Epilepsy Center Research Articles

Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study.

Blood-brain barrier dysfunction (BBBD) has been linked to various neurological disorders, including epilepsy. This study aims to utilize dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to identify and compare brain regions with BBBD in patients with epilepsy (PWE) and healthy individuals. We scanned 50 drug-resistant epilepsy (DRE) patients and 58 control participants from four global specialized epilepsy centers using DCE-MRI. The presence and extent of BBBD were analyzed and compared between PWE and healthy controls. Both greater brain volume and higher number of brain regions with BBBD were significantly present in PWE compared to healthy controls (p < 10-7). No differences in total brain volume with BBBD were observed in patients diagnosed with either focal seizures or generalized epilepsy, despite variations in the affected regions. Overall brain volume with BBBD did not differ in PWE with MRI-visible lesions compared with non-lesional cases. BBBD was observed in brain regions suspected to be related to the onset of seizures in 82% of patients (n = 39) and was typically identified in, adjacent to, and/or in the same hemisphere as the suspected epileptogenic lesion (n = 10). These findings are consistent with pre-clinical studies that highlight the role of BBBD in the development of DRE and identify microvascular stabilization as a potential therapeutic strategy.

The impact of SARS-CoV-2 (COVID-19) pandemic on educational and professional growth of young Italian epileptologists: a survey of the Young Epilepsy Section-Italian chapter.

In March 2020, the World Health Organization declared the coronavirus-related disease SARS-CoV-2 infection pandemic. Italy was one of the most affected countries and managed the emergency also by a health care reorganization. The Education and Career Development Task Force of the Young Epilepsy Section-Italy (YES-I) designed a survey to assess the impact of the pandemic on the training and work of young epileptologists (< 40years). Fifty-three responses were collected: 45.3% were resident, 9.4% PhD students and the remainder specialists. Clinical activity changed for most (83%) during the pandemic. Educational activity at epilepsy centers was reduced for 35.8% of the survey participants, while 30.2% of research projects involving patients participation were stopped to switch mainly to COVID-19-related research. For 73.6% of survey participants, attending online courses and congresses was easier in terms of cost and organization, although for 50.9% the level of training was lower in quality. In contrast, 58.5% rated the webinars organized by YES-I very educational. Less than 50% of the clinicians used telemedicine in the pandemic period and continue to use it. Despite several positive aspects of virtual medicine, a small number (32.1%) of our interviewees were satisfied from telemedicine and few of them (30.2%) reported that it led to improvement of clinical practice. Our survey showed that the pandemic has had a negative impact on training, research and clinical activity in the epilepsy field; moreover, it underlined the critical aspects of virtual communication methods in order to improve its use for the future.

Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study

BackgroundIn this study, we aimed to assess the efficacy of surgical treatment in children with drug-refractory infantile epileptic spasms syndrome (IESS) and examine the factors influencing the post-surgical outcomes.MethodsThe clinical data of 30 children (18 males and 12 females) with epileptic spasms (ES) who underwent surgery at the Epilepsy Center of Shenzhen Children’s Hospital between June 2018 and June 2020 were retrospectively analyzed. Post-surgical outcomes were evaluated using the Engel Epilepsy Surgery Outcome Scale. Scalp electroencephalography and developmental quotient were assessed preoperatively and postoperatively. Univariate analysis and exact logistic regression analyses were used to identify the factors affecting the postoperative efficacy.ResultsOf the 30 patients who underwent surgical resection, 22 (73.3%) achieved Engel’s class I–II outcomes. Additionally, motor and cognitive functions improved in 14 patients (46.7%). The development of 12 (40%) patients remained at the preoperative development level. The median number of antiseizure medications taken preoperatively was 5.27 (range 2–10), which decreased to 1.90 (range 0–4) at the last follow-up. Seizure duration, etiology, positive positron emission tomography-magnetic resonance imaging (PET-MRI), surgery type, and lesion location were significantly correlated with the postoperative efficacy (P < 0.05). Positive PET/MRI findings and lesion location predicted independently the postoperative outcomes. Permanent impairments of motor or language function were rare, with only two cases reporting hydrocephalus and one reporting hemiplegia.ConclusionsSurgery is an effective treatment option for children with IESS. Early referral and comprehensive preoperative evaluation are essential for identification of surgically treatable structural lesions. The primary surgically treatable cause is cortical malformation, followed by perinatal brain injury. Hemispheric disconnection is a preferred surgical approach. Positive PET/MRI findings and lesion location predicted the postoperative outcomes.

