approved dystonia classification, and new emerging knowledge.

Multimodal imaging of essential tremor and dystonic tremor

Despite recent advances in tremor and dystonia classification, it remains difficult to discriminate essential tremor from dystonic tremor as they are similar in appearance and no biomarker exists. Further, tremor can appear in the same or a different body part than the dystonia. The aim of the current study was to better understand the differential pathophysiology of these tremors.We designed a cross-sectional case-control study and recruited 16 patients with essential tremor, 16 patients with dystonic tremor, and 17 age-matched healthy volunteers. We used multi-modal imaging combining resting-state functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy. We measured functional connectivity of resting-state fMRI to assess connectivity in the tremor network, fractional anisotropy and mean diffusivity with diffusion tensor imaging, and GABA+, Glutamate/Glutamine, Choline, and N-Acetylaspartate with spectroscopy (adjusted to Creatine).Our results showed reduced functional connectivity of resting-state fMRI between the cerebellum and dentate nucleus bilaterally for the essential tremor group, but not the dystonic tremor group, compared to healthy volunteers. There was higher fractional anisotropy in the middle cerebellar peduncle bilaterally for the dystonic tremor group compared to the essential tremor group as well as for essential tremor group compared to healthy volunteers. There was also higher fractional anisotropy in the red nucleus and corticospinal tract for essential tremor and dystonic tremor groups compared to healthy volunteers. We also showed reduced mean diffusivity in the cerebellum of both essential tremor and dystonic tremor groups compared to healthy volunteers. Finally, we found elevated GABA+/Cr in the cerebellum of the essential tremor and dystonic tremor groups compared to healthy volunteers, but no difference emerged between essential tremor and dystonic tremor groups. We did not find group differences in the other metabolites.Our results indicate cerebellar alterations in essential tremor and dystonic tremor patients compared to healthy volunteers, and further changes in the cerebellum network for the dystonic tremor patients. suggesting that the cerebellum is affected differently in both tremors.

Dystonia in children

Dystonia is a motor disorder characterized by sustained muscle contractions producing twisting, repetitive, and patterned movements or abnormal postures. Dystonia is among the most commonly observed motor disorders in clinical practice in children. Unlike dystonia in adults that typically remains focal or spreads only to nearby muscle groups, childhood dystonia often generalizes. Classification of dystonia has direct implications for narrowing down the differential diagnosis, choosing the diagnostic work-up, predicting the prognosis, and choosing treatment options. The etiology of pediatric dystonia is quite heterogeneous. The etiological classification distinguishes primary dystonia with no identifiable exogenous cause or evidence of neurodegeneration and secondary syndromes. Dystonia can be secondary to any pathological process that affects the basal ganglia. The treatment options of childhood dystonia include several oral pharmaceutical agents, botulinum toxin injections, and deep brain stimulation therapy. Botulinum toxin treatment is the first choice treatment for most types of focal dystonia. In children it is less used because dystonic forms are mainly generalized, but it might also be helpful in controlling the most disabling symptoms of segmental or generalized dystonia. Long-term electrical stimulation of the globus pallidum internum is now established as an effective treatment for various types of movement disorders including dystonia. However, this method has not yet found its application in Russia due to the difficulty of implementation and the lack of patient routing. To increase the effectiveness of complex therapy of dystonia in children, new pathogenetic methods of treatment of common forms of primary dystonia and dystonic syndromes in the structure of degenerative diseases of the central nervous system are needed, as well as the development of optimal algorithms for the diagnosis and treatment of these patients.

Comparative study between idiopathic and non-idiopathic dystonia: a prospective observational study

Background There are very few studies based on the updated dystonia classification. However, a comparison of the idiopathic and non-idiopathic dystonias based on the newer classification has not been done previously. Objectives To study and compare the clinicoetiological profile of patients with idiopathic and non-idiopathic dystonia attending a movement disorder clinic of a tertiary care teaching institution. Methods All the consecutive dystonia patients from October 2017 to September 2019 fulfilling the inclusion criteria were subjected to a detailed clinical evaluation. Investigations were performed as per requirement. Patients were classified according to the consensus update on phenomenology and classification of dystonia. Results A total of 183 patients with dystonia were included, with 61.7% (113) males and 38.3% (70) females. The idiopathic group revealed a significantly earlier age of onset with cases slightly outnumbering (n = 96/183, 52.5%) the non-idiopathic group (n = 87/183, 47.5%). Focal dystonias were the commonest type in both the idiopathic (n = 58/96, 60.4%) and non-idiopathic groups (n = 30/87, 34.5%), while generalized dystonia accounted for 26.4% (n = 23/87) of the non-idiopathic cases and only 3.1% (n = 3/96) of the idiopathic cases. The majority of idiopathic cases were isolated dystonia (n = 93/96, 96.9%), while all hemidystonias were non-idiopathic. Conclusion Focal dystonias were the commonest in both idiopathic and non-idiopathic groups, while generalized dystonia was significantly commoner in the non-idiopathic group. Acquired causes like drugs, perinatal insult were the commonest etiology in the non-idiopathic group. Hemidystonia was found exclusively in the non-idiopathic acquired group.

