Invasive Neuromodulation Research Articles

Strength of activation and temporal dynamics of bioluminescent-optogenetics in response to systemic injections of the luciferin

BioLuminescent OptoGenetics (“BL-OG”) is a chemogenetic method that can evoke optogenetic reactions in the brain non-invasively. In BL-OG, an enzyme that catalyzes a light producing reaction (i.e., a luciferase) is tethered to an optogenetic element that is activated in response to bioluminescent light. Bioluminescence is generated by injecting a chemical substrate (luciferin, e.g., h-Coelenterazine; h-CTZ) that is catalyzed by the luciferase. By directly injecting the luciferin into the brain, we show that bioluminescent light is proportional to spiking activity, and this relationship scales as a function of luciferin dosage. Here, we build on these previous observations by characterizing the temporal dynamics and dose response curves of bioluminescence generated by luminopsins (LMOs), a proxy of BL-OG effects, to intravenous (IV) injections of the luciferin. We imaged bioluminescence through a thinned skull of mice running on a wheel, while delivering h-CTZ via the tail vein with different dosage concentrations and injection rates. The data reveal a systematic relationship between strength of bioluminescence and h-CTZ dosage, with higher concentration generating stronger bioluminescence. We also found that bioluminescent activity occurs rapidly (< 60 s after IV injection) regardless of concentration dosage. However, as expected, the onset time of bioluminescence is delayed as the injection rate decreases. Notably, the strength and time decay of bioluminescence is invariant to the injection rate of h-CTZ. Taken together, these data show that BL-OG effects are highly consistent across injection parameters of h-CTZ, highlighting the reliability of BL-OG as a minimally invasive neuromodulation method.

Neuromodulation for Neuropathic Pain Syndromes

ABSTRACT OBJECTIVE This article reviews the principles, applications, and emerging trends of neuromodulation as a therapeutic approach for managing painful neuropathic diseases. By parsing evidence for possible mechanisms of action and clinical trial outcomes for various diseases, this article focuses on five common therapy modalities: cutaneous, peripheral nerve, spinal cord, and brain stimulation, and intrathecal drug delivery. LATEST DEVELOPMENTS Recent advances in both invasive and noninvasive neuromodulation for pain have introduced personalized and closed-loop techniques, integrating real-time feedback mechanisms and combining therapies to improve physical and psychosocial function. Novel stimulation waveforms may influence distinct neural tissues to rectify pathologic pain signaling. ESSENTIAL POINTS With appropriate patient selection, peripheral nerve stimulation or epidural stimulation of the spinal cord can provide enduring relief for a variety of chronic pain syndromes. Newer technology using high frequencies, unique waveforms, or closed-loop stimulation may have selective advantages, but our current understanding of therapy mechanisms is very poor. For certain diagnoses and patients who meet clinical criteria, neuromodulation can provide profound, long-lasting relief that significantly improves quality of life. While many therapies are supported by data from large clinical trials, there is a risk of bias as most clinical studies were funded by device manufacturers or insurance companies, which increases the importance of real-world data analysis. Emerging methods like invasive or noninvasive brain stimulation may help us dissect basic mechanisms of pain processing and hold promise for personalized therapies for refractory pain syndromes. Finally, intrathecal delivery of drugs directly to segments of the spinal cord can also modify pain signaling to provide therapy for severe pain syndromes.

Spine Pain.

Spine pain is one of the most common presenting concerns in health care settings. This article reviews clinical strategies for evaluating and managing patients with spine pain. Minimally invasive interventional procedures, virtual reality, predictive analytics, neuromodulation, and other evolving technologies are significantly impacting the management of spine pain. Advances in modern pain science have also led to effective skills and treatment strategies, including patient interviews and queries for insight regarding pain, education, and cognitive restructuring, and adjusting the timing of examination (after reeducation) and examination techniques to encourage the experience of movement in the absence of assumed tissue damage. An evolving understanding of the influence of patient-centric thoughts, framing, emotional status, and cognitive restructuring's influence on the brain's response to perceived threat are important aspects of spine pain management. The correlation of clinical presentations with structural abnormalities is necessary but insufficient to evaluate and manage spine pain. Modern pain science acknowledges pain as a subjective experience but recognizes a critical distinction between tissue damage, nociception, and the experience of pain. What and how we communicate with patients, as well as evolving neuromodulation technologies, augment conventional approaches.