Associations Between Testing and Treatment Pathways in a Case of Pediatric Nonlesional Epilepsy: A Census Survey of NAEC Center Directors.

Epilepsy surgery is vital in managing of children with drug-resistant epilepsy. Noninvasive and invasive testing modalities allow for evaluation and treatment of children with drug-resistant epilepsy. Evidence-based algorithms for this process do not exist. This study examines expert response to a vignette of pediatric nonlesional epilepsy to assess associations in evaluation and treatment choices. We analyzed annual report data and an epilepsy practice survey reported in 2020 from 135 pediatric epilepsy center directors in the United States. Characteristics of centers along with noninvasive and invasive testing and surgical treatment strategies were collected. Multivariable logistic regression modeling was performed. The response rate was 100% with 135 responses included in the analyses. Most used noninvasive testing modalities included Neuropsychology evaluation (90%), interictal brain fluorodeoxyglucose-positron emission tomography (85%), and functional magnetic resonance imaging (MRI) (72%) with nearly half obtaining genetic testing. Choosing functional MRI was associated with stereo electroencephalography (EEG) (P = .025) and selecting Wada with subdural grid/strips (P = .038). Directors from pediatric-only centers were more likely to choose stereo EEG as opposed to combined centers (P = .042). Laser interstitial thermal therapy was almost 7 times as likely to be chosen as a treatment modality compared with open resection in dedicated pediatric centers (OR 6.96, P = .002). In a vignette of nonlesional childhood drug-resistant epilepsy, epilepsy center directors' patterns of noninvasive testing, invasive testing, and treatment were examined. Management choices were associated with pediatric versus combined pediatric/adult center characteristics. Expert opinions demonstrated equipoise in evaluation and management of children with drug-resistant epilepsy and the need for evidence-based management strategies.

Prodromal Phase of Idiopathic Generalized Epilepsy: A Register-Based Case Control Study.

Idiopathic generalized epilepsy (IGE) is associated with distinct behavioral traits, symptoms of frontal lobe dysfunction, and psychiatric comorbidity. Whether psychiatric symptoms are part of the IGE endophenotype or secondary to the burden of chronic disease is unknown. In this study, we aimed at describing the sequence of appearance of psychiatric and epilepsy symptoms in patients with IGE. Inclusion criteria for this cohort study were diagnosis of IGE with age at diagnosis at 10-25 years. We created 2 mutually exclusive cohorts, 1 based on ICD-10 codes in Danish registers with a first IGE diagnosis from January 1, 2005, to December 31, 2018, and a second patient cohort treated at Odense University Hospital and the Danish Epilepsy Centre in the same period. Each case was matched with 10 age-matched, sex-matched, and geography-matched normal population controls from the Danish registers. We compared social status, health care utilization, and psychiatric diagnoses between the groups in the 5 years preceding epilepsy diagnosis, at diagnosis, and at the end of the study period using the Wilcoxon rank-sum test and confirmatory logistic regression models. We identified 1,009 patients for the register-based cohort (55.1% female; mean age at diagnosis [SD]: 15.9 [±3.8] years) and 402 patients for the hospital-based cohort (56.2% female; mean age at diagnosis [SD]: 18.3 [±7.4] years) and matched them to 10,090 and 4,020 controls, respectively. IGE cohorts and controls did not differ at birth. In the 5 years before their IGE diagnosis, register patients had an increasing number of contacts with hospitals (mean visits [SD]: cases: 8.3 [±5.6], controls: 6.6 [±4.5]) and their general practitioners (mean visits [SD]: cases: 48.7 [±26.3], controls: 45.3 [±24.5]) and received more prescriptions for psychiatric medications (prescriptions: cases: 4.2%, controls: 2.5%, p = 0.003) compared with controls. Patients had a higher rate of psychiatric comorbidity (comorbidity: cases: 26.5%, controls: 17.8%, p < 0.0001) at the end of the study than controls. Data were similar in the hospital-based cohort. Our data suggest a prodromal phase of IGE detectable approximately 5 years before the first seizure characterized by increased health care utilization and greater use of prescription medicine for psychiatric symptoms.

