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Current Opinion in Neurology Aug 2019Our understanding of X-Linked Dystonia-Parkinsonism (XDP) has advanced considerably in recent years because of a wealth of new data describing its genetic basis,... (Review)
Review
PURPOSE OF REVIEW
Our understanding of X-Linked Dystonia-Parkinsonism (XDP) has advanced considerably in recent years because of a wealth of new data describing its genetic basis, cellular phenotypes, neuroimaging features, and response to deep brain stimulation (DBS). This review provides a concise summary of these studies.
RECENT FINDINGS
XDP is associated with a SINE-VNTR-Alu (SVA)-type retrotransposon insertion within the TAF1 gene. This element includes a hexameric DNA repeat expansion, (CCCTCT)n, the length of which varies among patients and is inversely correlated to age of disease onset. In cell models, the SVA alters TAF1 splicing and reduces levels of full-length transcript. Neuroimaging data have confirmed previous neuropathology studies that XDP involves a progressive striatal atrophy, while further detecting functional alterations in additional brain regions. In patients exhibiting features of both dystonia and parkinsonism, pallidal DBS has resulted in rapid improvement of hyperkinetic movements, but effects on hypokinetic features have been inconsistent.
SUMMARY
The discovery that XDP is linked to a polymorphic hexameric sequence suggests that it could share mechanisms with other DNA repeat disorders, whereas the transcriptional defect in cell models raises the possibility that strategies to correct TAF1 splicing could provide therapeutic benefit.
Topics: Brain; DNA Repeat Expansion; Deep Brain Stimulation; Dystonic Disorders; Genetic Diseases, X-Linked; Humans
PubMed: 31116117
DOI: 10.1097/WCO.0000000000000708 -
Journal of the Neurological Sciences Apr 2022Dystonia and tremor frequently co-occur. In some cases, they have shared biological mechanisms, while in others dystonia and tremor are two comorbid conditions. The term... (Review)
Review
Dystonia and tremor frequently co-occur. In some cases, they have shared biological mechanisms, while in others dystonia and tremor are two comorbid conditions. The term "dystonic tremor" is used to describe tremor in those who have dystonia. Two mutually exclusive definitions of "dystonic tremor" were proposed. According to one definition, dystonic tremor is the tremor in the dystonic body part. An alternate definition of dystonic tremor entails irregular and jerky oscillations that have saw tooth appearance with or without overt dystonia. This paper outlines the differences in two definitions of dystonic tremor and identifies their limitations. Given the diverse views defining "dystonic tremor", this paper will use the term "tremor in dystonia". In addition, we will outline different ways to separate the subtypes of tremor in dystonia. Then we will discuss pathophysiological mechanisms derived from the objective measures and single neuron physiology analyses of tremor in dystonia. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.
Topics: Dystonia; Dystonic Disorders; Essential Tremor; Humans; Tremor
PubMed: 35259651
DOI: 10.1016/j.jns.2022.120199 -
Clinical Medicine (London, England) Aug 2016Movement disorders comprise hyperkinetic involuntary movements (eg tremor, myoclonus, tics, dystonia and chorea) and hypokinetic (parkinsonism) disorders. Tics are... (Review)
Review
Movement disorders comprise hyperkinetic involuntary movements (eg tremor, myoclonus, tics, dystonia and chorea) and hypokinetic (parkinsonism) disorders. Tics are cardinal features of primary tic disorders encompassing Tourette syndrome (TS), but are also found in some neurodegenerative conditions and may be induced by psychoactive substances. The first line treatment for tics is pharmacological (mainly dopamine receptor blockers or alpha-2 adrenergic agonists) and behavioural. Dystonia and chorea syndromes are considerably heterogeneous in aetiology, and age at onset, body distribution of the movement disorder, accompanying neurological motor and non-motor features, and systemic manifestations are all important to reach a correct aetiological diagnosis. While symptomatic pharmacological treatment remains the mainstay of treatment for choreas, deep brain stimulation surgery has a well-defined place in the management of medically refractory dystonia.
