Dysgraphia as a Mild Expression of Dystonia in Children with Absence Epilepsy

PubMed Central

Guerrini, Renzo; Melani, Federico; Brancati, Claudia; Ferrari, Anna Rita; Brovedani, Paola; Biggeri, Annibale; Grisotto, Laura; Pellacani, Simona

2015-01-01

Background Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia. Objectives Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer’s cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia. Methods We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.7) and average intelligence and compared them with 89 age-, gender- and class-matched healthy children (mean age 10.57) using tests for handwriting fluency and quality, based on which we divided patients and controls into four subgroups: AE/dysgraphia, AE without dysgraphia, controls with dysgraphia and healthy controls. We compared the blink reflex recovery cycle in children belonging to all four subgroups. Results We identified dysgraphia in 17/82 children with AE and in 7/89 controls (20.7 vs 7.8%; P = 0.016) with the former having a 3.4-times higher risk of dysgraphia regardless of age and gender (odd ratio: 3.49; 95% CI 1.2, 8.8%). The AE/dysgraphia subgroup performed worse than controls with dysgraphia in one test of handwriting fluency (P = 0.037) and in most trials testing handwriting quality (P< 0.02). In children with AE/dysgraphia the blink reflex showed no suppression at short interstimulus intervals, with a difference for each value emerging when comparing the study group with the three remaining subgroups (P<0.001). Conclusions In children with AE, dysgraphia is highly prevalent and has a homogeneous, distinctive pathophysiological substrate consistent with idiopathic dystonia. PMID:26132164

What’s special about task in dystonia? A voxel-based morphometry and diffusion weighted imaging study

PubMed Central

Ramdhani, Ritesh A.; Kumar, Veena; Velickovic, Miodrag; Frucht, Steven J.; Tagliati, Michele; Simonyan, Kristina

2014-01-01

Background Numerous brain imaging studies have demonstrated structural changes in the basal ganglia, thalamus, sensorimotor cortex and cerebellum across different forms of primary dystonia. However, our understanding of brain abnormalities contributing to the clinically well-described phenomenon of task-specificity in dystonia remained limited. Methods We used high-resolution MRI with voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics of fractional anisotropy to examine gray and white matter organization in two task-specific dystonia forms, writer’s cramp and laryngeal dystonia, and two non-task-specific dystonia forms, cervical dystonia and blepharospasm. Results A direct comparison between the both dystonia forms revealed that characteristic gray matter volumetric changes in task-specific dystonia involve the brain regions responsible for sensorimotor control during writing and speaking, such as primary somatosensory cortex, middle frontal gyrus, superior/inferior temporal gyrus, middle/posterior cingulate cortex, occipital cortex as well as the striatum and cerebellum (lobules VI-VIIa). These gray matter changes were accompanied by white matter abnormalities in the premotor cortex, middle/inferior frontal gyrus, genu of the corpus callosum, anterior limb/genu of the internal capsule, and putamen. Conversely, gray matter volumetric changes in non-task-specific group were limited to the left cerebellum (lobule VIIa) only, while white matter alterations were found to underlie the primary sensorimotor cortex, inferior parietal lobule and middle cingulate gyrus. Conclusion Distinct microstructural patterns in task-specific and non-task-specific dystonias may represent neuroimaging markers and provide evidence that these two dystonia subclasses likely follow divergent pathophysiological mechanisms precipitated by different triggers. PMID:24925463

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.

How Many Dystonias? Clinical Evidence.

PubMed

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.

[Myths and evidence on the use of botulinum toxin: neuropharmacology and dystonia].

PubMed

Garcia-Ruiz, P J; Sanz-Cartagena, P; Martinez-Castrillo, J C; Ares-Pensado, B; Aviles-Olmos, I; Blazquez-Estrada, M; Fanjul-Arbos, S; Garcia-Caldentey, J; Gazulla, J; Gutierrez-Garcia, J; Huete-Anton, B; Lucas-Rodenas, C; Luquin, M R; Martinez-Torres, I; Medialdea-Natera, P; Mendoza-Rodriguez, A; Mir-Rivera, P; Posada, I J; Ruiz-Martinez, J; Sanchez-Alonso, P; Trejo-Gabriel Y Galan, J M; Vela, L; Pena-Segura, J L

2018-03-01

Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. To analyze and summarize different questions about the use of BTA in our clinical practice. A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia. A literature search at PubMed, mainly for English language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of neuropharmacology, such as mechanism of action, bioequivalence of the different preparations, immunogenicity, etc. were included. Regarding dystonia, the document included questions about methods of evaluation, cervical dystonia, blepharospasm, etc. This review does not pretend to be a guide, but rather a tool for continuous training of residents and specialists in neurology, about different specific areas of the management of BTA.

Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test.

PubMed

Kimmich, Okka; Bradley, David; Whelan, Robert; Mulrooney, Nicola; Reilly, Richard B; Hutchinson, Siobhan; O'Riordan, Sean; Hutchinson, Michael

2011-09-01

Adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance; patients with sporadic adult-onset primary torsion dystonia are much more prevalent than familial. The temporal discrimination threshold is the shortest time interval at which two stimuli are detected to be asynchronous and has been shown to be abnormal in adult-onset primary torsion dystonia. The aim was to determine the frequency of abnormal temporal discrimination thresholds in patients with sporadic adult-onset primary torsion dystonia and their first-degree relatives. We hypothesized that abnormal temporal discrimination thresholds in first relatives would be compatible with an autosomal dominant endophenotype. Temporal discrimination thresholds were examined in 61 control subjects (39 subjects <50 years of age; 22 subjects >50 years of age), 32 patients with sporadic adult-onset primary torsion dystonia (cervical dystonia n = 30, spasmodic dysphonia n = 1 and Meige's syndrome n = 1) and 73 unaffected first-degree relatives (36 siblings, 36 offspring and one parent) using visual and tactile stimuli. Z-scores were calculated for all subjects; a Z > 2.5 was considered abnormal. Abnormal temporal discrimination thresholds were found in 1/61 (2%) control subjects, 27/32 (84%) patients with adult-onset primary torsion dystonia and 32/73 (44%) unaffected relatives [siblings (20/36; 56%), offspring (11/36; 31%) and one parent]. When two or more relatives were tested in any one family, 22 of 24 families had at least one first-degree relative with an abnormal temporal discrimination threshold. The frequency of abnormal temporal discrimination thresholds in first-degree relatives of patients with sporadic adult-onset primary torsion dystonia is compatible with an autosomal dominant disorder and supports the hypothesis that apparently sporadic adult-onset primary torsion dystonia is genetic in origin.

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia.

PubMed

Liu, Xuguang; Yianni, John; Wang, Shouyan; Bain, Peter G; Stein, John F; Aziz, Tipu Z

2006-03-01

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.

Task-specific Dystonias

PubMed Central

Torres-Russotto, Diego; Perlmutter, Joel S.

2009-01-01

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions. PMID:18990127

Table tennis dystonia.

PubMed

Le Floch, Anne; Vidailhet, Marie; Flamand-Rouvière, Constance; Grabli, David; Mayer, Jean-Michel; Gonce, Michel; Broussolle, Emmanuel; Roze, Emmanuel

2010-02-15

Focal task-specific dystonia (FTSD) occurs exclusively during a specific activity that usually involves a highly skilled movement. Classical FTSD dystonias include writer's cramp and musician's dystonia. Few cases of sport-related dystonia have been reported. We describe the first four cases of FTSD related to table tennis (TT), two involving professional international competitors. We also systematically analyzed the literature for reports of sport-related dystonia including detailed clinical descriptions. We collected a total of 13 cases of sport-related dystonia, including our four TT players. Before onset, all the patients had trained for many years, for a large number of hours per week. Practice time had frequently increased significantly in the year preceding onset. As TT is characterized by highly skilled hand/forearm movements acquired through repetitive exercises, it may carry a higher risk of FTSD than other sports. Intensive training may result in maladaptive responses and overwhelm homeostatic mechanisms that regulate cortical plasticity in vulnerable individuals. Our findings support the importance of environmental risk factors in sport-related FTSD, as also suggested in classical FTSD, and have important implications for clinical practice. (c) 2010 Movement Disorder Society.

Successful treatment of open jaw and jaw deviation dystonia with botulinum toxin using a simple intraoral approach.

PubMed

Moscovich, Mariana; Chen, Zhongxing Peng; Rodriguez, Ramon

2015-03-01

Oromandibular dystonia (OMD) is a focal dystonia that involves the mouth, jaw, and/or tongue. It can be classified as idiopathic, tardive dystonia or secondary to other neurological disorders and subdivided into jaw opening, jaw closing, jaw deviation and lip pursing. The muscles involved in jaw opening dystonia are usually the digastrics and lateral pterygoids. It is known that the lateral pterygoids may be approached both internally and externally. The external approach is the most common; however neurologists experienced in treating patients with botulinum toxin can safely and with no extra cost perform the intraoral procedure. We report our experience in the treatment of jaw opening and jaw deviation dystonia using the intraoral injection approach. Eight patients were selected from the University of Florida with a clinical diagnosis of open jaw/jaw deviation dystonia. All of them were injected with onabotulinum toxin A using the internal approach and the clinical global impression scale was applied. The mean age of the patients was 67 (standard deviation [SD] 10.2) years, with a disease duration of 10.2 (SD 7.7) years and the mean distance they traveled to our institution was 448 km (278 miles). After treatment, six patients scored as very much improved in the clinical global impression scale and two patients scored as much improved. Only one patient reported an adverse event of nasal speech following one of the injections that improved after 4 weeks. Botulinum toxin injections for open jaw/jaw deviation dystonia can be safely performed with the intraoral approach without the need of special devices other than electromyography. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Cervical Dystonia Impact Profile (CDIP-58): Can a Rasch developed patient reported outcome measure satisfy traditional psychometric criteria?

PubMed Central

Cano, Stefan J; Warner, Thomas T; Thompson, Alan J; Bhatia, Kailash P; Fitzpatrick, Ray; Hobart, Jeremy C

2008-01-01

Background The United States Food and Drug Administration (FDA) are currently producing guidelines for the scientific adequacy of patient reported outcome measures (PROMs) in clinical trials, which will have implications for the selection of scales used in future clinical trials. In this study, we examine how the Cervical Dystonia Impact Profile (CDIP-58), a rigorous Rasch measurement developed neurologic PROM, stands up to traditional psychometric criteria for three reasons: 1) provide traditional psychometric evidence for the CDIP-58 in line with proposed FDA guidelines; 2) enable researchers and clinicians to compare it with existing dystonia PROMs; and 3) help researchers and clinicians bridge the knowledge gap between old and new methods of reliability and validity testing. Methods We evaluated traditional psychometric properties of data quality, scaling assumptions, targeting, reliability and validity in a group of 391 people with CD. The main outcome measures used were the CDIP-58, Medical Outcome Study Short Form-36, the 28-item General Health Questionnaire, and Hospital and Anxiety and Depression Scale. Results A total of 391 people returned completed questionnaires (corrected response rate 87%). Analyses showed: 1) data quality was high (low missing data ≤ 4%, subscale scores could be computed for > 96% of the sample); 2) item groupings passed tests for scaling assumptions; 3) good targeting (except for the Sleep subscale, ceiling effect = 27%); 4) good reliability (Cronbach's alpha ≥ 0.92, test-retest intraclass correlations ≥ 0.83); and 5) validity was supported. Conclusion This study has shown that new psychometric methods can produce a PROM that stands up to traditional criteria and supports the clinical advantages of Rasch analysis. PMID:18684327

The cervical dystonia impact profile (CDIP-58): can a Rasch developed patient reported outcome measure satisfy traditional psychometric criteria?

PubMed

Cano, Stefan J; Warner, Thomas T; Thompson, Alan J; Bhatia, Kailash P; Fitzpatrick, Ray; Hobart, Jeremy C

2008-08-06

The United States Food and Drug Administration (FDA) are currently producing guidelines for the scientific adequacy of patient reported outcome measures (PROMs) in clinical trials, which will have implications for the selection of scales used in future clinical trials. In this study, we examine how the Cervical Dystonia Impact Profile (CDIP-58), a rigorous Rasch measurement developed neurologic PROM, stands up to traditional psychometric criteria for three reasons: 1) provide traditional psychometric evidence for the CDIP-58 in line with proposed FDA guidelines; 2) enable researchers and clinicians to compare it with existing dystonia PROMs; and 3) help researchers and clinicians bridge the knowledge gap between old and new methods of reliability and validity testing. We evaluated traditional psychometric properties of data quality, scaling assumptions, targeting, reliability and validity in a group of 391 people with CD. The main outcome measures used were the CDIP-58, Medical Outcome Study Short Form-36, the 28-item General Health Questionnaire, and Hospital and Anxiety and Depression Scale. A total of 391 people returned completed questionnaires (corrected response rate 87%). Analyses showed: 1) data quality was high (low missing data < or = 4%, subscale scores could be computed for > 96% of the sample); 2) item groupings passed tests for scaling assumptions; 3) good targeting (except for the Sleep subscale, ceiling effect = 27%); 4) good reliability (Cronbach's alpha > or = 0.92, test-retest intraclass correlations > or = 0.83); and 5) validity was supported. This study has shown that new psychometric methods can produce a PROM that stands up to traditional criteria and supports the clinical advantages of Rasch analysis.

The neurophysiological features of myoclonus-dystonia and differentiation from other dystonias.

PubMed

Popa, Traian; Milani, Paolo; Richard, Aliénor; Hubsch, Cécile; Brochard, Vanessa; Tranchant, Christine; Sadnicka, Anna; Rothwell, John; Vidailhet, Marie; Meunier, Sabine; Roze, Emmanuel

2014-05-01

Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown. To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias. We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale. Myoclonus-dystonia with a proven SGCE mutation. We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores. We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other

All in the blink of an eye: new insight into cerebellar and brainstem function in DYT1 and DYT6 dystonia.

PubMed

Sadnicka, A; Teo, J T; Kojovic, M; Pareés, I; Saifee, T A; Kassavetis, P; Schwingenschuh, P; Katschnig-Winter, P; Stamelou, M; Mencacci, N E; Rothwell, J C; Edwards, M J; Bhatia, K P

2015-05-01

Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Patients with cervical and focal hand dystonia have impaired cerebellar associative learning using the paradigm eyeblink conditioning. This is perhaps the most direct evidence to date that the cerebellum is implicated in patients. Eleven patients with DYT1 dystonia and five patients with DYT6 dystonia were examined and rates of eyeblink conditioning were compared with age-matched controls. A marker of brainstem excitability, the blink reflex recovery, was also studied in the same groups. Patients with DYT1 and DYT6 dystonia have a normal ability to acquire conditioned responses. Blink reflex recovery was enhanced in DYT1 but this effect was not seen in DYT6. If the cerebellum is an important driver in DYT1 and DYT6 dystonia our data suggest that there is specific cerebellar dysfunction such that the circuits essential for conditioning function normally. Our data are contrary to observations in focal dystonia and suggest that the cerebellum may have a distinct role in different subsets of dystonia. Evidence of enhanced blink reflex recovery in all patients with dystonia was not found and recent studies calling for the blink recovery reflex to be used as a diagnostic test for dystonic tremor may require further corroboration. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Genetics Home Reference: dystonia 6

MedlinePlus

... neck, causing problems with speaking (dysarthria) and eating (dysphagia). Eyelid twitching (blepharospasm) may also occur. Involvement of ... dystonia, DYT6 type The Bachmann-Strauss Dystonia and Parkinson Foundation: What Is Dystonia? Patient Support and Advocacy ...

Full fusion of proximal thoracic curve helps to prevent postoperative cervical tilt in Lenke type 2 adolescent idiopathic scoliosis patients with right-elevated shoulder.

PubMed

Jiang, Jun; Qian, Bang-Ping; Qiu, Yong; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

2017-08-23

To date, no study had reported the phenomenon of deteriorated postoperative cervical tilt in Lenke type 2 adolescent idiopathic scoliosis patients. The purpose of this study is to evaluate the cervical tilt in Lenke type 2 adolescent idiopathic scoliosis patients with right-elevated shoulder treated by either full fusion or partial/non fusion of the proximal thoracic curve. A total of 30 Lenke type 2 AIS patients with preoperative right-elevated shoulder underwent posterior spinal instrumentation from 2009 to 2011 were included in this study. All the subjects were divided into 2 groups according to the selection of upper instrumented vertebra. There were 14 cases proximally fused to T1 or T2 (Group A) and 16 cases proximally fused to T3 or below (Group B). Both standing anteroposterior and sagittal X-ray films of the spine obtained preoperatively, one week after the operation, and at a minimum of two-year follow-up were analyzed with respect to the following parameters: cervical tilt, T1 tilt, proximal thoracic Cobb angle, main thoracic Cobb angle, apical vertebral translation of proximal thoracic curve, apical vertebral translation of main thoracic curve, radiographic shoulder height, cervical lordosis, proximal thoracic kyphosis and main thoracic kyphosis. Most (83.3%) of the patients in these two groups gained satisfactory shoulder balance after surgery. However, the cervical tilt significantly improved in group A (p < 0.001) but deteriorated in group B (p < 0.001). In group A, the decrease of cervical tilt significantly positively correlated with that of T1 tilt (p < 0.001). In group B, the increase of cervical tilt significantly positively correlated with both the increase of T1 tilt (p < 0.001) and the increase of apical vertebral translation of proximal thoracic curve (p < 0.05). Lenke type 2 AIS patients with right-elevated shoulder gain improved shoulder but deteriorated cervical tilt after partial/non fusion of proximal thoracic curve. Full

Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy?

PubMed

Jinnah, H A; Comella, Cynthia L; Perlmutter, Joel; Lungu, Codrin; Hallett, Mark

2018-06-01

Numerous studies have established botulinum toxin (BoNT) to be safe and effective for the treatment of cervical dystonia (CD). Despite its well-documented efficacy, there has been growing awareness that a significant proportion of CD patients discontinue therapy. The reasons for discontinuation are only partly understood. This summary describes longitudinal studies that provided information regarding the proportions of patients discontinuing BoNT therapy, and the reasons for discontinuing therapy. The data come predominantly from un-blinded long-term follow-up studies, registry studies, and patient-based surveys. All types of longitudinal studies provide strong evidence that BoNT is both safe and effective in the treatment of CD for many years. Overall, approximately one third of CD patients discontinue BoNT. The most common reason for discontinuing therapy is lack of benefit, often described as primary or secondary non-response. The apparent lack of response is only rarely related to true immune-mediated resistance to BoNT. Other reasons for discontinuing include side effects, inconvenience, cost, or other reasons. Although BoNT is safe and effective in the treatment of the majority of patients with CD, approximately one third discontinue. The increasing awareness of a significant proportion of patients who discontinue should encourage further efforts to optimize administration of BoNT, to improve BoNT preparations to extend duration or reduce side effects, to develop add-on therapies that may mitigate swings in symptom severity, or develop entirely novel treatment approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

PubMed

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.

Treatment strategies for dystonia

PubMed Central

Cloud, Leslie J; Jinnah, HA

2012-01-01

Importance of the field Dystonia is a neurological syndrome characterized by involuntary twisting movements and unnatural postures. It has many different manifestations and causes, and many different treatment options are available. These options include physical and occupational therapy, oral medications, intramuscular injection of botulinum toxins, and neurosurgical interventions. Areas covered in this review In this review, we first summarize the treatment options available, then we provide suggestions from our own experience for how these can be applied in different types of dystonia. In preparing this review article, an extensive literature search was undertaken using PubMed. Only selected references from 1970 to 2008 are cited. What the reader will gain This review is intended to provide the clinician with a practical guide to the treatment of dystonia. Take home message Treatment of dystonia begins with proper diagnosis and classification, followed by an appropriate search for underlying etiology, and an assessment of the functional impairment associated with the dystonia. The therapeutic approach, which is usually limited to symptomatic therapy, must then be tailored to the individual needs of the patient. PMID:20001425

A loud auditory stimulus overcomes voluntary movement limitation in cervical dystonia.

PubMed

Serranová, Tereza; Jech, Robert; Martí, Maria José; Modreanu, Raluca; Valldeoriola, Francesc; Sieger, Tomáš; Růžička, Evžen; Valls-Solé, Josep

2012-01-01

Patients with cervical dystonia (CD) present with an impaired performance of voluntary neck movements, which are usually slow and limited. We hypothesized that such abnormality could involve defective preparation for task execution. Therefore, we examined motor preparation in CD patients using the StartReact method. In this test, a startling auditory stimulus (SAS) is delivered unexpectedly at the time of the imperative signal (IS) in a reaction time task to cause a faster execution of the prepared motor programme. We expected that CD patients would show an abnormal StartReact phenomenon. Fifteen CD patients and 15 age matched control subjects (CS) were asked to perform a rotational movement (RM) to either side as quick as possible immediately after IS perception (a low intensity electrical stimulus to the II finger). In randomly interspersed test trials (25%) a 130 dB SAS was delivered simultaneously with the IS. We recorded RMs in the horizontal plane with a high speed video camera (2.38 ms per frame) in synchronization with the IS. The RM kinematic-parameters (latency, velocity, duration and amplitude) were analyzed using video-editing software and screen protractor. Patients were asked to rate the difficulty of their RMs in a numerical rating scale. In control trials, CD patients executed slower RMs (repeated measures ANOVA, p<0.10(-5)), and reached a smaller final head position angle relative to the midline (p<0.05), than CS. In test trials, SAS improved all RMs in both groups (p<0.10(-14)). In addition, patients were more likely to reach beyond their baseline RM than CS (χ(2), p<0.001) and rated their performance better than in control trials (t-test, p<0.01). We found improvement of kinematic parameters and subjective perception of motor performance in CD patients with StartReact testing. Our results suggest that CD patients reach an adequate level of motor preparation before task execution.

Genetics Home Reference: hypermanganesemia with dystonia

MedlinePlus

... of hypermanganesemia with dystonia , called hypermanganesemia with dystonia , polycythemia, and cirrhosis (HMDPC) and hypermanganesemia with dystonia 2, ... have an increased number of red blood cells (polycythemia) and low levels of iron stored in the ...

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

Analysis of cervical kyphosis and spinal balance in young idiopathic scoliosis patients classified by the apex of thoracic kyphosis.

PubMed

Ito, Kenyu; Imagama, Shiro; Ito, Zenya; Ando, Kei; Kobayashi, Kazuyoshi; Hida, Tetsuro; Tsushima, Mikito; Ishikawa, Yoshimoto; Matsumoto, Akiyuki; Nishida, Yoshihiro; Ishiguro, Naoki

2016-10-01

Sagittal balance has recently been the focus of studies aimed at understanding the correction force required for both coronal and sagittal malalignment. However, the correlation between cervical kyphosis and sagittal balance in AIS patients has yet to be thoroughly investigated. This study aimed to clarify the correlation between cervical alignment and spinal balance in patients with adolescent idiopathic scoliosis (AIS). Here, we hypothesized that cervical kyphosis patients can be classified into groups by the apex of thoracic kyphosis. This study included 92 AIS patients (84 females, 8 males; mean age, 15.1 years). Patients were divided into the cervical lordosis (CL), cervical sigmoid (CS), or cervical kyphosis (CK) groups and further classified according to the apex of thoracic kyphosis into High (above T3), Middle (T4-T9), and Low (below T10) groups. There were 17 (18.5 %), 22 (23.9 %), and 53 (57.6 %) patients with CL, CS, and CK, respectively. In the CK group, 13 had CK-High, 35 had CK-Middle, and 5 had CK-Low. The C7 sagittal vertical axis (C7SVA) measurements were most backward in CK-High and most forward in CK-Low. The T5-12 kyphosis (TK) measurement was significantly lower in CK-High. Most AIS patients had kyphotic cervical alignment. Patients with CK can be classified as having CK-High, CK-Middle, or CK-Low according to the apex of thoracic kyphosis. CK-High is due to thoracic hypokyphosis with a backward balanced C7SVA. CK-Middle is well-balanced cervical kyphosis. CK-Low has forward-bent global kyphosis of the cervicothoracic spine that positioned the C7SVA forward.

Markedly severe dystonia in Japanese encephalitis.

PubMed

Kalita, J; Misra, U K

2000-11-01

Encephalitis has been reported to be a rare cause of severe dystonia. We describe five patients with markedly severe dystonia from Japanese encephalitis. These patients with markedly severe dystonia were seen during the past 8 years as a subgroup of 50 patients with Japanese encephalitis. The diagnosis of markedly severe dystonia was based on increasingly frequent episodes of generalized dystonia with bulbar, respiratory, or metabolic derangement or leading to exhaustion or pain. The diagnosis of JE was based on clinicoradiologic features and a fourfold increase of hemagglutination-inhibiting antibody titers in paired serum. The outcome of the patients was defined as a good, partial, or poor recovery on the basis of 1-year clinical status. All the patients were males, and their ages ranged from 6 to 19 years. Movement disorders appeared 1 to 3 weeks after the illness as the level of consciousness started improving. During the next 1 to 4 weeks, patients began to experience markedly severe dystonia. It was associated with marked axial dystonia resulting in opisthotonus and retrocollis in five patients, jaw-opening dystonia in two patients, teeth clenching in one patient, and oculogyric crisis and neck deviation in another patient. The attacks of markedly severe dystonia lasted for 2 to 30 minutes and occurred as many as 20 to 30 times daily. Other developments included fixed limb dystonia in one patient, severe spasticity and rigidity in five patients, and focal muscle wasting in one patient. These patients had only a modest improvement after treatment. Markedly severe dystonia abated by 2 to 6 months in all the patients who were followed up. Cranial magnetic resonance imaging showed bilateral thalamic involvement in all patients, brainstem involvement in three patients, and basal ganglia involvement in two patients. At the 3-month follow-up, all patients had a poor outcome. At 1 year, one patient had a complete recovery; one had a partial recovery; and two were

Embouchure dystonia--Portrait of a task-specific cranial dystonia.

PubMed

Frucht, Steven J

2009-09-15

Focal task-specific dystonia (FTSD) is an unusual disorder of motor control, which typically affects the hand but may also involve the face, jaw, and tongue. We report 89 musicians with dystonia of the embouchure (ED), the muscles of the lower face, jaw, and tongue used to control the flow of air into the mouthpiece of a woodwind or brass instrument. Symptoms of ED began at an average age of 36, were typically painless and only rarely were preceded by trauma. Specific musical techniques commonly triggered dystonia, often in one instrumental register. Task-specific embouchure tremor and lip-pulling ED phenotypes were common among high-register brass players (trumpet and French horn), whereas lip-locking occurred exclusively in low-register brass players (trombone and tuba). Jaw and tongue ED phenotypes occurred predominantly in woodwind players, and once present, frequently spread to speaking or eating. Six percent of all ED patients had coincident writer's cramp, suggesting a possible genetic predisposition to develop dystonia. We assessed two-point sensory discrimination in the upper lip, lower lip, and hand in ED patients, normal musicians, and nonmusician age-matched controls--there were no differences between groups. Once present, symptoms of ED did not remit and often disrupted careers and livelihoods. Better treatments are urgently needed for this unusual disorder of oral motor control.

Age-related cutoffs for cervical movement behaviour to distinguish chronic idiopathic neck pain patients from unimpaired subjects.

PubMed

Niederer, Daniel; Vogt, Lutz; Wilke, Jan; Rickert, Marcus; Banzer, Winfried

2015-03-01

The present study aims to develop age-dependent cutoff values in a quasi-experimental, cross-sectional diagnostic test study. One hundred and twenty (120) asymptomatic subjects (n = 100, 36♀, 18 75 years, for normative values; n = 20, 23-75 years, 15♀, for selectivity analyses) and 20 patients suffering from idiopathic neck pain (selectivity analyses, 22-71 years, 15♀) were included. Subjects performed five repetitive maximal cervical flexion/extension movements in an upright sitting position. Cervical kinematic characteristics (maximal range of motion (ROM), coefficient of variation (CV) and mean conjunct movements in rotation and flexion (CM)) were calculated from raw 3D ultrasonic data. Regression analyses were conducted to reveal associations between kinematic characteristics and age and gender and thus to determine normative values for healthy subjects. Age explains 53 % of the variance in ROM (decrease 10.2° per decade), 13 % in CV (increase 0.003 per decade) and 9 % in CM (increase 0.57° per decade). Receivers operating characteristic (ROC) analyses were conducted for differences between individual values of the kinematic characteristics and normative values to optimise cutoff values for distinguishing patients from unimpaired subjects (20 patients and 20 healthy). Cutoff values distinguished asymptomatic subjects' and chronic nonspecific neck patient's movement characteristics with sufficient quality (sensitivity 70-80 %, specificity 65-70 %). By including such classifications, the present findings expand actual research stating an age-related decrease in kinematic behaviour only using categorising span widths across decades. Future study is warranted to reveal our results' potential applicability for intervention onset decision making for idiopathic neck pain patients.

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

Dystonia

MedlinePlus

... advocacy groups, as well as private sector pharmaceutical companies. This extensive cooperation will greatly facilitate research because there are many types of dystonia, often seen by different subspecialists, and ...

A case of Parkinson's disease following dystonia.

PubMed

Yasuda, Chiharu; Takei, Takanobu; Uozumi, Takenori; Toyota, Tomoko; Yuhi, Tomoaki; Adachi, Hiroaki

2016-09-29

Parkinsonism and dystonia are both disorders of the extrapyramidal motor system, and some patients exhibit a complex of the two symptoms. Although several reports have referred to the coexistence of these disorders as parkinsonian disorders with dystonia, in the majority of cases, dystonia appeared after parkinsonism. DAT-scan is useful for the early diagnosis of Parkinson's disease (PD) and other types of parkinsonism such as dementia with Lewy bodies. This case report describes a 67-year old woman diagnosed with axial dystonia without parkinsonism 6 years previously, which had worsened despite treatment with Botulinum toxin injections, and hindered the patient's gait. The patient visited the hospital because of gait disturbances and DAT-scan showed a levodopa transducer decrease in the putamen. A few weeks later, she was re-admitted to hospital and exhibited Parkinsonism. Levodopa improved the gait disturbances but axial dystonia was unchanged, and a clinical diagnosis of PD was made. In the authors' opinion, this was a rare case of parkinsonian disorders with dystonia, characterized by the development of PD after dystonia. DAT-scan may be helpful for the diagnosis of patients with parkinsonian disorders with dystonia.

Dystonia: Related and Differential Disorders

MedlinePlus

... respond, too. What is the difference between a Parkinson's disease patient with dystonia and a dystonia patient with Parkinson's symptoms? Parkinson's disease is a neurological movement disorder with a wide ...

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

Dystonias

MedlinePlus

... or walking some distance—or a worsening in handwriting after writing several lines. In other instances, the ... and sometimes the forearm, and only occurs during handwriting. Similar focal dystonias have also been called typist's ...

Dystonia: Emotional and Mental Health

MedlinePlus

... Support Frequently Asked Questions Faces of Dystonia Emotional & Mental Health Although dystonia is a movement disorder that impacts ... emotion as well as muscle movement. For years, mental health professionals have recognized that coping with a chronic ...

Recent Developments in Dystonia

PubMed Central

Jinnah, H. A.; Teller, Jan K.; Galpern, Wendy R.

2015-01-01

Purpose of review The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these disorders, focusing mainly on advances with direct clinical relevance from the past two years. Recent findings The dystonias are generally defined by their clinical characteristics, rather than by their underlying genetic or neuropathological defects. The many varied clinical manifestations and causes contribute to the fact that they are one of the most poorly recognized of all movement disorders. A series of recent publications has addressed these issues offering a revised definition and more logical means for classifying the many subtypes. Our understanding of the genetic and neurobiological mechanisms responsible for different types of dystonias also has grown rapidly, creating new opportunities and challenges for diagnosis and identifying increasing numbers of rare subtypes for which specific treatments are available. Summary Recent advances in describing the clinical phenotypes and determining associated genotypes have pointed to the need for new strategies for diagnosis, classification and treatment of the dystonias. PMID:26110799

Multiple idiopathic external apical root resorption: report of four cases.

PubMed

Cholia, S S; Wilson, P H R; Makdissi, J

2005-07-01

Multiple idiopathic external root resorption is an unusual condition that may present in a cervical or an apical form. In this article, we review the published literature relating to multiple idiopathic external apical root resorption and present four clinical cases. We consider the aetiology of this condition and discuss the various treatment options.

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

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.

[Bilateral Pallidotomy for Tardive Dystonia:A Case Report].

PubMed

Kohara, Kotaro; Taira, Takaomi; Horisawa, Shiro; Hanada, Tomoko; Kawamata, Takakazu

2017-11-01

Tardive dystonia is a movement disorder related to the use of dopamine-receptor-blocking drugs. Several reports have shown that deep brain stimulation of the globus pallidus internus(GPi-DBS)is effective in treating tardive dystonia. However, a few reports demonstrated the efficacy of ablation of the GPi(pallidotomy). We herein report a case of tardive dystonia successfully treated with bilateral pallidotomy. A 32-year-old man developed severe tardive dystonia 10 years after the chronic use of antipsychotic drugs. Withdrawal of the drugs and botulinum toxin injections were ineffective. The patient underwent bilateral pallidotomy for tardive dystonia because of rejection of the implanted DBS devices. Significant improvement was observed, with a 95% decrease in the Burke-Fahn-Marsden Dystonia Rating Scale(BFMDRS)movement score, and no severe adverse events occurred. Symptomatic relief persisted for nine months. Pallidotomy is a feasible and efficacious procedure for tardive dystonia treatment without the use of hardware implantations.

Finger muscle control in children with dystonia.

PubMed

Young, Scott J; van Doornik, Johan; Sanger, Terence D

2011-06-01

Childhood dystonia is a disorder that involves inappropriate muscle activation during attempts at voluntary movement. Few studies have investigated the muscle activity associated with dystonia in children, and none have done so in the hands. In this study, we measured surface electromyographic activity in four intrinsic hand muscles while participants attempted to perform an isometric tracking task using one of the muscles. Children with dystonia had greater tracking error with the task-related muscle and greater overflow to non-task muscles. Both tracking error and overflow correlated with the Barry-Albright Dystonia scale of the respective upper limb. Overflow also decreased when participants received visual feedback of non-task muscle activity. We conclude that two of the motor deficits in childhood dystonia--motor overflow and difficulties in actively controlling muscles--can be seen in the surface electromyographic activity of individual muscles during an isometric task. As expected from results in adults, overflow is an important feature of childhood dystonia. However, overflow may be at least partially dependent on an individual's level of awareness of their muscle activity. Most importantly, poor single-muscle tracking shows that children with dystonia have deficits of individual muscle control in addition to overflow or co-contraction. These results provide the first quantitative measures of the muscle activity associated with hand dystonia in children, and they suggest possible directions for control of dystonic symptoms. Copyright © 2011 Movement Disorder Society.

Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

PubMed Central

Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

2015-01-01

Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

Research Priorities in Limb and Task-Specific Dystonias.

PubMed

Pirio Richardson, Sarah; Altenmüller, Eckart; Alter, Katharine; Alterman, Ron L; Chen, Robert; Frucht, Steven; Furuya, Shinichi; Jankovic, Joseph; Jinnah, H A; Kimberley, Teresa J; Lungu, Codrin; Perlmutter, Joel S; Prudente, Cecília N; Hallett, Mark

2017-01-01

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer's cramp, runner's dystonia, or musician's dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of

Research Priorities in Limb and Task-Specific Dystonias

PubMed Central

Pirio Richardson, Sarah; Altenmüller, Eckart; Alter, Katharine; Alterman, Ron L.; Chen, Robert; Frucht, Steven; Furuya, Shinichi; Jankovic, Joseph; Jinnah, H. A.; Kimberley, Teresa J.; Lungu, Codrin; Perlmutter, Joel S.; Prudente, Cecília N.; Hallett, Mark

2017-01-01

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer’s cramp, runner’s dystonia, or musician’s dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of

An unusual cause of cervical kyphosis.

PubMed

Raj, Mamtha S; Schwab, Joseph H

2017-02-01

Acute fixed cervical kyphosis may be a rare presentation of conversion disorder, psychogenic dystonia, and potentially as a side effect from typical antipsychotic drugs. Haldol has been associated with acute dystonic reactions. In some cases, rigid deformities ensue. We are reporting a case of a fixed cervical kyphosis after the use of Haldol. To present a case of a potential acute dystonic reaction temporally associated with Haldol ingestion leading to fixed cervical kyphosis. This is a case report. A patient diagnosed with bipolar disorder presented to the emergency room several times with severe neck pain and stiffness. The neck appeared fixed in flexion with extensive osteophyte formation over a 3-month period. The patient's condition was resolved by a posterior-anterior-posterior surgical approach. It corrected the patient's cervical curvature from 88° to 5°. Acute dystonic reactions have the potential to apply enough pressure on bone to cause rapid osteophyte formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Strategies for treatment of dystonia.

PubMed

Dressler, Dirk; Altenmueller, Eckart; Bhidayasiri, Roongroj; Bohlega, Saeed; Chana, Pedro; Chung, Tae Mo; Frucht, Steven; Garcia-Ruiz, Pedro J; Kaelin, Alain; Kaji, Ryuji; Kanovsky, Petr; Laskawi, Rainer; Micheli, Federico; Orlova, Olga; Relja, Maja; Rosales, Raymond; Slawek, Jaroslaw; Timerbaeva, Sofia; Warner, Thomas T; Saberi, Fereshte Adib

2016-03-01

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

Continuation of Long-Term Care for Cervical Dystonia at an Academic Movement Disorders Clinic

PubMed Central

Gill, Chandler E.; Manus, Neil D.; Pelster, Michael W.; Cook, Jason A.; Title, Wallace; Molinari, Anna L.; Charles, David

2013-01-01

Patients with cervical dystonia (CD) receive much of their care at university based hospital outpatient clinics. This study aimed to describe the clinical characteristics and treatment experiences of patients who continued care at our university based movement disorders clinic, and to document the reasons for which a subset discontinued care. Seventy patients (77% female) were recruited from all patients at the clinic (n = 323). Most (93%) were treated with botulinum neurotoxin (BoNT) injection, and onabotulinumtoxinA was initially used in 97%. The average dose of onabotulinumtoxinA was 270.4 U (range 50–500) and the median number of injections was 14 (range: 1–39). Twenty one patients later received at least one cycle of rimabotulinumtoxinB (33%); of those, 10 switched back to onabotulinumtoxinA (48%). The initial rimabotulinumtoxinB dose averaged 11,996 units (range: 3000–25,000 over 1–18 injections). Twenty one patients (30%) discontinued care. Reasons cited included suboptimal response to BoNT therapy (62%), excessive cost (24%), excessive travel burden (10%), and side effects of BoNT therapy (10%). Most patients (76%) did not seek further care after leaving the clinic. Patients who terminated care received fewer treatment cycles (5.5 vs. 13.0, p = 0.020). There were no other identifiable differences between groups in gender, age, disease characteristics, toxin dose, or toxin formulation. These results indicate that a significant number of CD patients discontinue care due to addressable barriers to access, including cost and travel burden, and that when leaving specialty care, patients often discontinue treatment altogether. These data highlight the need for new initiatives to reduce out-of-pocket costs, as well as training for community physicians on neurotoxin injection in order to lessen the travel burden patients must accept in order to receive standard-of-care treatments. PMID:23612751

Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial.

PubMed

Volkmann, Jens; Wolters, Alexander; Kupsch, Andreas; Müller, Jörg; Kühn, Andrea A; Schneider, Gerd-Helge; Poewe, Werner; Hering, Sascha; Eisner, Wilhelm; Müller, Jan-Uwe; Deuschl, Günther; Pinsker, Marcus O; Skogseid, Inger-Marie; Roeste, Geir Ketil; Krause, Martin; Tronnier, Volker; Schnitzler, Alfons; Voges, Jürgen; Nikkhah, Guido; Vesper, Jan; Classen, Joseph; Naumann, Markus; Benecke, Reiner

2012-12-01

after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia. Medtronic. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of subthalamic nucleus deep brain stimulation on dual-task cognitive and motor performance in isolated dystonia

PubMed Central

Mills, Kelly A; Markun, Leslie C; Luciano, Marta San; Rizk, Rami; Allen, I Elaine; Racine, Caroline A; Starr, Philip A; Alberts, Jay L; Ostrem, Jill L

2015-01-01

Objective Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor complications of Parkinson's disease (PD) but may worsen specific cognitive functions. The effect of STN DBS on cognitive function in dystonia patients is less clear. Previous reports indicate that bilateral STN stimulation in patients with PD amplifies the decrement in cognitive-motor dual-task performance seen when moving from a single-task to dual-task paradigm. We aimed to determine if the effect of bilateral STN DBS on dual-task performance in isolated patients with dystonia, who have less cognitive impairment and no dementia, is similar to that seen in PD. Methods Eight isolated predominantly cervical patients with dystonia treated with bilateral STN DBS, with average dystonia duration of 10.5 years and Montreal Cognitive Assessment score of 26.5, completed working memory (n-back) and motor (forced-maintenance) tests under single-task and dual-task conditions while on and off DBS. Results A multivariate, repeated-measures analysis of variance showed no effect of stimulation status (On vs Off) on working memory (F=0.75, p=0.39) or motor function (F=0.22, p=0.69) when performed under single-task conditions, though as working memory task difficulty increased, stimulation disrupted the accuracy of force-tracking. There was a very small worsening in working memory performance (F=9.14, p=0.019) when moving from single-task to dual-tasks when using the ‘dual-task loss’ analysis. Conclusions This study suggests the effect of STN DBS on working memory and attention may be much less consequential in patients with dystonia than has been reported in PD. PMID:25012202

Secondary Dystonia-Clinical Clues and Syndromic Associations

PubMed Central

Schneider, Susanne A; Bhatia, Kailash P

2009-01-01

Background: Dystonia is a hyperkinetic movement disorder defined by involuntary sustained muscle spasms and unusual postures. Etiologically, dystonic syndromes can be broadly divided into primary and secondary forms, dystonia-plus syndromes and heredodegenerative forms. In particular, diagnosis of secondary dystonic syndromes can be challenging in view of the variety of causes. Purpose: The purpose of this article is to highlight some clinical clues and syndromic associations as well as investigational findings which may be helpful in the approach to a patient with suspected secondary dystonia. Methods: We outline characteristic clinical and neuroimaging findings which may be directive in the diagnostic process of dystonia patients and facilitate making the correct diagnosis, thus allowing initiating the best treatment. Results: Secondary causes of dystonia include, among others, strategic brain lesions of various origins, metabolic disease, neurodegenerative conditions, and previous exposure to drugs or toxins. Presence of clinical signs including prominent oromandibular involvement, eye movement disorders, retinitis pigmentosa, deafness, peripheral neuropathy, parkinsonism or progressive dementia should alert the clinician to consider a secondary cause. Strategic lesions within the basal ganglia, but also within the brainstem, cerebellum or cortical areas may underlie dystonia and should thus be excluded. Conclusions: When thorough clinical examination reveals features atypical of primary dystonia, syndromic associations may help the clinician to narrow down the list of differential diagnosis. Directive investigations like neuroimaging may confirm the clinical suspicion. PMID:24868358

Finger Muscle Control in Children with Dystonia

PubMed Central

Young, Scott J.; van Doornik, Johan; Sanger, Terence D.

2010-01-01

Childhood dystonia is a disorder that involves inappropriate muscle activation during attempts at voluntary movement. Few studies have investigated the muscle activity associated with dystonia in children, and none have done so in the hands. In this study, we measured surface electromyographic activity in four intrinsic hand muscles while participants attempted to perform an isometric tracking task using one of the muscles. Children with dystonia had greater tracking error with the task-related muscle and greater overflow to non-task muscles. Both tracking error and overflow correlated with the Barry-Albright Dystonia scale of the respective upper limb. Overflow also decreased when participants received visual feedback of non-task muscle activity. We conclude that two of the motor deficits in childhood dystonia—motor overflow and difficulties in actively controlling muscles—can be seen in the surface electromyographic activity of individual muscles during an isometric task. As expected from results in adults, overflow is an important feature of childhood dystonia. However, overflow may be at least partially dependent on an individual’s level of awareness of their muscle activity. Most importantly, poor single-muscle tracking shows that children with dystonia have deficits of individual muscle control in addition to overflow or co-contraction. These results provide the first quantitative measures of the muscle activity associated with hand dystonia in children, and they suggest possible directions for control of dystonic symptoms. PMID:21449015

kinesiotaping reduces pain and modulates sensory function in patients with focal dystonia: a randomized crossover pilot study.

PubMed

Pelosin, Elisa; Avanzino, Laura; Marchese, Roberta; Stramesi, Paola; Bilanci, Martina; Trompetto, Carlo; Abbruzzese, Giovanni

2013-10-01

Pain is one of the most common and disabling "nonmotor" symptoms in patients with dystonia. No recent study evaluated the pharmacological or physical therapy approaches to specifically treat dystonic pain symptoms. To evaluate the effectiveness of KinesioTaping in patients with cervical dystonia (CD) and focal hand dystonia (FHD) on self-reported pain (primary objective) and on sensory functions (secondary objective). Twenty-five dystonic patients (14 with CD and 11 FHD) entered a randomized crossover pilot study. The patients were randomized to 14-day treatment with KinesioTaping or ShamTaping over neck (in CD) or forearm muscles (in FHD), and after a 30-day washout period, they received the other treatment. The were 3 visual analog scales (VASs) for usual pain, worst pain, and pain relief. Disease severity changes were evaluated by means of the Toronto Western Spasmodic Torticollis Rating Scale (CD) and the Writer's Cramp Rating Scale (FHD). Furthermore, to investigate possible KinesioTaping-induced effects on sensory functions, we evaluated the somatosensory temporal discrimination threshold. Treatment with KinesioTape induced a decrease in the subjective sensation of pain and a modification in the ability of sensory discrimination, whereas ShamTaping had no effect. A significant, positive correlation was found in both groups of patients between the improvement in the subjective sensation of pain and the reduction of somatosensory temporal discrimination threshold values induced by KinesioTaping. These preliminary results suggest that KinesioTaping may be useful in treating pain in patients with dystonia.

Multilingual website and cyberconsultations for oromandibular dystonia

PubMed Central

Yoshida, Kazuya

2018-01-01

Oromandibular dystonia is a focal dystonia that manifests as involuntary masticatory and/or tongue muscle contractions. This movement disorder is frequently misdiagnosed as a temporomandibular disorder. Hence, it would be useful to establish a method that makes it possible for patients with the condition to find appropriate medical institutions by themselves. The author produced a website Involuntary movements of the stomatognathic region (https://sites. google.com/site/oromandibulardystoniaenglish/) for patients with oromandibular dystonia, which is available in twenty languages. It has been viewed more than 1,000,000 times by individuals from all over the world. The visitors to the site have completed questionnaires and/or sent images or videos of their involuntary movements over the internet. Cyberconsultations (remote diagnosis) were also performed via Skype™. Approximately 1000 patients with involuntary stomatognathic movements visited our department. Only 12.5% of the patients had previously been diagnosed with or were suspected to have dystonia. The findings of this study suggest that the multilingual website has contributed to increasing awareness of oromandibular dystonia and that the provision of basic telemedicine via the internet can aid the diagnosis and treatment of oromandibular dystonia. PMID:29844890

Multilingual website and cyberconsultations for oromandibular dystonia.

PubMed

Yoshida, Kazuya

2018-03-30

Oromandibular dystonia is a focal dystonia that manifests as involuntary masticatory and/or tongue muscle contractions. This movement disorder is frequently misdiagnosed as a temporomandibular disorder. Hence, it would be useful to establish a method that makes it possible for patients with the condition to find appropriate medical institutions by themselves. The author produced a website Involuntary movements of the stomatognathic region (https://sites. google.com/site/oromandibulardystoniaenglish/) for patients with oromandibular dystonia, which is available in twenty languages. It has been viewed more than 1,000,000 times by individuals from all over the world. The visitors to the site have completed questionnaires and/or sent images or videos of their involuntary movements over the internet. Cyberconsultations (remote diagnosis) were also performed via Skype ™ . Approximately 1000 patients with involuntary stomatognathic movements visited our department. Only 12.5% of the patients had previously been diagnosed with or were suspected to have dystonia. The findings of this study suggest that the multilingual website has contributed to increasing awareness of oromandibular dystonia and that the provision of basic telemedicine via the internet can aid the diagnosis and treatment of oromandibular dystonia.

ANIMAL MODELS OF DYSTONIA: LESSONS FROM A MUTANT RAT

PubMed Central

LeDoux, Mark S.

2010-01-01

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. PMID:21081162

Phenomenology and classification of dystonia: a consensus update.

PubMed

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

2013-06-15

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 3 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 2 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. © 2013 Movement Disorder Society. © 2013 Movement Disorder Society.

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

Effect of subthalamic nucleus deep brain stimulation on dual-task cognitive and motor performance in isolated dystonia.

PubMed

Mills, Kelly A; Markun, Leslie C; San Luciano, Marta; Rizk, Rami; Allen, I Elaine; Racine, Caroline A; Starr, Philip A; Alberts, Jay L; Ostrem, Jill L

2015-04-01

Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor complications of Parkinson's disease (PD) but may worsen specific cognitive functions. The effect of STN DBS on cognitive function in dystonia patients is less clear. Previous reports indicate that bilateral STN stimulation in patients with PD amplifies the decrement in cognitive-motor dual-task performance seen when moving from a single-task to dual-task paradigm. We aimed to determine if the effect of bilateral STN DBS on dual-task performance in isolated patients with dystonia, who have less cognitive impairment and no dementia, is similar to that seen in PD. Eight isolated predominantly cervical patients with dystonia treated with bilateral STN DBS, with average dystonia duration of 10.5 years and Montreal Cognitive Assessment score of 26.5, completed working memory (n-back) and motor (forced-maintenance) tests under single-task and dual-task conditions while on and off DBS. A multivariate, repeated-measures analysis of variance showed no effect of stimulation status (On vs Off) on working memory (F=0.75, p=0.39) or motor function (F=0.22, p=0.69) when performed under single-task conditions, though as working memory task difficulty increased, stimulation disrupted the accuracy of force-tracking. There was a very small worsening in working memory performance (F=9.14, p=0.019) when moving from single-task to dual-tasks when using the 'dual-task loss' analysis. This study suggests the effect of STN DBS on working memory and attention may be much less consequential in patients with dystonia than has been reported in PD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia

PubMed Central

Fuertinger, Stefan

2017-01-01

Isolated focal dystonia is a debilitating movement disorder of unknown pathophysiology. Early studies in focal dystonias have pointed to segregated changes in brain activity and connectivity. Only recently has the notion that dystonia pathophysiology may lie in abnormalities of large-scale brain networks appeared in the literature. Here, we outline a novel concept of functional connectome-wide alterations that are linked to dystonia phenotype and genotype. Using a neural community detection strategy and graph theoretical analysis of functional MRI data in human patients with the laryngeal form of dystonia (LD) and healthy controls (both males and females), we identified an abnormally widespread hub formation in LD, which particularly affected the primary sensorimotor and parietal cortices and thalamus. Left thalamic regions formed a delineated functional community that highlighted differences in network topology between LD patients with and without family history of dystonia. Conversely, marked differences in the topological organization of parietal regions were found between phenotypically different forms of LD. The interface between sporadic genotype and adductor phenotype of LD yielded four functional communities that were primarily governed by intramodular hub regions. Conversely, the interface between familial genotype and abductor phenotype was associated with numerous long-range hub nodes and an abnormal integration of left thalamus and basal ganglia. Our findings provide the first comprehensive atlas of functional topology across different phenotypes and genotypes of focal dystonia. As such, this study constitutes an important step toward defining dystonia as a large-scale network disorder, understanding its causative pathophysiology, and identifying disorder-specific markers. SIGNIFICANCE STATEMENT The architecture of the functional connectome in focal dystonia was analyzed in a large population of patients with laryngeal dystonia. Breaking with the

Clinical and MRI outcome of cervical spine lesions in children with juvenile idiopathic arthritis treated with anti-TNFα drugs early in disease course.

PubMed

Ključevšek, Damjana; Emeršič, Nina; Toplak, Nataša; Avčin, Tadej

2017-05-15

The purpose of the study was to evaluate the clinical and magnetic resonance imaging (MRI) outcome of cervical spine arthritis in children with juvenile idiopathic arthritis (JIA), who received anti-TNFα early in the course of cervical spine arthritis. Medical charts and imaging of JIA patients with cervical spine involvement were reviewed in this retrospective study. Data, including age at disease onset, JIA type, disease activity, treatment and clinical outcome were collected. Initial and followup MRI examinations of cervical spine were performed according to the hospital protocol to evaluate the presence of inflammation and potential chronic/late changes. Fifteen JIA patients with MRI proved cervical spine inflammation (11 girls, 4 boys, median age 6.3y) were included in the study: 9 had polyarthritis, 3 extended oligoarthritis, 2 persistent oligoarthritis and 1 juvenile psoriatic arthritis. All children were initially treated with high-dose steroids and methotrexate. In addition, 11 patients were treated with anti-TNFα drug within 3 months, and 3 patients within 7 months of cervical spine involvement confirmed by MRI. Mean observation time was 2.9y, mean duration of anti-TNFα treatment was 2.2y. Last MRI showed no active inflammation in 12/15 children, allowing to stop biological treatment in 3 patients, and in 3/15 significant reduction of inflammation. Mild chronic changes were found on MRI in 3 children. Early treatment with anti-TNFα drugs resulted in significantly reduced inflammation or complete remission of cervical spine arthritis proved by MRI, and prevented the development of serious chronic/late changes. Repeated MRI examinations are suggested in the follow-up of JIA patients with cervical spine arthritis.

Cervical lordotic alignment following posterior spinal fusion for adolescent idiopathic scoliosis: reciprocal changes and risk factors for malalignment.

PubMed

Hayashi, Kazunori; Toyoda, Hiromitsu; Terai, Hidetomi; Suzuki, Akinobu; Hoshino, Masatoshi; Tamai, Koji; Ohyama, Shoichiro; Nakamura, Hiroaki

2017-04-01

OBJECTIVE Numerous reports have been published on the effectiveness and safety of correction of the coronal Cobb angle and thoracolumbar sagittal alignment in patients with adolescent idiopathic scoliosis (AIS). Suboptimal sagittal alignment, such as decreased thoracic kyphosis (TK), after corrective surgery, is a possible cause of lumbar or cervical spinal degeneration and junctional malalignment; however, few reports are available on reciprocal changes outside of the fused segments, such as the cervical lordotic angle (CLA). This study aimed to investigate the relationship between the perioperative CLA and other radiographic factors or clinical results in AIS, and to identify independent risk factors of postoperative cervical hyperkyphosis. METHODS A total of 51 AIS patients who underwent posterior spinal fusion with the placement of pedicle screw (PS) constructs at thoracic levels were included in the study. Clinical and radiographic follow-up of patients was conducted for a minimum of 2 years, and the postoperative course was evaluated. The authors measured and identified the changes in the CLA and other radiographic parameters using whole-spine radiography, with the patient in the standing position, performed immediately before surgery, 2 weeks after surgery, and 2 years after surgery. The postoperative cervical hyperkyphosis group included patients whose CLA at 2-year follow-up was smaller than -10°. The reciprocal changes of the CLA and other parameters were also investigated. Univariate and multivariate analyses were conducted to determine the associated risk factors for postoperative cervical hyperkyphosis. RESULTS This study comprised 48 females and 3 males (mean age 16.0 years). The mean follow-up period was 47 months (range 24-90 months). The main coronal thoracic curve was corrected from 54.6° to 16.4°, and the mean correction rate was 69.8% at 2 years. The CLA significantly increased from the mean preoperative measurement (-5.4° ± 14°) to the 2

Task-specific singing dystonia: vocal instability that technique cannot fix.

PubMed

Halstead, Lucinda A; McBroom, Deanna M; Bonilha, Heather Shaw

2015-01-01

Singer's dystonia is a rare variation of focal laryngeal dystonia presenting only during specific tasks in the singing voice. It is underdiagnosed since it is commonly attributed to technique problems including increased muscle tension, register transition, or wobble. Singer's dystonia differs from technique-related issues in that it is task- and/or pitch-specific, reproducible and occurs independently from the previously mentioned technical issues.This case series compares and contrasts profiles of four patients with singer's dystonia to increase our knowledge of this disorder. This retrospective case series includes a detailed case history, results of singing evaluations from individual voice teachers, review of singing voice samples by a singing voice specialist, evaluation by a laryngologist with endoscopy and laryngeal electromyography (LEMG), and spectral analysis of the voice samples by a speech-language pathologist. Results demonstrate the similarities and unique differences of individuals with singer's dystonia. Response to treatment and singing status varied from nearly complete relief of symptoms with botulinum toxin injections to minor relief of symptoms and discontinuation of singing. The following are the conclusions from this case series: (1) singer's dystonia exists as a separate entity from technique issues, (2) singer's dystonia is consistent with other focal task-specific dystonias found in musicians, (3) correctly diagnosing singer's dystonia allows singer's access to medical treatment of dystonia and an opportunity to modify their singing repertoire to continue singing with the voice they have, and (4) diagnosis of singer's dystonia requires careful sequential multidisciplinary evaluation to isolate the instability and confirm dystonia by LEMG and spectral voice analysis. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia.

PubMed

Kazerooni, Rashid; Broadhead, Christine

2015-02-15

A cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia (CD) was conducted. A cost-utility analysis of botulinum toxin type A products was conducted from the U.S. government perspective using a decision-analysis model with a one-year time horizon. Probabilities of the model were taken from several studies using the three botulinum type A products approved by the Food and Drug Administration for the treatment of CD: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). The main outcome measurement was successful treatment response with botulinum toxin type A, measured in quality-adjusted life years (QALYs). Response was defined as a patient who experienced improvement of CD symptoms without a severe adverse event. Probabilistic sensitivity analysis was conducted to test robustness of the base-case results. All three botulinum toxin type A agents were cost-effective at a willingness-to-pay threshold of $100,000 per QALY. Xeomin was the most cost-effective with a cost-effectiveness ratio of $27,548 per QALY. Xeomin was dominant over the alternative agents with equivalent efficacy outcomes and lower costs. Dysport had the second lowest cost-effectiveness ratio ($36,678), followed by Botox ($49,337). The probabilistic sensitivity analysis supported the results of the base-case analysis. Dysport was associated with the lowest wastage (2.2%), followed by Xeomin (10%) and Botox (22.9%). A cost-utility analysis found that Xeomin was the more cost-effective botulinum toxin type A product compared with Botox and Dysport for the treatment of CD. Wastage associated with the respective products may have a large effect on the cost-effectiveness of the agents. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache

PubMed Central

Simpson, David M.; Hallett, Mark; Ashman, Eric J.; Comella, Cynthia L.; Green, Mark W.; Gronseth, Gary S.; Armstrong, Melissa J.; Gloss, David; Potrebic, Sonja; Jankovic, Joseph; Karp, Barbara P.; Naumann, Markus; So, Yuen T.; Yablon, Stuart A.

2016-01-01

Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria. Results and recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B). PMID:27164716

Current and emerging strategies for treatment of childhood dystonia

PubMed Central

Bertucco, Matteo; Sanger, Terence D.

2014-01-01

Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al. 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies. PMID:25835254

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

[The preliminary study of the efficiency of using cervical vertebral maturation of growth level of female adolescent idiopathic scoliosis].

PubMed

Zhang, Di-qing; Chen, Zi-qiang; Li, Ming

2011-03-01

To investigate the reliability of cervical vertebral maturation (CVM) and to verify the possibility in the growth evaluation of female adolescent idiopathic scoliosis patients as a helpful supplementary to the Risser sign. Coronal and lateral full-length spine X-ray film and left hand-wrist radiographs of 77 female adolescent patients with idiopathic scoliosis were selected from January 2010 to October 2010. The interval period between lateral length of the spine and left hand-wrist radiographs did not exceed 3 months. The CVM was assessed by a method developed by Baccetti and co-workers, whereas hand-wrist maturation was assessed by Fishman's method. The results were analyzed by Spearman correlation with patients Risser sign, chronological age, and menarche period. There were strong correlations between CVM and SMI or Risser sign (r = 0.862 and 0.762, P < 0.01). While in 26 patients whose Risser sign were 0-I, the correlation between CVM and SMI was more pronounced (r = 0.761, P < 0.01), compared with the correlation between Risser sign and SMI (r = 0.641, P < 0.01). CVM is a valid indicator of skeletal growth evaluation and can be used as a helpful supplementary to Risser sign.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2015-11-01

cause abnormal twisting postures. DYT1 dystonia is an autosomal dominant disease with onset of dystonia during childhood . The most common early onset...SUPPLEMENTARY NOTES 14. ABSTRACT Dystonia is a debilitating neurological disease with no cure. In dystonia, there are involuntary muscle contractions that...is a debilitating neurological disease with no cure that is characterized by involuntary muscle contractions that cause abnormal twisting postures

Tremor associated with focal and segmental dystonia.

PubMed

Rudzińska, M; Krawczyk, M; Wójcik-Pędziwiatr, M; Szczudlik, A; Wasielewska, A

2013-01-01

Tremor occurs in 10-85% of patients with focal dystonia as so-called dystonic tremor or tremor associated with dystonia. The aim of this study was to assess the incidence and to characterize parameters of tremor accompanying focal and segmental dystonia. One hundred and twenty-three patients with diagnosis of focal and segmental dystonia together with 51 healthy controls were included in the study. For each participant, clinical examination and objective assessment (accelerometer, electromyography, graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor); with hands extended (postural tremor); during 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, type of tremor was determined as essential tremor type or enhanced physiological type. The incidence of tremor was significantly higher in dystonic patients as compared to controls (p = 0.0001). In clinical examination, tremor was found in 50% of dystonic patients, and in instrumental assessment in an additional 10-20%. The most frequent type of tremor was postural and kinetic tremor with 7 Hz frequency and featured essential tremor type. In the control group, tremor was detected in about 10% of subjects as 9-Hz postural tremor of enhanced physiological tremor type. No differences were found between patients with different types of dystonia with respect to the tremor incidence, type and parameters (frequency and severity). No correlations between tremor severity and dystonia severity were found either.

Musician's Dystonias

MedlinePlus

... Your Doctor Find a Doctor Finding Support Emotional & Mental Health When a Child is Diagnosed - Resources for Families Frequently Asked Questions Faces of Dystonia Get Involved Donate Stay Connected Special Events Calendar Promote Awareness Join a Support Group Become a Legislative Advocate ...

Botulinum toxin for treatment of the focal dystonia.

PubMed

Nakamura, Yusaku

2017-07-29

Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.

High rates of fatigue and sleep disturbances in dystonia.

PubMed

Wagle Shukla, A; Brown, R; Heese, K; Jones, J; Rodriguez, R L; Malaty, I M; Okun, M S; Kluger, B M

2016-10-01

Nonmotor symptoms in dystonia are increasingly recognized to impair the quality of life. The primary objective of this study was to determine the prevalence of fatigue and sleep disturbances in dystonia and to ascertain their impact on quality of life using standardized questionnaires. Dystonia patients presenting to a Botulinum toxin clinic were prospectively administered Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory (MFI), Epworth Sleepiness Scale (ESS) and Parkinson's Disease Sleep Scale (PDSS) for assessment of fatigue and sleep disturbances. Health-related Quality of life (HRQOL) was determined using MOS SF-36 scale and depressive symptoms were assessed using the Beck Depression Inventory II. Ninety-one patients with dystonia participated (66 women, 25 men, mean age 60 ± 17 years). Nine subjects had generalized dystonia, 18 segmental dystonia and 64 had focal dystonia. Moderate to severe fatigue was present in 43% of the cohort (FSS), excessive daytime somnolence in 27% (ESS) and other sleep disturbances in 26% (PDSS). FSS and MFI scores correlated significantly with HRQOL even when controlled for depression and sleep disturbances. Excessive daytime somnolence and nocturnal sleep disturbances correlated significantly with the HRQOL; however, these effects were not seen for daytime somnolence when controlled for depression. Psychometric testing found adequate reliabilities and convergent validities for both fatigue and sleep scales. Fatigue and sleep disturbances revealed high prevalence rates in this large, first of its dystonia study. They negatively impacted the quality of life even when controlled for comorbid depression.

[Severe generalized dystonia due to postradiotherapy cerebral calcifications].

PubMed

Chanson, J-B; Anheim, M; Lagha-Boukbiza, O; Fleury, M; Sellal, F; Tranchant, C

2008-05-01

Cerebral calcifications are a cause of secondary dystonia and may be an uncommon complication of radiotherapy. We report a very severe case of generalized dystonia due to postradiotherapy basal ganglia calcifications. An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia. Computed tomography showed bilateral basal ganglia calcifications, especially of the lenticular nuclei. Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia; the course was complicated by dystonic storms and decompensations resulting from the iatrogenous panhypopituitarism. This case illustrates a severe complication of cranial irradiation which should be considered in the indications of this treatment, especially for children.

Mental rotation and working memory in musicians' dystonia.

PubMed

Erro, Roberto; Hirschbichler, Stephanie T; Ricciardi, Lucia; Ryterska, Agata; Antelmi, Elena; Ganos, Christos; Cordivari, Carla; Tinazzi, Michele; Edwards, Mark J; Bhatia, Kailash P

2016-11-01

Mental rotation of body parts engages cortical-subcortical areas that are actually involved in the execution of a movement. Musicians' dystonia is a type of focal hand dystonia that is grouped together with writer's cramp under the rubric of "occupational dystonia", but it is unclear to which extent these two disorders share common pathophysiological mechanisms. Previous research has demonstrated patients with writer's cramp to have deficits in mental rotation of body parts. It is unknown whether patients with musicians' dystonia would display similar deficits, reinforcing the concept of shared pathophysiology. Eight patients with musicians' dystonia and eight healthy musicians matched for age, gender and musical education, performed a number of tasks assessing mental rotation of body parts and objects as well as verbal and spatial working memories abilities. There were no differences between patients and healthy musicians as to accuracy and reaction times in any of the tasks. Patients with musicians' dystonia have intact abilities in mentally rotating body parts, suggesting that this disorder relies on a highly selective disruption of movement planning and execution that manifests only upon playing a specific instrument. We further demonstrated that mental rotation of body parts and objects engages, at least partially, different cognitive networks. Copyright © 2016 Elsevier Inc. All rights reserved.

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. © 2013 International Parkinson and Movement Disorder Society.

Emerging Common Molecular Pathways for Primary Dystonia

PubMed Central

LeDoux, Mark S; Dauer, William T; Warner, Thomas T

2013-01-01

Background The dystonias are a group of hyperkinetic movement disorders whose principal cause is neuron dysfunction at one or more interconnected nodes of the motor system. The study of genes and proteins which cause familial dystonia provides critical information about the cellular pathways involved in this dysfunction which disrupts the motor pathways at systems level. In recent years study of the increasing number of DYT genes has implicated a number of cell functions which appear to be involved in the pathogenesis of dystonia. Methods Review of literature published in English language publications available on Pubmed relating to the genetics and cellular pathology of dystonia Results and Conclusions Numerous potential pathogenetic mechanisms have been identified. We describe those which fall into three emerging thematic groups: cell cycle and transcriptional regulation in the nucleus, endoplasmic reticulum and nuclear envelope function, and control of synaptic function. PMID:23893453

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.

Genetics Home Reference: X-linked dystonia-parkinsonism

MedlinePlus

... X-linked dystonia-parkinsonism syndrome (XDP): clinical and molecular genetic analysis. Brain Pathol. 1992 Oct;2(4):287-95. Review. Citation on PubMed Kaji R, Goto S, Tamiya G, Ando S, Makino S, Lee LV. Molecular dissection and anatomical basis of dystonia: X-linked ...

Pharyngeal Dystonia Mimicking Spasmodic Dysphonia.

PubMed

Shi, Lucy L; Simpson, C Blake; Hapner, Edie R; Jinnah, Hyder A; Johns, Michael M

2018-03-01

The aim of this study was to describe the presentation of pharyngeal dystonia (PD), which can occur as a focal or segmental dystonia with a primarily pharyngeal involvement for the discussion of treatment methods for controlling consequent symptoms. PD is specific to speech-related tasks. A retrospective medical record review of four patients with PD was performed. All patients were initially misdiagnosed with adductor spasmodic dysphonia and failed standard treatment with botulinum toxin type A (BTX). On laryngoscopy, the patients were discovered to have segmental or focal dystonia primarily affecting the pharyngeal musculature contributing to their vocal manifestations. A novel treatment regimen was designed, which involved directing BTX injections into the muscles involved in spasmodic valving at the oropharyngeal level. After titrating to an optimal dose, all patients showed improvement in their voice and speech with only mild dysphagia. These patients have maintained favorable results with repeat injections at 6- to 12-week intervals. PD, or dystonia with predominant pharyngeal involvement, is a rare entity with vocal manifestations that are not well described. It can be easily mistaken for spasmodic dysphonia. PD is specific to speech-related tasks. A novel method of BTX injections into the involved muscles results in a significant improvement in voice without significant dysphagia. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Inherited dystonias: clinical features and molecular pathways.

PubMed

Weisheit, Corinne E; Pappas, Samuel S; Dauer, William T

2018-01-01

Recent decades have witnessed dramatic increases in understanding of the genetics of dystonia - a movement disorder characterized by involuntary twisting and abnormal posture. Hampered by a lack of overt neuropathology, researchers are investigating isolated monogenic causes to pinpoint common molecular mechanisms in this heterogeneous disease. Evidence from imaging, cellular, and murine work implicates deficiencies in dopamine neurotransmission, transcriptional dysregulation, and selective vulnerability of distinct neuronal populations to disease mutations. Studies of genetic forms of dystonia are also illuminating the developmental dependence of disease symptoms that is typical of many forms of the disease. As understanding of monogenic forms of dystonia grows, a clearer picture will develop of the abnormal motor circuitry behind this relatively common phenomenology. This chapter focuses on the current data covering the etiology and epidemiology, clinical presentation, and pathogenesis of four monogenic forms of isolated dystonia: DYT-TOR1A, DYT-THAP1, DYT-GCH1, and DYT-GNAL. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased task-uncorrelated muscle activity in childhood dystonia.

PubMed

Lunardini, Francesca; Maggioni, Serena; Casellato, Claudia; Bertucco, Matteo; Pedrocchi, Alessandra L G; Sanger, Terence D

2015-06-12

Even if movement abnormalities in dystonia are obvious on observation-based examinations, objective measures to characterize dystonia and to gain insights into its pathophysiology are still strongly needed. We hypothesize that motor abnormalities in childhood dystonia are partially due to the inability to suppress involuntary variable muscle activity irrelevant to the achievement of the desired motor task, resulting in the superposition of unwanted motion components on the desired movement. However, it is difficult to separate and quantify appropriate and inappropriate motor signals combined in the same muscle, especially during movement. We devise an innovative and practical method to objectively measure movement abnormalities during the performance of a continuous figure-eight writing task in 7 children with dystonia and 9 age-matched healthy controls. During the execution of a continuous writing task, muscle contractions should occur at frequencies that match the frequencies of the writing outcome. We compare the power spectra of kinematic trajectories and electromyographic signals of 8 upper limb muscles to separate muscle activity with the same frequency content of the figure-eight movement (task-correlated) from activity occurring at frequencies extraneous to the task (task-uncorrelated). Children with dystonia present a greater magnitude of task-uncorrelated muscle components. The motor performance achieved by children with dystonia is characterized by an overall lower quality, with high spatial and temporal variability and an altered trade-off between speed and accuracy. Findings are consistent with the hypothesis that, in childhood dystonia, the ability to appropriately suppress variable and uncorrelated elements of movement is impaired. Here we present a proof-of-concept of a promising tool to characterize the phenomenology of movement disorders and to inform the design of neurorehabilitation therapies.

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

Dystonia: Physical Therapy

MedlinePlus

... straight. Soft, sunken chairs and sofas do not foster proper alignment and may affect the position of ... dystonia, one should consider modifying the task to foster posture and muscle control. A person with trouble ...

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32-34.

PubMed

Kramer, P L; de Leon, D; Ozelius, L; Risch, N; Bressman, S B; Brin, M F; Schuback, D E; Burke, R E; Kwiatkowski, D J; Shale, H

1990-02-01

Idiopathic torsion dystonia (ITD) is a neurological disorder characterized by sustained muscle contractions that appear as twisting movements of the limbs, trunk, and/or neck, which can progress to abnormal postures. Most familial forms of ITD follow autosomal dominant transmission with reduced penetrance. The frequency of ITD in the Ashkenazi Jewish population is five to ten times greater than that in other groups. Recently, a gene for ITD (DYT1) in a non-Jewish kindred was located on chromosome 9q32-34, with tight linkage to the gene encoding gelsolin (GSN). In the present study linkage analysis using DNA polymorphisms is used to locate a gene responsible for susceptibility to ITD in 12 Ashkenazi Jewish families. This dystonia gene exhibits close linkage with the gene encoding argininosuccinate synthetase (ASS), and appears by multipoint analysis to lie in the q32-34 region of chromosome 9, a region that also contains the loci for gelsolin and dopamine-beta-hydroxylase. The same gene may be responsible for ITD both in the non-Jewish kindred mentioned above and in the Ashkenazi Jewish families presented here. However, because there is substantial difference between the penetrance of the dominant allele in these two groups, two different mutations may be operating to produce susceptibility to this disease in the two groups.

Focal dystonia in musicians: phenomenology, pathophysiology, triggering factors, and treatment.

PubMed

Altenmüller, Eckart; Jabusch, Hans-Christian

2010-03-01

Musician's dystonia is a task-specific movement disorder that manifests itself as a loss of voluntary motor control in extensively trained movements. Approximately 1% of all professional musicians develop musician's dystonia, and in many cases, the disorder terminates the careers of affected musicians. The pathophysiology of the disorder is not completely clarified. Findings include 1) reduced inhibition at different levels of the central nervous system, 2) maladaptive plasticity and altered sensory perception, and 3) alterations in sensorimotor integration. Epidemiological data demonstrate a higher risk for those musicians who play instruments requiring maximal fine-motor skills. For instruments where workload differs across hands, focal dystonia appears more often in the more intensely used hand. In psychological studies, musicians with dystonia have more anxiety and perfectionist tendencies than healthy musicians. These findings strengthen the assumption that behavioral factors may be involved in the etiology of musician's dystonia. Preliminary findings also suggest a genetic contribution to focal task-specific dystonia with phenotypic variations including musician's dystonia. Treatment options include pharmacological interventions, such as trihexyphenidyl or botulinum toxin-A, as well as retraining programs and ergonomic changes in the instrument. Patient-tailored treatment strategies may significantly improve the situation of musicians with focal dystonia. Positive results after retraining and unmonitored technical exercises underline the benefit of an active involvement of patients in the treatment process. Only a minority of musicians, however, return to normal motor control using the currently available therapies.

Idiopathic paroxysmal kinesigenic dyskinesia in Malaysia, a multi-racial Southeast Asian country.

PubMed

Tai, Mei-Ling Sharon; Lim, Shen-Yang; Tan, Chong Tin

2010-08-01

Paroxysmal kinesigenic dyskinesia is a rare disorder, and there are few reports of Asian patients with this condition. We reviewed the clinical features of all patients with idiopathic paroxysmal kinesigenic dyskinesia (PKD) seen at a major neurological centre in Malaysia. The charts of 11 patients with idiopathic PKD seen between 1995 and 2008 were reviewed retrospectively. The male:female ratio was 9:2. Ten patients were of Chinese ethnicity, and one was Malay. Three patients (from two families) had a family history of PKD. The involuntary movement was dystonia in 73% of patients. In one patient, attacks were precipitated by vestibular stimulation. One patient had generalized epilepsy. Another patient who did not have epilepsy demonstrated epileptiform discharges. Only slightly over one-quarter of patients had a positive family history. Males, and people of Chinese ancestry, seem to be affected more frequently by PKD in certain Asian populations. Copyright 2010 Elsevier Ltd. All rights reserved.

Successful treatment of childhood onset symptomatic dystonia with levodopa.

PubMed Central

Fletcher, N A; Thompson, P D; Scadding, J W; Marsden, C D

1993-01-01

Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms. PMID:8350101

Sonographic alteration of lenticular nucleus in focal task-specific dystonia of musicians.

PubMed

Walter, Uwe; Buttkus, Franziska; Benecke, Reiner; Grossmann, Annette; Dressler, Dirk; Altenmüller, Eckart

2012-01-01

In distinct movement disorders, transcranial sonography detects alterations of deep brain structures with higher sensitivity than other neuroimaging methods. Lenticular nucleus hyperechogenicity on transcranial sonography, thought to be caused by increased local copper content, has been reported as a characteristic finding in primary spontaneous dystonia. Here, we wanted to find out whether deep brain structures are altered in task-specific dystonia. The frequency of sonographic brainstem and basal ganglia changes was studied in an investigator-blinded setting in 15 musicians with focal task-specific hand dystonia, 15 musicians without dystonia, and 15 age- and sex-matched nonmusicians without dystonia. Lenticular nucleus hyperechogenicity was found in 12 musicians with task-specific dystonia, but only in 3 nondystonic musicians (Fisher's exact test, p = 0.001) and 2 nonmusicians (p < 0.001). The degree of lenticular nucleus hyperechogenicity in affected musicians correlated with age, but not with duration of music practice or duration of dystonia. In 2 of 3 affected musicians with normal echogenic lenticular nucleus, substantia nigra hyperechogenicity was found. Our findings support the idea of a pathogenetic link between primary spontaneous and task-specific dystonia. Sonographic basal ganglia alteration might indicate a risk factor that in combination with extensive fine motor training promotes the manifestation of task-specific dystonia. Copyright © 2011 S. Karger AG, Basel.

The challenge of diagnosing focal hand dystonia in musicians.

PubMed

Rosset-Llobet, J; Candia, V; Fàbregas i Molas, S; Dolors Rosinés i Cubells, D; Pascual-Leone, A

2009-07-01

To most clinicians, medical problems in musicians, particularly those concerning focal hand dystonia, constitute an unfamiliar domain difficult to manage. The latter can importantly influence diagnostics and the course of treatment. The purpose of this study was to enlighten the issue and to identify possible problems in diagnosing musicians' cramp within the Spanish medical community. We used a brief questions' catalog and clinical histories of 665 musicians seen at our clinic for performing artists. We analyzed patients' diagnosis records in 87 cases of focal hand dystonia (13.1%). In so doing, we surveyed previous diagnoses and diverse treatments prescriptions prior to referral to our clinic. Referrals came primarily from orthopaedists and neurologists. The 52.9% arrived at our clinic without a diagnosis or a suspicion of suffering from focal dystonia. The most frequently attempted diagnoses other than musicians' dystonia included nerve compression, tendonitis and trigger fingers. Commonly prescribed treatments included rest, various surgical procedures, physiotherapy and oral anti-inflammatory medication. This data depicts the diagnostic challenges of medical professionals may encounter when confronted with musician's focal dystonia.

Rating scales for musician's dystonia

PubMed Central

Berque, Patrice; Jabusch, Hans-Christian; Altenmüller, Eckart; Frucht, Steven J.

2013-01-01

Musician's dystonia (MD) is a focal adult-onset dystonia most commonly involving the hand. It has much greater relative prevalence than non-musician’s focal hand dystonias, exhibits task specificity at the level of specific musical passages, and is a particularly difficult form of dystonia to treat. For most MD patients, the diagnosis confirms the end of their music performance careers. Research on treatments and pathophysiology is contingent upon measures of motor function abnormalities. In this review, we comprehensively survey the literature to identify the rating scales used in MD and the distribution of their use. We also summarize the extent to which the scales have been evaluated for their clinical utility, including reliability, validity, sensitivity, specificity to MD, and practicality for a clinical setting. Out of 135 publications, almost half (62) included no quantitative measures of motor function. The remaining 73 studies used a variety of choices from among 10 major rating scales. Most used subjective scales involving either patient or clinician ratings. Only 25% (18) of the studies used objective scales. None of the scales has been completely and rigorously evaluated for clinical utility. Whether studies involved treatments or pathophysiologic assays, there was a heterogeneous choice of rating scales used with no clear standard. As a result, the collective interpretive value of those studies is limited because the results are confounded by measurement effects. We suggest that the development and widespread adoption of a new clinically useful rating scale is critical for accelerating basic and clinical research in MD. PMID:23884039

Forms of Dystonia

MedlinePlus

... Your Doctor Find a Doctor Finding Support Emotional & Mental Health When a Child is Diagnosed - Resources for Families Frequently Asked Questions Faces of Dystonia Get Involved Donate Stay Connected Special Events Calendar Promote Awareness Join a Support Group Become a Legislative Advocate ...

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

The occurrence of dystonia in upper-limb multiple sclerosis tremor.

PubMed

Van der Walt, A; Buzzard, K; Sung, S; Spelman, T; Kolbe, S C; Marriott, M; Butzkueven, H; Evans, A

2015-12-01

The pathophysiology of multiple sclerosis (MS) tremor is uncertain with limited phenotypical studies available. To investigate whether dystonia contributes to MS tremor and its severity. MS patients (n = 54) with and without disabling uni- or bilateral upper limb tremor were recruited (39 limbs per group). We rated tremor severity, writing and Archimedes spiral drawing; cerebellar dysfunction (SARA score); the Global Dystonia Scale (GDS) for proximal and distal upper limbs, dystonic posturing, mirror movements, geste antagoniste, and writer's cramp. Geste antagoniste, mirror dystonia, and dystonic posturing were more frequent and severe (p < 0.001) and dystonia scores were correlated with tremor severity in tremor compared to non-tremor patients. A 1-unit increase in distal dystonia predicted a 0.52-Bain unit (95% confidence interval (CI) 0.08-0.97), p = 0.022) increase in tremor severity and a 1-unit (95% CI 0.48-1.6, p = 0.001) increase in drawing scores. A 1-unit increase in proximal dystonia predicted 0.93-Bain unit increase (95% CI 0.45-1.41, p < 0.001) in tremor severity and 1.5-units (95% CI 0.62-2.41, p = 0.002) increase in the drawing score. Cerebellar function in the tremor limb and tremor severity was correlated (p < 0.001). Upper limb dystonia is common in MS tremor suggesting that MS tremor pathophysiology involves cerebello-pallido-thalamo-cortical network dysfunction. © The Author(s), 2015.

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

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

The challenge of diagnosing focal hand dystonia in musicians

PubMed Central

Rosset-Llobet, J.; Candia, V.; Molas, S. Fàbregas i; Dolors Rosinés i Cubells, D.; Pascual-Leone, A.

2012-01-01

Background and purpose To most clinicians, medical problems in musicians, particularly those concerning focal hand dystonia, constitute an unfamiliar domain difficult to manage. The latter can importantly influence diagnostics and the course of treatment. The purpose of this study was to enlighten the issue and to identify possible problems in diagnosing musicians’ cramp within the Spanish medical community. Methods We used a brief questions’ catalog and clinical histories of 665 musicians seen at our clinic for performing artists. We analyzed patients’ diagnosis records in 87 cases of focal hand dystonia (13.1%). In so doing, we surveyed previous diagnoses and diverse treatments prescriptions prior to referral to our clinic. Results Referrals came primarily from orthopaedists and neurologists. The 52.9% arrived at our clinic without a diagnosis or a suspicion of suffering from focal dystonia. The most frequently attempted diagnoses other than musicians’ dystonia included nerve compression, tendonitis and trigger fingers. Commonly prescribed treatments included rest, various surgical procedures, physiotherapy and oral anti-inflammatory medication. Conclusions This data depicts the diagnostic challenges of medical professionals may encounter when confronted with musician’s focal dystonia. PMID:19473363

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

Electromyographic and Joint Kinematic Patterns in Runner's Dystonia.

PubMed

Ahmad, Omar F; Ghosh, Pritha; Stanley, Christopher; Karp, Barbara; Hallett, Mark; Lungu, Codrin; Alter, Katharine

2018-04-20

Runner’s dystonia (RD) is a task-specific focal dystonia of the lower limbs that occurs when running. In this retrospective case series, we present surface electromyography (EMG) and joint kinematic data from thirteen patients with RD who underwent instrumented gait analysis (IGA) at the Functional and Biomechanics Laboratory at the National Institutes of Health. Four cases of RD are described in greater detail to demonstrate the potential utility of EMG with kinematic studies to identify dystonic muscle groups in RD. In these cases, the methodology for muscle selection for botulinum toxin therapy and the therapeutic response is discussed. Lateral heel whip, a proposed novel presentation of lower-limb dystonia, is also described.

An fMRI study of musicians with focal dystonia during tapping tasks.

PubMed

Kadota, Hiroshi; Nakajima, Yasoichi; Miyazaki, Makoto; Sekiguchi, Hirofumi; Kohno, Yutaka; Amako, Masatoshi; Arino, Hiroshi; Nemoto, Koichi; Sakai, Naotaka

2010-07-01

Musician's dystonia is a type of task specific dystonia for which the pathophysiology is not clear. In this study, we performed functional magnetic resonance imaging to investigate the motor-related brain activity associated with musician's dystonia. We compared brain activities measured from subjects with focal hand dystonia and normal (control) musicians during right-hand, left-hand, and both-hands tapping tasks. We found activations in the thalamus and the basal ganglia during the tapping tasks in the control group but not in the dystonia group. For both groups, we detected significant activations in the contralateral sensorimotor areas, including the premotor area and cerebellum, during each tapping task. Moreover, direct comparison between the dystonia and control groups showed that the dystonia group had greater activity in the ipsilateral premotor area during the right-hand tapping task and less activity in the left cerebellum during the both-hands tapping task. Thus, the dystonic musicians showed irregular activation patterns in the motor-association system. We suggest that irregular neural activity patterns in dystonic subjects reflect dystonic neural malfunction and consequent compensatory activity to maintain appropriate voluntary movements.

Impaired eye blink classical conditioning distinguishes dystonic patients with and without tremor.

PubMed

Antelmi, E; Di Stasio, F; Rocchi, L; Erro, R; Liguori, R; Ganos, C; Brugger, F; Teo, J; Berardelli, A; Rothwell, J; Bhatia, K P

2016-10-01

Tremor is frequently associated with dystonia, but its pathophysiology is still unclear. Dysfunctions of cerebellar circuits are known to play a role in the pathophysiology of action-induced tremors, and cerebellar impairment has frequently been associated to dystonia. However, a link between dystonic tremor and cerebellar abnormalities has not been demonstrated so far. Twenty-five patients with idiopathic isolated cervical dystonia, with and without tremor, were enrolled. We studied the excitability of inhibitory circuits in the brainstem by measuring the R2 blink reflex recovery cycle (BRC) and implicit learning mediated by the cerebellum by means of eyeblink classical conditioning (EBCC). Results were compared with those obtained in a group of age-matched healthy subjects (HS). Statistical analysis did not disclose any significant clinical differences among dystonic patients with and without tremor. Patients with dystonia (regardless of the presence of tremor) showed decreased inhibition of R2 blink reflex by conditioning pulses compared with HS. Patients with dystonic tremor showed a decreased number of conditioned responses in the EBCC paradigm compared to HS and dystonic patients without tremor. The present data show that cerebellar impairment segregates with the presence of tremor in patients with dystonia, suggesting that the cerebellum might have a role in the occurrence of dystonic tremor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Limb Amputations in Fixed Dystonia: A Form of Body Integrity Identity Disorder?

PubMed Central

Edwards, Mark J; Alonso-Canovas, Araceli; Schrag, Arnette; Bloem, Bastiaan R; Thompson, Philip D; Bhatia, Kailash

2011-01-01

Fixed dystonia is a disabling disorder mainly affecting young women who develop fixed abnormal limb postures and pain after apparently minor peripheral injury. There is continued debate regarding its pathophysiology and management. We report 5 cases of fixed dystonia in patients who sought amputation of the affected limb. We place these cases in the context of previous reports of patients with healthy limbs and patients with chronic regional pain syndrome who have sought amputation. Our cases, combined with recent data regarding disorders of mental rotation in patients with fixed dystonia, as well as previous data regarding body integrity identity disorder and amputations sought by patients with chronic regional pain syndrome, raise the possibility that patients with fixed dystonia might have a deficit in body schema that predisposes them to developing fixed dystonia and drives some to seek amputation. The outcome of amputation in fixed dystonia is invariably unfavorable. © 2011 Movement Disorder Society PMID:21484872

Limb amputations in fixed dystonia: a form of body integrity identity disorder?

PubMed

Edwards, Mark J; Alonso-Canovas, Araceli; Schrag, Arnette; Bloem, Bastiaan R; Thompson, Philip D; Bhatia, Kailash

2011-07-01

Fixed dystonia is a disabling disorder mainly affecting young women who develop fixed abnormal limb postures and pain after apparently minor peripheral injury. There is continued debate regarding its pathophysiology and management. We report 5 cases of fixed dystonia in patients who sought amputation of the affected limb. We place these cases in the context of previous reports of patients with healthy limbs and patients with chronic regional pain syndrome who have sought amputation. Our cases, combined with recent data regarding disorders of mental rotation in patients with fixed dystonia, as well as previous data regarding body integrity identity disorder and amputations sought by patients with chronic regional pain syndrome, raise the possibility that patients with fixed dystonia might have a deficit in body schema that predisposes them to developing fixed dystonia and drives some to seek amputation. The outcome of amputation in fixed dystonia is invariably unfavorable. Copyright © 2011 Movement Disorder Society.

New onset of idiopathic bilateral ear tics in an adult.

PubMed

Agrawal, Amit; Shrestha, Rabin

2009-04-01

Tic disorders are commonly considered to be childhood syndromes. Newly presenting tic disorders during adulthood are uncommon and mostly described in relation to an acquired brain lesion or as incidental tics, particularly in context with other neurological or psychiatric diseases. Tic disorder involving the ears is extremely uncommon with only few studies in English literature. In the present case, we describe an adult patient with new-onset idiopathic tics disorder involving both ears, causing social embarrassment. In addition, our patient had recent onset of the tics without any childhood or family history of tic disorders. The single most important component of management is an accurate diagnosis. At the same time, tics should be differentiated from other movement disorders such as chorea, stereotypy, and dystonias.

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. (c) 2010 Movement Disorder Society.

Specific muscle EMG biofeedback for hand dystonia.

PubMed

Deepak, K K; Behari, M

1999-12-01

Currently available therapies have only limited success in patients having hand dystonia (writer's cramp). We employed specific muscle EMG biofeedback (audio feedback of the EMG from proximal large muscles of the limb that show abnormally high activity during writing) in 10 of 13 consecutive patients (age, 19-62 years; all males) with a duration of illness from 6 months to 8 years. In three patients, biofeedback was not applicable due to lack of abnormal EMG values. Nine patients showed dystonic posture during writing and had hypertrophy of one or more large muscles of the dominant hand. The remaining four patients showed either involvement of small muscles or muscle wasting. Ten patients were given four or more sessions of EMG audio biofeedback from the proximal large limb muscles, which showed maximum EMG activity. They also practiced writing daily with the relaxed limb for 5 to 10 min. Nine patients showed improvement from 37 to 93% in handwriting, alleviation of discomfort, and pain (assessed on a visual analogue scale). One patient did not show any improvement. Thus EMG biofeedback improved the clinical and electromyographic picture in those patients with hand dystonia who showed EMG overactivity of proximal limb muscles during writing. This specific type of EMG biofeedback appears to be a promising tool for hand dystonia and might also be applied to other types of dystonias.

Abnormal tactile temporal discrimination in psychogenic dystonia.

PubMed

Morgante, F; Tinazzi, M; Squintani, G; Martino, D; Defazio, G; Romito, L; Albanese, A; Di Matteo, A; Quartarone, A; Girlanda, P; Fiorio, M; Berardelli, A

2011-09-20

Neurophysiologic studies demonstrated that patients with primary torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar abnormalities in the motor system. In this study, we evaluated somatosensory function in Psy-D by testing temporal discrimination threshold (TDT), and compared the results with those obtained in patients with PTD. TDT of tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and 16 control subjects. The 2 groups of patients were matched for age, gender, disease duration, and distribution of dystonia. Tactile stimuli consisted of pairs of non-noxious electrical shocks delivered to the right or left hand at interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was defined as the value at which subjects recognized the 2 stimuli as asynchronous. TDT was higher in Psy-D and PTD compared to control subjects, for both the right and the left hand. In a subgroup of patients with unilateral dystonia (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected side in both groups of patients. Disease duration was not correlated to the increased TDT value. Our study suggests an impaired processing of somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a neurophysiological trait predisposing to develop a dystonic posture triggered by psychiatric and psychological factors.

[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.

Development of future indications for BOTOX.

PubMed

Brin, Mitchell F

2009-10-01

Since the late 1970s, local injections of BoNT have provided clinical benefit for patients with inappropriately contracting muscles with or without pain or sensory disturbance. Marketing authorization for some BoNTs, depending on country, include core indications of dystonia (blepharospasm and cervical dystonia), large muscle spastic disorders (not yet approved in the United States, e.g., adult post-stroke spasticity and equinus foot deformity), hyperhidrosis and aesthetic. Subsequent development has extended to selected conditions characterized by recurrent or chronic pain (migraine headache), and urologic indications (neurogenic/idiopathic overactive bladder; prostate hyperplasia), with multiple additional opportunities available. Portfolio management requires a careful individual opportunity assessment of scientific and technical aspects (basic science foundation, potential to treat unmet medical need, product-specific risk in specific populations, therapeutic margin/safety profile, and probability of successful registration pathway). This article describes ongoing development targets for BOTOX.

Dystonia Medical Research Foundation

MedlinePlus

... Your Doctor Find a Doctor Finding Support Emotional & Mental Health When a Child is Diagnosed - Resources for Families Frequently Asked Questions Faces of Dystonia Get Involved Donate Stay Connected Special Events Calendar Promote Awareness Join a Support Group Become a Legislative Advocate ...

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.

Electromyographic and Joint Kinematic Patterns in Runner’s Dystonia

PubMed Central

Ahmad, Omar F.; Ghosh, Pritha; Stanley, Christopher; Karp, Barbara; Hallett, Mark; Lungu, Codrin

2018-01-01

Runner’s dystonia (RD) is a task-specific focal dystonia of the lower limbs that occurs when running. In this retrospective case series, we present surface electromyography (EMG) and joint kinematic data from thirteen patients with RD who underwent instrumented gait analysis (IGA) at the Functional and Biomechanics Laboratory at the National Institutes of Health. Four cases of RD are described in greater detail to demonstrate the potential utility of EMG with kinematic studies to identify dystonic muscle groups in RD. In these cases, the methodology for muscle selection for botulinum toxin therapy and the therapeutic response is discussed. Lateral heel whip, a proposed novel presentation of lower-limb dystonia, is also described. PMID:29677101

Regaining motor control in musician's dystonia by restoring sensorimotor organization.

PubMed

Rosenkranz, Karin; Butler, Katherine; Williamon, Aaron; Rothwell, John C

2009-11-18

Professional musicians are an excellent model of long-term motor learning effects on structure and function of the sensorimotor system. However, intensive motor skill training has been associated with task-specific deficiency in hand motor control, which has a higher prevalence among musicians (musician's dystonia) than in the general population. Using a transcranial magnetic stimulation paradigm, we previously found an expanded spatial integration of proprioceptive input into the hand motor cortex [sensorimotor organization (SMO)] in healthy musicians. In musician's dystonia, however, this expansion was even larger. Whereas motor skills of musicians are likely to be supported by a spatially expanded SMO, we hypothesized that in musician's dystonia this might have developed too far and now disrupts rather than assists task-specific motor control. If so, motor control should be regained by reversing the excessive reorganization in musician's dystonia. Here, we test this hypothesis and show that a 15 min intervention with proprioceptive input (proprioceptive training) restored SMO in pianists with musician's dystonia to the pattern seen in healthy pianists. Crucially, task-specific motor control improved significantly and objectively as measured with a MIDI (musical instrument digital interface) piano, and the amount of behavioral improvement was significantly correlated to the degree of sensorimotor reorganization. In healthy pianists and nonmusicians, the SMO and motor performance remained essentially unchanged. These findings suggest that the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks are significantly linked and finely balanced. Proprioceptive training restored this balance in musician's dystonia to the behaviorally beneficial level of healthy musicians.

[Focal dystonia in musicians: Phenomenology and musical triggering factors].

PubMed

Aránguiz, R; Chana-Cuevas, P; Alburquerque, D; Curinao, X

2015-06-01

Dystonias are defined as a joint sustained and involuntary contraction of agonist and antagonist muscles, which can cause torsion, repetitive abnormal involuntary movements, and/or abnormal postures. One special group of dystonias are those known as occupational, which include dystonia disorders triggered by a repetitive motor activity associated with a specific professional activity or task. Musicians are a population particularly vulnerable to these types of dystonia, which are presented as a loss of coordination and voluntary motor control movements highly trained in musical interpretation. Our aim is to describe a clinical series of focal dystonias in musicians evaluated and treated in our centre. Data is presented on a clinical series of 12 musicians with occupational dystonia. Their history and phenomenology are described, as well as well as their outcome after therapy. Demographic details: Mean age 34.8 ± 11.8 years, 10 males (83.3%) and 2 females (16.7%). History of trauma in dystonic segment, 6 patients (50%); family history of neurological diseases in first-degree relatives, 6 patients (50%); occupational history according to music category, 8 patients (66.6%) were classical musicians and 4 patients (33.3%) were popular musicians. The dystonia syndrome was characterised by having a mean age of onset of 28.2 ± 11.3 years (range 18-57 years). The segment affected was the hand (91.7%) in 11 patients. Of all the musicians seen in the clinic, 9 of them (75%) received therapy. The majority of patients appeared to have triggering factors specific to musical execution and linked to the requirement of fine motor control. It should be mentioned that 50% of the musicians treated maintained their professional activity or position in the orchestra to which they belonged. The majority of our phenomenological findings are consistent with those reported in the current literature. However, it is worth mentioning the presence of triggering factors attributed to the

Cognitive function in children with primary dystonia before and after deep brain stimulation.

PubMed

Owen, Tamsin; Gimeno, Hortensia; Selway, Richard; Lin, Jean-Pierre

2015-01-01

Dystonia is characterised by involuntary movements (twisting, writhing and jerking) and postures. The effects of deep brain stimulation (DBS) surgery on the motor aspect of primary dystonias have been well reported, however, there is a paucity of research investigating its impact on cognitive function, particularly in childhood dystonia. We performed a follow-up of cognitive function in children with primary dystonia following DBS pallidal surgery. Cognitive function was measured in a cohort of 13 children with primary or primary plus dystonia who had undergone DBS surgery using a retrospective case series design. Baseline pre-DBS neuropsychological measures were compared to scores obtained at least one year following DBS. Cognitive function was assessed using standardised measures of intellectual ability and memory. All children demonstrated improvements with regard to dystonia reduction, as measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Overall, cognition remained stable following DBS in the majority of the cohort. Individual case analysis revealed improvements in some domains of cognitive function in eight members of the cohort and a deterioration of certain domains in four. Cognition largely remained stable in children with primary/primary plus dystonia following DBS surgery, although further research with a larger sample is necessary to explore this statistically. Notwithstanding the limitations of a small size, this preliminary data has potentially positive implications for the impact of DBS on cognitive functioning within a paediatric population. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Sporadic adult onset dystonia: sensory abnormalities as an endophenotype in unaffected relatives

PubMed Central

Walsh, Richard; O'Dwyer, John P; Sheikh, Ifthikar H; O'Riordan, Sean; Lynch, Tim; Hutchinson, Michael

2007-01-01

Background Most patients with adult onset primary torsion dystonia (AOPTD) have the sporadic form of the disease. They may however be the only manifesting family members of a poorly penetrant genetic disorder. Sensory changes, including structural abnormalities of the primary sensory cortex, are found in AOPTD. Spatial discrimination threshold (SDT), a measure of sensory cortical organisation, is abnormal in AOPTD and in unaffected relatives of patients with familial AOPTD. Our hypothesis was that abnormal SDTs might be found in unaffected relatives of patients with sporadic AOPTD. Methods SDTs were assessed at the index finger bilaterally by a grating orientation task. Normal age related SDTs were derived from 141 control subjects aged 20–64 years. SDTs were considered abnormal when greater than 2.5 SD above the control mean. In total, 105 of 171 (61%) eligible unaffected siblings and offspring of patients with cervical dystonia had SDT examined. Results Fourteen of 48 siblings (29%) and 10 of 57 (18%) offspring were found to have an abnormal SDT. Only five of the 20 patients examined had abnormal SDTs. In 11 of the 25 families, no abnormality was found in an unaffected relative. In the 14 families where at least one unaffected relative had an abnormal SDT, 14 of 37 siblings (38%) and 10 of 33 offspring (30%) had abnormal SDTs. Conclusion Sensory abnormalities found in unaffected relatives of patients with apparently sporadic AOPTD may be a surrogate marker for the carriage of an abnormal gene. PMID:17702779

Acute hemifacial dystonia possibly induced by clebopride.

PubMed

Bosco, Domenico; Plastino, Massimiliano; Marcello, Maria Giovanna; Mungari, Pasquale; Fava, Antonietta

2009-01-01

Dystonic reactions produce twisting and repetitive movements or abnormal posturing. Severe dystonic reactions have been shown to occur in concert with numerous medications. This report details the case of a patient who developed hemifacial dystonia as acute side reaction from administration of clebopride for dyspeptic prophylaxis. When the drug was immediately stopped, the dystonic posture disappeared completely within 2 weeks. The use of clebopride may be associated with not only a reversible or persistent parkinsonism syndrome but also hemifacial dystonia; therefore, attention must be drawn to this possible side effect.

Pathogenic variants in TUBB4A are not found in primary dystonia

PubMed Central

Vemula, Satya R.; Xiao, Jianfeng; Bastian, Robert W.; Momčilović, Dragana; Blitzer, Andrew

2014-01-01

Objective: To determine the contribution of TUBB4A, recently associated with DYT4 dystonia in a pedigree with “whispering dysphonia” from Norfolk, United Kingdom, to the etiopathogenesis of primary dystonia. Methods: High-resolution melting and Sanger sequencing were used to inspect the entire coding region of TUBB4A in 575 subjects with primary laryngeal, segmental, or generalized dystonia. Results: No pathogenic variants, including the exon 1 variant (c.4C>G) identified in the DYT4 whispering dysphonia kindred, were found in this study. Conclusion: The c.4C>G DYT4 mutation appears to be private, and clinical testing for TUBB4A mutations is not justified in spasmodic dysphonia or other forms of primary dystonia. Moreover, given its allelic association with leukoencephalopathy hypomyelination with atrophy of basal ganglia and cerebellum and protean clinical manifestations (chorea, ataxia, dysarthria, intellectual disability, dysmorphic facial features, and psychiatric disorders), DYT4 should not be categorized as a primary dystonia. PMID:24598712

Children With and Without Dystonia Share Common Muscle Synergies While Performing Writing Tasks.

PubMed

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

2017-08-01

Childhood dystonia is a movement disorder characterized by muscle overflow and variability. This is the first study that investigates upper limb muscle synergies in childhood dystonia with the twofold aim of deepening the understanding of neuromotor dysfunctions and paving the way to possible synergy-based myocontrol interfaces suitable for this neurological population. Nonnegative matrix factorization was applied to the activity of upper-limb muscles recorded during the execution of writing tasks in children with dystonia and age-matched controls. Despite children with dystonia presented compromised kinematics of the writing outcome, a strikingly similarity emerged in the number and structure of the synergy vectors extracted from children in the two groups. The analysis also revealed that the timing of activation of the synergy coefficients did not significantly differ, while the amplitude of the peaks presented a slight reduction. These results suggest that the synergy analysis has the ability of capturing the uncorrupted part of the electromyographic signal in dystonia. Such an ability supports a possible future use of muscle synergies in the design of myocontrol interfaces for children with dystonia.

Genetics Home Reference: myoclonus-dystonia

MedlinePlus

... Page Esapa CT, Waite A, Locke M, Benson MA, Kraus M, McIlhinney RA, Sillitoe RV, Beesley PW, ... PubMed Gerrits MC, Foncke EM, Koelman JH, Tijssen MA. Pediatric writer's cramp in myoclonus-dystonia: maternal imprinting ...

Temporal discrimination in patients with dystonia and tremor and patients with essential tremor.

PubMed

Tinazzi, Michele; Fasano, Alfonso; Di Matteo, Alessandro; Conte, Antonella; Bove, Francesco; Bovi, Tommaso; Peretti, Alessia; Defazio, Giovanni; Fiorio, Mirta; Berardelli, Alfredo

2013-01-01

To investigate whether psychophysical techniques assessing temporal discrimination could help in differentiating patients who have tremor associated with dystonia or essential tremor. We tested somatosensory temporal discrimination thresholds (TDT) and temporal discrimination movement thresholds (TDMT) in 39 patients who had tremor associated with dystonia or essential tremor presenting with upper-limb tremor of comparable severity and compared their findings with those from a group of 25 sex- and age-matched healthy control subjects. TDT was higher in patients who had tremor associated with dystonia than in those with essential tremor and healthy controls (110.6 ± 31.3 vs 63.1 ± 15.2 vs 62.4 ± 9.2; p < 0.001). Conversely, TDMT was higher in patients with essential tremor than in those with tremor associated with dystonia and healthy controls (113.7 ± 14.7 vs 103.4 ± 11.3 vs 100.4 ± 4.2; p < 0.001). Combining the 2 tests in a pattern for essential tremor (abnormal TDMT/normal TDT) and tremor associated with dystonia (normal TDMT/abnormal TDT) yielded a positive predictive value (PPV) of 86.7% and a negative predictive value (NPV) of 70.8% for diagnosing essential tremor and a PPV of 100.0% and NPV of 74.1% for diagnosing tremor associated with dystonia. TDT and TDMT testing should prove a useful tool for differentiating tremor associated with dystonia and essential tremor. Our findings imply that the pathophysiologic mechanisms underlying tremor associated with dystonia differ from those for essential tremor.

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.

DYT1 dystonia increases risk taking in humans.

PubMed

Arkadir, David; Radulescu, Angela; Raymond, Deborah; Lubarr, Naomi; Bressman, Susan B; Mazzoni, Pietro; Niv, Yael

2016-06-01

It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans.

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;…

The clinical spectrum of laryngeal dystonia includes dystonic cough: observations of a large series.

PubMed

Payne, Susannah; Tisch, Stephen; Cole, Ian; Brake, Helen; Rough, Judy; Darveniza, Paul

2014-05-01

Laryngeal dystonia is a movement disorder of the muscles within the larynx, which most commonly manifests as spasmodic dysphonia (SD). Rarer reported manifestations include dystonic respiratory stridor and dyscoordinate breathing. Laryngeal dystonia has been treated successfully with botulinum neurotoxin (BTX) injections since 1984. We reviewed prospectively collected data in a consecutive series of 193 patients with laryngeal dystonia who were seen at St. Vincent's Hospital between 1991 and 2011. Patient data were analyzed in Excel, R, and Prism. Laryngeal dystonia manifested as SD (92.7%), stridor (11.9%), dystonic cough (6.2%), dyscoordinate breathing (4.1%), paroxysmal hiccups (1.6%), and paroxysmal sneezing (1.6%). There were more women (68.4%) than men (31.6%), and the average age at onset was 47 years. A positive family history of dystonia was present in 16.1% of patients. A higher incidence of extra-laryngeal dystonia (ie, torticollis and blepharospasm) and concurrent manifestations of laryngeal dystonia were present in patients with dystonic cough, dyscoordinate breathing, paroxysmal sneezing, and hiccups than in other patients (P = 0.003 and P < 0.0001, respectively). The average starting dose of BTX decreased from 2.3 to 0.5 units between 1991 and 2011. The median treatment rating was excellent across all subgroups. Patients with adductor SD, stridor, extra-laryngeal dystonia and male patients had relatively better treatment outcomes. Technical failures were rare (1.1%). Dysphonia secondary to vocal cord paresis followed 38.7% of treatments. Laryngeal dystonia manifests predominantly as SD, but other manifestations include stridor, dyscoordinate breathing, paroxysmal cough, hiccups, and sneezing. BTX injections are very effective across all subgroups. Severe adverse events are rare. © 2014 International Parkinson and Movement Disorder Society.

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.

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

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…

Mood and energy determinants of quality of life in dystonia.

PubMed

Soeder, Anne; Kluger, Benzi M; Okun, Michael S; Garvan, Cynthia W; Soeder, Thomas; Jacobson, Charles E; Rodriguez, Ramon L; Turner, Rick; Fernandez, Hubert H

2009-06-01

Prior research has demonstrated that dystonia patients may have reductions in numerous measures of quality of life (QOL) when compared to healthy age-matched controls. However, the determinants of QOL in this patient population have not been fully specified. To address this issue, we administered the Medical Outcomes Study Short Form 36 (SF-36) questionnaire along with the Visual Analogue Mood Scale (VAMS), the Beck Depression Inventory (BDI), the Unified Dystonia Rating Scale (UDRS), and the State and Trait Anxiety Index (STAI) to 73 patients diagnosed with primary dystonia. Dystonia patients demonstrated lower QOL on all subscales of the SF-36 compared to normative healthy age-matched data. While the UDRS, a predominantly motor scale, was not significantly correlated with QOL (r = -0.19, P = 0.11), the BDI (r = -0.79, P < 0.0001), the STAI (r = -0.63, P < 0.0001) and multiple subscales of the VAMS revealed significant correlations. The tired subscale was the item most strongly correlated with overall QOL (r = -0.52, P < 0.0001), and particularly QOL related to physical function. The association of tiredness with QOL remained significant even when adjusting for the BDI and STAI scores (P < 0.0001). This study highlights the importance of mood and energy in QOL among a cohort of patients with dystonia. Further studies will be needed to determine the effect of treatment on these associations and whether disturbances in energy are related to sleep disturbances or to primary fatigue issues.

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

DTIC Science & Technology

2013-04-01

was successful, and a mouse with the desired dystonic symptoms was obtained. It has two mutations , one a dominantly inherited gene with 100...the hallmark of dystonia. 15. SUBJECT TERMS Dystonia, genetically modified mice, stress, gene mutations , animal model of disease. 16...there are a variety of hypotheses that should be testable if there were a realistic animal model. Mice with mutations in genes known to cause dystonia

A unifying motor control framework for task-specific dystonia

PubMed Central

Rothwell, John C.; Edwards, Mark J.

2018-01-01

Task-specific dystonia is a movement disorder characterized by the development of a painless loss of dexterity specific to a particular motor skill. This disorder is prevalent among writers, musicians, dancers and athletes. No current treatment is predictably effective and the disorder generally ends the careers of affected individuals. There are a number of limitations with traditional dystonic disease models for task-specific dystonia. We therefore review emerging evidence that the disorder has its origins within normal compensatory mechanisms of a healthy motor system in which the representation and reproduction of motor skill is disrupted. We describe how risk factors for task-specific dystonia can be stratified and translated into mechanisms of dysfunctional motor control. The proposed model aims to define new directions for experimental research and stimulate therapeutic advances for this highly disabling disorder. PMID:29104291

Update on the Use of Botulinum Toxin Therapy for Focal and Task-Specific Dystonias.

PubMed

Lungu, Codrin; Ahmad, Omar F

2016-02-01

Focal dystonia is defined by anatomical distribution and represents a distinct entity from generalized dystonia. Task-specific dystonia occurs in the context of specific patterns of movement. Botulinum neurotoxin (BoNT) injections are the treatment of choice in most cases. Several formulations are available; the approved indications, dosing, and some administration details, differ between them. The major forms of focal and task-specific dystonia are reviewed, along with the evidence for BoNT therapy, the expected benefit and side effects, and practical points guiding the injections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

DYT1 dystonia increases risk taking in humans

PubMed Central

Arkadir, David; Radulescu, Angela; Raymond, Deborah; Lubarr, Naomi; Bressman, Susan B; Mazzoni, Pietro; Niv, Yael

2016-01-01

It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans. DOI: http://dx.doi.org/10.7554/eLife.14155.001 PMID:27249418

Ondansetron-induced dystonia, hypoglycemia, and seizures in a child.

PubMed

Patel, Aneet; Mittal, Shweta; Manchanda, Samiksha; Puliyel, Jacob Mammen

2011-01-01

To document ondansetron-induced dystonia, hypoglycemia, and seizures in a child. A 4-year-old boy was admitted with dystonia following an intravenous dose of ondansetron 2 mg (0.13 mg/kg) that he had received for vomiting that day. In the emergency department, he developed generalized tonicclonic seizures lasting for a few minutes. He was administered lorazepam 1.5 mg (0.1 mg/kg) to control the seizures. His blood glucose level was 10 mg/dL; the hypoglycemia responded promptly to intravenous dextrose 10% (7 mL/kg). Serum electrolytes, renal profile, capillary blood gas, and results of a computed tomography scan of the brain were normal. Subsequent blood glucose values were within normal range. On follow-up after 7 days, the child was healthy with no recurrences of the symptoms. A provisional diagnosis of ondansetron-induced acute dystonia with seizures and hypoglycemia was made. Ondansetron is an antiemetic known for its safety profile. There have been a few case reports of extrapyramidal adverse effects and seizures from this drug but none of ondansetron-associated hypoglycemia. 5-Hydroxytryptamine (5-HT(3)) receptors are involved in arginine vasopressin-mediated release of adrenocorticotropin hormone and cortisol in response to stress. Blunting of this stress response by ondansetron, a 5-HT(3) receptor antagonist, could have caused the hypoglycemia in this patient. According to the Naranjo scale, ondansetron was probably the cause of the dystonia and seizures, and possibly the cause of the hypoglycemia. Other potential explanations for hypoglycemia were considered but were thought to be less likely. Dystonia and seizures have been associated with ondansetron in a few case reports. In addition, clinicians need to consider hypoglycemia as a possible adverse effect of ondansetron.

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

PubMed Central

Batla, Amit; Bhatia, Kailash; Dauer, William T; Dresel, Christian; Niethammer, Martin; Eidelberg, David; Raike, Robert S.; Smith, Yoland; Jinnah, H. A.; Hess, Ellen J.; Meunier, Sabine; Hallett, Mark; Fremont, Rachel; Khodakhah, Kamran; LeDoux, Mark S.; Popa, Traian; Gallea, Cécile; Lehericy, Stéphane; Bostan, Andreea C.; Strick, Peter L.

2016-01-01

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin. PMID:27734238

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia.

PubMed

Shakkottai, Vikram G; Batla, Amit; Bhatia, Kailash; Dauer, William T; Dresel, Christian; Niethammer, Martin; Eidelberg, David; Raike, Robert S; Smith, Yoland; Jinnah, H A; Hess, Ellen J; Meunier, Sabine; Hallett, Mark; Fremont, Rachel; Khodakhah, Kamran; LeDoux, Mark S; Popa, Traian; Gallea, Cécile; Lehericy, Stéphane; Bostan, Andreea C; Strick, Peter L

2017-04-01

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed: The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia. Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia. Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include: Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems. Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

Functional Analysis of Dopaminergic Systems in a DYT1 Knock-in Mouse Model of Dystonia

PubMed Central

Song, Chang-Hyun; Fan, Xueliang; Exeter, Cicely J.; Hess, Ellen J.; Jinnah, H. A.

2012-01-01

The dystonias are a group of disorders characterized by involuntary twisting movements and abnormal posturing. The most common of the inherited dystonias is DYT1 dystonia, which is due to deletion of a single GAG codon (ΔE) in the TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked with dysfunction of brain dopamine pathways, the integrity of these pathways was explored in a knock-in mouse model of DYT1 dystonia. In DYT1(ΔE) knock-in mice, neurochemical measures revealed only small changes in the content of dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain, but microdialysis studies revealed robust decreases in baseline and amphetamine-stimulated extracellular dopamine in the caudoputamen. Quantitative stereological methods revealed no evidence for striatal or midbrain atrophy, but substantia nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in gross motor activity and motor coordination without overt dystonia. Neuropharmacological challenges of dopamine systems revealed normal behavioral responses to amphetamine and a minor increase in sensitivity to haloperidol. These results demonstrate that this DYT1(ΔE) knock-in mouse model of dystonia harbors neurochemical and structural changes of the dopamine pathways, as well as motor abnormalities. PMID:22659308

Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects.

PubMed

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

2014-05-01

The authors assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in 7 participants with dystonia and 9 healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the nondominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared with the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia can be explained by neural reorganization. Visual compensation for somatosensory changes in the nonstroke hemisphere may explain the lack of bilateral impairments in reaching.

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

Characteristics of bilateral hand function in individuals with unilateral dystonia due to perinatal stroke: sensory and motor aspects

PubMed Central

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

2014-01-01

We assessed bilateral motor and sensory function in individuals with upper limb dystonia due to unilateral perinatal stroke and explored interrelationships of motor function and sensory ability. Reach kinematics and tactile sensation were measured in seven participants with dystonia and nine healthy volunteers. The dystonia group had poorer motor (hold time, reach time, shoulder/elbow correlation) and sensory (spatial discrimination, stereognosis) outcomes than the control group on the non-dominant side. On the dominant side, only sensation (spatial discrimination, stereognosis) was poorer in the dystonia group compared to the control group. In the dystonia group, although sensory and motor outcomes were uncorrelated, dystonia severity was related to poorer stereognosis, longer hold and reach times, and decreased shoulder/elbow coordination. Findings of bilateral sensory deficits in dystonia may be explained by neural reorganization. Visual compensation for somatosensory changes in the non-stroke hemisphere may explain the lack of bilateral impairments in reaching. PMID:24396131

[The clinical features and surgical treatment strategies of cervical kyphosis].

PubMed

Fang, Jia-hu; Jia, Lian-shun; Zhou, Xu-hui; Song, Li-jun; Cai, Wei-hua; Li, Xiang

2010-10-15

To analyze the clinical characteristics and the surgical treatment strategy of cervical kyphosis. From March 2006 to October 2009, 31 cases of cervical kyphosis were treated. According to the clinical features and imaging findings, different treatment methods were used. There were 9 patients in operation group, including 4 male and 5 female patients, aged from 17 to 72 years (average age of 35 years). Among them, 5 cases were idiopathic kyphosis and 4 cases were caused by laminectomy or other reasons. There were 22 patients in conservative treatment group, including 11 male and 11 female patients, aged from 14 to 40 years (average age of 29 years), who were all idiopathic cervical kyphosis. Before and 1 week after operation, clinical assessment were taken for the patients in operation group using Spinal Cord Injuries Classification Standard of American Spinal Injury Association (AISA). During the periodic review, the anteroposterior, normal sagittal films of cervical spine were taken. At 1 week and every 6 months after operation, MRI films were also taken. These films were studied to evaluate the effects of the operations. In the conservative group, assessment of treatment results by studying anteroposterior and normal lateral views of cervical spine were were taken every month. The clinical characteristics and the surgical treatment strategies of these patients were analyzed. In operation group, 9 cases were followed up for 6 to 18 months, all patients did not failed in internal fixation and fusion. AISA neurological score and neurological function significantly improved. Three days after operation the average Cobb angle was -1.29 ° (preoperative 54.24 °). In conservative group, the average Cobb angle was -5.41 ° (before treatment 11.20 °) 4 months after the treatment. The symptoms of neck shoulder and back pain disappeared, and all patients were followed up for 3 to 24 months, with no recurrence of symptoms. In the early period of cervical kyphosis, adopt

Magnetic resonance imaging atlas of the cervical spine musculature.

PubMed

Au, John; Perriman, Diana M; Pickering, Mark R; Buirski, Graham; Smith, Paul N; Webb, Alexandra L

2016-07-01

The anatomy of the cervical spine musculature visible on magnetic resonance (MR) images is poorly described in the literature. However, the correct identification of individual muscles is clinically important because certain conditions of the cervical spine, for example whiplash associated disorders, idiopathic neck pain, cervical nerve root avulsion and cervical spondylotic myelopathy, are associated with different morphological changes in specific muscles visible on MR images. Knowledge of the precise structure of different cervical spine muscles is crucial when comparisons with the contralateral side or with normal are required for accurate description of imaging pathology, management and assessment of treatment efficacy. However, learning the intricate arrangement of 27 muscles is challenging. A multi-level cross-sectional depiction combined with three-dimensional reconstructions could facilitate the understanding of this anatomically complex area. This paper presents a comprehensive series of labeled axial MR images from one individual and serves as a reference atlas of the cervical spine musculature to guide clinicians, researchers, and anatomists in the accurate identification of these muscles on MR imaging. Clin. Anat. 29:643-659, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Muscle synergies in children with dystonia capture "healthy" patterns regardless the altered motor performance.

PubMed

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

2015-01-01

Muscle synergies are hypothesized to represent motor modules recruited by the nervous system to flexibly perform subtasks necessary to achieve movement. Muscle synergy analysis may offer a better view of the neural structure underlying motor behaviors and how they change in motor deficits and rehabilitation. The aim of this study is to investigate if muscle synergies are able to encode regularities in the musculoskeletal system organization and dynamic behavior of patients with dystonia, or if they are altered as a consequence of the nervous system dysfunction in dystonia. To do so, we applied muscle synergies analysis to muscle activity recorded during the execution of upper limb writing tasks in 10 children with dystonia and 9 age-matched healthy controls. We show that, although children with dystonia present movement abnormalities compared to control subjects, the muscle synergies extracted from the two groups are very similar, and that the two groups share a significant number of motor modules. Our finding therefore suggests that a regular modular organization of upper limb muscle coordination is preserved for childhood dystonia.

Idiopathic Syringomyelia in a Military Helicopter Pilot.

PubMed

Schiemer, Anthony

2017-10-01

A syrinx is a fluid-filled cavity within the spinal cord. They can lead to a variety of symptoms, including limb weakness and back pain. Incidental finding of syringomyelia provides a challenge for clinicians due to the wide variety of possible symptoms. In military aviation, neurological findings in pilots can result in extensive investigation that can lead to potentially invasive management. Conversely, the potential for chronic progression of a spinal syrinx and subsequent neurological deterioration makes early identification critical. Ultimately, the discovery of a lesion may have implications for flying status and operational capability. A 25-yr-old man working as a navy Seahawk helicopter pilot presented with episodes of right arm paraesthesia and pain between the scapulae. On at least one occasion, these symptoms woke him at night. Upon magnetic resonance imaging, dilatation of the central canal in a syrinx-like pattern in the lower cervical region was noted. Neurology review suggested the finding was persistent and unlikely to be responsible for his symptoms. No surgical input was recommended. His symptoms were attributed to mild cervical spondylosis, which resolved with ongoing physiotherapy, and he was returned to flying status. This case highlights several issues involved with the incidental finding of a syringomyelia. Surgical intervention has been known to worsen symptoms. Conversely, studies have identified minimal radiological progression in cases of idiopathic syringomyelia, with fewer individuals displaying neurological deterioration. For aircrew, potentially unnecessary neurosurgical intervention poses risks to a flying career and overall operational capability.Schiemer A. Idiopathic syringomyelia in a military helicopter pilot. Aerosp Med Hum Perform. 2017; 88(10):962-965.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2017-12-01

1 AWARD NUMBER: W81XWH-14-1-0282 TITLE: Developing Gene Silencing for the Study and Treatment of Dystonia PRINCIPAL INVESTIGATOR: Pedro...30/2014-9/29/2017 4. TITLE AND SUBTITLE Developing Gene Silencing for the Study and Treatment of Dystonia 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...function. More importantly, we will check if no side effects or toxicity occurs. Successful completion of our studies will move us a step closer to

Shock Waves in the Treatment of Muscle Hypertonia and Dystonia

PubMed Central

Mori, Laura; Currà, Antonio; Molfetta, Luigi; Abbruzzese, Giovanni

2014-01-01

Since 1997, focused shock waves therapy (FSWT) has been reported to be useful in the treatment of muscle hypertonia and dystonia. More recently, also radial shock wave therapy (RSWT) has been successfully used to treat muscle hypertonia. The studies where FSWT and RSWT have been used to treat muscle hypertonia and dystonia are reviewed in this paper. The more consistent and long lasting results were obtained in the lower limb muscles of patients affected by cerebral palsy with both FSWT and RSWT and in the distal upper limb muscles of adult stroke patients using FSWT. The most probable mechanism of action is a direct effect of shock waves on muscle fibrosis and other nonreflex components of muscle hypertonia. However, we believe that up to now the biological effects of shock waves on muscle hypertonia and dystonia cannot be clearly separated from a placebo effect. PMID:25309915

Activity and topographic changes in the somatosensory system in embouchure dystonia.

PubMed

Mantel, Tobias; Dresel, Christian; Altenmüller, Eckart; Zimmer, Claus; Noe, Jonas; Haslinger, Bernhard

2016-11-01

Embouchure dystonia is a highly disabling focal task-specific dystonia affecting professional brass players. This study was designed to analyze activity changes along with topographic representations in primary and nonprimary centers for somatosensory processing in patients with embouchure dystonia. We used event-related functional magnetic resonance imaging with automized tactile stimulation of dystonic (upper lip) and nondystonic (forehead and dorsal hand) body regions in 15 professional brass players with and without embouchure dystonia. Statistical analyses included whole-brain between-group comparisons of stimulation-induced activation and region-of-interest-based single patient analyses of topographic activation characteristics. Affected musicians revealed increased stimulation-induced activity in contralateral primary and bilateral secondary somatosensory representations of dystonic and nondystonic body regions as well as in the cerebellum ipsilateral to the left dystonic upper lip. Changes of somatotopic organization with altered intracortical distances and between-group differences of the centers of representations were found in the right primary and the bilateral secondary somatosensory cortex and in the left cerebellum. Positional variability of dystonic and nondystonic body regions was reduced with an emphasis on face representations. The present findings are supportive of the concept of an abnormal processing of somatosensory information in embouchure dystonia affecting multiple domains. The underlying neurophysiological mechanisms (eg, changes in inhibition, maladaptive plasticity, changes in baseline activity) remain unclear. The involvement of nondystonic body areas can be viewed in the context of possible compensation or an endophenotypic predisposition. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Motor cortex stimulation does not improve dystonia secondary to a focal basal ganglia lesion.

PubMed

Rieu, Isabelle; Aya Kombo, Magaly; Thobois, Stéphane; Derost, Philippe; Pollak, Pierre; Xie, Jing; Pereira, Bruno; Vidailhet, Marie; Burbaud, Pierre; Lefaucheur, Jean Pascal; Lemaire, Jean Jacques; Mertens, Patrick; Chabardes, Stephan; Broussolle, Emmanuel; Durif, Franck

2014-01-14

To assess the efficacy of epidural motor cortex stimulation (MCS) on dystonia, spasticity, pain, and quality of life in patients with dystonia secondary to a focal basal ganglia (BG) lesion. In this double-blind, crossover, multicenter study, 5 patients with dystonia secondary to a focal BG lesion were included. Two quadripolar leads were implanted epidurally over the primary motor (M1) and premotor cortices, contralateral to the most dystonic side. The leads were placed parallel to the central sulcus. Only the posterior lead over M1 was activated in this study. The most lateral or medial contact of the lead (depending on whether the dystonia predominated in the upper or lower limb) was selected as the anode, and the other 3 as cathodes. One month postoperatively, patients were randomly assigned to on- or off-stimulation for 3 months each, with a 1-month washout between the 2 conditions. Voltage, frequency, and pulse width were fixed at 3.8 V, 40 Hz, and 60 μs, respectively. Evaluations of dystonia (Burke-Fahn-Marsden Scale), spasticity (Ashworth score), pain intensity (visual analog scale), and quality of life (36-Item Short Form Health Survey) were performed before surgery and after each period of stimulation. Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of life were not statistically significantly modified by MCS. Bipolar epidural MCS failed to improve any clinical feature in dystonia secondary to a focal BG lesion. This study provides Class I evidence that bipolar epidural MCS with the anode placed over the motor representation of the most affected limb failed to improve any clinical feature in dystonia secondary to a focal BG lesion.

Surgical treatment analysis of idiopathic esophageal achalasia.

PubMed

Aquino, José Luis Braga de; Said, Marcelo Manzano; Pereira, Douglas Rizzanti; Amaral, Paula Casals do; Lima, Juliana Carolina Alves; Leandro-Merhi, Vânia Aparecida

2015-01-01

Idiopathic esophageal achalasia is an inflammatory disease of unknown origin, characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter in response to swallowing, with consequent dysphagia. To demonstrate the results of surgical therapy in these patients, evaluating the occurred local and systemic complications. Were studied retrospectively 32 patients, 22 of whom presented non-advanced stage of the disease (Stage I/II) and 10 with advanced disease (Stage III/IV). All of them had the clinical conditions to be submitted to surgery. The diagnoses were done by clinical, endoscopic, cardiological, radiological and esophageal manometry analysis. Pre-surgical evaluation was done with a questionnaire based on the most predisposing factors in the development of the disease and the surgical indication was based on the stage of the disease. The patients with non-advanced stages were submitted to cardiomyotomy with fundoplication, wherein in the post-surgical early assessment, only one (4,4%) presented pulmonary infection, but had a good outcome. In patients with advanced disease, seven were submitted to esophageal mucosectomy preserving the muscular layer, wherein one patient (14,2%) presented dehiscence of gastric cervical esophagus anastomosis as well as pulmonary infection; all of these complications were resolved with proper specific treatment; the other three patients with advanced stage were submitted to transmediastinal esophagectomy; two of them presented hydropneumothorax with good evolution, and one of them also presented fistula of the cervical esophagogastric anastomosis, but with spontaneous healing after conservative treatment and nutritional support. The two patients with fistula of the cervical anastomosis progressed to stenosis, with good results after endoscopic dilations. In the medium and long term assessment done in 23 patients, all of them reported improvement in life quality, with return to swallowing. The

Clustering of dystonia in some pedigrees with autosomal dominant essential tremor suggests the existence of a distinct subtype of essential tremor

PubMed Central

2010-01-01

Background There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET. Many patients with clinically definite ET develop dystonia. It remains unknown whether tremor associated with dystonia represent a subtype of ET. We hypothesized that ET with dystonia represents a distinct subtype of ET. Methods We studied patients diagnosed with familial ET and dystonia. We included only those patients whose first-degree relatives met diagnostic criteria for ET or dystonia with tremor. This cohort was ascertained for the presence of focal, segmental, multifocal, hemidystonia or generalized dystonia, and ET. Results We included 463 patients from 97 kindreds with autosomal dominant mode of inheritance (AD), defined by the vertical transmission of the disease. ET was the predominant phenotype in every ascertained family and each was phenotypically classified as AD ET. "Pure" ET was present in 365 individuals. Focal or segmental dystonia was present in 98 of the 463 patients; 87 of the 98 patients had ET associated with dystonia, one had dystonic tremor and ten had isolated dystonia. The age of onset and tremor severity did not differ between patients with "pure" ET and ET associated with dystonia. We did not observe a random distribution of dystonia in AD ET pedigrees and all patients with dystonia associated with ET were clustered in 28% of all included pedigrees (27/97, p < 0.001). Conclusions Our results suggest that familial ET associated with dystonia may represent a distinct subtype of ET. PMID:20670416

Regaining motor control in musician's dystonia by restoring sensorimotor organisation

PubMed Central

Rosenkranz, Karin; Butler, Katherine; Williamon, Aaron; Rothwell, John C.

2010-01-01

Professional musicians are an excellent human model of long term effects of skilled motor training on the structure and function of the motor system. However, such effects are accompanied by an increased risk of developing motor abnormalities, in particular musician's dystonia. Previously we found that there was an expanded spatial integration of proprioceptive input into the hand area of motor cortex (sensorimotor organisation, SMO) in healthy musicians as tested with a transcranial magnetic stimulation (TMS) paradigm. In musician's dystonia, this expansion was even larger, resulting in a complete lack of somatotopic organisation. We hypothesised that the disordered motor control in musician's dystonia is a consequence of the disordered SMO. In the present paper we test this idea by giving pianists with musician's dystonia 15 min experience of a modified proprioceptive training task. This restored SMO towards that seen in healthy pianists. Crucially, motor control of the affected task improved significantly and objectively as measured with a MIDI piano, and the amount of behavioural improvement was significantly correlated to the degree of sensorimotor re-organisation. In healthy pianists and non-musicians, the SMO and motor performance remained essentially unchanged. These findings suggest a link between the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks in highly skilled individuals. PMID:19923295

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2016-10-01

eliminate the symptoms? Are the motor deficits in DYT1 dystonia reversible? We propose to use a novel rat model of DYT1 dystonia and infuse antisense...suppressing expression of mutant torsinA in striatum or cerebellum using AAV1 reverses the motor phenotype in aged DYT1 rats . 4. IMPACT What was...different areas of the brain, and w e w ill measure if they are able to reverse known abnormalities that occur in the brain of DYT1 rats , including abnormal

Update on Deep Brain Stimulation for Dyskinesia and Dystonia: A Literature Review

PubMed Central

TODA, Hiroki; SAIKI, Hidemoto; NISHIDA, Namiko; IWASAKI, Koichi

2016-01-01

Deep brain stimulation (DBS) has been an established surgical treatment option for dyskinesia from Parkinson disease and for dystonia. The present article deals with the timing of surgical intervention, selecting an appropriate target, and minimizing adverse effects. We provide an overview of current evidences and issues for dyskinesia and dystonia as well as emerging DBS technology. PMID:27053331

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…

Quality and reporting of guidelines on the diagnosis and management of dystonia.

PubMed

Tamás, G; Abrantes, C; Valadas, A; Radics, P; Albanese, A; Tijssen, M A J; Ferreira, J J

2018-02-01

The quality of clinical practice guidelines on dystonia has not yet been assessed. Our aim was to appraise the methodological quality of guidelines worldwide and to analyze the consistency of their recommendations. We searched for clinical practice guidelines on dystonia diagnosis/treatment in the National Guideline Clearinghouse, PubMed, National Institute for Health and Care Excellence, Guidelines International Network and Web of Science databases. We also searched for guidelines on homepages of international neurological societies. We asked for guidelines from every Management Committee member of the BM1101 Action of the Cooperation between Science and Technology European framework and every member of the International Parkinson and Movement Disorders Society with special interest in dystonia. Fifteen guidelines were evaluated. Among guidelines on treatment, only one from the American Academy of Neurology could be considered as high quality. Among guidelines on diagnosis and therapy, the guideline from the European Federation of Neurological Societies was recommended by the appraisers. Clinical applicability and reports of editorial independence were the greatest shortcomings. The rigor of development was poor and stakeholder involvement was also incomplete in most guidelines. Discrepancies among recommendations may result from the weight given to consensus statements and expert opinions due to the lack of evidence, as well as inaccuracy of disease classification. The quality of appraised guidelines was low. It is necessary to improve the quality of guidelines on dystonia, and the applied terminology of dystonia also needs to be standardized. © 2017 EAN.

Deep Brain Stimulation for Dystonia: A Novel Perspective on the Value of Genetic Testing

PubMed Central

Jinnah, H. A.; Alterman, Ron; Klein, Christine; Krauss, Joachim K.; Moro, Elena; Vidailhet, Marie; Raike, Robert

2017-01-01

The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal movements and postures. There are many different clinical manifestations and underlying causes. Deep brain stimulation (DBS) provides an effect treatment, but outcomes can vary considerably among the different subtypes of dystonia. Several variables are thought to contribute to this variation including age of onset and duration of dystonia, specific characteristics of the dystonic movements, location of stimulation and stimulator settings, and others. The potential contributions of genetic factors have received little attention. In this review, we summarize evidence that some of the variation in DBS outcomes for dystonia is due to genetic factors. The evidence suggests that more methodical genetic testing may provide useful information in the assessment of potential surgical candidates, and in advancing our understanding of the biological mechanisms that influence DBS outcomes. PMID:28160152

Programming Deep Brain Stimulation for Tremor and Dystonia: The Toronto Western Hospital Algorithms.

PubMed

Picillo, Marina; Lozano, Andres M; Kou, Nancy; Munhoz, Renato Puppi; Fasano, Alfonso

2016-01-01

Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET) and dystonia. After surgery, a number of extensive programming sessions are performed, mainly relying on neurologist's personal experience as no programming guidelines have been provided so far, with the exception of recommendations provided by groups of experts. Finally, fewer information is available for the management of DBS in ET and dystonia compared with Parkinson's disease. Our aim is to review the literature on initial and follow-up DBS programming procedures for ET and dystonia and integrate the results with our current practice at Toronto Western Hospital (TWH) to develop standardized DBS programming protocols. We conducted a literature search of PubMed from inception to July 2014 with the keywords "balance", "bradykinesia", "deep brain stimulation", "dysarthria", "dystonia", "gait disturbances", "initial programming", "loss of benefit", "micrographia", "speech", "speech difficulties" and "tremor". Seventy-six papers were considered for this review. Based on the literature review and our experience at TWH, we refined three algorithms for management of ET, including: (1) initial programming, (2) management of balance and speech issues and (3) loss of stimulation benefit. We also depicted algorithms for the management of dystonia, including: (1) initial programming and (2) management of stimulation-induced hypokinesia (shuffling gait, micrographia and speech impairment). We propose five algorithms tailored to an individualized approach to managing ET and dystonia patients with DBS. We encourage the application of these algorithms to supplement current standards of care in established as well as new DBS centers to test the clinical usefulness of these algorithms in supplementing the current standards of care. Copyright © 2016 Elsevier Inc. All rights reserved.

Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia.

PubMed

Bradnam, Lynley V; Graetz, Lynton J; McDonnell, Michelle N; Ridding, Michael C

2015-01-01

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer's dystonia, 3 musician's dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer's Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia.

[A case of 77-year-old male with spinocerebellar ataxia type 31 with left dominant dystonia].

PubMed

Saito, Rie; Kikuno, Shota; Maeda, Meiko; Uesaka, Yoshikazu; Ida, Masahiro

2014-01-01

We report on the case of a 77-year-old male with genetically proven spinocerebellar ataxia type 31 (SCA31) who had dystonia. He was referred to our hospital for evaluation following a 6-year history of slowly progressive unsteadiness of his left leg during walking and dysarthria at the age of 62 years old. On the basis of his symptoms, we diagnosed him as spinocerebellar degeneration (SCD), and prescribed taltirelin hydrate. However, his symptoms continued to worsen. He required a cane for walking at the age of 63 years, and a wheelchair at the age of 66 years. He was admitted to our hospital following acute cerebral infarction at the age of 77 years. On examination at admission, right hemiparesis and cerebellar ataxia were detected. And left hallux moved involuntarily toward the top surface of the foot at rest, that is dystonia. The dystonia was not associated with cerebral infarction, because it had been several years with dystonia that he got cerebral infarction. Genetic analysis revealed that this patient harbored a heterozygous SCA31 mutation. Previously there have been no reports of SCA31 associated with dystonia. Our case report support clinical heterogeneity of SCA31, and highlight the importance of considering this type in patients with dystonia and ataxia. Patients with the combination of dystonia and ataxia and a family history of a neurodegenerative disorder should be tested for SCA31.

Vertebral artery injury associated with blunt cervical spine trauma: a multivariate regression analysis.

PubMed

Lebl, Darren R; Bono, Christopher M; Velmahos, George; Metkar, Umesh; Nguyen, Joseph; Harris, Mitchel B

2013-07-15

Retrospective analysis of prospective registry data. To determine the patient characteristics, risk factors, and fracture patterns associated with vertebral artery injury (VAI) in patients with blunt cervical spine injury. VAI associated with cervical spine trauma has the potential for catastrophical clinical sequelae. The patterns of cervical spine injury and patient characteristics associated with VAI remain to be determined. A retrospective review of prospectively collected data from the American College of Surgeons trauma registries at 3 level-1 trauma centers identified all patients with a cervical spine injury on multidetector computed tomographic scan during a 3-year period (January 1, 2007, to January 1, 2010). Fracture pattern and patient characteristics were recorded. Logistic multivariate regression analysis of independent predictors for VAI and subgroup analysis of neurological events related to VAI was performed. Twenty-one percent of 1204 patients with cervical injuries (n = 253) underwent screening for VAI by multidetector computed tomography angiogram. VAI was diagnosed in 17% (42 of 253), unilateral in 15% (38 of 253), and bilateral in 1.6% (4 of 253) and was associated with a lower Glasgow coma scale (P < 0.001), a higher injury severity score (P < 0.01), and a higher mortality (P < 0.001). VAI was associated with ankylosing spondylitis/diffuse idiopathic skeletal hyperosteosis (crude odds ratio [OR] = 8.04; 95% confidence interval [CI], 1.30-49.68; P = 0.034), and occipitocervical dissociation (P < 0.001) by univariate analysis and fracture displacement into the transverse foramen 1 mm or more (adjusted OR = 3.29; 95% CI, 1.15-9.41; P = 0.026), and basilar skull fracture (adjusted OR = 4.25; 95% CI, 1.25-14.47; P= 0.021), by multivariate regression model. Subgroup analyses of neurological events secondary to VAI occurred in 14% (6 of 42) and the stroke-related mortality rate was 4.8% (2 of 42). Neurological events were associated with male sex (P

[Effect analysis of anterior cervical operation for severe cervical kyphosis].

PubMed

Shen, X L; Wu, H Q; Hu, Z H; Liu, Y; Wang, X W; Chen, H J; Cao, P; Tian, Y; Yang, C; Yuan, W

2017-03-01

Objective: To determine the feasibility and safety of anterior cervical decompression and fusion in severe cervical kyphosis treatment. Methods: Totally 29 patients with severe cervical kyphosis(Cobb angle>50°) underwent anterior cervical decompression and fusion from June 2008 to May 2016 were studied retrospectively. There were 19 males and 10 females. The average age was 32.6 years ranging from 14 to 53 years. According to the etiology, 12 patients had iatrogenic deformity (11 had post-laminectomy cervical kyphosis, 1 had kyphosis due to anterior graft subsidence), 5 had neurofibromatosis, 4 had infective kyphosis, 8 had idiopathic cervical kyphosis. The curvature of cervical angle was measured by two-line Cobb method. The severity of cervical kyphosis was evaluated by kyphosis index (KI). Parameters including kyphosis levels, the apex of the kyphosis, C(2-7) sagittal vertical axis(SVA) and T(1) slope were also measured on lateral radiographs in the neutral position in each patient. The pre- and post-operative Japanese Orthopaedic Association(JOA) scores, visual analogue scale (VAS) of neek pain, neck disability index (NDI) and cervical alignment were compared. All patients were treated by skull traction. Motor evoked potential and somatosensory evoked potential were applied intraoperation as the spinal cord monitor. Results: Skull traction was performed for an average of 6.3 days. The mean vertebral number in kyphotic region was 4.7. The average operation time was 155 minutes and blood loss was 135 ml. The preoperative C(2-7)Cobb angle was 46.6°±18.1° in average. It was reduced to 11.4°±6.4° in average after operation. The Cobb angle of operation region was 72.9°±19.6° in average before operation. It was reduced to 11.2°±6.4° in average after operation. The kyphosis region correction rate was 84.6%. The mean preoperative C(2-7)SVA changed from (3.8±14.6) mm to (12.6±7.8) mm postoperatively. The mean preoperative T(1) slope changed from -10.6�

Distribution and Coexistence of Myoclonus and Dystonia as Clinical Predictors of SGCE Mutation Status: A Pilot Study.

PubMed

Zutt, Rodi; Dijk, Joke M; Peall, Kathryn J; Speelman, Hans; Dreissen, Yasmine E M; Contarino, Maria Fiorella; Tijssen, Marina A J

2016-01-01

Myoclonus-dystonia (M-D) is a young onset movement disorder typically involving myoclonus and dystonia of the upper body. A proportion of the cases are caused by mutations to the autosomal dominantly inherited, maternally imprinted, epsilon-sarcoglycan gene (SGCE). Despite several sets of diagnostic criteria, identification of patients most likely to have an SGCE mutation remains difficult. Forty consecutive patients meeting pre-existing diagnostic clinical criteria for M-D underwent a standardized clinical examination (20 SGCE mutation positive and 20 negative). Each video was reviewed and systematically scored by two assessors blinded to mutation status. In addition, the presence and coexistence of myoclonus and dystonia was recorded in four body regions (neck, arms, legs, and trunk) at rest and with action. Thirty-nine patients were included in the study (one case was excluded owing to insufficient video footage). Based on previously proposed diagnostic criteria, patients were subdivided into 24 "definite," 5 "probable," and 10 "possible" M-D. Motor symptom severity was higher in the SGCE mutation-negative group. Myoclonus and dystonia were most commonly observed in the neck and upper limbs of both groups. Truncal dystonia with action was significantly seen more in the mutation-negative group (p < 0.05). Coexistence of myoclonus and dystonia in the same body part with action was more commonly seen in the mutation-negative cohort (p < 0.05). Truncal action dystonia and coexistence of myoclonus and dystonia in the same body part with action might suggest the presence of an alternative mutation in patients with M-D.

Changes in resting-state connectivity in musicians with embouchure dystonia.

PubMed

Haslinger, Bernhard; Noé, Jonas; Altenmüller, Eckart; Riedl, Valentin; Zimmer, Claus; Mantel, Tobias; Dresel, Christian

2017-03-01

Embouchure dystonia is a highly disabling task-specific dystonia in professional brass musicians leading to spasms of perioral muscles while playing the instrument. As they are asymptomatic at rest, resting-state functional magnetic resonance imaging in these patients can reveal changes in functional connectivity within and between brain networks independent from dystonic symptoms. We therefore compared embouchure dystonia patients to healthy musicians with resting-state functional magnetic resonance imaging in combination with independent component analyses. Patients showed increased functional connectivity of the bilateral sensorimotor mouth area and right secondary somatosensory cortex, but reduced functional connectivity of the bilateral sensorimotor hand representation, left inferior parietal cortex, and mesial premotor cortex within the lateral motor function network. Within the auditory function network, the functional connectivity of bilateral secondary auditory cortices, right posterior parietal cortex and left sensorimotor hand area was increased, the functional connectivity of right primary auditory cortex, right secondary somatosensory cortex, right sensorimotor mouth representation, bilateral thalamus, and anterior cingulate cortex was reduced. Negative functional connectivity between the cerebellar and lateral motor function network and positive functional connectivity between the cerebellar and primary visual network were reduced. Abnormal resting-state functional connectivity of sensorimotor representations of affected and unaffected body parts suggests a pathophysiological predisposition for abnormal sensorimotor and audiomotor integration in embouchure dystonia. Altered connectivity to the cerebellar network highlights the important role of the cerebellum in this disease. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

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

Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia

PubMed Central

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

2015-01-01

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer’s dystonia, 3 musician’s dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer’s Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia. PMID:26042019

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

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

PubMed

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

2015-08-01

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. 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±3years) and healthy volunteers (age 17±5years). 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. 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. Cortical and motor dysfunction are correlated in patients with childhood stroke and may in part explain the genesis of dystonia. Published by Elsevier Ireland Ltd.

Comparison of segmental spinal movement control in adolescents with and without idiopathic scoliosis using modified pressure biofeedback unit.

PubMed

Luo, Hong-Ji; Lin, Shi-Xiang; Wu, Shyi-Kuen; Tsai, Mei-Wun; Lee, Shwn-Jen

2017-01-01

Postural rehabilitation emphasizing on motor control training of segmental spinal movements has been proposed to effectively reduce the scoliotic spinal deformities in adolescent idiopathic scoliosis (AIS). However, information regarding the impairments of segmental spinal movement control involving segmental spinal stabilizers in adolescent idiopathic scoliosis remains limited. Examination of segmental spinal movement control may provide a window for investigating the features of impaired movement control specific to spinal segments that may assist in the development of physiotherapeutic management of AIS. To compare segmental spinal movement control in adolescents with and without idiopathic scoliosis using modified pressure biofeedback unit. Segmental spinal movement control was assessed in twenty adolescents with idiopathic scoliosis (AISG) and twenty healthy adolescents (CG) using a modified pressure biofeedback unit. Participants performed segmental spinal movements that primarily involved segmental spinal stabilizing muscles with graded and sustained muscle contraction against/off a pressure cuff from baseline to target pressures and then maintained for 1 min. Pressure data during the 1-minute maintenance phase were collected for further analysis. Pressure deviation were calculated and compared between groups. The AISG had significantly greater pressure deviations for all segmental spinal movements of cervical, thoracic, and lumbar spine than the CG. Pressure biofeedback unit was feasible for assessing segmental spinal movement control in AIS. AISG exhibited poorer ability to grade and sustain muscle activities for local movements of cervical, thoracic, and lumbar spine, suggesting motor control training of segmental spinal movements involving segmental spinal stabilizing muscles on frontal, sagittal, and transverse planes were required.

Reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency.

PubMed

Serrano, Mercedes; Rebollo, Mónica; Depienne, Christel; Rastetter, Agnès; Fernández-Álvarez, Emilio; Muchart, Jordi; Martorell, Loreto; Artuch, Rafael; Obeso, José A; Pérez-Dueñas, Belén

2012-09-01

Thiamine transporter-2 deficiency, a condition resulting from mutations in the SLC19A3 gene, has been described in patients with subacute dystonia and striatal necrosis. The condition responds extremely well to treatment with biotin and has thus been named biotin-responsive basal ganglia disease. Recently, this deficiency has also been related to Wernicke's-like encephalopathy and atypical infantile spasms, showing heterogeneous responses to biotin and/or thiamine. Two Spanish siblings with a biotin-responsive basal ganglia disease phenotype and mutations in SLC19A3 presented with acute episodes of generalized dystonia, rigidity, and symmetrical lesions involving the striatum, midline nuclei of the thalami, and the cortex of cerebral hemispheres as shown by magnetic resonance imaging. The clinical features resolved rapidly after thiamine administration. Despite the rarity of thiamine transporter-2 deficiency, it should be suspected in patients with acute dystonia and basal ganglia injury, as thiamine can halt disease evolution and prevent further episodes. © 2012 Movement Disorder Society. Copyright © 2012 Movement Disorder Society.

Lower KV7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia.

PubMed

Sander, Svenja E; Diwan, Mustansir; Raymond, Roger; Nobrega, José N; Richter, Angelika

2016-01-01

Dystonia is a hyperkinetic disabling movement disorder. In the dt(sz) hamster, a model of paroxysmal dystonia, pronounced antidystonic effects of the KV7.2-5 potassium channel opener retigabine and aggravation of dystonia by a selective KV7.2-5 blocker indicated a pathophysiological role of an abnormal expression of KV7 channels. We therefore investigated the expression of KV7 subunits in brains of dystonic hamsters. While KV7.2 and KV7.3 subunits were unaltered, lower KV7.5 mRNA levels became evident in motor areas and in limbic structures of dystonic hamsters. The KV7.2/3 subunit-preferring channel opener N-(6-chloropyridin-3-yl)-3,4- difluorobenzamide (ICA 27243; 10-30 mg/kg i.p.) failed to reduce the severity of dystonia in mutant hamsters, suggesting that the previously observed antidystonic action of retigabine is mediated by the activation of KV7.5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of KV7 channels, i.e. for KV7.5, may provide new therapeutic approaches.

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. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Speed-accuracy trade-off in a trajectory-constrained self-feeding task: a quantitative index of unsuppressed motor noise in children with dystonia

PubMed Central

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

2015-01-01

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 towards 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. PMID:25895910

Impaired Inhibitory Force Feedback in Fixed Dystonia.

PubMed

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

2016-04-01

Complex regional pain syndrome (CRPS) is a multifactorial disorder associated with an aberrant host response to tissue injury. About 25% of CRPS patients suffer poorly understood involuntary sustained muscle contractions associated with dysfunctional reflexes that result in abnormal postures (fixed dystonia). A recent modeling study simulated fixed dystonia (FD) caused by aberrant force feedback. The current study aims to validate this hypothesis by experimentally recording the modulation of reflexive force feedback in patients with FD. CRPS patients with and without FD, patients with FD but without CRPS, as well as healthy controls participated in the experiment. Three task instructions and three perturbation characteristics were used to evoke a wide range of responses to force perturbations. During position tasks ("maintain posture"), healthy subjects as well as patients resisted the perturbations, becoming more stiff than when being relaxed (i.e., the relax task). Healthy subjects and CRPS patients without FD were both more compliant during force tasks ("maintain force") than during relax tasks, meaning they actively gave way to the imposed forces. Remarkably, the patients with FD failed to do so. A neuromuscular model was fitted to the experimental data to separate the distinct contributions of position, velocity and force feedback, as well as co-contraction to the motor behavior. The neuromuscular modeling indicated that inhibitory force feedback is deregulated in patients with FD, for both CRPS and non-CRPS patients. From previously published simulation results and the present experimental study, it is concluded that aberrant force feedback plays a role in fixed dystonia.

