Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.

BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.

Epileptic spasms in clusters with hypsarrhythmia in infancy and childhood: A single age-dependent type of epilepsy or well-defined epileptic syndrome?

OBJECTIVE: In this study, we present the electroclinical features and outcomes of 92 patients with epileptic spasms (ES) in clusters without modified or classical hypsarrhythmia that started in either in infancy or in childhood; we compared both groups in terms of electroclinical features, etiology, treatment, evolution, and outcome. METHODS: Between June 2000 and July 2022, 92 patients met the electroclinical diagnostic criteria of ES in clusters without hypsarrhythmia. Patients with ES associated with other epileptic encephalopathies including West Syndrome, as well as those with the specific etiology of ES and developmental and epileptic encephalopathy associated with CDKL5 were excluded. RESULTS: The patients were divided into two groups based on the age at ES onset: those with ES onset before (Group 1) and those with ES onset after 2 years of age (Group 2). The features of ES and the type of associated seizures before and after ES onset, as well as the interictal and ictal EEG and electromyography findings were similar in both groups. The etiologies were mainly structural (40.2%), genetic (11.9%), and unknown (44.6%) in majority of the patients in both groups. Thirty-one patients were seizure-free, while in the remaining patients the seizures continued. Nine patients (9.8%) with unilateral structural lesions underwent surgery with good results. The neurological abnormalities and developmental findings prior to ES onset depended on the underlying etiology. CONCLUSION: Our series of patients may represent a well-defined epileptic syndrome or type of epilepsy with onset in infancy or childhood characterized by ES in clusters without hypsarrhythmia associated with focal and generalized seizures and EEG paroxysms without neurological deterioration.

Crisis epilépticas sintomáticas agudas. Descripción clinicoelectroencefalográfica etiológica y pronóstico de una serie oncopediátrica / Acute symptomatic epileptic seizures. A clinical-electroencephalographic etiological description and prognosis of an oncopediatric series

Objetivo Determinar las características clínicas, electroencefalográficas, terapéuticas y evolutivas de una serie de pacientes oncopediátricos con convulsiones sintomáticas agudas. Pacientes y métodos Efectuamos un análisis descriptivo retrospectivo y prospectivo de registros clínicos de niños oncopediátricos evaluados por neurología en el Centro Ambulatorio Integral de Pacientes Hematooncológicos durante 2017-2021. Incluimos a niños de 1 mes a 17 años con tumores intracraneales y extracraneales que presentaron convulsiones sintomáticas agudas (CSA). Definimos convulsión sintomática aguda según la clasificación de la Liga Internacional contra la Epilepsia de 2010. Clasificamos las crisis epilépticas según la clasificación de la Liga Internacional contra la Epilepsia de 2017. Excluimos a todo paciente con diagnóstico de epilepsia previa y de episodios paroxísticos no epilépticos. Resultados Analizamos 44 casos, con una mediana de 4 años (rango: 1 mes-17 años) y una media de 5,75 meses (rango: 1 mes-11 meses) y 8,33 años (2-17 años). Registramos como principales etiologías la neurotoxicidad y el contexto posquirúrgico, con cuatro pacientes asociados a disnatremias y dos a hipertensión endocraneana. Se realizaron 41 electroencefalogramas, con resultados intercríticos con anormalidades en el ritmo de base, pero sin focos ni paroxismos. No hubo registros críticos. Las convulsiones focales fueron 25 (56,8%), y las generalizadas, 19 (43,18%). El levetiracetam fue el fármaco más utilizado para el tratamiento agudo. Conclusiones Nuestra cohorte muestra que las CSA, en esta población, no evidencian diferencias considerables entre convulsiones focales motoras y generalizadas, y ocurren mayormente en un contexto neurotóxico y posquirúrgico. También se registraron disnatremias e hipertensión endocraneana asociadas a CSA. Los electroencefalogramas poscrisis fueron sin focos o paroxismos y con evolución de las crisis. (AU)

AIM To determine clinical, electroencephalographic, therapeutic and evolutive characteristics of a series of oncopediatric patients with acute symptomatic seizures. PATIENTS AND METHODS We performed a retrospective and prospective descriptive analysis of clinical records of oncopediatric children evaluated by neurology at the comprehensive outpatient Center for Hemato-Oncological Patients during 2017-2021. We included children aged one month to 17 years with intracranial and extracranial tumors who presented with acute symptomatic seizure (ASC). We defined acute symptomatic seizure according to the 2010 International League Against Epilepsy. We classified seizures according to 2017 International League Against Epilepsy classification. We excluded any patient with a diagnosis of previous epilepsy and non-epileptic paroxysmal episodes. RESULTS We analyzed 44 cases with a median of 4 years (range: 1 month-17 years) and mean of 5.75 months (range: 1 month-11 months) and 8.33 years (2-17 years). The main etiologies were neurotoxicity and post-surgical context. Four patients presented dysnatremias and two associated with endocranial hypertension. Forty-one electroencephalograms were performed with intercritical results with abnormalities in the baseline rhythm, but without foci or paroxysms. There were no critical recordings. Focal seizures were 25 (56.8%) and generalized seizures 19 (43.18%). Levetiracetam was the most commonly used drug for acute management. CONCLUSIONS Our cohort shows that ASC, in this population, do not show considerable differences between focal motor and generalized seizures and occur mostly in neurotoxic and post-surgical contexts. Dysnatremias and endocranial hypertension associated with ASC were also recorded. Postcrisis electroencephalograms were without foci or paroxysms and good seizure evolution. (AU)

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

Purified cannabidiol as add-on therapy in children with treatment-resistant infantile epileptic spasms syndrome.

OBJECTIVE: The aim of this study was to assess efficacy, safety, and tolerability of highly purified cannabidiol oil (CBD) as add-on therapy for the treatment of a series of patients with infantile epileptic spasms syndrome (IESS) who were resistant to antiseizure medications and ketogenic dietary therapy. MATERIAL AND METHODS: We conducted a retrospective analysis of the medical records of 28 infants with treatment-resistant IESS aged 6 to 21 months who received highly purified CBD between July 2021 and June 2023. Data were collected on neurological examinations, EEG, Video-EEG and polygraphic recordings, imaging studies, laboratory testing, and seizure frequency, type, and duration, and adverse effects. As the primary outcome, a reduction of frequency of epileptic spasms (ES) was assessed. ES freedom was considered after a minimal time of 1 month without ES. RESULTS: Sixteen male and 12 female patients, aged 6-21 months, who received CBD for treatment-resistant IESS were included. The etiology was structural in 10, Down syndrome in seven, genetic in nine, and unknown in two. Initial CBD dose was 2 mg/kg/day, which was uptitrated to a median dose of 25 mg/kg/day (range, 2-50). Prior to CBD initiation, patients had a median of 69 ES in clusters per day (range, 41-75) and of 10 focal seizures per week (range, 7-13). After a mean and median follow-up of 15 and 12.5 months (range, 6-26 months), seven patients were ES free and 12 had a >50 % ES reduction. Five of seven patients (71 %) with Down syndrome and 3/5 (60 %) with cerebral palsy responded well. Adverse effects were mild. EEG improvements correlated with ES reductions. CONCLUSION: In this study evaluating the use of CBD in children with IESS, 19/28 (67.8 %) had a more than 50 % ES reduction with good tolerability.

Use of ketogenic dietary therapy for drug-resistant epilepsy in early infancy.

OBJECTIVE: There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug-resistant epilepsy in whom KDT was used. METHODS: A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug-resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival. RESULTS: Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow-up of 1 month were included; 13 had early-infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable. SIGNIFICANCE: Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary.

Cerebral hemiatrophy and hemiparesis following hemiclonic status epilepticus in Dravet syndrome.

Dravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss-of-function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies "Focal neurological findings" as alert criteria and "MRI showing a causal focal lesion" as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well-known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype-phenotype studies may provide additional insights into this electroclinical behavior.

