Search

While ataxia is a relatively common presenting feature in pediatric patients, it represents only one possible cause of uncoordinated movements. Other possible causes of uncoordinated movements include ingestion of toxic substances, musculoskeletal diseases, psychogenic disorders, extrapyramidal movement disorders, peripheral neuropathies, spasticity from any cause, and epilepsy. Therefore, primary health care providers must recognize and exclude other etiologies of uncoordinated movements before attaching the label “ataxia” to any patient presenting with poor coordination. Once the presence of ataxia is confirmed, the cause should be investigated. As ataxia may be vestibular, sensory, or cerebellar in origin, medical practitioners must evaluate the diverse symptoms and signs to effectively differentiate the various types of ataxia. Three case studies are presented to illustrate the complexity associated with the assessment of ataxia. Each case will discuss a pediatric patient who displays cerebellar ataxia as a concurrent feature of a gene-specific developmental and epileptic encephalopathy. These cases will provide an example of how ataxia may be differentiated from other causes of uncoordinated movements related to epilepsy and anti-seizure medications, namely: nonconvulsive seizures, postictal state, and medication side effects or toxicity. The assessment of poor balance can be challenging at times; however, with knowledge of the differential diagnosis of poor balance, medical practitioners will be able to confidently determine the presence of true ataxia from various ataxia mimickers, thereby allowing for timely and accurate diagnosis, and appropriate management.

Epilepsy is a common, often severe, feature of LAMA2-related muscular dystrophy (LAMA2-RD) and could represent its onset and main manifestation, even in the absence of overt muscle involvement. To date, there is no systematic characterization of epilepsy in LAMA2-RD, and its impact on neurodevelopment and on the clinical course remains poorly established. In view of this knowledge gap, we conducted a systematic review of the literature and, as an illustrative example, reported the clinical case of a boy with late-onset LAMA2-related limb-girdle muscular dystrophy presenting with severe epilepsy. Our analyses of the literature data revealed a mean age at first seizure of 8 years, with significant differences between early- versus late-onset disease (5.78 ± 4.11 and 9.00 ± 2.65 years, respectively; p = 0.0007), and complete versus partial merosin deficiency (5.33 ± 3.70 and 10.36 ± 5.49 years, respectively; p = 0.0176). A generalized onset was the most common seizure presentation, regardless of merosin expression levels or the timing of muscular distrophy onset. Cortical malformations were not significantly associated with an earlier epilepsy onset, and were found to be quasi-significantly associated with a greater incidence of focal, or focal and generalized, onset seizures. No clear conclusions could be reached on the electrophysiological and neurodevelopmental features of the disorder, or on the relative efficacy of anti-epileptic treatments; further research on these aspects is needed. This systematic review helps to show that epilepsy in LAMA2-RD may be more than an ancillary manifestation of the disease, but rather one of its core features. A targeted and prompt electroencephalographic and epilepsy assessment, in addition to the specific neuromuscular workup, is therefore mandatory in early clinical management to pursue the best possible outcome for affected children.

Objectives To describe and quantify the nature and severity of sleep disruptions in young people with Dravet syndrome (DS) based upon parent report. Methods Qualitative review of available pediatric sleep instruments with parent members of the Dravet syndrome Foundation led to the design of a series of questions customized to DS and other severe epilepsies. The questionnaire was administered as part of an on-line survey that reflected specific sleep-related concerns of parents of children with severe epilepsy. Results 76 parent-respondents completed the survey for their children-participants. Children’s median age was 7.5 years (IQR 4.7–15.3); 41 (54 %) were female. The majority of parents (70/76, 93 %) used some method to monitor children while sleeping; co-sleeping was the most common method (45/76, 59 %). Seizures disrupted sleep in 40/76 (53 %); 19(48 %) reported nocturnal seizures 3 or more nights per week. In addition, 58/76 (76 %) also reported non-seizure-related nocturnal awakenings with 30 reporting awakenings 3 or more nights affected per week. Significance Young people with Dravet syndrome have frequently disrupted sleep secondary to seizures and other factors. Co-sleeping practices, medication effects, enuresis during seizures and other factors are not considered on standard sleep questionnaires. Current findings highlight the frequency of epilepsy-specific concerns and lay groundwork for sleep measures more appropriate for this population.

Background Literature regarding congenital subependymal giant cell astrocytomas (SEGA) is limited, and suggests they are at risk of rapid growth and complications. We sought to characterise the growth patterns of congenital SEGA. The second part of the study was an exploratory analysis of congenital SEGA as a possible biomarker for poor neurological outcome. Methods This single-centre case series describes ten patients with TSC who had SEGA diagnosed before 12 months. SEGA diameter and volumetric growth were analysed using serial MRIs. Neurological outcomes were compared to a genotype-matched group. Results All children with congenital SEGA had a TSC2 mutation. Patients were followed for 1-8.7 years, during which median SEGA growth rate was 1.1 mm/yr in diameter or 150 mm3/yr volumetrically. SEGA with volume > 500 mm3 had a significantly higher growth rate compared with smaller SEGA (462 mm3/yr vs. 42 mm3/yr, p = 0.0095). Children with congenital SEGA had a high prevalence of severe epilepsy, developmental disability and autism spectrum disorder. Conclusion Congenital SEGA can follow a relatively benign course with a lower growth rate compared with published literature. Frequent neuroimaging surveillance is recommended for congenital SEGA with volumes exceeding 500 mm3. Impact Congenital SEGA occur in 9.2% of paediatric patients with tuberous sclerosis complex.There are few published cases of congenital SEGA to date. This case series of ten patients adds our experience seen in a tertiary referral hospital over 10 years.Congenital SEGA can follow a relatively benign course with a lower growth rate compared with published literature.Congenital SEGA with volume exceeding 500 mm3 had a significantly higher growth rate compared with smaller SEGA and should have more frequent neuroimaging surveillance.

