Infantile Seizures Research Articles

Expect the Unexpected in a Colonoscopy: A Case of Colonic Endometriosis

Endometriosis is defined by the presence and the proliferation of endometrial tissue outside the uterus. Estimate prevalence is nearly 10-15% in women of reproductive age group. Symptoms vary according to location where endometrial tissue is implanted. Intestinal endometriosis can occur in up to 37% of all cases of endometriosis, mainly affecting recto sigmoid part of colon. Our patient is a 32-year-old female with past history of infantile cerebral palsy, seizure disorder and chronic constipation presented to our gastroenterology clinic with abdominal pain. Symptoms have been waxing and waning for years, described as diffuse abdominal pain, cramping in nature and associated with severe constipation. Patient denied any other symptoms, including hematemesis, hematochezia or melena. Patient reported family history of unknown cancer. Physical exam was remarkable for scars from previous cesarean sections. No abdominal tenderness, guarding or rigidity was appreciated. Basic laboratory testing was unremarkable. Colonoscopy visualized a 1 cm sessile polyp (figure 1) in descending colon that was snared, cauterized and retrieved (figure 2). Histology of the polyp revealed benign endometrial glands and stroma, consistent with diagnosis of endometriosis. Patient was started on oral contraceptive medication with dramatic improvement of abdominal pain before patient preferentially stopped it due to weight gain. A follow up colonoscopy for recurrent abdominal pain visualized diminutive polyp in the sigmoid colon that was removed by snare polypectomy. Pathology was consistent with hyperplastic polyp. On outpatient follow up, patient denied any more symptoms of abdominal pain. Endometriosis is a hormone responsive pathological implanting of endometrial tissue outside the uterus. Symptoms of endometriosis vary. Intestinal endometriosis usually manifests as alteration in bowel habits, rectal bleeding and dyschezia. Our patient presented with non-specific abdominal pain that initially responded with oral contraceptive medication. Although patient with diagnosis of endometriosis usually tend to be infertile unless treated, our patient had delivered more than once before she was diagnosed with endometriosis. We present this case so we as gastroenterologist and internists would have low index of suspecion of this rare pathology.Figure: Colonoscopy visualized a 1 cm sessile polyp in the descending colon.Figure: Appearance of bleeding polyp after it was snared and cautarized.

SCN8A mutations in Chinese patients with early onset epileptic encephalopathy and benign infantile seizures

BackgroundSCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. This study aimed to broaden the phenotypic-spectrum of disease related with SCN8A mutations.MethodsTo identify the pathogenic gene of a Chinese family, in which six members suffered from epilepsy, whole-exome sequencing was performed. In addition, target next-generation sequencing (NGS) was performed on 178 sporadic patients, who had epilepsy of unknown etiology within 6 months after birth. A detailed clinical history was obtained.ResultsA heterozygous missense mutation of SCN8A was identified in the Chinese family. Six de novo mutations of SCN8A were detected in 6 sporadic patients with epilepsy. In the family, six members developed seizures within a few years after birth. Five of them had milder clinical performance, that they had normal cognition and developmental milestones, and seizure-free was achieved by mono-therapy. The other one affected member presented with refractory epilepsy and developmental regression. She died from sudden unexpected death in epilepsy (SUDEP) at 17-year-old. Clinical features of six sporadic patients with SCN8A mutations were diverse, ranging from severe epileptic encephalopathy to benign epilepsy with normal cognition. Seizures started at the mean age of 3.9 months (from 2 months to 6 months). Seizure-free was achieved in four of them by mono- or multi-antiepileptic drugs. Five of them demonstrated mild or severe psychomotor retardation, whereas the other one was normal in development and intelligence.ConclusionsOur findings extend the spectrum of SCN8A mutations and the clinical features of patients with SCN8A mutations. The majority of SCN8A mutations were de novo, inherited mutations from the heterozygous parents can also occur. The phenotypic spectrum of SCN8A mutation varied largely. Most affected patients manifested as refractory epilepsy and severe intellectual disability, only a small number of patients presented with milder clinical patterns. Additionally, our study confirmed that the same mutation can lead to different phenotypes.

Absence status epilepticus: Juvenile serine deficiency presenting with severe exacerbation of previously well controlled absence seizures

Objective: Serine biosynthesis defects are associated with congenital microcephaly, infantile seizures and global developmental delay. A juvenile phenotype has been described with later onset absence seizures, mild developmental delay and hyperactivity. This case expands this clinical phenotype. Method: Case report. Results: We report a case of serine deficiency in a male child born to consanguineous parents with a background of global developmental delay, microcephaly and attention deficit hyperactivity disorder. Aged 9 years he developed absence seizures with EEG correlation which were subsequently controlled with sodium valproate. Plasma amino acids at this time were normal apart from slightly reduced serine (78 umol/L; reference range 90–290). He re-presented 1 year later with clustering of absence seizures, which failed to respond to phenobarbitone and prednisolone. Initial EEG at this time was abnormal. A subsequent EEG identified absence status epilepticus which resolved within a week on ethosuximide. MRI brain was normal. Plasma amino acids showed several amino acids below the reference range with a marked decrease in serine concentration (32 μmol/L; reference range 70 – 174). These results prompted a lumbar puncture; CSF serine 10 umol/L (reference range 18–44) consistent with serine deficiency. Conclusion: This case contributes to the juvenile phenotype which should be considered in those with sudden exacerbation of absence seizures. There is speculation in the literature that there might be compensatory mechanisms in place which ensure an adequate serine supply during early development. Our observation of a marked decline in plasma serine levels in association with worsening seizures adds weight to this theory. Plasma amino acids are a first line investigation for children presenting with global developmental delay. While the laboratory recommends fasting samples and quotes fasting reference ranges this is rarely done in clinical practice. This case also reinforces the recommendation to repeat first line investigations when new symptoms present.

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p. Overexpression of PRRT2 strongly impaired the cell viability and promoted cell apoptosis and these anti-tumor effects could be largely reversed by microRNA-30a-5p. Mechanistically, PRRT2 expression was closely correlated genes involved in unfolded protein response (UPR) pathway and introduction of PRRT2 inhibited gene expression in the three branches of UPR, including PERK axis, IRE1 axis and ATF6 axis. Taken together, our findings identify PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention.

Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures

BackgroundVariants in the SCN2A gene that disrupt the encoded neuronal sodium channel NaV1.2 are important risk factors for autism spectrum disorder (ASD), developmental delay, and infantile seizures. Variants observed in infantile seizures are predominantly missense, leading to a gain of function and increased neuronal excitability. How variants associated with ASD affect NaV1.2 function and neuronal excitability are unclear. MethodsWe examined the properties of 11 ASD-associated SCN2A variants in heterologous expression systems using whole-cell voltage-clamp electrophysiology and immunohistochemistry. Resultant data were incorporated into computational models of developing and mature cortical pyramidal cells that express NaV1.2. ResultsIn contrast to gain of function variants that contribute to seizure, we found that all ASD-associated variants dampened or eliminated channel function. Incorporating these electrophysiological results into a compartmental model of developing excitatory neurons demonstrated that all ASD variants, regardless of their mechanism of action, resulted in deficits in neuronal excitability. Corresponding analysis of mature neurons predicted minimal change in neuronal excitability. ConclusionsThis functional characterization thus identifies SCN2A mutation and NaV1.2 dysfunction as the most frequently observed ASD risk factor detectable by exome sequencing and suggests that associated changes in neuronal excitability, particularly in developing neurons, may contribute to ASD etiology.

Holoprosencephaly.

