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Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, neurodegenerative disorder that manifests with progressive loss of ambulation and refractory dystonia, especially in the early-onset classic form. This leads to osteopenia and stress on long bones, which pose an increased risk of atraumatic femur fractures. The purpose of this study is to describe the unique challenges in managing femur fractures in PKAN and the effect of disease manifestations on surgical outcomes., Methods: A retrospective case review was conducted on 5 patients (ages 10 to 20 y) with PKAN with a femur fracture requiring surgical intervention. Data regarding initial presentation, surgical treatment, complications, and outcomes were obtained., Results: All patients were non-ambulatory, with 4 of 5 patients sustaining an atraumatic femur fracture in the setting of dystonia episode. One patient had an additional contralateral acetabular fracture. Postoperatively, 4 of the 5 patients sustained orthopaedic complications requiring surgical revision, with 3 of these secondary to dystonia. Overall, 4 required prolonged hospitalization in the setting of refractory dystonia., Conclusion: Femur fractures in PKAN present distinct challenges for successful outcomes. A rigid intramedullary rod with proximal and distal interlocking screws is most protective against surgical complications associated with refractory dystonia occurring during the postoperative period. Multidisciplinary planning for postoperative care is essential and may include aggressive sedation and pain management to decrease the risk of subsequent injuries or complications., Level of Evidence: Level IV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The aim of this review is to showcase the recent developments in the field of diagnosis and treatment of adult-onset focal dystonia., Recent Findings: Accurate phenotyping of focal dystonia is essential in the process of finding an underlying cause, including acquired, genetic, and idiopathic causes. Motor symptoms as well as the associated nonmotor symptoms and their detrimental impact on quality of life have received increased interest over the last years. The diagnostic process is complicated by the steadily increasing numbers of newly discovered genes associated with dystonia. Recent efforts have been aimed at further developing recommendations and algorithms to aid in diagnosis and in navigating the use of diagnostic tools. In terms of treatment, research on DBS is advancing towards a better understanding of the most effective stimulation locations within the globus pallidus. Moreover, with the introduction of the LFP-recording devices, the search continues for an accurate electrophysiological biomarker for dystonia., Summary: Accurate phenotyping and (sub)classification of patients with dystonia is important for improving diagnosis, subsequent treatment effect and population-based study outcomes in research. Medical practitioners should be attentive to the presence of nonmotor symptoms in dystonia., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: This article discusses the most recent findings regarding the diagnosis, classification, and management of genetic and idiopathic dystonia., Recent Findings: A new approach to classifying dystonia has been created with the aim to increase the recognition and diagnosis of dystonia. Molecular biology and genetic studies have identified several genes and biological pathways involved in dystonia., Summary: Dystonia is a common movement disorder involving abnormal, often twisting, postures and is a challenging condition to diagnose. The pathophysiology of dystonia involves abnormalities in brain motor networks in the context of genetic factors. Dystonia has genetic, idiopathic, and acquired forms, with a wide phenotypic spectrum, and is a common feature in complex neurologic disorders. Dystonia can be isolated or combined with another movement disorder and may be focal, segmental, multifocal, or generalized in distribution, with some forms only occurring during the performance of specific tasks (task-specific dystonia). Dystonia is classified by clinical characteristics and presumed etiology. The management of dystonia involves accurate diagnosis, followed by treatment with botulinum toxin injections, oral medications, and surgical therapies (mainly deep brain stimulation), as well as pathogenesis-directed treatments, including the prospect of disease-modifying or gene therapies., (Copyright © 2022 American Academy of Neurology.)

