Myoclonic Epilepsy In Infancy Research Articles

SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations.

SCN1A, the gene encoding for the Nav1.1 channel, exhibits dominant interneuron-specific expression, whereby variants disrupting the channel's function affect the initiation and propagation of action potentials and neuronal excitability causing various types of epilepsy. Dravet syndrome (DS), the first described clinical presentation of SCN1A channelopathy, is characterized by severe myoclonic epilepsy in infancy (SMEI). Variants' characteristics and other genetic or epigenetic factors lead to extreme clinical heterogeneity, ranging from non-epileptic conditions to developmental and epileptic encephalopathy (DEE). This current study reports on findings from 343 patients referred by physicians in hospitals and tertiary care centers in Greece between 2017 and 2023. Positive family history for specific neurologic disorders was disclosed in 89 cases and the one common clinical feature was the onset of seizures, at a mean age of 17 months (range from birth to 15 years old). Most patients were specifically referred for SCN1A investigation (Sanger Sequencing and MLPA) and only five for next generation sequencing. Twenty-six SCN1A variants were detected, including nine novel causative variants (c.4567A>Τ, c.5564C>A, c.2176+2T>C, c.3646G>C, c.4331C>A, c.1130_1131delGAinsAC, c.1574_1580delCTGAGGA, c.4620A>G and c.5462A>C), and are herein presented, along with subsequent genotype-phenotype associations. The identification of novel variants complements SCN1A databases extending our expertise on genetic counseling and patient and family management including gene-based personalized interventions.

Epileptic seizures worsen the gait and motor abnormalities in adult patients with Dravet syndrome (with a case report and literature review).

Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is considered the most serious "epileptic encephalopathy." Here, we present a man with a de novo SCN1A mutation who was diagnosed with DS at the age of 29. In addition to pharmaco-resistant seizures and cognitive delay, he also developed moderate to severe motor and gait problems, such as crouching gait and Pisa syndrome. Moreover, it deteriorated significantly following an epileptic seizure. The patient presented with severe flexion of the head and trunk in the sagittal plane and fulfilled the diagnostic criteria for camptocormia and antecollis. After a week, it spontaneously alleviated partially. We applied levodopa to the patient and had a good response. Functional Gait Assessment (FGA) was assessed at three different times: 4 days after the seizure, 1 week after the seizure, and after taking levodopa for 2 years. The results were 4, 12, and 19 points, respectively. We postulated that: (1) gait and motor deficits are somehow influenced by recurrent epileptic episodes;(2) the nigrostriatal dopamine system is involved. To our knowledge, we were the ones who first reported this phenomenon.

Features of epileptic encephalopathy caused by SCN1A mutation

Background. The development and availability of genetic research open both new possibilities in the diagnosis of epileptic encephalopathies and require the search for correlations between detected pathological mutation and the clinical and instrumental examination of a child. In particular, seizure disorders in children in whom SCN1A has been detected cover a spectrum that varies from simple febrile seizures and mild generalized epilepsy with febrile seizures plus, which was first described in 2003, to severe myoclonic epilepsy in infancy (more commonly known as Dravet syndrome) or severe intractable childhood epilepsy with generalized tonic-clonic seizures. Materials and methods. In our study, we examined 4 children (2 boys and 2 girls) with clinical and instrumental signs of epileptic encephalopathy with resistant seizures who were treated in the psychoneurology department for children with perinatal pathology and orphan diseases of the SI “Lukyanova Institute of Pediatrics, Obstetrics and Gynecology named of the National Academy of Medical Sciences of Ukraine”. The average age of patients was 2.20 ± 1.55 years. In addition to the laboratory and instrumental examination, all children underwent a medical genetic analysis (whole exome sequencing or next-generation sequencing) and the mutation of the SCN1A gene was detected. Subsequently, the relationship between the obtained laboratory instrumental and clinical anamnestic data was analyzed using statistical research methods. Results. It should be noted that the onset of genetic disorders caused by SCN1A occurs at the age of 5.5–6 months. During the onset, focal clonic seizures predominate, mainly against the background of hyperthermia, which are later modified into generalized tonic-clonic, myoclonic ones, and even absences. In three of four cases, the epileptiform activity was focal, with a predominant localization in the fronto-central regions followed by generalization. In all children, taking into account the focal onset of attacks, therapy was started with the use of carbamazepine, which is contraindicated in children with this mutation. After analyzing our cases, we saw that the course of the disease and the resistance of attacks were more severe in girls. The study of this phenomenon requires observation of a larger number of children. Conclusions. In children with genetically determined epileptic encephalopathy caused by the SCN1A mutation, the onset of the disease occurs in the first half of life and is usually manifested itself by focal seizures. In children with SCN1A mutation, frontal localization of epileptiform activity prevails. Considering this feature of the disease and based on our own long-term observation of children with epileptic encephalopathies of early age, we would like to warn against the use of carbamazepines in this age group. The course of SCN1A epileptic encephalopathy (Dravet syndrome) is difficult, given the resistance of attacks and regression in the development of a child, and often requires the use of more than 2–3 antiepileptic drugs, but a correctly selected combination allows long-term remission to be achieved.

