Exploring the efficacy of deep brain stimulation in pediatric neurological disorders: a comprehensive review.

Based on the success of deep brain stimulation (DBS) in the treatment of adult disorders, it is reasonable to assume that the application of DBS in the pediatric population is an emerging area worthy of study. The purpose of this paper is to outline the current movement disorder indications for DBS in the pediatric population, and to describe areas of investigation, including possible medically refractory psychiatric indications. We performed a structured review of the English language literature from 1990 to 2011 related to studies of DBS in pediatrics using Medline and PubMed search results. Twenty-four reports of DBS in the pediatric population were found. Based on published data on the use of DBS for pediatric indications, there is a spectrum of clinical evidence for the use of DBS to treat different disorders. Dystonia, a disease associated with a low rate of remission and significant disability, is routinely treated with DBS and is currently the most promising pediatric application of DBS. We caution the application of DBS to conditions associated with a high remission rate later in adulthood, like obsessive-compulsive disorder and Tourette's syndrome. Moreover, epilepsy and obesity are currently being investigated as indications for DBS in the adult population; however, both are associated with significant morbidity in pediatrics. While currently dystonia is the most promising application of DBS in the pediatric population, multiple conditions currently being investigated in adults also afflict children and adolescents, and thus warrant further research.

Deep brain stimulation in the management of paediatric neuropsychiatric conditions: Current evidence and future directions.

In the context of drug-resistant epilepsy, deep brain stimulation (DBS) has received FDA approval. However, there have been reports of potential adverse effects, such as depression and memory impairment associated with DBS.This systematic review and meta-analysis aimed to investigate the impact of DBS on the quality of life (QoL), and seizure frequency of patients who had DRE, and assess its potential adverse events. The study followed PRISMA guidelines and thoroughly assessed databases, including Pubmed, Scopus, Embase, Web of Science, and the Cochrane Library, up to 31 July. Statistical analysis, fixed effect model analysis, performed by the Comprehensive Meta-analysis software (CMA) version 3.0. Additionally, Cochran's Q test was conducted to determine the statistical heterogeneity. The systematic review encompassed 54 studies, with 38 studies included in the subsequent meta-analysis. The total number of patients included in the studies was 999. The findings indicated a significant decrease in the mean seizure frequency of subjects following DBS (SMD: 0.609, 95% CI: 0.519 to 0.700, p-value < 0.001). Moreover, patients' QoL significantly improved after DBS (SMD: -0.442, 95% CI: -0.576 to -0.308, p-value < 0.001). The hippocampus displayed the most notable effect size among the different DBS targets. Subgroup analysis based on follow-up duration revealed increased DBS efficacy after two years. There are few reports of adverse events, such as insertional-related complications, infection, and neuropsychiatric complications, but the majority of these were temporary and non-fatal. DBS emerged as an effective and safe procedure for reducing seizure frequency and enhancing the quality of life in DRE patients, with minimal adverse events. Furthermore, the efficacy of DBS was observed to improve over time.

Deep brain and cortical stimulation for epilepsy.

