Seizure-free Group Research Articles

Quality of life of children with residual seizures after epileptic resection surgery.

Epilepsy dramatically affects the quality of life (QoL) of children, and resection surgery can improve their QoL by reducing seizures or completely controlling them. Children who have postoperative seizures tend to show a poorer QoL. The aim of the present study was to investigate the QoL of children with seizures after resection surgery and its influencing factors. In the present study, we retrospectively reviewed 151 consecutive children who underwent resection surgery. We then divided them into two groups, seizure and seizure-free groups, according to the seizure outcomes 1 year after surgery. Variables were categorized into a number of factor types such as preoperative factors, surgery-related factors, postoperative factors, and family factors. QoL and seizure outcomes more than 3 years after surgery were assessed according to the ILAE seizure outcome classification and the CHEQOL-25 scale. Forty-three (28.5%) of the 151 children had seizures 1 year after surgery, and two children died during the follow-up period. The mean CHEQOL-25 scale for children with seizures was 63.5 ± 18.2, and 20 (48.8%) patients had poor QoL. Surgery-related factors, such as surgical complications and surgical sequelae, were not statistically associated with QoL. Preoperative language development retardation or language dysfunction [odds ratio (OR) = 29.3, P = 0.012) and postoperative ILAE seizure outcome classification (OR = 1.9, P = 0.045)] were significantly associated with QoL. Children with seizures after resection surgery had a relatively poor QoL. Surgery-related factors, such as surgical complications and surgical sequelae, cannot predict the QoL. Preoperative language development retardation or language dysfunction and postoperative ILAE seizure outcome classification were independent predictors of the quality of life (QoL). For children who could not achieve the expected freedom from seizure after surgery, a lower ILAE grade (ILAE 1-3) is also an acceptable outcome since it predicts a higher QoL.

Quantitative pretreatment EEG predicts efficacy of ACTH therapy in infantile epileptic spasms syndrome

ObjectiveThis study aimed to determine the correlation between outcomes following adrenocorticotrophic hormone (ACTH) therapy and measurements of relative power spectrum (rPS), weighted phase lag index (wPLI), and graph theoretical analysis on pretreatment electroencephalography (EEG) in infants with non-lesional infantile epileptic spasms syndrome (IESS). MethodsTwenty-eight patients with non-lesional IESS were enrolled. Outcomes were classified based on seizure recurrence following ACTH therapy: seizure-free (F, n = 21) and seizure-recurrence (R, n = 7) groups. The rPS, wPLI, clustering coefficient, and betweenness centrality were calculated on pretreatment EEG and were statistically analyzed to determine the correlation with outcomes following ACTH therapy. ResultsThe rPS value was significantly higher in the delta frequency band in group R than in group F (p < 0.001). The wPLI values were significantly higher in the delta, theta, and alpha frequency bands in group R than in group F (p = 0.007, <0.001, and <0.001, respectively). The clustering coefficient in the delta frequency band was significantly lower in group R than in group F (p < 0.001). ConclusionsOur findings demonstrate the significant differences in power and functional connectivity between outcome groups. SignificanceThis study may contribute to an early prediction of ACTH therapy outcomes and thus help in the development of appropriate treatment strategies.

Association of Levetiracetam Concentration With Seizure Frequency in Pregnant Women With Epilepsy.