Jerky dystonic tremor: a less-recognized feature of DYT-THAP1

Dystonia is a very complex movement disorder. Recently, the classification of dystonia has been updated by a group of experts to simplify the clinical approach to dystonia. As per this new classification, clinically we can divide dystonia into either isolated or combined dystonia. In the isolated group, dystonia is the only feature with or without tremor. In the isolated dystonia (DYT) group, DYT-TOR1A and DYT-THAP1 are the commoner entities worldwide. In DYT-THAP1 cases, apart from classic generalized dystonia phenotype, appendicular tremor has also been described. However, in some cases, it could be jerky and may create confusion with myoclonus. To prevent this confusion and subsequent investigations in the line of myoclonic dystonic syndromes, identification of this jerky tremor assumes great clinical significance. Hereby, we are describing a genetically confirmed DYT-THAP1 patient with a jerky dystonic tremor of upper limbs.

Sensorimotor Control in Dystonia.

This is an overview of the sensorimotor impairments in dystonia, a syndrome characterized by sustained or intermittent aberrant movement patterns leading to abnormal movements and/or postures with or without a tremulous component. Dystonia can affect the entire body or specific body regions and results from a plethora of etiologies, including subtle changes in gray and white matter in several brain regions. Research over the last 25 years addressing topics of sensorimotor control has shown functional sensorimotor impairments related to sensorimotor integration, timing, oculomotor and head control, as well as upper and lower limb control. In the context of efforts to update the classification of dystonia, sensorimotor research is highly relevant for a better understanding of the underlying pathology, and potential mechanisms contributing to global and regional dysfunction within the central nervous system. This overview of relevant research regarding sensorimotor control in humans with idiopathic dystonia attempts to frame the dysfunction with respect to what is known regarding motor control in patients and healthy individuals. We also highlight promising avenues for the future study of neuromotor control that may help to further elucidate dystonia etiology, pathology, and functional characteristics.

Implementation of the current dystonia classification from 2013 to 2017 (P4.8-013)

Implementation of the current dystonia classification from 2013 to 2017 (P4.8-013)

Implementation of the Current Dystonia Classification from 2013 to 2018.

There is a discrepancy in the way dystonia is classified in the literature, as articles continue to reference the old criteria or fail to use the 2013 criteria correctly. We performed a systematic review of the dystonia literature and distinguished between studies that use the new classification correctly, made errors in implementing the new classification, or continued to use the old classification methods. Of the 990 articles included in the study, 59.8% used the classification correctly, 31.3% used mixed terminology, and 8.9% continued to use the old classification. Articles relating to surgery were significantly less likely to use the new classification correctly. There is an upward trend in the annual rate of articles properly referencing the new classification. The 2013 classification has been well received in scientific literature, and more studies are adapting to its use.

Molecular Deconvolution Platform to Establish Disease Mechanisms by Surveying GPCR Signaling

SummaryDespite the wealth of genetic information available, mechanisms underlying pathological effects of disease-associated mutations in components of G protein-coupled receptor (GPCR) signaling cascades remain elusive. In this study, we developed a scalable approach for the functional analysis of clinical variants in GPCR pathways along with a complete analytical framework. We applied the strategy to evaluate an extensive set of dystonia-causing mutations in G protein Gαolf. Our quantitative analysis revealed diverse mechanisms by which pathogenic variants disrupt GPCR signaling, leading to a mechanism-based classification of dystonia. In light of significant clinical heterogeneity, the mechanistic analysis of individual disease-associated variants permits tailoring personalized intervention strategies, which makes it superior to the current phenotype-based approach. We propose that the platform developed in this study can be universally applied to evaluate disease mechanisms for conditions associated with genetic variation in all components of GPCR signaling.

Deep Brain Stimulation for the Dystonias: Evidence, Knowledge Gaps, and Practical Considerations.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi-DBS) is among the most effective treatment options for dystonias. Because the term "dystonia" is defined by a characteristic phenomenology of involuntary muscle contractions, which may present with a large clinical and pathogenetic heterogeneity, decision making for or against GPi-DBS can be difficult in individual patients. A search of the PubMed database for research and review articles, focused on "deep brain stimulation" and "dystonia" was used to identify clinical trials and to determine current concepts in the surgical management of dystonia. Patient selection in previous studies was recategorized by the authors using the new dystonia classification put forward by a consensus committee of experts in dystonia research. The evidence and knowledge gaps are summarized and commented by the authors taking into account expert opinion and personal clinical experience for providing practical guidance in patient selection for DBS in dystonia. The literature review shows that pallidal deep brain stimulation is most effective in patients with isolated dystonia irrespective of the underlying etiology. In contrast, patients with combined dystonias are less likely to benefit from DBS, because the associated neurological symptoms (e.g., hypotonia or ataxia), with the exception of myoclonus, do not respond to pallidal neurostimulation. It is important to recognize the clinical features of dystonia, because the distinction between isolated and combined dystonia syndromes may predict the treatment response to pallidal deep brain stimulation. The aim of this review is to help guide clinicians with advising patients about deep brain stimulation therapy for dystonia and refering appropriate candidates to surgical centers.

