Atypical absence seizures and gene variants: A gene-based review of etiology, electro-clinical features, and associated epilepsy syndrome.

Atypical absence seizures are generalized non-convulsive seizures that often occur in children with cognitive impairment. They are common in refractory epilepsy and have been recognized as one of the hallmarks of developmental epileptic encephalopathies. Notably, pathogenic variants associated with AAS, such as GABRG2, GABRG3, SLC6A1, CACNB4, SCN8A, and SYNGAP1, are also linked to developmental epileptic encephalopathies. Atypical absences differ from typical absences in that they are frequently drug-resistant and the prognosis is dependent on the etiology or related epileptic syndromes. To improve clinicians' understanding of atypical absences and provide novel perspectives for clinical treatment, we have reviewed the electro-clinical characteristics, etiologies, treatment, and prognosis of atypical absences, with a focus on the etiology of advancements in gene variants, shedding light on potential avenues for improved clinical management.

Headache attributed to cranial venous sinus stenting: A case series and literature review.

BACKGROUND: The diagnostic criteria for headache attributable to cranial venous sinus stenting were first formalized in the recently published third edition of the International Classification of Headache Disorders (ICHD-3). However, the diagnostic criteria for headache caused by cranial venous sinus stenting are based on very few data and the condition is poorly characterized. OBJECTIVES: To validate the diagnostic criteria for cranial venous sinus stenting headache by retrospectively studying the characteristics of headache in patients with isolated pulsatile tinnitus who underwent curative cranial venous sinus stenting and who had not previously complained of headache. PATIENTS AND METHODS: We retrospectively studied clinical, radiological, and manometric data from patients with isolated venous pulsatile tinnitus who had not previously reported headache. All patients underwent lateral sinus stenting in our institution between October 2010 and February 2018. RESULTS: Forty eight patients, 47 females and one male, were enrolled. The mean age at symptom onset was 36.2 ± 8.7 years and the mean body mass index was 24.0 ± 3.2 kg/m2. Lateral sinus stenosis was evident in 47 patients and a sigmoid diverticulum in one. Fourteen patients experienced headaches after recovering from general anesthesia. All were female, with a mean age of 35.5 ± 9.6 years. Headache persisted for less than 3 days in six patients (42.8%); for 3 days to 3 months in four (28.6%); and for longer than 3 months in four (28.6%). The headaches were located on the same sides as the cranial venous sinus stents in 13 patients (92.9%) and were principally occipital, being oppressive in nine patients (64.3%) and of moderate intensity in seven (50%). Age at onset of pulsatile tinnitus and body mass index were significantly associated with headache (p < 0.05; t-test). CONCLUSION: To the best of our knowledge, this is the first study to describe cranial venous sinus stenting headache in detail. We found that de novo headache developed after cranial venous sinus stenting, and was usually mild to moderate, unilateral, but oppressive; almost one-third of such headaches persisted for more than 3 months. Researchers and clinicians must become familiar with this headache spectrum; further prospective studies are required.

Characteristics of Headache After an Intracranial Endovascular Procedure: A Prospective Observational Study.

BACKGROUND: Two editions of the International Classification of Headache Disorders (ICHD) diagnostic criteria for "Headache attributed to an intracranial endovascular procedure" have been published, in 2004 and 2013.1,2 Despite studies that have suggested that the former is not very practical, the ICHD-3 beta did not contain major changes. Moreover, so far no consensus exists regarding characteristics of headache after intracranial endovascular procedure. Thus, there is a need for sound suggestions to improve the ICHD-3 beta diagnostic criteria. METHODS: Using a prospective design, we identified consecutive patients with unruptured intracranial aneurysms (UIAs) with neuroendovascular treatment from January 2014 to December 2014. RESULTS: In total, 73 patients were enrolled, and 58 patients ultimately completed the 6-month follow-up. After the procedure, five of the 29 patients (17.2%) with pre-existing headache experienced marked worsening after the procedure, while seven of the 29 patients without prior headache developed new-onset headache post-procedurally. The headaches started within 24 hours, with a mean duration of 24-72 hours. The headaches were moderate to severe. The eligibility of these events to be considered headaches caused by neuroendovascular procedures according to the ICHD-3 beta diagnostic criteria for designation was far from ideal. CONCLUSIONS: Most cases of markedly worsening headaches and new-onset headaches started within 24 hours and persisted longer than that specified in the ICHD-3 beta diagnostic criteria. Moreover, considering that some items are not very practical, the ICHD-3 beta diagnostic criteria should be revised in the light of recent literature reports.

