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Competing Interests: Declaration of competing interest All authors report no competing interests.

Deep brain stimulation (DBS) surgery is an established and effective treatment for several movement disorders (tremor, Parkinson's disease, and dystonia), and is under investigation in numerous other neurological and psychiatric disorders. However, the origins and development of this neurofunctional technique are not always well understood and recognized. In this mini-review, we review the history of DBS, highlighting important milestones and the most remarkable protagonists (neurosurgeons, neurologists, and neurophysiologists) who pioneered and fostered this therapy throughout the 20th and early 21st century. Alongside DBS historical markers, we also briefly discuss newer developments in the field, and the future challenges which accompany such progress., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elena Moro reports a relationship with Medtronic Inc that includes: consulting or advisory. Elena Moro reports a relationship with Ipsen that includes: funding grants. Elena Moro reports a relationship with AbelsonTaylor Inc that includes: funding grants. Elena Moro reports a relationship with French Association for Parkinson's Disease that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: The aim of this paper is to find the differences in the physiology of the pallidal neurons in DYT1 and non-DYT1 dystonia., Methods: We performed microelectrode recording of the single unit activity in both segments of the globus pallidus during stereotactic implantation of electrodes for deep brain stimulation (DBS)., Results: We found a reduced firing rate, reduced burst rate, and increased pause index in both pallidal segments in DYT1. Also, in DYT1 the activity in both pallidal segments was similar, but not so in non-DYT1., Conclusion: The results suggest a common pathological focus for both pallidal segments, located in the striatum. We also speculate that strong striatal influence on GPi and GPe overrides other input sources to the pallidal nuclei causing similarity in neuronal activity., Significance: We found significant differences in neuronal activity between DYT1 and non-DYT1 neurons. Our findings shed light on the pathophysiology of DYT-1 dystonia which can be very different from non-DYT1 dystonia and have other efficient treatment tactics., Competing Interests: Declaration of competing interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Status Dystonicus (SD) represents the most severe end of the spectrum of dystonia. We aimed to explore whether reported features of cases of SD have changed over time., Methods: A systematic review of cases of SD reported from 2017 to 2023 and comparison of features to data extracted from 2 previous literature reviews (epochs 2012-2017 and pre-2012)., Results: From 53 papers, a total 206 SD episodes in 168 patients were identified from 2017 to 2023. Combining data from all 3 epochs, a total of 339 SD episodes were reported from 277 patients. SD episodes occurred mostly in children, with a trigger identified in 63.4% of episodes, most commonly infection/inflammation. Most reported underlying aetiologies were genetic (e.g. 49.5% between 2017 and 2023), including new associated aetiologies in each epoch. Deep Brain Stimulation (DBS)-related SD increased over time. Neurosurgical interventions were more frequently reported in later epochs. Across the epochs, return to or improvement post SD episode, compared to baseline was reported above 70%. Reported mortality was 4.9% most recently, compared to 11.4% and 7.9%, previously., Conclusions: SD episodes reported have more than doubled in the last 5 years. Reports of medication change-induced SD have become less frequent, whilst episodes of DBS-related SD have become more frequent. More dystonia aetiologies, including novel aetiologies have been reported in recent cohorts, reflecting advances in genetic diagnosis. Neurosurgical interventions are increasingly reported in the management of SD episodes, including novel use of intraventricular baclofen. Overall outcomes from SD remain largely unchanged over time. No prospective epidemiological studies of SD were identified., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is an effective therapy for select patients with primary dystonia. DBS programming for dystonia is often challenging due to variable time to symptomatic improvement or stimulation induced side effects (SISE) such as capsular or optic tract activation which can prolong device optimization., Objective: To characterize the safety and tolerability of active recharge biphasic DBS (bDBS) in primary dystonia and to compare it to conventional clinical DBS (clinDBS)., Methods: Ten subjects with primary dystonia and GPi DBS underwent a single center, double blind, nonrandomized crossover study comparing clinDBS versus bDBS. The testing occurred over two-days. bDBS and clinDBS were administered on separate days and each was activated for 6 h. Rating scales were collected by video recording and scored by four blinded movement disorders trained neurologists., Results: The bDBS paradigm was safe and well-tolerated in all ten subjects. There were no persistent SISE reported. The mean change in the Unified Dystonia Rating Scale after 4 h of stimulation was greater in bDBS when compared to clinDBS (-6.5 vs 0.3, p < 0.04)., Conclusion: In this pilot study, we demonstrated that biphasic DBS is a novel stimulation paradigm which can be administered safely. The biphasic waveform revealed a greater immediate improvement. Further studies are needed to determine whether this immediate improvement persists with chronic stimulation or if clinDBS will eventually achieve similar levels of improvement to bDBS over time., Competing Interests: Declaration of competing interest RSR is an employee of Medtronic, Inc., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: In adults with dystonia Probabilistic Stimulation Mapping (PSM) has identified putative "sweet spots" for stimulation. We aimed to apply PSM to a cohort of Children and Young People (CYP) following DBS surgery., Methods: Pre-operative MRI and post-operative CT images were co-registered for 52 CYP undergoing bilateral pallidal DBS (n = 31 genetic/idiopathic dystonia, and n = 21 Cerebral Palsy (CP)). DBS electrodes (n = 104) were automatically detected, and Volumes of Tissue Activation (VTA) derived from individual patient stimulation settings. VTAs were normalised to the MNI105 space, weighted by percentage improvement in Burke-Fahn-Marsden Dystonia Rating scale (BFMDRS) at one-year post surgery and mean improvement was calculated for each voxel., Results: For the genetic/idiopathic dystonia group, BFMDRS improvement was associated with stimulation across a broad volume of the GPi. A spatial clustering of the upper 25th percentile of voxels corresponded with a more delineated volume within the posterior ventrolateral GPi. The MNI coordinates of the centroid of this volume (X = -23.0, Y = -10.5 and Z = -3.5) were posterior and superior to the typical target for electrode placement. Volume of VTA overlap with a previously published "sweet spots" correlated with improvement following surgery. In contrast, there was minimal BFMDRS improvement for the CP group, no spatial clustering of efficacious clusters and a correlation between established "sweet spots" could not be established., Conclusions: PSM in CYP with genetic/idiopathic dystonia suggests the presence of a "sweet spot" for electrode placement within the GPi, consistent with previous studies. Further work is required to identify and validate putative "sweet spots" across different cohorts of patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Low-frequency oscillations (LFO) detected in the internal globus pallidus of dystonia patients have been identified as a physiomarker for adaptive Deep Brain Stimulation (aDBS), since LFO correlate with dystonic symptoms and are rapidly suppressed by continuous DBS (cDBS). However, it is as yet unclear how LFO should be incorporated as feedback for aDBS., Objectives: to test the acute effects of aDBS, using the amplitude of short-lived LFO-bursts to titrate stimulation, to explore the immediate effects of cDBS on LFO-modulation and dystonic symptoms, and to investigate whether a difference in the resting-state LFO is present between DBS-naïve patients and patients with chronic DBS., Methods: seven patients were assessed during either DBS-implantation (n = 2) or battery replacement surgery (n = 5), and pseudorandomized in three conditions: no stimulation, cDBS, and aDBS. Additionally, resting-state LFP-recordings from patients undergoing battery replacement were compared to those obtained during DBS-implantation; LFP-recordings from a previous cohort of six dystonia patients undergoing DBS-implantation were incorporated into this analysis (total n = 8 newly implanted patients)., Results: we corroborated that a mild LFO-suppression rapidly occurs during cDBS. However, no acute changes in clinical symptoms were observed after cDBS or aDBS. Remarkably, we observed that resting-state LFO were significantly lower in patients who had been effectively treated with chronic cDBS compared to those of newly implanted patients, even when stimulation was suspended., Conclusions: our results indicate that LFO-suppression in dystonia, similar to symptom response to cDBS, might be gradual, and remain after stimulation is suspended. Therefore, tracking gradual changes in LFO may be required for aDBS implementation., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: KMT2B-related dystonia is a recently discovered hereditary dystonia that mostly occurs in childhood. This dystonia usually progresses to generalized dystonia with cervical, cranial, pharynx and larynx involvement. Our study summarizes genotype-phenotype features and deep brain stimulation (DBS) efficacy observed with KMT2B-related dystonia patients in China., Methods: We identified 20 patients with KMT2B variations from dystonia samples with a gene panel and whole exome sequencing. Genetic, clinical and treatment analyses of these patients with KMT2B mutations were further conducted., Results: We summarized the genotype and phenotypic characteristics of KMT2B-related patients in China, including 16 sporadic patients and 3 pedigrees (including 4 patients). Thirty-five percent (7/20) of patients had been published previously. The age of onset was between 1 month and 24 years (average 6.90 ± 5.72 years). Sixty-five percent (13/20) of patients had onset from lower limbs. Upper limbs or larynx accounted for 15% (3/20) and 20% (4/20) of patients, respectively. In the same family, male patients tended to have more severe symptoms than female patients. Carriers of KMT2B variants may present with nonmotor symptoms without dystonia. Abnormal endocrine metabolism could also be seen in our patients, including advanced bone age that had never been reported previously. Nine of our patients underwent DBS surgery. The mean follow-up time was 4.9 (range 1.3-16) months after DBS, and perceptible improvement of clinical symptoms were observed., Conclusions: The genotypic and phenotypic spectra of Chinese KMT2B-related dystonia patients were further expanded. DBS surgery might be the preferred option for severe KMT2B-related dystonia patients till now., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Dystonia-choreoathetosis is common in patients with cerebral palsy, and medical treatment is mostly unsatisfactory. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has shown some effect, but there is still a need to optimize treatment strategies. We aimed to assess whether the thalamic ventral intermediate nucleus (Vim) might be an alternative DBS target in dystonia-choreoathetosis., Methods: Three patients with cerebral palsy and dystonia-choreoathetosis underwent implantation of DBS electrodes concurrently in the GPi and Vim. Final selection of stimulation site and switches during follow-up with corresponding clinical outcomes were assessed., Results: One patient with initial GPi stimulation was switched to Vim, but likewise did not improve significantly (BFM: pre-OP 142, GPi 140, Vim 134) and stimulation was discontinued. In one patient Vim was chosen as initial target for chronic DBS. Since clinical benefit was not yet satisfying, stimulation was switched to GPi resulting in further mild clinical improvement (BFM: pre-OP 99.5, Vim 82.5, GPi 82). In one patient GPi was selected and kept on follow-up due to some therapeutic effect (BFM: pre-OP 135, GPi DBS 121)., Conclusions: The GPi still represents the most convenient DBS target in patients with dystonia-choreoathetosis. Vim DBS did not show a relevant long-term advantage in everyday life in our patients. Further alternative DBS targets need to be considered in acquired dystonia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Deep brain stimulation (DBS) has emerged as an effective treatment in medically intractable dystonia, with the globus pallidus internus (GPi) being most frequently targeted. Non-motor symptoms, including pain and psychiatric, cognitive and sleep disturbances, are increasingly recognized as important determinants of disease burden in dystonia patients. We reviewed non-motor outcomes of DBS in dystonia, focusing on GPi-DBS., Methods: A systematic literature search of Pubmed and Embase was performed according to the PRISMA guidelines., Results: Fifty-two studies were included. GPi-DBS reduced pain related to dystonia. No major effects on anxiety, mood, and cognition were found. In contrast to motor outcome, non-motor outcome seems more independent of the etiology of dystonia. However, the impact of potential confounders (e.g. patient factors, changes in pharmacological treatment) is unclear., Conclusion: Despite the growing interest in non-motor symptoms in dystonia, DBS studies still focus primarily on motor outcome. We recommend systematic evaluation of both non-motor and