Deep brain and cortical stimulation for epilepsy.

Deep Brain Stimulation in Patients with Refractory Temporal Lobe Epilepsy. Boon P, Vonck K, De Herdt V, Van Dycke A, Goethals M, Goossens L, Van Zandijcke M, De Smedt T, Dewaele I, Achten R, Wadman W, Dewaele F, Caemaert J, Van Roost D. Epilepsia 2007;48(8):1551–1560. PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12–52 months), one of 10 stimulated patients are seizure-free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of ≥50%; two of 10 patients had a seizure-frequency reduction of 30–49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.

Long-Term Evaluation of Anterior Thalamic Deep Brain Stimulation for Epilepsy in the European MORE RegistryKaufmann E, Peltola J, Colon AJ, Lehtimäki K, Majtanik M, Mai JK, Bóné B, Bentes C, Coenen V, Gil-Nagel A, Goncalves-Ferreira AJ, Ryvlin P, Taylor R, Brionne TC, Gielen F, Song S, Boon P; MORE study group. Epilepsia. 2024;65(8):2438-2458. doi: 10.1111/epi.18003Objective: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS. Methods: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. Results: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow up, respectively. Most discontinuations (68%) were due to planned study closure as follow up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow up (P < .001), with most-pronounced effects on focal-to-bilateral tonic–clonic seizures (n = 15, 77% reduction, P = .008). At last follow up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (P = .035) and a negative history of epilepsy surgery (P = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. Significance: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management.

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

The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters.

The majority of patients with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug. However, up to 30% develop refractory seizures, particularly those with partial seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as an add-on treatment for drug-resistant localization related (partial) epilepsy. To evaluate the effects of levetiracetam on seizures, side effects, quality of life and cognition, when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2000). In addition, we contacted UCB SA (makers of levetiracetam) and experts in the field to seek any ongoing studies or unpublished studies. Randomized placebo controlled add-on trials of levetiracetam in patients with a drug-resistant localization related (partial) epilepsy. Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects; (d) cognitive effects; (e) quality of life. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. Dose response was evaluated in regression models. Four trials (1023 patients) were included. All four trials had data for treatment withdrawal and side effect outcomes. Three trials (904 patients) had data for 50% or greater reduction in seizure frequency. Three trials (595 patients) had data for quality of life and cognitive outcomes. The overall Odds Ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in total seizure frequency outcome was 3.81 (2.78,5.22). Dose regression analysis shows clear evidence that levetiracetam reduces seizure frequency with an increase in efficacy with increasing dose of levetiracetam. Approximately 15% of patients taking 1000 mg and 20-30% of patients taking 3000 mg levetiracetam per day have a 50% or greater reduction in seizure frequency. Patients were not significantly more likely to have levetiracetam withdrawn, OR (95% CI) 1.25 (0.87,1.80). The following side effects were significantly associated with levetiracetam: dizziness 2.36 (1.21, 4.61) and infection 1.82 (1.05, 3.14) whereas accidental injury was significantly associated with placebo 0.55 (0.32, 0.93). Quality of life and cognitive effect outcomes suggest that levetiracetam has a positive effect on cognition and some aspects of quality of life. Levetiracetam reduces seizure frequency when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy, and seems well tolerated. Minimum effective and maximum tolerated doses have not been identified. The trials reviewed were of 16-24 weeks duration and results cannot be used to confirm longer term effects. Our results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes. Great care should also be taken with any attempt to apply these results to children.

The centromedian (CM) and anterior nucleus of the thalamus (ANT) are deep brain stimulation (DBS) targets for management of generalized, and focal drug resistant epilepsy (DRE), respectively. We report on a single center retrospective case series of 16 children and adults with DRE who underwent CM with simultaneous ANT (69 %) or CM without simultaneous ANT DBS (31 %). Seizure frequency, epilepsy severity, life satisfaction, and quality of sleep before and after DBS were compared. Baseline median seizure frequency was 323 seizures per month (IQR, 71–563 sz/mo). Median follow up time was 80 months (IQR 37–97 mo). Median seizure frequency reduction was 58 % (IQR 13–87 %, p = 0.002). Ten patients (63 %) reported ≥50 % seizure frequency reduction. Median seizure frequency reduction and responder rate were not significantly different for CM + ANT versus CM only. Seizure severity and life satisfaction were significantly improved. Three patients (19 %) developed device-related side effects, 2 of them (12.5 %) required surgical intervention. In a heterogenous population of children and adults with generalized, multifocal, posterior onset, and poorly localized DRE, CM with or without ANT DBS is feasible, relatively safe and is associated with reduced seizure frequency and severity, as well as improved life satisfaction.

Sudden unexpected death in epilepsy (SUDEP) is a serious threat to individuals with intractable epilepsies, contributing to premature mortality. Understanding the elusive pathophysiological mechanisms of SUDEP, especially in cases without observable terminal events, remains a crucial area for investigation. This study aimed to shed light on the burden of epileptiform activity preceding SUDEP by utilizing an automated electronic seizure diary derived from a sensing-enabled thalamic deep brain stimulator (DBS). Herein, we present the case of a 57-year-old man afflicted with intractable multifocal epilepsy secondary to cortical dysplasia and encephalomalacia resulting from severe traumatic brain injury. Despite an initial successful resection and subsequent resurgence of seizures necessitating DBS treatment, the patient tragically succumbed to SUDEP. In-depth analysis of the patient's electronic seizure diary, complemented by data from the sensing-enabled DBS, unveiled a terminal electrographic seizure. Notably, we observed a significant increase in power within specific frequency bands recorded from the thalamus preceding the terminal event. Furthermore, these heightened band power events displayed a discernible temporal clustering pattern, primarily manifesting during specific morning and evening hours. An autopsy conclusively confirmed the diagnosis of definite SUDEP. This unique case report underscores the feasibility of harnessing thalamic DBS sensing capabilities to monitor seizure burden and, potentially, to tailor interventions aimed at reducing seizure frequency and associated mortality risks.

Do patient's get angrier following STN, GPi, and thalamic deep brain stimulation

Clinical efficacy and safety of anterior thalamic deep brain stimulation for intractable drug resistant epilepsy

Back to table of contents Previous article Next article LettersFull AccessDBS, Parkinson's Disease, and SuicideChristian Saleh, M.D.Christian SalehSearch for more papers by this author, M.D.Published Online:1 Apr 2011AboutSectionsView articleView PDFView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleTo the Editor: I read with interest Dr. Mahgoub's and Dr. Kotbi's case report, “Acute depression and suicidal attempt following lowering the frequency of deep brain stimulation.”1 The authors report the case of a 66-year-old patient treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) of 20 years' duration, who suffered an acute depressive episode associated with a suicide attempt after the modification of his DBS stimulation parameters.In this patient, a reduction of the frequency of the stimulation from 185 Hz to 60 Hz was noted with the induction of an acute suicidal state. By increasing the frequency, the depressive state improved, and the suicidal ideations subsided. Dr. Mahgoub and Dr. Kotbi write that “Our case demonstrates the risk of suicide when lowering the frequency of the stimulation… Patients at high risk for suicide should be excluded from deep brain stimulation surgery.”Some differentiations and specifications here might be needed: The patient reported by the authors was treated with DBS of the subthalamic nucleus (STN). Although DBS STN for PD is known to be associated with a plethora of neuropsychiatric adverse effects, such as confusion, psychosis, depression, mania, and suicidal ideation,2 noteworthy within this context is that psychosis, depression, and suicidal ideation are known also in patients with PD not undergoing DBS treatment.3The authors write that DBS “has now also been extended to other neuropsychiatric conditions and has shown some promising results in patients suffering from profound depression.” It is advisable though to differentiate that while the main target for DBS for PD is the STN, DBS applied to treat depression has different targets, such as the nucleus accumbens, the subgenual cingulate (Cg25), and the ventral capsule and ventral striatum (VC/VS).4The relationship between stimulation settings of the DBS device and neuropsychiatric adverse effects is known; however it is important to note that the literature shows considerable contrasting findings in this matter.2Some authors reported that stimulation induced limbic effects, whereas termination of stimulation led to a resolution of the limbic symptoms;5 in contrast to the case reported by Dr. Mahgoub and Dr. Kotbi. Still other authors specified that limbic side effects were not affected by changing the stimulation parameters, but required the changing of the localization of the stimulating contacts or subsided solely after pharmacological treatment.2Although Dr. Mahgoub and Dr. Kotbi's report is important, the statement that “our case demonstrates the risk of suicide when lowering the frequency of the stimulation” cannot be made with such implicitness. The plethora of contrasting reports on this subject matter2 does not allow for generalization of findings, especially if they are based on a single case report. More research is yet needed to elucidate the polyhedral relation between STN DBS, PD, and suicide.Paris, France1. Mahgoub NA , Kotbi N : Acute depression and suicidal attempt following lowering the frequency of deep brain stimulation. J Neuropsychiatry Clin Neurosci 2009; 21:468Link, Google Scholar2. Saleh C , Okun MS : Clinical review of deep brain stimulation and its effects on limbic basal ganglia circuitry. Front Biosci 2008; 13:5708–5731Crossref, Medline, Google Scholar3. Nazem S , Siderowf AD , Duda JE , et al.: Suicidal and death ideation in Parkinson's disease. Mov Disord 2008; 23:1573–1579Crossref, Medline, Google Scholar4. Kuhn J , Grundler TO , Lenartz D , et al.: Deep brain stimulation for psychiatric disorders. Dtsch Arztebl Int 2010; 107:105–113Google Scholar5. Stefurak T , Mikulis D , Mayberg H , et al.: Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study. Mov Disord 2003; 18:1508–1516Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByBrain stimulation treatments in bipolar disorder: A review of the current literature4 December 2014 | The World Journal of Biological Psychiatry, Vol. 17, No. 7 Volume 23Issue 2 Spring 2011Pages E4-E4 Metrics History Published online 1 April 2011 Published in print 1 April 2011

A novel method for removal of deep brain stimulation artifact from electroencephalography.

Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

ObjectiveGait disturbances are frequent side effects occurring during chronic thalamic deep brain stimulation (DBS) in patients with essential tremor (ET). Adapting stimulation settings to shorter pulse widths has been shown...

Event Abstract Back to Event Objective measures of efficacy of Deep Brain Stimulation for treatment of tremor Colette M. Mckay1, 2, 3*, Thushara Perera1, Richard Peppard1, 4, Hugh J. McDermott1, 2 and Adam P. Vogel1, 5 1 The Bionics Institute of Australia, Australia 2 The University of Melbourne, Department of Medical Bionics, Australia 3 The University of Manchester, School of Psychological Sciences, United Kingdom 4 St. Vincent's Hospital, Australia 5 The University of Melbourne, Department of Audiology and Speech Pathology, Australia Patients with intractable tremor not alleviated by pharmaceutical therapies can be successfully treated using Deep Brain Stimulation of subcortical areas such as the Subthalamic Nucleus (STN). Current DBS devices produce constant-current or constant-voltage biphasic pulse trains and offer a range of pulse rate and pulse duration options as well as different current or voltage levels. The clinical method of setting the parameters by observation is non-ideal, firstly because of the number of possible parameter combinations, and a current lack of knowledge of how the parameters interact with each other, and secondly because subjective clinical observation is prone to observer error and bias. In this study, we aimed to develop an objective method of recording the severity of tremor and to use it to explore the effect on tremor of stimulus parameters. Six patients with Essential Tremor who had been fitted with a DBS device in the Posterior Subthalamic Area (PSA) participated in the study. Tremor was measured by position sensors attached to the arms and wrists while the patient was holding both arms stretched out in front of them and when performing a finger-nose pointing task. Clinical rating of tremor was also performed. Results of the experiments showed that the optimal stimulus parameters were subject specific and the effects of each parameter were non-monotonic, often with a very specific range providing therapeutic benefit (for example, Fig. 1). The objective measures were more sensitive than clinical judgement and show that an objective fitting method could improve benefits in individual patients. Figure 1 Acknowledgements Supported by the Helen McPherson Smith Trust and the Colonial Foundation. The Bionics Institute acknowledges the support it receives from the Victorian Government through its Operational Infrastructure Support Program References Blomstedt P, Sandvik U, Tisch S. Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor. Movement Disorders 2010;25(10):1350-1356. Rodriguez-Oroz MC, Obeso JA, Lang AE, et al. Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. Brain 2005;128(10):2240-2249. Keywords: deep brain stimulation (DBS), Tremor management, Essential Tremor, Parkinson Disease, stimulus-specific adaptation Conference: ACNS-2012 Australasian Cognitive Neuroscience Conference, Brisbane, Australia, 29 Nov - 2 Dec, 2012. Presentation Type: Poster Presentation Topic: Motor Citation: Mckay CM, Perera T, Peppard R, McDermott HJ and Vogel AP (2012). Objective measures of efficacy of Deep Brain Stimulation for treatment of tremor. Conference Abstract: ACNS-2012 Australasian Cognitive Neuroscience Conference. doi: 10.3389/conf.fnhum.2012.208.00067 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Oct 2012; Published Online: 07 Nov 2012. * Correspondence: Prof. Colette M Mckay, The Bionics Institute of Australia, East Melbourne, VIC, 3002, Australia, cmckay@bionicsinstitute.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Colette M Mckay Thushara Perera Richard Peppard Hugh J McDermott Adam P Vogel Google Colette M Mckay Thushara Perera Richard Peppard Hugh J McDermott Adam P Vogel Google Scholar Colette M Mckay Thushara Perera Richard Peppard Hugh J McDermott Adam P Vogel PubMed Colette M Mckay Thushara Perera Richard Peppard Hugh J McDermott Adam P Vogel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Despite the growing scientific evidence that supports the efficacy of deep brain stimulation (DBS) for controlling epileptic seizure dynamics, further research remains mandatory to optimize DBS parameters for an efficient clinical use. In particular, progress can be expected from detailed study of the still poorly understood mechanisms that are responsible for the modulation of neural activity by DBS. In this work, a computational model of the thalamocortical loop was developed to explore the mechanisms of thalamic DBS and its effects on cortical dynamics. The model was tuned using real intracerebral EEG (iEEG) signals recorded in an epileptic patient. Results confirmed the dependence of DBS activated mechanisms on the choice of stimulation frequency. They revealed that short-term depression, feed-forward inhibition, and stimulation-induced depolarization of inhibitory reticular neurons seem to be key factors of frequency-dependent effects.