Manifestation Of Dystonia Research Articles

Striatal cholinergic transmission in an inducible transgenic mouse model of paroxysmal non-kinesiogenic dyskinesia

Altered interaction between striatonigral dopaminergic (DA) inputs and local acetylcholine (ACh) in striatum has long been hypothesized to play a central role in the pathophysiology of dystonia and dyskinesia. Indeed, previous research using several genetic mouse models of human isolated dystonia identified a shared endophenotype with paradoxical excitation of striatal cholinergic interneuron (ChIs) activity in response to activation of dopamine D2 receptors (D2R). These mouse models lack a dystonic motor phenotype, which leaves a critical gap in comprehending the role of DA and ACh transmission in the manifestations of dystonia. To tackle this question, we used a combination of ex vivo slice physiology and in vivo monitoring of striatal ACh dynamics in the inducible, phenotypically penetrant, transgenic mouse model of paroxysmal non-kinesiogenic dyskinesia (PNKD), an animal with both dystonic and dyskinetic features. We found that, similarly to genetic models of isolated dystonia, the PNKD mouse displays D2R-induced paradoxical excitation of ChI firing in ex vivo striatal brain slices. In vivo, caffeine triggers dystonic symptoms while reversing the D2R-mediated excitation of ChIs and desynchronizing ACh release in PNKD mice. In WT littermate controls, caffeine stimulates spontaneous locomotion through a similar but reversed mechanism involving an excitatory switch of the D2R control of ChI activity, associated with enhanced synchronization of ACh release. These observations suggest that the “paradoxical excitation” of cholinergic interneurons described in isolated dystonia models could represent a compensatory or protective mechanism that prevents manifestation of movement abnormalities and that phenotypic dystonia is possible only when this is absent. These findings also suggest that D2Rs may play an important role in synchronizing the ChI network leading to rhythmic ACh release during heightened movement states. Dysfunction of this interaction and corresponding desynchrony of ACh release may contribute to aberrant movements.

Deep Brain Stimulation of the Subthalamic Nucleus in a Patient With X-Linked Dystonia-Parkinsonism. (P11-11.001)

<h3>Objective:</h3> N/A <h3>Background:</h3> X-linked dystonia-parkinsonism (XDP) is one of the genetic causes of generalized dystonia. Both dystonia and parkinsonism components of the disease are frequently resistant to pharmacologic treatment. Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective treatment modality, especially for dystonic manifestations of XDP. The subthalamic nucleus (STN) is a known DBS target in Parkinson disease but it is less frequently used for treatment of dystonia. In our case report we describe a patient with XDP who underwent bilateral STN DBS with notable improvement in parkinsonism and dystonia. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Our patient is a right-handed Filipino man from the island of Panay. He developed bilateral parkinsonism, blepharospasm, oromandibular and cervical dystonia at the age of 51. Diagnosis of XDP was confirmed with genetic testing. Marked improvement of Unified Parkinson Disease Rating Scale (UPDRS) motor score in response to levodopa administration was demonstrated (65 off and 36 on). His pre-DBS Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was 27.5. Bilateral GPi were initially selected as a target for DBS lead placement based on previously published data. Surgical target was subsequently changed to bilateral STN due to distortion in GPi anatomy likely secondary to long-standing disease. Medtronic Percept PC neurostimulator with Sensight DBS leads were used. There was no surgical complications. Patient had an immediate improvement in tremor, bradykinesia and rigidity after his first programming visit; antidystonic effects of stimulation became evident over the next few weeks. There was substantial improvement in limb and oromandibular dystonia and mild effect on cervical dystonia and blepharospasm. His speech clarity became better as well. His motor UPDRS and BFMDRS decreased to 21 and 19, respectively. Gait, posture, ability to perform activities of daily living significantly improved. <h3>Conclusions:</h3> The subthalamic nucleus may be considered an alternative deep brain stimulation target in patients with X-linked dystonia-parkinsonism. <b>Disclosure:</b> Dr. Redko has nothing to disclose. Brian Kopell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Brian Kopell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott Neuromodulation. Brian Kopell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Enspire DBS. Dr. Tse has nothing to disclose.