Objectives To assess symptoms of post-traumatic stress disorder (PTSD) in children with severe epilepsy and the associations of trauma symptoms across age, comorbid symptoms, epilepsy-specific factors, parental resources, and psychopathology. Methods Fifty children with severe epilepsy across three different age groups (0–5 yrs., 6–12 yrs., 13–18 yrs.) were assessed with developmental-sensitive and standardized PTSD assessment tools when hospitalized at the tertiary epilepsy center Filadelfia, Denmark. The Diagnostic Infant and Preschool Assessment (DIPA), the Darryl test, and the ITQ questionnaire were used to assess the three age groups, respectively. Results Twenty-two percent of the overall sample met the criteria for PTSD, with a prevalence of symptoms increasing with age (6%, 28%, and 40%). Comorbid psychiatric symptoms in preschoolers were present in 81% of the children witnessing a high level of distress in this group. Behavioral difficulties were elevated across all three age groups, and 40% of the children with trauma symptoms had a parent with concurrent psychopathology. Conclusion To the authors’ knowledge, this study is the first to assess trauma symptoms with standardized tests in children with more complicated epilepsies. Trauma symptoms in the group are high; however, there is a need for larger scale studies and research into trauma symptoms in children with more severe epilepsy than those assessable with the included assessment tools. The trauma perspective in severe childhood epilepsy might further clarify the complex associations of biological and contextual variables that affect the children’s life quality and enable better preventative treatment options for this group.

Objective: We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. Methods: We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association “KCNB1 France.” Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the longterm outcome in patients older than 12 years from our series and from literature. Results: Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. Significance: Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechanisms should facilitate the development of targeted therapies, much needed to improve the neurodevelopmental prognosis.

The parasitic helminth infection neurocysticercosis (NCC) is the most common cause of adult-acquired epilepsy in the world. Despite the serious consequences of epilepsy due to this infection, an in-depth review of the distinct characteristics of epilepsy due to neurocysticercosis has never been conducted. In this review, we evaluate the relationship between NCC and epilepsy and the unique characteristics of epilepsy caused by NCC. We also discuss recent advances in our understanding of NCC-related epilepsy, including the importance of anti-inflammatory therapies, the association between NCC and temporal lobe epilepsy, and the recent discovery of biomarkers of severe epilepsy development in individuals with NCC and seizures.

8q22.2q22.3 microdeletion syndrome has been described in only seven patients. We present a new case from Colombia. The characteristics of this condition are developmental delay, microcephaly, seizures, and typical facial dysmorphism. We discuss the clinical phenotype of the patient presenting relevant findings like hearing loss and severe epilepsy and the possible relations between the phenotype and the genes involved in the microdeletion. We describe a female with developmental delay, microcephaly, epilepsy, severe short stature, impaired speech, facial dysmorphism, and congenital deafness. A minimal/maximal deletion of 5.238 Mb and 5.374Mb, respectively, at 8q22.2q22.3 was diagnosed using a genome-wide array. The clinical phenotype is similar to the others seven patients previously reported; however, the severity of epilepsy and the concomitant hearing loss is remarkable, characteristics previously observed independently in only two patients. The KCNS2 gene is located in the deleted regions (8q22.2). Therefore it is a possible candidate for explaining the complex neurologic phenotype.

The majority of neonatal seizures are related to common diagnoses, including hypoxic-ischemic encephalopathy and intraventricular hemorrhage. While relatively uncommon, neonatal epileptic encephalopathies represent an important group of neonatal seizure disorders that require immediate diagnosis and intervention. In this review, we provide a summary of the benign and severe neonatal epilepsy syndromes. While benign epilepsy syndromes have favorable prognoses, rapid and accurate diagnosis may prevent an unnecessarily long course of antiseizure medications. The severe epilepsy syndromes may be related to a number of underlying genetic disorders and often carry a poor prognosis. Herein we review diagnostic and therapeutic strategies, and provide a set or algorithms for said purposes.

The article describes the phenomenon of dual pathology – a combination of structural changes in the brain and benign epileptiform discharge of childhood on electroencephalogram. The uniqueness lies in the observation that the child, since birth suffering from spastic form of cerebral palsy and severe epilepsy, demonstrated the development of Stevens–Johnson syndrome due to intolerance of one of the antiepileptic drugs. Therapeutic approaches to overcome a whole range of violations are discussed in the article.

RFT1-congenital disorder of glycosylation (CDG) syndrome, a recessive N-glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non-specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online].

Incontinentia pigmenti (IP) is an uncommon neurocutaneous syndrome characterized by skin lesions, ocular abnormalities, and central nervous system (CNS) involvement. Mutations in IKBKG gene were discovered as a cause of IP. The most frequent neurologic manifestations are seizures, usually observed in the first week, and sometimes in the first year of life or in childhood. The most frequent types of presenting seizures are partial clonic or generalized seizures. Epilepsy usually showed a good prognosis in most patients with a good response to treatment. However, in some patients a more severe epilepsy related to various degree of CNS involvement can occur. Clinicians should pay special attention to cutaneous signs of IP in infants presenting with neonatal seizures.

