Dystonia Syndrome Research Articles

Fasting Dependent Paroxysmal Exercise Induced Dystonia as Presenting Symptom in PRKN Type of Parkinson's Disease.

Paroxysmal exercise-induced dystonia (PED) can occur as a symptom of early-onset Parkinson's disease (EOPD), Dopa-responsive dystonia (DRD), or Glut1 deficiency syndrome (Glut1DS). Red flags of PED in Glut1DS include influence of diet, while diurnal fluctuations are characteristic for DRD.1 A 22-year-old White-European man presented with a 5-year history of paroxysmal involuntary movements of his left foot. Past medical history and family history were unremarkable without known consanguinity. At the age of 17 (BMI 38 kg/m2), he started a diet and regular physical exercise and lost 35 kg weight. After approximately 30 min of physical exercise, he occasionally noticed mild and involuntary abnormal posturing of his left foot. Symptoms only occurred in the evening or after fasting. Since then, symptoms have worsened, and abnormal movements started after 15 min of exercise in the morning and after 5 min in the evening or when fasting. Recently, he also noticed a mild tremor and clumsiness of his right hand. Physical examination revealed mild rigidity of neck and extremities, mild resting tremor of the right hand and mild bradykinesia of upper and lower limbs (right dominant). He had reduced arm swing, but otherwise walking was unremarkable (see Video 1). After 10 min of running, he developed dystonia of his left foot (see Video 2), which ceased shortly after resting. A 3-Tesla-MRI of the brain, CSF/serum fasting glucose ratio and a metabolic panel including blood/CSF amino acids and neurotransmitters were unremarkable. A (123)I-Ioflupane single-photon emission computed tomography was abnormal. A genetic panel including known genes causing EOPD, DRD and Glut1DS was ordered. Both next generation sequencing and exon-specific PCR detected a homozygous deletion of exons 2–4 of the PRKN gene. Levodopa/benserazide 50/12.5 mg QID led to marked improvement of parkinsonian symptoms and PED. To the best of our knowledge, this is the first reported case of the PRKN type of EOPD featuring PED with marked diurnal fluctuation and worsening with fasting as presenting symptom. In 16% of PRKN mutation carriers symptoms start in adolescence.2 Initial foot dystonia, in some cases induced by exercise,1, 3 and diurnal fluctuation are recognized features.4 However, symptom provocation by fasting is a novel finding. The products of several PD-associated genes including PRKN have important roles in mitochondrial biology and fasting induces an upregulation of protein markers of mitophagy. Our patient noticed remission of PED with regular carbohydrate intake. A low protein-to-carbohydrate ratio has been shown to increase lifespan, motor ability and mitochondrial function in a PRKN mutant Drosophila model of PD,5 providing a potential pathophysiological link to our finding. A deletion of exons represents the most common mutation of the PRKN gene; deletions of exons 2–4 are classified as definitely pathogenic.2 Another reported case presenting with juvenile-onset PED had a deletion of exon 4.3 Worsening with fasting was neither described in a published case series4 nor in patients with deletions of exons 2–4 of the PRKN gene within the MDS gene database. In conclusion, diurnally fluctuating PED that worsens with carbohydrate restriction may be the presenting symptom in the PRKN type of EOPD. We would like to thank our patient for giving us the opportunity to publish this case report. We also thank Johann Semmler-Bruckner for his assistance in genetic analyses and database research. 1. Research project: A. Conception, B. Organization, C. Execution; 2. Data Collection: A. Clinical Assessment, B. Genetic Analysis, C. Literature Review; 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. L.G.: 1B, 1C, 2A, 2C, 3A C.W.: 1B, 1C, 2B, 3B P.K.W.: 1B, 1C, 2A, 3B P.S.: 1A, 1B, 1C, 2A, 2C, 3B Ethical Compliance Statement: No formal approval by an ethics committee was required; the Journal's Ethical Publication guidelines and the Declaration of Helsinki were followed. Informed written consent on video acquisition and case publication was obtained from the patient using our standardized patient's video consent form. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for Previous 12 Months: L. Gattermeyer, C. Windpassinger and P. Katschnig-Winter declare that there are no additional disclosures to report. P. Schwingenschuh reports personal fees from Bial.