Dystonia as a prominent presenting feature in developmental and epileptic encephalopathies: A case series

IntroductionAlthough there has been increasing recognition of the occurrence of non-epileptic involuntary movements in developmental and epileptic encephalopathies (DEEs), the spectrum of dystonic presentations associated with these conditions remains poorly described. We sought to expand the catalogue of dystonia-predominant phenotypes in monogenic DEEs, building on the recently introduced concept of an epilepsy-movement disorder spectrum. MethodsCases were identified from a whole-exome-sequenced cohort of 45 pediatric index patients with complex dystonia (67% sequenced as parent-child trios). Review of molecular findings in DEE-associated genes was performed. For five individuals with identified DEE-causing variants, detailed information about presenting phenotypic features and the natural history of disease was obtained. ResultsDe-novo pathogenic and likely pathogenic missense variants in GABRA1, GABBR2, GNAO1, and FOXG1 gave rise to infantile-onset persistent and paroxysmal dystonic manifestations, beginning in the limb or truncal musculature and progressing gradually to a generalized state. Coexisting, less prominent movement-disorder symptoms were observed and included myoclonic, ballistic, and stereotypic abnormal movements as well as choreoathetosis. Dystonia dominated over epileptic neurodevelopmental comorbidities in all four subjects and represented the primary indication for molecular genetic analysis. We also report the unusual case of an adult female patient with dystonia, tremor, and mild learning disability who was found to harbor a pathogenic frameshift variant in MECP2. ConclusionsDystonia can be a leading clinical manifestation in different DEEs. A monogenic basis of disease should be considered on the association of dystonia and developmental delay-epilepsy presentations, justifying a molecular screening for variants in DEE-associated genes.

Variability of Movement Disorders: The Influence of Sensation, Action, Cognition, and Emotions.

Patients with movement disorders experience fluctuations unrelated to disease progression or treatment. Extrinsic factors that contribute to the variable expression of movement disorders are environment related. They influence the expression of movement disorders through sensory-motor interactions and include somatosensory, visual, and auditory stimuli. Examples of somatosensory effects are stimulus sensitivity of myoclonus on touch and sensory amelioration in dystonia but also some less-appreciated effects on parkinsonian tremor and gait. Changes in visual input may affect practically all types of movement disorders, either by loss of its compensatory role or by disease-related alterations in the pathways subserving visuomotor integration. The interaction between auditory input and motor function is reflected in simple protective reflexes and in complex behaviors such as singing or dancing. Various expressions range from the effect of music on parkinsonian bradykinesia to tics. Changes in body position affect muscle tone and may result in marked fluctuations of rigidity or may affect dystonic manifestations. Factors intrinsic to the patient are related to their voluntary activity and cognitive, motivational, and emotional states. Depending on the situation or disease, they may improve or worsen movement disorders. We discuss various factors that can influence the phenotypic variability of movement disorders, highlighting the potential mechanisms underlying these manifestations. We also describe how motor fluctuations can be provoked during the clinical assessment to help reach the diagnosis and appreciated to understand complaints that seem discrepant with objective findings. We summarize advice and interventions based on the variability of movement disorders that may improve patients' functioning in everyday life. © 2020 International Parkinson and Movement Disorder Society.

Hyperkinetic manifestations in superficial siderosis: evidence for pathogenic network disruption

Superficial siderosis (SS) of central nervous system is a rare condition characterized by hemosiderin deposition diffusely involving supratentorial and infratentorial compartments. SS usually manifests with ataxia and sensorineural hearing loss. Basal ganglia are almost always spared by the degenerative process, and movement disorders are only rarely reported. We describe the case of an aged woman with apparently idiopathic SS presenting with cerebellar ataxia, hearing loss, and orofacial dyskinesias. Together with some previously reported patients affected by SS and presenting with dystonic manifestations, our case reinforces the current hypothesis supporting a wide network disruption, rather than a direct basal ganglia damage, as the likely underlying cause of some dystonic syndromes.