Despite optimal medical treatment, including epilepsy surgery, many epilepsy patients have uncontrolled seizures. In the last decades, interest has grown in invasive intracranial neurostimulation as a treatment for these patients. Intracranial stimulation includes both deep brain stimulation (DBS) (stimulation through depth electrodes) and cortical stimulation (subdural electrodes). To assess the efficacy, safety and tolerability of deep brain and cortical stimulation for refractory epilepsy based on randomized controlled trials. We searched PubMed (6 August 2013), the Cochrane Epilepsy Group Specialized Register (31 August 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7 of 12) and reference lists of retrieved articles. We also contacted device manufacturers and other researchers in the field. No language restrictions were imposed. Randomized controlled trials (RCTs) comparing deep brain or cortical stimulation to sham stimulation, resective surgery or further treatment with antiepileptic drugs. Four review authors independently selected trials for inclusion. Two review authors independently extracted the relevant data and assessed trial quality and overall quality of evidence. The outcomes investigated were seizure freedom, responder rate, percentage seizure frequency reduction, adverse events, neuropsychological outcome and quality of life. If additional data were needed, the study investigators were contacted. Results were analysed and reported separately for different intracranial targets for reasons of clinical heterogeneity. Ten RCTs comparing one to three months of intracranial neurostimulation to sham stimulation were identified. One trial was on anterior thalamic DBS (n = 109; 109 treatment periods); two trials on centromedian thalamic DBS (n = 20; 40 treatment periods), but only one of the trials (n = 7; 14 treatment periods) reported sufficient information for inclusion in the quantitative meta-analysis; three trials on cerebellar stimulation (n = 22; 39 treatment periods); three trials on hippocampal DBS (n = 15; 21 treatment periods); and one trial on responsive ictal onset zone stimulation (n = 191; 191 treatment periods). Evidence of selective reporting was present in four trials and the possibility of a carryover effect complicating interpretation of the results could not be excluded in 4 cross-over trials without any washout period. Moderate-quality evidence could not demonstrate statistically or clinically significant changes in the proportion of patients who were seizure-free or experienced a 50% or greater reduction in seizure frequency (primary outcome measures) after 1 to 3 months of anterior thalamic DBS in (multi)focal epilepsy, responsive ictal onset zone stimulation in (multi)focal epilepsy patients and hippocampal DBS in (medial) temporal lobe epilepsy. However, a statistically significant reduction in seizure frequency was found for anterior thalamic DBS (-17.4% compared to sham stimulation; 95% confidence interval (CI) -32.1 to -1.0; high-quality evidence), responsive ictal onset zone stimulation (-24.9%; 95% CI -40.1 to 6.0; high-quality evidence) ) and hippocampal DBS (-28.1%; 95% CI -34.1 to -22.2; moderate-quality evidence). Both anterior thalamic DBS and responsive ictal onset zone stimulation do not have a clinically meaningful impact on quality life after three months of stimulation (high-quality evidence). Electrode implantation resulted in asymptomatic intracranial haemorrhage in 3% to 4% of the patients included in the two largest trials and 5% to 13% had soft tissue infections; no patient reported permanent symptomatic sequelae. Anterior thalamic DBS was associated with fewer epilepsy-associated injuries (7.4 versus 25.5%; P = 0.01) but higher rates of self-reported depression (14.8 versus 1.8%; P = 0.02) and subjective memory impairment (13.8 versus 1.8%; P = 0.03); there were no significant differences in formal neuropsychological testing results between the groups. Responsive ictal-onset zone stimulation was well tolerated with few side effects but SUDEP rate should be closely monitored in the future (4 per 340 [= 11.8 per 1000] patient-years; literature: 2.2-10 per 1000 patient-years). The limited number of patients preclude firm statements on safety and tolerability of hippocampal DBS. With regards to centromedian thalamic DBS and cerebellar stimulation, no statistically significant effects could be demonstrated but evidence is of only low to very low quality. Only short term RCTs on intracranial neurostimulation for epilepsy are available. Compared to sham stimulation, one to three months of anterior thalamic DBS ((multi)focal epilepsy), responsive ictal onset zone stimulation ((multi)focal epilepsy) and hippocampal DBS (temporal lobe epilepsy) moderately reduce seizure frequency in refractory epilepsy patients. Anterior thalamic DBS is associated with higher rates of self-reported depression and subjective memory impairment. SUDEP rates require careful monitoring in patients undergoing responsive ictal onset zone stimulation. There is insufficient evidence to make firm conclusive statements on the efficacy and safety of hippocampal DBS, centromedian thalamic DBS and cerebellar stimulation. There is a need for more, large and well-designed RCTs to validate and optimize the efficacy and safety of invasive intracranial neurostimulation treatments.

Efficacy of deep brain stimulation of the anterior-medial globus pallidus internus in tic and non-tic related symptomatology in refractory Tourette syndrome

Lay summary: This case report illustrates lack of clinical efficacy of deep brain stimulation (DBS) for control of tics in a case of mild Tourette syndrome (TS) with severe comorbid obsessive–compulsive disorder (OCD). The brain target for stimulation was the anterior limb internal capsule (ALIC). Objective: To investigate the effect of anterior limb of internal capsule/nucleus accumbens (ALIC-NA) DBS on mild motor and vocal tics in a Tourette syndrome (TS) patient with severe OCD. Background: The optimum target to address symptoms of TS with DBS remains unknown. Earlier lesional therapy utilized thalamic targets and also the ALIC for select cases which had been diagnosed with other psychiatric disorders. Evidence regarding the efficacy of DBS for the symptoms of TS may aid in better defining a brain target's suitability for use. We report efficacy data on ALIC-NA DBS in a patient with severe OCD and mild TS. Methods: A 33-year-old man underwent bilateral ALIC-NA DBS. One month following implantation, a post-operative CT scan was obtained to verify lead locations. Yale Global Tic Severity Scales (YGTSS) and modified Rush Videotape Rating scales (MRVRS) were obtained throughout the first 6 months, as well as careful clinical examinations by a specialized neurology and psychiatry team. The patient has been followed for 30 months. Results: YGTSS scores worsened by 17% during the first 6 months. MRVRS scores also worsened over 30 total months of follow-up. There was a lack of clinically significant tic reduction although subjectively the patient felt tics improved mildly. Conclusion: DBS in the ALIC-NA failed to effectively address mild vocal and motor tics in a patient with TS and severe comorbid OCD.