Purpose of Review: Deep brain stimulation (DBS) is currently the most effective treatment for medically refractory dystonia with globus pallidus internus (GPi) usually the preferred target. Despite the overall success of DBS in dystonia, there remains variability in treatment outcome in both short and long-term follow-up, due to various factors. Factors contributing to variability in outcome comprise 'Dystonia Related' including dystonia classification, semiology, duration, body distribution, orthopaedic deformity, aetiology and genetic cause. The majority of these factors are identifiable from clinical assessment, brain MRI and genetic testing, and therefore merit careful preoperative consideration. 'DBS related' factors include brain target, accuracy of lead placement, stimulation parameters, time allowed for response, neurostimulation technology employed and DBS induced side-effects. In this review, factors contributing to variability in short and long-term dystonia DBS outcome are reviewed and discussed., Recent Findings: The recognition of differential DBS benefit in monogenic dystonia, increasing experience with subthalamic nucleus (STN) DBS and in DBS for Meige syndrome, elucidation of DBS side effects and novel neurophysiological and imaging techniques to assist in predicting clinical outcome., Summary: Improved understanding of factors contributing to variability of DBS outcome in dystonia may assist in patient selection and predicting surgical outcomes., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: A 38-yr-old man presented to the emergency department with severe chest pain and was found to have a type A aortic dissection. Forty-eight hours after an emergency mechanical Bentall and ascending hemiarch replacement, the patient developed agitation prompting administration of high-dose haloperidol. He was found to have evidence of multiple acute infarcts on head computed tomography/computed tomography angiography and brain magnetic resonance imaging. Four days later, he began to complain of jaw pain and difficulty opening his mouth. After admission to inpatient rehabilitation, he was found to have strong activity in the masseters bilaterally at rest on electromyography, indicating a diagnosis of oromandibular dystonia. Starting in the intensive care unit, the patient reported jaw pain and dysfunction for 40 days before having a diagnosis of oromandibular dystonia. At this point, treatment with onabotulinumtoxinA injections and baclofen did not provide relief. Because of an extended delay in diagnosis, it is believed that the patient has developed joint contractures. Oromandibular dystonia is an important diagnosis to consider in patients who experience jaw pain or difficulty with mouth opening. Treatment of this condition can decrease pain and trauma to oral structures as well as improve ability to perform oral hygiene, eat, and communicate., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Tremor may be defined as an involuntary movement that is rhythmic (ie, regularly recurrent) and oscillatory (ie, rotating around a central plane) and may manifest in a variety of ways; accordingly, tremor has a rich clinical phenomenology. Consequently, the diagnosis of tremor disorders can be challenging, and misdiagnoses are common. The goal of this article is to provide the reader with straightforward approaches to the diagnosis and treatment of tremors., Recent Findings: Focused ultrasound thalamotomy of the ventral intermediate nucleus of the thalamus is an emerging and promising therapy for the treatment of essential tremor., Summary: The evaluation should start with a detailed tremor history followed by a focused neurologic examination, which should attend to the many subtleties of tremor phenomenology. Among other things, the history and examination are used to establish whether the primary tremor is an action tremor (ie, postural, kinetic, or intention tremor) or a resting tremor. The clinician should then formulate two sets of diagnoses: disorders in which action tremor is the predominant tremor versus those in which resting tremor is the predominant tremor. Among the most common of the former type are essential tremor, enhanced physiologic tremor, drug-induced tremor, dystonic tremor, primary writing tremor, orthostatic tremor, and cerebellar tremor. Parkinson disease is the most common disorder of resting tremor. This article details the clinical features of each of these disorders, as well as those of additional tremor disorders.

Purpose of Review: This article provides a summary of the state of the art in the diagnosis, classification, etiologies, and treatment of dystonia., Recent Findings: Although many different clinical manifestations of dystonia have been recognized for decades, it is only in the past 5 years that a broadly accepted approach has emerged for classifying them into specific subgroups. The new classification system aids clinical recognition and diagnosis by focusing on key clinical features that help distinguish the many subtypes. In the past few years, major advances have been made in the discovery of new genes as well as advances in our understanding of the biological processes involved. These advances have led to major changes in strategies for diagnosis of the inherited dystonias. An emerging trend is to move away from heavy reliance on the phenotype to target diagnostic testing toward a broader approach that involves large gene panels or whole exome sequencing., Summary: The dystonias are a large family of phenotypically and etiologically diverse disorders. The diagnosis of these disorders depends on clinical recognition of characteristic clinical features. Symptomatic treatments are useful for all forms of dystonia and include oral medications, botulinum toxins, and surgical procedures. Determination of etiology is becoming increasingly important because the number of disorders is growing and more specific and sometimes disease-modifying therapies now exist.

Motor learning is possible in dystonia, but distorted feedback results in distorted motor performance and information-seeking compensatory behavior, as observed in this case. With globus pallidus internal segment deep brain stimulation, the postural background of hand writing improved, but the learned left compensatory grip did not change.

Objective: To report on the long-term outcomes of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) in Parkinson disease (PD), essential tremor (ET), and dystonic tremor., Methods: One hundred fifty-nine patients with PD, ET, and dystonia underwent VIM DBS due to refractory tremor at the Grenoble University Hospital. The primary outcome was a change in the tremor scores at 1 year after surgery and at the latest follow-up (21 years). Secondary outcomes included the relationship between tremor score reduction over time and the active contact position. Tremor scores (Unified Parkinson's Disease Rating Scale-III, items 20 and 21; Fahn, Tolosa, Marin Tremor Rating Scale) and the coordinates of the active contacts were recorded., Results: Ninety-eight patients were included. Patients with PD and ET had sustained improvement in tremor with VIM stimulation (mean improvement, 70% and 66% at 1 year; 63% and 48% beyond 10 years, respectively; p < 0.05). There was no significant loss of stimulation benefit over time ( p > 0.05). Patients with dystonia exhibited a moderate response at 1-year follow-up (41% tremor improvement, p = 0.027), which was not sustained after 5 years (30% improvement, p = 0.109). The more dorsal active contacts' coordinates in the right lead were related to a better outcome 1 year after surgery ( p = 0.029). During the whole follow-up, forty-eight patients (49%) experienced minor side effects, whereas 2 (2.0%) had serious events (brain hemorrhage and infection)., Conclusions: VIM DBS is an effective long-term (beyond 10 years) treatment for tremor in PD and ET. Effects on dystonic tremor were modest and transient., Classification of Evidence: This provides Class IV evidence. It is an observational study., (© 2017 American Academy of Neurology.)