The International League Against Epilepsy Classification and Definitions of Epilepsy Syndromes with Onset in Neonates and Infants

The International League Against Epilepsy (ILAE) Task Force proposed a classification system containing definitions of epilepsy syndromes with onset in neonates and infants up to 2 years of age. Concordant with the 2017 ILAE Framework for Classification of the Epilepsies, this new classification emphasized the importance of classifying epilepsy both by electroclinical features and etiology. This classification was developed to clearly define a uniform group of each epilepsy syndrome and to support precision therapies for specific genetic factors. The ILAE Task Force classified epilepsy syndromes into two major categories; self-limited epilepsies and developmental and epileptic encephalopathies. Self-limited epilepsies include syndromes that are likely to show spontaneous remission, while developmental and epileptic encephalopathies are characterized by developmental impairment related to both the underlying etiology independent of epileptiform discharges and the epileptic encephalopathy. Etiology-specific epilepsy syndromes include disorders due to specific genetic, structural, and metabolic etiologies. The ILAE Task Force presented mandatory features, alerts, and exclusionary features for each epilepsy syndrome. Clinicians need to consider both the electroclinical features and the etiology when defining epilepsy syndromes and developing a management plan for each individual. Key words: Epilepsy syndromes; Benign neonatal epilepsies; Infantile spasms; Severe myoclonic epilepsy in infancy.

Psychomotor development and seizure features in idiopathic myoclonic epilepsy in infancy.

Myoclonic epilepsy in infancy (MEI) is a rare syndrome characterized by generalized myoclonic seizures (MS) that occur within the first 3 years of life. In the present study, the form of onset, and clinical and electroencephalogram (EEG) features were analyzed. A retrospective chart review was conducted for 16 MEI patients between March 2009 and July 2022 in Peking Union Medical College. The clinical and video EEG (VEEG) characteristics, treatment strategy, and follow-up information were analyzed. Four cases presented with afebrile generalized tonic-clonic seizures (GTCS) at the onset of MEI (GTCS at onset or atypical MEI), while 12 cases presented with MS at onset (MS at onset or typical MEI). The 24-hour VEEG revealed a generalized discharge of polyspike (or spike)-and-wave complexes that lasted for 1–3 seconds in the ictal phase. All patients were treated with valproic acid monotherapy, and none of the patients experienced seizure recurrence. Furthermore, all patients had normal psychomotor development at the end of the follow up period. Typical MEI (MS at onset) and atypical MEI (GTCS at onset) were described in the present study. These 2 groups differed in form of onset, but there were no significant differences in clinical or EEG features.

Slipped capital femoral epiphysis in a patient with dravet syndrome: A case report and literature review

In situ fixation of SCFE is the widely accepted treatment for both stable and unstable SCFE. Prophylactic fixation of the contralateral hip remains controversial. There is still no agreement about the removal of the screws in the absence of implant-related symptoms.The case A case of a slipped capital femoral epiphysis SCFE in an adolescent with Dravet Syndrome after a seizure attack. To the best of our knowledge, this is the first report worldwide about the presentation of SCFE in Dravet syndrome.Dravet syndrome is severe myoclonic epilepsy in infancy. Cases of SCFE after epileptic fit need more studies and long-term follow-up to understand the pathophysiology and consequences of treatment.Lessons learntThis rare case needs more follow-up till adulthood. Possible complications and further management are challenging culprits. Children presented with SCFE after epileptic fit, withdraw special attention. However, there is a lack of knowledge in the literature about their natural history & long-term follow-up.