Tourette's syndrome (TS) is defined by 1 year of persistent motor and vocal tics. Often, the tics are refractory to conventional pharmacologic and psychobehavioral interventions. In these patients, deep brain stimulation (DBS) may be an appropriate intervention. This paper reviews different DBS targets in TS, discusses existing evidence on the efficacy of DBS in TS, highlights adverse effects of the procedure, discusses indications and patient selection as well as future directions for DBS in TS. A literature review searching PubMed database entries between 2000 and 2015. Search terms included "DBS in Tourette Syndrome", "Deep brain stimulation in Tourette syndrome," and "Surgical management of Tourette Syndrome." Though there are no universally accepted guidelines defining ideal DBS candidates for TS, age, tic severity, and treatment refractoriness are important factors to consider in patient selection. A variety of targets exist for DBS in TS, but thalamic targets and GPi are the most widely studied. Psychiatric side effects that are target specific should be monitored closely and it is possible that these adverse effects may be resolved with programing. Small randomized controlled trials support the efficacy of DBS in TS. DBS for TS is safe and feasible, but large multi-center clinical trials are needed to determine the ideal target and optimal location within a particular target.

Epilepsy is a chronic neurological disorder affecting millions of people around the world. Even though the majority of patients gain seizure control with antiseizure medications (ASMs), many subjects may have drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) is a promising alternative, showing effectiveness in reducing seizures for some patients. This systematic review and meta-analysis aim to evaluate DBS's efficacy in DRE. A comprehensive search in PubMed, CENTRAL, Medline, Ovid, and Scopus was performed up to August 31, 2024, using the terms 'Drug-resistant Epilepsy' AND 'Deep Brain Stimulation'. Two independent researchers screened titles, abstracts, and full texts. The data extracted included study details, sample size, age at surgery, seizure duration, follow-up duration, seizure reduction (SR), responder rate (RR), and adverse events. Quality assessment was conducted using the Risk of Bias 2 (ROB2) tool (https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials), and data analysis was performed using Jamovi software (https://www.jamovi.org). The search yielded 707 studies that were initially screened. Out of them, 29 articles were retrieved for full-text screening, and 5 randomized controlled trials (RCTs) were included in the review and meta-analysis. The meta-analysis showed that the pooled effect size for SR was 0.51 (95% CI, 0.35-0.68; P < 0.001), and the pooled effect size for RR was 0.54 (95% CI, 0.35-0.74; P < 0.001), demonstrating significant improvements in seizure control. The pooled effect size for adverse events was 0.21 (95% CI, 0.08-0.34; P = 0.001). The risk-of-bias assessment revealed a low risk of randomization for most studies. However, concerns were noted in areas such as deviations from the intended intervention and missing outcome data. In conclusion, DBS is a viable intervention for DRE, with significant reductions in seizure frequency and a favorable safety profile. However, the variability in efficacy and RRs across studies underscores the need for continued research to refine patient selection criteria, optimize stimulation parameters, and explore the differential effects of targeting various thalamic nuclei.

Gilles de la Tourette syndrome (GTS) is a severe neuropsychiatric disorder with childhood onset, characterized by disabling motor and vocal tics lasting for more than 1 year and associated with a wide range of psychiatric comorbidities. Pharmacological treatment is indicated for moderate to severe GTS patients. However, when GTS is refractory to conventional medical and behavioral treatments, deep brain stimulation (DBS) can be considered as a last resort therapeutic avenue. To evaluate the efficacy of DBS and its comorbidities in the largest pool of GTS patients to date. Our cohort study was based on 48 patients' refractory to conventional treatment who underwent DBS for GTS at Galeazzi Institute, Milan, Italy. An exhaustive preoperative and a follow-up battery of tests was performed including the Yale Global Tic Severity Rating Scale, the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Subjective Social Impairment on a 10-point Visual Analogue Scale tests. Eleven patients in whom the device was removed for inflammatory complications or for poor compliance were excluded from final analysis. Twenty-seven of the remaining 37 patients had a Yale Global Tic Severity Rating Scale score at the last follow-up that was less than 35. Of the 37 patients, in 29 cases (78%) a reduction of more than 50% of the Yale Global Tic Severity Rating Scale score was observed. The clinical efficacy of DBS in GTS is promising. Although DBS is associated with risks, as is any surgical intervention, DBS should be considered as a last resort therapeutic option in carefully selected GTS patients.