Cognitive impairment and mental disorders in patients with focal muscular dystonia

Non-motor manifestations in focal muscular dystonia (FMD) have been little studied. Objective: to analyze the characteristics of cognitive impairment (CI) and mental disorders (MDs) in FMD. Patients and methods. Fifteen patients (7 men and 8 women) aged 25 to 80 years (mean age, 59.8±14.7 years) with FMD were examined. Cervical dystonia and blepharospasm were noted in 10 (66.7%) and 5 (33.3%) patients, respectively. A control group consisted of 15 healthy individuals (7 men and 8 women) (mean age, 58.2±14.9 years). Neurological and standardized psychiatric examinations and neuropsychological tests were performed; the Beck Depression Inventory and the Spielberger State-Trait Anxiety Inventory were used. Results and discussion. Patients with FMD were found to have moderate CI as impaired control functions. Depression was diagnosed in 9 (60%) patients; it corresponded to the pattern of protracted psychogenically provoked conditions in most cases (n = 8). Six (40%) patients with FMD had anxiety and somatic disorders. The pathophysiology of non-motor manifestations of FMD is likely to depend on many factors, including the relationship between different clinical factors and basal ganglia dysfunction. The data on the association between emotional disorders and CI in FMD are contradictory. MDs can seem to be as an additional factor that aggravates the manifestations of dystonia. Conclusion. In patients with FMD, moderate CI can be due to emotional disorders that aggravate the manifestations of the disease. The diagnosis and correction of emotional disorders are promising in the management of patients with FMD.

A case of segmental dystonia with mental/psychic nonmotor disorders

The paper discusses the specific features of clinical presentations in patients with muscle dystonia, the presence of cognitive and mental disorders in dystonia. It presents a clinical case of severe segmental dystonia in a 72-year-old patient with cognitive and mental disorders. The manifestations of dystonia regressed during treatment with botulinum toxin; however, the patient did not report any improvement. An improvement could not be achieved after a psychiatrist's consultation and treatment for mental disorders.

Therapeutic Management of the Overlapping Syndromes of Atypical Parkinsonism.

Progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy account for approximately 10% of neurodegenerative parkinsonism. Considerable clinical overlap exists between these disorders that extends to features considered characteristic of each disease. Clinical diagnostic criteria have attempted to increase the accuracy of clinical diagnosis as accurate diagnosis is necessary to inform prognosis and to facilitate the recognition of disease-modifying treatments. Currently no such treatment exists. Nevertheless, many clinical trials aiming to change the natural history of these diseases are ongoing. The spread and accumulation of abnormal proteins are among the pathophysiological mechanisms targeted. For the time being, however, only symptomatic treatment is available. Levodopa is used to treat parkinsonism, but patients usually show a poor or transient response. Amantadine is also used in practice for the same indication. Botulinum toxin can alleviate focal dystonic manifestations. Addressing non-motor manifestations is limited by the potential of available drugs to impact on other aspects of the disease. Most of the new symptomatic formulations under study are focused on orthostatic hypotension in multiple system atrophy. Exercise, occupational, physical, and speech therapy and psychotherapy should always accompany pharmacological approaches.

The progression rate of spinocerebellar ataxia type 2 changes with stage of disease

BackgroundSpinocerebellar ataxia type 2 (SCA2) affects several neurological structures, giving rise to multiple symptoms. However, only the natural history of ataxia is well known, as measured during the study duration. We aimed to describe the progression rate of ataxia, by the Scale for the Assessment and Rating of Ataxia (SARA), as well as the progression rate of the overall neurological picture, by the Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), and not only during the study duration but also in a disease duration model. Comparisons between these models might allow us to explore whether progression is linear during the disease duration in SCA2; and to look for potential modifiers.ResultsEighty–eight evaluations were prospectively done on 49 symptomatic subjects; on average (SD), study duration and disease duration models covered 13 (2.16) months and 14 (6.66) years of individuals’ life, respectively. SARA progressed 1.75 (CI 95%: 0.92–2.57) versus 0.79 (95% CI 0.45 to 1.14) points/year in the study duration and disease duration models. NESSCA progressed 1.45 (CI 95%: 0.74–2.16) versus 0.41 (95% CI 0.24 to 0.59) points/year in the same models. In order to explain these discrepancies, the progression rates of the study duration model were plotted against disease duration. Then an acceleration was detected after 10 years of disease duration: SARA scores progressed 0.35 before and 2.45 points/year after this deadline (p = 0.013). Age at onset, mutation severity, and presence of amyotrophy, parkinsonism, dystonic manifestations and cognitive decline at baseline did not influence the rate of disease progression.ConclusionsNESSCA and SARA progression rates were not constant during disease duration in SCA2: early phases of disease were associated with slower progressions. Modelling of future clinical trials on SCA2 should take this phenomenon into account, since disease duration might impact on inclusion criteria, sample size, and study duration. Our database is available online and accessible to future studies aimed to compare the present data with other cohorts.