Fever-Associated Seizures or Epilepsy: An Overview of Old and Recent Literature Acquisitions.

In addition to central nervous system infections, seizures and fever may occur together in several neurological disorders. Formerly, based on the clinical features and prognostic evolution, the co-association of seizure and fever included classical febrile seizures (FS) divided into simple, complex, and prolonged FS (also called febrile status epilepticus). Later, this group of disorders has been progressively indicated, with a more inclusive term, as “fever-associated seizures or epilepsy” (FASE) that encompasses: (a) FS divided into simple, complex, and prolonged FS; (b) FS plus; (c) severe myoclonic epilepsy in infancy (Dravet syndrome); (d) genetic epilepsy with FS plus; and (e) febrile infection-related epilepsy syndrome (FIRES). Among the FASE disorders, simple FS, the most common and benign condition, is rarely associated with subsequent epileptic seizures. The correlation of FS with epilepsy and other neurological disorders is highly variable. The pathogenesis of FASE is unclear but immunological and genetic factors play a relevant role and the disorders belonging to the FASE group show to have an underlying common clinical, immunological, and genetic pathway. In this study, we have reviewed and analyzed the clinical data of each of the heterogeneous group of disorders belonging to FASE.

Ictal vocalizations are relatively common in myoclonic-atonic seizures associated with Doose syndrome: an audio-video-polygraphic analysis.

The aim of this study was to investigate ictal vocalizations associated with myoclonic (MS) and myoclonic-atonic seizures (MAS) in patients with myoclonic epilepsy in infants (MEI) and epilepsy with myoclonic-atonic seizures (EMAS, Doose syndrome), respectively. Subjects were retrospectively recruited among patients with MEI and EMAS for whom ictal video-polygraphs were recorded between 1990 and 2019. We reviewed all MS and MAS in order to estimate how often they were associated with vocalizations, and analyze the temporal relationship between vocalizations and spike-wave complexes (SWCs) and myoclonic EMG potentials based on simultaneous examination of the polygraphs and sound signals. Ictal video-polygraphs from 15 patients with MEI (2-34 MS per patient) and 26 with EMAS (2-26 MAS per patient) were examined. Ictal vocalizations were audible in two patients with MEI (11%; 3-18 MS per patient) and nine with EMAS (35%; 2-11 MAS per patient). Sounds were always non-speech and were immediately followed by head or body dropping in the case of MAS. Detailed analysis based on simultaneous and synchronous examination of video-polygraphs and sound signals in one patient with MEI and five patients with EMAS demonstrated that the onset of the ictal vocalizations corresponded to that of the myoclonic EMG potentials and negative spike components of SWC. Comparison of the length of myoclonic EMG potentials as well as the strength of drop seizures between MAS with and without vocalizations revealed that MAS with vocalizations were associated with longer myoclonic EMG potentials and stronger drop seizures than MAS without vocalizations (p<0.05), suggesting that the vocalizations result from strong contraction of axial muscles. Ictal vocalizations due to massive motor seizure activity are a relatively common finding in MAS in Doose syndrome, which may help in the differential diagnosis of epileptic drop attacks.

Epilepsy Syndromes in the First Year of Life and Usefulness of Genetic Testing for Precision Therapy.

The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increasingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrumental in providing insights into the pathophysiology of both early-onset benign and self-limited syndromes and devastating developmental and epileptic encephalopathies (DEEs). Genetic heterogeneity is seen in many epilepsy syndromes such as West syndrome and epilepsy of infancy with migrating focal seizures (EIMFS), indicating that two or more genetic loci produce the same or similar phenotypes. At the same time, some genes such as SCN2A can be associated with a wide range of epilepsy syndromes ranging from self-limited familial neonatal epilepsy at the mild end to Ohtahara syndrome, EIFMS, West syndrome, Lennox–Gastaut syndrome, or unclassifiable DEEs at the severe end of the spectrum. The aim of this study was to review the clinical and genetic heterogeneity associated with epilepsy syndromes starting in the first year of life including: Self-limited familial neonatal, neonatal-infantile or infantile epilepsies, genetic epilepsy with febrile seizures plus spectrum, myoclonic epilepsy in infancy, Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, EIMFS, and unclassifiable DEEs. We also elaborate on the advantages and pitfalls of genetic testing in such conditions. Finally, we describe how a genetic diagnosis can potentially enable precision therapy in monogenic epilepsies and emphasize that early genetic testing is a cornerstone for such therapeutic strategies.

Morphometric analysis of spike-wave complexes (SWCs) causing myoclonic seizures in children with idiopathic myoclonic epilepsies – A positive SWC component correlates with myoclonic intensity

AimTo elucidate the morphological characteristics of spike-wave complexes (SWCs) causing myoclonic seizures (MS) in childhood-onset idiopathic myoclonic epilepsies. Subjects and MethodsThe subjects were 8 patients, including 4 with epilepsy with myoclonic-atonic seizures (EMAS), 3 with myoclonic epilepsy in infancy (MEI) and 1 with idiopathic unclassifiable myoclonic epilepsy. Morphometric parameters of the SWCs were compared between those with MS [SWC-MS (+)] and those without MS [SWC-MS (-)], and a correlation coefficient analysis was performed between the SWC parameters and the duration of myoclonic electromyogram (EMG) potentials. ResultsA total of 155 SWC-MS (+) (range: 7 ∼ 34) and 80 SWC-MS (-) (10 each as a control) were analyzed. Comparison of the parameters of the SWCs between SWC-MS (+) and SWC-MS (-) demonstrated that the depth and the width of the positive-sharp-components (PSC) in the SWC-MS (+) were significantly deeper in amplitude and longer in duration than those in the SWC-MS (-), respectively, in all 8 patients (P < 0.05), whereas the number of the polyphasic-multiple-spike-components (PMSC) and the height of negative-spike-components (NSC) were not significantly different in most of the patients, respectively. The depth and the width of PSC were also significantly correlated with the duration of myoclonic EMG potentials in all patients except one [depth of PSC (n = 7): r = 0.623 ∼ 0.888; width of PSC (n = 8): r = 0.676 ∼ 0.948, P < 0.05]. ConclusionsThis study revealed that the depth and width of PSC of the SWC are positively correlated with the MS intensity in childhood-onset idiopathic myoclonic epilepsies and are an important neurophysiological marker to generate MS.

Managing Status Epilepticus in a Child with Dravet Syndrome: How Difficult It Could Be?

AbstractPreviously known as severe myoclonic epilepsy of infancy, Dravet syndrome is characterized by febrile or afebrile prolonged hemiconvulsive seizures or generalized status epilepticus in an infant with previously normal development. Immediate management of status epilepticus is critical in these patients. Early control of status epilepticus prevents further brain damage; however, there is no consensus regarding the management of status epilepticus in children with Dravet syndrome, as many conventional antiseizure medications that are recommended in the management of status epilepticus worsen the seizures in these patients. A 2.5-year-old girl child patient was referred due to status epilepticus which was refractory to antiseizure medications. Sodium valproate, nitrazepam, ketogenic diet, intravenous phenytoin, and midazolam continuous infusion were administered. After controlling status epilepticus, the probable diagnosis of Dravet syndrome was proposed and confirmed by a mutation in SCN1A. As previously stated in numerous case reports, phenytoin worsens seizures in patients with Dravet syndrome. Therefore, it seems logical that in every infant with status epilepticus and probable Dravet syndrome, the practicing physician considers administering intravenous valproate or even midazolam continuous infusion instead of intravenous phenytoin.

P.052 Benign spasms of infancy - a mimicker of infantile epileptic disorders

Background: Benign spasms of infancy (BSI), previously described as benign non-epileptic infantile spasms or benign myoclonus of early infancy, are non-epileptic movements manifesting during the first year of life and spontaneously resolving in the second year of life. BSI are characterized by spasms typically lasting 1-2 seconds, involving to varying degrees the head, neck, trunk, shoulders and upper extremities. Ictal and interictal EEG recordings are normal. BSI are not associated with developmental retardation and do not require treatment. Distinction between BSI and infantile epileptic disorders, such as epileptic spasms or myoclonic epilepsy of infancy, can be challenging given the clinical similarities. Moreover, interictal EEGs can be normal in all conditions. Epileptic spasms and myoclonic epilepsy require timely treatment to improve neurodevelopmental outcomes. Methods: We describe a 6-month old infant presenting with spasm-like movements. His paroxysms as well as a positive family history for epileptic spasms were in keeping with a likely diagnosis of West syndrome. Results: Surprisingly, ictal video EEG did not reveal epileptiform activity, and suggested a diagnosis of BSI. Conclusions: We emphasize that ictal EEG is the gold standard for classification of infantile paroxysms as either epileptic or non-epileptic, thereby avoiding overtreatment of BSI and facilitating timely targeted treatment of infantile epilepsies.

Dravet Syndrome: Early Diagnosis and Emerging Therapies

AbstractDravet's syndrome (DS) or severe myoclonic epilepsy of infancy is a rare, genetic, and infantile-onset epileptic encephalopathy. DS presents with recurrent febrile seizures and/or febrile status epilepticus in developmentally normal infants, and subsequently evolves into a drug-resistant mixed-seizure disorder with developmental arrest or regression. As many defining clinical features of DS do not become evident until 3 to 4 years of age, diagnosis is often delayed. Early seizure control, particularly the prevention of status epilepticus in infancy, has been shown to correlate with better long-term outcomes. Thus, early diagnosis and seizure control is crucial. Several treatment algorithms have been published in recent years to guide antiepileptic drug selection and escalation. Last year, two agents, stiripentol and cannabidiol, were approved by the U.S. Food and Drug Administration specifically for use in DS, and a third has been submitted (fenfluramine). Additional therapies, including serotonin modulators lorcaserin and trazodone, verapamil, and several first-in-class medications, are currently in various phases of investigation.

Dravet Syndrome in Lebanon: First Report on Cases with SCN1A Mutations

Dravet syndrome, also known as severe myoclonic epilepsy in infancy, is a rare disease characterized by the appearance of different types of seizures in a healthy baby, triggered by various factors and stressful events. We report 8 Lebanese cases referred for molecular analysis of the SCN1A gene. Results were positive in 7 cases and revealed de novo variants at the heterozygous state in different exons of the gene for all except one, where the variant was intronic. Four variants were novel. Confirmation of Dravet syndrome is important for a better follow-up and treatment, preventing the occurrence of status epilepticus and severe neurological deterioration.

A Loss-of-Function HCN4 Mutation Associated With Familial Benign Myoclonic Epilepsy in Infancy Causes Increased Neuronal Excitability.

HCN channels are highly expressed and functionally relevant in neurons and increasing evidence demonstrates their involvement in the etiology of human epilepsies. Among HCN isoforms, HCN4 is important in cardiac tissue, where it underlies pacemaker activity. Despite being expressed also in deep structures of the brain, mutations of this channel functionally shown to be associated with epilepsy have not been reported yet. Using Next Generation Sequencing for the screening of patients with idiopathic epilepsy, we identified the p.Arg550Cys (c.1648C>T) heterozygous mutation on HCN4 in two brothers affected by benign myoclonic epilepsy of infancy. Functional characterization in heterologous expression system and in neurons showed that the mutation determines a loss of function of HCN4 contribution to activity and an increase of neuronal discharge, potentially predisposing to epilepsy. Expressed in cardiomyocytes, mutant channels activate at slightly more negative voltages than wild-type (WT), in accordance with borderline bradycardia. While HCN4 variants have been frequently associated with cardiac arrhythmias, these data represent the first experimental evidence that functional alteration of HCN4 can also be involved in human epilepsy through a loss-of-function effect and associated increased neuronal excitability. Since HCN4 appears to be highly expressed in deep brain structures only early during development, our data provide a potential explanation for a link between dysfunctional HCN4 and infantile epilepsy. These findings suggest that it may be useful to include HCN4 screening to extend the knowledge of the genetic causes of infantile epilepsies, potentially paving the way for the identification of innovative therapeutic strategies.

F14. Febrile myoclonus on EEG; benign or epileptic?

Introduction Febrile myoclonus is an infrequently seen entity in young children. It is thought to be different from febrile seizures and early childhood myoclonic epilepsy. These are reported to not carry an increased risk for epilepsy. Interictal EEG has been reported to vary from normal to generalized spike and wave discharges. Ictal EEG findings of febrile myoclonus are rare in the literature and usually described as not showing EEG correlate. Methods We describe a patient with febrile myoclonus with ictal and interictal EEG findings as well as follow up data of over 1 year. We compared findings with previously reported cases. Results 11 month old boy presented with febrile illness and brief jerks. He was a product of non-consanguineous marriage with unremarkable perinatal history and normal development. This was his first febrile illness and developed jerky movements within the first 24 h. Temperature was 39 °C. He appeared ill without nuchal rigidity or alteration of mental status. Brief myoclonic jerks mostly involving the upper extremities but sometimes the entire body were seen occurring every 2–5 min. Rest of the general examination was unremarkable. Labs revealed normal cell counts and electrolytes. An electroencephalogram(EEG) and MRI scan of the brain were obtained. EEG showed posterior background of 6–7 Hz with normal organization. Interictally there were intermittent generalized spike-wave complexes. The clinical myoclonic jerks were associated with generalized spike and wave discharges indicative of myoclonic seizures. Myoclonus resolved as the fever settled and his follow up EEG, 2 weeks later was completely normal for age. Chromosomal microarray and metabolic screening labs were normal. Patient had several febrile episodes after this when he did not develop febrile myoclonus. 1 year later parents reported 4 more similar episodes of self-resolved myoclonus while febrile. He developed one, 2 min typical generalized febrile seizure. At 2 years, he has not developed afebrile seizures and has normal development. Conclusion Febrile myoclonus is infrequent and likely under-reported. Fewer than 20 cases have been described in the literature. Febrile myoclonus is thought to be a self-limiting benign condition which does not lead to epilepsy. There are reports of concurrent febrile seizures. There is a lack of literature describing ictal EEG findings as most of the reported EEGs were done interictally. Differential diagnosis includes early childhood myoclonic epilepsy, genetic myoclonic epilepsies, and severe myoclonic epilepsy of infancy (Dravet Syndrome). Fever can potentially lower the seizure threshold and febrile myoclonus could be their initial presentation. Our patient had febrile myoclonus with an ictal EEG correlate unlike patients in the literature. Despite these findings the myoclonus was self-limiting and resolved with the resolution of fever and the EEG abnormalities were transient. He appears to have a benign course despite prominent ictal correlate.

Identification of a Novel Nonsense Variant in the SCN1A Gene that Causes Febrile Seizure Disorder

AbstractThe SCN1A gene, encoding for the voltage-gated sodium channel Nav1.1, is the most clinically relevant epilepsy gene, with most mutations having been documented in a spectrum of epilepsy syndromes, ranging from the relatively benign generalized epilepsy with febrile seizures plus (GEFS+) to severe myoclonic epilepsy in infancy (SMEI), and other rare febrile seizure disorders. To date, more than 1,250 mutations in SCN1A have been linked to epilepsy. In this case, we describe a novel nonsense pathogenic variant (NM_001202435.1; c.327C &gt; G) in SCN1A in a 10-month Moroccan infant with febrile seizure disorder.

Follow-up study of idiopathic generalized epilepsy with associated absence seizure and myoclonic epilepsy of infancy

We evaluated the long-term prognosis of patients featuring the association of absences and myoclonic epilepsy of infancy. Our cohort consisted of 10 male subjects with mean age at seizure onset of 29 months. Follow-up data included seizure outcome and EEG findings. All individuals received antiepileptic drugs (AEDs) as monotherapy (6 patients) or polytherapy (4 patients) for a mean period of 24 months. Over a 30–60 month evaluation period (mean: 43 months), all patients were seizure-free. Follow-up data after withdrawal of antiepileptic therapy were obtained for a mean period of 22 months. None of the children did develop other age-related epileptic syndrome after AEDs discontinuation. Furthermore, follow-up EEG data after drugs withdrawal were normal and none of the patients showed cognitive impairment. In conclusion, we confirm that absence seizures may occur in association with myoclonic epilepsy of infancy. This condition shows excellent prognosis with either favourable neurologic development and seizure outcome in these children.

Myoclonic epilepsy in infancy with preceding or concurrent afebrile generalized tonic-clonic seizures in Chinese children

ObjectiveTo investigate the general characteristics and the category of myoclonic epilepsy in infancy (MEI) with or without afebrile generalized tonic-clonic seizures (GTCS). MethodsThirty-three children were retrospectively recruited from approximately 42,814 video-electroencephalogram (VEEG) recordings monitored in our department over last nearly 10years. Myoclonic seizures (MS) must be identified by VEEG in all patients. The clinical, EEG features and outcome were analyzed among these patients. ResultsThe 33 patients (25 boys and 8 girls) were divided into three groups: 11 patients with typical MEI; 16 patients with MEI experienced afebrile GTCS before MS onset; and 6 patients with MEI presented afebrile GTCS occurring concurrently with MS. No significant differences were found among the three groups, including gender distribution, family history, personal history of febrile seizures, the age at seizure onset and control, the duration of MS, the interval between age at onset and seizure control, the age at EEG normalization, the interval between seizure onset age and EEG normalization age and normal psychomotor development at the end of follow-up. More patients in group two and group three were controlled by two or three kinds of antiepileptic drugs compared with those in group one. ConclusionsIn this study, three groups of patients had similar clinical, EEG features and outcome. Afebrile GTCS was associated with a stronger cortical hyperexcitability. It was worth considering whether MEI with preceding or concurrent afebrile GTCS should be recognized as subgroups or different epileptic syndromes independent of MEI.

Antiepileptic drugs for the treatment of infants with severe myoclonic epilepsy.

This is an updated version of the original Cochrane review published in 2015, Issue 10.Severe myoclonic epilepsy in infants (SMEI), also known as Dravet syndrome, is a rare, refractory form of epilepsy, for which stiripentol (STP) has been recently licensed as add-on therapy. To evaluate the efficacy and tolerability of STP and other antiepileptic drug treatments (including ketogenic diet) for patients with SMEI. For the latest update we searched the Cochrane Epilepsy Group Specialized Register (20 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 20 December 2016), MEDLINE (Ovid, 1946 to 20 December 2016) and ClinicalTrials.gov (20 December 2016). Previously we searched the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP, but this was not usable at the time of this update. We also searched the bibliographies of identified studies for additional references. We handsearched selected journals and conference proceedings and imposed no language restrictions. Randomised controlled trials (RCTs) or quasi-randomised controlled trials; double- or single-blinded or unblinded trials; and parallel-group studies. Administration of at least one antiepileptic drug therapy given singly (monotherapy) or in combination (add-on therapy) compared with add-on placebo or no add-on treatment. Review authors independently selected trials for inclusion according to predefined criteria, extracted relevant data and evaluated the methodological quality of trials. We assessed the following outcomes: 50% or greater seizure reduction, seizure freedom, adverse effects, proportion of dropouts and quality of life. We assessed outcomes by using a Mantel-Haenszel meta-analysis to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs). Since the last version of this review no new studies have been found. Specifically, we found no RCTs assessing drugs other than STP. The review includes two RCTs evaluating use of STP (total of 64 children). Both studies were generally at unclear risk of bias. A significantly higher proportion of participants had 50% or greater reduction in seizure frequency in the STP group compared with the placebo group (22/33 versus 2/31; RR 10.40, 95% CI 2.64 to 40.87). A significantly higher proportion of participants achieved seizure freedom in the STP group compared with the placebo group (12/33 versus 1/31; RR 7.93, 95% CI 1.52 to 41.21). Investigators found no significant differences in proportions of dropouts from the STP group compared with the placebo group (2/33 versus 8/31; RR 0.24, 95% CI 0.06 to 1.03). Only one study explicitly reported the occurrence of side effects, noting that higher proportions of participants in the STP group experienced side effects than in the placebo group (100% versus 25%; RR 3.73, 95% CI 1.81 to 7.67). We rated the quality of the evidence as low to moderate according to GRADE criteria, as most information is from studies judged to be at an unclear risk of bias. Data derived from two small RCTs indicate that STP is significantly better than placebo with regards to 50% or greater reduction in seizure frequency and seizure freedom. Adverse effects occurred more frequently with STP. Additional adequately powered studies with long-term follow-up should be conducted to unequivocally establish the long-term efficacy and tolerability of STP in the treatment of patients with SMEI.