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Sample records for dystonia musculorum deformans

  1. Characteristic alterations in responses to imposed wrist displacements in parkinsonian rigidity and dystonia musculorum deformans.

    PubMed

    Tatton, W G; Bedingham, W; Verrier, M C; Blair, R D

    1984-05-01

    The amplitude and temporal modulation of the segmented EMG activity in flexor carpi radialis, evoked by imposed angular wrist extension, was studied with respect to the level of pre-existing background activity in rigid parkinsonian (PK) and dystonia musculorum deformans (DMD) patients. The interdependence of the evoked M1 and M2-3 segments on pre-existing background EMG activity and initial velocity of imposed displacement was established previously for a normal population. Individual responses of 21 parkinsonian and 12 dystonic patients were compared to the established normal "response volume". The augmented magnitude of the M2-3 segment in rigid PK patients, which correlates to the measure of rigidity, could not be accounted for by the low level of pre-existing EMG activity. Therefore, increased descending facilitation does not impinge directly on alpha motoneurons. Paradoxical excitation in the shortened muscle and resetting of tonic tremor of the stretched muscle by the imposed wrist extension are two other demonstrated abnormalities which may also contribute to PK rigidity. In contrast, DMD patients demonstrated normal amplitude modulation of the M1 and M2-3 segments, but exhibited a disturbance of normal temporal mechanisms that result in constant duration of the M1 and M2-3 responses with imposed force step loads.

  2. Acetylcholinesterase activity in the brain of dystonia musculorum (Dst(dt-J)) mutant mice.

    PubMed

    Clément, C; Lalonde, R; Strazielle, C

    2012-01-01

    The dystonia musculorum (Dst(dt-J)) mutant mouse suffers from severe motor coordination deficits, characterized, among various symptoms, by a spastic ataxia and dystonic movements, indicating central defects in motor structures in addition to dystrophy of peripheral sensory tracts and partial degeneration of spinocerebellar tracts. Neurochemical alterations, notably in dopaminergic and noradrenergic systems, were previously observed in basal ganglia and cerebellum. A quantitative histochemical cartography of brain acetylcholinesterase activity in Dst(dt-J) mutants, in comparison with controls, revealed increases in the neostriatum, the habenula-interpeduncular pathway, the cholinergic pedunculopontine nucleus and its target structures, the thalamus, major regions of the basal ganglia, such as substantia nigra, ventral tegmental area, globus pallidum, and subthalamic nucleus, as well as in associated extrapyramidal regions, such as red nucleus, brainstem reticular formation, and superior colliculus. These acetylcholinesterase changes may play a role in motor deficits, particularly the dystonic symptomatology observed in the mutation.

  3. Disruption of actin-binding domain-containing Dystonin protein causes dystonia musculorum in mice.

    PubMed

    Horie, Masao; Watanabe, Keisuke; Bepari, Asim K; Nashimoto, Jun-Ichiro; Araki, Kimi; Sano, Hiromi; Chiken, Satomi; Nambu, Atsushi; Ono, Katsuhiko; Ikenaka, Kazuhiro; Kakita, Akiyoshi; Yamamura, Ken-Ichi; Takebayashi, Hirohide

    2014-11-01

    The Dystonin gene (Dst) is responsible for dystonia musculorum (dt), an inherited mouse model of hereditary neuropathy accompanied by progressive motor symptoms such as dystonia and cerebellar ataxia. Dst-a isoforms, which contain actin-binding domains, are predominantly expressed in the nervous system. Although sensory neuron degeneration in the peripheral nervous system during the early postnatal stage is a well-recognised phenotype in dt, the histological characteristics and neuronal circuits in the central nervous system responsible for motor symptoms remain unclear. To analyse the causative neuronal networks and roles of Dst isoforms, we generated novel multipurpose Dst gene trap mice, in which actin-binding domain-containing isoforms are disrupted. Homozygous mice showed typical dt phenotypes with sensory degeneration and progressive motor symptoms. The gene trap allele (Dst(Gt) ) encodes a mutant Dystonin-LacZ fusion protein, which is detectable by X-gal (5-bromo-4-chloro-3-indolyl-β-D-galactoside) staining. We observed wide expression of the actin-binding domain-containing Dystonin isoforms in the central nervous system (CNS) and peripheral nervous system. This raised the possibility that not only secondary neuronal defects in the CNS subsequent to peripheral sensory degeneration but also cell-autonomous defects in the CNS contribute to the motor symptoms. Expression analysis of immediate early genes revealed decreased neuronal activity in the cerebellar-thalamo-striatal pathway in the homozygous brain, implying the involvement of this pathway in the dt phenotype. These novel Dst(Gt) mice showed that a loss-of-function mutation in the actin-binding domain-containing Dystonin isoforms led to typical dt phenotypes. Furthermore, this novel multipurpose Dst(Gt) allele offers a unique tool for analysing the causative neuronal networks involved in the dt phenotype.

  4. Characterization of novel dystonia musculorum mutant mice: Implications for central nervous system abnormality.

    PubMed

    Horie, Masao; Mekada, Kazuyuki; Sano, Hiromi; Kikkawa, Yoshiaki; Chiken, Satomi; Someya, Takuro; Saito, Keisuke; Hossain, M Ibrahim; Nameta, Masaaki; Abe, Kuniya; Sakimura, Kenji; Ono, Katsuhiko; Nambu, Atsushi; Yoshiki, Atsushi; Takebayashi, Hirohide

    2016-12-01

    We identified a novel spontaneous mutant mouse showing motor symptoms that are similar to those of the dystonia musculorum (dt) mouse. The observations suggested that the mutant mice inherited the mild dt phenotype as an autosomal recessive trait. Linkage analysis showed that the causative gene was located near D1Mit373 and D1Mit410 microsatellite markers on chromosome 1, which are close to the dystonin (Dst) gene locus. To investigate whether Dst is the causative gene of the novel mutant phenotype, we crossed the mutant with Dst gene trap (Dst(Gt)) mice. Compound heterozygotes showed a typical dt phenotype with sensory degeneration and progressive motor symptoms. DNA sequencing analysis identified a nonsense mutation within the spectrin repeats of the plakin domain. The novel mutant allele was named dt(23Rbrc). Motor abnormalities in homozygous dt(23Rbrc)/dt(23Rbrc) mice are not as severe as homozygous Dst(Gt)/Dst(Gt) mice. Histological analyses showed abnormal neurofilament (NF) accumulation in the nervous system of homozygous dt(23Rbrc)/dt(23Rbrc) mice, which is characteristic of the dt phenotype. We mapped the distribution of abnormal NF-accumulated neurons in the brain and found that they were located specifically in the brainstem, spinal cord, and in regions such as the vestibular nucleus, reticular nucleus, and red nucleus, which are implicated in posture and motor coordination pathways. The quantification of abnormal NF accumulation in the cytoplasm and spheroids (axons) of neurons showed that abnormal NF immunoreactivity was lower in homozygous dt(23Rbrc)/dt(23Rbrc) mice than in homozygous Dst(Gt)/Dst(Gt) mice. Therefore, we have identified a novel hypomorphic allele of dt, which causes histological abnormalities in the central nervous system that may account for the abnormal motor phenotype. This novel spontaneously occurring mutant may become a good model of hereditary sensory and autonomic neuropathy type 6, which is caused by mutations in the human DST

  5. Disruption in the autophagic process underlies the sensory neuropathy in dystonia musculorum mice.

    PubMed

    Ferrier, Andrew; De Repentigny, Yves; Lynch-Godrei, Anisha; Gibeault, Sabrina; Eid, Walaa; Kuo, Daniel; Zha, Xiaohui; Kothary, Rashmi

    2015-01-01

    A homozygous mutation in the DST (dystonin) gene causes a newly identified lethal form of hereditary sensory and autonomic neuropathy in humans (HSAN-VI). DST loss of function similarly leads to sensory neuron degeneration and severe ataxia in dystonia musculorum (Dst(dt)) mice. DST is involved in maintaining cytoskeletal integrity and intracellular transport. As autophagy is highly reliant upon stable microtubules and motor proteins, we assessed the influence of DST loss of function on autophagy using the Dst(dt-Tg4) mouse model. Electron microscopy (EM) revealed an accumulation of autophagosomes in sensory neurons from these mice. Furthermore, we demonstrated that the autophagic flux was impaired. Levels of LC3-II, a marker of autophagosomes, were elevated. Consequently, Dst(dt-Tg4) sensory neurons displayed impaired protein turnover of autophagosome substrate SQTSM1/p62 and of polyubiquitinated proteins. Interestingly, in a previously described Dst(dt-Tg4) mouse model that is partially rescued by neuronal specific expression of the DST-A2 isoform, autophagosomes, autolysosomes, and damaged organelles were reduced when compared to Dst(dt-Tg4) mutant mice. LC3-II, SQTSM1, polyubiquitinated proteins and autophagic flux were also restored to wild-type levels in the rescued mice. Finally, a significant decrease in DNAIC1 (dynein, axonemal, intermediate chain 1; the mouse ortholog of human DNAI1), a member of the DMC (dynein/dynactin motor complex), was noted in Dst(dt-Tg4) dorsal root ganglia and sensory neurons. Thus, DST-A2 loss of function perturbs late stages of autophagy, and dysfunctional autophagy at least partially underlies Dst(dt) pathogenesis. We therefore conclude that the DST-A2 isoform normally facilitates autophagy within sensory neurons to maintain cellular homeostasis.

  6. Dystonias

    MedlinePlus

    ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation.org http:// ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation. ...

  7. Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia

    PubMed Central

    Broussolle, Emmanuel; Laurencin, Chloé; Bernard, Emilien; Thobois, Stéphane; Danaila, Teodor; Krack, Paul

    2015-01-01

    Background Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. Results In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called “simple mannerisms, childish behaviour or fake pathological movements” was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud’s pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim’s 1911 seminal description of dystonia musculorum deformans in Berlin. Discussion Brissaud-Meige’s misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970–1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society’s classification of dystonia. PMID:26417535

  8. Dystonias

    MedlinePlus

    ... Strategy Current Research Research Funded by NINDS Basic Neuroscience Clinical Research Translational Research Research at NINDS Focus ... by the latest discoveries from genetics and basic neuroscience, scientists and doctors hope to better understand dystonia ...

  9. Dystonia

    PubMed Central

    2008-01-01

    Introduction Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acetylcholine receptor inhibitors, acupuncture, anticholinergic drugs, anticonvulsants, atypical antipsychotic drugs, benzodiazepines, biofeedback, botulinum toxin, chiropractic manipulation, deep brain stimulation of thalamus and globus pallidus, dopaminergic agonists and antagonists, gamma-aminobutyric acid (GABA) inhibitors, microvascular decompression, myectomy, occupational therapy, osteopathy, pallidotomy, physiotherapy, selective peripheral denervation, serotonergic agonists and antagonists, speech therapy, and thalamotomy. PMID:19445800

  10. Dystonia

    PubMed Central

    2011-01-01

    Introduction Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acetylcholine release inhibitors (botulinum toxin), acupuncture, anticholinergic/antihistaminic drugs, anticonvulsants, atypical antipsychotic drugs, benzodiazepines, biofeedback, chiropractic manipulation, deep brain stimulation of thalamus and globus pallidus, dopaminergic agonists and antagonists, gamma-aminobutyric acid (GABA) analogues, microvascular decompression, muscle relaxants, myectomy, occupational therapy, osteopathy, pallidotomy, physiotherapy, selective peripheral denervation, serotonergic agonists and antagonists, speech therapy, and thalamotomy. PMID:21663705

  11. Musician's Dystonias

    MedlinePlus

    ... Dystonia (MWD) is a program of the Dystonia Medical Research Foundation implemented to acknowledge the unique challenges facing ... com/facesofdystonia Accelerating Research & Inspiring Hope The Dystonia Medical Research Foundation (DMRF) has served the dystonia community since ...

  12. Musician's Dystonia

    MedlinePlus

    ... Steven Frucht, MD in partnership with the Dystonia Medical Research Foundation. MWD established a network of health care ... the DMRF on Facebook, Twitter, and YouTube. © Dystonia Medical Research Foundation 2012

  13. [Tardive dystonia].

    PubMed

    van Harten, P N; Kamphuis, D J; Matroos, G E

    1992-08-01

    Two patients with tardive dystonia are presented. Tardive dystonia is a late-onset side effect of dopamine antagonist, which occurs in approximately 2% of the patients in the course of treatment with neuroleptic medication. The dystonia usually starts by affecting the musculature of face and (or) neck and is often progressive to a segmental localization. Of differential diagnostic importance are: conversion disorder, acute dystonia, Wilson's disease, idiopathic dystonia and dystonia triggered by other agents. Treatment starts with reevaluation of the need for ongoing neuroleptic treatment. Investigation of the pharmacotherapy of the dystonia concerns mostly treatment with dopamine depletors or with high doses of anticholinergic agents. Improvement of 50% of the patients is reported, although total recovery is rare. Many other substances and also some physical methods (ECT and surgery) have been used with varying results.

  14. Employees with Dystonia

    MedlinePlus

    ... be presented during childhood, adolescence, or adulthood (Dystonia Medical Research Foundation, 2010). How prevalent is dystonia? According to the Dystonia Medical Research Foundation, dystonia is the third most common movement ...

  15. The Genetics of Dystonias

    PubMed Central

    LeDoux, Mark S.

    2016-01-01

    Dystonia has been defined as a syndrome of involuntary, sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. Dystonia is also a clinical sign that can be the presenting or prominent manifestation of many neurodegenerative and neuro-metabolic disorders. Etiological categories include primary dystonia, secondary dystonia, heredodegenerative diseases with dystonia, and dystonia plus. Primary dystonia includes syndromes in which dystonia is the sole phenotypic manifestation with the exception that tremor can be present as well. Most primary dystonia begins in adults, and approximately 10% of probands report one or more affected family members. Many cases of childhood- and adolescent-onset dystonia are due to mutations in TOR1A and THAP1. Mutations in THAP1 and CIZ1 have been associated with sporadic and familial adult-onset dystonia. Although significant recent progress had been made in defining the genetic basis for most of the dystonia-plus and heredodegenerative diseases with dystonia, a major gap remains in understanding the genetic etiologies for most cases of adult-onset primary dystonia. Common themes in the cellular biology of dystonia include G1/S cell cycle control, monoaminergic neurotransmission, mitochondrial dysfunction, and the neuronal stress response. PMID:22989765

  16. Cervical Dystonia (Spasmodic Torticollis)

    MedlinePlus

    Cervical dystonia Overview By Mayo Clinic Staff Cervical dystonia, also called spasmodic torticollis, is a painful condition in which your neck muscles contract involuntarily, causing your head to twist or turn ...

  17. Dystonia Medical Research Foundation

    MedlinePlus

    ... Member Joins Peer Review of DOD Peer Reviewed Medical Research Program More News Support Groups Join the DMRF ... of Dystonia Research Research News Funding Programs Current Research Dystonia Coalition ... Connect Contact Us Privacy Policy Support Groups Calendar

  18. Untethering the Nuclear Envelope and Cytoskeleton: Biologically Distinct Dystonias Arising from a Common Cellular Dysfunction

    PubMed Central

    Atai, Nadia A.; Ryan, Scott D.; Kothary, Rashmi; Breakefield, Xandra O.; Nery, Flávia C.

    2012-01-01

    Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (ΔE) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding dystonin in mice results in a dystonic movement disorder termed dystonia musculorum, which resembles aspects of dystonia in humans. While torsinA and dystonin proteins do not share modular domain architecture, they participate in a similar function by modulating a structural link between the nuclear envelope and the cytoskeleton in neuronal cells. We suggest that through a shared interaction with the nuclear envelope protein nesprin-3α, torsinA and the neuronal dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane and the cytoskeleton, which is critical for some aspects of neuronal development and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in nuclear/endoplasmic reticulum dynamics should provide insights into the cellular mechanisms underlying the dystonic phenotype. PMID:22611399

  19. Art and dystonia.

    PubMed

    Garcia-Ruiz, Pedro J; Slawek, Jaroslaw; Sitek, Emilia J; Martinez Castrillo, Juan Carlos

    2015-09-15

    Dystonia has a recent history in medicine. Focal dystonia was described in the 19th century by classic authors including Gowers, whilst generalized dystonia was described at the turn of the century. However, it is possible to find precise descriptions of dystonia in art, centuries before the medical definition. We have reviewed several pieces of art (sculpture, painting and literature) across the history that might represent descriptions of dystonia, from ancient period to nowadays. In classic times, the first reference to abnormal postures can be tracked back to the new Empire of Egypt (equinus foot), not to mention some recently described examples of dystonia from the Moche sculptures in Peru or Veracruz culture from Mexico. In Middle Ages it is possible to find many examples of sculptures in European cathedrals representing peasants with dramatic, presumably dystonic postures that coexist with amputation of limbs. This unique combination of dystonia and limb amputation probably represents ergotism. The painters Brueghel, Ribera and Velazquez also represented figures with postures likely to be dystonic. Literature is also a source of precise pre-neurological descriptions, especially during the 19th century. In David Copperfield, Dickens depicts characters with generalized dystonia (Uriah Heep), cervical dystonia (Mr. Sharp) and spasmodic dysphonia (Mr Creakle). Finally, even in modern Art (19th and 20th centuries), there are dramatic descriptions of abnormal postures that are likely to be dystonic, such as painful cervical dystonia (Brancusi), cervical dystonia with sensory trick (Modigliani) and upper limb dystonia (Wyspianski). However some postures presented in works of art may simply be a form of artistic expression and only bear unintentional resemblance to the dystonic postures. Art may be a source of neurological information, and that includes primary and secondary dystonia.

  20. Oro-mandibular dystonia.

    PubMed

    Gandhi, Yazad R

    2010-07-01

    Dystonia is an involuntary, repetitive, sustained (tonic), or spasmodic (rapid or clonic) muscle contraction. The spectrum of dystonias can involve various regions of the body. Oromandibular dystonia (OMD) can involve the masticatory, lower facial and the tongue muscles which may results in trismus, bruxism, involuntary jaw opening or closure and involuntary tongue movement. Here, we report a case of OMD in a 68 year old man.

  1. Dystonia: a clinical approach.

    PubMed

    Edwards, Mark J

    2008-12-01

    Dystonia is a common movement disorder characterised by abnormal postures of the affected body part. It has a very varied presentation and numerous causes, and this can create difficulties with diagnosis and appropriate investigation. This article aims to provide a clinical approach to patients with dystonia, focussing on how to create a differential diagnosis and to plan rational testing.

  2. Hairdresser’s Dystonia: An Unusual Occupational Dystonia

    PubMed Central

    Giorelli, Maurizio; Zimatore, Giovanni Bosco

    2013-01-01

    Background Adult-onset focal dystonias (AOFDs) are non-task-specific or task-specific and may spread to other body segments of affected patients. Case report We report the case of a barber with non-task-specific craniocervical dystonia and a new occupational focal hand dystonia (while using scissors). Discussion Different AOFDs may develop and coexist in the same “vulnerable” patient. Hairdresser’s dystonia is a rare task-specific dystonia. PMID:24386610

  3. How Many Dystonias? Clinical Evidence

    PubMed Central

    Albanese, Alberto

    2017-01-01

    Literary reports on dystonia date back to post-Medieval times. Medical reports are instead more recent. We review here the early descriptions and the historical establishment of a consensus on the clinical phenomenology and the diagnostic features of dystonia syndromes. Lumping and splitting exercises have characterized this area of knowledge, and it remains largely unclear how many dystonia types we are to count. This review describes the history leading to recognize that focal dystonia syndromes are a coherent clinical set encompassing cranial dystonia (including blepharospasm), oromandibular dystonia, spasmodic torticollis, truncal dystonia, writer’s cramp, and other occupational dystonias. Papers describing features of dystonia and diagnostic criteria are critically analyzed and put into historical perspective. Issues and inconsistencies in this lumping effort are discussed, and the currently unmet needs are critically reviewed. PMID:28217105

  4. Early onset torsion dystonia (Oppenheim's dystonia)

    PubMed Central

    Kamm, Christoph

    2006-01-01

    Early onset torsion dystonia (EOTD) is a rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body. A US study estimated the prevalence at approximately 1 in 30,000. The estimated prevalence in the general population of Europe seems to be lower, ranging from 1 in 330,000 to 1 in 200,000, although precise numbers are currently not available. The estimated prevalence in the Ashkenazi Jewish population is approximately five to ten times higher, due to a founder mutation. Symptoms of EOTD typically develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. Distribution and severity of symptoms vary widely between affected individuals. The majority of cases from various ethnic groups are caused by an autosomal dominantly inherited deletion of 3 bp (GAG) in the DYT1 gene on chromosome 9q34. This gene encodes a protein named torsinA, which is presumed to act as a chaperone protein associated with the endoplasmic reticulum and the nuclear envelope. It may interact with the dopamine transporter and participate in intracellular trafficking, although its precise function within the cell remains to be determined. Molecular genetic diagnostic and genetic counseling is recommended for individuals with age of onset below 26 years, and may also be considered in those with onset after 26 years having a relative with typical early onset dystonia. Treatment options include botulinum toxin injections for focal symptoms, pharmacological therapy such as anticholinergics (most commonly trihexiphenydil) for generalized dystonia and surgical approaches such as deep brain stimulation of the internal globus pallidus or intrathecal baclofen application in severe cases. All patients have normal cognitive function, and despite a high rate of generalization of dystonia, 75% of those patients

  5. Forms of Dystonia

    MedlinePlus

    ... the symptoms, and associated features such as additional movement disorders or neurological symptoms, and 2. Cause (which includes ... prominent myoclonus symptoms. Paroxysmal dystonias and dyskinesias : Episodic movement disorders in which abnormal movements occur only during attacks. ...

  6. Genetics Home Reference: task-specific focal dystonia

    MedlinePlus

    ... Other Diagnosis and Management Resources (4 links) Dystonia Medical Research Foundation: How Is Dystonia Diagnosed? Dystonia Medical Research Foundation: Treatments GeneReview: Dystonia Overview Merck Manual Home ...

  7. Dystonia: Related and Differential Disorders

    MedlinePlus

    ... head and the voice. Dystonic tremors are quite variable in their presentation and on some occasions can ... Oromandibular dystonia may be misdiagnosed as TMJ. Accelerating Research & Inspiring Hope The Dystonia Medical Research Foundation (DMRF) ...

  8. Osteitis deformans (Paget's disease) in a Burmese python (Python molurus bivittatus)--a case report.

    PubMed

    Preziosi, Rosario; Diana, Alessia; Florio, Daniela; Gustinelli, Andrea; Nardini, Giordano

    2007-11-01

    Osteitis deformans (Paget's disease of bone) is a chronic focal disorder of bone remodelling characterized by an initial increase in osteoclast-mediated bone resorption, with subsequent compensatory increase in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone. In the Burmese python (Python molurus bivittatus) of this report, multifocal gross swellings involving the proximal third of the vertebral spine were observed and associated with anorexia, a relative inability to move or to fully extend the body, and to strike at prey. Serum biochemistry revealed elevated alkaline-phosphatase activity. Radiographic changes (irregular bone proliferation along the vertebral margins), computed tomography scan results (abnormal mineral density), and histopathological features (generalized thickening of the bony trabeculae at the expense of the intertrabecular spaces and irregular patches of lamellar bone with a characteristic "mosaic" pattern) indicated osteitis deformans.

  9. Genome Sequencing of the Plant Pathogen Taphrina deformans, the Causal Agent of Peach Leaf Curl

    PubMed Central

    Cissé, Ousmane H.; Almeida, João M. G. C. F.; Fonseca, Álvaro; Kumar, Ajay Anand; Salojärvi, Jarkko; Overmyer, Kirk; Hauser, Philippe M.; Pagni, Marco

    2013-01-01

    ABSTRACT Taphrina deformans is a fungus responsible for peach leaf curl, an important plant disease. It is phylogenetically assigned to the Taphrinomycotina subphylum, which includes the fission yeast and the mammalian pathogens of the genus Pneumocystis. We describe here the genome of T. deformans in the light of its dual plant-saprophytic/plant-parasitic lifestyle. The 13.3-Mb genome contains few identifiable repeated elements (ca. 1.5%) and a relatively high GC content (49.5%). A total of 5,735 protein-coding genes were identified, among which 83% share similarities with other fungi. Adaptation to the plant host seems reflected in the genome, since the genome carries genes involved in plant cell wall degradation (e.g., cellulases and cutinases), secondary metabolism, the hallmark glyoxylate cycle, detoxification, and sterol biosynthesis, as well as genes involved in the biosynthesis of plant hormones. Genes involved in lipid metabolism may play a role in its virulence. Several locus candidates for putative MAT cassettes and sex-related genes akin to those of Schizosaccharomyces pombe were identified. A mating-type-switching mechanism similar to that found in ascomycetous yeasts could be in effect. Taken together, the findings are consistent with the alternate saprophytic and parasitic-pathogenic lifestyles of T. deformans. PMID:23631913

  10. Peripherally induced oromandibular dystonia

    PubMed Central

    Sankhla, C.; Lai, E.; Jankovic, J.

    1998-01-01

    OBJECTIVES—Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary muscle contractions producing repetitive, patterned mouth, jaw, and tongue movements. Dystonia is usually idiopathic (primary), but in some cases it follows peripheral injury. Peripherally induced cervical and limb dystonia is well recognised, and the aim of this study was to characterise peripherally induced OMD.
METHODS—The following inclusion criteria were used for peripherally induced OMD: (1) the onset of the dystonia was within a few days or months (up to 1 year) after the injury; (2) the trauma was well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral).
RESULTS—Twenty seven patients were identified in the database with OMD, temporally and anatomically related to prior injury or surgery. No additional precipitant other than trauma could be detected. None of the patients had any litigation pending. The mean age at onset was 50.11 (SD 14.15) (range 23-74) years and there was a 2:1 female preponderance. Mean latency between the initial trauma and the onset of OMD was 65 days (range 1 day-1 year). Ten (37%) patients had some evidence of predisposing factors such as family history of movement disorders, prior exposure to neuroleptic drugs, and associated dystonia affecting other regions or essential tremor. When compared with 21 patients with primary OMD, there was no difference for age at onset, female preponderance, and phenomenology. The frequency of dystonic writer's cramp, spasmodic dysphonia, bruxism, essential tremor, and family history of movement disorder, however, was lower in the post-traumatic group (p<0.05). In both groups the response to botulinum toxin treatment was superior to medical therapy (p<0.005). Surgical intervention for temporomandibular disorders was more frequent in the post-traumatic group and was associated with

  11. Dopa responsive dystonia.

    PubMed Central

    Patel, K; Roskrow, T; Davis, J S; Heckmatt, J Z

    1995-01-01

    There may be insufficient awareness of dopa responsive dystonia (DRD), which has a characteristic diurnal variation of symptoms. Two children are reported in whom the diagnosis of DRD was missed. The first was thought to have hysteria and the second hereditary spastic paraparesis. A full history is vital for the diagnosis of this important treatable syndrome. PMID:7492170

  12. Treatment for dystonia in childhood.

    PubMed

    Roubertie, A; Mariani, L L; Fernandez-Alvarez, E; Doummar, D; Roze, E

    2012-10-01

    Management of childhood dystonia differs in certain respects from that of adult dystonia: (i) childhood dystonia is more often secondary than primary; (ii) mixed motor disorders are frequent; (iii) in children, the course of dystonia may be influenced by ongoing brain maturation and by the remarkable plasticity of the young brain; (iv) drug tolerability and effectiveness can be different in children; (v) the therapeutic strategy must be discussed with both the patient and his or her parents; and (vi) the child's education must be taken into account. Based on a systematic review of the literature through June 2011 and on our personal experience, we propose a therapeutic approach to childhood dystonia. After a detailed clinical evaluation and a comprehensive work-up to rule out a treatable cause of dystonia, symptomatic treatment may include various drugs, local botulinum toxin injections, and deep brain stimulation, in addition to rehabilitation.

  13. Invertebrate Models of Dystonia

    PubMed Central

    Caldwell, Kim A; Shu, Yilong; Roberts, Nathan B; Caldwell, Guy A; O’Donnell, Janis M

    2013-01-01

    The neurological movement disorder dystonia is an umbrella term for a heterogeneous group of related conditions where at least 20 monogenic forms have been identified. Despite the substantial advances resulting from the identification of these loci, the function of many DYT gene products remains unclear. Comparative genomics using simple animal models to examine the evolutionarily conserved functional relationships with monogenic dystonias represents a rapid route toward a comprehensive understanding of these movement disorders. Current studies using the invertebrate animal models Caenorhabditis elegans and Drosophila melanogaster are uncovering cellular functions and mechanisms associated with mutant forms of the well-conserved gene products corresponding to DYT1, DYT5a, DYT5b, and DYT12 dystonias. Here we review recent findings from the invertebrate literature pertaining to molecular mechanisms of these gene products, torsinA, GTP cyclohydrolase I, tyrosine hydroxylase, and the alpha subunit of Na+/K ATPase, respectively. In each study, the application of powerful genetic tools developed over decades of intensive work with both of these invertebrate systems has led to mechanistic insights into these human disorders. These models are particularly amenable to large-scale genetic screens for modifiers or additional alleles, which are bolstering our understanding of the molecular functions associated with these gene products. Moreover, the use of invertebrate models for the evaluation of DYT genetic loci and their genetic interaction networks has predictive value and can provide a path forward for therapeutic intervention. PMID:23814534

  14. Surgery for Dystonia and Tremor.

    PubMed

    Crowell, Jason L; Shah, Binit B

    2016-03-01

    Surgical procedures for dystonia and tremor have evolved over the past few decades, and our understanding of risk, benefit, and predictive factors has increased substantially in that time. Deep brain stimulation (DBS) is the most utilized surgical treatment for dystonia and tremor, though lesioning remains an effective option in appropriate patients. Dystonic syndromes that have shown a substantial reduction in severity secondary to DBS are isolated dystonia, including generalized, cervical, and segmental, as well as acquired dystonia such as tardive dystonia. Essential tremor is quite amenable to DBS, though the response of other forms of postural and kinetic tremor is not nearly as robust or consistent based on available evidence. Regarding targeting, DBS lead placement in the globus pallidus internus has shown marked efficacy in dystonia reduction. The subthalamic nucleus is an emerging target, and increasing evidence suggests that this may be a viable target in dystonia as well. The ventralis intermedius nucleus of the thalamus is the preferred target for essential tremor, though targeting the subthalamic zone/caudal zona incerta has shown promise and may emerge as another option in essential tremor and possibly other tremor disorders. In the carefully selected patient, DBS and lesioning procedures are relatively safe and effective for the management of dystonia and tremor.

  15. Deep brain stimulation for dystonia.

    PubMed

    Vidailhet, Marie; Jutras, Marie-France; Grabli, David; Roze, Emmanuel

    2013-09-01

    The few controlled studies that have been carried out have shown that bilateral internal globus pallidum stimulation is a safe and long-term effective treatment for hyperkinetic disorders. However, most recent published data on deep brain stimulation (DBS) for dystonia, applied to different targets and patients, are still mainly from uncontrolled case reports (especially for secondary dystonia). This precludes clear determination of the efficacy of this procedure and the choice of the 'good' target for the 'good' patient. We performed a literature analysis on DBS for dystonia according to the expected outcome. We separated those with good evidence of favourable outcome from those with less predictable outcome. In the former group, we review the main results for primary dystonia (generalised/focal) and highlight recent data on myoclonus-dystonia and tardive dystonia (as they share, with primary dystonia, a marked beneficial effect from pallidal stimulation with good risk/benefit ratio). In the latter group, poor or variable results have been obtained for secondary dystonia (with a focus on heredodegenerative and metabolic disorders). From this overview, the main results and limits for each subgroup of patients that may help in the selection of dystonic patients who will benefit from DBS are discussed.

  16. Alcohol-Sensitive Generalized Dystonia.

    PubMed

    Micheli, Federico; Uribe-Roca, Claudia; Saenz-Farret, Michel

    We report the case of a 29-year-old male patient with a generalized and progressive dystonia that led him unable to stand. Multiple antidystonic treatments were tried without benefit. Alcohol test was positive with a dramatic improvement. To the best of our knowledge, this is the first reported case of generalized dystonia without other clinical manifestations sensitive to alcohol.

  17. Egon Schiele and dystonia.

    PubMed

    Erbguth, Frank J

    2010-01-01

    Egon Schiele was a leading Austrian Expressionist painter who, after the era of Gustav Klimt, strongly influenced the artistic scene in Vienna in the early 20th century. Schiele's depiction of his body in his self-portraits in a twisted, contorted, dystonia-like pose raised questions about the possibility of his suffering from dystonia. However, there are no grounds whatsoever for such a hypothesis. Schiele's conception of distorted, at times bizarre, body postures reflects a concourse of the Expressionist formal style of displaying extroverted emotions and psychic confl icts with the emerging perception of photographs of patients with movement disorders in Vienna's art scene and intellectual circles. There are reliable indications that Schiele knew the images of diseases published in the 'Iconographie Photographique de la Salpetriere' and the later 'Nouvelle Iconographie de la Salpetriere' including hysterical and dystonic postures. The brevity of Schiele's life adds to the popular fantasy of the outlaw who lived fast and died young. In fact, however, his drawings sold well to discerning collectors, and his exhibitions were a financial success, so the myth of Schiele as a sacrificial outcast does not tell the whole story. It may be speculated that the figuration of the pathological body in Schiele's self-portraiture was part of modernist strategizing.

  18. Dystonia: Emotional and Mental Health

    MedlinePlus

    ... grieving a loss, such as a death or divorce. Common phases of dealing with dystonia include denial, ... only controlling muscle movement, but also mood and behaviors, so it is not surprising that there is ...

  19. Genetics Home Reference: dystonia 6

    MedlinePlus

    ... of the THAP1 protein, reducing the amount of functional THAP1 protein available for DNA binding. Other mutations ... THAP1 (DYT6) in early-onset dystonia: a genetic screening study. Lancet Neurol. 2009 May;8(5):441- ...

  20. Traumatic Brain Injury and Dystonia

    MedlinePlus

    Traumatic Brain Injury & Dystonia Traumatic brain injury (TBI) occurs when a sudden trauma damages to the brain. TBI can occur when the head suddenly and violently hits an object, or when an object pierces the skull and ...

  1. Genetics in Dystonia: An Update

    PubMed Central

    Fuchs, Tania; Ozelius, Laurie J.

    2013-01-01

    The past year has been extremely successful with regards to the genetics of dystonia with the identification of four new dystonia genes (CIZ1, ANO3, GNAL and TUBB4A). This progress was primarily achieved because of the application of a new technology, next generation DNA sequencing, which allows rapid and comprehensive assessment of patient’s genomes. In addition, a combination of next generation and traditional Sanger sequencing has expanded the phenotypic spectrum associated with some of the dystonia plus (ATP1A3) and paroxysmal loci (PRRT2). This article reviews the newly identified genes and phenotypes and discusses the future applications of next generation sequencing to dystonia research. PMID:24136457

  2. Diagnosis & Treatment of Dystonia

    PubMed Central

    Jinnah, H. A.

    2014-01-01

    Synopsis The dystonias are a group of disorders characterized by excessive involuntary muscle contractions leading to abnormal postures and/or repetitive movements. There are many different clinical manifestations and many different causes. A careful assessment of the clinical manifestations is helpful for identifying syndromic patterns that focus diagnostic testing on potential causes. If a cause can be identified, specific etiology-based treatments may be available. However, in the majority of cases, a specific cause cannot be identified, and treatments are based on symptoms. Treatment options include counseling and education, oral medications, botulinum toxin injections, and several surgical procedures. A substantial reduction in symptoms and improved quality of life can be achieved in the majority of patients by combining these various options. PMID:25432724

  3. Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis.

    PubMed

    Phukan, Julie; Albanese, Alberto; Gasser, Thomas; Warner, Thomas

    2011-12-01

    The dystonias are a heterogeneous group of hyperkinetic movement disorders characterised by involuntary sustained muscle contractions that lead to abnormal postures and repetitive movements. Dystonia syndromes represent common movement disorders and yet are often misdiagnosed or unrecognised. In recent years, there have been substantial advances in the understanding of the spectrum of clinical features that encompass dystonia syndromes, from severe generalised childhood dystonia that is often genetic in origin, to adult-onset focal dystonias and rarer forms of secondary dystonias, to dystonia as a feature of other types of CNS dysfunction. There has also been a rationalisation of the classification of dystonia and a greater understanding of the causes of dystonic movements from the study of genetics, neurophysiology, and functional imaging in the most prevalent form of dystonia syndrome, primary dystonia.

  4. Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias

    PubMed Central

    Casper, Catharina; Kalliolia, Eirini; Warner, Thomas T

    2013-01-01

    The majority of studies investigating the molecular pathogenesis and cell biology underlying dystonia have been performed in individuals with primary dystonia. This includes monogenic forms such as DYT1and DYT6 dystonia, and primary focal dystonia which is likely to be multifactorial in origin. In recent years there has been renewed interest in non-primary forms of dystonia including the dystonia-plus syndromes and heredodegenerative disorders. These are caused by a variety of genetic mutations and their study has contributed to our understanding of the neuronal dysfunction that leads to dystonia These findings have reinforced themes identified from study of primary dystonia including abnormal dopaminergic signalling, cellular trafficking and mitochondrial function. In this review we highlight recent advances in the understanding of the dystonia-plus syndromes and heredodegenerative dystonias. PMID:23814535

  5. Working capacity and cervical dystonia.

    PubMed

    Martikainen, Kirsti K; Luukkaala, Tiina H; Marttila, Reijo J

    2010-03-01

    The objective of this questionnaire study was to assess the effect of cervical dystonia on patients' working capacity. Of the 303 working-aged members of the Finnish Dystonia Association (N = 433) who participated in the study 247 (82%) had cervical dystonia. Their median age was 50 years, the median duration of CD symptoms was 12.3 years. Most (78%) subjects were on botulinum toxin treatment. Ninety-seven (39%) had retired because of CD at a median age of 48 years; 96 (39%) of the subjects were working: 87 full-time and 9 part-time. The remaining participants were on sick leave, unemployed, studying or retired of other reasons. Retirement occurred more than ten years earlier compared with the general Finnish population. All possibilities to help CD patients to continue longer in work should be considered early.

  6. Dystonia rating scales: critique and recommendations

    PubMed Central

    Albanese, Alberto; Sorbo, Francesca Del; Comella, Cynthia; Jinnah, H.A.; Mink, Jonathan W.; Post, Bart; Vidailhet, Marie; Volkmann, Jens; Warner, Thomas T.; Leentjens, Albert F.G.; Martinez-Martin, Pablo; Stebbins, Glenn T.; Goetz, Christopher G.; Schrag, Anette

    2014-01-01

    Background Many rating scales have been applied to the evaluation of dystonia, but only few have been assessed for clinimetric properties. The Movement Disorders Society commissioned this task force to critique existing dystonia rating scales and place them in the clinical and clinimetric context. Methods A systematic literature review was conducted to identify rating scales that have either been validated or used in dystonia. Results Thirty six potential scales were identified. Eight were excluded because they did not meet review criteria, leaving twenty-eight scales that were critiqued and rated by the task force. Seven scales were found to meet criteria to be “recommended”: the Blepharospasm Disability Index is recommended for rating blepharospasm; the Cervical Dystonia Impact Scale and the Toronto Western Spasmodic Torticollis Rating Scale for rating cervical dystonia; the Craniocervical Dystonia Questionnaire for blepharospasm and cervical dystonia; the Voice Handicap Index (VHI) and the Vocal Performance Questionnaire (VPQ) for laryngeal dystonia; and the Fahn-Marsden Dystonia Rating Scale for rating generalized dystonia. Two “recommended” scales (VHI and VPQ) are generic scales validated on few patients with laryngeal dystonia, whereas the others are disease-specific scales. Twelve scales met criteria for “suggested” and seven scales met criteria for “listed”. All the scales are individually reviewed in the online appendix. Conclusion The task force recommends five specific dystonia scales and suggests to further validate in dystonia two recommended generic voice-disorder scales. Existing scales for oromandibular, arm and task-specific dystonia should be refined and fully assessed. Scales should be developed for body regions where no scales are available, such as lower limbs and trunk. PMID:23893443

  7. Update on the Genetics of Dystonia.

    PubMed

    Lohmann, Katja; Klein, Christine

    2017-03-01

    Mainly due to the advent of next-generation sequencing (NGS), the field of genetics of dystonia has rapidly grown in recent years, which led to the discovery of a number of novel dystonia genes and the development of a new classification and nomenclature for inherited dystonias. In addition, new findings from both in vivo and in vitro studies have been published on the role of previously known dystonia genes, extending our understanding of the pathophysiology of dystonia. We here review the current knowledge and recent findings in the known genes for isolated dystonia TOR1A, THAP1, and GNAL as well as for the combined dystonias due to mutations in GCH1, ATP1A3, and SGCE. We present confirmatory evidence for a role of dystonia genes that had not yet been unequivocally established including PRKRA, TUBB4A, ANO3, and TAF1. We finally discuss selected novel genes for dystonia such as KMT2B and VAC14 along with the challenges for gene identification in the NGS era and the translational importance of dystonia genetics in clinical practice.

  8. Investigation of the osteitis deformans phases in snake vertebrae by double-pulse laser-induced breakdown spectroscopy.

    PubMed

    Galiová, M; Kaiser, J; Novotný, K; Ivanov, M; Nývltová Fisáková, M; Mancini, L; Tromba, G; Vaculovic, T; Liska, M; Kanický, V

    2010-09-01

    Double-pulse laser-induced breakdown spectroscopy (DP-LIBS) was optimized for microspatial analyses of fossil and recent snake vertebrae. As complimentary techniques, solution analysis by inductively coupled plasma mass spectrometry and synchrotron radiation X-ray microtomography was utilized in order to determine the overall concentration of the selected elements in the samples and to visualize nondestructively the fossil sample microstructure, respectively. Elemental mapping of pathological bony tissue by DP-LIBS has been proven as a powerful tool for considering the osteitis deformans phases in fossil vertebrae.

  9. Dissecting the links between cerebellum and dystonia.

    PubMed

    Malone, Ailish; Manto, Mario; Hass, Chris

    2014-12-01

    Dystonia is a common movement disorder characterized by sustained muscle contractions. These contractions generate twisting and repetitive movements or typical abnormal postures, often exacerbated by voluntary movement. Dystonia can affect almost all the voluntary muscles. For several decades, the discussion on the pathogenesis has been focused on basal ganglia circuits, especially striatal networks. So far, although dystonia has been observed in some forms of ataxia such as dominant ataxias, the link between the cerebellum and dystonia has remained unclear. Recent human studies and experimental data mainly in rodents show that the cerebellum circuitry could also be a key player in the pathogenesis of some forms of dystonia. In particular, studies based on behavioral adaptation paradigm shed light on the links between dystonia and cerebellum. The spectrum of movement disorders in which the cerebellum is implicated is continuously expanding, and manipulation of cerebellar circuits might even emerge as a candidate therapy in the coming years.

  10. Secondary and primary dystonia: pathophysiological differences.

    PubMed

    Kojovic, Maja; Pareés, Isabel; Kassavetis, Panagiotis; Palomar, Francisco J; Mir, Pablo; Teo, James T; Cordivari, Carla; Rothwell, John C; Bhatia, Kailash P; Edwards, Mark J

    2013-07-01

    Primary dystonia is thought to be a disorder of the basal ganglia because the symptoms resemble those of patients who have anatomical lesions in the same regions of the brain (secondary dystonia). However, these two groups of patients respond differently to therapy suggesting differences in pathophysiological mechanisms. Pathophysiological deficits in primary dystonia are well characterized and include reduced inhibition at many levels of the motor system and increased plasticity, while emerging evidence suggests additional cerebellar deficits. We compared electrophysiological features of primary and secondary dystonia, using transcranial magnetic stimulation of motor cortex and eye blink classical conditioning paradigm, to test whether dystonia symptoms share the same underlying mechanism. Eleven patients with hemidystonia caused by basal ganglia or thalamic lesions were tested over both hemispheres, corresponding to affected and non-affected side and compared with 10 patients with primary segmental dystonia with arm involvement and 10 healthy participants of similar age. We measured resting motor threshold, active motor threshold, input/output curve, short interval intracortical inhibition and cortical silent period. Plasticity was probed using an excitatory paired associative stimulation protocol. In secondary dystonia cerebellar-dependent conditioning was measured using delayed eye blink classical conditioning paradigm and results were compared with the data of patients with primary dystonia obtained previously. We found no difference in motor thresholds, input/output curves or cortical silent period between patients with secondary and primary dystonia or healthy controls. In secondary dystonia short interval intracortical inhibition was reduced on the affected side, whereas it was normal on the non-affected side. Patients with secondary dystonia had a normal response to the plasticity protocol on both the affected and non-affected side and normal eye blink

  11. Cervical dystonia and quality of life.

    PubMed

    Tomic, Svetlana; Petkovic, Ivana; Pucic, Tomislav; Resan, Bojan; Juric, Stjepan; Rotim, Tatjana

    2016-12-01

    Cervical dystonia is focal dystonia characterized by involuntary movement of the neck muscle, which leads to abnormal head posture. It can be accompanied with pain and tremor. In this study, we evaluated the presence of depression and anxiety in patients with cervical dystonia and the influence of dystonia symptoms on the quality of life. Psychiatric symptoms were evaluated by use of the Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to evaluate the cervical dystonia symptoms. Quality of life was assessed by the craniocervical dystonia questionnaire (CDQ-24) and short form 36 health survey (SF-36). Nineteen patients were analyzed. Most of the patients had mild cervical dystonia (mean TWSTRS 23.89). Depression was present in 42.1 % and anxiety in 57.9 % of the patients. Disability due to cervical dystonia correlated with the occurrence of depression (ρ = 0.534) and anxiety (r = 0.652). Disability was found to significantly influence the stigma, emotional state, pain, daily activity, social life, physical function, and physical and mental disability. Pain influenced some aspects of body pain, physical function, and physical and mental disability. Being associated with disability and pain, cervical dystonia decreases the quality of life in many aspects. Disability also influenced depression and anxiety, which were present in half of study patients. In addition to follow up for cervical dystonia symptoms, patients with cervical dystonia should also be assessed for psychiatric symptoms on routine clinical check-ups. In addition to botulinum toxin, psychopharmaceuticals should be considered as a treatment option in these patients.

  12. Sertraline induced mandibular dystonia and bruxism

    PubMed Central

    Uvais, N. A.; Sreeraj, V. S.; Sathish Kumar, S. V.

    2016-01-01

    Specific serotonin reuptake inhibitors have been associated with the occurrence of drug-induced parkinsonism, dystonia, dyskinesia, and akathisia. Here, we describe a young female patient with a diagnosis of the moderate depressive episode who developed mandibular dystonia and bruxism with sertraline in the absence of concurrent prescription of medications, which have potential action on the dopaminergic system. PMID:28349014

  13. Recent Advances in the Genetics of Dystonia

    PubMed Central

    Xiao, Jianfeng; Vemula, Satya R.

    2016-01-01

    Dystonia, a common and genetically heterogeneous neurological disorder, was recently defined as “a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both.” Via the application of whole-exome sequencing, the genetic landscape of dystonia and closely related movement disorders is becoming exposed. In particular, several “novel” genetic causes have been causally associated with dystonia or dystonia-related disorders over the past 2 years. These genes include PRRT2 (DYT10), CIZ1 (DYT23), ANO3 (DYT24), GNAL (DYT25), and TUBB4A (DYT4). Despite these advances, major gaps remain in identifying the genetic origins for most cases of adult-onset isolated dystonia. Furthermore, model systems are needed to study the biology of PRRT2, CIZ1, ANO3, Gαolf, and TUBB4A in the context of dystonia. This review focuses on these recent additions to the family of dystonia genes, genotype-phenotype correlations, and possible cellular contributions of the encoded proteins to the development of dystonia. PMID:24952478

  14. Update on the Pathology of Dystonia

    PubMed Central

    Standaert, David G.

    2011-01-01

    Dystonia is a clinical syndrome with sustained muscle contraction, twisting, and abnormal postures. A number of different genetic forms have been defined, but most cases are sporadic in nature and of uncertain cause. Relatively few cases of dystonia have been studied pathologically. In primary dystonias, where dystonia is the main symptom, most reports describe little or no detectable neuropathology, although changes in brainstem neurons have been described in some cases. Secondary dystonias are associated with degenerative or destructive diseases of the nervous system; the pathology may be located in the basal ganglia, but in some cases the primary pathological changes are found in the cerebellum or cerebellar outflow pathways, suggesting both regions may be involved in the pathogenesis of dystonic symptoms. Overall the number of well-documented pathological cases available for study are few, and there is an urgent need for additional postmortem studies. PMID:21220015

  15. Dystonia in Methylphenidate Withdrawal: A Case Report.

    PubMed

    Grau-López, Lara; Daigre, Constanza; Mercado, Nestor; Casas, Miquel; Roncero, Carlos

    Few studies have described movement disorders as withdrawal symptoms during psychostimulant detoxification. Although dystonia has been reported as an uncommon adverse effect of methylphenidate treatment, it has not been described in the context of methylphenidate withdrawal. We report a case of dystonia as the main withdrawal symptom in a methylphenidate-dependent adult participating in an inpatient methylphenidate detoxification program. Although movement disorders such as dystonia are very rare adverse effects of methylphenidate withdrawal, practitioners need to be alert to this risk in order to initiate appropriate treatment.

  16. Genetics Home Reference: myoclonus-dystonia

    MedlinePlus

    ... that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

  17. Intraoperative neurophysiology in deep brain surgery for psychogenic dystonia

    PubMed Central

    Ramos, Vesper Fe Marie L; Pillai, Ajay S; Lungu, Codrin; Ostrem, Jill; Starr, Philip; Hallett, Mark

    2015-01-01

    Psychogenic dystonia is a challenging entity to diagnose and treat because little is known about its pathophysiology. We describe two cases of psychogenic dystonia who underwent deep brain stimulation when thought to have organic dystonia. The intraoperative microelectrode recordings in globus pallidus internus were retrospectively compared with those of five patients with known DYT1 dystonia using spontaneous discharge parameters of rate and bursting, as well as movement-related discharges. Our data suggest that simple intraoperative neurophysiology measures in single subjects do not differentiate psychogenic dystonia from DYT1 dystonia. PMID:26125045

  18. Dystonia in childhood: clinical and objective measures and functional implications.

    PubMed

    Pavone, Larissa; Burton, Justin; Gaebler-Spira, Deborah

    2013-03-01

    Dystonia is a complex movement disorder that is challenging to identify and quantify. The aim of this article is to review the clinical scales, kinematic measures, and functional implications of dystonia. Clinical measures include the Barry-Albright Dystonia Scale, the Burke-Fahn-Marsden Movement Scale, the Unified Dystonia Rating Scale, the Global Dystonia Rating Scale, and the Movement Disorder-Childhood Rating Scale. The evidence, reliability, and validity of each scale will be outlined. The Hypertonia Assessment Tool will be discussed emphasizing the importance of discriminating hypertonia. The role of kinematic measures in analyzing dystonia will be explored, as well as the potential for its future clinical applications.

  19. Dopamine Dysfunction in DYT1 Dystonia

    DTIC Science & Technology

    2015-07-01

    Abstract Background DYT1 dystonia is a heritable, early-onset generalized movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene...Introduction Dystonia is the third most common movement disorder after essential tremor and Parkinson’s disease. It is a neurological disorder...characterized by involuntary muscle contractions with de- bilitating, painful, twisting movements and contorted postures [1]. Although the vast majority of

  20. Unraveling early events in the Taphrina deformans - Prunus persica interaction: an insight into the differential responses in resistant and susceptible genotypes.

    PubMed

    Svetaz, Laura A; Bustamante, Claudia A; Goldy, Camila; Rivero, Nery; Müller, Gabriela L; Valentini, Gabriel H; Fernie, Alisdair R; Drincovich, María F; Lara, María V

    2017-02-28

    Leaf peach curl is a devastating disease affecting leaves, flowers and fruits caused by the dimorphic fungus Taphrina deformans. To gain insight into the mechanisms of fungus pathogenesis and plant responses, leaves of a resistant and two susceptible P. persica genotypes were inoculated with blastospores (yeast), and the infection was monitored during 120 hpi. Fungal dimorphism to the filamentous form and induction of ROS, callose synthesis, cell death, and defense compound production was observed independently of the genotype. Fungal load significantly decreased after 120 hpi in the resistant genotype while the pathogen tended to grow in the susceptible genotypes. Metabolic profiling revealed a biphasic re-programming of plant tissue in susceptible genotypes, with an initial stage co-incident with the yeast form of the fungus and a second when the hyphae is developed. Transcriptional analysis of PRs and plant hormone-related genes indicated that PR proteins are involved in P. persica defense responses against T. deformans and that salicylic acid is induced in the resistant genotype. Conducted experiments allowed the elucidation of common and differential responses in susceptible vs resistant genotypes, and thus allows us to construct a picture of early events during T. deformans infection.

  1. Descriptive Epidemiology of Cervical Dystonia

    PubMed Central

    Defazio, Giovanni; Jankovic, Joseph; Giel, Jennifer L.; Papapetropoulos, Spyridon

    2013-01-01

    Background Cervical dystonia (CD), the most common form of adult-onset focal dystonia, has a heterogeneous clinical presentation with variable clinical features, leading to difficulties and delays in diagnosis. Owing to the lack of reviews specifically focusing on the frequency of primary CD in the general population, we performed a systematic literature search to examine its prevalence/incidence and analyze methodological differences among studies. Methods We performed a systematic literature search to examine the prevalence data of primary focal CD. Sixteen articles met our methodological criteria. Because the reported prevalence estimates were found to vary widely across studies, we analyzed methodological differences and other factors to determine whether true differences exist in prevalence rates among geographic areas (and by gender and age distributions), as well as to facilitate recommendations for future studies. Results Prevalence estimates ranged from 20–4,100 cases/million. Generally, studies that relied on service-based and record-linkage system data likely underestimated the prevalence of CD, whereas population-based studies suffered from over-ascertainment. The more methodologically robust studies yielded a range of estimates of 28–183 cases/million. Despite the varying prevalence estimates, an approximate 2:1 female:male ratio was consistent among many studies. Three studies estimated incidence, ranging from 8–12 cases/million person-years. Discussion Although several studies have attempted to estimate the prevalence and incidence of CD, there is a need for additional well-designed epidemiological studies on primary CD that include large populations; use defined CD diagnostic criteria; and stratify for factors such as age, gender, and ethnicity. PMID:24255801

  2. Dystonia

    MedlinePlus

    ... due to a problem in the part of the brain that handles messages about muscle contractions. There is no cure. Doctors use medicines, Botox injections, surgery, physical therapy, and other treatments to reduce or eliminate muscle ...

  3. Dystonia

    MedlinePlus

    ... clinical studies. Contact: NINDS Brain Resource and Information Network, PO Box 5801 Bethesda, MD 20824, (800) 352-9424 National Institute of ... of Science Policy Analysis | Office of Science Policy | Office of Extramural Research | ...

  4. Genetics Home Reference: hypermanganesemia with dystonia, polycythemia, and cirrhosis

    MedlinePlus

    ... Genetics Home Health Conditions HMDPC hypermanganesemia with dystonia, polycythemia, and cirrhosis Enable Javascript to view the expand/ ... Open All Close All Description Hypermanganesemia with dystonia, polycythemia, and cirrhosis ( HMDPC ) is an inherited disorder in ...

  5. Sensory-motor integration in focal dystonia.

    PubMed

    Avanzino, Laura; Tinazzi, Michele; Ionta, Silvio; Fiorio, Mirta

    2015-12-01

    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.

  6. Primary dystonias and genetic disorders with dystonia as clinical feature of the disease.

    PubMed

    Moghimi, Narges; Jabbari, Bahman; Szekely, Anna M

    2014-01-01

    Dystonia is probably the most common form of movement disorder encountered in the clinical practice. It is characterized by sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures or positions. Dystonias can be classified in several ways, including primarily by the clinical phenomenology or by the underlining etiology, in particular to understand if the presentation is genetically determined. By advances of genetics, including contemporary genomic technologies, there is a growing understanding of the molecular underpinnings of genetically determined dystonias. The intricacy of information requires a user friendly, novel database that may efficiently serve clinicians to inform of advances of the field and to diagnose and manage these often complex cases. Here we present an up to date, comprehensive review - in tabulated formats - of genetically determined primary dystonias and complex Mendelian disorders with dystonia as central feature. The detailed search up to December 24, 2012, identified 24 hereditary primary dystonias (DYT1 to DYT 25) that are mostly monogenic disorders, and a larger group (>70) of genetic syndromes in which dystonia is one of the characteristic clinical features. We organized the findings not only by individual information (name of the conditions, pattern of inheritance, chromosome and gene abnormality, clinical features, relevant ancillary tests and key references), but also provide symptom-oriented organization of the clinical entities for efficient inquiries.

  7. Unmet Needs in Dystonia: Genetics and Molecular Biology—How Many Dystonias?

    PubMed Central

    Verbeek, Dineke S.; Gasser, Thomas

    2017-01-01

    Genetic findings of the past years have provided ample evidence for a substantial etiologic heterogeneity of dystonic syndromes. While an increasing number of genes are being identified for Mendelian forms of isolated and combined dystonias using classical genetic mapping and whole-exome sequencing techniques, their precise role in the molecular pathogenesis is still largely unknown. Also, the role of genetic risk factors in the etiology of sporadic dystonias is still enigmatic. Only the systematic ascertainment and precise clinical characterization of very large cohorts with dystonia, combined with systematic genetic studies, will be able to unravel the complex network of factors that determine disease risk and phenotypic expression. PMID:28138320

  8. Mental dysfunctions in dystonia-plus syndromes.

    PubMed

    Sunga, Mary Anne P; Rosales, Raymond L

    2014-01-01

    With the increasing understanding of the involvement of basal ganglia circuits in the functions of movement, cognition, emotion and motivation, the network model of dystonia posits a plausible mechanism for the co-occurrence of mental dysfunctions in dystonia-plus syndromes. Genetic mutations that alter the production of neurotransmitters and receptors can potentially affect the function of these interconnecting circuits and yield non-motor symptoms as well. This article reviews the psychiatric findings in dystonia-plus syndromes reported thus far in the literature, both in animal models and human subjects. Based on this innovative understanding of the pathophysiology, implications to treatment of combined motor and non-motor symptoms (i.e. mental dysfunctions) are also briefly discussed.

  9. Botulinum toxin physiology in focal hand and cranial dystonia.

    PubMed

    Karp, Barbara Illowsky

    2012-11-20

    The safety and efficacy of botulinum toxin for the treatment of focal hand and cranial dystonias are well-established. Studies of these adult-onset focal dystonias reveal both shared features, such as the dystonic phenotype of muscle hyperactivity and overflow muscle contraction and divergent features, such as task specificity in focal hand dystonia which is not a common feature of cranial dystonia. The physiologic effects of botulinum toxin in these 2 disorders also show both similarities and differences. This paper compares and contrasts the physiology of focal hand and cranial dystonias and of botulinum toxin in the management of these disorders.

  10. Efficacy of aripiprazole in sulpiride-induced tardive oromandibular dystonia.

    PubMed

    Imai, Noboru; Ikawa, Masako

    2011-01-01

    Tardive dystonia is a side effect of dopamine receptor-blocking agents, which are mainly used as antipsychotic drugs. The treatment of tardive dystonia is difficult and often unsuccessful. An 82-year-old woman experienced mandibular deviation to the left due to spasm of the masticatory muscles with involuntary chewing movement and Parkinsonism. She had been treated with sulpiride for motility disorder for 5 years. Parkinsonism almost disappeared after the withdrawal of sulpiride, but tardive oromandibular dystonia showed no improvement. Aripiprazole treatment at 3 mg/day improved tardive oromandibular dystonia without worsening Parkinsonism. Low-dosage aripiprazole may be effective for tardive oromandibular dystonia in patients with no other psychiatric disorder.

  11. The "shirt collar sign" of cervical dystonia.

    PubMed

    Silver, Michael R; Hanfelt, John; Factor, Stewart A

    2017-05-01

    The diagnosis of cervical dystonia (CD) is clinical. We describe a physical examination observation that has been noted in CD patients. There is a tendency for their shirt collars to be shifted to one side. We validated this apparently consistent finding by having blinded evaluators rating the symmetry of the shirt collars in CD and non-cervical dystonia control subjects. A high correlation was found between the physical finding which we call "shirt collar sign" and the diagnosis. "Shirt collar sign" may be a helpful sign in diagnosing CD.

  12. Animal models of dystonia: Lessons from a mutant rat.

    PubMed

    LeDoux, Mark S

    2011-05-01

    Dystonia is a motor sign characterized by involuntary muscle contractions which produce abnormal postures. Genetic factors contribute significantly to primary dystonia. In comparison, secondary dystonia can be caused by a wide variety of metabolic, structural, infectious, toxic and inflammatory insults to the nervous system. Although classically ascribed to dysfunction of the basal ganglia, studies of diverse animal models have pointed out that dystonia is a network disorder with important contributions from abnormal olivocerebellar signaling. In particular, work with the dystonic (dt) rat has engendered dramatic paradigm shifts in dystonia research. The dt rat manifests generalized dystonia caused by deficiency of the neuronally restricted protein caytaxin. Electrophysiological and biochemical studies have shown that defects at the climbing fiber-Purkinje cell synapse in the dt rat lead to abnormal bursting firing patterns in the cerebellar nuclei, which increases linearly with postnatal age. In a general sense, the dt rat has shown the scientific and clinical communities that dystonia can arise from dysfunctional cerebellar cortex. Furthermore, work with the dt rat has provided evidence that dystonia (1) is a neurodevelopmental network disorder and (2) can be driven by abnormal cerebellar output. In large part, work with other animal models has expanded upon studies in the dt rat and shown that primary dystonia is a multi-nodal network disorder associated with defective sensorimotor integration. In addition, experiments in genetically engineered models have been used to examine the underlying cellular pathologies that drive primary dystonia. This article is part of a Special Issue entitled "Advances in dystonia".

  13. Non-motor symptoms in patients with adult-onset focal dystonia: Sensory and psychiatric disturbances.

    PubMed

    Conte, Antonella; Berardelli, Isabella; Ferrazzano, Gina; Pasquini, Massimo; Berardelli, Alfredo; Fabbrini, Giovanni

    2016-01-01

    Dystonia is characterized by the presence of involuntary muscle contractions that cause abnormal movements and posture. Adult onset focal dystonia include cervical dystonia, blepharospasm, arm dystonia and laryngeal dystonia. Besides motor manifestations, patients with focal dystonia frequently also display non-motor signs and symptoms. In this paper, we review the evidence of sensory and psychiatric disturbances in adult patients with focal dystonia. Clinical studies and neurophysiological investigations consistently show that the sensory system is involved in dystonia. Several studies have also demonstrated that neuropsychiatric disorders, particularly depression and anxiety, are more frequent in patients with focal dystonia, whereas data on obsessive compulsive disorders are more contrasting.

  14. Dystonia--new advances in classification, genetics, pathophysiology and treatment.

    PubMed

    Skogseid, I M

    2014-01-01

    Dystonia is a heterogeneous movement disorder and has been defined as 'a syndrome of sustained muscle contractions, frequently causing twisted and repetitive movements, or abnormal postures'. The classification of dystonia has developed along with increasing knowledge, and different schemes have been suggested, including age at onset, body distribution, and etiology as the main differentiating factors. A revised definition and a new classification of dystonia have now been proposed by a group of leading dystonia experts and will be referred here. The discovery of the first two gene mutations causing primary generalized dystonia (DYT1-TOR1A and DYT6-THAP1) has facilitated studies on pathogenesis and pathophysiology of primary dystonias, by comparing neurophysiology between manifesting and non-manifesting carriers, and by studying the molecular biology of the mutant gene products. During recent years, several other gene mutations causing primary dystonia, dystonia-plus, and paroxysmal dystonia disorders have been discovered. Only during the last year, by the use of whole-exome sequencing techniques, mutations in three different genes in families with predominantly cervical dystonia were found, which may lead to improved insight into the pathogenesis also of the more frequent focal dystonias. Botulinum neurotoxin (BoNT) and deep brain stimulation (DBS) have revolutionized the symptomatic treatment for dystonia during the last two decades and continue to be refined to improve efficacy and expand their indications. Unfortunately, no progress has been made in the oral medication of dystonia. Current and future new insights into pathogenetic and pathophysiological mechanisms of dystonia will hopefully lead to improvement also in this area soon.

  15. Acute Dystonia After Single Dose of Bupropion

    PubMed Central

    Elyasi, Forouzan; Mahtiyan, Elham

    2016-01-01

    Bupropion is an antidepressant that is effective in the treatment of major depressive disorders, smoking cessation, and sexual side effects of selective serotonin reuptake inhibitors. Acute dystonia is characterized by prolonged muscle contraction often represented by spasms of the head and neck muscles as well as occasional jaw clenching and temporomandibular joint syndrome. Although it is believed that dystonia is the result of an abnormality of the basal ganglia, its pathophysiology is still unclear. A few cases of dystonia resulting from bupropion have been reported in prior research papers. This case report discusses a patient who had a neck spasm painful enough to wake him up and dystonic distortion after taking only one dose of 75 mg bupropion. The patient was a young 34-year-old man with a diagnosis of obsessive-compulsive disorder treated with 60 mg fluoxetine. Bupropion was added to his medications because of sexual side effects caused by the fluoxetine. It seems that we must be careful to watch for dystonic symptoms when bupropion is mixed with other drugs that affect serotonin reuptake. Although dystonia is a rare side effect of bupropion, physicians should be aware of it and manage it if it occurs. PMID:27833231

  16. Dystonia and Paroxysmal Dyskinesias: Under-Recognized Movement Disorders in Domestic Animals? A Comparison with Human Dystonia/Paroxysmal Dyskinesias

    PubMed Central

    Richter, Angelika; Hamann, Melanie; Wissel, Jörg; Volk, Holger A.

    2015-01-01

    Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements, and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis, and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e., dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans and summarizes similar hereditary movement disorders reported in domestic animals. PMID:26664992

  17. Is acute dystonia an emergency? Sometimes, it really is!

    PubMed

    Kanburoglu, Mehmet Kenan; Derinoz, Oksan; Cizmeci, Mehmet Nevzat; Havali, Cengiz

    2013-03-01

    Most cases of acute dystonia are mild and easy to manage; nevertheless, some of them can be fatal because of the involvement of certain muscle groups such as the laryngeal muscles, thus requiring urgent intervention. In the literature, approach to life-threatening acute dystonia has not been investigated thoroughly, although the diagnosis is a challenge, and treatment should be offered immediately. Herein the management of life-threatening acute dystonia is discussed via 2 case reports.