Novel SERAC1 Variant Presenting With Adult-Onset Extrapyramidal Dystonia-Parkinsonism Phenotype: A Case Report.

To report a novel likely pathogenic variant in the SERAC1 gene associated with early adult-onset parkinsonism and progressive dystonia. Clinical, biochemical, and imaging assessments were performed on 2 affected adult brothers with a genetically unsolved progressive neurologic disorder followed by whole-genome sequencing. A homozygous likely pathogenic variant in the SERAC1 gene (c.[129-2A > C], p.[(?)];[(?)]) was discovered. We describe a novel homozygous variant in the serine active site-containing protein 1 gene (SERAC1) in 2 brothers with a progressive extrapyramidal movement disorder of early onset parkinsonism and dystonia. Previous variants have been associated with a severe 3-methylglutaconic aciduria with dystonia, deafness, hepatopathy, encephalopathy and Leigh-like syndrome, or juvenile onset complicated spastic paraparesis. Our cases expand the phenotype of SERAC1 variants, with an adult-onset presentation of dystonia-parkinsonism.

Driving Impairment in Movement Disorders.

Driving may be adversely affected by any movement disorder, but has been mostly studied in Parkinson's disease (PD). Few studies have addressed driving impairment in patients with Huntington's disease (HD); driving in other movement disorders such as dystonia, blepharospasm and Tourette syndrome (TS) has not been adequately evaluated. The aim of this review is to summarize the findings of driving impairment in movement disorders and evaluate the usefulness of clinical tools in guiding clinicians whether to refer patients for driving assessment. A review of literature was performed on PubMed and articles on driving and movement disorders were identified using a Boolean phrase. We were able to identify 66 articles that fulfilled the target subject: impairment of driving in PD, cervical dystonia, blepharospasm, HD and TS. We also included articles discussing the role of driving rehabilitation in patients with movement disorders. Driving is often impaired in patients with PD and other movement disorders not only due to motor symptoms but also because of cognitive and behavioral co-morbidities. Certain screening tools may be helpful in guiding the clinician in referring the patients for driving assessment.

Dystonias: Clinical Recognition and the Role of Additional Diagnostic Testing.

Dystonia is the third most common movement disorder, characterized by abnormal, frequently twisting postures related to co-contraction of agonist and antagonist muscles. Diagnosis is challenging. We provide a comprehensive appraisal of the epidemiology and an approach to the phenomenology and classification of dystonia, based on the clinical characteristics and underlying etiology of dystonia syndromes. We discuss the features of common idiopathic and genetic forms of dystonia, diagnostic challenges, and dystonia mimics. Appropriate workup is based on the age of symptom onset, rate of progression, whether dystonia is isolated or combined with another movement disorder or complex neurological and other organ system features. Based on these features, we discuss when imaging and genetic should be considered. We discuss the multidisciplinary treatment of dystonia, including rehabilitation and treatment principles according to the etiology, including when pathogenesis-direct treatment is available, oral pharmacological therapy, chemodenervation with botulinum toxin injections, deep brain stimulation and other surgical therapies, and future directions.

Persistent postural perceptual vertigo and vestibular migraine. Case report

Persistent postural perceptual vertigo (PPPV) and vestibular migraine (VM) are common causes of vertigo. However, despite the typical clinical presentation of PPPV and VM, these diagnoses are rarely made, and dizziness is considered a consequence of other diseases, such as cerebrovascular disorders (chronic cerebral ischemia, vertebrobasilar insufficiency), cervical spine instability, or the manifestation of vegetative dystonia syndrome. This article describes a clinical case of a patient with PPPV and VM. The diagnosis is based on the clinical presentation matched with the diagnostic criteria and an in-depth examination using additional methods to rule out other causes of dizziness. Current evidence on clinical and instrumental diagnostics of the disorders is presented.

Early-onset inherited dystonias versus late-onset idiopathic dystonias: Same or different biological mechanisms?