Research progress of diagnosis and treatment of dystonia

More than 100 years has passed since Oppenheim firstly named the term in 1911, the definition of which that adopted by doctors is outdated and the classification is not specific. Albanese, et al proposed the new definition and classification of dystonia in 2013, which help a lot to guide diagnosis and treatment of dystonia. Recently, there have been new development and recognition on the diagnosis and treatment of dystonia. This review summarizes the definition, classification, diagnosis and treatment of dystonia. DOI: 10.3969/j.issn.1672-6731.2017.01.005

Classification of dystonia in childhood

ObjectiveThe most recent international consensus update on dystonia classification proposed a system based on 2 axes, clinical characteristics and aetiology. We aimed to apply this system to Children and Young People (CAYP) selected for movement disorder surgery, and determine if meaningful groupings of cases could be extracted. MethodsThe 2013 Consensus Committee classification system for dystonia was retrospectively applied to 145 CAYP with dystonic movement disorders. Two-step cluster analysis was applied to the resulting categorisations to identify groupings of CAYP with similar characteristics. ResultsClassification resulted in a total of 43 unique groupings of categorisation. Cluster analysis detected 4 main clusters of CAYP, comparable to previously used patient groupings. ConclusionsThe 2013 consensus update on dystonia classification can be applied to CAYP with dystonia. The large number of categories provides a wealth of information for the clinician, and also facilitates data driven grouping into clinically meaningful subgroups.

Diagnosis and Management of Dystonia.

This article highlights the clinical and diagnostic tools used to assess and classify dystonia and provides an overview of the treatment approach. In the past 4 years, the definition and classification of dystonia have been revised, and new genes have been identified in patients with isolated hereditary dystonia (DYT23, DYT24, and DYT25). Expanded phenotypes were reported in patients with combined dystonia, such as those with mutations in ATP1A3. Treatment offerings have expanded as there are more neurotoxins, and deep brain stimulation has been employed successfully in diverse populations of patients with dystonia. Diagnosis of dystonia rests upon a clinical assessment that requires the examiner to understand the characteristic disease features that are elicited through a careful history and physical examination. The revised classification system uses two distinct nonoverlapping axes: clinical features and etiology. A growing understanding exists of both isolated and combined dystonia as new genes are identified and our knowledge of the phenotypic presentation of previously reported genes has expanded. Genetic testing is commercially available for some of these conditions. Treatment options for dystonia include pharmacologic therapy, chemodenervation, and surgical intervention. Deep brain stimulation benefits many patients with various types of dystonia.

Behavioural interventions for people living with adult-onset primary dystonia: a systematic review.

BackgroundPrimary dystonia is a chronic neurological movement disorder that causes abnormal muscle movements. Pain and emotional distress may accompany these physical symptoms. Behavioural interventions are used to help people with long term conditions improve their quality of life. Little is known about behavioural interventions applied to Dystonia. We report a systematic review of studies reporting current evidence of behavioural interventions for people with primary dystonia.MethodsWe did systematic searches of Medline, PsycINFO, AHMED and CINAHL. We assessed the methodological quality of included studies using a risk of bias tool. Any disagreements were resolved by liaising with an independent rater. Physiological outcomes such as dystonia severity and psychological outcomes such as sleep and depression were selected on the basis that primary dystonia causes motor and non-motor symptoms. No time limit was placed on the searches. A narrative synthesis of the results is presented.ResultsOf 1798 titles and abstracts screened, 14 full articles were retrieved and inclusion and exclusion criteria applied. Of these a final nine were eligible for the review (N = 73). Only two were Randomised Controlled Trials (RCTs). Using the Movement Disorders Society (MDS) dystonia classification, that was published after this work started, all of the included studies were of idiopathic adult onset focal dystonia without associated features. These included: blepharospasm (eye dystonia) (N = 1), cervical dystonia (neck dystonia) (N = 2), writer’s cramp (hand dystonia) (N = 3) and the yips (N = 3). No studies reported on dystonia that affects two or more body regions. Studies reported good adherence and response rates to treatment. Physiological and psychological improvements were noted in all studies at weekly, monthly and yearly follow-ups. Caution should be taken when interpreting the results because of the scarcity of RCTs identified, use of small sample sizes, and inappropriate statistical methods.ConclusionWe identified few studies; mainly of poor methodological quality that all studied a focal dystonia. It is not possible to draw firm conclusions. Nevertheless, the data suggests that a combined behavioural therapy approach including relaxation practice for people with idiopathic adult onset focal dystonia merits further investigation.