Efficacy of add-on Cenobamate treatment in refractory epilepsy due to Rasmussen's encephalitis.

To assess antiseizure effects of cenobamate, a new antiseizure medication with at least two mechanisms of action, in the rare, highly pharmacoresistant and progressive epilepsy syndrome related to Rasmussen's encephalitis. Three patients from the epilepsy centers in Freiburg, Kork, and Valencia are reported with focal epilepsy which had been pharmacoresistant to more than 10 prior treatment regimens. Assessment included at least 1 year of follow-up after cenobamate introduction and included seizure frequency, seizure severity (in particular status epilepticus) and changes in co-medication. In the three patients, cenobamate add on treatment proved superior to all prior antiseizure and immunomodulatory treatments which had been individually applied. Not only were focal to bilateral tonic-clonic seizure completely controlled, but also focal motor status epilepticus no longer occurred. Co-medication could be reduced in all patients. This case series in a rare and highly pharmacoresistant epilepsy syndrome suggests high efficacy of cenobamate add-on treatment for seizure control. This may be a valuable information in epilepsy related to Rasmussen encephalitis and calls for further elucidation of the mechanism involved in superior seizure control also compared to prior treatments including sodium channel blockers and benzodiazepines. Rasmussen's encephalitis is a rare type of epilepsy that gets worse over time and doesn't respond well to most seizure medications. We describe three patients who tried many treatments without much success, but when they added cenobamate to their treatment, it worked better than the other medications. This also let them lower the overall amount of medication they were taking.

Nationwide epidemiological study of epilepsy in Montenegro

The aim of this study was to estimate the incidence and prevalence of epilepsy in Montenegro over the period 2011–2022 using hospital case records. The main sources for this study were hospital case records in every outpatient and inpatient neurological department in Montenegro, including the Clinical Center of Montenegro in the capital, a primary referral national center for epilepsy. For every patient, aged 18 and above, two neurologists reviewed all data collected to verify the validity of the diagnosis and to establish the date of clinical onset of the disease. Information on age and sex, EEG, CT scan, and MRI were included. Prevalent cases were selected in 2022 population. Incident cases of epilepsy were identified in 2011 and the incidence trend was followed up for the next 12 years. Crude and standardized incidence and prevalence were calculated. Average crude incidence rate of epilepsy for study period was 56.0 per 100,000 individuals (men 58.1; women 54.2). The age-specific incidence was lowest in the 30 s, and early 40 s and highest after 65 years. Over the 12-year period, increasing trend of standardized epilepsy incidence rates was observed for the total population and for females (p = 0.024 and p = 0.020 respectively). The crude overall prevalence of epilepsy on December 31, 2022 was 13.0 per 1000 individuals (men 13.5; women 12.6). The highest prevalence was in patients in their early 20 s and in the seventh decade. In conclusion, the incidence of epilepsy in this study was similar to those of other industrialized countries, with increasing trend during study period. Prevalence was higher compared to European countries.

Association of Normative and Non-Normative Brain Networks With Cognitive Function in Patients With Temporal Lobe Epilepsy.