Topics: Chorea; Dystonic Disorders; Humans; Tic Disorders
PubMed: 27481387
DOI: 10.7861/clinmedicine.16-4-383 -
Progress in Neurological Surgery 2018Deep brain stimulation (DBS) has markedly changed how we treat movement disorders including Parkinson's disease (PD), dystonia, and essential tremor (ET). However,... (Review)
Review
Deep brain stimulation (DBS) has markedly changed how we treat movement disorders including Parkinson's disease (PD), dystonia, and essential tremor (ET). However, despite its demonstrable clinical benefit, DBS is often limited by side effects and partial efficacy. These limitations may be due in part to the fact that DBS interferes with both pathological and physiological neural activities. DBS could, therefore, be potentially improved were it applied selectively and only at times of enhanced pathological activity. This form of stimulation is known as closed-loop or adaptive DBS (aDBS). An aDBS approach has been shown to be superior to conventional DBS in PD in primates using cortical neuronal spike triggering and in humans employing local field potential biomarkers. Likewise, aDBS studies for essential and Parkinsonian tremor are advancing and show great promise, using both peripheral or central sensing and stimulation. aDBS has not yet been trialed in dystonia and yet exciting and promising biomarkers suggest it could be beneficial here too. In this chapter, we will review the existing literature on aDBS in movement disorders and explore potential biomarkers and stimulation algorithms for applying aDBS in PD, ET, and dystonia.
Topics: Animals; Deep Brain Stimulation; Dystonic Disorders; Essential Tremor; Humans; Parkinson Disease
PubMed: 29332087
DOI: 10.1159/000481107 -
Progress in Neurobiology Nov 2019A line of evidence suggests that the pathophysiology of dystonia involves the striatum, whose activity is modulated among other neurotransmitters, by the dopaminergic... (Review)
Review
A line of evidence suggests that the pathophysiology of dystonia involves the striatum, whose activity is modulated among other neurotransmitters, by the dopaminergic system. However, the link between dystonia and dopamine appears complex and remains unclear. Here, we propose a physiological approach to investigate the clinical and experimental data supporting a role of the dopaminergic system in the pathophysiology of dystonic syndromes. Because dystonia is a disorder of motor routines, we first focus on the role of dopamine and striatum in procedural learning. Second, we consider the phenomenology of dystonia from every angle in order to search for features giving food for thought regarding the pathophysiology of the disorder. Then, for each dystonic phenotype, we review, when available, the experimental and imaging data supporting a connection with the dopaminergic system. Finally, we propose a putative model in which the different phenotypes could be explained by changes in the balance between the direct and indirect striato-pallidal pathways, a process critically controlled by the level of dopamine within the striatum. Search strategy and selection criteria References for this article were identified through searches in PubMed with the search terms « dystonia », « dopamine", « striatum », « basal ganglia », « imaging data », « animal model », « procedural learning », « pathophysiology », and « plasticity » from 1998 until 2018. Articles were also identified through searches of the authors' own files. Only selected papers published in English were reviewed. The final reference list was generated on the basis of originality and relevance to the broad scope of this review.
Topics: Animals; Basal Ganglia; Corpus Striatum; Dopamine; Dystonia; Dystonic Disorders; Humans; Neural Pathways
PubMed: 31404592
DOI: 10.1016/j.pneurobio.2019.101678 -
International Review of Neurobiology 2018Dystonia is a neurological disorder characterized by involuntary, repetitive movements. Although the precise mechanisms of dystonia development remain unknown, the... (Review)
Review
Dystonia is a neurological disorder characterized by involuntary, repetitive movements. Although the precise mechanisms of dystonia development remain unknown, the diversity of its clinical phenotypes is thought to be associated with multifactorial pathophysiology, which is linked not only to alterations of brain organization, but also environmental stressors and gene mutations. This chapter will present an overview of the pathophysiology of isolated dystonia through the lens of applications of major neuroimaging methodologies, with links to genetics and environmental factors that play a prominent role in symptom manifestation.