Brivaracetam as add-on therapy in children with developmental epileptic encephalopathies: A study of 42 patients.

OBJECTIVE: Here we present a multicenter series of patients with developmental epileptic encephalopathies (DEE) who were treated with brivaracetam (BRV) as add-on therapy. METHODS: Medical records of 42 patients with DEE treated with add-on BRV seen at four pediatric neurology centers in Argentina between January 2021 and July 2023 were retrospectively analyzed. RESULTS: We included 42 patients (26 males, 16 females) with a mean age of 7 years (SD, ± 3.8; median, 9; range, 2-16). The children had different types of childhood-onset treatment-resistant DEEs and received BRV as add-on therapy for a mean period of 2 years (SD, ± 1.3 years; median, 1.5 years; range, 0.5-3 years). Thirty-three patients received levetiracetam (LEV) before the introduction of BRV. In nine patients, BRV was started without prior LEV because of behavioral disturbances. Three patients (9.5 %) became seizure free and 26/42 patients (62.1 %) had a greater than 50 % decrease in seizures after a mean follow-up of 21 months. Ten patients (23.8 %) had a 25-50 % seizure reduction, while seizure frequency remained unchanged in two (4.7 %) and increased in one patient (2.4 %). The interictal EEG abnormalities improved in all the responders. Adverse effects, consisting of drowsiness, irritability, and decreased appetite, were observed in seven patients (16.6 %), but did not lead to treatment discontinuation. CONCLUSION: Brivaracetam was found to be effective, safe, and well tolerated in children with DEE. In patients on LEV with behavioral disturbances, BRV may be tried. BRV may also be given without a previous trial with LEV in patients with behavioral problems.

[Benefit of surgery in a case of negative motor focal epileptic seizures secondary to parietal cortical dysplasia]. / Beneficio de la cirugía en un caso de crisis epilépticas focales motoras negativas secundarias a displasia cortical parietal.

Focal atonic seizures are recognized rarely as ictal phenomena, they can correspond to both generalized epilepsy and focal epilepsy. The areas of the brain involved in the management of this type of seizure are: the negative motor area and the primary motor and primary somatosensory cortices, although the neurophysiology that generates them is still unclear. We present the case of a patient with focal atonic seizures in the left upper limb, refractory to drug treatment. Neuroimaging was performed, a parietal cortical lesion was diagnosed. A scalp Video EEG and then a Stereo EEG was performed, defining the epileptogenic area and its relationship with eloquent areas. Surgical resection of the lesion was performed, achieving complete seizure control.

Las crisis atónicas focales son poco reconocidas como fenómenos ictales, pueden corresponder tanto a una epilepsia generalizada como a una epilepsia focal. Las áreas del cerebro implicadas en la gestión de este tipo de crisis son: el área motora negativa y las cortezas motora primaria y somatosensitiva primaria, aunque aún la neurofisiología que las genera no está aclarada. Presentamos el caso de un paciente con crisis atónicas focales farmacorresistentes en miembro superior izquierdo. Se realizó resonancia de cerebro con diagnóstico de displasia cortical parietal, se monitoreó con video EEG de scalp y luego a video EEG con electrodos profundos. Se definieron el área epileptógena y su relación con áreas elocuentes, se realizó resección quirúrgica de la lesión, logrando el control completo de las crisis.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy.

Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. Design, Setting, and Participants: This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Exposures: Levetiracetam or lamotrigine as initial monotherapy. Main Outcomes and Measures: Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. Results: A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Conclusions and Relevance: Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet.

