Older Patients May Have More Frequent Seizures among Children Diagnosed as Benign Convulsions with Mild Gastroenteritis.

PURPOSE: Benign convulsions with mild gastroenteritis (CwG) is a condition that does not usually require treatment. However, when the patient experiences multiple seizures or prolonged seizures, anticonvulsant treatment may be required. We investigated this study to identify the factors that may influence on the number or duration of seizures at CwG. METHODS: We retrospectively analyzed the medical records of CwG patients who were admitted to the Department of Pediatrics at Sanggye Paik Hospital. RESULTS: A total of 105 children with CwG were enrolled. The mean age was 19.59 ± 7.09 months. The mean duration of seizure was 2.79 ± 5.51 minutes and mean number of seizure was 2.33 ± 1.70. Sixty-nine children had seizures less than twice, whereas 36 experienced three times or more. These groups differed significantly according to age in CwG (18.16 ± 7.08, vs. 22.33 ± 6.34 months, p < 0.05). When patients were divided into two groups based on age in CwG using a cut-off of 20 months, we found significant differences in seizure number (1.91 ± 1.27 vs. 3.11 ± 2.10, p < 0.05). There was also a positive correlation between patient age and frequency of seizures (R = 0.316, p = 0.001). Patients who received anticonvulsants were older (17.60 ± 6.87 vs. 22.04 ± 6.63 months, p < 0.05) and had more frequent (1.59 ± 1.37 vs. 3.26 ± 1.63, p < 0.05) and longer seizures (1.76 ± 2.75 vs. 4.07 ± 7.49 minutes, p < 0.05). CONCLUSION: As the number of seizure in CwG was associated with age, treatment in older children may be required in acute stage.

Human Herpesvirus-6 may be Neurologically Injurious in Some Immunocompetent Children.

PURPOSE: Human herpesvirus 6 (HHV-6) can infect the central nervous system in immunocompromised individuals. Less is known, however, about HHV-6 infection in immunocompetent patients. This study evaluated the neurologic features and prognosis of HHV-6 infection in immunocompetent patients. METHODS: The medical records of patients aged 1 month to 18 years who underwent cerebrospinal fluid examinations and were tested for 6 viruses, including HHV-6, by multiplex polymerase chain reaction were evaluated retrospectively. RESULTS: During the study period, 252 children were included. None had underlying disease and all were immunocompetent. Their mean age at diagnosis was 40.98 ± 47.65 months. Of these 252 patients, 144 (57.1%) were diagnosed with meningitis, 84 (33.3%) with febrile seizure not induced by meningitis, and 24 (9.5%) with encephalitis. Of the 9 patients positive for HHV-6, 3 (33.3%) had encephalitis, 3 (33.3%) had meningitis, 1 (11.1%) had complex febrile seizure, and the other 2 patients had fever alone. Outcomes were worse in the seizure group (Fisher exact test, P = .048), especially in patients with status epilepticus (Fisher exact test, P = .012), than in the other groups. Encephalitis patients with and without HHV-6 differed significantly in age (24.0 ± 10.8 vs 63.4 ± 47.7 months, t-test P < .05), with status epilepticus being more frequent in those with HHV-6 (Fisher exact test, P = .010). All 3 encephalitis patients positive for HHV-6 had neurologic sequelae; 2 who had mild sequelae were treated with antiviral agents and intravenous immunoglobulin. CONCLUSIONS: HHV-6 may not be completely benign in immunocompetent children. It can be associated with encephalitis and poor prognosis.

Evaluation of hematologic profile may be needed for patients treated with oxcarbazepine.