Efficacy of deep brain stimulation for Tourette syndrome and its comorbidities: A meta-analysis

Following the established application of deep brain stimulation (DBS) in the treatment of movement disorders, new non-neurological indications have emerged, such as for obsessive-compulsive disorders, major depressive disorder, dementia, Gilles de la Tourette Syndrome, anorexia nervosa, and addictions. As DBS is a network modulation surgical treatment, the development of DBS for both neurological and psychiatric disorders has been partly driven by advances in neuroimaging, which has helped explain the brain networks implicated. Advances in magnetic resonance imaging connectivity and electrophysiology have led to the development of the concept of modulating widely distributed, complex brain networks. Moreover, the increasing number of targets for treating psychiatric disorders have indicated that there may be a convergence of the effect of stimulating different targets for the same disorder, and the effect of stimulating the same target for different disorders. The aim of this paper is to review the imaging studies of DBS for psychiatric disorders. Imaging, and particularly connectivity analysis, offers exceptional opportunities to better understand and even predict the clinical outcomes of DBS, especially where there is a lack of objective biomarkers that are essential to properly guide DBS pre- and post-operatively. In future, imaging might also prove useful to individualize DBS treatment. Finally, one of the most important aspects of imaging in DBS is that it allows us to better understand the brain through observing the changes of the functional connectome under neuromodulation, which may in turn help explain the mechanisms of action of DBS that remain elusive.

Despite the application of deep brain stimulation (DBS) as an efficient treatment modality for psychiatric disorders, such as obsessive-compulsive disorder (OCD), Gilles de la Tourette Syndrome (GTS), and treatment refractory major depression (TRD), few patients are operated or included in clinical trials, often for fear of the potential risks of an approach deemed too dangerous. To assess the surgical risks, we conducted an analysis of publications on DBS for psychiatric disorders. A PubMed search was conducted on reports on DBS for OCD, GTS, and TRD. Forty-nine articles were included. Only reports on complications related to DBS were selected and analyzed. Two hundred seventy-two patients with a mean follow-up of 22 months were included in our analysis. Surgical mortality was nil. The overall mortality was 1.1 %: two suicides were unrelated to DBS and one death was reported to be unlikely due to DBS. The majority of complications were transient and related to stimulation. Long-term morbidity occurred in 16.5 % of cases. Three patients had permanent neurological complications due to intracerebral hemorrhage (2.2 %). Complications reported in DBS for psychiatric diseases appear to be similar to those reported for DBS in movement disorders. But class I evidence is lacking. Our analysis was based mainly on small non-randomized studies. A significant number of patients (approximately 150 patients) who were treated with DBS for psychiatric diseases had to be excluded from our analysis as no data on complications was available. The exact prevalence of complications of DBS in psychiatric diseases could not be established. DBS for psychiatric diseases is promising, but remains an experimental technique in need of further evaluation. A close surveillance of patients undergoing DBS for psychiatric diseases is mandatory.

Introduction: Deep brain stimulation (DBS) is an effective therapy for resting tremor in Parkinson's disease (PD). However, quick and objective biomarkers for quantifying the efficacy of DBS intraoperatively are lacking. Therefore, we aimed to study how DBS modulates the intraoperative neuromuscular pattern of resting tremor in PD patients and to find predictive surface electromyography (sEMG) biomarkers for quantifying the intraoperative efficacy of DBS.Methods: Intraoperative sEMG of 39 PD patients with resting tremor was measured with the DBS on and off, respectively, during the intraoperative DBS testing stage. Twelve signal features (time and frequency domains) were extracted from the intraoperative sEMG data. These sEMG features were associated with the clinical outcome to evaluate the efficacy of intraoperative DBS. Also, an sEMG-based prediction model was established to predict the clinical improvement rate (IR) of resting tremor with DBS therapy.Results: A typical resting tremor with a peak frequency of 4.93 ± 0.98 Hz (mean ± SD) was measured. Compared to the baseline, DBS modulated significant neuromuscular pattern changes in most features except for the peak frequency, by decreasing the motor unit firing rate, amplitude, or power and by changing the regularity pattern. Three sEMG features were detected with significant associations with the clinical improvement rate (IR) of the tremor scale: peak frequency power (R = 0.37, p = 0.03), weighted root mean square (R = 0.42, p = 0.01), and modified mean amplitude power (R = 0.48, p = 0.003). These were adopted to train a Gaussian process regression model with a leave-one-out cross-validation procedure. The prediction values from the trained sEMG prediction model (1,000 permutations, p = 0.003) showed a good correlation (r = 0.47, p = 0.0043) with the true IR of the tremor scale.Conclusion: DBS acutely modulated the intraoperative resting tremor, mainly by suppressing the amplitude and motor unit firing rate and by changing the regularity pattern, but not by modifying the frequency pattern. Three features showed strong robustness and could be used as quick intraoperative biomarkers to quantify and predict the efficacy of DBS in PD patients with resting tremor.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience