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.
Summary
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.
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.
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.
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.
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.
•Seventy-two infants had epileptic spasms in clusters without classic or modified hypsarrhythmia.•Thirty children presented with epileptic spasms in clusters without classic or modified hypsarrhythmia.•Both groups had similar electroclinical patterns, etiologies, response to the treatment and evolution.•None of the patients, except one, developed features of epileptic encephalopathy.•These patients may represent a well-defined epileptic syndrome involving different age groups.
Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due ...to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre-KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow-up, side events, and KDT discontinuation. It has been helpful in outlining a state-of-the-art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.
Here we present a multicenter series of patients with developmental epileptic encephalopathies (DEE) who were treated with brivaracetam (BRV) as add-on therapy.
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.
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.
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.
Summary
The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally ...significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre‐KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow‐up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.
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.
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.
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.
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 ± 15.5 mg/kg per day (range, 19–75.4 mg/kg) if combined with valproic acid and of 35.4 ± 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%).
Rufinamide may be used as a treatment option in DEE and REP other than LGS.
•Rufinamide was particularly effective against myoclonic–atonic, tonic, and focal seizures.•Atypical absence seizures, epileptic spasms, and generalized tonic–clonic seizures were also reduced.•Rufinamide is useful in the treatment of epileptic encephalopathies other than Lennox–Gastaut syndrome.•Rufinamide is generally well-tolerated.
•VABAM were observed in infants treated with higher VGB dose (>165 mg/kg/day) and they appeared to be dose dependent.•Locations included globi pallidi, brainstem, thalami, and dentate nuclei.•Risk ...factors for VABAM may include age <11 months.•VABAM on MRI usually resolved following VGB discontinuation after a period of around 3 months.•Some of the patients developed movement disorders and acute encephalopathy associated with VABAM.
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.
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.
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.
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.
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