PURPOSE: The major side effects of treatment with oxcarbazepine (OXC) are skin rash and hyponatremia. Hematologic side effects are reported rarely. The aim of this study was to investigate the rate and types of the hematologic side effects of OXC. METHODS: The medical records of 184 patients diagnosed with epilepsy or movement disorder and on OXC monotherapy, at the Department of Pediatrics of Inje University Sanggye Paik Hospital from July 2001 to July 2018, were retrospectively reviewed. RESULTS: Of the 184 patients, 10 (5.4%) developed leukopenia in addition to pancytopenia and 2 (1.0%) developed pancytopenia. Leukopenia developed in 11 days to 14 years after OXC administration and was more frequent in males than in females (male vs. female, 9 vs. 1; Fisher exact test, P<0.05). Of the eight patients with leukopenia alone, 7 continued OXC treatment; 6 improved without intervention; 1 was lost to follow-up; and 1 received a reduced OXC dose, who improved after intervention. Pancytopenia developed within 2 months of initiation of OXC treatment. Both patients initially continued OXC. One improved within 1 month and continued treatment with OXC, but the other showed progression of the side effect, leading to the discontinuation of OXC and subsequent improvement within 1 month. There were no significant differences in the ages of the patients, OXC dose, and duration of OXC treatment between patients with and without these side effects of OXC (P >0.05, t -test). CONCLUSION: OXC-induced leukopenia is not rare and may result in pancytopenia. Patients being treated with OXC should be regularly monitored for abnormal complete blood count profiles.

Factors associated with electroencephalographic and clinical remission of benign childhood epilepsy with centrotemporal spikes.

PURPOSE: Benign childhood epilepsy with centrotemporal spikes (BECTS) is strongly related to age, both to age at the time of seizure onset and to age at remission. However, the age of remission varies. The present study analyzed factors associated with remission of BECTS. METHODS: Sixty-nine children with BECTS were retrospectively analyzed. Thirty-eight (55.1%) were boys and 31 (44.9%) were girls. Mean age at seizure onset was 86.36 ±â€¯24.55 months (range: 41-151 months). RESULTS: The mean age at the time of EEG improvement or remission was 138.31 ±â€¯19.71 months. Of the 69 patients, 36 (52.2%) exhibited electroencephalography (EEG) improvement or remission before age 11.5 years, whereas 33 (47.8%) showed later improvement or remission. The two groups differed significantly in age at seizure onset. When patients were divided into groups using an age cutoff for last seizure of 9 years, the two groups differed significantly in age at seizure onset. CONCLUSIONS: The most important predictor of early BECTS remission is age at seizure onset.

A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years.

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.

Short-Term Outcome of Intravenous Methylprednisolone Pulse Therapy in Patients With Infantile Spasms.

BACKGROUND: Many studies advocate hormonal treatments including high-dose oral prednisolone as an effective treatment for epileptic spasms. However, little is known about the effects of intravenous methylprednisolone pulse therapy on infantile spasms. We investigated the short-term response to intravenous methylprednisolone pulse therapy for the treatment of infantile spasms. METHODS: Patients with newly diagnosed infantile spasms and hypsarrhythmia on electroencephalography (EEG) at two tertiary centers in Korea were included. Patients received intravenous infusions of 30 mg/kg/day methylprednisolone for three days with tapering doses of oral prednisolone for two to four weeks for the treatment of infantile spasms. Response to methylprednisolone pulse therapy was evaluated by seizure frequency and follow-up EEG within three weeks. RESULTS: Fourteen patients were sudied. The mean age at the onset of spasms was 7.0 months (range, 2.0 to 11.0 months). Etiological factors included structural abnormalities (N = 11), chromosomal anomaly (N = 1), and unknown (N = 2). Nine of 14 participants (64.3%) demonstrated complete freedom from spasm and resolution of hypsarrhythmia on EEG within 3 weeks; however, only five of nine responders (55.5%) remained free of spasms after the discontinuation of oral steroids. Adverse effects, including irritability or infection, were observed in four patients but were tolerable in all. CONCLUSIONS: Short-term methylprednisolone pulse therapy for the treatment of infantile spasms or hypsarrhythmia demonstrated rapid improvement in EEG and cessation of spasms without serious adverse effects. Further studies are needed to determine the long-term effects of spasm control.

A 6-Month-Old Girl with Incontinentia Pigmenti Presenting as Status Epilepticus.

