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.

Lamotrigine vs levetiracetam in female patients of childbearing age with juvenile absence epilepsy: A Bayesian reanalysis.

OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.

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.

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.

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.

The spectrum of epilepsy with eyelid myoclonia: delineation of disease subtypes from a large multicenter study.

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) has been associated with marked clinical heterogeneity. Early epilepsy onset has been recently linked to lower chances of achieving sustained remission and to a less favorable neuropsychiatric outcome. However, much work is still needed to better delineate this epilepsy syndrome. METHODS: In this multicenter retrospective cohort study, we included 267 EEM patients from 9 countries. Data about electroclinical and demographic features, intellectual functioning, migraine with or without aura, family history of epilepsy and epilepsy syndromes in relatives were collected in each patient. The impact of age at epilepsy onset (AEO) on EEM clinical features was investigated, along with the distinctive clinical characteristics of patients showing sporadic myoclonia over body regions other than eyelids (body-MYO). RESULTS: Kernel density estimation revealed a trimodal distribution of AEO and Fisher-Jenks optimization disclosed three EEM subgroups: early-onset (EO-EEM), intermediate-onset (IO-EEM) and late-onset subgroup (LO-EEM). EO-EEM was associated with the highest rate of intellectual disability, antiseizure medication refractoriness and psychiatric comorbidities and with the lowest rate of family history of epilepsy. LO-EEM was associated with the highest proportion of body-MYO and generalized tonic-clonic seizures (GTCS), whereas IO-EEM had the lowest observed rate of additional findings. A family history of EEM was significantly more frequent in IO-EEM and LO-EEM compared with EO-EEM. In the subset of patients with body-MYO (58/267), we observed a significantly higher rate of migraine and GTCS but no relevant differences in other electroclinical features and seizure outcome. SIGNIFICANCE: Based on AEO, we identified consistent EEM subtypes characterized by distinct electroclinical and familial features. Our observations shed new light on the spectrum of clinical features of this generalized epilepsy syndrome and may help clinicians towards a more accurate classification and prognostic profiling of EEM patients.

Use of sulthiame as add-on therapy in children with myoclonic atonic epilepsy: A study of 35 patients.

PURPOSE: The aim of this retrospective study was to evaluate efficacy and tolerability of sulthiame (STM) as add-on treatment in 35 patients with myoclonic atonic epilepsy (MAE) resistant to other antiseizure medications (ASMs) and/or non-pharmacological treatment. METHODS: Patients were selected according to the diagnostic definition of MAE and were resistant to at least four previous to ASM, alone or in combination. Neurologic examinations, brain magnetic resonance imaging, and repeated prolonged electroencephalography (EEG) or video-EEG studies as well as neurometabolic studies were performed in all cases. Genetic studies were performed in 15 patients. Data on school achievements and/or neuropsychological evaluations were obtained over a mean follow-up of 30 months. Sulthiame was added in doses ranging from 10 to 30 mg/kg/day. Efficacy was assessed by comparing seizure frequency before and after initiating STM therapy. RESULTS: Twenty-one of 35 patients (60%) who received STM as add-on therapy had a greater than 50% seizure decrease after a mean follow-up of 30 months. Complete seizure freedom was achieved in two patients (5.8%). The remaining 14 patients (40%) had a 25-50% seizure reduction. Adverse effects, consisting of hyperpnea and dyspnea, decreased appetite, nausea, drowsiness, headache, and irritability, were observed in 11 (31.4%). The adverse effects were mild and transient in all cases. Discontinuation of STM was not necessary. CONCLUSION: Add-on STM led to a more than 50% seizure reduction in 21 of 35 patients with MAE with only mild or moderate adverse effects.

Vigabatrin-associated brain abnormalities on MRI and other neurological symptoms in patients with West syndrome.