Dystonia syndromes encompass a heterogeneous group of movement disorders which might be differentiated by several clinical-historical features. Among the latter, age-at-onset is probably the most important in predicting the likelihood both for the symptoms to spread from focal to generalized and for a genetic cause to be found. Accordingly, dystonia syndromes are generally stratified into early-onset and late-onset forms, the former having a greater likelihood of being monogenic disorders and the latter to be possibly multifactorial diseases, despite being currently labeled as idiopathic. Nonetheless, there are several similarities between these two groups of dystonia, including shared pathophysiological and biological mechanisms. Moreover, there is also initial evidence of age-related modifiers of early-onset dystonia syndromes and of critical periods of vulnerability of the sensorimotor network, during which a combination of genetic and non-genetic insults is more likely to produce symptoms. Based on these lines of evidence, we reappraise the double-hit hypothesis of dystonia, which would accommodate both similarities and differences between early-onset and late-onset dystonia in a single framework.

The efficacy of kicking and knee strike exercises in the rehabilitation of patients with walking disorders

The article is devoted to evaluating the effectiveness of exercises that were used in neurorehabilitation for patients with walking disorders. Disorders of walking, coordination of movement, balance are among the main symptoms of diseases such as Parkinson's disease (PD), Parkinsonism and dystonia. For such patients with motor disorders, exercise is a very important part of rehabilitation. At this time, the insufficiently studied problem remains therapeutic physical culture, exercises to improve patients' coordination of movement, gait, balance. The purpose of the study: to study the effectiveness of a set of kicking exercises for patients with walking disorders by evaluating rehabilitation scales (Test “Up and Go” (TUG) и mini BESTest). Methods. Prospective cohort study. The results of rehabilitation of patients treated at the clinic of neurology and neurorehabilitation "Shashkin clinic" are presented. The main criteria for inclusion in the study: patients with Parkinson's disease – at least 3 stages on the Hoehn-Yahr scale, patients with Parkinsonism and dystonia syndrome, patients who underwent surgery to install a deep brain stimulation system with walking disorders. The age of patients is from 50 to 78 years, men - 21, women - 29. The patients were divided into 2 groups of 25 people. The patients were randomly divided into two groups. The 1st group underwent neurorehabilitation without a set of exercises, the 2nd group - with a daily additional load – kicking and knee exercises. Before rehabilitation and 2 weeks after rehabilitation, a test was conducted. All patients prior to enrollment in the study signed informed consent voluntarily. Results. There was an improvement in the indicators of two scales used in the work (mini-test of balance assessment systems, or Mini-BESTest, "Up and Go” test) in the research group, compared with the control group. Conclusions. The inclusion of a set of kicks and knee exercises in rehabilitation has a positive effect on improving the patient's walking.

Modern principles of primary headaches prevention in children and adolescents

Headaches in children and adolescents are an actual problem of modern medicine. In most cases, headaches are regarded as a manifestation of vertebrogenic or cerebrovascular pathology, or as a manifestation of autonomic dystonia syndrome which leads to an erroneous diagnosis and treatment. The review considers the factors of occurrence and chronicity of primary headaches (hypodynamia, postural disorders, magnesium and vitamin D deficiency, anxiety and depression, central sensitization, alexithymia), methods for their diagnosis and treatment.

Chapter 21 - Isolated and combined dystonias: Update

Dystonia is a hyperkinetic movement disorder with a unique motor phenomenology that can manifest as an isolated clinical syndrome or combined with other neurological features. This chapter reviews the characteristic features of dystonia phenomenology and the syndromic approach to evaluating the disorders that may allow us to differentiate the isolated and combined syndromes. We also present the most common types of isolated and combined dystonia syndromes. Since accelerated gene discoveries have increased our understanding of the molecular mechanisms of dystonia pathogenesis, we also present isolated and combined dystonia syndromes by shared biological pathways. Examples of these converging mechanisms of the isolated and combined dystonia syndromes include (1) disruption of the integrated response pathway through eukaryotic initiation factor 2 alpha signaling, (2) disease of dopaminergic signaling, (3) alterations in the cerebello-thalamic pathway, and (4) disease of protein mislocalization and stability. The discoveries that isolated and combined dystonia syndromes converge in shared biological pathways will aid in the development of clinical trials and therapeutic strategies targeting these convergent molecular pathways.