Objective: To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS)., Methods: Twenty patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia were studied (14 were followed for 36 months). The primary endpoints were change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 36 months compared to preoperative baseline. Multiple secondary outcomes were also assessed (ClinicalTrials.gov NCT00773604)., Results: Eighteen of 20 patients showed improvement 12 months after STN DBS with sustained benefit persisting for 3 years (n = 14). At 36 months, BFMDRS motor scores improved 70.4% from a mean 17.9 ± 8.5 to 5.3 ± 5.6 (p = 0.0002) and total TWSTRS scores improved 66.6% from a mean 41.0 ± 18.9 to 13.7 ± 17.9 (p = 0.0002). Improvement at 36 months was equivalent to that seen at 6 months. Disability and quality of life measures were also improved. Three hardware-related and 24 stimulation-related nonserious adverse events occurred between years 1 and 3 (including 4 patients with dyskinesia)., Conclusions: This study offers support for long-term tolerability and sustained effectiveness of STN DBS in the treatment of severe forms of isolated dystonia., Classification of Evidence: This study provides Class IV evidence that STN DBS decreases long-term dystonia severity in patients with medically refractory isolated dystonia., (© 2016 American Academy of Neurology.)

Background: Movement disorder emergencies include any movement disorder which develops over hours to days, in which failure to appropriately diagnose and manage can result in patient morbidity or mortality.Movement disorder emergencies include acute dystonia: sustained or intermittent muscle contractions causing abnormal, often repetitive, movements. Acute dystonia is a serious challenge for emergency room doctors and neurologists, because of the high probability of misdiagnosis, due to the presence of several mimickers including partial seizures, meningitis, localized tetanus, serum electrolyte level abnormalities, strychnine poisoning, angioedema, malingering, catatonia, and conversion., Methods: We describe 2 examples, accompanied by videos, of acute drug-induced oro-mandibular dystonia, both subsequent to occasional haloperidol intake., Results: Management and treatment of this movement disorder are often difficult: neuroleptics withdrawal, treatment with benzodiazepines, and anticholinergics are recommended., Conclusion: Alternative treatment options are also discussed., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Purpose of Review: This article highlights the clinical and diagnostic tools used to assess and classify dystonia and provides an overview of the treatment approach., Recent Findings: In the past 4 years, the definition and classification of dystonia have been revised, and new genes have been identified in patients with isolated hereditary dystonia (DYT23, DYT24, and DYT25). Expanded phenotypes were reported in patients with combined dystonia, such as those with mutations in ATP1A3. Treatment offerings have expanded as there are more neurotoxins, and deep brain stimulation has been employed successfully in diverse populations of patients with dystonia., Summary: Diagnosis of dystonia rests upon a clinical assessment that requires the examiner to understand the characteristic disease features that are elicited through a careful history and physical examination. The revised classification system uses two distinct nonoverlapping axes: clinical features and etiology. A growing understanding exists of both isolated and combined dystonia as new genes are identified and our knowledge of the phenotypic presentation of previously reported genes has expanded. Genetic testing is commercially available for some of these conditions. Treatment options for dystonia include pharmacologic therapy, chemodenervation, and surgical intervention. Deep brain stimulation benefits many patients with various types of dystonia.

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 2 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 causes have pointed to the need for new strategies for diagnosis, classification, and treatment of the dystonias.

Lateral trunk flexion is often seen in patients with Parkinson disease, sometimes coming on as a subacute phenomenon associated with medication adjustments, and in others with gradual onset that seems related to a neurodegenerative process related to the evolution of the disease.Either acute or subacute presentations seem to be pure abnormalities in the coronal plane and are usually reversible. However, a chronic form occurs often in a combined fashion with anteroposterior flexion (camptocormia), improves only partially, remains stable, or even worsens over time.The acute/subacute phenotype is the condition originally named as Pisa syndrome (PS).The pathophysiology of PS remains poorly understood, and a cholinergic-dopaminergic imbalance has been suggested as being involved in the cause of this disorder. The role of other neurotransmitters and how they become dysfunctional in PS remains to be elucidated.Specific treatments, other than discontinuing the medications responsible for the disorder, whenever possible, are undeveloped because of the unknown etiology.