Pharmacologic treatment of epilepsy in pregnant women is balancing between risks for the mother and fetus. Levetiracetam (LEV) is considered to be safe during pregnancy because of its low teratogenic potential and lack of drug-drug interaction with other antiseizure medications (ASMs). Recent studies have shown decline of ASM concentrations during pregnancy because of physiologically based pharmacokinetic changes. In this study, we established this decrease in LEV concentration during pregnancy. In addition, we aimed at investigating the effect of the low LEV levels during pregnancy and developing a target value for the level during pregnancy. Pregnant patients using levetiracetam were studied in this retrospective cohort study. Blood samples were monthly collected through venous puncture or the dried blood spot method. ASM serum concentrations were determined at least 6 months before conception and for each month of pregnancy. Seizure frequency and ASM dosages during pregnancy were obtained from patient records. Patients were divided into 2 groups: a seizure-free group and a non-seizure-free group, which contained pregnancies in which the mother had experienced an epileptic seizure more than 12 months and less than 12 months before pregnancy, respectively. We found decreased concentration/dose ratios in 29 pregnancies throughout all months of pregnancy. In the non-seizure-free group, it was found that low LEV concentrations were associated with seizure increase frequency (p = 0.022). For this group, the cutoff value with the highest sum of sensitivity and specificity was 0.466. All in all, we recommend therapeutic drug monitoring for all pregnant patients on LEV as the concentrations of LEV significantly decrease throughout most months of pregnancy. However, this decrease in LEV concentration was only significantly correlated with seizure deterioration in patients who had a seizure in the year preceding the pregnancy. Therefore, we suggest more careful monitoring of non-seizure-free patients as they are at higher risk for experiencing an increase of seizure frequency. For this group, we advise physicians to keep LEV concentration above 65% of the preconceptional concentration. For seizure-free patients, we recommend an LEV threshold value of approximately 46% of the preconceptional concentration.

The role of glutamine synthetase expression and cystine/glutamate transporter (SLC7A11, xCT) in epilepsy pathogenesis of patients with supratentorial brain gliomas

Background. Epileptic seizures represent one of the leading clinical manifestations of glial brain tumors that develop on average in 51% of cases. In gliomas, epileptogenesis is quite complex and multifactorial. Objective: to study a role of the expressed glutamine synthetase enzyme, as well as cystine/glutamate transporter (xCT system, SLC7A11) in the pathogenesis of epilepsy developing in patients with cerebral gliomas. Material and methods. The study included 32 patients with supratentorial gliomas. The average age of the disease onset (diagnosis) was 50.69±18.01 years. All patients underwent inpatient examination and treatment at the Neurosurgery and Nervous Diseases Clinics of Kirov Military Medical Academy from 2018 to 2020. In all cases, a biopsy of tumor tissue was collected. Histological and immunohistochemical studies were performed (expression of glutamine synthetase and cystine/ glutamate transporter (SLC7A11, xCT)). Results. Significant (ANOVA p=0.027, Mann–Whitney U-test p=0.033) differences in the expression of cystine/glutamate transporter (xCT system, SLC7A11) were revealed, by showing the following median values (lower quartile; upper quartile): 50% (45; 75) in the group of patients with seizures, 40% (40; 50) in the seizure-free group. The expression level of glutamine synthetase did not significantly differ in the groups with and without seizures. Conclusion. The data obtained confirmed that one of the pathogenetic mechanisms for epilepsy development in patients with gliomas was related to highly expressed cystine/glutamate transporter (xCT system, SLC7A11) and, as a consequence, an increase in the extracellular glutamate level.

Subtotal hemispherotomy for intractable lesional hemispheric epilepsy without hemiparesis in children

PurposeWe analyzed the surgical indications, outcomes, and prognostic factors of subtotal hemispherotomy for intractable lesional hemispheric epilepsy in children with almost normal motor function and summarized its surgical strategies. MethodsWe retrospectively analyzed 20 children who underwent subtotal hemispherotomy (hemispheric disconnection sparing sensorimotor cortex) between March 2015 and May 2021. The children were divided into seizure-free group and residual seizures group according to their surgical outcomes. The surgical outcome was based on International League Against Epilepsy (ILAE) classification (class 1–6). All presurgical evaluation data were collected and analyzed. ResultsAmong the 20 children, the mean age at the time of seizure onset, mean age at the time of surgery, and mean follow-up time was 3.2 ± 2.8, 7.5 ± 4.4, and 3.5 ± 2.1 years, respectively. All children had hemispheric lesion on MRI. At the last follow-up evaluation, 75% (15/20) of children remained seizure-free. Univariate analyses revealed that the electrocorticogram finding of epileptiform discharges in the central cortex after disconnection were poor prognostic factors for seizure outcomes (P < 0.05). Disconnection of the central operculum and insula was a poor prognostic factor for motor function after surgery (P < 0.05). ConclusionsFor intractable lesional hemispheric epilepsy with no hemiparesis, subtotal hemispherotomy can be performed with favorable seizure outcome. Disconnection of the central operculum and insula may increase the possibility of motor function injury.

An EEG based real-time epilepsy seizure detection approach using discrete wavelet transform and machine learning methods

Epilepsy is one of the most common complex brain disorders which is a chronic non-communicable disease caused by paroxysmal abnormal super-synchronous electrical activity of brain neurons. This paper proposed an electroencephalogram (EEG) based real-time approach to detect epilepsy seizures. Discrete wavelet transform and eight eigenvalues’ algorithms are applied to extract features in different sub-frequency bands. Then support vector machine is employed for three-classes classification of health control, seizure free and seizure active, and finally RUSBoosted tree Ensemble method is used for real-time seizure onset detection. The proposed algorithm is evaluated using two public datasets: one short-term dataset named UB and one long-term dataset named CHB-MIT. The results show that the algorithm achieves 97% accuracy and 96.67% sensitivity in the three-classes classification of health control, seizure-free and seizure-active groups in UB dataset, and 96.38% accuracy, 96.15% sensitivity, 3.24% false positive rate for the real time seizure onset detection in CHB-MIT Dataset.

Amplitude of Low-Frequency Fluctuation With Different Clinical Outcomes in Patients With Generalized Tonic-Clonic Seizures.

BackgroundGeneralized tonic–clonic seizures (GTCS) are associated with significant disability and sudden unexpected death when they cannot be controlled. We aimed to explore the underlying neural substrate of the different responses to antiseizure drugs between the seizure-free (SF) and non-seizure-free (NSF) patients with GTCS through the amplitude of low-frequency fluctuation (ALFF) method.MethodsWe calculated ALFF among the SF group, NSF group, and healthy controls (HCs) by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data. One-way ANOVA was used to compare the ALFF of the three groups, and post-hoc analysis was done at the same time. Pearson's correlation analysis between ALFF in the discrepant brain areas and the clinical characteristics (disease course and age of onset of GTCS) was calculated after then.ResultsA significant group effect was found in the right fusiform gyrus (R.FG), left fusiform gyrus (L.FG), left middle occipital gyrus (L.MOG), right inferior frontal gyrus (R.IFG), right precentral gyrus (R.PreG), right postcentral gyrus (R.PostG), and left calcarine sulcus (L.CS). The SF and NSF groups both showed increased ALFF in all discrepant brain areas compared to HCs except the R.IFG in the NSF group. Significantly higher ALFF in the bilateral FG and lower ALFF in the R.IFG were found in the NSF group compared to the SF group.ConclusionsHigher ALFF in the bilateral FG were found in the NSF group compared to the SF and HC groups. Our findings indicate that abnormal brain activity in the FG may be one potential neural substrate to interpret the failure of seizure control in patients with GTCS.

Focal Epilepsy in Children With Tuberous Sclerosis Complex: Does Vigabatrin Control Focal Seizures?

We evaluated the efficacy and safety of vigabatrin in focal epilepsy associated with tuberous sclerosis complex by retrospectively reviewing patients with focal epilepsy and tuberous sclerosis complex treated with vigabatrin at a pediatric epilepsy center over an 8-year period. Of 85 patients, 20 (23.5%) were seizure-free for >12 months, 45 (52.9%) were responders (≥50% seizure reduction), and 20 (23.5%) were nonresponders. The median age (in months) at seizure onset in the seizure-free group (median, 15; interquartile range [IQR], 6-23.3) was higher than that of responders (median, 5; IQR, 3-14) and nonresponders (median, 6; IQR, 2-12). Fewer patients in the seizure-free group had calcification in their largest tubers, but the presence of tuber calcification did not differ among groups. Vigabatrin is more likely to result in seizure freedom in children with tuberous sclerosis complex who have later infantile onset of focal seizures and no calcification in their largest tuber.

The Relationship Between Depression and Anxiety Symptoms of Adult PWE and Caregivers in a Tertiary Center.

