Refractory Epileptic Encephalopathy Research Articles

Dravet syndrome an unusual cause of atypical febrile seizure: a case report

Dravet syndrome is a rare refractory epileptic encephalopathy with an underlying genetic basis. It presents with recurrent febrile seizures in infancy. Though development is normal in infancy, neurodevelopmental delay and neurologic disability begin after the onset of seizure at the age of around 2-4 years. The outcome can be improved by early diagnosis (genetic testing for SCN1A gene) and timely treatment. In this case report we are presenting a 3-year-old female child with recurrent refractory epilepsy associated with fever and was diagnosed with Dravet syndrome.

Distinct contribution of monocarboxylate transporter 2 to infantile epileptic spasms syndrome

Infantile epileptic spasms syndrome (IESS) is the most common refractory epileptic encephalopathy in early brain development, its pathogenesis remains elusive. In the adult brain, glucose serves as the predominant metabolic fuel. However, ketone bodies and lactate are more important in neural energy metabolism during early development. This has been further provided by the effectiveness of ketogenic diet (KD) therapy in IESS. When the circulatory pool of ketone bodies is increased by KD, the brain utilizes ketone bodies preferentially to meet the high energy demand of neurons which is beneficial to mitigate seizure activity and promote prognosis for children with IESS. Neuronal monocarboxylate transporter 2 (MCT2) is crucial in this process, transporting ketone bodies and lactate to mitochondria for adenosine triphosphate (ATP) generation for cellular energy. The inhibition of MCT2 has been linked to mitochondrial dysfunction and its reduction has been found in adult animal epilepsy models. The mitochondrial energy metabolism disorder is a recognized central pathological aspect of epileptogenesis. Therefore, we hypothesize that neuronal MCT2, an essential gatekeeper of energy metabolism, may play a critical role in the genesis and propagation of spasms in IESS by markedly affecting brain metabolic homeostasis and mitochondrial function. We propose to conduct animal studies and clinical studies to investigate the relationship among MCT2, severity of IESS, susceptibility of IESS, and mitochondrial dysfunction from a metabolic perspective.

A Novel De Novo Variant in KCNH5 in a Patient with Refractory Epileptic Encephalopathy.

We herein report a novel de novo KCNH5 variant in a patient with refractory epileptic encephalopathy. The patient exhibited seizures at 1 year and 7 months old, which gradually worsened, leading to a bedridden status. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and cerebellar hypoplasia. A trio whole-exome sequence analysis identified a de novo heterozygous c.640A>C, p.Lys214Gln variant in KCNH5 that was predicted to be deleterious. Recent studies have linked KCNH5 to various epileptic encephalopathies, with many patients showing normal MRI findings. The present case expands the clinical spectrum of the disease, as it is characterized by severe neurological prognosis, cerebral atrophy, and cerebellar hypoplasia.

Treatment of Refractory Epilepsy With MEK Inhibitor in Patients With RASopathy

BackgroundSeveral specific syndromes within the RASopathies spectrum lead to an increased risk of seizures up to developing refractory epileptic encephalopathy. Management remains symptomatic. MethodsHere we report two patients treated with trametinib, a MEK1-2 inhibitor, as a precision strategy for drug-resistant epilepsy. Patient 1 is a six-year-old girl with cardiofaciocutaneous syndrome (BRAF p.F595L, germline mutation), and Patient 2 is a 14-month-old boy with Schimmelpenning syndrome (KRAS p.G12D, postzygotic somatic mutation). Trametinib was initiated at a dosage of 0.025 mg/kg/day. ResultsPatient 1 had multiple seizures per day, multifocal motor to bilateral tonic-clonic. Electroencephalography (EEG) showed a dramatic reduction in EEG discharges three months after trametinib onset, while a marked clinical improvement occurred after about five months, at the same dosage, and the girl is currently seizure-free for more than six months.Patient 2 had left cerebral hemiatrophy leading to right focal motor seizures, multiple per week to multiple per day, since the age of three months. On trametinib, he experienced an early benefit, remaining seizure-free for more than three months. However, after six months we observed recurrence of seizures. After 22 months of treatment, trametinib was discontinued because of a suspected drug-induced inflammatory colitis. After discontinuation, we observed a significant clinical and EEG “rebound effect.” ConclusionsWe provide proof of concept that MEK inhibition is a promising approach for the treatment of patients with refractory epilepsy with selected germline and mosaic RASopathies. Future trials are encouraged to better investigate their potentials and limitations.

Pharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy.

Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil-based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21days after the beginning of treatment. Twelve patients who received a median (range) dose of 12.2 (5.3-19.4) mg/kg/d (twice daily) were included in the analysis. Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6hours after dosing were 3.2hours (1.9-6.2), 49.6ng/mL (14.4-302.0), and 226.3ng ⋅ h/mL (70.5-861.3), respectively. CBD systemic exposure parameters were in the lower range of previous reports in pediatric patients receiving doses in a similar range. Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system. CDB administration was generally safe and well tolerated, and a novel levothyroxine-CBD interaction was recorded. Similar to other studies, large interindividual variability in CBD exposure was observed, encouraging the use of CBD therapeutic drug monitoring.

KCNQ2 Encephalopathy Showing a Distinct Ictal Amplitude-Integrated Electroencephalographic Pattern

KCNQ2 mutations induce a neonatal-onset epileptic encephalopathy of widely varying severity, ranging from benign familial neonatal epilepsy to severe refractory epileptic encephalopathy. Refractory seizures with KCNQ2 mutations have a positive response to sodium-channel blockers. Recently, a distinctive ictal pattern has been reported during amplitude-integrated electroencephalographic (aEEG) monitoring in infants with KCNQ2 encephalopathy. Herein, we describe a case of KCNQ2 encephalopathy with this distinctive ictal aEEG pattern, which was confirmed using conventional electroencephalography (EEG). A 3-day-old female infant presented with neonatal seizures accompanied by cyanosis and desaturation. Her seizure semiology was tonic and focal clonic. Her ictal aEEG demonstrated a sudden rise in amplitude followed by a suppressed background pattern. This pattern was also confirmed on conventional EEG. Her seizures were refractory despite the administration of multiple conventional antiepileptic drugs. Finally, c.794C>T; p. (Ala265Val) mutation was observed in the KCNQ2 gene on genetic testing, and she was diagnosed with KCNQ2 encephalopathy. Identifying this distinctive ictal pattern on aEEG monitoring facilitates the early detection of KCNQ2 encephalopathy and timely targeted treatment in patients with refractory seizures. Keywords: KCNQ2; Mutation; Infant; Seizures; Epilepsy; Electroencephalography

Cognitive and functional status in late-onset Lennox–Gastaut syndrome: Variation on a classic phenotype

Lennox–Gastaut syndrome (LGS) denotes a refractory epileptic encephalopathy of childhood onset with the triad of generalized slow spike–wave (GSSW) on interictal scalp electroencephalogram (EEG), multiple seizure types, and intellectual impairment. The neurobiology of LGS is said to sustain abnormal patterns of brain activity and connectivity that ultimately impair normal cerebral developmental mechanisms. However, we describe eight patients from our combined practice who presented with electroclinical findings consistent with LGS but without significant cognitive impairment. All patients fulfilled the other criteria of LGS with multiple seizure types (three or more of generalized tonic–clonic, atonic, tonic, myoclonic, and atypical absence) and GSSW activity on EEG. Four subjects completed high school, two completed some college, two acquired college degrees, and all performed basic and instrumental activities of daily living (ADL) independently. Magnetic resonance imaging (MRI) was normal in all patients. We speculate that a variation of the classic phenotype of LGS can present with preserved cognitive and functional status, often with onset in the second decade of life, and associated with normal brain imaging.

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study.

Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study.Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified.Results: All seven participants tolerated the CHE up to 10–12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication.Conclusion: The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.

The use of the ketogenic diet in the treatment of epileptic encephalopathies

Epileptic encephalopathies(EE) are severe conditions characterized by paroxysmal activity on the electroencephalogram (EEG) that is often aggressive, seizures that are commonly multi-form and intractable, and severe cognitive and behavioral disturbances that present or worsen after the onset of epilepsy. The ketogenic diet (KD) has been shown to be effective in the treatment of refractory epileptic encephalopathies, and has been suggested as an early treatment option in very young children.
 Although the experience is often anecdotal and mostly consists of case reports and case series, the aim of this study was to present our own experience and an overview of the current literature on the diet in patients with EE.
 Some encephalopathies, such as epilepsy with myoclonic and atonic seizures, West syndrome, Dravet syndrome, or Lennox-Gastaut syndrome, are well recognized and known to have a good response to the ketogenic diet, while others are more rare or only recently identified, such as epilepsy with focal migrating seizures in infancy, febrile infection-related epilepsy syndrome, or myclonic status in non-progressive encephalopathy, about which little is known and the KD is only tried in sporadic cases.
 EE are typically refractory to the antiepileptic drugs and the KD should be considered earlier in the therapeutic scheme of these severe epileptic syndromes. The KD including the oral formula may be considered in all pediatric patients with EE even in infancy.

The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study

BackgroundInitial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life.MethodsTwenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10 years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects.DiscussionThis paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids.Trial registrationhttp://clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Dec 16. Identifier NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: http://clinicaltrials.gov/ct2/show/NCT03024827

Mozart's music in children with drug-refractory epileptic encephalopathies: Comparison of two protocols

In this prospective, randomized, open label study, we compared the effect on seizure recurrence and quality-of-life parameters, of two different protocols of music therapy in children and adolescents with refractory epileptic encephalopathies. Nine out of 19 patients (13 males and 6 females, aged between 1 and 24years) were randomized to listen to Mozart's sonata in D major for two pianos K448 for 2h/day for 2weeks; other 10 children were randomized on a set of Mozart's compositions.In group 1 (K448), 2/9 children (22.2%) had a ≥75% seizure decrease; two patients had less than 50% seizure reduction, and the other five were unchanged.In group 2 (set Mozart), 7/10 patients (70%) had a significant seizure reduction (specifically, ≥50% in 1/10; ≥75% in 4/10; 100% in 2/10).An overall more significant behavioral improvement including less irritability and tearfulness, reduced self-/heteroaggression, a better daytime vigilance, and nighttime sleep quality, was also reported in children from group 2.In conclusion, the present study seems to confirm that music therapy may be an additional, nonpharmacological, effective treatment for patients with refractory epileptic seizures in childhood. The Mozart's set of different compositions can be better accepted and effective than the K448.

The ketogenic diet in patients with myoclonic status in non-progressive encephalopathy

Myoclonic status in non-progressive encephalopathy (MSNPE) is characterized by the recurrence of long-lasting atypical status epilepticus associated with attention impairment and continuous polymorphous jerks, mixed with other complex abnormal movements, in infants suffering from a non-progressive encephalopathy. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. PurposeIn this study we assess the efficacy and tolerability of the KD in patients with MSNPE. MethodsBetween March 1, 1980 and August 31, 2013, 99 patients who met the diagnostic criteria of MSNPE were seen (58 patients in Verona and 41 patients in Buenos Aires). Six of these 99 patients were placed on the KD using the Hopkins protocol and followed for a minimum period of 24 months. ResultsTwelve months after initiating the diet, three patients had a 75%–99% decrease in seizures, two had a 50%–74% decrease in seizures, and the remaining child had a less than 50% seizure reduction. In five patients with a seizure reduction of more than 50%, the myoclonic status epilepticus disappeared within 6 months after starting the diet. All patients had very good tolerability and no adverse events were identified. In most of the patients AEDs were reduced. ConclusionThe KD is a promising therapy for MSNPE, with most of our patients showing a more than 50% seizure reduction. In patients that responded well to the diet cognitive performance and quality of life also improved.

Lennox-Gastaut Syndrome: a Current Review

The diagnosis of Lennox-Gastaut syndrome (LGS), a refractory epileptic encephalopathy, is often made late into disease progression based on the absence of classic EEG abnormalities or typical seizure types at disease onset. The goal of this article is to serve as a general review of LGS for the non-neurologist. As such, we hope to elucidate how a diagnosis is made, highlight novel treatment options, and encourage collaborative treatment decisions between care givers, primary care physicians, neurologists, and psychiatrists. Although a relatively limited number of randomized clinical trials have been performed to date, in recent years, two novel antiepileptics, rufinamide and clobazam, have shown promising efficacy in the treatment of this refractory epileptic encephalopathy. Ideally, after reading this review, the non-neurologist will feel equipped to recognize suspicion for an epileptic encephalopathy in a pediatric patient and subsequently refer that child to an epileptologist.

Autopsy findings of a patient with acute encephalitis and refractory, repetitive partial seizures

Chikako Ogawa *, Jun Natsume , Hiroyuki Yamamoto , Naoko Ishihara , Atsushi Tashiro , Hiroyuki Kidokoro , Tamiko Negoro , Mari Yoshida , Kazuyoshi Watanabe a Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Pediatrics, Social Insurance Chukyo Hospital, Nagoya, Japan Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan

A prospective study of dexamethasone therapy in refractory epileptic encephalopathy with continuous spike-and-wave during sleep.

Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) is an intractable form of epilepsy that has no consensus protocol for corticosteroid therapy. This prospective study aimed to evaluate the efficacy and tolerability of dexamethasone for the treatment of CSWS. Patients (age: 4 years to 12 years and 5 months) with CSWS that failed to respond to several antiepileptic drugs and prednisolone at our pediatric neurology outpatient clinic between 2007 and 2015 were treated with dexamethasone and prospectively analyzed. An initial 4-week dexamethasone (0.15 mg/kg/day p.o.) scheme was employed, and response was assessed. If effective, dexamethasone was maintained for 2-3 months and then slowly weaned over several months, depending on individual patient response at each follow-up. Systemic evaluations (clinical evaluations, electroencephalography recordings, and analysis of side effects) were performed regularly thereafter. Among 15 patients, 7 were defined as initial responders after 4-week dexamethasone treatment based on comprehensive clinical and electroencephalogram evaluations. The duration of dexamethasone treatment (including weaning) in these 7 patients was 6 to 10 months, and the follow-up duration was 6 months to 7 years. Three patients had no relapse after dexamethasone withdrawal at last follow-up. Among the other 4 patients, relapse was observed during dexamethasone withdrawal (n=1) or at 2-6 months after discontinuation of dexamethasone therapy (n=3). There were no serious or life-threatening side effects, and all observed side effects were reversible after discontinuation of dexamethasone. Continuous oral dexamethasone treatment is an effective and tolerable therapy and should be an option for the treatment of CSWS.

Serum concentration of brain-derived neurotrophic factor in epileptic children

There are interesting evidences for the involvement of the neurotrophin brain-derived neurotrophic factor in the mechanism of epileptogenesis. In this study we measured the serum concentrations of brain-derived neurotrophic factor in children with epilepsy and age-matched healthy controls. There was no statistically significant difference between the mean serum concentrations of brain-derived neurotrophic factor in epileptic children (13.8 ± 1.1 ng/mL) and age-matched healthy controls (13.9 ± 0.1 ng/mL). The mean concentration of serum brain-derived neurotrophic factor was not different between generalized epilepsy and partial epilepsy. We also did not find significant difference regarding the associated clinical features of epilepsy (the presence of history of febrile convulsion, cerebral palsy). However, epileptic children with mental retardation showed lower levels of brain-derived neurotrophic factor (P = 0.015). Here we studied serum brain-derived neurotrophic factor concentration in a group of children without an active epileptogenesis based on the clinical and electroencephalographic state. Brain-derived neurotrophic factor concentrations should be investigated in children with active epileptogenesis who had refractory epilepsy and epileptic encephalopathy.

Fast Facts: Epilepsy

“Fast Facts: Epilepsy” by M.J. Brodie, S.C. Schachter, P. Kwan, Health Press, Fifth Edition. 2012. ISBN 978-1-908541-12-3 This is the 5th edition of a popular handbook on epilepsy, first published in 1999, which updates the 4 edition published in 2009. Condensed into 140 pages, the book touches on epilepsy epidemiology, classification, diagnosis, and management. There is a comprehensive discussion of old and new antiepileptic drugs and very brief discussion of epilepsy surgery, therapeutic devices, and diets. Owing to the compact nature of the book, each of these topics is discussed only superficially, with the exception of antiepileptic drugs. The two chapters dealing with pharmacology – the general treatment approach as wel as details about specific drugs – are the greatest strength of this book. Overall, the book is very readable, with a fresh, direct style. It is small enough to fit into a lab coat pocket, and I envision that those pockets will belong to medical students or perhaps resident physicians in fields related to neurology such as internal medicine, family medicine, pediatrics, or rehabilitation medicine. The book is clearly not intended for specialists in epilepsy or even, I suspect, general adult or pediatric neurologists. The content, with the exception of certain tables in the pharmacology chapters, is too simplified to be much use to physicians who regularly treat patients with epilepsy. Certain specific aspects of the text could be improved for better accuracy and readability. This edition continues to use the old International League Against Epilepsy classifications of seizures and epilepsies, rather than updating those classifications with the current, preferred nomenclature. Some important, newly recognized epilepsy syndromes of relevance to child neurologists are not discussed, such as feverinduced refractory epileptic seizures or fever-induced refractory epileptic encephalopathy in school-aged children. The authors continue to use the term “seizure disorder”, disfavored in modern parlance as a nonspecific substitute for “epilepsy”. Another unfortunate word choice is “devastating” with reference to LennoxGastaut syndrome; true, patients with Lennox-Gastaut often have major neurologic impairments, but labeling them as devastated does them a disservice. Many parents of my acquaintance would reel at their child being categorized as devastated. Facts about prognosis are welcome; opinions about quality of life are best omitted. Moving beyond nomenclature, the authors state that temporal lobe epilepsy is “often” preceded by prolonged febrile seizures. Data as to how often this occurs would be informative here. There is little consensus on this point among authorities and it would be misleading for junior physicians to walk away with this conclusion. When discussing genetics, the authors state that the number of epilepsy genes is “set” to increase in coming years. Since the number of genes to be discovered is not on a predetermined schedule, the phrase “likely to” would be more accurate. *Address for correspondence: Carl E. Stafstrom, Department of Neurology, University of Wisconsin, Madison, WI, USA. Tel.: +1 608 262 2154; Fax: +1 608 263 0412; E-mail: stafstrom@neurology .wisc.edu. Journal of Pediatric Epilepsy 2 (2013) 93–94 DOI 10.3233/PEP-13043 IOS Press 93

Ketogenic diet exhibits anti-inflammatory properties.

The ketogenic diet (KD) is an established treatment for refractory epilepsy, including some inflammation-induced epileptic encephalopathies. In a lipopolysaccharide (LPS)-induced fever model in rats, we found that animals given the KD for 14 days showed less fever and lower proinflammatory cytokine levels than control animals. However, KD rats exhibited a decrease in circulating levels of arachidonic acid and long-chain n-3 polyunsaturated fatty acids (PUFAs), suggesting that the anti-inflammatory effect of KD was probably not due to an increase in anti-inflammatory n-3 PUFA derivatives. These properties might be of interest in some conditions such as fever-induced refractory epileptic encephalopathy in school-aged children.

Ketogenic diet in patients with epileptic encephalopathy with electrical status epilepticus during slow sleep

Epileptic encephalopathy with electrical status epilepticus during slow sleep (ESES) belongs to the group of epileptic encephalopathies that often prove refractory to AED treatment. The ketogenic diet (KD) has been used as an alternative to antiepileptic drugs (AEDs) for patients with refractory epileptic encephalopathies. In this retrospective study we assess the efficacy and tolerability of the KD in patients with ESES syndrome. Between March 1, 1990 and April 1, 2013, 65 patients who met diagnostic criteria of ESES syndrome were seen at our department. Twelve of them were placed on the KD and followed for a minimum of 18 months. The children had previously received a mean of 5.5 different AEDs and were on a mean of 3 AEDs when the diet was started. Eighteen months after initiating the diet, seven of the initial patients (58%) remained on the diet; one patient (8.3%) had become seizure free, one (8.3%) had a 75-99% decrease in seizures, two (16.6%) had a 50-74% decrease in seizures, and the remaining three children (24.9%) had a <50% decrease in seizures. In the patient who had become seizure free and in the one who had a 75-99% seizure decrease AEDs were reduced. The KD is a well-tolerated treatment option for patients with ESES syndrome, not only for structural cases but also for those with an unknown etiology. The diet should be considered in the management of this syndrome.

Sleep alterations in children with refractory epileptic encephalopathies: A polysomnographic study

Data on the relationship between sleep disturbances and refractory epileptic encephalopathies (EEs) are scarce. Our aim was to assess, by means of nocturnal polysomnography, if children with EEs present with objective alterations in sleep organization. Twenty-three children with EEs (12 males; mean age: 8.7±1.4years) and 40 healthy controls (22 males; mean age: 8.8±1.1years) underwent an overnight full polysomnography (PSG). Relative to controls, children with EEs showed a significant reduction in all PSG parameters related to sleep duration time in bed (TIB-min p<0.001), total sleep time (TST-min p<0.001), and sleep percentage (SPT-min p<0.001), as well as significantly higher REM latency (FRL-min p<0.001), rate in stage shifting (p=0.005), and number of awakenings/hour (p=0.002).Relative to controls, children with EEs also showed significant differences in respiratory parameters (AHI/h p<0.001, ODI/h p<0.001, SpO2% p<0.001, SpO2 nadir% p<0.001) and a higher rate of periodic limb movements (PLMs% p<0.001). Our findings suggest that sleep evaluation could be considered mandatory in children with refractory epileptic encephalopathy in order to improve the clinical management and the therapeutic strategies.