HUMANISE: Human-Inspired Smart Management, towards a Healthy and Safe Industrial Collaborative Robotics.

The workplace is evolving towards scenarios where humans are acquiring a more active and dynamic role alongside increasingly intelligent machines. Moreover, the active population is ageing and consequently emerging risks could appear due to health disorders of workers, which requires intelligent intervention both for production management and workers' support. In this sense, the innovative and smart systems oriented towards monitoring and regulating workers' well-being will become essential. This work presents HUMANISE, a novel proposal of an intelligent system for risk management, oriented to workers suffering from disease conditions. The developed support system is based on Computer Vision, Machine Learning and Intelligent Agents. Results: The system was applied to a two-arm Cobot scenario during a Learning from Demonstration task for collaborative parts transportation, where risk management is critical. In this environment with a worker suffering from a mental disorder, safety is successfully controlled by means of human/robot coordination, and risk levels are managed through the integration of human/robot behaviour models and worker's models based on the workplace model of the World Health Organization. The results show a promising real-time support tool to coordinate and monitoring these scenarios by integrating workers' health information towards a successful risk management strategy for safe industrial Cobot environments.

Connectivity-based parcellation of normal and anatomically distorted human cerebral cortex.

For over a century, neuroscientists have been working toward parcellating the human cortex into distinct neurobiological regions. Modern technologies offer many parcellation methods for healthy cortices acquired through magnetic resonance imaging. However, these methods are suboptimal for personalized neurosurgical application given that pathology and resection distort the cerebrum. We sought to overcome this problem by developing a novel connectivity-based parcellation approach that can be applied at the single-subject level. Utilizing normative diffusion data, we first developed a machine-learning (ML) classifier to learn the typical structural connectivity patterns of healthy subjects. Specifically, the Glasser HCP atlas was utilized as a prior to calculate the streamline connectivity between each voxel and each parcel of the atlas. Using the resultant feature vector, we determined the parcel identity of each voxel in neurosurgical patients (n = 40) and thereby iteratively adjusted the prior. This approach enabled us to create patient-specific maps independent of brain shape and pathological distortion. The supervised ML classifier re-parcellated an average of 2.65% of cortical voxels across a healthy dataset (n = 178) and an average of 5.5% in neurosurgical patients. Our patient dataset consisted of subjects with supratentorial infiltrating gliomas operated on by the senior author who then assessed the validity and practical utility of the re-parcellated diffusion data. We demonstrate a rapid and effective ML parcellation approach to parcellation of the human cortex during anatomical distortion. Our approach overcomes limitations of indiscriminately applying atlas-based registration from healthy subjects by employing a voxel-wise connectivity approach based on individual data.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Hypoactivity in the Paraterminal Gyrus Following Bilateral Anterior Capsulotomy.

OBJECTIVE: Bilateral anterior capsulotomy (BAC) is one of the ablative neurosurgical procedures used to treat major depressive disorder or obsessive-compulsive disorder when all other therapies fail. Tristolysis, a reduction in sadness, is the most striking clinical effect of BAC and is seen in the first 1 to 2 weeks after surgery. This retrospective study measured regional cerebral blood flow (rCBF) following surgery to identify which cortical regions were impacted and could account for this clinical effect. METHODS: All patients had their capsulotomies done in Vancouver by the same team. Pre- and postoperative single-photon emission computed tomography perfusion scans were analyzed for 10 patients with major depressive disorder and 3 with obsessive-compulsive disorder. rCBF was measured semiquantitatively by calculating the ratio between an identified region of interest and a whole brain reference area. RESULTS: Decreased rCBF was found in the paraterminal gyri. Increased rCBF was found in the dorsolateral prefrontal cortices and in the left lateral temporal lobe. CONCLUSIONS: BAC causes hypoactivity in the paraterminal gyri and is the most likely explanation for its tristolytic effect, suggesting that the paraterminal gyrus is the limbic cortical locus for the emotion of sadness. Increased activity in the dorsolateral prefrontal cortices may be occurring via connectional diaschisis, and suppression by overactive paraterminal gyri during depression may account for some of the neurocognitive deficits observed during depressive episodes.