Cathodal transcranial direct current stimulation in children with dystonia: a sham-controlled study.

PubMed

Young, Scott J; Bertucco, Matteo; Sanger, Terence D

2014-02-01

Increased motor cortex excitability is a common finding in dystonia, and transcranial direct current stimulation can reduce motor cortex excitability. In an earlier study, we found that cathodal direct-current stimulation decreased motor overflow for some children with dystonia. To investigate this observation further, we performed a sham-controlled, double-blind, crossover study of 14 children with dystonia. We found a significant reduction in overflow following real stimulation, when participants performed the experimental task with the hand contralateral to the cathode. While these results suggest that cathodal stimulation may help some children to reduce involuntary overflow, the size of the effect is small. Further research will need to investigate ways to increase the magnitude of the effect of cathodal transcranial direct current stimulation.

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.

Surmounting retraining limits in musicians' dystonia by transcranial stimulation.

PubMed

Furuya, Shinichi; Nitsche, Michael A; Paulus, Walter; Altenmüller, Eckart

2014-05-01

Abnormal cortical excitability is evident in various movement disorders that compromise fine motor control. Here we tested whether skilled finger movements can be restored in musicians with focal hand dystonia through behavioral training assisted by transcranial direct current stimulation to the motor cortex of both hemispheres. The bilateral motor cortices of 20 pianists (10 with focal dystonia, 10 healthy controls) were electrically stimulated noninvasively during bimanual mirrored finger movements. We found improvement in the rhythmic accuracy of sequential finger movements with the affected hand during and after cathodal stimulation over the affected cortex and simultaneous anodal stimulation over the unaffected cortex. The improvement was retained 4 days after intervention. Neither a stimulation with the reversed montage of electrodes nor sham stimulation yielded any improvement. Furthermore, the amount of improvement was positively correlated with the severity of the symptoms. Bihemispheric stimulation without concurrent motor training failed to improve fine motor control, underlining the importance of combined retraining and stimulation for restoring the dystonic symptoms. For the healthy pianists, none of the stimulation protocols enhanced movement accuracy. These results suggest a therapeutic potential of behavioral training assisted by bihemispheric, noninvasive brain stimulation in restoring fine motor control in focal dystonia. © 2014 American Neurological Association.

Improvement of Isolated Myoclonus Phenotype in Myoclonus Dystonia after Pallidal Deep Brain Stimulation

PubMed Central

Ramdhani, Ritesh A.; Frucht, Steven J.; Behnegar, Anousheh; Kopell, Brian H.

2016-01-01

Background Myoclonus–dystonia is a condition that manifests predominantly as myoclonic jerks with focal dystonia. It is genetically heterogeneous with most mutations in the epsilon sarcoglycan gene (SGCE). In medically refractory cases, deep brain stimulation (DBS) has been shown to provide marked sustainable clinical improvement, especially in SGCE-positive patients. We present two patients with myoclonus–dystonia (one SGCE positive and the other SGCE negative) who have the isolated myoclonus phenotype and had DBS leads implanted in the bilateral globus pallidus internus (GPi). Methods We review their longitudinal Unified Myoclonus Rating Scale scores along with their DBS programming parameters and compare them with published cases in the literature. Results Both patients demonstrated complete amelioration of all aspects of myoclonus within 6–12 months after surgery. The patient with the SGCE-negative mutation responded just as well as the patient who was SGCE positive. High-frequency stimulation (130 Hz) with amplitudes greater than 2.5 V provided therapeutic benefit. Discussion This case series demonstrates that high frequency GPi-DBS is effective in treating isolated myoclonus in myoclonus–dystonia, regardless of the presence of SGCE mutation. PMID:26989574

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. © The Author(s) 2015.

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

PubMed

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 improve

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

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Lack of efficacy of levetiracetam in oromandibular and cranial dystonia.

PubMed

Park, J E; Srivanitchapoom, P; Maurer, C W; Mathew, P; Sackett, J; Paine, R; Ramos, V L; Hallett, M

2017-08-01

To determine the efficacy of levetiracetam in oromandibular or cranial dystonia. We recruited seven subjects with oromandibular or cranial dystonia. Five completed the study, median age was 71 years (range 42-79 years), median disease duration was 12 years (range 2-30 years). Participants were randomized to receive levetiracetam or placebo and were then crossed over. They titrated up to a total daily dose of 4000 mg or the maximum tolerated dose over 3 weeks and maintained that dose for another 3 weeks. The primary endpoint was the percent change of the eyes, mouth, speech, and swallowing Burke-Fahn-Marsden (BFM) subscores from baseline to weeks 6 and 14. Additional endpoints included the BFM subscore at weeks 3 and 11, and the global dystonia severity (GDS) subscore at weeks 3, 6, 11, and 14, as well as all adverse side effects. The mean percent increase in the BFM subscore (placebo: 31.25%, levetiracetam: 12.16%) was not significantly different between the two arms according to the Friedman analysis. The Wilcoxon signed-rank test showed that these percent changes were not significant, indicating that there was no statistical clinical worsening in either arm. The mean percent change of the BFM subscore at weeks 3 and 11 and the mean percent change of the GDS subscore at weeks 3, 6, 11, and 14 were not significantly different between the two arms, and the Wilcoxon signed-rank test did not show statistical significance. Levetiracetam does not appear to be efficacious in patients with oromandibular or cranial dystonia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cranial dystonia, blepharospasm and hemifacial spasm: clinical features and treatment, including the use of botulinum toxin.

PubMed Central

Kraft, S P; Lang, A E

1988-01-01

Blepharospasm, the most frequent feature of cranial dystonia, and hemifacial spasm are two involuntary movement disorders that affect facial muscles. The cause of blepharospasm and other forms of cranial dystonia is not known. Hemifacial spasm is usually due to compression of the seventh cranial nerve at its exit from the brain stem. Cranial dystonia may result in severe disability. Hemifacial spasm tends to be much less disabling but may cause considerable distress and embarrassment. Patients affected with these disorders are often mistakenly considered to have psychiatric problems. Although the two disorders are quite distinct pathophysiologically, therapy with botulinum toxin has proven very effective in both. We review the clinical features, proposed pathophysiologic features, differential diagnosis and treatment, including the use of botulinum toxin, of cranial dystonia and hemifacial spasm. Images Fig. 2 Fig. 3 PMID:3052771

Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia.

PubMed

Belvisi, Daniele; Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Parvez, Ahmad Khandker; Agostino, Rocco; Fabbrini, Giovanni; Berardelli, Alfredo

2013-02-01

Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Interventional studies in childhood dystonia do not address the concerns of children and their carers.

PubMed

Lumsden, Daniel E; Gimeno, Hortensia; Tustin, Kylee; Kaminska, Margaret; Lin, Jean-Pierre

2015-05-01

This study aimed to determine the main concerns/priorities of the parents and carers of children with dystonia referred to our service and whether medical interventional studies addressed these concerns. Records of children assessed by our service from June 2005-December 2012 were reviewed and expressed parental/carer concerns at initial assessment categorized using the International Classification of Functioning (ICF) Framework. Medline, CINAHL and Embase databases were searched for outcome measures of medical and surgical interventional studies in childhood dystonia. Data was collected from 273 children and young people with dystonia. The most commonly expressed concerns were: pain (104/273, 38.1%); difficulties in delivering activities of daily-living (66/273, 24.2%), difficulties with hand-use (59/273, 21.6%) and seating (41/273, 15.0%). Literature review identified 70 interventional studies, 46 neurosurgical and 24 pharmacological. The majority of neurosurgical studies (34/46) used impairment scales to measure change, with pharmacological studies typically reporting more subjective changes in motor symptoms. Only a minority of studies used assessments or scales capable of objectively addressing the concerns reported by our cohort. Existing interventional studies in childhood dystonia poorly address the main concerns of children with dystonia and their carers, limiting the conclusions which may be drawn as to true impact of these interventions in childhood. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

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…

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

Reliability and concurrent validity of postural asymmetry measurement in adolescent idiopathic scoliosis

PubMed Central

Prowse, Ashleigh; Aslaksen, Berit; Kierkegaard, Marie; Furness, James; Gerdhem, Paul; Abbott, Allan

2017-01-01

AIM To investigate the reliability and concurrent validity of the Baseline® Body Level/Scoliosis meter for adolescent idiopathic scoliosis postural assessment in three anatomical planes. METHODS This is an observational reliability and concurrent validity study of adolescent referrals to the Orthopaedic department for scoliosis screening at Karolinska University Hospital, Stockholm, Sweden between March-May 2012. A total of 31 adolescents with idiopathic scoliosis (13.6 ± 0.6 years old) of mild-moderate curvatures (25° ± 12°) were consecutively recruited. Measurement of cervical, thoracic and lumbar curvatures, pelvic and shoulder tilt, and axial thoracic rotation (ATR) were performed by two trained physiotherapists in one day. The intraclass correlation coefficient (ICC) was used to determine the inter-examiner reliability (ICC2,1) and the intra-rater reliability (ICC3,3) of the Baseline® Body Level/Scoliosis meter. Spearman’s correlation analyses were used to estimate concurrent validity between the Baseline® Body Level/Scoliosis meter and Gold Standard Cobb angles from radiographs and the Orthopaedic Systems Inc. Scoliometer. RESULTS There was excellent reliability between examiners for thoracic kyphosis (ICC2,1 = 0.94), ATR (ICC2,1 = 0.92) and lumbar lordosis (ICC2,1 = 0.79). There was adequate reliability between examiners for cervical lordosis (ICC2,1 = 0.51), however poor reliability for pelvic and shoulder tilt. Both devices were reproducible in the measurement of ATR when repeated by one examiner (ICC3,3 0.98-1.00). The device had a good correlation with the Scoliometer (rho = 0.78). When compared with Cobb angle from radiographs, there was a moderate correlation for ATR (rho = 0.627). CONCLUSION The Baseline® Body Level/Scoliosis meter provides reliable transverse and sagittal cervical, thoracic and lumbar measurements and valid transverse plan measurements of mild-moderate scoliosis deformity. PMID:28144582

Reliability and concurrent validity of postural asymmetry measurement in adolescent idiopathic scoliosis.

PubMed

Prowse, Ashleigh; Aslaksen, Berit; Kierkegaard, Marie; Furness, James; Gerdhem, Paul; Abbott, Allan

2017-01-18

To investigate the reliability and concurrent validity of the Baseline ® Body Level/Scoliosis meter for adolescent idiopathic scoliosis postural assessment in three anatomical planes. This is an observational reliability and concurrent validity study of adolescent referrals to the Orthopaedic department for scoliosis screening at Karolinska University Hospital, Stockholm, Sweden between March-May 2012. A total of 31 adolescents with idiopathic scoliosis (13.6 ± 0.6 years old) of mild-moderate curvatures (25° ± 12°) were consecutively recruited. Measurement of cervical, thoracic and lumbar curvatures, pelvic and shoulder tilt, and axial thoracic rotation (ATR) were performed by two trained physiotherapists in one day. The intraclass correlation coefficient (ICC) was used to determine the inter-examiner reliability (ICC2,1) and the intra-rater reliability (ICC3,3) of the Baseline ® Body Level/Scoliosis meter. Spearman's correlation analyses were used to estimate concurrent validity between the Baseline ® Body Level/Scoliosis meter and Gold Standard Cobb angles from radiographs and the Orthopaedic Systems Inc. Scoliometer. There was excellent reliability between examiners for thoracic kyphosis (ICC2,1 = 0.94), ATR (ICC2,1 = 0.92) and lumbar lordosis (ICC2,1 = 0.79). There was adequate reliability between examiners for cervical lordosis (ICC2,1 = 0.51), however poor reliability for pelvic and shoulder tilt. Both devices were reproducible in the measurement of ATR when repeated by one examiner (ICC3,3 0.98-1.00). The device had a good correlation with the Scoliometer (rho = 0.78). When compared with Cobb angle from radiographs, there was a moderate correlation for ATR (rho = 0.627). The Baseline ® Body Level/Scoliosis meter provides reliable transverse and sagittal cervical, thoracic and lumbar measurements and valid transverse plan measurements of mild-moderate scoliosis deformity.

Acute focal dystonia induced by a tricyclic antidepressant in a patient with Wilson disease: a case report.

PubMed

Litwin, T; Chabik, G; Członkowska, A

2013-01-01

The authors present the case of a 19-year-old patient with Wilson disease (WD) who developed symptoms of acute focal dystonia of the left hand (a 'starfish' hand presentation) shortly after treatment with the tricyclic antidepressant clomipramine. The diagnosis of WD was made 8 months earlier based on abnormal copper metabolism parameters and was confirmed by genetic testing. Initially, the patient presented with akathisia, sialorrhea, oromandibular dystonia (occasionally grimacing) and slight dysarthria. The patient's symptoms diminished after treatment with d-penicillamine was initiated. No further deterioration was observed after copper-chelating therapy was started. The authors diagnosed acute focal dystonia induced by clomipramine. Botulinum toxin and intensive rehabilitation was initiated; complete regression of hand dystonia was observed. Based on the case, the authors suggest that care should be exercised with regard to starting medications that could potentially impact the extrapyramidal system in WD patients.

Reduced striatal D2 receptor binding in myoclonus-dystonia.

PubMed

Beukers, R J; Booij, J; Weisscher, N; Zijlstra, F; van Amelsvoort, T A M J; Tijssen, M A J

2009-02-01

To study striatal dopamine D(2) receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using (123)I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D(2) receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out.

[Paroxysmal stereotypy-tic-dystonia syndrome].

PubMed

Cabrera-López, J C; Martí-Herrero, M; Fernández-Burriel, M; Toledo-Bravo de Laguna, L; Domínguez-Ramírez, S; Fortea-Sevilla, S

We report the cases of four males from four different families, who presented paroxysmal episodes from the 1st 2nd year. These episodes were characterised by asymmetrical bilateral dystonia of the upper limbs, predominantly in both hands, and were associated with orofacial dyskinesias, stereotipies (jumping, arm flapping, etc.), facial tics and, occasionally, phonic tics. Consciousness is not affected in any of the cases. These movements are triggered in situations where the patient is relaxed or excited. They occur daily and last from a few seconds to 30 minutes. Between the bouts, they remain asymptomatic. Family cases suggest it is inherited by autosomal dominant transmission, perhaps linked to the X chromosome; in addition, two cases are sporadic. In the only adult, the movements progress to a series of rhythmic bilateral dystonic myoclonias and facial tics dyskinesias. All the studies carried out, EEG, hemogram, biochemical analysis, neuroimaging, copper and ceruloplasmin levels, were normal. 1. We report a non epileptic paroxysmal disorder originating in the extrapyramidal tracts with its own characteristics, with onset during early childhood, which is associated with stereotipies, tics and dystonia; 2. It occurs predominantly in males; 3. It is inherited by autosomal dominant transmission, or perhaps sex linked autosomal dominant inheritance, and there are also sporadic cases; 4. The range of clinical features is very wide and includes cases in which there are few symptoms to others where the extent and gravity of the disorder is very significant.

Genotype-phenotype correlations in THAP1 dystonia: molecular foundations and description of new cases

PubMed Central

LeDoux, Mark S.; Xiao, Jianfeng; Rudzińska, Monika; Bastian, Robert W.; Wszolek, Zbigniew K.; Van Gerpen, Jay A.; Puschmann, Andreas; Momčilović, Dragana; Vemula, Satya R.; Zhao, Yu

2012-01-01

An extensive variety of THAP1 sequence variants have been associated with focal, segmental and generalized dystonia with age of onset ranging from 3 to over 60 years. In previous work, we screened 1,114 subjects with mainly adult-onset primary dystonia (Neurology 2010;74:229-238) and identified 6 missense mutations in THAP1. For this report, we screened 750 additional subjects for mutations in coding regions of THAP1 and interrogated all published descriptions of THAP1 phenotypes (gender, age of onset, anatomical distribution of dystonia, family history and site of onset) to explore the possibility of THAP1 genotype-phenotype correlations and facilitate a deeper understanding of THAP1 pathobiology. We identified 5 additional missense mutations in THAP1 (p.A7D, p.K16E, p.S21C, p.R29Q, and p.I80V). Three of these variants are associated with appendicular tremors, which were an isolated or presenting sign in some of the affected subjects. Abductor laryngeal dystonia and mild blepharospasm can be manifestations of THAP1 mutations in some individuals. Overall, mean age of onset for THAP1 dystonia is 16.8 years and the most common sites of onset are the arm and neck, and the most frequently affected anatomical site is the neck. In addition, over half of patients exhibit either cranial or laryngeal involvement. Protein truncating mutations and missense mutations within the THAP domain of THAP1 tend to manifest at an earlier age and exhibit more extensive anatomical distributions than mutations localized to other regions of THAP1. PMID:22377579

Idiopathic Cervical Hematomyelia in an Infant: Spinal Cord Injury without Radiographic Abnormality Caused by a Trivial Trauma? Case Report and Review of the Literature.

PubMed

Fiaschi, Pietro; Severino, Mariasavina; Ravegnani, Giuseppe Marcello; Piatelli, Gianluca; Consales, Alessandro; Accogli, Andrea; Capra, Valeria; Cama, Armando; Pavanello, Marco

2016-06-01

Spontaneous or idiopathic intramedullary bleeding is a very rare event in pediatric patients. This diagnosis requires an extended clinical, laboratory, and radiologic work-up to rule out all potential causes of hematomyelia. However, children may present with hematomyelia or spinal cord injury without radiographic abnormality even after a minor trauma. A 15-month-old girl presented with a 24-hour history of progressive neurologic deficits. A trivial trauma had occurred a few days before the clinical onset. Head computed tomography scan and craniospinal magnetic resonance imaging revealed an isolated hemorrhagic central medullary lesion extending from the obex to C3 level. No underlying causes of intramedullary bleeding were identified. In the absence of obvious vascular abnormalities, the patient underwent an urgent occipitocervical decompression with hematoma evacuation. Postoperatively, the patient's motor symptoms rapidly resolved, and she was discharged with cervical collar immobilization. We discuss the differential diagnosis of intramedullary bleeding in children, focusing on the diagnostic protocol and therapeutic options in this age group. Copyright © 2016 Elsevier Inc. All rights reserved.

Reaching and writing movements: sensitive and reliable tools to measure genetic dystonia in children.

PubMed

Casellato, Claudia; Zorzi, Giovanna; Pedrocchi, Alessandra; Ferrigno, Giancarlo; Nardocci, Nardo

2011-07-01

The aim of this study was to provide a quantitative assessment of pure dystonia in a group of children. Kinematic and muscular characteristics of unconstrained movements of the upper limb, reaching and writing, were investigated. During reaching, the distinguishing factors of dystonic movement were reduced velocity, loss of muscular activation focalization, and impairment of rest-movement modulation. Muscular parameters were able to linearly discriminate the different levels of severity. These results support the hypothesis that basal ganglia dysfunction is responsible for compromising the motor activity focusing. The handwriting movement revealed that the kinematic coordination was altered depending on dystonia severity scores. The 2 protocols revealed themselves feasible and sensitive for detecting even local and subclinical signs. Hence, this work provides a contribution toward a reliable assessment of pure dystonia, crucial for clinical characterization of patients and evaluation of the different treatment options.

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-05-12

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.

Real-Time Ultrasound Segmentation, Analysis and Visualisation of Deep Cervical Muscle Structure.

PubMed

Cunningham, Ryan J; Harding, Peter J; Loram, Ian D

2017-02-01

Despite widespread availability of ultrasound and a need for personalised muscle diagnosis (neck/back pain-injury, work related disorder, myopathies, neuropathies), robust, online segmentation of muscles within complex groups remains unsolved by existing methods. For example, Cervical Dystonia (CD) is a prevalent neurological condition causing painful spasticity in one or multiple muscles in the cervical muscle system. Clinicians currently have no method for targeting/monitoring treatment of deep muscles. Automated methods of muscle segmentation would enable clinicians to study, target, and monitor the deep cervical muscles via ultrasound. We have developed a method for segmenting five bilateral cervical muscles and the spine via ultrasound alone, in real-time. Magnetic Resonance Imaging (MRI) and ultrasound data were collected from 22 participants (age: 29.0±6.6, male: 12). To acquire ultrasound muscle segment labels, a novel multimodal registration method was developed, involving MRI image annotation, and shape registration to MRI-matched ultrasound images, via approximation of the tissue deformation. We then applied polynomial regression to transform our annotations and textures into a mean space, before using shape statistics to generate a texture-to-shape dictionary. For segmentation, test images were compared to dictionary textures giving an initial segmentation, and then we used a customized Active Shape Model to refine the fit. Using ultrasound alone, on unseen participants, our technique currently segments a single image in [Formula: see text] to over 86% accuracy (Jaccard index). We propose this approach is applicable generally to segment, extrapolate and visualise deep muscle structure, and analyse statistical features online.

Altered dorsal premotor-motor interhemispheric pathway activity in focal arm dystonia.

PubMed

Koch, Giacomo; Schneider, Susanne; Bäumer, Tobias; Franca, Michele; Münchau, Alexander; Cheeran, Binith; Fernandez del Olmo, Miguel; Cordivari, Carla; Rounis, Elisabeth; Caltagirone, Carlo; Bhatia, Kailash; Rothwell, John C

2008-04-15

Given the possible role of dorsal premotor cortex (PMd) in the pathophysiology of dystonia, we used transcranial magnetic stimulation (TMS) methods to study PMd and PMd-primary motor cortex (M1) interactions in patients with focal arm dystonia. Here, we tested the connectivity between left PMd and right M1 as well as the intracortical excitability of PMd in 11 right-handed patients with focal arm/hand dystonia and nine age-matched healthy controls. The results showed that excitability of the inhibitory connection between PMd and M1 was reduced in patients, but there was no significant difference to healthy subjects in the excitability of the facilitatory connection. A triple stimulation technique in which pairs of TMS pulses are given over PMd and their interaction measured in terms of the effect on the baseline PMd-M1 connection failed to reveal the usual pattern of interaction between the pairs of PMd stimuli. Indeed, the results in patients were similar to those seen in a group of young healthy subjects after the excitability of PMd had been changed by pretreatment with high-frequency rTMS. We suggest that reduced transcallosal inhibition from the PMd may be involved in the altered pattern of abnormal muscle contractions of agonists and antagonists (overflow). 2007 Movement Disorder Society

Risk factors for postoperative retropharyngeal hematoma after anterior cervical spine surgery.

PubMed

O'Neill, Kevin R; Neuman, Brian; Peters, Colleen; Riew, K Daniel

2014-02-15

Retrospective review of prospective database. To investigate risk factors involved in the development of anterior cervical hematomas and determine any impact on patient outcomes. Postoperative (PO) hematomas after anterior cervical spine surgery require urgent recognition and treatment to avoid catastrophic patient morbidity or death. Current studies of PO hematomas are limited. Cervical spine surgical procedures performed on adults by the senior author at a single academic institution from 1995 to 2012 were evaluated. Demographic data, surgical history, operative data, complications, and neck disability index (NDI) scores were recorded prospectively. Cases complicated by PO hematoma were reviewed, and time until hematoma development and surgical evacuation were determined. Patients who developed a hematoma (HT group) were compared with those that did not (no-HT group) to identify risk factors. NDI outcomes were compared at early (<11 mo) and late (>11 mo) time points. There were 2375 anterior cervical spine surgical procedures performed with 17 occurrences (0.7%) of PO hematoma. In 11 patients (65%) the hematoma occurred within 24 hours PO, whereas 6 patients (35%) presented at an average of 6 days postoperatively. All underwent hematoma evacuation, with 2 patients (12%) requiring emergent cricothyroidotomy. Risk factors for hematoma were found to be (1) the presence of diffuse idiopathic skeletal hyperostosis (relative risk = 13.2, 95% confidence interval = 3.2-54.4), (2) presence of ossification of the posterior longitudinal ligament (relative risk = 6.8, 95% confidence interval = 2.3-20.6), (3) therapeutic heparin use (relative risk 148.8, 95% confidence interval = 91.3-242.5), (4) longer operative time, and (5) greater number of surgical levels. The occurrence of a PO hematoma was not found to have a significant impact on either early (HT: 30, no-HT: 28; P = 0.86) or late average NDI scores (HT: 28, no-HT 31; P = 0.76). With fast recognition and treatment, no

Effect of Transcranial Direct Current Stimulation on Neurorehabilitation of Task-Specific Dystonia: A Double-Blind, Randomized Clinical Trial.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Álvaro

2015-09-01

Task-specific focal hand dystonia can disable affected individuals. Although neurorehabilitation techniques such as sensory motor retuning can result in complete recovery in some patients, it requires many months of treatment. Combining transcranial direct current stimulation (tDCS) with neurorehabilitation is a new and promising approach that can help these patients. However, the results in different studies are contradictory. Analyze whether delivering tDCS (cathode over left and anode over right parietal region) during the neurorehabilitation process for musicians with dystonia can increase the effectiveness of therapy. A parallel double-blind randomized design was used to study 30 musicians with right-hand primary focal dystonia. All patients underwent a 2-week course of neurorehabilitation based on sensory motor retuning therapy coupled with either real or sham tDCS for the first 30 minutes of each daily 1-hour therapy session (total 10 sessions). The therapist and patient were blind to the tDCS condition. A dystonia severity score was obtained before and after the 2-week protocol. The therapist also rated the evolution of each patient. Both groups significantly improved their dystonia severity score during the 2 weeks. Score differences were 88.23 (±40.51) and 63.36 (±30.57) for the active and sham groups, respectively. The active group showed a statistically significant greater improvement. Biparietal tDCS with left-sided cathode is a safe technique that does not interfere with the neurorehabilitation procedure and can increase therapy effectiveness in rehabilitation patients with right-hand task-specific focal dystonia.

Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions

PubMed Central

Zakirova, Zuchra; Fanutza, Tomas; Bonet, Justine; Readhead, Ben; Zhang, Weijia; Yi, Zhengzi; Beauvais, Genevieve; Zwaka, Thomas P.; Ozelius, Laurie J.; Blitzer, Robert D.; Gonzalez-Alegre, Pedro

2018-01-01

Dystonia is characterized by involuntary muscle contractions. Its many forms are genetically, phenotypically and etiologically diverse and it is unknown whether their pathogenesis converges on shared pathways. Mutations in THAP1 [THAP (Thanatos-associated protein) domain containing, apoptosis associated protein 1], a ubiquitously expressed transcription factor with DNA binding and protein-interaction domains, cause dystonia, DYT6. There is a unique, neuronal 50-kDa Thap1-like immunoreactive species, and Thap1 levels are auto-regulated on the mRNA level. However, THAP1 downstream targets in neurons, and the mechanism via which it causes dystonia are largely unknown. We used RNA-Seq to assay the in vivo effect of a heterozygote Thap1 C54Y or ΔExon2 allele on the gene transcription signatures in neonatal mouse striatum and cerebellum. Enriched pathways and gene ontology terms include eIF2α Signaling, Mitochondrial Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and Synaptic LongTerm Depression, which are dysregulated in a genotype and tissue-dependent manner. Electrophysiological and neurite outgrowth assays were consistent with those enrichments, and the plasticity defects were partially corrected by salubrinal. Notably, several of these pathways were recently implicated in other forms of inherited dystonia, including DYT1. We conclude that dysfunction of these pathways may represent a point of convergence in the pathophysiology of several forms of inherited dystonia. PMID:29364887

Stuttering in Parkinson's disease after deep brain stimulation: A note on dystonia and low-frequency stimulation.

PubMed

Mendonça, Marcelo D; Barbosa, Raquel; Seromenho-Santos, Alexandra; Reizinho, Carla; Bugalho, Paulo

2018-04-01

Stuttering, a speech fluency disorder, is a rare complication of Deep Brain Stimulation (DBS) in Parkinson's Disease (PD). We report a 61 years-old patient with PD, afflicted by severe On and Off dystonia, treated with Subthalamic Nucleus DBS that developed post-DBS stuttering while on 130 Hz stimulation. Stuttering reduction was noted when frequency was changed to 80 Hz, but the previously observed dystonia improvement was lost. There are no reports in literature on patients developing stuttering with low-frequency stimulation. We question if low-frequency stimulation could have a role for managing PD's post-DBS stuttering, and notice that stuttering improvement was associated with dystonia worsening suggesting that they are distinct phenomena. Copyright © 2018 Elsevier Ltd. All rights reserved.

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

PubMed

Pareja, Juan A; Montojo, Teresa; Guerrero, Ángel L; Álvarez, Mónica; Porta-Etessam, Jesús; Cuadrado, María L

2015-01-01

Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually. © 2015 American Headache Society.

Spine Topographical Distribution of Skin α-Synuclein Deposits in Idiopathic Parkinson Disease.

PubMed

Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni; Scaglione, Cesa; Capellari, Sabina; Fileccia, Enrico; Avoni, Patrizia; Liguori, Rocco

2017-05-01

Phosphorylated α-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Continuous involuntary hand movements and schizencephaly: epilepsia partialis continua or dystonia?

PubMed

Marinelli, Lucio; Bonzano, Laura; Saitta, Laura; Trompetto, Carlo; Abbruzzese, Giovanni

2012-04-01

Schizencephaly is regarded as a malformation of cortical development (due to abnormal neuronal organization) and may be associated with continuous involuntary hand movements. The mechanisms underlying these movements are not clear and both dystonia and epilepsia partialis continua have been considered in previously reported cases. We describe a young patient affected by schizencephaly and continuous involuntary movements of the contralateral hand. Functional MRI showed bilateral cerebral activation, while the subject performed tapping movements with the affected hand and no significant difference in the activation pattern after diazepam infusion. Standard and back-averaged EEG showed no alterations. The results obtained from these investigations and the clinical features of the involuntary movements are not in favor of an epileptic genesis, while support the diagnosis of secondary dystonia.

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.

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

What parents think and feel about deep brain stimulation in paediatric secondary dystonia including cerebral palsy: A qualitative study of parental decision-making.

PubMed

Austin, Allana; Lin, Jean-Pierre; Selway, Richard; Ashkan, Keyoumars; Owen, Tamsin

2017-01-01

Dystonia is characterised by involuntary movements and postures. Deep Brain Stimulation (DBS) is effective in reducing dystonic symptoms in primary dystonia in childhood and to lesser extent in secondary dystonia. How families and children decide to choose DBS surgery has never been explored. To explore parental decision-making for DBS in paediatric secondary dystonia. Data was gathered using semi-structured interviews with eight parents of children with secondary dystonia who had undergone DBS. Interviews were analysed using Interpretative Phenomenological Analysis. For all parents the decision was viewed as significant, with life altering consequences for the child. These results suggested that parents were motivated by a hope for a better life and parental duty. This was weighed against consideration of risks, what the child had to lose, and uncertainty of DBS outcome. Decisions were also influenced by the perspectives of their child and professionals. The decision to undergo DBS was an ongoing process for parents, who ultimately were struggling in the face of uncertainty whilst trying to do their best as parents for their children. These findings have important clinical implications given the growing referrals for consideration of DBS childhood dystonia, and highlights the importance of further quantitative research to fully establish the efficacy of DBS in secondary dystonia to enhance informed decision-making. Copyright © 2016. Published by Elsevier Ltd.

Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Ability, and Communication Function Classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a 'Rosetta Stone' study.

PubMed

Elze, Markus C; Gimeno, Hortensia; Tustin, Kylee; Baker, Lesley; Lumsden, Daniel E; Hutton, Jane L; Lin, Jean-Pierre S-M

2016-02-01

Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales. Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales. All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, p<0.001), with worse dystonia severity implying worse function. Secondary dystonias had worse dystonia and less function than primary dystonias (p<0.001). A longer proportion of life lived with dystonia is associated with more severe dystonia (rs =0.42, p<0.001). The BFM-M is strongly linked with the GMFCS, MACS, and CFCS, irrespective of aetiology. Each scale offers interrelated but complementary information and is applicable to all aetiologies. Movement disorders including cerebral palsy can be effectively evaluated using these scales. © 2015 Mac Keith Press.

Dopamine Dysfunction in DYT1 Dystonia

DTIC Science & Technology

2015-07-01

20mM Tris-Cl (pH 7.6), 137 mM NaCl, 0.1% Tween 20, the membranes were incubated overnight at 4°C with rabbit anti-tor- sinA antibody (1:500; Abcam...during the juvenile period to changes in tor- sinA expression or function. Another consideration is the potential compensatory effects of torsinB, which...Buckley AC, Burdette AJ, et al. (2010) Chemical enhancement of tor- sinA function in cell and animal models of torsion dystonia. Dis Model Mech 3: 386–396

Rating scales for dystonia in cerebral palsy: reliability and validity.

PubMed

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

2010-06-01

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). Three raters independently scored videotapes of 10 patients (five males, five females; mean age 13 y 3 mo, SD 5 y 2 mo, range 5-22 y). One patient each was classified at levels I-IV in the Gross Motor Function Classification System and six patients were classified at level V. Reliability was measured by (1) intraclass correlation coefficient (ICC) for interrater reliability, (2) standard error of measurement (SEM) and smallest detectable difference (SDD), and (3) Cronbach's alpha for internal consistency. Validity was assessed by Pearson's correlations among the three scales used and by content analysis. Moderate to good interrater reliability was found for total scores of the three scales (ICC: BADS=0.87; BFMMS=0.86; UDRS=0.79). However, many subitems showed low reliability, in particular for the UDRS. SEM and SDD were respectively 6.36% and 17.72% for the BADS, 9.88% and 27.39% for the BFMMS, and 8.89% and 24.63% for the UDRS. High internal consistency was found. Pearson's correlations were high. Content validity showed insufficient accordance with the new CP definition and classification. Our results support the internal consistency and concurrent validity of the scales; however, taking into consideration the limitations in reliability, including the large SDD values and the content validity, further research on methods of assessment of dystonia is warranted.

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in dystonia cases vs. controls.

PubMed

Louis, Elan D; Factor-Litvak, Pam; Michalec, Monika; Jiang, Wendy; Zheng, Wei

2014-09-01

Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson's disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. Blood [HA] was quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. Mean log blood [HA] in dystonia cases was similar to that of controls (0.41±0.51g(-10)/ml vs. 0.38±0.61g(-10)/ml, t=0.42, p=0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR)unadjusted=1.11, 95% confidence interval (CI)=0.69-1.79, p=0.68; ORadjusted=1.07, 95% CI=0.58-1.97, p=0.84. In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson's disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Blood Harmane (1-methyl-9H-pyrido[3,4-b]indole) Concentration in Dystonia Cases vs. Controls

PubMed Central

Louis, Elan D.; Factor-Litvak, Pam; Michalec, Monika; Jiang, Wendy; Zheng, Wei

2014-01-01

Background Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson’s disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. Objectives We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. Methods Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. Results Mean log blood [HA] in dystonia cases was similar to that of controls (0.41 ± 0.51 g −10/ml vs. 0.38 ± 0.61 g−10/ml, t = 0.42, p = 0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR) unadjusted = 1.11, 95% confidence interval (CI) = 0.69 – 1.79, p = 0.68; OR adjusted = 1.07, 95% CI = 0.58 – 1.97, p = 0.84. Conclusions In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson’s disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders. PMID:24968164

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.

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

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

Coordination of Reach-to-Grasp Kinematics in Individuals With Childhood-Onset Dystonia Due to Hemiplegic Cerebral Palsy.

PubMed

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

2016-05-01

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.

A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome.

PubMed

Ezquerra, Mario; Campdelacreu, Jaume; Muñoz, Esteban; Tolosa, Eduardo; Martí, María J

2005-02-01

X-linked dystonia-deafness syndrome (Mohr-Tranebjaerg syndrome) is a rare neurodegenerative disease characterized by hearing loss and dystonia. So far, 7 mutations in the coding region of the DDP1 gene have been described. They consist of frameshift, nonsense, missense mutations or deletions. To investigate the presence of mutations in the DDP1 gene in a family with dystonia-deafness syndrome. Seven members belonging to 2 generations of a family with 2 affected subjects underwent genetic analysis. Mutational screening in the DDP1 gene was made through DNA direct sequencing. We found an intronic mutation in the DDP1 gene. It consists of an A-to-C substitution in the position -23 in reference to the first nucleotide of exon 2 (IVS1-23A>C). The mutation was present in 2 affected men and their respective unaffected mothers, whereas it was absent in the healthy men from this family and in 90 healthy controls. Intronic mutations in the DDP1 gene can also cause X-linked dystonia-deafness syndrome. In our case, the effect of the mutation could be due to a splicing alteration.

Electromyographic evidence in support of a knock-in mouse model of DYT1 Dystonia.

PubMed

DeAndrade, Mark P; Trongnetrpunya, Amy; Yokoi, Fumiaki; Cheetham, Chad C; Peng, Ning; Wyss, J Michael; Ding, Mingzhou; Li, Yuqing

2016-11-01

DYT1 dystonia is an autosomal-dominant movement disorder characterized by abnormal, often repetitive, movements and postures. Its hallmark feature is sustained or intermittent contractions of muscles involving co-contractions of antagonist muscle pairs. The symptoms are relieved with the anticholinergic drug trihexyphenidyl. The primary mutation is a trinucleotide deletion (ΔGAG) in DYT1/TOR1A, which codes for torsinA. Previous studies showed that (1) heterozygous Dyt1 ΔGAG knock-in mice, which have an analogous mutation in the endogenous gene, exhibit motor deficits and altered corticostriatal synaptic plasticity in the brain and (2) these deficits can be rescued by trihexyphenidyl. However, brain imaging studies suggest that the Dyt1 knock-in mouse models nonmanifesting mutation carriers of DYT1 dystonia. The aim of this work was to examine the hallmark features of DYT1 dystonia in the Dyt1 knock-in mice by analyzing muscular activities. Wireless telemetry devices with biopotential channels were implanted to the bicep and the rectus femori muscles in Dyt1 knock-in mice, and muscular activities were recorded before and after trihexyphenidyl administration. (1) Consistent with DYT1 dystonia patients, Dyt1 knock-in mice showed sustained contractions and co-contractions of the antagonistic bicep femoris and rectus femoris. (2) The abnormal muscle contractions were normalized by trihexyphenidyl. The results suggest that the motor deficits in Dyt1 knock-in mice are likely produced by abnormal muscle contractions, and Dyt1 knock-in mice can potentially be used as a manifesting disease model to study pathophysiology and develop novel therapeutics. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Evaluation of dystonia in children and adolescents treated with atomoxetine within the Truven MarketScan database: a retrospective cohort study.

PubMed

Meyers, Kristin J; Upadhyaya, Himanshu P; Goodloe, Robert; Kryzhanovskaya, Ludmila A; Liles-Burden, Marie A; Kellier-Steele, Nicole A; Mancini, Michele

2018-05-01

Atomoxetine is a non-stimulant drug indicated for the treatment of attention-deficit/hyperactivity disorder in children aged ≥6 years, adolescents, and adults. In this retrospective cohort study, the incidence and risk of dystonia in children and adolescents treated with atomoxetine was compared to a propensity score-matched cohort of stimulant users. Data between 1 January 2006 and 31 December 2014 from patients aged 6-17 years in the Truven Health Analytics MarketScan database were used to generate two cohorts of patients: (1) atomoxetine users and (2) stimulant (methylphenidates or amphetamines) users. A Cox proportional hazards regression model was used to compare incidence of dystonia across propensity score-matched cohorts. Of the 70,657 atomoxetine users, 70,655 users were propensity score-matched to a stimulant user. In the atomoxetine- and stimulant-treated cohorts, the crude incidence rates of dystonia were 54.9 (95% CI: 27.1-82.7) and 77.9 (95% CI: 49.1-106.8) per 100,000 person-years, respectively. The hazard ratio for occurrence of dystonia with atomoxetine use relative to stimulant use was 0.68 (95% CI: 0.36 - 1.28; P = 0.23). In this large retrospective cohort study, there was no significant difference in incidence or risk of dystonia among patients treated with atomoxetine compared to stimulants.

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), ...

Stereotactic ventrooralis thalamotomy for task-specific focal hand dystonia (writer's cramp).

PubMed

Taira, Takaomi; Hori, Tomokatsu

2003-01-01

Writer's cramp is a type of focal dystonia due to dysfunction of the pallido-thalamo-cortical circuit. The symptom is refractory to most conservative treatment, though botulinum toxin injection is generally used for symptomatic relief. As a surgical treatment of dystonia, we performed stereotactic nucleus ventrooralis (Vo) thalamotomy for dystonic cramp of the hand. Twelve patients (5 men, 3 women; age 26-40 years, mean 32.1 years) with medically intractable task-specific focal dystonia of the hand underwent Vo thalamotomy. The stereotactic target was chosen at the junction of the anterior and posterior Vo nuclei. The mean duration of the symptom ranged from 3 to 6 years (mean 4.5 years.) All patients had complained of difficulty in writing. Seven patients were professionals, such as a comic artist, guitarist and barber, and, because of the dystonic symptoms occurring during their work, they had stopped pursuing their profession. All patients showed immediate postoperative disappearance of dystonic symptoms, and the effect was sustained during the follow-up period (3-33 months, mean 13.1 months), except in one case. Two patients showed partial recurrence of the symptom and underwent second thalamotomy 5 months after the initial surgery with satisfactory results. The score on the writer's cramp rating scale decreased significantly (p < 0.001) after Vo thalamotomy. There were no permanent operative complications. There was no mortality or permanent morbidity. Although a longer follow-up is needed, stereotactic Vo thalamotomy is a useful and safe therapeutic option for writer's cramp. Copyright 2003 S. Karger AG, Basel

Juvenile Idiopathic Arthritis

MedlinePlus

... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

MedlinePlus

... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

Life satisfaction of musicians with focal dystonia.

PubMed

Lee, A; Eich, C; Ioannou, C I; Altenmüller, E

2015-07-01

Little is known about the effects of musicians' dystonia (MD) on patients' life satisfaction. To assess general life satisfaction in patients with MD with regard to their health and jobs, in relation to the duration and course of the condition. We asked patients with MD and a group of healthy musicians (controls) to complete a life satisfaction questionnaire. We analysed responses from those who had to change their profession and those who did not, and we assessed life satisfaction scores in relation to the duration and the course of the condition. Of the 642 patients contacted, 295 responded (46%). We excluded 52 amateur musicians and analysed a sample of 243 patients with MD. We contacted an unknown number of healthy musicians and 57 responded. We found no differences in life satisfaction between patients and controls or between patients who had to change their profession and those who did not and no correlations between life satisfaction and the duration or the course of the disease. Musicians find a way to cope with dystonia, irrespective of the course of the disease or a change of profession. Patients should be made aware of self-regulatory mechanisms and the probability of being able to cope and be supported in selecting their goals and achieving them. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validation of the XDP-MDSP rating scale for the evaluation of patients with X-linked dystonia-parkinsonism.

PubMed

Pasco, Paul Matthew D; Jamora, Roland Dominic G; Rosales, Raymond L; Diesta, Cid Czarina E; Ng, Arlene R; Teleg, Rosalia A; Go, Criscely L; Lee, Lillian; Fernandez, Hubert H

2017-01-01

X-linked dystonia-parkinsonism(XDP) is a neurodegenerative disorder endemic to the Philippines. A rating scale was developed by the authors under the guidance of the Movement Disorder Society of the Philippines (MDSP) to assess XDP severity and progression, functional impact, and response to treatment in future clinical trials. Our main objective was to validate our new scale, the XDP-MDSP scale. The initial validation process included pragmatic testing to XDP patients followed by a modified Delphi procedure with an international advisory panel of dystonia, parkinsonism and scale development experts. Pearson correlation was used to assess construct validity of our new scale versus the assess construct validity of our new scale versus standard dystonia, parkinsonism, non-motor and functional scales; and also to assess divergent validity against behavioral and cognitive scales. The 37-item XDP-MDSP scale has five parts: I-dystonia, II-parkinsonism, III-non-motor features, IV-ADL, and V-global impression. After initial validation, the scale was administered to 204 XDP patients. Inter-domain correlation for the first four parts was acceptable. The correlation between these domains and the global rating was slightly lower. Correlations between Parts I, II, III, and IV versus standard dystonia, parkinsonism, non-motor and functional scales were acceptable with values ranging from 0.323 to 0.428. For divergent validity, a significant correlation was seen with behavioral scales. No significant correlation was noted with the cognitive scale. The proposed XDP-MDSP scale is internally valid but the global rating subscale may need to be modified or eliminated. While there is convergent validity, divergent validation was successful only on cognitive and not behavioral scales. The frequent co-occurrence of anxiety and depression, and its effect on the motor and functional state, may explain this finding.

Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump

PubMed Central

Isaksen, Toke Jost; Vedovato, Natascia; Vitenzon, Ariel; Gadsby, David C.; Khodakhah, Kamran

2017-01-01

Mutations in the neuron-specific α3 isoform of the Na+/K+-ATPase are found in patients suffering from Rapid onset Dystonia Parkinsonism and Alternating Hemiplegia of Childhood, two closely related movement disorders. We show that mice harboring a heterozygous hot spot disease mutation, D801Y (α3+/D801Y), suffer abrupt hypothermia-induced dystonia identified by electromyographic recordings. Single-neuron in vivo recordings in awake α3+/D801Y mice revealed irregular firing of Purkinje cells and their synaptic targets, the deep cerebellar nuclei neurons, which was further exacerbated during dystonia and evolved into abnormal high-frequency burst-like firing. Biophysically, we show that the D-to-Y mutation abolished pump-mediated Na+/K+ exchange, but allowed the pumps to bind Na+ and become phosphorylated. These findings implicate aberrant cerebellar activity in α3 isoform-related dystonia and add to the functional understanding of the scarce and severe mutations in the α3 isoform Na+/K+-ATPase. PMID:28472154

Juvenile idiopathic arthritis.

PubMed

Boros, Christina; Whitehead, Ben

2010-09-01

Juvenile idiopathic arthritis is the most common rheumatic disease in childhood, occurring in approximately 1:500 children. Despite a recent expansion in treatment options and improvement of outcomes, significant morbidity still occurs. This article outlines the clinical manifestations, assessment, detection of complications, treatment options and monitoring requirements, with the aid of guidelines recently published by The Royal Australian College of General Practitioners, which provide practical support for general practitioners to ensure best practice care and to prevent lifelong disability in patients with juvenile idiopathic arthritis. General practice plays an important role in the early detection, initial management and ongoing monitoring of children with juvenile idiopathic arthritis. Early detection involves understanding the classification framework for subtypes of juvenile idiopathic arthritis, and being aware of the clinical manifestations and how to look for them, through history, examination and appropriate investigation. The major extra-articular manifestations of juvenile idiopathic arthritis are uveitis and growth disturbance. Treatment options include nonsteroidal anti-inflammatory drugs, methotrexate, biologic agents, and corticosteroids. Management using a multidisciplinary approach can prevent long term sequelae. Unfortunately, approximately 50% of children will have active disease as adults.

Deep anterior cerebellar stimulation reduces symptoms of secondary dystonia in patients with cerebral palsy treated due to spasticity.

PubMed

Sokal, Paweł; Rudaś, Marcin; Harat, Marek; Szylberg, Łukasz; Zieliński, Piotr

2015-08-01

Deep anterior cerebellar stimulation (DACS) is a neuromodulation therapy of spasticity. Bilateral DACS is applied in young patients with cerebral palsy (CP). In these patients symptoms of spasticity coexist with symptoms of focal or segmental dystonia, which can cause chronic pain. We performed the study to investigate the therapeutic effects of DACS in spasticity, secondary dystonia and pain. We examined 10 from 13 patients with CP treated with DACS due to spasticity in years 2006-2012. We compared Ashworth scores of spasticity, VAS scale of pain and UDRS (Unified Dystonia Rating Scale) score before DACS and after it in follow-up lasting from 2 to 11 years it in these patients basing on clinical examination and evaluating forms given by the patients or parents. We received statistically significant reduction of spasticity in upper extremities (median: from 3 to 1,5 in Ashworth scale) in 8 patients (p = 0,01), in lower extremities in 7 patients (median: from 3 to 1,75) (p = 0,02). Symptoms of focal dystonia were reduced. Total score for the UDRS (median = 18,0 before surgery) after DACS decreased significantly (median = 10,3) (p = 0,043). Change in consecutive parts of UDRS before (median = 1,6) and after (median = 1,0) surgery in 7 patients had statistical significance (p = 0,0179). There were not significant changes in intensity of pain before and after surgery (p = 0,108). Chronic bilateral DACS aimed for spasticity treatment not only decreases muscular tone in quadriplegic or paraplegic patients with CP but also is associated with reduction of symptoms of focal or segmental, secondary dystonia. Copyright © 2015 Elsevier B.V. All rights reserved.

Vocal cord paralysis: What matters between idiopathic and non-idiopathic cases?

PubMed

Özbal Koç, Ayça Eltaf; Türkoğlu, Seda Babakurban; Erol, Ozan; Erbek, Selim

2016-01-01

This study aims to evaluate the demographic and clinical characteristics of patients with idiopathic and non-idiopathic vocal cord paralysis (VCP). This retrospective cohort was performed on data extracted from medical files of 92 consecutive patients (43 males, 49 females; median age 52.1±23.1 years; min. 1 - max. 87) with VCP diagnosed in the otorhinolaryngology department between April 2012 and December 2015. Diagnoses associated with VCP, side of involvement (right, left or bilateral) and previous medical histories were noted and compared between patients with idiopathic and non-idiopathic VCP. Vocal cord paralysis occurred on the left side (n=56, 60.9%), right side (n=28, 30.4%) or bilaterally (n=8, 8.7%). A clinical entity related with VCP was identified in 63 patients (68.5%), while 29 (31.5%) patients had idiopathic VCP. Most common etiologies for VCP were thyroid surgery (n=32, 34.8%), cardiovascular surgery (n=9, 9.8%), lung cancer (n=6, 6.5%) and cardiac anomalies (n=4, 4.3%), respectively. Patients with idiopathic VCP were significantly older (p<0.001), while gender distribution (p=0.121) and side of involvement (p=0.340) did not differ between two groups. Vocal cord paralysis is a relatively common clinical entity with substantial rate of morbidity. Identification of the underlying etiology and awareness on the clinical characteristics are keystones for foreseeing complications and determining the appropriate therapeutic modality.

Thalamic Deep Brain Stimulation for Writer's Cramp.

PubMed

Cho, Chul Bum; Park, Hae Kwan; Lee, Kyung Jin; Rha, Hyoung Kyun

2009-07-01

Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. There has been renewed interest in neurosurgical procedures for the treatment of dystonia over the past several years. In particular, deep brain stimulation (DBS) has received increasing attention as a therapeutic option for patients with dystonia. However, to date, limited reporters made investigations into DBS in relation to the Writer's cramp. In this case, unilateral Ventro-oralis complex (Vo) DBS resulted in a major improvement in patient's focal dystonic movement disorders. Her post-operative Burke-Fahn-Marsden Dystonia Rating (BFMDR) scale demonstrated 1 compared with pre-operative BFMDR scale 4. We conclude that thalamic Vo complex DBS may be an important neurosurgical therapeutic option for Writer's cramp.

Idiopathic hypersomnia.

PubMed

Billiard, Michel; Sonka, Karel

2016-10-01

Idiopathic hypersomnia continues to evolve from the concept of "sleep drunkenness" introduced by Bedrich Roth in Prague in 1956 and the description of idiopathic hypersomnia with two forms, polysymptomatic and monosymptomatic, by the same Bedrich Roth in 1976. The diagnostic criteria of idiopathic hypersomnia have varied with the successive revisions of the International classifications of sleep disorders, including the recent 3rd edition. No epidemiological studies have been conducted so far. Disease onset occurs most often during adolescence or young adulthood. A familial background is often present but rigorous studies are still lacking. The key manifestation is hypersomnolence. It is often accompanied by sleep of long duration and debilitating sleep inertia. Polysomnography (PSG) followed by a multiple sleep latency test (MSLT) is mandatory, as well as a 24 h PSG or a 2-wk actigraphy in association with a sleep log to ensure a total 24-h sleep time longer than or equal to 66O minutes, when the mean sleep latency on the MSLT is longer than 8 min. Yet, MSLT is neither sensitive nor specific and the polysomnographic diagnostic criteria require continuous readjustment and biologic markers are still lacking. Idiopathic hypersomnia is most often a chronic condition though spontaneous remission may occur. The condition is disabling, sometimes even more so than narcolepsy type 1 or 2. Based on neurochemical, genetic and immunological analyses as well as on exploration of the homeostatic and circadian processes of sleep, various pathophysiological hypotheses have been proposed. Differential diagnosis involves a number of diseases and it is not yet clear whether idiopathic hypersomnia and narcolepsy type 2 are not the same condition. Until now, the treatment of idiopathic hypersomnia has mirrored that of the sleepiness of narcolepsy type 1 or 2. The first randomized, double-blind, placebo-controlled trials of modafinil have just been published, as well as a double

Successful tocolysis: does cervical change affect time to delivery?

PubMed

Lewis, D F; Gallaspy, J W; Fontenot, M T; Burlison, R D; Imseis, J M; Edwards, M S

1997-11-01

Generally, it is preferable to tocolyze patients with idiopathic preterm labor (PTL). Little information is available about ultimate outcomes after successful tocolysis. Our objective is to evaluate the relationship between cervical change after the initiation of tocolysis and the delay in time to delivery in patients with preterm labor. A historical analysis of all patients with successful tocolysis after PTL between January 1992 and December 1993 was undertaken. The patients were then placed in one of three categories (regression, unchanged, or progression) based on cervical change after the initiation of tocolysis. Various demographic pregnancy characteristics and pregnancy outcome data were analyzed. One hundred and twenty-six patients had successful tocolysis and met the admission criteria. Patients who had cervical progression had shorter delay to delivery, delivered at an earlier gestational age (31.7 weeks compared to 34.0 and 34.1 weeks, respectively, p < 0.05), and were more likely to deliver before 35 weeks (88% compared to 50.0 and 55.0%, respectively, p < 0.05). Also, neonates remained in the hospital longer and were more likely to have respiratory distress syndrome when compared to the other two groups. Patients who had cervical progression after the initiation of tocolysis are more likely to deliver prematurely, had a shorter delay to delivery, and delivered lower birth weight infants than did patients whose cervix regressed or remained unchanged. In our population, patients who had successful tocolysis had a preterm delivery rate of 59.5% before the 35th week of gestation.

Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study

PubMed Central

Argyelan, Miklos; Habeck, Christian; Ghilardi, M. Felice; Fitzpatrick, Toni; Dhawan, Vijay; Pourfar, Michael; Bressman, Susan B.; Eidelberg, David

2010-01-01

Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used 15Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal

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. © The Author(s) 2015.

"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…

The relationship of dystonia and choreoathetosis with activity, participation and quality of life in children and youth with dyskinetic cerebral palsy.

PubMed

Monbaliu, Elegast; De Cock, Paul; Mailleux, Lisa; Dan, Bernard; Feys, Hilde

2017-03-01

To relate dystonia and choreoathetosis with activity, participation and quality of life (QOL) in children and youth with dyskinetic Cerebral Palsy (CP). Fifty-four participants with dyskinetic CP (mean age 14y6m, SD 4y2m, range 6-22y) were included. The Dyskinesia Impairment Scale (DIS) was used to evaluate dystonia and choreoathetosis. Activity, participation and quality of life (QOL) were assessed with the Gross Motor Function Measure (GMFM), the Functional Mobility Scale (FMS), the Jebsen-Taylor Hand Function Test (JTT), the ABILHAND-Kids Questionnaire (ABIL-K), the Life Habits Kids (LIFE-H) and the Quality of Life Questionnaire for children with CP (CP-QOL). Spearman's rank correlation coefficient (r s ) was used to assess the relationship between the movement disorders and activity, participation and QOL measures. Significant negative correlations were found between dystonia and the activity scales with Spearman's rank correlation coefficient (r s ) varying between -0.65 (95% CI = -0.78 to -0.46) and -0.71 (95% CI = -0,82 to -0.55). Correlations were also found with the LIFE-H (r s  = -0.43; 95%CI = -0.64 to -0.17) and the CP-QOL (r s  = -0.32; 95%CI = -0.56 to -0.03). As far as choreoathetosis is concerned, no or only weak relationships were found with the activity, participation and quality of life scales. This cross-sectional study is the first to examine the relationship of dystonia and choreoathetosis in dyskinetic CP with the level of activity, participation and QOL. The results revealed dystonia has a higher impact on activity, participation and quality of life than choreoathetosis. These findings seem to suggest it is necessary to first focus on dystonia reducing intervention strategies and secondly on choreoathetosis. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

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

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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinical outcome and intraoperative neurophysiology for focal limb dystonic tremor without generalized dystonia treated with deep brain stimulation.

PubMed

Ramirez-Zamora, Adolfo; Kaszuba, Brian; Gee, Lucy; Prusik, Julia; Molho, Eric; Wilock, Meghan; Shin, Damian; Pilitsis, Julie G

2016-11-01

Dystonic tremor (DT) is defined as a postural/kinetic tremor occurring in the body region affected by dystonia. DT is typically characterized by focal tremors with irregular amplitudes and variable frequencies typically below 7Hz. Pharmacological treatment is generally unsuccessful and guidelines for deep brain stimulation (DBS) targeting and indications are scarce. In this article, we present the outcome and neurophysiologic data of two patients with refractory, focal limb DT treated with Globus Pallidus interna (Gpi) DBS and critically review the current literature regarding surgical treatment of DT discussing stereotactic targets and treatment considerations. A search of literature concerning treatment of DT was conducted. Additionally, Gpi DBS was performed in two patients with DT and microelectrode recordings for multi unit analysis (MUAs) and local field potentials (LFPs) were obtained. The mean percentage improvement in tremor severity was 80.5% at 3 years follow up. MUAs and LFPs did not show significant differences in DT patients compared with other forms of dystonia or PD except for higher interspikes bursting indices. LFP recordings in DT demonstrated high power at low frequencies with action (<3.5Hz). Gpi DBS is an effective treatment in patients with focal limb DT without associated generalized dystonia. Intraoperative neurophysiologic findings suggest that DT is part of phenotypic motor manifestations in dystonia. Copyright © 2016 Elsevier B.V. All rights reserved.

Spinal Cord Herniation After Cervical Corpectomy with Cerebrospinal Fluid Leak: Case Report and Review of the Literature.

PubMed

Guppy, Kern H; Silverthorn, James W

2017-04-01

Spinal cord herniation (SCH) is rare, is mostly idiopathic, and occurs predominantly in the thoracic spine. SCH is less common in the cervical spine and has been reported after posterior cervical spine surgery associated with the development of pseudomeningoceles. Two cases of SCH have been reported after anterior cervical corpectomies for ossified posterior longitudinal ligament with cerebrospinal fluid (CSF) leaks. We report the third such case, but the first in a patient without ossified posterior longitudinal ligament (degenerative disc disease and pseudarthrosis). A 56-year-old woman presented with bilateral arm pain and weakness. She had undergone 3 previous anterior cervical spine surgeries at an outside medical center with the most recent 7 years ago with C5 and C6 corpectomies and fusion with a persistent CSF leak. Magnetic resonance imaging and computed tomography myelography showed spinal cord herniation through the mesh cage at C6. The patient underwent a redo C5 and C6 corpectomy with untethering of the spinal cord. The patient was asymptomatic 2 years later. This is the first reported case of anterior cervical SCH in a patient without ossified posterior longitudinal ligament after multiple anterior cervical fusions including a cervical corpectomy for pseudarthrosis with a CSF leak. We hypothesize that persistent CSF leak causes a pressure gradient across the dura mater through the cage to the lower pressure in the retropharyngeal space, which led to herniation of the spinal cord into the anterior cage. We review the literature and discuss the treatment choices for anterior cervical SCH. Copyright © 2017 Elsevier Inc. All rights reserved.

Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in Mice Implicates Novel Pathways in Dystonia Pathogenesis.

PubMed

Beauvais, Genevieve; Bode, Nicole M; Watson, Jaime L; Wen, Hsiang; Glenn, Kevin A; Kawano, Hiroyuki; Harata, N Charles; Ehrlich, Michelle E; Gonzalez-Alegre, Pedro

2016-10-05

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. 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 the ER in DYT1 mice by

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

Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more.

PubMed

Lungu, Codrin; Karp, Barbara I; Alter, Katharine; Zolbrod, Regina; Hallett, Mark

2011-03-01

Previous studies have explored the efficacy and safety of botulinum neurotoxin (BoNT) treatment for Focal hand dystonia (FHD), but none have followed a large number of patients for 10 years or more. Retrospective study, with benefit and weakness assessed on a 0 to 4 subjective scale. Demographic, clinical and treatment characteristics were analyzed using t tests and Pearson correlations. Twenty FHD patients had 10 years or longer treatment. Interinjection intervals were variable. Musicians were more likely to wait longer between injections and had less complex dystonia. There was a trend for larger benefit in women and with shorter intervals. The dose increased over time. Dystonia characteristics did not predict response or side-effects, but benefit magnitude predicted longer compliance. No serious side-effects or antibody-mediated resistance occurred. This is the longest reported period of BoNT treatment in the largest FHD cohort. BoNT therapy for FHD remains safe and effective after more than a decade of treatment. Copyright © 2011 Movement Disorder Society.

Scaled vibratory feedback can bias muscle use in children with dystonia during a redundant, one-dimensional myocontrol task

PubMed Central

Liyanagamage, Shanie A.; Bertucco, Matteo; Bhanpuri, Nasir H.; Sanger, Terence D.

2016-01-01

Vibratory feedback can be a useful tool for rehabilitation. We examined its use in children with dystonia to understand how it affects muscle activity in a population that does not respond well to standard rehabilitation. We predicted scaled vibration (i.e. vibration that was directly or inversely proportional to muscle activity) would increase use of the vibrated muscle because of task-relevant sensory information, while non-scaled vibration would not change muscle use. The study was conducted on 11 subjects with dystonia and 14 controls. Each subject underwent 4 different types of vibration on the more dystonic biceps muscle (or non-dominant arm in controls) in a one-dimensional, bimanual myocontrol task. Our results showed that only scaled vibratory feedback could bias muscle use without changing overall performance in children with dystonia. We believe there may be a role in rehabilitation for scaled vibratory feedback to retrain abnormal muscle patterns. PMID:27798370

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

Using the shared genetics of dystonia and ataxia to unravel their pathogenesis

PubMed Central

Nibbeling, Esther A.R.; Delnooz, Cathérine C.S.; de Koning, Tom J.; Sinke, Richard J.; Jinnah, Hyder A.; Tijssen, Marina A.J.; Verbeek, Dineke S.

2018-01-01

In this review we explore the similarities between spinocerebellar ataxias and dystonias, and suggest potentially shared molecular pathways using a gene co-expression network approach. The spinocerebellar ataxias are a group of neurodegenerative disorders characterized by coordination problems caused mainly by atrophy of the cerebellum. The dystonias are another group of neurological movement disorders linked to basal ganglia dysfunction, although evidence is now pointing to cerebellar involvement as well. Our gene co-expression network approach identified 99 shared genes and showed the involvement of two major pathways: synaptic transmission and neurodevelopment. These pathways overlapped in the two disorders, with a large role for GABAergic signaling in both. The overlapping pathways may provide novel targets for disease therapies. We need to prioritize variants obtained by whole exome sequencing in the genes associated with these pathways in the search for new pathogenic variants, which can than be used to help in the genetic counseling of patients and their families. PMID:28143763

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

Genetics Home Reference: familial idiopathic basal ganglia calcification

MedlinePlus

... Children Living with Inherited Metabolic Diseases Dystonia Medical Research Foundation Family Caregiver Alliance National Ataxia Foundation National Organization for Rare Disorders (NORD) University of Kansas Medical ...

GCH1 mutations are common in Serbian patients with dystonia-parkinsonism: Challenging previously reported prevalence rates of DOPA-responsive dystonia.

PubMed

Dobričić, Valerija; Tomić, Aleksandra; Branković, Vesna; Kresojević, Nikola; Janković, Milena; Westenberger, Ana; Rašić, Vedrana Milić; Klein, Christine; Novaković, Ivana; Svetel, Marina; Kostić, Vladimir S

2017-12-01

GTP cyclohydrolase 1-deficient DOPA-responsive dystonia, caused by autosomal dominant mutation in the gene coding for GTP cyclohydrolase 1, is a rare disorder with a reported prevalence of 0.5 per million. A correct diagnosis of DRD is crucial, given that this is an exquisitely treatable neurogenetic disorder. Although genetic testing is now widely available, we hypothesize that DRD is still underdiagnosed and its prevalence underestimated. Molecular genetic analysis of the GCH1 gene was performed in a representative cohort of 47 Serbian patients with clinical features of DRD and in their 16 available relatives. The DRD prevalence rate in Serbia was estimated based on population size, catchment area, and the centralized Serbian referral system for rare diseases. We identified 9 different GCH1 mutations in 23 individuals from 11 families, 5 of which are novel. Patients displayed a broad range of clinical phenotypes. The estimated prevalence of GCH1-related DOPA-responsive dystonia in Serbia was 2.96 per million individuals and there was no evidence for a common founder. Our data expand the genotypic spectrum of GCH1 and confirm the broad phenotypic spectrum of DRD in the Serbian population. The number of detected mutation carriers in this sample implies that the frequency of DRD in the Serbian population is considerably higher than expected based on published prevalence rates, suggesting that the prevalence of this treatable disease should be revisited also in other populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regions of botulinum neurotoxin A light chain recognized by human anti-toxin antibodies from cervical dystonia patients immunoresistant to toxin treatment. The antigenic structure of the active toxin recognized by human antibodies.

PubMed

Atassi, M Zouhair; Dolimbek, Behzod Z; Jankovic, Joseph; Steward, Lance E; Aoki, K Roger

2011-07-01

This work was aimed at determining the BoNT/A L-chain antigenic regions recognized by blocking antibodies in human antisera from cervical dystonia patients who had become immunoresistant to BoNT/A treatment. Antisera from 28 immunoresistant patients were analyzed for binding to each of 32 overlapping synthetic peptides that spanned the entire L-chain. A mixture of the antisera showed that antibodies bound to three peptides, L11 (residues 141-159), L14 (183-201) and L18 (239-257). When mapped separately, the antibodies were bound only by a limited set of peptides. No peptide bound antibodies from all the patients and amounts of antibodies bound to a given peptide varied with the patient. Peptides L11, L14 and L18 were recognized predominantly. A small but significant number of patients had antibodies to peptides L27 (365-383) and L29 (379-397). Other peptides were recognized at very low and perhaps insignificant antibody levels by a minority (15% or less) of patients or had no detectable antibody with any of the sera. In the 3-dimensional structure, antibody-binding regions L11, L14 and L18 of the L-chain occupy surface areas and did not correlate with electrostatic potential, hydrophilicity/hydrophobicity, or temperature factor. These three antigenic regions reside in close proximity to the belt of the heavy chain. The regions L11 and L18 are accessible in both the free light chain and the holotoxin forms, while L14 appears to be less accessible in the holotoxin. Antibodies against these regions could prevent delivery of the L-chain into the neurons by inhibition of the translocation. Copyright © 2011 Elsevier GmbH. All rights reserved.

Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India.

PubMed

Prabhakaran, Vasudevan; Drevets, Douglas A; Ramajayam, Govindan; Manoj, Josephine J; Anderson, Michael P; Hanas, Jay S; Rajshekhar, Vedantam; Oommen, Anna; Carabin, Hélène

2017-06-01

Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches. Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications. Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to

Inhibitory rTMS applied on somatosensory cortex in Wilson's disease patients with hand dystonia.

PubMed

Lozeron, Pierre; Poujois, Aurélia; Meppiel, Elodie; Masmoudi, Sana; Magnan, Thierry Peron; Vicaut, Eric; Houdart, Emmanuel; Guichard, Jean-Pierre; Trocello, Jean-Marc; Woimant, France; Kubis, Nathalie

2017-10-01

Hand dystonia is a common complication of Wilson's disease (WD), responsible for handwriting difficulties and disability. Alteration of sensorimotor integration and overactivity of the somatosensory cortex have been demonstrated in dystonia. This study investigated the immediate after effect of an inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the somatosensory cortex on the writing function in WD patients with hand dystonia. We performed a pilot prospective randomized double-blind sham-controlled crossover rTMS study. A 20-min 1-Hz rTMS session, stereotaxically guided, was applied over the left somatosensory cortex in 13 WD patients with right dystonic writer's cramp. After 3 days, each patient was crossed-over to the alternative treatment. Patients were clinically evaluated before and immediately after each rTMS session with the Unified Wilson's Disease rating scale (UWDRS), the Writers' Cramp Rating Scale (WCRS), a specifically designed scale for handwriting difficulties in Wilson's disease patients (FAR, flow, accuracy, and rhythmicity evaluation), and a visual analog scale (VAS) for handwriting discomfort. No significant change in UWDRS, WCRS, VAS, or FAR scores was observed in patients treated with somatosensory inhibitory rTMS compared to the sham protocol. The FAR negatively correlated with UWDRS (r = -0.6; P = 0.02), but not with the WCRS score, disease duration, MRI diffusion lesions, or with atrophy scores. In our experimental conditions, a single inhibitory rTMS session applied over somatosensory cortex did not improve dystonic writer cramp in WD patients.

[A boy with cervical focal myositis].

PubMed

Prop, Serge; van Vuurden, Dannis; van der Kuip, Martijn; van der Voorn, J Patrick; Plötz, Frans B

2014-01-01

Focal myositis is a rare idiopathic pseudotumour that mostly occurs in the extremities in adults. An 8-year-old boy presented with a few months history of swelling in the neck and fever. Ultrasound investigation revealed an inhomogenous mass consistent with lymphadenitis. After nine days of antibiotic therapy, the clinical picture of fever and swelling was unchanged. MRI imaging revealed continuity of the swelling in the sternocleidomastoid muscle and a malignant process was suspected. Microscopy showed no malignant cells, however, but a lymphoplasmocytic infiltration with fibrosis and degeneration of muscle fibres, consistent with focal myositis. No intervention was undertaken and one year after presentation the tumour had regressed almost entirely. Focal myositis can present as a cervical tumour. On ultrasound, the condition is hard to distinguish from lymphadenopathy or malignancy. In cases of insufficient response to empirical antibiotic therapy, focal myositis should be considered.

Reliability of a quantitative clinical posture assessment tool among persons with idiopathic scoliosis.

PubMed

Fortin, Carole; Feldman, Debbie Ehrmann; Cheriet, Farida; Gravel, Denis; Gauthier, Frédérique; Labelle, Hubert

2012-03-01

To determine overall, test-retest and inter-rater reliability of posture indices among persons with idiopathic scoliosis. A reliability study using two raters and two test sessions. Tertiary care paediatric centre. Seventy participants aged between 10 and 20 years with different types of idiopathic scoliosis (Cobb angle 15 to 60°) were recruited from the scoliosis clinic. Based on the XY co-ordinates of natural reference points (e.g., eyes) as well as markers placed on several anatomical landmarks, 32 angular and linear posture indices taken from digital photographs in the standing position were calculated from a specially developed software program. Generalisability theory served to estimate the reliability and standard error of measurement (SEM) for the overall, test-retest and inter-rater designs. Bland and Altman's method was also used to document agreement between sessions and raters. In the random design, dependability coefficients demonstrated a moderate level of reliability for six posture indices (ϕ=0.51 to 0.72) and a good level of reliability for 26 posture indices out of 32 (ϕ≥0.79). Error attributable to marker placement was negligible for most indices. Limits of agreement and SEM values were larger for shoulder protraction, trunk list, Q angle, cervical lordosis and scoliosis angles. The most reproducible indices were waist angles and knee valgus and varus. Posture can be assessed in a global fashion from photographs in persons with idiopathic scoliosis. Despite the good reliability of marker placement, other studies are needed to minimise measurement errors in order to provide a suitable tool for monitoring change in posture over time. Copyright © 2011 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Selective decrease in central nervous system serotonin turnover in children with dopa-nonresponsive dystonia.

PubMed

Assmann, Birgit; Köhler, Martin; Hoffmann, Georg F; Heales, Simon; Surtees, Robert

2002-07-01

Childhood dystonia that does not respond to treatment with levodopa (dopa-nonresponsive dystonia, DND) has an unclear pathogenesis and is notoriously difficult to treat. To test the hypothesis that there may be abnormalities in serotonin turnover in DND we measured cerebrospinal fluid (CSF) concentrations of homovanillic (HVA) and 5-hydroxyindoleacetic (HIAA) acids, metabolites of dopamine and serotonin, respectively, in 18 children with dystonia not responsive to levodopa. These were combined with a reference population of 85 children with neurologic or metabolic disease known not to affect dopamine or serotonin metabolism. Because of the known natural age-related decrement in HVA and HIAA concentrations, the results were analyzed using multiple regression using age and DND as predictors of CSF HIAA and HVA concentrations. DND was a highly significant predictor of CSF HIAA concentration (p < 0.001) but not of CSF HVA concentration (p = 0.59). After fitting a regression model, the geometric mean ratio of CSF HIAA in DND compared with the reference range was 0.53 whereas that for CSF HVA was 0.95. We also analyzed CSF HIAA/HVA ratios. After fitting a regression model, we found no dependence on age, and the mean of CSF HIAA/HVA in DND was 0.28 whereas that for the reference range was 0.49 (p < 0.001). We conclude that a significant number of children with DND have reduced CNS serotonin turnover. Treatment with drugs that increase serotonin concentration in the synaptic cleft should be considered in this group of patients.

Haptic Feedback Manipulation During Botulinum Toxin Injection Therapy for Focal Hand Dystonia Patients: A Possible New Assistive Strategy.

PubMed

Atashzar, Seyed Farokh; Shahbazi, Mahya; Ward, Christopher; Samotus, Olivia; Delrobaei, Mehdi; Rahimi, Fariborz; Lee, Jack; Jackman, Mallory; Jog, Mandar S; Patel, Rajni V

2016-01-01

Abnormality of sensorimotor integration in the basal ganglia and cortex has been reported in the literature for patients with task-specific focal hand dystonia (FHD). In this study, we investigate the effect of manipulation of kinesthetic input in people living with writer's cramp disorder (a major form of FHD). For this purpose, severity of dystonia is studied for 11 participants while the symptoms of seven participants have been tracked during five sessions of assessment and Botulinum toxin injection (BoNT-A) therapy (one of the current suggested therapies for dystonia). BoNT-A therapy is delivered in the first and the third session. The goal is to analyze the effect of haptic manipulation as a potential assistive technique during BoNT-A therapy. The trial includes writing, hovering, and spiral/sinusoidal drawing subtasks. In each session, the subtasks are repeated twice when (a) a participant uses a normal pen, and (b) when the participant uses a robotics-assisted system (supporting the pen) which provides a compliant virtual writing surface and manipulates the kinesthetic sensory input. The results show (p-value using one-sample t-tests) that reducing the writing surface rigidity significantly decreases the severity of dystonia and results in better control of grip pressure (an indicator of dystonic cramping). It is also shown that (p-value based on paired-samples t-test) using the proposed haptic manipulation strategy, it is possible to augment the effectiveness of BoNT-A therapy. The outcome of this study is then used in the design of an actuated pen as a writing-assistance tool that can provide compliant haptic interaction during writing for FHD patients.

Functional Aspects of Gait in Essential Tremor: A Comparison with Age-Matched Parkinson's Disease Cases, Dystonia Cases, and Controls.

