Outcomes of Unilateral Pallidotomy in Focal and Hemidystonia Cases: A Single-Blind Cohort Study.

BACKGROUND: The role of deep brain stimulation in the treatment of dystonia has been widely documented. However, there is limited literature on the outcome of lesioning surgery in unilateral dystonia. OBJECTIVE: We restrospectively reviewed our cases of focal and hemidystonia undergoing unilateral Pallidotomy at our institute to evaluate the short-term and long-term outcome. METHODS: Patients who underwent radiofrequency lesioning of GPi for unilateral dystonia between 1999 and 2019 were retrospectively reviewed. All patients were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Dystonia Disability Scale (DDS) preoperatively at the short term follow-up (<1 year) and at long-term follow-up (2-7.5 years). Video recordings performed at these time points were independently reviewed by a blinded movement disorders specialist. RESULTS: Eleven patients were included for analysis. The preoperative, short-term, and long-term follow-up motor BFMDRS and DDS scores were 15.5 (IQR [interquartile range]: 10.5, 23.75) and 10.5 (IQR: 6.0, 14.5); 3.0 (IQR: 1.0, 6.0, P = 0.02) and 3.0 (IQR: 3.0, 8.0, P = 0.016); and 14.25 (IQR: 4.0, 20.0, P = 0.20) and 10.5 (IQR: 2.0, 15.0, P = 0.71) respectively. For observers B, the BFMDRS scores at the same time points were 19 (IQR: 12.5, 27.0), 7.5 (IQR: 6.0, 15.0, P = 0.002), and 21 (IQR: 7.0, 22.0, P = 0.65) respectively. The improvement was statistically significant for all observations at short-term follow-up but not at long-term follow-up. CONCLUSION: Pallidotomy is effective for hemidystonia or focal dystonia in the short term. Continued benefit was seen in the longer term in some patients, whereas others worsened. Larger studies may be able to explain this in future.

Practice Trends of Neuromodulation Therapies for Pain and Spasticity in India.

BACKGROUND: Neuromodulation has been successfully used globally to address severe refractory chronic pain for over five decades. Compared to the wide acceptance that it enjoys in United States and Europe, it is fairly underutilized in Asia, including India. OBJECTIVES: We conducted the first systematic nationwide survey to provide an overview of neuromodulation in the past 20 years to investigate the practice trends for severe refractory chronic pain and barriers for the uptake of neuromodulation therapies for pain in India. DESIGN: A 20-point detailed questionnaire survey was sent out for online completion in August 2020 to practitioners in India involved in interventions for pain. The survey was completed by 112 practitioners (10% return rate). The response data collected were analyzed, tabulated, and presented as percentages. RESULTS: The average duration of pain practice in India for the majority of respondents was less than a decade. About 70% of practitioners expressed that they manage severe refractory pain without neuromodulation. This survey confirms that neuromodulation is grossly underutilized for pain, comprising only 10% of total neuromodulation implants performed per annum in India. The most common indications were neuropathic pain (45%) and failed back surgery syndrome (42%). The respondents expressed the main barriers to be related to the cost (85%), lack of awareness (68%), and lack of good training (59%). More than 50% of respondents also expressed difficulty of access to neuromodulation therapies for pain and acceptance by patients. CONCLUSION: The younger generation of pain practitioners in India is becoming more aware and convinced about the role of neuromodulation to alleviate severe pain and suffering. An all-round approach combining improved training, awareness at various levels, more flexible options of newer technology and reimbursement approval can positively influence its use. This can be achieved with the collective efforts of physicians, insurers, industry, and focused academic activities of clinical societies.

Deep brain stimulation for extreme behaviors associated with autism spectrum disorder converges on a common pathway: a systematic review and connectomic analysis.