  18. The Italian Dystonia Registry: rationale, design and preliminary findings.

    PubMed

    Defazio, Giovanni; Esposito, M; Abbruzzese, G; Scaglione, C L; Fabbrini, G; Ferrazzano, G; Peluso, S; Pellicciari, R; Gigante, A F; Cossu, G; Arca, R; Avanzino, L; Bono, F; Mazza, M R; Bertolasi, L; Bacchin, R; Eleopra, R; Lettieri, C; Morgante, F; Altavista, M C; Polidori, L; Liguori, R; Misceo, S; Squintani, G; Tinazzi, M; Ceravolo, R; Unti, E; Magistrelli, L; Coletti Moja, M; Modugno, N; Petracca, M; Tambasco, N; Cotelli, M S; Aguggia, M; Pisani, A; Romano, M; Zibetti, M; Bentivoglio, A R; Albanese, A; Girlanda, P; Berardelli, A

    2017-02-18

    The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

  19. The syndrome of deafness-dystonia: clinical and genetic heterogeneity.

    PubMed

    Kojovic, Maja; Pareés, Isabel; Lampreia, Tania; Pienczk-Reclawowicz, Karolina; Xiromerisiou, Georgia; Rubio-Agusti, Ignacio; Kramberger, Milica; Carecchio, Miryam; Alazami, Anas M; Brancati, Francesco; Slawek, Jaroslaw; Pirtosek, Zvezdan; Valente, Enza Maria; Alkuraya, Fowzan S; Edwards, Mark J; Bhatia, Kailash P

    2013-06-01

    The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions.

  20. Early surgical treatment in a case of myoclonus dystonia syndrome.

    PubMed

    Kühn, Andrea A; Krause, Patricia; Lauritsch, Katharina; Zentner, Christian; Brücke, Christof; Schneider, Gerd-Helge

    2014-11-01

    Myoclonus dystonia syndrome is often misdiagnosed in young children and appropriate treatment is delayed, which has a negative impact on motor development, participation, and emotional well-being. In severely affected patients, deep brain stimulation of the globus pallidus internus has been used successfully to treat both dystonia and myoclonus. Here, the authors present a case of early successful treatment of myoclonus dystonia syndrome by pallidal deep brain stimulation in a patient at the age of 17 years leading to 83% reduction in dystonia score and 89% reduction in myoclonus. The patient gained significant improvement in motor function as well as increased participation and reduced stigma.

  1. Reaching movements in childhood dystonia contain signal-dependent noise.

    PubMed

    Sanger, Terence D; Kaiser, Jason; Placek, Brian

    2005-06-01

    When reaching, children with dystonia exhibit movements that are slower and more variable than normal children. We hypothesize that in dystonia there is an increase in signal-dependent noise so that there is increased variability with increasing speed. This hypothesis predicts that slower movement in children with dystonia is at least partly due to a compensatory strategy to reduce variability by decreasing speed. To test this hypothesis, we measured the speed of arm movement while children attempted to contact buttons of different sizes. We tested 23 control children and 15 children between the ages of 4 and 16 years with dystonia owing to either cerebral palsy, idiopathic dystonia not due to the DYT1 (torsin A) mutation, or other identified causes. A consistent inverse relationship between movement time and button size was seen for both the control children and the children with dystonia. The variance of movement speed increased with the average speed for all subjects. Children with dystonia moved significantly more slowly at all button sizes, and their movement speed was more sensitive to changes in button size. Therefore, part of the reduction in speed in dystonia is due to relatively greater difficulty in contacting small targets. This finding is consistent with the hypothesis of increased signal-dependent noise in children with dystonia, and we present a simple computational model that provides a possible explanation for the origin of this noise.

  2. A reflection on plasticity research in writing dystonia.

    PubMed

    Sadnicka, Anna; Hamada, Masashi; Bhatia, Kailash P; Rothwell, John C; Edwards, Mark J

    2014-07-01

    Much attention has focused on the hypothesis that there is enhanced plasticity of sensorimotor circuits in patients with dystonia. A common experimental method to assess plasticity in dystonia research is paired associative stimulation (PAS). Excessive, nonfocal effects of PAS were observed in early studies of dystonia; however, these large effects have not been uniformly replicated. In this viewpoint, data from 15 patients with writing dystonia are presented. We suggest that, as in healthy individuals, the effects of PAS are highly variable. A review of previous studies examining PAS in writing dystonia highlights the range of results that have been observed. We conclude that current experimental evidence cannot be fully explained by the notion that PAS responses in writing dystonia are consistently excessive or nonspecific. The variability of PAS responses is such that enhanced plasticity should not be considered a dystonic fingerprint, because the direction of response can vary, and there is overlap between patient and healthy data. We also discuss evidence questioning the assumption that PAS responses are a clear correlate to levels of synaptic plasticity; we need to define more specifically what PAS responses signify in the dystonic brain. Our conclusions are limited to PAS in writing dystonia; however, much variation exists with other plasticity protocols. Large multicenter studies of both focal and generalized forms of dystonia, probing variability of individual neurophysiological profiles, are encouraged. This will reveal the true role of plasticity in the pathophysiology of dystonia and may expose subject-specific therapeutic interventions that are currently concealed.

  3. Dystonia and Tremor: The Clinical Syndromes with Isolated Tremor

    PubMed Central

    Albanese, Alberto; Sorbo, Francesca Del

    2016-01-01

    Background Dystonia and tremor share many commonalities. Isolated tremor is part of the phenomenological spectrum of isolated dystonia and of essential tremor. The occurrence of subtle features of dystonia may allow one to differentiate dystonic tremor from essential tremor. Diagnostic uncertainty is enhanced when no features of dystonia are found in patients with a tremor syndrome, raising the question whether the observed phenomenology is an incomplete form of dystonia. Methods Known forms of syndromes with isolated tremor are reviewed. Diagnostic uncertainties between tremor and dystonia are put into perspective. Results The following isolated tremor syndromes are reviewed: essential tremor, head tremor, voice tremor, jaw tremor, and upper-limb tremor. Their varied phenomenology is analyzed and appraised in the light of a possible relationship with dystonia. Discussion Clinicians making a diagnosis of isolated tremor should remain vigilant for the detection of features of dystonia. This is in keeping with the recent view that isolated tremor may be an incomplete phenomenology of dystonia. PMID:27152246

  4. Motor and Sensory Dysfunction in Musician's Dystonia.

    PubMed

    Chang, Florence C F; Frucht, Steven J

    2013-01-01

    Musicians' dystonia is a task-specific and painless loss of motor control in a previously well-executed task. It is increasingly recognized in the medical and musical community. Recent advances in neuroimaging, transcranial magnetic stimulation and novel techniques in electroencephalography have shed light on its underlying pathophysiology. To date, a deranged cortical plasticity leading to abnormal sensorimotor integration, combined with reduced inhibition across several levels of the motor pathway are likely mechanisms.This paper reviews the various phenomenology of musician's dystonia across keyboard, string, brass, flute and drum players. Treatment is often challenging. Medical therapies like botulinum toxin injection and rehabilitation method with sensorimotor training offer symptomatic relief and return to baseline performance to some musicians.

  5. Tricks in dystonia: ordering the complexity

    PubMed Central

    Ramos, Vesper Fe Marie Llaneza; Karp, Barbara I.; Hallett, Mark

    2016-01-01

    Sensory tricks are various maneuvers that can ameliorate dystonia. Common characteristics are well known, but their variety is wide, sensory stimulation is not necessarily the critical feature, and their physiology is unknown. To enumerate the various forms of sensory tricks and describe their nature, research findings and theories that may elucidate their neurophysiologic mechanism, we reviewed the literature pertaining to sensory tricks, including variants like motor tricks, imaginary tricks, forcible tricks and reverse sensory tricks. On the basis of this information, we propose a new classification of sensory tricks to include its variants. We highlight neurophysiologic evidence suggesting that sensory tricks work by decreasing abnormal facilitation. We tie this with established dystonia pathogenesis and postulate that sensory tricks decrease abnormally increased facilitation-to-inhibition ratios in the dystonic brain. It appears worthwhile for patients to search for possible sensory tricks. PMID:24487380

  6. Cervical Dystonia: From Pathophysiology to Pharmacotherapy

    PubMed Central

    Patel, Sejal; Martino, Davide

    2013-01-01

    Background: Dystonia is a chronic disorder characterised by an aberration in the control of movement. Sustained co-contraction of opposing agonist and antagonist muscles can cause repetitive and twisting movements, or abnormal postures. Cervical dystonia (CD), often referred to as spasmodic torticollis, is a type of focal dystonia involving the muscles of the neck and sometimes the shoulders. Methods: This systematic review collates the available evidence regarding the safety and efficacy of a range of treatments for CD, focusing on their effectiveness as shown by double-blinded, randomised controlled trials. Results: Our review suggests that botulinum toxin type A (BTA), botulinum toxin type B (BTB) and trihexyphenidyl are safe and efficacious treatments for CD. Evidence shows that botulinum toxin therapies are more reliable for symptomatic relief and have fewer adverse effects than trihexyphenidyl. When comparing BTA to BTB, both are found to have similar clinical benefits, with BTA possibly having a longer duration of action and a marginally better side effect profile. BTB is also safe and probably just as efficacious a treatment in those patients who are unresponsive or have become resistant to BTA. Discussion: The current evidence shows that the pharmacological management of CD relies on BTA and BTB, two agents with established efficacy and tolerability profiles. PMID:22713419

  7. Rating Scales for Dystonia in Cerebral Palsy: Reliability and Validity

    ERIC Educational Resources Information Center

    Monbaliu, E.; Ortibus, E.; Roelens, F.; Desloovere, K.; Deklerck, J.; Prinzie, P.; De Cock, P.; Feys, H.

    2010-01-01

    Aim: This study investigated the reliability and validity of the Barry-Albright Dystonia Scale (BADS), the Burke-Fahn-Marsden Movement Scale (BFMMS), and the Unified Dystonia Rating Scale (UDRS) in patients with bilateral dystonic cerebral palsy (CP). Method: Three raters independently scored videotapes of 10 patients (five males, five females;…

  8. Cetirizine and albendazole induced dystonia in a child.

    PubMed

    Yılmaz-Topa, Özge; Tuygun, Nilden; Akça, Halise; Polat, Emine; Karacan, Can Demir

    2015-01-01

    Drug-induced dystonic reactions are a common presentation to the Pediatric Emergency Department frequently with antiemetics, antidepressants, dopamineblocking agents and antipyschotics. We report a case of generalized form of dystonia after taking albendazole and cetirizine. There is only one case with albendazole induced and two cases with cetirizine induced dystonia in the literature.

  9. Cervical dystonia: about familial and sporadic cases in 88 patients.

    PubMed

    Camargo, Carlos Henrique F; Camargos, Sarah Teixeira; Becker, Nilson; Munhoz, Renato Puppi; Raskin, Salmo; Cardoso, Francisco Eduardo C; Teive, Hélio Afonso G

    2014-02-01

    Cervical dystonia (CD) affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic). Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001). The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01). Generalized cases were more severe in patients with a family history (p<0.01). Sporadic patients had higher levels of pain than familial cases (p<0.05). We expect soon to present the results of genetic analyzes of these patients.

  10. A case of mitochondrial cytopathy with exertion induced dystonia

    PubMed Central

    Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor

    2015-01-01

    Paroxysmal dystonias are a group of relatively benign hyperkinetic childhood movement disorders of varied etiology. Mitochondrial diseases are well known to produce persistent dystonias as sequelae, but paroxysmal exertion induced dystonia has been reported in only one case to the best of our knowledge. Two siblings born to consanguineous parents presented with early-onset exertion induced dystonia, which was unresponsive to diphenylhydantoin and carbamazepine. A trial with valproate in one of the siblings turned fatal within 24 h. Based on this clue, the second child was investigated and found to suffer from complex I deficiency with a paternally inherited dominant nuclear DNA mutation, which is responsive to the mitochondrial cocktail. Exertion induced dystonia can be a rare manifestation of complex I deficiency. PMID:26557169

  11. Convergent evidence for abnormal striatal synaptic plasticity in dystonia

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

    2010-01-01

    Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes

  12. Does abnormal interhemispheric inhibition play a role in mirror dystonia?

    PubMed

    Sattler, Virginie; Dickler, Maya; Michaud, Martin; Meunier, Sabine; Simonetta-Moreau, Marion

    2014-05-01

    The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual-site transcranial magnetic stimulation with a 10-millisecond (short IHI) and a 40-millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia.

  13. Thalamic Volume Is Reduced in Cervical and Laryngeal Dystonias

    PubMed Central

    Waugh, Jeff L.; Kuster, John K.; Levenstein, Jacob M.; Makris, Nikos; Multhaupt-Buell, Trisha J.; Sudarsky, Lewis R.; Breiter, Hans C.; Sharma, Nutan; Blood, Anne J.

    2016-01-01

    Background Dystonia, a debilitating movement disorder characterized by abnormal fixed positions and/or twisting postures, is associated with dysfunction of motor control networks. While gross brain lesions can produce secondary dystonias, advanced neuroimaging techniques have been required to identify network abnormalities in primary dystonias. Prior neuroimaging studies have provided valuable insights into the pathophysiology of dystonia, but few directly assessed the gross volume of motor control regions, and to our knowledge, none identified abnormalities common to multiple types of idiopathic focal dystonia. Methods We used two gross volumetric segmentation techniques and one voxelwise volumetric technique (voxel based morphometry, VBM) to compare regional volume between matched healthy controls and patients with idiopathic primary focal dystonia (cervical, n = 17, laryngeal, n = 7). We used (1) automated gross volume measures of eight motor control regions using the FreeSurfer analysis package; (2) blinded, anatomist-supervised manual segmentation of the whole thalamus (also gross volume); and (3) voxel based morphometry, which measures local T1-weighted signal intensity and estimates gray matter density or volume at the level of single voxels, for both whole-brain and thalamus. Results Using both automated and manual gross volumetry, we found a significant volume decrease only in the thalamus in two focal dystonias. Decreases in whole-thalamic volume were independent of head and brain size, laterality of symptoms, and duration. VBM measures did not differ between dystonia and control groups in any motor control region. Conclusions Reduced thalamic gross volume, detected in two independent analyses, suggests a common anatomical abnormality in cervical dystonia and spasmodic dysphonia. Defining the structural underpinnings of dystonia may require such complementary approaches. PMID:27171035

  14. Memantine-induced chorea and dystonia.

    PubMed

    Borges, Letizia Goncalves; Bonakdarpour, Borna

    2017-04-01

    Memantine is an uncompetitive N-methyl-d-aspartate receptor antagonist and probably also has an indirect dopaminergic action at high concentrations. We describe a person with Alzheimer's disease who developed chorea and dystonia after inadvertently doubling of her daily dose by taking extended-release (XR) memantine twice daily, rather than once daily (planned dose memantine XR, 21 mg once daily), after the drug was switched from immediate release (IR, 10 mg twice daily). Memantine is rarely associated with movement disorders, but this case emphasises the need for awareness of potential problems when switching from memantine IR to XR.

  15. The genetics of dystonia: new twists in an old tale

    PubMed Central

    Charlesworth, Gavin; Bhatia, Kailash P.

    2013-01-01

    Dystonia is a common movement disorder seen by neurologists in clinic. Genetic forms of the disease are important to recognize clinically and also provide valuable information about possible pathogenic mechanisms within the wider disorder. In the past few years, with the advent of new sequencing technologies, there has been a step change in the pace of discovery in the field of dystonia genetics. In just over a year, four new genes have been shown to cause primary dystonia (CIZ1, ANO3, TUBB4A and GNAL), PRRT2 has been identified as the cause of paroxysmal kinesigenic dystonia and other genes, such as SLC30A10 and ATP1A3, have been linked to more complicated forms of dystonia or new phenotypes. In this review, we provide an overview of the current state of knowledge regarding genetic forms of dystonia—related to both new and well-known genes alike—and incorporating genetic, clinical and molecular information. We discuss the mechanistic insights provided by the study of the genetic causes of dystonia and provide a helpful clinical algorithm to aid clinicians in correctly predicting the genetic basis of various forms of dystonia. PMID:23775978

  16. Phenomenology and classification of dystonia: a consensus update

    PubMed Central

    Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B.; DeLong, Mahlon R.; Fahn, Stanley; Fung, Victor S.C.; Hallett, Mark; Jankovic, Joseph; Jinnah, H.A.; Klein, Christine; Lang, Anthony E.; Mink, Jonathan W.; Teller, Jan K.

    2013-01-01

    This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during three in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along two axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features), and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. PMID:23649720

  17. Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

    PubMed

    Hagenacker, Tim; Gerwig, Marcus; Gasser, Thomas; Miller, Dorothea; Kastrup, Oliver; Jokisch, Daniel; Sure, Ulrich; Frings, Markus

    2013-07-01

    Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

  18. Motor sequence learning and motor adaptation in primary cervical dystonia.

    PubMed

    Katschnig-Winter, Petra; Schwingenschuh, Petra; Davare, Marco; Sadnicka, Anna; Schmidt, Reinhold; Rothwell, John C; Bhatia, Kailash P; Edwards, Mark J

    2014-06-01

    Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect "contamination" rather than being directly pathological.

  19. [acute dystonias in combined abuse of cocaine and neuroleptics].

    PubMed

    Horwitz, E H; van Harten, P N

    1994-11-26

    A 25-year-old mildly retarded black cocaine user was hospitalized 15 times in 10 years for recurrent maniform psychosis. During the last intake he developed severe dystonia following zuclopenthixol 50 mg and droperidol 10 mg i.m. In view of current knowledge regarding the pathophysiology of acute neuroleptic induced dystonias, this suggests that cocaine may be a risk factor for development of acute dystonia. However, only a few studies with small numbers of patients and/or poor design have been reported. Therefore the conclusion cannot be drawn that an anticholinergic should be added to neuroleptics in patients with cocaine abuse.

  20. Quality of life in patients with craniocervical dystonia: Italian validation of the "Cervical Dystonia Impact Profile (CDIP-58)" and the "Craniocervical Dystonia Questionnaire (CDQ-24)".

    PubMed

    Fabbri, Margherita; Superbo, Maria; Defazio, Giovanni; Scaglione, Cesa Lorella Maria; Antelmi, Elena; Basini, Giacomo; Nassetti, Stefania; Pizza, Fabio; Plasmati, Rosaria; Liguori, Rocco

    2014-07-01

    Dystonia is a disabling and disfiguring disorder that can often affect many aspects of patients' daily lives, and lower their self-esteem. To date, quality of life (QoL) has been assessed in dystonic patients using generic measures that do not address the specific problems of this diagnostic group. Recently, two disease-specific scales "The Cervical Dystonia Impact Profile (CDIP-58)" and the "Craniocervical Dystonia Questionnaire (CDQ-24)" were validated for measuring QoL in craniocervical dystonia patients. No disease-specific scales for QoL for dystonic patients are currently available in Italian. The aim of our study was to produce and validate the Italian version of the CDIP-58 and CDQ-24. We obtained the Italian version of CDQ-24 and CDIP-58 with a back-translation design. Both scales were applied to a population of 94 craniocervical dystonia patients along with the Short Form 36 health-survey questionnaire (SF-36), both before and 4 weeks after botulinum toxin therapy. A group of 65 controls matched for sex, age and comorbidity underwent the SF-36. Internal consistency was satisfactory for all subscales. Both the CDIP-58 and CDQ-24 showed moderate to high correlations with similar items of the SF-36. Sensitivity to change was confirmed by highly significant improvements in all CDQ-24 subscales and by moderate improvements in three out of eight CDIP-58 subscales and total score. This is the first Italian study on QoL in dystonia patients. We validated the Italian version of two disease-specific questionnaires to evaluate QoL in craniocervical dystonia patients. These scales could be useful for both clinical practice and clinical trials.

  1. Oral methylphenidate for the treatment of refractory facial dystonias.

    PubMed

    Eftekhari, Kian; Choe, Christina H; Vagefi, M Reza; Gausas, Roberta E; Eckstein, Lauren A

    2015-01-01

    Oral methylphenidate (Ritalin, Novartis) has been reported to alleviate symptoms of benign essential blepharospasm in an off-label application. This series presents 3 patients with refractory periorbital and facial dystonias, including blepharospasm, apraxia of eyelid opening, and oromandibular dystonia unresponsive to standard treatments who experienced a response to oral methylphenidate therapy. While the mechanisms for facial dystonias have not been elucidated, there is evidence to suggest that they are on the spectrum with Parkinson disease. Given the role of dopamine loss in the pathogenesis of Parkinson, the authors' speculate that methylphenidate may be acting on the pathway directly involved in facial dystonias. To the authors' knowledge, this is the first report of a case of successful treatment of blepharospasm refractory to upper eyelid myectomy with methylphenidate monotherapy.

  2. Dystonia not dystopia: effects of the legal high, 'Clockwork Orange'.

    PubMed

    Mackey, Helen Elizabeth; Hawksley, Oliver

    2015-12-10

    A 27-year-old man presented to hospital after smoking a legal high named 'Clockwork Orange'. He suffered dystonia, acute kidney injury, rhabdomyolysis, lactic acidosis and a troponin rise. He was treated with procyclidine and intravenous fluids.

  3. Genetics Home Reference: X-linked dystonia-parkinsonism

    MedlinePlus

    ... This condition affects men much more often than women. Parkinsonism is usually the first sign of X-linked dystonia-parkinsonism . Parkinsonism is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, ...

  4. Genetic and clinical features of primary torsion dystonia

    PubMed Central

    Ozelius, Laurie J.; Bressman, Susan B.

    2011-01-01

    Primary torsion dystonia (PTD) is defined as a syndrome in which dystonia is the only clinical sign (except for tremor), and there is no evidence of neuronal degeneration or an acquired cause by history or routine laboratory assessment. Seven different loci have been recognized for PTD but only two of the genes have been identified. In this review we will described the phenotypes associated with these loci and discuss the responsible gene. PMID:21168499

  5. Intrathecal baclofen for dystonia of complex regional pain syndrome.

    PubMed

    van Rijn, M A; Munts, A G; Marinus, J; Voormolen, J H C; de Boer, K S; Teepe-Twiss, I M; van Dasselaar, N T; Delhaas, E M; van Hilten, J J

    2009-05-01

    Dystonia in complex regional pain syndrome (CRPS) responds poorly to treatment. Intrathecal baclofen (ITB) may improve this type of dystonia, but information on its efficacy and safety is limited. A single-blind, placebo-run-in, dose-escalation study was carried out in 42 CRPS patients to evaluate whether dystonia responds to ITB. Thirty-six of the 38 patients, who met the responder criteria received a pump for continuous ITB administration, and were followed up for 12 months to assess long-term efficacy and safety (open-label study). Primary outcome measures were global dystonia severity (both studies) and dystonia-related functional limitations (open-label study). The dose-escalation study showed a dose-effect of baclofen on dystonia severity in 31 patients in doses up to 450 microg/day. One patient did not respond to treatment in the dose-escalation study and three patients dropped out. Thirty-six patients entered the open-label study. Intention-to-treat analysis revealed a substantial improvement in patient and assessor-rated dystonia scores, pain, disability and quality-of-life (Qol) at 12 months. The response in the dose-escalation study did not predict the response to ITB in the open-label study. Eighty-nine adverse events occurred in 26 patients and were related to baclofen (n=19), pump/catheter system defects (n=52), or could not be specified (n=18). The pump was explanted in six patients during the follow-up phase. Dystonia, pain, disability and Qol all improved on ITB and remained efficacious over a period of one year. However, ITB is associated with a high complication rate in this patient group, and methods to improve patient selection and catheter-pump integrity are warranted.

  6. Familial leukoencephalopathy with slowly progressive dystonia and ataxia.

    PubMed

    Blumkin, Lubov; Mandel, Hanna; Anca-Herschkovitsch, Marieta; Kivity, Sara; Lev, Dorit; Lerman-Sagie, Tally

    2009-11-01

    We describe two siblings with childhood onset, slowly progressive generalized dystonia and cerebellar signs. Brain neuroimaging revealed white matter abnormalities compatible with a neuronal degenerative disorder. An extensive evaluation for mitochondrial, metabolic, autoimmune or other known neurodegenerative disorders did not reveal the etiology of the disease. During a three-year follow-up other neurological signs appeared, but progression was very slow. We believe that our patients have a new type of a leukoencephalopathy with slowly progressive dystonia and cerebellar signs.

  7. Basic Timing Abilities Stay Intact in Patients with Musician's Dystonia

    PubMed Central

    van der Steen, M. C.; van Vugt, Floris T.; Keller, Peter E.; Altenmüller, Eckart

    2014-01-01

    Task-specific focal dystonia is a movement disorder that is characterized by the loss of voluntary motor control in extensively trained movements. Musician's dystonia is a type of task-specific dystonia that is elicited in professional musicians during instrumental playing. The disorder has been associated with deficits in timing. In order to test the hypothesis that basic timing abilities are affected by musician's dystonia, we investigated a group of patients (N = 15) and a matched control group (N = 15) on a battery of sensory and sensorimotor synchronization tasks. Results did not show any deficits in auditory-motor processing for patients relative to controls. Both groups benefited from a pacing sequence that adapted to their timing (in a sensorimotor synchronization task at a stable tempo). In a purely perceptual task, both groups were able to detect a misaligned metronome when it was late rather than early relative to a musical beat. Overall, the results suggest that basic timing abilities stay intact in patients with musician's dystonia. This supports the idea that musician's dystonia is a highly task-specific movement disorder in which patients are mostly impaired in tasks closely related to the demands of actually playing their instrument. PMID:24667273

  8. Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology

    PubMed Central

    Comella, Cynthia L.; Fox, Susan H.; Bhatia, Kailash P.; Perlmutter, Joel S.; Jinnah, Hyder A.; Zurowski, Mateusz; McDonald, William M.; Marsh, Laura; Rosen, Ami R.; Waliczek, Tracy; Wright, Laura J.; Galpern, Wendy R.; Stebbins, Glenn T.

    2016-01-01

    We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation. During this workshop, deficiencies in the standard TWSTRS were identified and recommendations for revision of the severity and pain subscales were incorporated into the TWSTRS-2. Given that no scale currently evaluates the psychiatric features of cervical dystonia (CD), we used a modified Delphi methodology and a reiterative process of item selection to develop the TWSTRS-PSYCH. We also included the CDIP-58 to capture the impact of CD on quality of life. The three scales (TWSTRS2, TWSTRS-PSYCH, and CDIP-58) were combined to construct the CCDRS. Clinimetric testing of reliability and validity of the CCDRS are described. The CCDRS was designed to be used in a modular fashion that can measure the full spectrum of CD. This scale will provide rigorous assessment for studies of natural history as well as novel symptom-based or disease-modifying therapies. PMID:27088112

  9. Emerging concepts in the physiological basis of dystonia.

    PubMed

    Quartarone, Angelo; Hallett, Mark

    2013-06-15

    Work over the past 2 decades has led to substantial changes in our understanding of dystonia pathophysiology. Three general abnormalities appear to underlie the pathophysiological substrate. The first is a loss of inhibition. This makes sense considering that it may be responsible for the excess of movement and for the overflow phenomena seen in dystonia. A second abnormality is sensory dysfunction which is related to the mild sensory complaints in patients with focal dystonias and may be responsible for some of the motor dysfunction. Third, evidence from animal models of dystonia as well as from patients with primary dystonia has revealed significant alterations of synaptic plasticity characterized by a disruption of homeostatic plasticity, with a prevailing facilitation of synaptic potentiation, together with the loss of synaptic inhibitory processes. We speculate that during motor learning this abnormal plasticity may lead to an abnormal sensorimotor integration, leading to consolidation of abnormal motor engrams. If so, then removing this abnormal plasticity might have little immediate effect on dystonic movements because bad motor memories have already been ''learned'' and are difficult to erase. These considerations might explain the delayed clinical effects of deep brain stimulation (DBS) in patients with generalized dystonia. Current lines of research will be discussed from a network perspective. © 2013 Movement Disorder Society.

  10. The Most Cited Works in Essential Tremor and Dystonia

    PubMed Central

    King, Nicolas K. K.; Tam, Joseph; Fasano, Alfonso; Lozano, Andres M

    2016-01-01

    Background The study of the most cited works in a particular field gives an indication of the important advances, developments, and discoveries that have had the highest impact in that discipline. Our aim was to identify the most cited works in essential tremor (ET) and dystonia. Methods A bibliometric search was performed using the ISI Web of Science database using selected search terms for ET and dystonia for articles published from 1900 to 2015. The resulting citation counts were analyzed to identify the most cited works, and the studies were categorized. Results Using the criterion of more than 400 citations, there were four citation classics for ET and six for dystonia. The most cited studies were those on pathophysiology followed by medical treatments, clinical classification, genetic studies, surgical treatments, review articles, and epidemiology studies. A comparison of the most cited articles for ET and dystonia showed that there was a divergence, with ET and dystonia having a higher number of epidemiologic and genetic studies, respectively. Whereas the peak period for the number of publications was 2000–2004 for ET, it was 1995–1999 for dystonia. Discussion Given the large number of patients with these disorders, there appears to be an unmet need for further research advances in both areas, but particularly for ET as the most common movement disorder. PMID:27119049

  11. Development of the Comprehensive Cervical Dystonia Rating Scale: Methodology.

    PubMed

    Comella, Cynthia L; Fox, Susan H; Bhatia, Kailash P; Perlmutter, Joel S; Jinnah, Hyder A; Zurowski, Mateusz; McDonald, William M; Marsh, Laura; Rosen, Ami R; Waliczek, Tracy; Wright, Laura J; Galpern, Wendy R; Stebbins, Glenn T

    2015-06-01

    We present the methodology utilized for development and clinimetric testing of the Comprehensive Cervical Dystonia (CD) Rating scale, or CCDRS. The CCDRS includes a revision of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), a newly developed psychiatric screening tool (TWSTRS-PSYCH), and the previously validated Cervical Dystonia Impact Profile (CDIP-58). For the revision of the TWSTRS, the original TWSTRS was examined by a committee of dystonia experts at a dystonia rating scales workshop organized by the Dystonia Medical Research Foundation. During this workshop, deficiencies in the standard TWSTRS were identified and recommendations for revision of the severity and pain subscales were incorporated into the TWSTRS-2. Given that no scale currently evaluates the psychiatric features of cervical dystonia (CD), we used a modified Delphi methodology and a reiterative process of item selection to develop the TWSTRS-PSYCH. We also included the CDIP-58 to capture the impact of CD on quality of life. The three scales (TWSTRS2, TWSTRS-PSYCH, and CDIP-58) were combined to construct the CCDRS. Clinimetric testing of reliability and validity of the CCDRS are described. The CCDRS was designed to be used in a modular fashion that can measure the full spectrum of CD. This scale will provide rigorous assessment for studies of natural history as well as novel symptom-based or disease-modifying therapies.

  12. Dystonia redefined as central non-paretic loss of control of muscle action: a concept including inability to activate muscles required for a specific movement, or 'negative dystonia'.

    PubMed

    Mezaki, Takahiro

    2007-01-01

    Dystonia is defined as a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements, or abnormal postures. Although this definition comprises an essential feature of dystonia, the clinical observation indicates that there is an additional aspect of dystonia; failure to adequately activate muscles required for specific movement, exemplified by the lack of contractions of the levator palpebrae superioris muscles in apraxia of lid opening, as well as by inability to activate appropriate muscles in cervical dystonia or in the paretic form of writer's cramp, and possibly by dropped head syndrome or camptocormia seen in parkinsonian patients without apparent truncal dystonia or rigidity. Taking this "negative dystonia" into consideration, the author proposes a revised definition of dystonia as a symptom characterized by the central non-paretic loss of voluntary control of muscle activities, which may result in either excessive or deficient contractions of muscles, frequently causing twisting and repetitive movements, limitation of movements, or abnormal postures.

  13. Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

    PubMed

    Kimmich, Okka; Molloy, Anna; Whelan, Robert; Williams, Laura; Bradley, David; Balsters, Joshua; Molloy, Fiona; Lynch, Tim; Healy, Daniel G; Walsh, Cathal; O'Riordan, Seán; Reilly, Richard B; Hutchinson, Michael

    2014-05-01

    The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits.

  14. Botulinum toxin type A in the treatment of patients with cervical dystonia

    PubMed Central

    Brashear, Allison

    2009-01-01

    Dystonia is an involuntary movement involving twisting and turning of agonist and antagonist muscles. Cervical dystonia is isolated to neck musculature. Botulinum toxin type A is a safe and effective treatment of this disabling and often painful syndrome. Three forms of botulinum toxin type A are available worldwide to treat patients with cervical dystonia. This is a review of the studies of botulinum toxin type A to treat cervical dystonia. PMID:19707390

  15. Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency

    ERIC Educational Resources Information Center

    Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

    2010-01-01

    Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

  16. Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

    PubMed

    Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S

    2012-09-01

    Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

  17. Pain Relief in Cervical Dystonia with Botulinum Toxin Treatment

    PubMed Central

    Camargo, Carlos Henrique Ferreira; Cattai, Lígia; Teive, Hélio Afonso Ghizoni

    2015-01-01

    Dystonia is a neurological disorder characterized by intermittent or sustained muscle contractions that cause abnormal, usually repetitive, movements and postures. Dystonic movements can be tremulous and twisting and often follow a pattern. They are frequently associated with overflow muscle activation and may be triggered or worsened by voluntary action. Most voluntary muscles can be affected and, in the case of the neck muscles, the condition is referred to as cervical dystonia (CD), the most common form of dystonia. The high incidence of pain distinguishes CD from other focal dystonias and contributes significantly to patient disability and low quality of life. Different degrees of pain in the cervical region are reported by more than 60% of patients, and pain intensity is directly related to disease severity. Botulinum toxin (BoNT) is currently considered the treatment of choice for CD and can lead to an improvement in pain and dystonic symptoms in up to 90% of patients. The results for BoNT/A and BoNT/B are similar. The complex relationship between pain and dystonia has resulted in a large number of studies and more comprehensive assessments of dystonic patients. When planning the application of BoNT, pain should be a key factor in the choice of muscles and doses. In conclusion, BoNT is highly effective in controlling pain, and its analgesic effect is sustained for a long time in most CD patients. PMID:26110508

  18. Long-term outcome of focal dystonia in string instrumentalists.

    PubMed

    Schuele, Stephan; Lederman, Richard J

    2004-01-01

    This study describes the clinical characteristics and long-term outcome in string instrumentalists with focal task-specific dystonia. We present the results of a follow-up telephone survey of 21 violin and viola players with focal dystonia. Eighteen musicians responded to the questionnaire. Information on long-term outcome was available on average 13.8 years after onset of symptoms. Main complaints were playing-related loss of control and involuntary movements affecting the fingering hand in 16 and the bow arm in 5 patients. In 18 patients (86%), signs of abnormal posture could be detected by watching them play their instrument. Treatment attempts included nerve decompression, physical therapy, retraining, and anticholinergic medication. In selected patients, botulinum toxin injections or splint devices were offered. Only 38% of the performing artists were able to maintain their professional careers, among them none with bow arm dystonia. Focal dystonia may affect the fingering hand or bow arm in violin and viola instrumentalists. Treatment benefit is limited and in more than half of the patients, dystonia leads to the end of their musical career.

  19. Abnormal plasticity in dystonia: Disruption of synaptic homeostasis.

    PubMed

    Quartarone, Angelo; Pisani, Antonio

    2011-05-01

    Work over the past two decades lead to substantial changes in our understanding of dystonia, which was, until recently, considered an exclusively sporadic movement disorder. The discovery of several gene mutations responsible for many inherited forms of dystonia has prompted much effort in the generation of transgenic mouse models bearing mutations found in patients. The large majority of these rodent models do not exhibit overt phenotypic abnormalities, or neuronal loss in specific brain areas. Nevertheless, both subtle motor abnormalities and significant alterations of synaptic plasticity have been recorded in mice, suggestive of an altered basal ganglia circuitry. In addition, robust evidence from experimental and clinical work supports the assumption that dystonia may indeed be considered a disorder linked to the disruption of synaptic "scaling", with a prevailing facilitation of synaptic potentiation, together with the loss of synaptic inhibitory processes. Notably, neurophysiological studies from patients carrying gene mutations as well as from non-manifesting carriers have shown the presence of synaptic plasticity abnormalities, indicating the presence of specific endophenotypic traits in carriers of the gene mutation. In this survey, we review findings from a broad range of data, obtained both from animal models and human research, and propose that the abnormalities of synaptic plasticity described in mice and humans may be considered an endophenotype to dystonia, and a valid and powerful tool to investigate the pathogenic mechanisms underlying this movement disorder. This article is part of a Special Issue entitled "Advances in dystonia".

  20. Treatment of Myoclonus-Dystonia Syndrome with Tetrabenazine

    PubMed Central

    Luciano, Angelo Y.; Jinnah, H. A.; Pfeiffer, Ronald F.; Truong, Daniel D.; Nance, Martha A.; LeDoux, Mark S.

    2014-01-01

    Background Many cases of myoclonus-dystonia (M-D) are due to mutations in SGCE (DYT11). For the majority of patients, myoclonus is relatively more severe than dystonia and can lead to significant functional disability. Deep brain stimulation has been chosen as a treatment option in some patients given that M-D often responds poorly to oral pharmacotherapy. Methods Two siblings with M-D due to the same SGCE deletion mutation were evaluated with the Global Dystonia Rating Scale (GDRS), Fahn-Marsden Rating Scale (FM) and Unified Myoclonus Rating Scale (UMRS) on and off tetrabenazine. Results Both subjects showed marked improvement in myoclonus and mild-to-moderate improvement in dystonia with tetrabenazine. In addition, the response to tetrabenazine has been sustained for years. Conclusions A therapeutic trial of tetrabenazine should be considered in patients with M-D, especially before consideration of deep brain stimulation. An adequately powered multi-center, double-blind study of tetrabenazine will be required to determine the relative contributions of tetrabenazine therapy to myoclonus, dystonia, quality of life, and activities of daily living in patients with M-D. PMID:25406829

  1. Brainstem pathology in DYT1 primary torsion dystonia.

    PubMed

    McNaught, Kevin St P; Kapustin, Alexander; Jackson, Tehone; Jengelley, Toni-Ann; Jnobaptiste, Ruth; Shashidharan, Pullanipally; Perl, Daniel P; Pasik, Pedro; Olanow, C Warren

    2004-10-01

    DYT1 dystonia is a severe form of young-onset dystonia caused by a mutation in the gene that encodes for the protein torsinA, which is thought to play a role in protein transport and degradation. We describe, for the first time to our knowledge, perinuclear inclusion bodies in the midbrain reticular formation and periaqueductal gray in four clinically documented and genetically confirmed DYT1 patients but not in controls. The inclusions were located within cholinergic and other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum centrale mesencephali and stained positively for ubiquitin, torsinA, and the nuclear envelope protein lamin A/C. No evidence of inclusion body formation was detected in the substantia nigra pars compacta, striatum, hippocampus, or selected regions of the cerebral cortex. We also noted tau/ubiquitin-immunoreactive aggregates in pigmented neurons of the substantia nigra pars compacta and locus coeruleus in all four DYT1 dystonia cases, but not in controls. This study supports the notion that DYT1 dystonia is associated with impaired protein handling and the nuclear envelope. The role of the pedunculopontine and cuneiform nuclei, and related brainstem brainstem structures, in mediating motor activity and controlling muscle tone suggests that alterations in these structures could underlie the pathophysiology of DYT1 dystonia [corrected

  2. Inclusion and exclusion criteria for DBS in dystonia.

    PubMed

    Bronte-Stewart, Helen; Taira, Takaomi; Valldeoriola, Francesc; Merello, Marcello; Marks, William J; Albanese, Alberto; Bressman, Susan; Moro, Elena

    2011-06-01

    When considering a patient with dystonia for deep brain stimulation (DBS) surgery several factors need to be considered. Level B evidence has shown that all motor features and associated pain in primary generalized and segmental dystonia are potentially responsive to globus pallidus internus (GPi) DBS. However, improvements in clinical series of ≥ 90% may reflect methods that need improvement, and larger prospective studies are needed to address these factors. Nevertheless, to date the selection criteria for DBS-specifically in terms of patient features (severity and nature of symptoms, age, time of evolution, or any other demographic or disease aspects)--have not been assessed in a systematic fashion. In general, dystonia patients are not considered for DBS unless medical therapies have been previously and extensively tested. The vast majority of reported patients have had DBS surgery when the disease was provoking important disability, with loss of independence and impaired quality of life. There does not appear to be an upper age limit or a minimum age limit, although there are no published data regarding the outcome of GPi DBS for dystonia in children younger than 7 years of age. There is currently no enough evidence to prove that subjects with primary--generalized dystonia who undergo DBS at an early age and sooner rather than later after disease onset may gain more benefit from DBS than those undergoing DBS after the development of fixed skeletal deformities. There is no enough evidence to refuse or support consideration of DBS in patients with previous ablative procedures.

  3. Delays to the diagnosis of cervical dystonia.

    PubMed

    Bertram, Kelly L; Williams, David R

    2016-03-01

    The diagnosis of cervical dystonia (CD) is based on physical examination and is therefore reliant on clinician experience. Due to variability of presenting symptoms it may be misdiagnosed, thus delaying the provision of effective treatment. We sought to determine the average time taken to make a diagnosis of CD in our clinical cohort and explore contributing factors to diagnostic delay. Forty-nine patients with a diagnosis of CD attending a movement disorder specialist for treatment completed a questionnaire regarding symptoms and clinical interactions at onset and diagnosis. The mean time from symptom onset to diagnosis was 6.8 years (range 0-53 years). More than 50% of patients sought physical therapies initially, prior to consulting their general practitioner. Only 40% of patients sought medical advice within the first 6 months of symptom onset and only 10% were given an initial diagnosis of CD. The first referral from the general practitioner was to a specialist other than a neurologist in 31% of patients. Patients were seen by a mean of three doctors (range one to nine) before being given the correct diagnosis of CD. Delay to diagnosis of CD may in part be due to lack of awareness of the condition amongst health care professionals. Improved diagnostic skill appears likely to have had a substantial impact on the delivery of appropriate treatment in this population.

  4. Isolated and combined dystonia syndromes - an update on new genes and their phenotypes.

    PubMed

    Balint, B; Bhatia, K P

    2015-04-01

    Recent consensus on the definition, phenomenology and classification of dystonia centres around phenomenology and guides our diagnostic approach for the heterogeneous group of dystonias. Current terminology classifies conditions where dystonia is the sole motor feature (apart from tremor) as 'isolated dystonia', while 'combined dystonia' refers to dystonias with other accompanying movement disorders. This review highlights recent advances in the genetics of some isolated and combined dystonic syndromes. Some genes, such as ANO3, GNAL and CIZ1, have been discovered for isolated dystonia, but they are probably not a common cause of classic cervical dystonia. Conversely, the phenotype associated with TUBB4A mutations expanded from that of isolated dystonia to a syndrome of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). Similarly, ATP1A3 mutations cause a wide phenotypic spectrum ranging from rapid-onset dystonia-parkinsonism to alternating hemiplegia of childhood. Other entities entailing dystonia-parkinsonism include dopamine transporter deficiency syndrome (SLC63 mutations); dopa-responsive dystonias; young-onset parkinsonism (PARKIN, PINK1 and DJ-1 mutations); PRKRA mutations; and X-linked TAF1 mutations, which rarely can also manifest in women. Clinical and genetic heterogeneity also characterizes myoclonus-dystonia, which includes not only the classical phenotype associated with epsilon-sarcoglycan mutations but rarely also presentation of ANO3 gene mutations, TITF1 gene mutations typically underlying benign hereditary chorea, and some dopamine synthesis pathway conditions due to GCH1 and TH mutations. Thus, new genes are being recognized for isolated dystonia, and the phenotype of known genes is broadening and now involves different combined dystonia syndromes.

  5. Hemi-dystonia secondary to localised basal ganglia tumour.

    PubMed Central

    Narbona, J; Obeso, J A; Tuñon, T; Martinez-Lage, J M; Marsden, C D

    1984-01-01

    An 8-year-old boy with an 18 month history of left limb hemi-dystonia due to a right lenticular nucleus astrocytoma originating in the putamen is reported. Subsequent neuropathological study demonstrated that the tumour was mainly localised to the right lenticular nucleus, with cystic necrosis in the infero-lateral putamen. Solid tumour also infiltrated the right hypothalamus, the anterior commisure and the optic chiasm, and there was perivascular spread into the globus pallidus, internal capsule and roof of the right lateral ventricle. This case, and the few other published reports of symptomatic dystonia due to focal brain lesions verified pathologically, indicate that damage to the lenticular nucleus, and to the putamen in particular, can cause limb dystonia in man. Images PMID:6747646

  6. Dopa-Responsive Dystonia in a Ten-Year-Old Girl

    PubMed Central

    Soma, Venkatesh; Mohammed, Hussain Sadiq; Riyas, Ebrahim; Murugesan, Karuppasamy

    2012-01-01

    Children with recent onset dystonia and gait abnormalities may pose a diagnostic challenge. A ten-year-old, developmentally normal girl, presented with a six-month history of gait abnormality and dystonia. Her complaint worsened as the day progressed. In view of typical diurnal variation of dystonia, a therapeutic challenge with levodopa/carbidopa was given and there was a dramatic response. Hence, a diagnosis of dopa-responsive dystonia (DRD) was made. DRD is an inherited disorder characterized by dystonia with diurnal variation and favorable response to levodopa/carbidopa. The inheritance is usually autosomal dominant, however, in some cases, autosomal-recessive inheritance is also seen. PMID:24479026

  7. Impairment of the rubber hand illusion in focal hand dystonia.

    PubMed

    Fiorio, Mirta; Weise, David; Önal-Hartmann, Cigdem; Zeller, Daniel; Tinazzi, Michele; Classen, Joseph

    2011-05-01

    Patients with dystonia display a number of disturbances in the cognitive processing of movements, such as movement simulation and prediction, but whether these deficits point to a deeper rooted disturbance of perceptual bodily representations remains unknown. A useful way to investigate the sense of body ownership is the rubber hand paradigm, in which an illusion of ownership is established by synchronous stroking of the participants' real unseen hand and a visible fake hand, whereas similar asynchronous stroking does not bring about the illusion. This paradigm allows testing of both the subjective experience of feeling ownership over the rubber hand and the proprioceptive relocation of the real unseen hand towards the viewed rubber hand. Previous studies have mapped these different aspects onto two anatomically distinct neuronal substrates, with the ventral premotor cortex processing the illusory feeling of ownership and the inferior parietal lobule and cerebellum processing proprioceptive drift. We applied the rubber hand illusion task to healthy subjects and to patients affected by two different types of focal dystonia-one specifically affecting the hand (focal hand dystonia) and one not affecting the hand (torticollis and blepharospasm). Results showed that in patients with focal hand dystonia, the proprioceptive drift was selectively disrupted on the dystonic hand while the subjective experience of the illusion was retained. In the non-dystonic hand and in the other two groups (non-hand dystonia and healthy subjects), the rubber hand illusion resembled the typical pattern with synchronous stroking eliciting the illusion. These findings provide support for the contention that the mechanisms underlying the presence of the illusory feeling of ownership and the proprioceptive drift are different. Selective impairment of the limb recalibration on the dystonic hand points to underlying deficits in integrating the visual-tactile input with the proprioceptive

  8. Familial dystonia and visual failure with striatal CT lucencies.

    PubMed Central

    Marsden, C D; Lang, A E; Quinn, N P; McDonald, W I; Abdallat, A; Nimri, S

    1986-01-01

    A unique disorder is described in seven members of two families in whom dystonia was variably associated with subacute visual loss or asymptomatic optic atrophy, and striking bilateral symmetrical lucencies on CT scan, especially involving the putamen. It is possible that this is a variant of Leigh's disease. However, there were considerable differences between these patients and those with pathologically proven Leigh's disease. This condition must be excluded in all patients thought to have idiopathic dystonia, subacute visual failure similar to Leber's optic neuropathy, or a combination of these disorders. Images PMID:3711913

  9. Overuse Cervical Dystonia: A Case Report and Literature Review

    PubMed Central

    Hogg, Elliot; Tagliati, Michele

    2016-01-01

    Background Overuse or task-specific dystonia has been described in a number of professions characterized by repetitive actions, typically affecting the upper extremities. Cervical dystonia (CD), however, has rarely been associated with overuse. Case Report We present a case report of typical CD that developed in the context of chronic repetitive movements associated with the patient’s professional occupation as an office manager who spent many hours per day holding a phone to his ear. Discussion Overuse CD should be suspected when typical symptoms and signs of CD develop in the context of chronic repetitive use or overuse of cervical muscles, especially where exacerbating tasks involve asymmetric postures. PMID:27708983

  10. [Paradoxical kinesis phenomenon in focal hand dystonia--writer's cramp].

    PubMed

    Shavlovskaia, O A; Orlova, O R; Golubev, V L

    2005-01-01

    Paradoxical kinesis (PK) phenomenon and its variants, exerting a beneficial influence on dystonia dynamics, are described using self clinical examination of 57 writer's cramp patients. PK was found in all the patients independently of writer's cramp variant, duration and severity. The most frequent writing maneuvers were as follows: hand printed (100%), proximal arm muscles writing (82.5%), individually selected writing instrument (67.5-80%), unusual means (67.5-75%), writing imitation with unlike-pen object (70%), marked papers (52.5%). The beneficial influence of PK phenomenon on dystonia expression may be considered as one of the directions of writer's cramp rehabilitation.

  11. Lessons from a remarkable family with dopa-responsive dystonia.

    PubMed Central

    Harwood, G; Hierons, R; Fletcher, N A; Marsden, C D

    1994-01-01

    A family is described in which dopa-responsive dystonia affected six members and segregated in an autosomal dominant fashion. Patients either presented in childhood with dystonia of the legs, going to develop parkinsonism and pseudo-pyramidal deficits, or in adult life with parkinsonian tremor and rigidity, with pseudo-pyramidal signs. Remarkably, in the three cases with childhood onset the symptoms and signs of the condition were abolished 36 to 52 years later by small doses of levodopa. No long term side effects of levodopa have appeared after 15 years of treatment. PMID:8163996

  12. A role for cerebellum in the hereditary dystonia DYT1

    PubMed Central

    Fremont, Rachel; Tewari, Ambika; Angueyra, Chantal; Khodakhah, Kamran

    2017-01-01

    DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA. How these mutations cause dystonia remains unknown. Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients, possibly due to differential developmental compensation between rodents and humans. To address this issue, torsinA was acutely knocked down in select brain regions of adult mice using shRNAs. TorsinA knockdown in the cerebellum, but not in the basal ganglia, was sufficient to induce dystonia. In agreement with a potential developmental compensation for loss of torsinA in rodents, torsinA knockdown in the immature cerebellum failed to produce dystonia. Abnormal motor symptoms in knockdown animals were associated with irregular cerebellar output caused by changes in the intrinsic activity of both Purkinje cells and neurons of the deep cerebellar nuclei. These data identify the cerebellum as the main site of dysfunction in DYT1, and offer new therapeutic targets. DOI: http://dx.doi.org/10.7554/eLife.22775.001 PMID:28198698

  13. A Beautician's Dystonia: Long-Lasting Effect of Botulinum Toxin

    PubMed Central

    Di Martino, Siria; Dalise, Stefania; Lamola, Giuseppe; Venturi, Martina; Rossi, Bruno; Chisari, Carmelo

    2014-01-01

    Treatment options for dystonia are not curative but symptomatic; the treatment of choice for focal dystonias is repeated botulinum toxin injections. Here, we present the case of a 46-year-old beautician with focal dystonia in her left hand that affected her ability to work. Pharmacological treatment with clonazepam and gabapentin failed to resolve her symptoms and was discontinued due to side effects (sleepiness, gastrointestinal disorders). Intramuscular injection of botulinum toxin (incobotulinumtoxinA, Xeomin) into the extensor digitorum communis (35 U), flexor carpi radialis (35 U), and flexor digitorum superficialis (30 U) muscles resulted in complete resolution of symptoms at clinical assessments at 1, 3, 6, and 10 months after the injections, confirmed by the results of surface electromyography 10 months after treatment. The patient was able to work again 1 month after treatment. No reinjection has been necessary at the last evaluation (12 months after treatment). In conclusion, botulinum toxin is an effective treatment for focal dystonia that can have long-lasting effects and can improve patients' ability to work and quality of life. PMID:25143844

  14. [The new pathogenetic treatment of cervical dystonia: rationale, methods, outcomes].

    PubMed

    Naryshkin, A G; Preobrazhenskaia, I G; Timofeev, I S; Filimonov, V N; Sheliakin, A M

    2000-01-01

    The paper presents data obtained from studies of the impact of the otolithic apparatus of the inner ear on the degree of symptoms of cervical dystonia. The findings make it possible to substantiate a pathogenetic treatment of this disease, which involves intratimpanal unilateral injection of the vestibulotoxic antibiotic streptomycin. The results achieved and the mechanisms of the therapeutical effect observed are discussed.

  15. Therapeutic immobilisation for small guitar player's dystonia: a case report.

    PubMed

    Waissman, Flavia; Pereira, João Santos; Nascimento, Osvaldo J M

    2009-01-01

    The development of focal hand dystonia through repetitive tasks is a result of degradation of cortical somatosensory representation due to repetitive fast stimuli sufficient to alter the sensory-motor stimulus, harming the motor control. A sensory-motor training program can modify this disorder. A behavioural intervention focusing on movement could help reduce or eliminate these conditions.

  16. X-linked dystonia parkinsonism: clinical phenotype, genetics and therapeutics.

    PubMed

    Rosales, Raymond L

    2010-10-01

    The clinical phenotype of X-Linked Dystonia Parkinsonism (XDP) is typically one that involves a Filipino adult male whose ancestry is mostly traced in the Philippine island of Panay. Dystonia usually starts focally in the lower limbs or oromandibular regions, then spreads to become generalized eventually. Parkinsonism sets in later into the disease and usually in combination with dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP. An SVA retrotransposon insertion in an intron of /TAF1/ may reduce neuron-specific expression of the /TAF1/ isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes. Polypharmacy with oral benzodiazepines, anticholinergic agents and muscle relaxants leaves much to be desired in terms of efficacy. The medications to date that may appear beneficial, especially in disabling dystonias, are zolpidem, muscle afferent block with lidocaine-ethanol and botulinum toxin type A. Despite the few cases undergoing deep brain stimulation, this functional surgery has shown the greatest promise in XDP. An illustrative case of XDP in a family depicts the variable course of illness, including a bout of "status dystonicus," challenges in therapy, reckoning with the social impact of the disease, and eventual patient demise. Indeed, there remains some gaps in understanding some phenomenological, genetic and treatment aspects of XDP, the areas upon which future research directions may be worthwhile.

  17. Cortico-pallidal oscillatory connectivity in patients with dystonia.

    PubMed

    Neumann, Wolf-Julian; Jha, Ashwani; Bock, Antje; Huebl, Julius; Horn, Andreas; Schneider, Gerd-Helge; Sander, Tillmann H; Litvak, Vladimir; Kühn, Andrea A

    2015-07-01

    Primary dystonia has been associated with an underlying dysfunction of a wide network of brain regions including the motor cortex, basal ganglia, cerebellum, brainstem and spinal cord. Dystonia can be effectively treated by pallidal deep brain stimulation although the mechanism of this effect is not well understood. Here, we sought to characterize cortico-basal ganglia functional connectivity using a frequency-specific measure of connectivity-coherence. We recorded direct local field potentials from the human pallidum simultaneously with whole head magnetoencephalography to characterize functional connectivity in the cortico-pallidal oscillatory network in nine patients with idiopathic dystonia. Three-dimensional cortico-pallidal coherence images were compared to surrogate images of phase shuffled data across patients to reveal clusters of significant coherence (family-wise error P < 0.01, voxel extent 1000). Three frequency-specific, spatially-distinct cortico-pallidal networks have been identified: a pallido-temporal source of theta band (4-8 Hz) coherence, a pallido-cerebellar source of alpha band (7-13 Hz) coherence and a cortico-pallidal source of beta band (13-30 Hz) coherence over sensorimotor areas. Granger-based directionality analysis revealed directional coupling with the pallidal local field potentials leading in the theta and alpha band and the magnetoencephalographic cortical source leading in the beta band. The degree of pallido-cerebellar coupling showed an inverse correlation with dystonic symptom severity. Our data extend previous findings in patients with Parkinson's disease describing motor cortex-basal ganglia oscillatory connectivity in the beta band to patients with dystonia. Source coherence analysis revealed two additional frequency-specific networks involving the temporal cortex and the cerebellum. Pallido-cerebellar oscillatory connectivity and its association with dystonic symptoms provides further confirmation of cerebellar involvement

  18. "Off" painful dystonia in Parkinson's disease treated with botulinum toxin.

    PubMed

    Pacchetti, C; Albani, G; Martignoni, E; Godi, L; Alfonsi, E; Nappi, G

    1995-05-01

    The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in

  19. Creation of a Mouse with Stress-Induced Dystonia: Control of an ATPase Chaperone

    DTIC Science & Technology

    2012-10-01

    inherited human dystonia triggered by stress. There were problems with one of the mouse strains, however, which lost one of its genetic modifications ...showing the co-contraction of opposing muscles , the hallmark of dystonia. 15. SUBJECT TERMS Dystonia, genetically modified mice, stress, gene...mutations, animal model of disease . 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE

  20. Comparison of oscillatory activity in subthalamic nucleus in Parkinson's disease and dystonia

    PubMed Central

    Jiang, Yin; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander; Aziz, Tipu; Brown, Peter; Wang, Shouyan

    2017-01-01

    Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been successfully used to treat both Parkinson's disease (PD) and dystonia. Local field potentials (LFPs) recorded from the STN of PD patients demonstrate prominent beta frequency band activity. It is unclear whether such activity occurs in the STN in dystonia, and, if not, whether dystonia has another distinctive neural population activity in the STN. Methods Twelve patients with PD, and eight patients with dystonia underwent DBS electrode implantation targeting the STN. Seven dystonia patients were off medication and one was on aripiprazole and clonazepam. LFPs were recorded from the DBS electrodes in PD in the on/off medication states and in dystonia. Power spectra and temporal dynamics measured by the with Lempel-Ziv complexity of the LFPs were compared among these states. Results Normalised power spectra and Lempel-Ziv complexity of subthalamic LFPs differed between dystonia off and PD on/off, and between PD off and on over the low frequency, beta and high gamma bands. Patients with dystonia and off medication had lower beta power but higher low frequency and high gamma power than PD. Spectral power in the low beta frequency (11–20 Hz) range was attenuated in medicated PD. Conclusion The results suggest that dystonia and PD are characterized by different patterns of oscillatory activities even within the same nucleus, and exaggerated beta activity may relate to hypo-dopaminergic status. PMID:27940307

  1. Spatial reorganization of putaminal dopamine D2-like receptors in cranial and hand dystonia.

    PubMed

    Black, Kevin J; Snyder, Abraham Z; Mink, Jonathan W; Tolia, Veeral N; Revilla, Fredy J; Moerlein, Stephen M; Perlmutter, Joel S

    2014-01-01

    The putamen has a somatotopic organization of neurons identified by correspondence of firing rates with selected body part movements, as well as by complex, but organized, differential cortical projections onto putamen. In isolated focal dystonia, whole putaminal binding of dopamine D2-like receptor radioligands is quantitatively decreased, but it has not been known whether selected parts of the putamen are differentially affected depending upon the body part affected by dystonia. The radioligand [(18)F]spiperone binds predominantly to D2-like receptors in striatum. We hypothesized that the spatial location of [(18)F]spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To address statistical and methodological concerns, we chose a straightforward but robust image analysis method. An automated algorithm located the peak location of [(18)F]spiperone binding within the striatum, relative to a brain atlas, in each of 14 patients with cranial dystonia and 8 patients with hand dystonia. The mean (left and right) |x|, y, and z coordinates of peak striatal binding for each patient were compared between groups by t test. The location of peak [(18)F]spiperone binding within the putamen differed significantly between groups (cranial dystonia zdystonia z, p = 0.016). We conclude that in isolated focal dystonia, dopamine D2-like receptors are distributed differently in the putamen depending on the body part manifesting dystonia.

  2. Clinical spectrum of dopa-responsive dystonia and related disorders.

    PubMed

    Lee, Woong-Woo; Jeon, Beom Seok

    2014-07-01

    Dopa-responsive dystonia (DRD) has a classic presentation of childhood or adolescent-onset dystonia, mild parkinsonism, marked diurnal fluctuations, improvement with sleep or rest, and a dramatic and sustained response to low doses of L-dopa without motor fluctuations or dyskinesias. However, there have been many papers on patients with a wide range of features, which report them as DRD mainly because they had dystonic syndromes with L-dopa responsiveness. Many mutations in the dopaminergic system have been found as molecular genetic defects. Therefore, the clinical and genetic spectra of DRD are unclear, which lead to difficulties in diagnostic work-ups and planning treatments. We propose the concept of DRD and DRD-plus to clarify the confusion in this area and to help understand the pathophysiology and clinical features, which will help in guiding diagnostic investigations and planning treatments. We critically reviewed the literature on atypical cases and discussed the limitations of the gene study.

  3. Assessment of postexcitatory inhibition in patients with focal dystonia.

    PubMed

    Schwenkreis, P; Vorgerd, M; Malin, J P; Tegenthoff, M

    1999-10-01

    The aim of our present study was to detect whether a generalized disturbance of intracortical inhibitory mechanisms as assessed by transcranial magnetic stimulation (TMS) can be observed in a movement disorder with localized clinical expression, that is, in focal cervical dystonia. We measured motor threshold intensity, central motor conduction time and the duration of postexcitatory inhibition evoked by single and paired stimuli TMS from a small hand muscle in 20 patients with idiopathic cervical dystonia, and 21 healthy volunteers. A significant difference could not be found in any of the neurophysiological parameters between patients and controls. These findings are unlike the observations made in Parkinson's disease and Huntington's disease, where significant changes of postexcitatory inhibition after TMS can be observed. This suggests a lack of widespread change in activity of underlying cortical inhibitory mechanisms, as seen in other diseases of the extrapyramidal system with more generalized clinical involvement.

  4. Developing Gene Silencing for the Study and Treatment of Dystonia

    DTIC Science & Technology

    2015-11-01

    suppressing expression of torsinA(ΔE) through gene silencing techniques would be beneficial. We have already achieved this goal in cultured cells through RNA ...hypothesis is suppressing expression of torsinA(∆E) through RNA interference (RNAi) or antisense oligos (ASO) will be a safe an effective treatment...neuroanatomical substrate that causes motor dysfunction in dystonia. 2. KEYWORDS adeno-associated virus (AAV); antisense oligonucleotide (ASO); RNA

  5. Unmet Needs in the Management of Cervical Dystonia

    PubMed Central

    Contarino, Maria Fiorella; Smit, Marenka; van den Dool, Joost; Volkmann, Jens; Tijssen, Marina A. J.

    2016-01-01

    Cervical dystonia (CD) is a movement disorder which affects daily living of many patients. In clinical practice, several unmet treatment needs remain open. This article focuses on the four main aspects of treatment. We describe existing and emerging treatment approaches for CD, including botulinum toxin injections, surgical therapy, management of non-motor symptoms, and rehabilitation strategies. The unsolved issues regarding each of these treatments are identified and discussed, and possible future approaches and research lines are proposed. PMID:27733842

  6. Cannabis in the Treatment of Dystonia, Dyskinesias, and Tics.

    PubMed

    Koppel, Barbara S

    2015-10-01

    Cannabis has been used for many medicinal purposes, including management of spasms, dystonia, and dyskinesias, with variable success. Its use for tetanus was described in the second century BCE, but the literature continues to include more case reports and surveys of its beneficial effects in managing symptoms of hyperkinetic movement disorders than randomized controlled trials, making evidence-based recommendations difficult. This paper reviews clinical research using various formulations of cannabis (botanical products, oral preparations containing ∆(9)-tetrahydrocannabinol and/or cannabidiol) and currently available preparations in the USA (nabilone and dronabinol). This has been expanded from a recent systematic review of cannabis use in several neurologic conditions to include case reports and case series and results of anonymous surveys of patients using cannabis outside of medical settings, with the original evidence classifications marked for those papers that followed research protocols. Despite overlap in some patients, dyskinesias will be treated separately from dystonia and chorea; benefit was not established beyond individual patients for these conditions. Tics, usually due to Tourettes, did respond to cannabis preparations. Side effects reported in the trials will be reviewed but those due to recreational use, including the dystonia that can be secondary to synthetic marijuana preparations, are outside the scope of this paper.

  7. Neural correlates of abnormal sensory discrimination in laryngeal dystonia.

    PubMed

    Termsarasab, Pichet; Ramdhani, Ritesh A; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J; Reilly, Richard B; Hutchinson, Michael; Ozelius, Laurie J; Simonyan, Kristina

    2016-01-01

    Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

  8. Writer’s cramp: is focal dystonia the best explanation?

    PubMed Central

    Pritchard, Michael H

    2013-01-01

    Often considered no more than an historical curiosity, writer’s cramp remains an important disability in the workplace and the mechanism, which has puzzled the best medical minds for generations, remains contentious. A remarkable range of hypotheses has been put forward to try and explain a disability which periodically reached epidemic and economically worrying levels, but in the end medical opinion has accepted the explanation put forward by neurologists Sheehy and Marsden in 1983 that this was caused by a form of focal dystonia. However, the majority of the historical descriptions of writer’s cramp do not fit the classical parameters of focal dystonia and are more accurately described as a progressive forearm muscle fatigue. Today’s keyboard operators continue to complain of symptoms identical to their clerical forebears demonstrating that this is a problem which has evolved but not disappeared; this has the paradoxical advantage that modern research techniques enable this complaint to be revisited. The result shows that two varieties of writer’s cramp have always existed and while focal dystonia remains a valid explanation for a minority of cases, the much more common fatigue-based complaint is better explained by chronic compartment syndrome of the forearm. PMID:23885297

  9. Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation

    PubMed Central

    Pauls, K. A. M.; Wieland, K.; Jech, R.; Kurlemann, G.; Sharma, N.; Gill, S. S.; Haenggeli, C. A.; Hayflick, S. J.; Hogarth, P.; Leenders, K. L.; Limousin, P.; Malanga, C. J.; Moro, E.; Ostrem, J. L.; Revilla, F. J.; Santens, P.; Schnitzler, A.; Tisch, S.; Valldeoriola, F.; Vesper, J.; Volkmann, J.; Woitalla,, D.; Peker, S.

    2010-01-01

    Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale—Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale—Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2–6 and 9–15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2–6 months and 25.7% at 9–15 months. At 9–15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia

  10. Sleep in patients with primary dystonia: A systematic review on the state of research and perspectives.

    PubMed

    Hertenstein, Elisabeth; Tang, Nicole K Y; Bernstein, Celia J; Nissen, Christoph; Underwood, Martin R; Sandhu, Harbinder K

    2016-04-01

    Patients with primary dystonia, the third most prevalent movement disorder, suffer from a markedly reduced quality of life. This might, at least in part, be mediated by non-motor symptoms, including sleep disturbances. Characterising and treating sleep disturbances might provide new inroads to improve relevant patient-centred outcomes. This review evaluates the state of research on sleep in patients with dystonia and outlines an agenda for future research. A literature search was performed in July 2014 using PubMed, Medline via Ovid, PsycInfo, PsycArticles via Proquest and Embase via Ovid. Search results were screened for eligibility by two independent raters. Peer-reviewed publications reporting on sleep in patients with primary dystonia were included. Of 1445 studies identified through the search strategy, 18 met the inclusion criteria. In total, the included studies reported on 708 patients diagnosed with focal dystonia (cervical dystonia or blepharospasm), torsion dystonia, and dopa-responsive dystonia. The results indicate that at least half of the patients with focal cranial dystonia suffer from sleep disturbances, but excessive daytime sleepiness is uncommon. Sleep disturbance is associated with depressive symptoms. The frequency and duration of dystonic movements is markedly reduced during sleep. Reduced sleep quality appears to persist after treatment with botulinum toxin that successfully reduces motor symptoms. The findings are limited by a high clinical and methodological heterogeneity. Future research is needed to i) further characterize subjective and PSG sleep in patients with different types of dystonia, ii) determine the aetiology of sleep disturbances (e.g., abnormal brain function associated with dystonia, side effects of medication, psychological reasons), and iii) test whether targeted sleep interventions improve sleep and quality of life in patients with primary dystonia.