PubMed

Louis, Elan D; Rao, Ashwini K

2015-01-01

An understanding of the functional aspects of gait and balance has wide ramifications. Individuals with balance disorders often restrict physical activity, travel, and social commitments to avoid falling, and loss of balance confidence, itself, is a source of disability. We studied the functional aspects of gait in patients with essential tremor (ET), placing their findings within the context of two other neurological disorders (Parkinson's disease [PD] and dystonia) and comparing them with age-matched controls. We administered the six-item Activities of Balance Confidence (ABC-6) Scale and collected data on number of falls and near-falls, and use of walking aids in 422 participants (126 ET, 77 PD, 46 dystonia, 173 controls). Balance confidence was lowest in PD, intermediate in ET, and relatively preserved in dystonia compared with controls. This ordering reoccurred for each of the six ABC-6 items. The number of near-falls and falls followed a similar ordering. Use of canes, walkers, and wheelchairs was elevated in ET and even greater in PD. Several measures of balance confidence (ABC-6 items 1, 4, 5, and 6) were lower in torticollis cases than in those with blepharospasm, although the two groups did not differ with respect to falls or use of walking aids. Lower balance confidence, increased falls, and greater need for walking aids are variably features of a range of movement disorder patients compared to age-matched controls. While most marked among PD patients, these issues affected ET patients as well and, to a small degree, some patients with dystonia.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

PubMed

Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

2012-02-15

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

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.

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. To compare cochlear implant (CI) neuromodulation with deep brain stimulation (DBS) for dystonia in childhood and explore relations between age and duration of symptoms at implantation and outcome. Comparison of published annual UK CI figures for 1985-2009 with a retrospective cohort of the first 9 years of DBS for dystonia in children at a single-site Functional Neurosurgery unit from 2006 to 14. From 2006 to 14, DBS neuromodulation of childhood dystonia increased by a factor of 3.8 to a total of 126 cases over the first 9 years, similar to the growth in cochlear implants which increased by a factor of 4.1 over a similar period in the 1980s rising to 527 children in 2009. The CI saw a dramatic shift in practice from implantation at >5 years of age at the start of the programme towards earlier implantation by the mid-1990s. Best language results were seen for implantation <5 years of age and duration of cochlear neuromodulation >4 years, hence implantation <1 year of age, indicating that severely deaf, pre-lingual children could benefit from cochlear neuromodulation if implanted early. Similar to initial CI use, the majority of children receiving DBS for dystonia in the first 9 years were 5-15 years of age, when the proportion of life lived with dystonia exceeds 90% thus limiting benefits. Early DBS neuromodulation for acquired motor disorders should be explored to maximise the benefits of dystonia reduction in a period of maximal developmental plasticity before the onset of disability. Learning from cochlear implantation, DBS can become an accepted management option in children under the age of 5 years who have a reduced proportion of life lived with dystonia, and not viewed as a last resort reserved

Molecular immune recognition of botulinum neurotoxin B. The light chain regions that bind human blocking antibodies from toxin-treated cervical dystonia patients. Antigenic structure of the entire BoNT/B molecule.

PubMed

Atassi, M Zouhair; Jankovic, Joseph; Steward, Lance E; Aoki, K Roger; Dolimbek, Behzod Z

2012-01-01

We recently mapped the regions on the heavy (H) chain of botulinum neurotoxin, type B (BoNT/B) recognized by blocking antibodies (Abs) from cervical dystonia (CD) patients who develop immunoresistance during toxin treatment. Since blocking could also be effected by Abs directed against regions on the light (L) chain, we have mapped here the L chain, using the same 30 CD antisera. We synthesized, purified and characterized 32 19-residue L chain peptides that overlapped successively by 5 residues (peptide L32 overlapped with peptide N1 of the H chain by 12 residues). In a given patient, Abs against the L chain seemed less intense than those against H chain. Most sera recognized a limited set of L chain peptides. The levels of Abs against a given region varied with the patient, consistent with immune responses to each epitope being under separate MHC control. The peptides most frequently recognized were: L13, by 30 of 30 antisera (100%); L22, by 23 of 30 (76.67%); L19, by 15 of 30 (50.00%); L26, by 11 of 30 (36.70%); and L14, by 12 of 30 (40.00%). The activity of L14 probably derives from its overlap with L13. The levels of Ab binding decreased in the following order: L13 (residues 169-187), L22 (295-313), L19 (253-271), and L26 (351-369). Peptides L12 (155-173), L18 (239-257), L15 (197-215), L1 (1-19) and L23 (309-327) exhibited very low Ab binding. The remaining peptides had little or no Ab-binding activity. The antigenic regions are analyzed in terms of their three-dimensional locations and the enzyme active site. With the previous localization of the antigenic regions on the BoNT/B H chain, the human Ab recognition of the entire BoNT/B molecule is presented and compared to the recognition of BoNT/A by human blocking Abs. Copyright © 2011. Published by Elsevier GmbH.

Natural history of idiopathic diabetes insipidus.

PubMed

Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin

2011-10-01

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.

Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation.

PubMed

Carecchio, Miryam; Picillo, Marina; Valletta, Lorella; Elia, Antonio E; Haack, Tobias B; Cozzolino, Autilia; Vitale, Annalisa; Garavaglia, Barbara; Iuso, Arcangela; Bagella, Caterina F; Pappatà, Sabina; Barone, Paolo; Prokisch, Holger; Romito, Luigi; Tiranti, Valeria

2017-07-01

Mutations in PSEN1 are responsible for familial Alzheimer's disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Brain MRI showed signs of iron accumulation in the basal ganglia mimicking neurodegeneration with brain iron accumulation (NBIA) as well as fronto-temporal atrophy. Whole exome sequencing revealed a novel PSEN1 mutation and segregation within the family demonstrated the mutation arose de novo.We suggest considering PSEN1 mutations in cases of dystonia-parkinsonism with positive DAT-Scan, later complicated by progressive cognitive decline and cortical myoclonus even without a dominant family history.

Visuo-motor and cognitive procedural learning in children with basal ganglia pathology.

PubMed

Mayor-Dubois, C; Maeder, P; Zesiger, P; Roulet-Perez, E

2010-06-01

We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage. Copyright 2010 Elsevier Ltd. All rights reserved.

Vitamin D deficiency in chronic idiopathic urticaria.

PubMed

Movahedi, Masoud; Tavakol, Marzieh; Hirbod-Mobarakeh, Armin; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Tavakol, Zahra; Momenzadeh, Kaveh; Nabavi, Mohammad; Dabbaghzade, Abbas; Mosallanejad, Asieh; Rezaei, Nima

2015-04-01

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

Restoring balance in focal limb dystonia with botulinum toxin.

PubMed

Sheean, Geoffrey

2007-12-15

Focal task-specific dystonia of the hand is rare in the general population, where it usually manifests as writer's cramp, but seems relatively common among musicians. The disability may be so severe as to prevent writing altogether or to end a professional musician's career. The cause is usually unknown but it is thought to be primarily a basal ganglia disorder with dysfunction of cortical-striatothalamic-cortical circuits. Abnormalities have been found in cortical movement preparation, intracortical inhibition, sensory and motor maps, and patterns of cortical activation during movement. Much evidence supports disordered processing of sensory information with disturbed sensorimotor integration. Underlying this may be maladaptive neural plasticity mechanisms. Treatment is difficult. Oral medications are generally ineffective and have troublesome side-effects. Intensive rehabilitation techniques based on neural plasticity theory show promise but are rarely available and are time-intensive. Botulinum toxin injections appear to be effective in writer's cramp and musician's dystonia, at least initially; long-term benefit is less common. Despite definite improvement, some patients abandon treatment because the gain is insufficient for meaningful function: this is particularly so for musicians. Much of the benefit from botulinum toxin injection comes from simply reducing muscle overactivity through muscle paralysis, restoring balance to motor control. However, some evidence suggests that botulinum toxin injections can produce transient improvement in some of the various cortical abnormalities described, probably through alteration of sensory input from the periphery, by direct and indirect means. These changes in cortical function might be usefully combined with those brought about by sensorimotor retraining programs, but such studies are awaited.

Idiopathic ventricular tachycardia and fibrillation.

PubMed

Belhassen, B; Viskin, S

1993-06-01

Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healty patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellent.

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. Copyright © 2011 Movement Disorder Society.

[Treatment of early-onset generalized dystonia by chronic bilateral stimulation of the internal globus pallidus. Apropos of a case].

PubMed

Coubes, P; Echenne, B; Roubertie, A; Vayssière, N; Tuffery, S; Humbertclaude, V; Cambonie, G; Claustres, M; Frerebeau, P

1999-05-01

Dystonia musculorum deformans is an inherited severe disease, with a wide clinical polymorphism. The most severe clinical forms with early onset carry a high risk of life-threatening complications. In the absence of any efficient medical treatment, bilateral pallidotomy has previously been reported to be of value in the management of this disease. We report the first clinical case of a severe early-onset generalized dystonia dramatically improved by a bilateral stimulation of the internal globus pallidus. In November 1996, we proposed this neurosurgical procedure for a 8-year-old girl, who had suffered since the age of 3 from severe generalized dystonia, and who progressively became totally dependent and bedridden. She had been under sedation and permanent controlled respiratory assistance for the last two months. The etiology of the disease remained unknown (the DYT1 mutation was absent). Under general anesthesia, we bilaterally implanted a four-contacts electrode in the internal globus pallidus, using the Leksell's stereotactic frame and a 1.5 tesla MRI control. A dramatic improvement was noted 6 weeks later and led us to connect the two electrodes to neurostimulators inserted under the abdominal skin.

Spasmodic torticollis: the dental connection.

PubMed

Sims, Anthony B; Stack, Brendan C; Demerjian, G Gary

2012-07-01

Spasmodic torticollis or cervical dystonia (CD) is the most common form of focal dystonia and is characterized by sustained abnormal muscle contractions in the head and neck area resulting in abnormal positioning or posturing of the head. The dystonic muscle spasms associated with spasmodic torticollis may affect any combination of neck muscles. Three cases are reported of spasmodic torticollis that were treated by a dental appliance with individual varying occlusal heights to open the maxillomandibular vertical dimension. Upon increasing the vertical dimension of occlusion, there was a slowing and/or discontinuance of the symptoms of cervical dystonia. The proposed hypothesis for this reversal is that there may be neuritis of the auriculotemporal branch of the trigeminal nerve, which has direct input into the reticular formation (RF), and it may activate the cells of the pontine region of the RF known for the control and deviation of head posture. There is growing clinical evidence that temporomandibular joint (TMJ) dysfunction may be a factor in this neurological and painful disorder when it coexists.

Relation between adolescent idiopathic scoliosis and morphologic somatotypes.

PubMed

LeBlanc, R; Labelle, H; Rivard, C H; Poitras, B

1997-11-01

A prospective and controlled comparative study. To verify the difference in morphologic appearance between a group of adolescents with progressive adolescent idiopathic scoliosis and a control group of normal adolescents. In a previous retrospective study, the possibility of a relation between progressive adolescent idiopathic scoliosis and specific morphotypes was demonstrated. Fifty-two adolescent girls with progressive adolescent idiopathic scoliosis were compared with an age-matched control group of 62 unaffected girls using a classification technique based on morphologic somatotypes. Morphotypes were evaluated with standardized pre-established criteria based on Sheldon's technique. Patients with progressive adolescent idiopathic scoliosis showed significantly less mesomorphism (mean value of 0.88 +/- 0.51) than control girls (mean value of 1.72 +/- 0.52). Adolescent girls with progressive adolescent idiopathic scoliosis have a morphologic somatotype that is different from the normal adolescent population. Subjects with progressive adolescent idiopathic scoliosis are significantly less mesomorphic than control girls. This observation may be of value as a predictive factor for early identification of subjects with adolescent idiopathic scoliosis at greater risk of progression.

Perspective: Update on Idiopathic Intracranial Hypertension

PubMed Central

Bruce, Beau B.; Biousse, Valérie; Newman, Nancy J.

2011-01-01

Purpose Provide an update on various features of idiopathic intracranial hypertension. Design Perspective. Methods Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience. Results Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting. Conclusions Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension. PMID:21696699

Prevalence, predictors, and perceived effectiveness of complementary, alternative and integrative medicine in adult-onset primary dystonia

PubMed Central

Fleming, Brandy M.; Schwab, Emiko L.; Nouer, Simonne S.; Wan, Jim Y.; LeDoux, Mark S.

2012-01-01

Background Complementary and Alternative Medicine (CAM) use is on the rise in both the US and Europe, despite questions about its safety, effectiveness and lack of national standards. We aimed to determine the prevalence and predictors of CAM and integrative medicine use (CAM-I) and perceived effectiveness compared to the standard treatment of botulinum toxin injections in patients with adult-onset primary dystonia. Methods This was a retrospective questionnaire study of 389 dystonia patients examining the effects age, gender, education level and number of anatomical regions affected on botulinum toxin and CAM-I use and their perceived effectiveness. Results 53% (208) of patients reported CAM-I use, while 90% (349) used the standard treatment (botulinum toxin), and 48% used both. Education was the only significant predictor of CAM-I use – individuals with bachelor’ s degrees were more likely to try CAM-I whereas those with high school diplomas were less likely. The mean effectiveness rate for botulinum toxin injections (59%) significantly exceeded that for and CAM-I (28%, p<0.0001). Conclusions Our work highlights the need for scientifically sound studies to determine the safety, effectiveness and expense of CAM-I treatments for dystonia and other neurological disorders given that CAM-I use is steadily increasing, there is great variability in what is classified as CAM-I, and the effectiveness of some modalities may be significantly less than conventional medical treatments. PMID:22633698

Prevalence, predictors, and perceived effectiveness of complementary, alternative and integrative medicine in adult-onset primary dystonia.

PubMed

Fleming, Brandy M; Schwab, Emiko L; Nouer, Simonne S; Wan, Jim Y; LeDoux, Mark S

2012-09-01

Complementary and Alternative Medicine (CAM) use is on the rise in both the US and Europe, despite questions about its safety and effectiveness, and lack of national standards. We aimed to determine the prevalence and predictors of CAM and integrative medicine use (CAM-I) and perceived effectiveness compared to the standard treatment of botulinum toxin injections in patients with adult-onset primary dystonia. This was a retrospective questionnaire study of 389 dystonia patients examining the effects age, gender, education level and number of affected anatomical regions on botulinum toxin and CAM-I use and their perceived effectiveness. 53% (208) of patients reported CAM-I use, while 90% (349) used the standard treatment (botulinum toxin), and 48% used both. Education was the only significant predictor of CAM-I use - individuals with bachelor's degrees were more likely to try CAM-I whereas those with high school diplomas were less likely. The mean effectiveness rate for botulinum toxin injections (59%) significantly exceeded that for CAM-I (28%, p < 0.0001). Our work highlights the need for scientifically sound studies to determine the safety, effectiveness and expense of CAM-I treatments for dystonia and other neurological disorders given that CAM-I use is steadily increasing, there is great variability in what is classified as CAM-I, and the effectiveness of some modalities may be significantly less than conventional medical treatments. Copyright © 2012 Elsevier Ltd. All rights reserved.

Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

PubMed Central

Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

2012-01-01

DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

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

Complex and Dynamic Chromosomal Rearrangements in a Family With Seemingly Non-Mendelian Inheritance of Dopa-Responsive Dystonia.

PubMed

Lohmann, Katja; Redin, Claire; Tönnies, Holger; Bressman, Susan B; Subero, Jose Ignacio Martin; Wiegers, Karin; Hinrichs, Frauke; Hellenbroich, Yorck; Rakovic, Aleksandar; Raymond, Deborah; Ozelius, Laurie J; Schwinger, Eberhard; Siebert, Reiner; Talkowski, Michael E; Saunders-Pullman, Rachel; Klein, Christine

2017-07-01

Chromosomal rearrangements are increasingly recognized to underlie neurologic disorders and are often accompanied by additional clinical signs beyond the gene-specific phenotypic spectrum. To elucidate the causal genetic variant in a large US family with co-occurrence of dopa-responsive dystonia as well as skeletal and eye abnormalities (ie, ptosis, myopia, and retina detachment). We examined 10 members of a family, including 5 patients with dopa-responsive dystonia and skeletal and/or eye abnormalities, from a US tertiary referral center for neurological diseases using multiple conventional molecular methods, including fluorescence in situ hybridization and array comparative genomic hybridization as well as large-insert whole-genome sequencing to survey multiple classes of genomic variations. Of note, there was a seemingly implausible transmission pattern in this family due to a mutation-negative obligate mutation carrier. Genetic diagnosis in affected family members and insight into the formation of large deletions. Four members were diagnosed with definite and 1 with probable dopa-responsive dystonia. All 5 affected individuals carried a large heterozygous deletion encompassing all 6 exons of GCH1. Additionally, all mutation carriers had congenital ptosis requiring surgery, 4 had myopia, 2 had retinal detachment, and 2 showed skeletal abnormalities of the hands, ie, polydactyly or syndactyly or missing a hand digit. Two individuals were reported to be free of any disease. Analyses revealed complex chromosomal rearrangements on chromosome 14q21-22 in unaffected individuals that triggered the expansion to a larger deletion segregating with affection status. The expansion occurred recurrently, explaining the seemingly non-mendelian inheritance pattern. These rearrangements included a deletion of GCH1, which likely contributes to the dopa-responsive dystonia, as well as a deletion of BMP4 as a potential cause of digital and eye abnormalities. Our findings alert

The Natural History of Idiopathic Scoliosis During Growth: A Meta-Analysis.

PubMed

Di Felice, Francesca; Zaina, Fabio; Donzelli, Sabrina; Negrini, Stefano

2018-05-01

The aim of the study was to provide a meta-analysis of current literature concerning the natural history of idiopathic scoliosis during growth. A comprehensive search of Medline, Embase, And Scopus databases was conducted up to November 2016. Eligible works were prospective or retrospective studies that enrolled patients with infantile idiopathic scoliosis, juvenile idiopathic scoliosis, or adolescent idiopathic scoliosis, followed up without any treatment from the time of detection. A meta-analysis for proportion was performed. The following studies were grouped per diagnosis: infantile idiopathic scoliosis, juvenile idiopathic scoliosis, and adolescent idiopathic scoliosis. Of the 1797 citations screened, we assessed 61 full-text articles and included 13 of these (2301 participants). Three studies included infantile idiopathic scoliosis patients (347 participants), five studies included a mixed population of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis (1330 participants), and five studies included adolescent idiopathic scoliosis patients only (624 participants). The random pooled estimated progression rate was 49% (95% confidence interval = 1%-97%) for infantile idiopathic scoliosis, 49% in a mixed group of patients affected by juvenile idiopathic scoliosis or adolescent idiopathic scoliosis (95% confidence interval = 19%-79%), and 42% in adolescent idiopathic scoliosis (95% confidence interval = 11%-73%). During growth, idiopathic scoliosis tends to progress in a high percentage of cases. The progression rate varies according to the age at diagnosis, with infantile scoliosis being the most unpredictable. There are many confounders, such as age, Risser sign and baseline Cobb angles that were not consistent among studies, making the data very heterogeneous.

Cervical Cap

MedlinePlus

... Videos for Educators Search English Español The Cervical Cap KidsHealth / For Teens / The Cervical Cap What's in ... Call the Doctor? Print What Is a Cervical Cap? A cervical cap is a small cup made ...

Focal dystonia secondary to cavernous angioma of the basal ganglia: case report and review of the literature.

PubMed

Lorenzana, L; Cabezudo, J M; Porras, L F; Polaina, M; Rodriguez-Sanchez, J A; Garcia-Yagüe, L M

1992-12-01

The case of a young woman with focal dystonia of the hand due to a cavernous angioma of the basal ganglia is presented. The lesion involved the anterior third of the lentiform nucleus and a large portion of white matter anterior to this nucleus and lateral to the head of the caudate, as shown by magnetic resonance imaging; it was completely removed through a computed tomography-assisted stereotactic craniotomy by microsurgical technique, resulting in the cure of the patient. These facts support the pathophysiological hypothesis of a disruption of the striatopallidothalamic projection to the premotor cortex as the cause of symptomatic dystonia. A review of the reported cases of cavernous angiomas of the deep cerebral gray nuclei shows that this is the first case of cavernous angioma associated with movement disorder.

Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia.

PubMed

Casellato, Claudia; Pedrocchi, Alessandra; Zorzi, Giovanna; Rizzi, Giorgio; Ferrigno, Giancarlo; Nardocci, Nardo

2012-07-23

Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions) and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A), constant disturbing force (B) and deactivation of the additive external force again (C). The path length for each trial was computed, from the recorded position data and interaction events. The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment.The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining of the existing but strongly imprecise motor scheme and

Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia

PubMed Central

2012-01-01

Background Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. Methods As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions) and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A), constant disturbing force (B) and deactivation of the additive external force again (C). The path length for each trial was computed, from the recorded position data and interaction events. Results The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment. The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. Conclusions The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining of the existing but

Infantile parkinsonism-dystonia: a dopamine "transportopathy".

PubMed

Blackstone, Craig

2009-06-01

The dopamine transporter (DAT) retrieves the neurotransmitter dopamine from the synaptic cleft at dopaminergic synapses. Variations in solute carrier family 6A, member 3 (SLC6A3/DAT1), the human gene encoding DAT, have been implicated in attention deficit hyperactivity and bipolar disorders, and DAT is a prominent site of action for drugs such as amphetamines and cocaine. In this issue of the JCI, Kurian et al. report that an autosomal recessive infantile parkinsonism-dystonia is caused by loss-of-function mutations in DAT that impair dopamine reuptake (see the related article beginning on page 1595). Though this might be predicted to result in dopamine excess in the synaptic cleft, it likely also causes depletion of presynaptic dopamine stores and possibly downregulation of postsynaptic dopamine receptor function, resulting in impairments in dopaminergic neurotransmission consistent with the clinical presentation. This is the first report of a genetic alteration in DAT function underlying a parkinsonian disorder.

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.

Idiopathic Hypersomnia: A Study of 77 Cases

PubMed Central

Anderson, Kirstie N.; Pilsworth, Samantha; Sharples, Linda D.; Smith, Ian E.; Shneerson, John M.

2007-01-01

Study Objectives: To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. Setting: The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. Patients and Design: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Measurements and Results: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Conclusions: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve. Citation: Anderson KN; Pilsworth S; Sharples LD; Smith IE; Shneerson JM. Idiopathic

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.

Aetiology of idiopathic granulomatous mastitis.

PubMed

Altintoprak, Fatih; Kivilcim, Taner; Ozkan, Orhan Veli

2014-12-16

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail.

Aetiology of idiopathic granulomatous mastitis

PubMed Central

Altintoprak, Fatih; Kivilcim, Taner; Ozkan, Orhan Veli

2014-01-01

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail. PMID:25516860

Temporal expectation in focal hand dystonia.

PubMed

Avanzino, Laura; Martino, Davide; Martino, Isadora; Pelosin, Elisa; Vicario, Carmelo M; Bove, Marco; Defazio, Gianni; Abbruzzese, Giovanni

2013-02-01

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 with dystonia to process the time-dependent features (e.g. speed) of movement in real time. The processing of time-dependent features of movement has a crucial role in predicting whether the outcome of a complex motor sequence, such as handwriting or playing a musical passage, will be consistent with its ultimate goal, or results instead in an execution error. In this study, we sought to evaluate the implicit ability to perceive the temporal outcome of different movements in a group of patients with writer's cramp. Fourteen patients affected by writer's cramp in the right hand and 17 age- and gender-matched healthy subjects were recruited for the study. Subjects were asked to perform a temporal expectation task by predicting the end of visually perceived human body motion (handwriting, i.e. the action performed by the human body segment specifically affected by writer's cramp) or inanimate object motion (a moving circle reaching a spatial target). Videos representing movements were shown in full before experimental trials; the actual tasks consisted of watching the same videos, but interrupted after a variable interval ('pre-dark') from its onset by a dark interval of variable duration. During the 'dark' interval, subjects were asked to indicate when the movement represented in the video reached its end by clicking on the space bar of the keyboard. We also included a visual working memory task. Performance on the timing task was analysed measuring the absolute value of timing error, the coefficient of variability and the percentage of anticipation responses. Patients with writer's cramp exhibited greater absolute timing

Expanding the phenotype in aminoacylase 1 (ACY1) deficiency: characterization of the molecular defect in a 63-year-old woman with generalized dystonia.

PubMed

Sass, Jörn Oliver; Vaithilingam, Jathana; Gemperle-Britschgi, Corinne; Delnooz, Cathérine C S; Kluijtmans, Leo A J; van de Warrenburg, Bart P C; Wevers, Ron A

2016-06-01

Aminoacylase 1 (ACY1) deficiency is an organic aciduria due to mutations in the ACY1 gene. It is considered much underdiagnosed. Most individuals known to be affected by ACY1 deficiency have presented with neurologic symptoms. We report here a cognitively normal 63-year-old woman who around the age of 12 years had developed dystonic symptoms that gradually evolved into generalized dystonia. Extensive investigations, including metabolic diagnostics and diagnostic exome sequencing, were performed to elucidate the cause of dystonia. Findings were only compatible with a diagnosis of ACY1 deficiency: the urinary metabolite pattern with N-acetylated amino acids was characteristic, there was decreased ACY1 activity in immortalized lymphocytes, and two compound heterozygous ACY1 mutations were detected, one well-characterized c.1057C>T (p.Arg353Cys) and the other novel c.325A>G (p.Arg109Gly). Expression analysis in HEK293 cells revealed high residual activity of the enzyme with the latter mutation. However, following co-transfection of cells with stable expression of the c.1057C>T variant with either wild-type ACY1 or the c.325A>G mutant, only the wild-type enhanced ACY1 activity and ACY1 presence in the Western blot, suggesting an inhibiting interference between the two variants. Our report extends the clinical spectrum of ACY1 deficiency to include dystonia and indicates that screening for organic acidurias deserves consideration in patients with unexplained generalized dystonia.

Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature.

PubMed

Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Maheswaran, Anupama; Rajasekaran, S

2016-05-01

Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. Case report. We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis.

Acute Idiopathic Scrotal Edema: Systematic Literature Review.

PubMed

Santi, Maristella; Lava, Sebastiano A G; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

2018-06-01

 Existing information on acute idiopathic scrotal edema relies on small case series and textbooks.  We searched reports with no date limits on acute idiopathic scrotal edema.  Thirty-seven studies were included. Sixteen case series addressed the prevalence of acute idiopathic scrotal edema among males with acute scrotum: among 3,403 cases, the diagnosis of acute idiopathic scrotal edema was made in 413 cases (12%). Twenty-four reports addressed history, findings, management, and course of acute idiopathic scrotal edema in 311 patients. The patients mostly ranged in age from 5 to 8 years, presented with acute scrotal redness and swelling, associated or not with mild pain. Ninety percent or more of the cases developed in patients without atopic diathesis and were not preceded by inguinoscrotal surgery, acute febrile illnesses, or trauma. They were afebrile; in good general condition; and presented without pruritus, nausea or vomiting, or abdominal pain. The lesions were bilateral in two-thirds and unilateral in one-third of the cases. The condition resolved spontaneously within 2 to 3 days without sequelae. Approximately 10% of the cases experienced a recurrence.  Acute idiopathic scrotal edema is a self-limiting condition that accounts for ≥ 10% of cases of acute scrotum in children and adolescents. Georg Thieme Verlag KG Stuttgart · New York.

Idiopathic hypersomnia: a study of 77 cases.

PubMed

Anderson, Kirstie N; Pilsworth, Samantha; Sharples, Linda D; Smith, Ian E; Shneerson, John M

2007-10-01

To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

PubMed Central

Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio

2018-01-01

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. PMID:29504938

Rechargeable or Nonrechargeable Deep Brain Stimulation in Dystonia: A Cost Analysis.

PubMed

Perez, Jerome; Gonzalez, Victoria; Cif, Laura; Cyprien, Fabienne; Chan-Seng, Emilie; Coubes, Philippe

2017-04-01

Deep brain stimulation of the internal Globus Pallidus (GPi DBS) delivered by an implantable neurostimulator (INS) is an established, effective, and safe treatment option for patients with medically refractory primary dystonia. Compared to other DBS targets, the battery life of the INS is substantially shorter due to the higher energy demands required to penetrate the GPi resulting in faster battery depletion and more frequent hospitalizations for INS replacement. We, therefore, performed a cost analysis to compare a rechargeable DBS system, Activa®RC, with nonrechargeable systems, from the perspective of the French public health insurer. To estimate the cost of INS replacement in the nonrechargeable cohort, and costs potentially avoided in the hypothetical Activa ® RC cohort, the medical records of patients who had undergone GPi DBS with a nonrechargeable INS between 1996 and 2010 at a center in France were accessed. Replacement rates were estimated for up to nine years. With Activa ® RC, a total of 315 hospitalizations for replacement procedures would have been avoided over nine years compared with a nonrechargeable INS, resulting in a discounted mean direct medical cost per patient over nine years of €50,119 with a nonrechargeable INS and €33,306 with Activa ® RC, a reduction of 34%. The adoption of a rechargeable instead of a nonrechargeable INS for eligible patients with dystonia may provide substantial savings to the public health insurer in France. © 2017 International Neuromodulation Society.

Sensorimotor Control in Individuals With Idiopathic Neck Pain and Healthy Individuals: A Systematic Review and Meta-Analysis.

PubMed

de Zoete, Rutger M J; Osmotherly, Peter G; Rivett, Darren A; Farrell, Scott F; Snodgrass, Suzanne J

2017-06-01

(1) To identify reported tests used to assess sensorimotor control in individuals with idiopathic neck pain and (2) to investigate whether these tests can quantify differences between individuals with idiopathic neck pain and healthy individuals. Allied and Complementary Medicine Database, CINAHL, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Physiotherapy Evidence Database, Scopus, and SPORTDiscus. Studies reporting sensorimotor outcomes in individuals with idiopathic neck pain or healthy individuals were identified. There were 1,677 records screened independently by 2 researchers for eligibility: 43 studies were included in the review, with 30 of these studies included in the meta-analysis. Methodologic quality was determined using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data were extracted using a standardized extraction table. Sensorimotor control was most commonly assessed by joint position error and postural sway. Pooled means for joint position error after cervical rotation in individuals with neck pain (range, 2.2°-9.8°) differed significantly (P=.04) compared with healthy individuals (range, 1.66°-5.1°). Postural sway with eyes open ranged from 4.85 to 10.5cm 2 (neck pain) and 3.5 to 6.6cm 2 (healthy) (P=.16), and postural sway with eyes closed ranged from 2.51 to 16.6cm 2 (neck pain) and 2.74 to 10.9cm 2 (healthy) (P=.30). Individual studies, but not meta-analysis, demonstrated differences between neck pain and healthy groups for postural sway. Other test conditions and other tests were not sufficiently investigated to enable pooling of data. The findings from this review suggest sensorimotor control testing may be clinically useful in individuals with idiopathic neck pain. However, results should be interpreted with caution because clinical differences were small; therefore, further cross-sectional research with larger samples is needed to determine the magnitude of the relation between

Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

PubMed

Kissoon, Narayan R; Watson, James C; Boes, Christopher J; Kantarci, Orhun H

2018-01-01

Background The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. Methods We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. Results The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. Conclusions A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

Treatment effectiveness of brain-computer interface training for patients with focal hand dystonia: A double-case study.

PubMed

Hashimoto, Yasunari; Ota, Tetsuo; Mukaino, Masahiko; Ushiba, Junichi

2013-01-01

Neuronal mechanism underlying dystonia is poorly understood. Dystonia can be treated with botulinum toxin injections or deep brain stimulation but these methods are not available for every patient therefore we need to consider other methods Our study aimed to develop a novel rehabilitation training using brain-computer interface system that decreases neural overexcitation in the sensorimotor cortex by bypassing brain and external world without the normal neuromuscular pathway. To achieve this purpose, we recorded electroencephalograms (10 channels) and forearm electromyograms (3 channels) from 2 patients with the diagnosis of writer's cramp and healthy control participants as a preliminary experiment. The patients were trained to control amplitude of their electroencephalographic signal using feedback from the brain-computer interface for 1 hour a day and then continued the training twice a month. After the 5-month training, a patient clearly showed reduction of dystonic movement during writing.

[Idiopathic facial paralysis in children].

PubMed

Achour, I; Chakroun, A; Ayedi, S; Ben Rhaiem, Z; Mnejja, M; Charfeddine, I; Hammami, B; Ghorbel, A

2015-05-01

Idiopathic facial palsy is the most common cause of facial nerve palsy in children. Controversy exists regarding treatment options. The objectives of this study were to review the epidemiological and clinical characteristics as well as the outcome of idiopathic facial palsy in children to suggest appropriate treatment. A retrospective study was conducted on children with a diagnosis of idiopathic facial palsy from 2007 to 2012. A total of 37 cases (13 males, 24 females) with a mean age of 13.9 years were included in this analysis. The mean duration between onset of Bell's palsy and consultation was 3 days. Of these patients, 78.3% had moderately severe (grade IV) or severe paralysis (grade V on the House and Brackmann grading). Twenty-seven patients were treated in an outpatient context, three patients were hospitalized, and seven patients were treated as outpatients and subsequently hospitalized. All patients received corticosteroids. Eight of them also received antiviral treatment. The complete recovery rate was 94.6% (35/37). The duration of complete recovery was 7.4 weeks. Children with idiopathic facial palsy have a very good prognosis. The complete recovery rate exceeds 90%. However, controversy exists regarding treatment options. High-quality studies have been conducted on adult populations. Medical treatment based on corticosteroids alone or combined with antiviral treatment is certainly effective in improving facial function outcomes in adults. In children, the recommendation for prescription of steroids and antiviral drugs based on adult treatment appears to be justified. Randomized controlled trials in the pediatric population are recommended to define a strategy for management of idiopathic facial paralysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Physical mapping of the torsion dystonia region of human chromosome 9q34

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozelius, L.J.; Hewett, J.; Shalish, C.

1994-09-01

Torsion dystonia is a syndrome characterized by loss of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. The DYT1 gene is responsible for a subtype of torsion dystonia in which onset of symptoms tends to occur in a limb at an early age (mean 13 years) and to progress to a generalized state. Expression of the disease gene follows an autosomal dominant mode of inheritance with reduced penetrance. We initially mapped this gene to human chromosome 9q34 and have now defined its location to a < 1 cM region near the ASS locus based on historic recombination eventsmore » around a founder mutation in the Ashkenazic Jewish population. Using the CEPH YAC library and a chromosome 9 flow-sorted YAC library, we have generated a YAC contig spanning about 500 kb of this region. These YACs are being used to identify cosmids by direct hybridization to chromosome 9-specific cosmid libraries. Cosmids are being aligned by restriction digest patterns and by hybridization with oligonucleotide repeat probes. In addition, the cosmids are being {open_quotes}trapped{close_quotes} by exon amplification and these exons used to screen cDNA libraries. Thus far we have identified several candidate transcripts in this region.« less

Quantitative gait analysis in parkin disease: Possible role of dystonia.

PubMed

Castagna, Anna; Frittoli, Serena; Ferrarin, Maurizio; Del Sorbo, Francesca; Romito, Luigi M; Elia, Antonio E; Albanese, Alberto

2016-11-01

Parkin disease (PARK2, OMIM 602544) is an autosomal-recessive early-onset parkinsonism characterized by an early occurrence of lower limb dystonia. The aim of this study was to analyze spatiotemporal, kinematic, and kinetic gait parameters in patients with parkin disease in the OFF and ON conditions compared to healthy age-matched controls. Fifteen patients with parkin disease and 15 healthy age-matched controls were studied in a gait analysis laboratory with an integrated optoelectronic system. Spatiotemporal, kinematic, and kinetic gait parameters at a self-selected speed were recorded in the OFF and ON conditions. A jerk index was computed to quantify the possible reduction of smoothness of joint movements. Compared to controls, parkin patients had, either in the OFF or in the ON conditions, significant reduction of walking velocity, increased step width, and decreased percentage of double support. Kinematic analysis in both conditions showed: increased ankle dorsiflexion and knee flexion at the initial contact; maximal flexion and increased range of motion in mid stance; increased hip flexion and max extension in stance at pelvis; and increased mean tilt antiversion. Kinetics showed increased hip and knee power generation in stance in either condition. The jerk index was increased at all joints both in OFF and ON. There were no correlations between individual gait parameters and clinical ratings. Parkin patients have an abnormal gait pattern that does not vary between the OFF and the ON conditions. Variations recorded with instrumented analysis are more evident for kinematic than kinetic parameters at lower limbs. Severity of dystonia does not correlate with any individual kinematic parameter. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Cervical spinal stenosis and sports-related cervical cord neurapraxia in children.

PubMed

Boockvar, J A; Durham, S R; Sun, P P

2001-12-15

Congenital spinal stenosis has been demonstrated to contribute to cervical cord neurapraxia after cervical spinal cord injury in adult athletes. A sagittal canal diameter <14 mm and/or a Torg ratio (sagittal diameter of the spinal canal: midcervical sagittal vertebral body diameter) of <0.8 are indicative of significant cervical spinal stenosis. Although sports-related cervical spine injuries are common in children, the role of congenital cervical stenosis in the etiology of these injuries remains unclear. The authors measured the sagittal canal diameter and the Torg ratio in children presenting with cervical cord neurapraxia resulting from sports-related cervical spinal cord injuries to determine the presence of congenital spinal stenosis. A total of 13 children (9 male, 4 female) presented with cervical cord neurapraxia after a sports-related cervical spinal cord injury. Age ranged from 7 to 15 years (mean +/- SD, 11.5 +/- 2.7 years). The sports involved were football (n = 4), wrestling (n = 2), hockey (n = 2), and soccer, gymnastics, baseball, kickball, and pogosticking (n = 1 each). Lateral cervical spine radiographs were used to determine the sagittal canal diameter and the Torg ratio at C4. The sagittal canal diameter (mean +/- SD, 17.58 +/- 1.63 mm) and the Torg ratio (mean +/- SD, 1.20 +/- 0.24) were normal in all of these children. Using the sagittal canal diameter and the Torg ratio as a measurement of congenital spinal stenosis, the authors did not find evidence of congenital cervical spinal stenosis in a group of children with sports-related cervical spinal cord neurapraxia. The occurrence of cervical cord neurapraxia in pediatric patients can be attributed to the mobility of the pediatric spine rather than to congenital cervical spinal stenosis.

Laminoplasty for Cervical Myelopathy

PubMed Central

Ito, Manabu; Nagahama, Ken

2012-01-01

This article reviews cervical laminoplasty. The origin of cervical laminoplasty dates back to cervical laminectomy performed in Japan ~50 years ago. To overcome poor surgical outcomes of cervical laminectomy, many Japanese orthopedic spine surgeons devoted their lives to developing better posterior decompression procedures for the cervical spine. Thanks to the development of a high-speed surgical burr, posterior decompression procedures for the cervical spine showed vast improvement from the 1970s to the 1980s, and the original form of cervical laminoplasty was determined. Since around 2000, surgeons performing cervical laminoplasty have been adopting less invasive procedures for the posterior cervical muscle structures so as to minimize postoperative axial neck pain and obtain better functional outcomes of the cervical spine. This article covers the history of cervical laminoplasty, surgical procedures, the benefits and limitation of this procedure, and surgery-related complications. PMID:24353967

Is focal hand dystonia associated with psychopathology?

PubMed

Grafman, J; Cohen, L G; Hallett, M

1991-01-01

The purpose of this study was to determine if patients with focal hand dystonia have any significant psychopathology. We studied 20 patients with hand cramps who were participating in a therapeutic trial of botulinum toxin injections. Patients were interviewed and administered the Minnesota Multiphasic Personality Inventory (MMPI). Beck Depression Inventory, Spielberger State-Trait Anxiety Scale, a finger tapping test, and a choice serial reaction time test. Behavioral ratings were also obtained. Group statistics indicated that all personality scale scores and performances on motor tasks were within normal limits. Four out of 20 patients demonstrated mild depression. Trait anxiety scores were higher than state anxiety scores, suggesting that receiving medical treatment had a beneficial effect on mood. The number of depressive symptoms endorsed on the MMPI was correlated with reaction time speed but not finger dexterity. None of the 20 patients reported a remarkable psychiatric history. These results indicate that hand cramps are not associated with serious psychopathology.

Infantile parkinsonism-dystonia: a dopamine “transportopathy”

PubMed Central

Blackstone, Craig

2009-01-01

The dopamine transporter (DAT) retrieves the neurotransmitter dopamine from the synaptic cleft at dopaminergic synapses. Variations in solute carrier family 6A, member 3 (SLC6A3/DAT1), the human gene encoding DAT, have been implicated in attention deficit hyperactivity and bipolar disorders, and DAT is a prominent site of action for drugs such as amphetamines and cocaine. In this issue of the JCI, Kurian et al. report that an autosomal recessive infantile parkinsonism-dystonia is caused by loss-of-function mutations in DAT that impair dopamine reuptake (see the related article beginning on page 1595). Though this might be predicted to result in dopamine excess in the synaptic cleft, it likely also causes depletion of presynaptic dopamine stores and possibly downregulation of postsynaptic dopamine receptor function, resulting in impairments in dopaminergic neurotransmission consistent with the clinical presentation. This is the first report of a genetic alteration in DAT function underlying a parkinsonian disorder. PMID:19504720

A Novel Animal Model for Investigating the Neural Basis of Focal Dystonia

DTIC Science & Technology

2016-09-01

basal ganglia as the predisposing condition and dry eye as an environmental trigger. Based on experiments during the 1st year of the grant, our...experiments and preliminary recordings from the superior colliculus. 15. SUBJECT TERMS Dystonia, benign essential blepharospasm, dry eye , motor...that hypersynchronized, 7 Hz neuronal oscilla‐ tions of the basal ganglia created the predisposing condition and that  eye  irritation from  dry   eye  was

Multilevel cervical laminectomy and fusion with posterior cervical cages

PubMed Central

Bou Monsef, Jad N; Siemionow, Krzysztof B

2017-01-01

Context: Cervical spondylotic myelopathy (CSM) is a progressive disease that can result in significant disability. Single-level stenosis can be effectively decompressed through either anterior or posterior techniques. However, multilevel pathology can be challenging, especially in the presence of significant spinal stenosis. Three-level anterior decompression and fusion are associated with higher nonunion rates and prolonged dysphagia. Posterior multilevel laminectomies with foraminotomies jeopardize the bone stock required for stable fixation with lateral mass screws (LMSs). Aims: This is the first case series of multilevel laminectomy and fusion for CSM instrumented with posterior cervical cages. Settings and Design: Three patients presented with a history of worsening neck pain, numbness in bilateral upper extremities and gait disturbance, and examination findings consistent with myeloradiculopathy. Cervical magnetic resonance imaging demonstrated multilevel spondylosis resulting in moderate to severe bilateral foraminal stenosis at three cervical levels. Materials and Methods: The patients underwent a multilevel posterior cervical laminectomy and instrumented fusion with intervertebral cages placed between bilateral facet joints over three levels. Oswestry disability index and visual analog scores were collected preoperatively and at each follow-up. Pre- and post-operative images were analyzed for changes in cervical alignment and presence of arthrodesis. Results: Postoperatively, all patients showed marked improvement in neurological symptoms and neck pain. They had full resolution of radicular symptoms by 6 weeks postoperatively. At 12-month follow-up, they demonstrated solid arthrodesis on X-rays and computed tomography scan. Conclusions: Posterior cervical cages may be an alternative option to LMSs in multilevel cervical laminectomy and fusion for cervical spondylotic myeloradiculopathy. PMID:29403242

Juvenile idiopathic arthritis

MedlinePlus

... www.ncbi.nlm.nih.gov/pubmed/21452260 . Long AR, Rouster-Stevens KA. The role of exercise therapy ... nlm.nih.gov/pubmed/21131338 . Wu EY, Bryan AR, Rabinovich CE. Juvenile idiopathic arthritis. In: Kliegman RM, ...

Cervicitis

MedlinePlus

... vagina. Possible symptoms of cervicitis include bleeding between menstrual periods, pain with intercourse or during a cervical ... Frequent, painful urination Pain during intercourse Bleeding between menstrual periods Vaginal bleeding after intercourse, not associated with ...

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum.

PubMed

Maltese, Marta; Stanic, Jennifer; Tassone, Annalisa; Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Martella, Giuseppina; Imbriani, Paola; Bonsi, Paola; Mercuri, Nicola Biagio; Gardoni, Fabrizio; Pisani, Antonio

2018-03-05

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a +/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a +/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a +/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers. © 2018, Maltese et al.

Sonographic detection of basal ganglia abnormalities in spasmodic dysphonia.

PubMed

Walter, U; Blitzer, A; Benecke, R; Grossmann, A; Dressler, D

2014-02-01

Abnormalities of the lenticular nucleus (LN) on transcranial sonography (TCS) are a characteristic finding in idiopathic segmental and generalized dystonia. Our intention was to study whether TCS detects basal ganglia abnormalities also in spasmodic dysphonia, an extremely focal form of dystonia. Transcranial sonography of basal ganglia, substantia nigra and ventricles was performed in 14 patients with spasmodic dysphonia (10 women, four men; disease duration 16.5 ± 6.1 years) and 14 age- and sex-matched healthy controls in an investigator-blinded setting. Lenticular nucleus hyperechogenicity was found in 12 spasmodic dysphonia patients but only in one healthy individual (Fisher's exact test, P < 0.001) whilst other TCS findings did not differ. The area of LN hyperechogenic lesions quantified on digitized image analysis correlated with spasmodic dysphonia severity (Spearman test, r = 0.82, P < 0.001). Our findings link the underlying pathology of spasmodic dysphonia to that of more widespread forms of dystonia. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression.

PubMed

Cheng, Fu Bo; Ozelius, Laurie J; Wan, Xin Hua; Feng, Jia Chun; Ma, Ling Yan; Yang, Ying Mai; Wang, Lin

2012-02-01

Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In addition, the mutation frequency in Chinese early-onset primary dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT1 early-onset primary dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP1 gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP1 sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP1 in human lymphocytes. Our findings indicated that THAP1 sequence variants are not common in non-DYT1 early-onset primary dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP1 expression.

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

Intraspinal anomalies in early-onset idiopathic scoliosis.

PubMed

Pereira, E A C; Oxenham, M; Lam, K S

2017-06-01

In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

January Monthly Spotlight: Cervical Health and Cervical Cancer Disparities

Cancer.gov

In January, CRCHD joins the nation in raising awareness for Cervical Health and Cervical Cancer Disparities. This month we share a special focus on NCI/CRCHD research programs that are trying to reduce cervical cancer disparities in underserved communities and the people who are spreading the word about the importance of early detection.

Does rehabilitation of cervical lordosis influence sagittal cervical spine flexion extension kinematics in cervical spondylotic radiculopathy subjects?

PubMed

Moustafa, Ibrahim Moustafa; Diab, Aliaa Attiah Mohamed; Hegazy, Fatma A; Harrison, Deed E

2017-01-01

To test the hypothesis that improvement of cervical lordosis in cervical spondylotic radiculopathy (CSR) will improve cervical spine flexion and extension end range of motion kinematics in a population suffering from CSR. Thirty chronic lower CSR patients with cervical lordosis < 25° were included. IRB approval and informed consent were obtained. Patients were assigned randomly into two equal groups, study (SG) and control (CG). Both groups received stretching exercises and infrared; the SG received 3-point bending cervical extension traction. Treatments were applied 3 × per week for 10 weeks, care was terminated and subjects were evaluated at 3 intervals: baseline, 30 visits, and 3-month follow-up. Radiographic neutral lateral cervical absolute rotation angle (ARA C2-C7) and cervical segmental (C2-C7 segments) rotational and translational flexion-extension kinematics analysis were measured for all patients at the three intervals. The outcome were analyzed using repeated measures one-way ANOVA. Tukey's post-hoc multiple comparisons was implemented when necessary. Pearson correlation between ARA and segmental translational and rotational displacements was determined. Both groups demonstrated statistically significant increases in segmental motion at the 10-week follow up; but only the SG group showed a statistically significant increase in cervical lordosis (p < 0.0001). At 3-month follow up, only the SG improvements in segmental rotation and translation were maintained. Improved lordosis in the study group was associated with significant improvement in the translational and rotational motions of the lower cervical spine. This finding provides objective evidence that cervical flexion/extension is partially dependent on the posture and sagittal curve orientation. These findings are in agreement with several other reports in the literature; whereas ours is the first post treatment analysis identifying this relationship.

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage.

PubMed

Pietrowski, Detlef; Tempfer, Clemens; Bettendorf, Hertha; Bürkle, Bernd; Nagele, Fritz; Unfried, Gertrud; Keck, Christoph

2003-10-01

To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. Prospective case control study. Academic research institution. One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.

Impact of Isometric Contraction of Anterior Cervical Muscles on Cervical Lordosis.

PubMed

Fedorchuk, Curtis A; McCoy, Matthew; Lightstone, Douglas F; Bak, David A; Moser, Jacque; Kubricht, Brett; Packer, John; Walton, Dustin; Binongo, Jose

2016-09-01

This study investigates the impact of isometric contraction of anterior cervical muscles on cervical lordosis. 29 volunteers were randomly assigned to an anterior head translation (n=15) or anterior head flexion (n=14) group. Resting neutral lateral cervical x-rays were compared to x-rays of sustained isometric contraction of the anterior cervical muscles producing anterior head translation or anterior head flexion. Paired sample t-tests indicate no significant difference between pre and post anterior head translation or anterior head flexion. Analysis of variance suggests that gender and peak force were not associated with change in cervical lordosis. Chamberlain's to atlas plane line angle difference was significantly associated with cervical lordosis difference during anterior head translation (p=0.01). This study shows no evidence that hypertonicity, as seen in muscle spasms, of the muscles responsible for anterior head translation and anterior head flexion have a significant impact on cervical lordosis.

Long Term Follow-up of Botulinum Toxin Therapy for Focal Hand Dystonia: Outcome at 10 or More Years

PubMed Central

Lungu, Codrin; Karp, Barbara I; Alter, Katharine; Zolbrod, Regina; Hallett, Mark

2010-01-01

Background Prior studies have explored the efficacy and safety of BoNT treatment for FHD, but none have followed a large number of patients for 10 or more years. Methods Retrospective study, with benefit and weakness assessed on a 0-4 subjective scale. Demographic, clinical and treatment characteristics were analyzed using t-tests and Pearson correlations. Results 20 FHD patients had 10 years or longer treatment. Inter-injection intervals were variable. Musicians were more likely to wait longer between injections and had less complex dystonia. There was a trend for larger benefit in women and with shorter intervals. The dose increased over time. Dystonia characteristics did not predict response or side-effects, but benefit magnitude predicted longer compliance. No serious side-effects or antibody-mediated resistance occurred. Conclusion This is the longest reported period of BoNT treatment in the largest FHD cohort. BoNT therapy for FHD remains safe and effective after more than a decade of treatment. PMID:21506157

The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond.

PubMed

Sweney, Matthew T; Newcomb, Tara M; Swoboda, Kathryn J

2015-01-01

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. 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

Cervical interfacet spacers and maintenance of cervical lordosis.

PubMed

Tan, Lee A; Straus, David C; Traynelis, Vincent C

2015-05-01

OBJECT The cervical interfacet spacer (CIS) is a relatively new technology that can increase foraminal height and area by facet distraction. These offer the potential to provide indirect neuroforaminal decompression while simultaneously enhancing fusion potential due to the relatively large osteoconductive surface area and compressive forces exerted on the grafts. These potential benefits, along with the relative ease of implantation during posterior cervical fusion procedures, make the CIS an attractive adjuvant in the management of cervical pathology. One concern with the use of interfacet spacers is the theoretical risk of inducing iatrogenic kyphosis. This work tests the hypothesis that interfacet spacers are associated with loss of cervical lordosis. METHODS Records from patients undergoing posterior cervical fusion at Rush University Medical Center between March 2011 and December 2012 were reviewed. The FacetLift CISs were used in all patients. Preoperative and postoperative radiographic data were reviewed and the Ishihara indices and cervical lordotic angles were measured and recorded. Statistical analyses were performed using STATA software. RESULTS A total of 64 patients were identified in whom 154 cervical levels were implanted with machined allograft interfacet spacers. Of these, 15 patients underwent anterior-posterior fusions, 4 underwent anterior-posterior-anterior fusions, and the remaining 45 patients underwent posterior-only fusions. In the 45 patients with posterior-only fusions, a total of 110 levels were treated with spacers. There were 14 patients (31%) with a single level treated, 16 patients (36%) with two levels treated, 5 patients (11%) with three levels treated, 5 patients (11%) with four levels treated, 1 patient (2%) with five levels treated, and 4 patients (9%) with six levels treated. Complete radiographic data were available in 38 of 45 patients (84%). On average, radiographic follow-up was obtained at 256.9 days (range 48-524 days

Comparison of CSF Distribution between Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease.

PubMed

Yamada, S; Ishikawa, M; Yamamoto, K

2016-07-01

CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating

Intestinal Volvulus in Idiopathic Steatorrhea

PubMed Central

Warner, H. A.; Kinnear, D. G.; Cameron, D. G.

1963-01-01

Volvulus of the intestine has recently been observed in three patients with idiopathic steatorrhea in relapse. Two patients gave a history of intermittent abdominal pain, distension and obstipation. Radiographic studies during these attacks revealed obstruction at the level of the sigmoid colon. Reduction under proctoscopic control was achieved in one instance, spontaneous resolution occurring in the other. The third patient presented as a surgical emergency and underwent operative reduction of a small intestinal volvulus. Persistence of diarrhea and weight loss postoperatively led to further investigation and a diagnosis of idiopathic steatorrhea. In all cases, treatment resulted in clinical remission with a coincident disappearance of obstructive intestinal symptoms. The pathogenesis of volvulus in sprue is poorly understood. Atonicity and dilatation of the bowel and stretching of the mesentery likely represent important factors. The symptoms of recurrent abdominal pain and distension in idiopathic steatorrhea necessitate an increased awareness of intestinal volvulus as a complication of this disease. ImagesFig. 1Fig. 2Fig. 3Figs. 4 and 5Fig. 6 PMID:13998948

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

DTIC Science & Technology

2012-10-01

Mice with mutations in genes known to cause dystonia in humans are so far virtually asymptomatic. Only mild motor deficiencies have been seen, such...identified the gene for one of the subunits of Na,K- ATPase, ATP1A3, as the site of mutations in RDP (de Carvalho Aguiar et al. 2004). Our prior work in...first paper, and to be able to give the mouse line an official name based on the mutated gene . Funding has been applied for from the following

Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models

PubMed Central

Yokoi, Fumiaki; Dang, Mai T.; Yang, Guang; Li, JinDong; Doroodchi, Atbin; Zhou, Tong; Li, Yuqing

2011-01-01

Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for ε-sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M-D. We developed a mouse model of DYT11 M-D using paternally-inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since ε-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of ε-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally-inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that ε-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of ε-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. PMID:22040906

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

Cervical pneumatocyst.

PubMed

Hoover, Jason M; Wenger, Doris E; Eckel, Laurence J; Krauss, William E

2011-09-01

The authors present the case of a 56-year-old right hand-dominant woman who was referred for chronic neck pain and a second opinion regarding a cervical lesion. The patient's pain was localized to the subaxial spine in the midline. She reported a subjective sense of intermittent left arm weakness manifesting as difficulty manipulating small objects with her hands and fingers. She also reported paresthesias and numbness in the left hand. Physical and neurological examinations demonstrated no abnormal findings except for a positive Tinel sign over the left median nerve at the wrist. Electromyography demonstrated bilateral carpal tunnel syndrome with no cervical radiculopathy. Cervical spine imaging demonstrated multilevel degenerative disc disease and a pneumatocyst of the C-5 vertebral body. The alignment of the cervical spine was normal. A review of the patient's cervical imaging studies obtained in 1995, 2007, 2008, and 2010 demonstrated that the pneumatocyst was not present in 1995 but was present in 2007. The lesion had not changed in appearance since 2007. At an outside institution, multilevel fusion of the cervical spine was recommended to treat the pneumatocyst prior to evaluation at the authors' institution. The authors, however, did not think that the pneumatocyst was the cause of the patient's neck pain, and cervical pneumatocysts typically have a benign course. As such, the authors recommended conservative management and repeated MR imaging in 6 months. Splinting was used to treat the patient's carpal tunnel syndrome.

[Analysis of clinical phenotype and CGH1 gene mutations in a family affected with dopa-responsive dystonia].

PubMed

Yan, Yaping; Chen, Xiaohong; Luo, Wei

2017-04-10

To explore genetic mutations and clinical features of a pedigree affected with dopa-responsive dystonia. PCR and Sanger sequencing were applied to detect mutations of the GCH1 gene among 7 members from the pedigree. The family was detected to have a known heterozygous mutation of the GCH1 gene (c.550C>T). For the 7 members from the pedigree, the age of onset has ranged from 13 to 60 years. The mother of the proband has carried the same mutation but was still healthy at 80. The symptoms of the other three patients were in slow progression, with diurnal fluctuation which can be improved with sleeping, dystonias of lower limbs, and tremor of both hands. Treatment with small dose of levodopa has resulted in significant improvement of clinical symptoms. By database analysis, the c.550C>T mutation was predicted as probably pathological. The c.550C>T mutation probably underlies the disease in this pedigree. The clinical phenotypes of family members may be variable for their ages of onset. Some may even be symptom free.

Detection of Actinomyces spp. in cervical exudates from women with cervical intraepithelial neoplasia or cervical cancer.

PubMed

García-García, Alejandra; Coronel-Martínez, Jaime; Leon, David Cantú-de; Romero-Figueroa, María Del Socorro; Caballero-Pantoja, Yolanda Elizabeth; Manzanares-Leal, Gauddy Lizeth; Rodriguez-Morales, Miguel; Sandoval-Trujillo, Horacio; Ramírez-Durán, Ninfa

2017-06-01

Under certain circumstances, Actinomyces behaves as an opportunistic microorganism and can cause actinomycosis, a chronic and inflammatory granulomatous infection. The purpose of this project was to detect the presence of Actinomyces in cervical exudates from women with cervical intraepithelial neoplasia (CIN) and women with cervical cancer. Cervical samples from 92 women were divided into three groups: CIN, cervical cancer and healthy women. Metagenomic DNA extraction was performed following the Qiagen QIAamp Mini Kit protocol. A specific fragment (675 bp) was amplified by PCR in order to detect the presence of Actinomycetales. Samples in which Actinomycetales was detected were subjected to separate amplification reactions with primer pairs for A. israelii, A. viscosus, A. meyeri and A. odontolyticus. Amplified products were observed by 2 % agarose gel electrophoresis. Actinomyces were found in 10 % of women with CIN, 36.6 % of women with cervical cancer and 9 % of healthy women. The species identified in this study were A. meyeri in 14/92 samples (15.2 %), A. viscosus in 10/92 samples (10.8 %), A. odontolyticus in 4/92 samples (4.3 %) and A. israelii in 6/92 samples (6.5 %). Patients with cervical cancer had a higher prevalence of the presence of Actinomyces compared to the CIN and control groups. This is the first study in which a deliberate search of this genus has been performed in women with cervical pathologies. The use of specific primers for each species facilitated their detection in comparison with traditional isolation methods. More information is necessary to understand the molecular mechanisms involved in the complex role that bacterial communities may play in the development of cancer (and vice versa).

The Mayo Clinic Arizona Spasmodic Dysphonia Experience: A Demographic Analysis of 718 Patients.

PubMed

Patel, Alpen B; Bansberg, Stephen F; Adler, Charles H; Lott, David G; Crujido, Lisa

2015-11-01

Analyze demographic data collected over a 25-year experience of 718 patients with spasmodic dysphonia (SD) who have been treated with botulinum toxin-A (BoNT-A) and compare our data with previously published studies. Seven hundred eighteen patients with SD were treated with 6621 BoNT-A injections at Mayo Clinic Arizona between 1989 and 2014. All patients were treated by the same physician team. Background demographic data for each patient were recorded. Of 718 patients, 557 patients were female (77.6%). Six hundred sixty of 718 (91.8%) patients had adductor SD (AdSD), and 58 of 718 (8.1%) patients had abductor SD (AbSD). Average age of onset was 51 years. Of 718 patients, 378 (52.6%) had vocal tremor (VT); VT was present in 54.4% of AdSD patients and 32.1% of AbSD patients. Thirty-seven of 718 (5.2%) patients had other dystonias, including cervical dystonia (2.3%), blepharospasm (1.4%), limb dystonia (1.1%), and oromandibular dystonia (0.3%). A positive family history of SD was present in only 6 of 718 patients (0.8%) and of other dystonias in 11 of 718 patients (1.5%). Spasmodic dysphonia is a chronic and potentially disabling focal laryngeal dystonia. The Mayo Clinic Arizona SD experience compares to prior reports and reveals a female preponderance, onset in middle age, infrequent hereditary pattern, high co-occurrence of VT, and low co-occurrence of other dystonias. © The Author(s) 2015.

Nonsurgical Management of Adolescent Idiopathic Scoliosis.

PubMed

Gomez, Jaime A; Hresko, M Timothy; Glotzbecker, Michael P

2016-08-01

Pediatric patient visits for spinal deformity are common. Most of these visits are for nonsurgical management of scoliosis, with approximately 600,000 visits for adolescent idiopathic scoliosis (AIS) annually. Appropriate management of scoliotic curves that do not meet surgical indication parameters is essential. Renewed enthusiasm for nonsurgical management of AIS (eg, bracing, physical therapy) exists in part because of the results of the Bracing in Adolescent Idiopathic Scoliosis Trial, which is the only randomized controlled trial available on the use of bracing for AIS. Bracing is appropriate for idiopathic curves between 20° and 40°, with successful control of these curves reported in >70% of patients. Patient adherence to the prescribed duration of wear is essential to maximize the effectiveness of the brace. The choice of brace type must be individualized according to the deformity and the patient's personality as well as the practice setting and brace availability.

Anterior cervical discectomy and fusion versus cervical arthroplasty for the management of cervical spondylosis: a meta-analysis.

PubMed

Ma, Zhuo; Ma, Xun; Yang, Huilin; Guan, Xiaoming; Li, Xiang

2017-04-01

The aim of this study was to compare the efficacy and safety of anterior cervical discectomy and fusion (ACDF) and cervical arthroplasty for patients with cervical spondylosis. PubMed, Embase, and Cochrane Library were used to search for relevant articles published prior to April 2016 to identify studies comparing ACDF and cervical arthroplasty involving patients with cervical spondylosis. Relative risks (RR) and mean differences (MD) were used to measure the efficacy and safety of ACDF and cervical arthroplasty using the random effects model. The meta-analysis of 17 studies involved 3122 patients diagnosed with cervical spondylosis. Patients undergoing ACDF showed lower overall success rate (RR 0.84; 95 % CI 0.77-0.92; P < 0.001), higher VAS score (MD 0.36; 95 % CI 0.08-0.64; P = 0.011), and shorter mean surgical duration (MD -1.62; 95 % CI -2.80 to -0.44; P = 0.007) when compared with cervical arthroplasty. However, the association between ACDF therapy and the risk of mean blood loss (MD -0.16; 95 % CI -0.34 to 0.02; P = 0.082), mean hospitalization (MD 0.02; 95 % CI -0.31 to 0.36; P = 0.901), patient satisfaction (RR 0.96; 95 % CI 0.92-1.00; P = 0.066), neck disability index (MD 0.20; 95 % CI -0.05 to 0.44; P = 0.113), reoperation (RR 1.25; 95 % CI 0.64-2.41; P = 0.514), or complication (RR 1.17; 95 % CI 0.90-1.52; P = 0.242) was not statistically significant. Patients undergoing ACDF therapy tended to exhibit lower overall success rate, higher VAS score, and decreased mean surgical duration when compared with patients treated with cervical arthroplasty.

Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report.

PubMed

Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca; Luppi, Fabrizio

2016-05-25

Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate. We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant. This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis.

Amplitude and timing of somatosensory cortex activity in Task Specific Focal Hand Dystonia

PubMed Central

Dolberg, Rebecca; Hinkley, Leighton B. N.; Honma, Susanne; Zhu, Zhao; Findlay, Anne M.; Byl, Nancy N.; Nagarjan, Srikantan S.

2011-01-01

Objective Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. Methods In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from thirteen patients and matched controls. Results Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. Conclusions There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Significance Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning based sensorimotor interventions. PMID:21802357

Amplitude and timing of somatosensory cortex activity in task-specific focal hand dystonia.

PubMed

Dolberg, Rebecca; Hinkley, Leighton B N; Honma, Susanne; Zhu, Zhao; Findlay, Anne M; Byl, Nancy N; Nagarajan, Srikantan S

2011-12-01

Task-specific focal hand dystonia (tspFHD) is a movement disorder diagnosed in individuals performing repetitive hand behaviors. The extent to which processing anomalies in primary sensory cortex extend to other regions or across the two hemispheres is presently unclear. In response to low/high rate and novel tactile stimuli on the affected and unaffected hands, magnetoencephalography (MEG) was used to elaborate activity timing and amplitude in the primary somatosensory (S1) and secondary somatosensory/parietal ventral (S2/PV) cortices. MEG and clinical performance measures were collected from 13 patients and matched controls. Compared to controls, subjects with tspFHD had increased response amplitude in S2/PV bilaterally in response to high rate and novel stimuli. Subjects with tspFHD also showed increased response latency (low rate, novel) of the affected digits in contralateral S1. For high rate, subjects with tspFHD showed increased response latency in ipsilateral S1 and S2/PV bilaterally. Activation differences correlated with functional sensory deficits (predicting a latency shift in S1), motor speed and muscle strength. There are objective differences in the amplitude and timing of activity for both hands across contralateral and ipsilateral somatosensory cortex in patients with tspFHD. Knowledge of cortical processing abnormalities across S1 and S2/PV in dystonia should be applied towards the development of learning-based sensorimotor interventions. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Ictal dystonia and secondary generalization in temporal lobe seizures: a video-EEG study.

PubMed

Popovic, Ljubica; Vojvodic, Nikola; Ristic, Aleksandar J; Bascarevic, Vladimir; Sokic, Dragoslav; Kostic, Vladimir S

2012-12-01

The aim of this study was to determine whether the occurrence of unilateral ictal limb dystonia (ID) during complex partial seizures (CPS) reduces the possibility of contralateral propagation (CP) and secondary generalization (SG) in patients with temporal lobe epilepsy (TLE). We assessed 216 seizures recorded in 33 patients with pharmacoresistant TLE. All patients underwent video-EEG telemetry prior to surgical treatment with good postoperative outcomes (Engel I). Ictal limb dystonia was observed in 16 of the 33 patients (48%) and 58 of the 216 seizures (26.8%). We found highly significant differences in the frequency of SG between seizures with ID and seizures without ID (2/58 vs. 41/158; 3.45% vs. 25.95%; p<0.001). Contralateral propagation was seen in 13 of the 57 analyzed seizures with ID compared to 85 of the 158 seizures without ID (22.8% vs. 53.8%; p<0.001). Among the CPS without SG, we found that the mean duration of seizures with ID was significantly longer than the duration of seizures without ID (81.66±40.10 vs. 68.88±25.01 s; p=0.011). Our findings that CP and SG occur less often in patients with ID, yet the duration of CPS without SG is longer in patients with ID, suggest that the basal ganglia might inhibit propagation to the contralateral hemisphere but not ictal activity within the unilateral epileptic network. Copyright © 2012 Elsevier Inc. All rights reserved.

Is the cervical spine clear? Undetected cervical fractures diagnosed only at autopsy.

PubMed

Sweeney, J F; Rosemurgy, A S; Gill, S; Albrink, M H

1992-10-01

Undetected cervical-spine injuries are a nemesis to both trauma surgeons and emergency physicians. Radiographic protocols have been developed to avoid missing cervical-spine fractures but are not fail-safe. Three case reports of occult cervical fractures documented at autopsy in the face of normal cervical-spine radiographs and computerized tomography scans are presented.

Cervical spondylotic amyotrophy.

PubMed

Jiang, Sheng-Dan; Jiang, Lei-Sheng; Dai, Li-Yang

2011-03-01

Cervical spondylotic amyotrophy is characterized with weakness and wasting of upper limb muscles without sensory or lower limb involvement. Two different mechanisms have been proposed in the pathophysiology of cervical spondylotic amyotrophy. One is selective damage to the ventral root or the anterior horn, and the other is vascular insufficiency to the anterior horn cell. Cervical spondylotic amyotrophy is classified according to the most predominantly affected muscle groups as either proximal-type (scapular, deltoid, and biceps) or distal-type (triceps, forearm, and hand). Although cervical spondylotic amyotrophy always follows a self-limited course, it remains a great challenge for spine surgeons. Treatment of cervical spondylotic amyotrophy includes conservative and operative management. The methods of operative management for cervical spondylotic amyotrophy are still controversial. Anterior decompression and fusion or laminoplasty with or without foraminotomy is undertaken. Surgical outcomes of distal-type patients are inferior to those of proximal-type patients.

Analysis of digitized cervical images to detect cervical neoplasia

NASA Astrophysics Data System (ADS)

Ferris, Daron G.

2004-05-01

Cervical cancer is the second most common malignancy in women worldwide. If diagnosed in the premalignant stage, cure is invariably assured. Although the Papanicolaou (Pap) smear has significantly reduced the incidence of cervical cancer where implemented, the test is only moderately sensitive, highly subjective and skilled-labor intensive. Newer optical screening tests (cervicography, direct visual inspection and speculoscopy), including fluorescent and reflective spectroscopy, are fraught with certain weaknesses. Yet, the integration of optical probes for the detection and discrimination of cervical neoplasia with automated image analysis methods may provide an effective screening tool for early detection of cervical cancer, particularly in resource poor nations. Investigative studies are needed to validate the potential for automated classification and recognition algorithms. By applying image analysis techniques for registration, segmentation, pattern recognition, and classification, cervical neoplasia may be reliably discriminated from normal epithelium. The National Cancer Institute (NCI), in cooperation with the National Library of Medicine (NLM), has embarked on a program to begin this and other similar investigative studies.

IgG abnormality in narcolepsy and idiopathic hypersomnia.

PubMed

Tanaka, Susumu; Honda, Makoto

2010-03-05

A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia.

PubMed

Buttkus, Franziska; Baur, Volker; Jabusch, Hans-Christian; de la Cruz Gomez-Pellin, Maria; Paulus, Walter; Nitsche, Michael A; Altenmüller, Eckart

2011-01-01

Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument. Nine professional pianists suffering from MD were included in a placebo-controlled double-blinded study. Retraining consisted of slow, voluntarily controlled movements on the piano and was combined with tDCS. Patients were treated with three stimulation protocols: anodal tDCS, cathodal tDCS and placebo stimulation. No beneficial effects of single-session tDCS-supported sensorimotor retraining on fine motor control in pianists with MD were found in all three conditions. The main cause of the negative result of this study may be the short intervention time. One retraining session with a duration of 20 min seems not sufficient to improve symptoms of MD. Additionally, a single tDCS session might not be sufficient to modify sensorimotor learning of a highly skilled task in musicians with dystonia.

General Information about Cervical Cancer

MedlinePlus

... Research Cervical Cancer Treatment (PDQ®)–Patient Version General Information About Cervical Cancer Go to Health Professional Version ... is also available. Cervical Cancer During Pregnancy General Information About Cervical Cancer During Pregnancy Treatment of cervical ...

Pathology of idiopathic non-cirrhotic portal hypertension.

PubMed

Guido, Maria; Sarcognato, Samantha; Sacchi, Diana; Colloredo, Guido

2018-04-12

Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.

Reliability and validity of CODA motion analysis system for measuring cervical range of motion in patients with cervical spondylosis and anterior cervical fusion.

PubMed

Gao, Zhongyang; Song, Hui; Ren, Fenggang; Li, Yuhuan; Wang, Dong; He, Xijing

2017-12-01

The aim of the present study was to evaluate the reliability of the Cartesian Optoelectronic Dynamic Anthropometer (CODA) motion system in measuring the cervical range of motion (ROM) and verify the construct validity of the CODA motion system. A total of 26 patients with cervical spondylosis and 22 patients with anterior cervical fusion were enrolled and the CODA motion analysis system was used to measure the three-dimensional cervical ROM. Intra- and inter-rater reliability was assessed by interclass correlation coefficients (ICCs), standard error of measurement (SEm), Limits of Agreements (LOA) and minimal detectable change (MDC). Independent samples t-tests were performed to examine the differences of cervical ROM between cervical spondylosis and anterior cervical fusion patients. The results revealed that in the cervical spondylosis group, the reliability was almost perfect (intra-rater reliability: ICC, 0.87-0.95; LOA, -12.86-13.70; SEm, 2.97-4.58; inter-rater reliability: ICC, 0.84-0.95; LOA, -13.09-13.48; SEm, 3.13-4.32). In the anterior cervical fusion group, the reliability was high (intra-rater reliability: ICC, 0.88-0.97; LOA, -10.65-11.08; SEm, 2.10-3.77; inter-rater reliability: ICC, 0.86-0.96; LOA, -10.91-13.66; SEm, 2.20-4.45). The cervical ROM in the cervical spondylosis group was significantly higher than that in the anterior cervical fusion group in all directions except for left rotation. In conclusion, the CODA motion analysis system is highly reliable in measuring cervical ROM and the construct validity was verified, as the system was sufficiently sensitive to distinguish between the cervical spondylosis and anterior cervical fusion groups based on their ROM.

Transcranial direct current stimulation improves neurorehabilitation of task-specific dystonia: a pilot study.

PubMed

Rosset-Llobet, Jaume; Fàbregas-Molas, Sílvia; Pascual-Leone, Alvaro

2014-03-01

Sensory-motor returning (SMR) can help the symptoms of task-specific focal hand dystonia. However, effects vary across patients and take many sessions. Here, we present proof of principle evidence that transcranial direct current stimulation (tDCS) can enhance these effects. We compared the effects of a combined tDCS-SMR protocol (n=4 patients) with the efficacy of SMR alone (n=30 patients). All 4 patients treated with the combined protocol showed greater improvement than those undergoing SMR alone. Results encourage a larger, parallel-group clinical trial with sham tDCS control.

[Adolescent idiopathic scoliosis].

PubMed

2016-12-01

Adolescent idiopathic scoliosis is a 3D spinal deformity in frontal, sagittal and axial planes, with high relevance in the pediatric population especially in adolescents and females between 10 years of age and the end of growth spurt and skeletal maturity. The radiographic manifestation is a curve greater than 10° measured by Cobb method associated with vertebral rotation. "Idiopathic" diagnosis has to be done after neuroanatomical anomalies of the posterior cerebral fosa and spinal canal have been ruled out. The physical finding of a thoracic or lumbar hump is the clinical manifestation of vertebral rotation seen in a forward bending test (Adam's Test). It is recommended that all curves with a magnitude greater than 20° have to be controlled and treated by a spinal surgeon being observation, bracing and surgery the different treatment options based on the extent, progression of deformity and basically the clinical condition of the patient. Sociedad Argentina de Pediatría.

Idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

2017-02-23

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Idiopathic toe walking.

PubMed

Oetgen, Matthew E; Peden, Sean

2012-05-01

Toe walking is a bilateral gait abnormality in which a normal heel strike is absent and most weight bearing occurs through the forefoot. This abnormality may not be pathologic in patients aged <2 years, but it is a common reason for referral to an orthopaedic surgeon. Toe walking can be caused by several neurologic and developmental abnormalities and may be the first sign of a global developmental problem. Cases that lack a definitive etiology are categorized as idiopathic. A detailed history, with careful documentation of the developmental history, and a thorough physical examination are required in the child with a primary report of toe walking. Treatment is based on age and the severity of the abnormality. Management includes observation, stretching, casting, bracing, chemodenervation, and surgical lengthening of the gastrocnemius-soleus complex and/or Achilles tendon. An understanding of idiopathic toe walking as well as treatment options and their outcomes can help the physician individualize treatment to achieve optimal results.

[Cervical cerclage].

PubMed

Akladios, C Y; Sananes, N; Gaudineau, A; Boudier, E; Langer, B

2015-10-01

Cervical cerclage aims to strengthen not only the mechanical properties of the cervix, but also its immunological and anti-infectious functions. The demonstration of a strong interrelation between cervical insufficiency as well as decreased cervical length at endo-vaginal ultrasonography and infection has changed the indications cerclage. Actually we can distinguish three indications for cerclage: prophylactic, for obstetrical history; therapeutic, for shortened cervical length at ultrasonography in patients at risk and; emergency cerclage in case of threatening cervix at physical examination. The McDonald's technique is the most recommended. In case of failure, it is proposed to realize cerclage at a higher level on the cervix either by vaginal or abdominal route. Copyright © 2015 Elsevier Masson SAS. All rights reserved.