Comorbid pathology issues in pediatric gynecology

The problems of diagnosis, therapeutic tactics and medical prognosis in comorbid, polymorbid pathology stand out among the most actual problems of modern health care. Purpose - to study the frequency and nature of comorbid conditions in patients with pubertal abnormal uterine bleeding (PAUB). Materials and methods. The study included 342 girls aged 11-17 suffering from PAUB. All patients were examined by a multidisciplinary team of doctors. Results. It has been shown that menstrual irregularities are combined with other somatic, mental and endocrine pathologies in the vast majority of patients. Only 9.6% of the patients examined had no concomitant pathologies. More than half of girls have a combination of more than three comorbidities. The first three ranks are occupied by endocrine, mental and digestive system disorders. More than a third of patients with endocrine disorders had deviations in terms of body weight - overweight and obesity, which is much more often accompanied by changes in carbohydrate and lipid metabolism. In patients with mental disorders astheno-neurotic syndrome and vegetative-vascular dystonia syndrome prevailed. Functional disorders of the biliary tract were mainly recorded among the disorders of the digestive system, about 18% of girls suffered from gastritis, cholecystitis. The presence of comorbid pathology reduced the effectiveness of non-hormonal therapy by 1.5 times and increased the number of relapses by 3.5-4 times. The effectiveness of non-hormonal therapy was 81.8% on the absence of concomitant pathology; relapses were recorded only in 16.7%. Conclusions. Comorbid pathologies in patients with PAUB aggravate the severity of the girl’s condition, reduces adaptive capabilities, adversely affects the effectiveness of non-hormonal therapy, contributes to the recurrence of the disease and is a risk factor for the development of serious metabolic, endocrine and cardiovascular diseases in the future. The category of patients with concomitant pathology requires a special examination algorithm and the appointment of an adequate therapeutic intervention, taking into account all the identified nosological forms and drug compatibility. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Adult-Onset Idiopathic Cervical Dystonia

Adult-onset idiopathic focal dystonia is the most common type of primary dystonia, and adult-onset idiopathic cervical dystonia (AOICD) is its most prevalent phenotype. AOICD is an autosomal-dominant disorder with markedly reduced penetrance; clinical expression is dependent on age, sex, and environmental exposure. Motor symptoms at presentation are poorly recognised by non-specialists, leading to long delays in diagnosis. Certain features of history and examination can help diagnose cervical dystonia. There is a relatively high prevalence of anxiety and/or depression, which adversely affects health-related quality of life. Recent studies indicate that patients with AOICD also have disordered social cognition, particularly affecting emotional sensory processing. AOICD can be treated reasonably effectively with botulinum toxin injections, given at 3-month intervals. Oral antidystonic medications are often trialled initially, but are largely ineffective. Comprehensive modern management of patients with AOICD requires recognition of presence of mood disorders, and actively treating the endogenous mood disorder with antidepressant therapy. Botulinum toxin injections alone, no matter how expertly given, will not provide optimal therapy and improved health-related quality of life without an holistic approach to patient management. Increasing evidence indicates that AOICD is a neurophysiological network disorder of GABAergic inhibition, causing a syndrome of dystonia, mood disturbance, and social cognitive dysfunction, with the superior colliculus playing a central role.

Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions.

Infantile striatonigral degeneration is caused by a homozygous variant of the nuclear-pore complex (NPC) gene NUP62, involved in nucleo-cytoplasmic trafficking. By querying sequencing-datasets of patients with dystonia and/or Leigh(-like) syndromes, we identified 3 unrelated individuals with biallelic variants in NUP54. All variants clustered in the C-terminal protein region that interacts with NUP62. Associated phenotypes were similar to those of NUP62-related disease, including early-onset dystonia with dysphagia, choreoathetosis, and T2-hyperintense lesions in striatum. In silico and protein-biochemical studies gave further evidence for the argument that the variants were pathogenic. We expand the spectrum of NPC component-associated dystonic conditions with localized basal-ganglia abnormalities. ANN NEUROL 2023;93:330-335.