Objectives: Deep brain stimulation of the internal pallidum (GPi-DBS) is an established therapeutic option in treatment-refractory dystonia, and the identification of factors predicting surgical outcome is needed to optimize patient selection., Methods: In this retrospective multicenter study, GPi-DBS outcome of 8 patients with DYT6, 9 with DYT1, and 38 with isolated dystonia without known monogenic cause (non-DYT) was assessed at early (1-16 months) and late (22-92 months) follow-up using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores., Results: At early follow-up, mean reduction of dystonia severity was greater in patients with DYT1 (BFMDRS score: -60%) and non-DYT dystonia (-52%) than in patients with DYT6 dystonia (-32%; p = 0.046). Accordingly, the rate of responders was considerably lower in the latter group (57% vs >90%; p = 0.017). At late follow-up, however, GPi-DBS resulted in comparable improvement in all 3 groups (DYT6, -42%; DYT1, -44; non-DYT, -61%). Additional DBS of the same or another brain target was performed in 3 of 8 patients with DYT6 dystonia with varying results. Regardless of the genotype, patients with a shorter duration from onset of dystonia to surgery had better control of dystonia postoperatively., Conclusions: Long-term GPi-DBS is effective in patients with DYT6, DYT1, and non-DYT dystonia. However, the effect of DBS appears to be less predictable in patients with DYT6, suggesting that pre-DBS genetic testing and counseling for known dystonia gene mutations may be indicated. GPi-DBS should probably be considered earlier in the disease course., Classification of Evidence: This study provides Class IV evidence that long-term GPi-DBS improves dystonia in patients with DYT1, DYT6, and non-DYT dystonia., (© 2015 American Academy of Neurology.)

Purpose of Review: This article will highlight recent advances in dystonia with focus on clinical aspects such as the new classification, syndromic approach, new gene discoveries and genotype-phenotype correlations. Broadening of phenotype of some of the previously described hereditary dystonias and environmental risk factors and trends in treatment will be covered., Recent Findings: Based on phenomenology, a new consensus update on the definition, phenomenology and classification of dystonia and a syndromic approach to guide diagnosis have been proposed. Terminology has changed and 'isolated dystonia' is used wherein dystonia is the only motor feature apart from tremor, and the previously called heredodegenerative dystonias and dystonia plus syndromes are now subsumed under 'combined dystonia'. The recently discovered genes ANO3, GNAL and CIZ1 appear not to be a common cause of adult-onset cervical dystonia. Clinical and genetic heterogeneity underlie myoclonus-dystonia, dopa-responsive dystonia and deafness-dystonia syndrome. ALS2 gene mutations are a newly recognized cause for combined dystonia. The phenotypic and genotypic spectra of ATP1A3 mutations have considerably broadened. Two new genome-wide association studies identified new candidate genes. A retrospective analysis suggested complicated vaginal delivery as a modifying risk factor in DYT1. Recent studies confirm lasting therapeutic effects of deep brain stimulation in isolated dystonia, good treatment response in myoclonus-dystonia, and suggest that early treatment correlates with a better outcome., Summary: Phenotypic classification continues to be important to recognize particular forms of dystonia and this includes syndromic associations. There are a number of genes underlying isolated or combined dystonia and there will be further new discoveries with the advances in genetic technologies such as exome and whole-genome sequencing. The identification of new genes will facilitate better elucidation of pathogenetic mechanisms and possible corrective therapies.

Objective: 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., Methods: 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., Results: Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of life were not statistically significantly modified by MCS., Conclusions: Bipolar epidural MCS failed to improve any clinical feature in dystonia secondary to a focal BG lesion., Classification of Evidence: 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.

Purpose of Review: This review considers the recent literature pertaining to the clinical features, genetics, neuropathology and treatment of dystonia syndromes., Recent Findings: The term dystonia indicates at the same time a clinical phenotype and a collection of neurological syndromes mainly of genetic origin. The physical signs contributing to the phenomenology of dystonia have been recently assembled into a coherent set. The molecular genetics of primary dystonia syndromes (DYT1 and DYT6) have been the object of extensive analysis, providing converging views on their causative mechanisms. The relationship between genotype, phenotype, and endophenotypes has been explored for hereditary and sporadic dystonia syndromes. Neurophysiological studies on DYT1 and DYT6 patients, as well as on nonmanifesting carriers, have demonstrated the presence of altered synaptic plasticity. Several recent data indicate a role of dopamine and acetylcholine (ACh) transmission in the pathophysiology of primary dystonia., Summary: Recent findings have led to novel, testable hypotheses on cellular mechanisms and physiopathological abnormalities underlying dystonia. Neurophysiological studies, imaging data and animal models support the view that corticostriatal, cerebellar, and dopaminergic dysfunctions converge to produce the pathophysiological abnormalities of dystonia.