OBJECTIVES: Report a series of children with West syndrome (WS) treated with vigabatrin (VGB) who developed characteristic MRI alterations. In the majority, these adverse events were asymptomatic; however, some of the patients developed movement disorders and acute encephalopathy. METHODS: This is a retrospective analysis of our epilepsy clinical and EEG database of 288 patients with WS seen between 2014 and 2020. All patients who received VGB alone or with concomitant therapies, such as adrenocorticotropic hormone (ACTH), high-dose oral corticosteroids, ketogenic diet, valproate, levetiracetam, or topiramate, were evaluated. RESULTS: In 44 of 288 patients with WS receiving VGB, MRI findings compatible with VGB-associated brain abnormalities were identified; median age at diagnosis was 6.29 months (range, 2 weeks to 11 months). The etiology of WS with vigabatrin-associated brain abnormalities on MRI (VABAM) was unknown in 22 (52.27%), genetic in seven (15.9%), genetic-structural in three (6.8%), structural malformative in three others (6.8%), and structural acquired in eight patients (18.2%). Vigabatrin-associated brain abnormalities on MRI was asymptomatic in 25 of 44 patients. Ten of 44 (22.7%) infants were reported to have had a movement disorder (choreoathetosis, dystonic posturing). Nine of 42 infants exhibited progressive psychomotor deterioration associated with signs and symptoms of encephalopathy. CONCLUSION: MRI abnormalities were observed in infants treated with VGB and they appeared to be dose dependent. In our study common locations for MRI abnormalities included globi pallidi and brainstem, followed by thalami and dentate nuclei. Risk factors for the development of VABAM may include age younger than 11 months and higher VGB dose of VGB (>165 mg/kg/day). Vigabatrin-associated brain abnormalities on MRI usually resolved following VGB discontinuation, probably after a period of 3 months.

Panayiotopoulos syndrome: Unusual clinical manifestations.

PURPOSE: We retrospectively analyzed the electroclinical features, treatment, and outcome of patients with Panayiotopoulos syndrome (PS) who presented with unusual clinical manifestations. METHOD: A retrospective, descriptive, multicenter study was conducted evaluating 44 patients with PS who had seizures with an unusual semiology. Data from patients with PS seen at eight Argentine centers between April 2000 and April 2019 were collected. RESULTS: Twelve patients (29.2%) had ictal syncope or syncope-like epileptic seizures. Three children (7.3%) had recurrent episodes of vomiting. Four patients (9.7%) presented with urinary incontinence associated with autonomic signs and consciousness impairment. One child had hiccups with autonomic manifestations followed by eye deviation. One boy had episodes of laughter with autonomic symptoms followed by loss of consciousness. Six patients (14.6%) had hyperthermia without acute febrile illness with autonomic symptoms as the first manifestation. Six others (14.6%) had focal motor seizures characterized by eye and head deviation in four and eyelid blinking in two. Four patients (9.7%) had ictal headache as the initial manifestation followed by nausea and vomiting. Two children (4.8%) had their first seizure while asleep associated with cardiorespiratory arrest. Two children (4.8%) had oral automatisms, such as sucking and chewing. In two children (4.8%) coughing was the initial manifestation followed by emetic symptoms. One patient (2.3%) had vertigo with a sensation of fear, with eye deviation and unresponsiveness. One child started with continuous spikes and waves during slow sleep, behavior disturbances, and emetic symptoms. CONCLUSION: In this study, evidence of the existence of unusual clinical cases of PS with typical EEG patterns was found. Outcome was excellent.

An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy.

BACKGROUND: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients. METHODS: Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma. RESULTS: The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates. CONCLUSIONS: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.

Self-limited epilepsy of childhood with affective seizures: A well-defined epileptic syndrome?

OBJECTIVE: Here we present cases of focal epilepsy with affective symptoms analyzing seizure characteristics, EEG pattern, treatment, and outcome. METHODS: A multicenter, descriptive, retrospective study was conducted evaluating 18 patients with self-limited epilepsy who presented with seizures with affective symptoms seen between April 2000 and April 2018 at eight Argentinian centers. RESULTS: Eighteen patients had focal seizures with affective symptoms; all of them had affective symptoms characterized by sudden fright or terror and screaming. Seizures started with manifestations of sudden fright or terror manifested by a facial expression of fear; consciousness was mildly impaired in 15/18 patients. Eleven of the patients also had autonomic manifestations, such as pallor, sweating, and abdominal pain. In addition, four of these 11 patients had ictus emeticus and one also presented with unilateral deviation of the eyes and head. Speech arrest, salivation, glottal noises, and chewing or swallowing movements were observed in 2/18 patients at the onset of the affective seizures. Two others also had mild asymmetric dystonic seizures involving both hands and arms. Three patients had tonic deviation of the mouth involving the lips and tongue as well pharyngeal and laryngeal muscles, resulting in anarthria and drooling. Two patients had brief hemifacial focal clonic seizures. CONCLUSION: Affective manifestations associated or not with motor and/or autonomic manifestations and associated with typical EEG features of the idiopathic focal epilepsies of childhood is a particular presentation of self-limited focal epilepsy in childhood.

Rufinamide as add-on therapy in children with epileptic encephalopathies other than Lennox-Gastaut syndrome: A study of 34 patients.