Structural and bioenergetic changes in muscle tissue in idiopathic muscular dystonia

BACKGROUND. Muscular dystonia is a syndrome with localization of the pathological process in the central nervous system and the formation of local muscle hypertonicity. It is relevant to study changes in the muscles involved in hyperkinesis in dystonia as one of the possible symptoms of the disease.
 AIM. To identify structural and bioenergetic changes in muscles in patients with idiopathic muscular dystonia.
 MATERIAL AND METHODS. 10 patients were examined with a diagnosis of idiopathic segmental and generalized dystonia, including cervical dystonia syndrome. The control group included 5 conditionally healthy individuals. All patients received injections of botulinum toxin type A with a TWSTRS and Tsui efficacy score before injection and 3 weeks after injection. Structural changes in the muscles were assessed by magnetic resonance imaging (MRI) (1.5 Tl). To assess bioenergetic changes, the parameters of mitochondrial respiration were studied, including basal respiration during oxidation of substrates (pyruvate and pyruvate-malate), respiration during oxidative phosphorylation with various participation of respiratory chain complexes, electron transport chain capacity (ETC), ATP-associated respiration in a trapezius muscle biopsy.
 RESULTS. Bioenergetic changes in muscle tissue were revealed in the form of a decrease in the indices of initial respiration, basal respiration with the participation of the I complex (KI) ETC in the process of oxidation of pyruvate and pyruvate-malate substrates, oxidative phosphorylation with the participation of KI. Structural changes of muscle tissue in the form of asymmetric hypertrophy and partial fat replacement of the involved muscles are demonstrated. The presence of fat replacement reduced the difference on the TWSTRS scale before botulinum therapy and 3 weeks after injection.
 CONCLUSIONS. Patients with dystonia have bioenergetic changes in muscle tissue in the form of a defect in the work of the KI respiratory chain, but these changes do not affect the effectiveness of botulinum therapy. Structural changes in the form of partial fat replacement of muscle tissue reduce the effectiveness of botulinum therapy.

ODP261 Non-Ketotic Hyperosmolar Hyperglycemia Induced Hemichorea-Dystonia Syndrome, Without Radiologic Striatopathy

Abstract Background Movement disorder is an uncommon complication of Hyperglycemic crisis. It is often associated with diabetic striatopathy which is a clinico-radiologic entity that is associated with acute changes of the contralateral basal ganglia. Isolated dyskinetic-dystonic disorder without obvious radiologic lesion is a rare clinical entity. Case Report A 42-years-old woman with a history of type 2 diabetes mellitus was admitted with a 1-week history of involuntary right arm and face movements and 3 weeks of polyuria. She had recurrent choreiform right arm movements without athetosis or hemiballismus lasting about 2. Additionally, she experiences right cervicofacial dystonia. There was no involvement of the lower extremities, no loss of consciousness and no other neurologic deficit between attacks. Physical examination was essentially unveiling with no focal neurologic deficits or tremors. Initial work up showed elevated; blood glucose to 620mg/dl (65–110), serum sodium of 148mEq/L (135–145) and serum osmolality of 330mmol/kg (275–295). Work up was negative for acidosis, with pH of 7.39 (7.32–7.42), bicarbonate of 23mEq/L (23–31) and no ketones on urinalysis. Other relevant test including serum bilirubin, transaminases, ammonia level, calcium, ceruloplasmin and cupper were normal. An initial non-contrast CT scan of the brain was negative for acute pathology and MRI did not show any lesions in basal ganglia. E. E. G was also normal. Movements recurred twice in hospital, and she received IV lorazepam without much response. She was diagnosed with non-Ketotic hyperosmolar hyperglycemic chorea- dystonia syndrome. She received IV normal saline and started on insulin therapy resulting in improvement in serum glucose to 255 by the next morning. She was discharge after 72 hours with no recurrence at 2 weeks follow up visit. Discussion Hyperglycemic crisis may rarely be associated with dyskinetic syndromes, often due to the development of diabetic striatopathy and about 80% are without ketosis. The mechanism is believed to be due to impaired GABA synthesis in the basal ganglia. Prevalence of hyperglycemia induced striatopathy stands at 1 per 100,000. The commonest manifestation is that of hemiballismus and chorea. Very few cases of dystonia have been reported. It is a clinico-radiologic diagnosis with basal ganglia abnormalities on imaging stemming from edema, microhemorrhages or calcific changes. There are very few case reports of hyperglycemic dyskinetic syndromes without CNS changes on MRI. The average time for resolution of MRI changes is 60 days thus we believe our patient had no radiologic striatopathy. In majority of cases, resolution of hyperglycemia leads to clinical resolution of dyskinetic spells. Occasionally, some patients may require medications such as antipsychotics including haloperidol, or benzodiazepines such as clonazepam to control movements. In conclusion, movement disorder related to hyperglycemia though rare, can be disabling. Prognosis is excellent if a timely clinical diagnosis is made. Presentation: No date and time listed

CT-guided radiofrequency ablation of the extracranial cranial nerve for the treatment of Meige's syndrome.

