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Continuum (Minneapolis, Minn.) Oct 2022This article discusses the most recent findings regarding the diagnosis, classification, and management of genetic and idiopathic dystonia. (Review)
Review
PURPOSE OF REVIEW
This article discusses the most recent findings regarding the diagnosis, classification, and management of genetic and idiopathic dystonia.
RECENT FINDINGS
A new approach to classifying dystonia has been created with the aim to increase the recognition and diagnosis of dystonia. Molecular biology and genetic studies have identified several genes and biological pathways involved in dystonia.
SUMMARY
Dystonia is a common movement disorder involving abnormal, often twisting, postures and is a challenging condition to diagnose. The pathophysiology of dystonia involves abnormalities in brain motor networks in the context of genetic factors. Dystonia has genetic, idiopathic, and acquired forms, with a wide phenotypic spectrum, and is a common feature in complex neurologic disorders. Dystonia can be isolated or combined with another movement disorder and may be focal, segmental, multifocal, or generalized in distribution, with some forms only occurring during the performance of specific tasks (task-specific dystonia). Dystonia is classified by clinical characteristics and presumed etiology. The management of dystonia involves accurate diagnosis, followed by treatment with botulinum toxin injections, oral medications, and surgical therapies (mainly deep brain stimulation), as well as pathogenesis-directed treatments, including the prospect of disease-modifying or gene therapies.
Topics: Botulinum Toxins; Brain; Dystonia; Dystonic Disorders; Humans; Movement Disorders
PubMed: 36222773
DOI: 10.1212/CON.0000000000001159 -
Nature Reviews. Neurology Feb 2021Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential... (Review)
Review
Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.
Topics: Biomedical Technology; Deep Brain Stimulation; Depressive Disorder, Major; Dystonic Disorders; Essential Tremor; Forecasting; Humans; Implantable Neurostimulators; Parkinson Disease
PubMed: 33244188
DOI: 10.1038/s41582-020-00426-z -
Journal of Neural Transmission (Vienna,... Apr 2021A plethora of heterogeneous movement disorders is grouped under the umbrella term dystonia. The clinical presentation ranges from isolated dystonia to multi-systemic... (Review)
Review
A plethora of heterogeneous movement disorders is grouped under the umbrella term dystonia. The clinical presentation ranges from isolated dystonia to multi-systemic disorders where dystonia is only a co-occurring sign. In the past, definitions, nomenclature, and classifications have been repeatedly refined, adapted, and extended to reflect novel findings and increasing knowledge about the clinical, etiologic, and scientific background of dystonia. Currently, dystonia is suggested to be classified according to two axes. The first axis offers precise categories for the clinical presentation grouped into age at onset, body distribution, temporal pattern and associated features. The second, etiologic, axis discriminates pathological findings, as well as inheritance patterns, mode of acquisition, or unknown causality. Furthermore, the recent recommendations regarding terminology and nomenclature of inherited forms of dystonia and related syndromes are illustrated in this article. Harmonized, specific, and internationally widely used classifications provide the basis for future systematic dystonia research, as well as for more personalized patient counseling and treatment approaches.
Topics: Age of Onset; Causality; Dystonia; Dystonic Disorders; Humans; Movement Disorders
PubMed: 33604773
DOI: 10.1007/s00702-021-02314-2 -
Journal of Neural Transmission (Vienna,... Apr 2021Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for... (Review)
Review
Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for BT therapy. When BT is injected into dystonic muscles, it produces a peripheral paresis which is localised, well controllable and follows a distinct and predictable time course of around 3 months. Adverse effects are always transient and usually mild, long-term application is safe. With this profile BT can be used to treat cranial dystonia, cervical dystonia and limb dystonia including writer's and musician's cramps. The recent introduction of BT high dose therapy also allows to treat more wide-spread dystonia including segmental and generalised dystonia. BT can easily be combined with other anti-dystonic treatments such as deep brain stimulation and intrathecal baclofen application. Best treatment results are obtained when BT therapy is integrated in the multimodal and long-term 'multilayer concept of treatment of dystonia'. The biggest challenge for the future will be to deliver state of the art BT therapy to all dystonia patients in need, regardless of whether they live in developed countries or beyond.
Topics: Botulinum Toxins; Botulinum Toxins, Type A; Dystonic Disorders; Humans; Muscles; Torticollis; Treatment Outcome
PubMed: 33125571
DOI: 10.1007/s00702-020-02266-z -
Indian Pediatrics Sep 2021Movement disorders represent a common presentation in pediatrics and are often a source of clinical and diagnostic dilemmas. In this review, we provide an overview of... (Review)
Review
CONTEXT
Movement disorders represent a common presentation in pediatrics and are often a source of clinical and diagnostic dilemmas. In this review, we provide an overview of common causes along with simplified clinical approach and management options for major movement disorders.