[Only overlapping stents therapy for intracranial vertebral artery dissection aneurysms].

OBJECTIVE: To evaluate the feasibility, safety, clinical, and angiographic follow-up of only overlapping stents therapy for intracranial vertebral artery dissection aneurysms (VADA). METHODS: Eight consecutive patients (6 men, 2 women; mean age 46.8 years ranging from 34 to 62 years) with intracranial VADA admitted to Department of Neurology, Chinese People's Liberation Army General Hospital from June 2008 to June 2014 were retrospectively reviewed. All patients were diagnosed intracranial VADA by MRI or digital subtraction angiography (DSA). All patients were treated by only overlapping stents therapy under general anesthesia. In the endovascular treatment process 2 to 3 Solitaire, Neuroform or Wingspan self-expandable stents were overlapping implanted in the segment of the aneurysms. All patients received routine antiplatelet therapy before and after endovascular treatment. RESULTS: The operative procedures were succeeded in all patients. Eight patients were implanted 18 stents (2 patients, 3 stents; 6 patients, 2 stents). The stents were located accurately and implanted smoothly, none perioperative complications occurred. All patients lived and worked normally and had no recurrent symptoms on follow-up of 6 to 48 months. All patients performed DSA reexamination on follow-up. The aneurysm blocked in 2 patients, the size lessened in 2 patients, and the size had no change in 3 patients. CONCLUSIONS: Only overlapping stents therapy for treating intracranial VADA is feasible and has good operation safety. Preliminary follow-up results show that it can reduce the probability of thrombosis or hemorrhage and can improve the patients' life quality.

Thirty-Day Outcome of a Multicenter Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China.

BACKGROUND AND PURPOSE: Although recent trials have suggested that stenting is worse than medical therapy for patients with severe symptomatic intracranial atherosclerotic stenosis, it is not clear whether this conclusion applies to a subset of patients with hypoperfusion symptoms. To justify for a new trial in China, we performed a multicenter prospective registry study to evaluate the safety and efficacy of endovascular stenting within 30 days for patients with severe symptomatic intracranial atherosclerotic stenosis. METHODS: Patients with symptomatic intracranial atherosclerotic stenosis caused by 70% to 99% stenosis combined with poor collaterals were enrolled. The patients were treated either with balloon-mounted stent or with balloon predilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome within 30 days is stroke, transient ischemic attack, and death after stenting. The secondary outcome is successful revascularization. The baseline characteristics and outcomes of the 2 treatment groups were compared. RESULTS: From September 2013 to January 2015, among 354 consecutive patients, 300 patients (aged 58.3±9.78 years) were recruited, including 159 patients treated with balloon-mounted stent and 141 patients with balloon plus self-expanding stent. The 30-day rate of stroke, transient ischemic attack, and death was 4.3%. Successful revascularization was 97.3%. Patients treated with balloon-mounted stent were older, less likely to have middle cerebral artery lesions, more likely to have vertebral artery lesions, more likely to have Mori A lesions, less likely to have Mori C lesions, and likely to have lower degree of residual stenosis than patients treated with balloon plus self-expanding stent. CONCLUSIONS: The short-term safety and efficacy of endovascular stenting for patients with severe symptomatic intracranial atherosclerotic stenosis in China is acceptable. Balloon-mounted stent may have lower degree of residual stenosis than self-expanding stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01968122.

Maternal immune activation increases seizure susceptibility in juvenile rat offspring.

Epidemiological data suggest a relationship between maternal infection and a high incidence of childhood epilepsy in offspring. However, there is little experimental evidence that links maternal infection with later seizure susceptibility in juvenile offspring. Here, we asked whether maternal immune challenge during pregnancy can alter seizure susceptibility and seizure-associated brain damage in adolescence. Pregnant Sprague-Dawley rats were treated with lipopolysaccharide (LPS) or normal saline (NS) on gestational days 15 and 16. At postnatal day 21, seizure susceptibility to kainic acid (KA) was evaluated in male offspring. Four groups were studied, including normal control (NS-NS), prenatal infection (LPS-NS), juvenile seizure (NS-KA), and "two-hit" (LPS-KA) groups. Our results demonstrated that maternal LPS exposure caused long-term reactive astrogliosis and increased seizure susceptibility in juvenile rat offspring. Compared to the juvenile seizure group, animals in the "two-hit" group showed exaggerated astrogliosis, followed by worsened spatial learning ability in adulthood. In addition, prenatal immune challenge alone led to spatial learning impairment in offspring but had no effect on anxiety. These data suggest that prenatal immune challenge causes a long-term increase in juvenile seizure susceptibility and exacerbates seizure-induced brain injury, possibly by priming astroglia.

[Image anatomic characteristics and clinical diagnosis and treatment of cerebral venous sinus stenosis].

OBJECTIVE: To explore the imaging anatomic features of symptomatic cerebral venous sinus stenosis, and evaluate the efficacy and feasibility of different treatment methods. METHODS: From August 2001 to September 2004, 173 patients (transverse sinus stenosis 150, middle of the superior sagittal sinus stenosis 18, proximal part of sigmoid sinus stenosis 3, straight sinus stenosis 2; combined with sinus diverticulum 14, combined with Labbe's vein stenosis 3) were confirmed venous sinus stenosis by digital subtraction angiography (DSA). Among these patients, 121 were treated by stent implantation and the other 52 with mild symptoms by anticoagulation and/or thrombolysis treatment. RESULT: The treatment procedures were succeeded in all patients. 2 patients developed temporal and occipital hemorrhage during the procedure of artery thrombolysis, and 1 patient developed epidural hematoma in the transverse sinus area.All the 3 patients had a satisfactory prognosis through symptomatic treatment.There was no recurrence for all the patients during the follow-up period ranging from 1 to 9 years.9 patients who had recurring dizziness were confirmed no stent stenosis or thrombosis by DSA. The sites of stenosis in 168 patients (97%) were in the connect area of sigmoid and transverse sinuses or in the middle segment of superior sagittal sinus, where arachnoid granulations were focused on according to the anatomic characteristics. CONCLUSIONS: There is significant correlation between the cerebral venous sinuses stenosis and the abnormal growth of arachnoid granulations in the sinuses; the neurologic deficits caused by venous sinus stenosis can be relieved and eliminated by anticoagulation, thrombolysis, or stent implantation. Favorable medium-long term outcome is showed in the study population.

[Short term effect of multiple stents parallel placement and reconstruction technique for the treatment of giant fusiform vertebrobasilar dissecting aneurysms].

OBJECTIVE: To investigate the feasibility,safety and follow-up results of multiple stents parallel placement and reconstruction technique for treating giant vertebrobasilar dissecting aneurysms. METHODS: Five consecutive patients with giant fusiform vertebrobasilar dissecting aneurysms in Department of Neurology,Chinese People's Liberation Army General Hospital were retrospectively reviewed from April 2011 to October 2013. All patients were diagnosed vertebrobasilar dissecting aneurysms by MRI and digital subtraction angiography (DSA), the aneurysm size ranged 8.2-15.0 mm. All patients were treated by multiple stents parallel placement and reconstruction technique under general anesthesia. In the endovascular treatment process, 2-3 Solitaire or Neuroform self-expandable stents were parallel implanted in the maximum extension segment of the aneurysms to reconstruct the cavity of the aneurysm and solved the problem that the diameter of the intracranial stent is less than the diameter of the aneurysms. Multiple stents parallel placement can keep the stents stable in the cavity. The parallel stent can close the dissection as well as strengthen the aneurysm walls to alleviate the vessel pulsative compression of the brain stem. Furthermore, one of the parallel stents was selected for the main blood flow channel. Based on the main channel, telescope technique was used to completely covering the dissection. It can not only prevent the progress of dissection to normal regions, but also be helpful for blood flow channel reconstruction to reduce the hemodynamic disorders. All Patients received routine antiplatelet therapy before and after endovascular treatment. RESULTS: The operative procedures were succeeded in all patients. Five patients were implanted 18 stents (3 stents in 3 patients; 4 stents in 1 patient; 5 stents in 1 patient; parallel 3 stents in 2 patients; parallel 2 stents in 3 patients). The signs and symptoms of brain stem and posterior group of cranial nerves improved significantly. All patients lived and worked normally and had no recurrent symptoms on follow-up of 6-24 months. All patients performed DSA reexamination at 6-12 months postoperation. The aneurysm size lessened in 2 patients and had no change in 3 patients. CONCLUSIONS: Multiple stents parallel placement and reconstruction technique for treating giant fusiform vertebrobasilar dissecting aneurysms is feasible and have good operation safety. It may control the dilatation of the aneurysm and reduce the probability of thrombosis or hemorrhage. It can improve the patients' clinical symptoms and quality of life in short term follow-up. The long term result need for further follow-up.

[The clinical diagnosis and treatment of blood-blister-like cerebral aneurysms in supra-clinoid segment of internal carotid artery].

OBJECTIVE: To study the clinical characteristics, surgical principles and treatment options of blood-blister-like cerebral aneurysms in supra-clinoid segment of internal carotid artery. METHODS: Twelve blood-blister-like aneurysms were retrospectively studied including 4 open-surgery cases and 8 endovascular-treated cases from November 2008 to December 2012. Patients comprised 8 female and 4 male patients, whose mean age was 46.6 (range 38-56) years. Eleven patients presented with severe headache as the primary symptom, and 1 patient was found with aneurysm incidentally. Preoperative Hunt-Hess graded 0 in 1 patient, graded I in 5 patients, graded II in 4 patients, and graded III in 2 patients. By DSA examinations, 4 blood-blister-like aneurysms located in anterior wall and 8 in medial-anterior wall of supra-clinoid segment of internal carotid artery. Open surgical treatment included direct clipping, trapping, or wrapping and interventional treatment included stent-assisted coiling or simple stent placement. Intra-operative electroencephalogram and somatosensory evoked potentials monitoring was regularly used. Microvascular Doppler ultrasonography and indocyanine green videoangiography were used to assess blood flow in parent and branch vessels. The patients were followed up at 6 months by CT angiography (CTA) examination in outpatient clinic. RESULTS: For 4 open surgeries, 2 aneurysms were directly clipped, 1 was trapped and 1 was wrapped. The patient underwent trapping paralyzed postoperatively. For endovascular treatment, 6 patients were coiled assisted with stents and 2 patients were treated with simple stent placement. All the patients were followed with a mean follow-up time of 16 months (range, 6-61 months). At 6 months follow-up, 3 out of 4 surgical treated patients had good outcome and 1 was moderately severe disabled by modified Rankin scale; 1 patient underwent wrapping recurred and was transferred to endovascular treatment. Of the 6 patients treated with stent-assisted coiling, 4 patients were recurrent and coil replacements were performed. Two patients with simple stent placement had no recurrences. CONCLUSIONS: Blood-blister-like aneurysm is a special type of complex cerebral aneurysm. Comprehensive understanding of blood-blister-like aneurysm is the key to successful treatment.Open surgery is difficult procedure with high risk and complications while stent-assisted coiling has a high recurrent rate. To date, neither is the safe and effective treatment option.

Attention-deficit/hyperactivity disorder in children with epilepsy: A systematic review and meta-analysis of prevalence and risk factors.

OBJECTIVE: To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). METHODS: We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis. RESULTS: Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD. SIGNIFICANCE: The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment. PLAIN LANGUAGE SUMMARY: This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.

Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms.

INTRODUCTION: Epilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms. METHODS: Lithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group. RESULTS: First, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced. Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses. Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2. CONCLUSION: The current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.

Analysis of factors influencing the efficacy of vagus nerve stimulation for the treatment of drug-resistant epilepsy in children and prediction model for efficacy evaluation.

Objective: Vagus nerve stimulation (VNS) has been widely used in the treatment of drug-resistant epilepsy (DRE) in children. We aimed to explore the efficacy and safety of VNS, focusing on factors that can influence the efficacy of VNS, and construct a prediction model for the efficacy of VNS in the treatment of DRE children. Methods: Retrospectively analyzed 45 DRE children who underwent VNS at Qilu Hospital of Shandong University from June 2016 to November 2022. A ≥50% reduction in seizure frequency was defined as responder, logistic regression analyses were performed to analyze factors affecting the efficacy of VNS, and a predictive model was constructed. The predictive model was evaluated by receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA). Results: A total of 45 DRE children were included in this study, and the frequency of seizures was significantly reduced after VNS treatment, with 25 responders (55.6%), of whom 6 (13.3%) achieved seizure freedom. There was a significant improvement in the Quality of Life in Childhood Epilepsy Questionnaire (15.5%) and Seizure Severity Score (46.2%). 16 potential factors affecting the efficacy of VNS were included, and three statistically significant positive predictors were ultimately screened: shorter seizure duration, focal seizure, and absence of intellectual disability. We developed a nomogram for predicting the efficacy of VNS in the treatment of DRE children. The ROC curve confirmed that the predictive model has good diagnostic performance (AUC = 0.864, P < 0.05), and the nomogram can be further validated by bootstrapping for 1,000 repetitions, with a C-index of 0.837. Besides, this model showed good fitting and calibration and positive net benefits in decision curve analysis. Conclusion: VNS is a safe and effective treatment for DRE children. We developed a predictive nomogram for the efficacy of VNS, which provides a basis for more accurate selection of VNS patients.

Improvement of hypoxia-ischemia-induced white matter injury in immature rat brain by ethyl pyruvate.

Ethyl pyruvate (EP) has been reported to be neuroprotective in several models of brain injury, yet its influence on periventricular leukomalacia still remains elusive. Here we investigated whether repeated administration of EP could protect against white matter injury after hypoxia-ischemia (HI) (right common carotid artery ligation and 6 % O2 for 60 min) in post-natal 3 day rat pups. EP was injected (50 mg/kg, intraperitoneally) 10 min, 1 and 24 h after HI insult. Treatment with EP significantly reduced HI-induced ventricular enlargement, loss of developing oligodendrocytes, and hypomyelination. We further demonstrated a marked inhibitory effect of EP on inflammatory responses, as indicated by the decreased number of activated microglia and astrocytes and the reduced release of proinflammatory cytokines. Moreover, EP down-regulated the expression of cleaved caspase-3 and Bax, and up-regulated Bcl-2 expression after HI exposure. In conclusion, our results demonstrated that EP was able to provide potent protection on white matter injury through blocking the cerebral inflammatory responses and modulating the apoptotic death program of oligodendrocytes, indicating a potential neuroprotective agent in neonatal brain injury.

[Chemical constituents of Camellia sinensis var. assamica].

To study the chemical constituents of Camellia sinensis var. assamica. The compounds were isolated by NKA Macroporous resin silica gel, Sephadex LH-20, RP-C18 column chromatographies and semi-preparative HPLC,and their structures were elucidated by physicochemical properties and spectral analysis. Thirteen compounds were isolated and identified as caffeine (1), theobromine (2), gallic acid (3), (+)-catechin (4), ampelopsin (5), (-)-epicatechin (6), (-)-epiafzelechin (7), (-)-epicatechin-3-O-gallate (8), (-)-epiafzelechin-3-O-gallate (9) , (+)-catechin-3-O-gallate (10) , (+)-afzelechin-3-O-gallate (11), quemefin-3-O-alpha-L-arabinopyranosid (12), and (-)-epicatechin-3-O-p-hydroxybenzoate (13). Compounds 2, 5, 10-13 were isolated from this plant for the first time, and compound 11 is a new natural product.

Risk factors of recurrence after drug withdrawal in children with epilepsy.

This study aimed to evaluate the risk factors for recurrence in pediatric patients with epilepsy following normal antiseizure medication (ASM) treatment and drug withdrawal. We retrospectively analyzed 80 pediatric patients who received treatment at the Qilu Hospital of Shandong University between January 2009 and December 2019 after at least 2 years of seizure-free and normal electroencephalography (EEG) before the regular drug reduction. Patients were followed-up for at least 2 years and divided into the recurrence and nonrecurrence groups based on whether relapse occurred. Clinical information was gathered, and the risk variables for recurrence were statistically analyzed. Post 2 years of drug withdrawal, 19 patients showed relapses. The recurrence rate was 23.75%, and the mean time of recurrence was 11.09 ± 7.57 months, where 7 (36.8%) were women and 12 (63.2%) were men. In all, 41 pediatric patients were followed-up until the 3rd year, of which 2 (4.9%) patients experienced a relapse. Among the remaining 39 patients without relapse, 24 were followed-up until the 4th year, and no recurrence occurred. After being monitored for >4 years, 13 patients experienced no recurrence. The differences in the history of febrile seizures, combined use of ≥2 ASMs, and EEG abnormalities after drug withdrawal between the two groups were statistically significant (p < 0.05). Multivariate binary logistic regression analysis revealed that these factors are independent risk factors for recurrence after drug withdrawal in children with epilepsy: history of febrile seizures (OR = 4.322, 95% CI: 1.262-14.804), combined ASM use (OR = 4.783, 95% CI: 1.409-16.238), and EEG abnormalities after drug withdrawal (OR = 4.688, 95% CI: 1.154-19.050). In summary, our results suggest that the probability of seizure recurrence following drug cessation may be greatly increased by a history of febrile seizures, concomitant use of ≥2 ASMs, and EEG abnormalities after drug cessation. The majority of recurrences occurred in the first 2 years following drug discontinuation, whereas the rate of recurrence was minimal thereafter.

Anti-LGI1 encephalitis with initiating symptom of seizures in children.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Methods: Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Results: Case 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Conclusion: Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.

Safety and Tolerability of COVID-19 Vaccine in Children With Epilepsy: A Prospective, Multicenter Study.

BACKGROUND: We designed this study to investigate the effects of the coronavirus disease 2019 (COVID-19) vaccine on epileptic seizures, as well as its adverse effects, in children with epilepsy (<18 years). METHODS: This anonymous questionnaire study involved a multicenter prospective survey of outpatients and inpatients with epilepsy (＜18 years) registered in epilepsy clinics in eight hospitals in six cities of Shandong Province. RESULTS: A total of 224 children with epilepsy were included in the study. Fifty of them experienced general adverse events after vaccination. The most common local adverse events were pain or tenderness at the injection site. The most common systemic adverse effects were muscle soreness and headache. No severe adverse events were reported. There were no significant differences in the number of antiseizure medications (P = 0.459), gender (P = 0.336), etiology (P = 0.449), age (P = 0.499), duration of disease (P = 0.546), or seizure type (P = 0.475) between the patients with and without general adverse events. We found that the risk of seizure after vaccination was decreased in children who were seizure free for more than six months before vaccination. There was no significant difference in the number of seizures during the first month before vaccination, the first month after the first dose, and the first month after the second dose (P = 0.091). CONCLUSION: The benefits of vaccination against COVID-19 outweighed the risks of seizures/relapses and severe adverse events after vaccination for children with epilepsy.

The ketogenic diet for Dravet syndrome: A multicenter retrospective study.

OBJECTIVE: The ketogenic diet (KD) is one of the main treatments for drug-resistant epilepsy. However, there have been few multicenter reports on the use of the KD for the treatment of Dravet syndrome (DS). The aim of this study was to analyze the efficacy and safety of this approach based on a large number of multicenter cases. METHODS: This was a retrospective, multicenter cohort study from 14 centers in China. All patients were treated with the KD. We compared the effects of KD intervention time, age, and other factors. RESULTS: From March 2014 to March 2020, we treated 114 patients with DS with the KD. The male-to-female ratio was 67:47. The KD median initiation age was 3 y and 4 mo, and the median number of antiseizure medications (ASMs) was 2.4. KD therapy was the first choice for three patients. Exactly 10.5% of the patients started KD therapy after failure of the first ASM therapy, with 35.1% after failure of the second, 44.7% after the third, and 7% after the fourth or more. After KD therapy for 1, 3, 6, and 12 mo, the seizure-free rates were 14%, 32.5%, 30.7%, and 19.3%, respectively; KD efficacy (≥50% reduction in seizure frequency) were 57.9%, 76.3%, 59.6%, and 43%, respectively; the retention rates were 97.4%, 93%, 71.9%, and 46.5%, respectively; and the rates of adverse events were 25.2%, 19.9%, 11%, and 5.7%, respectively. CONCLUSIONS: Real-world, multicenter data analysis showed that the KD is effective for patients with DS and has a low incidence of side effects.

Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction.

The aim of present work was to elucidate the role of actin-depolymerizing factor (ADF), an important regulator of actin cytoskeleton, in the oxidized low-density lipoprotein (ox-LDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to ox-LDL. Treatment with LDL served as control. It was found that ADF mRNA level and protein expression were decreased when exposed to ox-LDL in MBMECs. Then, we investigated the influence of ADF overexpression on ox-LDL-treated MBMECs. Structurally, overexpression of ADF inhibited ox-LDL-induced F-actin formation. Functionally, overexpression of ADF attenuated ox-LDL-induced disruption of endothelial barrier marked by restoration of transendothelial electrical resistance, permeability of Evans Blue and expression of tight junction-associated proteins including ZO-1 and occludin, and blocked ox-LDL-induced oxidative stress marked by inhibition of reactive oxygen species (ROS) formation and activity of NADPH oxidase and Nox2 expression. However, overexpression of ADF in control cells had no significant effect on endothelial permeability and ROS formation. In conclusion, overexpression of ADF blocks ox-LDL-induced disruption of endothelial barrier. In addition, siRNA-mediated downregulation of ADF expression aggravated ox-LDL-induced disruption of endothelial barrier and ROS formation. These findings identify ADF as a key signaling molecule in the regulation of BBB integrity and suggest that ADF might be used as a target to modulate diseases accompanied by ox-LDL-induced BBB compromise.

Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway.

BACKGROUND: Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions. RESULTS: In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-ß1 (TGF-ß1). CONCLUSIONS: Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.