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor.

BACKGROUND: Voice tremor (VT) is the involuntary and rhythmical phonatory instability of the voice. Recent findings suggest that unilateral deep brain stimulation of the ventral intermediate nucleus (Vim-DBS) can sometimes be effective for VT. In this exploratory analysis, we investigated the effect of Vim-DBS on VT and tested the hypothesis that unilateral thalamic stimulation is effective for patients with VT. METHODS: Seven patients with VT and previously implanted bilateral Vim-DBS were enrolled in the study. Each patient was randomized and recorded performing sustained phonation during the following conditions: left thalamic stimulation, right thalamic stimulation, bilateral thalamic stimulation (Bil-ON), and no stimulation (Bil-OFF). Perceptual VT ratings and an acoustic analysis to find the rate of variation of the fundamental frequency measured by the standard deviation of the pitch (f0SD) were performed in a blinded manner. For the purposes of this study, a "dominant" side was defined as one with more than twice as much reduction in VT following Vim-DBS compared to the contralateral side. The Wilcoxon signed-rank test was performed to compare the effect of the dominant side stimulation in the reduction of VT scores and f0SD. The volume of activated tissue (VAT) of the dominant stimulation side was modelled against the degree of improvement in VT to correlate the significant stimulation cluster with thalamic anatomy. Finally, tractography analysis was performed to analyze the connectivity of the significant stimulation cluster. RESULTS: Unilateral stimulation was beneficial in all 7 patients. Five patients clearly had a "dominant" side with either benefit only seen following stimulation of one side or more than twice as much benefit from one side compared to the other. Two patients had similar benefit with unilateral stimulation from either side. The Wilcoxon paired test showed significant differences between unilateral dominant and unilateral nondominant stimulation for VT scores (p = 0.04), between unilateral dominant and Bil-OFF (p = 0.04), and between Bil-ON and unilateral nondominant stimulation (p = 0.04). No significant differences were found between Bil-ON and unilateral dominant condition (p = 0.27), or between Bil-OFF and unilateral nondominant (p = 0.23). The dominant VAT showed that the significant voxels associated with the best VT control were located in the most ventral and medial part of the Vim nucleus and the ventralis caudalis anterior internus nucleus. The connectivity analysis showed significant connectivity with the cortical areas of the speech circuit. CONCLUSIONS: Unilateral dominant-side thalamic stimulation and bilateral thalamic stimulation were equally effective in reducing VT. Nondominant unilateral stimulation alone did not significantly improve VT.

Cyclization of Motor Cortex Stimulation for Neuropathic Pain: A Prospective, Randomized, Blinded Trial.

OBJECTIVES: Programming guidelines for motor cortex stimulation (MCS) in neuropathic pain requires further investigation. After optimizing voltage as a percentage of motor threshold, we evaluated the effect of cyclizing time of stimulation on pain relief for chronic neuropathic pain. METHODS: Six patients were enrolled into this trial. In a prospective, randomized, double-blinded manner, patients were programmed to receive stimulation 100, 83.3, 66.7, or 50% of the time in 30-min intervals. Outcomes were assessed after 14 days on each setting with a visual analogue scale (VAS) for pain and the SF36 quality of life questionnaire. RESULTS: There was no significant difference (p > 0.05) between the different cyclized settings as measured by the VAS, MGPQ, or SF36 in our cohort. There were two distinct subgroups: responders (n = 4) and nonresponders (n = 2) to cyclization. Responders continued to have pain relief when stimulation was reduced to only 50% of the time (15 min ON/15 min off). Interestingly, this group subjectively preferred the 50% stimulation timing compared to 100%. Nonresponders could not tolerate cyclizing because of increased pain. CONCLUSIONS: In this small cohort, cyclization of MCS settings revealed two distinct subgroups: responders and nonresponders. Responders tolerated stimulation in all settings and 50% stimulation (15 min ON/15 min off) was their subjectively preferred setting. Cyclization in responders will prolong battery life and delay the need for INS replacement and may offer improved pain relief. Building from our previous work, we recommend clinicians consider following the Vancouver MCS programming algorithm presented in this manuscript.

