A spike is a spike: On the universality of spike features in four epilepsy models.

OBJECTIVE: Frequency properties of the EEG characteristics of different seizure types including absence seizures have been described for various rodent models of epilepsy. However, little attention has been paid to the frequency properties of individual spike-wave complexes (SWCs), the constituting elements characterizing the different generalized seizure types. Knowledge of their properties is not only important for understanding the mechanisms underlying seizure generation but also for the identification of epileptiform activity in various seizure types. Here, we compared the frequency properties of SWCs in different epilepsy models. METHODS: A software package was designed and used for the extraction and frequency analysis of SWCs from long-term EEG of four spontaneously seizing, chronic epilepsy models: a post-status epilepticus model of temporal lobe epilepsy, a lateral fluid percussion injury model of post-traumatic epilepsy, and two genetic models of absence epilepsy-GAERS and rats of the WAG/Rij strain. The SWCs within the generalized seizures were separated into fast (three-phasic spike) and slow (mostly containing the wave) components. Eight animals from each model were used (32 recordings, 104 510 SWCs in total). A limitation of our study is that the recordings were hardware-filtered (high-pass), which could affect the frequency composition of the EEG. RESULTS: We found that the three-phasic spike component was similar in all animal models both in time and frequency domains, their amplitude spectra showed a single expressed peak at 18-20 Hz. The slow component showed a much larger variability across the rat models. SIGNIFICANCE: Despite differences in the morphology of the epileptiform activity in different models, the frequency composition of the spike component of single SWCs is identical and does not depend on the particular epilepsy model. This fact may be used for the development of universal algorithms for seizure detection applicable to different rat models of epilepsy. PLAIN LANGUAGE SUMMARY: There is a large variety between people with epilepsy regarding the clinical manifestations and the electroencephalographic (EEG) phenomena accompanying the epileptic seizures. Here, we show that one of the EEG signs of epilepsy, an epileptic spike, is universal, since it has the same shape and frequency characteristics in different animal models of generalized epilepsies, despite differences in recording sites and location.

Microangiopathy in temporal lobe epilepsy with diffusion MRI alterations and cognitive decline.

White matter microvascular alterations in temporal lobe epilepsy (TLE) may be relevant to acquired neurodegenerative processes and cognitive impairments associated with this condition. We quantified microvascular changes, myelin, axonal, glial and extracellular-matrix labelling in the gyral core and deep temporal lobe white matter regions in surgical resections from 44 TLE patients with or without hippocampal sclerosis. We compared this pathology data with in vivo pre-operative MRI diffusion measurements in co-registered regions and neuropsychological measures of cognitive impairment and decline. In resections, increased arteriolosclerosis was observed in TLE compared to non-epilepsy controls (greater sclerotic index, p < 0.001), independent of age. Microvascular changes included increased vascular densities in some regions but uniformly reduced mean vascular size (quantified with collagen-4, p < 0.05-0.0001), and increased pericyte coverage of small vessels and capillaries particularly in deep white matter (quantified with platelet-derived growth factor receptorß and smooth muscle actin, p < 0.01) which was more marked the longer the duration of epilepsy (p < 0.05). We noted increased glial numbers (Olig2, Iba1) but reduced myelin (MAG, PLP) in TLE compared to controls, particularly prominent in deep white matter. Gene expression analysis showed a greater reduction of myelination genes in HS than non-HS cases and with age and correlation with diffusion MRI alterations. Glial densities and vascular size were increased with increased MRI diffusivity and vascular density with white matter abnormality quantified using fixel-based analysis. Increased perivascular space was associated with reduced fractional anisotropy as well as age-accelerated cognitive decline prior to surgery (p < 0.05). In summary, likely acquired microangiopathic changes in TLE, including vascular sclerosis, increased pericyte coverage and reduced small vessel size, may indicate a functional alteration in contractility of small vessels and haemodynamics that could impact on tissue perfusion. These morphological features correlate with white matter diffusion MRI alterations and might explain cognitive decline in TLE.

Low-frequency rTMS Plays a Neuroprotective role in Pilocarpine-induced Status Epilepticus Rat Models Through the AMPAR GluA1-STIM-Ca2+ Pathway.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) refers to the stimulation of the brain using repetitive magnetic field pulses at a low frequency (≤ 1 Hz) to reduce seizures. Currently, the mechanism is not well understood. Male Sprague-Dawley rats underwent pilocarpine-induced status epilepticus (SE) and were then stimulated with low-frequency rTMS. An epilepsy cell model was then established by incubating rat hippocampal neurons with Mg2+-free extracellular fluids. The effects of the low-frequency rTMS on epileptogenesis and hippocampal neuron injury were evaluated using a video electroencephalogram (vEEG) and Nissl staining, and the expression of AMPAR GluA1 and STIM in the hippocampus and hippocampal neurons was assessed using western blot and immunofluorescence. Additionally, the intracellular Ca2+ concentration and reactive oxygen species (ROS) were measured using flow cytometry. Low-frequency rTMS attenuated spontaneous recurrent seizures in rats with epilepsy, with the SE group exhibiting a higher incidence (100%) and frequency (3.00 ± 0.18 times/day) than the SE + 0.3 (50% incidence, 0.06 ± 0.03 times/day), SE + 0.5 (0.20 ± 0.02 times/day) and SE + 1 Hz (1.02 ± 0.05 times/day) groups. Additionally, rTMS reduced the damage and apoptosis of hippocampal pyramidal neurons, increasing their numbers in the CA1 and CA3 regions. Furthermore, AMPAR GluA1 and STIM expression were upregulated in the hippocampus when using rTMS, reversing the downregulation caused by seizures. Immunofluorescence verified the increased fluorescence intensity of AMPAR GluA1 and STIM. Moreover, rTMS inhibited Ca2+ overload and ROS in epileptic neuron models. Low-frequency rTMS may exert neuroprotective effects through the AMPAR GluA1-STIM-Ca2+ pathway.

Exploration of epileptic networks in temporal lobe encephaloceles with stereotactic EEG: Electroclinical characteristics and surgical outcomes.

OBJECTIVE: Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network. METHODS: A retrospective review was performed of patients with TLE related to TLEN who underwent SEEG implantation. Medical charts were reviewed for demographic data, the results of noninvasive and invasive investigations, and operative details. Surgical outcomes were based on Engel classification with at least 6 months follow-up. RESULTS: Nine patients were identified. The mean age at epilepsy onset was 28 years (range, 15-41 years), and 7/9 patients were female. Scalp EEG revealed interictal epileptiform activity most often maximum in the frontotemporal and/or temporal regions. A discrete TLEN was often not identified on initial imaging, but was identified during re-review or at the time of surgery. Seizure onset zones during SEEG were localized to the mesial temporal structures, the temporal pole, or both. One patient became seizure-free following SEEG and another refused further surgery. Of the 7 patients who underwent epilepsy surgery, 5/7 underwent an anterior temporal lobectomy-surgical outcomes were favorable, with 5/7 achieving Engel I outcomes. SIGNIFICANCE: Invasive SEEG monitoring demonstrated ictal onsets may not be restricted to the TLEN, and often the temporal pole and mesial structures are involved at seizure onset. Ictal propagation patterns vary significantly, which may be related to the underlying pathology and explain the variability in semiology. These findings may inform surgical treatment options. PLAIN LANGUAGE SUMMARY: Temporal lobe encephaloceles can cause intractable epilepsy, although their presence may be missed on routine imaging. The management of encephaloceles is primarily surgical; however, the optimal surgical approach can be unclear. Invasive monitoring with SEEG may help characterize the epileptogenic network and result in more optimal surgical outcomes.

Seronegative herpes simplex virus (HSV) encephalitis causing temporal lobe epilepsy resulting in new-onset psychosis: a case report and literature review.

Background: Herpes simplex virus (HSV) encephalitis is the most common nonepidemic encephalitis and can result in temporal lobe necrosis. Inflammation of the temporal lobe can result in temporal lobe epilepsy which is known to cause psychiatric symptoms. Case Description: We describe the case of a geriatric male patient who was admitted for new-onset visual hallucinations and other neuropsychiatric symptoms which began five days prior to admission. His lab work was unremarkable, and a computed tomography (CT) scan of the brain demonstrated small vessel ischemic disease. There was clinical suspicion for seizures, and electroencephalogram (EEG) monitoring showed focal seizure activity in the right hemisphere. He received a brain magnetic resonance imaging (MRI) which was suspicious for encephalitis. Various etiologies were considered, and he received an extensive workup including cerebrospinal fluid evaluation. Ultimately, he improved with empiric antiviral treatment added alongside multiple antiepileptic agents. The seizure control and resolution of symptoms with antiviral treatment, in addition to the findings of his central nervous system (CNS) workup, confirmed the presumptive diagnosis of HSV encephalitis. Conclusions: Understanding the multifactorial causes of neuropsychiatric symptoms is important in determining an appropriate workup. The acute onset of specific symptoms in our patient increased suspicion for a structural neurological process. His initial presentation could largely be explained by the vascular dementia and epileptiform activity that were discovered during hospitalization. However, his refractory seizures were suggestive of another underlying etiology. The localization of his seizures and MRI findings were suggestive of HSV encephalitis despite negative HSV polymerase chain reaction (PCR). A patient may benefit from antiviral treatment when the clinical picture is consistent with HSV encephalitis even in the setting of negative serological studies. Clinicians should also be mindful of false negatives on serological tests.

Positron Emission Tomography (PET) in presurgical planning of anterior temporal lobectomy: A systematic review of efficacy and limitations.

INTRODUCTION: Temporal lobe epilepsy (TLE), a debilitating neurological disorder, necessitates refined diagnostic and treatment strategies. This comprehensive review appraises the potential of positron emission tomography (PET) in enhancing the presurgical planning of Anterior Temporal Lobectomy (ATL) for patients afflicted with TLE. METHODS: A comprehensive literature search was conducted using the PubMed, SCOPUS, and ScienceDirect databases from 1985 to 2022, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies investigating PET and ATL. This review studied a range of radiotracers, including FDG, H2O, FMZ, MPPF, and FCWAY, analyzing their efficacy in detecting epileptogenic foci, establishing resection boundaries, and predicting postoperative outcomes. The study paid special attention to cases where MRI findings were inconclusive. RESULTS: A total of 52 studies were included in the final analysis. Our analysis revealed that FDG-PET imaging was instrumental in identifying seizure foci and predicting postoperative results. It exhibited significant value in situations where structural abnormalities were absent on MRI scans. Furthermore, newer radiotracers such as 5-HT1A antagonists, FCWAY and MPPF, presented promising potential for localizing seizure foci, particularly in MRI-negative TLE, despite their comparatively limited current usage. CONCLUSION: PET imaging, although challenged by issues such as radiation exposure, limited accessibility, and high costs, offers considerable promise. Integration with other imaging modalities, such as EEG and MRI, has contributed to improved localization of epileptogenic foci and subsequently, enhanced surgical outcomes. Further research must focus on establishing the relative efficacy and optimal combinations of these radiotracers in the orchestration of ATL surgical planning and prognostication of postoperative outcomes for TLE patients. Encouragingly, these advancements hold the potential to revolutionize the management of TLE, delivering a better quality of life for patients.

Hunger, Satiety, and Their Vulnerabilities.

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Stereotactic radiosurgery for medically refractory non-lesional epilepsy: A case-based Radiosurgery Society (RSS) practice review.

INTRODUCTION: Medically refractory epilepsy (MRE) occurs in about 30 % of patients with epilepsy, and the treatment options available to them have evolved over time. The classic treatment for medial temporal lobe epilepsy (mTLE) is anterior temporal lobectomy (ATL), but an initiative to find less invasive options has resulted in treatments such as neuromodulation, ablative procedures, and stereotactic radiosurgery (SRS). SRS has been an appealing non-invasive option and has developed an increasing presence in the literature over the last few decades. This article provides an overview of SRS for MRE with two example cases, and we discuss the optimal technique as well as the advantages, alternatives, and risks of this therapeutic option. CASES: We present two example cases of patients with MRE, who were poor candidates for invasive surgical treatment options and underwent SRS. The first case is a 65-year-old female with multiple medical comorbidities, whose seizure focus was localized to the left temporal lobe, and the second case is a 19-year-old male with Protein C deficiency and medial temporal lobe sclerosis. Both patients underwent SRS to targets within the medial temporal lobe, and both achieve significant improvements in seizure frequency and severity. DISCUSSION: SRS has generally been shown to be inferior to ATL for seizure reduction in medically refractory mTLE. However, there are patients with epilepsy for which SRS can be considered, such as patients with medical comorbidities that make surgery high risk, patients with epileptogenic foci in eloquent cortex, patients who have failed to respond to surgical management, patients who choose not to undergo surgery, and patients with geographic constraints to epilepsy centers. Patients and their physicians should be aware that SRS is not risk-free. Patients should be counseled on the latency period and monitored for risks such as delayed cerebral edema, visual field deficits, and radiation necrosis.

Wnt Signaling Modulators Exhibit Neuroprotective Effects via Combating Astrogliosis and Balancing Synaptic Density at Early and Late Stage Temporal Lobe Epilepsy.

Temporal Lobe Epilepsy (TLE) is a severe neurological condition characterized by recurrent seizures that often do not respond well to available anti-seizure medications. TLE has been associated with epileptogenesis, a process that starts during the latent period following a neurologic insult and is followed by chronic phase. Recent research has linked canonical Wnt signaling to the pathophysiology of epileptogenesis and TLE. Our previous study demonstrated differential regulation of canonical Wnt signaling during early and late stage post status epilepticus (SE) induction. Building on these findings, our current study utilized Wnt modulators: GSK-3ß inhibitor 6-bromoindirubin-3'-oxime (6-Bio) and disheveled inhibitor niclosamide and investigated their impact on canonical Wnt signaling during the early (30 days) and later stages (60 days) following SE induction. We assessed several parameters, including seizure frequency, astrogliosis, synaptic density, and neuronal counts in hippocampal tissue. We used immunohistochemistry and Nissl staining to evaluate gliosis, synaptic density, and neuronal counts in micro-dissected hippocampi. Western blotting was used to examine the expression of proteins involved in canonical Wnt/ß-catenin signaling, and real-time PCR was conducted to analyze their relative mRNA expression. Wnt modulators, 6-Bio and Niclosamide were found to reduce seizure frequency and various other parameters including behavioral parameters, hippocampal morphology, astrogliosis and synaptic density at different stages of TLE.

PPARß/δ Agonist GW0742 Modulates Microglial and Astroglial Gene Expression in a Rat Model of Temporal Lobe Epilepsy.

The role of astroglial and microglial cells in the pathogenesis of epilepsy is currently under active investigation. It has been proposed that the activity of these cells may be regulated by the agonists of peroxisome proliferator-activated nuclear receptors (PPARs). This study investigated the effects of a seven-day treatment with the PPAR ß/δ agonist GW0742 (Fitorine, 5 mg/kg/day) on the behavior and gene expression of the astroglial and microglial proteins involved in the regulation of epileptogenesis in the rat brain within a lithium-pilocarpine model of temporal lobe epilepsy (TLE). TLE resulted in decreased social and increased locomotor activity in the rats, increased expression of astro- and microglial activation marker genes (Gfap, Aif1), pro- and anti-inflammatory cytokine genes (Tnfa, Il1b, Il1rn), and altered expression of other microglial (Nlrp3, Arg1) and astroglial (Lcn2, S100a10) genes in the dorsal hippocampus and cerebral cortex. GW0742 attenuated, but did not completely block, some of these impairments. Specifically, the treatment affected Gfap gene expression in the dorsal hippocampus and Aif1 gene expression in the cortex. The GW0742 injections attenuated the TLE-specific enhancement of Nlrp3 and Il1rn gene expression in the cortex. These results suggest that GW0742 may affect the expression of some genes involved in the regulation of epileptogenesis.

Abnormal Weakening of DNA Methylation around the SLC6A1 Gene Promoter in Temporal Lobe Epilepsy.

BACKGROUND: The solute carrier (SLC) superfamily, which transports solutes across biological membranes, includes four members (SLC2A1, SLC6A1, SLC9A64, and SLC35A2) that have been linked to epilepsy. This study sought to examine the DNA methylation patterns near the promoters of these genes in temporal lobe epilepsy (TLE), as DNA methylation is a crucial epigenetic modification that can impact gene expression. METHODS: The study comprised 38 individuals with TLE and 38 healthy controls. Methylation experiments were performed using peripheral blood, while demethylation experiments were carried out using SH-SY5Y cells with the DNA methylation inhibitor decitabine. RESULTS: A significant difference was observed in the DNA methylation rate of SLC6A1 between TLE patients and controls, with TLE patients showing a lower rate (4.81% vs. 5.77%, p = 0.0000), which remained significant even after Bonferroni correction (p = 0.0000). Based on the hypomethylated SLC6A1 in TLE, a predictive model was established that showed promise in distinguishing and calibrating TLE. In the TLE group, there were differences in DNA methylation rates of SLC6A1 between the young patients and the older controls (4.42% vs. 5.22%, p = 0.0004). A similar trend (p = 0.0436) was noted after adjusting for sex, age at onset, and drug response. In addition, the study found that DNA methylation had a silencing impact on the expression of the SLC6A1 gene in SH-SY5Y cells, which were treated with decitabine at a set dose gradient. CONCLUSIONS: The evidence suggests that lower methylation of SLC6A1 may stimulate transcription in TLE, however, further investigation is necessary to confirm the exact mechanism.

The Effect of Stereoelectroencephalography on the Long-Term Outcomes of Different Side Anterior Temporal Lobectomy: A Single-Center Retrospective Study.

PURPOSE: Anterior temporal lobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE), and Stereoelectroencephalography (SEEG) plays a critical role in precisely localizing the epileptogenic zone (EZ). This study aimed to explore the effect of SEEG on the long-term outcomes of different side ATL. METHODS: From March 2012 to February 2020, a retrospective analysis was conducted on 231 TLE patients who underwent standard ATL surgery. According to the surgical sides and the utilization of SEEG during preoperative evaluation, the patients were categorized into 4 groups, with a follow-up period exceeding 2 years. RESULTS: Among the 231 TLE patients, the probability of being seizure-free 2 years after the surgery was 80.52%, which decreased to 65.65% after 5 years. There was no significant difference in outcomes between SEEG and non-SEEG patients. For overall and non-SEEG patients, there was no significant difference in short-term outcomes between different surgical sides. However, the long-term outcomes of right ATL patients were significantly better than left. Interestingly, for patients who underwent SEEG, there was no significant difference in both short-term and long-term outcomes between different surgical sides. CONCLUSIONS: Some TLE patients encounter challenges in localizing the EZ through noninvasive evaluation, necessitating the use of SEEG for precise localization. Furthermore, their seizure outcomes after surgery can be the same with the patients who have a clear EZ in noninvasive evaluation. And SEEG patients can achieve a more stable long-term prognosis than non-SEEG patients.

Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats.

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.

Laser interstitial thermal therapy versus open surgery for mesial temporal lobe epilepsy: A systematic review and meta-analysis.

Epilepsy surgery offers a vital treatment option for drug-resistant mesial temporal lobe epilepsy (mTLE), with Temporal Lobe Resection (TLR) and Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) being fundamental interventions. This meta-analysis specifically examines seizure outcomes at extended follow-up periods exceeding 24 months, visual field deficits as measured by perimetry, and complication rates both overall and categorized based on duration as minor (transient <6 months) or major (persistent >6 months) to inform clinical decision-making. For seizure freedom, TLR was superior, with 72.5% [65.6%, 78.5%] of patients achieving postoperative seizure freedom compared to 57.1% [51.2%, 62.7%] for MRgLITT (P-value <0.01). Visual field deficits were observed in 79.4% [59.5%, 91.0%] of TLR patients and 49.8% [23.6%, 76.0%] of MRgLITT patients, a difference not reaching statistical significance (P-value: 0.08). Overall complication rates were 11.4% [7.4%, 17.2%] for TLR and 6.5% [3.3%, 12.3%] for MRgLITT (P-value 0.15). Major complications occurred in 2.0% [1.1%, 3.09%] of TLR cases and 2.7% [1.4%, 5.2%] of MRgLITT cases (P-value 0.54), while minor complications were significantly more frequent with TLR at 9.9% [6.4%, 15.0%] versus MRgLITT's 4.1% [1.9%, 8.4%] (P-value 0.04). MRgLITT had a more favorable outcome regarding confrontation naming while more studies are needed regarding verbal memory to be able to draw firm conclusions. TLR provides superior seizure freedom but comes with an increased risk of transient complications. Although there was no statistical significance in visual field deficits, the trend suggests a higher frequency with TLR. The study's extensive data analysis, including rigorous sensitivity checks, ensures the robustness of these conclusions, reflecting a comprehensive analysis of the available data at this time point.

Epileptic variant in the spectrum of Alzheimer's disease - practical implications.

Alzheimer's disease (AD) is known to be associated with an increased risk of epilepsy, which is not exclusively related to the late stage of the disease - when a major cognitive impairment is observed, previously known as the dementia stage - but also to its prodromal stage (mild cognitive impairment). Moreover, published case reports and cohorts have shown that epilepsy may occur even earlier, at the preclinical stage of AD: Epileptic seizures may therefore be the sole objective manifestation of the disease. Such a situation is called the epileptic variant of AD (evAD). EvAD is one of the etiologies of late-onset epilepsy, which means that it carries a risk of later progression to dementia and that it can only be diagnosed by assessing amyloid and tau biomarkers. However, evAD is a window of therapeutic opportunity that is probably optimal for preventing, through antiseizure medication treatment, the accelerated cognitive decline associated with AD-related brain hyperexcitability (manifested by seizures or interictal epileptiform activities).

Impact of seizure outcome and extent of neocortical resection on emotional well-being in patients with epilepsy one year after temporal lobe surgery.

BACKGROUND: Seizure frequency and cognitive function are common parameters in assessing epilepsy surgery outcomes. However, psychobehavioral outcomes, such as symptoms of depression and quality of life (QOL), have not found equal attention yet. OBJECTIVE: To assess the effect of seizure frequency, the extent of resection, and cognitive function on the psychobehavioral outcome of patients after temporal lobe surgery for pharmacoresistant epilepsy. METHODS: We retrospectively reviewed all consecutive patients who underwent surgery for intractable temporal lobe epilepsy between 09/2015 and 07/2019. We examined seizure outcome, surgical plan, resection volume, cognitive functions, and psychobehavioral outcome. RESULTS: This study included 77 patients (31 males, 46 females) who underwent temporal lobe surgery. One year after surgery, 53 patients (68.8 %) were completely seizure-free (Engel IA) and 92.2 % of patients showed a worthwhile improvement in seizure frequency (Engel I-III). Resection volume was significantly negatively correlated with QOL (r =  - 0.284, p = 0.041). However, after controlling for the effect of seizure outcome, no significant correlation remained. Patients with a worthwhile improvement in seizure frequency showed significantly fewer symptoms of depression (p = 0.024) and a significantly higher QOL (p = 0.012) one year after surgery. The differences in symptoms of depression (p = 0.044) and QOL (p = 0.030) between patients with and without improvements in seizure frequency remained significant after controlling for the effect of resection volume. After procedures sparing the amygdala and hippocampus (neocortical resection), patients presented significantly fewer symptoms of depression (p = 0.044) and significantly better QOL (p = 0.008) than patients after procedures involving mesial-temporal structures, independent of the resection volume, and after controlling for the side of the procedure (dominant vs. non-dominant). After also controlling for seizure outcome, the difference remained for QOL (p = 0.014) but not for symptoms of depression. CONCLUSIONS: A patient's emotional well-being one year after surgery for pharmacoresistant temporal lobe epilepsy strongly depends on their seizure outcome. As an individual factor, the extent of neocortical resection negatively affects postsurgical emotional well-being, but a favorable seizure outcome outweighs this effect, independent of the resection volume. A favorable seizure outcome even outweighs the negative effects of procedures involving mesial-temporal structures on symptoms of depression.

TRPV4 Blockage Inhibits the Neurogenesis in the Adult Hippocampal Dentate Gyrus Following Pilocarpine­Induced Status Epilepticus.

Aberrant neurogenesis in the adult hippocampal dentate gyrus (DG) contributes to synapse remodeling during temporal lobe epilepsy (TLE). Transient receptor potential vanilloid 4 (TRPV4) is involved in the pathogenesis of TLE. Activation of TRPV4 can modulate neurogenesis in the adult hippocampal DG. The present study examined whether TRPV4 is responsible for the aberrant neurogenesis in the adult hippocampal DG during TLE. Herein, administration of a TRPV4-specific antagonist, HC-067047, attenuated the enhanced neural stem cell proliferation in the adult hippocampal DG in mice following pilocarpine­induced status epilepticus (PISE). HC-067047 reduced the heightened hippocampal protein levels of cyclin-dependent kinase (CDK) 2, CDK6, cyclin E1, cyclin A2, and phosphorylated retinoblastoma (p-Rb) observed following PISE. Meanwhile, HC-067047 inhibited the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) pathways that were enhanced and responsible for the increased proliferation of stem cells and higher levels of CDKs, cyclins, and p-Rb protein. HC-067047 reduced the 28-day-old BrdU+ cells but increased the ratio of 28-day-old BrdU+ cells to 1-day-old BrdU+ cells, indicating that TRPV4 blockage reduced the number but increased the survival rate of newborn cells following PISE. Finally, HC-067047 increased the Akt signaling that was inhibited and responsible for the decreased survival rate of newborn cells following PISE. It is concluded that TRPV4 blockage inhibits stem cell proliferation in the hippocampal DG following PISE, likely through inhibiting ERK1/2 and p38 MAPK signaling to decrease cell cycle-related protein expression, and increases newborn cell survival rate likely through increasing phosphoinositide 3 kinase-Akt signaling.

Expanded gray matter atrophy with severity stages of adult comorbid insomnia and sleep apnea.

OBJECTIVE: To investigate gray matter volume (GMV) changes in patients with comorbid insomnia and sleep apnea (COMISA) of differing severity and relationships between GMV alterations and clinical measures. METHODS: Thirty-four COMISA patients and 24 healthy controls (HC) were recruited. All patients underwent structural MRI and completed measures related to respiration, sleep, mood, and cognition. COMISA patients were further divided into a mild and moderate COMISA (MC) and a severe COMISA (SC) group. Changes in GMV of COMISA patients were investigated via VBM. The voxel-wise differences in GMV were compared between HC group and COMISA group. Analysis of covariance (ANCOVA) was performed on individual GMV maps in MC, SC, and HC groups to further investigate effects of different stages of COMISA severity on GMV. Partial correlation analysis was then performed to analyze relationships between altered GMV and clinical measures. RESULTS: GMV atrophy was mainly located in the temporal lobes and fusiform gyrus in COMISA group. The post-hoc analysis of the ANCOVA revealed temporal lobes and fusiform gyrus atrophy in MC and SC groups compared to HC and the temporal lobe atrophy was expanded in SC group based on cluster size. Moreover, the SC group showed GMV atrophy of the right amygdala compared to both MC and HC groups. Partial correlation analysis revealed positive relationships between the GMV and mood-and cognitive-related measures and negative correlation between GMV and respiration measure. CONCLUSIONS: Our findings showed GMV atrophy expansion from temporal lobe to limbic system (right amygdala) as severity stages increase in COMISA patients. These findings contribute to our understanding of neurobiological mechanisms underlying different stages of severity in COMISA patients.

Single-neuron representation of nonsymbolic and symbolic number zero in the human medial temporal lobe.

The number zero holds a special status among numbers, indispensable for developing a comprehensive number theory.1,2,3,4 Despite its importance in mathematics, the neuronal foundation of zero in the human brain is unknown. We conducted single-neuron recordings in neurosurgical patients5,6,7 while they made judgments involving nonsymbolic number representations (dot numerosity), including the empty set, and symbolic numbers (Arabic numerals), including numeral zero. Neurons showed responsiveness to either the empty set or numeral zero, but not both. Neuronal activity to zero in both nonsymbolic and symbolic formats exhibited a numerical distance effect, indicating that zero representations are integrated together with countable numerosities and positive integers at the low end of the number line.8,9 A boundary in neuronal coding existed between the nonsymbolic empty set and small numerosities, correlating with the relative difficulty in discriminating numerosity zero behaviorally. Conversely, no such boundary was found for symbolic zero activity, suggesting that symbolic representations integrate zero with other numerals along the number line, reconciling its outlier role. The status of zero as a special nonsymbolic numerical quantity is reflected in the activity of neurons in the human brain, which seems to serve as a scaffold for more advanced representations of zero as a symbolic number.