Despite their temporal lobe pathology, a significant subgroup of patients with temporal lobe epilepsy (TLE) is able to maintain normative cognitive functioning. In this study, we identify patients with TLE with intact vs impaired neurocognitive profiles and interrogate for the presence of both normative and highly individual intrinsic connectivity networks (ICNs)-all toward understanding the transition from impaired to intact neurocognitive status. This retrospective cross-sectional study included patients with TLE and matched healthy controls (HCs) from the Thomas Jefferson Comprehensive Epilepsy Center. Functional MRI data were decomposed using independent component analysis to obtain individualized ICNs. In this article, we calculated the degree of match between individualized ICNs and canonical ICNs (e.g., 17 resting-state networks by Yeo et al.) and divided each participant's ICNs into normative or non-normative status based on the degree of match. 100 patients with TLE (mean age 42.0 [SD: 13.7] years, 47 women) and 92 HCs were included in this study. We found that the individualized networks matched to the canonical networks less well in the cognitively impaired (n = 24) compared with the cognitively intact (n = 63) patients with TLE by 2-way mixed-measures analysis of variance (impaired vs intact mean difference [MD] -0.165 [-0.317, -0.013], p = 0.028). The cognitively impaired patients showed significant abnormalities in the profiles of both normative (impaired vs intact MD -0.537 [-0.998, -0.076], p = 0.017, intact vs HC MD -0.221 [-0.536, 0.924], p = 0.220, and impaired vs HC MD -0.759 [-1.200, -0.319], p < 0.001) and non-normative networks (impaired vs intact MD 0.484 [0.030, 0.937], p = 0.033, intact vs HC MD 0.369 [0.059, 0.678], p = 0.014, and impaired vs HC MD 0.853 [0.419, 1.286], p < 0.001) while the intact patients showed abnormalities only in non-normative networks. At the same time, we found that normative networks held a strong, positive association with the neuropsychological measures, with this association negative in non-normative networks. Our data demonstrated that significant cognitive deficits are associated with the status of both canonical and highly individual ICNs, making clear that the transition from intact to impaired cognitive status is not simply the result of disruption to normative brain networks.

Generalized spike-waves in idiopathic generalized epilepsies: Does their frequency matter?

We hypothesized that the frequency (in Hertz) of generalized spike-waves (GSWs) in patients with idiopathic generalized epilepsy (IGE) has associations with the syndromic diagnosis as well as with the prognosis of patients (their response to medical treatment). This was a retrospective study of a prospectively developed database. All patients with a diagnosis of IGE were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. Patients were classified into four IGE syndromes: childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and generalized tonic-clonic seizures alone. Five hundred and eighty-three patients were studied. GSWs were commonly observed in all four syndromes of IGE. Frequency of GSW (in Hertz) did not have a significant association with the syndromic diagnosis of the patients (p=.179). The presence of GSW did not have a significant association with the seizure outcome (becoming seizure free or not) of the patients (p=.416). Frequency of GSW did not have a significant association with the seizure outcome of the patients either (p=.574). GSWs are the hallmark electroencephalographic footprints of idiopathic generalized epilepsies; however, neither their presence nor their frequency has practical associations with the syndromic diagnosis of IGEs or their outcome (response to treatment).

Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program.

The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC. Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks. Thirty-four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8-31.2), and patients were receiving a median of 3 (range, 1-7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25-28 mg/kg/d for 36 weeks and then 20-50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%-81%, 51%-87%, and 44%-87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%-71%, 14%-58%, and 0%-25% for convulsive seizures; 52%-75%, 35%-60%, and 7%-32% for focal seizures; and 46%-79%, 26%-65%, and 0%-13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment-related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths. Long-term add-on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports. In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%-79% of patients had at least 50% reduction and 26%-65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment-related side effects. These results show that long-term CBD treatment was associated with fewer seizures and mild/moderate side effects.

Italian report on RARE epilepsies (i-RARE): A consensus on multidisciplinarity.

Rare and complex epilepsies encompass a diverse range of disorders characterized by seizures. We aimed to establish a consensus on key issues related to these conditions through collaboration among experienced neurologists, neuropediatricians, and patient advocacy representatives. Employing a modified Delphi method, a scientific board comprising 20 physicians and 4 patient advocacy representatives synthesized existing literature with their expertise to formulate statements on contentious topics. A final 32-member expert panel, representing diverse regions of Italy, validated these statements through a two-round voting process, with consensus defined as an average score ≥7. Sixteen statements reached a consensus, emphasizing the necessity for epidemiological studies to ascertain the true prevalence of rare epilepsies. Etiology emerged as a crucial factor influencing therapeutic strategies and outcome prediction, with particular concern regarding prolonged and tonic-clonic seizures. The importance of early implementation of specific drugs and non-pharmacological interventions in the treatment algorithm for developmental and epileptic encephalopathies (DEEs) was underscored. Multidisciplinary care involving experts with diverse skills was deemed essential, emphasizing non-seizure outcomes in adolescence and adulthood. This national consensus underscores the imperative for personalized, comprehensive, and multidisciplinary management of rare epilepsies/DEEs. It advocates for increased research, particularly in epidemiology and therapeutic approaches, to inform clinical decision-making and healthcare policies, ultimately enhancing patients' outcomes. The modified Delphi method is broadly used to evaluate debated topics. In this work, we sought the consensus on integrated and social care in epilepsy management. Both representatives of high-level epilepsy centers and patients' caregivers were directly involved.

Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy.

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic zone (EZ) while preserving the eloquent brain areas. The development of a reliable and noninvasive localization method that provides clinically useful information for the localization of the EZ is, therefore, crucial to achieving successful surgical outcomes. Electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of these patients showing promising findings in the delineation of epileptogenic as well as eloquent brain areas. Moreover, the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) recordings has shown higher source localization accuracy than either modality alone. Despite these encouraging findings, such techniques are performed in only a few tertiary epilepsy centers, are rarely recorded simultaneously, and are underutilized in pediatric cohorts. This study illustrates the experimental setup for recording simultaneous MEG and HD-EEG data as well as the methodological framework for analyzing these data aiming to localize the irritative zone, the seizure onset zone, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM).

B - 7 Factor Structure of the Beck Depression Inventory-II in Epilepsy

Abstract Objective This study aimed to explore the factor structure of the Beck Depression Inventory, Second Edition (BDI-II) in persons with epilepsy (PWE) and assess its correspondence with validated BDI-II cognitive and somatic-affective factors associated with depression in other populations. Method Retrospective data from 69 PWE (ages 18–72) who completed the BDI-II at a National Association of Epilepsy Centers level 4 epilepsy center were analyzed. Patients with diagnoses of bipolar disorder and schizophrenia spectrum disorders were excluded. An Exploratory Factor Analysis (EFA) using the psych package in R Studio was conducted, allowing factors to correlate with oblique factor rotation. The number of factors was determined using eigenvalues &amp;gt;1 and scree plots. Results Statistical support is strongest for a one-factor solution with eigenvalue 7.91; however, a two-factor solution (Factor two eigenvalue = 1.16) also met criteria. These factors accounted for 30% and 10% of the variance, respectively. Due to the low eigenvalue, few item loadings (3), and low variance explained by the second factor, item-level considerations were implemented to determine whether a two-factor solution added clinically relevant information. Conclusion Although a one-factor solution was best supported by the data, a second factor including sadness, feeling of punishment, and suicidal thoughts may be clinically relevant given elevated suicide risk and qualitative research reporting punishment feelings among PWE.

Association of baseline sleep duration and sleep quality with seizure recurrence in newly treated patients with epilepsy.

Although sleep duration and sleep quality are considered to be significant factors associated with epilepsy and seizure risk, findings are inconsistent, and their joint association remains uncertain. This study aimed to determine independent and joint associations of these two modifiable sleep features with seizure recurrence risk in newly treated patients with epilepsy (PWE). This is a prospective cohort study of newly treated PWE at a comprehensive epilepsy center in northeast China between June 2020 and December 2023. Self-reported sleep duration and sleep quality were collected at baseline. All patients were followed for 12 months for recurrent seizures. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of seizure recurrence. Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. A total of 209 patients were included, and 103 experienced seizure recurrence during follow-up. Baseline short sleep was significantly associated with greater risk of seizure recurrence (adjusted HR = 2.282, 95% confidence interval [CI] = 1.436-3.628, p < .001). Sleep duration (h/day) and recurrent seizure risk showed a significant nonlinear U-shaped association, with a nadir at 8 h/day. Baseline poor sleep quality was significantly associated with greater risk of seizure recurrence (adjusted HR = 1.985, 95% CI = 1.321-2.984, p < .001). Pittsburgh Sleep Quality Index score and seizure recurrence risk exhibited a positive linear association. Participants with a combination of poor quality-short sleep showed the highest risk of seizure recurrence (adjusted HR = 3.13, 95% CI = 1.779-5.507, p < .001) compared to the referent good quality-intermediate sleep group. Baseline sleep duration and sleep quality were independently and jointly associated with risk of seizure recurrence in newly treated PWE. Our results point to an important potential role of baseline sleep duration and sleep quality in shaping seizure risk.