  11. Central Motor Conduction Studies and Diagnostic Magnetic Resonance Imaging in Children with Severe Primary and Secondary Dystonia

    ERIC Educational Resources Information Center

    McClelland, Verity; Mills, Kerry; Siddiqui, Ata; Selway, Richard; Lin, Jean-Pierre

    2011-01-01

    Aim: Dystonia in childhood has many causes. Imaging may suggest corticospinal tract dysfunction with or without coexistent basal ganglia damage. There are very few published neurophysiological studies on children with dystonia; one previous study has focused on primary dystonia. We investigated central motor conduction in 62 children (34 males, 28…

  12. A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia

    PubMed Central

    Vemula, Satya R; Xiao, Jianfeng; Zhao, Yu; Bastian, Robert W; Perlmutter, Joel S; Racette, Brad A; Paniello, Randal C; Wszolek, Zbigniew K; Uitti, Ryan J; Van Gerpen, Jay A; Hedera, Peter; Truong, Daniel D; Blitzer, Andrew; Rudzińska, Monika; Momčilović, Dragana; Jinnah, Hyder A; Frei, Karen; Pfeiffer, Ronald F; LeDoux, Mark S

    2014-01-01

    Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia. PMID:24936516

  13. Creation of a Mouse with Stress-Induced Dystonia: Control of an ATPase Chaperone

    DTIC Science & Technology

    2013-04-01

    There were problems with one of the mouse strains, however, which lost one of its genetic modifications , and a different strategy was adopted. This...a moderate dystonic baseline. As planned, electrophysiology and electromyography were performed, showing the co-contraction of opposing muscles ...the hallmark of dystonia. 15. SUBJECT TERMS Dystonia, genetically modified mice, stress, gene mutations, animal model of disease . 16

  14. Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation

    PubMed Central

    Shaikh, Aasef G.; Mewes, Klaus; DeLong, Mahlon R.; Gross, Robert E.; Triche, Shirley D.; Jinnah, H.A.; Boulis, Nicholas; Willie, Jon T.; Freeman, Alan; Alexander, Garrett E.; Aia, Pratibha; Butefisch, Cathrine M.; Esper, Christine D.; Factor, Stewart A.

    2016-01-01

    Background Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown. Methods We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. Results: Consistent with previous studies, deep brain stimulation improved the overall the Burkee–Fahn–Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. Conclusion Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia. PMID:25465373

  15. Integration of sensory force feedback is disturbed in CRPS-related dystonia.

    PubMed

    Mugge, Winfred; van der Helm, Frans C T; Schouten, Alfred C

    2013-01-01

    Complex regional pain syndrome (CRPS) is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. The origin of this movement disorder is poorly understood, although recent insights suggest involvement of disturbed force feedback. Assessment of sensorimotor integration may provide insight into the pathophysiology of fixed dystonia. Sensory weighting is the process of integrating and weighting sensory feedback channels in the central nervous system to improve the state estimate. It was hypothesized that patients with CRPS-related dystonia bias sensory weighting of force and position toward position due to the unreliability of force feedback. The current study provides experimental evidence for dysfunctional sensory integration in fixed dystonia, showing that CRPS-patients with fixed dystonia weight force and position feedback differently than controls do. The study shows reduced force feedback weights in CRPS-patients with fixed dystonia, making it the first to demonstrate disturbed integration of force feedback in fixed dystonia, an important step towards understanding the pathophysiology of fixed dystonia.

  16. The non-motor syndrome of primary dystonia: clinical and pathophysiological implications

    PubMed Central

    Stamelou, Maria; Edwards, Mark J.; Hallett, Mark

    2012-01-01

    Dystonia is typically considered a movement disorder characterized by motor manifestations, primarily involuntary muscle contractions causing twisting movements and abnormal postures. However, growing evidence indicates an important non-motor component to primary dystonia, including abnormalities in sensory and perceptual functions, as well as neuropsychiatric, cognitive and sleep domains. Here, we review this evidence and discuss its clinical and pathophysiological implications. PMID:21933808

  17. Striatal cholinergic dysfunction as a unifying theme in the pathophysiology of dystonia

    PubMed Central

    Jaunarajs, K.L. Eskow; Bonsi, P.; Chesselet, M.F.; Standaert, D.G.; Pisani, A.

    2015-01-01

    Dystonia is a movement disorder of both genetic and non-genetic causes, which typically results in twisted posturing due to abnormal muscle contraction. Evidence from dystonia patients and animal models of dystonia indicate a crucial role for the striatal cholinergic system in the pathophysiology of dystonia. In this review, we focus on striatal circuitry and the centrality of the acetylcholine system in the function of the basal ganglia in the control of voluntary movement and ultimately clinical manifestion of movement disorders. We consider the impact of cholinergic interneurons (ChIs) on dopamine-acetylcholine interactions and examine new evidence for impairment of ChIs in dysfunction of the motor systems producing dystonic movements, particularly in animal models. We have observed paradoxical excitation of ChIs in the presence of dopamine D2 receptor agonists and impairment of striatal synaptic plasticity in a mouse model of DYT1 dystonia, which are improved by administration of recently developed M1 receptor antagonists. These findings have been confirmed across multiple animal models of DYT1 dystonia and may represent a common endophenotype by which to investigate dystonia induced by other types of genetic and non-genetic causes and to investigate the potential effectiveness of pharmacotherapeutics and other strategies to improve dystonia. PMID:25697043

  18. Exhaustive Analysis of BH4 and Dopamine Biosynthesis Genes in Patients with Dopa-Responsive Dystonia

    ERIC Educational Resources Information Center

    Clot, Fabienne; Grabli, David; Cazeneuve, Cecile; Roze, Emmanuel; Castelnau, Pierre; Chabrol, Brigitte; Landrieu, Pierre; Nguyen, Karine; Ponsot, Gerard; Abada, Myriem; Doummar, Diane; Damier, Philippe; Gil, Roger; Thobois, Stephane; Ward, Alana J.; Hutchinson, Michael; Toutain, Annick; Picard, Fabienne; Camuzat, Agnes; Fedirko, Estelle; San, Chankannira; Bouteiller, Delphine; LeGuern, Eric; Durr, Alexandra; Vidailhet, Marie; Brice, Alexis

    2009-01-01

    Dopa-responsive dystonia is a childhood-onset dystonic disorder, characterized by a dramatic response to low dose of L-Dopa. Dopa-responsive dystonia is mostly caused by autosomal dominant mutations in the "GCH1" gene (GTP cyclohydrolase1) and more rarely by autosomal recessive mutations in the "TH" (tyrosine hydroxylase) or "SPR" (sepiapterin…

  19. Dystonia and the cerebellum: a new field of interest in movement disorders?

    PubMed

    Filip, Pavel; Lungu, Ovidiu V; Bareš, Martin

    2013-07-01

    Although dystonia has traditionally been regarded as a basal ganglia dysfunction, recent provocative evidence has emerged of cerebellar involvement in the pathophysiology of this enigmatic disease. This review synthesizes the data suggesting that the cerebellum plays an important role in dystonia etiology, from neuroanatomical research of complex networks showing that the cerebellum is connected to a wide range of other central nervous system structures involved in movement control to animal models indicating that signs of dystonia are due to cerebellum dysfunction and completely disappear after cerebellectomy, and finally to clinical observations in secondary dystonia patients with various types of cerebellar lesions. We propose that dystonia is a large-scale dysfunction, involving not only cortico-basal ganglia-thalamo-cortical pathways, but the cortico-ponto-cerebello-thalamo-cortical loop as well. Even in the absence of traditional "cerebellar signs" in most dystonia patients, there are more subtle indications of cerebellar dysfunction. It is clear that as long as the cerebellum's role in dystonia genesis remains unexamined, it will be difficult to significantly improve the current standards of dystonia treatment or to provide curative treatment.

  20. Patient considerations in the treatment of cervical dystonia: focus on botulinum toxin type A

    PubMed Central

    Mills, Reversa R; Pagan, Fernando L

    2015-01-01

    Cervical dystonia is the most common form of focal dystonia characterized by involuntary muscle contractions causing abnormal movements and posturing of the head and neck and is associated with significant pain. Botulinum toxin is considered first-line therapy in the treatment of pain and abnormal head posturing associated with cervical dystonia. There are currently three botulinum toxin type A neurotoxins and one botulinum type B neurotoxin commercially available and US Food and Drug Administration (FDA) labeled for the treatment of cervical dystonia. This review will focus on the efficacy, safety, and therapeutic use of botulinum type A neurotoxins in the treatment of cervical dystonia. We conclude with a discussion of factors influencing toxin selection including therapeutic effect, duration of effect, side effect profile, cost, and physician preference. PMID:26082621

  1. Heavy metal curse: a task-specific dystonia in the proximal lower limb of a professional percussionist.

    PubMed

    Lee, André; Altenmüller, Eckart

    2014-09-01

    Task-specific musician's dystonia is highly disabling and mostly affects the upper limb or the embouchure. In a recent paper, lower limb dystonia was reported in a drummer, although no details were given as to its phenomenology and electromyography (EMG). In this paper, we report on the case of a 28-year-old drummer with a task-specific dystonia of the right thigh and describe the phenomenology of the dystonia, the EMG recording, and treatment. Furthermore, we discuss stiff leg syndrome and paroxysmal exercise-induced dystonia as two important differential diagnoses.

  2. Stimulation-induced parkinsonism after posteroventral deep brain stimulation of the globus pallidus internus for craniocervical dystonia.

    PubMed

    Zauber, S Elizabeth; Watson, Nidhi; Comella, Cynthia L; Bakay, Roy A E; Metman, Leo Verhagen

    2009-02-01

    The authors report on a patient with craniocervical dystonia who was treated with bilateral GPi stimulation, with excellent improvement in dystonia but at the cost of stimulation-induced, reversible parkinsonism. Stimulation through ventral contacts resulted in maximal relief of craniocervical dystonia but induced considerable hypophonia, bradykinesia, rigidity, freezing, and impaired postural reflexes. Stimulation through dorsal contacts alleviated parkinsonism, but resulted in the return of dystonia. No stimulation parameters could alleviate the dystonia without inducing parkinsonism over the course of his 4-year follow-up.

  3. Case report: Physical therapy management of axial dystonia.

    PubMed

    Voos, Mariana Callil; Oliveira, Tatiana de Paula; Piemonte, Maria Elisa Pimentel; Barbosa, Egberto Reis

    2014-01-01

    Few studies have described physical therapy approaches to provide functional independence and reduce pain in individuals with dystonia. This report describes the physical therapy treatment of a 46-year-old woman diagnosed with idiopathic segmental axial dystonia. For two years, the patient was treated with kinesiotherapy (active and resisted movements and stretching of neck and trunk muscles), abdominal taping (kinesiotaping techniques), functional training, and sensory tricks. She was assessed with parts I, II and III of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-I, TWSTRS-II and TWSTRS-III), Berg Balance Scale (BBS), Six-Minute Walk Test (6-MWT), and the motor domain of Functional Independence Measure (FIM-motor) before and after the two-year treatment and after the one year follow-up. Postural control and symmetry improved (TWSTRS-I: from 30 to 18), functional independence increased (TWSTRS-II: from 27 to 15; BBS: from 36 to 46; 6-MWT: from 0 to 480 meters (m); FIM-motor: from 59 to 81), and the pain diminished (TWSTRS-III: from 12 to 5). The functional improvement was retained after one year (TWSTRS-I: 14/35; TWRTRS-II: 12/30; TWRTRS-III: 5/20; BBS: 48/56; 6-MWT: 450 m; FIM-motor: 81/91). This program showed efficacy on providing a better control of the dystonic muscles and thus the doses of botulinum toxin needed to treat them could be reduced. Outcomes support the therapeutic strategies used to deal with this type of dystonia.

  4. Descending control of muscles in patients with cervical dystonia.

    PubMed

    Tijssen, Marina A J; Münchau, Alex; Marsden, John F; Lees, Andrew; Bhatia, Kailash P; Brown, Peter

    2002-05-01

    It was reported recently that specific features in the frequency analysis of electromyographic (EMG) activity in the sternocleidomastoid (SCM) and splenius (SPL) muscles were able to distinguish between rotational idiopathic cervical dystonia (CD) and voluntary torticollis in individual subjects. Those with CD showed an abnormal drive to muscles at 5 to 7 Hz and an absence of the normal 10 to 12 Hz peak in the autospectrum of SPL. We sought to determine whether the same abnormalities in the frequency domain are found in complex CD, in which the head is displaced in more than two planes. EMG activity was recorded in the SCM, SPL, trapezius, and levator scapulae muscles bilaterally in 10 patients with complex CD. Frequency analysis of EMG was compared with conventional clinical and polymyographic assessment. The autospectrum of SPL during free dystonic contraction showed an absence of a significant peak at 10 to 12 Hz in 8 of the 10 patients. The presence of a 5 to 7 Hz frequency drive showed a significant association with muscle pairs determined as dystonic by means of polymyography (P < 0.005). The neck posture predicted blindly, based on the low-frequency drive, correlated significantly with the clinical assessment of posture (P < 0.01). Conventional assessment and the results of frequency analysis correlated, suggesting that a low-frequency drive to neck muscle may be a general feature of simple rotational and more complex cervical dystonia. The pattern of coherence between the EMG in different neck muscles may provide a means of identifying leading dystonic muscles, especially in patients with complex cervical dystonia.

  5. Alcohol responsiveness in laryngeal dystonia: A survey study

    PubMed Central

    Kirke, Diana N.; Frucht, Steven J.; Simonyan, Kristina

    2015-01-01

    Laryngeal dystonia (LD) is a task-specific focal dystonia of unknown pathophysiology affecting speech production. We examined the demographics of anecdotally reported alcohol use and its effects on LD symptoms using an online survey based on Research Electronic Data Capture (REDCap™) and National Spasmodic Dysphonia Association’s patient registry. From 641 participants, 531 were selected for data analysis, and 110 were excluded because of unconfirmed diagnosis. A total of 406 patients (76.5%) had LD and 125 (23.5%) had LD and voice tremor (LD/VT). The consumption of alcohol was reported by 374 LD (92.1%) and 109 LD/VT (87.2%) patients. Improvement of voice symptoms after alcohol ingestion was noted by 227 LD (55.9% of all patients) and 73 LD/VT (58.4%), which paralleled the improvement observed by patient’s family and/or friends in 214 LD (57.2%) and 69 LD/VT (63.3%) patients. The benefits lasted 1–3 hours in both groups with the maximum effect after 2 drinks in LD patients (p = 0.002), whereas LD/VT symptoms improved independent of the consumed amount (p = 0.48). Our data suggest that isolated dystonic symptoms, such as in LD, are responsive to alcohol intake and this responsiveness is not attributed to the presence of VT, which is known to have significant benefits from alcohol ingestion. Alcohol may modulate the pathophysiological mechanisms underlying abnormal neurotransmission of γ-aminobutyric acid (GABA) in dystonia and as such provide new avenues for novel therapeutic options in these patients. PMID:25929664

  6. Paroxysmal autonomic instability with dystonia (PAID) syndrome following cardiac arrest

    PubMed Central

    Kapoor, Dheeraj; Singla, Deepak; Singh, Jasveer; Jindal, Rohit

    2014-01-01

    Paroxysmal autonomic instability with dystonia (PAID) appears to be a unique syndrome following brain injury. It can echo many life-threatening conditions, making its early recognition and management a challenge for intensivists. A delay in early recognition and subsequent management may result in increased morbidity, which is preventable in affected patients. Herein, we report the case of a patient who was diagnosed with PAID syndrome following prolonged cardiac arrest, and discuss the pathophysiology, clinical presentation and management of this rare and under-recognised clinical entity. PMID:25189311

  7. TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion.

    PubMed

    Rostasy, Kevin; Augood, Sarah J; Hewett, Jeffrey W; Leung, Joanne Chung-on; Sasaki, Hikaru; Ozelius, Laurie J; Ramesh, Vijaya; Standaert, David G; Breakefield, Xandra O; Hedreen, John C

    2003-02-01

    Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. Most cases are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A (DYT1) gene, which is widely expressed in human brain and encodes the protein torsinA. This study compares neuropathology and torsinA expression in the normal human brain with that in dystonia cases with and without the GAG deletion. TorsinA-like protein was expressed in neuronal cytoplasm throughout the human brain, including cerebellum, substantia nigra, hippocampus, and neostriatum, with higher levels in specific neurons. This immunostaining pattern was not discernibly different in dystonia and normal brains in midbrain and neostriatal regions. However, nigral dopaminergic neurons appeared to be larger in both GAG-deletion and non-GAG-deletion dystonia brains compared to normal, and may be more closely spaced in GAG-deletion brains. Beyond these apparent changes in neuronal size and spacing in dystonia brains, there was no indication of neuron loss, inflammation, DNA strand breaks, or altered distribution of torsin-like immunoreactivity, supporting a functional rather than degenerative etiology of early onset torsion dystonia.

  8. Normal motor adaptation in cervical dystonia: a fundamental cerebellar computation is intact.

    PubMed

    Sadnicka, Anna; Patani, Bansi; Saifee, Tabish A; Kassavetis, Panagiotis; Pareés, Isabel; Korlipara, Prasad; Bhatia, Kailash P; Rothwell, John C; Galea, Joseph M; Edwards, Mark J

    2014-10-01

    The potential role of the cerebellum in the pathophysiology of dystonia has become a focus of recent research. However, direct evidence for a cerebellar contribution in humans with dystonia is difficult to obtain. We examined motor adaptation, a test of cerebellar function, in 20 subjects with primary cervical dystonia and an equal number of aged matched controls. Adaptation to both visuomotor (distorting visual feedback by 30°) and forcefield (applying a velocity-dependent force) conditions were tested. Our hypothesis was that cerebellar abnormalities observed in dystonia research would translate into deficits of cerebellar adaptation. We also examined the relationship between adaptation and dystonic head tremor as many primary tremor models implicate the cerebellothalamocortical network which is specifically tested by this motor paradigm. Rates of adaptation (learning) in cervical dystonia were identical to healthy controls in both visuomotor and forcefield tasks. Furthermore, the ability to adapt was not clearly related to clinical features of dystonic head tremor. We have shown that a key motor control function of the cerebellum is intact in the most common form of primary dystonia. These results have important implications for current anatomical models of the pathophysiology of dystonia. It is important to attempt to progress from general statements that implicate the cerebellum to a more specific evidence-based model. The role of the cerebellum in this enigmatic disease perhaps remains to be proven.

  9. Childhood Laryngeal Dystonia Following Bilateral Globus Pallidus Abnormality: A Case Study and Review of Literature

    PubMed Central

    Saeedi Borujeni, Mohammad Javad; Esfandiary, Ebrahim; Almasi-Dooghaee, Mostafa

    2017-01-01

    Introduction: Dystonia is a disorder of movement caused by various etiologies. Laryngeal dystonia is caused by the spasm of laryngeal muscles. It is a disorder caused by vocal fold movement in which excessive adduction or abduction of the vocal folds occurs during speech. The pathophysiology of this type of dystonia is not fully known. Some researchers have suggested that basal ganglia structures and their connections with cortical areas have been involved in the pathogenesis of dystonia. Case Report: In this paper a 7.5-year-old boy suffering from laryngeal dystonia with bilateral lesions in Globus Pallidus is presented. The patient also suffered from swallowing problems, monotone voice, vocal tremor, hypersensitivity of gag reflex, and stuttering. Drug treatment failed to cure him; therefore, he was referred to rehabilitation therapy. Conclusion: In conclusion, special attention should be brought upon laryngeal dystonia, especially in patients showing Extra-pyramidal symptoms and/or abnormalities of the basal ganglia. In children, laryngeal dystonia may be potentially fatal. Lack of consideration for this condition during rehabilitation therapy can lead to serious consequences for a child. PMID:28229063

  10. Sensory tricks in primary cervical dystonia depend on visuotactile temporal discrimination.

    PubMed

    Kägi, Georg; Katschnig, Petra; Fiorio, Mirta; Tinazzi, Michele; Ruge, Diane; Rothwell, John; Bhatia, Kailash P

    2013-03-01

    A characteristic feature of primary cervical dystonia is the presence of "sensory tricks" as well as the impairment of temporal and spatial sensory discrimination on formal testing. The aim of the present study was to test whether the amount of improvement of abnormal head deviation due to a sensory trick is associated with different performance of temporal sensory discrimination in patients with cervical dystonia. We recruited 32 patients with cervical dystonia. Dystonia severity was assessed using the Toronto Western Spasmodic Torticollis Rating Scale. Patients were rated according to clinical improvement to a sensory trick and assigned to 1 of the following groups: (1) no improvement (n = 6), (2) partial improvement (n = 17), (3) complete improvement (n = 9). Temporal discrimination thresholds were assessed for visual, tactile, and visuotactile modalities. Disease duration was shorter (P = .026) and dystonia severity lower (P = .033) in the group with complete improvement to sensory tricks compared with the group with partial improvement to sensory tricks. A significant effect for group and modality and a significant interaction between group × modality were found, with lower visuotactile discrimination thresholds in the group with complete improvement to sensory tricks compared with the other groups. In primary cervical dystonia, a complete resolution of dystonia during a sensory trick is associated with better visuotactile discrimination and shorter disease duration compared with patients with less effective sensory tricks, which may reflect progressive loss of adaptive mechanisms to basal ganglia dysfunction.

  11. The role of the trigeminal sensory nuclear complex in the pathophysiology of craniocervical dystonia.

    PubMed

    Bradnam, Lynley; Barry, Christine

    2013-11-20

    Isolated focal dystonia is a neurological disorder that manifests as repetitive involuntary spasms and/or aberrant postures of the affected body part. Craniocervical dystonia involves muscles of the eye, jaw, larynx, or neck. The pathophysiology is unclear, and effective therapies are limited. One mechanism for increased muscle activity in craniocervical dystonia is loss of inhibition involving the trigeminal sensory nuclear complex (TSNC). The TSNC is tightly integrated into functionally connected regions subserving sensorimotor control of the neck and face. It mediates both excitatory and inhibitory reflexes of the jaw, face, and neck. These reflexes are often aberrant in craniocervical dystonia, leading to our hypothesis that the TSNC may play a central role in these particular focal dystonias. In this review, we present a hypothetical extended brain network model that includes the TSNC in describing the pathophysiology of craniocervical dystonia. Our model suggests the TSNC may become hyperexcitable due to loss of tonic inhibition by functionally connected motor nuclei such as the motor cortex, basal ganglia, and cerebellum. Disordered sensory input from trigeminal nerve afferents, such as aberrant feedback from dystonic muscles, may continue to potentiate brainstem circuits subserving craniocervical muscle control. We suggest that potentiation of the TSNC may also contribute to disordered sensorimotor control of face and neck muscles via ascending and cortical descending projections. Better understanding of the role of the TSNC within the extended neural network contributing to the pathophysiology of craniocervical dystonia may facilitate the development of new therapies such as noninvasive brain stimulation.

  12. Childhood onset generalised dystonia can be modelled by increased gain in the indirect basal ganglia pathway.

    PubMed

    Sanger, T D

    2003-11-01

    Clinical experience suggests an important role of the indirect basal ganglia pathway in the genesis of childhood onset generalised dystonia, but it has been difficult to reconcile the increased muscle activity in dystonia with the current model of basal ganglia function in which the indirect pathway is considered primarily inhibitory. The aim of this study was to present a modification of the direct-indirect pathway model, in which the indirect pathway is inverting rather than purely inhibitory, so that while high signals are inhibited, low signals are amplified. As the basal ganglia may be a feedback loop that modifies cortical activity, instability from excessive gain in this feedback loop could explain features of dystonia. A detailed mathematical model is provided, together with simulations of cortical cell population spiking behaviour when connected through a basal ganglia loop. The simulations show that increased gain in the indirect pathway relative to the direct pathway can lead to unstable uncontrolled synchronous oscillations in cortex and basal ganglia. This behaviour could result in dystonia. The model provides a consistent explanation for the association of dystonia with parkinsonism and disorders characterised by dopamine depletion, the ability to treat some dystonias with dopamine, the ability of neuroleptic drug treatment to cause an acute dystonic reaction treatable with anticholinergic drugs, and the ability of pallidotomy or deep brain stimulation of the internal pallidum to alleviate symptoms of generalised dystonia.

  13. The anatomical basis of upper limb dystonia: lesson from secondary cases.

    PubMed

    Liuzzi, Daniele; Gigante, Angelo Fabio; Leo, Antonio; Defazio, Giovanni

    2016-09-01

    Upper limb dystonia is a focal dystonia that may affect muscles in the arm, forearm and hand. The neuroanatomical substrates involved in upper limb dystonia are not fully understood. Traditionally, dysfunction of the basal ganglia is presumed to be the main cause of dystonia but a growing body of evidence suggests that a network of additional cortical and subcortical structures may be involved. To identify the brain regions that are affected in secondary upper limb dystonia may help to better understand the neuroanatomical basis of the condition. We considered only patients with focal upper limb dystonia associated with a single localized brain lesion. To identify these patients, we conducted a systematic review of the published literature as well as the medical records of 350 patients with adult-onset dystonia seen over past 15 years at our movement disorder clinic. The literature review revealed 36 articles describing 72 cases of focal upper limb dystonia associated with focal lesions. Among patients at our clinic, four had focal lesions on imaging studies. Lesions were found in multiple regions including thalamus (n = 39), basal ganglia (n = 17), cortex (n = 4), brainstem (n = 4), cerebellum (n = 1), and cervical spine (n = 7). Dystonic tremor was not associated with any particular site of lesion, whereas there was a trend for an inverse association between task specificity and thalamic involvement. These data in combination with functional imaging studies of idiopathic upper limb dystonia support a model in which a network of different regions plays a role in pathogenesis.

  14. A gait paradigm reveals different patterns of abnormal cerebellar motor learning in primary focal dystonias.

    PubMed

    Hoffland, B S; Veugen, L C; Janssen, M M H P; Pasman, J W; Weerdesteyn, V; van de Warrenburg, B P

    2014-12-01

    Accumulating evidence points to a role of the cerebellum in the pathophysiology of primary dystonia. The aim of this study was to investigate whether the abnormalities of cerebellar motor learning in primary dystonia are solely detectable in more pure forms of cerebellum-dependent associative motor learning paradigms, or whether these are also present in other motor learning paradigms that rely heavily on the cerebellum but in addition require a more widespread sensorimotor network. Twenty-six patients with various forms of focal dystonia and 10 age-matched healthy controls participated in a motor learning paradigm on a split-belt treadmill. By using reflective markers, three-dimensional kinematics were recorded using a 6-camera motion analysis system. Adaptation walking parameters were analyzed offline, comparing the different dystonia groups and healthy controls. Patients with blepharospasm and writer's cramp were significantly impaired on various adaptation walking parameters. Whereas results of cervical dystonia patients did not differ from healthy controls in terms of adaptation walking parameters, differences in parameters of normal gait were found. We have here demonstrated abnormal sensorimotor adaptation with the split-belt paradigm in patients with blepharospasm and writer's cramp. This reinforces the current concept of cerebellar dysfunction in primary dystonia, and that this extends beyond more pure forms of cerebellum-dependent associative motor learning paradigms. However, the finding of normal adaptation in cervical dystonia patients indicates that the pattern of cerebellar dysfunction may be slightly different for the various forms of primary focal dystonia, suggesting that actual cerebellar pathology may not be a primary driving force in dystonia.

  15. Mental rotation of body parts and sensory temporal discrimination in fixed dystonia.

    PubMed

    Katschnig, Petra; Edwards, Mark J; Schwingenschuh, Petra; Aguirregomozcorta, Maria; Kägi, Georg; Rothwell, John C; Bhatia, Kailash P

    2010-06-15

    Fixed dystonia is an uncommon but severely disabling condition typically affecting young women following a minor peripheral injury. There is no evidence of any structural lesions of the central nervous system nor any clear peripheral nerve or root damage. Electrophysiological techniques such as short intracortical inhibition, cortical silent period and a plasticity inducing protocol have revealed similarities but also differences compared to classical mobile dystonia. To further explore the pathophysiology of fixed dystonia we compared mental rotation of body parts and sensory temporal discrimination in 11 patients with fixed dystonia, 11 patients with classical mobile dystonia and 10 healthy controls. In the mental rotation task subjects were presented with realistic photos of left or right hands, feet and the head of a young women with a black patch covering the left or the right eye in six different orientations. Subjects had to verbally report the laterality of the presented stimuli. To assess sensory temporal discrimination subjects were asked to discriminate whether pairs of visual, tactile (electrical), or visuo-tactile stimuli were simultaneous or sequential (temporal discrimination threshold) and in the latter case which stimulus preceded the other (temporal order judgement). In accordance with previous studies patients with mobile dystonia were abnormal in mental rotation and temporal discrimination, whereas patients with fixed dystonia were only impaired in mental rotation. Possible explanations for this deficit may include the influence of the abnormal body posture itself, a shared predisposing pathophysiology for mobile and fixed dystonia, or a body image disturbance. These findings add information to the developing pathophysiological picture of fixed dystonia.

  16. Focal dystonia in musicians: linking motor symptoms to somatosensory dysfunction.

    PubMed

    Konczak, Jürgen; Abbruzzese, Giovanni

    2013-01-01

    Musician's dystonia (MD) is a neurological motor disorder characterized by involuntary contractions of those muscles involved in the play of a musical instrument. It is task-specific and initially only impairs the voluntary control of highly practiced musical motor skills. MD can lead to a severe decrement in a musician's ability to perform. While the etiology and the neurological pathomechanism of the disease remain unknown, it is known that MD like others forms of focal dystonia is associated with somatosensory deficits, specifically a decreased precision of tactile and proprioceptive perception. The sensory component of the disease becomes also evident by the patients' use of "sensory tricks" such as touching dystonic muscles to alleviate motor symptoms. The central premise of this paper is that the motor symptoms of MD have a somatosensory origin and are not fully explained as a problem of motor execution. We outline how altered proprioceptive feedback ultimately leads to a loss of voluntary motor control and propose two scenarios that explain why sensory tricks are effective. They are effective, because the sensorimotor system either recruits neural resources normally involved in tactile-proprioceptive (sensory) integration, or utilizes a fully functioning motor efference copy mechanism to align experienced with expected sensory feedback. We argue that an enhanced understanding of how a primary sensory deficit interacts with mechanisms of sensorimotor integration in MD provides helpful insights for the design of more effective behavioral therapies.

  17. Focal dystonia in musicians: linking motor symptoms to somatosensory dysfunction

    PubMed Central

    Konczak, Jürgen; Abbruzzese, Giovanni

    2013-01-01

    Musician's dystonia (MD) is a neurological motor disorder characterized by involuntary contractions of those muscles involved in the play of a musical instrument. It is task-specific and initially only impairs the voluntary control of highly practiced musical motor skills. MD can lead to a severe decrement in a musician's ability to perform. While the etiology and the neurological pathomechanism of the disease remain unknown, it is known that MD like others forms of focal dystonia is associated with somatosensory deficits, specifically a decreased precision of tactile and proprioceptive perception. The sensory component of the disease becomes also evident by the patients' use of “sensory tricks” such as touching dystonic muscles to alleviate motor symptoms. The central premise of this paper is that the motor symptoms of MD have a somatosensory origin and are not fully explained as a problem of motor execution. We outline how altered proprioceptive feedback ultimately leads to a loss of voluntary motor control and propose two scenarios that explain why sensory tricks are effective. They are effective, because the sensorimotor system either recruits neural resources normally involved in tactile-proprioceptive (sensory) integration, or utilizes a fully functioning motor efference copy mechanism to align experienced with expected sensory feedback. We argue that an enhanced understanding of how a primary sensory deficit interacts with mechanisms of sensorimotor integration in MD provides helpful insights for the design of more effective behavioral therapies. PMID:23805090

  18. Rescue pallidotomy for dystonia through implanted deep brain stimulation electrode

    PubMed Central

    Blomstedt, Patric; Taira, Takaomi; Hariz, Marwan

    2016-01-01

    Background: Some patients with deep brain stimulation (DBS), where removal of implants is indicated due to hardware related infections, are not candidates for later re-implantation. In these patients a rescue lesion through the DBS electrode has been suggested as an option. In this case report we present a patient where a pallidotomy was performed using the DBS electrode. Case Description: An elderly woman with bilateral Gpi DBS suffered an infection around the left burr hole involving the DBS electrode. A unilateral lesion was performed through the DBS electrode before it was removed. No side effects were encountered. Burke-Fahn-Marsden (BFM) dystonia movement scale score was 39 before DBS. With DBS before lesioning BFM score was 2.5 points. The replacement of the left sided stimulation with a pallidotomy resulted in only a minor deterioration of the score to 5 points. Conclusions: In the case presented here a small pallidotomy performed with the DBS electrode provided a satisfactory effect on the patient's dystonic symptoms. Thus, rescue lesions through the DBS electrodes, although off-label, might be considered in patients with Gpi DBS for dystonia when indicated. PMID:27990311

  19. Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP)

    PubMed Central

    Lee, L V; Munoz, E L; Tan, K T; Reyes, M T

    2001-01-01

    Sex linked dystonia parkinsonism (XDP), also referred to as “lubag” in American literature, was described in 1975 occurring endemically in Panay, Philippines. It is an adult onset, sex linked, predominantly male, severe, progressive movement disorder with high penetrance and a high frequency of generalisation. The movement disorder is characterised by dystonic movements, usually starting in the 3rd or 4th decade, spreading to generalisation within two to five years. The dystonia coexists or is replaced by parkinsonism usually beyond the 10th year of illness. No treatment has been found to be effective. Neuroimaging shows caudate and putamenal atrophy in patients reaching the parkinsonian stage. Neuropathology reveals pronounced atrophy of the caudate and putamen, mostly in the cases with long standing illness. The sex linked pattern of inheritance has been established. Genetic studies have located the affected gene (DYT3) to Xq13.1, with one group mapping the XDP gene to a < 350 kb locus in the DXS 7117–DXS 559 region. PMID:11724910

  20. Tolerance of early pallidal stimulation in pediatric generalized dystonia.

    PubMed

    Miyagi, Yasushi; Koike, Yu

    2013-11-01

    The authors report on 2 cases of pediatric generalized dystonia with a DYT1 mutation; the patients, an 11-year-old girl and a 9-year-old boy, underwent chronic, pallidal deep brain stimulation (DBS) of the globus pallidus internus (GPi). The dystonic postures in both cases showed dramatic improvements with pallidal DBS, but each patient's symptoms gradually recurred within a year, irrespective of exhaustive readjustments of the stimulation settings. After the recurrence of the dystonic symptoms, the DBS leads were replaced within the GPi in one patient (Case 1) and additional DBS leads were implanted into the bilateral subthalamic nuclei in the other patient (Case 2). Neither measure produced any further clinical benefit, and the patient in Case 2 died of status dystonicus 2 days after reoperation. These findings suggest that early pallidal DBS for pediatric dystonia is indeed effective, although there are some cases in which its therapeutic effect is lost. One possible reason may be the ability of the preadolescent brain to tolerate chronic electrical stimuli during the active maturation process.

  1. Dopa-responsive dystonia--clinical and genetic heterogeneity.

    PubMed

    Wijemanne, Subhashie; Jankovic, Joseph

    2015-07-01

    Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia and exhibit a robust and sustained response to levodopa treatment. Autosomal dominant GTP cyclohydrolase 1 deficiency, also known as Segawa disease, is the most common and best-characterized condition that manifests as DRD, but a similar presentation can be seen with genetic abnormalities that lead to deficiencies in tyrosine hydroxylase, sepiapterin reductase or other enzymes that are involved in the biosynthesis of dopamine. In rare cases, DRD can result from conditions that do not affect the biosynthesis of dopamine; single case reports have shown that DRD can be a manifestation of hereditary spastic paraplegia type 11, spinocerebellar ataxia type 3 and ataxia telangiectasia. This heterogeneity of conditions that underlie DRD frequently leads to misdiagnosis, which delays the appropriate treatment with levodopa. Correct diagnosis at an early stage requires use of the appropriate diagnostic tests, which include a levodopa trial, genetic testing (including whole-exome sequencing), cerebrospinal fluid neurotransmitter analysis, the phenylalanine loading test, and enzyme activity measurements. The selection of tests for use depends on the clinical presentation and level of complexity. This Review presents the common and rarer causes of DRD and their clinical features, and considers the most appropriate approaches to ensure early diagnosis and treatment.

  2. Noninvasive brain stimulation for Parkinson's disease and dystonia.

    PubMed

    Wu, Allan D; Fregni, Felipe; Simon, David K; Deblieck, Choi; Pascual-Leone, Alvaro

    2008-04-01

    Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising noninvasive cortical stimulation methods for adjunctive treatment of movement disorders. They avoid surgical risks and provide theoretical advantages of specific neural circuit neuromodulation. Neuromodulatory effects depend on extrinsic stimulation factors (cortical target, frequency, intensity, duration, number of sessions), intrinsic patient factors (disease process, individual variability and symptoms, state of medication treatment), and outcome measures. Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson's disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects. Multiple mechanisms likely contribute to the clinical effects of rTMS and tDCS in movement disorders, including normalization of cortical excitability, rebalancing of distributed neural network activity, and induction of dopamine release. It remains unclear how to individually adjust rTMS or tDCS factors for the most beneficial effects on symptoms of PD or dystonia. Nonetheless, the noninvasive nature, minimal side effects, positive effects in preliminary clinical studies, and increasing evidence for rational mechanisms make rTMS and tDCS attractive for ongoing investigation.

  3. Focal hand dystonia in a patient with thoracic outlet syndrome

    PubMed Central

    Quartarone, A; Girlanda, P; Risitano, G; Picciolo, G; Sinicropi, S; Nicolosi, C; Macaione, V; Messina, C

    1998-01-01

    A patient affected by thoracic outlet syndrome, with an involvement of the left lower primary trunk due to a rudimentary cervical rib, developed a severe hand dystonia on the same side. The dystonic posture was characterised by a flexion of the wrist with the fingers curled into the palm. Polygraphic recordings performed on the left flexor digitorum superficialis (FDS4) and extensor digitorum superficialis (EDC4) muscles, during a repetitive tapping task of the fourth digit, showed a loss of well formed bursts without a clear silent period along with long duration bursts of cocontraction in antagonistic muscles. The study of reciprocal inhibition between forearm flexor and extensor muscles showed a reduced amount of inhibition in both the disynaptic and the later presynaptic phase of inhibition. The patient underwent an operation with resection of the cervical rib. Twelve hours after the operation the patient experienced a significant improvement of the hand dystonia; the distonia had disappeared completely by two months with a progressive normalisation of reciprocal inhibition.

 PMID:9703190

  4. Focal hand dystonia in a patient with thoracic outlet syndrome.

    PubMed

    Quartarone, A; Girlanda, P; Risitano, G; Picciolo, G; Sinicropi, S; Nicolosi, C; Macaione, V; Messina, C

    1998-08-01

    A patient affected by thoracic outlet syndrome, with an involvement of the left lower primary trunk due to a rudimentary cervical rib, developed a severe hand dystonia on the same side. The dystonic posture was characterised by a flexion of the wrist with the fingers curled into the palm. Polygraphic recordings performed on the left flexor digitorum superficialis (FDS4) and extensor digitorum superficialis (EDC4) muscles, during a repetitive tapping task of the fourth digit, showed a loss of well formed bursts without a clear silent period along with long duration bursts of cocontraction in antagonistic muscles. The study of reciprocal inhibition between forearm flexor and extensor muscles showed a reduced amount of inhibition in both the disynaptic and the later presynaptic phase of inhibition. The patient underwent an operation with resection of the cervical rib. Twelve hours after the operation the patient experienced a significant improvement of the hand dystonia; the distonia had disappeared completely by two months with a progressive normalisation of reciprocal inhibition.

  5. Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole

    PubMed Central

    Başay, Ömer; Basay, Burge Kabukcu; Öztürk, Önder; Yüncü, Zeki

    2016-01-01

    The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine prior to the initiation of aripiprazole treatment; thus, this report also discussed the possible mechanisms underlying the manifestation of dystonia from the perspective of neurotransmitter activity. PMID:27121436

  6. Fixed Dystonia of the Left Hand in a Violinist: a Rare Functional Disorder

    PubMed Central

    Lee, André; Jahnke, Andreas K.; Altenmüller, Eckart

    2013-01-01

    Background Fixed dystonia leads to an immobile abnormal posturing of the affected limb. There is an ongoing debate whether this condition is psychogenic in origin. Case report We present a 21-year-old violinist with fixed dystonia after an acute overuse injury with a transient cyanosis but no signs for psychological trauma. After Incobotulinumtoxin injection, symptoms subsided within 8 hours. Discussion Our case corroborates the notion that fixed dystonias after minor injuries are functional disorders. It underlines the necessity of a biopsychosocial approach to functional disorders, considering the possibility of an overlay between organic and non-organic disorders. PMID:24032089

  7. A novel gene mutation in PANK2 in a patient with severe jaw-opening dystonia.

    PubMed

    Yapici, Zuhal; Akcakaya, Nihan Hande; Tekturk, Pinar; Iseri, Sibel Aylin Ugur; Ozbek, Ugur

    2016-09-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative condition. Major clinical features include progressive dystonia, pigmentary retinopathy, spasticity, and cognitive decline. The typical MRI sign of the disease, known as "eye-of-the-tiger", is what makes differential diagnosis possible. We here describe a 16-year-old male patient with PKAN presenting with severe and sustained jaw-opening dystonia which may be due to heterogeneous etiologies showing poor response to treatment. Herein, long-term follow-up and genetic results of a PKAN case who experienced severe jaw-opening dystonia are presented and discussed.

  8. Botulinum toxin in the treatment of lingual dystonia induced by speaking.

    PubMed

    Budak, F; Aydın, E; Koçkaya, A; Ilbay, G

    2013-01-01

    Primary lingual dystonia is a rare condition, especially when it is only induced by speaking. Trihexyphenidyl failed to improve the symptoms. Several case series have demonstrated the effectiveness of botulinum toxin injection for the management of focal lingual movement disorders. Only 1 case of botulinum toxin injection for primary lingual dystonia induced by speaking has been reported, but this treatment has limited effectiveness. Our patient was treated with botulinum toxin using a superficial approach for injection into the tongue with continuing excellent results. Lingual botulinum toxin injection is a fairly simple, safe and viable treatment option for lingual dystonia induced by speaking.

  9. Combined pallidal and subthalamic nucleus stimulation in sporadic dystonia-parkinsonism.

    PubMed

    Wöhrle, Johannes C; Blahak, Christian; Capelle, Hans-Holger; Fogel, Wolfgang; Bäzner, Hansjoerg; Krauss, Joachim K

    2012-01-01

    Multifocal deep brain stimulation (DBS) is a new technique that has been introduced recently. A 39-year-old man with dystonia-parkinsonism underwent the simultaneous implantation of subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS electrodes. While bilateral STN DBS controlled the parkinsonian symptoms well and allowed for a reduction in levodopa, the improvement of dystonia was only temporary. Additional GPi DBS also alleviated dystonic symptoms. Formal assessment at the 1-year follow-up showed that both the parkinsonian symptoms and the dystonia were markedly improved via continuous bilateral combined STN and GPi stimulation. Sustained benefit was achieved at 3 years postoperatively.

  10. Recognizing the Common Origins of Dystonia and the Development of Human Movement: A Manifesto of Unmet Needs in Isolated Childhood Dystonias

    PubMed Central

    Lin, Jean-Pierre; Nardocci, Nardo

    2016-01-01

    Dystonia in childhood may be severely disabling and often unremitting and unrecognized. Considered a rare disorder, dystonic symptoms in childhood are pervasive in many conditions including disorders of developmental delay, cerebral palsy (CP), autism, neurometabolic, neuroinflammatory, and neurogenetic disorders. Collectively, there is a need to recognize the role of early postures and movements which characterize phases of normal fetal, infant, and child development as a backdrop to the many facets of dystonia in early childhood neurological disorders and to be aware of the developmental context of dystonic symptoms. The role of cocontraction is explored throughout infancy, childhood, young adulthood, and in the elderly. Under-recognition of pervasive dystonic disorders of childhood, including within CP is reviewed. Original descriptions of CP by Gowers are reviewed and contemporary physiological demonstrations are used to illustrate support for an interpretation of the tonic labyrinthine response as a manifestation of dystonia. Early recognition and molecular diagnosis of childhood dystonia where possible are desirable for appropriate clinical stratification and future precision medicine and functional neurosurgery where appropriate. A developmental neurobiological perspective could also be useful in exploring new clinical strategies for adult-onset dystonia disorders focusing on environmental and molecular interactions and systems behaviors. PMID:28066314

  11. Cervical dystonia mimicking dropped-head syndrome after radiotherapy for laryngeal carcinoma.

    PubMed

    Astudillo, Leonardo; Hollington, L; Game, X; Benyoucef, A; Boladeras, A M; Delisle, M B; Simonetta-Moreau, M

    2003-12-01

    We report a case of cervical dystonia mimicking dropped-head syndrome (DHS) in a 57-year-old man treated for laryngeal carcinoma by radiotherapy (74.4 Gy) 3 months before. Cervical computerized tomographic scan and magnetic resonance imaging (MRI) did not find any muscle fat changes but found a high-intensity signal on T2 weighted images in the cervical spinal cord. Clinical and electromyographic findings were consistent with cervical dystonia. A trapezius biopsy was normal. Spontaneous remission of the dystonia was observed for 1 month whereas the laryngeal carcinoma progressed. The link between cervical dystonia and radiotherapy might be acute radiation-induced damage to the cervical spinal cord.

  12. [Questionnaire survey of musician's dystonia among students of a music college].

    PubMed

    Konaka, Kuni; Mochizuki, Hideki

    2015-01-01

    Musician's dystonia is known as a task specific dystonia. Though it is thought to occur during a long course of repetitive performance, the actual circumstances that precipitate this condition are not clear. According to factual reports this disease is not commonly known, probably because many of these patients may not have been visiting a hospital. We prepared a questionnaire and did a survey among the students of a music college. This is the first questionnaire survey aimed at finding out the prevalence of musician's dystonia among the students of music. Among the 480 participants of this survey, 29% of the students had knowledge of this disorder and 1.25% of the students had dystonia while performing music.

  13. Integration of Osteopathic Manual Treatments in Management of Cervical Dystonia with Tremor: A Case Series

    PubMed Central

    Halimi, Miriam; Leder, Adena; Mancini, Jayme D.

    2017-01-01

    Background Cervical dystonia, also known as spasmodic torticollis, is a chronic disorder in which patients exhibit involuntary repetitive contractions of neck muscles resulting in abnormal postures or movements. Occasionally, there is also a dystonic head tremor. The underlying mechanisms for cervical dystonia and dystonic tremor are not clear, and treatments are limited. Case Report In the present cases, two females with head tremor starting in adolescence developed worsening symptoms of cervical dystonia with dystonic tremor in their 60s. On osteopathic physical examination, both had a vertical type strain to the sphenobasilar synchondrosis. Discussion Vertical strains are more frequently found in patients after head trauma, congenital or later in life, than in healthy patients, and head trauma may have been a precipitating factor in these patients. There were improvements in cervical dystonia symptoms, including tremor, in both patients after osteopathic manual treatment. PMID:28119789

  14. Patterns of reoccurrence of segmental dystonia after discontinuation of deep brain stimulation

    PubMed Central

    Grips, E; Blahak, C; Capelle, H H; Bäzner, H; Weigel, R; Sedlaczek, O; Krauss, J K; Wöhrle, J C

    2007-01-01

    The pattern of reoccurrence of symptoms after discontinuation of deep brain stimulation (DBS) has not been systematically studied in dystonia. Eight patients (mean age (SD) 53.8 (14.4) years) with segmental dystonia at a mean follow‐up of 11.3 (4.2) months were studied after implantation of bilateral DBS electrodes in the internal globus pallidus using a standard video protocol and clinical rating scales, immediately and at 2 and 4 h after switching off DBS. Dystonic signs returned sequentially, with a rapid worsening of phasic and a slower worsening of tonic dystonic components. In all patients, phasic dystonic features appeared within a few minutes, whereas the tonic elements of dystonia reoccurred with a more variable delay. Differential clinical effects when withdrawing DBS might reflect its influence on different pathophysiological mechanisms in dystonia. PMID:17030588

  15. Physiotherapy in cervical dystonia: six experimental single-case studies.

    PubMed

    Zetterberg, Lena; Halvorsen, Kjartan; Färnstrand, Catarina; Aquilonius, Sten-Magnus; Lindmark, Birgitta

    2008-01-01

    The aim of the study was to explore the outcome of a physiotherapy program targeted to improve the quality of life of people with cervical dystonia (CD) by reducing pain, improving awareness of postural orientation, increasing muscle strength, and reducing the effort of moving the head and neck. In six single case studies, the primary outcome measure for each case was the Cervical Dystonia Questionnaire (CDQ) to measure the impact of the program on the individuals' quality of life. Secondary outcome measures were identified for the different components of the physiotherapy program: Visual Analogue Scale (pain); Postural Orientation Index (postural orientation awareness); and Movement Energy Index (effort of moving head and neck). Each of the cases had the severity of their problems scored on the Toronto Western Spasmodic Torticollis Scale. The study period was 26 weeks: 2 weeks' baseline period, 4 weeks' treatment period, and 20 weeks' follow-up. All measures except the Movement Energy Index (MEI) and CDQ-24 were taken three times per week for the first 6 weeks of the study and then once at 3 and 6 months. The MEI was taken once a week during the pretreatment and the treatment periods and during the first 2 weeks of follow-up and also after 3 and 6 months of follow-up. The CDQ-24 was taken once in the pretreatment period, once after completion of treatment, once 2 weeks after treatment, and once at 3 and 6 months of follow-up. Five of the six case studies reported an increase in quality of life at 6-month follow-up, as measured on the CDQ-24. Three of the six cases reported a reduction in pain and severity of the dystonia and had improved scores on the postural orientation measure at 6-month follow-up. All six patients had a reduction in the movement energy scores, but this was not significant. The outcomes of the six case studies would suggest that further investigation is required to show the effectiveness of physiotherapy programs in the management of CD.

  16. Botulinum Toxin Treatment of Blepharospasm, Orofacial/Oromandibular Dystonia, and Hemifacial Spasm.

    PubMed

    Karp, Barbara Illowsky; Alter, Katharine

    2016-02-01

    Blepharospasm is a focal dystonia characterized by involuntary, repetitive eye closure. Orofacial and oromandibular dystonia describe involuntary dystonic movements of orofacial and oromandibular musculature. Hemifacial spasm is characterized by repetitive synchronous contraction of facial nerve innervated muscles on one side of the face. In this article, the clinical presentation, epidemiology, and approaches to treatment are reviewed. Technical aspects of using botulinum toxin for treatment and reported outcomes are discussed.

  17. Focal dystonia of the jaw and the differential diagnosis of unilateral jaw and masticatory spasm.

    PubMed Central

    Thompson, P D; Obeso, J A; Delgado, G; Gallego, J; Marsden, C D

    1986-01-01

    The clinical features, differential diagnosis and treatment of unilateral spasms of the jaw and masticatory muscles are discussed and illustrated by eight cases of unilateral jaw spasms of various aetiologies. These include focal dystonia of the jaw, hemimasticatory spasm with and without facial hemiatrophy, paroxysmal events in multiple sclerosis and tetany. Attention is particularly drawn to four cases of unilateral dystonia of the jaw which has not been described before. Images PMID:3734821

  18. Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder Dystonia

    DTIC Science & Technology

    2015-08-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0301 TITLE: Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder...Affected in the Movement Disorder Dystonia 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0301 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT The movement disorder dystonia is characterized by involuntary muscle contractions in the limbs, hands, feet or neck. The aim

  19. Cerebellar Intermittent Theta-Burst Stimulation and Motor Control Training in Individuals with Cervical Dystonia

    PubMed Central

    Bradnam, Lynley V.; McDonnell, Michelle N.; Ridding, Michael C.

    2016-01-01

    Background: There is emerging evidence that cervical dystonia is a neural network disorder with the cerebellum as a key node. The cerebellum may provide a target for neuromodulation as a therapeutic intervention in cervical dystonia. Objective: This study aimed to assess effects of intermittent theta-burst stimulation of the cerebellum on dystonia symptoms, quality of life, hand motor dexterity and cortical neurophysiology using transcranial magnetic stimulation. Methods: Sixteen participants with cervical dystonia were randomised into real or sham stimulation groups. Cerebellar neuromodulation was combined with motor training for the neck and an implicit learning task. The intervention was delivered over 10 working days. Outcome measures included dystonia severity and pain, quality of life, hand dexterity, and motor-evoked potentials and cortical silent periods recorded from upper trapezius muscles. Assessments were taken at baseline and after 5 and 10 days, with quality of life also measured 4 and 12 weeks later. Results: Intermittent theta-burst stimulation improved dystonia severity (Day 5, −5.44 points; p = 0.012; Day 10, −4.6 points; p = 0.025), however, effect sizes were small. Quality of life also improved (Day 5, −10.6 points, p = 0.012; Day 10, −8.6 points, p = 0.036; Week 4, −12.5 points, p = 0.036; Week 12, −12.4 points, p = 0.025), with medium or large effect sizes. There was a reduction in time to complete the pegboard task pre to post intervention (both p < 0.008). Cortical neurophysiology was unchanged by cerebellar neuromodulation. Conclusion: Intermittent theta-burst stimulation of the cerebellum may improve cervical dystonia symptoms, upper limb motor control and quality of life. The mechanism likely involves promoting neuroplasticity in the cerebellum although the neurophysiology remains to be elucidated. Cerebellar neuromodulation may have potential as a novel treatment intervention for cervical dystonia, although larger

  20. Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia

    PubMed Central

    Park, Hye Ran; Lee, Jae Meen; Ehm, Gwanhee; Yang, Hui-Jun; Song, In Ho; Lim, Yong Hoon; Kim, Mi-Ryoung; Kim, Keyoung Ran; Lee, Woong-Woo; Kim, Young Eun; Hwang, Jae Ha; Shin, Chae Won; Park, Hyeyoung; Kim, Jin Wook; Kim, Han-Joon; Kim, Cheolyoung; Kim, Dong Gyu; Jeon, Beom Seok; Paek, Sun Ha

    2016-01-01

    Background GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia. Objectives This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital. Methods Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84) Results The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement. Conclusions GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center. PMID:26745717

  1. The Role of TOR1A Polymorphisms in Dystonia: A Systematic Review and Meta-Analysis

    PubMed Central

    Siokas, Vasileios; Dardiotis, Efthimios; Tsironi, Evangelia E.; Tsivgoulis, Georgios; Rikos, Dimitrios; Sokratous, Maria; Koutsias, Stylianos; Paterakis, Konstantinos; Deretzi, Georgia; Hadjigeorgiou, Georgios M.

    2017-01-01

    Importance A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution. Methods We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates. Results Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14–2.93), Pz = 0.01]. In addition, rs1801968 was associated with writer’s cramp in both recessive and dominant modes [OR (95%C.I.): 5.99 (2.08–17.21), Pz = 0.00009] and [2.48 (1.36–4.51), Pz = 0.003) respectively and in model free-approach [ORG (95%C.I.): 2.58 (1.45–4.58)]. Conclusions Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer’s cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype. PMID:28081261

  2. Spatiotemporal integration of sensory stimuli in complex regional pain syndrome and dystonia.

    PubMed

    van Rijn, Monique A; van Hilten, Jacobus J; van Dijk, J Gert

    2009-05-01

    The aetiology of dystonia in complex regional pain syndrome (CRPS-I) is incompletely understood. In primary dystonia, somatosensory-evoked potentials (SSEP) after spatially or temporally separated stimulation revealed impaired central sensory integration. Information on somatosensory processing in dystonia in CRPS-I patients may provide better insight into the underlying pathophysiological mechanism. We studied SSEPs in 33 patients with CRPS-I and dystonia and 19 healthy controls. N9, N14, N20 and N35 amplitudes were recorded after paired stimulation of median and ulnar nerves ("spatial") and after stimulation of both nerves with single stimuli and with interstimulus intervals of 20 and 40 ms ("temporal" stimulation). Finally, both methods were integrated resulting in spatiotemporal stimulation. Statistical testing was performed using linear mixed model analysis of variance. SSEP amplitudes were significantly suppressed after spatial and temporal stimulation. No difference was observed between patients and healthy controls. Spatiotemporal stimulation did not show an additional suppressive effect in any group. Central sensory integration of proprioceptive afferent input is normal in patients with CPRS-related dystonia. Other mechanisms may underlie the development of dystonia in this disorder.

  3. Biperiden hydrochlorate ameliorates dystonia of rats produced by microinjection of sigma ligands into the red nucleus.

    PubMed

    Yoshida, K; Takahashi, H; Sato, K; Higuchi, H; Shimizu, T

    2000-11-01

    It has been reported that the imbalance of anticholinergic and antidopaminergic activity of each neuroleptic drug correlates with the capacity to produce neuroleptic-induced acute dystonia (NAD) and the major focus of NAD is thought to be the striatum. Anticholinergic drugs are highly effective on NAD, but they are partially effective on neuroleptic-induced tardive dystonia and their effect on idiopathic dystonia is disappointing. Recently, it has been reported that the unilateral microinjection of sigma (sigma) ligands into the red nucleus induces torticollis of rats. This animal model appears to be a model of dystonia, but it is not clear whether it is suitable for NAD in man. To clarify this issue, we investigated the effect of an anticholinergic drug, biperiden hydrochlorate (BH), on this animal model. This study revealed that BH dose-dependently ameliorated dystonia of rats induced by two sigma ligands, whether each sigma ligand had dopaminergic affinity or not. This animal model of dystonia appears to be a model of NAD in man from the viewpoint of treatment-response. The results also suggest that not only dopaminergic and cholinergic systems but also sigma system, and not only the striatum but also the red nucleus, may play an important role in the pathophysiology of NAD.

  4. Dystonia and tremor following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Klawans, H.L.

    1987-01-01

    Forty-seven railroad workers who were exposed to polychlorinated phenols, including dioxin (TCDD), during 1979 while cleaning up the chemical spillage following damage to a tank car filled with these chemicals were followed medically for the subsequent 6 years. Two committed suicide. The initial neurological complaints included a sense of fatigue and muscle aching, both of which have been reported in other individuals following dioxin exposure. On detailed neurological examination in December, 1985, 24 of 45 had dystonic writer's cramp and/or other action dystonias of the hands. None of the involved individuals had a family history of dystonia, and all 24 dated the onset of the dystonia to the first 2 to 3 years subsequent to their toxic exposure. The dystonias varied in severity but were usually mild. No other types of dystonic involvement were recognized. Thirty-five of the 45 individuals also manifested postural and terminal intention tremor which resembled benign essential tremor. None of the involved individuals had a family history of tremor, and all 35 of those affected dated the onset of the tremor to some time subsequent to their toxic exposure. Forty-three of 45 patients had histories and findings suggestive of peripheral neuropathy. This is the first report relating any type of dystonia to prior dioxin exposure and the first report relating action dystonia, such as dystonic writer's cramp, and postural/terminal intention tremor, to toxic exposure of any type.

  5. Syndrome of fixed dystonia in adolescents--short term outcome in 4 cases.

    PubMed

    Majumdar, Anirban; López-Casas, Jesús; Poo, Pilar; Colomer, Jaume; Galvan, Marta; Lingappa, Lokesh; Short, Clare; Jardine, Philip E; Fernández-Alvarez, Emilio

    2009-09-01

    We describe the clinical features, investigations and outcome of 4 adolescents aged 13, 16, 17 and 19 years, with fixed dystonia. The diagnosis was made within 6 months of the onset of symptoms. One patient had an identifiable traumatic precipitant. All the affected extremities had pain, sudomotor and vascular changes which were consistent with complex regional pain syndrome. The extremities affected by dystonia were the foot and the hand. The dystonia spread to affect other extremities in one patient. One patient had hemifacial spasm. Examination of the central and peripheral nervous system and allied investigations failed to reveal an organic cause. Common genetic causes for dystonia were excluded. The response to physical treatments for the affected extremities, such as Botulinum Toxin and surgery was poor. In all our cases there were significant psychological and psychiatric factors. Three patients fully met the criteria for psychogenic dystonia and responded well to psychological intervention. Fixed dystonia in adolescents is an uncommon disorder of unknown aetiology, usually presenting in girls, which can be very disabling and difficult to treat. The affected parts of the body are usually painful and show vascular changes. The condition is allied to CRPS. Treatment with multidisciplinary approach including psychological measures and physiotherapy is more likely to be successful and may prevent unnecessary physical measures.

  6. Val66Met polymorphism of brain-derived neurotrophic factor is associated with idiopathic dystonia.

    PubMed

    Sako, Wataru; Murakami, Nagahisa; Izumi, Yuishin; Kaji, Ryuji

    2015-03-01

    The Val66Met (G196A; rs6265) single nucleotide polymorphism of brain-derived neurotrophic factor (BDNF) affects morphology and neuronal activity, and is expected to be associated with central nervous system disorders. However, it remains controversial whether Val66Met polymorphism is a risk factor for idiopathic dystonia. We aimed to clarify the impact of BDNF polymorphism on idiopathic dystonia. A literature search of PubMed was carried out. A random-effects model was employed for the meta-analysis. A pooled odds ratio (OR) was calculated along with 95% confidence intervals (CI) to reflect the risk of idiopathic dystonia in each genotype (GG, AG, AA) or minor allele. The proportion of variation due to heterogeneity was computed and expressed as I(2). Five case-control studies, comprising a total sample size of 1804 subjects (784 idiopathic dystonia patients, 1020 normal controls), were included in this meta-analysis. AA genotype was significantly more frequent in patients with idiopathic dystonia (OR=1.47, 95% CI 1.09-1.99, p=0.01, four studies, n=1716). This finding was derived from homogeneous studies (p=0.97, I(2)=0%). Our meta-analysis has revealed a significant overall effect of the AA genotype on the development of idiopathic dystonia.

  7. Dystonia after striatopallidal and thalamic stroke: clinicoradiological correlations and pathophysiological mechanisms

    PubMed Central

    Krystkowiak, P; Martinat, P; Defebvre, L; Pruvo, J; Leys, D; Destee, A

    1998-01-01

    OBJECTIVE—To establish the pathophysiological mechanisms of striatopallidal and thalamic dystonia.
METHODS—Five patients from among 26 who presented (between March 1987 and July 1996) with focal dystonia, segmental dystonia, or hemidystonia caused by a single localised vascular lesion, were selected. Patients with lesions with indefinite boundaries, and diffuse, or multiple, or large brain lesions were excluded. Three dimensional T1 weighted MRI (1.5 tesla) was performed to determine the topography of the lesions. The atlas of Hassler allowed the stereotactic localisation of the lesions to be specified exactly.
RESULTS—Three patients had dystonic spasms associated with striatopallidal lesions and one with a thalamic and striatopallidal lesion. One other patient presented with a myoclonic dystonia related to a thalamic lesion. The striatopallidal lesions were located in the sensorimotor area with a somatotopical distribution. The pure thalamic lesion involved the centromedian nucleus, the sensory nuclei, and the pulvinar whereas the thalamic and striatopallidal lesion was located in the pallidonigral thalamic territory, which receives pallidonigral inputs.
CONCLUSION—The striatopallidal dystonia might be the consequence of the interruption of the cortico-striato-pallido-thalamo-cortical loop induced by lesions located within the sensorimotor part of the striatopallidal complex. By contrast, it is suggested that thalamic dystonia might be caused by lesions located in the centromedian or the ventral intermediate nuclei, outside the pallidonigral territory, but leading also to a dysfunction of the cort ico -striat o - pallido - thalamo - cort ica l loop.

 PMID:9810942

  8. Olanzapine-related repetitive focal seizures with lingual dystonia.

    PubMed

    Anzellotti, Francesca; Capasso, Margherita; Frazzini, Valerio; Onofrj, Marco

    2016-03-01

    Olanzapine-related seizures have rarely been reported despite associated proconvulsant risk factors described in the literature: myoclonic status, increased frequency of seizures, tonic-clonic seizures, as well as fatal status epilepticus. We present a psychiatric patient who developed repetitive focal motor seizures and lingual dystonia when olanzapine was added for psychomotor agitation and aggressiveness. Olanzapine was immediately suspended and the seizures progressively disappeared. A control EEG showed no paroxysmal discharges. Olanzapine shares some pharmacological similarities with clozapine, a neuroleptic with a high risk of dose-dependent seizures. This adverse effect should be taken into account, and olanzapine should be used with caution if concomitant circumstances decrease the seizure threshold. [Published with video sequence online].

  9. Cochlear implantation in deafness-dystonia-optic neuronopathy (DDON) syndrome.

    PubMed

    Brookes, James T; Kanis, Adam B; Tan, Lih Yeen; Tranebjaerg, Lisbeth; Vore, Abram; Smith, Richard J H

    2008-01-01

    To report the results of the first known cochlear implantation in a patient with deafness-dystonia-optic neuronopathy (DDON) syndrome (Mohr-Tranebaerg syndrome, DFN-1). DDON syndrome is an X-linked condition characterized by postlingual sensorineural hearing loss in early childhood followed by dystonia, psychosis, and optic atrophy in adolescence and adulthood. The gene responsible for the condition maps to Xq22 adjacent to the gene causally related to X-linked agammaglobulinemia. The audiometric characteristics of DDON syndrome are typical of auditory neuropathy, with spiral ganglion cells being the suspected site of pathology. Performance following cochlear implantation in auditory neuropathy patients is variable and has yet to be reported in any patients with DDON syndrome. The reported case describes a male initially diagnosed with X-linked agammaglobulinemia due to recurrent infections. Speech, language and hearing were typical of a child in the first year of life; however profound hearing loss developed and cochlear implantation was performed at age 4. Following implantation, further genetic workup determined that the patient carries a deletion that includes BTK and DDP1/TIMM8a, consistent with the diagnosis of X-linked agammaglobulinemia and DDON syndrome. The patient's performance with the cochlear implant was marginal even after 2 years of use, with continued poor scores in standardized speech, language and audiometric tests. Additionally, his most-comfortable-level implant setting requires higher-than-normal current applied to the electrode array. This case report supports other studies showing that DDON syndrome results in an auditory neuropathy. Further investigation is required to determine the efficacy of cochlear implantation in this patient population. DDON syndrome should be considered in patients with X-linked agammaglobulinemia and hearing loss.