Transient alteration of Awareness triggered by direct electrical stimulation of the brain

BackgroundAwareness is a state of consciousness that enables a subject to interact with the environment. Transient alteration of awareness (AA) is a disabling sign of many types of epileptic seizures. The brain mechanisms of awareness and its alteration are not well known. Objective/HypothesisTransient and isolated AA induced by electrical brain stimulation during a stereoelectroencephalography (SEEG) recording represents an ideal model for studying the associated modifications of functional connectivity and locating the hubs of awareness networks. MethodsWe investigated the SEEG signals-based brain functional connectivity (FC) changes vs background occurring during AA triggered by three thalamic and two insular stimulations in three patients explored by SEEG in the frame of presurgical evaluation for focal drug-resistant epilepsy. The results were compared to the stimulations of the same sites that did not induce clinical changes (negative stimulations). ResultsWe observed decreased node strength in the pulvinar, insula, and parietal associative cortices during the thalamic and insular stimulations that induced AA. The link strengths characterizing functional coupling between the thalamus and the insular, prefrontal, temporal, or parietal associative cortices were also decreased. In contrast, there was an increased synchronization between the precuneus and the temporal lateral cortex. These FC changes were absent during the negative stimulations. ConclusionOur study highlights the role of the pulvinar, insular, and parietal hubs in maintaining the awareness networks and paves the way for invasive or non-invasive neuromodulation protocols to reduce AA manifestations during epileptic seizures.

Invasive Neuromodulation: Present and Future

Invasive Neuromodulation: Present and Future

Cell‐Anchored Lead‐Free Piezoelectric KNN NPs Resisting Washout for Low‐Intensity Ultrasound Driven Neuromodulation

AbstractPiezoelectric nanomaterials for wireless neuromodulation is a promising alternative to traditional electrical stimulation. However, the low‐avidity between piezoelectric nanomaterials and cellular membranes leads to low efficiency of electrical signal transmission, which requires high‐intensity thresholds of ultrasound stimulation (US). Here, lead‐free piezoelectric (K,Na)NbO3 (KNN) nanoparticles (NPs) with cholesterol coating (KNNC) are presented, in which Cholesterol can be accommodated in the membrane and make them append on the plasma membrane. Compared to non‐modified nanoparticles, cell‐anchored KNNC NPs highly resist convective washout owing to high affinity of cholesterol to biological membranes, which enables highly efficient wireless electrical stimulation to activate cell impulses under low‐intensity ultrasound. Meanwhile, after perfusion washing, the KNNC NPs distributed around the cells are washed away, while part of KNNC NPs remain on the surface of cell membrane still can induce significant Ca2+ influx under US, similar to the group without washing, indicating the KNNC NPs appended on the cell play a major role in wireless electrical stimulation. Furthermore, the highly efficient electrical transmission of KNNC enables neural differentiation of stem cells in regulating synaptic plasticity by modulating Ca2+ influx, demonstrating that KNNC NPs offer a perspective toward minimally invasive wireless neuromodulation therapies for neurological diseases.

Interventional neurorehabilitation for glioma patients: A systematic review

Abstract Harnessing the neuroplastic potential of the human brain is being increasingly recognized as an important neuro-oncological paradigm to facilitate safe resection of brain tumors while preserving neurological function and quality of life. Interventional neurorehabilitation, employing both invasive and noninvasive neuromodulation techniques, represents an important emerging therapeutic strategy to induce or enhance neural plasticity to promote functional recovery in brain tumor patients. This study aimed to conduct a comprehensive review of interventional neurorehabilitation techniques for glioma patients. Methods: In accordance with PRISMA guidelines, searches of Medline, Embase, Web of Science, APA PsycINFO, and Cochrane were undertaken from database inception to November 28, 2023. Studies reporting on neuromodulation applied to glioma patients were included. Results: Seven studies reporting findings from 118 patients met the inclusion criteria. Three neuromodulation techniques were identified and included transcranial magnetic stimulation (TMS) reported in 5 out of 7 (71.4%) studies; transcranial direct current stimulation (tDCS); and continuous cortical electrical stimulation (cCES) using grid electrodes, reported in one study each. All studies applying noninvasive stimulation to ameliorate postoperative deficits demonstrated an improvement on at least one outcome measure. The 2 studies applying tDCS and cCES to induce plasticity reported evidence of functional reorganization. Conclusions: There is emerging evidence of benefits of neuromodulation to improve postoperative outcome in glioma patients. In the current literature, noninvasive stimulation has shown to have a favorable safety profile. Large-scale, double-blind, sham-controlled trials are warranted to further investigate the effectiveness of these interventions for modulating different cognitive networks in patients undergoing glioma surgery.