BackgroundAlthough several studies have emphasized the association between epilepsy and psychiatric disorders, fewer have investigated the impact of epilepsy on caregivers' emotional status, mainly in adult people with epilepsy (PWE). Here we investigated depressive symptoms, suicidal ideation, and anxiety symptoms in a large group of adult PWE and their caregivers.MethodsWe analyzed symptoms of depression [with the Beck Depression Inventory-II (BDI-II)], suicidal ideation (with BDI-II item 9), and anxiety symptoms (with the Beck Anxiety Inventory) in a large group of adult PWE [N = 548 (60% women; median age 41)] and caregivers [N = 191 (72% women; median age 47)] from a Brazilian tertiary center, considering sociodemographic and clinical aspects. We also applied the Liverpool Adverse Events Profile to assess anti-seizure drugs adverse events.ResultsWhile the presence (p = 0.026) (and intensity, p = 0.007) of depressive symptoms and suicidal ideation (p = 0.02) were higher in PWE compared to caregivers, the proportion of clinical anxiety symptoms (p = 0.32) (and the intensity, p = 0.13) was similar in both groups. Although the rates of suicidal ideation were higher in focal epilepsy (20%), both generalized genetic epilepsy and caregivers also presented elevated frequencies (11%) of suicidal ideation. The analyses of 120 patient-caregiver dyads revealed that the intensity of depressive symptoms in PWE (but not anxiety) correlated with the intensity of depressive (r = 0.35; p < 0.001) and anxiety (r = 0.25; p = 0.01) symptoms in their caregivers. In the multivariate analyses of PWE, focal epilepsy (compared to GGE) was associated with clinical depressive symptoms (odds ratio, OR 2.1) and suicidal ideation (OR 3.2), while recurrent seizures (compared to the seizure-free group) were associated with suicidal ideation (OR 2.6) and anxiety symptoms (OR 2.1). Also, caregivers with anxiety symptoms were 8 times more likely to exhibit depressive symptoms, and those with depressive symptoms were 8 times more likely to present anxiety symptoms.ConclusionOur study suggests that specific attention for the caregivers' mental health is as essential as PWE. There is an urgent need for more studies involving caregivers to identify their emotional distress and provide adequate treatment.

NPRL3 loss alters neuronal morphology, mTOR localization, cortical lamination and seizure threshold.

Mutations in nitrogen permease regulator-like 3 (NPRL3), a component of the GATOR1 complex within the mTOR pathway, are associated with epilepsy and malformations of cortical development. Little is known about the effects of NPRL3 loss on neuronal mTOR signalling and morphology, or cerebral cortical development and seizure susceptibility. We report the clinical phenotypic spectrum of a founder NPRL3 pedigree (c.349delG, p.Glu117LysFS; n = 133) among Old Order Mennonites dating to 1727. Next, as a strategy to define the role of NPRL3 in cortical development, CRISPR/Cas9 Nprl3 knockout in Neuro2a cells in vitro and in foetal mouse brain in vivo was used to assess the effects of Nprl3 knockout on mTOR activation, subcellular mTOR localization, nutrient signalling, cell morphology and aggregation, cerebral cortical cytoarchitecture and network integrity. The NPRL3 pedigree exhibited an epilepsy penetrance of 28% and heterogeneous clinical phenotypes with a range of epilepsy semiologies, i.e. focal or generalized onset, brain imaging abnormalities, i.e. polymicrogyria, focal cortical dysplasia or normal imaging, and EEG findings, e.g. focal, multi-focal or generalized spikes, focal or generalized slowing. Whole exome analysis comparing a seizure-free group (n = 37) to those with epilepsy (n = 24) to search for gene modifiers for epilepsy did not identify a unique genetic modifier that explained the variability in seizure penetrance in this cohort. Nprl3 knockout in vitro caused mTOR pathway hyperactivation, cell soma enlargement and the formation of cellular aggregates seen in time-lapse videos that were prevented with the mTOR inhibitors rapamycin or torin1. In Nprl3 knockout cells, mTOR remained localized on the lysosome in a constitutively active conformation, as evidenced by phosphorylation of ribosomal S6 and 4E-BP1 proteins, even under nutrient starvation (amino acid-free) conditions, demonstrating that Nprl3 loss decouples mTOR activation from neuronal metabolic state. To model human malformations of cortical development associated with NPRL3 variants, we created a focal Nprl3 knockout in foetal mouse cortex by in utero electroporation and found altered cortical lamination and white matter heterotopic neurons, effects which were prevented with rapamycin treatment. EEG recordings showed network hyperexcitability and reduced seizure threshold to pentylenetetrazol treatment. NPRL3 variants are linked to a highly variable clinical phenotype which we propose results from mTOR-dependent effects on cell structure, cortical development and network organization.