motor features before and after DBS interventions to improve quality of life and management of patients with dystonia., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Pallidal Deep Brain Stimulation (GPi-DBS) is an efficient treatment for primary dystonia. We investigated stimulation-induced dysarthria, which is the most frequent side-effect of GPi-DBS., Methods: Speech was recorded while reading a standard text, and performing rapid syllable repetitions ON and OFF DBS in ten dystonia patients (6 men; 3 cervical, 4 segmental, 3 generalized, unselected for DBS-related speech impairments). Speech and articulation rate, pauses, and syllable repetition rates were extracted via acoustic analysis. Locations of active stimulation contacts and volumes of tissue activated (VTA) were calculated., Results: The number of pauses increased significantly ON vs. OFF stimulation (Wilcoxon test, p < 0.05). More posteriorly localized active contacts were associated with slower syllable repetition (Pearson correlation, p < 0.05). VTA size did not correlate with any measure of dysarthria., Conclusion: Using quantitative acoustic signal analysis, this study demonstrates that GPi-DBS alters motor aspects of speech. Both inadvertent stimulation of parts of the internal capsule, or interference with GPi function and outflow are possible causes. Understanding causes of GPi-DBS-induced speech changes can improve DBS programming., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Dystonia is a rare disorder that has undergone extensive scientific investigation leading to a transformation of understanding over the past century., Methods: This manuscript was prepared through a review of relevant literature for each topic., Results: Historically dystonia was considered the manifestation of psychiatric disorders. Subsequently, investigations have firmly established this as a neurological disorder. Though electrophysiological and imaging, dystonia is thought to arise from a loss inhibition of motor programs, defective sensorimotor integration and abnormal plasticity. The genetic studies in dystonia have revealed the hereditary nature of many forms of familial dystonia. Treatment of dystonia has focused primarily on botulinum toxin for focal and segmental dystonia and deep brain stimulation of the globus pallidus interna for generalized and medically refractory focal dystonia., Conclusion: The progress in dystonia in the past century has revised the concepts of this disorder, increased knowledge of genetics and underlying pathophysiology, and provides new therapeutic targets. To promote future research the development of diagnostic criteria, biomarkers and validated rating scales for each form of dystonia is essential., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Pallidal deep brain stimulation (GPi-DBS) is an effective therapy for isolated dystonia, but 10-20% of patients show improvement below 25-30%. We here investigated causes of insufficient response to GPi-DBS in isolated dystonia in a cross-sectional study., Methods: Patients with isolated dystonia at time of surgery, and <30% improvement on the Burke-Fahn-Marsden dystonia-rating-scale (BFMDRS) after ≥6 months of continuous GPi-DBS were videotaped ON and OFF stimulation, and history, preoperative videos, brain MRI, medical records, stimulation settings, stimulation system integrity, lead location, and genetic information were obtained and reviewed by an expert panel., Results: 22 patients from 11 centres were included (8 men, 14 women; 9 generalized, 9 segmental, 3 focal, 1 bibrachial dystonia; mean (range): age 48.7 (25-72) years, disease duration 22.0 (2-40) years, DBS duration 45.5 (6-131) months). Mean BFMDRS-score was 31.7 (4-93) preoperatively and 32.3 (5-101) postoperatively. Half of the patients (n = 11) had poor lead positioning alone or in combination with other problems (combined with: other disease n = 6, functional dystonia n = 1, other problems n = 2). Other problems were disease other than isolated inherited or idiopathic dystonia (n = 5), fixed deformities (n = 2), functional dystonia (n = 3), and other causes (n = 1). Excluding patients with poor lead location from further analysis, non-isolated dystonia accounted for 45.5%, functional dystonia for 27.3%, and fixed deformities for 18.2%. In patients with true isolated dystonia, lead location was the most frequent problem., Conclusion: After exclusion of lead placement and stimulation programming issues, non-isolated dystonia, functional dystonia and fixed deformities account for the majority of GPi-DBS failures in dystonia., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dystonia is a hyperkinetic movement disorder