Incontinentia pigmenti (IP) is an uncommon neurocutaneous syndrome. Its initial diagnosis is based primarily on characteristic papulovesicular skin lesions and early-onset neonatal seizures. In contrast to typical early neurologic manifestations, we encountered a normally developed 6-month-old female patient with hyperpigmented whorls on her body. Following respiratory syncytial virus infection and fever, the patient exhibited status epilepticus. Brain magnetic resonance imaging studies of the patient were compatible with the findings of acute encephalopathy in IP. Genetic analysis showed an 11.7 kb deletion within the gene encoding inhibitor of kappa-B kinase gamma. The patient was treated with anticonvulsants and subsequently reached expected developmental milestones after discharge. These findings indicate that when a patient presents with status epilepticus, meticulous examination for skin lesions should be performed to determine whether the patient has a neurocutaneous syndrome, such as IP.

An interictal EEG can predict the outcome of vagus nerve stimulation therapy for children with intractable epilepsy.

PURPOSE: This study aimed to evaluate the long-term efficacy of vagus nerve stimulation (VNS) in children and adolescents with intractable epilepsy and identify predictive factors for responsiveness to VNS. METHODS: Medical records of pediatric patients who underwent VNS implantation at two Korean tertiary centers were reviewed. At 0.5, 1, 3, and 5 years post-VNS implantation, the frequency of the most disabling seizures in each patient was assessed. Responders were defined as showing an overall 50 % reduction from baseline seizure frequency during follow-up. The clinical characteristics of responders and non-responders were compared. RESULTS: Among 58 patients, approximately half (29/58) were responders. The mean age at implantation was 10.9 years (range, 2.7-20.9) and the mean follow-up duration after VNS implantation was 8.4 years (range, 1-15.5). At 0.5, 1, 3, and 5 years after implantation, 43.1, 50.0, 56.9, and 58.1 % of patients exhibited ≥50 % seizure frequency reduction disabling seizures. The patients with focal or multifocal epileptiform discharges were more likely to be responders than those with generalized epileptiform activities by video or conventional EEG at the time of VNS implantation (Pearson's and χ 2 test, p = 0.001). No other clinical variables were found to be associated with seizure outcomes. Wound infections caused VNS removal in two cases. All other adverse events, including cough and hoarseness, were tolerable. CONCLUSION: VNS is a well-tolerated and effective adjuvant therapy in pediatric patients with intractable epilepsy. Notably, patients with focal epileptiform discharges alone rather than those with generalized epileptiform discharges maybe better candidates for VNS.

Paroxysmal kinesigenic dyskinesia in a patient with a PRRT2 mutation and centrotemporal spike discharges on electroencephalogram: case report of a 10-year-old girl.

Coexistence of paroxysmal kinesigenic dyskinesia (PKD) with benign infantile convulsion (BIC) and centrotemporal spikes (CTS) is very rare. A 10-year-old girl presented with a 3-year history of frequent attacks of staggering while laughing and of suddenly collapsing while walking. Interictal electroencephalogram (EEG) revealed bilateral CTS, but no changes in EEG were observed during movement. The patient's medical history showed afebrile seizures 6 months after birth, while the family history showed that the patient's mother and relatives on the mother's side had similar dyskinesia. Genetic testing demonstrated that the patient had a heterozygous mutation, c.649_650insC, in the PRRT2 gene. To our knowledge, this constitutes only the second report of a patient with PKD, BIC, CTS, and a PRRT2 mutation.

Prognostic factors of neurological outcomes in late-preterm and term infants with perinatal asphyxia.

PURPOSE: This study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia. METHODS: All late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2 years were included in this retrospective study. Abnormal neurological outcomes were defined as cerebral palsy, developmental delay and epilepsy. RESULTS: Of the 114 infants with perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10 died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%), 13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were significantly more frequent in infants with later onset seizure, clinical seizure, poor electroencephalography (EEG) background activity, lower Apgar score at 1 and 5 minutes and abnormal brain imaging (P<0.05). Infants with and without epilepsy showed significant differences in EEG background activity, clinical and electrographic seizures on EEG, Apgar score at 5 minutes and brain imaging findings. CONCLUSION: We should apply with long-term video EEG or amplitude integrated EEG in order to detect and management subtle clinical or electrographic seizures in neonates with perinatal asphyxia. Also, long-term, prospective studies with large number of patients are needed to evaluate more exact prognostic factors in neonates with perinatal asphyxia.