BackgroundMeige’ s syndrome, a rare form of dystonia, lacks effective treatment. The purpose of this study was to determine the effects of CT-guided percutaneous extracranial radiofrequency ablation of the facial and/or trigeminal nerves in the treatment of Meige’s syndrome.MethodsA total of 10 patients were enrolled in this study, with the numbers of blepharospasm dystonia syndrome (BDS), oromandibular dystonia syndrome (ODS), and blepharospasm combined with oromandibular dystonia syndrome (B-ODS) being 7, 1, and 2, respectively. BDS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve; ODS patients underwent radiofrequency ablation of the bilateral foramen oval trigeminal mandibular branch, and B-ODS patients underwent radiofrequency ablation of the bilateral stylomastoid foramen facial nerve and foramen oval trigeminal mandibular branch. The therapeutic effects and complications were observed.ResultsAll 10 patients in this series experienced improved Meige’s syndrome-related symptoms after extracranial radiofrequency ablation of the cranial and/or mandibular branches of the extracranial trigeminal nerve. Adverse events included class II–III facial paralysis and/or mandibular skin numbness. Two patients had recurrences at the 18th and 22nd months postoperatively, respectively; the other patients were being followed up.ConclusionThese results shown that CT-guided radiofrequency ablation of bilateral stylomastoid foramen facial nerve and/or oval foramen trigeminal mandibular branch can effectively treat the corresponding types of Meige’s syndrome. According to preliminary observations, the therapeutic effect may last more than 18 months.

MRM2 variants in families with complex dystonic syndromes: evidence for phenotypic heterogeneity

BackgroundDystonia involves repetitive movements and muscle contractions leading to abnormal postures. We investigated patients in two families, DYAF11 and M, exhibiting dystonic or involuntary movement disorders.MethodsClinical investigations were performed for...

Editorial introductions.

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Martin J. McKeownMartin J. McKeownDr McKeown is the John Nichol Chair in Parkinson's Research, Director at the Pacific Parkinson's Research Centre (PPRC), Professor in the Department of Medicine, and adjunct professor in the Department of Electrical and Computer Engineering at the University of British Columbia, Canada. The PPRC is deemed an International Centre of Excellence by the (US-based) Parkinson's Foundation. He did his Engineering Physics, Medicine and Neurology training at McMaster, University of Toronto, and University of Western Ontario, Canada respectively. He did a three-year research fellowship at the Computational Neurobiology Laboratory at the Salk Institute for Biological Studies in San Diego before being hired as an Assistant Professor of Medicine and Biomedical Engineering at Duke University, USA. He was recruited to UBC in 2003. He is currently the Medical Advisor to the Parkinson's Society of BC, and Chair, Research and Clinical Advisory committee, Parkinson Canada. His research interests include privacy-compliant video monitoring technologies for Parkinson's disease and non-invasive neuromodulation. Marie VidailhetMarie VidailhetMarie Vidailhet is Professor of Neurology, Head of the Movement Disorders section and of the Dystonia and rare movement disorders National Reference Centre at Salpêtrière Hospital, Sorbonne Université, France; Head of the Research Team (Movement, investigations, and of the Therapeutics MOV’IT research group) at Paris Brain Institute, ICM (co-head Stephane Lehéricy), Paris, France, focused on the pathophysiology of motor and behaviour dysfunctions in movement disorders including dystonia, tremor and Tourette syndrome. She part of the ERN (European Reference Network) and of several international working groups in movement disorders and Parkinson's disease. She held the positions of Head of Neurology Department, Saint-Antoine University Hospital, Pierre et Marie Curie University, from 1997 to 2007, and previously of Assistant Professor, then Associate Professor in Salpêtriere, Paris, France. As a Visiting Research Fellow, Institute of Neurology, Queen Square, London, UK, she worked at the Human Movement Balance Unit research section London, UK with Pr CD Marsden, JC Rothwell and Ph Thompson. She is involved in the Movement Disorders Society including the MDS-ES (European section) and in the European Academy of Neurology (EAN) as board, and in international mentorship and fellowships programs (EAN, MDS). She was Vice-chair du COST action BM1101 European network for dystonia. She co-authored over 400 publications (total H index 85) with her group, with a focus on pathophysiology of dystonia, tremors and Tourette syndrome, deep brain stimulation and non-invasive stimulation both for research and experimental therapeutics. The other focus is multimodal/neuroimaging characterization of Parkinson's disease and isolated REM sleep disorders, current research programs, JP-RD Eurodyscover E-Rare (Europe), Dystonia Coalition (USA) on dystonia and several collaborative programs on Parkinson's disease. She was awarded the MDS Presidential lecture (Stanley Fahn Lecture) and the Prix Memin-Pelletier (Biology) French Academy of Science.