OBJECTIVE: Here, we present a multicenter series of patients with developmental and epileptic encephalopathies (DEE) and related electroclinical patterns (REP) other than Lennox-Gastaut syndrome (LGS) who were treated with rufinamide as add-on therapy. METHODS: Medical records of 34 patients with DEE and REP other than LGS treated with add-on rufinamide seen at four pediatric neurology centers in Argentina between May 2014 and March 2019 were retrospectively analyzed. RESULTS: We evaluated 34 patients (18 males, 16 females), aged between 2 and 15 years with a mean and median age of 6 and 8 years, respectively. The children had different types of childhood-onset refractory DEE and REP other than LGS and were treated with rufinamide for a mean period of 20 months (range, 12-60 months). Twenty-two of 34 patients (64.5%) who received rufinamide as add-on therapy had a greater than 50% decrease in seizures, and two patients (5.8%) became seizure-free. Four patients (11.7%) had a 25-50% seizure reduction, while seizure frequency remained unchanged in four others (11.7%) and increased in two patients (5.8%). The final mean dosage of rufinamide was 31.5 ±â€¯15.5 mg/kg per day (range, 19-75.4 mg/kg) if combined with valproic acid and of 35.4 ±â€¯11.5 mg/kg per day (range, 8-60.5 mg/kg) without valproic acid. Adverse effects were recorded in nine patients (26.4%). A seizure increase was reported in two of 24 patients (7.3%). CONCLUSION: Rufinamide may be used as a treatment option in DEE and REP other than LGS.

Dravet syndrome: Treatment options and management of prolonged seizures.

Over time, with careful delineation of Dravet syndrome, we have gained experience in treatments most likely to lead to improvement in seizures, as well as those that should be avoided. Sodium valproate, clobazam, stiripentol, and topiramate are all medications that may lead to benefit, as well as the ketogenic diet. Bromides may be utilized in resistant cases. However, equally important are outlining prompt rescue treatment for prolonged seizures and avoidance of precipitants. Newer agents including cannabidiol and fenfluramine have been demonstrated to be of benefit in clinical trials. We propose an algorithm for management, but appreciate that the positioning of newer agents is yet to be established.

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

BACKGROUND: Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in GRIN2A accounting for >5% of cases. OBJECTIVE: To identify rare, causal CNV in patients with RE. METHODS: We used high-density SNP arrays to analyse the presence of rare CNVs in 186 patients with RE from the UK, the USA, Sardinia, Argentina and Kerala, India. RESULTS: We identified 84 patients with one or more rare CNVs, and, within this group, 14 (7.5%) with recurrent risk factor CNVs and 15 (8.0%) with likely pathogenic CNVs. Nine patients carried recurrent hotspot CNVs including at 16p13.11 and 1p36, with the most striking finding that four individuals (three from Sardinia) carried a duplication, and one a deletion, at Xp22.31. Five patients with RE carried a rare CNV that disrupted genes associated with other epilepsies (KCTD7, ARHGEF15, CACNA2D1, GRIN2A and ARHGEF4), and 17 cases carried CNVs that disrupted genes associated with other neurological conditions or that are involved in neuronal signalling/development. Network analysis of disrupted genes with high brain expression identified significant enrichment in pathways of the cholinergic synapse, guanine-exchange factor activation and the mammalian target of rapamycin. CONCLUSION: Our results provide a CNV profile of an ethnically diverse cohort of patients with RE, uncovering new areas of research focus, and emphasise the importance of studying non-western European populations in oligogenic disorders to uncover a full picture of risk variation.

Treatment of electrical status epilepticus in sleep: A pooled analysis of 575 cases.

OBJECTIVE: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Treatment of ESES is assumed to improve cognitive outcome. The aim of this study is to create an overview of the current evidence for different treatment regimens in children with ESES syndrome. METHODS: A literature search using PubMed and Embase was performed. Articles were selected that contain original treatment data of patients with ESES syndrome. Authors were contacted for additional information. Individual patient data were collected, coded, and analyzed using logistic regression analysis. The three predefined main outcome measures were improvement in cognitive function, electroencephalography (EEG) pattern, and any improvement (cognition or EEG). RESULTS: The literature search yielded 1,766 articles. After applying inclusion and exclusion criteria, 112 articles and 950 treatments in 575 patients could be analyzed. Antiepileptic drugs (AEDs, n = 495) were associated with improvement (i.e., cognition or EEG) in 49% of patients, benzodiazepines (n = 171) in 68%, and steroids (n = 166) in 81%. Surgery (n = 62) resulted in improvement in 90% of patients. In a subgroup analysis of patients who were consecutively reported (585 treatments in 282 patients), we found improvement in a smaller proportion treated with AEDs (34%), benzodiazepines (59%), and steroids (75%), whereas the improvement percentage after surgery was preserved (93%). Possible predictors of improved outcome were treatment category, normal development before ESES onset, and the absence of structural abnormalities. SIGNIFICANCE: Although most included studies were small and retrospective and their heterogeneity allowed analysis of only qualitative outcome data, this pooled analysis suggests superior efficacy of steroids and surgery in encephalopathy with ESES.