that can be highly stigmatizing and disabling. Substantial evidence from animal models, neuropathological, neurophysiological, neuroimaging and clinical studies emphasizes the role of dopaminergic dysfunction in the pathophysiology of dystonia, illustrating possible pathophysiological overlap with parkinsonism. Furthermore, basal ganglia dysfunction has been implicated in the pathogenesis of dystonia, and is well established to underlie the manifestations of Parkinson's disease. Clinically, parkinsonian features are a key characteristic of some combined dystonias, including dopa-responsive dystonia, and Parkinson's disease often presents with dystonia. Moreover, many treatments effective in Parkinson's disease, both medical and surgical, also offer some benefit in dystonia. Therefore, mild parkinsonian features might logically accompany idiopathic and inherited isolated dystonias. However, as the current literature is particularly scant, the present review aimed to investigate mild parkinsonism in idiopathic and inherited dystonia. We found limited evidence alluding to the presence of mildly reduced arm-swing, increased tone, and non-decremental bradykinesia in adult-onset focal dystonia. Tremor, with postures, action and rest, also occurs commonly in idiopathic isolated dystonia, and can simulate Parkinson's disease tremor and be a cause of 'scans without evidence of dopaminergic deficit'. Parkinsonian features in monogenic isolated dystonias have been less well investigated, despite the potential benefit of correlating pathophysiological and clinical findings. The recognition and improved clinical characterization of parkinsonian features in idiopathic and inherited isolated dystonia extends the clinical spectrum of motor features in dystonia, which may help avoid incorrect diagnosis and inform therapeutic research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The most recent international consensus update on dystonia classification proposed a system based on 2 axes, clinical characteristics and aetiology. We aimed to apply this system to Children and Young People (CAYP) selected for movement disorder surgery, and determine if meaningful groupings of cases could be extracted., Methods: The 2013 Consensus Committee classification system for dystonia was retrospectively applied to 145 CAYP with dystonic movement disorders. Two-step cluster analysis was applied to the resulting categorisations to identify groupings of CAYP with similar characteristics., Results: Classification resulted in a total of 43 unique groupings of categorisation. Cluster analysis detected 4 main clusters of CAYP, comparable to previously used patient groupings., Conclusions: The 2013 consensus update on dystonia classification can be applied to CAYP with dystonia. The large number of categories provides a wealth of information for the clinician, and also facilitates data driven grouping into clinically meaningful subgroups., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Pallidal deep brain stimulation (DBS) is effective in alleviating motor symptoms of medication refractory cervical dystonia, but little is known about effects on cognitive functions., Methods: As part of the first randomized, sham-controlled multicenter trial on DBS in medication-refractory primary cervical dystonia (ClinicalTrials.gov, number NCT00148889), a subgroup of 13 patients aged 39 to 69 underwent prospective neuropsychological long-term follow-up assessments. Various cognitive domains (memory, executive functions, attention, visual perception, mental arithmetic and verbal intelligence) were examined before and after 12 months of continuous DBS., Results: Only the number of produced words in a verbal fluency task which included alternating categories decreased after stimulation (p = 0.020). All other cognitive domains remained unchanged., Conclusions: These findings indicate that long-term pallidal DBS for the treatment of primary cervical dystonia seems to be safe regarding global cognitive functioning., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Pallidal deep brain stimulation (DBS) is an effective treatment for patients with primary dystonia leading to a substantial reduction of symptom severity. However, stimulation induced side effects such as bradykinesia have also been reported recently. The influence of stimulation parameters on such side effects have not yet been systemically assessed in these patients., Methods: Here we tested the effect of stimulation frequency and duration of stimulation period on hand motor function in 22 patients with primary cervical and segmental dystonia using an unimanual tapping task. Patients performed the task at 4 