Introduction: Ketogenic dietary therapies (KDT) are well-established, safe, non-pharmacologic treatments used for children and adults with drug-resistant epilepsy and other neurological disorders. Ketone bodies (KBs) levels are recognized as helpful to check compliance to the KDT and to attempt titration of the diet according to the individualized needs. KBs might undergo inter-individual and intra-individual variability and can be affected by several factors. Possible variations in glycemia and ketone bodies blood levels according to the menstrual cycle have not been systematically assessed yet, but this time window deserves special attention because of hormonal and metabolic related changes. Methods: This study aims at searching for subtle changes in KBs blood level during menstrual cycle in female patients undergoing a stable ketogenic diet, by analyzing 3-months daily measurement of ketone bodies blood levels and glucose blood levels throughout the menstrual cycle. Results: We report the preliminary results on six female patients affected by GLUT1DS or drug resistant epilepsy, undergoing a stable classic ketogenic diet. A significant increase in glucose blood levels during menstruation was found in the entire cohort. As far as the ketone bodies blood levels, an inversely proportional trend compared to glycemia was noted. Conclusion: Exploring whether ketonemia variations might occur according to the menstrual cycle is relevant to determine the feasibility of transient preventive diet adjustments to assure a continuative treatment efficacy and to enhance dietary behavior support. Clinical trial registration: clinicaltrials.gov, identifier NCT05234411.

Real-World Evidence of Factors Affecting Cannabidiol Exposure in Children with Drug-Resistant Developmental and Epileptic Encephalopathies.

The identification of factors that affect cannabidiol (CBD) systemic exposure may aid in optimizing treatment efficacy and safety in clinical practice. In this study, we aimed to correlate CBD plasma concentrations at a steady state to demographic, clinical, and pharmacological characteristics as well as seizure frequency after the administration of a purified CBD oil solution in a real-world setting of children with drug-resistant developmental and epileptic encephalopathies (DEEs). Patients receiving oral CBD pharmaceutical products at maintenance were enrolled. Venous blood samples were drawn before the CBD morning dose, 12 h apart from the last evening dose (C0 or CBD trough concentration). A linear mixed-effect analysis was implemented to assess the correlation between C0 and clinical, laboratory, pharmacological, and lifestyle factors. Fifteen females and seven males with a median age of 12.8 years (ranging between 4.7 and 17.2) were included. The median CBD dose was 8.8 mg/kg/day (ranging between 2.6 and 22.5), and the CBD C0 median (range) was 48.2 ng/mL (3.5-366.3). The multivariate model showed a 109.6% increase in CBD C0 in patients with concomitant levothyroxine (ß = 0.74 ± 0.1649, p < 0.001), 56.8% with food (ß = 0.45 ± 0.1550, p < 0.01), and 116.0% after intake of a ketogenic diet (ß = 0.77 ± 0.3141, p < 0.05). All patients included were responders without evidence of an association between C0 and response status. In children with DEEs, systemic concentrations of CBD may be significantly increased when co-administered with levothyroxine, food, or a ketogenic diet.

Epileptic spasms in infants: can video-EEG reveal the disease's etiology? A retrospective study and literature review.

Objective: Epileptic spasms are a type of seizure defined as a sudden flexion or extension predominantly of axial and/or truncal limb muscles that occur with a noticeable periodicity. Routine electroencephalogram supports the diagnosis of epileptic spasms, which can occur due to different causes. The present study aimed to evaluate a possible association between the electro-clinical pattern and the underlying etiology of epileptic spasms in infants. Materials and methods: We retrospectively reviewed the clinical and video-EEG data on 104 patients (aged from 1 to 22 months), admitted to our tertiary hospital in Catania and the tertiary hospital in Buenos Aires, from January 2013 to December 2020, with a confirmed diagnosis of epileptic spasms. We divided the patient sample into structural, genetic, infectious, metabolic, immune, and unknown, based on etiology. Fleiss' kappa (К) was used to assess agreement among raters in the electroencephalographic interpretation of hypsarrhythmia. A multivariate and bivariate analysis was conducted to understand the role of the different video-EEG variables on the etiology of epileptic spasms. Furthermore, decision trees were constructed for the classification of variables. Results: The results showed a statistically significant correlation between epileptic spasms semiology and etiology: flexor spasms were associated with spasms due to genetic cause (87.5%; OR < 1); whereas mixed spasms were associated with spasms from a structural cause (40%; OR < 1). The results showed a relationship between ictal and interictal EEG and epileptic spasms etiology: 73% of patients with slow waves and sharp waves or slow waves on the ictal EEG, and asymmetric hypsarrhythmia or hemi hypsarrhythmia on the interictal EEG, had spasms with structural etiology, whereas 69% of patients with genetic etiology presented typical interictal hypsarrhythmia with high-amplitude polymorphic delta with multifocal spike or modified hypsarrhythmia on interictal EEG and slow waves on the ictal EEG. Conclusion: This study confirms that video-EEG is a key element for the diagnosis of epileptic spasms, also playing an important role in the clinical practice to determine the etiology.