Lesional Temporal Lobe Epilepsy: Does the “Uncommon” Differ from the Common?

Abstract Objectives This study aims to evaluate the subgroup consisting of uncommon pathological entities presenting with temporal lobe epilepsy (TLE). Methodology Twenty-four consecutively operated patients of lesional temporal lobe epilepsy were included in the study. Eleven cases were identified that had pathologies implicated as “uncommon” in previously done studies on the pathology of TLE. A subgroup analysis consisting of these uncommon lesions was done for clinical presentation and seizure outcome. The seizure outcome was assessed in terms of Engel and International League Against Epilepsy (ILAE) classification. Results Nine different pathological entities were identified within the study group. The mean age at surgery was 18.6 years (range 2–30 years). The mean duration of epilepsy was 48.3 months and the average duration of follow-up was 39.2months. All patients had seizures as the only complaint except three. Three patients had focal-aware seizures, two had focal motor onset, and the rest all had focal-unaware seizures. Seven patients were seizure free and the average age at diagnosis for these patients was 15.4 years (range 2–24 years.). The duration of seizure in the postoperative seizure-free group was 29.7 months and it was 81 months for the other group. All the patients with persistent postoperative seizures had focal-unaware seizures preoperatively. Conclusion Despite the small and heterogeneous nature of this subgroup of uncommon lesions causing temporal lobe epilepsy, the clinical presentation, prognostic factors, and seizure outcome are similar to the cohort of common pathologies, including mesial temporal sclerosis.

Predictors of seizure control in patients with cerebral arteriovenous malformation

PurposeWe aimed to define the predictors of a 2-year seizure-free outcome among patients with cerebral arteriovenous malformation (AVM). MethodsA retrospective cohort study recruited patients diagnosed with AVM admitted in the hospital between 2002 and 2020. The demographic data, clinical presentations, seizure semiology, neuro-imaging findings, modality of treatment, and clinical outcomes were compared between the 2-year seizure-free and non-2-year seizure-free groups. A logistic regression model was applied to determine the significant predictors of a 2-year seizure-free outcome. ResultsOf 372 radiologically confirmed patients with cerebral AVM, 105 (28.23%) experienced seizure and a 2-year seizure-free outcome was achieved in 76.19%. Most seizures presented as the initial symptom. Generalized onset seizure was the most common seizure semiology. A nidus diameter < 3 cm (adjusted odds ratio [aOR] 3.102; 95% CI 1.129–9.683; p = 0.046) was the independent predictor of a 2-year seizure-free period, whereas underlying epilepsy (aOR 0.141; 95% CI 0.010–0.688; p = 0.015) was an independent predictor against a 2-year seizure-free outcome. ConclusionA nidus diameter < 3 cm was the independent predictor of a 2-year seizure-free outcome, whereas underlying epilepsy was the factor against a 2-year seizure-free outcome.

Recognizing seizure using Poincaré plot of EEG signals and graphical features in DWT domain.

Electroencephalography (EEG) signals are considered one of the oldest techniques for detecting disorders in medical signal processing. However, brain complexity and the non-stationary nature of EEG signals represent a challenge when applying this technique. The current paper proposes new geometrical features for classification of seizure (S) and seizure-free (SF) EEG signals with respect to the Poincaré pattern of discrete wavelet transform (DWT) coefficients. DWT decomposes EEG signal to four levels, and thus Poincaré plot is shown for coefficients. Due to patterns of the Poincaré plot, novel geometrical features are computed from EEG signals. The computed features are involved in standard descriptors of 2‑D projection (STD), summation of triangle area using consecutive points (STA), as well as summation of shortest distance from each point relative to the 45-degree line (SSHD), and summation of distance from each point relative to the coordinate center (SDTC). The proposed procedure leads to discriminate features between S and SF EEG signals. Thereafter, a binary particle swarm optimization (BPSO) is developed as an appropriate technique for feature selection. Finally, k-nearest neighbor (KNN) and support vector machine (SVM) classifiers are used for classifying features in S and SF groups. By developing the proposed method, we have archived classification accuracy of 99.3 % with respect to the proposed geometrical features. Accordingly, S and SF EEG signals have been classified. Also, Poincaré plot of SF EEG signals has more regular geometrical shapes as compared to S group. As a final remark, we notice that the Poincaré plot of coefficients in S EEG signals has occupied more space as compared to SF EEG signals (Tab. 3, Fig. 11, Ref. 57). Text in PDF www.elis.sk Keywords: EEG signal, DWT, Poincaré plot, geometrical feature, BPSO, SVM, KNN.

Predictive factors of postoperative outcome in the elderly after resective epilepsy surgery

ObjectiveTo evaluate the efficiency of resective epilepsy surgery (RES) in patients over 50 years and determine prognostic factors. ResultsOver the 147 patients over 50 years (54.9±3.8 years [50–69]) coming from 8 specialized French centres for epilepsy surgery, 72.1%, patients were seizure-free and 91.2% had a good outcome 12 months after RES. Seizure freedom was not associated with the age at surgery or duration of epilepsy. In multivariate analysis, seizure freedom was associated with MRI and neuropathological hippocampal sclerosis (HS) (P=0.009 and P=0.028 respectively), PET hypometabolism (P=0.013), temporal epilepsy (P=0.01). On the contrary, the need for intracranial exploration was associated with a poorer prognosis (P=0.001). Postoperative number of antiepileptic drugs was significantly lower in the seizure-free group (P=0.001). Neurological adverse event rate after surgery was 21.1% and 11.7% of patients had neuropsychological adverse effects overall transient. ConclusionsRES is effective procedure in the elderly. Even safe it remains at higher risk of complication and population should be carefully selected. Nevertheless, age should not be considered as a limiting factor, especially when good prognostic factors are identified.

Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms.

We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period. Scalp ripples were detected and compared during the interictal periods before and after 2weeks of treatment. After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure-free group than in the non-seizure-free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non-relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.

Temporal lobe epilepsy: A never-ending story

IntroductionSemiology and anatomo-electroclinical correlations remain invaluable for maintaining the level of excellence in temporal lobe epilepsy (TLE) surgery, in parallel to the constantly evolving technical progress. The aim of this study was to address semiological frequent and not so frequent signs, rarities and red flags in a long follow-up surgical series of patients suffering from TLE. MethodsPatients operated within the boundaries of the TL at our center, with presurgical video-EEG recorded seizures and seizure free after a postoperative follow-up of at least 24 months were included. Ictal semiology was systematically described and new red flags were explored by comparing with a second group of patients with the same inclusion criteria but whose outcome had been unfavorable (Engel II-IV). ResultsSixty-two patients were included, 46 seizure free and 16 with outcome Engel II-IV. Most seizure-free patients had a classical semiological presentation including aura (69.6%, abdominal the most frequent), followed by loss of responsiveness (90.2%) oral automatisms (90.7%), ipsilateral gestural automatisms (53.5%), contralateral upper limb dystonia (37.5%) or immobility (39.1%), and early ipsilateral non-versive head orientation (33.3%). More infrequent presentations were also present in the group of seizure-free patients: ictal language disturbance (13%), maintenance of responsiveness during seizures (9.8%), and contralateral rhythmic non manipulative automatism (6.9%). The presence of an isolated viscerosensory and/or psychic aura was significantly more frequent in the seizure-free group (p = 0.017), as well as oroalimentary automatisms (p = 0.005). Two signs were only present in the group with outcome Engel II-IV, constituting possible red flags (0.06 < p < 0.07): inferior limbs stepping-like automatisms and postictal dysarthria. ConclusionAn adequate clinical exam during seizures and a careful analysis of video recordings allow to recognize infrequent but well-characterized ictal signs that are part of the range of semiology in TLE, together with the most frequent and classical ictal presentations. Special attention to the localization hypothesis must be paid in the absence of oroalimentary automatisms or when the signs classified as possible red flags emerge.

