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INTRODUCTION: Emerging evidence illustrates that temporal lobe epilepsy (TLE) involves network disruptions represented by hyperexcitability and other seizure-related neural plasticity. However, these associations are not well-characterized. Our study characterizes the whole brain white matter connectome abnormalities in TLE patients compared to healthy controls (HCs) from the prospective Epilepsy Connectome Project study. Furthermore, we assessed whether aberrant white matter connections are differentially related to cognitive impairment and a history of focal-to-bilateral tonic-clonic (FBTC) seizures. METHODS: Multi-shell connectome MRI data were preprocessed using the DESIGNER guidelines. The IIT Destrieux gray matter atlas was used to derive the 162 × 162 structural connectivity matrices (SCMs) using MRTrix3. ComBat data harmonization was applied to harmonize the SCMs from pre- and post-scanner upgrade acquisitions. Threshold-free network-based statistics were used for statistical analysis of the harmonized SCMs. Cognitive impairment status and FBTC seizure status were then correlated with these findings. RESULTS: We employed connectome measurements from 142 subjects, including 92 patients with TLE (36 males, mean age = 40.1 ± 11.7 years) and 50 HCs (25 males, mean age = 32.6 ± 10.2 years). Our analysis revealed overall significant decreases in cross-sectional area (CSA) of the white matter tract in TLE group compared to controls, indicating decreased white matter tract integrity and connectivity abnormalities in addition to apparent differences in graph theoretic measures of connectivity and network-based statistics. Focal and generalized cognitive impaired TLE patients showcased higher trend-level abnormalities in the white matter connectome via decreased CSA than those with no cognitive impairment. Patients with a positive FBTC seizure history also showed trend-level findings of association via decreased CSA. CONCLUSIONS: Widespread global aberrant white matter connectome changes were observed in TLE patients and characterized by seizure history and cognitive impairment, laying a foundation for future studies to expand on and validate the novel biomarkers and further elucidate TLE's impact on brain plasticity.

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This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration.

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Transient receptor potential canonical 3 (TRPC3) channels are important in regulating Ca2+ homeostasis and have been implicated in the pathophysiology of chemically induced seizures. Inherited seizure susceptibility in genetically epilepsy-prone rats (GEPR-3s) has been linked to increased voltage-gated Ca2+ channel currents in the inferior colliculus neurons, which can affect intraneuronal Ca2+ homeostasis. However, whether TRPC3 channels also contribute to inherited seizure susceptibility in GEPR-3s is unclear. This study investigated the effects of JW-65, a potent and selective inhibitor of TRPC3 channels, on acoustically evoked seizure susceptibility in adult male and female GEPR-3s. These seizures consisted of wild running seizures (WRSs) that evolved into generalized tonic-clonic seizures (GTCSs). The results showed that acute administration of low doses of JW-65 significantly decreased by 55-89% the occurrence of WRSs and GTCSs and the seizure severity in both male and female GEPR-3s. This antiseizure effect was accompanied by increased seizure latency and decreased seizure duration. Additionally, female GEPR-3s were more responsive to JW-65's antiseizure effects than males. Moreover, JW-65 treatment for five consecutive days completely suppressed acoustically evoked seizures in male and female GEPR-3s. These findings suggest that inhibiting TRPC3 channels could be a promising antiseizure strategy targeting Ca2+ signaling mechanisms in inherited generalized tonic-clonic epilepsy.

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ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

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OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is the least studied syndrome within the idiopathic generalized epilepsy (IGE) spectrum. We characterize a large cohort of adult patients with GTCA to understand natural history and drug responsiveness. METHODS: In this retrospective single-center study using our epilepsy electronic record, we evaluated clinical characteristics, seizure outcomes, anti-seizure medication (ASM) response including seizure recurrence after ASM withdrawal, and sex differences in a cohort of GTCA patients aged ≥17 years. RESULTS: Within a cohort of 434 IGE patients, 87 patients (20 %) with GTCA were included. The mean age was 34.9 years (range 17-73 years). Forty-six patients (52.8 %) were females. Seventy-two patients (82.8 %) were seizure-free and 15 (17.2 %) had active epilepsy over the previous 12 months. Thirty-four patients (39.1 %) had ≤5 lifetime seizures, aligning with a prior definition of 'oligoepilepsy'. Sixty-five patients (74.7 %) were treated with monotherapy, 19 (21.8 %) were treated with polytherapy, and three were not taking any ASM. Levetiracetam (37.9 %) was the most commonly prescribed ASM, followed by lamotrigine (32.1 %) and valproate (31 %). Seventeen patients (19.5 %) attempted to withdraw their ASM. The rate of seizure recurrence after ASM withdrawal was 88.2 % (15/17), including two patients who relapsed more than 20 years after ASM discontinuation. Females had more seizures in their lifetime and had trialed more ASM compared to males. SIGNIFICANCE: GTCA has a relatively good prognosis, with most patients becoming seizure-free on monotherapy. The high rate of seizure recurrence after ASM withdrawal supports lifetime seizure susceptibility. We found potential sex differences in seizure outcomes and ASM response, although further research is needed to validate this finding.

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AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

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A key aspect of management of genetic generalized epilepsy involves assessing seizure control and deciding suitability for driving motor vehicles. We surveyed child neurologists and pediatric epileptologists on key questions that practitioners should ask prior to providing clearance for driving. The results showed a wide variability of practice among responders. We propose a likely appropriate process necessary to determine seizure control.

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AIM: Electroencephalogram (EEG) is specific, but not sensitive, for the diagnosis of epilepsy. This study aimed to correlate the clinico-electrographic and radiological features of seizure disorders in children attending a tertiary care centre in northern India. METHODS: Children aged between one to 18 years with seizure episodes were included. Clinical details, including historical as well as physical findings, were evaluated along with EEG and neuroimaging (Magnetic resonance imaging). Details were noted on pre-designed proforma. Variables were analysed by using appropriate statistical methods. RESULTS: A total of 110 children with seizures were enrolled in the study. Male to female ratio was 1.6: 1, and the mean age of the study children was 8 years. The majority of the children were symptomatic for more than one year. The most common seizure type was Generalised Tonic Clonic Seizure (GTCS), and Hypoxic-ischemic Encephalopathy (HIE) sequelae was the most commonly attributed etiology, followed by neurocysticercosis. EEG and neuroimaging findings were found to correlate well with seizure semiology from history. The incidence of febrile seizures was 10% in this study, with nearly three-fourths of them being simple febrile seizures. CONCLUSION: Microcephaly and developmental delay were the most distinctive clinical correlates in children with seizures. There was a fair agreement between the types of seizures described in history and depicted on EEG with Cohen's kappa of 0.4. Also, there was a significant association between the type of seizures on EEG and the duration of symptoms.

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Top of the basilar syndrome (TBS) is defined as the presence of multiple ischemic lesions on magnetic resonance image (MRI) including more than two territories supplied by branches of the distal portion of the basilar artery, causing symptoms such as dizziness, diplopia, ataxia, and acute cognitive decline that can lead to quadriplegia and death. Diagnosing TBS is challenging because it can mimic other conditions such as thalamic hemorrhages or vertebrobasilar ischemia, and requires advanced imaging. Although the prognosis for these patients is poor, rehabilitation is essential for their recovery. This case describes a healthy 28-year-old woman who presented with headache, vomiting, and tonic-clonic seizures sent to the hospital with a stroke diagnosis.

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OBJECTIVE: Perampanel is an oral anti-seizure medication, which is approved in Japan for focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, as monotherapy/adjunctive therapy in patients aged 4 years and older. Treatment for generalized tonic-clonic seizures as adjunctive therapy in patients aged 12 years and older is approved as well. We evaluated the feasibility of intravenous (IV) administration of perampanel as an alternative to oral administration. METHODS: Study 240 (NCT03754582) was an uncontrolled, open-label study of IV perampanel, conducted in 21 Japanese patients with epilepsy who received a stable dose of 8-12 mg/day of oral perampanel. Patients received 30-minute IV infusions at equivalent daily doses of oral perampanel for 4 days, then were switched back to oral perampanel. Safety, tolerability, plasma concentration, and maintenance of efficacy throughout the transition between IV and oral dosing of perampanel were assessed. As supportive data, a subgroup analysis was also conducted using data from healthy Japanese subjects (n = 18) who were enrolled in Study 050 (NCT03376997) investigating the pharmacokinetics and safety of IV perampanel in healthy subjects who received an IV infusion (30-, 60-, or 90-minute) of perampanel 12 mg and a single oral administration of perampanel 12-mg tablet. RESULTS: In Study 240, the transition between 30-minute IV and oral perampanel dosing was associated with a ≤1.4-fold increase in the mean change in maximum observed concentration of perampanel. Seizure outcomes demonstrated no considerable changes in efficacy before, during, or after 30-minute IV dosing of perampanel. The safety profiles were similar between IV and oral formulations. In Study 050, the pharmacokinetics of 30- or 60-minute IV infusion of perampanel further support the interchangeability between oral and IV formulations in the Japanese subjects. SIGNIFICANCE: These results support that 30-minute IV perampanel may be a potential short-term alternative to oral formulations for patients with epilepsy.

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Polycystic kidney disease (PKD) is the most common hereditary disorder of kidneys. In adults, PKD1 gene mutation almost always signifies its subtype, autosomal dominant polycystic kidney disease (ADPKD), or adult polycystic kidney disease. ADPKD is a multisystemic disorder giving rise to renal and extra-renal manifestations. The renal shutdown is the most feared renal complication while the development of intracranial aneurysms is considered the most lethal extra-renal feature. This can be attributed to the increased risk of rupture associated with aneurysms leading to a condition called subarachnoid hemorrhage (SAH). While being notorious for the subtle situations SAH often leads to, its association with the onset of seizures is a matter of high clinical significance. We present a patient with a kidney disorder (ADPKD) that has led to the onset of epilepsy. Five years after the diagnosis of ADPKD, he developed an aneurysm in the right internal carotid artery, for which he was treated conservatively. After four months, he presented with the onset of symptoms of SAH, which was confirmed by computed tomography angiography. Clipping was unable to be performed, and the patient was treated conservatively, this time as well. Recently, the patient presented with the onset of generalized tonic-clonic seizures, unable to be controlled with single anti-epileptics. He was stabilized by dual intravenous antiepileptics but on further workup, he was found to have a recurrence of a berry aneurysm for which he was referred to a neurosurgeon for a clipping procedure to be performed. The operation was successful, but the patient was still found to be an epileptic for which he was discharged with a long-term course of double anti-epileptics.

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Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2). This disease caused one of the largest pandemics in human history. During the second COVID-19 surge, the Indian government faced the threat posed by the growing COVID-19 pandemic by informing citizens and encouraging the use of preventive measures such as face masks, hand sanitization, personal protective equipment, quarantines, and vaccination. Vaccination is an effective prophylactic intervention in public health, and COVID-19 vaccines have been developed to achieve immunity against viruses and stop the transmission of infection. However, vaccines have side effects, and by early 2021, many doubts arose regarding COVID-19 vaccinations. Few people were not taking immunization because post-immunization adverse events were reported. We are reporting a case of seizures after immunization with Covaxin.

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Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400 mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded that G. tiliaefolia showed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

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Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome that is being increasingly recognized due to the advancements in brain imaging, specifically MRI. This syndrome is characterized by symptoms including, but not limited to, headache, seizures, altered mental status, and vision loss. There are various underlying etiologies which lead to PRES occurrence; the etiology of focus in this report is preeclampsia and eclampsia. PRES is associated with the development of various types of intracerebral hemorrhage which can lead to detrimental and even fatal consequences in a patient. In our case, a 22-year-old female developed PRES within one week postpartum, which was complicated by parenchymal hemorrhage development in the fronto-parietal lobe. MRI findings were characteristic for PRES with multiple subcortical hyperintensities within the bilateral occipital lobe. The patient improved symptomatically after management with intravenous fluids, antihypertensives, antiepileptics, and antibiotics. This report aims to explore the association between preeclampsia/eclampsia (PE/E) and PRES and underscore the importance of prompt diagnosis and treatment, which can lead to recovery within a week and significantly reduce morbidity and mortality.

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Mapping neuronal circuits that generate focal to bilateral tonic-clonic seizures is essential for understanding general principles of seizure propagation and modifying the risk of death and injury due to bilateral motor seizures. We used novel techniques developed over the past decade to study these circuits. We propose the general hypothesis that at the mesoscale, seizures follow anatomical projections of the seizure focus, preferentially activating more excitable neurons.

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OBJECTIVE: This study was undertaken to evaluate perampanel (PER) when used under real-world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study. METHODS: The multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic-clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation. RESULTS: The Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months. SIGNIFICANCE: This subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad-spectrum antiseizure medication for the treatment of IGE.

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Nitrofurantoin and cephalexin are commonly used antibiotics for treating urinary tract infections. Hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been reported as a rare side effect of nitrofurantoin but has never been a reported side effect of cephalexin. We report a case of a 48-year-old female who developed severe hyponatremia complicated by generalized tonic-clonic seizures after a course of antibiotics (nitrofurantoin followed by cephalexin) used for treating a urinary tract infection. She presented to the emergency department with a one-week history of dizziness, nausea, fatigue, and listlessness. She also had a two-week history of persistent urinary frequency despite completing a course of nitrofurantoin followed by a course of cephalexin. While in the emergency department waiting room, she had two episodes of generalized tonic-clonic seizures. Immediate post-ictal blood test results revealed severe hyponatremia and lactic acidosis. Results were consistent with severe SIADH and she was subsequently managed with hypertonic saline and fluid restriction. She was discharged after 48 hours of admission when her serum sodium levels normalized. Though we believe that nitrofurantoin was the culprit drug, we still asked the patient to avoid future use of both nitrofurantoin and cephalexin. Healthcare providers need to be aware of antibiotic-induced SIADH when assessing patients with hyponatremia.

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Damage to the blood-brain barrier (BBB) may result from on-going neuroinflammation, which can lead to leakage of blood components, such as leukocytes and serum proteins, into the brain, resulting in disturbed brain homeostasis. The aim of the project was to examine the involvement of modulatory proteins in the processes of BBB integration after epileptic seizures. We investigated serum changes in the levels of MMP-2 and MMP-7 and its inhibitors after seizures in epilepsy patients. Concentrations of these proteins were measured by ELISA in 50 patients at 1-3, 24, and 72 h after generalized tonic-clonic seizures and once in participants of the control group. The level of MMP-2 in serum was slightly higher after seizures (at 1-3 h time point), but the difference was not statistically significant. The levels of trombospondine (TSP) - 1 and - 2 were decreased at 1-3 h after seizures. The expression of TIMP-2 was increased 1 and 24 h after seizures. There were no significant changes in the level of α2-macroglobulin and MMP-7. Changes in the expression of both specific and non-specific inhibitors indicate the initiation of repair processes of the blood-brain barrier and improvement of its integrity. Since we performed serum analysis, further studies are necessary to investigate the correlation with the expression of the investigated markers in the brain. Perhaps this will allow for the identification of new biomarkers associated with epileptic seizures.

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OBJECTIVE: We aimed to determine whether alterations in spontaneous regional brain activity in those with generalized tonic-clonic seizures (GTCS) and focal to bilateral tonic-clonic seizures (FBTCS) and explore whether the alterations could be used as biomarkers to classify disease subtypes through support vector machine analysis (SVM). METHODS: The fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) from resting-state functional magnetic resonance imaging (rs-fMRI) data were extracted from 57 patients with GTCS, 35 patients with FBTCS, and 50 age-matched and sex-matched normal controls (NCs) using the DPARSF 5.0 toolbox. Between-group comparisons were adjusted for covariates (age, sex, and equipment). Correlation analyses between imaging biomarkers and the frequency or duration of seizure activity were calculated using partial correlations. The differential imaging indicators, age, and sex were considered as the discriminative features in the SVM to evaluate classification performance. RESULTS: The patients with GTCS showed lower fALFF values (voxel p < 0.001, cluster p < 0.05, Gaussian random field corrected, GRF corrected) in the right postcentral gyrus and precentral gyrus and lower ReHo values (GRF corrected) in the middle temporal gyrus than the NCs. The patients with FBTCS showed higher fALFF (GRF corrected) values in the right postcentral and precentral gyrus and higher ReHo (GRF corrected) values in the right postcentral gyrus. Both fALFF (GRF corrected) and ReHo (GRF corrected) values were lower in the right postcentral gyrus and precentral gyrus in the GTCS group than in the FBTCS group. In patients with FBTCS, fALFF values in the right postcentral and precentral gyrus were positively correlated with duration (r = 0.655, p = 0.008, Bonferroni corrected) in the low-duration group, and ReHo values in the right postcentral gyrus were positively correlated with frequency (r = 0.486, p = 0.022, uncorrected) in the low-frequency group. SVM results showed receiver operating characteristic curves of 0.89, 0.87, and 0.76 for the classification between GTCS and NC, between FBTCS and NC, and GTCS and FBTCS, respectively. SIGNIFICANCE: This study detected alterations in fALFF and ReHo in the postcentral gyrus and precentral gyrus in patients with GTCS and FBTCS, which might contribute to understanding the pathogenesis, disease classification, and clinical targeted therapy.

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The inferior colliculus (IC) is critical in initiating acoustically evoked alcohol withdrawal-induced seizures (AWSs). Recently, we reported that systemic inhibition of Ca2+ entry via the reverse mode activity of the Na+/Ca2+ exchanger (NCXrev) suppressed AWSs, suggesting remodeling of NCX expression and function, at least in the IC, the site of AWS initiation. Here, we probe putative changes in protein expression in the IC of NCX isoforms, including NCX type 1 (NCX1), 2 (NCX2), and 3 (NCX3). We also evaluated the efficacy of targeted inhibition of NCX1rev and NCX3rev activity in the IC on the occurrence and severity of AWSs using SN-6 and KB-R943, respectively. We used our well-characterized alcohol intoxication/withdrawal model associated with enhanced AWS susceptibility. IC tissues from the alcohol-treated group were collected 3 h (before the onset of AWS susceptibility), 24 h (when AWS susceptibility is maximal), and 48 h (when AWS susceptibility is resolved) following alcohol withdrawal; in comparison, IC tissues from the control-treated group were collected at 24 h after the last gavage. Analysis shows that NCX1 protein levels were markedly higher 3 and 24 h following alcohol withdrawal. However, NCX3 protein levels were only higher 3 h following alcohol withdrawal. The analysis also reveals that bilateral microinjections of SN-6 (but not KB-R7943) within the IC markedly suppressed the occurrence and severity of AWSs. Together, these findings indicate that NCX1 is a novel molecular target that may play an essential role in the pathogenesis and pathophysiology of AWSs.

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