Advances in DBS Technology and Novel Applications: Focus on Movement Disorders.

Deep brain stimulation (DBS) is an established treatment in several movement disorders, including Parkinson's disease, dystonia, tremor, and Tourette syndrome. In this review, we will review and discuss the most recent findings including but not limited to clinical evidence. New DBS technologies include novel hardware design (electrodes, cables, implanted pulse generators) enabling new stimulation patterns and adaptive DBS which delivers potential stimulation tailored to moment-to-moment changes in the patient's condition. Better understanding of movement disorders pathophysiology and functional anatomy has been pivotal for studying the effects of DBS on the mesencephalic locomotor region, the nucleus basalis of Meynert, the substantia nigra, and the spinal cord. Eventually, neurosurgical practice has improved with more accurate target visualization or combined targeting. A rising research domain emphasizes bridging neuromodulation and neuroprotection. Recent advances in DBS therapy bring more possibilities to effectively treat people with movement disorders. Future research would focus on improving adaptive DBS, leading more clinical trials on novel targets, and exploring neuromodulation effects on neuroprotection.

The apparent paradox of phenotypic diversity and shared mechanisms across dystonia syndromes.

We describe here how such mechanisms shared by different genetic forms can give rise to motor performance dysfunctions with a clinical aspect of dystonia. The continuing discoveries of genetic causes for dystonia syndromes are transforming our view of these disorders. They share unexpectedly common underlying mechanisms, including dysregulation in neurotransmitter signaling, gene transcription, and quality control machinery. The field has further expanded to include forms recently associated with endolysosomal dysfunction. The discovery of biological pathways shared between different monogenic dystonias is an important conceptual advance in the understanding of the underlying mechanisms, with a significant impact on the pathophysiological understanding of clinical phenomenology. The functional relationship between dystonia genes could revolutionize current dystonia classification systems, classifying patients with different monogenic forms based on common pathways. The most promising effect of these advances is on future mechanism-based therapeutic approaches.

Connecting tremors - a circuits perspective.

Tremor is one of the most prevalent movement disorders in clinical practice. Here, we review new insights in the pathophysiology of tremor. We focus on the three most common tremor disorders: essential tremor (ET), dystonic tremor syndrome (DTS), and Parkinson's disease (PD) tremor. Converging evidence suggests that ET, DTS, and PD tremor are all associated with (partly) overlapping cerebral networks involving the basal ganglia and cerebello-thalamo-cortical circuit. Recent studies have assessed the role of these networks in tremor by measuring tremor-related activity and connectivity with electrophysiology and neuroimaging, and by perturbing network components using invasive and noninvasive brain stimulation. The cerebellum plays a more dominant and causal role in action tremors than in rest tremor, as exemplified by recent findings in ET, DTS, and re-emergent tremor in PD. Furthermore, the role of the cerebellum in DTS is related to clinical differences between patients, for example, whether or not the tremor occurs in a dystonic limb, and whether the tremor is jerky or sinusoidal. Insight into the pathophysiological mechanisms of tremor may provide a more direct window into mechanism-based treatment options than either the etiology or the clinical phenotype of a tremor syndrome.