OBJECTIVE: Individuals with autism spectrum disorder (ASD) may display extreme behaviors such as self-injury or aggression that often become refractory to psychopharmacology or behavioral intervention. Deep brain stimulation (DBS) is a surgical alternative that modulates brain circuits that have yet to be clearly elucidated. In the current study the authors performed a connectomic analysis to identify brain circuitry engaged by DBS for extreme behaviors associated with ASD. METHODS: A systematic review was performed to identify prior reports of DBS as a treatment for extreme behaviors in patients with ASD. Individual patients' perioperative imaging was collected from corresponding authors. DBS electrode localization and volume of tissue activated modeling were performed. Volumes of tissue activated were used as seed points in high-resolution normative functional and structural imaging templates. The resulting individual functional and structural connectivity maps were pooled to identify networks and pathways that are commonly engaged by all targets. RESULTS: Nine patients with ASD who were receiving DBS for symptoms of aggression or self-injurious behavior were identified. All patients had some clinical improvement with DBS. Connectomic analysis of 8 patients (from the systematic review and unpublished clinical data) demonstrated a common anatomical area of shared circuitry within the anterior limb of the internal capsule. Functional analysis of 4 patients identified a common network of distant brain areas including the amygdala, insula, and anterior cingulate engaged by DBS. CONCLUSIONS: This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD. Using network mapping, the authors identified key circuitry common to DBS targets.

Surgical and Hardware Complications of Deep Brain Stimulation-A Single Surgeon Experience of 519 Cases Over 20 Years.

OBJECTIVE: Deep brain stimulation (DBS) surgery has its own set of risks and complications. This study from a single center and a single surgeon analyzes various risk factors for complications and tries to establish if there is a learning curve effect in minimizing the complications. MATERIALS AND METHODS: A retrospective analysis of 519 patients (1024 leads) who underwent DBS surgery and 232 patients who underwent implantable pulse generator replacement (IPG), by a single surgeon, between the years 1999 and 2019 was performed. Perioperative and hardware related complications were evaluated. RESULTS: The follow-up period ranged from six months to 20 years. Surgery-related complications occurred in 46 (8.9%) cases which included confusion in 31 (5.98%), intracerebral hemorrhage in 7 (1.3%), vasovagal attack in 3 (0.58%), respiratory distress in 2 (0.38%), postoperative aggressiveness in 1 (0.19%), and blepharospasm in 2 (0.38%) patients. Complications related to the DBS hardware were found in 35 cases, including erosion and infection in 22 (2.95%), inaccurate lead placement or migration in 6 (0.6%) lead fracture/extension wire failure in 2 (0.26%), IPG malfunction in 2 (0.26%), and hardware discomfort in 3 (0.4%) cases. In three patients, one lead was repositioned. In cases of infection, 87% of patients had either partial or complete removal of hardware. There was no mortality. The complications were analyzed for every 100 DBS procedures. There was a significant drop in the percentage of complications in from 23% in the first 100 cases to 7% in the last 100 cases (p < 0.0001). CONCLUSION: Confusion remains the most frequent operative and perioperative complication. Erosion and infection of the surgical site represents the most frequent hardware complication. DBS surgery is safe and the complication rates are acceptably low. The complication rate also decreases with cumulative years of experience, demonstrating a learning curve effect.

Radiofrequency Lesioning for Movement and Psychiatric Disorders-Experience of 107 Cases.

BACKGROUND: Radiofrequency lesioning (RFL) though used since the 1950s, had been replaced by DBS in the 1990s. The availability of magnetic resonance-guided focused ultrasound for lesioning has renewed the interest in RFL. OBJECTIVE: This paper analysis RFL in contemporary Functional Neurosurgery for various indications and its outcome. Complication rates of RFL are compared with the same author's experience of DBS. METHODS: One hundred and seven patients underwent RFL between 1998 and 2019. Indications included Parkinson's Disease (PD), tremors, dystonia, and obsessive-compulsive disorders (OCD). The surgeries performed include thalamotomy (29), pallidotomy (49), subthalamotomy (23), and anterior capsulotomy/nucleus accumbens lesioning (6). Appropriate rating scales were used for preoperative and postoperative evaluations. RESULTS: There was a 25% recurrence rate of tremors for PD after thalamotomy. Writer's cramp rating scale improved from a mean of 10.54-1.6 in task specific dystonia (TSD) patients, after thalamotomy. In PD patients, after pallidotomy, contralateral motor Unified Parkinson's Disease Rating Scale (UPDRS) and dyskinesia scores, improved by 41 and 57%, respectively, at 1-year. Burke-Fahn-Marsden Dystonia Rating Scale in hemidystonia patients improved from 18.04 to 6.91, at 1-year. There was 32 and 31% improvement in total and motor UPDRS, respectively, in the subthalamotomy patients, at 2-year. All patients of OCD were in remission. There were three deaths in the pallidotomy group. Postoperative, dysarthria, confusion, hemiparesis, dyskinesia, and paraesthesia occurred in 12 patients, of which, 7 were transient. CONCLUSION: RFL is a useful option in a select group of patients with tremors and dystonia. It is our preferred treatment option for TSD and OCD.