Interventional neurorehabilitation for promoting functional recovery post-craniotomy: a proof-of-concept.

The human brain is a highly plastic 'complex' network-it is highly resilient to damage and capable of self-reorganisation after a large perturbation. Clinically, neurological deficits secondary to iatrogenic injury have very few active treatments. New imaging and stimulation technologies, though, offer promising therapeutic avenues to accelerate post-operative recovery trajectories. In this study, we sought to establish the safety profile for 'interventional neurorehabilitation': connectome-based therapeutic brain stimulation to drive cortical reorganisation and promote functional recovery post-craniotomy. In n = 34 glioma patients who experienced post-operative motor or language deficits, we used connectomics to construct single-subject cortical networks. Based on their clinical and connectivity deficit, patients underwent network-specific transcranial magnetic stimulation (TMS) sessions daily over five consecutive days. Patients were then assessed for TMS-related side effects and improvements. 31/34 (91%) patients were successfully recruited and enrolled for TMS treatment within two weeks of glioma surgery. No seizures or serious complications occurred during TMS rehabilitation and 1-week post-stimulation. Transient headaches were reported in 4/31 patients but improved after a single session. No neurological worsening was observed while a clinically and statistically significant benefit was noted in 28/31 patients post-TMS. We present two clinical vignettes and a video demonstration of interventional neurorehabilitation. For the first time, we demonstrate the safety profile and ability to recruit, enroll, and complete TMS acutely post-craniotomy in a high seizure risk population. Given the lack of randomisation and controls in this study, prospective randomised sham-controlled stimulation trials are now warranted to establish the efficacy of interventional neurorehabilitation following craniotomy.

The Frontal Aslant Tract and Supplementary Motor Area Syndrome: Moving towards a Connectomic Initiation Axis.

Connectomics is the use of big data to map the brain's neural infrastructure; employing such technology to improve surgical planning may improve neuro-oncological outcomes. Supplementary motor area (SMA) syndrome is a well-known complication of medial frontal lobe surgery. The 'localizationist' view posits that damage to the posteromedial bank of the superior frontal gyrus (SFG) is the basis of SMA syndrome. However, surgical experience within the frontal lobe suggests that this is not entirely true. In a study on n = 45 patients undergoing frontal lobe glioma surgery, we sought to determine if a 'connectomic' or network-based approach can decrease the likelihood of SMA syndrome. The control group (n = 23) underwent surgery avoiding the posterior bank of the SFG while the treatment group (n = 22) underwent mapping of the SMA network and Frontal Aslant Tract (FAT) using network analysis and DTI tractography. Patient outcomes were assessed post operatively and in subsequent follow-ups. Fewer patients (8.3%) in the treatment group experienced transient SMA syndrome compared to the control group (47%) (p = 0.003). There was no statistically significant difference found between the occurrence of permanent SMA syndrome between control and treatment groups. We demonstrate how utilizing tractography and a network-based approach decreases the likelihood of transient SMA syndrome during medial frontal glioma surgery. We found that not transecting the FAT and the SMA system improved outcomes which may be important for functional outcomes and patient quality of life.

Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial.

BACKGROUND: Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS). OBJECTIVE: To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit. METHODS: Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634). RESULTS: There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr. CONCLUSION: This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.

Parcellation-based modeling of the supplementary motor area.

