Neurostimulation for the Treatment of Epilepsy: A Review of Current Surgical Interventions

Objectives: Epilepsy continues to provide challenges to clinicians, as a significant proportion of patients continue to suffer from seizures despite medical and surgical treatments. Neurostimulation has emerged as a new treatment modality that has the potential to improve quality of life and occasionally be curative for patients with medically refractory epilepsy who are not surgical candidates. In order to continue to advance the frontier of this field, it is imperative to have a firm grasp of the current body of knowledge. Methods: We performed a thorough review of the current literature regarding the three main modalities of vagus nerve stimulation, deep brain stimulation, and closed‐loop stimulation (responsive neurostimulator [RNS]) for the treatment of refractory epilepsy. For each of these forms of treatment, we discuss the current understanding of the underlying mechanism of action, patient selection, outcomes to date, and associated side effects or adverse reactions. We also provide an overview of related ongoing clinical trials. Results: A total of 189 sources from 1938 to 2012 pertaining to neuromodulation for the treatment of epilepsy were reviewed. Sources included review articles, clinical trials, case reports, conference proceedings, animal studies, and government data bases. Conclusions: This review shows us how neurostimulation provides us with yet another tool with which to treat the complex disease of medically refractory epilepsy.     

Economic evaluations of nonpharmacological treatments for drug-resistant epilepsy: A systematic review

This study was undertaken to systematically identify and critically appraise all published full economic evaluations assessing the cost-effectiveness of nonpharmacological interventions for patients with drug-resistant epilepsy. The Population, Intervention, Comparison, Outcome, Study criteria was used to design search strategies for the identification and selection of relevant studies. Literature search was performed using the MEDLINE (via PubMed), Embase, International Health Technology Assessment, National Institute for Health Research Economic Evaluation Database, and Cost-Effectiveness Analysis Registry databases to identify articles published between January 2000 and May 2023. Web of Science was additionally used to perform forward and backward referencing. Title, abstract, and full-text screening was performed by two independent researchers. The Consensus Health Economic Criteria (CHEC) checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 were applied for quality assessment. A total of 4470 studies were identified, of which 18 met our inclusion criteria. Twelve of the studies conducted model-based economic evaluation, and others were trial-based. Three studies showed that epilepsy surgery was cost-effective in adults, whereas this remained inconclusive for children (two positive, three negative). Three studies showed negative economic outcome for ketogenic diet in children. One of four studies showed positive results for self-management. For vagus nerve stimulation, one study showed positive results in adults and another one negative results in children. One recent study showed cost-effectiveness of responsive neurostimulation (RNS) in adults. Finally, one study showed promising but inconclusive results for deep brain stimulation (DBS). The mean scores for risk of bias assessment (based on CHEC) and for reporting quality (CHEERS 2022) were 95.8% and 80.5%, respectively. This review identified studies that assessed the cost-effectiveness of nonpharmacological treatments in both adults and children with drug-resistant epilepsy, suggesting that in adults, epilepsy surgery, vagus nerve stimulation, and RNS are cost-effective, and that DBS and self-management appear to be promising. In children, the cost-effectiveness of epilepsy surgery remains inconclusive. Finally, the use of ketogenic diet was shown not to be cost-effective. However, limited long-term data were available for newer interventions (i.e., ketogenic diet, DBS, and RNS).     

“Getting physical”: the management of neuropsychiatric disorders using novel physical treatments

Objective

To summarize and review the utility of physical interventions in the treatment of psychiatric disorders.

Methods

A systematic review of the literature pertaining to novel physical interventions, namely, transcranial magnetic stimulation, deep brain stimulation, vagus nerve stimulation, and neurosurgery, was conducted using MEDLINE, EMBASE, and PSYCHLIT. Bibliographies of papers were scrutinized for further relevant references along with literature known to the authors.