Holoprosencephaly (HPE) is a brain malformation resulting from failure of prosencephalon (the forebrain of the embryo) to divide into two distinct cerebral hemispheres. It is the most common brain malformation with an incidence of 1:250 during embryogenesis and 1:16,000 among live births.1 HPE has four subtypes: alobar holoprosencephaly, semilobar holoprosencephaly, lobar holoprosencephaly, and a middle interhemispheric fusion variant (syntelencephaly).2 Alobar holoprosencephaly is the most severe form, and as the name implies, there is no separation of the cerebral hemispheres. In semilobar holoprosencephaly, the cerebral hemispheres separate posteriorly, however are fused anteriorly. Lobar holoprosencephaly is characterized by almost complete separation of the cerebral hemispheres. Syntelencephaly results from failure of separation of posterior frontal and parietal lobes. Since both the forebrain and midface arise from the prechordal mesoderm, majority of patients with HPE also manifest craniofacial abnormalities such as microcephaly, microphthalmia, cleft lip and palate, flat nose, absent nasal bridge, and cyclopia. Multiple genetic and environmental factors are involved in the pathogenesis of HPE. Maternal diabetes mellitus is a well-known risk factor.3 Exposure to retinoic acid, diphenylhydantoin, aspirin, misoprostol, methotrexate, cholesterol-lowering agents and alcohol during pregnancy have been associated with HPE.4-9 Other environmental factors include TORCH infections during early pregnancy.1 Genetic abnormalities associated with HPE include trisomy 13, trisomy 18, and triploidy.10,11 Syndromic association of HPE includes, but is not limited to Smith-Lemli-Opitz syndrome, Genoa syndrome, Meckel-Gruber syndrome, Lambotte syndrome, Pallister-Hall syndrome, Steinfeld syndrome, caudal dysgenesis and Aicardi syndrome.12-19 Mutations in SHH, ZIC2, SIX3, and TGIF genes have been implicated in non-syndrome associated HPE.20 Central nervous system abnormalities are identified on routine prenatal imaging and etiologic diagnosis can be done by prenatal or postnatal karyotype and testing for known gene mutations. Sub classification is based on MRI findings or autopsy findings if one is requested. Infants who survive have a myriad of clinical presentation. Some of the common physical findings include spasticity, hypotonia, choreoathetosis and dystonia. Infantile spasms and seizures are common. Feeding difficulties, gastroesophageal reflux, and malnutrition occur commonly. Other problems include temperature dysregulation and respiratory tract infections. Death usually occurs due to brainstem dysfunction or manifestation and complications of associated syndromes. Treatment is mainly supportive. Prognosis depends upon subtype and associated syndrome.21 Those with alobar type die within days of birth.22 Around 50% with the isolated semilobar form survive beyond 1 year.22 Recurrence risk in subsequent pregnancies is high in established cases of parental carrier state and is low if the genetic abnormalities occur de novo.23,24 Figure 1 refers to gross appearance of brain in a 7-hour old female infant born to a 41-year old G1 P0 lady with limited prenatal care, past medical history of diabetes mellitus type 2 and alcohol use during first trimester of the pregnancy. On prenatal ultrasonography, the fetus had hydrocephalous and suboptimal development of cerebral and cerebellar hemispheres. Karyotyping showed normal signal pattern for chromosomes 13, 18 and 21. Figure 1Macroscopic appearance of the brain depicting complex gyration without classical sulcal landmarks (A and B) and focal polymicrogyria (A), flattened cerebral hemispheres surrounding a single cystically dilated ventricle (C), fused right and left basal ganglia and diencephalic structures (C), unremarkable midbrain, cerebellum and medulla (D).: Pictures courtesy Dr. Ameer Hamza Autopsy findings included fetal macrosomia; craniofacial dysmorphogenesis to include hypertelorism, low set ears, cleft palate, absent nasal bridge and bossing of forehead; biventricular cardiomegaly, muscular ventricular septal defect and imperforated anus. The detailed brain examination revealed flattened frontal, temporal and occipital lobes with a rudimentary C-shaped interhemispheric fissure. The surface of the cystically dilated forebrain displayed complex gyration; however, without classical sulcal landmarks (Figure 1A and 1B). There were focal polymicrogyria patches (Figure 1A). Cortical pallium surrounded a single large cystic cavity (telencephalic vesicle) in which lateral ventricles and ventricular horns could not be discerned (Figure 1 C). At the base of cystically dilated cerebrum, there were fused right and left basal ganglia and diencephalic structures (Figure 1C). There was no corpus callosum. The midbrain, cerebellum and medulla appeared unremarkable (Figure 1D).