Basal ganglia mechanisms in action selection, plasticity, and dystonia

Basal ganglia circuits are organized to selected desired actions and to inhibit potentially competing unwanted actions. This is accomplished through a complex circuitry that is modified through development and learning. Mechanisms of neural plasticity underlying these modifications are increasingly understood, but new mechanisms continue to be discovered. Dystonia, a movement disorder characterized by involuntary muscle contractions that cause abnormal postures and movements. Emerging evidence points to important links between mechanisms of plasticity and the manifestations of dystonia. Investigation of these mechanisms has improved understanding of the action of currently used medication and is informing the development of new treatments.

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

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.

Oscillatory head movements in cervical dystonia: Dystonia, tremor, or both?

Cervical dystonia is characterized by abnormal posturing of the head, often combined with tremor-like oscillatory head movements. The nature and source of these oscillatory head movements is controversial, so they were quantified to delineate their characteristics and develop a hypothetical model for their genesis. A magnetic search coil system was used to measure head movements in 14 subjects with cervical dystonia. Two distinct types of oscillatory head movements were detected for most subjects, even when they were not clinically evident. One type had a relatively large amplitude and jerky irregular pattern, and the other had smaller amplitude with a more regular and sinusoidal pattern. The kinematic properties of these two types of oscillatory head movements were distinct, although both were often combined in the same subject. Both had features suggestive of a defect in a central neural integrator. The combination of different types of oscillatory head movements in cervical dystonia helps to clarify some of the current debates regarding whether they should be considered as manifestations of dystonia or tremor and provides novel insights into their potential pathogenesis.

Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study

Factors modifying the clinical penetrance of DYT1 dystonia are incompletely defined. Particularly, the contribution of extragenetic factors has been subject to only limited investigation and remains largely unexplored. A possible effect of childhood infections has been proposed, and the effect of other factors, such as perinatal adversity and trauma, has not been systematically investigated. We performed an exploratory analysis of the exposure to perinatal adversity, childhood infections, general anaesthesia and trauma comparing 39 manifesting carriers of the ∆GAG mutation, 23 non-manifesting carriers and 48 non-carriers from a multi-centre European series of 28 families with DYT1 dystonia, by means of a self-completed questionnaire and clinical interview. Detailed information on perinatal adversities (pre-term birth, complications at natural delivery, urgent caesarean section), previous childhood infections, and prior general anaesthesia or physical trauma was recorded. A positive association between a history of complications of vaginal delivery and manifestation of dystonia was detected, which was not confounded by age, gender, or education level (odds ratio 8.47, 95 % confidence interval 1.45-49.4, p = 0.02). We could not observe any significant association between presence of dystonia and the other investigated variables. Comparing non-manifesting carriers to non-carriers, the presence of the ∆GAG mutation per se was not associated with any of the environmental exposures explored. Perinatal adversities might modulate the clinical penetrance of DYT1 dystonia; their interaction with known genetic factors modifying penetrance of this condition should be investigated in new, larger collaborative studies.

Role of Female Reproductive Hormones in Musicians' Dystonia

Musicians' dystonia is an occupational focal dystonia affecting men more often than women. We identified all patients presenting with musicians' dystonia and prospectively collected data on reproductive and menstrual history from the women with musician's dystonia and female musicians without dystonia. 149 men and 23 women (13.37%) with musician's dystonia where identified. We did not identify any effect of contraceptive hormones, pregnancy, or menstrual phases on dystonia symptoms, but as compared with women without dystonia, those with musician's dystonia reported oligomenorrhea and menometrorrhagia significantly less frequently. Our data reinforce the relation between sex hormones variations and musicians' dystonia. This link should be further explored to identify mechanisms and assess whether certain hormonal interventions might protect from the manifestation of dystonia.