  10. Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.

    PubMed

    Clot, Fabienne; Grabli, David; Cazeneuve, Cécile; Roze, Emmanuel; Castelnau, Pierre; Chabrol, Brigitte; Landrieu, Pierre; Nguyen, Karine; Ponsot, Gérard; Abada, Myriem; Doummar, Diane; Damier, Philippe; Gil, Roger; Thobois, Stéphane; Ward, Alana J; Hutchinson, Michael; Toutain, Annick; Picard, Fabienne; Camuzat, Agnès; Fedirko, Estelle; Sân, Chankannira; Bouteiller, Delphine; LeGuern, Eric; Durr, Alexandra; Vidailhet, Marie; Brice, Alexis

    2009-07-01

    Dopa-responsive dystonia is a childhood-onset dystonic disorder, characterized by a dramatic response to low dose of L-Dopa. Dopa-responsive dystonia is mostly caused by autosomal dominant mutations in the GCH1 gene (GTP cyclohydrolase1) and more rarely by autosomal recessive mutations in the TH (tyrosine hydroxylase) or SPR (sepiapterin reductase) genes. In addition, mutations in the PARK2 gene (parkin) which causes autosomal recessive juvenile parkinsonism may present as Dopa-responsive dystonia. In order to evaluate the relative frequency of the mutations in these genes, but also in the genes involved in the biosynthesis and recycling of BH4, and to evaluate the associated clinical spectrum, we have studied a large series of index patients (n = 64) with Dopa-responsive dystonia, in whom dystonia improved by at least 50% after L-Dopa treatment. Fifty seven of these patients were classified as pure Dopa-responsive dystonia and seven as Dopa-responsive dystonia-plus syndromes. All patients were screened for point mutations and large rearrangements in the GCH1 gene, followed by sequencing of the TH and SPR genes, then PTS (pyruvoyl tetrahydropterin synthase), PCBD (pterin-4a-carbinolamine dehydratase), QDPR (dihydropteridin reductase) and PARK2 (parkin) genes. We identified 34 different heterozygous point mutations in 40 patients, and six different large deletions in seven patients in the GCH1 gene. Except for one patient with mental retardation and a large deletion of 2.3 Mb encompassing 10 genes, all patients had stereotyped clinical features, characterized by pure Dopa-responsive dystonia with onset in the lower limbs and an excellent response to low doses of L-Dopa. Dystonia started in the first decade of life in 40 patients (85%) and before the age of 1 year in one patient (2.2%). Three of the 17 negative GCH1 patients had mutations in the TH gene, two in the SPR gene and one in the PARK2 gene. No mutations in the three genes involved in the biosynthesis and

  11. Body weight gain in patients with bilateral deep brain stimulation for dystonia.

    PubMed

    Wolf, Marc E; Capelle, Hans-Holger; Lütjens, Götz; Ebert, Anne D; Hennerici, Michael G; Krauss, Joachim K; Blahak, Christian

    2016-03-01

    In patients with Parkinson's disease, significant weight gain following chronic deep brain stimulation (DBS) has been reported. Recently, relevant weight gain could be demonstrated also following subthalamic nucleus DBS in patients with primary cervical dystonia. Prospective analyses of body weight changes following DBS in patients with dystonia, however, have not been published so far. We aimed to analyse the changes of body weight following DBS in patients with dystonia. The body mass index (BMI) of 17 consecutive patients with segmental or generalised dystonia (mean age 54.6 ± 16.1 years) treated with bilateral DBS of the globus pallidus internus (GPi) (n = 14) or the thalamic ventral intermediate nucleus (n = 3) was measured preoperatively (pre-OP) and at three follow-up (FU) time points post-DBS surgery (FU1 = 7 months, FU2 = 17 months, FU3 = 72 months). All patients benefited from marked improvement in their dystonia. The mean BMI pre-OP (SD) was 22.5 (±3.7) kg/m(2) and increased stepwise to 24.0 (±3.3) kg/m(2) at FU1, 24.4 (±3.7) kg/m(2) at FU2 and 24.9 (±3.7) kg/m(2) at FU3 (p < 0.05 at all three FUs compared to pre-OP). Relative BMI increase and improvement of dystonia were correlated (p = 0.025). Chronic bilateral GPi DBS in patients with dystonia is associated with significant body weight gain, in particular during the first 6 months post-OP. This probably is a result of improvement of dystonic motor symptoms and recovery of eating dysfunction rather than a target-specific phenomenon.

  12. Basal ganglia modulation of thalamocortical relay in Parkinson's disease and dystonia.

    PubMed

    Guo, Yixin; Park, Choongseok; Worth, Robert M; Rubchinsky, Leonid L

    2013-01-01

    Basal ganglia dysfunction has being implied in both Parkinson's disease and dystonia. While these disorders probably involve different cellular and circuit pathologies within and beyond basal ganglia, there may be some shared neurophysiological pathways. For example, pallidotomy and pallidal Deep Brain Stimulation (DBS) are used in symptomatic treatment of both disorders. Both conditions are marked by alterations of rhythmicity of neural activity throughout basal ganglia-thalamocortical circuits. Increased synchronized oscillatory activity in beta band is characteristic of Parkinson's disease, while different frequency bands, theta and alpha, are involved in dystonia. We compare the effect of the activity of GPi, the output nuclei of the basal ganglia, on information processing in the downstream neural circuits of thalamus in Parkinson's disease and dystonia. We use a data-driven computational approach, a computational model of the thalamocortical (TC) cell modulated by experimentally recorded data, to study the differences and similarities of thalamic dynamics in dystonia and Parkinson's disease. Our analysis shows no substantial differences in TC relay between the two conditions. Our results suggest that, similar to Parkinson's disease, a disruption of thalamic processing could also be involved in dystonia. Moreover, the degree to which TC relay fidelity is impaired is approximately the same in both conditions. While Parkinson's disease and dystonia may have different pathologies and differ in the oscillatory content of neural discharge, our results suggest that the effect of patterning of pallidal discharge is similar in both conditions. Furthermore, these results suggest that the mechanisms of GPi DBS in dystonia may involve improvement of TC relay fidelity.

  13. The visual perception of natural motion: abnormal task-related neural activity in DYT1 dystonia.

    PubMed

    Sako, Wataru; Fujita, Koji; Vo, An; Rucker, Janet C; Rizzo, John-Ross; Niethammer, Martin; Carbon, Maren; Bressman, Susan B; Uluğ, Aziz M; Eidelberg, David

    2015-12-01

    Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of healthy subjects performing this task have revealed selective activation of motor regions during the perception of 'natural' versus 'unnatural' motion (defined respectively as trajectories with kinematic properties that either comply with or violate the two-thirds power law of motion). Several regions with significant connectivity changes in primary dystonia were situated in proximity to normal motion perception pathways, suggesting that abnormalities of these circuits may also be present in this disorder. To determine whether activation responses to natural versus unnatural motion in primary dystonia differ from normal, we used functional magnetic resonance imaging to study 10 DYT1 dystonia and 10 healthy control subjects at rest and during the perception of 'natural' and 'unnatural' motion. Both groups exhibited significant activation changes across perceptual conditions in the cerebellum, pons, and subthalamic nucleus. The two groups differed, however, in their responses to 'natural' versus 'unnatural' motion in these regions. In healthy subjects, regional activation was greater during the perception of natural (versus unnatural) motion (P < 0.05). By contrast, in DYT1 dystonia subjects, activation was relatively greater

  14. A new knock-in mouse model of l-DOPA-responsive dystonia

    PubMed Central

    Rose, Samuel J.; Yu, Xin Y.; Heinzer, Ann K.; Harrast, Porter; Fan, Xueliang; Raike, Robert S.; Thompson, Valerie B.; Pare, Jean-Francois; Weinshenker, David; Smith, Yoland; Jinnah, Hyder A.

    2015-01-01

    Abnormal dopamine neurotransmission is associated with many different genetic and acquired dystonic disorders. For instance, mutations in genes critical for the synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia. Despite evidence that implicates abnormal dopamine neurotransmission in dystonia, the precise nature of the pre- and postsynaptic defects that result in dystonia are not known. To better understand these defects, we generated a knock-in mouse model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the core features of the human disorder, including reduced TH activity, dystonia that worsened throughout the course of the active phase, and improvement in the dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the microstructure of striatal synapses was affected whereby the ratio of axo-spinous to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of l-DOPA directly into the striatum ameliorated the dystonic movements but cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal dopamine concentration was reduced to ∼1% of normal, a concentration more typically associated with akinesia, suggesting that (mal)adaptive postsynaptic responses may also play a role in the development of dystonia. Administration of D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced the dystonic movements, whereas administration of D1- or D2-like dopamine receptor antagonists to further reduce dopamine signalling worsened the dystonia, suggesting that both receptors mediate the abnormal movements. Further, D1-dopamine receptors were supersensitive; adenylate cyclase activity, locomotor activity and stereotypy were exaggerated in DRD mice in response to the D1-dopamine receptor agonist SKF

  15. Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia.

    PubMed

    Zittel, S; Helmich, R C; Demiralay, C; Münchau, A; Bäumer, T

    2015-08-01

    Previous studies indicated that sensorimotor integration and plasticity of the sensorimotor system are impaired in dystonia patients. We investigated motor evoked potential amplitudes and short latency afferent inhibition to examine corticospinal excitability and cortical sensorimotor integration, before and after inhibitory 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex in patients with cervical dystonia (n = 12). Motor evoked potentials were recorded from the right first dorsal interosseous muscle after application of unconditioned transcranial magnetic test stimuli and after previous conditioning electrical stimulation of the right index finger at short interstimulus intervals of 25, 30 and 40 ms. Results were compared to a group of healthy age-matched controls. At baseline, motor evoked potential amplitudes did not differ between groups. Short latency afferent inhibition was reduced in cervical dystonia patients compared to healthy controls. Inhibitory 1 Hz sensory cortex repetitive transcranial magnetic stimulation but not motor cortex repetitive transcranial magnetic stimulation increased motor evoked potential amplitudes in cervical dystonia patients. Additionally, both 1 Hz repetitive transcranial magnetic stimulation over primary sensory and primary motor cortex normalized short latency afferent inhibition in these patients. In healthy subjects, sensory repetitive transcranial magnetic stimulation had no influence on motor evoked potential amplitudes and short latency afferent inhibition. Plasticity of sensorimotor circuits is altered in cervical dystonia patients.

  16. Pallidal stimulation for segmental dystonia: long term follow up of 11 consecutive patients.

    PubMed

    Sensi, Mariachiara; Cavallo, Michele A; Quatrale, Rocco; Sarubbo, Silvio; Biguzzi, Sara; Lettieri, Cristian; Capone, Jay G; Tugnoli, Valeria; Tola, Maria Rosaria; Eleopra, Roberto

    2009-09-15

    Pallidal stimulation is a convincing and valid alternative for primary generalized dystonia refractory to medical therapy or botulinum toxin. However, the clinical outcome reported in literature is variable most likely because of heterogeneity DBS techniques employed and /or to clinical dystonic pattern of the patients who undergo surgery. In this study, we report the long term follow up of a homogeneous group of eleven subjects affected by segmental dystonia who were treated with bilateral stimulation of the Globus Pallidus pars interna (GPi) from the years 2000 to 2008. All the patients were evaluated, before surgery and at 6-12-24-36 months after the treatment, in accordance with the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS). Our study indicates that DBS promotes an early and significant improvement at 6 months with an even and a better outcome later on. The analysis of specific sub items of the BFMDRS revealed an earlier and striking benefit not only as far as segmental motor function of the limbs but also for the complex cranial functions like face, (eyes and mouth), speech and swallowing, differently from results reported in primary generalized dystonia. Deep Brain Stimulation of GPi should be considered a valid indication for both generalized and segmental dystonia when other therapies appear ineffective.

  17. Pallidal stimulation in children: comparison between cerebral palsy and DYT1 dystonia.

    PubMed

    Marks, Warren; Bailey, Laurie; Reed, Maryann; Pomykal, Angela; Mercer, Mary; Macomber, David; Acosta, Fernando; Honeycutt, John

    2013-07-01

    The authors compared the outcomes of 17 children aged 7 to 15 years with DYT1 dystonia or cerebral palsy following deep brain stimulation. While patients with cerebral palsy presented with significantly greater motor disability than the DYT1 cohort at baseline, both groups demonstrated improvement at 1 year (cerebral palsy = 24%; DYT1 = 6%). The group as a whole demonstrated significant improvement on the Barry-Albright Dystonia Scale across time. Gains in motor function were apparent in both axial and appendicular distributions involving both upper and lower extremities. Gains achieved by 6 months were sustained in the cerebral palsy group, whereas the DYT1 group demonstrated continued improvement with ongoing pallidal stimulation beyond 18 months. Young patients with dystonia due to cerebral palsy responded comparably to patients with DYT1 dystonia. The severity of motor impairment in patients with cerebral palsy at baseline and follow-up raises the issue of even earlier intervention with neuromodulation in this population to limit long-term motor impairments due to dystonia.

  18. The mechanisms of movement control and time estimation in cervical dystonia patients.

    PubMed

    Filip, Pavel; Lungu, Ovidiu V; Shaw, Daniel J; Kasparek, Tomas; Bareš, Martin

    2013-01-01

    Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological "cerebellar signs" in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction.

  19. Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model

    PubMed Central

    Wang, Tsui-chin; Ngampramuan, Sukonthar; Kotchabhakdi, Naiphinich

    2016-01-01

    Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements. The exaggerated movements have been studied and have implicated basal ganglia as the point of origin. In more recent studies, the cerebellum has also been identified as the possible target of dystonia, in the search for alternative treatments. Tiagabine is a selective GABA transporter inhibitor, which blocks the reuptake and recycling of GABA. The study of GABAergic drugs as an alternative treatment for cerebellar induced dystonia has not been reported. In our study, tiagabine was i.p. injected into kainic acid induced, cerebellar dystonic adult rats, and the effects were compared with non-tiagabine injected and sham-operated groups. Beam walking apparatus, telemetric electromyography (EMG) recording, and histological verification were performed to confirm dystonic symptoms in the rats on post-surgery treatment. Involuntary dystonic spasm was observed with repetitive rigidity, and twisting movements in the rats were also confirmed by a high score on the dystonic scoring and a high amplitude on the EMG data. The rats with tiagabine treatment were scored based on motor amelioration assessed via beam walking. The result of this study suggests and confirms that low dose of kainic acid microinjection is sufficient to induce dystonia from the cerebellar vermis. In addition, from the results of the EMG recording and the behavioral assessment through beam walking, tiagabine is demonstrated as being effective in reducing dystonic spasm and may be a possible alternative therapeutic drug in the treatment of dystonia. PMID:28337103

  20. Finger-specific loss of independent control of movements in musicians with focal dystonia.

    PubMed

    Furuya, S; Altenmüller, E

    2013-09-05

    The loss of independent control of finger movements impairs the dexterous use of the hand. Focal hand dystonia is characterised by abnormal structural and functional changes at the cortical and subcortical regions responsible for individuated finger movements and by the loss of surround inhibition in the finger muscles. However, little is known about the pathophysiological impact of focal dystonia on the independent control of finger movements. Here we addressed this issue by asking pianists with and without focal dystonia to repetitively strike a piano key with one of the four fingers as fast as possible while the remaining digits kept the adjacent keys depressed. Using principal component analysis and cluster analysis to the derived keystroke data, we successfully classified pianists according to the presence or absence of dystonic symptoms with classification rates and cross-validation scores of approximately 90%. This confirmed the effects of focal dystonia on the individuated finger movements. Interestingly, the movement features that contributed to successful classification differed across fingers. Compared to healthy pianists, pianists with an affected index finger were characterised predominantly by stronger keystrokes, whereas pianists with affected middle or ring fingers exhibited abnormal temporal control of the keystrokes, such as slowness and rhythmic inconsistency. The selective alternation of the movement features indicates a finger-specific loss of the independent control of finger movements in focal dystonia of musicians.

  1. The Mechanisms of Movement Control and Time Estimation in Cervical Dystonia Patients

    PubMed Central

    Lungu, Ovidiu V.; Shaw, Daniel J.; Kasparek, Tomas; Bareš, Martin

    2013-01-01

    Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological “cerebellar signs” in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction. PMID:24198973

  2. Explicit Agency in Patients with Cervical Dystonia: Altered Recognition of Temporal Discrepancies between Motor Actions and Their Feedback

    PubMed Central

    Delorme, Cécile; Roze, Emmanuel; Grabli, David; Mayer, Jean-Michel; Degos, Bertrand; Vidailhet, Marie; Worbe, Yulia

    2016-01-01

    Background Abnormalities in the cognitive processing of movement have been demonstrated in patients with dystonia. The sense of agency, which is the experience of initiating and controlling one’s own actions, has never before been studied in these patients. Objectives We investigated whether the sense of agency is altered in patients with cervical dystonia. Methods We used an explicit metacognitive agency task in which participants had to catch targets with a cursor by moving a computer’s mouse. The task included several conditions in which the control over the cursor could be disrupted by adding a spatial or a temporal discrepancy between the mouse and the cursor’s movements. Participants had to acknowledge these discrepancies and reflect them in metacognitive judgements of agency. Results Twenty cervical dystonia patients and 20 matched controls were included in the study. Despite performing equally well as the matched controls, cervical dystonia patients did not fully recognize alterations of agency when a temporal lag was added between their movement and the visual feedback. Moreover, they relied predominantly on their perceived performance to provide judgements of agency and less on their objective degree of controls. There was no correlation between agency scores and clinical severity of dystonia measured by the Toronto Western Spasmodic Torticollis Rating Scale. Conclusion We demonstrated an abnormal processing of agency in cervical dystonia patients, even for motor actions not affected by dystonia. The exact contribution of abnormal agency to dystonia pathophysiology remains to be clarified. PMID:27575487

  3. An aggressive approach to limb dystonia: a case report.

    PubMed

    Moberg-Wolff, E A

    1998-05-01

    A 15-year-old boy presented with a severe fluctuating foot and ankle dystonia resulting from a basal ganglia insult at the age of 4. This followed an embolic event related to an undiagnosed prolapsed mitral valve. Functionally, the patient was ambulatory with rocker bottom crutches and an ankle-foot orthosis, but there were periods of up to a year when pain and increased dystonic deformity required him to use a wheelchair. A new orthotic was made nearly every month because the orthotist could find no material that would withstand his tone without breaking, yet he could not ambulate without one. Multiple interventions, including biofeedback, contrast baths, stretching and strengthening, oral lioresal (Baclofen), diazepam (Valium), benztropine mesylate (Cogentin), carbidopa-levodopa (Sinemet), carbamazepine (Tegretol), and injections of botulism toxin (BOTOX) were tried, all with minimal effects. Amputation was recommended, based on anatomic and functional considerations. The patient and his family adjusted well to this decision, although not all orthopedists and therapists adjusted easily to the choice. The patient is now functionally independent with a prosthesis and has a normal teenage lifestyle for the first time.

  4. Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

    PubMed

    Meyer, Esther; Carss, Keren J; Rankin, Julia; Nichols, John M E; Grozeva, Detelina; Joseph, Agnel P; Mencacci, Niccolo E; Papandreou, Apostolos; Ng, Joanne; Barral, Serena; Ngoh, Adeline; Ben-Pazi, Hilla; Willemsen, Michel A; Arkadir, David; Barnicoat, Angela; Bergman, Hagai; Bhate, Sanjay; Boys, Amber; Darin, Niklas; Foulds, Nicola; Gutowski, Nicholas; Hills, Alison; Houlden, Henry; Hurst, Jane A; Israel, Zvi; Kaminska, Margaret; Limousin, Patricia; Lumsden, Daniel; McKee, Shane; Misra, Shibalik; Mohammed, Shekeeb S; Nakou, Vasiliki; Nicolai, Joost; Nilsson, Magnus; Pall, Hardev; Peall, Kathryn J; Peters, Gregory B; Prabhakar, Prab; Reuter, Miriam S; Rump, Patrick; Segel, Reeval; Sinnema, Margje; Smith, Martin; Turnpenny, Peter; White, Susan M; Wieczorek, Dagmar; Wiethoff, Sarah; Wilson, Brian T; Winter, Gidon; Wragg, Christopher; Pope, Simon; Heales, Simon J H; Morrogh, Deborah; Pittman, Alan; Carr, Lucinda J; Perez-Dueñas, Belen; Lin, Jean-Pierre; Reis, Andre; Gahl, William A; Toro, Camilo; Bhatia, Kailash P; Wood, Nicholas W; Kamsteeg, Erik-Jan; Chong, Wui K; Gissen, Paul; Topf, Maya; Dale, Russell C; Chubb, Jonathan R; Raymond, F Lucy; Kurian, Manju A

    2017-02-01

    Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.

  5. Eligibility Criteria for Deep Brain Stimulation in Parkinson's Disease, Tremor, and Dystonia.

    PubMed

    Munhoz, Renato P; Picillo, Marina; Fox, Susan H; Bruno, Veronica; Panisset, Michel; Honey, Christopher R; Fasano, Alfonso

    2016-07-01

    In this review, the available evidence to guide clinicians regarding eligibility for deep brain stimulation (DBS) in the main conditions in which these forms of therapy are generally indicated-Parkinson's disease (PD), tremor, and dystonia-is presented. In general, the literature shows that DBS is effective for PD, essential tremor, and idiopathic dystonia. In these cases, key points in patient selection must include the level of disability and inability to manage symptoms using the best available medical therapy. Results are, however, still not optimal when dealing with other aetiologies, such as secondary tremors and symptomatic dystonia. Also, in PD, issues such as age and neuropsychiatric profile are still debatable parameters. Overall, currently available literature is able to guide physicians on basic aspects of patient selection and indications for DBS; however, a few points are still debatable and controversial. These issues should be refined and clarified in future studies.

  6. Subthalamic local field potentials in Parkinson's disease and isolated dystonia: An evaluation of potential biomarkers.

    PubMed

    Wang, Doris D; de Hemptinne, Coralie; Miocinovic, Svjetlana; Qasim, Salman E; Miller, Andrew M; Ostrem, Jill L; Galifianakis, Nicholas B; San Luciano, Marta; Starr, Philip A

    2016-05-01

    Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13-30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non-parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers.

  7. Focal dystonia of right hand with mirror movements upon use of left arm.

    PubMed

    Rana, Abdul Qayyum; Athar, Aysha

    2013-05-01

    Dystonia is a movement disorder characterized by sustained muscle contractions, causing twisting and repetitive movements or abnormal postures of affected body parts. Here, we present a novel case of focal dystonia of a 51 years old right-handed woman who had developed difficulty in writing and performing fine motor tasks. Due to a discomfort in her right hand at use, she started using her left hand instead and noticed inconsistent mirror movements in her right hand upon use of left hand. She was treated with trihexyphenidyl which allowed her right hand to function better, though writing still remained a problem.

  8. Acute Dystonia in a Patient with 22q11.2 Deletion Syndrome

    PubMed Central

    Kontoangelos, Konstantinos; Maillis, Antonis; Maltezou, Maria; Tsiori, Sofia; Papageorgiou, Charalambos C.

    2015-01-01

    The 22q11.2 deletion syndrome (di George syndrome) is one of the most prevalent genetic disorders. The clinical features of the syndrome are distinct facial appearance, velopharyngeal insufficiency, conotruncal heart disease, parathyroid and immune dysfunction; however, little is known about possible neurodegenerative diseases. We describe the case of an 18-year old patient suffering from 22q11.2 deletion syndrome. Since adolescence, he presented with behavioral disorders, recommended treatment with 2 mg aloperidin and he presented cervical dystonia and emergence of torticollis and trunk dystonia. Antipsychotic medications either accelerate or reveal dystonic symptoms. PMID:26605035

  9. Analysis of D216H polymorphism in Argentinean patients with primary dystonia.

    PubMed

    Caputo, Mariela; Irisarri, Maximiliano; Perandones, Claudia; Alechine, Evguenia; Pellene, Luis Alejandro; Roca, Claudia Uribe; Micheli, Federico E; Corach, Daniel

    2013-06-01

    The D216H polymorphism (rs1801968) in TOR1A has been suggested as a risk factor for developing primary dystonia in German subjects not carrying the deletion c.904-906delGAG (∆GAG). However, this association could not be confirmed in other populations with different ethnic backgrounds. The purpose of this study is to evaluate the D216H polymorphism in an Argentinean cohort of 40 patients with primary dystonia and 200 unrelated control subjects. The authors could observe a significantly higher frequency of the H216 variant in dystonic patients lacking ∆GAG as compared with controls.

  10. [A case of juvenile Huntington's disease presenting dystonia and confirmed by DNA analysis].

    PubMed

    Ozawa, H; Takeda, M; Sasaki, M; Sugai, K; Hashimoto, T; Honma, T

    1997-07-01

    We reported a 13-year-old boy with juvenile Huntington disease diagnosed by DNA analysis. Symptoms started with dysarthria at 6 years of age, which was followed by progressive dysgraphia and gait disturbance due to dystonia from 7 years, and by epileptic seizures from 12 years. Magnetic resonance imaging revealed atrophy of the bilateral caudate nuclei and T2- and proton-weighted high intensity area in both putamina. The CAG (cytosine-adenine-guanine) trinucleotide repeat on chromosome 4 p16 was markedly expanded to 81. For a child with dystonia with mental deterioration, juvenile Huntington disease should be considered in the differential diagnosis.

  11. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  12. Growth hormone deficiency in a dopa-responsive dystonia patient with a novel mutation of guanosine triphosphate cyclohydrolase 1 gene.

    PubMed

    Lin, Yu; Wang, Dan-Ni; Chen, Wan-Jin; Lin, Xiang; Lin, Min-Ting; Wang, Ning

    2015-05-01

    Dopa-responsive dystonia is a rare hereditary movement disorder caused by mutations in the guanosine triphosphate cyclohydrolase 1 (GCH1) gene. This disease typically manifests in dystonia, with marked diurnal fluctuation and a dramatic response to levodopa. However, growth retardation in dopa-responsive dystonia has rarely been reported, and the etiology of short stature is not clarified. Here, we report a 14-year-old patient with extremities dystonia and short stature. Treatment with levodopa relieved his symptoms and resulted in a height increase. We also investigated the mutation in GCH1 and the etiology of short stature in this case. Sequence analysis of GCH1 revealed a novel mutation (c.695G>T). Laboratory examinations and imaging confirmed the diagnosis of growth hormone deficiency. We conclude that our case reveals a rare feature for dopa-responsive dystonia and suggests a possible pathogenic link between growth hormone deficiency and dopa-responsive dystonia. We recommend levodopa as the first choice for treating dopa-responsive dystonia in children with growth hormone deficiency.

  13. Recessive mutations in the α3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.

    PubMed

    Zech, Michael; Lam, Daniel D; Francescatto, Ludmila; Schormair, Barbara; Salminen, Aaro V; Jochim, Angela; Wieland, Thomas; Lichtner, Peter; Peters, Annette; Gieger, Christian; Lochmüller, Hanns; Strom, Tim M; Haslinger, Bernhard; Katsanis, Nicholas; Winkelmann, Juliane

    2015-06-04

    Isolated dystonia is a disorder characterized by involuntary twisting postures arising from sustained muscle contractions. Although autosomal-dominant mutations in TOR1A, THAP1, and GNAL have been found in some cases, the molecular mechanisms underlying isolated dystonia are largely unknown. In addition, although emphasis has been placed on dominant isolated dystonia, the disorder is also transmitted as a recessive trait, for which no mutations have been defined. Using whole-exome sequencing in a recessive isolated dystonia-affected kindred, we identified disease-segregating compound heterozygous mutations in COL6A3, a collagen VI gene associated previously with muscular dystrophy. Genetic screening of a further 367 isolated dystonia subjects revealed two additional recessive pedigrees harboring compound heterozygous mutations in COL6A3. Strikingly, all affected individuals had at least one pathogenic allele in exon 41, including an exon-skipping mutation that induced an in-frame deletion. We tested the hypothesis that disruption of this exon is pathognomonic for isolated dystonia by inducing a series of in-frame deletions in zebrafish embryos. Consistent with our human genetics data, suppression of the exon 41 ortholog caused deficits in axonal outgrowth, whereas suppression of other exons phenocopied collagen deposition mutants. All recessive mutation carriers demonstrated early-onset segmental isolated dystonia without muscular disease. Finally, we show that Col6a3 is expressed in neurons, with relevant mRNA levels detectable throughout the adult mouse brain. Taken together, our data indicate that loss-of-function mutations affecting a specific region of COL6A3 cause recessive isolated dystonia with underlying neurodevelopmental deficits and highlight the brain extracellular matrix as a contributor to dystonia pathogenesis.

  14. Therapeutic immobilisation for small guitar player’s dystonia: a case report

    PubMed Central

    Waissman, Flavia; Pereira, João Santos; Nascimento, Osvaldo J M

    2009-01-01

    The development of focal hand dystonia through repetitive tasks is a result of degradation of cortical somatosensory representation due to repetitive fast stimuli sufficient to alter the sensory-motor stimulus, harming the motor control. A sensory-motor training program can modify this disorder. A behavioural intervention focusing on movement could help reduce or eliminate these conditions. PMID:21686815

  15. Abnormal functional connectivity in focal hand dystonia: mutual information analysis in EEG.

    PubMed

    Jin, Seung-Hyun; Lin, Peter; Auh, Sungyoung; Hallett, Mark

    2011-06-01

    The aim of the present study was to investigate functional connectivity in focal hand dystonia patients to understand the pathophysiology underlying their abnormality in movement. We recorded EEGs from 58 electrodes in 15 focal hand dystonia patients and 15 healthy volunteers during rest and a simple finger-tapping task that did not induce any dystonic symptoms. We investigated mutual information, which provides a quantitative measure of linear and nonlinear coupling, in the alpha, beta, and gamma bands. Mean mutual information of all 58 channels and mean of the channels of interest representative of regional functional connectivity over sensorimotor areas (C3, CP3, C4, CP4, FCz, and Cz) were evaluated. For both groups, we found enhanced mutual information during the task compared with the rest condition, specifically in the beta and gamma bands for mean mutual information of all channels, and in all bands for mean mutual information of channels of interest. Comparing the focal hand dystonia patients with the healthy volunteers for both rest and task, there was reduced mutual information in the beta band for both mean mutual information of all channels and mean mutual information of channels of interest. Regarding the properties of the connectivity in the beta band, we found that the majority of the mutual information differences were from linear connectivity. The abnormal beta-band functional connectivity in focal hand dystonia patients suggests deficient brain connectivity.

  16. Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex

    PubMed Central

    Neymotin, Samuel A.; Dura-Bernal, Salvador; Lakatos, Peter; Sanger, Terence D.; Lytton, William W.

    2016-01-01

    A large number of physiomic pathologies can produce hyperexcitability in cortex. Depending on severity, cortical hyperexcitability may manifest clinically as a hyperkinetic movement disorder or as epilpesy. We focus here on dystonia, a movement disorder that produces involuntary muscle contractions and involves pathology in multiple brain areas including basal ganglia, thalamus, cerebellum, and sensory and motor cortices. Most research in dystonia has focused on basal ganglia, while much pharmacological treatment is provided directly at muscles to prevent contraction. Motor cortex is another potential target for therapy that exhibits pathological dynamics in dystonia, including heightened activity and altered beta oscillations. We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. These models demonstrated degeneracy, meaning that there were many ways of obtaining the pathological syndrome. There was no single parameter alteration which would consistently distinguish pathological from physiological dynamics. At higher dimensions in parameter space, we were able to use support vector machines to distinguish the two patterns in different regions of space and thereby trace multitarget routes from dystonic to physiological dynamics. These results suggest the use of in silico models for discovery of multitarget drug cocktails. PMID:27378922

  17. Stereotyped paroxysmal psychiatric symptoms during oculogyric crisis or 'cognitive dystonia': a case report.

    PubMed

    Praharaj, Samir Kumar; Sarkhel, Sujit; Akhtar, Sayeed

    2011-02-01

    Oculogyric crisis (OGC) is an acute dystonia which can occur after initiation of antipsychotic treatment. Stereotypic paroxysmal psychiatric symptoms have been described along with OGC that resolve spontaneously when the later remits. We report a case of tardive OGC associated with zuclopenthixol in which there were associated paroxysmal auditory pseudohallucinations.

  18. Pallidal stimulation for primary generalised dystonia: effect on cognition, mood and quality of life.

    PubMed

    Jahanshahi, Marjan; Torkamani, Mariam; Beigi, Mazda; Wilkinson, Leonora; Page, Donna; Madeley, Laura; Bhatia, Kailash; Hariz, Marwan; Zrinzo, Ludvic; Limousin, Patricia; Ruge, Diane; Tisch, Stephen

    2014-01-01

    We investigated the effect of pallidal deep brain stimulation (GPi-DBS) in dystonia on cognition, mood, and quality of life and also assessed if DYT1 gene status influenced cognitive outcome following GPi-DBS. Fourteen patients with primary generalized dystonia (PGD) were assessed, measuring their estimated premorbid and current IQ, memory for words and faces, and working memory, language, executive function, and sustained attention, one month before and one year or more after surgery. Changes in mood and behaviour and quality of life were also assessed. There was a significant improvement of dystonia with GPi-DBS (69 % improvement in Burke-Fahn-Marsden score, p < 0.0001). Performance on five cognitive tests either improved or declined at post-surgical follow-up. Calculation of a reliable change index suggested that deterioration in sustained attention on the PASAT was the only reliable change (worse after surgery) in cognition with GPi-DBS. DYT1 gene status did not influence cognitive outcome following GPi-DBS. Depression, anxiety and apathy were not significantly altered, and ratings of health status on the EQ5D remained unchanged. In our sample, GPi-DBS was only associated with an isolated deficit on a test of sustained attention, confirming that GPi-DBS in PGD is clinically effective and safe, without adverse effects on the main domains of cognitive function. The dissociation between GPi-DBS improving dystonia, but not having a significant positive impact on the patients' QoL, warrants further investigation.

  19. Clinicopathological Correlates in a PRNP P102L Mutation Carrier with Rapidly Progressing Parkinsonism-dystonia.

    PubMed

    Umeh, Chizoba C; Kalakoti, Piyush; Greenberg, Michael K; Notari, Silvio; Cohen, Yvonne; Gambetti, Pierluigi; Oblak, Adrian L; Ghetti, Bernardino; Mari, Zoltan

    2016-01-01

    Parkinsonism-dystonia is rare in carriers of PRNP P102L mutation. Severity and distribution of prion protein (PrP) deposition may influence the clinical presentation. We present such clinic-pathological correlation in a 56-year-old male with a PRNP P102L mutation associated with a phenotype characterized by rapidly progressing parkinsonism-dystonia. The patient was studied clinically (videotaped exams, brain MRIs); molecular genetically (gene sequence analysis); and neuropathologically (histology, immunohistochemistry) during his 7-month disease course. The patient had parkinsonism, apraxia, aphasia, and dystonia, which progressed rapidly. Molecular genetic analysis revealed PRNP P102L mutation carrier status. Brain MRIs revealed progressive global volume loss and T2/FLAIR hyperintensity in neocortex and basal ganglia. Postmortem examination showed neuronal loss, gliosis, spongiform changes, and PrP deposition in the striatum. PrP immunohistochemistry revealed widespread severe PrP deposition in the thalamus and cerebellar cortex. Based on the neuropathological and molecular-genetic analysis, the rapidly progressing parkinsonism-dystonia correlated with nigrostriatal, thalamic, and cerebellar pathology.

  20. Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions.

    PubMed

    Golanska, Ewa; Gajos, Agata; Sieruta, Monika; Szybka, Malgorzata; Rudzinska, Monika; Ochudlo, Stanislaw; Kmiec, Tomasz; Liberski, Pawel P; Bogucki, Andrzej

    2015-01-01

    The aim of this study was to assess the presence of DYT6 mutations in Polish patients with isolated dystonia and to characterize their phenotype. We sequenced THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5'UTR fragment in 96 non-DYT1 dystonia patients. In four individuals single nucleotide variations were identified. The coding substitutions were: c. 238A>G (p.Ile80Val), found in two patients, and c.167A>G (p.Glu56Gly), found in one patient. The same variations were present also in the patients' symptomatic as well as asymptomatic relatives. Mutation penetration in the analyzed families was 50-66.7%. In the fourth patient, a novel c.-249C>A substitution in the promoter region was identified. The patient, initially suspected of idiopathic isolated dystonia, finally presented with pantothenate kinase 2-associated neurodegeneration phenotype and was a carrier of two PANK2 mutations. This is the first identified NBIA1 case carrying mutations in both PANK2 and THAP1 genes. In all symptomatic THAP1 mutation carriers (four probands and their three affected relatives) the first signs of dystonia occurred before the age of 23. A primary localization typical for DYT6 dystonia was observed in six individuals. Five subjects developed the first signs of dystonia in the upper limb. In one patient the disease began from laryngeal involvement. An uncommon primary involvement of lower limb was noted in the THAP1 and PANK2 mutations carrier. Neither of these THAP1 substitutions were found in 150 unrelated healthy controls. To the contrary, we identified a heterozygous C/T genotype of c.57C>T single nucleotide variation (p.Pro19Pro, rs146087734) in one healthy control, but in none of the patients. Therefore, a previously proposed association between this substitution and DYT6 dystonia seems unlikely. We found also no significant difference between cases and controls in genotypes distribution of the two-nucleotide -237-236 GA>TT (rs370983900 & rs1844977763) polymorphism.

  1. Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions

    PubMed Central

    Golanska, Ewa; Gajos, Agata; Sieruta, Monika; Szybka, Malgorzata; Rudzinska, Monika; Ochudlo, Stanislaw; Kmiec, Tomasz; Liberski, Pawel P.; Bogucki, Andrzej

    2015-01-01

    The aim of this study was to assess the presence of DYT6 mutations in Polish patients with isolated dystonia and to characterize their phenotype. We sequenced THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5’UTR fragment in 96 non-DYT1 dystonia patients. In four individuals single nucleotide variations were identified. The coding substitutions were: c. 238A>G (p.Ile80Val), found in two patients, and c.167A>G (p.Glu56Gly), found in one patient. The same variations were present also in the patients’ symptomatic as well as asymptomatic relatives. Mutation penetration in the analyzed families was 50-66.7%. In the fourth patient, a novel c.-249C>A substitution in the promoter region was identified. The patient, initially suspected of idiopathic isolated dystonia, finally presented with pantothenate kinase 2-associated neurodegeneration phenotype and was a carrier of two PANK2 mutations. This is the first identified NBIA1 case carrying mutations in both PANK2 and THAP1 genes. In all symptomatic THAP1 mutation carriers (four probands and their three affected relatives) the first signs of dystonia occurred before the age of 23. A primary localization typical for DYT6 dystonia was observed in six individuals. Five subjects developed the first signs of dystonia in the upper limb. In one patient the disease began from laryngeal involvement. An uncommon primary involvement of lower limb was noted in the THAP1 and PANK2 mutations carrier. Neither of these THAP1 substitutions were found in 150 unrelated healthy controls. To the contrary, we identified a heterozygous C/T genotype of c.57C>T single nucleotide variation (p.Pro19Pro, rs146087734) in one healthy control, but in none of the patients. Therefore, a previously proposed association between this substitution and DYT6 dystonia seems unlikely. We found also no significant difference between cases and controls in genotypes distribution of the two-nucleotide -237-236 GA>TT (rs370983900 & rs1844977763

  2. Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis.

    PubMed

    Moro, E; LeReun, C; Krauss, J K; Albanese, A; Lin, J-P; Walleser Autiero, S; Brionne, T C; Vidailhet, M

    2017-02-10

    The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated inherited or idiopathic dystonia. Eligible studies were identified after a systematic literature review of the effects of bilateral GPi-DBS in isolated dystonia. Absolute and percentage changes from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability scores were pooled, and associations between treatment effect and patient characteristics were explored using meta-regression. In total, 24 studies were included in the meta-analysis, comprising 523 patients. The mean absolute and percentage improvements in BFMDRS motor score at the last follow-up (mean 32.5 months; 24 studies) were 26.6 points [95% confidence interval (CI), 22.4-30.8] and 65.2% (95% CI, 59.6-70.7), respectively. The corresponding changes in disability score at the last follow-up (mean 32.9 months; 14 studies) were 6.4 points (95% CI, 5.0-7.8) and 58.6% (95% CI, 50.3-66.9). Multivariate meta-regression of absolute scores indicated that higher BFMDRS motor and disability scores before surgery, together with younger age at time of surgery, were the main factors associated with significantly better DBS outcomes at the latest follow-up. Reporting of safety data was frequently inconsistent and could not be included in the meta-analysis. In conclusion, patients with isolated inherited or idiopathic dystonia significantly improved after GPi-DBS. Better outcomes were associated with greater dystonia severity at baseline. These findings should be taken into consideration for improving patient selection for DBS.

  3. SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype.

    PubMed

    Peall, Kathryn J; Kurian, Manju A; Wardle, Mark; Waite, Adrian J; Hedderly, Tammy; Lin, Jean-Pierre; Smith, Martin; Whone, Alan; Pall, Hardev; White, Cathy; Lux, Andrew; Jardine, Philip E; Lynch, Bryan; Kirov, George; O'Riordan, Sean; Samuel, Michael; Lynch, Timothy; King, Mary D; Chinnery, Patrick F; Warner, Thomas T; Blake, Derek J; Owen, Michael J; Morris, Huw R

    2014-12-01

    Myoclonus dystonia syndrome (MDS) is a young-onset movement disorder. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. We assembled the largest cohort of MDS patients to date, and determined the frequency and type of SGCE mutations. The aim was to establish the motor phenotype in mutation carriers and utility of current diagnostic criteria. Eighty-nine probands with clinical features compatible with MDS were recruited from the UK and Ireland. Patients were phenotypically classified as "definite", "probable" or "possible" MDS according to previous guidelines. SGCE was analyzed using direct sequencing and copy number variant analysis. In those where no mutation was found, DYT1 (GAG deletion), GCH1, THAP1 and NKX2.1 genes were also sequenced. Nineteen (21.3%) probands had an SGCE mutation. Three patterns of motor symptoms emerged: (1) early childhood onset upper body myoclonus and dystonia, (2) early childhood onset lower limb dystonia, progressing later to more pronounced myoclonus and upper body involvement, and (3) later childhood onset upper body myoclonus and dystonia with evident cervical involvement. Five probands had large contiguous gene deletions ranging from 0.7 to 2.3 Mb in size with distinctive clinical features, including short stature, joint laxity and microcephaly. Our data confirms that SGCE mutations are most commonly identified in MDS patients with (1) age at onset ≤10 years and (2) predominant upper body involvement of a pure myoclonus-dystonia. Cases with whole SGCE gene deletions had additional clinical characteristics, which are not always predicted by deletion size or gene involvement.

  4. Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia

    PubMed Central

    Ruiz, Marta; Perez-Garcia, Georgina; Ortiz-Virumbrales, Maitane; Méneret, Aurelie; Morant, Andrika; Kottwitz, Jessica; Fuchs, Tania; Bonet, Justine; Gonzalez-Alegre, Pedro; Hof, Patrick R.; Ozelius, Laurie J.; Ehrlich, Michelle E.

    2015-01-01

    DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations. PMID:26376866

  5. Correlation of Clinical Neuromusculoskeletal and Central Somatosensory Performance: Variability in Controls and Patients With Severe and Mild Focal Hand Dystonia

    PubMed Central

    Byl, Nancy N.; Nagarajan, Srikantan S.; Merzenich, Michael M.; Roberts, Tim; McKenzie, Alison

    2002-01-01

    Focal hand dystonia (FHd) is a recalcitrant, disabling movement disorder, characterized by involuntary co-contractions of agonists and antagonists, that can develop in patients who overuse or misuse their hands. The aim of this study was to document clinical neuromusculoskeletal performance and somatosensory responses (magnetoencephalography) in healthy controls and in FHd subjects with mild versus severe hand dystonia. The performance of healthy subjects (n = 17) was significantly better than that of FHd subjects (n = 17) on all clinical parameters. Those with mild dystonia (n = 10) demonstrated better musculoskeletal skills, task-specific motor performance, and sensory discrimination, but the performance of sensory and fine motor tasks was slower than that of patients with severe dystonia. In terms of somatosensory evoked field responses (SEFs), FHd subjects demonstrated a significant difference in the location of the hand representation on the x and y axes, lower amplitude of SEFs integrated across latency, and a higher ratio of mean SEF amplitude to latency than the controls. Bilaterally,. those with FHd (mild and severe) lacked progressive sequencing of the digits from inferior to superior. On the affected digits, subjects with severe dystonia had a significantly higher ratio of SEF amplitude to latency and a significantly smaller mean volume of the cortical hand representation than those with mild dystonia. Severity of dystonia positively correlated with the ratio of SEF mean amplitude to latency (0.9029 affected, 0.8477 unaffected; p<0.01). The results of the present study strengthen the evidence that patients with FHd demonstrate signs of somatosensory degradation of the hand that correlates with clinical sensorimotor dysfunction, with characteristics of the dedifferentiation varying by the severity of hand dystonia. If these findings represent aberrant learning, then effective rehabilitation must incorporate the principles of neuroplasticity. Training must

  6. Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value.

    PubMed

    Zoons, E; Dijkgraaf, M G W; Dijk, J M; van Schaik, I N; Tijssen, M A

    2012-12-01

    Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharmaco-therapeutic and pharmaco-economic value of botulinum toxin as treatment for focal dystonia, which yielded the following results. Botulinum toxin is the most effective treatment for reducing dystonic symptoms measured with dystonia-specific and general questionnaires, and pain in patients with focal dystonia. Seventy-one percent of patients with cervical dystonia had a reduction in neck pain compared to 12 % in placebo groups. Adverse events occur in 58 % of patients during treatment with botulinum toxin compared to 46 % treated with placebo. Especially dry mouth, neck weakness, dysphagia, and voice changes are common. Adverse events are usually mild and self-limiting. Health-related quality of life, measured with the SF-36 is 20-50 points lower in patients with focal dystonia compared to controls and the effect of botulinum toxin on health-related quality of life is unclear. Botulinum toxin treatment is expensive because the drug itself is expensive. Yearly costs for treating a patient with focal dystonia with botulinum toxin range from EUR 347 to EUR 3,633 and the gain in QALYs with BTX treatment is small. Focal dystonia impairs the productivity and the ability to work. At start of botulinum toxin treatment only 47-50 % was working. Botulinum toxin partly improves this. Overall, we conclude that botulinum toxin is an expensive drug with good effects. From a societal perspective, the costs may well weigh up to the regained quality of life. However, the available literature concerning costs, health-related quality of life and labor participation is very limited. An extensive cost-effectiveness study should be performed incorporating all these aspects.

  7. 1H-NMR metabolic profiling of cerebrospinal fluid in patients with complex regional pain syndrome-related dystonia.

    PubMed

    Meissner, Axel; van der Plas, Anton A; van Dasselaar, Nick T; Deelder, André M; van Hilten, Jacobus J; Mayboroda, Oleg A

    2014-01-01

    In complex regional pain syndrome (CRPS)-related dystonia, compelling evidence points to the involvement of the central nervous system, but the underpinning pathobiology is still unclear. Thus, to enable a hypothesis-free, unbiased view of the problem and to obtain new insight into the pathobiology of dystonia in CRPS, we applied an exploratory metabolomics analysis of cerebrospinal fluid (CSF) of patients with CRPS-related dystonia. (1)H-NMR spectroscopy in combination with multivariate modeling were used to investigate metabolic profiles of a total of 105 CSF samples collected from patients with CRPS-related dystonia and controls. We found a significantly different metabolic profile of CSF in CRPS patients compared to controls. The differences were already reflected in the first two principal components of the principal component analysis model, which is an indication that the variance associated with CRPS is stronger than variance caused by such classical confounders as gender, age, or individual differences. A supervised analysis generated a strong model pinpointing the most important metabolites contributed to the metabolic signature of patients with CRPS-related dystonia. From the set of identified discriminators, the most relevant metabolites were 2-keto-isovalerate, glucose, glutamine, and lactate, which all showed increased concentrations, and urea, which showed decreased concentration in CRPS subjects. Our findings point at a catabolic state in chronic CRPS patients with dystonia that is likely associated with inflammation.

  8. Clinical improvement of secondary focal limb dystonia in neurodegenerative disease following a five-day lidocaine infusion: a case report.

    PubMed

    Irwin, D; Revuelta, G; Lippa, C F

    2009-02-15

    Dystonia associated with neurodegenerative disease has minimal effective treatment options and can be devastating to a patient's ability to perform tasks of daily living. We present a case of a 55 year-old man who had progressive symptoms of an atypical asymmetric parkinsonian neurodegenerative disease. This patient presented with a dystonic left upper extremity that was refractory to treatment. In an attempt to treat worsening pain associated with the dystonia, he was given a five-day lidocaine infusion for associated pain and within 24 h had improvement in mobility of his dystonic extremity. Dystonia was measured by the Burke-Fahn-Marsden (BFM) dystonia rating and disability scales on hospital day five and at an eight week follow up visit. These scores were compared with scores derived from his previous pre-treatment neurologic examination. The BFM dystonia scale score was initially 16 and improved to 12 on both immediate post-treatment and eight-week follow-up. The BFM disability score improved from 16 to 6 post treatment and to 8 on follow-up appointment. Most importantly, the patient could feed and dress himself for the first time in several years. No adverse events of treatment were encountered. Treatment effect lasted three months with a slow return to baseline motor function. This case report raises interesting questions regarding the mechanism of dystonia in neurodegenerative disease and suggests the afferent sensory system as a potential target for therapeutics.

  9. Cortical activation and inter-hemispheric sensorimotor coherence in individuals with arm dystonia due to childhood stroke

    PubMed Central

    Kukke, Sahana N.; de Campos, Ana Carolina; Damiano, Diane; Alter, Katharine E.; Patronas, Nicholas; Hallett, Mark

    2014-01-01

    Objective Dystonia is a disabling motor disorder often without effective therapies. To better understand the genesis of dystonia after childhood stroke, we analyzed electroencephalographic (EEG) recordings in this population. Methods Resting spectral power of EEG signals over bilateral sensorimotor cortices (Powrest), resting inter-hemispheric sensorimotor coherence (Cohrest), and task-related changes in power (TRPow) and coherence (TRCoh) during wrist extension were analyzed in individuals with dystonia (age 20±3 years) and healthy volunteers (age 17±5 years). Results Ipsilesional TRPow decrease was significantly lower in patients than controls during the more affected wrist task. Force deficits of the affected wrist correlated with reduced alpha TRPow decrease on the ipsilesional and not the contralesional hemisphere. Cohrest was significantly lower in patients than controls, and correlated with more severe dystonia and poorer hand function. Powrest and TRCoh were similar between groups. Conclusions The association between weakness and cortical activation during wrist extension highlights the importance of ipsilesional sensorimotor activation on function. Reduction of Cohrest in patients reflects a loss of inter-hemispheric connectivity that may result from structural changes and neuroplasticity, potentially contributing to the development of dystonia. Significance Cortical and motor dysfunction are correlated in patients with childhood stroke and may in part explain the genesis of dystonia. PMID:25499610

  10. Aristotle's illusion reveals interdigit functional somatosensory alterations in focal hand dystonia.

    PubMed

    Tinazzi, Michele; Marotta, Angela; Fasano, Alfonso; Bove, Francesco; Bentivoglio, Anna Rita; Squintani, Giovanna; Pozzer, Lara; Fiorio, Mirta

    2013-03-01

    In focal hand dystonia, the cortical somatosensory representation of the fingers is abnormal, with overlapping receptive fields and reduced interdigit separation. These abnormalities are associated with deficits in sensory perception, as previously demonstrated by applying tactile stimuli to one finger at a time. What is still unknown is whether the sensory deficits can be observed when tactile perception involves more than one finger. To address this issue, we applied 'Aristotle's illusion' to 15 patients with focal hand dystonia, 15 patients with dystonia not affecting the hand (blepharospasm and cervical dystonia) and 15 healthy control subjects. In this illusion, one object touching the contact point of two crossed fingertips is perceived as two objects by a blindfolded subject. The same object placed between two parallel fingertips is correctly perceived as one. The illusory doubling sensation is because of the fact that the contact point between the crossed fingers consists of non-adjacent and functionally unrelated skin regions, which usually send sensory signals to separate spots in the somatosensory cortex. In our study, participants were touched by one sphere between the second-third digits, the second-fourth digits and the fourth-fifth digits of both hands, either in crossed or in parallel position, and had to refer whether they felt one or two stimuli. The percentage of 'two stimuli' responses was an index of the illusory doubling. Both healthy control subjects and dystonic patients presented Aristotle's illusion when the fingers were crossed. However, patients with focal hand dystonia presented a significant reduction of the illusion when the sphere was placed between the crossed fourth and fifth digits of the affected hand. This reduction correlated with the severity of motor disease at the fingers. Similar findings were not observed in non-hand dystonia and control groups. The reduction of Aristotle's illusion in non-affected fingers and its

  11. Patterns of Cortical Synchronization in Isolated Dystonia Compared With Parkinson Disease

    PubMed Central

    Miocinovic, Svjetlana; de Hemptinne, Coralie; Qasim, Salman; Ostrem, Jill L.; Starr, Philip A.

    2016-01-01

    IMPORTANCE Isolated dystonia and Parkinson disease (PD) are disorders of the basal gangliothalamocortical network. They have largely distinct clinical profiles, but both disorders respond to deep brain stimulation (DBS) in the same subcortical targets using similar stimulation paradigms, suggesting pathophysiologic overlap. We hypothesized that, similar to PD, isolated dystonia is associated with elevated cortical neuronal synchronization. OBJECTIVE To investigate the electrophysiologic characteristics of the sensorimotor cortex arm-related area using a temporary subdural electrode strip in patients with isolated dystonia and PD undergoing DBS implantation in the awake state. DESIGN, SETTING, AND PARTICIPANTS An observational study recruited patients scheduled for DBS at the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center. Data were collected from May 1, 2008, through April 1, 2015. Findings are reported for 22 patients with isolated cervical or segmental dystonia (8 with [DYST-ARM] and 14 without [DYST] arm symptoms] and 14 patients with akinetic rigid PD. Data were analyzed from November 1, 2014, through May 1, 2015. MAIN OUTCOMES AND MEASURES Cortical local field potentials, power spectral density, and phase-amplitude coupling (PAC). RESULTS Among our 3 groups that together included 36 patients, cortical PAC was present in primary motor and premotor arm-related areas for all groups, but the DYST group was less likely to exhibit increased PAC (P = .008). Similar to what has been shown for patients with PD, subthalamic DBS reversibly decreased PAC in a subset of patients with dystonia who were studied before and during intraoperative test stimulation (n = 4). At rest, broadband gamma (50–200 Hz) power in the primary motor cortex was greater in the DYST-ARM and PD groups compared with the DYST group, whereas alpha (8–13 Hz) and beta (13–30 Hz) power was comparable in all 3 groups. During movement, the DYST

  12. Aberrant Purkinje cell activity is the cause of dystonia in a shRNA-based mouse model of Rapid Onset Dystonia-Parkinsonism.

    PubMed

    Fremont, Rachel; Tewari, Ambika; Khodakhah, Kamran

    2015-10-01

    Loss-of-function mutations in the α3 isoform of the sodium pump are responsible for Rapid Onset Dystonia-Parkinsonism (RDP). A pharmacologic model of RDP replicates the most salient features of RDP, and implicates both the cerebellum and basal ganglia in the disorder; dystonia is associated with aberrant cerebellar output, and the parkinsonism-like features are attributable to the basal ganglia. The pharmacologic agent used to generate the model, ouabain, is selective for sodium pumps. However, close to the infusion sites in vivo it likely affects all sodium pump isoforms. Therefore, it remains to be established whether selective loss of α3-containing sodium pumps replicates the pharmacologic model. Moreover, while the pharmacologic model suggested that aberrant firing of Purkinje cells was the main cause of abnormal cerebellar output, it did not allow the scrutiny of this hypothesis. To address these questions RNA interference using small hairpin RNAs (shRNAs) delivered via adeno-associated viruses (AAV) was used to specifically knockdown α3-containing sodium pumps in different regions of the adult mouse brain. Knockdown of the α3-containing sodium pumps mimicked both the behavioral and electrophysiological changes seen in the pharmacologic model of RDP, recapitulating key aspects of the human disorder. Further, we found that knockdown of the α3 isoform altered the intrinsic pacemaking of Purkinje cells, but not the neurons of the deep cerebellar nuclei. Therefore, acute knockdown of proteins associated with inherited dystonias may be a good strategy for developing phenotypic genetic mouse models where traditional transgenic models have failed to produce symptomatic mice.

  13. Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia

    PubMed Central

    Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

    2016-01-01

    Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to

  14. Differences in globus pallidus neuronal firing rates and patterns relate to different disease biology in children with dystonia

    PubMed Central

    McClelland, V M; Valentin, A; Rey, H G; Lumsden, D E; Elze, M C; Selway, R; Alarcon, G; Lin, J-P

    2016-01-01

    Background The pathophysiology underlying different types of dystonia is not yet understood. We report microelectrode data from the globus pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe firing rates differ between dystonia types. Methods Single pass microelectrode data were obtained to guide electrode position in 44 children (3.3–18.1 years, median 10.7) with the following dystonia types: 14 primary, 22 secondary Static and 8 progressive secondary to neuronal brain iron accumulation (NBIA). Preoperative stereotactic MRI determined coordinates for the GPi target. Digitised spike trains were analysed offline, blind to clinical data. Electrode placement was confirmed by a postoperative stereotactic CT scan. Findings We identified 263 GPi and 87 GPe cells. Both GPi and GPe firing frequencies differed significantly with dystonia aetiology. The median GPi firing frequency was higher in the primary group than in the secondary static group (13.5 Hz vs 9.6 Hz; p=0.002) and higher in the NBIA group than in either the primary (25 Hz vs 13.5 Hz; p=0.006) or the secondary static group (25 Hz vs 9.6 Hz; p=0.00004). The median GPe firing frequency was higher in the NBIA group than in the secondary static group (15.9 Hz vs 7 Hz; p=0.013). The NBIA group also showed a higher proportion of regularly firing GPi cells compared with the other groups (p<0.001). A higher proportion of regular GPi cells was also seen in patients with fixed/tonic dystonia compared with a phasic/dynamic dystonia phenotype (p<0.001). The GPi firing frequency showed a positive correlation with 1-year outcome from DBS measured by improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m) score (p=0.030). This association was stronger for the non-progressive patients (p=0.006). Interpretation Pallidal firing rates and patterns differ significantly with dystonia aetiology

  15. Treatment of focal dystonias of the hand with botulinum toxin injections.

    PubMed Central

    Cohen, L G; Hallett, M; Geller, B D; Hochberg, F

    1989-01-01

    The effects of botulinum toxin injections have been studied on 19 patients with hand dystonia. The dystonic muscles were identified by clinical examination and EMG findings of localised bursts of muscle activation with fine wire electrodes during the tasks that precipitated the dystonia. Injections into the most active muscles were given to each patient every 2 weeks in increasing doses (up to 20 U the first week, up to 40 U the second week, and up to 80 U the third week) until performance improvement was achieved. Subjective improvement of cramping, pain and/or tension was associated with temporary weakness in injected muscles. Benefit was seen in 16 patients, lasted between 1 and 6 months, and was reproducible. PMID:2926421

  16. Paget's disease of bone (osteitis deformans).

    PubMed

    Ankrom, M A; Shapiro, J R

    1998-08-01

    Paget's disease of bone is important in geriatric populations because it is the second most common bone disorder after osteoporosis. In older people, it may be responsible for chronic back pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression. Paget's disease can reduce both function and mobility in the older people. In addition to newer tests for assessing the activity of Paget's disease, effective therapy is available in the form of salmon calcitonin for nasal administration and new third generation bisphosphonates. Frequently, treatment can reverse the course of the disease. For these reasons, it is feasible for the physician to adopt an aggressive approach to diagnosis and treatment. The objective should be to relieve pain, improve mobility, and forestall debilitating complications. This review will focus on the manifestations and clinical management of Paget's disease. Two cases are presented that illustrate common management problems in older patients.

  17. Altered postnatal maturation of striatal GABAergic interneurons in a phenotypic animal model of dystonia.

    PubMed

    Bode, Christoph; Richter, Franziska; Spröte, Christine; Brigadski, Tanja; Bauer, Anne; Fietz, Simone; Fritschy, Jean-Marc; Richter, Angelika

    2017-01-01

    GABAergic disinhibition has been suggested to play a critical role in the pathophysiology of several basal ganglia disorders, including dystonia, a common movement disorder. Previous studies have shown a deficit of striatal GABAergic interneurons (IN) in the dt(sz) mutant hamster, one of the few phenotypic animal models of dystonia. However, mechanisms underlying this deficit are largely unknown. In the present study, we investigated the migration and maturation of striatal IN during postnatal development (18days of age) and at age of highest severity of dystonia (33days of age) in this hamster model. In line with previous findings, the density of GAD67-positive IN and the level of parvalbumin mRNA, a marker for fast spiking GABAergic IN, were lower in the dt(sz) mutant than in control hamsters. However, an unaltered density of Nkx2.1 labeled cells and Nkx2.1 mRNA level suggested that the migration of GABAergic IN into the striatum was not retarded. Therefore, different factors that indicate maturation of GABAergic IN were determined. While mRNA of the KCC2 cation/chloride transporters and the cytosolic carboanhydrase VII, used as markers for the so called GABA switch, as well as BDNF were unaltered, we found a reduced number of IN expressing the alpha1 subunit of the GABAA-receptor (37.5%) in dt(sz) hamsters at an age of 33days, but not after spontaneous remission of dystonia at an age of 90days. Since IN shift expression from alpha2 to alpha1 subunits during postnatal maturation, this result together with a decreased parvalbumin mRNA expression suggest a delayed maturation of striatal GABAergic IN in this animal model, which might underlie abnormal neuronal activity and striatal plasticity.

  18. Cholinergic dysregulation produced by selective inactivation of the dystonia-associated protein torsinA.

    PubMed

    Sciamanna, Giuseppe; Hollis, Robert; Ball, Chelsea; Martella, Giuseppina; Tassone, Annalisa; Marshall, Andrea; Parsons, Dee; Li, Xinru; Yokoi, Fumiaki; Zhang, Lin; Li, Yuqing; Pisani, Antonio; Standaert, David G

    2012-09-01

    DYT1 dystonia, a common and severe primary dystonia, is caused by a 3-bp deletion in TOR1A which encodes torsinA, a protein found in the endoplasmic reticulum. Several cellular functions are altered by the mutant protein, but at a systems level the link between these and the symptoms of the disease is unclear. The most effective known therapy for DYT1 dystonia is the use of anticholinergic drugs. Previous studies have revealed that in mice, transgenic expression of human mutant torsinA under a non-selective promoter leads to abnormal function of striatal cholinergic neurons. To investigate what pathological role torsinA plays in cholinergic neurons, we created a mouse model in which the Dyt1 gene, the mouse homolog of TOR1A, is selectively deleted in cholinergic neurons (ChKO animals). These animals do not have overt dystonia, but do have subtle motor abnormalities. There is no change in the number or size of striatal cholinergic cells or striatal acetylcholine content, uptake, synthesis, or release in ChKO mice. There are, however, striking functional abnormalities of striatal cholinergic cells, with paradoxical excitation in response to D2 receptor activation and loss of muscarinic M2/M4 receptor inhibitory function. These effects are specific for cholinergic interneurons, as recordings from nigral dopaminergic neurons revealed normal responses. Amphetamine stimulated dopamine release was also unaltered. These results demonstrate a cell-autonomous effect of Dyt1 deletion on striatal cholinergic function. Therapies directed at modifying the function of cholinergic neurons may prove useful in the treatment of the human disorder.

  19. A Missense Mutation in KCTD17 Causes Autosomal Dominant Myoclonus-Dystonia

    PubMed Central

    Mencacci, Niccolo E.; Rubio-Agusti, Ignacio; Zdebik, Anselm; Asmus, Friedrich; Ludtmann, Marthe H.R.; Ryten, Mina; Plagnol, Vincent; Hauser, Ann-Kathrin; Bandres-Ciga, Sara; Bettencourt, Conceição; Forabosco, Paola; Hughes, Deborah; Soutar, Marc M.P.; Peall, Kathryn; Morris, Huw R.; Trabzuni, Daniah; Tekman, Mehmet; Stanescu, Horia C.; Kleta, Robert; Carecchio, Miryam; Zorzi, Giovanna; Nardocci, Nardo; Garavaglia, Barbara; Lohmann, Ebba; Weissbach, Anne; Klein, Christine; Hardy, John; Pittman, Alan M.; Foltynie, Thomas; Abramov, Andrey Y.; Gasser, Thomas; Bhatia, Kailash P.; Wood, Nicholas W.

    2015-01-01

    Myoclonus-dystonia (M-D) is a rare movement disorder characterized by a combination of non-epileptic myoclonic jerks and dystonia. SGCE mutations represent a major cause for familial M-D being responsible for 30%–50% of cases. After excluding SGCE mutations, we identified through a combination of linkage analysis and whole-exome sequencing KCTD17 c.434 G>A p.(Arg145His) as the only segregating variant in a dominant British pedigree with seven subjects affected by M-D. A subsequent screening in a cohort of M-D cases without mutations in SGCE revealed the same KCTD17 variant in a German family. The clinical presentation of the KCTD17-mutated cases was distinct from the phenotype usually observed in M-D due to SGCE mutations. All cases initially presented with mild myoclonus affecting the upper limbs. Dystonia showed a progressive course, with increasing severity of symptoms and spreading from the cranio-cervical region to other sites. KCTD17 is abundantly expressed in all brain regions with the highest expression in the putamen. Weighted gene co-expression network analysis, based on mRNA expression profile of brain samples from neuropathologically healthy individuals, showed that KCTD17 is part of a putamen gene network, which is significantly enriched for dystonia genes. Functional annotation of the network showed an over-representation of genes involved in post-synaptic dopaminergic transmission. Functional studies in mutation bearing fibroblasts demonstrated abnormalities in endoplasmic reticulum-dependent calcium signaling. In conclusion, we demonstrate that the KCTD17 c.434 G>A p.(Arg145His) mutation causes autosomal dominant M-D. Further functional studies are warranted to further characterize the nature of KCTD17 contribution to the molecular pathogenesis of M-D. PMID:25983243

  20. Failure of cathodal direct current stimulation to improve fine motor control in musician's dystonia.

    PubMed

    Buttkus, Franziska; Weidenmüller, Matthias; Schneider, Sabine; Jabusch, Hans-Christian; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

    2010-02-15

    Musician's dystonia (MD) is a task-specific movement disorder with a loss of voluntary motor control in highly trained movements. Defective inhibition on different levels of the central nervous system is involved in its pathophysiology. Cathodal transcranial direct current stimulation (ctDCS) diminishes excitability of the motor cortex and improves performance in overlearned tasks in healthy subjects. The aim of this study was to investigate whether ctDCS improves fine motor control in MD. Professional guitarists (n = 10) with MD played exercises before, directly after ctDCS, and 60 min after ctDCS. ctDCS (2 mA, 20 min) was applied on the primary motor cortex contralateral to the affected hand. Guitar exercises were video-documented and symptoms were evaluated by three independent experts. No beneficial effect of ctDCS on fine motor control was found for the entire group. However, motor control of one guitarist improved after stimulation. This patient suffered from arm dystonia, whereas the other guitarists suffered from hand dystonia.