Preliminary observation on clinical outcome and safety of surgery in early infants (

ObjectiveTo investigate the clinical outcomes and safety of surgery in infants (< 12 months of age) with drug-resistant epilepsy, clarify surgical indications, and select appropriate surgical methods. MethodsThis was a retrospective analysis of infants with drug-resistant epilepsy who underwent epilepsy surgery and were followed up for > 6 months at the Epilepsy Center of Shenzhen Children's Hospital. Clinical data included etiology, seizure type, surgical procedure, preoperative auxiliary examinations, pathological findings, and intraoperative and postoperative complications. Clinical outcomes were assessed based on postoperative seizure frequency, antiseizure medicines (ASMs) use, and neurocognitive development. Intraoperative blood loss, operative duration, postoperative complications, and duration of intensive care were evaluated to assess the safety of epilepsy surgery. Univariate and logistic analyses were performed to explore the factors influencing prognosis. ResultsEpilepsy surgery was performed on 44 infants with drug-resistant epilepsy, including 7 patients who underwent two operations. The age of seizure onset ranged from 1 day to 11 months (median: 1 month, interquartile range (IQR): 0.1–3.8), the disease course was 1–11 months (median: 4 months, IQR: 2–7), and the age at surgery was 6.9±3.6 months. Twenty-three patients underwent hemispherectomy (52.3%), and two underwent subtotal hemispherectomy. Five patients underwent multilobar disconnection, five underwent frontal lobotomy, and the remaining nine underwent focal resection. The surgical duration was 7.5±2 hours. Intraoperative blood loss ranged from 50–1800 ml (median: 275 ml, IQR: 200–500), with all patients receiving an intraoperative blood transfusion of 0.5–6 U (median: 1.5 U, IQR: 1.5–3). The intensive care unit stay was 1–4 days (median: 1 day, IQR: 1–2). The postoperative complication rate was 13.6% (6/44; two cases of hydrocephalus with intracranial infection, two isolated hydrocephalus, and two subdural hematomas). Excluding one child who died of severe lung infection approximately one year after surgery and one child lost to follow-up after surgery, all other cases were regularly followed up for 10 –49 months (median: 30 months, IQR: 16.5–36). After surgery, patients were treated with 0–3 ASMs (median: 1 ASM, IQR: 0–2); 27.9% (12/43) stopped taking ASMs and 51.2% (22/43) had reduced number of ASMs. Engel I was achieved in 76.7% (33/43) of the patients at the last follow-up. In 17 cases with complete developmental quotient follow-up data, the preoperative and postoperative developmental quotient means were 28.8±21 and 43.2±20.1, showing statistically significant differences (p<0.05) SignificanceEpilepsy surgery in infants under 12 months of age is safe and effective. Early preoperative evaluation is crucial for identifying structural lesions and suitable candidates for surgery among infants with drug-resistant epilepsy. The timeliness of surgery is essential for achieving favorable clinical outcomes.

Effect evaluation of outpatient long-term video EEGs for people with seizure disorders – study protocol of the ALVEEG project: a randomized controlled trial in Germany

