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Current Opinion in Neurology Aug 2015The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these... (Review)
Review
PURPOSE OF REVIEW
The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these disorders, focusing mainly on advances with direct clinical relevance from the past 2 years.
RECENT FINDINGS
The dystonias are generally defined by their clinical characteristics, rather than by their underlying genetic or neuropathological defects. The many varied clinical manifestations and causes contribute to the fact that they are one of the most poorly recognized of all movement disorders. A series of recent publications has addressed these issues, offering a revised definition and more logical means for classifying the many subtypes. Our understanding of the genetic and neurobiological mechanisms responsible for different types of dystonias also has grown rapidly, creating new opportunities and challenges for diagnosis, and identifying increasing numbers of rare subtypes for which specific treatments are available.
SUMMARY
Recent advances in describing the clinical phenotypes and determining associated causes have pointed to the need for new strategies for diagnosis, classification, and treatment of the dystonias.
Topics: Dystonia; Dystonic Disorders; Humans; Phenotype
PubMed: 26110799
DOI: 10.1097/WCO.0000000000000213 -
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 -
Child's Nervous System : ChNS :... Oct 2023Non-spastic movement disorders in children are common, although true epidemiologic data is difficult to ascertain. Children are more likely than adults to have... (Review)
Review
BACKGROUND
Non-spastic movement disorders in children are common, although true epidemiologic data is difficult to ascertain. Children are more likely than adults to have hyperkinetic movement disorders defined as tics, dystonia, chorea/athetosis, or tremor. These conditions manifest from acquired or heredodegenerative etiologies and often severely limit function despite medical and surgical management paradigms. Neurosurgical management for these conditions is highlighted.
METHODS
We performed a focused review of the literature by searching PubMed on 16 May 2023 using key terms related to our review. No temporal filter was applied, but only English articles were considered. We searched for the terms (("Pallidotomy"[Mesh]) OR "Rhizotomy"[Mesh]) OR "Deep Brain Stimulation"[Mesh], dystonia, children, adolescent, pediatric, globus pallidus, in combination. All articles were reviewed for inclusion in the final reference list.
RESULTS
Our search terms returned 37 articles from 2004 to 2023. Articles covering deep brain stimulation were the most common (n = 34) followed by pallidotomy (n = 3); there were no articles on rhizotomy.
DISCUSSION
Non-spastic movement disorders are common in children and difficult to treat. Most of these patients are referred to neurosurgery for the management of dystonia, with modern neurosurgical management including pallidotomy, rhizotomy, and deep brain stimulation. Historically, pallidotomy has been effective and may still be preferred in subpopulations presenting either in status dystonicus or with high risk for hardware complications. Superiority of DBS over pallidotomy for secondary dystonia has not been determined. Rhizotomy is an underutilized surgical tool and more study characterizing efficacy and risk profile is indicated.
Topics: Adult; Adolescent; Humans; Child; Dystonia; Movement Disorders; Tremor; Dystonic Disorders; Neurosurgical Procedures; Globus Pallidus; Deep Brain Stimulation; Treatment Outcome
PubMed: 37522933
DOI: 10.1007/s00381-023-06100-1 -
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 -
Brain : a Journal of Neurology Jul 2023ATP5F1B is a subunit of the mitochondrial ATP synthase or complex V of the mitochondrial respiratory chain. Pathogenic variants in nuclear genes encoding assembly...
ATP5F1B is a subunit of the mitochondrial ATP synthase or complex V of the mitochondrial respiratory chain. Pathogenic variants in nuclear genes encoding assembly factors or structural subunits are associated with complex V deficiency, typically characterized by autosomal recessive inheritance and multisystem phenotypes. Movement disorders have been described in a subset of cases carrying autosomal dominant variants in structural subunits genes ATP5F1A and ATP5MC3. Here, we report the identification of two different ATP5F1B missense variants (c.1000A>C; p.Thr334Pro and c.1445T>C; p.Val482Ala) segregating with early-onset isolated dystonia in two families, both with autosomal dominant mode of inheritance and incomplete penetrance. Functional studies in mutant fibroblasts revealed no decrease of ATP5F1B protein amount but severe reduction of complex V activity and impaired mitochondrial membrane potential, suggesting a dominant-negative effect. In conclusion, our study describes a new candidate gene associated with isolated dystonia and confirms that heterozygous variants in genes encoding subunits of the mitochondrial ATP synthase may cause autosomal dominant isolated dystonia with incomplete penetrance, likely through a dominant-negative mechanism.
Topics: Humans; Dystonia; Dystonic Disorders; Mitochondrial Proton-Translocating ATPases; Mutation, Missense; Pedigree; Proteins
PubMed: 36860166
DOI: 10.1093/brain/awad068 -
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 -
Tidsskrift For Den Norske Laegeforening... Nov 2018Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske... (Review)
Review
BAKGRUNN
Doparesponsiv dystoni er en gruppe sykdommer som gir endrede nivåer av nevrotransmittere. Dette kan behandles med god effekt. Økt innsikt i patofysiologiske årsaksforhold har bedret forståelsen av sykdommene.
KUNNSKAPSGRUNNLAG
Artikkelen bygger på 39 artikler fra et systematisk søk i databasen Medline, to nettsteder og en lærebok.
RESULTATER
Doparesponsiv dystoni debuterer som oftest i barne- eller ungdomsårene og gir motoriske, kognitive, psykiatriske og/eller autonome symptomer og funn. Disse kan være uspesifikke og lett mistolkes som annen nevrologisk sykdom. Sykdommen skyldes feilkoding i ett enkelt gen og arves autosomalt recessivt eller dominant. Sykdomsgivende varianter er beskrevet fra tre ulike gener: guanosintrifosfat (GTP)-syklohydrolase-1-genet, sepiapterinreduktase-genet og tyrosinhydroksylase-genet. De sykdomsgivende variantene fører til enzymdefekt og gir tidlig debuterende dystoni, som responderer godt på levodopa. Nivåbestemmelse av pteriner, biogene monoaminer og deres metabolitter i spinalvæsken samt genetiske undersøkelser gir den eksakte diagnosen.
FORTOLKNING
Dagens kunnskap baserer seg på kasuistikker og mindre pasientmaterialer. Her fremgår det at pasientgruppen har stor nytte av levodopa. Diagnostikken har blitt enklere de siste årene med nyere biokjemiske og molekylærgenetiske analysemetoder. Basert på dagens litteratur er det grunn til å tro at vi har udiagnostiserte pasienter i Norge med doparesponsiv dystoni.
Topics: Adolescent; Age of Onset; Child; Diagnostic Errors; Dopamine Agents; Dystonic Disorders; Humans; Levodopa
PubMed: 30497245
DOI: 10.4045/tidsskr.17.0595 -
Neuropsychologia Dec 2015Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is... (Review)
Review
Traditional definitions of focal dystonia point to its motor component, mainly affecting planning and execution of voluntary movements. However, focal dystonia is tightly linked also to sensory dysfunction. Accurate motor control requires an optimal processing of afferent inputs from different sensory systems, in particular visual and somatosensory (e.g., touch and proprioception). Several experimental studies indicate that sensory-motor integration - the process through which sensory information is used to plan, execute, and monitor movements - is impaired in focal dystonia. The neural degenerations associated with these alterations affect not only the basal ganglia-thalamic-frontal cortex loop, but also the parietal cortex and cerebellum. The present review outlines the experimental studies describing impaired sensory-motor integration in focal dystonia, establishes their relationship with changes in specific neural mechanisms, and provides new insight towards the implementation of novel intervention protocols. Based on the reviewed state-of-the-art evidence, the theoretical framework summarized in the present article will not only result in a better understanding of the pathophysiology of dystonia, but it will also lead to the development of new rehabilitation strategies.
Topics: Cerebral Cortex; Dystonic Disorders; Humans; Movement; Neural Pathways; Sensation
PubMed: 26164472
DOI: 10.1016/j.neuropsychologia.2015.07.008 -
Journal of Neurology Jul 2017In this review, we summarize recent advances in understanding the etiology, risk factors and pathophysiology of focal task specific dystonia (FTSD), movement disorders... (Review)
Review
In this review, we summarize recent advances in understanding the etiology, risk factors and pathophysiology of focal task specific dystonia (FTSD), movement disorders characterized by abnormal motor activation during the performance of specific, repetitive actions. We focus on two common FTSD, musician's dystonia and writer's cramp. FTSD may pose a threat to the patient's livelihood, and improved therapeutic treatments are needed.
Topics: Dystonic Disorders; Humans
PubMed: 28039522
DOI: 10.1007/s00415-016-8373-z