different stimulation frequencies (0 Hz = OFF stimulation, 20, 50 and ≥130 Hz = high frequency stimulation) after either an SHORT (5 min, N = 16) or a LONG (60 min, N = 6) stimulation period (i.e. changing of DBS-frequency). The change of overall mobility under HFS compared to the preoperative state was assessed with a 5-point Likert-scale. Tapping performance was analysed using a repeated measures ANOVA with the main factor 'FREQUENCY'. Tapping performance at HFS and changes in general mobility were correlated using Spearman's Rho., Results: We found a frequency specific modulation of hand motor function: HFS led to deterioration and 20 Hz stimulation to improvement of tapping rate. The effects were predominant in the 'LONG' group suggesting a significant contribution of stimulation duration., Conclusions: This is important to consider during DBS-programming and evaluation of potential side effects. Furthermore, the impairment in hand motor function under HFS was mirrored by the patients' observation of a deterioration of general mobility., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Neurogenic bladder dysfunction is well described in Parkinson's disease and has a major impact on quality of live. In contrast, little is known about the extent of urinary symptoms in other movement disorders such as dystonia and about the role of the basal ganglia in bladder control.., Patients and Methods: A consecutive series of 11 patients with severe dystonia undergoing deep brain stimulation (DBS) of the globus pallidus internus was prospectively enrolled. Bladder function was assessed by the International Prostate Symptom Score and urodynamic investigation (UDI) before DBS surgery and afterwards in the conditions with and without DBS., Results: In UDI before DBS surgery, detrusor overactivity was found in 36% (4/11) of dystonia patients. With pallidal DBS ON, maximum flow rate significantly decreased, post-void residual significantly increased and detrusor overactivity disappeared.., Conclusions: Pathological urodynamic changes can be found in a relevant percentage of dystonia patients. Pallidal DBS has a relaxing effect on detrusor function indicating a role of the basal ganglia in lower urinary tract control. Thus, a better understanding on how subcortical networks influence lower urinary tract function might open new therapeutic perspectives.., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Surgery for dystonia has a history stretching back for centuries including myotomy and other procedures on the musculoskeletal system. In the last century lesional procedures, mainly involving the pallidum became popular. More recently, with the advent of deep brain stimulation, bilateral medial pallidal stimulation has become commonplace. This review describes the issues with patient selection, technical aspects of implantation and effects as well as complications of the technique. Some of the rarer types of dystonia that have also been treated with DBS are also described.

Background: The syndrome of fixed dystonia includes both CRPS-dystonia and psychogenic dystonia. The underlying mechanisms are unclear, but a high prevalence of neuropsychiatric illness has previously been reported., Methods: Clinical and neuropsychiatric follow-up study by telephone and self-administered instruments (HADS, SDQ-20, DES II, EQ-5D), on 41 patients with fixed dystonia after a mean of 7.6 (+/-3.6) years., Results: We obtained information on clinical outcome in 35 (85.4%) patients and neuropsychiatric questionnaire data in 22 (53.7%). Eighty-three percent were women. Thirty-one percent had worsened, 46% were the same and 23% had improved, of whom 6% had major remissions. At follow-up, mean duration of illness was 11.8 (+/-4.9) years and mean age 43.2 (+/-14.8) years. Except for 1 patient who was re-diagnosed with corticobasal degeneration, the diagnosis remained unchanged in others. Forty-one percent had scores indicating anxiety and 18% indicating depression; 18% scored within the range of dissociative/somatoform disorders on DES II and 19% on SDQ-20. The mean EQ-5D index and VAS scores were 0.34 and 56.1%. Comparison between the 3 outcome groups revealed significant difference only in the EQ-5D (p=0.003). Only baseline CRPS predicted a worse outcome (chi(2)=0.006)., Conclusions: Our findings revealed that the prognosis of this syndrome is poor, with improvement in less than 25% of patients, major remission in only 6% and continued worsening in a third. A high rate of neuropsychiatric findings was noted and new neuropsychiatric features had occurred in some. Average health status was poor. Of the baseline parameters, only CRPS predicted poorer outcome.