Objectives: Stimulation-induced hypokinetic gait disorders with freezing of gait (FOG) have been reported only recently as adverse effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with dystonia. The aim of this work was to determine the frequency and the nature of this GPi-DBS-induced phenomenon., Methods: We retrospectively screened our database of patients with dystonia who underwent DBS. Patients with focal, segmental, or generalized dystonia of primary or tardive origin and no gait disorder due to lower limb dystonia before DBS, bilateral pallidal stimulation, and a follow-up for more than 6 months were included. Reports of adverse events were analyzed, and gait abnormalities were scored by comparing preoperative and postoperative video recordings using Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) items 3.10 (gait) and 3.11 (FOG). To assess the role of GPi-DBS in gait abnormalities, DBS was paused for 24 hours. Gait and FOG were assessed 30 minutes, 2 hours, and 24 hours after restarting DBS. Finally, a standardized adjustment algorithm was performed trying to eliminate the gait disorder., Results: Of a collective of 71 patients with dystonia, 6 presented with a new gait disorder (8.5%; 2 men, 4 women, mean age 61.3 years [48-69 years], 2 craniocervical, 1 DYT-1 segmental, 1 truncal, 2 tardive dystonia). GPi-DBS improved Burke-Fahn-Marsden Dystonia Rating Scale motor score by 54% and disability score by 52%. MDS-UPDRS item 3.10 worsened from 0.5 (±0.8) to 2.0 (±0.9) and item 3.11 from 0 to 2.5 (±0.5). The gait disorder displayed shuffling steps and difficulties with gait initiation and turning. Increasing voltages improved dystonia but triggered FOG, sometimes worsening over a period of a few hours. It vanished within minutes after ceasing DBS. Electrode misplacement was ruled out. In all but one patient, no optimal configuration was found despite extensive testing of settings (monopolar, bipolar, pulse width 60-210 μs, frequency 60-180 Hz). Nevertheless, a compromise between optimal stimulation for dystonia and eliciting FOG was achieved in each case., Conclusions: A hypokinetic gait disorder with FOG can be a complication of GPi-DBS.

Previous research has shown that low-frequency repetitive transcranial magnetic stimulation over the primary motor area and supplementary motor area can reduce L-dopa-induced dyskinesias in Parkinson's disease; however, it involved only patients with peak-dose or diphasic dyskinesia. We report a case of a patient with severely painful off-period dystonia in the unilateral lower limb who underwent 0.9-Hz subthreshold repetitive transcranial magnetic stimulation over contralateral primary motor area and supplementary motor area. Repetitive transcranial magnetic stimulation over the primary motor area significantly reduced the painful dystonia and walking disturbances but repetitive transcranial magnetic stimulation over the supplementary motor area did not. The cortical silent period also prolonged after repetitive transcranial magnetic stimulation over the primary motor area. At 5 mos of approximately once a week repetitive transcranial magnetic stimulation over the primary motor area, the Unified Parkinson's Disease Rating Scale motor score also improved. This report shows that repetitive transcranial magnetic stimulation over the inhibitory primary motor area can be useful for rehabilitating patients with Parkinson's disease with off-period dystonia and suggests that this treatment should be further verified in such patients.

Purpose of Review: This review focuses on new insights in deep brain stimulation (DBS) for patients with hyperkinetic movement disorders: dystonia, tardive dyskinesia and Gille de la Tourette's syndrome, during the last 18 months., Recent Findings: The recent literature confirms the efficacy of high-frequency stimulation of the globus pallidus internus (GPi) for primary dystonia, generalized or not, with a stable effect over time. The benefit of DBS in other forms of localized dystonia remains to be demonstrated in larger studies. Some clinical and radiological predictive factors have been determined with a predominant influence of the disease duration. Tardive dystonia and myoclonus-dystonia are also improved by GPi stimulation. Encouraging results obtained in cerebral palsy may pave the way for the application of DBS in other secondary dystonia. In Gilles de la Tourette's syndrome, both stimulation of the centre-median/parafascicular nucleus of the thalamus and GPi stimulation (ventromedial) have demonstrated efficacy with stable long-term effect. Thalamic stimulation failed to improve obsessions and compulsions in some patients. Stimulation of the nucleus accumbens has been tested in few cases with contradictory efficacy. In both diseases, complications are rare with no major side effects., Summary: The few controlled studies showed that bilateral GPi stimulation is a well tolerated and a long-term effective treatment for hyperkinetic disorders. However, recent published data of DBS applied in different targets or patients (especially secondary dystonia) are mainly uncontrolled case reports, precluding the clear determination of the efficacy of this procedure and the choice of the 'good' target for the 'good' patient.

