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The Neurologist Mar 2006Dystonia refers to a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Although age at onset,... (Review)
Review
BACKGROUND
Dystonia refers to a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Although age at onset, anatomic distribution, and family history are essential elements in the evaluation of dystonia, new classification increasingly relies on etiologic and genetic data. In recent years, much progress has been made on the genetics of various forms of dystonia and its pathophysiology underlying the clinical signs. The treatment of dystonia has continued to evolve to include newer medications, different forms of botulinum toxin, and various surgical procedures.
REVIEW SUMMARY
In this article, the author reviewed and summarized the history of dystonia, its evolving classification, and recent genetic data, as well as its clinical investigation and treatment.
CONCLUSIONS
Recent advances in molecular biology have led to the discovery of novel dystonia genes and loci, updating classification schemes, and better understanding of underlying pathophysiology. Treatment strategies for dystonia have significantly been updated with the introduction of different forms of botulinum toxin therapy, new pharmacologic agents, and most recently pallidal deep brain stimulation. A systematic approach to the diagnosis and treatment evaluation of dystonic patients provides optimal care for long-term management.
Topics: Baclofen; Botulinum Toxins; Cholinergic Antagonists; Dystonia; Dystonia Musculorum Deformans; GABA Agonists; Humans
PubMed: 16534444
DOI: 10.1097/01.nrl.0000195831.46000.2d -
Neurologic Clinics Aug 2009The torsion dystonias encompass a broad collection of etiologic subtypes, often divided into primary and secondary classes. Tremendous advances have been made in... (Review)
Review
The torsion dystonias encompass a broad collection of etiologic subtypes, often divided into primary and secondary classes. Tremendous advances have been made in uncovering the genetic basis of dystonia, including discovery of a gene causing early onset primary torsion dystonia-a GAG deletion in exon 5 of the DYT1 gene that encodes torsinA. Although the exact function of torsinA remains elusive, evidence suggests aberrant localization and interaction of mutated protein; this may result in an abnormal response to stress or interference with cytoskeletal events and the development of neuronal brain pathways. Breakthroughs include the discovery of a genetic modifier that protects against clinical expression in DYT1 dystonia and the identification of the gene causing DYT6, THAP1. The authors review genetic etiologies and discuss phenotypes as well as counseling of patients regarding prognosis and progression of the disease. They also address pharmacologic and surgical treatment options for various forms of dystonia.
Topics: Age of Onset; Animals; Apoptosis Regulatory Proteins; DNA-Binding Proteins; Disease Progression; Dystonia; Dystonia Musculorum Deformans; Genetic Counseling; Genetic Predisposition to Disease; Humans; Molecular Chaperones; Mutation; Myoclonus; Nuclear Proteins; Parkinsonian Disorders; Phenotype; Prognosis
PubMed: 19555827
DOI: 10.1016/j.ncl.2009.04.010 -
Neurology Feb 1986We studied trihexyphenidyl in the treatment of torsion dystonia in a prospective, double-blind crossover protocol. Thirty-one patients completed the protocol. Twenty-two... (Clinical Trial)
Clinical Trial
We studied trihexyphenidyl in the treatment of torsion dystonia in a prospective, double-blind crossover protocol. Thirty-one patients completed the protocol. Twenty-two (71%) had a clinically significant response. After a mean follow-up of 2.4 years, 68% of patients continued to take trihexyphenidyl, and 42% continued to show a considerable or dramatic benefit. The 30-mg dose used was generally well tolerated. High-dosage trihexyphenidyl therapy is effective in the management of torsion dystonia.
Topics: Adolescent; Adult; Child; Clinical Trials as Topic; Double-Blind Method; Dystonia Musculorum Deformans; Female; Humans; Male; Movement; Prospective Studies; Random Allocation; Trihexyphenidyl
PubMed: 3511401
DOI: 10.1212/wnl.36.2.160 -
Neurobiology of Disease May 2011The hereditary dystonias comprise a set of diseases defined by a common constellation of motor deficits. These disorders are most likely associated with different... (Review)
Review
The hereditary dystonias comprise a set of diseases defined by a common constellation of motor deficits. These disorders are most likely associated with different molecular etiologies, many of which have yet to be elucidated. Here we discuss recent advances in three forms of hereditary dystonia, DYT1, DYT6 and DYT16, which share a similar clinical picture: onset in childhood or adolescence, progressive spread of symptoms with generalized involvement of body regions and a steady state affliction without treatment. Unlike DYT1, the genes responsible for DYT6 and DYT16 have only recently been identified, with relatively little information about the function of the encoded proteins. Nevertheless, recent data suggest that these proteins may fit together within interacting pathways involved in dopaminergic signaling, transcriptional regulation, and cellular stress responses. This review focuses on these molecular pathways, highlighting potential common themes among these dystonias which may serve as areas for future research. This article is part of a Special Issue entitled "Advances in dystonia".
Topics: Animals; Apoptosis Regulatory Proteins; DNA-Binding Proteins; Dopamine; Dystonia Musculorum Deformans; Humans; Molecular Chaperones; Mutation; Nuclear Proteins; RNA-Binding Proteins; Signal Transduction; Synaptic Transmission
PubMed: 21134457
DOI: 10.1016/j.nbd.2010.11.015 -
Acta Neurochirurgica. Supplement 2002Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for... (Review)
Review
Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for Parkinson's disease (PD) and tremor dominant movement disorders. We report on two cases of generalized dystonia which were successfully treated by chronic high frequency stimulation in the Globus pallidus internus (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints were initially treated with orally administered benzodiazepines, anticholinergic drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a patient with a history of left side dominated dystonia since the age of 8. It was first diagnosed as a psychogenic movement disorder. Prior to surgery he was treated with L-DOPA, anticholinergics, Baclofen without any effect. There was only a limited effect on high doses of diazepam. The patient is DYT1 negative. The target point was on both sides the GPI. Intraoperative computerized tomography (CT) and ventriculography (VG) were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode position. Surgery was performed under analgosedation. Two weeks after surgery we first observed a relief of symptoms in both cases. A significant reduction in the Burke-Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The medication was continuously reduced. At the 24 month follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).
Topics: Adult; Dystonia Musculorum Deformans; Electric Stimulation Therapy; Globus Pallidus; Humans; Male; Severity of Illness Index; Treatment Outcome
PubMed: 11974995
DOI: 10.1007/978-3-7091-6105-0_19 -
Revista de Medicina de La Universidad... 1991
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American Journal of Human Genetics Aug 1991Idiopathic torsion dystonia (ITD) is characterized by sustained, involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal...
Idiopathic torsion dystonia (ITD) is characterized by sustained, involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Most familial forms of ITD display autosomal dominant inheritance with reduced penetrance. Linkage analysis has been previously used to localize a dystonia gene to the 9q32-34 region in a large non-Jewish family and in a group of Ashkenazi Jewish families. Utilizing GT repeat polymorphisms from this region, here we demonstrate that the gene causing dystonia in Ashkenazi Jews can be localized to the 11-cM interval between AK1 and D9S10. Linkage analysis in the non-Jewish family is also consistent with occurrence of the gene in this region, although positive lod scores extend over a greater than 20-cM interval in that family. These results set the stage for positional cloning of the dystonia gene. Currently there are no known candidate genes in this region.
Topics: Base Sequence; Chromosome Banding; Chromosomes, Human, Pair 9; DNA; Dystonia Musculorum Deformans; Gene Frequency; Genetic Linkage; Genetic Markers; Humans; Jews; Molecular Sequence Data; Oligonucleotide Probes
PubMed: 1867195
DOI: No ID Found -
Movement Disorders : Official Journal... Oct 1992
Topics: Asphyxia Neonatorum; Case-Control Studies; Dystonia Musculorum Deformans; Fetal Hypoxia; Humans; Hypoxia, Brain; Infant, Newborn; Risk Factors
PubMed: 1484541
DOI: 10.1002/mds.870070421 -
Brain : a Journal of Neurology Sep 2011Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are...
Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige's syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1/61 (2%) control subjects, 27/32 (84%) patients with adult-onset primary torsion dystonia and 32/73 (44%) unaffected relatives [siblings (20/36; 56%), offspring (11/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.
Topics: Adult; Aged; Discrimination, Psychological; Dystonia; Dystonia Musculorum Deformans; Family; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Pedigree; Time Perception; Young Adult
PubMed: 21840890
DOI: 10.1093/brain/awr194 -
Brain : a Journal of Neurology Dec 1974
Comparative Study
Topics: Adolescent; Adult; Child; Child, Preschool; Chlorpromazine; Diagnostic Errors; Diazepam; Disability Evaluation; Dystonia Musculorum Deformans; Female; Gait; Globus Pallidus; Humans; Infant; Levodopa; Male; Mental Disorders; Middle Aged; Perphenazine; Phenothiazines; Prognosis; Remission, Spontaneous; Tetrabenazine; Thalamus; Trihexyphenidyl
PubMed: 4474046
DOI: 10.1093/brain/97.1.793