Cannabidiol in children with treatment-resistant epilepsy with myoclonic-atonic seizures.

PURPOSE: This multicenter study aimed to evaluate the efficacy and tolerability of add-on cannabidiol (CBD) in treatment-resistant patients with epilepsy with myoclonic-atonic seizures (EMAtS) (n = 22) and Sturge Weber syndrome (SWS) with myoclonic-atonic seizures (n = 4). METHODS: Patients who met the diagnostic criteria of treatment-resistant EMAtS or SWS with myoclonic-atonic seizures were included. Cannabidiol was added in doses ranging from 8 to 40 mg/kg/day. Efficacy was assessed by comparing seizure frequency before and after initiating CBD therapy. Neurologic examinations, brain magnetic resonance imaging, repeated prolonged electroencephalography (EEG) and/or video-EEG recordings, and neurometabolic studies were performed in all patients, and genetic investigations in 15. RESULTS: After a mean follow-up of 19 months, 15/26 patients (57.7%) who received add-on CBD had a >50% seizure decrease; three (11.5%) became seizure-free. The remaining 11 patients (42.3%) had a 25-50% seizure reduction. Drop attacks, including myoclonic-atonic seizures and generalized tonic-clonic seizures, as well as atypical absences and nonconvulsive status epilepticus responded well to CBD. In SWS patients, focal motor seizures without consciousness impairment and focal non-motor seizures with consciousness impairment were recognized in two each; in three a 30% reduction of focal seizures was observed. Side effects were mild and did not lead to CBD discontinuation. CONCLUSION: This study evaluating the use of add-on CBD in children with EMAtS or SWS with myoclonic-atonic seizures found that 15/26 (57.7%) had a >50% seizure reduction with good tolerability; three (11.5%) became seizure-free.

Sex-based electroclinical differences and prognostic factors in epilepsy with eyelid myoclonia.

Although a striking female preponderance has been consistently reported in epilepsy with eyelid myoclonia (EEM), no study has specifically explored the variability of clinical presentation according to sex in this syndrome. Here, we aimed to investigate sex-specific electroclinical differences and prognostic determinants in EEM. Data from 267 EEM patients were retrospectively analyzed by the EEM Study Group, and a dedicated multivariable logistic regression analysis was developed separately for each sex. We found that females with EEM showed a significantly higher rate of persistence of photosensitivity and eye closure sensitivity at the last visit, along with a higher prevalence of migraine with/without aura, whereas males with EEM presented a higher rate of borderline intellectual functioning/intellectual disability. In female patients, multivariable logistic regression analysis revealed age at epilepsy onset, eyelid myoclonia status epilepticus, psychiatric comorbidities, and catamenial seizures as significant predictors of drug resistance. In male patients, a history of febrile seizures was the only predictor of drug resistance. Hence, our study reveals sex-specific differences in terms of both electroclinical features and prognostic factors. Our findings support the importance of a sex-based personalized approach in epilepsy care and research, especially in genetic generalized epilepsies.

Use of sulthiame as add-on therapy in children with non-self-limited focal epilepsies of childhood.