INTRODUCTION: The supplementary motor area (SMA) plays an important role in the initiation and coordination of internally and externally cued movements. Such movements include reaching, grasping, speaking, and bilateral hand coordination. While many studies discuss the SMA and its relationship to other parts of the motor network, there is minimal literature examining the connectivity of the SMA outside of the motor network. Using region-based fMRI studies, we built a neuroanatomical model to account for these extra-motor connections. METHODS: Thirty region-based fMRI studies were used to generate an activation likelihood estimation (ALE) using BrainMap software. Cortical parcellations overlapping the ALE were used to construct a preliminary model of the SMA connections outside the motor network. DSI-based fiber tractography was performed to determine the connectivity between cortical parcellations. The resulting connections were described using the cortical parcellation scheme developed by the Human Connectome Project (HCP). RESULTS: Four left hemisphere regions were found to comprise the SMA. These included areas SFL, SCEF, 6ma, and 6mp. Across mapped brains, these areas showed consistent interconnections between each other. Additionally, ipsilateral connections to the primary motor cortex, left inferior and middle frontal gyri, the anterior cingulate gyrus, and insula were demonstrated. Connections to the contralateral SMA, anterior cingulate, lateral premotor, and inferior frontal cortices were also identified. CONCLUSIONS: We describe a preliminary cortical model for the underlying structural connectivity of the supplementary motor area outside the motor network. Future studies should further characterize the neuroanatomic underpinnings of this network for the purposes of medical application.

A Cortical Parcellation Based Analysis of Ventral Premotor Area Connectivity.

Introduction. The ventral premotor area (VPM) plays a crucial role in executing various aspects of motor control. These include hand reaching, joint coordination, and direction of movement in space. While many studies discuss the VPM and its relationship to the rest of the motor network, there is minimal literature examining the connectivity of the VPM outside of the motor network. Using region-based fMRI studies, we built a neuroanatomical model to account for these extra-motor connections.Methods. Thirty region-based fMRI studies were used to generate an activation likelihood estimation (ALE) using BrainMap software. Cortical parcellations overlapping the ALE were used to construct a preliminary model of the VPM connections outside the motor network. Diffusion spectrum imaging (DSI)-based fiber tractography was performed to determine the connectivity between cortical parcellations in both hemispheres, and a laterality index (LI) was calculated with resultant tract volumes. The resulting connections were described using the cortical parcellation scheme developed by the Human Connectome Project (HCP).Results. Four cortical regions were found to comprise the VPM. These four regions included 6v, 4, 3b, and 3a. Across mapped brains, these areas showed consistent interconnections between each other. Additionally, ipsilateral connections to the primary motor cortex, supplementary motor area, and dorsal premotor cortex were demonstrated. Inter-hemispheric asymmetries were identified, especially with areas 1, 55b, and MI connecting to the ipsilateral VPM regions.Conclusion. We describe a preliminary cortical model for the underlying connectivity of the ventral premotor area. Future studies should further characterize the neuroanatomic underpinnings of this network for neurosurgical applications.

Analysis of Fine Motor Skills in Essential Tremor: Combining Neuroimaging and Handwriting Biomarkers for Early Management.

Essential tremor (ET) is a highly prevalent neurological disorder characterized by action-induced tremors involving the hand, voice, head, and/or face. Importantly, hand tremor is present in nearly all forms of ET, resulting in impaired fine motor skills and diminished quality of life. To advance early diagnostic approaches for ET, automated handwriting tasks and magnetic resonance imaging (MRI) offer an opportunity to develop early essential clinical biomarkers. In this study, we present a novel approach for the early clinical diagnosis and monitoring of ET based on integrating handwriting and neuroimaging analysis. We demonstrate how the analysis of fine motor skills, as measured by an automated Archimedes' spiral task, is correlated with neuroimaging biomarkers for ET. Together, we present a novel modeling approach that can serve as a complementary and promising support tool for the clinical diagnosis of ET and a large range of tremors.

The cortical organization of language: distilling human connectome insights for supratentorial neurosurgery.