Effect of Botulinum Toxin Therapy on the Sensorimotor Feedback Loop in Cervical Dystonia (IN6-1.009)

Objective: To study the effects of botulinum toxin on intracortical inhibition and somatosensory organization. Background The cardinal manifestations of dystonia may be explained by excessive gain through a sensorimotor loop. Expanded overlapped receptor fields induce sustained, uncontrolled motor activity with co-contraction and overflow movements. There is a decreased cortical and spinal inhibition in dystonic patients. Increased motor and supplemental cortical excitability was demonstrated in trans-cranial magnetic stimulation studies. Somatosensory evoked potential studies have shown an increased sensory cortical excitability. Our group recently found synchronous (Coherent) neuronal oscillations to be higher in Epilepsy patients compared to controls which correlated with epileptogenic focus. The current study evaluated the alteration of neuroplasticity in dystonic patients treated with botulinum treatment (BTx). Design/Methods: Six patients with cervical dystonia were studied using MEG. Two MEG scans were obtained, one just prior to the Btx injections, and the second scan when patient felt maximum relief (at approximately 4 weeks). Tsui Torticollis Rating Scale (TTRS) was employed to evaluate treatment response. A whole head Neuromagnetometer (148 channel, Magnus 2500 system) was used. Spontaneous resting brain activity for Coherence (C) analysis was obtained. Somatosensory evoked field scans (SES) were obtained through sensory evoked responses to pressure tapping of the second digit. Results: All patients achieved significant improvement which corresponds to a reduction in their TTRS. Average pretreatment coherent rest values of 0.42 + 0.09 decreased to 0.38 + 0.07 after Btx. These were much higher than the resting state coherent values of normal controls of 0.17 +/-0.09 (p Conclusions: 1. Reduced Coherence values for resting brain activity indicate Btx restores intra-cortical inhibition. 2. Btx induced SES alteration modifies somatosensory processing contributing to the near normalization of dystonic posturing. Supported by: Research support from Allergan for the project : Effects of Botulinum on the Afferent Input Modulation of Neuronal Circuits Involved in Cervical Dystonia. Disclosure: Dr. Sripathi has nothing to disclose. Dr. Grover has nothing to disclose. Dr. Sidiropoulos has nothing to disclose. Dr. Bowyer has nothing to disclose.

Fatigue, Sleepiness and Sleep Issues in Patients with Dystonia (P01.224)

Objective: To determine the prevalence of fatigue, excessive daytime somnolence (EDS) and sleep issues in patients with dystonia and examine its impact on quality of life (QOL). Background Dystonia is a movement disorder that is primarily described by its motor manifestations but is also associated with several non-motor symptoms. Prior research suggests tiredness and energy as important determinants of QOL independent of mood. However, there is a lack of specific data on fatigue, EDS and sleep disorders in dystonia determined using standardized questionnaires. Design/Methods: We administered the following scales to ninety-one patients with primary and secondary dystonia followed at a Movement Disorders clinic: the Fatigue Severity Scale, Epworth Sleepiness Scale, and Parkinson9s Disease Sleep Scale to measure fatigue, EDS and sleep issues respectively; Short Form 36 Health Survey questionnaire to measure QOL, Beck Depression Inventory for depression, and the Unified Dystonia Rating Scale to assess dystonia severity. Results: The mean age of the patients was 60 +/- 17 years, mean duration of dystonia was 7.5 +/- 8 years and dystonia types were focal (74%), segmental (21%) and generalized (5%). Patients with dystonia showed high rates of clinically significant fatigue (46%), EDS (27%) and sleep issues (26%). These prevalence rates did not vary significantly based upon dystonia type, dystonia severity or body parts affected. Depression showed strong correlations with fatigue (r = +0.47, p = 0.0003), EDS (r = +0.35, p = 0.003) and sleep issues (r = -0.40, p = 0.0007). While EDS, sleep issues and fatigue were all associated with reduced QOL, only fatigue remained correlated with QOL when controlling for depression (p = 0.04). Conclusions: This study demonstrates fatigue, EDS and sleep issues are common non-motor manifestations of dystonia that are associated with depression and adversely impact QOL. However amongst the three factors, fatigue affects QOL independent of depression. Disclosure: Dr. Heese has nothing to disclose. Dr. Wagle-Shukla has nothing to disclose. Dr. Okun has received personal compensation for activities with National Parkinson Foundation, Ask the Expert, and Neuropace Devices. Dr. Okun has received research support from the Michael J. Fox Foundation, the National Parkinson Foundation, the Parkinson Alliance and the National Institutes of Health. Dr. Kluger has received research support from Teva Neuroscience.

Musician's cramp as manifestation of maladaptive brain plasticity: arguments from instrumental differences

Musician's cramp is a task-specific movement disorder that presents itself as muscular incoordination or loss of voluntary motor control of extensively trained movements while a musician is playing the instrument. It is characterized by task specificity and gender bias, affecting significantly more males than females. The etiology is multifaceted: a combination of a genetic predisposition, termed endophenotype, and behavioral triggering factors being the leading features for the manifestation of the disorder. We present epidemiological data from 591 musician patients from our outpatient clinic demonstrating an influence of fine-motor requirements on the manifestation of dystonia. Brass, guitar, and woodwind players were at greater risk than other instrumentalists. High temporospatial precision of movement patterns, synchronous demands on tonic and phasic muscular activation, in combination with fine-motor burdens of using the dominant hand in daily life activities, constitute as triggering factors for the disorder and may explain why different body parts are affected.

Diagnosis of dystonic syndromes—a new eight-question approach

Dystonia is a syndrome of abnormal involuntary movements that are repetitive, twisting or patterned, and can result in abnormal postures. Dystonia may be generalized or focal, and can occur as a primary syndrome or secondary to another disease--over 50 clinical conditions are reported to cause dystonia. Classification of dystonia is based on genetic background, anatomical distribution, age at onset, and neurodegenerative processes. In many cases, manifestations of dystonia are identical regardless of the aetiology, which makes accurate diagnosis challenging, if not impossible, without additional investigations. Exhaustive lists of the causes of dystonia are not practical to aid clinicians when attempting to determine if a hyperkinetic movement can be diagnosed as dystonic. The existing diagnostic algorithms for dystonic syndromes rely on the clinician's experience, without a streamlined diagnostic pathway. Non-specialist clinicians and neurologists may, therefore, find diagnosis of dystonic syndromes difficult. In this Review, an eight-question approach is proposed, with a summary of the evidence for investigations that enable successful diagnosis of dystonic syndromes. The aim of this approach is to inform both specialists and general neurologists on the appropriate diagnostic test for each patient who presents with a possible dystonic syndrome.

Arm tremor in cervical dystonia—Is it a manifestation of dystonia or essential tremor?

The classification of arm tremor in cervical dystonia is a controversial issue. There have been many, at times passionate disputes in the movement disorder community about whether it should be classified as a manifestation of dystonia or essential tremor associated with dystonia. There are arguments in favor of both views. Settling the issue might be relevant to the understanding of the etiological, presumably genetic, background because phenomenological grouping is the starting point for genetic analyses. From this point of view, we outline this tremor debate and add some new clinical data.

Bilateral dystonia in type 1 diabetes: a case report

IntroductionDiabetic hemichorea-hemiballismus is a rare complication of type 2 diabetes. Here, we report a case with type 1 diabetes, with hemichorea and bilateral dystonia manifested as hyperglycemia-induced involuntary movement.Case presentationA 62-year-old Japanese women with body weight loss of 30 kg during the past year developed symptoms of thirst, polydipsia and polyuria. She also presented with hemichorea and bilateral dystonia for 5 days and extremely high plasma glucose (774 mg/dl), hemoglobin A1c (21.2%) and glycated albumin (100%) with ketosis. Based on the presence of glutamic acid decarboxylase antibodies (18,000 U/ml; normal <1.3 U/ml), low daily urinary excretion of C-peptide (7.8 μg), ketosis and human leucocyte antigen typing DR-4, we diagnosed type 1 diabetes mellitus. We treated the patient with a continuous intravenous regular insulin infusion and medication with haloperidol, and dystonia completely disappeared within 3 days.ConclusionHyperglycemia-induced involuntary movement is one of the manifestations of dystonia and hemichorea-hemiballism.