Showing papers in "Acta epileptologica in 2022"
TL;DR: In this paper , a case of ASM-acquired long QT syndrome (LQTS) was diagnosed and relevant literature was reviewed to realize the clinical characteristics of LQTS caused by antiseizure medicines (ASMs), and to improve the prevention and management of ASCM-associated LQT syndrome.
Abstract: Abstract Background To realize the clinical characteristics of long QT syndrome (LQTS) caused by antiseizure medicines (ASMs), and to improve the prevention and management of ASM-acquired QT syndrome. Case presentation A case of ASM-acquired QT syndrome was diagnosed and relevant literature was reviewed. The case was a 7-year-old boy who presented with a sudden onset of panic followed by changes in consciousness, with or without convulsions, lasting from tens of seconds to 3 min. The patient then received antiepileptic treatment with valproic acid, levetiracetam and oxcarbazepine and was seizure free for about a year. However, on August 12, 2021, his illness flared up again. Electroencephalogram (EEG) showed the background activity was slow, and no obvious epileptic discharge was detected. But electrocardiogram (ECG) showed a surprisingly prolonged QT interval (770 ms). Torsades de Pointes was found during Holter monitoring, while electrolyte levels were normal. The ECG recordings gradually returned to normal after stopping ASMs. For literature search, only 21 related papers were obtained after reading titles and full-texts of 105 English-language papers retrieved using keywords "acquired QT interstitial syndrome/acquired Long QT Syndrome (aLQTS)" and "anti-epileptic seizure drugs/ASMs", in the databases of Wanfang, CNKI, Pubmed, and other databases, from publication year 1965 to October 26, 2021. There are 12 types of drug-acquired LQTS caused by ASMs, most of which are Na + blockers, but LQTS caused by oxcarbazepine had not been reported previously. Conclusions ASMs such as oxcarbazepine can cause acquired LQTS. When Na + or K + channel blockers are used clinically, ECG should be reviewed regularly and abnormal ECG should be intervened in time to reduce iatrogenic accidents in patients with epilepsy.
2 citations
TL;DR: In this paper , a meta-analysis showed that patients with epilepsy are at a significantly increased risk of deficits in social cognition, while TLE and FLE patients perform worse than those with eTLE/eFLE, without significant differences between FLE and TLE regarding ToM ability.
Abstract: Abstract Background The aim of this review is to (a) characterize social cognition impairments in the domains of emotion recognition (ER) and theory of mind (ToM) in patients with epilepsy and (b) to review assessment tools with a focus on their validity and usability in clinical practice. Methods An electronic search for clinical studies investigating social cognition in epilepsy populations vs healthy control subjects (HC) yielded 53 studies for the meta-analysis and descriptive review. Results Results suggest that (1) social cognition is significantly impaired in patients with temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE) and patients with epilepsy not originating within the temporal or frontal lobes including idiopathic generalized epilepsies (eTLE/eFLE); (2) there is no significant difference between eTLE/eFLE and TLE regarding ER, while TLE and FLE patients perform worse than those with eTLE/eFLE, without significant differences between FLE and TLE regarding ToM ability. A descriptive analysis of the most commonly used assessment tools and stimulus material in this field revealed a lack of ecological validity, usability, and economic viability for everyday clinical practice. Conclusions Our meta-analysis shows that patients with epilepsy are at a significantly increased risk of deficits in social cognition. However, the underlying multifactorial mechanisms remain unclear. Future research should therefore specifically address the impairment of processing and methodological problems of testing.
2 citations
TL;DR: In this paper , the authors described two cases of childhood absence epilepsy (CAE) who showed seizure disappearance after ethosuximide (ESM) drug eruption, suggesting the possibility that the epilepsy disappears due to immune responses to ASM.
Abstract: Abstract Background Recent studies suggest potential roles of immune response in the pathophysiology of epilepsy. Anti-seizure medications (ASMs) are known to have side effects of drug eruption caused by immune responses. A few reports in adults have demonstrated disappearance of seizures after an ASM drug eruption episode. In this paper, we described 2 cases of childhood absence epilepsy (CAE) who showed seizure disappearance after ethosuximide (ESM) drug eruption, suggesting the possibility that the epilepsy disappears due to immune responses to ASM. Case presentation Case 1 was an 8-year-old girl diagnosed with CAE. She was treated with valproate acid (VPA) initially, and then ESM was administered as an additional treatment. Her epileptic seizure disappeared 4 days after initiation of ESM. However, drug eruption appeared 1 week after the administration of ESM. Even after discontinuation of ESM administration, she maintains no seizure after the drug eruption. Case 2 was a 5-year-old boy diagnosed as CAE. He was treated with VPA initially, and ESM was administered additionally. Drug eruption appeared 1 month after the administration of ESM. Even after ESM was terminated, he maintained seizure freedom after the appearance of eruption. Conclusions Epileptic seizures may have been suppressed due to the immune responses caused by ASM eruption. Further studies are needed to elucidate the pathophysiologic effects of drug eruption on epilepsy through immune responses.
2 citations
TL;DR: In this article , a large multicenter study was conducted to investigate the efficacy of KD therapy in the treatment of infantile spasms, where patients were classified into different groups according to age, type of drug and whether glucocorticoid was used before initiation.
Abstract: Abstract Background Ketogenic diet (KD) therapy is one of the main treatments for drug-resistant epilepsy. However, the KD therapy has been applied in only a small number of infantile spasm cases. In this large multicenter study, we investigated the efficacy of KD therapy in the treatment of infantile spasms. Methods In this retrospective, multicenter cohort study, clinical data from main epilepsy centers were analyzed. Patients were classified into different groups according to age, type of drug and whether glucocorticoid was used before initiation of KD. Results From October 2014 to March 2020, 481 patients (308 males and 173 females) with infantile spasms were treated with the KD therapy. The age of the patients ranged from 2 months to 20 years, with a mean age of 1 year and 10 months. The number of anti-seizure medications (ASMs) used before KD initiation ranged 0–6, with a median of 3. In different time from initiation(1, 3, 6, and 12 months), the rates of seizure freedom after KD were 6.9, 11.6, 16.0 and 16.8%, respectively ( χ 2 = 27.1772, P < 0.0001). There was a significant difference in the rate of seizure freedom between 3 months and 1 month ( χ 2 = 6.5498, P = 0.0105) groups, and 6 months and 3 months ( χ 2 = 3.8478, P = 0.0498) groups, but not between 12 months and 6 months ( χ 2 = 0.1212, P = 0.7278) groups. The rates of effectiveness were 44.7, 62.8, 49.1 and 32.0% ( χ 2 = 93.2674, P < 0.0001), respectively. The retention rates were 94.0, 82.5, 55.7 and 33.1% ( χ 2 = 483.7551, P < 0.0001), correspondingly. The rate of effectiveness and the retention rate of KD were significantly different among the 1, 3, 6 and 12 months. KD treatment was the first choice in 25 patients (5.2%), 55 patients (11.4%) started KD after the failure of the first ASM, 158 patients (32.8%) started KD after the failure of the second ASM, 157 patients (32.6%) started KD after the failure of the third drug, and 86 patients (17.9%) started KD after the failure of the fourth and more. The KD effect was not related to the number of ASMs used before KD startup ( P > 0.05). Two hundred and eighteen patients (45.3%) failed to respond to corticotropin or glucocorticoid before initiation. There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure ( χ 2 = 0.8613, P = 0.8348). The rate of adverse events of KD in 1, 3, 6, and 12 months after KD initiation were 22.3, 21.7, 16.8 and 6.9%, respectively. The adverse events mainly occurred during the first 3 months of KD, and the main adverse events were gastrointestinal disturbance and constipation. Conclusions The efficacy of the KD treatment for infantile spasms was not affected by age, medication, and glucocorticoid use before initiation. KD is one of the effective treatments for infantile spasms. Trial registration ChiCTR-IIR-16008342. Registered on 22 April, 2016 - Retrospectively registered, https://www.chictr.org.cn .
2 citations
TL;DR: In this paper , a 5-year-old boy with non-syndromic EVA due to homozygous mutations of c.919-2A>G (IVS7-2AU>);G was diagnosed with Landau-Kleffner syndrome (LKS).
Abstract: Abstract Background Landau-Kleffner syndrome (LKS) is an acquired aphasia and electroencephalogram (EEG) abnormalities mainly in temporoparietal areas. SLC26A4 mutations can cause hearing loss associated with enlarged vestibular aqueduct (EVA). Case presentations We report a case of LKS in a 5-year-old boy with non-syndromic EVA due to homozygous mutations of c.919-2A>G (IVS7-2A>G) in SLC26A4 . He had normal language development before 2 years old. At the age of 2.5 years, he was admitted to the hospital due to remarkable language delay, and diagnosed with hearing loss with EVA. The seizures started at 4.4 years of age and EEG recording showed electrical status epilepticus during sleep (ESES) with a posterior-temporal predominance. He received cochlear implantation in the right ear at 4.7 years of age, which improved his hearing and language skills. The nocturnal focal motor seizures recurred at 4.9 years of age. Then a remarkable inability to respond to calls and reduction in spontaneous speech were noticed. He was treated with methylprednisolone at 5 years old, which controlled the seizures, suppressed ESES, and remarkably improved the language ability. The absence of seizures maintained until the last follow-up at 5.3 years of age, with further improvements in EEG recording and language ability. Conclusions The co-existence of LKS and hearing loss caused by SLC26A4 mutations increases the difficulty of LKS diagnosis, especially in the presence of hearing loss and impaired language skills. EEG discharges predominantly in temporoparietal areas, the occurrence of ESES, and language improvement after antiepileptic medications are potential indicators for LKS diagnosis.
1 citations
TL;DR: In this article , a 40-year-old woman with drug-resistant focal epilepsy monitored by presurgical intracranial EEG was found to have acute and non-withdrawal seizure onset in the temporal pole.
Abstract: Abstract Background It has long been an interesting question of whether withdrawal seizures in epileptic patients differ from habitual seizures in terms of semiology and electrophysiology. Case presentation Here, we addressed this issue in a 40 year-old woman with drug-resistant focal epilepsy monitored by presurgical intracranial EEG. As a part of this routine pre-operative investigation, anti-seizure medications (ASMs) were halted; as a result, multiple withdrawal seizures were recorded before ASM readministration. During 4 days of invasive monitoring, we noticed three different phases in seizure organization: Acute withdrawal seizure (AWS): The first recorded seizure 10h after the implantation; the stabilized withdrawal seizures (SWS) : seven habitual seizures recorded from 24h post implantation to readministration of ASMs; and the Non-withdrawal seizures (NWS) : ten seizures recorded 24h after readministration of ASMs. AWS and SWS had the same semiology and same epileptic network, but the propagation time from the temporal pole to the para-hippocampal gyrus (PHG) and hippocampus ranged from no latency in AWS to up to 50 s in SWS. NWS were electrographic seizures, without any apparent clinical manifestation. Seizure onset in this type of seizure, as in the first two types, was in the temporal pole. However, NWS could last up to 3 min without involving the PHG or hippocampus. Conclusions We concluded that in acute withdrawal seizures the propagation time of epileptic activity is significantly reduced without affecting ictal organization network or semiology. Furthermore, ASM in this case had a remarkable influence on propagation rather than initiation of epileptic activity.
1 citations
TL;DR: In this paper , the authors investigated the long-term outcomes and the possible predictive factors of Vagus nerve stimulation in patients with refractory epilepsy and found that earlier exposure to VNS improves the prognosis.
Abstract: Abstract Background Vagus nerve stimulation (VNS) is an effective treatment for patients with refractory epilepsy, yet with varied predictive factors and heterogeneous long-term outcomes. Adjustment of VNS parameters is critical for obtaining favorable efficacy. In this study, we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy. Methods Eighty-six patients (59 males and 27 females) who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled. The clinical data, including sex, age at epilepsy onset, VNS implantation, epilepsy duration, seizure type, MRI findings, history of neurosurgical operations, and responder rate (responders were those with ≥50% seizure reduction), were analyzed. Results Four-year follow-up data were available for 76 patients (53 males and 23 females). The mean current intensity at the last follow-up was 1.8 ± 0.3 mA (range: 0.75–2.5 mA). The mean seizure reduction was 36.2% at 6 months, 38.5% at 1 year, 69.4% at 3 years, and 56.7% at 4 years. A favorable outcome of ≥50% reduction in seizure frequency occurred in 40.0% of the patients at 6 months, 55.9% at 1 year with 4 patients being seizure-free, 63.2% at 3 years with 5 patients being seizure-free, and 68.4% at 4 years with 5 patients being seizure-free. Earlier onset age ( P < 0.001) and shorter duration ( P = 0.042) were associated with favorable prognosis. Compared with generalized tonic-clonic seizures, tonic seizures had a favorable outcome ( P = 0.026). Twenty-three patients underwent neurosurgical operations before VNS implantation, and the responder rate was 60.9% at the last follow-up. Conclusions VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment. The stimulation efficacy increases over time after implantation, and earlier exposure to VNS improves the prognosis.
1 citations
TL;DR: In this article , an epilepsy management aid application (app) has been described, which enables a non-physician health worker (NPHW) to communicate with an epilepsy specialist using a smartphone.
Abstract: Abstract Background There is no single way to improve epilepsy care in low- and middle-income countries (LMICs). An epilepsy management aid application (app) has been described, which enables a non-physician health worker (NPHW) to communicate with an epilepsy specialist using a smartphone. In this study, we aimed to assess the validity and quality of this care system in building connections between NPHWs and specialists in Pakistan and the UK. Methods A NPHW in Pakistan used the app on a series of referrals and sent the app-generated summary by email to a neurologist in the UK, who replied and suggested possible management. Patients were later seen in a face-to-face (FF) manner by the UK neurologist and a local neurologist, and diagnostic accuracy and quality parameters were assessed. Results Over 10 months, 59 patients were recruited and 33 of them were available for FF assessment. The misdiagnosis rate of the app was 6% (2 cases). Treatment advice provided by the app was judged appropriate in 32 patients (97%). In addition, 46% of the referrals were completed within 2 h and 85% within 24 h. Conclusions Consistent with an earlier study, this system is a safe method to provide care for patients who cannot access neurological services in person. In addition, it has advantage of timeliness compared to FF assessment and requires less specialist time, both of which are especially important during the coronavirus disease 2019 pandemic. This system can be generalised easily, depending on the willingness of referrers and specialists to use it.
1 citations
TL;DR: Wang et al. as mentioned in this paper used a Trios whole-exome sequencing (WES) test and protein structural model prediction to diagnose a child with West syndrome, which is characterized by a triad of epileptic spasms, abnormal electroencephalography (EEG), and developmental arrest or psychomotor delay.
Abstract: Abstract Background West syndrome is a devastating disorder characterized by a triad of epileptic spasms, abnormal electroencephalography (EEG), and developmental arrest or psychomotor delay. In addition to early diagnosis, knowing the etiology of the condition is also important for its treatment. Among various etiologies, the genetic factors, especially mutations of ion channel genes, are very common and strongly linked to West syndrome. Case presentation A boy who had epileptic spasms from the age of 4 months was diagnosed with West syndrome based on the clinical manifestation and EEG results in Shenzhen Children’s Hospital in June 2019. Trios whole-exome sequencing (WES) test and protein structural model prediction were performed. We also reviewed the clinical and genetic features of this syndrome and the mechanisms of action of topiramate (TPM) by literature search in databases of Online Mendelian Inheritance in Man, Clinical Genome Resource, PubMed, Chinese National Knowledge Infrastructure and Wanfang database using keywords “ KCNA2 ” “West syndrome” and “Topiramate” by December 2020. The relationship between the effect of TPM and the pathogenesis of the KCNA2 variant was also assessed. The WES test revealed c.244C > T/p. Arg82Cys varaint of KCNA2 (NM_004974.3) in this patient, and Sanger sequencing identified this was a de novo mutation. As far as we know, this is the first report of the c.244C > T/p. Arg82Cys variant in KCNA2 , which was likely a pathogenic mutation. The seizures were successfully controlled for 10 months by TPM after failure of sodium valproate, large doses of vitamin B6, and adrenocorticotropic hormone. We speculate that the therapeutic effect of TPM in this patient is partially due to the inhibition of carbonic anhydrase. Conclusions Mutations in the KCNA2 gene should be considered for patients with West syndrome. The TPM treatment is probably effective for KCNA2 -associated disorders.
1 citations
TL;DR: In this article , the current situation of QEEG utilization in China and further compare the situations among different regions and different levels of hospitals was discussed. But the authors did not consider the use of EEG in clinical applications.
Abstract: Abstract Background Quantitative electroencephalogram (QEEG) is a tool that uses a computer to analyze brain activity monitored by electroencephalogram (EEG) according to measurements such as frequency, amplitude, and slope. The purpose of this study was to understand the current situation of QEEG utilization in China and further compare the situations among different regions and different levels of hospitals. Methods An online questionnaire comprising 14 questions was designed. Statistical description and analysis were made for the results of the questionnaire survey. Results A total of 158 people from 134 medical institutions participated in the survey. The participants came from 21 provinces, accounting for 61.76% (21/34) of the 34 provincial administrative regions in China. The Eastern China region accounted for 66.42% (89/134) of all the medical institutions that participated in this survey. Among the institutions surveyed, QEEG was routinely used in only 23.88% (32/134) of them. Among the medical institutions in which QEEG was routinely used, 87.50% (28/32) of them were 3A-grade hospitals. Among the institutions with routine use of QEEG, 56.25% (18/32) were affiliated hospitals of medical schools. There was a significant difference in the utilization of QEEG between the 3A-grade and non-3A-grade hospitals ( P = 0.040) and between the hospitals affiliated to medical schools and those non-affiliated to medical schools ( P = 0.020). Conclusions The utilization of QEEG is still limited in China. There are differences in the use of QEEG among different hospitals and regions.
1 citations
TL;DR: In this article , the authors presented four cases of nonconvulsive status epilepticus (NCSE) and their semiology, electroencephalogram (EEG) features, etiology, treatment and prognosis were retrospectively analyzed.
Abstract: Abstract Background The nonconvulsive status epilepticus (NCSE) is an epileptic condition characterized by little or no obvious symptoms, thus is often easily to be underrecognized, underdiagnosed or even undetected by clinicians. This article is written to advance the recognition and diagnosis of NCSE. Case presentation Four cases of NCSE were reported and their semiology, electroencephalogram (EEG) features, etiology, treatment and prognosis were retrospectively analyzed. Most of the 4 cases presented with impaired consciousness (confused, slow reaction and lags in response) and some strange behaviors (being upset and restless or washing hands repeatedly). None of them had any obvious motor symptoms like tonic or clonic movements. EEG of the 4 cases initially manifested with either a focal or a generalized onset, then evolved into spike-and-wave pattern gradually. With a favorable response to antiepileptic drugs, they all had a good outcome without any sequela. Conclusions NCSE is much more common than was considered in the past, which is featured by little or no evidence of movement or other symptoms. NCSE can lead to a favorable outcome in most patients.
TL;DR: In this paper , the reciprocal relationship between CR and epileptic activities from aspects of sleep effect, genetic modulation and brain biochemistry was presented, and precise predictive algorithms and chronotherapy strategies based on different temporal patterns of seizure occurrence for patients with epilepsy were discussed.
Abstract: Abstract Evidence about the interaction between circadian rhythms (CR) and epilepsy has been expanded with the application of advanced detection technology. An adequate understanding of how circadian system and epilepsy interact with each other could contribute to more accurate seizure prediction as well as rapid development of potential treatment timed to specific phases of CR. In this review, we present the reciprocal relationship between CR and epileptic activities from aspects of sleep effect, genetic modulation and brain biochemistry. It has been found that sleep-wake patterns, circadian timing systems and multidien rhythms have essential roles in seizure activities and interictal epileptiform discharge (IED). For instance, specific distribution patterns of seizures and IED have been reported, i.e., lighter non-rapid eye movement (NREM) sleep stage (stage 2) induces seizures while deeper NREM sleep stage (stage 3) activates IEDs. Furthermore, the epilepsy type, seizure type and seizure onset zone can significantly affect the rhythms of seizure occurrence. Apart from the common seizure types, several specific epilepsy syndromes also have a close correlation with sleep-wakefulness patterns. Sleep influences the epilepsy rhythm, and conversely, epilepsy alters the sleep rhythm through multiple pathways. Clock genes accompanied by two feedback loops of regulation have an important role in cortical excitability and seizure occurrence, which may be involved in the mTORopathy. The suprachiasmatic nuclei (SCN) has a rhythm of melatonin and cortisol secretion under the circadian pattern, and then these hormones can feed back into a central oscillator to affect the SCN-dependent rhythms, leading to variable but prominent influence on epilepsy. Furthermore, we discuss the precise predictive algorithms and chronotherapy strategies based on different temporal patterns of seizure occurrence for patients with epilepsy, which may offer a valuable indication for non-invasive closed-loop treatment system. Optimization of the time and dose of antiseizure medications, and resynchronization of disturbed CR (by hormone therapy, light exposure, ketogenic diet, novel small molecules) would be beneficial for epileptic patients in the future. Before formal clinical practice, future large-scale studies are urgently needed to assist prediction and treatment of circadian seizure activities and address unsolved restrictions.
TL;DR: In this article , the synchronization in multichannel electrocorticography (ECoG) recordings from patients with neocortical epilepsy and characterize neural activity inside and outside the onset zone was explored.
Abstract: Abstract Background Brain function is thought to rely on complex interactions of dynamic neural systems, which depend on the integrity of structural and functional networks. Focal epilepsy is considered to result from excessive focal synchronization in the network. Synchronization analysis of multichannel electrocorticography (ECoG) contributes to the understanding of and orientation of epilepsy. The aim of this study was to explore the synchronization in multichannel ECoG recordings from patients with neocortical epilepsy and characterize neural activity inside and outside the onset zone. Methods Four patients with neocortical epilepsy, who became seizure-free for more than 1 year after surgery guided by ECoG monitoring, were included in this study. ECoG data recorded during pre-surgical evaluation were analyzed. Synchronizations in phase and amplitude of different frequency bands between ECoG channels was analyzed using MATLAB. We generated 100 surrogate data from the original ECoG data using Amplitude Adjusted Fourier Transform to calculate the enhanced synchronization. The relationship between synchronization characteristics and seizure onset zone was analyzed. Results We found synchronization clusters in the 14–30 Hz and 30–80 Hz bands around the onset areas during both interictal and the beginning of ictal periods in all four patients. Conclusions The enhanced-synchronization clusters play a central role in epilepsy, and may activate the onset areas and contribute to the spreading of epileptiform activity.
TL;DR: In this paper , the efficacy and utility of KD in adult status epilepticus (SE) patients were reviewed and highlighted for clinical reference and management, and the application of KD was highlighted.
Abstract: Abstract Status epilepticus (SE) is a common fatal neurological disease with high morbidity and mortality. Even if a large proportion of patients might be relieved from anti-seizure medications, sedatives and anesthetics, some still remain out of control. The ketogenic dietary (KD) has been proven useful in patients refractory to medications and/or who have failed to respond to surgical intervention. Recently, KD has shown beneficial therapeutic effects in children with SE, but studies in adults have rarely been reported. In this paper, we review the efficacy and utility of KD in adult SE patients and highlight its application for clinical reference and management.
TL;DR: In this paper , the focal cortical myoclonus was detected on conventional electroencephalogram (EEG) was rarely observed in Dravet syndrome (DS) patients, which may broaden the types of seizures and may provide some diagnostic clues for DS.
Abstract: Abstract Background Dravet syndrome (DS) is a severe epileptic encephalopathy in children dominated by polymorphic seizures. Focal cortical myoclonus indicated on conventional electroencephalogram (EEG) was rarely observed in DS. Case presentation The child, boy, thirteen months old, suffered from clonic seizures during bathing at two months old. Later he suffered from recurrent afebrile or febrile generalized tonic–clonic seizures often developing into status epilepticus. A genetic analysis of the SCN1A gene revealed a de novo heterozygous frame shift mutation in exon 21(c.3836_c.3837del AT).His myoclonic jerks of unilateral arm occurred spontaneously in response to movement. A spike wave from right central-parietal cortex immediately preceded a left myoclonic muscle activity, while a spike wave from left immediately preceded a right myoclonic muscle activity. The onset of the detected spike preceded the onset of myoclonic muscle activity by 42 ms using jerk-locked back-averaging of electroencephalogram data. The focal cortical myoclonus was not noted when one year old. Conclusions Focal cortical myoclonus could be a form of seizures during the first year of life in DS, which may broaden the types of seizures of DS and may provide some diagnostic clues for DS.
TL;DR: In this article , the authors used three complementary parameters of resting-state functional magnetic resonance imaging (rs-fMRI) to investigate aberrant brain activity in Juvenile myoclonic epilepsy (JME) patients in comparison to that of healthy controls.
Abstract: Abstract Background Juvenile myoclonic epilepsy (JME) is the most common syndrome of idiopathic generalized epilepsy. Although resting-state functional magnetic resonance imaging (rs-fMRI) studies have found thalamocortical circuit dysfunction in patients with JME, the pathophysiological mechanism of JME remains unclear. In this study, we used three complementary parameters of rs-fMRI to investigate aberrant brain activity in JME patients in comparison to that of healthy controls. Methods Rs-fMRI and clinical data were acquired from 49 patients with JME undergoing monotherapy and 44 age- and sex-matched healthy controls. After fMRI data preprocessing, the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated and compared between the two groups. Correlation analysis was conducted to explore the relationship between local brain abnormalities and clinical features in JME patients. Results Compared with the controls, the JME patients exhibited significantly decreased fALFF, ReHo and DC in the cerebellum, inferior parietal lobe, and visual cortex (including the fusiform and the lingual and middle occipital gyri), and increased DC in the right orbitofrontal cortex. In the JME patients, there were no regions with reduced ReHo compared to the controls. No significant correlation was observed between regional abnormalities of fALFF, ReHo or DC, and clinical features. Conclusions We demonstrated a wide range of abnormal functional activity in the brains of patients with JME, including the prefrontal cortex, visual cortex, default mode network, and cerebellum. The results suggest dysfunctions of the cerebello-cerebral circuits, which provide a clue on the potential pathogenesis of JME.
TL;DR: The most frequent types of surgery performed were lobectomography, lesionectomies, and cortical resections in posterior quadrant epilepsy (PCE) patients as mentioned in this paper .
Abstract: Abstract Background Posterior quadrant epilepsy (PCE) is a type of focal epilepsy that originates in the parietal lobe, occipital lobe, and the parietal-occipital border of the temporal lobe, or in any combination of these regions. PCE has a low incidence, but it can cause a great burden in disability-adjusted life years. In this retrospective cohort, patients of all ages with a diagnosis of PCE between 2006 and 2019 were evaluated in a referral center in Bogotá, Colombia. A descriptive analysis of demographic data, clinical history, imaging findings, type of surgery, histopathological diagnosis, outcome, and follow-up was performed using the Engel scale. Methods This study included refractory PCE patients of all ages who were evaluated by the epilepsy surgery group of the Hospital Universitario San Ignacio from 2006 to 2019. Clinical, imaging and surgical variables were obtained from the medical records and analyzed. Results Thirteen patients were included in the study, including 8 males and 5 females. The mean age of diagnosis was 8.8 years, while the mean age of surgery was 25 years. The most frequent clinical finding was intellectual disability. The most common findings on magnetic resonance imaging were encephalomalacia and gliosis. In 61.5% of the patients, the lateralization of video-EEG matched with brain magnetic resonance imaging alteration. The most frequent types of surgery performed were lobectomies, lesionectomies and cortical resections. Seizure-freedom was achieved in approximately one third of the patients; however, more than half of the patients were free of disabling seizures or had significant improvement after surgery. Conclusions PCE surgery is scarcely performed worldwide, therefore the effectiveness and outcomes are quite variable in the reported literature. In this study, we show that patients with PCE can obtain great benefits in terms of reduction of seizures with a low risk of surgical complications, encouraging the use of this type of procedure in carefully selected patients.
TL;DR: The treatment of super-refractory status epilepticus; multi-center trial of for the treatment of in effect of on a of therapy for of and mechanism; assessment of efficacy of effect on of and application of.
TL;DR: In this paper , a multicenter expert panel within the China Association Against Epilepsy (CAAE) Ketogenic Diet Commission has worked out the Chinese expert recommendations on KD for super-refractory status epilepticus (SRSE).
Abstract: Abstract Super-refractory status epilepticus (SRSE) is a serious and life-threatening neurological condition. Ketogenic diet (KD) is a diet characterized by high fat, low carbohydrate, and moderate protein. As KD shows effectiveness in controlling seizures in more than half of SRSE patients, it can be a treatment option for SRSE. Currently, KD treatment for SRSE is based on personal experience and observational evidence has been published. In the context of a lack of a validated guideline, we convened a multicenter expert panel within the China Association Against Epilepsy (CAAE) Ketogenic Diet Commission to work out the Chinese expert recommendations on KD for SRSE. We summarize and discuss the latest clinical practice of KD for SRSE in critical care settings. Recommendations are given on patient selection, the timing of KD, diet implementation, and follow-up. More research data are needed in this area to support better clinical practice.
TL;DR: In this article , the practical aspects of KD-PN therapy for treatment of status epilepticus, including the dietary composition, potential drug-diet interactions, and monitoring, are discussed.
Abstract: Abstract Super-refractory status epilepticus (SRSE) is an important neurological emergency associated with high mortality and morbidity and poses a heavy economic burden on patients. Ketogenic diet parenteral nutrition (KD-PN) is ketogenic diet therapy provided through parenteral administration and may be an adjuvant treatment for these who cannot accept enteral diet. However, the calculation and management of KD-PN presents a challenge for clinicians. This review focuses on the practical aspects of KD-PN therapy for treatment of SRSE, including the dietary composition, potential drug-diet interactions, and monitoring during KD-PN treatment. As with all SRSE treatments, KD-PN has many adverse effects, like hyperlipemia, hepatotoxicity, metabolic acidosis, insufficient ketosis or hyper-ketosis, and propofol infusion syndrome. We summarize monitoring and treatment methods in our review. This review provides some practical aspects for treatment of SRSE.
TL;DR: In this paper , the authors conducted an in-depth literature search on the clinically available neuromodulatory approaches for TLE, focusing on the possible mechanism of action and the clinical outcomes including adverse effects.
Abstract: Abstract Temporal lobe epilepsy (TLE) is difficult to treat as it is often refractory to treatment. Apart from traditional medical treatment, surgical resection is also a choice of treatment, but it may be associated with significant cognitive deficits. As a result, treatment strategies using targeted and adjustable stimulation of malfunctioning brain circuits have been developed. These neuromodulatory therapies using approaches of electric and magnetic neuromodulation are already in clinical use for refractory epilepsy while others such as optogenetics, chemo-genetics and ultrasound modulation are being tested in pre-clinical TLE animal models. In this review, we conducted an in-depth literature search on the clinically available neuromodulatory approaches for TLE, focusing on the possible mechanism of action and the clinical outcomes including adverse effects. Techniques that are currently explored in preclinical animal models but may have therapeutic applications in future are also discussed. The efficacy and subsequent adverse effects vary among the different neuromodulatory approaches and some still have unclear mechanisms of action in TLE treatment. Further studies evaluating the benefits and potential limitations are needed. Continued research on the therapeutic mechanisms and the epileptic brain network is critical for improving therapies for TLE.
TL;DR: In this paper , the effectiveness of frontal lobe epilepsy (FLE) surgery in children with intractable epilepsy due to malformation of cortical development (MCD) was assessed and its prognostic factors were studied.
Abstract: Abstract Background Malformation of cortical development (MCD) is a common cause of intractable epilepsy in children. In this study, the effectiveness of frontal lobe epilepsy (FLE) surgery in children with intractable epilepsy due to MCD was assessed and its prognostic factors were studied. Methods Seventy-six patients with intractable FLE who received epilepsy surgery between January 2016 and March 2018 in Peking University First Hospital were recruited in this study. All the resected brain tissues were demonstrated to be MCD. All patients were followed up for at least 3 years. The clinical data and prognosis were analyzed retrospectively. Univariate and multivariate analyses were performed to investigate the correlations between clinical variables and prognostic outcome (Engel classification). Results Sixty (78.9%) patients had Engel class I postoperative outcome. The mean age at surgery was 6.00 ± 4.24 years. Sixty-six patients (86.8%) had daily seizures, 40.2% of the patients had epileptic spasm, and 33% of the patients had extensive interictal EEG abnormalities, which, however, could not provide any helpful information for localizing epileptogenic zones. About 29% of the patients had normal MRI findings even by experienced radiologists, and 26% of the patients had epileptogenic lesion involving adjacent lobes. There was a significant correlation between acute postoperative seizure (APOS) and prognosis ( P < 0.05): APOS predicted poor prognosis. There was a significant correlation between pathology and prognosis ( P < 0.05): FCD IA and FCD IIB were correlated with a good outcome. Both variables with a significance level of P < 0.05 during univariate analysis, including pathology and APOS, were included in multivariate analysis, which were significant independent predictors of prognosis. Conclusions The clinical manifestations of pediatric intractable FLE due to MCD are more complicated than those in adults. Multidisplinary presurgical evaluation in pediatric epilepsy is mandatory. The surgical outcome of pediatric FLE due to MCD could reach a seizure-free rate of 78.9% with the follow-up of at least 3 years. The post-operative pathology and APOS may be related to the prognosis of surgery in this group of pediatric patients.
TL;DR: In this paper , a 24-year-old Caucasian male developed a refractory status epilepticus after a surgical attempt to remove a cerebral ganglioglioma, and the postoperative magnetic resonance imaging revealed that the lesion was intact, and that only the perilesional area and adjacent cortex had been resected.
Abstract: Abstract Background Gangliogliomas are brain tumors associated with drug-resistant focal epilepsy. In most cases, seizures improve after surgical treatment. It is still not concluded to what extent the lesion itself or the perilesional area contributes to the epileptogenicity. Case presentation In the case presented in this report, the patient, a 24-year-old Caucasian male, developed a refractory status epilepticus after a surgical attempt to remove a cerebral ganglioglioma. The postoperative magnetic resonance imaging revealed that the lesion was intact, and that inadvertently only the perilesional area and adjacent cortex had been resected. The patient underwent a new surgical procedure where the ganglioglioma was removed, and the status epilepticus cessated. Conclusions This clinical case suggests that the lesion itself plays an important role in seizure generation and propagation, and notably, that the surrounding cortex by an inhibitory action can act as a gate to seizure spread.
TL;DR: In this paper , the authors investigated whether Tug1 is involved in microglial inflammation in status epilepticus (SE) rats and found that Tug 1 directly interacted with p65.
Abstract: Abstract Background Inflammation plays an important role in the pathogenesis of status epilepticus (SE). The long non-coding RNA (lncRNA) taurine up-regulated gene1 (Tug1) plays a well-defined role in inflammatory diseases. However, the molecular mechanism of Tug1 in SE progression remains unknown. In present study, we investigated whether Tug1 is involved in microglial inflammation in SE rats. Methods The SE rat model was established via intraperitoneal injection of lithium chloride-pilocarpine. RNA-binding protein immunoprecipitation (RIP) and RIP sequencing were carried out in rat microglia (RM). Tug1 cloned into the adenovirus was overexpressed in the microglia. Knockdown of Tug1 was performed via siRNA transfection. The level of Tug1 and inflammatory factors IL-1β and TNF-α was examined by real-time polymerase chain reaction (RT-PCR) and western blotting. Protein levels of p65, p-p65, p-ΙκΒα and ΙκΒα were assessed by western blotting. Results The RIP-seq result showed 14 lncRNAs that bound to the NF-κB p65 protein in RM. The lncRNA Tug1 directly interacted with p65. The level of declined Tug1 was decreased in the hippocampus of SE rats. Overexpression of Tug1 reduced the LPS-induced inflammation and M1/M2 polarization of microglia, while knockdown of Tug1 aggravated the inflammatory response in microglia. Accordingly, the protein levels of p-p65/p65 and p-ΙκΒα/ΙκΒα were reduced in the Tug1-overexpression microglia and elevated in the Tug1-knockdown microglia. Conclusions These findings indicate that Tug1 modulates the inflammation in microglia through the NF-κB signal pathway, and the Tug1/P65 axis are like to play a significant role in the inflammatory processes, providing a valid target for the therapy of SE.
TL;DR: Lentini et al. as discussed by the authors showed that reprogramming reactive glia into interneurons reduced chronic seizure activity in a mouse model of mesial temporal lobe epilepsy.
Abstract: Abstract This commentary highlights a research article published recently in Cell Stem Cell “Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy”. Generally, Lentini et al. reveal a strategy to fulfill in vivo glia-to-neuron reprogramming, which is a potential disease-modifying strategy for treatment of intractable seizures. Here, we describe exciting research advances in the treatment of intractable seizures based on this research article, summarizing its key findings, emphasizing its importance and providing further discussions. Further, issues worthy of further investigations are also postulated so that clinic translation can be better achieved.
TL;DR: In this paper , a linear regression analysis with stepwise selection was performed to analyze the independent variables associated with social support for adults with epilepsy (AWEs) and found that poor social support is associated with childhood onset of epilepsy and the unmarried status.
Abstract: Abstract Background The lack of social support for adults with epilepsy (AWEs) is receiving increased attention, as it may result in low quality of life. This study was aimed to confirm the demographic characteristics of and clinical factors associated with social support for AWEs. Methods AWEs were consecutively recruited from our hospital. The 10-term Social Support Rating Scale (SSRS) was used to measure social support. A linear regression analysis with stepwise selection was performed to analyze the independent variables associated with social support for AWEs. Results In total, 165 AWEs were consecutively included in the present study. Linear regression analysis showed that the marital status ( t = -3.550, β = -0.272, P = 0.001), the age at onset ( t = 2.545, β = 0.192, P = 0.012), and the QOLIE-31 score ( t = 3.144, β = 0.221, P = 0.002) were independent variables associated with social support for AWEs. Conclusions Our findings suggest that the poor social support is associated with childhood onset of epilepsy and the unmarried status. This study also confirmed a negative influence of low social support on quality of life in AWEs.
TL;DR: In this paper , a cross-sectional study was conducted to assess the gender differences in incidence and factors of sleep disturbances in patients with epilepsy (PWE) and found that depression mood was the only factor associated with sleep disturbances.
Abstract: Abstract Background Sleep disturbances are frequently observed in patients with epilepsy (PWE), with adversely effects on life quality and seizure control. The study aimed to assess the gender differences in incidence and factors of sleep disturbances in PWE. Methods PWE confirmed the diagnosis of epilepsy were consecutively enrolled in this cross-sectional study, with detailed information recorded. A group of healthy participants were recruited as the control. Sleep and mood disorders were evaluated with the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results One hundred and thirty-three patients (age: 30.2 ± 10.6 years, men: 51%) and 150 healthy subjects were recruited in this study. Compared with healthy controls, PWE had higher mean scores of the ISI and BDI ( p < 0.001 and p = 0.01). There were no significant gender differences in the prevalence and scores of sleep disturbances in PWE. In the overall PWE, nocturnal seizures and focal epilepsy were respectively related to insomnia and poor sleep quality (OR = 3.35, p = 0.024; OR = 3.08, p = 0.013), and mood disorders were also important factors in sleep disturbances ( p < 0.05). In the analysis by gender, depression, anxiety, nocturnal seizures and focal epilepsy were associated with insomnia and poor sleep quality in men. For women, however, depression mood was the only factor of sleep disturbances. Conclusions Though no gender difference was observed in the incidence of sleep disturbances, factors contributing to insomnia and sleep quality were different by gender. The factors and gender differences of sleep disturbances should be taken into account in the clinical treatment.
TL;DR: In this article , a nonverbal 9-year-old male carrying a KCNT1 gene mutation, who presented with drug-resistant focal-onset seizures, was treated with vagus nerve stimulation (VNS).
Abstract: Abstract Background The KCNT1 gene encodes a Na + -activated K + channel. Gain-of-function mutations of KCNT1 lead to autosomal dominant sleep-related hypermotor epilepsy, early-onset epileptic encephalopathy, focal epilepsy and other epileptic encephalopathies. In this paper, we report a boy carrying a KCNT1 gene mutation, who presented with drug-resistant focal-onset seizures. He had decreased seizure frequency and improvement of background changes in electroencephalography (EEG) after vagus nerve stimulation (VNS). Case presentation The case was a nonverbal 9-year-old male who presented with drug-resistant focal-onset seizures since age 3 and had underwent VNS therapy for 2 years. He had hypermotor symptoms, automatism and bilateral asymmetric tonic seizures with cognitive decline and aphasis from age 3. The patient had a variety of seizure types that only occurred at night. The most common seizure type was automatisms, and ictal video EEG showed high-amplitude delta waves, followed by a fast rhythmic sharp activity in the mesial frontal and bitemporal regions. The patient was diagnosed with KCNT1-related epilepsy, epileptic encephalopathy and cognitive disorder. He was refractory to multiple anti-seizure medicines (ASM) and ketogenic diet. After VNS treatment at age 7, the frequency of seizures was reduced significantly and EEG was improved in background slowing. Conclusions Children with KCNT1-related epilepsy usually have early onset of disease, are nonverbal, and are refractory to ASM. This boy with drug-resistant KCNT1-related epilepsy showed significantly reduced seizure frequency after VNS. This report may provide reference for management of cases of KCNT1-related epilepsy.
TL;DR: In this paper , the potential role of miR-9-5p in seizures and its effect on the survival of glioma patients, in order to provide new targets for the treatment of epilepsy and Glioma.
Abstract: Abstract Background Epilepsy affects over 70 million people worldwide; however, the underlying mechanisms remain unclear. MicroRNAs (miRNAs) have essential functions in epilepsy. miRNA-9, a brain-specific/enriched miRNA, plays a role in various nervous system diseases and tumors, but whether miRNA-9 is involved in epilepsy and glioma-associated epilepsy remains unknown. Therefore, we aimed to explore the potential role of miR-9-5p in seizures and its effect on the survival of glioma patients, in order to provide new targets for the treatment of epilepsy and glioma. Methods The YM500v2 database was used to validate the expression of hsa-miR-9-5p in tissues. Moreover, qRT-PCR was performed to investigate the expression of miR-9-5p in temporal lobe epilepsy patients and rats with lithium-pilocarpine-induced seizures. Recombinant adeno-associated virus containing miR-9-5p was constructed to overexpress miR-9-5p in vivo. The effects of miR-9-5p on the behavior and electroencephalographic activities of the lithium-pilocarpine rat model of epilepsy were tested. Bioinformatics analysis was used to predict the targets of miR-9-5p and explore its potential role in epilepsy and glioma-associated epilepsy. Results The expression of miR-9-5p increased at 6 h and 7 days after lithium-pilocarpine-induced seizures in rats. Overexpression of miR-9-5p significantly shortened the latency of seizures and increased seizure intensity at 10 min and 20 min after administration of pilocarpine ( P < 0.05). Predicted targets of miR-9-5p were abundant and enriched in the brain, and affected various pathways related to epilepsy and tumor. Survival analysis revealed that overexpression of miR-9-5p significantly improved the survival of patients from with low-grade gliomas and glioblastomas. The involvement of miR-9-5p in the glioma-associated epileptic seizures and the improvement of glioma survival may be related to multiple pathways, including the Rho GTPases and hub genes included SH3PXD2B, ARF6, and ANK2. Conclusions miR-9-5p may play a key role in promoting epileptic seizures and improving glioma survival, probably through multiple pathways, including GTPases of the Rho family and hub genes including SH3PXD2B, ARF6 and ANK2. Understanding the roles of miR-9-5p in epilepsy and glioma and the underlying mechanisms may provide a theoretical basis for the diagnosis and treatment of patients with epilepsy and glioma.
TL;DR: In this paper , a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types.
Abstract: Abstract Background Lennox-gastaut syndrome (LGS) is an epileptic encephalopathy often associated with behavioral and psychiatric disorders. Vagus nerve stimulation (VNS) has been approved effective for LGS treatment. Surgical resection is also an option for LGS patients with focal pathology, offering a high probability of seizure control. However, it is challenging to accurately localize the seizure focus. Case presentation The case presented here is a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders. He was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types. He was treated with VNS in 2017 at the age of 15. After that, the frequency of the short tonic seizures decreased from 4–5 times per day to 2–5 times per year, and the generalized tonic–clonic seizure pattern did not recur, which had a frequency of 2–4 times per month before the surgery. In 2019, the generalized abnormal interictal epileptiform discharges changed to be localized in the right frontal–temporal lobe at the age of 17 years (2019). Conclusions This case report suggested that the generalized epileptiform discharges evolve into localized discharges after VNS treatment, which may help reveal the primary seizure focus for resection surgery in patients with LGS.