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Introduction: Deep brain stimulation (DBS) is currently considered a promising neuromodulation therapy for refractory epilepsy not suitable for resective surgery. Several anatomical targets and different stimulation approaches have been proposed in order to obtain satisfactory seizures reduction. As expected, according with different patterns of neural pathways involvement, the efficacy of each anatomical target stimulation in reducing seizure frequency varies among the different epileptic syndromes., Evidence Acquisition: We reviewed the current literature on this topic to provide an overview of the clinical efficacy of the main stimulation targets (anterior nucleus of the thalamus [ANT], hippocampus formation [HF] and centromedian nucleus of the thalamus [CMT]) related to the different epileptic syndromes. We also summarized the available data concerning side effects, neuropsychological outcome, quality of life and future perspective of DBS in intractable epilepsy., Evidence Synthesis: Encouraging results were reported for each target stimulation. However, only in ANT and responsive neurostimulation (RNS) the efficacy and safety were tested on large series of patients and achieving class I evidence level., Conslusions: We concluded that responsive stimulation could be more appropriate in focal epilepsy, while ANT stimulation could be properly performed also in multifocal seizures with predominant limbic involvement. Despite the small samples size, HF stimulation reduces seizure frequency in (bi) temporal lobe epilepsy, as well as CMT stimulation is able to reduce, seizure frequency, in generalized epilepsy.

Background: Intracellular Ca2+ modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca2+ concentration ([Ca2+]i). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca2+-mediated response triggered by purinergic signaling.Methods: Fura-2 based fluorescence microscopy was used to measure [Ca2+]i in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca2+-dependent whole-cell currents.Results: In human microglia extracellular ATP evoked [Ca2+]i increases depend on Ca2+ entry from the extracellular space and on Ca2+ mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca2+]i increases were prevented by removing external Ca2+ and using an intracellular Ca2+ chelator. TRAM-34, a selective KCa3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl- in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca2+ transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca2+ mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca2+-evoked K+ current led to a less sustained ATP-evoked Ca2+ entry, as shown by the faster Ca2+ transient kinetics observed in LPS-treated microglia.Conclusions: Our study confirms a functional role for KCa3.1 channels in human microglia, linking ATP-evoked Ca2+ transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the KCa3.1-mediated microglial response to purinergic signaling may be reduced. [ABSTRACT FROM AUTHOR]

Abstract Purpose The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery. Method This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001–2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome. Results Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I–II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357). Conclusion Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates. Highlights • Surgery is a safe option in drug-resistant FLE with a satisfying long-term outcome. • The presence of focal lesions predicts favorable outcome. • Focal ictal scalp EEG onset is associated with a favorable long-term outcome. [ABSTRACT FROM AUTHOR]

We previously found that the endogenous anticonvulsant adenosine, acting through A2A and A3 adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether AR5 alter the stability (desensitization) of IGABA expressed in focal cortical dysplasia (FCD) and in penglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABAA receptors revealed instability, manifested by a large IGABA rundown, which in most of the oocytes (≈70%) was obviously impaired by the new A2A antagonists ANR82, ANR94, and ANR152. In most MILE tissue-microtransplanted oocytes, a new A3 receptor antagonist (ANR235) significantly improved IGABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered IGABA rundown on ANR94 treatment. Our findings indicate that antagonizing A2A and A3 receptors increases the IGABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy. [ABSTRACT FROM AUTHOR]

Background: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. Methods: From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R–R interval of ≥3 s during a seizure). Results: IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal (n = 5), temporo-parietal (n = 1) or frontal (n = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. Conclusion: IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure. [ABSTRACT FROM AUTHOR]