Effects of various antiepileptic drugs in benign infantile seizures with mild gastroenteritis

Effects of various antiepileptic drugs in benign infantile seizures with mild gastroenteritis

Clinical and genetic characteristics and diagnosis of hereditary variants of neonatal epilepsy

One of the most common neurological symptoms in children of the first year of life is seizures, the etiology of which is manifold. Investigations in recent years have shown that a significant number of infantile seizures are hereditary in nature. The review identifies the main groups of hereditary diseases and syndromes, in whose symptom complex convulsions are observed, outlines the main features of their clinical manifestations and methods of diagnosis. Correct and timely diagnosis of hereditary pathology helps not only to determine the nature of the course of the disease and the effectiveness of the use of various antiepileptic drugs, but also to significantly improve the effectiveness of genetic counseling of burdened families and to prevent the occurrence of recurrent cases оf disease.

Proline-rich Transmembrane Protein 2 Gene Mutation in a Sporadic Paroxysmal Kinesigenic Dyskinesia.

Dear Sir, A 12-year-old boy presented with paroxysmal events for the last 3 months. He had no adverse perinatal events and was developmentally normal. He experienced brief episodes of abnormal posturing of upper and lower limbs, usually on the right side. These episodes were triggered by sudden movements like sudden rise from sitting or lying position and sometimes by startle. There was absent premonitory sensation, preserved consciousness during the events, and no “postictal” drowsiness. The frequency was variable from 3 to 5 episodes/day to once in 2–3 days. There were no other body movements, myoclonus, dance-like movements, neuroregression, and hearing or vision impairment. There was no history of headaches or seizures in infancy. The family history was unremarkable for any seizures, movement disorder, or migraine. Examination was normal. Magnetic resonance imaging of his brain and his “interictal” electroencephalogram (EEG) were normal. He had poor response to oral valproate, started by a local practitioner. A possibility of paroxysmal kinesigenic dyskinesia (PKD) was considered in view of sudden movement/startle-induced paroxysmal dyskinesia. He had complete resolution of symptoms on oxcarbazepine. By direct sequencing of the entire coding region and exon-intron boundaries of the proline-rich transmembrane protein 2 (PRRT2) gene, the heterozygous mutation, c. 649dupC p. Arg217Profs*8 mutation, was identified in the patient. This mutation has been previously reported in patients with PKD from several parts of the world. PKD or DYT10, a rare movement disorder, may be sporadic or familial (autosomal dominant with incomplete penetrance). PRRT2 is the major gene responsible for PKD. The encoded protein, PRRT2, has presynaptic localization and appears to be involved in exocytosis and neurotransmitter release. The classical PKD phenotype is characterized by onset in childhood or adolescence; frequent brief attacks of dystonia, choreoathetosis, and/or ballismus with preserved consciousness; precipitation by sudden voluntary movements or startle; frequent aura; normal interictal neurological examination; and excellent response to anticonvulsants. The most effective drugs in PKD are voltage-gated sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin, lacosamide). The common misdiagnosis is epilepsy, but preserved consciousness during the attacks, absence of postictal state, and absence of “ictal” EEG abnormalities favor PKD. The spectrum of PRRT2-associated diseases also includes benign familial infantile seizures, infantile convulsions with choreoathetosis, episodic ataxia, hemiplegic migraine, and benign paroxysmal torticollis of infancy.

Case report: Homozygous PRRT2 mutation in ICCA Egyptian family with reduced penetrance

Infantile convulsions and choreoathetosis (ICCA) syndrome is a rare neurological genetic disorder inherited in an autosomal dominant manner with incomplete penetrance. It is characterized by the association of benign infantile seizures (BIS) at age 3–12months with paroxysmal kinesigenic choreoathetosis (PKC) later in life. Mutations in proline-rich transmembrane protein 2 (PRRT2) gene have been recently identified as the main cause of ICCA and other related disorders. Few ICCA cases with homozygous mutations have been reported, where they exhibited more severe clinical phenotype including intellectual disability. Here we report two Egyptian siblings with ICCA whose molecular analysis of PRRT2 revealed homozygous c.649dupC mutation. However, they have not developed any physical or cognitive disabilities. Moreover, their parents, who found to be heterozygous for the mutation, did not display any of the disease phenotype during their infancy and childhood. Low penetrance and variable expressivity of ICCA could be attributed to specific genetic modifiers and/or environmental factors that require further investigations to be identified.