[Contribution of the Ibero-American Academy of Neuropediatrics to the knowledge of self-limited epilepsy in infants]. / Aporte de la Academia Iberoamericana de Neuropediatría al conocimiento de la epilepsia autolimitada del lactante.

Since the first presentation at the IV Iberoamerican Academy of Neuropediatrics Congress in 1995, our group has studied self-limited infantile epilepsy (SeLIE), both familial and non-familial, corroborating that they belong to the same entity due to their clinical and electroencephalographic characteristics and excellent prognosis. Associations were found with paroxysmal dyskinesias and migraine, as well as with hemiplegic migraine, episodic ataxia and intellectual disability in atypical cases. Mutations in PRRT2 are the main cause of SeLIE, however, other genes, such as SCN2A, KCNQ2-3 and SCN8A, have been recognized. Drugs for focal seizures that act on sodium channels are indicated. In emergencies, during cluster seizures, the use of benzodiazepines is important. In this publication, we review our contribution in SeLIE from our first report to the present and review the existing literature on the subject.

Desde la primera presentación en el IV Congreso de la Academia Iberoamericana de Neurología Pediátrica en 1995, nuestro grupo ha estudiado las epilepsias autolimitadas del lactante (EAL), tanto familiares y no familiares, corroborando que pertenecen a una misma entidad por sus características clínicas, electroencefalográficas y excelente pronóstico. Se encontraron asociaciones con discinesias paroxísticas y migraña, como también con la migraña hemipléjica, la ataxia episódica y la discapacidad intelectual en casos atípicas. Las mutaciones en PRRT2 son la principal causa de EAL. Sin embargo, otros genes, como SCN2A, KCNQ2-3 y SCN8A, han sido reconocidos. Los fármacos para las crisis focales que actúan sobre los canales de sodio son los indicados. En emergencias, durante las convulsiones agrupadas, es importante el uso de benzodiacepinas. En esta publicación, hacemos un recorrido de nuestro aporte en EAL desde nuestra primera contribución hasta la actualidad y además realizamos una revisión de la literatura existente sobre el tema.

Epileptic spasms in clusters without 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.

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.

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.

Myoclonic epilepsy in infancy: an electroclinical study and long-term follow-up of 38 patients.

PURPOSE: Myoclonic epilepsy in infancy (MEI) is characterized by brief generalized myoclonic seizures associated with generalized spike-wave paroxysms without other seizure types occurring in the first 3 years of life in developmentally normal children. In this study we analyze the electroclinical features, treatment, and outcome of 38 patients with MEI. METHODS: A retrospective chart review was conducted in 38 patients followed at the Neurology Department of the Pediatric Hospital Juan P. Garrahan in Buenos Aires, Argentina, between 1990 and 2012. KEY FINDINGS: A total of 24 boys and 14 girls were identified. The mean and median ages at seizure onset were 16 and 18 months, respectively (range 3-40 months). Ten patients (28.9%) had a family history of epilepsy, and six (15.8%) had a family history of febrile seizures. All patients had several daily brief and isolated myoclonic seizures during wakefulness and predominantly in the first two stages of sleep. Twelve children (31.5%) had reflex myoclonus, triggered by a tactile stimulus in 10 and additionally by noise and light in 2. The remaining two had photosensitive myoclonic jerks. The interictal electroencephalography (EEG) recordings evidenced generalized spike waves, polyspikes, and polyspike-wave paroxysms. The interictal EEG was normal in 12 patients. The abnormalities on the ictal EEG were similar to those on the interictal EEG. Most of the patients responded well to valproic acid. After a mean follow-up of 13.5 years, 24 patients (63%) were without treatment. At the last examination, 32 patients had normal neurologic and neuropsychological evaluations. Two patients (5.2%) had significant cognitive impairment (an IQ of 60 and 63, respectively) despite good seizure control. Four patients (10.4%) had significant learning impairment, two of whom also had attention deficit hyperactivity disorder. SIGNIFICANCE: MEI is a well-defined epileptic syndrome of unknown etiology, but likely of a genetic cause. It is self-limited and pharmacosensitive mainly to valproic acid.