Peripheral Nerve Stimulation for Arm Pain in an Adolescent Girl with Ewing Sarcoma as Bridge Therapy to Chemotherapy: A Case Report

BACKGROUND: Cancer commonly presents discomfort from abnormal cell growth in healthy tissue and is often inadequately managed. Peripheral nerve stimulation (PNS), mainly for non-cancer chronic pain, has emerged as a minimally invasive option for neuropathic cancer-related pain when conventional methods fail. Limited research, primarily in adults, has focused on PNS in the non-oncological population. CASE REPORT: A 14-year-old adolescent girl with a history of obesity, diabetes, and Ewing sarcoma in her left proximal humerus experienced severe pain, initially rated at 10/10. After undergoing ultrasound-guided left suprascapular PNS as a 60-day bridge therapy to chemotherapy, her pain improved to 3/10 at lead removal and remained at 4/10 at 3 months postremoval. CONCLUSION: PNS is a promising and less invasive neuromodulation approach for managing tumor-related bone pain. Our case study illustrates the effectiveness of PNS placement for significant pain reduction, although limitations, such as delayed response and the need for further randomized-controlled studies, are acknowledged. KEY WORDS: Neuromodulation, peripheral nerve stimulation, Ewing sarcoma, arm pain, bone pain, chemotherapy, teen, adolescent

The deep and the deeper: Spinal cord and deep brain stimulation for neuropathic pain

Neuropathic pain occurs in people experiencing lesion or disease affecting the somatosensorial system. It is present in 7 % of the general population and may not fully respond to first- and second-line treatments in up to 40 % of cases. Neuromodulation approaches are often proposed for those not tolerating or not responding to usual pharmacological management. These approaches can be delivered surgically (invasively) or non-invasively. Invasive neuromodulation techniques were the first to be employed in neuropathic pain. Among them is spinal cord stimulation (SCS), which consists of the implantation of epidural electrodes over the spinal cord. It is recommended in some guidelines for peripheral neuropathic pain. While recent studies have called into question its efficacy, others have provided promising data, driven by advances in techniques, battery capabilities, programming algorithms and software developments. Deep brain stimulation (DBS) is another well-stablished neuromodulation therapy routinely used for movement disorders; however, its role in pain management remains limited to specific research centers. This is not only due to variable results in the literature contesting its efficacy, but also because several different brain targets have been explored in small trials, compromising comparisons between these studies. Structures such as the periaqueductal grey, posterior thalamus, anterior cingulate cortex, ventral striatum/anterior limb of the internal capsule and the insula are the main targets described to date in literature. SCS and DBS present diverse rationales for use, mechanistic backgrounds, and varying levels of support from experimental studies. The present review aims to present their methodological details, main mechanisms of action for analgesia and their place in the current body of evidence in the management of patients with neuropathic pain, as well their particularities, effectiveness, safety and limitations.