BackgroundEpilepsy and other seizure disorders account for a high disease burden in Germany. As a timely diagnosis and accurate treatment are crucial, improving the management of these disorders is important. Outside of Germany, outpatient long-term video EEGs (ALVEEGs) have demonstrated the potential to support the diagnosis and management of epilepsy and other seizure disorders. This study aims to evaluate the implementation of ALVEEGs as a new diagnostic pathway in eastern parts of Germany to diagnose epilepsy and other seizure disorders and to assess if ALVEEGs are equally effective as the current inpatient-monitoring gold standard, which is currently only available at a limited number of specialized centers in Germany.MethodsALVEEG is a prospective, multicenter, randomized controlled equivalence trial, involving five epilepsy centers in the eastern states of Germany. Patients will be randomized into either intervention (IG) or control group (CG), using a permuted block randomization. The sample size targeted is 688 patients, continuously recruited over the trial. The IG will complete an ALVEEG in a home setting, including getting access to a smartphone app to document seizure activity. The CG will receive care as usual, i.e., inpatient long-term video-EEG monitoring. The primary outcome is the proportion of clinical questions being solved in the IG compared to the CG. Secondary outcomes include hospital stays, time until video EEG, time until diagnosis and result discussion, patients’ health status, quality of life and health competence, and number and form of epilepsy-related events and epileptiform activity. Alongside the trial, a process implementation and health economic evaluation will be conducted.DiscussionThe extensive evaluation of this study, including an implementation and health economic evaluation, will provide valuable information for health policy decision-makers to optimize future delivery of neurological care to patients affected by epilepsy and other seizure disorders and on the uptake of ALVEEG into standard care in Germany.Trial registrationGerman Clinical Trials Register (DRKS00032220), date registered: December 11, 2023.

Seizure outcome in drug-resistant epilepsy in the setting of polymicrogyria

ObjectiveWe aimed to analyze seizure outcomes and define ictal onset with intracranial electroencephalography (ICEEG) in patients with polymicrogyria (PMG)-related drug-resistant epilepsy (DRE), considering surrounding cortex and extent of surgical resection. MethodsRetrospective study of PMG-diagnosed patients (2001 to June 2018) at a single epilepsy center was performed. Primary outcome was complete seizure freedom (SF), based on Engel classification with follow-up of ≥ 1 year. Univariate analyses identified predictive clinical variables, later integrated into multivariate Cox proportional hazards models. ResultsThirty-five patients with PMG-related DRE (19 adults/16 pediatric: 20 unilateral/15 bilateral) were studied. In surgical group (n = 23), 52 % achieved SF (mean follow-up:47 months), whereas none in non-resective treatment group (n = 12) attained SF (mean follow-up:39.3 months) (p = 0.002). In surgical group, there were no significant differences in SF, based on the laterality of the PMG [uni or bilateral,p = 0.35], involvement of perisylvian region(p = 0.714), and extent of the PMG resection [total vs. partial,p = 0.159]. Patients with ictal ICEEG onset in both PMG and non-PMG cortices, and those limited to non- PMG cortices had a greater chance of achieving SF compared to those limited to the PMG cortices. ConclusionResective surgery guided by ICEEG for defining the epileptogenic zone (EZ), in DRE patients with PMG, leads to favorable seizure outcomes. ICEEG-guided focal surgical resection(s) may lead to SF in patients with bilateral or extensive unilateral PMG. ICEEG aids in EZ localization within and/or outside the MRI-identified PMG. Complete removal of PMG identified on MRI does not guarantee SF. Hence, developing preimplantation hypotheses based on epileptogenic networks evaluation during presurgical assessment is crucial in this patient population.

The spectrum of indications for ultralong-term EEG monitoring

PurposeWe assessed clinical cases to investigate the spectrum of indications for ultra-longterm EEG monitoring using a subcutaneous implantable device in adult patients with focal epilepsy. MethodsElectronic charts were reviewed from patients undergoing ultra-longterm recordings at the European Epilepsy centers Barcelona, Freiburg and Vienna. Specific patient settings approached in the three centers were analyzed, and the main clinical question was extracted. Results from recordings were analyzed based on the specific results and information obtained. Results24 patients in whom ultra-longterm recordings were available were analyzed. A total of 11 main indications for subcutaneous long-term EEG recordings were identified, including the identification of active epilepsy in patients with low seizure frequency, under- and overreporting of patients, differentiation of non-epileptic from epileptic events, assessment of seizure severity, circadian and multidian rhythms of seizure occurrence, validation of treatment efficacy, improvement of patient-based reporting and medicolegal evidence for seizure freedom. This is reported with patient-specific case vignettes. ConclusionUltra-longterm monitoring using subcutaneous implantable EEG devices can provide relevant diagnostic and treatment information in a large spectrum of clinical situations. This is discussed considering the intrinsic limitations of the method related to spatial coverage, sensitivity and validity as a biomarker of ongoing seizures.