SOURCES
This narrative review is based on contemporary evidence and personal experience. Medline was searched for recent advances, current understanding and consensus on classification, clinical features, diagnosis and treatment.
RESULTS
Movement disorders are classified as hyperkinetic and hypokinetic disorders, the latter being rare in childhood. The hyperkinetic disorders include dystonia, chorea, athetosis, tics and tremor, stereotypies, myoclonus, startle syndromes and functional disorders. Some movement disorders can be benign and developmental. A large proportion of conditions are genetic in origin with a guarded prognosis. Some of the conditions may be post-infectious, immune-mediated or drug induced. Multiple types of movement disorders are present in many conditions. The age at onset, type and distribution of abnormal movements and presence of associated neurological and systemic features help in narrowing the differential diagnosis. The pharmacotherapy of movement disorders is complex and evolving.
CONCLUSION
A synopsis of movement disorders presenting in pediatric age has been provided, incorporating the latest evidence. A simplified approach for clinical diagnosis has been developed for dystonia and chorea.
Topics: Child; Diagnosis, Differential; Dystonia; Dystonic Disorders; Humans; Movement Disorders; Tremor
PubMed: 34016797
DOI: No ID Found -
Annual Review of Pathology Jan 2024Dystonia is a clinically and genetically highly heterogeneous neurological disorder characterized by abnormal movements and postures caused by involuntary sustained or... (Review)
Review
Dystonia is a clinically and genetically highly heterogeneous neurological disorder characterized by abnormal movements and postures caused by involuntary sustained or intermittent muscle contractions. A number of groundbreaking genetic and molecular insights have recently been gained. While they enable genetic testing and counseling, their translation into new therapies is still limited. However, we are beginning to understand shared pathophysiological pathways and molecular mechanisms. It has become clear that dystonia results from a dysfunctional network involving the basal ganglia, cerebellum, thalamus, and cortex. On the molecular level, more than a handful of, often intertwined, pathways have been linked to pathogenic variants in dystonia genes, including gene transcription during neurodevelopment (e.g., , ), calcium homeostasis (e.g., , ), striatal dopamine signaling (e.g., ), endoplasmic reticulum stress response (e.g., , , ), autophagy (e.g., ), and others. Thus, different forms of dystonia can be molecularly grouped, which may facilitate treatment development in the future.
Topics: Humans; Dystonia; Dystonic Disorders; Dopamine; Molecular Chaperones; DNA-Binding Proteins; Apoptosis Regulatory Proteins; Anoctamins
PubMed: 37738511
DOI: 10.1146/annurev-pathmechdis-051122-110756 -
Neurology Oct 2022is associated with a broad spectrum of predominantly neurologic disorders, which continues to expand beyond the initially defined phenotypes of alternating hemiplegia... (Review)
Review
BACKGROUND AND OBJECTIVES
is associated with a broad spectrum of predominantly neurologic disorders, which continues to expand beyond the initially defined phenotypes of alternating hemiplegia of childhood, rapid-onset dystonia parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndrome. This phenotypic variability makes it challenging to assess the pathogenicity of an variant found in an undiagnosed patient. We describe the phenotypic features of individuals carrying a pathogenic/likely pathogenic variant and perform a literature review of all variants published thus far in association with human neurologic disease. Our aim is to demonstrate the heterogeneous clinical spectrum of the gene and look for phenotypic overlap between patients that will streamline the diagnostic process.
METHODS
Undiagnosed individuals with variants were identified within the cohort of the Deciphering Developmental Disorders study with additional cases contributed by collaborators internationally. Detailed clinical data were collected with consent through a questionnaire completed by the referring clinicians. PubMed was searched for publications containing the term "ATP1A3" from 2004 to 2021.
RESULTS
Twenty-four individuals with a previously undiagnosed neurologic phenotype were found to carry 21 variants. Eight variants have been previously published. Patients experienced on average 2-3 different types of paroxysmal events. Permanent neurologic features were common including microcephaly (7; 29%), ataxia (13; 54%), dystonia (10; 42%), and hypotonia (7; 29%). All patients had cognitive impairment. Neuropsychiatric diagnoses were reported in 16 (66.6%) individuals. Phenotypes were extremely varied, and most individuals did not fit clinical criteria for previously published phenotypes. On review of the literature, 1,108 individuals have been reported carrying 168 different variants. The most common variants are associated with well-defined phenotypes, while more rare variants often result in very rare symptom correlations, such as are seen in our study. Combined Annotation-Dependent Depletion (CADD) scores of pathogenic and likely pathogenic variants were significantly higher and variants clustered within 6 regions of constraint.