Background: The Segawa syndrome is an autosomal dominant form of guanosine triphosphate cyclohydrolase deficiency, resulting in decreased dopamine and serotonin levels, typically presenting as a dopa-responsive dystonia., Method: Case presentation of a 56-year-old man with dopa-responsive dystonia, treated with electroconvulsive therapy for a psychotic depression., Results: Scores on the Inventory of Depressive Symptomatology dropped from 35 before treatment to 3 after the eighth treatment session. Etomidate and succinylcholine were used as anesthetics. Apart from 2 sessions with postictal agitation, the course of electroconvulsive therapy was finished uneventfully. Electroconvulsive therapy and anesthesia had no untoward effects on motor function., Conclusions: Electroconvulsive therapy can be administered safely and effectively in a patient with dopa-responsive dystonia (Segawa syndrome).

Background: Deep brain stimulation (DBS) for the treatment of neurologic diseases has markedly increased in popularity over the past 15 years. This review primarily focuses on movement disorder applications and efficacy of DBS, but also briefly reviews other promising new and old uses of DBS., Review Summary: A multidisciplinary team consisting of a movement disorders neurologist, a functional neurosurgeon, and a neuropsychologist optimally selects patients for DBS. Patients must be significantly disabled despite optimal medical therapy and be cognitively healthy without significant psychiatric disorders. Although this surgery is elective, it should not be withheld until the patient suffers marked loss of quality of life. Patients must have support from caregivers and postoperatively multiple DBS programming visits may be required. DBS of the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) significantly improves motor performance, activities of daily living, and quality of life in advanced Parkinson disease. In addition, STN DBS allows for marked reductions of antiparkinson medication. Stimulation of the ventralis intermedius nucleus of the thalamus is an effective treatment for essential tremor with sustained long-term effects. The GPi may be the preferred site of stimulation for dystonia with movement scores typically improved by 75% in patients with primary dystonia., Conclusions: DBS is an effective surgical treatment for movement disorders with sustained long-term benefits. Further research is ongoing to better understand the mechanism of DBS, refine the hardware to improve efficacy and reduce adverse effects, and identify additional applications and new anatomic targets.

Electroconvulsive therapy (ECT) has been reported to be beneficial in various movement disorders, especially tardive dystonic reactions. In this article, we report an interesting case of drug-induced blepharospasm with ocular dystonia which improved with ECT. To our knowledge, a case of ocular dystonia improving with ECT has not been previously reported in the literature.

Background: Deep brain stimulation (DBS) has emerged as an important treatment for medication refractory movement and neuropsychiatric disorders. General neurologists and even general practitioners may be called upon to screen potential candidates for DBS. The patient selection process plays an important role in this procedure., Review Summary: In this article, we discuss "pearls" for the clinician who may be called upon to identify appropriate candidates for DBS. Additionally, we will discuss the important points that should be considered when referring patients for surgical intervention., Conclusion: Diagnosis, response to levodopa, cognitive status, psychiatric status, access to care, and patient expectations are all essential elements of the patient selection process for DBS. These areas must be adequately addressed prior to any surgical procedure.

Background: Dystonia refers to a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Although age at onset, anatomic distribution, and family history are essential elements in the evaluation of dystonia, new classification increasingly relies on etiologic and genetic data. In recent years, much progress has been made on the genetics of various forms of dystonia and its pathophysiology underlying the clinical signs. The treatment of dystonia has continued to evolve to include newer medications, different forms of botulinum toxin, and various surgical procedures., Review Summary: In this article, the author reviewed and summarized the history of dystonia, its evolving classification, and recent genetic data, as well as its clinical investigation and treatment., Conclusions: Recent advances in molecular biology have led to the discovery of novel dystonia genes and loci, updating classification schemes, and better understanding of underlying pathophysiology. Treatment strategies for dystonia have significantly been updated with the introduction of different forms of botulinum toxin therapy, new pharmacologic agents, and most recently pallidal deep brain stimulation. A systematic approach to the diagnosis and treatment evaluation of dystonic patients provides optimal care for long-term management.