Objective Pediatric epilepsy is associated with a wide range of neurodevelopmental challenges. Few studies have established children’s cognitive function prior to seizure onset making study of the direct impact of seizures challenging. This is especially true in cases with preexisting neurological disorders. The present case provides insight into the impact that new onset of seizures (including status epilepticus) have on cognitive development and illustrates how documented cognitive change informs clinical decision-making. Method The patient is a 10-year-old boy with a history of cerebral palsy who initially completed neuropsychological testing in the fall of 2018. New onset of drug-resistant seizures presented in January 2019, including episodes of status epilepticus leading to repeat neuropsychological evaluation in the fall of 2019. EEG studies in infancy showed poorly regulated background rhythm and MRI showed dysplastic corpus callosum and bilateral occipital heterotopias. Following the onset of seizures EEG showed independent seizure foci over temporal regions bilaterally. MRI showed extensive bilateral temporal and occipital subependymal gray matter heteropi, and dysgenesis of the corpus callosum, cerebral vermis, and anterior commissure. Results Repeated neuropsychological assessment documented significant declines in intellectual function, visual and verbal memory (visual worse than verbal), and executive function, with limited academic progression. Persistent epileptic symptoms throughout testing complicated interpretation. Conclusions Findings were highly concerning for cognitive deterioration and the neurosurgical team deemed him as high risk for sudden unexpected death in epilepsy. He underwent right anterior temporal lobectomy and left stereoelectroencephalography placement in January 2020. Scheduled repeat neuropsychological evaluation will further monitor neurocognitive functioning post neurosurgical intervention.

Introduction Children with epilepsy report lower health-related quality of life (QOL) compared with healthy children and those with other chronic disorders. This study piloted the recently published Pediatric Quality of Life Inventory (PedsQL) Epilepsy Module (PedsQL-EM) in an ambulatory setting and studied epilepsy-related factors contributing to QOL in children with epilepsy. Methods Children with epilepsy aged 8–18 years who were ambulant and verbal were recruited from pediatric neurology clinics. Children and their caregivers completed age-appropriate versions of the PedsQL-EM (8–12 or 13–18 years) in the clinic waiting area. Treating neurologists completed medical questionnaires about their patients' epilepsy. Results We collected 151 parent-report and 127 self-report PedsQL-EMs. Administration time was 5–10 min with some children receiving assistance from the researcher. Mean age of children was 12.9+/-3.0, with 77 females (51%). Parents reported lower mean QOL scores across all subdomains compared with their children. Parents reported significantly lower QOL for children with earlier age at epilepsy onset, longer epilepsy duration, presence of seizures during the last month, more severe epilepsy, increased number of antiepileptic drugs (AEDs), and cognitive comorbidity. The same factors impacted on child self-reporting, but with more variability across subdomains. Conclusions The PedsQL-EM is an epilepsy-specific measure of QOL that is quick and easy to administer and is sensitive to the clinical factors reported to impact on QOL in pediatric epilepsy.

The incidence of seizures is greatest during the neonatal period, with an estimated rate of 2–4 per 1,000 live births. Although the majority of seizures in the newborn are due to acquired brain disorders, a substantial proportion are due to metabolic and genetic disorders causing neonatal- and infantile-onset epilepsies. For decades, genetics has played a critical role in identification and treatment of seizures in the newborn and infantile period.1,2 With newborn screening, disorders such as phenylketonuria and biotinidase deficiency can be identified before patients develop seizures. Early identification and treatment prevents the development of often severe epilepsy syndromes and associated comorbidities. Detection and early treatment will continue to improve as newborn screening methods advance, whether based in genetics or clinical observation: the first channelopathy that causes epilepsy was identified in families with benign familial neonatal convulsions in the 1990s, before completion of the human genome project and modern genomics.3

BackgroundPeople with epilepsy have more concomitant medical conditions than the general population; these comorbidities play an important role in premature mortality. We sought to generate explanatory hypotheses about the co-occurrence of somatic comorbidities and epilepsy, avoiding causal and treatment-resultant biases.MethodsWe collected clinical, demographic and somatic comorbidity data for 2016 consecutive adults with epilepsy undergoing assessment at a tertiary centre and in 1278 people with epilepsy in the community. Underlying causes of epilepsy were not classed as comorbidities.ResultsSomatic comorbidities were more frequent in the referral centre (49%) where people more frequently had active epilepsy than in the community (36%). Consistent risk factors for comorbidities were found in both cohorts. Using multivariable ordinal regression adjusted for age, longer epilepsy duration and an underlying brain lesion were independently associated with a smaller burden of somatic conditions. The treatment burden, measured by the number of drugs to which people were exposed, was not an independent predictor. Shorter epilepsy duration was a predictor for conditions that conceivably harbour significant mortality risks.ConclusionsSomatic comorbidities do not occur randomly in relation to epilepsy; having more severe epilepsy seems to be a risk factor. Independently from age, the early period after epilepsy onset appears to be at particular risk, although it is not clear whether this relates to an early mortality or to a later decrease in the burden of comorbidities. These results suggest that, for some people, epilepsy should be considered a systemic condition not limited to the CNS.

This article summarizes the emerging landscape of pediatric epilepsy, highlighting genetic contributions, and reviews approaches to genetic evaluation for pediatric epilepsy in this context. Advances in understanding the genetic basis for epilepsy over the last several years have been due in large part to the identification of de novo genetic variation underlying sporadic severe epilepsy in children; the genetic underpinnings of the more common epilepsies remain largely unknown. Next-generation sequencing approaches have been added to the repertoire of clinical tests for the evaluation of pediatric epilepsy, improving our ability to make positive diagnoses. Yields of over 50% are now being reported in selected groups of patients. Genetic variation contributing to the risk for pediatric epilepsy spans continua of scale and influence. The highest yield of genetic testing is currently in children with sporadic severe epilepsy caused by de novo variation. The approach to genetic evaluation and interpretation of results requires an understanding of (1) the epilepsy phenotype and (2) the particular advantages and limitations of the different genetic tests available. Our understanding of genetic variation will continue to improve over time and “negative” results are best conceptualized as “unresolved” or “negative for now.”

Epilepsy is one of the most common presentations associated with chromosome aberrations. Detailed descriptions of some aberration-specific epileptic and electroencephalographic (EEG) phenotypes have been reported (i.e., Angelman syndrome, ring 20 etc.). However there is limited and mixed information about the characteristics of epilepsy related to trisomy 18. Thus a common seizure phenotype has not been characterized yet. Here we describe in detail a patient with refractory epilepsy and partial 18q trisomy.

Background In 2003, several hundred Israeli infants risked thiamine deficiency after being fed a soy-based formula deficient in thiamine. Approximately 20 patients were seriously affected, and three of them died. We report the clinical presentation of acute encephalopathy in 11 children and the long-term sequelae of eight children who initially survived. Patients In the acute phase, six had bulbar signs, five had ophthalmologic signs and two had phrenic neuropathy. Three of the five patients with cardiac involvement had cardiomyopathy and died in the acute phase. One patient presented with a complete atrioventricular block. Results In the long-term, one patient, who was in a chronic vegetative state, died after 6 years. Seven children exhibited mental retardation and motor abnormalities, six developed severe epilepsy, two early kyphoscoliosis, and one patient remained with a complete atrioventricular block. Conclusions Infants who survive severe infantile thiamine deficiency have serious residual motor and cognitive sequelae as well as epilepsy.

Should patients with epilepsy be monitored during sleep to prevent sudden unexpected death in epilepsy (SUDEP)? The study by van der Lende et al.1 provides additional evidence that the answer is probably yes in certain populations. These investigators compared the incidence of SUDEP at 2 residential centers for adults with severe epilepsy (>90% had convulsive seizures, and ∼50% were on ≥3 antiepileptic drugs). The center with less intensive nocturnal monitoring had a nearly 3-fold higher SUDEP incidence that was not explained by other factors (e.g., seizure severity). Sadly, despite monitoring, supervision, and expert care at both centers, the SUDEP rate remained 2- to 5-fold greater than population-based studies of patients with epilepsy. Unlike some other case-control studies, the incidence of SUDEP was higher among individuals with higher IQ and less benzodiazepine use.

Summary Objectives Population characteristics of epileptic patients remain poorly documented in France. Health Insurance claims database may be useful to perform cost and epidemiological studies provided that patients’ diagnosis could be identified especially through drugs used as markers. This study explored the possibility to use the French Sickness Fund (FSF) database to determine the prevalence and direct cost of epilepsy. Method The “FSF” reimbursement database is a 1/97 representative sample of the population covered under the French General Scheme. Only the fraction of patients fully covered for epilepsy may be identified by a diagnosis in the database. Others can only be identified through their claims for antiepileptic drugs (AEDs) with the limitation that, among the 19 AEDs used, some are not specific for epilepsy. An algorithm was built to select patients to get a range of prevalence estimates whereas medical expenses of patients were derived on the fully covered sub-population. Results Only patients treated in polytherapy (≥ 2 AEDs) were deemed to be identified in a relevant way by an algorithm based on drug usage. The prevalence of epilepsy in this sub-group in 2009 was estimated between 1.83 and 2.79‰ (93,000–142,000 patients). A proportion of 70.1 to 71.6% were fully covered for their expenses, with epilepsy alone as a cause in only 27 to 33% of them. The most frequent other co-morbidities were psychiatric disorders and invalidating stroke. The annual per capita expenses were in the range 6.696–6.601 € in patients in polytherapy. Inpatient care and drug costs represented about 50 and 27% of overall expenses, respectively. The increase by 24.4% of polytherapy patients mean costs as compared to monotherapy raised to 72% (IC 95: 44–106%) after adjustment for age, gender and presence of severe co-morbidity. Conclusion In France, in 2009, 93,000 to 142,000 epileptic patients have been treated for epilepsy with a polytherapy. About one out of three patients only benefited from a full coverage of their medical expenses for epilepsy but half of them were fully covered for another disease. This resulted from the frequent presence of a severe co-morbidity especially psychiatric or due to a history of an invalidating stroke. Conversely, about 30% of epileptic patients in polytherapy, fully eligible to a full coverage did not benefit from it, which suggested an important sub-declaration of severe epilepsy.

Summary Dravet syndrome is a severe epilepsy syndrome of infancy characterised by seizures of multiple types, often prolonged and particularly fever-sensitive, with onset in the first year of life, and subsequent developmental delay. This article aims to present updated data on this syndrome, for which complete and extensive clinical descriptions led to the discovery of a link with a major gene, SCN1A, on which abnormalities are found in at least 70% of the patients tested. Our review article follows and summarises the data published in a 2011 supplement issue of Epilepsia, entitled Severe Myoclonic Epilepsy –

Investigators from the Universities of Salerno and Perugio, Italy, studied the effect of listening to a set of Mozart's compositions on sleep quality, behavior, and seizure recurrence in 11 outpatients (7 males and 4 females), between 1.5 and 21 years of age (mean age, 11.9 years), with drug-resistant epilepsy.

Epileptic encephalopathies are an epileptic condition characterized by epileptiform abnormalities associated with progressive cerebral dysfunction. In the classification of the International League Against Epilepsy eight age-related epileptic encephalopathy syndromes are recognized. These syndromes include early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, West syndrome and Dravet syndrome in infancy, myoclonic status in nonprogressive encephalopathies, and Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and epilepsy with continuous spike waves during slow wave sleep in childhood and adolescences. Other epileptic syndromes such as migrating partial seizures in infancy and severe epilepsy with multiple independent spike foci may be reasonably added. In this paper, we provide an overview of epileptic encephalopathies including clinical neurophysiological features, cognitive deterioration, and management options especially that these conditions are generally refractory to standard antiepileptic drugs.

Epileptic encephalopathies represent a group of devastating epileptic disorders that appear early in life and are characterized by pharmacoresistant generalized or focal seizures, persistent severe electroencephalography (EEG) abnormalities, and cognitive dysfunction or decline. The ictal and interictal epileptic discharges are age-specific and are the main etiologic factors causing cognitive deterioration. This is most obvious in the idiopathic group. In the symptomatic group, the most common causes are structural, congenital, or acquired and rarely some metabolic disorders. In certain cases, clinical and EEG abnormalities persist and may evolve from one type to another as the child grows older. Various factors trigger and sustain the underlying pathophysiologic process and the ongoing epileptic and epileptiform activity during the most critical periods of brain maturation, perpetuating their deleterious effect on the brain. Immune-mediated mechanisms may have a role, suggested by certain encephalopathies responding to immune-modulating treatments and by the finding of various autoimmune antibodies. The chance of a better cognitive outcome improves with early diagnosis and treatment that is appropriate and effective. Current antiepileptic drugs are, in general, not effective: we urgently need new trials in this very special epileptic category. This article briefly reviews the most common epileptic encephalopathies and analyzes the most important clinical issues.

CDKL5 mutations cause severe epilepsy in infancy with subsequent epileptic encephalopathy. As yet, few studies report on long-term observations in patients with CDKL5-related epileptic encephalopathy. In this study, we describe the evolution of the epilepsy phenotype and the electroencephalographic (EEG) features in 4 patients during a maximum observation period of 22 years. All 4 patients had epilepsy starting with focal seizures in the first 3 months of life, evolving to epileptic spasms between the ages of 2 and 6 years and later on to tonic seizures. In 3 patients, epilepsy was resistant to antiepileptic therapy. Although there was no common EEG pattern in all patients, late hypsarrhythmia until the age of 9 years was observed in 2 patients. CDKL5-related epileptic encephalopathies are a group of refractory seizure disorders starting in early infancy. The phenomenon of late hypsarrhythmia may help define a subgroup of patients with severe and adverse outcomes.

Dravet syndrome was described in 1978 by Dravet (1978) under the name of severe myoclonic epilepsy in infancy (SMEI). The characteristics of the syndrome were confirmed and further delineated by other authors over the years. According to the semiologic features, two forms have been individualized: (1) the typical, core, SMEI; and (2) the borderline form, SMEIB, in which the myoclonic component is absent or subtle. Clinical manifestations at the onset, at the steady state, and during the course of the disease are analyzed in detail for the typical Dravet syndrome, and the differential diagnosis is discussed. Onset in the first year of life by febrile or afebrile clonic and tonic-clonic, generalized, and unilateral seizures, often prolonged, in an apparently normal infant is the first symptom, suggesting the diagnosis. Later on, multiple seizure types, mainly myoclonic, atypical absences, and focal seizures appear, as well as a slowing of developmental and cognitive skills, and the appearance of behavioral disorders. Mutation screening for the SCN1A gene confirms the diagnosis in 70-80% of patients. All seizure types are pharmacoresistent, but a trend toward less severe epilepsy and cognitive impairment is usually observed after the age of 5 years.

We report a six-year-old girl with Cardio-facio-cutaneous (CFC) syndrome who developed acute encephalopathy after the recurrence of status epilepticus. While epileptic encephalopathy and severe epilepsy have been mentioned as frequent complications of the CFC syndrome, no previous reports have shown a case of the CFC syndrome complicated with acute encephalopathy. Here we discuss the possibility for the linkage between the development of acute encephalopathy and CFC syndrome which is generally susceptible to seizures or epilepsy.

Background and purpose We present the epilepsy surgery activity in infants and children at the Fondation Rothschild Hospital, the main center dedicated to this activity in France. Method A prospective study was conducted from 2003 to 2007 based on three populations: (1) children selected as candidates for surgery, (2) children undergoing presurgical evaluation and (3) children undergoing surgical procedures for epilepsy. Results Children selected as candidates for surgery: 304 children were referred and discussed by our multidisciplinary staff. They came from Paris and its suburbs (40%), the provinces (43%) or from other countries (14%). Sixty-one percent of them were included in our surgery program and 24% were excluded. Sixty-one percent of them were under 10 years of age. Children undergoing presurgical evaluation: 296 children were recorded: 140 EEG (47%), 46 with foramen ovale electrodes (16%) and 110 with invasive recording techniques (37%). Seventy percent of these children were under 10 years of age. Children undergoing surgical procedures: 316 children underwent surgery; 68% of them were under 10 years of age. The surgical procedures were focal resection (136 children), vertical parasagittal hemispherotomy (77 children), resection and or disconnection for hypothalamic hamartoma (69 children) and 34 had palliative surgery (callosotomy or vagal nerve stimulation). Conclusion Eighty to 100 children undergo surgery each year in our department for drug-resistant partial epilepsy; 70% of them are less than 10 years of age. This activity is part of a network of pediatric neurologists who are deeply involved in treatment of severe epilepsy in children.

Introduction: About one-half of children with Lennox–Gastaut syndrome (LGS) have history of birth hypoxia or other perinatal event but the knowledge about clinical, radiological profile and severity of epilepsy in these children as compared to those without a perinatal event is not known. Materials and Methods: Thirty-one children with LGS were enrolled in this study and divided into two groups: One group with the perinatal event and other group without evidence of the perinatal event. We hypothesized that LGS with the perinatal event will have an early age of onset of LGS, more motor deficits and abnormal brain magnetic resonance imaging (MRI) and more severe epilepsy. Results: There were 17 children in the perinatal event group and 14 in the other group. The mean age of onset of illness was significantly earlier in the perinatal event group (P < 0.05). More children in the perinatal event group had delayed milestones (P < 0.05), had higher seizure frequency (P < 0.05) however; there was no significant difference in number of anti-epileptic drugs consumed, motor deficits or MRI abnormalities. Conclusion: LGS children with the perinatal event have more severe epilepsy with early onset of disease and delayed milestones. History of perinatal insult in these children may help in predicting prognosis in LGS.

Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 2% of deaths in population-based cohorts of epilepsy, and up to 25% of deaths in cohorts of more severe epilepsy. When it occurs, SUDEP usually follows a generalised tonic-clonic seizure. Unresponsiveness, apnoea, and cardiac arrest occur in SUDEP, rather than the typical gradual recovery. The great majority of tonic-clonic seizures occur without difficulty and how the rare seizure associated with SUDEP differs from others is unknown.Three mechanisms have been proposed for SUDEP: cardiac arrhythmia, neurogenic pulmonary oedema, and postictal suppression of brainstem respiratory centres leading to central apnoea. Recent studies have found that the incidence of SUDEP increases with the severity of epilepsy in the population studied. The duration of epilepsy, number of tonic-clonic seizures, mental retardation, and simultaneous treatment with more than two antiepileptic drugs are independent risk factors for SUDEP. Some studies have reported that carbamazepine use, carbamazepine toxicity, and frequent, rapid changes in carbamazepine levels, may be associated with SUDEP. Other evidence indicates that carbamazepine could potentially increase the risk for SUDEP by causing arrhythmia or by altering cardiac autonomic function. However, this evidence is tenuous and most studies have not found an association between the use of carbamazepine or any other individual antiepileptic drug and SUDEP. There is little information regarding antiepileptic drugs other than phenytoin and carbamazepine. The incidence of SUDEP with gabapentin, tiagabine, and lamotrigine clinical development programmes is in the range found in other populations with refractory epilepsy. This suggests that these individual antiepileptic drugs are no more likely to cause SUDEP than antiepileptic drugs in general. Best current evidence indicates that the risk of SUDEP can be decreased by aggressive treatment of tonic-clonic seizures with as few antiepileptic drugs as necessary to achieve complete control. At present there is no strong reason to avoid any particular antiepileptic drug. Further studies are needed to elucidate the potential role of individual antiepileptic drugs in SUDEP and establish clinical relevance, if any. These studies may be challenging to conduct and interpret because SUDEP is relatively uncommon and large numbers will be necessary to narrow confidence intervals to determine the clinical relevance. Also adjustments will be needed to account for the potent risks associated with other independent factors.

The occurrence of seizures in patients with fragile X syndrome (Fra-X) is reported. Among the 30 patients, six had epilepsy that was particularly severe and two also showed atypical facial dysmorphism that was different from that seen in classical Fra-X. From the study performed in this series of Fra-X patients the authors arrived at the following conclusions. (1) The occurrence of seizures in Fra-X population is around 20%, as reported in the literature. (2) The EEG pattern of benign childhood epilepsy with central-temporal spikes (BCECTS) was found in only three patients (10%). (3) According to the pattern of seizures and EEGs, four groups may be recognizable, the less frequent being the uncommon group characterized by severe epilepsy unresponsive to treatment. (4) In this group atypical facial dysmorphism (although not similar in the two patients and different from the classical facial pattern of Fra-X) was found. The authors maintain that additional genetic factors might influence the clinical course and neurological aspects of Fra-X syndrome.

There are many monogenic disorders associated with epilepsy that begin in childhood and persist into adult life. Each of these disorders raises specific issues for transition, in addition to common issues facing this group of patients as they move from pediatric to adult care. Such comorbidities include psychiatric and movement disorders. Epileptic encephalopathies may be caused by monogenic disorders, with Dravet syndrome being the best characterized. Although some patients have a relatively good adult outcome, others have persisting severe epilepsy complicated by autistic spectrum disorder and problems with gait. When reevaluating a patient as they transition to adult care, a thorough reconsideration of the genetic etiology of their epilepsy should be performed. This should be followed by genetic counseling for the patient and their family members.

We aimed to evaluate the health-related quality of life (HRQoL) of schoolchildren with epilepsy and its determinants and the HRQoL of their parents in comparison with those of healthy children and their parents.The study sample comprised 100 children with epilepsy (58 males), 8-16 years of age, diagnosed at least 6 months earlier. The children with epilepsy were divided into two subgroups: A, with well controlled idiopathic epilepsy, and B, with drug-resistant or symptomatic epilepsy and with concomitant neurodevelopmental problems. A control group consisted of 100 healthy age- and gender-matched children. One parent in each family completed two questionnaires standardized for use in Greece: KIDSCREEN-27 (version for parents) to assess the HRQoL of the children and SF-12 to assess the parental HRQoL. For each of the five dimensions of KIDSCREEN-27 and for the physical and mental component scales of the SF-12 tool, the standardized mean difference (SMD) was used for comparison between the various groups and subgroups. Linear regression analysis was used to explore the effect of specific illness-related factors on the five dimensions of KIDSCREEN-27 in the children with epilepsy.The parent-reported scores on KIDSCREEN-27 of the children with epilepsy were worse overall than those of healthy children, but the difference reached statistical significance only for the dimensions of "physical well-being" (p = 0.001) and "school environment" (p0.001). The differences were greater in adolescents (age group: 13.5-16years). The worst scores were recorded in subgroup B, the children with severe epilepsy, in the dimensions "physical well-being" (p0.001), "school environment" (p0.0001), and "peers and social support" (p = 0.044). The factors found to have a significant effect on all dimensions were mental retardation, physical disability, abnormal brain imaging findings, learning problems, and, to a lesser degree, administration of a large number of antiepileptic drugs and prolonged treatment. The parents of children with resistant epilepsy and accompanying neurodevelopmental problems scored significantly worse on the SF-12 mental health scale than those of healthy children (p0.001).Epilepsy, particularly severe epilepsy with concomitant neurodevelopmental problems, adversely affects the HRQoL of both schoolchildren and their parents.

Infantile spasms (IS) is a relatively common and severe epilepsy of infants and young children. IS likely contributes to up to 10% of all mental retardation, and it evolves into further epilepsies in about 50% of cases.1 Although this catastrophic epilepsy was first identified more than 160 years ago, its cause and mechanism are poorly understood and treatment is unsatisfactory, particularly in preventing the postulated effects of these seizures on cognitive function.1,2

A retrospective survey was carried out of add-on treatment with lamotrigine (LTG) and vigabatrin (GVG) in 109 children with severe epilepsy, treated between 1987 and 1994, identified from a total population of 300 patients seen annually, in a tertiary referral outpatient clinic in Cardiff, Wales. Of 79 patient treatments with LTG and 86 with GVG, 42 patients were treated with add-on LTG, 52 with add-on GVG and 20 with both drugs simultaneously. A Kaplan-Meier curve, applied to each of the two index drugs, indicated that 71 and 62% of patients would be expected to continue taking LTG or GVG, respectively after 40 months. Improved seizure control (or = 50%) at the time of audit was seen in 65% of LTG and 58% of GVG patient treatments for all epilepsy syndromes, but there was a higher proportion of patients with generalized epilepsy improved by LTG (28/41, 68%) than that improved by GVG (8/20, 40%), and only those with generalized epilepsy treated with LTG became seizure free (8/38, 21%). Similar proportions of patients discontinued LTG (16%) and GVG (15%) due to an adverse experience, but a higher proportion discontinued GVG (18%) compared with LTG (6%) because of lack of efficacy. This study supports the relative clinical effectiveness of LTG and GVG in the real world, where children with severe epilepsy are treated in clinical practice and serves to generate hypotheses to enable design of prospectively controlled trials, which should enable more rational use of these two drugs in the paediatric population with epilepsy.

Epilepsia é uma das condições neurológicas mais comuns em crianças e adolescentes. Infelizmente, pacientes com epilepsias refratárias ao tratamento medicamentoso estão mais susceptíveis a complicações clínicas e óbito. Neste trabalho reportamos, em uma análise prospectiva, um cohort de crianças acompanhadas por aproximadamente dez anos. Cinquenta e três de 1012 pacientes foram a óbito. Quarenta e dois pacientes morreram em decorrência da epilepsia ou de suas complicações clínicas; as principais causas foram pneumonia (16 casos), sepse (9 casos) e estado de mal epiléptico (8 casos). Em 11 pacientes a causa da morte foi SUDEP. A presença de retardo mental foi significantemente associada a mortalidade em crianças e adolescentes com epilepsia. Epilepsy is the main neurological condition in children and adolescents. Unfortunately patients with medical refractory epilepsy are more susceptible for clinical complications and death. We report a prospectively evaluated cohort of children followed for approximately 10 years. Fifty-three of 1012 patients died. Forty-two patients died due to epilepsy or its clinical complications and the main causes of death were pneumonia (in 16 cases), sepses (in 9 patients), status epilepticus (in 8 patients). In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP). Mental retardation was significantly more frequent in patients who did not die from SUDEP. SUDEP may be a significant condition associated with mortality in children and adolescents with epilepsy. Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina UNIFESP, EPM SciELO

Approximately 30 to 40 percent of adults with epilepsy treated chronically with vigabatrin develop concentric visual field constrictions. These deficits are generally mild and asymptomatic, but are usually irreversible, so risks and benefits for vigabatrin treatment must be carefully reviewed. Infantile spasms, a particularly severe form of epilepsy, may respond to vigabatrin; however, some infants treated with the drug develop MRI evidence of possible intramyelinic edema in subcortical structures. This article reviews the benefits of vigabatrin treatment, the risks it poses to the retina and the developing brain, as well as possible subgroups of adults and infants with severe epilepsy for whom treatment may, nevertheless, be warranted.

Managing severe epilepsy syndromes of early childhood is challenging as the seizures are typically resistant to treatment and may cause disabling mental and behavioral problems in later life. A comprehensive treatment plan includes pharmacologic, nonpharmacologic, and surgical options. This article reviews clinical studies examining the efficacies of antiepileptic medications in reducing seizure frequency in Dravet syndrome, Doose syndrome, and Lennox-Gastaut syndrome. The benefits of the ketogenic diet for children with these severe epilepsies, together with the advantages of vagus nerve stimulation and corpus callosotomy in those patients with Lennox-Gastaut syndrome, are also discussed. Special treatment considerations for each syndrome are also highlighted to improve the management of patients with these syndromes.

Nine severely mentally retarded patients with severe epilepsy who were living in an institution were studied during a three-year period by a multi-disciplinary team. A seizure rate serum level chart was made for each patient. It served as the basis for monthly discussions in the team about medication changes. Drug plasma concentrations were monitored monthly. Statistical comparisons between seizure frequency on different drug regimens were made by chi 2 test. Withdrawal of all medication was possible in one case and reduction to monotherapy in two cases. In the remainder of the patients a combination of two or three anticonvulsants gave the best clinical effect. We thus found polypharmacotherapy necessary for some severely retarded patients with epilepsy. Our multidisciplinary approach and chart monitoring system has many advantages and is valuable for the medical care and drug treatment of this patient category.

A long-term follow-up study of 89 patients of Lennox-Gastaut syndrome (LGS) disclosed the persistent occurrence of seizures in 68 patients (76.4%) and severe mental defect in 48 (53.9%). An analysis of the correlation between the mental and seizure prognoses confirmed that the persistence of minor seizures could result in mental deterioration. An examination of the evolutional changes in EEG demonstrated that diffuse slow spike-waves characteristic of LGS gradually disappeared, while focal epileptic discharges, especially multifocal spikes, appeared in spite of the persistence of minor seizures. The diagnostic criteria were satisfied in only 31 (47.0%) of 66 patients with the persistence of minor seizures. Patients with multiple independent spike foci and minor seizures were considered to belong to a specific type of epilepsy, namely the severe epilepsy with multiple independent spike foci (the severe epilepsy with MISF). The seizure and mental prognoses were poorer in patients who evolved into the severe epilepsy with MISF than others.

Introduction Mutations in the gene GRIN2A have been reported as an etiology for epilepsy in case of ESES. We here present an unusual presentation in an infant carrying a mutation in GRIN2A, expanding the phenotypic spectrum associated with mutations in this gene. Case report An 8 month-old infant presented with severe development delay and a very extensive range of different electrical and clinical seizures including focal clonic seizures, spasms (generalized or unilateral), stereotyped behaviour, and tonic seizures since the age of 2 months. Seizures were refractory to multiple anti-epileptic drugs. Massive parallel sequencing with a gene panel for epileptic encephalopathies revealed a mutation in GRIN2A, which occurred de novo. In the recent literature, only 2 cases with the same clinical presentation have been reported so far. Conclusion In case of severe epilepsy in infancy, it is important to extend the spectrum of the genes to be studied. Mutations in GRIN2A are not only associated with ESES but must also be explored in case of epileptic encephalopathy with a great diversity of seizures in infancy

Objective Study of progressive epileptic encephalopathy at destructive epilepsy forms in small premature infants. Methods 5-years clinical-paraclinical (brain MRI, 24-hour Holter and video EEG monitoring) examination of 103 children with extremely low birth weight and 108 children with very low birth weight (ELBW and VLBW) with epileptic encephalopathy in the form of behavior and progressive dementia developed due to age-dependent epilepsy form who are primarily resistant to antiepileptic drugs. Results Rate of severe epileptic encephalopathy in children with ELBW and VLBW was 15% and 11% correspondingly at early infantile encephalopathy with suppressive-explosive pattern at EEG (Othahara syndrome); 9% and 6% at severe epilepsy with multiple independent spike focuses (Markand-Blume-Othahara syndrome); 6% and 4% at malignant migrating partial seizures at infancy (MMPSI). At epilepsy onset epileptic encephalopathy developed in 3% and 2% of children with ELBW and VLBW after 1 year of life at Doose syndrome; 5% and 3% at Lennox-Gastaut syndrome; 4% and 2% at hemiconvulsive seizures and hemiplegia syndrome provoked by hyperthermia; 5% and 4% at destructive epileptic encephalopathy in school-aged children caused by hyperthermia (FIRES-syndrome); 3% and 2% at Landau-Kleffner syndrome (acquired epileptic aphasia). Cognitive epileptiform disintegration with epileptic activity at EEG and without epileptic attacks occurred in 5% and 3% of children correspondingly. Often hyperthermia was the marker of life-threatening epileptic status occurrence in small premature infants – 10 to 100 per day. Primarily these epilepsy forms were resistant, rapidly transferred to epileptic encephalopathy. Conclusion Often cerebral pathology in small premature infants causes development of early destructive epileptic encephalopathy. Hyperthermia promotes to febrile-provoked epilepsy development at which infant psychic disorder progresses and dementia increases.

Objective Ring chromosome 20 syndrome (R20) has an almost constant association with refractory epilepsy and intellectual and behavioral disabilities. Though early diagnosis is usually difficult and rarely made, Particular electroclinical patterns have been found to be very helpful for the R20 diagnosis that is usually difficult and rarely early made. Here, we present the clinical, EEG and cytogenetic correlations in three patients with R20. Methods Three patients, aged 17, 13 and 4 years, respectively, were studied by video-EEG monitoring (VEEG) for drug-resistant seizures. Brain MRI was normal; standard EEGs showed anterior epileptiform activity with one-sided predominance, correlating to some ictal clinical features; intellectual and behavioral problems increased with age and disease course. VEEG as a part of presurgical evaluation was considered because of drug-resistant epilepsy. Results All three patients presented an electroclinical pattern consistent with frontal epilepsy. They also had subclinical or “subtle” clinical episodes, both awake and in sleep, corresponding to nonconvulsive status epilepticus (NCSE). The epilepsy started earlier (age 3 years) in the youngest patient with more severe epilepsy. The seizures started later (age 7 and 9 years, respectively) and were rarer in the older patients, who also showed mild cognitive and behavioral disability. Due to the particular electroclinical picture R20 was suspected and cytogenetic analysis was performed. It revealed R20 mosaic karyotype, at 10%, 25% and 40%, respectively. Conclusion The presented cases show again that the diagnosis of R20 syndrome is usually delayed and is based on the very helpful and characteristic for the syndrome electroclinical NCSE pattern and the overall “frontal” seizure appearance. Our cases add further evidence for the genotype-phenotype correlation in the syndrome, since the degree of mosaicism reflects the age of epilepsy onset, the severity and refractoriness of the seizures, and the severity of the associated intellectual and behavioral disabilities.

The cases of a brother and sister with dentato-olivary dysplasia are described. Both had severe developmental delay, severe epilepsy of early onset, evolving hypertonic quadriplegia, and death in early childhood. Postmortem examination of the brain in one child showed a particular form of dentato-olivary dysplasia. These children show many features in common with previously described cases of this condition, but this is the first report of occurrence in sibs.