Frequently, blepharospasm is associated with involuntary movements of the platysma, lower face and masticatory muscles. Similarly, masticatory dystonia may occur in isolation or in combination with dystonia of other cranial and cervical muscles. The non-possessive and possessive forms of Meige and Brueghel syndromes have been variably and imprecisely ascribed to various anatomical variations of craniocervical dystonia. Herein, the origin of eponymic terms as applied to craniocervical dystonia is reviewed as support for proposed elimination of these eponyms from clinical usage. Although the term "segmental craniocervical dystonia" more accurately captures the combination of blepharospasm and dystonia of other head and neck muscles, delineation of craniocervical subphenotypes is essential for etiological/genetic and treatment studies. To conclude, the clinical features, epidemiology, pathophysiology and therapeutic management of segmental craniocervical dystonia are examined with a particular focus on "blepharospasm-plus" subphenotypes.

Deep brain stimulation (DBS) was applied in the internal segment of the globus pallidus (GPi) to treat dystonia in 10 patients. One year after surgery the Burke-Fahn-Marsden movement scores were significantly lower than preoperative values (P=0.01). Two years after surgery the mean decrease reached 65% (P=0.001) with no motor symptoms worsening. Single unity activity was recorded in the operating room: GPi cells discharged with tonic (n=19; 29%), irregular (n=32; 48%), or burst-like activity (n=15; 23%) and fired with a mean discharge rate of 39 Hz+/-22. Some neurons demonstrated an oscillatory activity with periods lasting several seconds. Pairs of pallidal cells (n=8) recorded simultaneously displayed discharge synchronization. Movement modulated 64.4% of the cells tested, with increases in firing in 89% of cells and decreases in firing in 10% of cells. GPi cells responded to flexion and extension movements and to several passive manipulations indicating an important sensory role in dystonia. GPi neurons fired in advance of the electromyography (EMG) when the surface EMG was recorded simultaneously with the neuronal activity. Spectral analysis of the co-contracting muscles during dystonia demonstrated prominent high peaks at a low frequency band (20 Hz) during involuntary and voluntary movements. The high amplitude EMG profile recorded at rest diminished to very low values with GPi stimulation, allowing an ease of voluntary contractions. We conclude that DBS in the GPi is a reliable surgical technique for dystonia. GPi cells discharge with distinct electrophysiological characteristics that may explain some of the symptoms in dystonia. EMG recording in the operating room helps to determine which DBS contacts produce the best benefit.

Neuromodulation is the functional modification of neural structures through the use of electrical stimulation. Its most clinically applicable use is deep brain stimulation (DBS) of basal ganglia structures in Parkinson's disease (PD) and essential tremor (ET). More recently, it has been used as a means of treating dystonic movement disorders. The main target of DBS for dystonia is the posteroventral globus pallidus internus (GPi), although the thalamus has been used as an alternate target in a minority of cases. In comparison to the effects seen in PD, the improvement in dystonic postures appear to differ in several ways--delay of clinical benefit, higher voltage requirements, and varied stimulator settings. In this review, the authors discuss the clinical characteristics, pathophysiology, microelectrode recording (MER) signatures, optimal surgical targets, programming parameters and outcomes in dystonia.

It is now possible to probe the plasticity of some neural circuits in the human motor cortex using transcranial magnetic stimulation (TMS). This article illustrates how changes in the plasticity of these circuits is linked to the expression of dyskinesias in Parkinson's disease, and may even underlie the tendency of some individuals to develop focal dystonia. Indeed, gradual normalisation of this excessive plasticity occurs after initiating deep brain stimulation of the internal globus pallidus in patients with generalised dystonia. It may therefore relate to the slow onset of clinical improvement that occurs over the first 6 weeks or so of treatment.