Deep Brain Stimulation for Parkinson's Disease: Currents Status and Emerging Concepts.

The clinical application of DBS has become manifold and there has been a tremendous growth in DBS technology in the last few decades making it safer and user friendly. The earlier concept of its delayed application in motor fluctuations of Parkinson's disease has been replaced by Class-I evidence of EARLY-STIM trial in 2013, leading to its FDA approval to be used in early-stage despite criticism. Various studies have provided evidence of beneficial effects of bilateral STN-DBS on both motor as well as nonmotor symptoms and different new targets such as the pedunculopontine nucleus, posterior subthalamic area or caudal zona incerta, centromedian-parafascicular complex, and substantia nigra pars reticulata have now become a new area of interest in addition to the subthalamic nucleus and globus pallidus internus for the alleviation of both motor and nonmotor symptoms of Parkinson's disease. New data has confirmed that the DBS is clinically as effective and safe in elderly patients as it is in younger ones. Technological advances like current steering, directional leads, and closed-loop DBS are directed towards reducing the stimulation-induced adverse effects and preservation of the battery life for a longer period. Results of the long-term efficacy of DBS on Parkinson's disease are now available. These have shown that as the motor benefit continues, the clinical progression of Parkinson's disease also continues. We plan to discuss all these in this paper.

An International Survey of Deep Brain Stimulation Utilization in Asia and Oceania: The DBS Think Tank East.

Introduction: To evaluate the current utilization and challenges in fully implementing the use of deep brain stimulation (DBS) treatment in Asia and Oceania. Methods: We conducted a medical literature search to identify DBS research performed by investigators with a primary affiliation in Asian and Oceania countries between March 1, 2013, and March 1, 2019, followed by an international survey-based study. Additionally, we obtained added information regarding the DBS challenges and opportunities from the technology/industry perspective within China and Japan. We also described the current situation of DBS in India. Results: Most publications (390/494; 78.95%) in the English language originated from East Asia. In West Asia, Turkey, Israel, and Iran accounted for most DBS publications. We found no publications from the remaining 35 Asian countries. Lack of community referrals to tertiary centers was identified as the most common limitation for the widespread use of DBS in Asia (68.97%). In China, despite an increasing number of centers performing DBS surgeries, most of them accomplished less than 10 cases per year. In contrast, the number of DBS cases in Japan has been decreasing. Centers offering DBS surgeries as well as corresponding fellowship training in India are limited. Conclusion: Appropriate referrals, access, infrastructure, and the presence of full multidisciplinary DBS teams are common limitations of DBS in Asia. Most centers in China, Japan, and India performed less than 10 cases per year and a future study is expected to address the impact on quality in centers performing such few cases.

Nucleus Accumbens Deep Brain Stimulation for Obsessive-Compulsive Disorder and Aggression in an Autistic Patient: A Case Report and Hypothesis of the Role of Nucleus Accumbens in Autism and Comorbid Symptoms.

BACKGROUND: Autism spectrum disorder represents a set of developmental disorders characterized by lack of social interaction and verbal and nonverbal communication in the first 3 years of life. It is also associated with several comorbidities, including epilepsy, aggression, self-mutilating behavior, and obsessive-compulsive behavior. In some cases, obsessive-compulsive disorder (OCD) develops. The nucleus accumbens (NAc) plays a key role in reward circuitry and is involved in the control of OCD and aggression. CASE DESCRIPTION: A 42-year-old woman with autism was offered NAc deep brain stimulation for her comorbidities of OCD and aggression. The NAc was targeted using standard stereotactic methods, and postoperative scans confirmed the position of the active electrode to be within the NAc. The patient experienced significant symptom relief. At 1-year follow-up, the Yale-Brown Obsessive Compulsive Scale score for OCD, excluding items 1-5 of the scale, improved from 19 to 5. Hamilton Depression Scale and Hamilton Anxiety Scale scores similarly improved from 20 to 15 and from 30 to 18, respectively. Social Communication Questionnaire Current version for autism score improved from 26 to 16. Subscores for reciprocal social interactionimproved from 13 to 8; for communication improved from 5 to 4; and for restricted, repetitive, and stereotyped patterns of behavior improved from 6 to 3. CONCLUSIONS: This case report illustrated the role of the NAc in OCD and aggression in an autistic patient. We discussed the role of the NAc as a target to explain the outcome of this case.