DISCUSSION
Our study shows that looking for a combination of paroxysmal events, hyperkinesia, neuropsychiatric symptoms, and cognitive impairment and evaluating the CADD score and variant location can help identify an -related condition, rather than applying diagnostic criteria alone.
Topics: Cerebellar Ataxia; Dystonic Disorders; Hemiplegia; Humans; Mutation; Phenotype; Sodium-Potassium-Exchanging ATPase
PubMed: 36192182
DOI: 10.1212/WNL.0000000000200927 -
Toxins Apr 2020Blepharospasm and oromandibular dystonia are focal dystonias characterized by involuntary and often patterned, repetitive muscle contractions. There is a long history of... (Review)
Review
Blepharospasm and oromandibular dystonia are focal dystonias characterized by involuntary and often patterned, repetitive muscle contractions. There is a long history of medical and surgical therapies, with the current first-line therapy, botulinum neurotoxin (BoNT), becoming standard of care in 1989. This comprehensive review utilized MEDLINE and PubMed and provides an overview of the history of these focal dystonias, BoNT, and the use of toxin to treat them. We present the levels of clinical evidence for each toxin for both, focal dystonias and offer guidance for muscle and site selection as well as dosing.
Topics: Blepharospasm; Botulinum Toxins; Dystonic Disorders; Humans; Mandibular Diseases; Muscular Diseases; Neuromuscular Agents
PubMed: 32331272
DOI: 10.3390/toxins12040269 -
Tremor and Other Hyperkinetic Movements... 2023Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close... (Review)
Review
BACKGROUND
Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.
METHODS
A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 to identify relevant articles for this narrative review.
RESULTS
The spectrum of the phenomenology of PIMD is broad and it encompasses both hyperkinetic and hypokinetic movements. Hemifacial spasm is probably the most common PIMD. Others include dystonia, tremor, parkinsonism, myoclonus, painful leg moving toe syndrome, tics, polyminimyoclonus, and amputation stump dyskinesia. We also highlight conditions such as neuropathic tremor, pseudoathetosis, and -associated myogenic tremor as examples of PIMD.
DISCUSSION
There is considerable heterogeneity among PIMD in terms of severity and nature of injury, natural course, association with pain, and response to treatment. As some patients may have co-existing functional movement disorder, neurologists should be able to differentiate the two disorders. While the exact pathophysiology remains elusive, aberrant central sensitization after peripheral stimuli and maladaptive plasticity in the sensorimotor cortex, on a background of genetic (two-hit hypothesis) or other predisposition, seem to play a role in the pathogenesis of PIMD.
Topics: Humans; Tremor; Movement Disorders; Dystonic Disorders; Tic Disorders; Dyskinesias; Myoclonus
PubMed: 37008994
DOI: 10.5334/tohm.758 -
Tremor and Other Hyperkinetic Movements... 2021Task-specific dystonia (TSD) is a form of focal dystonia that occurs in the context of the performance of selective, highly skilled, often repetitive, motor activity.... (Review)
Review
BACKGROUND
Task-specific dystonia (TSD) is a form of focal dystonia that occurs in the context of the performance of selective, highly skilled, often repetitive, motor activity. TSD may be apparent during certain tasks such as writing, playing musical instruments, or other activities requiring fine motor control, but may also occur during certain sports, and maybe detrimental to professional athletes' careers. Therefore, sports physicians and movement disorder neurologists need to be aware of the presentation and phenomenology of sports-related dystonia (SRD), the topic of this review.
METHODS
A broad PubMed search using a wide range of keywords and combinations was done in October 2021 to identify suitable articles for this review.
RESULTS
Most of the publications are on yips in golfers and on runners' dystonia. Other sports in which SRD has been reported are ice skating, tennis, table tennis, pistol shooting, petanque, baseball, and billiards.
DISCUSSION
Yips, which may affect up to half of the golfers and rarely athletes in other sports (e.g., baseball, cricket, basketball, speed skating, gymnastics) seems to be a multi-factorial form of TSD that is particularly troublesome in highly skilled professional golfers. Runners' dystonia, affecting the foot, leg, and hip (in decreasing order), may evolve into more generalized and less specific dystonia. The pathophysiologic mechanisms of SRD are not well understood. Botulinum toxin has been reported to alleviate dystonia in golfers', runners', and other forms of SRD. Future studies should utilize neurophysiologic, imaging, and other techniques to elucidate mechanisms of this underrecognized group of movement disorders.
Topics: Dystonia; Dystonic Disorders; Golf; Humans; Movement Disorders
PubMed: 35036047
DOI: 10.5334/tohm.670