Computational modeling of dorsal root ganglion stimulation using an Injectrode

Objective. Minimally invasive neuromodulation therapies like the Injectrode, which is composed of a tightly wound polymer-coated Platinum/Iridium microcoil, offer a low-risk approach for administering electrical stimulation to the dorsal root ganglion (DRG). This flexible electrode is aimed to conform to the DRG. The stimulation occurs through a transcutaneous electrical stimulation (TES) patch, which subsequently transmits the stimulation to the Injectrode via a subcutaneous metal collector. However, it is important to note that the effectiveness of stimulation through TES relies on the specific geometrical configurations of the Injectrode-collector-patch system. Hence, there is a need to investigate which design parameters influence the activation of targeted neural structures. Approach. We employed a hybrid computational modeling approach to analyze the impact of Injectrode system design parameters on charge delivery and neural response to stimulation. We constructed multiple finite element method models of DRG stimulation, followed by the implementation of multi-compartment models of DRG neurons. By calculating potential distribution during monopolar stimulation, we simulated neural responses using various parameters based on prior acute experiments. Additionally, we developed a canonical monopolar stimulation and full-scale model of bipolar bilateral L5 DRG stimulation, allowing us to investigate how design parameters like Injectrode size and orientation influenced neural activation thresholds. Main results. Our findings were in accordance with acute experimental measurements and indicate that the minimally invasive Injectrode system predominantly engages large-diameter afferents (Aβ-fibers). These activation thresholds were contingent upon the surface area of the Injectrode. As the charge density decreased due to increasing surface area, there was a corresponding expansion in the stimulation amplitude range before triggering any pain-related mechanoreceptor (Aδ-fibers) activity. Significance. The Injectrode demonstrates potential as a viable technology for minimally invasive stimulation of the DRG. Our findings indicate that utilizing a larger surface area Injectrode enhances the therapeutic margin, effectively distinguishing the desired Aβ activation from the undesired Aδ-fiber activation.

Racial disparities in the utilization of invasive neuromodulation devices for the treatment of drug-resistant focal epilepsy.

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

A retrospective, naturalistic study of deep brain stimulation and vagal nerve stimulation in young patients.

Invasive neuromodulation interventions such as deep brain stimulation (DBS) and vagal nerve stimulation (VNS) are important treatments for movement disorders and epilepsy, but literature focused on young patients treated with DBS and VNS is limited. This retrospective study aimed to examine naturalistic outcomes of VNS and DBS treatment of epilepsy and dystonia in children, adolescents, and young adults. We retrospectively assessed patient demographic and outcome data that were obtained from electronic health records. Two researchers used the Clinical Global Impression scale to retrospectively rate the severity of neurologic and psychiatric symptoms before and after patients underwent surgery to implant DBS electrodes or a VNS device. Descriptive and inferential statistics were used to examine clinical effects. Data from 73 patients were evaluated. Neurologic symptoms improved for patients treated with DBS and VNS (p<.001). Patients treated with DBS did not have a change in psychiatric symptoms, whereas psychiatric symptoms worsened for patients treated with VNS (p=.008). The frequency of postoperative complications did not differ between VNS and DBS groups. Young patients may have distinct vulnerabilities for increased psychiatric symptoms during treatment with invasive neuromodulation. Child and adolescent psychiatrists should consider a more proactive approach and greater engagement with DBS and VNS teams that treat younger patients.

Phantom limb pain: actual concepts of pathophysiology and treatment methods from the standpoint of evidence-based medicine

Rationale. Despite a large number of studies on the effectiveness of various pharmacological and non- pharmacological therapies, PLP treatment tactics have not yet been developed, which is largely due to the complex mechanism of the formation of this pathology. Although PLP is classified as neuropathic pain, standard methods of neuropathic pain therapy are not always effective for this syndrome. To optimize the regimens of existing methods of PLP treatment, as well as the search and clinical trials of new therapeutic approaches, it is necessary to take into account the currently available evidence base.Material and methods. Our analysis included publications on phantom pain treatment methods with a high level of evidence (randomized controlled trials, systematic reviews and meta-analyses). Literature search was performed in Medline PubMed and eLIBRARY systems.Results. The review provides an evidence base for pharmacotherapy methods (opioids, NMDA-receptor antagonists, tricyclic antidepressants, anticonvulsants, local anesthetics), for methods based on the phantom illusion (mirror therapy, motion representation, virtual reality), for non-invasive (transcutaneous electrical neurostimulation, transcranial magnetic stimulation, transcranial electrical stimulation) and invasive (deep brain stimulation, motor cortex stimulation, spinal cord stimulation, dorsal root ganglion stimulation) neuromodulation. Data on the most studied dosing regimens of different methods of pharmacological and non-pharmacological therapy are presented.