Indian guidelines on neurosurgical interventions in psychiatric disorders.

Neurosurgery for psychiatric disorders (NPD) has been practiced for >80 years. However, the interests have waxed and waned, from 1000s of surgeries in 1940-1950s to handful of surgery in 60-80s. This changed with the application of deep brain stimulation surgery, a surgery, considered to be "reversible" there has been a resurgence in interest. The Indian society for stereotactic and functional neurosurgery (ISSFN) and the world society for stereotactic and functional neurosurgery took the note of the past experiences and decided to form the guidelines for NPD. In 2011, an international task force was formed to develop the guidelines, which got published in 2013. In 2018, eminent psychiatrists from India, functional neurosurgeon representing The Neuromodulation Society and ISSFN came-together to deliberate on the current status, need, and legal aspects of NPD. In May 2018, Mental Health Act also came in to force in India, which had laid down the requirements to be fulfilled for NPD. In light of this after taking inputs from all stakeholders and review of the literature, the group has proposed the guidelines for NPD that can help to steer these surgery and its progress in India.

Deep brain stimulation of anteromedial globus pallidus internus for severe Tourette syndrome.

Tourette syndrome (TS) is a complex disorder characterized by tics and is associated with behavioral problems. Although its intensity decreases in adolescence and adult life, in some cases it continues to remain severe and refractory to medical treatment. Deep brain stimulation has been offered as a treatment option in such cases. We report two cases of TS treated with of anteromedial globus pallidum internus. Both the cases had good postoperative control of tics and associated obsessive-compulsive behavior.

Expanding indications for deep brain stimulation.

It has been three decades since the first application of deep brain stimulation (DBS) for tremors was described by Benabid. Over the years, the indications for the performance of DBS have been expanding. There are now more than 1,50,000 patients around the world who have undergone DBS for various disorders. The main appeal of DBS is in its reversibility and titratability. Though the initial interest in DBS was for pain, the main indications for DBS have been movement disorders. Despite its wide appeal and "perceived" advantage, United States Food and Drug Administration, the nodal agency for approving therapies, has been cautious and guarded in providing approvals. Only two indications, i.e., Parkinson's disease and tremors, have been approved; the two other indications, i.e., dystonia and obsessive compulsive disorder (OCD), have been granted exemption under the humanitarian device usage. However, the European community has been more liberal and several of these indications have CE (Conformite Europeene) approval. Most of them will be reviewed in this article. There have been numerous indications for which DBS has been applied, which in turn has helped to change the lives of several patients. Unfortunately, due to the paucity of the number of procedures performed and the inherent difficulty in conducting "surgical" double blind randomized trials, Class 1 or Class 2 evidence for several of these indications is lacking. Hence, it is advisable that one does not embark on using each and any target for each and any indication without having the understanding or the team backup. It is cautionary that most of these therapies should be conducted in an institutional setting with an ethics and scientific committee backup and ably assisted by an experienced team.

Surgical Interventions for Task-specific Dystonia (Writer's Dystonia).

OBJECTIVES: Writer's cramp is a focal dystonia producing abnormal postures during selective motor activities. Thalamotomy or globus pallidus internus deep brain stimulation (GPi DBS) has been used as a surgical treatment in patients not responding to medical treatment. MATERIALS AND METHODS: Eight patients (all men, age 16-47 years) with refractory focal hand dystonia underwent either ventrooralis (Vo) thalamotomy (seven patients) or GPi DBS (one patient) using stereotactic techniques. Preoperative video recordings, Writing movment score for dystonic posture and latency of dystonia (WMS), and symptom severity scores (SSSs) were evaluated at baseline and latest follow-up ranging from 1 to 4 years. RESULTS: All patients had difficulty in performing their most common tasks. The duration of symptoms ranged from 6 months to 12 years. All patients obtained immediate postoperative relief from the dystonic symptoms, and the effect was sustained during the follow-up period. The WMS (range 0-28) improved from a mean of 14.5 before surgery to 2, whereas the SSS (maximum 43 and minimum 10) improved from a mean of 15.3 before surgery to 2 at the last follow-up. There were no surgical complications, morbidity, or mortality. CONCLUSION: Vo thalamotomy or GPi DBS offers successful symptom relief in patients with task-specific dystonia.

Bilateral pedunculopontine nucleus stimulation for progressive supranuclear palsy.

The pedunculopontine nucleus (PPN) is a potential target for gait disorders. We report 4 cases of bilateral PPN stimulation in progressive supranuclear palsy (PSP) patients with short-term (6 months) and long-term (18 months) follow-ups. Patients with PSP who had gait disturbances, but were able to walk with or without assistance, were selected. The patients' median age was 64 years and the disease duration 3 years. Bilateral PPN deep brain stimulation (DBS) was performed. The pacemaker was programmed using a bipolar mode and lower frequencies (20-45 Hz). The PSP rating scores (PSPRS) and their gait subscores (No. 25, 26, 27 and 28) along with PSP staging scores were used as primary end points. The total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS III and the 39-item Parkinson's Disease Questionnaire were considered as secondary end points. Video recordings of the gaits were performed before surgery and at the 6- and 18-month follow-ups. These were retrospectively reviewed by a blinded neurologist for the primary end points. At the 6- and 18-month follow-ups, the median change in PSPRS was from 33 (baseline) to 37.5 and 47, respectively. Similarly, the PSP staging changed from 3 to 2.5 and 3.5, item 25 from 1.5 to 2 and 3.5, item 26 from 2.5 to 2 and 3.5, item 27 from 3.5 to 3 and 3.5 and item 28 from 1.5 to 1.5 and 3. Two patients in the study with the PSP-parkinsonism phenotype experienced improvement in their gait until the last follow-up. Bilateral PPN DBS can be safely performed in PSP patients despite mid-brain atrophy.

Deep brain stimulation improves quality of life in pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is an uncommon extrapyramidal movement disorder characterized by the progressive incapacitating dystonia. Medical management is often incapable of reversing the dystonic symptoms. In recent years, stereotactic procedure like deep brain stimulation has been found effective in resolving the disabling dystonia and improving the quality of life. There are few cases in the world literature highlighting the usefulness of this technique. We report a case of 10-year-old girl who underwent bilateral Globus pallidus internus stimulation for PKAN.

Anterior capsulotomy for refractory OCD: First case as per the core group guidelines.

Obsessive-compulsive disorder (OCD) is a psychiatric disease characterized by anxiety-provoking thoughts (obsessions) leading to repeated, time-consuming behaviors (compulsions) that may or may not provide temporary relief. With an approximate prevalence of 2-3% of the general population and 0.6% in the Indian population, OCD is a debilitating disorder that can significantly affect nearly every aspect of a patient's life, and in some cases, lead to suicide.

Long-term surgical and hardware-related complications of deep brain stimulation.

OBJECTIVE: To evaluate the incidence of surgical and hardware-associated complications of deep brain stimulation (DBS) for a range of movement disorders. METHODS: The study design is a retrospective analysis and review of surgical and hardware complications of DBS performed by a single surgeon from 1999 to 2009. A total of 153 cases of DBS (298 electrodes) for various movement disorders and a minimum follow-up of 1 year have been included. Two patients could not be implanted. A further 54 patients who underwent change of the implantable pulse generator (IPG) have been included for analysis of hardware-related complications. RESULTS: The mean follow-up was 64 ± 36.15 (range = 12-129) months for the DBS group. Twenty-four (15.6%) patients developed complications. Confusion occurred in 3.9%, vasovagal attack in 1.9%, lead migration/misplaced lead in 2.5%, erosion and infection in 4.5% and IPG malfunction occurred in 1.4% of the patients. When calculated with respect to the number of electrodes and IPG replacements, the complication rate was lower (11.9%). Three patients had their system explanted, two of them being patients with dystonia who had inadvertently damaged their operative site. CONCLUSION: DBS surgery is a relatively safe surgery, with most of the complications being minor, without long-term morbidity. The complication rate in elderly (age ≥65 years) is comparable to that in younger patients. However, confusion is more frequent in this age group, and patients and relatives can be prepared to accept this as a transient morbidity.