PURPOSE: This retrospective study aimed to evaluate the efficacy and tolerability of sulthiame (STM) as an add-on treatment in 49 patients with non-self-limited focal epilepsies of childhood (non-SeLFE) resistant to other antiseizure medications (ASM) and/or non-pharmacological treatment. METHODS: Patients with non-SeLFE who had failed to respond to at least five previous ASM, alone or in combination, were included in the study. All patients underwent neurological examination, brain magnetic resonance imaging repeated prolonged electroencephalography (EEG) or video-EEG studies, and neurometabolic studies. School achievements and/or performance on neuropsychological tests were also assessed. Sulthiame was added in doses ranging from 10 to 40 mg/kg/day. Efficacy was measured by comparing seizure frequency before and after initiating STM therapy. RESULTS: Twenty-nine of 49 patients (59.1%) who received STM as add-on therapy had a greater than 50% decrease in seizures after a mean follow-up of 35 months. One patient (2%) became seizure-free. Fourteen patients (40%) had a 25-50% seizure reduction. The mean time of response was 5 months (range, 3.5 to 6 months). No differences were found either between patients with a response of more or less than 50% or between the response of the focal seizure types (motor or non-motor, with or without consciousness impairment). CONCLUSION: In our study, STM was found to be effective and well-tolerated in children and adolescents with non-SeLFE. In the patients who responded, improvement in the EEG was seen.

Telemedicine for Individuals with epilepsy: Recommendations from the International League Against Epilepsy Telemedicine Task Force.

Worldwide, People with Epilepsy (PWE) are confronted with several barriers to face-to-face consultations. These obstacles hamper appropriate clinical follow-up and also increase the treatment gap for Epilepsy. Telemedicine holds the potential to enhance management as follow-up visits for PWE are focused on more on clinical history and counselling rather than physical examination. Besides consultation, telemedicine can also be used for remote EEG diagnostics and tele-neuropsychology assessments. In this article, the Telemedicine Task Force of the International League Against Epilepsy (ILAE) outlines recommendations regarding optimal practice in utilizing in the management of individuals with epilepsy. We formulated recommendations for minimum technical requirements, preparing for the first tele-consultation and the specificities for follow-up consultations. Special considerations are necessary for specific populations, including paediatric patients, patients who are not conversant with tele-medicine and those with intellectual disability. Telemedicine for individuals with epilepsy should be vigorously promoted with the aim of improving the quality of care and ultimately reduce the wide clinician access related treatment gap across several regions of the globe.

CDKL5-associated developmental and epileptic encephalopathy: A long-term, longitudinal electroclinical study of 22 cases.

OBJECTIVE: The study was conducted to analyze the possible diagnostic value of the electroclinical semiology of the epileptic seizures. METHODS: We evaluated the medical records of 17 females and 5 males with CDKL5 deficiency disorder (CDD) considering the long-term evolution, including the polygraphic video-EEG recordings. RESULTS: We recognized three disease phases. We found that the seizure semiology was already recognizable in the first phase of the syndrome. In the short-term evolution, all patients had focal motor and 12/21 hypermotor seizures. Both epileptic spasms and myoclonic seizures were already present in more than half of the cases in the first 2 months after onset. In the second phase, the intermediate period, the polymorphic pattern was maintained, but in eight patients the electroclinical pattern of epileptic encephalopathy with hypsarrhythmia appeared. In the long-term period, the seizure polymorphism continued but myoclonic and epileptic spasms diminished. Tonic seizures appeared in the last 2 phases. Progressively, with the aggravation of seizures and paroxysmal EEG abnormalities impairment of the neurocognitive status was observed. Severe behavioral disturbances were seen in eight and autistic-like features in 14. CONCLUSION: CDD is a true developmental and epileptic encephalopathy with a specific etiology characterized by the early appearance of epileptic seizures that quickly become polymorphic and drug resistant in infants that are most often female and already have neurological impairment. Polygraphic video-EEG recordings are important to recognize ictal events of the association of hypermotor seizures, epileptic spasms in clusters, and massive myoclonic jerks, already present at onset.

Deficiencia del transportador de glucosa tipo 1: aspectos clínicos, diagnóstico y terapéutica / Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment

El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.

Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid, and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.