Exploring Non Invasive Neuromodulation to Ameliorate Radiculopathic Pain: A Systematic Review of Randomised Controlled Trials

Introduction: Despite numerous investigations has delved into Non invasive Neuromodulation (NINM) for alleviating neuropathic pain from various origins, its efficacy in addressing radiculopathic pain specifically remains inadequately explored. Aim: To comprehensively synthesise existing literature on the use of NINM in managing radiculopathy-induced pain. Materials and Methods: A thorough search of four databases—Scopus, PubMed, Physiotherapy Evidence Database (PEDro), and Cochrane Library was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines from October 2023 to January 2024. Included articles in the study must have patients with cervical or lumbar radiculopathy, aged over 18 years, and included atleast one non invasive neuromodulation intervention, with outcomes measuring pain. Case reports, reviews, and meta-analyses were reviewed for additional references. “Radiculopathy” and “Neuromodulation” were the primary keywords used to extract data and the studies’ quality and findings were critically appraised using tools such as PEDro, Grading of Recommendations, Assessment, Development and Evaluations (GRADE), Level of Evidence, and Risk of Bias. Results: Six out of 75,182 studies that were identified met the inclusion criteria and underwent thorough evaluation. The remaining 75,176 articles were excluded for reasons such as duplicates (32,156), patients not related to radiculopathy (15,637), lack of the desired intervention or outcome (27,094), and various other reasons (289). NINM methods showed a significant reduction in pain severity for radiculopathy patients, with no reported adverse effects. Conclusion: In summary, integrating NINM approaches alongside conventional therapeutic strategies showed promising effects in enhancing the efficacy and sustainability of pain management for radiculopathy.

Difficult Single-Lead Spinal Cord Stimulator Trial for Failed Back Surgery Syndrome Salvages Treatment

BACKGROUND: Spinal cord stimulation (SCS) is a minimally invasive neuromodulation treatment modality primarily used for failed back surgery syndrome (FBSS), complex regional pain syndrome, and diabetic neuropathy. Specifically, when utilized for the treatment of FBSS, placement can be complicated by the excessive scarring, adhesions, and altered anatomy limiting the access to the epidural space and advancement of the leads. CASE REPORT: Our patient is a 58-year-old woman with a history of scoliosis and severe lumbar spinal stenosis who presented for trial of an SCS for FBSS. Given the refractory nature to medical and minimally invasive management, an SCS trial was performed. Unfortunately, due to the extensive fibrosis and adhesions in her epidural space, only a single lead could be placed but experienced pain relief. During the permanent SCS, 2 leads were successfully placed with the patient ultimately receiving &gt; 50% pain relief. CONCLUSIONS: Here, we present a case of FBSS refractory to medical and minimally invasive management where a single SCS lead was placed during the trial, due to scarring and adhesions, and 2 leads during the permanent SCS procedure. Our case report suggests considering even the trial of a single-lead placement during an SCS trial in patients with an otherwise difficult anatomy, as the placement of the permanent lead offers greater access to the epidural space potentially allowing for the placement of a second lead and potentially salvaging the entire therapy. KEY WORDS: Spinal cord stimulator, spinal stenosis, single lead, failed back surgery syndrome

From dawn till dusk: Time-adaptive bayesian optimization for neurostimulation.

Stimulation optimization has garnered considerable interest in recent years in order to efficiently parametrize neuromodulation-based therapies. To date, efforts focused on automatically identifying settings from parameter spaces that do not change over time. A limitation of these approaches, however, is that they lack consideration for time dependent factors that may influence therapy outcomes. Disease progression and biological rhythmicity are two sources of variation that may influence optimal stimulation settings over time. To account for this, we present a novel time-varying Bayesian optimization (TV-BayesOpt) for tracking the optimum parameter set for neuromodulation therapy. We evaluate the performance of TV-BayesOpt for tracking gradual and periodic slow variations over time. The algorithm was investigated within the context of a computational model of phase-locked deep brain stimulation for treating oscillopathies representative of common movement disorders such as Parkinson's disease and Essential Tremor. When the optimal stimulation settings changed due to gradual and periodic sources, TV-BayesOpt outperformed standard time-invariant techniques and was able to identify the appropriate stimulation setting. Through incorporation of both a gradual "forgetting" and periodic covariance functions, the algorithm maintained robust performance when a priori knowledge differed from observed variations. This algorithm presents a broad framework that can be leveraged for the treatment of a range of neurological and psychiatric conditions and can be used to track variations in optimal stimulation settings such as amplitude, pulse-width, frequency and phase for invasive and non-invasive neuromodulation strategies.

Case Series: Spinal Cord Stimulator Therapy Alleviates Neuropathic Pain in Patients with Failed Back Surgery Syndrome in the Setting of Spinal Cord Injury

BACKGROUND: Spinal cord stimulation (SCS) is a minimally invasive neuromodulation treatment modality primarily indicated for failed back surgery syndrome (FBSS). When FBSS occurs in the setting of spinal cord injury (SCI) it can often be refractory to treatment with opioids and anticonvulsants; in such cases, SCS has demonstrated promising results. Here, we present a case series of 2 patients with FBSS in the setting of SCI who received pain relief with SCS therapy. CASE REPORT: Our first patient is a 49-year-old man with a history of SCI (T10-11) with resulting paraplegia, who presented after failure of conservative management of his neuropathic abdominal and lumbar back pain with radiculopathy to the right groin. Our second patient is a 50-year-old man with a history of insulin-dependent diabetes mellitus, coronary artery disease, and thoracic arachnoid cyst excision, who presented for treatment of worsening intractable neuropathic pain in his thorax, abdomen, and midback. Both patients received SCS therapy with significant improvement in their neuropathic pain. CONCLUSION: By delivering targeted electrical stimulation to the spinal cord, SCS can improve the pain resulting from FBSS. Recent literature has highlighted the successful use of SCS in alleviating neuropathic pain following SCI; our case series further adds to the literature supporting the use of SCS in this pain setting. SCS continues to offer chronic pain physicians alternative, effective options for patients suffering from FBSS in the setting of SCI. KEY WORDS: Spinal cord stimulator, failed back surgery syndrome, spinal cord injury, neuropathy

Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol.

Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy. Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery. Ethics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses. ClinicalTrials.gov, identifier NCT05844605.

Neuromodulation techniques in medically refractory epilepsy: A comprehensive assessment

The aim of this research is to explore the efficacy and safety of neurostimulation techniques, particularly responsive neurostimulation, in treating medically refractory epilepsy. The study reviews relevant literature, discusses the mechanisms of action, and presents evidence of reduced seizure frequency and improved quality of life in patients receiving neurostimulation. To evaluate invasive Neuromodulation’s efficiency for medically refractory epilepsy, we searched databases like Google Scholar, Medline, and Elsevier using keywords ‘Neuromodulation and epilepsy’. Numerous relevant results emerged. We conducted rapid abstract reviews to identify key articles, cross-referencing for valuable references, ensuring a comprehensive analysis of pertinent research. Neuromodulation techniques, particularly VNS, DBS, and RNS, offer promising therapeutic options for medically refractory epilepsy. Ongoing research and clinical trials are vital for refining these treatments, adapting them for diverse populations, and enhancing outcomes. The potential to improve patients’ quality of life through innovative approaches is encouraging, driving further progress in neuromodulation.

Non-Pharmacological Treatment for Chronic Migraine.

Chronic migraine (CM) affects a large proportion of the population and is a significant source of disability and lost productivity. Numerous non-pharmacological approaches have been attempted during the past decades. This review discusses the most recent and evidence-based advances in acute and preventive non-pharmacological therapeutic approaches for CM, offering alternatives to drug treatment. A growing number of non-pharmacological treatment options, including non-invasive or invasive neuromodulation, acupuncture, psychotherapy, and physiotherapy, have shown promising efficacy in CM. There is strong evidence for the effectiveness of non-invasive neuromodulation such as transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (TENS) in CM, but less evidence for approaches such as invasive neuromodulation, physical therapy, or dietary approaches. Acupuncture for migraine remains controversial, with the main point of contention still being the placebo effect. Non-pharmacological approaches can be offered as a reliable alternative for patients with CM, and more research is being done to evaluate the efficacy of non-invasive neuromodulation with different parameters and the combination of different treatments in CM.