Results

Currently available physical interventions worldwide are reviewed with respect to efficacy, applications, and putative indications. Physical interventions have experienced a resurgence of interest for both the investigation of brain function and the treatment of neuropsychiatric disorders. The widespread availability of neuroimaging technology has advanced our understanding of brain function and allowed closer examination of the effects of physical treatments. Clinically, transcranial magnetic stimulation seems likely to have a role in the management of depression, and its use in other neuropsychiatric disorders appears promising. Following on from its success in the management of intractable epilepsy, vagus nerve stimulation is undergoing evaluation in the treatment of depression with some success in refractory cases. Deep brain stimulation has improved mood in patients with Parkinson’s disease and may also relieve symptoms of obsessive-compulsive disorder. Neurosurgery has re-invented itself by way of increased technical sophistication, and although further assessment of its efficacy and clinical utility is still needed, its widespread practice reflects its increasing acceptance as a viable treatment of last resort.

Conclusion

It is clear that physical treatments are here to stay and “getting physical” offers a useful addition to the neuropsychiatrist’s therapeutic armamentarium. However, like all new treatments these interventions need to remain under rigorous scientific scrutiny to determine accurately their immediate and long-term effects.     

Brain stimulation: a therapeutic approach for the treatment of neurological disorders

Brain stimulation has become one of the most acceptable therapeutic approaches in recent years and a powerful tool in the remedy against neurological diseases. Brain stimulation is achieved through the application of electric currents using non-invasive as well as invasive techniques. Recent technological advancements have evolved into the development of precise devices with capacity to produce well-controlled and effective brain stimulation. Currently, most used non-invasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In last decade, application of these brain stimulation techniques has not only exploded but also expanded to wide variety of neurological disorders. Therefore, in the current review, we will provide an overview of the potential of both non-invasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques in the treatment of such brain diseases.     

The Adjunct of Electric Neurostimulation to Rehabilitation Approaches in Upper Limb Stroke Rehabilitation: A Systematic Review With Network Meta-Analysis of Randomized Controlled Trials

ObjectiveThis review analyzed the current evidence and the potential for the application of electric neurostimulation such as transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS) in upper limb stroke rehabilitation.Materials and MethodsWe performed a systematic review of randomized controlled trials (RCTs) using network meta-analysis (NMA), searching the following data bases: PubMed, Web of Science, Cochrane, and Google Scholar, using specific keywords, from January 2010 to April 2021, and assessing the effects of “tDCS” or “VNS” combined with other therapies on upper limb motor function and activities of daily living (ADL) after stroke.ResultsWe included 38 RCTs with 1261 participants. Pairwise NMA showed transcutaneous VNS (tVNS) and anodal tDCS were effective in improving upper limb motor function (tVNS: mean difference [MD]: 5.50; 95% CI [0.67–11.67]; p < 0.05; anodal tDCS: MD: 5.23; 95% CI [2.45–8.01]; p < 0.05). tVNS and tDCS (anodal and cathodal) were also effective in improving ADL performance after stroke (tVNS: standard MD [SMD]: 0.96; 95% CI [0.15–2.06]; p < 0.05; anodal tDCS: SMD: 3.78; 95% CI [0.0–7.56]; p < 0.05; cathodal tDCS: SMD: 5.38; 95% CI [0.22–10.54]; p < 0.05). Surface under the cumulative ranking curve analysis revealed that tVNS is the best ranked treatment in improving upper limb motor function and performance in ADL after stroke. There was no difference in safety between VNS and its control interventions, measured by reported adverse events (VNS: risk ratio = 1.02 [95% CI = 0.48–2.17; I² = 0; p = 0.96]).ConclusionModerate- to high-quality evidence suggests that tVNS and anodal tDCS were effective in improving upper limb motor function in both acute/subacute and chronic stroke. In addition to tVNS and anodal tDCS, cathodal tDCS is also effective in improving ADL performance after stroke.     

Peripheral Neurostimulation for the Treatment of Refractory Cluster Headache,Long-Term Follow-Up: Case Report

Introduction: Cluster headache is a headache syndrome characterized by periodic episodes of intense headache with spontaneous remission. There are recent reports utilizing occipital nerve stimulation for the successful management of medically refractory cases of cluster headache. Methods: The case of an 18‐year‐old boy with chronic, refractory, recurrent cluster headaches is presented. He was treated surgically with combined occipital, supraorbital, and infraorbital nerve stimulation. Results: Prior to operation, the patient suffered three to four episodes of cluster headache per day, for four years. After implantation of occipital, supraorbital, and infraorbital nerve stimulators, the patient averages at most three to four headaches per month, at 36‐month follow‐up. Conclusion: Peripheral neurostimulation is safe and efficacious in the management of chronic, medically refractory cluster headache syndrome. The efficacy of treatment was found to be persistent after three years.     

Therapeutic potential of brain stimulation techniques in the treatment of mental,psychiatric, and cognitive disorders

Treatment for brain diseases has been disappointing because available medications have failed to produce clinical response across all the patients. Many patients either do not respond or show partial and inconsistent effect, and even in patients who respond to the medications have high relapse rates. Brain stimulation has been seen as an alternative and effective remedy. As a result, brain stimulation has become one of the most valuable therapeutic tools for combating against brain diseases. In last decade, studies with the application of brain stimulation techniques not only have grown exponentially but also have expanded to wide range of brain disorders. Brain stimulation involves passing electric currents into the cortical and subcortical area brain cells with the use of noninvasive as well as invasive methods to amend brain functions. Over time, technological advancements have evolved into the development of precise devices; however, at present, most used noninvasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In the current review, we will provide an overview of the potential of noninvasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques focusing on the treatment of mental, psychiatric, and cognitive disorders.     

FDA Perspectives on the Regulation of Neuromodulation Devices

The United States Food and Drug Administration (FDA) ensures that patients in the United States have access to safe and effective medical devices. The division of neurological and physical medicine devices reviews medical technologies that interface with the nervous system, including many neuromodulation devices. This article focuses on neuromodulation devices and addresses how to navigate the FDA's regulatory landscape to successfully bring devices to patients.     

Neuroanatomical correlates of therapeutic efficacy of low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression

Aims: Low‐frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment‐resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low‐frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment‐resistant depression. Methods: Twenty‐six patients with treatment‐resistant depression received five 60‐s 1‐Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with ^99mTc‐ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS). Results: Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula. Conclusion: The antidepressant effects of LFRS in treatment‐resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.     

Existing and emerging applications for the neuromodulation of nerve activity through targeted delivery of electric stimuli

Abstract

The effective treatment of many diseases requires the use of multiple treatment strategies among which neuromodulation is playing an increasingly important role. Neuromodulation devices that act to normalize or modulate nerve activity through the targeted delivery of electrical stimuli will be the focus of this review. These devices encompass deep brain stimulators, vagus nerve stimulators, spinal cord simulators and sacral nerve stimulators. Already neuromodulation has proven successful in the treatment of a broad range of conditions from Parkinson’s disease to chronic pain and urinary incontinence. Many of these approaches seek to exploit the activities of the autonomic nervous system, which influences organ function through the release of neurotransmitters and associated signalling cascades. This review will outline existing and emerging applications for each of these neuromodulation devices, proposed mechanisms of action and clinical studies evaluating both their safety and therapeutic efficacy.     

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially. Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability.     

Brain stimulation treatments in bipolar disorder: A review of the current literature

Objectives. Brain stimulation techniques are non-pharmacologic strategies which offer additional therapeutic options for treatment-resistant depression (TRD). The purpose of this paper is to review the current literature regarding the use of brain stimulation in resistant bipolar disorder (BD), with particular reference to hypomanic/manic symptoms. Methods. Keywords pertaining to the brain simulation techniques used in the treatment of depression (either unipolar or bipolar) along with their role in regard to hypomanic/manic symptoms were used to conduct an electronic search of the literature. Pertinent findings were identi?ed by the authors and reviewed. Results. Brain stimulation techniques represent a valid therapeutic option in TRD. They have been extensively studied in unipolar depression and, to a minor extent, in the depressive phase of BD, showing encouraging but often limited results. With exception of electroconvulsive therapy, the efficacy of brain stimulation in the treatment of manic symptoms of bipolar patients is still uncertain and needs to be fully evaluated. Conclusions. Brain stimulation in BD is derived from its use in unipolar depression. However, there are many important differences between these two disorders and more studies with a systematic approach need to be conducted on larger samples of bipolar patients with treatment-resistant characteristics.