Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures that often originate within limbic networks involving amygdala and hippocampus. The limbic network is involved in crucial physiologic functions involving memory, emotion and sleep. Temporal lobe epilepsy is frequently drug-resistant, and people often experience comorbidities related to memory, mood and sleep. Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for temporal lobe epilepsy. However, the optimal stimulation parameters and their impact on memory, mood and sleep comorbidities remain unclear. We used an investigational brain sensing-stimulation implanted device to accurately track seizures, interictal epileptiform spikes (IES), and memory, mood and sleep comorbidities in five ambulatory subjects. Wireless streaming of limbic network local field potentials (LFPs) and subject behaviour were captured on a mobile device integrated with a cloud environment. Automated algorithms applied to the continuous LFPs were used to accurately cataloged seizures, IES and sleep-wake brain state. Memory and mood assessments were remotely administered to densely sample cognitive and behavioural response during ANT-DBS in ambulatory subjects living in their natural home environment. We evaluated the effect of continuous low-frequency and duty cycle high-frequency ANT-DBS on epileptiform activity and memory, mood and sleep comorbidities. Both low-frequency and high-frequency ANT-DBS paradigms reduced seizures. However, continuous low-frequency ANT-DBS showed greater reductions in IES, electrographic seizures and better sleep and memory outcomes. These results highlight the potential of synchronized brain sensing and dense behavioural tracking during ANT-DBS for optimizing neuromodulation therapy. While studies with larger patient numbers are needed to validate the benefits of low-frequency ANT-DBS, these findings are potentially translatable to individuals currently implanted with ANT-DBS systems.

• Klíčová slova
• artificial intelligence and machine learning, electrical brain stimulation, epilepsy comorbidities, intracranial EEG,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions. METHODS AND ANALYSIS: Non-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion. ETHICS AND DISSEMINATION: Prospective multicentre validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences. TRIAL REGISTRATION NUMBER: NCT06138808.

• Klíčová slova
• EEG, EPILEPSY, EPILEPSY, SURGERY, NEUROPHYSIOLOGY,
• Publikační typ
• časopisecké články MeSH

The network nature of focal epilepsy is exemplified by mesial temporal lobe epilepsy (mTLE), characterized by focal seizures originating from the mesial temporal neocortex, amygdala, and hippocampus. The mTLE network hypothesis is evident in seizure semiology and interictal comorbidities, both reflecting limbic network dysfunction. The network generating seizures also supports essential physiological functions, including memory, emotion, mood, and sleep. Pathology in the mTLE network often manifests as interictal behavioral disturbances and seizures. The limbic circuit is a vital network, and here we review one of the most common focal epilepsies and its comorbidities. We describe two people with drug resistant mTLE implanted with an investigational device enabling continuous hippocampal local field potential sensing and anterior nucleus of thalamus deep brain stimulation (ANT-DBS) who experienced reversible psychosis during continuous high-frequency stimulation. The mechanism(s) of psychosis remain poorly understood and here we speculate that the anti-epileptic effect of high frequency ANT-DBS may provide insights into the physiology of primary disorders associated with psychosis.

• Klíčová slova
• ANT-DBS, Epilepsy, limbic network, psychosis, seizure,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Epilepsy is a complex disorder affecting the central nervous system and is characterised by spontaneously recurring seizures (SRSs). Epileptic patients undergo symptomatic pharmacological treatments, however, in 30% of cases, they are ineffective, mostly in patients with temporal lobe epilepsy. Therefore, there is a need for developing novel treatment strategies. Transplantation of cells releasing γ-aminobutyric acid (GABA) could be used to counteract the imbalance between excitation and inhibition within epileptic neuronal networks. We generated GABAergic interneuron precursors from human embryonic stem cells (hESCs) and grafted them in the hippocampi of rats developing chronic SRSs after kainic acid-induced status epilepticus. Using whole-cell patch-clamp recordings, we characterised the maturation of the grafted cells into functional GABAergic interneurons in the host brain, and we confirmed the presence of functional inhibitory synaptic connections from grafted cells onto the host neurons. Moreover, optogenetic stimulation of grafted hESC-derived interneurons reduced the rate of epileptiform discharges in vitro. We also observed decreased SRS frequency and total time spent in SRSs in these animals in vivo as compared to non-grafted controls. These data represent a proof-of-concept that hESC-derived GABAergic neurons can exert a therapeutic effect on epileptic animals presumably through establishing inhibitory synapses with host neurons.

• Klíčová slova
• GABA, cell integration, epilepsy, human embryonic stem cells, interneurons, optogenetics, synaptic integration,
• MeSH
• GABA metabolismus   MeSH
• hipokampus metabolismus   patologie   MeSH
• interneurony cytologie   metabolismus   MeSH
• kmenové buňky cytologie   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kyselina kainová škodlivé účinky   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• recidiva MeSH
• status epilepticus chemicky indukované   metabolismus   patologie   terapie   MeSH
• transplantace kmenových buněk metody   MeSH
• záchvaty chemicky indukované   metabolismus   patologie   terapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• GABA MeSH
• kyselina kainová MeSH

BACKGROUND: This paper presents our experience of stereotactic radiofrequency amygdalohippocampectomy performed for intractable mesial temporal lobe epilepsy. METHODS: The article describes the cases of 61 patients who were treated during the period from 2004 to 2010. Mean postoperative follow-up was 5.3 years. Neuropsychological results were obtained for a subset of 31 patients. RESULTS: At their last postsurgical visit, 43 (70.5%) patients were Engel class I, six (9.8%) class II, nine (14.8%) class III, and three (4.9%) class IV. The surgery was complicated by four intracranial hematomas. One of them caused acute hydrocephalus and was treated by shunting and resolved without sequelae, while another caused transitory aphasia. The remaining hematomas were asymptomatic. There were two cases of meningitis which required antibiotic treatment. One patient committed suicide due to postoperative depression. After the procedure, we performed open epilepsy surgery and rethermolesions in three and two patients, respectively (8.2%). Patients showed increases in their mean full scale, verbal, and performance intelligence quotient (IQ) scores of 4, 3, and 4 IQ points, respectively (P<0.05). Five (17.2%), four (13.8%), and four (13.3%) patients improved their full scale, verbal, and performance IQ scores, respectively. No significant changes were found in memory performance, with a mean increase of 1, 3, and 0 memory quotient points in global, verbal, and visual memory, respectively (P<0.05). Global memory improved in three (10.3%) patients, verbal memory in one (3.4%), and one patient (3.3%) showed deterioration in visual memory. CONCLUSION: Stereotactic radiofrequency amygdalohippocampectomy offers a safe, effective, and less aggressive treatment modality in cases of well-defined mesial temporal lobe epilepsy. Seizure outcome is comparable with the results of conventional epilepsy surgery and cognitive results could be even better.

• Klíčová slova
• epilepsy surgery, hippocampal sclerosis, neuropsychology, seizure outcome, temporal lobe epilepsy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH