Myoclonic Epilepsy In Infancy Research Articles

Epilepsia mioclónica benigna del lactante: evolución natural y pronóstico neurocognitivo y conductual

Benign myoclonic epilepsy in infancy (BMEI) is a well-defined electro-clinical syndrome, classically associated with a good prognosis. However, in the last years several studies have been published with variable results of neuropsychological outcome in BMEI. AIM. To analyze the natural history and the cognitive and behavioral outcome in BMEI patients. We report a long-term follow-up of 10 patients with BMEI. During the follow-up, all the patients underwent neurocognitive and behavioral evaluations. Sixty percent of patients became seizure free on valproic acid. The intelligence quotient of the whole cohort was between 74 and 93, with three patients in the range of borderline intelligence and six in the range of medium-to-low intelligence. Nine of the 10 patients met criteria for attention deficit hyperactivity disorder, and two patients associated another learning disorder. All patients showed poor motor and visuospatial coordination signs and three patients had a behavior disorder. The term 'benign' in BMEI has to be used with caution in refer to its behavioral and cognitive outcome. Early onset of seizures and a worse epilepsy control may be risk factors of a poor neuropsychological outcome.

Myoclonic epilepsy in infancy: one or two diseases?

epd.2013.0606 Auteur(s) : Stephane Auvin1,2,3 auvin@invivo.edu, Julitta de Bellescize4, Charlotte Dravet5,6 1 APHP, Hopital Robert Debre, Service de Neurologie Pediatrique 2 Inserm, U676 3 Univ Paris Diderot, Sorbonne Paris Cite, INSERM UMR676, Paris 4 Epilepsy, Sleep and Paediatric Neurophysiology (ESEFNP), University Hospitals of Lyon (HCL), Lyon, France 5 Child Neurology and Psychiatry, Catholic University School of Medicine, Rome, 6 Epilepsy, Neurophysiology, Neurogenetics Unit, IRCCS, [...]

O95 – 1739 Severe myoclonic epilepsy in infancy: clinical and neuropsychological analysis according to age at diagnosis of SMEI

O95 – 1739 Severe myoclonic epilepsy in infancy: clinical and neuropsychological analysis according to age at diagnosis of SMEI

Myoclonic epilepsy in infancy: An electroclinical study and long‐term follow‐up of 38 patients

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. 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. 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. 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.

Reflex myoclonic epilepsy in infancy: a critical review

Benign myoclonic epilepsy in infancy, classified among the generalised idiopathic epilepsies, is characterised by the occurrence of myoclonic seizures in the first three years of life in otherwise normal infants. Some authors have described cases of myoclonic seizures as a reflex response to sudden unexpected tactile or acoustic stimuli and this clinical entity has been proposed as a separate nosographic syndrome, referred to as "reflex myoclonic epilepsy in infancy" (RMEI). We reviewed all published articles and case reports on RMEI in order to clarify clinical and electroencephalographic findings, with particular attention to outcome and treatment. RMEI appears to be a benign variant of idiopathic myoclonic epilepsy in infancy with specific features that occur in neurologically and developmentally normal children. This rare clinical entity is often under-described and under-diagnosed, and for this reason should be brought to the attention of paediatricians in order to avoid extensive investigations and reassure parents of the lack of long-term complications.

Les épilepsies myocloniques juvéniles

To describe the clinical and electroencephalographic (EEG) features of reflex myoclonic epilepsy in infancy (RMEI) and long-term cognitive outcome.We enrolled 31 children from 16 neuropediatric centres in Italy, who underwent clinical and video-EEG evaluation. Cognitive assessment was performed in all patients using standardized psychometric tests.The age at onset ranged from 3 to 24 months of age. Seizures were characterised in all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%) or both (29%). Spontaneous attacks were reported in 32.2% of the cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges, synchronous with brief rhythmic bursts of electromyographic activity. Patients were re-evaluated after a period of 7.2 ± 5.6 years. The prognosis for seizure control was excellent in all cases and reflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome was excellent in 90.3% of children.RMEI appears to be a variety of idiopathic generalized epilepsy with specific features that occurs in developmentally normal children.

Detection of SCN1A mutations in patients with severe myoclonic epilepsy in infancy by custom resequence array

Detection of SCN1A mutations in patients with severe myoclonic epilepsy in infancy by custom resequence array

A case of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) coexisting with pervasive developmental disorder harboring SCN1A mutation in addition to CHRNB2 mutation

We report a case of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) with several characteristics distinct from previously reported cases, in which genetic studies identified mutations in two different genes. This case differed from typical ADNFLE with respect to the following: (1) slightly younger onset and refractory to antiepileptic drugs and (2) borderline intellectual functioning and coexistence of pervasive developmental disorder from infancy. Genetic testing revealed a novel mutation and a silent substitution in SCN1A (c.4285G>T, A1429S and c.4371G>C, silent) in addition to a known mutation in CHRNB2 (c.1200C>G, I312M). SCN1A is a gene that codes for the voltage-dependent sodium channel α1 subunit and has been implicated in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in infancy. However, the relation between SCN1A and ADNFLE is unknown. We report the clinical course and symptomatic characteristics of this case although the relationship between ADNFLE mutation and SCN1A mutation remains to be elucidated.

How Dravet syndrome became a model for studying childhood genetic epilepsies

In this issue of Brain , Brunklaus et al. report a study of 241 patients with Dravet syndrome carrying a SCN1A mutation, with the aim of identifying predictors of developmental outcome and determining specific clinical and demographic characteristics. The electroclinical features of a large cohort were collected and analysed prior to genetic testing. A total of 355 patients were diagnosed with Dravet syndrome, but the authors selected only the 241 (68%) who were positive for a mutation of SCN1A . Patients who were excluded had not been tested for mutations in other genes that could potentially cause overlapping phenotypes, such as protocadherin 19 (Depienne et al ., 2009). Dravet syndrome was first described briefly in French as severe myoclonic epilepsy in infancy (Dravet, 1978). In 1981, the same series was presented at the XIIIth Epilepsy International Congress and published 1 year later. Over the last 20 years, numerous series of patients have been reported, confirming the initial description, but also underlining variability of the clinical picture. The classic syndrome is defined by onset in an otherwise healthy infant during the first year of life, presenting febrile or afebrile and generalized or unilateral clonic or tonic clonic seizures, often long lasting, later associated with myoclonic, atypical absence and focal seizures. These are all resistant to drug treatment, and accompanied by slowing of developmental skills, as well as motor and behavioural disturbances. The EEG shows generalized and multifocal abnormalities whereas neuroimaging is normal. It quickly became apparent that a number of patients do not present with the complete semiology, mainly because the myoclonic component may be missing, and typical and atypical or ‘borderline’ forms are recognized, also showing an unfavourable prognosis. With time, the syndrome …

Reflex myoclonic epilepsy in infancy: A multicenter clinical study

To describe the clinical and electroencephalographic (EEG) features of reflex myoclonic epilepsy in infancy (RMEI) and long-term cognitive outcome. We enrolled 31 children from 16 neuropediatric centres in Italy, who underwent clinical and video-EEG evaluation. Cognitive assessment was performed in all patients using standardized psychometric tests. The age at onset ranged from 3 to 24 months of age. Seizures were characterised in all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%) or both (29%). Spontaneous attacks were reported in 32.2% of the cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges, synchronous with brief rhythmic bursts of electromyographic activity. Patients were re-evaluated after a period of 7.2 ± 5.6 years. The prognosis for seizure control was excellent in all cases and reflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome was excellent in 90.3% of children. RMEI appears to be a variety of idiopathic generalized epilepsy with specific features that occurs in developmentally normal children.

Efficacy of stiripentol in hyperthermia‐induced seizures in a mouse model of Dravet syndrome

We previously reported a mutant mouse carrying a severe myoclonic epilepsy in infancy (SMEI) mutation in Scn1a. In this study, we examined the susceptibility to hyperthermia-induced seizures of heterozygous Scn1a mutant mice (Scn1a(RX/+)) and wild-type (Scn1a(+/+) ) mice. Then we assessed the efficacy of stiripentol (STP) monotherapy versus STP and clobazam (CLB) combination therapy to prevent hyperthermia-induced seizures in Scn1a(RX/+) mice. The seizure-inducing body temperatures in Scn1a(RX/+) mice and age-matched Scn1a(+/+) mice were compared in three age groups (1 month, 3-5 months, > 6 months). Then STP, CLB, or STP + CLB was administered intraperitoneally to Scn1a(RX/+) mice of two age groups (p1M, aged 1 month; p5M, aged 5-10 months). The efficacy of medications was assessed by comparing the seizure-inducing body temperature and the duration of seizures. The seizure-inducing body temperature was significantly lower in Scn1a(RX/+) than in Scn1a(+/+) mice for all age groups (p < 0.01). The seizure-inducing body temperature was significantly elevated after administration of STP in p1M (p < 0.05) but not in p5M (p > 0.05), and it was significantly elevated after administration of CLB in both age groups (p < 0.05). The seizure-inducing body temperature was significantly higher after administration of STP + CLB than after administration of CLB in p5M (p < 0.05). Scn1a (RX/+) mice have increased susceptibility to hyperthermia-induced seizure in all age groups. STP monotherapy is effective in preventing hyperthermia-induced seizures in Scn1a(RX/+) mice aged 1 month, but not in those aged 5 months and older. When used in combination therapy with CLB, STP inhibits the metabolism of CLB and probably synergistically enhances the anticonvulsant effect in mice aged 1 month.

Benign myoclonic epilepsy in infancy with preceding afebrile generalized tonic–clonic seizures in Japan

Benign myoclonic epilepsy in infancy (BMEI) is the youngest form of idiopathic generalized epilepsy, characterized by myoclonic seizures (MS) in the first three years of life in otherwise normal infants, and the lack of other seizure types except for rare simple febrile seizures. Although afebrile generalized tonic–clonic seizures (GTCS) have been described to develop later in the clinical course of BMEI, mostly during adolescence, an association with GTCS in the early stage of BMEI has never been recognized. We herein report seven children who satisfied the criteria of BMEI except for the recurrence of GTCS before the onset of MS. The age of onset and ictal video-polygraphic features of MS, as well as the long-term seizure and developmental outcome in these children were similar to those of children with typical BMEI. Furthermore, these GTCS mostly disappeared within several months and were replaced by MS. Our study indicates that these children may constitute a BMEI subgroup, expanding the spectrum of BMEI.

Suivi thérapeutique pharmacologique du stiripentol

Stiripentol is a third generation antiepileptic, marketed since 2007 under the name of Diacomit(®). It is indicated, always in combination, in the treatment of severe myoclonic epilepsy in infancy or Dravet syndrome. Its pharmacokinetics is not linear. It is a potent inhibitor of CYP3A4, 1A2 and 2C19 and increases the plasma concentrations of many other antiepileptic drugs. Without this being considered as a validated therapeutic range, the trough plasma concentrations at steady-state, corresponding to the usual doses are between 10 and 15 mg/L. The concentration-efficacy relationship is not established, but there is some evidence for a concentration-related toxicity. However, because of its non-linear kinetics, stiripentol should be a good candidate for therapeutic drug monitoring (TDM). Nonetheless, the current level of evidence for the advantage of TDM is "remains to be estimated".

A patient with myoclonic epilepsy in infancy followed by myoclonic astatic epilepsy

Myoclonic epilepsy in infancy (MEI) is a primary generalized epilepsy. According to the literature, the outcome of MEI is usually benign. Here we report a patient who developed myoclonic astatic epilepsy at age four, having been seizure free without antiepileptic drug treatment for 2 years after his recovery from MEI. At age four, a video-EEG-recording showed frequent head nodding (atonic seizures) and myoclonic astatic seizures associated with diffuse spikes or polyspikes and waves. The interictal EEG revealed frequent bursts of generalized 100–200μV, 2–4Hz spike-and-slow-wave complexes. Despite a general favorable outcome, more severe epilepsy syndromes may develop after MEI, and mental retardation is sometimes observed. Our case and the previous literature suggest that epilepsies following on from MEI often involve myoclonic seizures.

Dravet syndrome: a genetic epileptic disorder.

Dravet syndrome (DS), or severe myoclonic epilepsy in infancy, is one of the most severe types of genetic epilepsy. It is characterized by the initial occurrence of febrile or afebrile seizures that often evolve into status epilepticus in infants with normal development, and by the subsequent appearance of myoclonic and/or atypical absence seizures as well as complex partial seizures. The key feature that characterizes DS is fever sensitivity, although photosensitivity and pattern-sensitivity are also often seen. The prognosis is unfavorable in most cases. Seizures become drug-resistant and persist, with many patients suffering from motor and cognitive impairment. Mutations of SCN1A, which encodes the voltage-gated sodium channel NaV1.1, are the most frequent genetic cause of this syndrome. SCN1A mutations and/or microchromosomal rearrangements involving SCN1A are detected in about 85ｵ of patients. Mutations of PCDH19 have also been reported in female patients with clinical findings compatible with DS. PCDH19 mutations might account for 5ｵ of overall DS cases. Thirty years after its first description, DS is considered as a model of channelopathy. This survey reviews recent developments in the research literature on DS, focusing on the clinical course, as well as its genetic causes.

乳児重症ミオクロニーてんかん (SMEI) 症例のワクチン接種状況調査

乳児重症ミオクロニーてんかん (SMEI) 症例のワクチン接種状況調査

Abstract P081: Voltage-Gated TTX-Sensitive Nav1.1 Brain Sodium Channels Are Important for Cardiac Contractile Function

Background: Mutations in voltage gated brain sodium channel Nav1.1 have been linked to many disorders, including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). Recent studies have identified TTX- sensitive Nav1.1 brain sodium channels in the SA node and ventricular T-tubules of the heart, though their role in cardiac function is still controversial. We tested the functional significance of Nav1.1 sodium channels in the heart by creating a novel knock-in of human epilepsy GEFS+ mutation SCN1A-R1648H at the Scn1a locus of a C57BL/6J X 129 mouse. Method: In vivo 2-D echocardiography was performed on 2 week old (juvenile) and 8 week old (adult) wild-type and heterozygote (Scn1aRH/+) mice after extracardiac neuronal block through intraperitoneal injections of atropine and propranolol (2.5mg/kg each). Calcium and contractility studies on adult ventricular cardiomyocytes isolated from the wild type and Scn1aRH/+ mice paced at 0.5Hz were followed by administration of TTX (100nM, a brain sodium channel inhibitor) and pacing at 2Hz. qRT-PCR and Western blot of the isolated cells and whole heart samples was also done. Results: A decrease in Nav1.1 gene expression in the Scn1aRH/+ juvenile (by 31%, 0.69 of 1) and adult (by 60%, 0.4 of 1) whole heart samples and isolated cells (p&lt;0.05) was seen. Echocardiography revealed concentric hypertrophy in the juvenile Scn1aRH/+ mice by a significant increase in LV mass, LV mass/body weight ratio, and relative wall thickness (p&lt;0.05). In the adult Scn1aRH/+ mice, systolic isovolumic contraction time (IVCT) was reduced (p=0.03) and decrease in diastolic function was evident through significant decreases in isovolumic relaxation time (IVRT) and E’/A’ ratio, and increase in E/E’ ratio. Isolated adult ventricular Scn1aRH/+ cardiomyocytes showed significant reduction in percent sarcomere shortening, maximum rate of contraction and relaxation, and time to peak contraction, exaggerated with TTX and pacing at 2Hz (p&lt;0.5). Conclusions: Our study demonstrates the importance of voltage gated TTX-sensitive Nav1.1 brain sodium channels in cardiac contractile function and their possible role in cardiac complications in epilepsy.

Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy

Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE). We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1–2 s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA). At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW. Our case is the first patient with BMEI reported in the literature who later developed a CAE. This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes.

P23.5 Benign myoclonic epilepsy of infancy as the initial clinical presentation of a SLC2A1 mutation

P23.5 Benign myoclonic epilepsy of infancy as the initial clinical presentation of a SLC2A1 mutation

Leber’s Hereditary Optic Neuropathy Mutations Associated With Infantile-Onset Myoclonic Epilepsy

Epilepsy syndromes with onset in the first year of life, especially when they include myoclonic features, have special significance since they are associated with long-term developmental and neurological abnormalities. Dravet's severe myoclonic epilepsy in infancy is especially interesting as it is associated with fever-provoked seizures and mutations in the alpha subunit of the sodium channel (SCN1A) in about one-third of the cases. Here, we report 2 children who had clinical features of severe myoclonic epilepsy of infancy without mutations in the SCN1A gene who were found to have mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. These 2 children demonstrated markers of mitochondrial dysfunction, drug-resistant epilepsy, and dysfunction of nonneurological systems. These cases demonstrate that mitochondrial DNA mutations, especially those associated with Leber's hereditary optic neuropathy, should be considered in cases of myclonic epilepsy starting in infancy, especially when mutations in the SCN1A gene are not found.