Impact of KCNQ2 mutations in Bulgarian patients with electroclinical syndromes with onset in the first year of life

ABSTRACTMutations in KCNQ2 are associated with a range of electroclinical syndromes with dominant inheritance that are differentiated by the age at onset of the seizures and are associated with good prognosis. These are benign familial neonatal seizures (BFNS), benign familial neonatal--infantile seizures (BFNIS) and benign familial infantile seizures. Herein, we report the results of a systematic screening of KCNQ2 in 27 unrelated Bulgarian patients with compatible clinical diagnoses. Two pathogenic point mutations were identified: a novel splice-site c.1526-2A>G variation causing BFNS and a missense c.998G>A alteration in a patient with BFNIS, who subsequently developed benign epilepsy with centro-temporal spikes. Additionally, multiplex ligation-dependent probe amplification analysis and array comparative genomic hybridization assay detected a de novo deletion on 20q13.3 encompassing 0.41 Mb genomic region and covering 11 genes, including KCNQ2 and CHRNA4. This large-scale rearrangement was found in a patient with typical BFNS and no additional developmental abnormalities. Overall, KCNQ2 genetic defects were found in 11% of the patients in our cohort. These findings enrich the genetic epidemiology and mutation spectrum of KCNQ2 and allow adequate genetic counselling in the affected families.

Rapid and safe response to low-dose carbamazepine in neonatal epilepsy.

To evaluate treatment responses in benign familial neonatal epilepsy (BFNE). We recruited patients with BFNE through a multicenter international collaboration and reviewed electroclinical and genetic details, and treatment response. All patients were tested at minimum for mutations/deletions in the KCNQ2, KCNQ3, and SCN2A genes. Nineteen patients were included in this study. A family history of neonatal seizures was positive in 16 patients, and one additional patient had a family history of infantile seizures. Mutations or deletions of KCNQ2 were found in 14, and of KCNQ3 in 2, of the 19 patients. In all patients, seizures began at 2-5 days of life and occurred multiple times per day. Four patients developed status epilepticus. Seizures were focal, alternating between hemispheres, and characterized by asymmetric tonic posturing associated with apnea and desaturation, followed by unilateral or bilateral asynchronous clonic jerking. Twelve of 19 patients were treated with multiple medications prior to seizure cessation. Seventeen of (88%) 19 patients were seizure-free within hours of receiving oral carbamazepine (CBZ) or oxcarbazepine (OXC). Earlier initiation of CBZ was associated with shorter hospitalization (p < 0.01). No side effects of CBZ were reported. All patients had normal development and remain seizure-free at a mean follow-up period of 7.8 years (6 months-16 years). This study provides evidence that CBZ is safe and rapidly effective in neonates with BFNE, even in status epilepticus. We propose that CBZ should be the drug of choice in benign familial neonatal seizures.

Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes. The 7 family members had episodic ataxia (5), self-limited infantile seizures (5), evolving to genetic generalized epilepsy (4), focal seizures (2), and EE (1). They had a segregating novel mutation in the shaker type voltage-gated potassium channel KCNA2 (CCDS_827.1: c.765_773del; p.255_257del). A rare missense SCN2A (rs200884216) variant was also found in 2 affected siblings and their unaffected mother. The p.255_257del mutation caused dominant negative loss of channel function. Molecular modeling predicted repositioning of critical arginine residues in the voltage-sensing domain. KCNA2 sequencing revealed 1 de novo mutation (CCDS_827.1: c.890G>A; p.Arg297Gln) in a girl with EE, ataxia, and tremor. A KCNA2 mutation caused dominantly inherited episodic ataxia, mild infantile-onset seizures, and later generalized and focal epilepsies in the setting of normal intellect. This observation expands the KCNA2 phenotypic spectrum from EE often associated with chronic ataxia, reflecting the marked variation in severity observed in many ion channel disorders.

A.05 Ten years of experience with lamotrigine for the treatment of neonatal and infantile seizures

Background: The therapeutic value of second-generation anticonvulsants such as lamotrigine has not been clearly established in neonates and infants with seizures. To address this issue, we assessed the efficacy of lamotrigine for treating neonatal and infantile seizures, detailed the dosing regimens used, and described its tolerability and safety profile. Methods: This retrospective study included patients (age 0-12 months) diagnosed with seizures and treated with lamotrigine, as monotherapy or adjunctive therapy, by pediatric neurologists at Centre mère-enfant Soleil du CHUQ from 2004 to 2014. The frequency of seizures and EEG patterns were compared before and after introduction of lamotrigine during the first months of life. Data on initial and maintenance doses, rate and magnitude of dosing increments, and adverse effects were collected. Results: Treatment with lamotrigine was initiated in 32 neonates and 13 infants. At first follow-up (mean duration 3 months), 76 % (n = 34) showed a significant (≥50%) reduction of seizures and 64% (n= 29) improvement of EEG pattern compared to baseline. The efficacy in monotherapy and adjunctive therapy was similar. A single case of cutaneous hypersensitivity reaction requiring cessation of treatment was reported. Conclusions: This study suggests that lamotrigine is a useful, safe, and well-tolerated anticonvulsant alternative for the treatment of seizures in neonates and infants.

Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat

Long-term stress during pregnancy causes neurologic deficits to offspring with altered gamma-aminobutyric acid (GABA) system in the brain. However, it is not clear how prenatal stress affects the maturing GABAergic interneurons and the resulting abnormalities in infantile seizures. Here, we showed that prenatal stress alters the maturation of GABA inhibitory system using a seizure model induced by prenatal stress. Prenatal stress with betamethasone or acute immobilization stress (AIS) on gestational day 15 increased the seizure susceptibility to N-methyl-d-aspartate-triggered spasms on postnatal day 15. The expression of GABA was lower in the prenatally stressed group, which compromise the decrease of glutamate decarboxylase 67-immunopositive cells. Prenatal stress markedly decreased the expression of K+/Cl− co-transporter (KCC2) in the cortex. GABA induced membrane depolarization demonstrated prenatal stress models had significant higher membrane depolarization compared to control. GABA increased KCC2 expression in cultured cortex-containing slices. Taken together, our results showed that prenatal stress with betamethasone or AIS altered the maturation of GABAergic progenitors and resulted in the lack of GABA input, which in turn, decreased KCC2 expression and lowered seizure threshold. We conclude that delayed GABA excitatory/inhibitory shift would render the cortical neuronal circuit more susceptible to excitatory input in prenatal stress induced seizure.

Assessment of the association between Apgar scores and seizures in infants less than 1 year old

PurposeThe study aimed to assess the association between Apgar scores at 1 and 5min after birth and seizures in infants less than 1 year old. MethodsWe conducted a retrospective, observational, hospital-based study by utilising medical records from the Chung-Ang University Hospital admissions from January 2006 to May 2015 in order to identify infants less than 1 year old who had a history of seizures. Using electronic medical records, infants who were diagnosed with infantile seizures at the Chung-Ang University Hospital from January 2006 to May 2015 were included in the seizure group (n=93), and a control group consisting of 296 age-matched cases without a history of seizures was selected from a group of infants born at Chung-Ang University Hospital during the same study period. ResultsWe found that Apgar scores were significant risk factors for infantile seizures. Apgar scores differed depending on gestational age and birth weight. We found strong associations between Apgar scores and infantile seizures in the full-term and the normal-birth weight groups (bodyweight ≥2.5kg), regardless of delivery mode. The Apgar scores were inversely correlated with the EEG class, and only the 1-min Apgar scores were correlated with MRI findings. ConclusionLow Apgar scores are significant perinatal risk factors for infantile seizures, especially in full-term and normal-birth weight infants, and have a strong negative linear relationship with EEG and brain MRI results in the seizure group.

Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling.

It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS.

Abstract 17733: Some Epilepsy Patients Die Suddenly Without a Preceding Seizure Episode: What are the Mechanisms?

Introduction: Epilepsy is associated with a significantly increased risk of sudden cardiac arrest (SCA), and we have previously reported that this devastating outcome does not always require a preceding seizure. Based on the hypothesis that the pathophysiology of SCA for epilepsy patients may be heterogeneous, we compared the clinical profile of epilepsy patients with and without seizure activity prior to SCA. Methods: Subjects of all ages with SCA occurring in the setting of prior documented epilepsy were identified from a large, ongoing, population-based study of SCA in the Northwest US (community pop. approx. 1 million). We explored the relationships between baseline demographics, lifetime medical history and SCA circumstances among those who had a witnessed seizure within 24 hours of the SCA event (seizure-dependent) and those who did not (seizure-independent). Data were obtained from multiple sources (first responders, medical practitioners and medical examiner) between 2002 and 2015. Patients with terminal illnesses and non-cardiac causes of arrest were excluded, as well as those with infantile febrile seizures or alcoholic withdrawal seizures. Results: Among 142 subjects with SCA and seizure disorder, 64 (45.1%) were witnessed during the event and, among these, 26 (40.6%) were seizure-dependent while 38 (59.4%) were seizure-independent. The seizure-independent subjects were significantly older (mean age 61.9 years; 95% CI, 43.1 to 80.7 years; vs 47.6 years; 95% CI, 27.0 to 68.2 years; p=0.006). However the younger seizure-dependent group had higher prevalence of cardiac arrest due to pulseless electrical activity (PEA) or asystole (81.0% vs 58.3%; p=0.081). There was no notable difference in the burden of comorbidities (Charlson index 1.92 vs 2.37; p=0.941), periarrest characteristics, ECG and echo parameters. Conclusions: Seizure-independent SCA occurs at an older age, supporting the hypothesis that over time, neuro-cardiac remodeling may lead to cardiac arrest in the absence of hypoxia. In younger, seizure-dependent patients hypoxia may be a pre-requisite, but both hypotheses warrant further detailed investigation.

Profile, recommendation criteria, and outcome of gastrostomy tube insertions in a pediatric teaching hospital

Objective: To describe the profile of patients undergoing a gastrostomy, the recommendations and outcome of this insertion in a Pediatric Teaching Hospital. Method: This was a retrospective, quantitative, and descriptive study that researched the records of patients who underwent a gastrostomy between January 2010 and December 2012. Results: The diseases and conditions most frequent were chronic infantile encephalopathy (77.5%), pneumonia (67.5%), seizures (57.5%), and malnutrition (42.5%). Although most patients presented a history of dysphagia (62.5%), oral feeding was observed most frequently as the most common form of nutrition, before the gastrostomy insertion (42.5%), followed by nasoenteric tube (40%). The introduction of nutrition by gastrostomy was successful and occurred an average of 2.82 (± 1.19) days after insertion. Six months after their gastrostomy, 80% of patients continued feeding only through this access tube and only 2.5% had removed the gastrostomy; 45% of the participants had gastrostomy complications, with extravasation of gastric material (15%) and local inflammation (15%) being the most frequent. Conclusion: The profile of patients undergoing gastrostomy is mostly of individuals with neurological and respiratory diseases, without respiratory support, of the male gender, and feeding by oral cavity or nasoenteric tube for a prolonged period. The main recommendation criteria were dysphagia and neurological diseases. Regarding the outcome, the introduction of nutrition by gastrostomy was successful; most individuals remained with this long-term nutritional support and the most common complications were gastric material extravasation and local inflammations

Glut1 deficiency syndrome: Absence epilepsy and La Soupe du Jour

For some time, paediatric neurologists have recognised glucose transporter type 1 (GluT1) deficiency syndrome as a cause of intractable infantile seizures, microcephaly, developmental delay and hypoglycorrhachia in the presence of...