Widespread service fragmentation for patients and families with tuberous sclerosis complex (TSC) in the Republic of Ireland

BackgroundTuberous sclerosis complex (TSC) is a rare approximate 1:6000 birth incidence, a genetic disease with a wide variability of physical and neuropsychiatric symptoms. Patients require lifelong care from multiple healthcare specialities, for which International and United Kingdom (UK) TSC consensus recommendations exist. Personalised care delivered by a centralised coordinated team of TSC experts is recommended. There is no such service for the estimated 600 TSC patients in the Republic of Ireland (ROI) and there is a paucity of information regarding the healthcare of this group.PurposeEvaluate the baseline care of patients with TSC attending epilepsy services in the Republic of Ireland (ROI) against UK TSC consensus recommendations.MethodsPatients with a diagnosis of TSC attending 12 adult and paediatric epilepsy centres in the ROI were identified. Clinical audits measured the baseline care of a subset of these patients against UK, TSC clinical recommendations. Data was anonymised and analysed at Trinity College Dublin.ResultsOne hundred thirty-five TSC patients attending twelve epilepsy centres were identified. Adults (n = 67) paediatric (n = 68). The care of 83 patients was audited (n = 63 ≥ 18 years) and (n = 20 < 18 years). Many baseline tests were completed, however, they required intra or interhospital referral. Care appears fragmented and there was no evidence of formal disease surveillance plans.ConclusionsThe number of TSC patients attending epilepsy services is lower than expected (n = 135). Specialist services and treatments for TSC are available through informal referral pathways. Although UK, TSC consensus baseline recommendations are roughly adhered to, care is fragmented. Increased coordination of care could benefit disease management.

Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real-world study.

Dravet syndrome is a developmental and epileptic encephalopathy characterized by early onset epilepsy with multiple seizure types often intractable to treatment. Randomized clinical trials have demonstrated how treatment with fenfluramine significantly reduces seizure frequency in patients with Dravet syndrome. The study aims to (1) describe the efficacy and tolerability of fenfluramine in a Danish cohort of patients with Dravet syndrome; and (2) evaluate whether treatment with fenfluramine reduces epilepsy-related hospital contacts administrated by pediatricians or epilepsy-trained nurses. A retrospective registry-based cohort study at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark, enrolled 30 pediatric patients with Dravet syndrome treated with fenfluramine between 2017 and 2023. Thirty patients with Dravet syndrome (aged 3-21 years, 12 females) with a verified pathogenic SCN1A variant were included. They were treated with fenfluramine at a mean duration of 29 months with a mean maintenance dose of 0.5 mg/kg/day. The number of patient-years on treatment was 75 years. At last follow-up, 6 patients had discontinued treatment due to lack of efficacy or adverse effects. In the remaining 24 patients, generalized tonic-clonic seizures were reduced by ≥30% in 83%, by ≥50% in 67%, and by 100% in 25%. Additionally, 71% of the patients were reduced in concomitant anti-seizure medication, and 75% experienced a reduction (mean reduction at 52%, range 11%-94%) in epilepsy-related hospital contacts from baseline to the end of the treatment period. Treatment with fenfluramine effectively reduced seizure frequency and concomitant antiseizure medication in patients with Dravet syndrome. Furthermore, a decrease in epilepsy-related contacts by 80% was observed over 6 years of treatment, which may indicate cost-effective benefits. Patients with Dravet syndrome suffer from severe epileptic seizures that are difficult to treat with medication. Earlier, treatment with fenfluramine (an anti-seizure medication) has been documented to decrease the total number of seizures in patients with Dravet syndrome. This publication summarizes the experiences with fenfluramine in children with Dravet syndrome at the Danish Epilepsy Centre, Filadelfia, Dianalund, Denmark. Our publication also illustrates that treatment with fenfluramine may reduce the patients' number of yearly contacts with doctors and nurses specialized in epilepsy treatment, which may indicate cost-effectiveness.