The pathophysiology of dystonia is unclear. The authors recorded local field potentials (LFPs) from deep brain stimulation electrodes implanted in the pallidum of 13 dystonic patients. LFP power correlated with the level of dystonic EMG in the sternocleidomastoid, with maximal positive correlations at the lower contacts of pallidal electrodes. The data suggest that the neuronal synchronization indexed by LFP oscillations in the globus pallidus may be mechanistically linked to dystonic EMG activity.

Primary writing tremor (PWT) is task-specific and interferes with handwriting. Several reports have shown a beneficial response of this disorder to stereotactic functional neurosurgery. Significant improvement with a writing device was demonstrated with blind rating of handwriting and spiral drawing samples collected before and during its use in nine patients with PWT, suggesting that this therapeutic modality should be tried before considering chronic pharmacotherapy or functional neurosurgery.

Within the past few years, there has been a renaissance of functional neurosurgery for the treatment of dystonic movement disorders. In particular, deep brain stimulation (DBS) has widened the spectrum of therapeutical options for patients with otherwise intractable dystonia. It has been introduced only with a delay after DBS became an accepted treatment for advanced Parkinson' disease (PD). In this overview, the authors summarize the current status of its clinical application in dystonia. Deep brain stimulation for dystonia has been developed from radiofrequency lesioning, but it has replaced the latter largely in most centers. The main target used for primary dystonia is the posteroventral globus pallidus internus (GPi), and its efficacy has been shown in generalized dystonia, segmental dystonia, and complex cervical dystonia. The optimal target for secondary dystonias is still unclear, but some patients appear to benefit more from thalamic stimulation. The improvement of dystonia with chronic DBS frequently is delayed, in particular concerning tonic dystonic postures. Because more energy is needed for stimulation than in other movement disorders such as PD, more frequent battery replacements are necessary, which results in relatively higher costs for chronic DBS. The study of intraoperative microelectrode recordings and of local field potentials by the implanted DBS electrodes has yielded new insights in the pathophysiology of dystonia. Larger studies are underway presently to validate the observations being made.

STN-HFS is well known to improve patients with IPD. Because off-period dystonia mimics focal or generalized dystonia of other causes, we proposed bilateral STN-HFS to some patients with generalized dystonia. The aim of this study was to compare the efficacy of STN stimulation on off-period dystonia and generalized dystonia. From a larger series of patients with IPD, we selected 22 patients based on the presence of severe preoperative off-period dystonia rated > or = 3 in least one limb on a severity score ranging from 0 to 4. Four patients with generalized dystonia (Hallervorden-Spatz disease, n = 3; primary, n = 1) underwent bilateral STN-HFS. Dystonia of the four limbs was rated on video recordings in all patients before surgery and 3 months after surgery. In IPD, bilateral STN stimulation reduced the severity of off-period dystonia by 70% on the four limbs (preoperative mean severity score = 2.03 +/- 1.49; postoperative mean severity score = 0.60 +/- 0.78). In contrast, bilateral STN-HFS had no effect on generalized dystonia (preoperative mean severity score = 3.25 +/- 0.77; postoperative mean severity score = 3.12 +/- 0.62). Despite clinical similarities between off-period dystonia in Parkinson's disease and generalized dystonia in certain cases, the effect of chronic bilateral STN-HFS differs. STN stimulation is highly effective in off-period dystonia of IPD, whereas it does not improve generalized dystonia. The pathophysiologic mechanisms underlying dystonia in these two disorders are still unknown. Assuming that the mechanism of action of STN-HFS is similar regardless of the cause of dystonia, our findings suggest that the STN is not similarly involved in off-period dystonia of IPD and others dystonias.

The net output of the basal ganglia is tightly regulated by the activity and balance of driving and inhibitory circuitry. In pathologic states, disrupted activity in the main outflow nucleus, the globus pallidus interna (GPi), is relayed to the motor areas of the thalamus and brainstem. The behavior of these targets receiving this disrupted outflow is consequently also disrupted, which in turn produces the profound disturbances in motor function that are characteristic of parkinsonian states and certain forms of dystonia. Therapeutic efforts are directed at reversing or canceling the pathologic basal ganglia output. When drugs are ineffective or have shortcomings, surgical approaches can be considered. It is interesting and paradoxical that elimination of this abnormal activity with destruction of the motor GPi is usually well tolerated and produces little in the way of overt motor deficit. Indeed having no motor pallidum appears to be preferable to having a pallidum generating and transmitting pathologic inputs to down-stream targets. This observation brings into question the mysterious role of the GPi in normal motor function. Nevertheless, bilateral pallidal lesions can be associated with significant adverse effects including speech difficulties and cognitive disturbances. It is for this reason that neurosurgeons have sought to develop surgical procedures that offer the efficacy of selective pallidal lesions but have a better index of safety. With the introduction of DBS to treat first chronic pain and then PD, it became logical to apply DBS to treat dystonia. There is now increasing experience in the use of DBS to treat various forms of dystonia. The initial results suggest that certain primary dystonias can show a strong improvement with GPi DBS.