Mortality in adult epilepsy patients in Malaysia: a hospital-based study

Background: The standardized mortality ratio (SMR) of epilepsy in Asia ranges from 2.5 to 5.1. However, there are no such published data in Malaysia to date. Understanding the mortality rate and related factors will allow us to better assess and monitor the health status of PWE, thereby, preventing premature deaths among PWE. Hence, this study aimed to determine the mortality rate of adults with epilepsy (PWE) at the University Malaya Medical Centre (UMMC), a tertiary hospital in Malaysia. Method: A total of 2218 PWE were recruited retrospectively into this study. Deceased cases from 2009-2018 were identified from the National Registry Department of Malaysia. Age-, gender-, and ethnic-specific SMR were calculated. Result: There was a total of 163 deaths, of which 111 (68.1%) were male. The overall case-fatality rate (CFR) was 7.3%. Male PWE had higher CFR (9.2%) compared to females (5.1%, p<0.001). The annual death rate of PWE was 867 per 100, 000 persons. The overall all-cause SMR was 1.6 (CI 95% 1.3-1.8). The SMR for younger age groups (15-19 and 20-29 years) were higher (5.4-5.5) compared to other age groups (0.4-2.5). Overall SMR for male PWE (1.8, 95% CI 1.5-2.1) was higher than females (1.2, 95% CI 0.9-1.6). However, the SMR for female PWE in the younger age groups (15-19, 20-29 and 30-39 years) was higher. SMR among the Indian PWE was the highest (1.6, 95% CI 1.2-2.0) compared to the Chinese (1.5, 95% CI 1.2-1.9) and the Malays (1.4, 95% 1.0-1.9). The CFR was higher in those with focal epilepsy (8.5% vs. 2.5-3.7% in genetic and other generalized epilepsies, p=0.003), epilepsy with structural cause (9.5% vs. 5.9% in others, p=0.005) and uncontrolled seizures (7.9% vs. 5.2% in seizure-free group, p<0.001). Conclusion: The mortality rate of PWE in Malaysia is higher than that of the general population but lower compared to other Asian countries. Specifically, the rates are higher in the younger age group, male gender, and Indian ethnicity. Those with focal epilepsy, structural causes and uncontrolled seizures have higher mortality rates.

Patterns of Brain Injury in Perinatal Arterial Ischemic Stroke and the Development of Infantile Spasms.

Perinatal arterial ischemic stroke (PAIS) underlies approximately 10% of infantile spasms (IS). We aim to identify patterns of brain injury in ischemic stroke that may predispose infants to infantile spasms. Sixty-four perinatal arterial ischemic stroke patients were identified meeting the following inclusion criteria: term birth, magnetic resonance imaging (MRI) showing ischemic stroke or encephalomalacia in an arterial distribution, and follow-up records. Patients who developed infantile spasms (PAIS-IS) were analyzed descriptively for ischemic stroke injury patterns and were compared to a seizure-free control group (PAIS-only). Stroke injury was scored using the modified pediatric ASPECTS (modASPECTS). The PAIS-IS (n = 9) group had significantly higher modASPECTS than the PAIS-only (n = 16) group (P = .002, Mann-Whitney). A greater proportion of PAIS-IS patients had injury to deep cerebral structures (67%) than PAIS-only (25%). Infarct size was significantly associated with infantile spasms development. Results support theories implicating deep cerebral structures in infantile spasms pathogenesis. This may help identify perinatal arterial ischemic stroke patients at risk of infantile spasms, facilitating more timely diagnosis.