Dystonia varies in severity from simple focal dystonia, such as writer's cramp to life-threatening status dystonicus. Even though the pathophysiology is still elusive, symptomatic treatments may provide marked relief. Botulinum toxin is considered the treatment of choice for most focal and segmental dystonias. Deep brain stimulation of the basal ganglia, particularly the globus pallidus internum, is emerging as an important treatment for refractory, generalized, and segmental forms of dystonia. Gene therapy is also being explored as a possible treatment of inherited dystonias. This article reviews the therapeutic options available for the various types of dystonia.

We describe the outcome of deep brain stimulation of the internal pallidum in a 57-year old patient with multiple system atrophy. Although the prominent dystonic features of this patient were markedly attenuated post-operatively, the outcome was to be considered unfavourable. There was a severe increase in akinesia resulting in overall decrease of mobility in limbs as well as in the face. As a result, the patient was anarthric and displayed dysphagia. A laterality effect of stimulation on oro-facial movements was demonstrated. The patient died 7 months post-operatively. This report adds to the growing consensus that multiple system atrophy patients are unsuitable candidates for deep brain stimulation.

Object: The parameter adjustment process during deep brain stimulation (DBS) for dystonia remains time consuming and based on clinical observation alone. The aim was to correlate the electric field with the GPi anatomy to be able to study the stimulated volume., Methods: We developed a computer-assisted method (model) for visualizing electric field in reference to the stereotactic space. Electric field values were correlated with the GPi anatomy (stereotactic Magnetic Resonance Imaging) in one reference patient., Results: Using this methodology it becomes possible to correlate the electric field distributions for patient specific parameters with the anatomical information. The application to one patient showed that the 0.1V/mm isofieldline fits best with the lateral GPi borders at the level of the stimulated contacts., Conclusions: The electric field is a crucial parameter as it is assumed to be responsible for triggering action potentials. Electric field visualisation allows the calculation of the stimulated volume for a given isoline. Its application to our whole patient population might help in determining a threshold for obtaining a therapeutic effect, to date unknown, and consequently in optimizing the parameter setting in each patient.

Parkinsonism and dystonia may coexist in a number of neurodegenerative, genetic, toxic, and metabolic disorders and as a result of structural lesions in the basal ganglia. Parkinson's disease (PD) and the 'Parkinson-plus' syndromes (PPS) account for the majority of patients with the parkinsonism-dystonia combination. Dystonia, particularly when it involves the foot, may be the presenting sign of PD or PPS and these disorders should be suspected when adults present with isolated foot dystonia. Young age, female gender, and long disease duration are risk factors for PD-related dystonia, but dystonia in patients with PD is usually related to levodopa therapy. The mechanism of dystonia in PD is not well understood and the management is often challenging because levodopa and other dopaminergic agents may either improve or worsen dystonia. Other therapeutic strategies include oral medications (baclofen, anticholinergics and benzodiazepines), local injections of botulinum toxin, intrathecal baclofen, and surgical lesions or high frequency stimulation of the thalamus, globus pallidus, or subthalamus.

Essential blepharospasm is an idiopathic disorder of progressive involuntary spasms of the orbicularis oculi and upper facial (corrugator, procerus) muscles. Blepharospasm literally means spasm of the eyelids; however, most patients with blepharospasm also have or will develop squeezing in the lower face and neck muscles (Meige's syndrome, orofacial dystonia, or oromandibular dystonia). Some patients develop dystonic, uncontrolled movements in areas outside the facial nerve distribution (segmental cranial dystonia or craniocervical dystonia). Chronic, forceful squeezing by the periocular muscles becomes debilitating for the patient and leads to functional and cosmetic eyelid deformities. Treatment has included a variety of modalities and oral medications that are of limited efficacy. Botulinum-A toxin injections have delivered the best temporary relief from this disorder, while the periorbital myectomy operation has been shown to give the best long-term results.