Topics: Brain; Dystonic Disorders; Gray Matter; Humans; Magnetic Resonance Imaging; Neuroimaging; Positron-Emission Tomography; White Matter
PubMed: 30473192
DOI: 10.1016/bs.irn.2018.09.007 -
Journal of Neural Transmission (Vienna,... Apr 2021Dystonia is a disabling movement disorder characterized by abnormal postures or patterned and repetitive movements due to co-contraction of muscles in proximity to... (Review)
Review
Dystonia is a disabling movement disorder characterized by abnormal postures or patterned and repetitive movements due to co-contraction of muscles in proximity to muscles desired for a certain movement. Important and well-established pathophysiological concepts are the impairment of sensorimotor integration, a loss of inhibitory control on several levels of the central nervous system and changes in synaptic plasticity. These mechanisms collectively contribute to an impairment of the gating function of the basal ganglia which results in an insufficient suppression of noisy activity and an excessive activation of cortical areas. In addition to this traditional view, a plethora of animal, genetic, imaging and electrophysiological studies highlight the role of the (1) cerebellum, (2) the cerebello-thalamic connection and (3) the functional interplay between basal ganglia and the cerebellum in the pathophysiology of dystonia. Another emerging topic is the better understanding of the microarchitecture of the striatum and its implications for dystonia. The striosomes are of particular interest as they likely control the dopamine release via inhibitory striato-nigral projections. Striosomal dysfunction has been implicated in hyperkinetic movement disorders including dystonia. This review will provide a comprehensive overview about the current understanding of the functional neuroanatomy and pathophysiology of dystonia and aims to move the traditional view of a 'basal ganglia disorder' to a network perspective with a dynamic interplay between cortex, basal ganglia, thalamus, brainstem and cerebellum.
Topics: Animals; Basal Ganglia; Corpus Striatum; Dystonia; Dystonic Disorders; Neuroanatomy
PubMed: 33486625
DOI: 10.1007/s00702-021-02299-y -
Neurobiology of Disease May 2022This review provides an overview of the synaptic dysfunctions of neuronal circuits and underlying neurochemical alterations observed in the hyperkinetic movement... (Review)
Review
This review provides an overview of the synaptic dysfunctions of neuronal circuits and underlying neurochemical alterations observed in the hyperkinetic movement disorders, dystonia and dyskinesia. These disorders exhibit similar changes in expression of synaptic plasticity and neuromodulation. This includes alterations in physical attributes of synapses, synaptic protein expression, and neurotransmitter systems, such as glutamate and gamma-aminobutyric acid (GABA), and neuromodulators, such as dopamine, acetylcholine, serotonin, adenosine, and endocannabinoids. A full understanding of the mechanisms and consequences of disruptions in synaptic function and plasticity will lend insight into the development of these disorders and new ways to combat maladaptive changes.
Topics: Antiparkinson Agents; Corpus Striatum; Dyskinesias; Dystonia; Dystonic Disorders; Humans; Levodopa
PubMed: 35139431
DOI: 10.1016/j.nbd.2022.105650 -
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 -
Movement Disorders : Official Journal... Jun 2013With increasing understanding of dystonia genetic etiologies and pathophysiology there has been renewed scrutiny and reappraisal of dystonia classification schemes and... (Review)
Review
With increasing understanding of dystonia genetic etiologies and pathophysiology there has been renewed scrutiny and reappraisal of dystonia classification schemes and nomenclature. One important category that includes both clinical and etiologic criteria is primary dystonia. This editorialized review discusses the impact of recent findings on primary dystonia criteria and argues that it remains useful in clinical and research practice. © 2013 Movement Disorder Society.
Topics: Brain; Dystonic Disorders; Genetic Predisposition to Disease; Humans; Terminology as Topic
PubMed: 23893447
DOI: 10.1002/mds.25528