Manufacturer switch of anti-seizure drugs may not increase the risk of seizure recurrence in Children: A nationwide study of prescription data in Germany

ObjectiveSeveral publications on the exchangeability of antiepileptic drugs in clinical settings revealed an increased risk for seizure recurrence after changing the manufacturer of anti-seizure drugs (ASD) in adults, possibly due to a decline of adherence. It is unclear whether this holds true in children and adolescents. MethodsPatient data of children and adolescents (<18 years) were collected anonymously from 236 German pediatricians and pediatric neurologists between January 2011 and December 2018 using the IMS® Disease Analyzer database (IQVIA, Frankfurt, Germany). Patients with epilepsy were included if at least 2 prescriptions within 360 days and 1 within 180 days prior to the index date were available. The cohort was separated into a seizure group and seizure-free controls. Both groups were matched 1:1 according to age, gender, insurance status, and treating pediatrician. The risk for seizure recurrence after a manufacturer switch of the same ASD at the last prescription before the index date was analyzed using a multivariate regression model. ResultsA total of 678 children and adolescents with epilepsy were included (each group: n = 339; age: 9.6 ± 4.4 years). Comparing both groups, the risk for seizures recurrence was not increased after a manufacturer switch had occurred. Albeit changes during the last prescription before the index date had occurred more often in the seizure-free group, neither change of branded and generic products nor substances reached significance. Only change of ASD strength showed a significantly reduced odds ratio for seizures (OR 0.40, 95% CI 0.24–0.65, p < 0.001). SignificanceIn contrast to the available evidence in adults, changing the manufacturer did not appear to increase the risk for seizure recurrence in previously seizure-free children and adolescents with epilepsy.

Pregnancy with pre-excitation syndrome influence on pregnancy outcomes

Objective: To investigate the characteristics of pregnancy with pre-excitation syndrome and its influence on pregnancy outcomes. Methods: A retrospective analysis was made on the clinical data of 62 cases of pregnancy complicated with pre-excitation syndrome in Beijing Anzhen Hospital from Jan. 2008 to Dec. 2008. According to whether there was a supraventricular tachycardia (SVT) in pregnancy, they were divided into two groups. There were 16 pregnant women in the SVT seizure group during pregnancy, and 46 pregnant women in no SVT seizure group, with a multi-disciplinary comprehensive diagnosis and treatment model. SPSS software was used to analyze the data and compare the gestational age, age and weight of the newborn, and then compare the pregnancy outcomes. Results: (1) The total number of deliveries in Beijing Anzhen Hospital during the study period was 21 786, and the patients with pregnancy combined with pre-excitation syndrome account for 0.28% (62/21 786). (2) Totally 44 patients (71%, 44/62) were diagnosed with pre-excitation syndrome before pregnancy, and 18 patients (29%, 18/62) were diagnosed for the first-time during pregnancy. Among patients diagnosed with pre-excitation syndrome before pregnancy, 16 patients (36%, 16/44) had seizures before pregnancy, 28 patients (64%, 28/44) had asymptomatic before pregnancy, and 4 of asymptomatic patients had SVT during pregnancy. (3) Of the 16 pregnant women in the SVT seizure group during pregnancy, 2 patients (2/16) had SVT episodes in the first trimester, 5 patients (5/16) had SVT episodes in the second trimester, 9 patients (9/16) had SVT episodes in the third trimester. In the SVT seizure group, 8 patients (8/16) had SVT episodes before pregnancy, and 8 patients (8/16) had no SVT episodes before pregnancy. There were 46 patients in the SVT seizure-free group during pregnancy, including 9 patients with SVT attacks before pregnancy and 37 patients without SVT before pregnancy. (4) Compared with the pregnant women in the SVT seizure group, the age, weight gained during pregnancy, delivery gestation week, newborn weight, and the time of the first and second labors were not statistically different between the two groups of pregnant women (all P>0.05). However, the total duration of labor in the SVT seizure group during pregnancy was shorter and pre-pregnancy weight was lower (all P<0.05). The rate of cesarean section in pregnant women with SVT attack was 12/16, and the rate of cesarean section in pregnant women without SVT was 50% (23/46; P=0.051). No pregnant woman had an arrhythmia during delivery. Conclusions: SVT episode in patients during pregnancy most occurs in the third trimester. Patients who are asymptomatic before pregnancy may also have SVT during pregnancy. Pre-excitation syndrome patients with SVT attacks during pregnancy increase adverse pregnancy outcomes. Multidisciplinary comprehensive management could effectively control pregnant women with pre-excitation syndrome, effectively reduce the occurrence of serious arrhythmia risk events during pregnancy, so that most patients could get good pregnancy outcomes.