  1. Needs and Requirements of Modern Biobanks on the Example of Dystonia Syndromes

    PubMed Central

    Lohmann, Ebba; Gasser, Thomas; Grundmann, Kathrin

    2017-01-01

    Dystonia belongs to a group of rare diseases (RDs) characterized by etiologic heterogeneity, affection often in childhood, severe and variable clinical manifestation. The burden of this disease is aggravated by the lack of effective and specific treatment. In the field of dystonia as in other RDs the number of available biospecimens is, in general, limited. Here, we report a new approach to collect clinical and genetic data in biospecimens maintained collaboratively by researchers and their associated institutions in a decentralized system. Allowing researchers to have access to significant numbers of samples and corresponding clinical data, biobanking in dystonia might not only provide a powerful tool in the identification of disease genes but also the classification of variants detected in known genes with respect to their clinical relevance. Growing data in genetics due to the technical progress demand for well-annotated and well-managed biobanks, which in near future hold even the potential for biomarker research and generating medical treatment based on clinical and genetic data currently summarized as “personalized medicine.” PMID:28194131

  2. Intrathecal baclofen in the treatment of post-stroke central pain, dystonia, and persistent vegetative state.

    PubMed

    Taira, T; Hori, T

    2007-01-01

    Intrathecal baclofen (ITB) administration is a fully established treatment for severe spasticity. However, it is not widely known that baclofen, an agonist of the GABA-B receptor, has additional beneficial effects in other conditions such as chronic pain, coma, dystonia, tetanus, and hyypothalamic storm. Sporadic cases of dramatic recovery from persistent vegetative state after intrathecal administration of baclofen have been reported. There have been also reports on the use of baclofen for control of dystonia due to cerebral palsy, neuropathic central pain syndrome or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation (SCS) has been used in the management not only of pain but also of spasticity, dystonia, and in order to improve deteriorated consciousness, but the effects so far have been modest and variable. Similarities between ITB and SCS are interesting as both involve the spinal GABAergic system. Based on a 15-year personal experience of intrathecal baclofen, I would stress the importance of this treatment not only for spasticity but also for other difficult neurological disorders.

  3. Intrathecal glycine for pain and dystonia in complex regional pain syndrome.

    PubMed

    Munts, Alexander G; van der Plas, Anton A; Voormolen, Joan H; Marinus, Johan; Teepe-Twiss, Irene M; Onkenhout, Willem; van Gerven, Joop M; van Hilten, Jacobus J

    2009-11-01

    Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information, intrathecal glycine (ITG) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome (CRPS). Aims of the current study, which is the first report on ITG in humans, were to evaluate its safety and efficacy. ITG treatment during 4 weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment. Twenty patients were assessed and after exclusion of one patient, the remaining 19 patients were randomized in a double-blind placebo-controlled crossover study. Safety was assessed by clinical evaluation, blood examinations and electrocardiograms. Efficacy measures involved pain (numeric rating scale, McGill pain questionnaire), movement disorders (Burke-Fahn-Marsden dystonia rating scale, unified myoclonus rating scale, tremor research group rating scale), activity (Radboud skills questionnaire, walking ability questionnaire), and a clinical global impression (CGI) and patient's global impression score (PGI). Treatment-emergent adverse events were generally mild to moderate and not different from placebo treatment. During ITG treatment growth hormone levels were slightly increased. Although there was a trend to worsening on the CGI and PGI during ITG treatment, there were no significant differences between ITG and placebo treatment in any of the outcomes. ITG given over 4 weeks was ineffective for pain or dystonia in CRPS. Although no serious adverse events occurred, further studies are required to rule out potential neurotoxicity of ITG.

  4. Multiday Transcranial Direct Current Stimulation Causes Clinically Insignificant Changes in Childhood Dystonia: A Pilot Study.

    PubMed

    Bhanpuri, Nasir H; Bertucco, Matteo; Young, Scott J; Lee, Annie A; Sanger, Terence D

    2015-10-01

    Abnormal motor cortex activity is common in dystonia. Cathodal transcranial direct current stimulation may alter cortical activity by decreasing excitability while anodal stimulation may increase motor learning. Previous results showed that a single session of cathodal transcranial direct current stimulation can improve symptoms in childhood dystonia. Here we performed a 5-day, sham-controlled, double-blind, crossover study, where we measured tracking and muscle overflow in a myocontrol-based task. We applied cathodal and anodal transcranial direct current stimulation (2 mA, 9 minutes per day). For cathodal transcranial direct current stimulation (7 participants), 3 subjects showed improvements whereas 2 showed worsening in overflow or tracking error. The effect size was small (about 1% of maximum voluntary contraction) and not clinically meaningful. For anodal transcranial direct current stimulation (6 participants), none showed improvement, whereas 5 showed worsening. Thus, multiday cathodal transcranial direct current stimulation reduced symptoms in some children but not to a clinically meaningful extent, whereas anodal transcranial direct current stimulation worsened symptoms. Our results do not support transcranial direct current stimulation as clinically viable for treating childhood dystonia.

  5. The clinical phenomenology and associations of trick maneuvers in cervical dystonia.

    PubMed

    Filip, Pavel; Šumec, Rastislav; Baláž, Marek; Bareš, Martin

    2016-03-01

    Sensory trick is an unusual clinical feature in cervical dystonia that attenuates disease symptoms by slight touch to a specific area of the face or head. Using a semi-quantitative questionnaire-based study of 197 patients with idiopathic cervical dystonia, we sought to determine probable pathophysiologic correlates, with the wider aim of examining its eventual clinical significance. The typical sensory trick, i.e., light touch, not necessitating the use of force leading to simple overpowering of dystonic activity, was present in 83 (42.1 %) patients. The vast majority of the patients required a specific sequence of sensorimotor inputs, including touch sensation on the face or different areas of the head, and also sensory and motor input of the hand itself. Deviations often led to a significant decrease in effectiveness and lack of expected benefit. Moreover, patients able to perform the maneuver reported compellingly higher subjective effect of botulinum toxin treatment (median 7 vs. 5 on a scale of 0-10; p < 0.0001) and lower depression score (median 10 vs. 14 on the Montgomery Åsberg Depression Rating scale; p < 0.001). Overall, the results point to marked disruption of sensorimotor networks in cervical dystonia. The mechanism of the sensory trick action may be associated with balancing the abnormal activation patterns by specific sensorimotor inputs. Its presence may be considered a positive predictive factor for responsiveness to botulinum toxin treatment.

  6. A distinct variant of mixed dysarthria reflects parkinsonism and dystonia due to ephedrone abuse.

    PubMed

    Rusz, Jan; Megrelishvili, Marika; Bonnet, Cecilia; Okujava, Michael; Brožová, Hana; Khatiashvili, Irine; Sekhniashvili, Madona; Janelidze, Marina; Tolosa, Eduardo; Růžička, Evžen

    2014-06-01

    A distinctive alteration of speech has been reported in patients suffering from ephedrone-induced parkinsonism. However, an objective assessment of dysarthria has not been performed in ephedrone users. We studied 28 young Caucasian men from Georgia with a previous history of ephedrone abuse and compared them to 25 age-matched healthy controls. Speech examination, brain MRI, and NNIPPS-Parkinson plus scale were performed in all patients. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analyses of 15 speech dimensions. We revealed a distinct variant of mixed dysarthria with a combination of hyperkinetic and hypokinetic components representing the altered motor programming of dystonia and bradykinesia in ephedrone-induced parkinsonism. According to acoustic analyses, all patients presented at least one affected speech dimension, whereas dysarthria was moderate in 43% and severe in 36% of patients. Further findings indicated relationships between motor subscores of dystonia and bradykinesia and speech components of loudness (r = -0.54, p < 0.01), articulation (r = 0.40, p < 0.05), and timing (r = -0.53, p < 0.01). In ephedrone-induced parkinsonism a prominent mixed hyperkinetic-hypokinetic dysarthria occurs that appears related to marked dystonia and bradykinesia and probably reflects manganese induced toxic and neurodegenerative damage to the globus pallidus internus and substantia nigra.

  7. Genetic Diagnosis of Two Dopa-Responsive Dystonia Families by Exome Sequencing

    PubMed Central

    Sun, Zhan-fang; Zhang, Yu-han; Guo, Ji-feng; Sun, Qi-ying; Mei, Jun-pu; Zhou, Han-lin; Guan, Li-ping; Tian, Jin-yong; Hu, Zheng-mao; Li, Jia-da; Xia, Kun; Yan, Xin-xiang; Tang, Bei-sha

    2014-01-01

    Dopa-responsive dystonia, a rare disorder typically presenting in early childhood with lower limb dystonia and gait abnormality, responds well to levodopa. However, it is often misdiagnosed with the wide spectrum of phenotypes. By exome sequencing, we make a rapid genetic diagnosis for two atypical dopa-responsive dystonia pedigrees. One pedigree, presented with prominent parkinsonism, was misdiagnosed as Parkinson's disease until a known mutation in GCH1 (GTP cyclohydrolase 1) gene (NM_000161.2: c.631_632delAT, p.Met211ValfsX38) was found. The other pedigree was detected with a new compound heterozygous mutation in TH (tyrosine hydroxylase) gene [(NM_000360.3: c.911C>T, p.Ala304Val) and (NM_000360.3: c.1358G>A, p.Arg453His)], whose proband, a pregnant woman, required a rapid and less-biased genetic diagnosis. In conclusion, we demonstrated that exome sequencing could provide a precise and rapid genetic testing in the diagnosis of Mendelian diseases, especially for diseases with wide phenotypes. PMID:25181484

  8. Abnormal cortical sensory activation in dystonia: an fMRI study.

    PubMed

    Butterworth, Stephen; Francis, Sue; Kelly, Edward; McGlone, Francis; Bowtell, Richard; Sawle, Guy V

    2003-06-01

    Despite the obvious motor manifestations of focal dystonia, it is recognised that the sensory system plays an important role in this condition. This functional magnetic resonance imaging study examines the sensory representations of individual digits both within the subregions of the primary sensory cortex (SI) and in other nonprimary sensory areas. Patients with focal dystonia and controls were scanned during vibrotactile stimulation of both the index (digit 2) and little (digit 5) fingers of their dominant hand (which was the affected hand in all the dystonic subjects). The activation maps obtained were analysed for location, size, and magnitude of activation and three-dimensional (3-D) orientation of digit representations. Data from both groups were compared. There were significant differences in the average 3-D separation between the two digit representations in area 1 of SI between subject groups (9.6 +/- 1.2 mm for controls and 4.1 +/- 0.2 mm for dystonic subjects). There were also strong trends for reversed ordering of the representation of the two digits in both the secondary sensory cortex and posterior parietal area between the two groups. In addition, in dystonic subjects, there was significant under activation in the secondary somatosensory cortex (SII/area 40) for both digits and in the posterior parietal area for digit 5. These results indicate the presence of widespread activation abnormalities in the cortical sensory system in dystonia.

  9. Persistent changes of corticostriatal plasticity in dt(sz) mutant hamsters after age-dependent remission of dystonia.

    PubMed

    Avchalumov, Y; Volkmann, C E; Rückborn, K; Hamann, M; Kirschstein, T; Richter, A; Köhling, R

    2013-10-10

    Abnormal plasticity in the cortico-basal ganglia-thalamocortical loop has been suggested to represent a key factor in the pathophysiology of dystonia. In a model of primary paroxysmal dystonia, the dt(sz) mutant hamster, previous experiments have shown a strongly increased long-term potentiation (LTP) in comparison to non-dystonic control hamsters. These basal changes, i.e. in the absence of dystonia, were found in young animals at an age of 5 weeks, when the age-dependent dystonia in dt(sz) mutant reaches highest severity. In the present study we examined in corticostriatal slices (1) whether the increases in synaptic plasticity can be modulated by stressful stimuli which induce dystonic episodes in young mutant hamsters, and (2) whether increases of LTP persist after spontaneous remission of dystonia in animals older than 10 weeks. The present data show that in slices of young mutant hamsters the extent of LTP was not influenced by the presence of dystonia: In comparison to age-matched control hamsters, LTP was increased in mutant hamsters independent of preceding stressful stimulation. After remission of dystonia, i.e., in older dt(sz) mutant hamsters >10 weeks, only LTP could be elicited, while in preparations from age-matched control hamsters, either LTP or long-term depression developed, depending on previous behavioral challenge. We conclude that in mature brain, corticostriatal connections have the potential for changes in metaplasticity, while in dt(sz) mutant hamsters this metaplasticity is persistently infringed even though stress-inducible dystonic symptoms are lost.

  10. Effect of chronic pallidal deep brain stimulation on off period dystonia and sensory symptoms in advanced Parkinson's disease

    PubMed Central

    Loher, T; Burgunder, J; Weber, S; Sommerhalder, R; Krauss, J

    2002-01-01

    Objective: To investigate the efficacy of chronic pallidal deep brain stimulation (DBS) on off period dystonia, cramps, and sensory symptoms in advanced Parkinson's disease (PD). Methods: 16 patients (6 women, 10 men; mean age at surgery 65 years) suffering from advanced PD were followed up prospectively for one year after implantation of a monopolar electrode in the posteroventral lateral globus pallidus internus. Unilateral DBS was performed in 9 patients. 10 patients had bilateral procedures (contemporaneous bilateral surgery in 7 and staged bilateral surgery in 3 instances). The decision whether to perform unilateral or bilateral surgery depended on the clinical presentation of the patient. Patients were formally assessed preoperatively, at 3–5 days, 3 months, and 12 months after surgery. Results: In patients who underwent unilateral surgery, pain was present in 7 (78%), off dystonia in 5 (56%), cramps in 6 (67%), and dysaesthesia in 4 (44%). In patients who underwent bilateral surgery, pain was present in 7 (70%), off dystonia in 6 (60%), cramps in 7 (70%), and dysaesthesia in 4 (40%). With unilateral DBS, contralateral off period dystonia was improved by 100% at 1 year postoperatively, pain by 74%, cramps by 88%, and dysaesthesia by 100%. There was less pronounced amelioration of ipsilateral off period dystonia and sensory symptoms. With bilateral DBS, total scores for dystonia were improved by 86%, for pain by 90%, for cramps by 90%, and for dysaesthesia by 88%. The benefit appeared early at the first evaluation 3–5 days after surgery and was stable throughout the follow up period. Conclusions: Pallidal DBS yields major improvement of off period dystonia, cramps, and sensory symptoms in patients with advanced PD. PMID:12235307

  11. Dopamine release is impaired in a mouse model of DYT1 dystonia.

    PubMed

    Balcioglu, Aygul; Kim, Mee-Ohk; Sharma, Nutan; Cha, Jang-Ho; Breakefield, Xandra O; Standaert, David G

    2007-08-01

    Early onset torsion dystonia, the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein torsinA. This form of dystonia is referred to as DYT1. We have used a transgenic mouse model of DYT1 dystonia [human mutant-type (hMT)1 mice] to examine the effect of the mutant human torsinA protein on striatal dopaminergic function. Analysis of striatal tissue dopamine (DA) and metabolites using HPLC revealed no difference between hMT1 mice and their non-transgenic littermates. Pre-synaptic DA transporters were studied using in vitro autoradiography with [(3)H]mazindol, a ligand for the membrane DA transporter, and [(3)H]dihydrotetrabenazine, a ligand for the vesicular monoamine transporter. No difference in the density of striatal DA transporter or vesicular monoamine transporter binding sites was observed. Post-synaptic receptors were studied using [(3)H]SCH-23390, a ligand for D(1) class receptors, [(3)H]YM-09151-2 and a ligand for D(2) class receptors. There were again no differences in the density of striatal binding sites for these ligands. Using in vivo microdialysis in awake animals, we studied basal as well as amphetamine-stimulated striatal extracellular DA levels. Basal extracellular DA levels were similar, but the response to amphetamine was markedly attenuated in the hMT1 mice compared with their non-transgenic littermates (253 +/- 71% vs. 561 +/- 132%, p < 0.05, two-way anova). These observations suggest that the mutation in the torsinA protein responsible for DYT1 dystonia may interfere with transport or release of DA, but does not alter pre-synaptic transporters or post-synaptic DA receptors. The defect in DA release as observed may contribute to the abnormalities in motor learning as previously documented in this transgenic mouse model, and may contribute to the clinical symptoms of the human disorder.

  12. Speed-Accuracy Trade-Off in a Trajectory-Constrained Self-Feeding Task: A Quantitative Index of Unsuppressed Motor Noise in Children With Dystonia.

    PubMed

    Lunardini, Francesca; Bertucco, Matteo; Casellato, Claudia; Bhanpuri, Nasir; Pedrocchi, Alessandra; Sanger, Terence D

    2015-10-01

    Motor speed and accuracy are both affected in childhood dystonia. Thus, deriving a speed-accuracy function is an important metric for assessing motor impairments in dystonia. Previous work in dystonia studied the speed-accuracy trade-off during point-to-point tasks. To achieve a more relevant measurement of functional abilities in dystonia, the present study investigates upper-limb kinematics and electromyographic activity of 8 children with dystonia and 8 healthy children during a trajectory-constrained child-relevant task that emulates self-feeding with a spoon and requires continuous monitoring of accuracy. The speed-accuracy trade-off is examined by changing the spoon size to create different accuracy demands. Results demonstrate that the trajectory-constrained speed-accuracy relation is present in both groups, but it is altered in dystonia in terms of increased slope and offset toward longer movement times. Findings are consistent with the hypothesis of increased signal-dependent noise in dystonia, which may partially explain the slow and variable movements observed in dystonia.

  13. Homozygous mutation of VPS16 gene is responsible for an autosomal recessive adolescent-onset primary dystonia

    PubMed Central

    Cai, Xiaodong; Chen, Xin; Wu, Song; Liu, Wenlan; Zhang, Xiejun; Zhang, Doudou; He, Sijie; Wang, Bo; Zhang, Mali; Zhang, Yuan; Li, Zongyang; Luo, Kun; Cai, Zhiming; Li, Weiping

    2016-01-01

    Dystonia is a neurological movement disorder that is clinically and genetically heterogeneous. Herein, we report the identification a novel homozygous missense mutation, c.156 C > A in VPS16, co-segregating with disease status in a Chinese consanguineous family with adolescent-onset primary dystonia by whole exome sequencing and homozygosity mapping. To assess the biological role of c.156 C > A homozygous mutation of VPS16, we generated mice with targeted mutation site of Vps16 through CRISPR-Cas9 genome-editing approach. Vps16 c.156 C > A homozygous mutant mice exhibited significantly impaired motor function, suggesting that VPS16 is a new causative gene for adolescent-onset primary dystonia. PMID:27174565

  14. Influence of dystonia on the response to long-term L-dopa therapy in Parkinson's disease.

    PubMed

    Andrews, C J

    1973-08-01

    The gait of normal subjects was examined electromyographically and the pattern was altered during preferential blockade of large nerve fibres to alternating activity in flexor and extensor muscles.The EMG activity was disrupted more in flexor than extensor muscles by preferential ischaemic blockade. Normal gait was associated with flexor contraction only when the foot was lifted and placed on the ground, whereas during ischaemic blockade flexor contraction continued during the interval between foot lifting and foot placement.The `freezing' or `blocking' gait in Parkinson's disease was found to be associated with coactivation of flexor and extensor muscles and this phenomenon occurred only in patients with features of flexion dystonia in the electromyographic recordings of their tonic stretch reflexes. Eight of nine patients with evidence of flexion dystonia showed a deterioration in their response to l-dopa therapy over a two year period, whereas four patients without flexion dystonia maintained their clinical improvement.

  15. Cervical dystonia: effectiveness of a standardized physical therapy program; study design and protocol of a single blind randomized controlled trial

    PubMed Central

    2013-01-01

    Background Cervical dystonia is characterized by involuntary muscle contractions of the neck and abnormal head positions that affect daily life activities and social life of patients. Patients are usually treated with botulinum toxin injections into affected neck muscles to relief pain and improve control of head postures. In addition, many patients are referred for physical therapy to improve their ability to perform activities of daily living. A recent review on allied health interventions in cervical dystonia showed a lack of randomized controlled intervention studies regarding the effectiveness of physical therapy interventions. Methods/design The (cost-) effectiveness of a standardized physical therapy program compared to regular physical therapy, both as add-on treatment to botulinum toxin injections will be determined in a multi-centre, single blinded randomized controlled trial with 100 cervical dystonia patients. Primary outcomes are disability in daily functioning assessed with the disability subscale of the Toronto Western Spasmodic Torticollis Rating Scale. Secondary outcomes are pain, severity of dystonia, active range of motion of the head, quality of life, anxiety and depression. Data will be collected at baseline, after six months and one year by an independent blind assessor just prior to botulinum toxin injections. For the cost effectiveness, an additional economic evaluation will be performed with the costs per quality adjusted life-year as primary outcome parameter. Discussion Our study will provide new evidence regarding the (cost-) effectiveness of a standardized, tailored physical therapy program for patients with cervical dystonia. It is widely felt that allied health interventions, including physical therapy, may offer a valuable supplement to the current therapeutic options. A positive outcome will lead to a greater use of the standardized physical therapy program. For the Dutch situation a positive outcome implies that the standardized

  16. Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy.

    PubMed

    Sanger, Terence D; Bastian, Amy; Brunstrom, Jan; Damiano, Diane; Delgado, Mauricio; Dure, Leon; Gaebler-Spira, Deborah; Hoon, Alec; Mink, Jonathan W; Sherman-Levine, Sara; Welty, Leah J

    2007-05-01

    Although trihexyphenidyl is used clinically to treat both primary and secondary dystonia in children, limited evidence exists to support its effectiveness, particularly in dystonia secondary to disorders such as cerebral palsy. A prospective, open-label, multicenter pilot trial of high-dose trihexyphenidyl was conducted in 23 children aged 4 to 15 years with cerebral palsy judged to have secondary dystonia impairing function in the dominant upper extremity. All children were given trihexyphenidyl at increasing doses over a 9-week period up to a maximum of 0.75 mg/kg/d. Trihexyphenidyl was subsequently tapered off over the next 5 weeks. Objective motor assessments were performed at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne Assessment of Unilateral Upper Limb Function, tested in the dominant arm. Tolerability and safety were monitored closely throughout the trial. Of the 31 children who agreed to participate in the study, 5 failed to meet entry criteria and 3 withdrew due to nonserious adverse events (chorea, drug rash, and hyperactivity). Three children required a dosage reduction because of nonserious adverse events but continued to participate. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (P = .045) but not at 9 weeks (P = .985). Post hoc analysis showed that a subgroup (n = 10) with hyperkinetic dystonia (excess involuntary movements) worsened at 9 weeks (P = .04) but subsequently returned to baseline following taper of the medicine. The authors conclude that scientific evidence for the clinical use of trihexyphenidyl in cerebral palsy remains equivocal. Trihexyphenidyl may be a safe and effective for treatment for arm dystonia in some children with cerebral palsy if given sufficient time to respond to the medication. Post hoc analyses based on the type of movement disorder suggested that children with hyperkinetic forms of dystonia may worsen. A larger, randomized

  17. A neuromorphic model of motor overflow in focal hand dystonia due to correlated sensory input

    NASA Astrophysics Data System (ADS)

    Sohn, Won Joon; Niu, Chuanxin M.; Sanger, Terence D.

    2016-10-01

    Objective. Motor overflow is a common and frustrating symptom of dystonia, manifested as unintentional muscle contraction that occurs during an intended voluntary movement. Although it is suspected that motor overflow is due to cortical disorganization in some types of dystonia (e.g. focal hand dystonia), it remains elusive which mechanisms could initiate and, more importantly, perpetuate motor overflow. We hypothesize that distinct motor elements have low risk of motor overflow if their sensory inputs remain statistically independent. But when provided with correlated sensory inputs, pre-existing crosstalk among sensory projections will grow under spike-timing-dependent-plasticity (STDP) and eventually produce irreversible motor overflow. Approach. We emulated a simplified neuromuscular system comprising two anatomically distinct digital muscles innervated by two layers of spiking neurons with STDP. The synaptic connections between layers included crosstalk connections. The input neurons received either independent or correlated sensory drive during 4 days of continuous excitation. The emulation is critically enabled and accelerated by our neuromorphic hardware created in previous work. Main results. When driven by correlated sensory inputs, the crosstalk synapses gained weight and produced prominent motor overflow; the growth of crosstalk synapses resulted in enlarged sensory representation reflecting cortical reorganization. The overflow failed to recede when the inputs resumed their original uncorrelated statistics. In the control group, no motor overflow was observed. Significance. Although our model is a highly simplified and limited representation of the human sensorimotor system, it allows us to explain how correlated sensory input to anatomically distinct muscles is by itself sufficient to cause persistent and irreversible motor overflow. Further studies are needed to locate the source of correlation in sensory input.

  18. Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

    PubMed

    Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

    2011-08-15

    Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia.

  19. Early deep brain stimulation in patients with myoclonus-dystonia syndrome.

    PubMed

    Rocha, Helena; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Vaz, Rui

    2016-05-01

    Myoclonus-dystonia (MD) is a rare movement disorder which is disabling and frequently refractory to medical treatment. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been used to treat some patients. Although there is significant motor improvement with DBS, the impact on disability and on quality of life has been infrequently reported. Also, the benefit of the procedure is not established in patients without ε-sarcoglycan gene (SGCE) mutations. We present two patients with severe MD treated with GPi-DBS, one of the patients without a SGCE mutation. Motor improvements (rest/action/total subscores of the Unified Myoclonus Rating Scale and movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale [BFMRS]) and disability (BFMRS disability subscore) were carefully evaluated preoperatively and at 6 and 12months after surgery. Quality of life (addressed using the Portuguese version of the Medical Outcomes Study 36-item Short-Form General Health Survey, version 2.0 [SF-36v2]) was tested preoperatively and 12months after DBS. At 12-month follow-up, myoclonus improved 78.6% in Patient 1 and 80.7% in Patient 2, while dystonia improved 37% and 86.7%, respectively. Improvements in disability ranged from 71.4% to 75%. With regard to quality of life, all parameters addressed by the SF-36v2 improved or stabilized in both patients. No major adverse effects were noticed. Improvements in motor symptoms are consistent with reports in the literature and were obtained regardless of the identification of a SGCE gene mutation. There were also significant benefits on disability and quality of life. DBS should be considered for MD.

  20. An unusual cause of focal hand dystonia due to a retained implant of the distal radius.

    PubMed

    Vaishya, Raju; Agarwal, Amit Kumar; Vijay, Vipul

    2016-01-08

    Focal hand dystonia (FHD) is characterised clinically by a task-specific symptom and typical electromyography findings of a characteristic pattern of cocontraction of the agonist and antagonist muscles of the hand and forearm. The aetiopathogenesis of this condition is still not clear. We present a case of a patient with an unusual aetiology for this condition, in the form of retained hardware in the distal radius. This patient had complete resolution of symptoms after removal of a retained radial plate. Thorough history-taking, clinical examination and necessary investigations are the cornerstones for making a diagnosis of FHD.

  1. Arm Posturing in a Patient Following Stroke: Dystonia, Levitation, Synkinesis, or Spasticity?

    PubMed Central

    Irmady, Krithi; Jabbari, Bahman; Louis, Elan D.

    2015-01-01

    Background Post-stroke movement disorders occur in up to 4% of stroke patients. The movements can be complex and difficult to classify, which presents challenges when attempting to understand the clinical phenomenology and provide appropriate treatment. Case Report We present a 64-year-old male with an unusual movement in the arm contralateral to his ischemic stroke. The primary feature of the movement was an involuntary elevation of the arm, occurring only when he was walking. Discussion The differential diagnosis includes dystonia, spontaneous arm levitation, synkinesis, and spasticity. We discuss each of these diagnostic possibilities in detail. PMID:26682091

  2. Paroxysmal myoclonic dystonia with vocalisations: new entity or variant of preexisting syndromes?

    PubMed Central

    Feinberg, T E; Shapiro, A K; Shapiro, E

    1986-01-01

    From among 1377 patients with movement disorders, four patients had an unusual movement disorder characterised by paroxysmal bursts of involuntary, regular, repetitive, rhythmic, bilateral, coordinated, simultaneous, stereotypic myoclonus and vocalisations, often associated with tonic symptoms, interference with voluntary functioning, presence of hyperactivity, attention and learning disabilities, and resistance to treatment with haloperidol and other drugs. This symptom complex may represent a new disease entity, referred to here as paroxysmal myoclonic dystonia with vocalisations or a variant or combination of other movement disorders such as Gilles de la Tourette, myoclonic, or dystonic syndromes. PMID:3457101

  3. Speech-activated Myoclonus Mimicking Stuttering in a Patient with Myoclonus–Dystonia Syndrome

    PubMed Central

    Isaacs, David A.; Hedera, Peter

    2016-01-01

    Background Acquired neurogenic stuttering has been considered a fairly uncommon clinical occurrence; speech-activated myoclonus is a rare entity that can mimic stuttering and is caused by a wide array of etiologies. Case Report Here we report a patient with myoclonus–dystonia syndrome (MDS), due to an identified disease-causing mutation, who displayed speech-activated myoclonus mimicking stuttering. Discussion In MDS, myoclonus has only infrequently been reported to affect speech. This case further expands the spectrum of conditions causing the rare clinical phenomenon of speech-activated myoclonus. PMID:27441098

  4. An elderly female patient with tardive oromandibular dystonia after prolonged use of the histamine analog betahistine.

    PubMed

    De Riu, G; Sanna, M P; De Riu, P L

    2010-10-01

    Tardive oromandibular dystonia (OMD) is iatrogenic in origin and is characterised by orofacial and lingual stereotypes more frequently than the idiopathic form of OMD Tardive OMD is often associated with anti-dopaminergic treatment involving drugs such as anti-psychotics, anti-emetics, and anti-vertigo agents, although the syndrome can also be triggered by anti-epileptic or anti-depressant drugs that do not have anti-dopaminergic properties. We report an elderly female patient with OMD after prolonged, self-administered treatment with betahistine dihydrochloride, a histamine analogue.

  5. Craniocervical Dystonia Questionnaire (CDQ-24): validation and cross-cultural adaptation in Serbian patients.

    PubMed

    Tepavcević, Darija Kisić; Svetel, Marina; Pekmezović, Tatjana; Petrović, Igor; Kostić, Vladimir S

    2009-12-01

    The purpose of this study was to investigate the validation of the translated and culturally adapted CDQ-24 questionnaire on a group of Serbian patients. The study was comprised of 100 consecutive patients with idiopathic cervical dystonia (CD) and blepharospasm (BSP) who were evaluated at the Institute of Neurology, Clinical Centre of Serbia in Belgrade between March and June 2007. The linguistic validation of CDQ-24 involved 3 steps, according to an internationally accepted methodology. Most of the patients with CD and BSP accepted the CDQ-24 questionnaire. The internal consistency reliability ranged from 0.81 to 0.97. The mean total score of the CDQ-24 was 35.6 +/- 23.5. Patients with BSP had better HRQoL scores in the Pain subscale (p = 0.025) compared with CD patients. However, patients with CD had better HRQoL sores in the Activities of Daily Living subscale (p = 0.028) compared with BSP patients. Statistically significant positive correlations were registered between the Dystonia Movement Scale score and almost all CDQ-24 scales. The Serbian version of CDQ-24 should be recommended for HRQoL evaluation among patients with CD and BSP as an important outcome measure.

  6. [A boy with nystagmus, refractory dystonia and apneic attack due to alternating hemiplegia of childhood].

    PubMed

    Shiota, Naoki; Shimono, Masayuki; Tomioka, Shiho; Takano, Kenichi; Kato, Ayako; Kawakami, Akihiro; Ishizuka, Takehiro

    2007-07-01

    We herein report the findings of a 2-year-6-month-old boy, who had been experiencing monocular pendular nystagmus, strabismus, and episodic eye deviation nystagmus, intractable dystonia and apneic attack which all began when he was 2 days of age. He underwent a complete blood count test, blood chemistry test, analysis of amino acids in the blood and urine, analysis of pyruvate/lactate in blood and cerebrospinal fluid, head computed tomography and magnetic resonance imaging and no abnormal results were identified. His attacks were resistant to multiple antiepileptic and dopaminergic drugs. He showed transient left and/or right hemiplegia after nystagmus, dystonia and/or apneic attacks at 8-months of age with retardation in intelligence. We diagnosed him to have alternating hemiplegia of childhood (AHC). We were unsure how to deal with his attacks after he was discharged from the hospital, however, resuscitation with the ambu bag by his mother at home and the intravenous infusion of diazepam or thiamylal at the hospital together was proven to be an effective method for treating his severe apneic attacks. The effect of diazepam and amantadine on these attacks was transient, however, the administration of flunarizine with amantadine resulted in an improvement in his attacks. We therefore consider the administration of flunarizine to be essential for the effective treatment of AHC in this case.

  7. Pitfalls in phenylalanine loading test in the diagnosis of dopa-responsive dystonia.

    PubMed

    Opladen, Thomas; Hoffmann, Georg F; Kühn, Andrea A; Blau, Nenad

    2013-03-01

    Phenylalanine (Phe) loading test is a useful tool in the differential diagnosis of dopa-responsive dystonia due to autosomal dominant or recessive GTP cyclohydrolase I (GTPCH) deficiency or autosomal recessive sepiapterin reductase (SR) deficiency. In these patients hepatic phenylalanine hydroxylase system is compromised due to subnormal tetrahydrobiopterin (BH(4)) levels and hydroxylation of phenylalanine (Phe) to tyrosine (Tyr) is reduced with elevated Phe/Tyr ratio 1-2 h after oral Phe administration (100 mg/kg bw) administration. In healthy persons there is only a modest increase in Tyr production and blood Phe normalizes after 4 h. We report on a challenge with Phe (100 mg/kg bw) in a patient with dopa-responsive dystonia while on therapy with BH(4) and l-dopa. During Phe challenge Phe concentration remained below the normal range while a transient mild hypertyrosinemia was observed, leading to an extremely low Phe/Tyr ratio. A repeated test, after BH(4) withdrawal, reversed the findings and resulted normal. These data suggest activation of hepatic phenylalanine hydroxylase by BH(4). Thus, the Phe loading test should not be performed during substitution with BH(4).

  8. Mixed effectiveness of rTMS and retraining in the treatment of focal hand dystonia

    PubMed Central

    Kimberley, Teresa J.; Schmidt, Rebekah L. S.; Chen, Mo; Dykstra, Dennis D.; Buetefisch, Cathrin M.

    2015-01-01

    Though the pathophysiology of dystonia remains uncertain, two primary factors implicated in the development of dystonic symptoms are excessive cortical excitability and impaired sensorimotor processing. The aim of this study was to determine the functional efficacy of an intervention combining repetitive transcranial magnetic stimulation (rTMS) and sensorimotor retraining. A randomized, single-subject, multiple baseline design with crossover was used to examine participants with focal hand dystonia (FHD) (n = 9). Intervention: 5 days rTMS + sensorimotor retraining (SMR) vs. Five days rTMS + control therapy (CTL) (which included stretching and massage). The rTMS was applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed. Each session in both groups consisted of rTMS followed immediately by 30 min of the therapy intervention (SMR or CTL). Contrary to our hypothesis, group analyses revealed no additional benefit from the SMR training vs. CTL. When analyzed across group however, there was significant improvement from the first baseline assessment in several measures, including tests of sensory ability and self-rated changes. The patient rated improvements were accompanied by a moderate effect size suggesting clinical meaningfulness. These results provide encouragement for further investigation of rTMS in FHD with a need to optimize a secondary intervention and determine likely responders vs. non-responders. PMID:26217209

  9. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin

    PubMed Central

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H.; Lokkegaard, Annemette; Marti, Maria J.; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D.; Zoons, Evelien; Ferreira, Joaquim J.; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A. J.

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored. PMID:28286494

  10. What we can learn about hereditary dystonia from HSDI of the glottis

    NASA Astrophysics Data System (ADS)

    Pedersen, Mette; Eeg, Martin

    2012-02-01

    This study examined efficacy of the innate immune defence via the mannose binding lectin (MBL) in a cohort of 55 dystonic patients prospectively referred to the clinic with laryngeal mucosal complaints, who were placed on local steroids (budesonid inhaler, 400 μg 2 times daily) and antihistamines (fexofenadin 180 mg mostly 3 times daily) with adjuvant lifestyle corrections. Treatment efficacy of the larynx was assessed based on mucosal findings of the vocal folds examined with High speed mucosa studies comprising simultaneous high speed digital imagines (HSDI), kymography, electroglottography (EGG) and voice acoustics combined with a visual score of arytenoids oedema, as these measures are indicative of the magnitude of laryngitis. Lactose and gluten intolerance and immunological analyses of the innate system were made systematically. Results showed that the genetic aspects of immunology did not reveal a role for the innate immune system, represented by the mannose binding lectin (MBL). An unexpected positive effect of the larynx treatment on dystonia symptoms was found evidenced by reduction of dystonic complaints and more normative results of High speed mucosa, and a reduction of oedema of the inter arytenoids region. Symptoms relieve and better quality of life was observed on follow up for the dystonia complaints.

  11. Brain cortical activation during guitar-induced hand dystonia studied by functional MRI.

    PubMed

    Pujol, J; Roset-Llobet, J; Rosinés-Cubells, D; Deus, J; Narberhaus, B; Valls-Solé, J; Capdevila, A; Pascual-Leone, A

    2000-09-01

    Focal hand dystonia in musicians is a strongly task-related movement disorder. Typically, symptoms become apparent only when players execute specific overpracticed skilled exercises on their instrument. We therefore examined five guitarists with functional MRI during dystonic symptom provocation by means of an adapted guitar inside the magnet. The activation patterns obtained in comparable nondystonic guitarists and in the study patients when performing normal-hand exercise served as references. A 1.5-T system equipped with echo-speed gradients and single-shot echoplanar imaging software was used. Data acquisition was centered on the cortical motor system encompassed in eight contiguous slices. Dystonic musicians compared with both control situations showed a significantly larger activation of the contralateral primary sensorimotor cortex that contrasted with a conspicuous bilateral underactivation of premotor areas. Our results coincide with studies of other dystonia types in that they show an abnormal recruitment of cortical areas involved in the control of voluntary movement. However, they do suggest that the primary sensorimotor cortex, rather than being underactive in idiopathic dystonic patients, may be overactive when tested during full expression of the task-induced movement disorder.

  12. Clinical Practice: Evidence-Based Recommendations for the Treatment of Cervical Dystonia with Botulinum Toxin.

    PubMed

    Contarino, Maria Fiorella; Van Den Dool, Joost; Balash, Yacov; Bhatia, Kailash; Giladi, Nir; Koelman, Johannes H; Lokkegaard, Annemette; Marti, Maria J; Postma, Miranda; Relja, Maja; Skorvanek, Matej; Speelman, Johannes D; Zoons, Evelien; Ferreira, Joaquim J; Vidailhet, Marie; Albanese, Alberto; Tijssen, Marina A J

    2017-01-01

    Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians. Key questions from the clinical practice were explored. Results suggest that while the beneficial effect of botulinum toxin treatment on different aspects of CD is well established, robust evidence is still missing concerning some practical aspects, such as dose equivalence between different formulations, optimal treatment intervals, treatment approaches, and the use of supportive techniques including electromyography or ultrasounds. Established strategies to prevent or manage common side effects (including excessive muscle weakness, pain at injection site, dysphagia) and potential contraindications to this treatment (pregnancy and lactation, use of anticoagulants, neurological comorbidities) should also be further explored.

  13. Combined Anterior and Posterior Lumbar Rhizotomy for Treatment of Mixed Dystonia and Spasticity in Children With Cerebral Palsy

    PubMed Central

    Nada, Mohamed; Mahran, Mahmoud A.; Aboud, Ahmed; Mahran, Moustafa G.; Nasef, Marwa A.A.; Gaber, Mohamed; Sabry, Tamer; Ibrahim, Mohamed H.; Taha, Mohamed H.

    2016-01-01

    BACKGROUND: Children with cerebral palsy (CP) can present with severe secondary dystonia with or without associated spasticity of their extremities. OBJECTIVE: To assess the outcomes of combined anterior and posterior lumbar rhizotomy for the treatment of mixed hypertonia in the lower extremities of children with CP. METHODS: Fifty children with CP were subjected to combined anterior and posterior lumbar rhizotomies in a prospective study. Clinical outcome measurements were recorded preoperatively and were evaluated at 2, 6, and 12 months postoperatively. The operative techniques were performed by laminotomy from L1-S1, and intraoperative monitoring was used in all cases. All patients underwent intensive postoperative physiotherapy programs. RESULTS: Changes in muscle tone, joint range of motion, and dystonia were significant (P = .000) at postoperative assessment visits. CONCLUSION: This study demonstrated the potential of combined anterior and posterior lumbar rhizotomies to improve activities of daily living in children with CP and with mixed spasticity and dystonia. ABBREVIATIONS: BAD, Barry-Albright Dystonia Scale CAPR, combined anterior and posterior lumbar rhizotomy CP, cerebral palsy ITB, intrathecal baclofen MAS, modified Ashworth Scale ROM, range of motion SDR, selective dorsal rhizotomy PMID:27244465

  14. Coordination of reach-to-grasp kinematics in individuals with childhood-onset dystonia due to hemiplegic cerebral palsy

    PubMed Central

    Kukke, Sahana N.; Curatalo, Lindsey A.; de Campos, Ana Carolina; Hallett, Mark; Alter, Katharine E.; Damiano, Diane L.

    2015-01-01

    Functional reaching is impaired in dystonia. Here, we analyze upper extremity kinematics to quantify timing and coordination abnormalities during unimanual reach-to-grasp movements in individuals with childhood-onset unilateral wrist dystonia. Kinematics were measured during movements of both upper limbs in a patient group (n = 11, age = 17.5 ± 5 years), and a typically developing control group (n = 9, age = 16.6 ± 5 years). Hand aperture was computed to study the coordination of reach and grasp. Time-varying joint synergies within one upper limb were calculated using a novel technique based on principal component analysis to study intra-limb coordination. In the non-dominant arm, results indicate reduced coordination between reach and grasp in patients who could not lift the grasped object compared to those who could lift it. Lifters exhibit incoordination in distal upper extremity joints later in the movement and non-lifters lacked coordination throughout the movement and in the whole upper limb. The amount of atypical coordination correlates with dystonia severity in patients. Reduced coordination during movement may reflect deficits in the execution of simultaneous movements, motor planning, or muscle activation. Rehabilitation efforts can focus on particular time points when kinematic patterns deviate abnormally to improve functional reaching in individuals with childhood-onset dystonia. PMID:26208359

  15. Combined cognitive–behavioural and mindfulness programme for people living with dystonia: a proof-of-concept study

    PubMed Central

    Sandhu, H; Bernstein, C J; Davies, G; Tang, N K Y; Belhag, M; Tingle, A; Field, M; Foss, J; Lindahl, A; Underwood, M; Ellard, D R

    2016-01-01

    Objectives To design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population. Design A proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia. Setting Participants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community. Participants 14 participants consented to take part (2 withdrew prior to the starting of intervention). The average age was 60 years (range 44–77), 8 of whom were female. After drop-out, 9 participants completed the 3-day programme. Intervention A 3-day group residential programme. Primary and secondary outcome measures Process evaluation and interviews were carried out before and after the intervention to explore participant's views and expectations, as well as experiences of the intervention. Select questionnaires were completed at baseline, 1-month and 3-month follow-up. Results Although participants were not sure what to expect from the programme, they found it informative and for many this together with being in a group with other people with dystonia legitimised their condition. Mindfulness was accepted and adopted as a coping strategy. This was reflected in the 1-month follow-up. Conclusions We successfully delivered a 3-day residential programme to help those living with dystonia manage their condition. Further improvements are suggested. The quantitative outcome measures were acceptable to this group of patients with dystonia. PMID:27496234

  16. Increased long-latency reflex activity as a sufficient explanation for childhood hypertonic dystonia: a neuromorphic emulation study

    NASA Astrophysics Data System (ADS)

    Sohn, Won J.; Niu, Chuanxin M.; Sanger, Terence D.

    2015-06-01

    Objective. Childhood dystonia is a movement disorder that interferes with daily movements and can have a devastating effect on quality of life for children and their families. Although injury to basal ganglia is associated with dystonia, the neurophysiological mechanisms leading to the clinical manifestations of dystonia are not understood. Previous work suggested that long-latency stretch reflex (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We hypothesize that abnormal activity in motor cortices may cause an increase in the LLSR leading to hypertonia. Approach. We modeled two possibilities of hyperactive LLSR by either creating a tonic involuntary drive to cortex, or increasing the synaptic gain in cortical neurons. Both models are emulated using programmable very-large-scale-integrated-circuit hardware to test their sufficiency for producing dystonic symptoms. The emulation includes a joint with two Hill-type muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons. The muscles are regulated by a monosynaptic spinal pathway with 32 ms delay and a long-latency pathway with 64 ms loop-delay representing transcortical/supra-spinal connections. Main results. When the limb is passively stretched, both models produce involuntary resistance with increased antagonist EMG responses similar to human data; also the muscle relaxation is delayed similar to human data. Both models predict reduced range of motion in voluntary movements. Significance. Although our model is a highly simplified and limited representation of reflex pathways, it shows that increased activity of the LLSR is by itself sufficient to cause many of the features of hypertonic dystonia.

  17. Dopa responsive dystonia with Turner's syndrome: clinical, genetic, and neuropsychological studies in a family with a new mutation in the GTP-cyclohydrolase I gene

    PubMed Central

    Nitschke, M; Steinberger, D; Heberlein, I; Otto, V; Muller, U; Vieregge, P

    1998-01-01

    A 26 year old woman with dopa responsive dystonia and cytogenetically confirmed Turner's syndrome had bilateral globus pallidus hypointensity on brain MRI. Among the living members of a five generation pedigree the patient's mother and the mother's sister also had dopa responsive dystonia; a maternal grandfather had senile parkinsonism, his niece isolated postural tremor. No other family member had Turner's syndrome. A new missense mutation in exon I of the gene of GTP-cyclohydrolase I was found in the three family members with dopa responsive dystonia. With levodopa substitution the patients with dopa responsive dystonia improved clinically as well as in quantitative tests on hand tapping, verbal and performance IQ, concept formation, and set shifting abilities.

 PMID:9647318

  18. "ATP1A3" Mutations in Infants: A New Rapid-Onset Dystonia-Parkinsonism Phenotype Characterized by Motor Delay and Ataxia

    ERIC Educational Resources Information Center

    Brashear, Allison; Mink, Jonathan W.; Hill, Deborah F.; Boggs, Niki; McCall, W. Vaughn; Stacy, Mark A.; Snively, Beverly; Light, Laney S.; Sweadner, Kathleen J.; Ozelius, Laurie J.; Morrison, Leslie

    2012-01-01

    We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the "ATP1A3" gene. In adults, mutations in "ATP1A3" cause rapid-onset dystonia-Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and…

  19. Globus pallidus internus neuronal activity: a comparative study of linear and non-linear features in patients with dystonia or Parkinson's disease.

    PubMed

    Alam, M; Sanghera, M K; Schwabe, K; Lütjens, G; Jin, X; Song, J; von Wrangel, C; Stewart, R M; Jankovic, J; Grossman, R G; Darbin, O; Krauss, Joachim K

    2016-03-01

    Movement disorders such as Parkinson's disease (PD) and dystonia are associated with alterations of basal ganglia motor circuits and abnormal neuronal activity in the output nucleus, the globus pallidus internus (GPi). This study aims to compare the electrophysiological hallmarks for PD and dystonia in the linear and non-linear time stamp domains in patients who underwent microelectrode recordings during functional stereotactic surgery for deep brain stimulation (DBS) or pallidotomy. We analyzed single-unit neuronal activity in the posteroventral lateral region of the GPi in awake patients prior to pallidotomy or the implantation of DBS electrodes in 29 patients with PD (N = 83 neurons) and 13 patients with dystonia (N = 41 neurons) under comparable conditions. The discharge rate and the instantaneous frequency of the GPi in dystonia patients were significantly lower than in PD patients (P < 0.001), while the total number of bursts, the percentage of spikes in bursts and the mean duration of bursts were higher (P < 0.001). Further, non-linear analysis revealed higher irregularity or entropy in the data streams of GPi neurons of PD patients compared to the dystonia patients group (P < 0.001). This study indicates that both linear and non-linear features of neuronal activity in the human GPi differ between PD and dystonia. Our results may serve as the basis for future studies on linear and non-linear analysis of neuronal firing patterns in various movement disorders.

  20. A Rare Cervical Dystonia Mimic in Adults: Congenital Muscular Torticollis (Fibromatosis colli), a Follow-up.

    PubMed

    Uluer, Mehmet C; Bojovic, Branko

    2016-01-01

    Neglected or undiagnosed congenital muscular torticollis in adults is quite rare, although it is the third most common congenital deformity in the newborn (1). When left untreated at an early age, deficits in lateral and rotational range of motion can occur along with irreversible facial and skeletal deformities that develop over time. Subtle cases can go unnoticed until early adulthood, with predominant fibrotic replacement in the sternocleidomastoid (SCM) making physical therapy and chemodenervation mostly ineffective. Surgical intervention, in these cases, can prove effective in alleviating pain, improving function and cosmesis (2). We report an update on a previously reported case, misdiagnosed as cervical dystonia, which had undergone partial myectomy of the anterior belly of the SCM with some relief of symptoms but without total resolution after the correct diagnosis of fibromatosis colli (3).

  1. A Rare Cervical Dystonia Mimic in Adults: Congenital Muscular Torticollis (Fibromatosis colli), a Follow-up

    PubMed Central

    Uluer, Mehmet C.; Bojovic, Branko

    2016-01-01

    Neglected or undiagnosed congenital muscular torticollis in adults is quite rare, although it is the third most common congenital deformity in the newborn (1). When left untreated at an early age, deficits in lateral and rotational range of motion can occur along with irreversible facial and skeletal deformities that develop over time. Subtle cases can go unnoticed until early adulthood, with predominant fibrotic replacement in the sternocleidomastoid (SCM) making physical therapy and chemodenervation mostly ineffective. Surgical intervention, in these cases, can prove effective in alleviating pain, improving function and cosmesis (2). We report an update on a previously reported case, misdiagnosed as cervical dystonia, which had undergone partial myectomy of the anterior belly of the SCM with some relief of symptoms but without total resolution after the correct diagnosis of fibromatosis colli (3). PMID:26869987

  2. Somatosensory temporal discrimination tested in patients receiving botulinum toxin injection for cervical dystonia.

    PubMed

    Scontrini, Alessandra; Conte, Antonella; Fabbrini, Giovanni; Colosimo, Carlo; Di Stasio, Flavio; Ferrazzano, Gina; Berardelli, Alfredo

    2011-03-01

    We designed this study to find out more about the relationship between the sensory effects of Botulinum toxin type A (BTX) and the clinical benefits of BTX therapy in patients with cervical dystonia (CD). In 24 patients with CD, we tested sensory temporal discrimination (STD) in the affected and two unaffected body regions (neck, hand, and eye) before and 1 month after BTX injection. In 8 out of the 24 patients with CD, STDT values were tested bilaterally in the three body regions before, 1 and 2 months after BTX injection. As expected, STD testing disclosed altered STD threshold values in all three body regions tested (affected and unaffected by dystonic spasms) in patients with CD. STD threshold values remained unchanged at all time points of the follow-up in all CD patients. The lack of BTX-induced effects on STD thresholds suggests that STD recruits neural structures uninvolved in muscle spindle afferent activation.

  3. Cathodal transcranial direct current stimulation in children with dystonia: a pilot open-label trial.

    PubMed

    Young, Scott J; Bertucco, Matteo; Sheehan-Stross, Rebecca; Sanger, Terence D

    2013-10-01

    Studies suggest that dystonia is associated with increased motor cortex excitability. Cathodal transcranial direct current stimulation can temporarily reduce motor cortex excitability. To test whether stimulation of the motor cortex can reduce dystonic symptoms in children, we measured tracking performance and muscle overflow using an electromyogram tracking task before and after stimulation. Of 10 participants, 3 showed a significant reduction in overflow, and a fourth showed a significant reduction in tracking error. Overflow decreased more when the hand contralateral to the cathode performed the task than when the hand ipsilateral to the cathode performed the task. Averaged over all participants, the results did not reach statistical significance. These results suggest that cathodal stimulation may allow a subset of children to control muscles or reduce involuntary overflow activity. Further testing is needed to confirm these results in a blinded trial and identify the subset of children who are likely to respond.

  4. Paroxysmal dystonia and pathological laughter as a first manifestation of multiple sclerosis.

    PubMed

    Aguirregomozcorta, M; Ramió-Torrentà, Ll; Gich, J; Quiles, A; Genís, D

    2008-03-01

    Paroxysmal dystonia is an uncommon but well-established feature of multiple sclerosis (MS). Attacks can occur in established MS and may even occasionally be the initial symptom of this disorder. Pathological laughter is usually seen as a pseudobulbar palsy in some diffuse neurological diseases, but cases have been described, mostly in ischaemic attacks or tumours, where it is presented as bursts of laughter of variable duration. The pathogenesis of neither of the two phenomena has been fully established but both have been reported as being positive phenomena resulting from ectopic activation with ephaptic spread. We describe the first reported case of a paroxysmal hemidystonia together with bursts of pathological laughter as the first manifestation of MS.

  5. Severe Tardive Dystonia on Low Dose Short Duration Exposure to Atypical Antipsychotics: Factors Explored

    PubMed Central

    Chandra, Nilanjan C.; Sheth, Shabina A.; Mehta, Ritambhara Y.; Dave, Kamlesh R.

    2017-01-01

    Tardive dystonia (TD) is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics. PMID:28250568

  6. Ataxia with Parkinsonism and dystonia after intentional inhalation of liquefied petroleum gas

    PubMed Central

    Godani, Massimiliano; Canavese, Francesca; Migliorini, Sonia; Del Sette, Massimo

    2015-01-01

    The practice of inhaling liquefied petroleum gas (LPG) to commit suicide is uncommon and almost exclusively a prerogative of the prison population. Numerous cases of sudden deaths caused by intentional propane and/or butane inhalation have been described, but these cases survived and a description of the consequences is very rare. We describe a prisoner who survived after voluntary inhalation of LPG, and who developed ataxia, Parkinsonism, and dystonia. Brain MRI showed bilateral hyperintensity in the basal ganglia and in the cerebellar hemispheres. The clinical evolution and the MRI abnormalities are similar to those described in cases of poisoning by CO where the mechanism of brain injury is related to histotoxic hypoxia. We believe that LPG, considered until now a mixture of gas with low neurotoxic power, may have caused direct toxic damage to the brain, mediated by a mechanism of hypoxia, such as in CO intoxication. PMID:26005350

  7. Impairment of bidirectional synaptic plasticity in the striatum of a mouse model of DYT1 dystonia: role of endogenous acetylcholine

    PubMed Central

    Martella, Giuseppina; Tassone, Annalisa; Sciamanna, Giuseppe; Platania, Paola; Cuomo, Dario; Viscomi, Maria Teresa; Bonsi, Paola; Cacci, Emanuele; Biagioni, Stefano; Usiello, Alessandro; Bernardi, Giorgio; Sharma, Nutan

    2009-01-01

    DYT1 dystonia is a severe form of inherited dystonia, characterized by involuntary twisting movements and abnormal postures. It is linked to a deletion in the dyt1 gene, resulting in a mutated form of the protein torsinA. The penetrance for dystonia is incomplete, but both clinically affected and non-manifesting carriers of the DYT1 mutation exhibit impaired motor learning and evidence of altered motor plasticity. Here, we characterized striatal glutamatergic synaptic plasticity in transgenic mice expressing either the normal human torsinA or its mutant form, in comparison to non-transgenic (NT) control mice. Medium spiny neurons recorded from both NT and normal human torsinA mice exhibited normal long-term depression (LTD), whereas in mutant human torsinA littermates LTD could not be elicited. In addition, although long-term potentiation (LTP) could be induced in all the mice, it was greater in magnitude in mutant human torsinA mice. Low-frequency stimulation (LFS) can revert potentiated synapses to resting levels, a phenomenon termed synaptic depotentiation. LFS induced synaptic depotentiation (SD) both in NT and normal human torsinA mice, but not in mutant human torsinA mice. Since anti-cholinergic drugs are an effective medical therapeutic option for the treatment of human dystonia, we reasoned that an excess in endogenous acetylcholine could underlie the synaptic plasticity impairment. Indeed, both LTD and SD were rescued in mutant human torsinA mice either by lowering endogenous acetylcholine levels or by antagonizing muscarinic M1 receptors. The presence of an enhanced acetylcholine tone was confirmed by the observation that acetylcholinesterase activity was significantly increased in the striatum of mutant human torsinA mice, as compared with both normal human torsinA and NT littermates. Moreover, we found similar alterations of synaptic plasticity in muscarinic M2/M4 receptor knockout mice, in which an increased striatal acetylcholine level has been

  8. Negative Dystonia of the Palate: A Novel Entity and Diagnostic Consideration in Hypernasal Speech

    PubMed Central

    Sinclair, Catherine F.; Simonyan, Kristina; Brin, Mitchell F.; Blitzer, Andrew

    2016-01-01

    Objective To present the first documented series of patients with negative dystonia (ND) of the palate, including clinical symptoms, functional MRI findings, and management options. Study Design Case series ascertained from clinical research centers that evaluated patients with both hyperkinetic and hypokinetic movement disorders. Methods Between July 1983 and March 2013, data was collected on patient demographics, disease characteristics, functional MRI findings, long-term management options, and outcomes. We sought patients whose clinical examination demonstrated absent palatal movement on speaking, despite normal palatal activity on other activities. Results Five patients (2 males, 3 females) met clinical criteria. All patients presented with hypernasal speech without associated dysphagia. Clinical examination revealed absent palatal movement on speaking despite intact gag reflexes, normal palate elevation on swallowing, and normal cranial nerve examinations. Other cranial and/or limb dystonias were present in four patients (80.0%). Three patients (60.0%) had previously failed oral pharmacologic therapy. Two patients underwent functional magnetic resonance imaging (fMRI) studies, which demonstrated an overall decrease of cortical and subcortical activation during production of symptomatic syllables and asymptomatic coughing. Management included speech therapy (all patients) and palatal lift (2 patients) with limited improvement. Calcium hydroxyapatite injection (1 patient) into the soft palate and Passavants’ ridge was beneficial. Conclusions This is the first report of ND of the palate. Characteristic findings were task-specific absent palatal movement with speech, despite normal movement on swallowing, coughing, and an intact gag reflex, as well as disorder-specific decreased brain activation on functional MRI. A diagnosis of ND of the palate should be considered for patients who present with hypernasal speech. Level of Evidence 4. PMID:25646795

  9. Diffuse Decreased Gray Matter in Patients with Idiopathic Craniocervical Dystonia: A Voxel-Based Morphometry Study

    PubMed Central

    Piccinin, Camila C.; Piovesana, Luiza G.; Santos, Maria C. A.; Guimarães, Rachel P.; De Campos, Brunno M.; Rezende, Thiago J. R.; Campos, Lidiane S.; Torres, Fabio R.; Amato-Filho, Augusto C.; França, Marcondes C.; Lopes-Cendes, Iscia; Cendes, Fernando; D’Abreu, Anelyssa

    2015-01-01

    Background: Recent studies have addressed the role of structures other than the basal ganglia in the pathophysiology of craniocervical dystonia (CCD). Neuroimaging studies have attempted to identify structural abnormalities in CCD but a clear pattern of alteration has not been established. We performed whole-brain evaluation using voxel-based morphometry (VBM) to identify patterns of gray matter (GM) changes in CCD. Methods: We compared 27 patients with CCD matched in age and gender to 54 healthy controls. VBM was used to compare GM volumes. We created a two-sample t-test corrected for subjects’ age, and we tested with a level of significance of p < 0.001 and false discovery rate (FDR) correction (p < 0.05). Results: Voxel-based morphometry demonstrated significant reductions of GM using p < 0.001 in the cerebellar vermis IV/V, bilaterally in the superior frontal gyrus, precuneus, anterior cingulate and paracingulate, insular cortex, lingual gyrus, and calcarine fissure; in the left hemisphere in the supplementary motor area, inferior frontal gyrus, inferior parietal gyrus, temporal pole, supramarginal gyrus, rolandic operculum, hippocampus, middle occipital gyrus, cerebellar lobules IV/V, superior, and middle temporal gyri; in the right hemisphere, the middle cingulate and precentral gyrus. Our study did not report any significant result using the FDR correction. We also detected correlations between GM volume and age, disease duration, duration of botulinum toxin treatment, and the Marsden–Fahn dystonia scale scores. Conclusion: We detected large clusters of GM changes chiefly in structures primarily involved in sensorimotor integration, motor planning, visuospatial function, and emotional processing. PMID:25620953

  10. The 'yips' in golf: a continuum between a focal dystonia and choking.

    PubMed

    Smith, Aynsley M; Adler, Charles H; Crews, Debbie; Wharen, Robert E; Laskowski, Edward R; Barnes, Kelly; Valone Bell, Carolyn; Pelz, Dave; Brennan, Ruth D; Smith, Jay; Sorenson, Matthew C; Kaufman, Kenton R

    2003-01-01

    The definition of the 'yips' has evolved over time. It is defined as a motor phenomenon of involuntary movements affecting golfers. In this paper, we have extended the definition to encompass a continuum from the neurologic disorder of dystonia to the psychologic disorder of choking. In many golfers, the pathophysiology of the 'yips' is believed to be an acquired deterioration in the function of motor pathways (e.g. those involving the basal ganglia) which are exacerbated when a threshold of high stress and physiologic arousal is exceeded. In other golfers, the 'yips' seems to result from severe performance anxiety. Physically, the 'yips' is manifested by symptoms of jerks, tremors or freezing in the hands and forearms. These symptoms can result in: (i) a poor quality of golf performance (adds 4.9 strokes per 18 holes); (ii) prompt use of alcohol and beta-blockers; and (iii) contribute to attrition in golf. Golfers with the 'yips' average 75 rounds per year, although many 'yips'-affected golfers decrease their playing time or quit to avoid exposure to this embarrassing problem. While more investigation is needed to determine the cause of the 'yips', this review article summarises and organises the available research. A small study included in this paper describes the 'yips' phenomenon from the subjective experience of 'yips'-affected golfers. The subjective experience (n = 72) provides preliminary support for the hypothesis suggesting that the 'yips' is on a continuum. Based on the subjective definitions of 72 'yips'-affected golfers, the 'yips' was differentiated into type I (dystonia) and type II (choking). A theoretical model provides a guide for future research on golfers with either type I or type II 'yips'.

  11. Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation

    PubMed Central

    Kimberley, Teresa Jacobson; Borich, Michael R.; Schmidt, Rebekah; Carey, James R.; Gillick, Bernadette

    2016-01-01

    Objective Examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); present method for determining the optimal stimulation to increase inhibition in a given patient; and examine individual responses to prolonged intervention. Design A single-subject design to determine optimal parameters to increase inhibition for a given subject and to employ the selected parameters 1/wk for 6 weeks, with 1 wk follow up, to determine response. Setting Clinical research laboratory Participants A volunteer sample of 2 subjects with FHD. One participant had TMS responses indicating impaired inhibition, the other had responses within normal limits. Interventions 1200 pulses of 1 Hz rTMS delivered using 4 different stimulation site/intensity combinations: primary motor cortex (M1) at 90% or 110% resting motor threshold (RMT); dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as intervention. Main outcome measures Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short-latency intracortical inhibition and facilitation. Results The individual with baseline TMS responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, increase in CSP and subjective report of “moderate” symptom improvement at 1-wk follow-up. The individual with normal baseline responses failed to respond to the intervention. In both subjects, 90% RMT to PMd produced greatest lengthening of CSP and was used as intervention. Conclusions An individualized understanding of neurophysiologic measures may be indicators of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine 3 likely responders vs. non-responders. PMID:25256555

  12. Occurrence of Dysphagia Following Botulinum Toxin Injection in Parkinsonism-related Cervical Dystonia: A Retrospective Study

    PubMed Central

    Patterson, Addie; Almeida, Leonardo; Hess, Christopher W.; Martinez-Ramirez, Daniel; Okun, Michael S.; Rodriguez, Ramon L.; Rundle-Gonzalez, Valerie; Shukla, Aparna Wagle; Malaty, Irene A.

    2016-01-01

    Background The aim was to compare the occurrence of post-injection dysphagia in parkinsonism-related cervical dystonia (PRCD) versus cervical dystonia (CD) of other etiologies (non-PRCD). A secondary objective was to explore potential clinical differences between PRCD and non-PRCD and their respective responses to botulinum toxin (BoNT). Methods A cross-sectional chart review was carried out of patients treated for CD with Onabotulinumtoxin A at the University of Florida. We collected demographic information, dose of BoNT injected, patient-reported presence of dysphagia as a side effect, patient-perceived duration of benefit and efficacy according to the Clinical Global Impression Scale (CGIS). Results Of the 144 patients included, 24 patients were diagnosed with PRCD and 120 were diagnosed as non-PRCD. Data analysis showed no significant differences in number of weeks of benefit from BoNT (PRCD 9.1±3.7 versus non-PRCD 9.4±3.7 weeks, p = 0.830), BoNT dosage (PRCD 235.0±95.6 versus non-PRCD 263.7±101.3 units, p = 0.181), median CGIS score (median = 2 or “much improved” for both groups, p = 0.88), or the presence of dysphagia after BoNT (PRCD 17% versus non-PRCD 19 %, p = 0.753, n = 132). In a subgroup analysis of the non-PRCD group, patients who experienced dysphagia were older than those who did not (63.9±8.9 years versus 58.1±14.4 years, p = 0.02). Discussion Despite an increased baseline risk of dysphagia in patients with PRCD, BoNT appears to be equally safe and equally beneficial in PRCD and non-PRCD patients. PMID:27830106

  13. Motor cortical hyperexcitability in idiopathic scoliosis: could focal dystonia be a subclinical etiological factor?

    PubMed

    Doménech, Julio; Tormos, José María; Barrios, Carlos; Pascual-Leone, Alvaro

    2010-02-01

    The aetiology of idiopathic scoliosis (IS) remains unknown; however, there is a growing body of evidence suggesting that the spine deformity could be the expression of a subclinical nervous system disorder. A defective sensory input or an anomalous sensorimotor integration may lead to an abnormal postural tone and therefore the development of a spine deformity. Inhibition of the motor cortico-cortical excitability is abnormal in dystonia. Therefore, the study of cortico-cortical inhibition may shed some insight into the dystonia hypothesis regarding the pathophysiology of IS. Paired pulse transcranial magnetic stimulation was used to study cortico-cortical inhibition and facilitation in nine adolescents with IS, five teenagers with congenital scoliosis (CS) and eight healthy age-matched controls. The effect of a previous conditioning stimulus (80% intensity of resting motor threshold) on the amplitude of the motor-evoked potential induced by the test stimulus (120% of resting motor threshold) was examined at various interstimulus intervals (ISIs) in both abductor pollicis brevis muscles. The results of healthy adolescents and those with CS showed a marked inhibitory effect of the conditioning stimulus on the response to the test stimulus at interstimulus intervals shorter than 6 ms. These findings do not differ from those reported for normal adults. However, children with IS revealed an abnormally reduced cortico-cortical inhibition at the short ISIs. Cortico-cortical inhibition was practically normal on the side of the scoliotic convexity while it was significantly reduced on the side of the scoliotic concavity. In conclusion, these findings support the hypothesis that a dystonic dysfunction underlies in IS. Asymmetrical cortical hyperexcitability may play an important role in the pathogenesis of IS and represents an objective neurophysiological finding that could be used clinically.

  14. Mental rotation of body parts and non-corporeal objects in patients with idiopathic cervical dystonia.

    PubMed

    Fiorio, Mirta; Tinazzi, Michele; Ionta, Silvio; Fiaschi, Antonio; Moretto, Giuseppe; Edwards, Mark J; Bhatia, Kailash P; Aglioti, Salvatore M

    2007-06-11

    Mental rotation of body parts is performed through inner simulation of actual movements, and is likely to rely upon cortical and subcortical systems (e.g. motor and premotor areas and basal ganglia) involved in motor planning and execution. Studies indicate that sensory and motor deficits, such as for example pain, limb amputation or focal hand dystonia, bring about a specific impairment in mental rotation of the affected body parts. Here we explored the ability of patients affected by idiopathic cervical dystonia (CD) to mentally rotate affected (neck) and unaffected (hands and feet) body districts. The experimental stimuli consisted of realistic photos of left or right hands or feet and the head of a young men with a black patch on the left or the right eye. As non-corporeal stimulus the front view of a car with a black patch on the left or the right headlight was used. The stimuli were presented at six different degrees of orientations. Twelve CD patients and 12 healthy participants were asked to verbally report whether the hands or feet were left or right, or whether the patch was on the left or the right eye or headlight. Reaction times and accuracy in performing the laterality tasks on the four stimuli were collected. Results showed that CD patients are slow in mental rotation of stimuli representing body parts, namely hand, foot and head. This abnormality was not due to a general impairment in mental rotation per se, since patients' ability to rotate a non-corporeal object (a car) was not significantly different from that of healthy participants. We posit that the deficit in mental rotation of body parts in CD patients may derive from a defective integration of body- and world-related knowledge, a process that is likely to allow a general representation of "me in the external world".

  15. Does dystonic muscle activity affect sense of effort in cervical dystonia?

    PubMed Central

    Carment, Loïc; Maier, Marc A.; Sangla, Sophie; Guiraud, Vincent; Mesure, Serge; Vidailhet, Marie

    2017-01-01

    Background Focal dystonia has been associated with deficient processing of sense of effort cues. However, corresponding studies are lacking in cervical dystonia (CD). We hypothesized that dystonic muscle activity would perturb neck force control based on sense of effort cues. Methods Neck extension force control was investigated in 18 CD patients with different clinical features (7 with and 11 without retrocollis) and in 19 control subjects. Subjects performed force-matching and force-maintaining tasks at 5% and 20% of maximum voluntary contraction (MVC). Three task conditions were tested: i) with visual force feedback, ii) without visual feedback (requiring use of sense of effort), iii) without visual feedback, but with neck extensor muscle vibration (modifying muscle afferent cues). Trapezius muscle activity was recorded using electromyography (EMG). Results CD patients did not differ in task performance from healthy subjects when using visual feedback (ANOVA, p>0.7). In contrast, when relying on sense of effort cues (without visual feedback, 5% MVC), force control was impaired in patients without retrocollis (p = 0.006), but not in patients with retrocollis (p>0.2). Compared to controls, muscle vibration without visual feedback significantly affected performance in patients with retrocollis (p<0.001), but not in patients without retrocollis. Extensor EMG during rest, included as covariate in ANOVA, explained these group differences. Conclusion This study shows that muscle afferent feedback biases sense of effort cues when controlling neck forces in patients with CD. The bias acts on peripheral or central sense of effort cues depending on whether the task involves dystonic muscles. This may explain why patients with retrocollis more accurately matched isometric neck extension forces. This highlights the need to consider clinical features (pattern of dystonic muscles) when evaluating sensorimotor integration in CD. PMID:28192488

  16. Motor cortical hyperexcitability in idiopathic scoliosis: could focal dystonia be a subclinical etiological factor?

    PubMed Central

    Tormos, José María; Barrios, Carlos; Pascual-Leone, Alvaro

    2009-01-01

    The aetiology of idiopathic scoliosis (IS) remains unknown; however, there is a growing body of evidence suggesting that the spine deformity could be the expression of a subclinical nervous system disorder. A defective sensory input or an anomalous sensorimotor integration may lead to an abnormal postural tone and therefore the development of a spine deformity. Inhibition of the motor cortico-cortical excitability is abnormal in dystonia. Therefore, the study of cortico-cortical inhibition may shed some insight into the dystonia hypothesis regarding the pathophysiology of IS. Paired pulse transcranial magnetic stimulation was used to study cortico-cortical inhibition and facilitation in nine adolescents with IS, five teenagers with congenital scoliosis (CS) and eight healthy age-matched controls. The effect of a previous conditioning stimulus (80% intensity of resting motor threshold) on the amplitude of the motor-evoked potential induced by the test stimulus (120% of resting motor threshold) was examined at various interstimulus intervals (ISIs) in both abductor pollicis brevis muscles. The results of healthy adolescents and those with CS showed a marked inhibitory effect of the conditioning stimulus on the response to the test stimulus at interstimulus intervals shorter than 6 ms. These findings do not differ from those reported for normal adults. However, children with IS revealed an abnormally reduced cortico-cortical inhibition at the short ISIs. Cortico-cortical inhibition was practically normal on the side of the scoliotic convexity while it was significantly reduced on the side of the scoliotic concavity. In conclusion, these findings support the hypothesis that a dystonic dysfunction underlies in IS. Asymmetrical cortical hyperexcitability may play an important role in the pathogenesis of IS and represents an objective neurophysiological finding that could be used clinically. PMID:20033462

  17. Treatment and Physiology in Parkinson’s Disease and Dystonia: Using TMS to Uncover the Mechanisms of Action

    PubMed Central

    Shukla, Aparna Wagle; Vaillancourt, David E.

    2014-01-01

    Transcranial magnetic stimulation (TMS) has served as an important technological breakthrough in the field of movement disorders physiology over the last three decades. TMS has grown popular due to the ease of application as well as its painless and noninvasive character. The technique has shed important insights into understanding the pathophysiology of movement disorders particularly Parkinson’s disease and dystonia. The basic applications have included the study of motor cortex excitability, functioning of excitatory and inhibitory circuits, study of interactions between sensory and motor systems, and the plasticity response of the brain. TMS has also made important contributions in understanding response to treatments such as the dopaminergic medications, botulinium toxin injections and deep brain stimulation surgery. This review summarizes the knowledge gained to date with TMS in Parkinson’s disease and dystonia and highlights the current challenges in utilization of TMS technology. PMID:24771105

  18. Alternating hemidystonia following traumatic brain injury as an unusual presentation of paroxysmal autonomic instability with dystonia syndrome

    PubMed Central

    Buerger, Kelly J; Salazar, Richard

    2014-01-01

    A 20-year-old man presented to the neurotrauma intensive care unit following blunt head injury. MRI revealed subarachnoid haemorrhage and multiple intraparenchymal haemorrhages suggesting severe brain injury. During recovery, the patient displayed intermittent episodes of alternating hemibody spasms with decerebrate/decorticate dystonic posturing. Episodes presented with autonomic dysregulation including hyperthermia, diaphoresis, tachypnoea, tachycardia and hypertension. Concern for seizure activity prompted simultaneous video monitoring and EEG testing. Results were without epileptiform activity suggesting against seizure as cause for alternating hemibody spasms. Paroxysmal autonomic instability with dystonia (PAID) was considered despite the unusual presentation. Intravenous hydromorphone was used for treatment, which relieved symptoms of autonomic dysregulation and dystonic posturing. PAID syndrome was diagnosed based on presentation with intermittent episodes of dystonia, autonomic dysregulation, absence of epileptiform activity and rapid response to opioid treatment. This case illustrates the clinical variability of this uncommon syndrome because alternating hemidystonia as main manifestation has not been previously described. PMID:25414239

  19. Craniocervical dystonia questionnaire (CDQ-24): development and validation of a disease-specific quality of life instrument

    PubMed Central

    Muller, J; Wissel, J; Kemmler, G; Voller, B; Bodner, T; Schneider, A; Wenning, G; Poewe, W

    2004-01-01

    Objective: To develop and test a questionnaire for measuring quality of life in patients with craniocervical dystonia. Methods: A 29-item pool was developed based on semi-structured interviews of patients with cervical dystonia (CD) and blepharospasm (BSP). This preliminary questionnaire was administered to 203 consecutive patients with CD and BSP from Austrian dystonia and botulinum toxin outpatient clinics. For scale generation, a combination of exploratory factor and cluster analysis was applied. This resulted in the 24-item version of the instrument (CDQ-24) based on five subscales: Stigma, Emotional wellbeing, Pain, Activities of daily living, and Social/family life. The validity and reliability of the CDQ-24 was assessed in 231 consecutive patients with CD and BSP different from those examined with the preliminary questionnaire. This second survey included the CDQ-24, a generic QoL instrument (SF-36) and clinical rating scales. Sensitivity to change was analysed in 51 previously untreated (de novo) patients four weeks and one year following the first botulinum toxin treatment. Results: Internal consistency reliability was satisfactory for all subscales, with values of Cronbach's α ranging from 0.77 to 0.89. The CDQ-24 subscales showed moderate to high correlations with those SF-36 subscales measuring similar aspects (Pearson's correlation r = 0.50–0.73; p<0.001, each). Sensitivity to change was confirmed by highly significant improvements of all CDQ-24 subscores in the de novo patients from baseline to four week follow up. One year follow up data revealed a stable improvement. Conclusion: The CDQ-24 is the first fully validated and disease specific questionnaire to evaluate quality of life of patients with cervical dystonia and blepharospasm and we propose its use in clinical trials as well as in daily clinical practice. PMID:15090572

  20. Pregnancy and Delivery in a Generalized Dystonia Patient Treated with Internal Globus Pallidal Deep Brain Stimulation: a Case Report

    PubMed Central

    2017-01-01

    Internal globus pallidus (GPi) deep brain stimulation (DBS) has been widely accepted as an effective treatment modality of medically refractory dystonia. However, there have been few studies regarding the safety issue of pregnancy and childbirth related with DBS. This report describes a female patient who was pregnant and delivered a baby after GPi DBS surgery. A 33-year-old female patient with acquired generalized dystonia underwent bilateral GPi DBS implantation. She obtained considerable improvement in both movement and disability after DBS implantation. Four years later, she was pregnant and the obstetricians consulted us about the safety of the delivery. At 38-weeks into pregnancy, a scheduled caesarian section was carried out under general anesthesia. After induction using thiopental and succinylcholine, intubation was done quickly, followed by DBS turn off. For hemostasis, only bipolar electrocautery was used. Before awakening from the anesthesia, DBS was turned on as the same parameters previously adjusted. After delivery, she could feed her baby by herself, because the dystonia of left upper extremity and hand was improved. Until now, she has been showing continual improvement and being good at housework, carrying for children, with no trouble in daily life. This observation indicates that the patients who underwent DBS could safely be pregnant and deliver a baby. PMID:27914146

  1. Quality of life in cervical dystonia after treatment with botulinum toxin A: a 24-week prospective study

    PubMed Central

    Kongsaengdao, Subsai; Maneeton, Benchalak; Maneeton, Narong

    2017-01-01

    Objective This study aimed to identify possible improvements in disease-specific health-related quality of life (HRQoL) after multiple injections of botulinum toxin A over 24 weeks in Thai cervical dystonia (CD) patients. Materials and methods A 24-week prospective study comparing HRQoL of Thai CD patients before and after multiple injections of botulinum toxin A at 3-month intervals was performed. Disease-specific HRQoL was assessed by using the Cervical Dystonia Impact Profile-58 questionnaire (CDIP-58) and the Craniocervical Dystonia Questionnaire-24 (CDQ-24). General HRQoL was assessed by using the Medical Outcomes’ 36-Item Short Form Health Survey (SF-36) and the EuroQoL 5-dimension questionnaire (EQ-5D). All the assessments were performed before and after the 24-week treatment period. Results A total of 20 CD patients were enrolled in this study from April to December 2011. CDIP-58 and CDQ-24 scores, which assess disease-specific HRQoL, showed a significant improvement after 24 weeks of treatment by botulinum toxin A (P<0.001). However, EQ-5D and SF-36 scores, which assess general HRQoL, showed no significant improvement after the treatment (P>0.05). Conclusion CD patients’ disease-specific HRQoL improved after being treated with multiple botulinum toxin A injections. However, general HRQoL was not improved. PMID:28138245

  2. Clinical and Epidemiological Correlates of Task-Specific Dystonia in a Large Cohort of Brazilian Music Players

    PubMed Central

    Moura, Rita C.; de Carvalho Aguiar, Patrícia Maria; Bortz, Graziela; Ferraz, Henrique Ballalai

    2017-01-01

    Musician’s dystonia is a task-specific dystonia (TSD) worldwide disabling disorder, and most of the affected individuals may have severe difficulty to play their instrument. Many professional music players may have to quit working as a player. The objective of the present study was to evaluate the clinical characteristics and frequency of TSD in Brazilian music players and to promote awareness of this condition among musicians. We visited orchestras and music schools delivering lectures on TSD and about the scope of our survey. Musicians were invited to answer a questionnaire, and those with possible neurological dysfunction associated with musical performance were recorded by video while playing the instrument. We visited 51 orchestras and music schools in 19 Brazilian cities between March 2013 and March 2015. We collected 2,232 questionnaires, and 72 subjects with suspicion of dystonia were video recorded during specific tasks and evaluated regarding motor impairment. Forty-nine individuals (2.2%) were diagnosed as having TSD (mean age 36.4 years; 92% male). The instruments most associated with TSD were acoustic guitar (36.7%) and brass instruments (30.6%). We concluded that Brazilian TSD music players are mainly male, classical music professionals, around 30 years of age, with arms, hands, or oromandibular muscles affected. TSD is a neurological condition that can impair musical performance and should receive more attention from musicians, teachers, and health professionals. PMID:28321203

  3. Clinical and Epidemiological Correlates of Task-Specific Dystonia in a Large Cohort of Brazilian Music Players.

    PubMed

    Moura, Rita C; de Carvalho Aguiar, Patrícia Maria; Bortz, Graziela; Ferraz, Henrique Ballalai

    2017-01-01

    Musician's dystonia is a task-specific dystonia (TSD) worldwide disabling disorder, and most of the affected individuals may have severe difficulty to play their instrument. Many professional music players may have to quit working as a player. The objective of the present study was to evaluate the clinical characteristics and frequency of TSD in Brazilian music players and to promote awareness of this condition among musicians. We visited orchestras and music schools delivering lectures on TSD and about the scope of our survey. Musicians were invited to answer a questionnaire, and those with possible neurological dysfunction associated with musical performance were recorded by video while playing the instrument. We visited 51 orchestras and music schools in 19 Brazilian cities between March 2013 and March 2015. We collected 2,232 questionnaires, and 72 subjects with suspicion of dystonia were video recorded during specific tasks and evaluated regarding motor impairment. Forty-nine individuals (2.2%) were diagnosed as having TSD (mean age 36.4 years; 92% male). The instruments most associated with TSD were acoustic guitar (36.7%) and brass instruments (30.6%). We concluded that Brazilian TSD music players are mainly male, classical music professionals, around 30 years of age, with arms, hands, or oromandibular muscles affected. TSD is a neurological condition that can impair musical performance and should receive more attention from musicians, teachers, and health professionals.

  4. Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons

    PubMed Central

    Pappas, Samuel S; Darr, Katherine; Holley, Sandra M; Cepeda, Carlos; Mabrouk, Omar S; Wong, Jenny-Marie T; LeWitt, Tessa M; Paudel, Reema; Houlden, Henry; Kennedy, Robert T; Levine, Michael S; Dauer, William T

    2015-01-01

    Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twisting movements that emerge during juvenile CNS maturation. The onset of these movements coincides with selective degeneration of dorsal striatal large cholinergic interneurons (LCI), and surviving LCI exhibit morphological, electrophysiological, and connectivity abnormalities. Consistent with the importance of this LCI pathology, murine dystonic-like movements are reduced significantly with an antimuscarinic agent used clinically, and we identify cholinergic abnormalities in postmortem striatal tissue from DYT1 dystonia patients. These findings demonstrate that dorsal LCI have a unique requirement for torsinA function during striatal maturation, and link abnormalities of these cells to dystonic-like movements in an overtly symptomatic animal model. DOI: http://dx.doi.org/10.7554/eLife.08352.001 PMID:26052670

  5. Deep brain stimulation for myoclonus-dystonia syndrome with double mutations in DYT1 and DYT11

    PubMed Central

    Wang, Jia-Wei; Li, Ji-Ping; Wang, Yun-Peng; Zhang, Xiao-Hua; Zhang, Yu-Qing

    2017-01-01

    Myoclonus-dystonia syndrome (MDS) is a rare autosomal dominant inherited disorder characterized by the presentation of both myoclonic jerks and dystonia. Evidence is emerging that deep brain stimulation (DBS) may be a promising treatment for MDS. However, there are no studies reporting the effects of DBS on MDS with double mutations in DYT1 and DYT11. Two refractory MDS patients with double mutations were treated between 2011 and 2015 in our center. Genetic testing for DYT1 and DYT11 was performed through polymerase chain reaction amplification and direct sequencing of the specific exons of genes. For the first patient, initial bilateral ventral intermediate thalamus nucleus (Vim) DBS was performed. Because of worsening dystonia after initial improvement in symptoms, subsequent bilateral globus pallidus internus (GPi) DBS was offered at 43 months after initial surgery, which reversed the deterioration and restored the motor function. For the second patient, initial improvement in motor symptoms and quality of life was sustained at the follow-up 6 months after bilateral Vim DBS treatment. Thus, DBS may be an effective therapeutic option for MDS, even in patients with double mutations. Moreover, GPi DBS may be used as a supplementary treatment when initial Vim DBS fails to control MDS symptoms. PMID:28102337

  6. [Case of oromandibular dystonia presenting with severe impairment of mouth-opening, and a marked effect by administration of baclofen].

    PubMed

    Ikawa, Masamichi; Yoneda, Makoto; Nakagawa, Hiroto; Kuriyama, Masaru

    2006-09-01

    We report a 67-year-old woman with idiopathic oromandibular dystonia (OMD). She could neither open the mouth nor take meals due to involuntarily strong mouth-closing. The movement of face, pharynx and tongue were normal, and she could open the mouth slightly when jaw and cheek were touched (sensory trick). Chvostek sign and Trousseau sign were negative, and opisthotonus was not recognized. The laboratory data including calcium, phosphorous and cerebrospinal fluid were within normal limits, head and cervical MRI, temporomandibular joints-Xp and needle electromyography were normal. The surface electromyography revealed that masseter and chin muscles contracted synchronously. This result meant dystonia around the mouth. The clinical course and physical examination did not support the diagnosis of tetanus, tetany or bulldog response. She was diagnosed as OMD. She had peroral administration of baclofen, because this drug is a GABA-derivative and acts as a muscular relaxant. Her clinical symptoms and dystonic pattern on the surface electromyography improved markedly after the administration. Baclofen is an effective drug for treatment of oromandibular dystonia.

  7. Modulation of Muscle Tone and Sympathovagal Balance in Cervical Dystonia Using Percutaneous Stimulation of the Auricular Vagus Nerve.

    PubMed

    Kampusch, Stefan; Kaniusas, Eugenijus; Széles, Jozsef C

    2015-10-01

    Primary cervical dystonia is characterized by abnormal, involuntary, and sustained contractions of cervical muscles. Current ways of treatment focus on alleviating symptomatic muscle activity. Besides pharmacological treatment, in severe cases patients may receive neuromodulative intervention such as deep brain stimulation. However, these (highly invasive) methods have some major drawbacks. For the first time, percutaneous auricular vagus nerve stimulation (pVNS) was applied in a single case of primary cervical dystonia. Auricular vagus nerve stimulation was already shown to modulate the (autonomous) sympathovagal balance of the body and proved to be an effective treatment in acute and chronic pain, epilepsy, as well as major depression. pVNS effects on cervical dystonia may be hypothesized to rely upon: (i) the alteration of sensory input to the brain, which affects structures involved in the genesis of motoric and nonmotoric dystonic symptoms; and (ii) the alteration of the sympathovagal balance with a sustained impact on involuntary movement control, pain, quality of sleep, and general well-being. The presented data provide experimental evidence that pVNS may be a new alternative and minimally invasive treatment in primary cervical dystonia. One female patient (age 50 years) suffering from therapy refractory cervical dystonia was treated with pVNS over 20 months. Significant improvement in muscle pain, dystonic symptoms, and autonomic regulation as well as a subjective improvement in motility, sleep, and mood were achieved. A subjective improvement in pain recorded by visual analog scale ratings (0-10) was observed from 5.42 to 3.92 (medians). Muscle tone of the mainly affected left and right trapezius muscle in supine position was favorably reduced by about 96%. Significant reduction of muscle tone was also achieved in sitting and standing positions of the patient. Habituation to stimulation leading to reduced stimulation efficiency was observed and

  8. Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia

    PubMed Central

    Kim, Edward Y.; Hettich, Jasmin; Mempel, Thorsten R.; Breakefield, Xandra O.; Irimia, Daniel

    2014-01-01

    Background Microfluidic platforms for quantitative evaluation of cell biologic processes allow low cost and time efficient research studies of biological and pathological events, such as monitoring cell migration by real-time imaging. In healthy and disease states, cell migration is crucial in development and wound healing, as well as to maintain the body's homeostasis. New Method The microfluidic chambers allow precise measurements to investigate whether fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary neurologic disease - DYT1 dystonia, have decreased migration properties when compared to control cells. Results We observed that fibroblasts from DYT1 patients showed abnormalities in basic features of cell migration, such as reduced velocity and persistence of movement. Comparison with Existing Method The microfluidic method enabled us to demonstrate reduced polarization of the nucleus and abnormal orientation of nuclei and Golgi inside the moving DYT1 patient cells compared to control cells, as well as vectorial movement of single cells. Conclusion We report here different assays useful in determining various parameters of cell migration in DYT1 patient cells as a consequence of the TOR1A gene mutation, including a microfluidic platform, which provides a means to evaluate real-time vectorial movement with single cell resolution in a three-dimensional environment. PMID:24880044

  9. Long-term efficacy and safety of botulinum toxin injections in dystonia.

    PubMed

    Ramirez-Castaneda, Juan; Jankovic, Joseph

    2013-02-04

    Local chemodenervation with botulinum toxin (BoNT) injections to relax abnormally contracting muscles has been shown to be an effective and well-tolerated treatment in a variety of movement disorders and other neurological and non-neurological disorders. Despite almost 30 years of therapeutic use, there are only few studies of patients treated with BoNT injections over long period of time. These published data clearly support the conclusion that BoNT not only provides safe and effective symptomatic relief of dystonia but also long-term benefit and possibly even favorably modifying the natural history of this disease. The adverse events associated with chronic, periodic exposure to BoNT injections are generally minor and self-limiting. With the chronic use of BoNT and an expanding list of therapeutic indications, there is a need to carefully examine the existing data on the long-term efficacy and safety of BoNT. In this review we will highlight some of the aspects of long-term effects of BoNT, including efficacy, safety, and immunogenicity.

  10. Cholinergic dysfunction alters synaptic integration between thalamostriatal and corticostriatal inputs in DYT1 dystonia.

    PubMed

    Sciamanna, Giuseppe; Tassone, Annalisa; Mandolesi, Georgia; Puglisi, Francesca; Ponterio, Giulia; Martella, Giuseppina; Madeo, Graziella; Bernardi, Giorgio; Standaert, David G; Bonsi, Paola; Pisani, Antonio

    2012-08-29

    Projections from thalamic intralaminar nuclei convey sensory signals to striatal cholinergic interneurons. These neurons respond with a pause in their pacemaking activity, enabling synaptic integration with cortical inputs to medium spiny neurons (MSNs), thus playing a crucial role in motor function. In mice with the DYT1 dystonia mutation, stimulation of thalamostriatal axons, mimicking a response to salient events, evoked a shortened pause and triggered an abnormal spiking activity in interneurons. This altered pattern caused a significant rearrangement of the temporal sequence of synaptic activity mediated by M(1) and M(2) muscarinic receptors in MSNs, consisting of an increase in postsynaptic currents and a decrease of presynaptic inhibition, respectively. Consistent with a major role of acetylcholine, either lowering cholinergic tone or antagonizing postsynaptic M(1) muscarinic receptors normalized synaptic activity. Our data demonstrate an abnormal time window for synaptic integration between thalamostriatal and corticostriatal inputs, which might alter the action selection process, thereby predisposing DYT1 gene mutation carriers to develop dystonic movements.

  11. Focal dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE)

    PubMed Central

    Perruchoud, David; Murray, Micah M.; Lefebvre, Jeremie; Ionta, Silvio

    2014-01-01

    Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized by sensory and motor deficits in the absence of basic motor impairments. Despite the fundamental impact of sensory-motor integration mechanisms on daily life, the general principles of healthy and pathological anatomic–functional organization of sensory-motor integration remain to be clarified. Based on the available data from experimental psychology, neurophysiology, and neuroimaging, we propose a bio-computational model of sensory-motor integration: the Sensory-Motor Integrative Loop for Enacting (SMILE). Aiming at direct therapeutic implementations and with the final target of implementing novel intervention protocols for motor rehabilitation, our main goal is to provide the information necessary for further validating the SMILE model. By translating neuroscientific hypotheses into empirical investigations and clinically relevant questions, the prediction based on the SMILE model can be further extended to other pathological conditions characterized by impaired sensory-motor integration. PMID:24999327

  12. Losing dexterity: patterns of impaired coordination of finger movements in musician’s dystonia

    PubMed Central

    Furuya, Shinichi; Tominaga, Kenta; Miyazaki, Fumio; Altenmüller, Eckart

    2015-01-01

    Extensive training can bring about highly-skilled action, but may also impair motor dexterity by producing involuntary movements and muscular cramping, as seen in focal dystonia (FD) and tremor. To elucidate the underlying neuroplastic mechanisms of FD, the present study addressed the organization of finger movements during piano performance in pianists suffering from the condition. Principal component (PC) analysis identified three patterns of fundamental joint coordination constituting finger movements in both patients and controls. The first two coordination patterns described less individuated movements between the “dystonic” finger and key-striking fingers for patients compared to controls. The third coordination pattern, representing the individuation of movements between the middle and ring fingers, was evident during a sequence of strikes with these fingers in controls, which was absent in the patients. Consequently, rhythmic variability of keystrokes was more pronounced during this sequence of strikes for the patients. A stepwise multiple-regression analysis further identified greater variability of keystrokes for individuals displaying less individuated movements between the affected and striking fingers. The findings suggest that FD alters dexterous joint coordination so as to lower independent control of finger movements, and thereby degrades fine motor control. PMID:26289433

  13. Imaging insights into basal ganglia function, Parkinson’s disease, and dystonia

    PubMed Central

    Stoessl, A. Jon; Lehericy, Stephane; Strafella, Antonio P.

    2015-01-01

    Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson’s disease from healthy controls, and show great promise for differentiation between Parkinson’s disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson’s disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson’s disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression. PMID:24954673

  14. Eyes on MEGDEL: distinctive basal ganglia involvement in dystonia deafness syndrome.

    PubMed

    Wortmann, Saskia B; van Hasselt, Peter M; Barić, Ivo; Burlina, Alberto; Darin, Niklas; Hörster, Friederike; Coker, Mahmut; Ucar, Sema Kalkan; Krumina, Zita; Naess, Karin; Ngu, Lock H; Pronicka, Ewa; Riordan, Gilian; Santer, Rene; Wassmer, Evangeline; Zschocke, Johannes; Schiff, Manuel; de Meirleir, Linda; Alowain, Mohammed A; Smeitink, Jan A M; Morava, Eva; Kozicz, Tamas; Wevers, Ron A; Wolf, Nicole I; Willemsen, Michel A

    2015-04-01

    Pediatric movement disorders are still a diagnostic challenge, as many patients remain without a (genetic) diagnosis. Magnetic resonance imaging (MRI) pattern recognition can lead to the diagnosis. MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739) is a clinically and biochemically highly distinctive dystonia deafness syndrome accompanied by 3-methylglutaconic aciduria, severe developmental delay, and progressive spasticity. Mutations are found in SERAC1, encoding a phosphatidylglycerol remodeling enzyme essential for both mitochondrial function and intracellular cholesterol trafficking. Based on the homogenous phenotype, we hypothesized an accordingly characteristic MRI pattern. A total of 43 complete MRI studies of 30 patients were systematically reevaluated. All patients presented a distinctive brain MRI pattern with five characteristic disease stages affecting the basal ganglia, especially the putamen. In stage 1, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an "eye" that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. This "eye" was found in all patients with MEGDEL syndrome during a specific age range, and has not been reported in other disorders, making it pathognomonic for MEDGEL and allowing diagnosis based on MRI findings.

  15. Physical therapy program for cervical dystonia: a study of 20 cases

    PubMed Central

    Queiroz, Mariana Araujo Ribeiro; Chien, Hsin Fen; Sekeff-Sallem, Flávio Augusto; Barbosa, Egberto Reis

    2012-01-01

    Summary Botulinum toxin (BTX) is the best therapeutic option in patients with cervical dystonia (CD), but physical therapy (PT) can be added to the treatment to achieve better results. Forty of our 70 patients with CD were enrolled in a controlled open study. Subjects were divided into two groups: G1 (intervention group comprising patients receiving BTX and PT) and G2 (control group comprising patients receiving BTX only). Both groups were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the 36-Item Short-Form Health Survey (SF-36). On the TWSTRS, significant improvements in disease severity were seen in G1 and G2 but significant improvements on the pain and disability subscales were seen only in G1 patients. There was a significant difference only on the pain sub-scale between G2 and G1 following treatment. An analysis of the physical aspects of SF-36 showed significant improvement in G1 on three subscales. An intergroup difference was also seen on two subscales. Regarding emotional aspects, G1 showed a significant improvement on three subscales. A significant difference on two subscales was also seen between G2 and G1 following treatment. BTX plus PT treatment achieved symptom relief in patients with CD and improved their quality of life. PMID:23402680

  16. Speed-accuracy testing on the Apple iPad provides a quantitative test of upper extremity motor performance in children with dystonia.

    PubMed

    Bertucco, Matteo; Sanger, Terence D

    2014-11-01

    The currently available scales for quantitative measurement of the severity of childhood dystonia require human observer ratings and provide poor granularity in the scores for individual limbs. We evaluated the use of new-generation high-quality touchscreens (an iPad) according with the Fitts law, which is a mathematical model that takes into account the relation between movement time and the task accuracy. We compared the abilities of healthy subjects and children with dystonia. The linear relation described by Fitts law held for all the groups. The movement time and the information transmitted were age and severity related. Our results provide evidence for the usability and validity of using Fitts law as a quantitative diagnostic tool in children with dystonia. Furthermore, testing on touchscreen tablets may help to guide the design of user interfaces to maximize the communication rate for children who depend upon assistive communication devices.

  17. Bilateral subthalamic nucleus deep brain stimulation for refractory total body dystonia secondary to metabolic autopallidotomy in a 4-year-old boy with infantile methylmalonic acidemia: case report.

    PubMed

    Chakraborti, Santo; Hasegawa, Harutomo; Lumsden, Daniel E; Ali, Wisam; Kaminska, Margaret; Lin, Jean-Pierre; Ashkan, Keyoumars

    2013-10-01

    The methylmalonic acidemias (MMAs) are a group of inborn errors of metabolism resulting in the accumulation of methylmalonic acid in body tissues and fluids. A recognized complication of MMA is bilateral liquefaction of the globus pallidi, resulting in a fulminant total body dystonia of childhood often refractory to medical treatment. This case of total body dystonia due to MMA in a 4-year-old boy had been medically refractory for 15 months. Complete metabolic destructive liquefaction of the pallidi, that is, autopallidotomy, necessitated an alternative, bilateral subthalamic nucleus (STN) target for deep brain stimulation (DBS) with a marked improvement in dystonia and reduction in pain. The case illustrates the efficacy of STN DBS in this condition and the technical challenges in targeting the STN in a small child.

  18. Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system?

    PubMed Central

    Caparros-Lefebvre, D; Destee, A; Petit, H

    1997-01-01

    BACKGROUND—Striatal necrosis has been related to various clinical syndromes, with acute or chronic progression, and juvenile or late occurrence, but the most common type is Leigh's encephalopathy.
METHODS—Between 1967 and 1995, six out of seven related patients with chronic familial dystonia were examined. MRIs were performed in four, between 1992-1994. The seven members, affected over three generations, were the father, three daughters (one surviving), and three surviving grandsons.
RESULTS—The leading symptoms were gait disorders and dystonia in all, dysarthria in six, verbal and motor stereotypies in two, and parkinsonian and cerebellar signs in three. Optic neuropathy was found in three. A frontal lobe syndrome without amnesia occurred in two. Symptoms occurred between the second and the fifth decade, with progressive deterioration. Magnetic resonance imaging, performed in four, showed in the two patients with severe neurological signs diffuse striatopallidal abnormal hyposignal (comparable with CSF signal) in T1 weighted images, suggesting extensive necrosis of the striatum and pallidum, associated with thalamo-subthalamo-rubro-dentato-nigral and substantia innominata hypersignals in T2 weighted images suggesting gliosis in these respective areas. The same images were described to a lesser extent in a third patient. Concentrations of lactate in CSF and serum were normal in three. Muscle biopsy, performed in four, was shown to be normal. Enzyme histochemistry showed complex I, III, and IV deficiency in surviving patients.
CONCLUSION—This familial dystonia of chronic progression may be related to basal ganglia necrosis or gliosis, associated with alterations in the respiratory chain. These metabolic alterations probably play a part in the pathophysiology of these unusual brain lesions.

 PMID:9285458

  19. A novel conditional knock-in approach defines molecular and circuit effects of the DYT1 dystonia mutation

    PubMed Central

    Weisheit, Corinne E.; Dauer, William T.

    2015-01-01

    DYT1 dystonia, the most common inherited form of primary dystonia, is a neurodevelopmental disease caused by a dominant mutation in TOR1A. This mutation (‘ΔE’) removes a single glutamic acid from the encoded protein, torsinA. The effects of this mutation, at the molecular and circuit levels, and the reasons for its neurodevelopmental onset, remain incompletely understood. To uniquely address key questions of disease pathogenesis, we generated a conditional Tor1a knock-in allele that is converted from wild-type to DYT1 mutant (‘induced’ ΔE: Tor1ai-ΔE), following Cre recombination. We used this model to perform a gene dosage study exploring the effects of the ΔE mutation at the molecular, neuropathological and organismal levels. These analyses demonstrated that ΔE-torsinA is a hypomorphic allele and showed no evidence for any gain-of-function toxic properties. The unique capabilities of this model also enabled us to test a circuit-level hypothesis of DYT1 dystonia, which predicts that expression of the DYT1 genotype (Tor1aΔE/+) selectively within hindbrain structures will produce an overtly dystonic animal. In contrast to this prediction, we find no effect of this anatomic-specific expression of the DYT1 genotype, a finding that has important implications for the interpretation of the human and mouse diffusion tensor-imaging studies upon which it is based. These studies advance understanding of the molecular effects of the ΔE mutation, challenge current concepts of the circuit dysfunction that characterize the disease and establish a powerful tool that will be valuable for future studies of disease pathophysiology. PMID:26370418

  20. Focal lingual dystonia, urinary incontinence, and sensory deficits secondary to low voltage electrocution: case report and literature review.

    PubMed

    Baskerville, J R; McAninch, S A

    2002-07-01

    Electrocution injuries are well reported in review articles and cases of high voltage electrocution injury are abundant. However, reports of low voltage electrocution injury are few. A case is presented of low voltage shock from a 120 volt AC source with presentation, acute and chronic course, and a five year follow up. The patient experienced several unusual complications of low voltage electrocution: a persistent right tongue deviation, which initially presents as an isolated hypoglossal nerve palsy, but subsequently manifests as a focal lingual dystonia; total body paresthesia with urinary incontinence; and persistent sensory deficits to the face and tongue.

  1. Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms.

    PubMed

    Ruge, Diane; Cif, Laura; Limousin, Patricia; Gonzalez, Victoria; Vasques, Xavier; Hariz, Marwan I; Coubes, Philippe; Rothwell, John C

    2011-07-01

    Long-term results show that benefits from chronic deep brain stimulation in dystonia are maintained for many years. Despite this, the neurophysiological long-term consequences of treatment and their relationship to clinical effects are not well understood. Previous studies have shown that transcranial magnetic stimulation measures of abnormal long-term potentiation-like plasticity (paired associative stimulation) and GABAa-ergic inhibition (short-interval intracortical inhibition), which are seen in dystonia, normalize after several months of deep brain stimulation. In the present study, we examine the same measures in a homogenous group of 10 DYT1 gene-positive patients after long-term deep brain stimulation treatment for at least 4.5 years. Recordings were made 'on' deep brain stimulation and after stopping deep brain stimulation for 2 days. The results show that: (i) on average, prior to discontinuing deep brain stimulation, the paired associative stimulation response was almost absent and short-interval intracortical inhibition was reduced compared with normal. This pattern differs from that in both healthy volunteers and from the typical pattern of enhanced plasticity and reduced inhibition seen in deep brain stimulation-naïve dystonia. It is similar to that seen in untreated Parkinson's disease and may relate to thus far unexplained clinical phenomena like parkinsonian symptoms that have sometimes been observed in patients treated with deep brain stimulation. (ii) Overall, there was no change in average physiological or clinical status when deep brain stimulation was turned off for 2 days, suggesting that deep brain stimulation had produced long-term neural reorganization in the motor system. (iii) However, there was considerable variation between patients. Those who had higher levels of plasticity when deep brain stimulation was 'on', had the best retention of clinical benefit when deep brain stimulation was stopped and vice versa. This may indicate that

  2. PET Neuroimaging: Insights on Dystonia and Tourette Syndrome and Potential Applications

    PubMed Central

    Alongi, Pierpaolo; Iaccarino, Leonardo; Perani, Daniela

    2014-01-01

    Primary dystonia (pD) is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Gilles de la Tourette syndrome (GTS) is a childhood-onset neuropsychiatric developmental disorder characterized by motor and phonic tics, which could progress to behavioral changes. GTS and obsessive–compulsive disorders are often seen in comorbidity, also suggesting that a possible overlap in the pathophysiological bases of these two conditions. PET techniques are of considerable value in detecting functional and molecular abnormalities in vivo, according to the adopted radioligands. For example, PET is the unique technique that allows in vivo investigation of neurotransmitter systems, providing evidence of changes in GTS or pD. For example, presynaptic and post-synaptic dopaminergic studies with PET have shown alterations compatible with dysfunction or loss of D2-receptors bearing neurons, increased synaptic dopamine levels, or both. Measures of cerebral glucose metabolism with 18F-fluorodeoxyglucose PET (18F-FDG PET) are very sensitive in showing brain functional alterations as well. 18F-FDG PET data have shown metabolic changes within the cortico-striato-pallido-thalamo-cortical and cerebello-thalamo-cortical networks, revealing possible involvement of brain circuits not limited to basal ganglia in pD and GTS. The aim of this work is to overview PET consistent neuroimaging literature on pD and GTS that has provided functional and molecular knowledge of the underlying neural dysfunction. Furthermore, we suggest potential applications of these techniques in monitoring treatments. PMID:25295029

  3. Plasticity of cortical inhibition in dystonia is impaired after motor learning and Paired-Associative Stimulation

    PubMed Central

    Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

    2012-01-01

    Summary Artificial induction of plasticity by paired associative stimulation (PAS) in healthy subjects (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory ones. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long interval intracortical inhibition (LICI, reflecting activity of GABAB interneurons) and long latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced LTP-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.“ PMID:22429246

  4. A Functional Magnetic Resonance Imaging Study of Head Movements in Cervical Dystonia

    PubMed Central

    Prudente, Cecília N.; Stilla, Randall; Singh, Shivangi; Buetefisch, Cathrin; Evatt, Marian; Factor, Stewart A.; Freeman, Alan; Hu, Xiaoping Philip; Hess, Ellen J.; Sathian, K.; Jinnah, H. A.

    2016-01-01

    Cervical dystonia (CD) is a neurological disorder characterized by abnormal movements and postures of the head. The brain regions responsible for these abnormal movements are not well understood, because most imaging techniques for assessing regional brain activity cannot be used when the head is moving. Recently, we mapped brain activation in healthy individuals using functional magnetic resonance imaging during isometric head rotation, when muscle contractions occur without actual head movements. In the current study, we used the same methods to explore the neural substrates for head movements in subjects with CD who had predominantly rotational abnormalities (torticollis). Isometric wrist extension was examined for comparison. Electromyography of neck and hand muscles ensured compliance with tasks during scanning, and any head motion was measured and corrected. Data were analyzed in three steps. First, we conducted within-group analyses to examine task-related activation patterns separately in subjects with CD and in healthy controls. Next, we directly compared task-related activation patterns between participants with CD and controls. Finally, considering that the abnormal head movements in CD occur in a consistently patterned direction for each individual, we conducted exploratory analyses that involved normalizing data according to the direction of rotational CD. The between-group comparisons failed to reveal any significant differences, but the normalization procedure in subjects with CD revealed that isometric head rotation in the direction of dystonic head rotation was associated with more activation in the ipsilateral anterior cerebellum, whereas isometric head rotation in the opposite direction was associated with more activity in sensorimotor cortex. These findings suggest that the cerebellum contributes to abnormal head rotation in CD, whereas regions in the cerebral cortex are involved in opposing the involuntary movements. PMID:27895619

  5. Aberrant Oscillatory Activity during Simple Movement in Task-Specific Focal Hand Dystonia.

    PubMed

    Hinkley, Leighton B N; Dolberg, Rebecca; Honma, Susanne; Findlay, Anne; Byl, Nancy N; Nagarajan, Srikantan S

    2012-01-01

    In task-specific focal hand dystonia (tspFHD), the temporal dynamics of cortical activity in the motor system and how these processes are related to impairments in sensory and motor function are poorly understood. Here, we use time-frequency reconstructions of magnetoencephalographic (MEG) data to elaborate the temporal and spatial characteristics of cortical activity during movement. A self-paced finger tapping task during MEG recording was performed by 11 patients with tspFHD and 11 matched healthy controls. In both groups robust changes in beta (12-30 Hz) and high gamma (65-90 Hz) oscillatory activity were identified over sensory and motor cortices during button press. A significant decrease [p < 0.05, 1% False Discovery Rate (FDR) corrected] in high gamma power during movements of the affected hand was identified over ipsilateral sensorimotor cortex in the period prior to (-575 ms) and following (725 ms) button press. Furthermore, an increase (p < 0.05, 1% FDR corrected) in beta power suppression following movement of the affected hand was identified over visual cortex in patients with tspFHD. For movements of the unaffected hand, a significant (p < 0.05, 1% FDR corrected) increase in beta power suppression was identified over secondary somatosensory cortex (S2) in the period following button press in patients with tspFHD. Oscillatory activity within in the tspFHD group was however not correlated with clinical measures. Understanding these aberrant oscillatory dynamics can provide the groundwork for interventions that focus on modulating the timing of this activity.

  6. Persistent neuroleptic-induced rigidity and dystonia in AIDS dementia complex: a clinico-pathological case report.

    PubMed

    Factor, S A; Podskalny, G D; Barron, K D

    1994-12-01

    Patients with AIDS dementia complex (ADC) appear to have an increased likelihood of developing acute onset parkinsonism and dystonia when treated with dopamine antagonists. It has been hypothesized, based on clinical evidence, that hypersensitivity to these drugs in ADC is probably related to direct invasion of the basal ganglia by the HIV virus and a secondary alteration in dopaminergic mechanisms. We report the first pathological description of a patient with ADC who developed acute onset, generalized rigidity and dystonia after a brief trial of low dose neuroleptic therapy administered for psychotic symptoms. An unusual clinical feature of this case was the persistence of his movement disorder. Pathological examination revealed a generalized encephalitic process with substantial neuronal loss observed primarily in the medial and lateral globus pallidus. Correlation with a current model of basal ganglia pathophysiology and other disorders with pallidal lesions is discussed. Clinical and pathological features of this case confirm the previous contention and indicate that dopamine antagonists should be utilized with extreme caution in patients with ADC.

  7. Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior

    PubMed Central

    Gantois, Ilse; Fang, Ke; Jiang, Luning; Babovic, Daniela; Lawrence, Andrew J.; Ferreri, Vincenzo; Teper, Yaroslav; Jupp, Bianca; Ziebell, Jenna; Morganti-Kossmann, Cristina M.; O'Brien, Terence J.; Nally, Rachel; Schütz, Günter; Waddington, John; Egan, Gary F.; Drago, John

    2007-01-01

    Huntington's disease is characterized by death of striatal projection neurons. We used a Cre/Lox transgenic approach to generate an animal model in which D1 dopamine receptor (Drd1a)+ cells are progressively ablated in the postnatal brain. Striatal Drd1a, substance P, and dynorphin expression is progressively lost, whereas D2 dopamine receptor (Drd2) and enkephalin expression is up-regulated. Magnetic resonance spectroscopic analysis demonstrated early elevation of the striatal choline/creatine ratio, a finding associated with extensive reactive striatal astrogliosis. Sequential MRI demonstrated a progressive reduction in striatal volume and secondary ventricular enlargement confirmed to be due to loss of striatal cells. Mutant mice had normal gait and rotarod performance but displayed hindlimb dystonia, locomotor hyperactivity, and handling-induced electrographically verified spontaneous seizures. Ethological assessment identified an increase in rearing and impairments in the oral behaviors of sifting and chewing. In line with the limbic seizure profile, cell loss, astrogliosis, microgliosis, and down-regulated dynorphin expression were seen in the hippocampal dentate gyrus. This study specifically implicates Drd1a+ cell loss with tail suspension hindlimb dystonia, hyperactivity, and abnormal oral function. The latter may relate to the speech and swallowing disturbances and the classic sign of tongue-protrusion motor impersistence observed in Huntington's disease. In addition, the findings of this study support the notion that Drd1a and Drd2 are segregated on striatal projection neurons. PMID:17360497

  8. Faithful SGCE imprinting in iPSC-derived cortical neurons: an endogenous cellular model of myoclonus-dystonia

    PubMed Central

    Grütz, Karen; Seibler, Philip; Weissbach, Anne; Lohmann, Katja; Carlisle, Francesca A.; Blake, Derek J.; Westenberger, Ana; Klein, Christine; Grünewald, Anne

    2017-01-01

    In neuropathology research, induced pluripotent stem cell (iPSC)-derived neurons are considered a tool closely resembling the patient brain. Albeit in respect to epigenetics, this concept has been challenged. We generated iPSC-derived cortical neurons from myoclonus-dystonia patients with mutations (W100G and R102X) in the maternally imprinted ε-sarcoglycan (SGCE) gene and analysed properties such as imprinting, mRNA and protein expression. Comparison of the promoter during reprogramming and differentiation showed tissue-independent differential methylation. DNA sequencing with methylation-specific primers and cDNA analysis in patient neurons indicated selective expression of the mutated paternal SGCE allele. While fibroblasts only expressed the ubiquitous mRNA isoform, brain-specific SGCE mRNA and ε-sarcoglycan protein were detected in iPSC-derived control neurons. However, neuronal protein levels were reduced in both mutants. Our phenotypic characterization highlights the suitability of iPSC-derived cortical neurons with SGCE mutations for myoclonus-dystonia research and, in more general terms, prompts the use of iPSC-derived cellular models to study epigenetic mechanisms impacting on health and disease. PMID:28155872

  9. [Acute Dystonia due to Aripiprazole Use in Two Children with Autism Spectrum Disorder in the First Five Years of Life].

    PubMed

    Küçükköse, Mustafa; Kabukçu Başay, Bürge

    2017-01-01

    Autism spectrum disorders (ASD) are neuropsychiatric disorders characterized by impairment in social interactions, in verbal and non-verbal communication, and restricted and stereotyped patterns of interest and behavior within the first 3 years of life. Pharmacologic interventions may be needed for the treatment of temper tantrums, aggression, hyperactivity, and stereotypes in children with ASD. The approval of aripiprazole by the United States Food and Drug Administration (USFDA) for the treatment of temper tantrums in children and adolescents with ASD has gained increased interest for the use in these patients. Aripiprazole is a partial agonist for the dopamine D2, serotonin 5-HT1A receptors, and an antagonist for 5HT2A receptors. Because aripiprazole is a partial agonist, it has been is speculated that aripiprazole has a protective effect for extrapyramidal side effects, movement disorders, and metabolic problems. But the increased use in children and adolescents is associated with an increase in the number of case reports related with such problems. Nevertheless, our review of the literature uncovered limited data regarding the association between acute dystonia and aripiprazole use in ASD children under five years of age is. In this paper, we present two cases of autistic spectrum disorder children with ages under 5 years that developed acute dystonia taking aripiprazole.

  10. Impact of Neu-botulinumtoxinA on the Severity and Quality of Life of Cervical Dystonia Patients

    PubMed Central

    Jagota, Priya; Kaewwilai, Lalita; Boonrod, Nonglak; Singmaneesakulchai, Surat; Boonpang, Kamolwan; Sringean, Jirada; Jitkritsadakul, Onanong; Petchrutchatachart, Sitthi

    2016-01-01

    Background Cervical dystonia (CD) is a debilitating neurological disorder that may gravely affect a patient’s quality of life (QoL). Botulinum toxin treatment has been approved as a first-line treatment for this condition. This study aims to look at the efficacy and impact on the QoL of neu-botulinumtoxinA, a newer and cheaper botulinum toxin type A, in patients with CD. Methods This is a prospective, open-label, single-arm study. CD patients were recruited and evaluated for severity of CD using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and for QoL using the Craniocervical Dystonia Questionnaire (CDQ-24), and the 36-item Short Form Health Survey questionnaire (SF-36) at baseline and 6 weeks after injection. Results Twenty patients were recruited. Significant improvement was shown in part 1 and total TWSTRS score and total CDQ-24 scores. Analysis of individual items of the TWSTRS scale showed significant improvement in rotation, duration of CD, and work ability. Significant improvements in the QoL were also seen in some items of the stigma, emotional wellbeing, and energy/fatigue domains of the CDQ-24 and SF-36 questionnaires. Discussion Neu-botulinumtoxinA is efficacious in treating CD symptoms and improving QoL of patients with CD. A larger, double-blinded study is needed to study the extent of improvements. PMID:27536464

  11. The optimal pallidal target in deep brain stimulation for dystonia: a study using a functional atlas based on non-linear image registration

    PubMed Central

    Tolleson, Christopher; Pallavaram, Srivatsan; Li, Chen; Fang, John; Phibbs, Fenna; Konrad, Peter; Hedera, Peter; Francois-D'Haese, Pierre; Dawant, Benoit M.; Davis, Thomas L.

    2014-01-01

    Background Deep Brain Stimulation (DBS) of the globus pallidus interna (GPi) is established as efficacious for dystonia yet the optimal target within this structure is not well defined. Published evidence suggests that spatial normalization provides a better estimate of DBS lead location than traditional methods based on standard stereotactic coordinates. Methods We retrospectively reviewed our pallidal implanted dystonia population. Patient imaging scans were morphed into an MRI atlas using a non-linear image registration algorithm. Active contact locations were projected onto the atlas and clusters analyzed for the degree of variance in two groups: 1) good and poor responders and 2) cervical (CD) and generalized dystonia (GD). Results Average active contact location between CD and GD good responders was distinct but not significantly different. Mean active contact for CD poor responders was significantly different from CD responders and GD poor responders in the dorsoventral direction. Conclusions A normalized imaging space is arguably more accurate in visualizing postoperative leads. Despite some separation between groups, this data suggests there was not an optimal pallidal target for common dystonia patients. Degrees of variance overlapped due to a large degree of individual target variation. Patient selection may ultimately be the key to maximizing patient outcomes. PMID:25502118

  12. Long-term follow-up of DYT1 dystonia patients treated by deep brain stimulation: an open-label study.

    PubMed

    Cif, Laura; Vasques, Xavier; Gonzalez, Victoria; Ravel, Patrice; Biolsi, Brigitte; Collod-Beroud, Gwenaelle; Tuffery-Giraud, Sylvie; Elfertit, Hassan; Claustres, Mireille; Coubes, Philippe

    2010-02-15

    Long-term efficacy of internal globus pallidus (GPi) deep-brain stimulation (DBS) in DYT1 dystonia and disease progression under DBS was studied. Twenty-six patients of this open-label study were divided into two groups: (A) with single bilateral GPi lead, (B) with a second bilateral GPi lead implanted owning to subsequent worsening of symptomatology. Dystonia was assessed with the Burke Scale. Appearance of new symptoms and distribution according to body region were recorded. In the whole cohort, significant decreases in motor and disability subscores (P < 0.0001) were observed at 1 year and maintained up to 10 years. Group B showed worsening of the symptoms. At 1 year, there were no significant differences between Groups A (without subsequent worsening) and B; at 5 years, a significant difference was found for motor and disability scores. Within Group B, four patients exhibited additional improvement after the second DBS surgery. In the 26 patients, significant difference (P = 0.001) was found between the number of body regions affected by dystonia preoperatively and over the whole follow-up. DBS efficacy in DYT1 dystonia can be maintained up to 10 years (two patients). New symptoms appear with long-term follow-up and may improve with additional leads in a subgroup of patients.

  13. Treatment of inferior lateral pterygoid muscle dystonia with zolpidem tartrate, botulinum toxin injections, and physical self-regulation procedures: a case report.

    PubMed

    Vazquez-Delgado, Eduardo; Okeson, Jeffrey P

    2004-10-01

    The following case report depicts the management of a patient suffering with a jaw opening oromandibular dystonia using a combination of botulinum toxin injections, zolpidem, and relaxation procedures. Eventually the botulinum toxin injections were eliminated, and the patient was maintained with only zolpidem and relaxation procedures.

  14. Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in Mice Implicates Novel Pathways in Dystonia Pathogenesis

    PubMed Central

    Beauvais, Genevieve; Bode, Nicole M.; Watson, Jaime L.; Wen, Hsiang; Glenn, Kevin A.; Kawano, Hiroyuki; Harata, N. Charles; Ehrlich, Michelle E.

    2016-01-01

    Dystonia type 1 (DYT1) is a dominantly inherited neurological disease caused by mutations in TOR1A, the gene encoding the endoplasmic reticulum (ER)-resident protein torsinA. Previous work mostly completed in cell-based systems suggests that mutant torsinA alters protein processing in the secretory pathway. We hypothesized that inducing ER stress in the mammalian brain in vivo would trigger or exacerbate mutant torsinA-induced dysfunction. To test this hypothesis, we crossed DYT1 knock-in with p58(IPK)-null mice. The ER co-chaperone p58(IPK) interacts with BiP and assists in protein maturation by helping to fold ER cargo. Its deletion increases the cellular sensitivity to ER stress. We found a lower generation of DYT1 knock-in/p58 knock-out mice than expected from this cross, suggesting a developmental interaction that influences viability. However, surviving animals did not exhibit abnormal motor function. Analysis of brain tissue uncovered dysregulation of eiF2α and Akt/mTOR translational control pathways in the DYT1 brain, a finding confirmed in a second rodent model and in human brain. Finally, an unbiased proteomic analysis identified relevant changes in the neuronal protein landscape suggesting abnormal ER protein metabolism and calcium dysregulation. Functional studies confirmed the interaction between the DYT1 genotype and neuronal calcium dynamics. Overall, these findings advance our knowledge on dystonia, linking translational control pathways and calcium physiology to dystonia pathogenesis and identifying potential new pharmacological targets. SIGNIFICANCE STATEMENT Dystonia type 1 (DYT1) is one of the different forms of inherited dystonia, a neurological disorder characterized by involuntary, disabling movements. DYT1 is caused by mutations in the gene that encodes the endoplasmic reticulum (ER)-resident protein torsinA. How mutant torsinA causes neuronal dysfunction remains unknown. Here, we show the behavioral and molecular consequences of stressing

  15. Striving for more good days: patient perspectives on botulinum toxin for the treatment of cervical dystonia

    PubMed Central

    Poliziani, Michele; Koch, Marco; Liu, Xierong

    2016-01-01

    Background The recommended reinjection interval for botulinum neurotoxin (BoNT) formulations in the treatment of cervical dystonia (CD) is generally ≥12 weeks, though intervals ≥10 weeks are approved for incobotulinumtoxinA in Europe. However, recurring symptoms can occur before the end of this period. Using qualitative research, we sought a greater understanding of disease burden, unmet patient needs, and barriers to treatment. Methods We conducted online semistructured, focus-group discussions, and online forum follow-up discussions among patients with CD, focusing on disease burden, patient needs, injection cycle preferences, and relationships with health care professionals. A subset of patients was also questioned in telephone interviews about individual experiences of CD and BoNT treatment. All participants were UK residents who had received onabotulinumtoxinA or abobotulinumtoxinA for CD for ≥1 year. Results Thirty-one patients (81% female; mean duration of CD 16.4 [range 4–31] years; mean BoNT injection cycle length 12.8 weeks) participated in the online focus-group and forum follow-up discussions. Of these, seven patients participated in telephone interviews. All had recurring symptoms between treatments, which substantially impacted on their work, family, and social life. Symptom severity fluctuated throughout an injection cycle and differed between patients and across injection cycles. Participants’ relationships with health care professionals and treatment satisfaction varied greatly. Many participants wanted longer-lasting and/or more stable symptom relief with shorter and/or more flexible injection intervals, according to individual needs. Lack of health care resources, long journeys to treatment centers, and immunogenicity/side-effect concerns were perceived as the main barriers to more flexible treatment. Conclusion The high burden of recurring primary and secondary symptoms of CD considerably affects patients’ quality of life. Patient

  16. Paroxysmal Autonomic Instability With Dystonia Managed Using Chemodenervation Including Alcohol Neurolysis and Botulinum Toxin Type A Injection: A Case Report

    PubMed Central

    Lee, Hye-Sun; Oh, Hyun-Seung

    2015-01-01

    Paroxysmal autonomic instability with dystonia (PAID) is a rare complication of brain injury. Symptoms of PAID include diaphoresis, hyperthermia, hypertension, tachycardia, and tachypnea accompanied by hypertonic movement. Herein, we present the case of a 44-year-old female patient, who was diagnosed with paraneoplastic limbic encephalopathy caused by thyroid papillary cancer. The patient exhibited all the symptoms of PAID. On the basis that the symptoms were unresponsive to antispastic medication and her liver function test was elevated, we performed alcohol neurolysis of the musculocutaneous nerve followed by botulinum toxin type A (BNT-A) injection into the biceps brachii and brachialis. Unstable vital signs and hypertonia were relieved after chemodenervation. Accordingly, alcohol neurolysis and BNT-A injection are proposed as a treatment option for intractable PAID. PMID:25932429

  17. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

    PubMed Central

    Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E.; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y.; Simpson, Michael A.; Chong, W. K.; Jacques, Thomas S.; Woltjer, Randy L.; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M.; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R.; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A. M.; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S.; Yoganathan, Sangeetha; Dale, Russell C.; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A.; Enns, Caroline A.; Hayflick, Susan J.; Clayton, Peter T.; Mills, Philippa B.; Kurian, Manju A.; Wilson, Stephen W.

    2016-01-01

    Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism–dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates. PMID:27231142

  18. Myoclonus dystonia and muscular dystrophy: ɛ‐sarcoglycan is part of the dystrophin‐associated protein complex in brain

    PubMed Central

    Waite, Adrian J.; Carlisle, Francesca A.; Chan, Yiumo Michael

    2016-01-01

    ABSTRACT Background Myoclonus‐dystonia is a neurogenic movement disorder caused by mutations in the gene encoding ɛ‐sarcoglycan. By contrast, mutations in the α‐, β‐, γ‐, and δ‐sarcoglycan genes cause limb girdle muscular dystrophies. The sarcoglycans are part of the dystrophin‐associated protein complex in muscle that is disrupted in several types of muscular dystrophy. Intriguingly, patients with myoclonus‐dystonia have no muscle pathology; conversely, limb‐girdle muscular dystrophy patients have not been reported to have dystonia‐associated features. To gain further insight into the molecular mechanisms underlying these differences, we searched for evidence of a sarcoglycan complex in the brain. Methods Immunoaffinity chromatography and mass spectrometry were used to purify ubiquitous and brain‐specific ɛ‐sarcoglycan directly from tissue. Cell models were used to determine the effect of mutations on the trafficking and assembly of the brain sarcoglycan complex. Results Ubiquitous and brain‐specific ɛ‐sarcoglycan isoforms copurify with β‐, δ‐, and ζ‐sarcoglycan, β‐dystroglycan, and dystrophin Dp71 from brain. Incorporation of a muscular dystrophy‐associated β‐sarcoglycan mutant into the brain sarcoglycan complex impairs the formation of the βδ‐sarcoglycan core but fails to abrogate the association and membrane trafficking of ɛ‐ and ζ‐sarcoglycan. Conclusions ɛ‐Sarcoglycan is part of the dystrophin‐associated protein complex in brain. Partial preservation of ɛ‐ and ζ‐sarcoglycan in brain may explain the absence of myoclonus dystonia‐like features in muscular dystrophy patients. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:27535350

  19. Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses

    PubMed Central

    Iacono, Diego; Geraci-Erck, Maria; Peng, Hui; Rabin, Marcie L.; Kurlan, Roger

    2015-01-01

    Background Dystonias (Dys) represent the third most common movement disorder after essential tremor (ET) and Parkinson's disease (PD). While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG), and specifically in the substantia nigra (SN). Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia) have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. Methods Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age-matched control subjects (C). Results We observed a significant reduction (∼20%) of pigmented neurons in the SN of Dys compared to C (p<0.01). Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co-occurring SN pathologies including Lewy pathology, tau-neurofibrillary tangles, β-amyloid deposits, ubiquitin (ubiq), and phosphorylated-TAR DNA-binding protein 43 (pTDP43)-positive inclusions. Discussion A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN. PMID:26069855

  20. The early-onset torsion dystonia-associated protein, torsinA, displays molecular chaperone activity in vitro

    PubMed Central

    Burdette, Alexander J.; Churchill, Perry F.; Caldwell, Guy A.

    2010-01-01

    TorsinA is a member of the AAA+ ATPase family of proteins and, notably, is the only known ATPase localized to the ER lumen. It has been suggested to act as a molecular chaperone, while a mutant form associated with early-onset torsion dystonia, a dominantly inherited movement disorder, appears to result in a net loss of function in vivo. Thus far, no studies have examined the chaperone activity of torsinA in vitro. Here we expressed and purified both wild-type (WT) and mutant torsinA fusion proteins in bacteria and examined their ability to function as molecular chaperones by monitoring suppression of luciferase and citrate synthase (CS) aggregation. We also assessed their ability to hold proteins in an intermediate state for refolding. As measured by light scattering and SDS-PAGE, both WT and mutant torsinA effectively, and similarly, suppressed protein aggregation compared to controls. This function was not further enhanced by the presence of ATP. Further, we found that while neither form of torsinA could protect CS from heat-induced inactivation, they were both able to reactivate luciferase when ATP and rabbit reticulocyte lysate were added. This suggests that torsinA holds luciferase in an intermediate state, which can then be refolded in the presence of other chaperones. These data provide conclusive evidence that torsinA acts as a molecular chaperone in vitro and suggests that early-onset torsion dystonia is likely not a consequence of a loss in torsinA chaperone activity but might be an outcome of insufficient torsinA localization at the ER to manage protein folding or trafficking. PMID:20169475

  1. Repetitive Transcranial Magnetic Stimulation in Cervical Dystonia: Effect of Site and Repetition in a Randomized Pilot Trial

    PubMed Central

    Pirio Richardson, Sarah; Tinaz, Sule; Chen, Robert

    2015-01-01

    Dystonia is characterized by abnormal posturing due to sustained muscle contraction, which leads to pain and significant disability. New therapeutic targets are needed in this disorder. The objective of this randomized, sham-controlled, blinded exploratory study is to identify a specific motor system target for non-invasive neuromodulation and to evaluate this target in terms of safety and tolerability in the cervical dystonia (CD) population. Eight CD subjects were given 15-minute sessions of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (MC), dorsal premotor cortex (dPM), supplementary motor area (SMA), anterior cingulate cortex (ACC) and a sham condition with each session separated by at least two days. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was rated in a blinded fashion immediately pre- and post-intervention. Secondary outcomes included physiology and tolerability ratings. The mean change in TWSTRS severity score by site was 0.25 ± 1.7 (ACC), -2.9 ± 3.4 (dPM), -3.0 ± 4.8 (MC), -0.5 ± 1.1 (SHAM), and -1.5 ± 3.2 (SMA) with negative numbers indicating improvement in symptom control. TWSTRS scores decreased from Session 1 (15.1 ± 5.1) to Session 5 (11.0 ± 7.6). The treatment was tolerable and safe. Physiology data were acquired on 6 of 8 subjects and showed no change over time. These results suggest rTMS can modulate CD symptoms. Both dPM and MC are areas to be targeted in further rTMS studies. The improvement in TWSTRS scores over time with multiple rTMS sessions deserves further evaluation. Trial Registration ClinicalTrials.gov NCT01859247 PMID:25923718

  2. The Expanding Spectrum of Neurological Phenotypes in Children With ATP1A3 Mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and Beyond

    PubMed Central

    Sweney, Matthew T.; Newcomb, Tara M.; Swoboda, Kathryn J.

    2015-01-01

    BACKGROUND ATP1A3 mutations have now been recognized in infants and children presenting with a diverse group of neurological phenotypes, including Rapid-onset Dystonia-Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and most recently, Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss (CAPOS) syndrome. METHODS Existing literature on ATP1A3-related disorders in the pediatric population were reviewed, with attention to clinical features and associated genotypes among those with RDP, AHC, or CAPOS syndrome phenotypes. RESULTS While classically defined phenotypes associated with AHC, RDP, and CAPOS syndromes are distinct, common elements among ATP1A3-related neurological disorders include characteristic episodic neurological symptoms and signs that vary in severity, duration, and frequency of occurrence. Affected children typically present in the context of an acute onset of paroxysmal, episodic neurological symptoms ranging from oculomotor abnormalities, hypotonia, paralysis, dystonia, ataxia, seizure-like episodes, or encephalopathy. Neurodevelopmental delays or persistence of dystonia, chorea, or ataxia after resolution of an initial episode are common, providing important clues for diagnosis. CONCLUSIONS The phenotypic spectrum of ATP1A3-related neurological disorders continues to expand beyond the distinct yet overlapping phenotypes in patients with AHC, RDP, and CAPOS syndromes. ATP1A3 mutation analysis is appropriate to consider in the diagnostic algorithm for any child presenting with episodic or fluctuating ataxia, weakness or dystonia whether they manifest persistence of neurological symptoms between episodes. Additional work is needed to better identify and classify affected patients and develop targeted treatment approaches. PMID:25447930

  3. Clinical Response to IncobotulinumtoxinA, after Demonstrated Loss of Clinical Response to OnabotulinumtoxinA and RimabotulininumtoxinB in a Patient with Musician’s Dystonia

    PubMed Central

    Ramos, Vesper Fe Marie Llaneza; Karp, Barbara I.; Lungu, Codrin; Alter, Katharine; Hallett, Mark

    2016-01-01

    Botulinum toxin is a mainstay therapy for dystonia. Formulations available are three types of botulinumtoxinA and one type of botulinumtoxinB.1 Antibodies can develop against the toxin, leading to treatment failure. IncobotulinumtoxinA (Xeomin; Merz Pharmaceuticals GmbH, Frankfurt, Germany) is differentiated from other types of botulinumtoxinA preparations by being free from complexing proteins, speculated to make the product less antigenic.2 PMID:27066521

  4. Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal dystonia--an fMRI-TMS study.

    PubMed

    Schneider, Susanne A; Pleger, Burkhard; Draganski, Bogdan; Cordivari, Carla; Rothwell, John C; Bhatia, Kailash P; Dolan, Ray J

    2010-01-15

    Dystonia is associated with impaired somatosensory ability. The electrophysiological method of repetitive transcranial magnetic stimulation (rTMS) can be used for noninvasive stimulation of the human cortex and can alter cortical excitability and associated behavior. Among others, rTMS can alter/improve somatosensory discrimation abilities, as shown in healthy controls. We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients with right-sided writer's dystonia and 5 controls. We studied rTMS effects on tactile discrimination accuracy and concomitant rTMS-induced changes in hemodynamic activity measured by functional magnetic resonance imaging (fMRI). Before rTMS, patients performed worse on the discrimination task than controls even though fMRI showed greater task-related activation bilaterally in the basal ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed this was associated with increased activity of the stimulated S1, bilateral premotor cortex and BG. In dystonia patients, rTMS had no effect on discrimination; fMRI showed similar cortical effects to controls except for no effects in BG. Improved discrimination after rTMS in controls is linked to enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in dystonia may be associated with the lack of effect on sensory discrimination in this group and may reflect impaired processing in BG-S1 connections. Alternatively, the increased BG activation seen in the baseline state without rTMS may reflect a compensatory strategy that saturates a BG contribution to this task.

  5. Effect of low-frequency repetitive transcranial magnetic stimulation combined with physical therapy on L-dopa-induced painful off-period dystonia in Parkinson's disease.

    PubMed

    Kodama, Mitsuhiko; Kasahara, Takashi; Hyodo, Masaki; Aono, Koji; Sugaya, Mutsumi; Koyama, Yuji; Hanayama, Kozo; Masakado, Yoshihisa

    2011-02-01

    Previous research has shown that low-frequency repetitive transcranial magnetic stimulation over the primary motor area and supplementary motor area can reduce L-dopa-induced dyskinesias in Parkinson's disease; however, it involved only patients with peak-dose or diphasic dyskinesia. We report a case of a patient with severely painful off-period dystonia in the unilateral lower limb who underwent 0.9-Hz subthreshold repetitive transcranial magnetic stimulation over contralateral primary motor area and supplementary motor area. Repetitive transcranial magnetic stimulation over the primary motor area significantly reduced the painful dystonia and walking disturbances but repetitive transcranial magnetic stimulation over the supplementary motor area did not. The cortical silent period also prolonged after repetitive transcranial magnetic stimulation over the primary motor area. At 5 mos of approximately once a week repetitive transcranial magnetic stimulation over the primary motor area, the Unified Parkinson's Disease Rating Scale motor score also improved. This report shows that repetitive transcranial magnetic stimulation over the inhibitory primary motor area can be useful for rehabilitating patients with Parkinson's disease with off-period dystonia and suggests that this treatment should be further verified in such patients.

  6. Facial Dystonia with Facial Grimacing and Vertical Gaze Palsy with "Round the Houses" Sign in a 29-Year-Old Woman.

    PubMed

    Crespi, J; Bråthen, G; Quist-Paulsen, P; Pagonabarraga, J; Roig-Arnall, C

    2016-02-01

    A 29-year-old woman developed progressive dysarthria and coordination problems from the age of 15. Examination showed dysarthria, facial dystonia, bibrachial dystonia, hyperreflexia, ataxia, and emotional incontinence. Downward supranuclear gaze palsy was prominent with a "Round the Houses" sign. Magnetic resonance imaging of the brain and medulla, electroneurography, and cerebrospinal fluid were normal. A computed tomography scan showed hepatosplenomegaly. This combination of progressive neurological symptoms together with hepatosplenomegaly was suggestive of inborn error of metabolism. A bone marrow biopsy showed an increased number of macrophages with foamy content, highly suggestive of lysosomal disease. Plasmatic chitotriosidase activity and CCL18 were increased. Genetic testing showed heterozygosis for the variation c.1070C→T (p.Ser357Leu) and c.1843→T (Arg615Cys), confirming the diagnosis of Niemann-Pick type C (NPC). The "Round the Houses" sign has only been described in patients with progressive supranuclear palsy (PSP). This sign is described as an inability to produce pure vertical saccades along the midline and instead moving the eyes in a lateral arc to accomplish the movement. The observation of this sign in a patient with NPC indicates that this bedside finding is not specific for PSP, but a sign of medial longitudinal fasciculus dysfunction. The presence of facial dystonia with facial grimacing together with supranuclear gaze palsy is highly characteristic and useful for the diagnosis of NPC. NPC is an important underdiagnosed condition, given the availability of treatment and a mean diagnostic delay of 6 years.

  7. Phosphodiesterase-10A Inverse Changes in Striatopallidal and Striatoentopeduncular Pathways of a Transgenic Mouse Model of DYT1 Dystonia.

    PubMed

    D'Angelo, Vincenza; Castelli, Valentina; Giorgi, Mauro; Cardarelli, Silvia; Saverioni, Ilaria; Palumbo, Francesca; Bonsi, Paola; Pisani, Antonio; Giampà, Carmela; Sorge, Roberto; Biagioni, Stefano; Fusco, Francesca R; Sancesario, Giuseppe

    2017-02-22

    We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 receptors and inhibited by D2 receptors preferentially expressed in striatoentopeducuncular/substantia nigra or striatopallidal pathways, respectively. PDE10A was studied in control mice (NT) and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT). Quantitative analysis of PDE10A expression was assessed in different brain areas by rabbit anti-PDE10A antibody immunohistochemistry and Western blotting. PDE10A-dependent cAMP hydrolyzing activity and PDE10A mRNA were also assessed. Striatopallidal neurons were identified by rabbit anti-enkephalin antibody.In NT mice, PDE10A is equally expressed in medium spiny striatal neurons and in their projections to entopeduncular nucleus/substantia nigra and to external globus pallidus. In hMT mice, PDE10A content selectively increases in enkephalin-positive striatal neuronal bodies; moreover, PDE10A expression and activity in hMT mice, compared with NT mice, significantly increase in globus pallidus but decrease in entopeduncular nucleus/substantia nigra. Similar changes of PDE10A occur in hWT mice, but such changes are not always significant. However, PDE10A mRNA expression appears comparable among NT, hWT, and hMT mice.In DYT1 transgenic mice, the inverse changes of PDE10A in striatoentopeduncular and striatopallidal projections might result over time in an imbalance between direct and indirect pathways for properly focusing movement. The decrease of PDE10A in the striatoentopeduncular/nigral projections might lead to increased intensity and duration of D1-stimulated cAMP/cGMP signaling; conversely, the increase of PDE10A in the striatopallidal projections might lead to increased intensity and duration of D2

  8. Botulinum toxin therapy of cervical dystonia: comparing onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin (®)).

    PubMed

    Dressler, Dirk; Tacik, Pawel; Adib Saberi, Fereshte

    2014-01-01

    Several botulinum toxin (BT) drugs are licensed for the treatment of cervical dystonia (CD). We wanted to compare the efficacy and the potency labelling of incobotulinumtoxinA (Xeomin(®)) and onabotulinumtoxinA (Botox(®)) by analysing the duration of their therapeutic effect in a cross-over study. For this we studied 40 CD patients (26 females, 14 males, age at therapy onset 52.6 ± 12.0 years, duration of dystonia at therapy onset 10.0 ± 9.2 years, Tsui score 9.1 ± 3.9) who first received Botox(®) and then Xeomin(®) for at least 4 injection series each. BT doses were exchanged based on a 1:1 conversion ratio. Altogether 1,101 treatment cycles were evaluated. For each patient 27.5 ± 13.1 treatment cycles were recorded. Patients received 18.4 ± 12.4 treatment cycles with Botox(®) and 9.2 ± 4.5 with Xeomin(®). The treatment duration (TD) throughout the treatment course was 11.3 ± 1.0 weeks (Botox(®) 11.2 ± 1.1 weeks, Xeomin(®) 11.4 ± 1.3 weeks). The interinjection interval (II) throughout the treatment course was 14.8 ± 1.9 weeks (Botox(®) 14.7 ± 1.6 weeks, Xeomin(®) 15.0 ± 2.2 weeks). The mean difference between Botox(®) and Xeomin(®) was 0.3 weeks for TD (two-sided 95 % confidence interval [-0.3; 0.9]) and 0.5 weeks for II (two-sided 95 % confidence intervals [-0.4; 1.4]). The confidence intervals of both parameters were within the predefined therapeutic equivalence range set to ±1.5 weeks, thus indicating similar efficacy of both BT drugs. Having based the exchange of Botox(®) and Xeomin(®) on a conversion factor of 1:1 our data confirm previous findings of an identical potency labelling of both products, thus allowing comparisons of efficacy, adverse effects and costs.

  9. Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells

    PubMed Central

    Hewett, Jeffrey W.; Tannous, Bakhos; Niland, Brian P.; Nery, Flavia C.; Zeng, Juan; Li, Yuqing; Breakefield, Xandra O.

    2007-01-01

    TorsinA is an AAA+ protein located predominantly in the lumen of the endoplasmic reticulum (ER) and nuclear envelope responsible for early onset torsion dystonia (DYT1). Most cases of this dominantly inherited movement disorder are caused by deletion of a glutamic acid in the carboxyl terminal region of torsinA. We used a sensitive reporter, Gaussia luciferase (Gluc) to evaluate the role of torsinA in processing proteins through the ER. In primary fibroblasts from controls and DYT1 patients most Gluc activity (95%) was released into the media and processed through the secretory pathway, as confirmed by inhibition with brefeldinA and nocodazole. Fusion of Gluc to a fluorescent protein revealed coalignment and fractionation with ER proteins and association of Gluc with torsinA. Notably, fibroblasts from DYT1 patients were found to secrete markedly less Gluc activity as compared with control fibroblasts. This decrease in processing of Gluc in DYT1 cells appear to arise, at least in part, from a loss of torsinA activity, because mouse embryonic fibroblasts lacking torsinA also had reduced secretion as compared with control cells. These studies demonstrate the exquisite sensitivity of this reporter system for quantitation of processing through the secretory pathway and support a role for torsinA as an ER chaperone protein. PMID:17428918

  10. Developing a Deep Brain Stimulation Neuromodulation Network for Parkinson Disease, Essential Tremor, and Dystonia: Report of a Quality Improvement Project

    PubMed Central

    O’Suilleabhain, Padraig E.; Sanghera, Manjit; Patel, Neepa; Khemani, Pravin; Lacritz, Laura H.; Chitnis, Shilpa; Whitworth, Louis A.; Dewey, Richard B.

    2016-01-01

    Objective To develop a process to improve patient outcomes from deep brain stimulation (DBS) surgery for Parkinson disease (PD), essential tremor (ET), and dystonia. Methods We employed standard quality improvement methodology using the Plan-Do-Study-Act process to improve patient selection, surgical DBS lead implantation, postoperative programming, and ongoing assessment of patient outcomes. Results The result of this quality improvement process was the development of a neuromodulation network. The key aspect of this program is rigorous patient assessment of both motor and non-motor outcomes tracked longitudinally using a REDCap database. We describe how this information is used to identify problems and to initiate Plan-Do-Study-Act cycles to address them. Preliminary outcomes data is presented for the cohort of PD and ET patients who have received surgery since the creation of the neuromodulation network. Conclusions Careful outcomes tracking is essential to ensure quality in a complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap database system is well suited to store outcomes data for the purpose of ongoing quality assurance monitoring. PMID:27711133

  11. Self-awareness of motor dysfunction in patients with Huntington's disease in comparison to Parkinson's disease and cervical dystonia.

    PubMed

    Sitek, Emilia J; Sołtan, Witold; Wieczorek, Dariusz; Schinwelski, Michał; Robowski, Piotr; Reilmann, Ralf; Guzińska, Katarzyna; Harciarek, Michał; Krysa, Wioletta; Sławek, Jarosław

    2011-09-01

    Individuals suffering from Huntington's disease (HD) have been shown to present with poor self-awareness of a variety of symptoms. The aim of this study was to better assess the self-awareness of motor symptoms and activities of daily living (ADL) impairment in HD, in comparison to Parkinson's disease (PD) and cervical dystonia (CD). In particular, the anosognosia/anosodiaphoria of involuntary movements has been investigated. Self-awareness was tested in 23 patients with HD by comparing patient and caregiver ratings in reference to clinical control groups (25 PD with dyskinesias, PDdys; 21 PD without dyskinesias, PDndys; and 20 with CD). Patients were assessed neurologically by relevant rating scales. Self-awareness was tested using a scale based on 15 films demonstrating 3 types of motor symptoms (chorea/dyskinesias, parkinsonism, torticollis) as well as the Self-Assessment Parkinson's Disease Disability Scale. General cognitive status, verbal learning, cognitive control, and mood were also analyzed. Our results indicate that self-awareness of choreic movements was affected more severely in HD than in PDdys, despite comparable cognitive status. Patient-proxy agreement on ADL impairment was roughly similar in all clinical groups. The results are discussed in the context of orbitofrontal-limbic pathology as a potential trigger of anosognosia/anosodiaphoria in individuals with HD.

  12. Contiguous deletion of SLC6A8 and BAP31 in a patient with severe dystonia and sensorineural deafness.

    PubMed

    Osaka, Hitoshi; Takagi, Atsushi; Tsuyusaki, Yu; Wada, Takahito; Iai, Mizue; Yamashita, Sumimasa; Shimbo, Hiroko; Saitsu, Hirotomo; Salomons, Gajja S; Jakobs, Cornelis; Aida, Noriko; Toshihiro, Shinka; Kuhara, Tomiko; Matsumoto, Naomichi

    2012-05-01

    We report here a 6-year-old boy exhibiting severe dystonia, profound intellectual and developmental disability with liver disease, and sensorineural deafness. A deficient creatine peak in brain (1)H-MR spectroscopy and high ratio of creatine/creatinine concentration in his urine lead us to suspect a creatine transporter (solute carrier family 6, member 8; SLC6A8) deficiency, which was confirmed by the inability to take up creatine into fibroblasts. We found a large ~19 kb deletion encompassing exons 5-13 of SLC6A8 and exons 5-8 of the B-cell receptor-associated protein (BAP31) gene. This case is the first report in which the SLC6A8 and BAP31 genes are both deleted. The phenotype of BAP31 mutations has been reported only as a part of Xq28 deletion syndrome or contiguous ATP-binding cassette, sub-family D, member 1 (ABCD1)/DXS1375E (BAP31) deletion syndrome [MIM ID #300475], where liver dysfunction and sensorineural deafness have been suggested to be attributed to the loss of function of BAP31. Our case supports the idea that the loss of BAP31 is related to liver dysfunction and hearing loss.

  13. Severity and impact of xerostomia in patients treated with botulinum toxin type b for cervical dystonia: Observations on the quality of life of patients with xerostomia

    PubMed Central

    Hogan, Patrick; Charles, P.David; Wooten Watts, Maureen; Massey, Janice M.; Miller, Tamara; Mackowiack, John

    2004-01-01

    Background: Although dry mouth (xerostomia) has been reported with botulinum toxin type B used as treatment for cervical dystonia, the impact of this adverse effect (AE) on patients' activities of daily living (ADLs) has not been assessed. tObjective: The aim of this study was to examine the severity, duration, and impact of xerostomia in patients with cervical dystonia who reported this AE in routine clinical practice following treatment with botulinum toxin type B. Methods: In this uncontrolled study, investigators at 5 study centers across the United States retrospectively identified patients who were diagnosed with cervical dystonia and had received ≥ 1 treatment with botulinum toxin type B injection and who had reported xerostomia, based on patients' charts. These patients were mailed a survey that included questions about their treatment history, disease severity, and xerostomia (severity, onset, duration, change with subsequent injections, and effects on dental and oral health), as well as an 8-item Patient Benefit Questionnaire (PBQ), which was designed to assess the impact of xerostomia symptoms on patients' ADLs. Results: A total of 45 patients received a mean of 2.91 injections with botulinum toxin type B (mean dose per injection, 11,958 U), with a total of 131 injections. The mean severity of patient-rated xerostomia following the first injection of botulinum toxin type B was 3.88 on a scale of 1 (mild) to 5 (severe), and this rating did not change for patients who received subsequent injections (mean, 3.76). Following atypical injection of botulinum toxin type B, xerostomia began a mean (SD) of 4.82 (3.32) days later and persisted for a mean (SD) duration of 5.56 (3.57) weeks. The overall mean score on the 10-point PBQ prior to botulinum toxin treatment was 8.89, which decreased to 5.42 following botulinum toxin type B injection (lower scores indicate more severe xerostomia). Conclusions: This study of patients with cervical dystonia suggests that

  14. A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma

    PubMed Central

    2013-01-01

    Background In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Methods Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. Results The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). Conclusions We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions. PMID:24165294

  15. Reduced Neck Muscle Strength and Altered Muscle Mechanical Properties in Cervical Dystonia Following Botulinum Neurotoxin Injections: A Prospective Study

    PubMed Central

    Mustalampi, Sirpa; Ylinen, Jari; Korniloff, Katariina; Weir, Adam; Häkkinen, Arja

    2016-01-01

    Objective To evaluate changes in the strength and mechanical properties of neck muscles and disability in patients with cervical dystonia (CD) during a 12-week period following botulinum neurotoxin (BoNT) injections. Methods Eight patients with CD volunteered for this prospective clinical cohort study. Patients had received BoNT injections regularly in neck muscles at three-month intervals for several years. Maximal isometric neck strength was measured by a dynamometer, and the mechanical properties of the splenius capitis were evaluated using two myotonometers. Clinical assessment was performed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before and at 2, 4, 8, and 12 weeks after the BoNT injections. Results Mean maximal isometric neck strength at two weeks after the BoNT injections decreased by 28% in extension, 25% in rotation of the affected side and 17% in flexion. At four weeks, muscle stiffness of the affected side decreased by 17% and tension decreased by 6%. At eight weeks, the muscle elasticity on the affected side increased by 12%. At two weeks after the BoNT injections, the TWSTRS-severity and TWSTRS-total scores decreased by 4.3 and 6.4, respectively. The strength, muscle mechanical properties and TWSTRS scores returned to baseline values at 12 weeks. Conclusions Although maximal neck strength and muscle tone decreased after BoNT injections, the disability improved. The changes observed after BoNT injections were temporary and returned to pre-injection levels within twelve weeks. Despite having a possible negative effect on function and decreasing neck strength, the BoNT injections improved the patients reported disability. PMID:26828215

  16. Decreased N-TAF1 expression in X-linked dystonia-parkinsonism patient-specific neural stem cells

    PubMed Central

    Ito, Naoto; Hendriks, William T.; Dhakal, Jyotsna; Vaine, Christine A.; Liu, Christina; Shin, David; Shin, Kyle; Wakabayashi-Ito, Noriko; Dy, Marisela; Multhaupt-Buell, Trisha; Sharma, Nutan; Breakefield, Xandra O.; Bragg, D. Cristopher

    2016-01-01

    ABSTRACT X-linked dystonia-parkinsonism (XDP) is a hereditary neurodegenerative disorder involving a progressive loss of striatal medium spiny neurons. The mechanisms underlying neurodegeneration are not known, in part because there have been few cellular models available for studying the disease. The XDP haplotype consists of multiple sequence variations in a region of the X chromosome containing TAF1, a large gene with at least 38 exons, and a multiple transcript system (MTS) composed of five unconventional exons. A previous study identified an XDP-specific insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon in intron 32 of TAF1, as well as a neural-specific TAF1 isoform, N-TAF1, which showed decreased expression in post-mortem XDP brain compared with control tissue. Here, we generated XDP patient and control fibroblasts and induced pluripotent stem cells (iPSCs) in order to further probe cellular defects associated with this disease. As initial validation of the model, we compared expression of TAF1 and MTS transcripts in XDP versus control fibroblasts and iPSC-derived neural stem cells (NSCs). Compared with control cells, XDP fibroblasts exhibited decreased expression of TAF1 transcript fragments derived from exons 32-36, a region spanning the SVA insertion site. N-TAF1, which incorporates an alternative exon (exon 34′), was not expressed in fibroblasts, but was detectable in iPSC-differentiated NSCs at levels that were ∼threefold lower in XDP cells than in controls. These results support the previous findings that N-TAF1 expression is impaired in XDP, but additionally indicate that this aberrant transcription might occur in neural cells at relatively early stages of development that precede neurodegeneration. PMID:26769797

  17. Defining the epsilon-sarcoglycan (SGCE) gene phenotypic signature in myoclonus-dystonia: a reappraisal of genetic testing criteria.

    PubMed

    Carecchio, Miryam; Magliozzi, Monia; Copetti, Massimiliano; Ferraris, Alessandro; Bernardini, Laura; Bonetti, Monica; Defazio, Giovanni; Edwards, Mark J; Torrente, Isabella; Pellegrini, Fabio; Comi, Cristoforo; Bhatia, Kailash P; Valente, Enza Maria

    2013-06-01

    Mutations or exon deletions of the epsilon-sarcoglycan (SGCE) gene cause myoclonus-dystonia (M-D), but a subset of M-D patients are mutation-negative and the sensitivity and specificity of current genetic testing criteria are unknown. We screened 46 newly enrolled M-D patients for SGCE mutations and deletions; moreover, 24 subjects previously testing negative for SGCE mutations underwent gene dosage analysis. In our combined cohorts, we calculated sensitivity, specificity, positive and negative predictive values, and area under the curve of 2 published sets of M-D diagnostic criteria. A stepwise logistic regression was used to assess which patients' characteristics best discriminated mutation carriers and to calculate a new mutation predictive score ("new score"), which we validated in previously published cohorts. Nine of 46 (19.5%) patients of the new cohort carried SCGE mutations, including 5 novel point mutations and 1 whole-gene deletion; in the old cohort, 1 patient with a complex phenotype carried a 5.9-Mb deletion encompassing SGCE. Current diagnostic criteria had a poor ability to discriminate SGCE-positive from SGCE-negative patients in our cohort; conversely, age of onset, especially if associated with psychiatric features (as included in the new score), showed the best discriminatory power to individuate SGCE mutation carriers, both in our cohort and in the validation cohort. Our results suggest that young age at onset of motor symptoms, especially in association with psychiatric disturbance, are strongly predictive for SGCE positivity. We suggest performing gene dosage analysis by multiple ligation-dependent probe amplification (MLPA) to individuate large SGCE deletions that can be responsible for complex phenotypes.

  18. A mixed treatment comparison to compare the efficacy and safety of botulinum toxin treatments for cervical dystonia.

    PubMed

    Han, Yi; Stevens, Andrea L; Dashtipour, Khashayar; Hauser, Robert A; Mari, Zoltan

    2016-04-01

    A systematic pair-wise comparison of all available botulinum toxin serotype A and B treatments for cervical dystonia (CD) was conducted, as direct head-to-head clinical trial comparisons are lacking. Five botulinum toxin products: Dysport(®) (abobotulinumtoxinA), Botox(®) (onabotulinumtoxinA), Xeomin(®) (incobotulinumtoxinA), Prosigne(®) (Chinese botulinum toxin serotype A) and Myobloc(®) (rimabotulinumtoxinB) have demonstrated efficacy for managing CD. A pair-wise efficacy and safety comparison was performed for all toxins based on literature-reported clinical outcomes. Multi-armed randomized controlled trials (RCTs) were identified for inclusion using a systematic literature review, and assessed for comparability based on patient population and efficacy outcome measures. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was selected as the efficacy outcome measurement for assessment. A mixed treatment comparison (MTC) was conducted using a Bayesian hierarchical model allowing indirect comparison of the interventions. Due to the limitation of available clinical data, this study only investigated the main effect of toxin treatments without explicitly considering potential confounding factors such as gender and formulation differences. There was reasonable agreement between the number of unconstrained data points, residual deviance and pair-wise results. This research suggests that all botulinum toxin serotype A and serotype B treatments were effective compared to placebo in treating CD, with the exception of Prosigne. Based on this MTC analysis, there is no significant efficacy difference between Dysport, Botox, Xeomin and Myobloc at week four post injection. Of the adverse events measured, neither dysphagia nor injection site pain was significantly greater in the treatment or placebo groups.

  19. Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia

    SciTech Connect

    Demircioglu, F. Esra; Sosa, Brian A.; Ingram, Jessica; Ploegh, Hidde L.; Schwartz, Thomas U.

    2016-08-04

    The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia.

  20. Structures of TorsinA and its disease-mutant complexed with an activator reveal the molecular basis for primary dystonia

    PubMed Central

    Demircioglu, F Esra; Sosa, Brian A; Ingram, Jessica; Ploegh, Hidde L; Schwartz, Thomas U

    2016-01-01

    The most common cause of early onset primary dystonia, a neuromuscular disease, is a glutamate deletion (ΔE) at position 302/303 of TorsinA, a AAA+ ATPase that resides in the endoplasmic reticulum. While the function of TorsinA remains elusive, the ΔE mutation is known to diminish binding of two TorsinA ATPase activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a 1.4 Å crystal structure of human TorsinA in complex with LULL1. This nanobody likewise stabilized the weakened TorsinAΔE-LULL1 interaction, which enabled us to solve its structure at 1.4 Å also. A comparison of these structures shows, in atomic detail, the subtle differences in activator interactions that separate the healthy from the diseased state. This information may provide a structural platform for drug development, as a small molecule that rescues TorsinAΔE could serve as a cure for primary dystonia. DOI: http://dx.doi.org/10.7554/eLife.17983.001 PMID:27490483

  1. A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1.

    PubMed

    Liu, Yi Bessie; Tewari, Ambika; Salameh, Johnny; Arystarkhova, Elena; Hampton, Thomas G; Brashear, Allison; Ozelius, Laurie J; Khodakhah, Kamran; Sweadner, Kathleen J

    2015-12-24

    A new mutant mouse (lamb1t) exhibits intermittent dystonic hindlimb movements and postures when awake, and hyperextension when asleep. Experiments showed co-contraction of opposing muscle groups, and indicated that symptoms depended on the interaction of brain and spinal cord. SNP mapping and exome sequencing identified the dominant causative mutation in the Lamb1 gene. Laminins are extracellular matrix proteins, widely expressed but also known to be important in synapse structure and plasticity. In accordance, awake recording in the cerebellum detected abnormal output from a circuit of two Lamb1-expressing neurons, Purkinje cells and their deep cerebellar nucleus targets, during abnormal postures. We propose that dystonia-like symptoms result from lapses in descending inhibition, exposing excess activity in intrinsic spinal circuits that coordinate muscles. The mouse is a new model for testing how dysfunction in the CNS causes specific abnormal movements and postures.

  2. Dystonia: Physical Therapy

    MedlinePlus

    ... Your Doctor Find a Doctor Finding Support Emotional & Mental Health When a Child is Diagnosed - Resources for Families ... Find a Doctor Finding Support Coping Articles Emotional & Mental Health When a Child is Diagnosed Online Support Frequently ...

  3. Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol.

    PubMed

    Deutsch, Stephen I; Rosse, Richard B; Connor, Julie M; Burket, Jessica A; Murphy, Mary E; Fox, Fiona J

    2008-05-01

    Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.

  4. Survey of practices employed by neurologists for the definition and management of secondary non-response to botulinum toxin in cervical dystonia.

    PubMed

    Ferreira, Joaquim J; Bhidayasiri, Roongroj; Colosimo, Carlo; Marti, Maria Jose; Zakine, Benjamin; Maisonobe, Pascal

    2012-01-01

    Secondary non-response (SNR) to botulinum toxin (BoNT) in cervical dystonia (CD) lacks a universal definition. We conducted a retrospective survey to develop a definition based on clinicians' practice. Fifty-seven neurologists completed a 17-item questionnaire. In defining SNR, insufficiently improved posture was considered to be more relevant (98% of physicians) than insufficiently improved pain (86%). The most frequently used diagnostic test for SNR was the frontalis test (68%); antibody testing was performed by only 13% of physicians. Three consecutive unsuccessful injection cycles were considered the most appropriate indicator of SNR (55% of physicians). Physicians reported that 5.9% (median) of patients treated in 2008 became secondary non-responders to BoNT-A. The most common strategy for SNR was optimization of physiotherapy, considered by 98% of the physicians. On the basis of our findings, SNR can be defined as insufficiently improved posture after ≥3 unsuccessful injection cycles in CD patients previously achieving satisfactory results.

  5. Mutations in BCAP31 Cause a Severe X-Linked Phenotype with Deafness, Dystonia, and Central Hypomyelination and Disorganize the Golgi Apparatus

    PubMed Central

    Cacciagli, Pierre; Sutera-Sardo, Julie; Borges-Correia, Ana; Roux, Jean-Christophe; Dorboz, Imen; Desvignes, Jean-Pierre; Badens, Catherine; Delepine, Marc; Lathrop, Mark; Cau, Pierre; Lévy, Nicolas; Girard, Nadine; Sarda, Pierre; Boespflug-Tanguy, Odile; Villard, Laurent

    2013-01-01

    BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways, including ER-associated degradation, export of ER proteins to the Golgi apparatus, and programmed cell death. BAP31 is encoded by BCAP31, located in human Xq28 and highly expressed in neurons. We identified loss-of-function mutations in BCAP31 in seven individuals from three families. These persons suffered from motor and intellectual disabilities, dystonia, sensorineural deafness, and white-matter changes, which together define an X-linked syndrome. In the primary fibroblasts of affected individuals, we found that BCAP31 deficiency altered ER morphology and caused a disorganization of the Golgi apparatus in a significant proportion of cells. Contrary to what has been described with transient-RNA-interference experiments, we demonstrate that constitutive BCAP31 deficiency does not activate the unfolded protein response or cell-death effectors. Rather, our data demonstrate that the lack of BAP31 disturbs ER metabolism and impacts the Golgi apparatus, highlighting an important role for BAP31 in ER-to-Golgi crosstalk. These findings provide a molecular basis for a Mendelian syndrome and link intracellular protein trafficking to severe congenital brain dysfunction and deafness. PMID:24011989

  6. A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy.

    PubMed

    Zazo Seco, Celia; Castells-Nobau, Anna; Joo, Seol-Hee; Schraders, Margit; Foo, Jia Nee; van der Voet, Monique; Velan, S Sendhil; Nijhof, Bonnie; Oostrik, Jaap; de Vrieze, Erik; Katana, Radoslaw; Mansoor, Atika; Huynen, Martijn; Szklarczyk, Radek; Oti, Martin; Tranebjærg, Lisbeth; van Wijk, Erwin; Scheffer-de Gooyert, Jolanda M; Siddique, Saadat; Baets, Jonathan; de Jonghe, Peter; Kazmi, Syed Ali Raza; Sadananthan, Suresh Anand; van de Warrenburg, Bart P; Khor, Chiea Chuen; Göpfert, Martin C; Qamar, Raheel; Schenck, Annette; Kremer, Hannie; Siddiqi, Saima

    2017-02-01

    A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2.

  7. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    SciTech Connect

    De Vries, D.D.; Oost, B.A. van; Went, L.N.; Bruyn, G.W.

    1996-04-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. 80 refs., 2 figs., 3 tabs.

  8. A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy

    PubMed Central

    Zazo Seco, Celia; Castells-Nobau, Anna; Joo, Seol-hee; Schraders, Margit; Foo, Jia Nee; van der Voet, Monique; Velan, S. Sendhil; Nijhof, Bonnie; Oostrik, Jaap; de Vrieze, Erik; Katana, Radoslaw; Mansoor, Atika; Huynen, Martijn; Szklarczyk, Radek; Oti, Martin; Tranebjærg, Lisbeth; van Wijk, Erwin; Scheffer-de Gooyert, Jolanda M.; Siddique, Saadat; Baets, Jonathan; de Jonghe, Peter; Sadananthan, Suresh Anand; van de Warrenburg, Bart P.; Khor, Chiea Chuen; Göpfert, Martin C.; Qamar, Raheel; Schenck, Annette

    2017-01-01

    ABSTRACT A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2. PMID:28067622

  9. Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia, and central hypomyelination and disorganize the Golgi apparatus.

    PubMed

    Cacciagli, Pierre; Sutera-Sardo, Julie; Borges-Correia, Ana; Roux, Jean-Christophe; Dorboz, Imen; Desvignes, Jean-Pierre; Badens, Catherine; Delepine, Marc; Lathrop, Mark; Cau, Pierre; Lévy, Nicolas; Girard, Nadine; Sarda, Pierre; Boespflug-Tanguy, Odile; Villard, Laurent

    2013-09-05

    BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways, including ER-associated degradation, export of ER proteins to the Golgi apparatus, and programmed cell death. BAP31 is encoded by BCAP31, located in human Xq28 and highly expressed in neurons. We identified loss-of-function mutations in BCAP31 in seven individuals from three families. These persons suffered from motor and intellectual disabilities, dystonia, sensorineural deafness, and white-matter changes, which together define an X-linked syndrome. In the primary fibroblasts of affected individuals, we found that BCAP31 deficiency altered ER morphology and caused a disorganization of the Golgi apparatus in a significant proportion of cells. Contrary to what has been described with transient-RNA-interference experiments, we demonstrate that constitutive BCAP31 deficiency does not activate the unfolded protein response or cell-death effectors. Rather, our data demonstrate that the lack of BAP31 disturbs ER metabolism and impacts the Golgi apparatus, highlighting an important role for BAP31 in ER-to-Golgi crosstalk. These findings provide a molecular basis for a Mendelian syndrome and link intracellular protein trafficking to severe congenital brain dysfunction and deafness.

  10. A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1

    PubMed Central

    Liu, Yi Bessie; Tewari, Ambika; Salameh, Johnny; Arystarkhova, Elena; Hampton, Thomas G; Brashear, Allison; Ozelius, Laurie J; Khodakhah, Kamran; Sweadner, Kathleen J

    2015-01-01

    A new mutant mouse (lamb1t) exhibits intermittent dystonic hindlimb movements and postures when awake, and hyperextension when asleep. Experiments showed co-contraction of opposing muscle groups, and indicated that symptoms depended on the interaction of brain and spinal cord. SNP mapping and exome sequencing identified the dominant causative mutation in the Lamb1 gene. Laminins are extracellular matrix proteins, widely expressed but also known to be important in synapse structure and plasticity. In accordance, awake recording in the cerebellum detected abnormal output from a circuit of two Lamb1-expressing neurons, Purkinje cells and their deep cerebellar nucleus targets, during abnormal postures. We propose that dystonia-like symptoms result from lapses in descending inhibition, exposing excess activity in intrinsic spinal circuits that coordinate muscles. The mouse is a new model for testing how dysfunction in the CNS causes specific abnormal movements and postures. DOI: http://dx.doi.org/10.7554/eLife.11102.001 PMID:26705335

  11. A-TWinnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity.

    PubMed

    Nakamura, Kotoka; Fike, Francesca; Haghayegh, Sara; Saunders-Pullman, Rachel; Dawson, Angelika J; Dörk, Thilo; Gatti, Richard A

    2014-07-01

    We studied 10 Mennonite patients who carry the c.6200C>A missense mutation (p.A2067D) in the ATM gene, all of whom exhibited a phenotypic variant of ataxia-telangiectasia (A-T) that is characterized by early-onset dystonia and late-onset mild ataxia, as previously described. This report provides the pathogenetic evidence for this mutation on cellular functions. Several patients have developed cancer and subsequently experienced life-threatening adverse reactions to radiation (radiotoxicity) and/or chemotherapy. As the c.6200C>A mutation is, thus far, unique to the Mennonite population and is always associated with the same haplotype or haplovariant, it was important to rule out any possible confounding DNA variant on the same haplotype. Lymphoblastoid cells derived from Mennonite patients expressed small amounts of ATM protein, which had no autophosphorylation activity at ATM Ser1981, and trace-to-absent transphosphorylation of downstream ATM targets. A-T lymphoblastoid cells stably transfected with ATM cDNA which had been mutated for c.6200C>A did not show a detectable amount of ATM protein. The same stable cell line with mutated ATM cDNA also showed a trace-to-absent transphosphorylation of downstream ATM targets SMC1pSer966 and KAP1pSer824. From these results, we conclude that c.6200A is the disease-causing ATM mutation on this haplotype. The presence of at least trace amounts of ATM kinase activity on some immunoblots may account for the late-onset, mild ataxia of these patients. The cause of the dystonia remains unclear. Because this dystonia-ataxia phenotype is often encountered in the Mennonite population in association with cancer and adverse reactions to chemotherapy, an early diagnosis is important.

  12. Clinical Characteristics and Response to Long-Term Botulinum Toxin Type A Therapy in Patients with Cervical Dystonia at a Neurology Clinic

    PubMed Central

    ŞEN, Aysu; SOYSAL, Aysun; ARPACI, Baki

    2014-01-01

    Introduction To determine the demographic and clinical characteristics and response to botulinum toxin type A (BoNT-A) therapy in patients with cervical dystonia (CD). Method A retrospective analysis of the detailed medical records of the patients with CD, followed up at our Botulinum Toxin Outpatient Clinic from 1998 to 2012, was performed. The treatment data were compared between the patients with primary CD and those with secondary CD; between patients receiving BoNT-A treatment for more than 5 years and less than five years, and between first applications and last applications. Results Fifty-seven patients (56.15% women) with CD were included in this study. The mean age was 41.01±13.42 years, the mean age at symptom onset was 32.93±15.45 years, and the mean dystonia duration was 8.10±8.5 years. The interval between onset of symptom and first BoNT-A treatment was 5.94±9.06 years, the duration of BoNT-A treatment was 36.13±29.17 months, and the number of applications was 8.48±6.23 in 45 patients with CD who were under treatment with BoNT-A for more than 1 year and had received at least three injections before. There was no difference between the patients with primary and secondary CD in terms of treatment results. The injection interval of the patients receiving BoNT-A treatment for more than 5 years and less than 5 years was 18.37±5.10 and 14.43±2.36 weeks, respectively (p=.001). There were no differences in the other treatment values. The mean doses were 559.00±147.60 vs. 681.66±188.09 units (p=.0001), the durations of improvement were 11.82±2.71 vs. 13.00±4.00 weeks (p=.014), the response scores were 2.71±.3 vs. 3.02±.5 (p=.002), the response ratings were 64.66%±16.18 vs. 71.22%±17.29 (p=.001), and the numbers of muscles applied were 3.15±1.16 vs. 3.51±0.99 (p=.012) in the first and last applications, respectively. Conclusion There were no differences between the response of the patients with primary and secondary CD. Our results showed a

  13. A multifactorial conceptual model of peripheral neuromusculoskeletal predisposing factors in task-specific focal hand dystonia in musicians: etiologic and therapeutic implications.

    PubMed

    Leijnse, J N A L; Hallett, M; Sonneveld, G J

    2015-02-01

    A model is presented showing how peripheral factors may cause a process of movement adaptation that leads to task-specific focal hand dystonia in musicians (FHDM). To acquire a playing technique, the hand must find effective and physiologically sustainable movements within a complex set of functional demands and anatomic, ergonomic, and physiological constraints. In doing so, individually discriminating constraints may become effective, such as limited anatomic independence of finger muscles/tendons, limited joint ranges of motion, or (subclinical) neuromusculoskeletal defects. These factors may, depending on the instrument-specific playing requirements, compromise or exclude functional playing movements. The controller (i.e., the brain) then needs to develop alternative motions to execute the task, which is called compensation. We hypothesize that, if this compensation process does not converge to physiologically sustainable muscle activation patterns that satisfy all constraints, compensation could increase indefinitely under the pressure of practice. Dystonic symptoms would become manifest when overcompensation occurs, resulting in motor patterns that fail in proper task execution. The model presented in this paper only concerns the compensatory processes preceding such overcompensations and does not aim to explain the nature of the dystonic motions themselves. While the model considers normal learning processes in the development of compensations, neurological predispositions could facilitate developing overcompensations or further abnormal motor programs. The model predicts that if peripheral factors are involved, FHDM symptoms would be preceded by long-term gradual changes in playing movements, which could be validated by prospective studies. Furthermore, the model implies that treatment success might be enhanced by addressing the conflict between peripheral factors and playing tasks before decompensating/retraining the affected movements.

  14. Genetic Analysis of PLA2G6 in 22 Indian Families with Infantile Neuroaxonal Dystrophy, Atypical Late-Onset Neuroaxonal Dystrophy and Dystonia Parkinsonism Complex

    PubMed Central

    Rather, Mohammad Iqbal; Bhat, Vishwanath; Gopinath, Sindhura; Bindu, Parayil Sankaran; Taly, Arun B.; Sinha, Sanjib; Nagappa, Madhu; Bharath, Rose Dawn; Mahadevan, Anita; Narayanappa, Gayathri; Chickabasaviah, Yasha T.; Kumar, Arun

    2016-01-01

    Mutations in PLA2G6 were identified in patients with a spectrum of neurodegenerative conditions, such as infantile neuroaxonal dystrophy (INAD), atypical late-onset neuroaxonal dystrophy (ANAD) and dystonia parkinsonism complex (DPC). However, there is no report on the genetic analysis of families with members affected with INAD, ANAD and DPC from India. Therefore, the main aim of this study was to perform genetic analysis of 22 Indian families with INAD, ANAD and DPC. DNA sequence analysis of the entire coding region of PLA2G6 identified 13 different mutations, including five novel ones (p.Leu224Pro, p.Asp283Asn, p.Arg329Cys, p.Leu491Phe, and p.Arg649His), in 12/22 (54.55%) families with INAD and ANAD. Interestingly, one patient with INAD was homozygous for two different mutations, p.Leu491Phe and p.Ala516Val, and thus harboured four mutant alleles. With these mutations, the total number of mutations in this gene reaches 129. The absence of mutations in 10/22 (45.45%) families suggests that the mutations could be in deep intronic or promoter regions of this gene or these families could have mutations in a yet to be identified gene. The present study increases the mutation landscape of PLA2G6. The present finding will be useful for genetic diagnosis, carrier detection and genetic counselling to families included in this study and other families with similar disease condition. PMID:27196560

  15. Dysport and Botox at a ratio of 2.5:1 units in cervical dystonia: a double-blind, randomized study.

    PubMed

    Yun, Ji Young; Kim, Jae Woo; Kim, Hee-Tae; Chung, Sun Ju; Kim, Jong-Min; Cho, Jin Whan; Lee, Jee-Young; Lee, Ha Neul; You, Sooyeoun; Oh, Eungseok; Jeong, Heejeong; Kim, Young Eun; Kim, Han-Joon; Lee, Won Yong; Jeon, Beom S

    2015-02-01

    We aimed to compare Dysport (abobotulinumtoxinA, Ipsen Biopharm, Slough, UK) and Botox (onabotulinumtoxinA, Allergan, Irvine, CA, USA) at a 2.5:1 ratio in the treatment of cervical dystonia (CD). A Dysport/Botox ratio of lower than 3:1 was suggested as a more appropriate conversion ratio, considering its higher efficacy and more frequent incidence of adverse effects not only in the treatment of CD but also in other focal movement disorders. A randomized, double-blind, multicenter, non-inferiority, two-period crossover study was done in CD, with a duration of at least 18 months. Patients were randomly assigned to treatment for the first period with Dysport or Botox, and they were followed up for 16 weeks after the injection. After a 4-week washout period, they were switched to the other formulation and then followed up for 16 weeks. The primary outcome was the changes in the Tsui scale between the baseline value and that at 1 month after each injection. A total of 103 patients were enrolled, and 94 completed the study. Mean changes in the Tsui scale between baseline and 4 weeks after each injection tended to favor Botox; however, this was not statistically significant (4.0 ± 3.9 points for the Dysport treatment vs. 4.8 ± 4.1 points for Botox; 95% confidence interval, -0.1-1.7; P = 0.091). The mean change of the Toronto western spasmodic torticollis rating scale score, the proportion of improvement in clinical global impression and patient global impression, and the incidences of adverse events were not significantly different between the two treatments. With regard to safety and efficacy, Dysport was not inferior to Botox in patients with CD at a conversion factor of 2.5:1. [clinicaltrial.gov: NCT00950664

  16. Effect of Paget's disease of bone (osteitis deformans) on the progression of prostate cancer bone metastasis

    PubMed Central

    Tu, S-M; Som, A; Tu, B; Logothetis, C J; Lee, M-H; Yeung, S-CJ

    2012-01-01

    Background: Patients with prostate cancer tend to die from bone metastases. Until now, no evidence has shown that Paget's disease of bone (PDB) affects the progression of bone metastasis or overall survival of patients with prostate cancer. Methods: We searched our patient database for men who had presented with prostate cancer and PDB between June 1993 and March 2009, and identified best-matched control patients according to stage, grade, age, date of diagnosis, treatment, and race. Results: Among 1346 consecutive patients with prostate cancer diagnosed before 2008, 15 were confirmed to have comorbid PDB. Twenty-six more were identified from the institutional billing search. Including the 41 best-matched controls, our total study population was 82 patients. In the Kaplan–Meier analysis, we estimated median times from diagnosis of prostate cancer to bone metastasis to be 21.5 years for those with PDB and 9.4 years for those without PDB (P=0.044). Median overall survival times were 11.8 and 9.2 years for the two groups, respectively (P=0.008). Conclusion: For the first time, we have obtained evidence that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone. PMID:22805323

  17. X-linked dystonia parkinsonism syndrome (XDP, lubag): disease-specific sequence change DSC3 in TAF1/DYT3 affects genes in vesicular transport and dopamine metabolism.

    PubMed

    Herzfeld, Thilo; Nolte, Dagmar; Grznarova, Maria; Hofmann, Andrea; Schultze, Joachim L; Müller, Ulrich

    2013-03-01

    X-chromosomal dystonia parkinsonism syndrome (XDP, 'lubag') is associated with sequence changes within the TAF1/DYT3 multiple transcript system. Although most sequence changes are intronic, one, disease-specific single-nucleotide change 3 (DSC3), is located within an exon (d4). Transcribed exon d4 occurs as part of multiple splice variants. These variants include exons d3 and d4 spliced to exons of TAF1, and an independent transcript composed of exons d2-d4. Location of DSC3 in exon d4 and utilization of this exon in multiple splice variants suggest an important role of DSC3 in the XDP pathogenesis. To test this hypothesis, we transfected neuroblastoma cells with four expression constructs, including exons d2-d4 [d2-d4/wild-type (wt) and d2-d4/DSC3] and d3-d4 (d3-d4/wt and d3-d4/DSC3). Expression profiling revealed a dramatic effect of DSC3 on overall gene expression. Three hundred and sixty-two genes differed between cells containing d2-d4/wt and d2-d4/DSC3. Annotation clustering revealed enrichment of genes related to vesicular transport, dopamine metabolism, synapse function, Ca(2+) metabolism and oxidative stress. Two hundred and eleven genes were differentially expressed in d3-d4/wt versus d3-d4/DSC3. Annotation clustering highlighted genes in signal transduction and cell-cell interaction. The data show an important role of physiologically occurring transcript d2-d4 in normal brain function. Interference with this role by DSC3 is a likely pathological mechanism in XDP. Disturbance of dopamine function and of Ca(2+) metabolism can explain abnormal movement; loss of protection against reactive oxygen species may account for the neurodegenerative changes in XDP. Although d3-d4 also affect genes potentially related to neurodegenerative processes, their physiologic role as splice variants of TAF1 awaits further exploration.

  18. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder: Part 1.

    PubMed

    Preskorn, Sheldon; Flynn, Alexandra; Macaluso, Matthew

    2015-09-01

    This series of columns has 2 main goals: (1) to explain the use of class warnings by the US Food and Drug Administration and (2) to increase clinicians' awareness of movement disorders that may occur in patients being treated with antipsychotic medications and why it is appropriate and good practice to refrain from immediately assuming the diagnosis is tardive dyskinesia/dystonia (TD). This first column in the series will focus on the second goal, which will then serve as a case example for the first goal. Clinicians should refrain from jumping to a diagnosis of TD because a host of other causes need to be ruled out first before inferring iatrogenic causation. The causal relationship between chronic treatment with dopamine antagonists and TD is based on pharmacoepidemiology (ie, the prevalence of such movement disorders is higher in individuals receiving chronic treatment with such agents than in a control group). There is nothing pathognomonic about movement disorders, nor is there any test that can currently prove a drug caused a movement disorder in a specific individual. Another goal of this series is to describe the types of research that would be needed to establish whether a specific agent has a meaningful risk of causing TD. In this first column of the series, we present the case of a patient who developed orofacial dyskinesia while being treated with aripiprazole. In this case, the movement disorder was prematurely called TD, which led to a malpractice lawsuit. This case highlights a number of key questions clinicians are likely to encounter in day-to-day practice. We then review data concerning the historical background, incidence, prevalence, and risk factors for 2 movement disorders, TD and spontaneous dyskinesia. Subsequent columns in this series will review: (1) unique aspects of the psychopharmacology of aripiprazole, (2) the limited and inconsistent data in the literature concerning the causal relationship between aripiprazole and TD, (3) the use of

  19. [The autonomic regulation of the cardiovascular system in subjects with the autonomic dystonia syndrome subjected to ionizing radiation exposure as a result of the accident at the Chernobyl Atomic Electric Power Station].

    PubMed

    Niagu, A I; Zazimko, R N

    1995-01-01

    180 males in the age of 21-50, all the participants of Chernobyl accident consequences liquidation were examined. In all individuals vegetative dystonia (VD) syndrome was diagnosed (total radiation doses 0.1-1.0 Grey according to D. Erwin method). It was established that VD syndrome differed in these persons by pronounced stages of disorders manifestation as well as by polymorphism of vegetative disturbances. These findings testify central and peripheral vegetative nervous system parts involvement. In 40.2% of cases in individuals which were examined in rest and in 56.2% after dosed physical loading the functional disorders of vegetative cardiovascular system regulation of vagal type mainly (76.5%) were revealed. Clear correlation was not observed between vegetative disorders and radiation dose value. The estimation of contribution of each of the possible pathogenic factors (exactly stressogenic, radioactive and others) in vegetative disturbances development is not possible now.

  20. An open-label cohort study of the improvement of quality of life and pain in de novo cervical dystonia patients after injections with 500 U botulinum toxin A (Dysport)

    PubMed Central

    Hefter, H; Benecke, R; Erbguth, F; Jost, W; Reichel, G; Wissel, J

    2013-01-01

    Objectives It remains to be determined whether the benefits of botulinum toxin type A (BoNT-A) on cervical dystonia (CD) motor symptoms extend to improvements in patient's quality of life (QoL). This analysis of a large, multicentre study was conducted with the aim of investigating changes in QoL and functioning among de novo patients receiving 500 U BoNT-A (abobotulinumtoxinA; Dysport) for the treatment of the two most frequent forms of CD, predominantly torticollis and laterocollis. Design A prospective, open-label study of Dysport (500 U; Ipsen Biopharm Ltd) administered according to a defined intramuscular injection algorithm. Setting German and Austrian outpatient clinics. Participants 516 male and female patients (aged ≥18 years) with de novo CD. The majority of patients had torticollis (78.1%). 35 patients had concomitant depression (MedDRA-defined). Main outcome measures Change from baseline to weeks 4 and 12 in Craniocervical Dystonia Questionnaire (CDQ-24) total and subscale scores, patient diary items (‘day-to-day capacities and activities’, ‘pain’ and ‘duration of pain’) and global assessment of pain. Results Significant improvements were observed in CDQ-24 total and subscale scores at week 4 and were sustained up to week 12 (p<0.001). Changes in CDQ-24 scores did not significantly differ between the torticollis and laterocollis groups or between patients with or without depression. There were also significant reductions in patient diary item scores for activities of daily living, pain and pain duration at weeks 4 and 12 (p<0.001). Pain relief (less or no pain) was reported by 66% and 74.1% of patients at weeks 4 and 12, respectively. Changes in pain parameters demonstrated a positive relationship with change in Tsui score. Conclusions After standardised open-label treatment with Dysport 500 U, improvements in QoL and pain intensity up to 12 weeks in patients with CD were observed. PMID:23604344

  1. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination

    PubMed Central

    Bonin, Sawyer R.; Gibeault, Sabrina; De Repentigny, Yves; Kothary, Rashmi

    2016-01-01

    Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as was myelin basic

  2. [Non-steroidal anti-inflammatory drugs and tramadol in the treatment of osteoarthrosis deformans in patients with arterial hypertension].

    PubMed

    Lazebnik, L B; Kotsiubinskaia, O B; Konev, Iu V; Drozdov, V N

    2004-01-01

    The prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can be manifested by the decreased efficiency of antihypertensive therapy. The tactics of their differential use in relation to the its effect on blood pressure (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not been developed for the most effective and safe therapy. In this connection, it is extremely urgent to study the comparative safety of used NSAIDs as to their prohypertensive effect and to work out the management of patients with AH and OA. Ninety-eight patients with second-third degree OA of the knee and hip joints concurrent with the pain syndrome and first-second grade AH were followed up. Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a control group, the analgesic tramadol was supplemented to the therapy. AH was controlled by enalapril monotherapy. In groups of patients receiving diclofenac, arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the prohypertensive effect of these drugs; this trend was most pronounced in the diclofenac and arthrotec groups. Despite its marked prohypertensive effect, nimesulide did not impair circadian BP variations. The central-acting analgesic tramadol exerted no prohypertensive effect and it did not increase BP values. The prohypertensive effect of the tested NSAIDs and tramadol increases in the following order: tramadol, ketoprofen, meloxicam, nimesulide, arthrotec, diclofenac.

  3. Factors affecting the health-related quality of life of patients with cervical dystonia and impact of treatment with abobotulinumtoxinA (Dysport): results from a randomised, double-blind, placebo-controlled study

    PubMed Central

    Mordin, Margaret; Masaquel, Catherine; Abbott, Chandra; Copley-Merriman, Catherine

    2014-01-01

    Objective To describe the health-related quality of life (HRQOL) burden of cervical dystonia (CD) and report on the HRQOL and patient perception of treatment benefits of abobotulinumtoxinA (Dysport). Design The safety and efficacy of a single injection of abobotulinumtoxinA for CD treatment were evaluated in a previously reported international, multicenter, double-blind, randomised trial. HRQOL measures were assessed in the trial and have not been previously reported. Setting Movement disorder clinics in the USA and Russia. Participants Patients had to have a diagnosis of CD with symptoms for at least 18 months, as well as a total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score of at least 30; a Severity domain score of at least 15; and a Disability domain score of at least 3. Key exclusion criteria included treatment with botulinum toxin type A (BoNT-A) or botulinum toxin type B (BoNT-B) within 16 weeks of enrolment. Interventions Patients were randomised to receive either 500 U abobotulinumtoxinA (n=55) or placebo (n=61). Primary and secondary outcome measures Efficacy assessments included TWSTRS total (primary end point) and subscale scores at weeks 0, 4, 8, 12; a pain visual analogue scale at weeks 0 and 4; and HRQOL assessed by the SF-36 Health Survey (SF-36; secondary end point) at weeks 0 and 8. Results Patients with CD reported significantly greater impairment for all SF-36 domains relative to US norms. Patients treated with abobotulinumtoxinA reported significantly greater improvements in Physical Functioning, Role Physical, Bodily Pain, General Health and Role Emotional domains than placebo patients (p≤0.03 for all). The TWSTRS was significantly correlated with Physical Functioning, Role Physical and Bodily Pain scores, for those on active treatment. Conclusions CD has a marked impact on HRQOL. Treatment with a single abobotulinumtoxinA injection results in significant improvement in patients’ HRQOL. Trial registration number The

  4. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 2: Preclinical and Early Phase Human Proof of Concept Studies.

    PubMed

    Macaluso, Matthew; Flynn, Alexandra; Preskorn, Sheldon

    2016-01-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients treated with antipsychotics. The first column in this series began with the case of a 76-year-old man with major depressive disorder who developed orofacial dyskinesias while being treated with aripiprazole as an antidepressant augmentation strategy. It was alleged that a higher than intended dose of aripiprazole (ie, 20 mg/d for 2 wk followed by 10 mg/d for 4 wk instead of the intended dose of 2 mg/d) was the cause of the dyskinetic movements in this man, and the authors were asked to review the case and give their opinion. The principal basis for this theory of causation was the class warning about TD in the package insert for aripiprazole. The rationale for concluding aripiprazole caused TD in the 76-year-old man led to this series of columns about aripiprazole, its potential--if any--to cause TD, and the presence of a class warning about TD in its package insert. The central point is to illustrate why class warnings exist and their implications for practice. The first column in this series focused on the historical background, incidence, prevalence, risk factors, and clinical presentations of tardive and spontaneous dyskinesias and concluded with a discussion of diagnostic considerations explaining why clinicians should avoid making a diagnosis of TD until a thorough differential diagnosis has been considered. This second column in the series reviews the pharmacology of aripiprazole and the preclinical and phase I translational human studies that suggest aripiprazole should have a low to nonexistent risk of causing TD compared with other antipsychotics. The third column in the series

  5. [Effect of a complex treatment, including glutargin and erbisol on the blood plasma content of protein P53, apoptotic markers of type II, activity of caspases and the level of sCD 117 in patients with autonomic-vascular dystonia].

    PubMed

    Krychun, I I

    2008-01-01

    It has been established that the blood content of protein P53 diminishes by 27%, the blood level of sTRAIL increases by 22%, sCD 117 increases by 44% in patients with vegeto-vascular dystonia of the hypertonic type that is accompanied by an increase of the activity of caspases-1 however the activity of caspases-3 and - 8 as well as the blood content of TNF-alpha do not change. Multimodality therapy using glutargin does not influence on the level of the blood plasma TNF-alpha and the activity of caspases-1,-3,-8, normalizes the blood content of sTRAIL and sCD 117, however does not change the plasma concentration of protein P53 which remains lower by 35% than the control indices. In patients with vegeto-vascular dystonia of the hypotonic type the concentration of blood plasma protein P53, TNF-alpha and sTRAIL and the activity of caspases-1,-3,-8 correspond to the control values against a background of an almost twofold increase of the plasma sCD 117 level. The use of erbisol in a complex of therapeutic agents does not change the activity of caspases-l,-3,-8 and does not influence on the blood content of protein p53, TNF-alpha and sTRAIL and diminishes the plasma level of sCD 117 up to control values. A considerable elevation of the blood content of type II apoptotic factors is characteristic of the mixed type of vegeto-vascular dystonia: the level of protein p53 increases 2,4 times, TNF-alpha - 1,9 times, sTRAIL - 2,3 times that is accompanied by an increased activity of caspase-1 - 4,1 times, caspase-3 - 3,3 times, caspase-8 - 3,8 times and an increase of the plasma concentration of sCD 117 - 3,5 times. The use of erbisol and glutargin in multimodality therapy normalizes the plasma concentration of TNF-alpha and diminishes the blood content of protein P53 by 33% and sTRAIL - by 42% which, nevertheless remains higher than the control value by 58% and 36% respectively. The combined effects of glutargin and erbisol in patients of this group are characterized by a

  6. Genetics Home Reference: dopa-responsive dystonia

    MedlinePlus

    ... is involved in the last step of tetrahydrobiopterin production. Tetrahydrobiopterin helps process several protein building blocks ( amino acids ), and is involved in the production of chemicals called neurotransmitters, which transmit signals between ...

  7. Temporal Expectation in Focal Hand Dystonia

    ERIC Educational Resources Information Center

    Avanzino, Laura; Martino, Davide; Martino, Isadora; Pelosin, Elisa; Vicario, Carmelo M.; Bove, Marco; Defazio, Gianni; Abbruzzese, Giovanni

    2013-01-01

    Patients with writer's cramp present sensory and representational abnormalities relevant to motor control, such as impairment in the temporal discrimination between tactile stimuli and in pure motor imagery tasks, like the mental rotation of corporeal and inanimate objects. However, only limited information is available on the ability of patients…

  8. Dystonin/Bpag1 is a necessary endoplasmic reticulum/nuclear envelope protein in sensory neurons

    SciTech Connect

    Young, Kevin G.; Kothary, Rashmi

    2008-09-10

    Dystonin/Bpag1 proteins are cytoskeletal linkers whose loss of function in mice results in a hereditary sensory neuropathy with a progressive loss of limb coordination starting in the second week of life. These mice, named dystonia musculorum (dt), succumb to the disease and die of unknown causes prior to sexual maturity. Previous evidence indicated that cytoskeletal defects in the axon are a primary cause of dt neurodegeneration. However, more recent data suggests that other factors may be equally important contributors to the disease process. In the present study, we demonstrate perikaryal defects in dorsal root ganglion (DRG) neurons at stages preceding the onset of loss of limb coordination in dt mice. Abnormalities include alterations in endoplasmic reticulum (ER) chaperone protein expression, indicative of an ER stress response. Dystonin in sensory neurons localized in association with the ER and nuclear envelope (NE). A fusion protein ofthe dystonin-a2 isoform, which harbors an N-terminal transmembrane domain, associated with and reorganized the ER in cell culture. This isoform also interacts with the NE protein nesprin-3{alpha}, but not nesprin-3{beta}. Defects in dt mice, as demonstrated here, may ultimately result in pathogenesis involving ER dysfunction and contribute significantly to the dt phenotype.

  9. Genetics Home Reference: deafness-dystonia-optic neuronopathy syndrome

    MedlinePlus

    ... usually develop a gradual decline in thinking and reasoning abilities (dementia) in their forties. The lifespan of ... Bäzner H, Krauss JK, Hennerici MG, Bauer MF. Clinical and molecular findings in a patient with a ...

  10. [Functional cramps or functional dystonias in writers and musicians].

    PubMed

    Chamagne, P

    1986-01-01

    The clinical evaluation in the "dystonies of function" or "impaired dexterity" reveals certain physical anomalies which either appear spontaneously or are triggered by specific tests: abnormal postures involving the trunck, head, and upper limb. During the professional gesture the physiological "pulley effect" on flexor tendons is accompanied with an interference effect produced by the displacement of the segments; this, adds up to an unbalance of the digital kinetic chain, building a locked functional system. The antagonist muscles begin to supply the deficiency of the agonist muscles. In addition, patients with a characteristic psychological ground suffer a more acute "disorganization" or a performing career.

  11. Genetics Home Reference: rapid-onset dystonia parkinsonism

    MedlinePlus

    ... Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro ... Keane V, Hugle B, Hardiman MO, Brett F, Green AJ, Barton DE, King MD, Webb DW. Rapid- ...

  12. Respiratory dynamics and speech intelligibility in speakers with generalized dystonia.

    PubMed

    LaBlance, G R; Rutherford, D R

    1991-04-01

    This study investigated aspects of respiratory function, during quiet breathing and monologue, in six adult dystonic subjects and compared the findings to a control group of four neurologically intact adults. Additionally, breathing dynamics were compared with speech intelligibility. Respiratory inductive plethysmography was used to assess breathing rate, periodicity of the breathing pattern, and inspiratory lung volume. Ear oximetry was used to assess arterial blood oxygen saturation. Speech intelligibility was rated by a panel of five judges. Breathing patterns differed between groups; the dystonic subjects showed a faster breathing rate, less rhythmic breathing pattern, decreased lung volume, and apnealike periods accompanied by a decrease in arterial blood oxygen saturation. These differences were observed during quiet breathing and monologue. Decreased speech intelligibility was strongly related to differences in breathing dynamics.

  13. Respiratory Dynamics and Speech Intelligibility in Speakers with Generalized Dystonia.

    ERIC Educational Resources Information Center

    LaBlance, Gary R.; Rutherford, David R.

    1991-01-01

    This study compared respiratory function during quiet breathing and monologue, in six adult dystonic subjects and a control group of four neurologically intact adults. Dystonic subjects showed a faster breathing rate, less rhythmic breathing pattern, decreased lung volume, and apnea-like periods. Decreased speech intelligibility was related to…

  14. Developing Gene Silencing for the Study and Treatment of Dystonia

    DTIC Science & Technology

    2016-10-01

    Subsequently, an osmotic pump with ASO (active or missense control) was 2 inserted in the mid-scapular subcutaneous space and its tip placed into the lateral...littermates (n: 86) underwent behavioral evaluation at 3-4 weeks of age before implantation of an Alzet pump to receive ASO or control injections 8...month worked: 12 Contribution to Project: Ms. Watson assists Dr. Beauvais in colony maintenance , animal genotyping, surgeries, behavioral, histological

  15. Genetics Home Reference: early-onset primary dystonia

    MedlinePlus

    ... disorder that involves involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an ... of the brain that would explain the abnormal muscle contractions. Instead, the altered torsinA protein may have subtle ...

  16. Hypertonia

    MedlinePlus

    ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation.org http:// ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation. ...

  17. Paroxysmal Choreoathetosis Disease

    MedlinePlus

    ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation.org http:// ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation. ...

  18. Benign Essential Blepharospasm

    MedlinePlus

    ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation.org http:// ... Research Foundation 1 East Wacker Drive Suite 2810 Chicago IL Chicago, IL 60601-1905 dystonia@dystonia-foundation. ...

  19. Analysis of stimuli triggering attacks of paroxysmal dystonia induced by exertion

    PubMed Central

    Meyer, B; Irlbacher, K; Meierkord, H

    2001-01-01

    In a patient with a familial form of paroxysmal exertion induced dyskinesia (PED), the efficacy of different stimuli and manoeuvres in triggering dystonic attacks in the arm was studied. As a new approach, transcranial magnetic stimulation (TMS) of the motor cortex was used to trigger motor paroxysms and to monitor cortical excitability during attacks. Motor paroxysms could be provoked by muscle vibration, passive movements, TMS, magnetic stimulation of the brachial plexus, and electrical nerve stimulation. Sham stimulation over the motor cortex and thermal and tactile cutaneous stimuli were ineffective in triggering attacks. It is concluded that dystonic attacks are triggered by proprioceptive afferents rather than cutaneous stimuli or the descending motor command itself. Outside the attacks, motor cortical excitatory and inhibitory neuronal mechanisms as assessed by TMS (response threshold and amplitudes, duration of the contralateral and ipsilateral silent period, corticocortical inhibition, and facilitation) were normal, which underlines the paroxysmal character of the disorder.