Connectomics is the production and study of detailed "connection" maps within the nervous system. With unprecedented advances in imaging and high-performance computing, the construction of individualized connectomes for routine neurosurgical use is on the horizon. Multiple projects, including the Human Connectome Project (HCP), have unraveled new and exciting data describing the functional and structural connectivity of the brain. However, the abstraction from much of these data to clinical relevance remains elusive. In the context of preserving neurological function after supratentorial surgery, abstracting surgically salient points from the vast computational data in connectomics is of paramount importance. Herein, the authors discuss four interesting observations from the HCP data that have surgical relevance, with an emphasis on the cortical organization of language: 1) the existence of a motor speech area outside of Broca's area, 2) the eloquence of the frontal aslant tract, 3) the explanation of the medial frontal cognitive control networks, and 4) the establishment of the second ventral stream of language processing. From these connectome observations, the authors discuss the anatomical basis of their insights as well as relevant clinical applications. Together, these observations provide a firm platform for neurosurgeons to advance their knowledge of the cortical networks involved in language and to ultimately improve surgical outcomes. It is hoped that this report encourages neurosurgeons to explore new vistas in connectome-based neurosurgery.

Parcellation-based modeling of the dorsal premotor area.

BACKGROUND: The dorsal premotor area (DPM) plays an important role in hand coordination and muscle recruitment for lifting activities. Lesions in the area have demonstrated that the DPM is critical in the integration of movements that require combinations of reaching, grasping, and lifting. While many have looked at its functional connectivity, few studies have shown the full anatomical connectivity of DPM including its connections beyond the motor network. Using region-based fMRI studies, we built a neuroanatomical model to account for these extra-motor connections. OBJECTIVE: In this study, we performed meta-analysis and tractography with the goal of creating a map of the dorsal premotor network using the Human Connectome Project parcellation scheme nomenclature (i.e. the Glasser Atlas). While there are other possible ways to map this, we feel that it is critical that neuroimaging begin to move towards all of its data expressed in a single nomenclature which can be compared across studies, and a potential framework that we can build upon in future studies. METHODS: Thirty region-based fMRI studies were used to generate an activation likelihood estimation (ALE) using BrainMap software (Research Imaging Institute of Texas Health Science Center San Antonio). Cortical parcellations overlapping the ALE were used to construct a preliminary model of the Dorsal Premotor Area. Diffusion spectrum imaging (DSI) based tractography was performed to determine the connectivity between cortical parcellations and connections throughout cortex. The resulting connectivities were described using the cortical parcellation scheme developed by the Human Connectome Project (HCP). RESULTS: Three left hemisphere regions were found to comprise the Dorsal Premotor Area. These included areas 6a, 6d. and 6v, Across mapped brains, these areas showed consistent interconnections between each other. Additionally, ipsilateral connections to the premotor cortex, sensorimotor cortex, superior and inferior parietal lobule, middle and inferior frontal gyrus, and insula were demonstrated. Connections to the contralateral supplementary motor area and premotor cortex were also identified. CONCLUSIONS: We describe a preliminary cortical model for the underlying structural connectivity of the Dorsal Premotor Area. Future studies should further characterize the neuroanatomic underpinnings of this network.

Practical Application of Networks in Neurosurgery: Combined 3-Dimensional Printing, Neuronavigation, and Preoperative Surgical Planning.

BACKGROUND: A plethora of cutting-edge neuroimaging analyses have been developed and published, yet they have not hitherto been realized as improvements in neurosurgical outcomes. In this paper we propose a novel interface between neuroimaging and neurosurgery for aiding translational research. Our objective is to create a method for applying advanced neuroimaging and network analysis findings to neurosurgery and illustrate its application through the presentation of 2 detailed case vignettes. METHODS: This interface comprises a combination of network visualization, 3-dimensional printing, and ex-vivo neuronavigation to enable preoperative planning according to functional neuroanatomy. Clinical cases were selected from a prospective cohort study. RESULTS: The first case vignette describes a low-grade glioma with potential language and executive function network involvement that underwent a successful complete resection of the lesion with preservation of network features. The second case describes a low-grade glioma in an apparently noneloquent location that underwent a subtotal resection but demonstrated unexpected and significant impairment in executive function postoperatively that subsequently abated during follow-up. In both examples the neuroimaging and network data highlight the complexity of the surrounding functional neuroanatomy at the individual level, beyond that which can be perceived on standard structural sequences. CONCLUSIONS: The described interface has widespread applications for translational research including preoperative planning, neurosurgical training, and detailed patient counseling. A protocol for assessing its effectiveness and safety is proposed. Finally, recommendations for effective translation of findings from neuroimaging to neurosurgery are discussed, with the aim of making clinically meaningful improvements to neurosurgical practice.

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits.

Spasmodic dysphonia (SD) is a neurological disorder of the voice where a patient's ability to speak is compromised due to involuntary contractions of the intrinsic laryngeal muscles. Since the 1980s, SD has been treated with botulinum toxin A (BTX) injections into the throat. This therapy is limited by the delayed-onset of benefits, wearing-off effects, and repeated injections required every 3 months. In a patient with essential tremor (ET) and coincident SD, the authors set out to quantify the effects of thalamic deep brain stimulation (DBS) on vocal function while investigating the underlying motor thalamic circuitry. A 79-year-old right-handed woman with ET and coincident adductor SD was referred to our neurosurgical team. While primarily treating her limb tremor, the authors studied the effects of unilateral, thalamic DBS on vocal function using the Unified Spasmodic Dysphonia Rating Scale (USDRS) and voice-related quality of life (VRQOL). Since dystonia is increasingly being considered a multinodal network disorder, an anterior trajectory into the left thalamus was deliberately chosen such that the proximal contacts of the electrode were in the ventral oralis anterior (Voa) nucleus (pallidal outflow) and the distal contacts were in the ventral intermediate (Vim) nucleus (cerebellar outflow). In addition to assessing on/off unilateral thalamic Vim stimulation on voice, the authors experimentally assessed low-voltage unilateral Vim, Voa, or multitarget stimulation in a prospective, randomized, doubled-blinded manner. The evaluators were experienced at rating SD and were familiar with the vocal tremor of ET. A Wilcoxon signed-rank test was used to study the pre- and posttreatment effect of DBS on voice. Unilateral left thalamic Vim stimulation (DBS on) significantly improved SD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and VRQOL (p < 0.01). In the experimental interrogation, both low-voltage Vim (p < 0.01) and multitarget Vim + Voa (p < 0.01) stimulation were significantly superior to low-voltage Voa stimulation. For the first time, the effects of high-frequency stimulation of different neural circuits in SD have been quantified. Unexpectedly, focused Voa (pallidal outflow) stimulation was inferior to Vim (cerebellar outflow) stimulation despite the classification of SD as a dystonia. While only a single case, scattered reports exist on the positive effects of thalamic DBS on dysphonia. A Phase 1 pilot trial (DEBUSSY; clinical trial no. NCT02558634, clinicaltrials.gov) is underway at the authors' center to evaluate the safety and preliminary efficacy of DBS in SD. The authors hope that this current report stimulates neurosurgeons to investigate this new indication for DBS.

A prospective, randomized, blinded assessment of multitarget thalamic and pallidal deep brain stimulation in a case of hemidystonia.

OBJECTIVE: Dystonia is increasingly being interpreted as a multi-nodal "network" disorder. We aimed to investigate multitarget DBS (pallidal and thalamic) versus each target alone in a prospective, randomized, blinded trial in a case of hemidystonia secondary to putaminal stroke. METHODS: DBS leads were implanted in the GPi and Vim/Vop and each stimulation combination (GPi, Vim/Vop, and both) was tested for three months in a single patient. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Short-Form 36 (SF-36) were completed at the end of each trial period. RESULTS: Multitarget (GPi+Vim/Vop) stimulation was clinically the most effective treatment and resulted in the most improvement in function and quality of life. The patient's hemidystonia improved by 25% as measured by the BFMDRS during the multitarget stimulation trial period and at the 6-month follow-up. The patient's quality of life improved by 86% and 59% during the multitarget stimulation trial period and at the 6 month follow-up respectively. CONCLUSION: Multitarget thalamic and pallidal DBS proved to be the most effective therapy for this patient with secondary hemidystonia due to a putaminal stroke. A single-lead approach may not be sufficient in neuromodulating a highly disorganized motor network seen in hemidystonia. Multitarget DBS should be further explored in post-stroke dystonia and may offer improved outcome in other forms of secondary dystonia with limited response to GPi DBS.