Purpose of Review: Dystonia is a movement disorder with a complex and not fully understood pathophysiology. Its better understanding would enable more focused treatment for the disorder. In this review, we provide an overview of recent studies of the pathophysiology of primary and secondary dystonia, with an emphasis on functional brain imaging. Potential mechanisms underlying the beneficial effects of deep brain stimulation for dystonia are also summarized., Recent Findings: The recognition of dysfunction at different levels of the nervous system has extended the classical notions of localized striatal abnormalities in primary dystonia. Recent biochemical studies have revealed evidence of abnormal torsion activity in DYT1 dystonia. Abnormal patterns of brain metabolism have also been identified using functional brain imaging in different dystonia genotypes. These findings, in conjunction with new electrophysiological techniques, can be utilized to help define a common mechanism for the neural dysfunction in dystonia., Summary: New insights into the pathophysiology of dystonia have been provided by recent studies using electrophysiology, biochemistry and human genetics, as well as functional brain imaging studies. These advances together may create the basis for new therapies for this disorder.

Objective: To study the influence of continuous high-frequency electrical stimulation with electrodes implanted in the globus pallidus internus (GPi) on motor cortex excitability in nine patients with dystonia., Methods: Short-term effects related to switching off and on the deep brain stimulator were investigated >3 months after electrode implantation. Activation of motor cortical excitatory and inhibitory neurons was examined with transcranial magnetic stimulation (TMS) by analysis of electromyographic activity in the hand muscles. Parameters of corticospinally mediated excitatory motor responses included latency, threshold, and response sizes with increasing stimulus intensities (stimulus-response curves). Other measures of motor cortex excitability comprised the duration of the contralateral silent period and intracortical inhibition and facilitation in a paired-pulse paradigm., Results: Switching off GPi stimulation led to a decrease of motor cortex excitability, as reflected by an increase in motor thresholds (GPi stimulation on 37.5 +/- 6.1%, mean +/- SD; GPi stimulation off for 15 to 120 minutes, 40.5 +/- 6.7% of maximum stimulator output), and reduced the size of contralateral responses in the stimulus-response curves established for relaxed muscles. The changes were reversible within minutes after switching on GPi stimulation. They were associated with mild changes of dystonia. By contrast, measures of intracortical inhibition were not altered by switching off GPi stimulation. Spinal excitability did not change as assessed by H-reflex., Conclusion: GPi stimulation influences motor cortex excitability by a rapid modulation of thalamocortical outputs.

Purpose of Review: The present review covers recent advances in dystonia research related to dystonia genetics and treatment. These have led to the discovery of novel dystonia genes and loci, to changing classification schemes, and to the introduction of improved and new treatment options., Recent Findings: Currently 13 different forms of dystonia can be distinguished on a genetic basis (dystonia types 1-13). Recently, a novel gene locus (DYT13) was detected in a family with segmental dystonia, and the gene causing myoclonus-dystonia was identified (SGCE). Furthermore, a novel mutation in the DYT1 gene is associated with a myoclonus-dystonia phenotype. Regarding dystonia treatment, patients refractory to botulinum toxin type A can now be treated with botulinum toxin type B. Selective peripheral denervation remains an effective form of treatment for patients with secondary, but probably not with primary botulinum toxin treatment failure. Finally, a renaissance of functional surgical ablative procedures has taken place, with high frequency deep brain stimulation being introduced in dystonia treatment. Bilateral pallidotomy or pallidal stimulation may provide major benefit especially in patients with generalized, disabling dystonia with the most dramatic improvements in dystonia type 1 patients. Neurostimulation may also be effective in primary segmental axial dystonia, myoclonus-dystonia, and tardive dystonia., Summary: The recent mapping of additional dystonia gene loci, the identification of novel dystonia genes, and the characterization of proteins encoded by these genes have enhanced our understanding of various forms and aspects of the dystonias and have opened up new avenues for research. Treatment options include both medical and surgical therapies, with deep brain simulation being the most recent development.

A patient with severe postanoxic dystonia and bilateral necrosis of the basal ganglia, who was confined to a wheelchair, underwent bilateral ventralis oralis anterior deep brain stimulation (Voa-DBS) after 6 weeks of unsuccessful bilateral pallidal DBS (GPi-DBS). After 4 months of high intensity Voa-DBS, cognitively unimpaired, he showed major improvement in dystonia, became ambulant, but committed suicide. Brain examination confirmed the correct location of the electrodes in GPi and Voa on both sides.