 PMID:11160479

  20. Are the yips a task-specific dystonia or "golfer's cramp"?

    PubMed

    Adler, Charles H; Crews, Debra; Kahol, Kanav; Santello, Marco; Noble, Brie; Hentz, Joseph G; Caviness, John N

    2011-09-01

    This study compared golfers with and without the yips using joint movement and surface electromyographic detectors. Fifty golfers (25 with and 25 without complaints of the yips) were studied while putting. All putts were videotaped. Surface electromyography assessed arm cocontraction. A CyberGlove II (Immersion Technologies, Palo Alto, CA) assessed right-arm angular movements. Primary analysis was done by subjective complaint of the yips, whereas secondary analysis was done by video evidence of an involuntary movement. When grouped by subjective complaints, there were no differences in any movement parameter. When grouped by video evidence of an involuntary movement, yips cases had more (P < 0.001) angular movement in wrist pronation/supination and a trend (P = 0.08) for wrist flexor/extensor cocontraction (yips: 7 of 17, 41.2%; no yips: 6 of 33, 18.2%). Golfers with video evidence of an involuntary movement while putting have excessive rotation of the right wrist in a pronation/supination motion and, as previously reported, a trend for wrist flexor/extensor cocontraction.

  1. Extrapyramidal Motor Dysfunction and Resultant Orofacial Dystonia Post-Cocaine Abuse: A Clinical Case Study

    ERIC Educational Resources Information Center

    McMicken, Betty L.; Ostergren, Jennifer A.; Vento-Wilson, Margaret

    2010-01-01

    This case study investigated the consequences of cocaine use and resultant extrapyramidal motor dysfunction. The study focused on a female client, post-long-term drug abuse with concomitant untreated head trauma, experiencing extraneous motor movements of the lips, tongue, jaw, and upper and lower extremities. The goals of this study were to (a)…

  2. Degenerative Changes of the Spine of Pilots of the RNLAF

    DTIC Science & Technology

    2000-08-01

    loads. Therefore, acute in-flight arthrosis deformans was found in the cervical neck injury is a common complaint among pilots spine. Further...views of the spine taken in standing 7-3 Table 2 Classification of disorders Disorder Levels General: Osteo- arthrosis / Spondylosis / Arthrosis ...significant relationship between II found Arthrosis Deformans. Agreement exists these disorders and high +G, forces was not between both radiologists on levels

  3. Botulinum Neurotoxin Injections

    MedlinePlus

    ... for which you are being treated. The Dystonia Medical Research Foundation can help you locate the nearest, most ... learn more. Accelerating Research & Inspiring Hope The Dystonia Medical Research Foundation (DMRF) has served the dystonia community since ...

  4. [Was Beethoven's deafness caused by Paget's disease? Report of findings and study of skull fragments of Ludwig van Beethoven].

    PubMed

    Jesserer, H; Bankl, H

    1986-10-01

    Paget's disease of bone (osteitis deformans) has been repeatedly named as a possible cause for Ludwig van Beethoven's deafness. In 1985 a descendent of Franz Romeo Seligmann (a Viennese medical historian who in 1863 had studied Beethoven's mortal remains on the occasion of their relocation) presented to us three bone fragments allegedly from Beethoven's cranium. They represented fragments of the left parietal bone and the occiputum. It was possible to prove nearly with certainty that these bone fragments actually are Beethoven's. They did not show signs of Paget's disease of bone. It must therefore be concluded that Beethoven's deafness was not caused by Paget's osteitis deformans.

  5. A comparative historical and demographic study of the neuromodulation management techniques of deep brain stimulation for dystonia and cochlear implantation for sensorineural deafness in children.

    PubMed

    Hudson, V E; Elniel, A; Ughratdar, I; Zebian, B; Selway, R; Lin, J P

    2017-01-01

    Cochlear implants for sensorineural deafness in children is one of the most successful neuromodulation techniques known to relieve early chronic neurodisability, improving activity and participation. In 2012 there were 324,000 recipients of cochlear implants globally.

  6. Localization to Xq22 and clinical update of a family with X-linked recessive mental retardation with progression sensorineural deafness, progressive tapeto-retinal degeneration and dystonia

    SciTech Connect

    Tranebjaerg, L.; Schwartz, C.; Huggins, K.; Barker, D.; Stevenson, R.; Arena, J.F.; Gedde-Dahl, T.; Mikkelsen, M.; Mellgren, S.; Anderson, K. ||||

    1994-07-15

    In a reinvestigation of a six-generation Norwegian family, originally reported with non-syndromic X-linked recessive deafness by Mohr and Mageroy, we have demonstrated several syndromic manifestations. The 10 clinically characterized affected males range in age from 14-61 years, and show progressive mental deterioration and visual disability. Ophthalmological and electrophysiological studies showed myopia, decreased visual acuity, combined cone-rod dystrophy as well as central areolar dystrophy by means of ERG. Brain CT-scans showed cortical and central atrophy without predilection to specific areas. Linkage analysis, using X-chromosomal RFLPs and CA-repeats, yielded a maximum LOD score of 4.37 with linkage to DXS17. DXS17 is localized to Xq22. One recombinant with COL4A5 (deficient in Alport syndrome) was observed. Results from the studies of this family will be important in reclassification of non-syndromic X-linked deafness since the family now represents syndromic deafness and XLMR with a specific phenotype.

  7. A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

    PubMed

    Siddiqi, Saima; Foo, Jia Nee; Vu, Anthony; Azim, Saad; Silver, David L; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E Shyong; Yeo, Gene W; Khor, Chiea Chuen

    2014-01-01

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

  8. A Novel Splice-Site Mutation in ALS2 Establishes the Diagnosis of Juvenile Amyotrophic Lateral Sclerosis in a Family with Early Onset Anarthria and Generalized Dystonias

    PubMed Central

    Vu, Anthony; Azim, Saad; Silver, David L.; Mansoor, Atika; Tay, Stacey Kiat Hong; Abbasi, Sumiya; Hashmi, Asraf Hussain; Janjua, Jamal; Khalid, Sumbal; Tai, E. Shyong; Yeo, Gene W.; Khor, Chiea Chuen

    2014-01-01

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes. PMID:25474699

  9. Paget disease of the bone

    MedlinePlus

    ... that may indicate Paget disease include: Bone scan Bone x-ray Elevated markers of bone breakdown (for example, N-telopeptide) This disease may ... of Paget disease. Alternative Names Osteitis deformans Images ... X-ray References Ralston SH. Paget disease of bone. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  10. [The use of transcranial electrotherapy in the rehabilitation of osteoarthrosis patients].

    PubMed

    Komarova, L A; Kir'ianova, V V; Zabolotnykh, I I; Zabolotnykh, V A

    1998-01-01

    Rehabilitation of 39 patients with osteoarthrosis deformans (OD) consisted of transcranial electrostimulation (TCES) which was performed by means of Transair unit generating impulse current (77 Hz, frontal-retroauricular electrodes position). There was a positive trend in clinical indices, pain intensity, skin temperature. TCES mechanism of action involves stimulation of endorphine brain structures which elevates blood levels of beta-endorphines.

  11. Measure of the Regularity of Events in Stochastic Point Processes, Application to Neuron Activity Analysis

    DTIC Science & Technology

    2008-04-01

    movement mechanisms and their related pathologies such as Parkinson’s disease or dystonia . Dystonia is characterized by involuntary movements and...prolonged muscle contractions, resulting in twisting body motions and abnormal postures. The pathophysiology of dystonia remains largely unknown. Deep...and dystonia . However, the effects of DBS are not completely understood. In this context, we have tested the proposed method to analyze neuronal

  12. Consideration of genetic contributions to the risk for spasmodic dysphonia.

    PubMed

    Sharma, Nutan; Franco, Ramon A

    2011-09-01

    Spasmodic dysphonia, a form of the neurologic condition known as dystonia, results from involuntary spasms of the larynx, producing interruptions of speech and changes in voice quality. The pathogenesis of spasmodic dysphonia is not well understood. However, several genetic mutations have been identified that cause different forms of dystonia. In some individuals, these genetic mutations result in spasmodic dysphonia, either with no other signs of dystonia or as part of a broader dystonia phenotype. Thus, research in the growing field of dystonia genetics may help to inform our understanding of the pathogenesis of spasmodic dysphonia.

  13. Instrumentation for Investigating the Regenerative Potential of Bone-Tissue-Engineered Scaffolds

    DTIC Science & Technology

    2015-05-12

    hypothesized that PCL/HA and PLGA/HA scaffolds will mimic the nano -features of the natural extracellular matrix (ECM) and are expected to be effective...With the continual aging of the population in the United States, bone fractures and diseases such as osteoporosis, osteomalacia and osteitis deformans...Paget’s disease of bone) present a need for the development and perfection of bone regeneration methods [1]. While numerous bone fractures can be

  14. Meige Syndrome: What’s in a Name?

    PubMed Central

    LeDoux, Mark S.

    2009-01-01

    Frequently, blepharospasm is associated with involuntary movements of the platysma, lower face and masticatory muscles. Similarly, masticatory dystonia may occur in isolation or in combination with dystonia of other cranial and cervical muscles. The non-possessive and possessive forms of Meige and Brueghel syndromes have been variably and imprecisely ascribed to various anatomical variations of craniocervical dystonia. Herein, the origin of eponymic terms as applied to craniocervical dystonia is reviewed as support for proposed elimination of these eponyms from clinical usage. Although the term “segmental craniocervical dystonia” more accurately captures the combination of blepharospasm and dystonia of other head and neck muscles, delineation of craniocervical subphenotypes is essential for etiological/genetic and treatment studies. To conclude, the clinical features, epidemiology, pathophysiology and therapeutic management of segmental craniocervical dystonia are examined with a particular focus on “blepharospasm-plus” subphenotypes. PMID:19457699

  15. “Club-Cutting” Dystonic Tremor: a Case Report

    PubMed Central

    Roberts, Kinley; Mahon, Barry; O’Rourke, Killian; Lynch, Timothy

    2013-01-01

    Background Focal task-specific dystonic postures are well recognized. Often a tremor may be the main feature with little or no dystonia. These have been well reported in writers, musicians, and sportspeople. Case Report Herein we report a novel task-specific dystonic tremor in a 44-year-old Irish hairdresser due to club-cutting, a standard haircutting technique. Discussion Hairdresser’s dystonia is a novel task-specific dystonia. PMID:24156085

  16. Theoretical Analyses of the Functional Regions of the Heavy Chain of Botulinum Neurotoxin

    DTIC Science & Technology

    1994-01-01

    dystonias and other neurological disorders (I). A number of clinical reports of BTX-A administration (1-3) have empha- sized that BTX-A is safe and...J. Schwartz K. Botulinum toxin injections for cervical dystonia . Neurology 1990:40:277-280. 4. Brin MF. Fahn S. Moskowitz C. Friedman A. Shale HM...Greene PE. Blitzer A. List T. Lange D. Lovelace RE, McMahon D. Localized injections of botulinum toxin for the treatment of focal dystonia and

  17. 78 FR 21613 - Prescription Drug User Fee Act Patient-Focused Drug Development; Announcement of Disease Areas...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-11

    ... obstructive pulmonary disease, lysosomal storage disorders, peripheral neuropathy, dystonia, and fibromyalgia... Chagas disease; female sexual dysfunction; fibromyalgia; hemophilia A, hemophilia B, von...

  18. The Phenotypic Spectrum of DYT24 Due to ANO3 Mutations

    PubMed Central

    Stamelou, Maria; Charlesworth, Gavin; Cordivari, Carla; Schneider, Susanne A; Kägi, Georg; Sheerin, Una-Marie; Rubio-Agusti, Ignacio; Batla, Amit; Houlden, Henry; Wood, Nicholas W; Bhatia, Kailash P

    2014-01-01

    Genes causing primary dystonia are rare. Recently, pathogenic mutations in the anoctamin 3 gene (ANO3) have been identified to cause autosomal dominant craniocervical dystonia and have been assigned to the dystonia locus dystonia-24 (DYT24). Here, we expand on the phenotypic spectrum of DYT24 and provide demonstrative videos. Moreover, tremor recordings were performed, and back-averaged electroencephalography, sensory evoked potentials, and C-reflex studies were carried out in two individuals who carried two different mutations in ANO3. Ten patients from three families are described. The age at onset ranged from early childhood to the forties. Cervical dystonia was the most common site of onset followed by laryngeal dystonia. The characteristic feature in all affected individuals was the presence of tremor, which contrasts DYT24 from the typical DYT6 phenotype. Tremor was the sole initial manifestation in some individuals with ANO3 mutations, leading to misdiagnosis as essential tremor. Electrophysiology in two patients with two different mutations showed co-contraction of antagonist muscles, confirming dystonia, and a 6-Hz arm tremor at rest, which increased in amplitude during action. In one of the studied patients, clinically superimposed myoclonus was observed. The duration of the myoclonus was in the range of 250 msec at about 3 Hz, which is more consistent with subcortical myoclonus. In summary, ANO3 causes a varied phenotype of young-onset or adult-onset craniocervical dystonia with tremor and/or myoclonic jerks. Patients with familial cervical dystonia who also have myoclonus-dystonia as well as patients with prominent tremor and mild dystonia should be tested for ANO3 mutations. © 2014 The Authors. Movement Disorders published by International Parkinson and Movement Disorder Society PMID:24442708

  19. Onset Dynamics of Type A Botulinum Neurotoxin-Induced Paralysis

    DTIC Science & Technology

    2008-01-01

    In the clinical study [18], the patient reported the alleviation of subjective symptoms of cervical dystonia following i.m. injections of BoNT/A...0.00015min−1 Fig. 3 are from a patient with cervical- dystonia -related complaints receiving BoNT/A intramuscularly (data from Fig. 1, injection series 1 in

  20. CHANGES OF PULMONARY BLOOD VESSELS IN CHRONIC RADIATION SICKNESS,

    DTIC Science & Technology

    revealed during angiocardiography. In the initial period of disease in connection with dystonia , developed in contraction of big vessels and...the characteristics of vascular circulator dystonia are absent or are weakly expressed, but the unusual flow of contrast medium from the arteries

  1. [An endoapparatus for restoration of hip joint].

    PubMed

    Lapinskaia, V S; Gatiatulin, R R; Trubnikov, V I; Velichko, M V; Froliakin, T V; Kovalenko, A E; Froliakina, L A

    2008-01-01

    The possibility of prolonging the anatomic and functional longevity of joints in young patients with coxarthrosis deformans under conditions of long-term unloading using a submersible distraction device is considered. A submersible endoapparatus for restoration of hip joint is described. Its functional capabilities as an unloading device were corroborated by experimental testing. Clinical examples illustrated with X-ray photographs demonstrate the possibility of long-term unloading of the injured joint and postponement of endoprosthesis replacement in young patients by 20-25 years. It is suggested to use the developed method for organ-sparing surgery in young working-age patients.

  2. Fungal remains in Pleistocene ground squirrel dung from Yukon Territory, Canada

    NASA Astrophysics Data System (ADS)

    Pirozynski, Kris A.; Carter, Adrian; Day, Richard G.

    1984-11-01

    Fungi in dung of the Arctic ground squirrel ( Spermophilus parryii) collected near Dominion Creek, Yukon Territory, Canada, have a radiocarbon age of 12,200 ± 100 yr B.P. Most of the fungal remains are assignable to modern taxa, and most of these are either widespread saprobes or nonspecific coprophiles. However, specimens identified as Chaetomium simile and Thecaphora deformans represent fungi that may be more characteristic of rodent dung than that of other animals, inviting consideration of dung fungi as a potential source of paleontological data.

  3. [Possibilities of treatment of dystonic syndromes with akineton].

    PubMed

    Karabanov, A V; Illarioshkin, S N

    2012-01-01

    Treatment of dystonia is a complex problem of current neurology due to the etiological and neurochemical heterogeneity of this clinical syndrome. Central cholinolytics is a most effective group of drugs for patients with dystonia and dystonic tremor. The authors present the results of the successful treatment with biperiden (akineton), a centrally active anticholinergic drug with additional peripheral choline- and ganglion-blocking effect in cervical dystonia. The time of response to treatment and duration of clinical effect, its possible predictors are analyzed. Perspectives of using cholinolytics in treatment of different forms of dystonic hyperkineses are discussed.

  4. Use of chemodenervation in dystonic conditions.

    PubMed

    Hanson, Maurice

    2012-07-01

    Dystonia, an uncommon movement disorder that causes sustained muscle contractions and painful body positions, is a difficult diagnostic challenge; misdiagnosis is common. Classification may include etiology, area of physical involvement, or age of onset. Bodily distribution is varied, and dystonias can present as primary (genetic) or secondary (caused by other disease processes or use of neuroleptic drugs). Although there is no cure, the use of botulinum toxins for chemodenervation provides symptomatic relief and is considered the treatment of choice in focal dystonia. The dose of botulinum toxin may be titrated to provide significant relief for 12 weeks or more.

  5. Effects of Azaprophen, Scopolamine and Trihexyphenidyl on Schedule-Controlled Behavior, Before and After Chronic Physostigmine

    DTIC Science & Technology

    1990-01-01

    clinically in the treatment of dystonia , such fects on behavior when administered alone (Mc- as the extra-pyramidal effects produced by the Master and... dystonia . Can. J. Neurol. Sci. 13, 42. Loullis, C.C.. R.L. Dean, D.I. Benson, L.R. Meverson and The author thanks Timothy F. Elsmore for helpful com- R.T...Fahq, 1983, Double-blind evaluation of Behav. 12, 409. trihexyphenidyl in dystonia , in: Adv. Neurol., Vol. 37, eds. McMaster. S.B. and J.M. Carney, 1986

  6. [Hemo- and neurodynamics of the human brain during exposure to moderate hypoxic hypoxia].

    PubMed

    Alekseev, D A; Zubarev, A F; Krupina, T N; Iarullin, Kh Kh; Kuznets, E I

    1984-01-01

    Synchronous electro- and rheoencephalography were used to study tolerance to moderate hypoxic hypoxia for 30 min at an altitude of 5000 m without additional oxygen supply. As test subject, men with autonomic-vascular dystonia (29-39 years old), 15 men over 40 (41-56 years old), and 16 essentially healthy controls (23-36 years old) were used. The aged volunteers (41-56 years old) did not differ from the controls with respect to their tolerance to hypoxic hypoxia. The men with early symptoms of hypertonic-type dystonia also showed high tolerance to hypoxic hypoxia. The subjects with hypotonic-type dystonia displayed lower tolerance.

  7. [The mucisian's cramp. About the illness of Robert Schumann].

    PubMed

    Ochsner, F

    2012-01-11

    The musicians are seen in daily neurological practice facing various problems sometimes simple such as skeletal or tendon pain or even compression of a nerve trunk and sometimes more complicated such as focal dystonia. Dystonia often has a dramatic impact on the career of a musician given the complexity of the clinical and therapeutic approach and the results are often disappointing. The history of the German Romantic composer Robert Schumann illustrates this reality; through his story a discussion of both the different pathophysiological hypotheses responsible for focal dystonia, a disorder of brain plasticity, and of the multimodal therapeutic approaches, revisited in the light of neurophysiological findings will be described.

  8. Neurologic features of chronic minamata disease (organic mercury poisoning) and incidence of complications with aging.

    PubMed

    Uchino, M; Tanaka, Y; Ando, Y; Yonehara, T; Hara, A; Mishima, I; Okajima, T; Ando, M

    1995-09-01

    To elucidate the neurologic features of chronic Minamata disease, and the incidence of complications with aging, we studied 80 patients with documented Minamata disease (organic mercury poisoning) from 1986 to 1994 (mean age: 63 years). Of the cardinal neurologic findings, sensory impairment was seen with highest frequency in 98.8% of patients limited to the extremities in 86.3%. Impairment of lower extremity coordination was observed in 60%, constriction of the visual field in 51.9%, and retrocochlear hearing loss in 41%. To assess age-related complications, patients were separated into three groups by age: Group I (10 to 39 years); Group II (40 to 69 years); Group III (> or = 70 years). The incidences of hypertension and cerebrovascular diseases, organic ophthalmologic disorders (including cataracts), presbyacusis, and cervical spondylosis deformans increased significantly with age. Compared with a preceding survey (1981 to 1985, 171 patients, mean age: 63.5 years), the incidences of complicated hypertension and cataracts had decreased, whereas those of cerebrovascular disease and retinitis pigmentosa remained unchanged. The incidences of abnormal brain computed tomography (CT), presbyacusis, cervical spondylosis deformans, and positive tests for urine sugar also increased. The incidences of these complications other than retinitis pigmentosa were similar to those in the general population. These results accurately reflect the recent epidemiological disease tendencies in Japan toward a decreased incidence of hypertension and an increased incidence of diabetes.

  9. Genetics Home Reference: MEGDEL syndrome

    MedlinePlus

    ... gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness. Nat Genet. 2012 ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

  10. Symptoms and Diagnosis

    MedlinePlus

    ... often involve the fingers and hands or the mouth. If symptoms only occur in "episodes" that last for minutes or hours, the terms paroxysmal dystonia and dyskinesias are used. The word torsion is sometimes used, usually in reference to ...

  11. Torticollis (wry neck) (image)

    MedlinePlus

    Torticollis is a form of dystonia (prolonged muscle contractions) in which the neck muscles, particularly the sternocleidomastoid muscle, contract involuntarily causing the head to turn. Torticollis may occur without known cause (idiopathic), ...

  12. Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration

    PubMed Central

    Garcia-Ruiz, Pedro J.; Ayerbe, Joaquin; Vela Desojo, Lydia; Feliz, Cici E.; del Val Fernandez, Javier

    2015-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is usually associated with dystonia, which is typically severe and progressive over time. Pallidal stimulation (GPi DBS) has been carried out in selected cases of PKAN with drug-resistant dystonia with variable results. We report a 30-month follow-up study of a 30-year-old woman with PKAN-related dystonia treated with GPi DBS. Postoperatively, the benefit quickly became evident, as the patient exhibited a marked improvement in her dystonia, including her writing difficulty. This result has been maintained up to the present. GPi DBS should be considered in dystonic PKAN patients provided fixed contractures and/or pyramidal symptoms are not present. PMID:25802776

  13. Bilateral Lower Sternocleidomastoid Botulinum Toxin Injections to Address Refractory Anterocollis.

    PubMed

    Peng-Chen, Zhongxing; Thompson, Amanda; Rodriguez, Ramon L

    2016-03-01

    Anterocollis is a type of cervical dystonia characterized by simultaneous and repetitive antagonist muscles contractions, resulting in abnormal neck flexion. It was described with a frequency of 6.8% from 399 patients with diagnosis of cervical dystonia and usually coexists with torticollis and/or laterocollis, as mixed cervical dystonia patterns. Botulinum toxin is usually a practical and effective treatment for cervical dystonia. The target muscles to inject in anterocollis are usually sternocleidomastoid and scalene muscles. There is also a case report suggesting longus collis involvement. Nevertheless, the dosage of the medication in anterocollis is limited by frequent side effects of dysphagia. We described 2 cases of refractory anterocollis. They did not benefit from conventional bilateral upper portion of sternocleidomastoid muscle injections with OnabotulinumtoxinA, but notably improved their symptoms and clinical global impression after switching to injections into bilateral lower portion of sternocleidomastoid muscles, without significant side effects.

  14. Torticollis

    MedlinePlus

    ... new symptoms develop. Torticollis that occurs after an injury or with illness may be serious. Seek medical ... Editorial team. Related MedlinePlus Health Topics Dystonia Neck Injuries and Disorders Browse the Encyclopedia A.D.A. ...

  15. Writer's cramp in spinocerebellar ataxia Type 1

    PubMed Central

    Khwaja, Geeta Anjum; Srivastava, Abhilekh; Ghuge, Vijay Vishwanath; Chaudhry, Neera

    2016-01-01

    Dystonia can be encountered in a small subset of patients with spinocerebellar ataxia (SCA), but task specific dystonia is extremely rare. We report a case of a 48-year-old male with confirmed SCA Type 1 (SCA1) with mild progressive cerebellar ataxia and a prominent and disabling Writer's cramp. This case highlights the ever-expanding phenotypic heterogeneity of the SCA's in general and SCA1 in particular. PMID:27695243

  16. Deep Brain Stimulation for Tremor Associated with Underlying Ataxia Syndromes: A Case Series and Discussion of Issues

    PubMed Central

    Oyama, Genko; Thompson, Amanda; Foote, Kelly D.; Limotai, Natlada; Abd-El-Barr, Muhammad; Maling, Nicholas; Malaty, Irene A.; Rodriguez, Ramon L.; Subramony, Sankarasubramoney H.; Ashizawa, Tetsuo; Okun, Michael S.

    2014-01-01

    Background Deep brain stimulation (DBS) has been utilized to treat various symptoms in patients suffering from movement disorders such as Parkinson's disease, dystonia, and essential tremor. Though ataxia syndromes have not been formally or frequently addressed with DBS, there are patients with ataxia and associated medication refractory tremor or dystonia who may potentially benefit from therapy. Methods A retrospective database review was performed, searching for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS at the University of Florida Center for Movement Disorders and Neurorestoration between 2008 and 2011. Five patients were found who had DBS implantation to address either medication refractory tremor or dystonia. The patient's underlying diagnoses included spinocerebellar ataxia type 2 (SCA2), fragile X associated tremor ataxia syndrome (FXTAS), a case of idiopathic ataxia (ataxia not otherwise specified [NOS]), spinocerebellar ataxia type 17 (SCA17), and a senataxin mutation (SETX). Results DBS improved medication refractory tremor in the SCA2 and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS improved dystonia in the SCA17 and SETX patients, although dystonia did not improve in the lower extremities of the SCA17 patient. All patients reported a transient gait dysfunction postoperatively, and there were no reports of improvement in ataxia-related symptoms. Discussion DBS may be an option to treat tremor, inclusive of dystonic tremor in patients with underlying ataxia; however, gait and other symptoms may possibly be worsened. PMID:25120941

  17. Diagnosis of dystonic syndromes--a new eight-question approach.

    PubMed

    Bertram, Kelly L; Williams, David R

    2012-03-20

    Dystonia is a syndrome of abnormal involuntary movements that are repetitive, twisting or patterned, and can result in abnormal postures. Dystonia may be generalized or focal, and can occur as a primary syndrome or secondary to another disease--over 50 clinical conditions are reported to cause dystonia. Classification of dystonia is based on genetic background, anatomical distribution, age at onset, and neurodegenerative processes. In many cases, manifestations of dystonia are identical regardless of the aetiology, which makes accurate diagnosis challenging, if not impossible, without additional investigations. Exhaustive lists of the causes of dystonia are not practical to aid clinicians when attempting to determine if a hyperkinetic movement can be diagnosed as dystonic. The existing diagnostic algorithms for dystonic syndromes rely on the clinician's experience, without a streamlined diagnostic pathway. Non-specialist clinicians and neurologists may, therefore, find diagnosis of dystonic syndromes difficult. In this Review, an eight-question approach is proposed, with a summary of the evidence for investigations that enable successful diagnosis of dystonic syndromes. The aim of this approach is to inform both specialists and general neurologists on the appropriate diagnostic test for each patient who presents with a possible dystonic syndrome.

  18. Effects of deep brain stimulation in dyskinetic cerebral palsy: a meta-analysis.

    PubMed

    Koy, Anne; Hellmich, Martin; Pauls, K Amande M; Marks, Warren; Lin, Jean-Pierre; Fricke, Oliver; Timmermann, Lars

    2013-05-01

    Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P < .001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P < .001). There was a significant negative correlation between severity of dystonia and clinical outcome (P < .05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society.

  19. Clinical variability in ataxia-telangiectasia.

    PubMed

    Lohmann, Ebba; Krüger, Stefanie; Hauser, Ann-Kathrin; Hanagasi, Hasmet; Guven, Gamze; Erginel-Unaltuna, Nihan; Biskup, Saskia; Gasser, Thomas

    2015-07-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive inherited disease characterized by progressive childhood-onset cerebellar ataxia, oculomotor apraxia, choreoathetosis and telangiectasias of the conjunctivae. Further symptoms may be immunodeficiency and frequent infections, and an increased risk of malignancy. As well as this classic manifestation, several other non-classic forms exist, including milder or incomplete A-T phenotypes caused by homozygous or compound heterozygous mutations in the ATM gene. Recently, ATM mutations have been found in 13 Canadian Mennonites with early-onset, isolated, predominantly cervical dystonia, in a French family with generalized dystonia and in an Indian family with dopa-responsive cervical dystonia. In this article, we will describe a Turkish family with three affected sibs. Their phenotypes range from pure cervical dystonia associated with hand tremor to truncal and more generalized dystonic postures. Exome sequencing has revealed the potentially pathogenic compound heterozygous variants p.V2716A and p.G301VfsX19 in the ATM gene. The variants segregated perfectly with the phenotypes within the family. Both mutations detected in ATM have been shown to be pathogenic, and the α-fetoprotein, a marker of ataxia telangiectasia, was found to be increased. This report supports recent literature showing that ATM mutations are not exclusively associated with A-T but may also cause a more, even intra-familial variable phenotype in particular in association with dystonia.

  20. Comparative Genomics of Taphrina Fungi Causing Varying Degrees of Tumorous Deformity in Plants

    PubMed Central

    Tsai, Isheng J.; Tanaka, Eiji; Masuya, Hayato; Tanaka, Ryusei; Hirooka, Yuuri; Endoh, Rikiya; Sahashi, Norio; Kikuchi, Taisei

    2014-01-01

    Taphrina fungi are biotrophic plant pathogens that cause plant deformity diseases. We sequenced the genomes of four Taphrina species—Taphrina wiesneri, T. deformans, T. flavorubra, and T. populina—which parasitize Prunus, Cerasus, and Populus hosts with varying severity of disease symptoms. High levels of gene synteny within Taphrina species were observed, and our comparative analysis further revealed that these fungi may utilize multiple strategies in coping with the host environment that are also found in some specialized dimorphic species. These include species-specific aneuploidy and clusters of highly diverged secreted proteins located at subtelomeres. We also identified species differences in plant hormone biosynthesis pathways, which may contribute to varying degree of disease symptoms. The genomes provide a rich resource for investigation into Taphrina biology and evolutionary studies across the basal ascomycetes clade. PMID:24682155

  1. [Sudden hearing loss and the cranio-cervical junction].

    PubMed

    Bernal Sprekelsen, M; Hörmann, K; Weh, L

    1990-01-01

    Morphological alterations of the craniocervical junction as basilar impressions, a ponticulus posterior, an atlas assimilation, an intervertebral narrowing and spondylosis deformans, were found radiologically in patients with sudden hearing loss. There were no radiological differences to a healthy population. No relationship could be established between static morphological changes of the craniocervical junction of the upper cervical spine and the sudden hearing loss. However, there was a statistically significant reduction of the mobility in the upper cervical spine in patients suffering from sudden hearing loss. Very high standard deviations in the atlanto-occipital and the atlanto-odontoid joints are interpreted as hyper- as well as hypomobile joints. These results indicate a possible correlation between sudden hearing loss and a functional pathology of the craniocervical junction.

  2. Spondylitic changes in long-finned pilot whales (Globicephala melas) stranded on Cape Cod, Massachusetts, USA, between 1982 and 2000.

    PubMed

    Sweeny, Melinda M; Price, Janet M; Jones, Gwilym S; French, Thomas W; Early, Greg A; Moore, Michael J

    2005-10-01

    The primary bone pathology diagnoses recognized in cetacea are osteomyelitis and spondylosis deformans. In this study, we determined the prevalence, type, and severity of vertebral pathology in 52 pilot whales, a mass stranding species that stranded on Cape Cod, Massachusetts, between 1982 and 2000. Eleven whales (21%) had hyperostosis and ossification of tendon insertion points on and between vertebrae, chevron bones, and costovertebral joints, with multiple fused blocks of vertebrae. These lesions are typical of a group of interrelated diseases described in humans as spondyloarthropathies, specifically ankylosing spondylitis, which has not been fully described in cetacea. In severe cases, ankylosing spondylitis in humans can inhibit mobility. If the lesions described here negatively affect the overall health of the whale, these lesions may be a contributing factor in stranding of this highly sociable species.

  3. Fifteen year experience of intrathecal baclofen treatment in Japan.

    PubMed

    Taira, T; Ochiai, T; Goto, S; Hori, T

    2006-01-01

    Intrathecal baclofen administration is a fully established treatment for severe spasticity. However, it is scarcely known that Baclofen, an agonist of GABA-B receptor, has other potential effects on pain, restoration coma, dystonia, tetanus, and hypothalamic storm. Sporadic episodes of dramatic recovery from persistent vegetative state are reported after intrathecal administration of baclofen. There are also reports on the use of baclofen for neuropathic pain including poststroke central pain syndrome. Baclofen is also used for control of dystonia due to cerebral palsy or reflex sympathetic dystrophy. On the other hand, epidural spinal cord stimulation has been used for pain, spasticity, dystonia, or attempt to improve deteriorated consciousness, though the effects seem variable and modest. Similarity between baclofen and spinal cord stimulation is interesting in that both involve the spinal GABAergic system. Based on the 15-year personal experience of intrathecal baclofen, I would stress importance of this treatment not only for spasticity but also for other difficult neurological disorders.

  4. A subtle mimicker in emergency department

    PubMed Central

    Angelis, Maria Vittoria De; Giacomo, Roberta Di; Muzio, Antonio Di; Onofrj, Marco; Bonanni, Laura

    2016-01-01

    Abstract Background: Movement disorder emergencies include any movement disorder which develops over hours to days, in which failure to appropriately diagnose and manage can result in patient morbidity or mortality. Movement disorder emergencies include acute dystonia: sustained or intermittent muscle contractions causing abnormal, often repetitive, movements. Acute dystonia is a serious challenge for emergency room doctors and neurologists, because of the high probability of misdiagnosis, due to the presence of several mimickers including partial seizures, meningitis, localized tetanus, serum electrolyte level abnormalities, strychnine poisoning, angioedema, malingering, catatonia, and conversion. Methods: We describe 2 examples, accompanied by videos, of acute drug-induced oro-mandibular dystonia, both subsequent to occasional haloperidol intake. Results: Management and treatment of this movement disorder are often difficult: neuroleptics withdrawal, treatment with benzodiazepines, and anticholinergics are recommended. Conclusion: Alternative treatment options are also discussed. PMID:27741141

  5. Yips and other movement disorders in golfers.

    PubMed

    Dhungana, Samish; Jankovic, Joseph

    2013-05-01

    Golf is a sport that requires perfect motor coordination and a balance between mobility and stability. Golfer's "yips," an intermittent motor disturbance manifested as transient tremor, jerk, or spasm that primarily occurs when the player is trying to chip or make a putt, is a movement disorder frequently encountered in both amateur and professional golfers. In addition, other movement disorders, such as tremors and dystonia, also can interfere with playing golf. Although the pathophysiology of the yips remains poorly understood, recent studies suggest that it may be a form of a task-specific, focal dystonia involving the hand and arm. Because task-specific dystonias and tremors are best treated by botulinum toxin injections, this also may be an effective therapy for the yips. The aim of this article is to systematically review the literature and our own experience with the yips and other movement disorders in golfers.

  6. Myoclonus in fraternal twin toddlers: a French family with a novel mutation in the SGCE gene.

    PubMed

    Thümmler, Susanne; Giuliano, Fabienne; Pincemaille, Olivier; Saugier-Veber, Pascale; Perelman, Serge

    2009-11-01

    Myoclonus dystonia is a rare movement disorder caused by mutations in the SGCE gene on chromosome 7q21 (DYT11) encoding the epsilon-sarcoglycan. Myoclonus is present in almost all patients and affects most often neck, trunk and upper limbs. Dystonia is present in about half of the patients. The mode of inheritance is autosomal dominant with variable clinical expression and maternal imprinting. Onset is usually in childhood or adolescence. Alcohol might relieve symptoms. We present a 33 month old girl and her twin brother with disabling involuntary jerky movements during intentional tasks. Family history of this French family was positive for the paternal uncle, his two daughters and the paternal great grandfather. Sequencing of the SGCE gene revealed a novel nonsense mutation c.942C>A (p.Tyr314X) in exon 7, confirming the diagnosis of myoclonus dystonia. Treatment with valproic acid significantly reduced myoclonic episodes and ameliorated life quality.

  7. Botulinum Toxin in Secondarily Nonresponsive Patients with Spasmodic Dysphonia.

    PubMed

    Mor, Niv; Tang, Christopher; Blitzer, Andrew

    2016-09-01

    Chemodenervation with botulinum toxin (BoNT) has been effective and well tolerated for all types of dystonia for >30 years. We reviewed outcomes of our patients treated with BoNT serotype A (BoNT-A) for spasmodic dysphonia (SD) who became secondarily nonresponsive. We found that 8 of 1400 patients became nonresponsive to BoNT-A (0.57%), which is lower than the secondary nonresponse rate in other dystonias. After a cessation period, 4 of our patients resumed BoNT-A injections, and recurrence of immunoresistance was not seen in any of them. When compared with patients with other dystonias, patients with SD receive extremely low doses of BoNT. Small antigen challenge may explain the lower rate of immunoresistance and long-lasting efficacy after BoNT-A is restarted among secondary nonresponsive patients with SD.

  8. Neuropathological Diagnostic Considerations in Hyperkinetic Movement Disorders

    PubMed Central

    den Dunnen, Wilfred F. A.

    2013-01-01

    Neuropathology of hyperkinetic movement disorders can be very challenging. This paper starts with basic functional anatomy of the basal ganglia in order to appreciate that focal lesions like for instance tumor or infarction can cause hyperkinetic movement disorders like (hemi)ballism. The neuropathology of different causes of chorea (amongst others Huntington’s disease, neuroacanthosis, and HLD-2) and dystonia (DYT1, PD, and Dopa-Responsive Dystonia) are described. Besides the functional anatomy of the basal ganglia a wider anatomical network view is provided. This forms the basis for the overview of the neuropathology of different forms of tremor. PMID:23420606

  9. Development of Parkinson's disease in patients with blepharospasm.

    PubMed

    Micheli, Federico; Scorticati, María Clara; Folgar, Silvia; Gatto, Emilia

    2004-09-01

    The liability to develop parkinsonian symptoms was evaluated in 105 outpatients with idiopathic blepharospasm (IBS; 54 cases) or IBS associated to oromandibular dystonia (Meige's syndrome; 51 cases) mean age 70.3 +/- 9.6 years, and compared with an age- and sex-matched population. Eleven patients developed Parkinson's disease in the blepharospasm group, whereas only 2 of 105 patients were affected in the control group. Our results suggest that patients with IBS either isolated or associated with oromandibular dystonia are more prone to develop parkinsonian symptoms.

  10. Hallervorden-Spatz Syndrome with Seizures.

    PubMed

    Gothwal, Sunil; Nayan, Swati

    2016-04-01

    Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene.

  11. Hallervorden–Spatz Syndrome with Seizures

    PubMed Central

    Gothwal, Sunil; Nayan, Swati

    2016-01-01

    Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene. PMID:27303611

  12. The basal ganglia and cerebellum interact in the expression of dystonic movement.

    PubMed

    Neychev, Vladimir K; Fan, Xueliang; Mitev, V I; Hess, Ellen J; Jinnah, H A

    2008-09-01

    Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements or abnormal posturing. Traditional views place responsibility for dystonia with dysfunction of basal ganglia circuits, yet recent evidence has pointed towards cerebellar circuits as well. In the current studies we used two strategies to explore the hypothesis that the expression of dystonic movements depends on influences from a motor network that includes both the basal ganglia and cerebellum. The first strategy was to evaluate the consequences of subthreshold lesions of the striatum in two different animal models where dystonic movements are thought to originate from abnormal cerebellar function. The second strategy employed microdialysis to search for changes in striatal dopamine release in these two animal models where the cerebellum has been already implicated. One of the animal models involved tottering mice, which exhibit paroxysmal dystonia due to an inherited defect affecting calcium channels. In keeping with prior results implicating the cerebellum in this model, surgical removal of the cerebellum eliminated their dystonic attacks. In contrast, subclinical lesions of the striatum with either 6-hydroxydopamine (6OHDA) or quinolinic acid (QA) exaggerated their dystonic attacks. Microdialysis of the striatum revealed dystonic attacks in tottering mice to be associated with a significant reduction in extracellular striatal dopamine. The other animal model involved the induction of dystonia via pharmacological excitation of the cerebellar cortex by local application of kainic acid in normal mice. In this model the site of stimulation determines the origin of dystonia in the cerebellum. However, subclinical striatal lesions with either 6OHDA or QA again exaggerated their generalized dystonia. When dystonic movements were triggered by pharmacological stimulation of the cerebellum, microdialysis revealed significant reductions in striatal

  13. ALS2 mutations

    PubMed Central

    Schneider, Susanne A.; Carr, Lucinda; Deuschl, Guenther; Hopfner, Franziska; Stamelou, Maria; Wood, Nicholas W.; Bhatia, Kailash P.

    2014-01-01

    Objective: To determine the genetic etiology in 2 consanguineous families who presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral sclerosis associated with generalized dystonia. Methods: A combination of homozygosity mapping and whole-exome sequencing in the first family and Sanger sequencing of candidate genes in the second family were used. Results: Both families were found to have homozygous loss-of-function mutations in the amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene. Conclusions: We report generalized dystonia and cerebellar signs in association with ALS2-related disease. We suggest that the ALS2 gene should be screened for mutations in patients who present with a similar phenotype. PMID:24562058

  14. Adult onset asymmetric upper limb tremor misdiagnosed as Parkinson’s disease: A clinical and electrophysiological study

    PubMed Central

    Schwingenschuh, Petra; Ruge, Diane; Edwards, Mark J; Terranova, Carmen; Katschnig, Petra; Carrillo, Fatima; Silveira-Moriyama, Laura; Schneider, Susanne A; Kägi, Georg; Dickson, John; Lees, Andrew J; Quinn, Niall; Mir, Pablo; Rothwell, John C; Bhatia, Kailash P

    2010-01-01

    Summary Approximately 10% of subjects thought clinically to have early Parkinson’s disease (PD) have normal dopaminergic functional imaging (SWEDDs – Scans Without Evidence of Dopaminergic Deficit). SWEDDs are a heterogeneous group. Here we aimed to delineate clinical and electrophysiological characteristics of a distinct subgroup of SWEDDs patients from PD and to clarify the underlying pathophysiology of this subgroup as a form of parkinsonism or dystonia. Therefore we compared clinical details of 25 patients referred with a diagnosis of tremor-dominant PD but with normal DaT SPECT scans (SWEDDs) with 12 tremor-dominant PD patients with abnormal DaT SPECT scans. We performed tremor analysis using accelerometry in the following patients with 1) SWEDDs, 2) PD, 3) primary segmental dystonia with dystonic limb tremor and 4) essential tremor (ET). We used transcranial magnetic stimulation with a facilitatory paired associative stimulation (PAS) paradigm to test if sensorimotor plasticity in SWEDDs resembled the pattern seen in PD, dystonia or ET. Although PD and SWEDDs patients shared several clinical features, the lack of true bradykinesia, occurrence of dystonia, and position- and task-specificity of tremor favoured a diagnosis of SWEDDs, whereas re-emergent tremor, true fatiguing or decrement, good response to dopaminergic drugs as well as presence of nonmotor symptoms made PD more likely. Basic tremor parameters overlapped between SWEDDs, PD, segmental dystonia and ET. However, a combination of re-emergent tremor and highest tremor amplitude in the resting condition was characteristic of PD tremor, while SWEDDs, dystonia and ET subjects had the highest tremor amplitude during action. Both SWEDDs and segmental dystonia patients exhibited an exaggerated pattern of sensorimotor plasticity in response to the PAS paradigm, with spread of excitation to an adjacent hand muscle. In contrast, PD patients showed no response to PAS, and the response of ET patients was no

  15. The effect of deep brain stimulation on quality of life in movement disorders

    PubMed Central

    Diamond, A; Jankovic, J

    2005-01-01

    Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis. PMID:16107348

  16. Update on blepharospasm

    PubMed Central

    Hallett, Mark; Evinger, Craig; Jankovic, Joseph; Stacy, Mark

    2008-01-01

    This review updates understanding and research on blepharospasm, a subtype of focal dystonia. Topics covered include clinical aspects, pathology, pathophysiology, animal models, dry eye, photophobia, epidemiology, genetics, and treatment. Blepharospasm should be differentiated from apraxia of eyelid opening. New insights into pathology and pathophysiology are derived from different types of imaging, including magnetic resonance studies. Physiologic studies indicate increased plasticity and trigeminal sensitization. While botulinum neurotoxin injections are the mainstay of therapy, other therapies are on the horizon. GLOSSARY BFMDRS = Burke-Fahn-Marsden dystonia rating scale; BoNT = botulinum neurotoxin; DBS = deep brain stimulation; DTI = diffusion tensor imaging; FDG = 18fluorodeoxyglucose; VBM = voxel-based morphometry. PMID:18852443

  17. A new deletion in autosomal dominant guanosine triphosphate cyclohydrolase I deficiency gene--Segawa disease.

    PubMed

    Bianca, S; Bianca, M

    2006-02-01

    Hereditary Progressive Dystonia with marked diurnal fluctuation (HPD) is an autosomally dominantly inherited dystonia which is characterized by marked diurnal fluctuation of symptoms and by marked and sustained response to levodopa associated with mutations in guanosine triphosphate cyclohydrolase (GCH-1) deficiency gene. We report an italian patient with a new 18 bp deletion at 267 in exon 1 in the GCH-1 gene. The peculiarity of our patient is the new mutations never reported and mnemonic disturbances that are also not reported in the classical HPD.A genotype-phenotype relationship may be suggested between different gene mutations and non classical clinical manifestations.

  18. Deep brain stimulation for medically refractory life-threatening status dystonicus in children.

    PubMed

    Walcott, Brian P; Nahed, Brian V; Kahle, Kristopher T; Duhaime, Ann-Christine; Sharma, Nutan; Eskandar, Emad N

    2012-01-01

    Generalized dystonic syndromes may escalate into persistent episodes of generalized dystonia known as status dystonicus that can be life-threatening due to dystonia-induced rhabdomyolysis and/or respiratory compromise. Treatment of these conditions usually entails parenteral infusion of antispasmodic agents and sedatives and occasionally necessitates a medically induced coma for symptom control. The authors report a series of 3 children who presented with medically intractable, life-threatening status dystonicus and were successfully treated with bilateral pallidal deep brain stimulation. Bilateral globus pallidus internus stimulation appears to be effective in the urgent treatment of medically refractory and life-threatening movement disorders.

  19. Lesch-Nyhan Disease.

    ERIC Educational Resources Information Center

    Barabas, Gabor, Ed.

    1993-01-01

    This special edition explores the serious genetic disorder, Lesch-Nyhan Disease (LND), which is characterized by severe dystonia, spasticity, speech impairment, renal disease, varying degrees of cognitive deficit, and, especially, compulsive self-injury. The information provided is based on experience at the Matheny School and Hospital (New…

  20. Writer's Cramp

    MedlinePlus

    ... cramp is a focal dystonia of the fingers, hand, and/or forearm. Symptoms usually appear when a person is trying to do a task that requires fine motor movements such as writing or playing a musical instrument. The symptoms may ...

  1. Hand orthosis as a writing aid in writer's cramp.

    PubMed

    Taş, N; Karataş, G K; Sepici, V

    2001-11-01

    Writer's cramp is a focal, task-specific dystonia of the hand and wrist. It primarily affects people who do a significant amount of writing, and causes difficulties in writing. We present five cases with writer's cramp who showed improvement in their writing ability with an applied hand orthosis.

  2. Proprioceptive reflexes in patients with reflex sympathetic dystrophy.

    PubMed

    Schouten, A C; Van de Beek, W J T; Van Hilten, J J; Van der Helm, F C T

    2003-07-01

    Reflex sympathetic dystrophy (RSD) is a syndrome that frequently follows an injury and is characterized by sensory, autonomic and motor features of the affected extremities. One of the more common motor features of RSD is tonic dystonia, which is caused by impairment of inhibitory interneuronal spinal circuits. In this study the circuits that modulate the gain of proprioceptive reflexes of the shoulder musculature are quantitatively assessed in 19 RSD patients, 9 of whom presented with dystonia. The proprioceptive reflexes are quantified by applying two types of force disturbances: (1) disturbances with a fixed low frequency and a variable bandwidth and (2) disturbances with a small bandwidth around a prescribed centre frequency. Compared to controls, patients have lower reflex gains for velocity feedback in response to the disturbances around a prescribed centre frequency. Additionally, patients with dystonia lack the ability to generate negative reflex gains for position feedback, for these same disturbances. Proprioceptive reflexes to the disturbances with a fixed low frequency and variable bandwidth present no difference between patients and controls. Although dystonia in the RSD patients was limited to the distal musculature, the results suggest involvement of interneuronal circuits that mediate postsynaptic inhibition of the motoneurons of the proximal musculature.

  3. Functional brain networks and abnormal connectivity in the movement disorders

    PubMed Central

    Poston, Kathleen L.; Eidelberg, David

    2012-01-01

    Clinical manifestations of movement disorders, such as Parkinson’s disease (PD) and dystonia, arise from neurophysiological changes within the cortico-striato-pallidothalamocortical (CSPTC) and cerebello-thalamo-cortical (CbTC) circuits. Neuroimaging techniques that probe connectivity within these circuits can be used to understand how these disorders develop as well as identify potential targets for medical and surgical therapies. Indeed, network analysis of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has identified abnormal metabolic networks associated with the cardinal motor symptoms of PD, such as akinesia and tremor, as well as PD-related cognitive dysfunction. More recent task-based and resting state functional magnetic resonance imaging studies have reproduced several of the altered connectivity patterns identified in these abnormal PD-related networks. A similar network analysis approach in dystonia revealed abnormal disease related metabolic patterns in both manifesting and non-manifesting carriers of dystonia mutations. Other multimodal imaging approaches using magnetic resonance diffusion tensor imaging in patients with primary genetic dystonia suggest abnormal connectivity within the CbTC circuits mediate the clinical manifestations of this inherited neurodevelopmental disorder. Ongoing developments in functional imaging and future studies in early patients are likely to enhance our understanding of these movement disorders and guide novel targets for future therapies. PMID:22206967

  4. Posterior occipitocervical instrumented fusion for dropped head syndrome after deep brain stimulation.

    PubMed

    Pereira, E A C; Wilson-MacDonald, J; Green, A L; Aziz, T Z; Cadoux-Hudson, T A D

    2010-04-01

    We describe dropped head syndrome in a patient with Parkinson's disease receiving subthalamic nucleus deep brain stimulation (DBS). Posterior occipitocervical instrumented fusion after transarticular screw fixation of an odontoid fracture is shown and its rationale explained. Pedunculopontine nucleus DBS as treatment for fall-predominant Parkinson's disease, and globus pallidus interna DBS for dystonia-predominant Parkinson's disease, are discussed.

  5. A Mutation Affecting the Sodium/Proton Exchanger, "SLC9A6," Causes Mental Retardation with Tau Deposition

    ERIC Educational Resources Information Center

    Garbern, James Y.; Neumann, Manuela; Trojanowski, John Q.; Lee, Virginia M.-Y.; Feldman, Gerald; Norris, Joy W.; Friez, Michael J.; Schwartz, Charles E.; Stevenson, Roger; Sima, Anders A. F.

    2010-01-01

    We have studied a family with severe mental retardation characterized by the virtual absence of speech, autism spectrum disorder, epilepsy, late-onset ataxia, weakness and dystonia. Post-mortem examination of two males revealed widespread neuronal loss, with the most striking finding being neuronal and glial tau deposition in a pattern reminiscent…

  6. Acoustic Variations in Adductor Spasmodic Dysphonia as a Function of Speech Task.

    ERIC Educational Resources Information Center

    Sapienza, Christine M.; Walton, Suzanne; Murry, Thomas

    1999-01-01

    Acoustic phonatory events were identified in 14 women diagnosed with adductor spasmodic dysphonia (ADSD), a focal laryngeal dystonia that disturbs phonatory function, and compared with those of 14 age-matched women with no vocal dysfunction. Findings indicated ADSD subjects produced more aberrant acoustic events than controls during tasks of…

  7. Identification of Dysarthria Types Based on Perceptual Analysis.

    ERIC Educational Resources Information Center

    Zyski, Barbara Jean; Weisiger, Bradford E.

    1987-01-01

    The study evaluated the degree of accuracy with which three groups of listeners (all speech language pathologists) could use perceptual analysis alone for identification of the following specific dysarthria types: flaccid, spastic, ataxic, hypokinetic, hyperkinetic chorea, hyperkinetic dystonia, and mixed. Listeners demonstrated minimal success in…

  8. Attenuated Variants of Lesch-Nyhan Disease

    ERIC Educational Resources Information Center

    Jinnah, H. A.; Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David J.; Verdu, Alfonso; Larovere, Laura E.; Chen, Chung-Jen; Cossu, Antonello; Wu, Chien-Hui; Sampat, Radhika; Chang, Shun-Jen; de Kremer, Raquel Dodelson; Nyhan, William; Harris, James C.; Reich, Stephen G.; Puig, Juan G.

    2010-01-01

    Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the…

  9. Cognitive Functioning in Children with Pantothenate-Kinase-Associated Neurodegeneration Undergoing Deep Brain Stimulation

    ERIC Educational Resources Information Center

    Mahoney, Rachel; Selway, Richard; Lin, Jean-Pierre

    2011-01-01

    Aim: To examine the cognitive functioning of young people with pantothenate-kinase-associated neurodegeneration (PKAN) after pallidal deep brain stimulation (DBS). PKAN is characterized by progressive generalized dystonia and has historically been associated with cognitive decline. With growing evidence that DBS can improve motor function in…

  10. THE DYT1 CARRIER STATE INCREASES ENERGY DEMAND IN THE OLIVOCEREBELLAR NETWORK

    PubMed Central

    Zhao, Yu; Sharma, Nutan; LeDoux, Mark S.

    2011-01-01

    DYT1 dystonia is caused by a GAG deletion in TOR1A, the gene which encodes torsinA. Gene expression studies in rodents and functional imaging studies in humans suggest that DYT1 dystonia may be a network disorder of neurodevelopmental origin. To generate high resolution metabolic maps of DYT1 dystonia and pinpoint dysregulated network elements, we performed 2-deoxyglucose autoradiography and cytochrome oxidase (CO) histochemistry in transgenic mice expressing human mutant (hMT1) torsinA and wild-type littermates. In comparison with controls, hMT1 mice showed increased glucose utilization (GU) in the inferior olive (IO) medial nucleus (IOM), IO dorsal accessory nucleus and substantia nigra compacta, and decreased GU in the medial globus pallidus (MGP) and lateral globus pallidus. The hMT1 mice showed increased CO activity in the IOM and Purkinje cell layer of cerebellar cortex, and decreased CO activity in the caudal caudate-putamen, substantia nigra reticulata and MGP. These findings suggest that (1) the DYT1 carrier state increases energy demand in the olivocerebellar network and (2) the IO may be a pivotal node for abnormal basal ganglia-cerebellar interactions in dystonia. PMID:21241782

  11. Excessive blinking as an initial manifestation of juvenile Huntington's disease.

    PubMed

    Xing, Shihui; Chen, Ling; Chen, Xi; Pei, Zhong; Zeng, Jinsheng; Li, Jinru

    2008-09-01

    Juvenile Huntington's disease (JHD) is mostly characterized by rigidity, myoclonus, bradykinesia, dystonia and seizure. We report a 9-year-old male JHD patient presenting excessive blinking as the initial symptom two years prior to typical JHD symptoms. Genetic analysis revealed expansion of 108 CAG repeats and magnetic resonance imaging showed caudate atrophy with lateral ventricular enlargement.

  12. Genetic Characterization of Movement Disorders and Dementias

    ClinicalTrials.gov

    2017-01-24

    Ataxia; Dystonia; Parkinson's Disease; Amyotrophic Lateral Sclerosis; Corticobasal Degeneration; Multiple System Atrophy; Alzheimer's Disease; Lewy Body Dementia; Parkinson Disease-Dementia; Dentatorubral-pallidoluysian Atrophy; Creutzfeldt-Jakob Disease and Fatal Familial Insomnia; Fragile X-associated Tremor/Ataxia Syndrome; Krabbe's Disease; Niemann-Pick Disease, Type C; Neuronal Ceroid Lipofuscinosis

  13. Intrathecal Baclofen Therapy: Benefits and Complications

    ERIC Educational Resources Information Center

    Zdolsek, Helena Aniansson; Olesch, Christine; Antolovich, Giuliana; Reddihough, Dinah

    2011-01-01

    Background: Spasticity and dystonia in children with cerebral palsy has been treated with intrathecal baclofen therapy (ITB) at the Royal Children's Hospital, Melbourne, Australia (RCH) since 1999. Methods: The records of children having received or still receiving ITB during the period September 1999 until August 2005 were studied to evaluate…

  14. Case-Control Study of Writer's Cramp

    ERIC Educational Resources Information Center

    Roze, E.; Soumare, A.; Pironneau, I.; Sangla, S.; de Cock, V. Cochen; Teixeira, A.; Astorquiza, A.; Bonnet, C.; Bleton, J. P.; Vidailhet, M.; Elbaz, A.

    2009-01-01

    Task-specific focal dystonias are thought to be due to a combination of individual vulnerability and environmental factors. There are no case-control studies of risk factors for writer's cramp. We undertook a case-control study of 104 consecutive patients and matched controls to identify risk factors for the condition. We collected detailed data…

  15. Aristotle's illusion in Parkinson's disease: evidence for normal interdigit tactile perception.

    PubMed

    Fiorio, Mirta; Marotta, Angela; Ottaviani, Sarah; Pozzer, Lara; Tinazzi, Michele

    2014-01-01

    Sensory alterations, a common feature of such movement disorders as Parkinson's disease (PD) and dystonia, could emerge as epiphenomena of basal ganglia dysfunction. Recently, we found a selective reduction of tactile perception (Aristotle's illusion, the illusory doubling sensation of one object when touched with crossed fingers) in the affected hand of patients with focal hand dystonia. This suggests that reduced tactile illusion might be a specific feature of this type of dystonia and could be due to abnormal somatosensory cortical activation. The aim of the current study was to investigate whether Aristotle's illusion is reduced in the affected hand of patients with PD. We tested 15 PD patients, in whom motor symptoms were mainly localised to one side of the body, and 15 healthy controls. Three pairs of fingers were tested in crossed (evoking the illusion) or parallel position (not evoking the illusion). A sphere was placed in the contact point between the two fingers and the blindfolded participants had to say whether they felt one or two stimuli. Stimuli were applied on the affected and less or unaffected side of the PD patients. We found no difference in illusory perception between the PD patients and the controls, nor between the more affected and less/unaffected side, suggesting that Aristotle's illusion is preserved in PD. The retained tactile illusion in PD and its reduction in focal hand dystonia suggest that the basal ganglia, which are dysfunctional in both PD and dystonia, may not be causally involved in this function. Instead, the level of activation between digits in the somatosensory cortex may be more directly involved. Finally, the similar percentage of illusion in the more affected and less or unaffected body sides indicates that the illusory perception is not influenced by the presence or amount of motor symptoms.

  16. Aristotle’s Illusion in Parkinson’s Disease: Evidence for Normal Interdigit Tactile Perception

    PubMed Central

    Fiorio, Mirta; Marotta, Angela; Ottaviani, Sarah; Pozzer, Lara; Tinazzi, Michele

    2014-01-01

    Sensory alterations, a common feature of such movement disorders as Parkinson’s disease (PD) and dystonia, could emerge as epiphenomena of basal ganglia dysfunction. Recently, we found a selective reduction of tactile perception (Aristotle’s illusion, the illusory doubling sensation of one object when touched with crossed fingers) in the affected hand of patients with focal hand dystonia. This suggests that reduced tactile illusion might be a specific feature of this type of dystonia and could be due to abnormal somatosensory cortical activation. The aim of the current study was to investigate whether Aristotle’s illusion is reduced in the affected hand of patients with PD. We tested 15 PD patients, in whom motor symptoms were mainly localised to one side of the body, and 15 healthy controls. Three pairs of fingers were tested in crossed (evoking the illusion) or parallel position (not evoking the illusion). A sphere was placed in the contact point between the two fingers and the blindfolded participants had to say whether they felt one or two stimuli. Stimuli were applied on the affected and less or unaffected side of the PD patients. We found no difference in illusory perception between the PD patients and the controls, nor between the more affected and less/unaffected side, suggesting that Aristotle’s illusion is preserved in PD. The retained tactile illusion in PD and its reduction in focal hand dystonia suggest that the basal ganglia, which are dysfunctional in both PD and dystonia, may not be causally involved in this function. Instead, the level of activation between digits in the somatosensory cortex may be more directly involved. Finally, the similar percentage of illusion in the more affected and less or unaffected body sides indicates that the illusory perception is not influenced by the presence or amount of motor symptoms. PMID:24523929

  17. Atlas-based functional radiosurgery: Early results

    SciTech Connect

    Stancanello, J.; Romanelli, P.; Pantelis, E.; Sebastiano, F.; Modugno, N.

    2009-02-15

    Functional disorders of the brain, such as dystonia and neuropathic pain, may respond poorly to medical therapy. Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the centromedian nucleus of the thalamus (CMN) may alleviate dystonia and neuropathic pain, respectively. A noninvasive alternative to DBS is radiosurgical ablation [internal pallidotomy (IP) and medial thalamotomy (MT)]. The main technical limitation of radiosurgery is that targets are selected only on the basis of MRI anatomy, without electrophysiological confirmation. This means that, to be feasible, image-based targeting must be highly accurate and reproducible. Here, we report on the feasibility of an atlas-based approach to targeting for functional radiosurgery. In this method, masks of the GPi, CMN, and medio-dorsal nucleus were nonrigidly registered to patients' T1-weighted MRI (T1w-MRI) and superimposed on patients' T2-weighted MRI (T2w-MRI). Radiosurgical targets were identified on the T2w-MRI registered to the planning CT by an expert functional neurosurgeon. To assess its feasibility, two patients were treated with the CyberKnife using this method of targeting; a patient with dystonia received an IP (120 Gy prescribed to the 65% isodose) and a patient with neuropathic pain received a MT (120 Gy to the 77% isodose). Six months after treatment, T2w-MRIs and contrast-enhanced T1w-MRIs showed edematous regions around the lesions; target placements were reevaluated by DW-MRIs. At 12 months post-treatment steroids for radiation-induced edema and medications for dystonia and neuropathic pain were suppressed. Both patients experienced significant relief from pain and dystonia-related problems. Fifteen months after treatment edema had disappeared. Thus, this work shows promising feasibility of atlas-based functional radiosurgery to improve patient condition. Further investigations are indicated for optimizing treatment dose.

  18. Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements.

    PubMed

    Barow, Ewgenia; Neumann, Wolf-Julian; Brücke, Christof; Huebl, Julius; Horn, Andreas; Brown, Peter; Krauss, Joachim K; Schneider, Gerd-Helge; Kühn, Andrea A

    2014-11-01

    Deep brain stimulation of the globus pallidus internus alleviates involuntary movements in patients with dystonia. However, the mechanism is still not entirely understood. One hypothesis is that deep brain stimulation suppresses abnormally enhanced synchronized oscillatory activity within the motor cortico-basal ganglia network. Here, we explore deep brain stimulation-induced modulation of pathological low frequency (4-12 Hz) pallidal activity that has been described in local field potential recordings in patients with dystonia. Therefore, local field potentials were recorded from 16 hemispheres in 12 patients undergoing deep brain stimulation for severe dystonia using a specially designed amplifier allowing simultaneous high frequency stimulation at therapeutic parameter settings and local field potential recordings. For coherence analysis electroencephalographic activity (EEG) over motor areas and electromyographic activity (EMG) from affected neck muscles were recorded before and immediately after cessation of high frequency stimulation. High frequency stimulation led to a significant reduction of mean power in the 4-12 Hz band by 24.8 ± 7.0% in patients with predominantly phasic dystonia. A significant decrease of coherence between cortical EEG and pallidal local field potential activity in the 4-12 Hz range was revealed for the time period of 30 s after switching off high frequency stimulation. Coherence between EMG activity and pallidal activity was mainly found in patients with phasic dystonic movements where it was suppressed after high frequency stimulation. Our findings suggest that high frequency stimulation may suppress pathologically enhanced low frequency activity in patients with phasic dystonia. These dystonic features are the quickest to respond to high frequency stimulation and may thus directly relate to modulation of pathological basal ganglia activity, whereas improvement in tonic features may depend on long-term plastic changes within the

  19. Magnetic resonance imaging diagnosis of intervertebral disc disease and myelomalacia in an American black bear (Ursus americanus).

    PubMed

    Knafo, S Emmanuelle; Divers, Stephen J; Rech, Raquel; Platt, Simon R

    2012-06-01

    A 23-yr-old black bear (Ursus americanus) was examined because of paralysis of unknown duration. The precise onset of clinical signs was unknown as a result of seasonal torpor. The bear was immobilized and transported to a university veterinary teaching hospital for further evaluation and treatment. Radiography revealed increased mineral opacity and ventral bridging across vertebral segments T8-11. Magnetic resonance imaging demonstrated dorsal and ventral compression of the spinal cord at T8-9. Given the bear's advanced age, the unknown duration of spinal cord compression, unknown presence of deep pain perception, and thus an unknown prognosis for surgical success, euthanasia was elected. Postmortem examination revealed severe spondylosis deformans from T7 to L3 and dorsal extradural extruded disc material in the area of T8-9. Histopathology demonstrated the dorsal horns of the spinal cord at T9 were replaced by foamy macrophages extending into the dorsal and lateral funiculi of the white matter compatible with focal, severe, chronic myelomalacia. This is the first report of intervertebral disc disease and myelomalacia diagnosed using MRI in a large carnivore.

  20. [Paget's disease of bone and basilar impression associated with an Arnold-Chiari type-1 malformation].

    PubMed

    Iglesias-Osma, C; Gómez Sánchez, J C; Suquia Múgica, B; Querol Prieto, R; de Portugal Alvarez, J

    1997-10-01

    The patient, a 78-year-old female with history of headache and progressive gait disturbance for almost one year, was admitted to our department because of dysphagia and dysphonia since three months before. Neurological examination revealed nystagmus, cerebellar ataxia, deafness, and vesical incontinence. No cerebral injuries were detected by computed tomography (CT) scan, although Paget's. Disease of Bone (PDB) was suggested, confirmed by biochemical and scintigraphic studies. The plain skull X-ray showed platybasia. As all the disarrangements were not explained by PDB complications alone, nuclear magnetic resonance imaging (MRI) was performed which demonstrated an Arnold-Chiari malformation (ACM) type I, with mild tonsillar herniation and anterior compression of the brainstem due to basilar impression, without syringomyelia. The association of PDB and ACM is a peculiarity seldom reported. The surgical approach was rejected, but the severity of symptoms and osteitis deformans biochemical activity needed a treatment; it was orientated to modify bone turnover using etidronate, a bisphosphonate, which induced clinical improvement and a decrease in serum alkaline phosphatase as well as in other bone resorption markers, without side effects. The good status and biochemical remission have been maintained a year later.