The relationship between primary headache and constipation in children and adolescents.

PURPOSE: Many patients presenting with headache also complain of constipation; the relationship between these two symptoms has not been explored in detail. The aim of this study was to investigate the association between primary headache and constipation. METHODS: This retrospective study included all children who attended the Inje University Sanggye Paik Hospital complaining of headache, and who had been followed up for at least 100 days. Patients were divided into 2 groups: group A, in whom the headache improved after treatment for constipation, and group B, in whom headache was not associated with constipation. RESULTS: Of the 96 patients with primary headache, 24 (25.0%) also had constipation (group A). All 24 received treatment for constipation. Follow-up revealed an improvement in both headache and constipation in all patients. Group B contained the remaining 72 children. Comparison of groups A and B indicated a significant difference in sex ratio (P=0.009, chi-square test). Patients with probable tension-type headache were more likely to be in Group A (P=0.006, chi-square test). CONCLUSION: Resolution of constipation improves headache in many patients diagnosed with primary headache, especially those with probable tension-type headache. We suggest that either constipation plays a key role in triggering headache, or that both constipation and headache share a common pathophysiology.

Maternal immune activation promotes hippocampal kindling epileptogenesis in mice.

OBJECTIVE: Maternal immune activation (MIA) triggered by infections has been identified as a cause of autism in offspring. Considering the involvement of perturbations in innate immunity in epilepsy, we examined whether MIA represents a risk factor for epilepsy as well. The role of specific MIA components interleukin (IL)-6 and IL-1ß was also addressed. METHODS: MIA was induced in C57BL/6 mice by polyinosinic-polycytidylic acid (PIC) injected during embryonic days 12 to 16. Beginning from postnatal day 40, the propensity of the offspring to epilepsy was examined using hippocampal kindling; autismlike behavior was studied using the sociability test. The involvement of IL-6 and IL-1ß in PIC-induced effects was studied by the coadministration of the cytokine antibodies with PIC, and by delivering recombinant cytokines in lieu of PIC. RESULTS: The offspring of PIC-exposed mice exhibited increased hippocampal excitability, accelerated kindling rate, prolonged increase of seizure susceptibility after kindling, and diminished sociability. Epileptic impairments were abolished by antibodies to IL-6 or IL-1ß. Neither of the recombinant cytokines alone increased the propensity to seizures; however, when combined, they produced effects similar to those induced by PIC. PIC-induced behavioral deficits were abolished by IL-6 antibodies and were mimicked by recombinant IL-6; IL-1ß was not involved. INTERPRETATION: In addition to confirming the previously established critical role of IL-6 in the development of autismlike behavior following MIA, the present study shows that concurrent involvement of IL-6 and IL-1ß is required for priming the offspring for epilepsy. These data shed light on mechanisms of comorbidity between autism and epilepsy.

Human parechovirus-3 infection in children, South Korea.

BACKGROUND: Human parechoviruses (HPeVs) have recently been recognized as important viral pathogens causing sepsis-like illness and meningitis in children, but the data on these infections in Korea is limited. Klassevirus is emerging as a novel etiologic agent of acute gastroenteritis, but its role in meningitis remains unclear. OBJECTIVES: To understand the epidemiology of HPeVs and klassevirus in sepsis-like illness and meningitis through the detection and typing of the virus in cerebrospinal fluid (CSF) samples. STUDY DESIGN: One hundred and eighty-three CSF samples collected from 183 patients ranging in the age group 1 day to 15 years were tested by using a RT-PCR assay for HPeV, EV and klassevirus. Amplification products of the VP3/VP1 and 3D region of the HPeV, and VP1 region of the EV were sequenced to identify the type. RESULTS: A total of 12 HPeV positive samples (6.5%) were detected from 183 CSF samples and all the samples were typed as HPeV-3. EVs were detected in 39 patients (21.3%) in which echovirus 25 and CVA6 were frequently detected, but mixed infection of HPeV-3 and EV was not observed. Klassevirus was not detected in the study population. Most of the HPeV-3 positive patients were under 3 months of age. HPeV-3 infection was detected mostly in the summer season. The VP3/VP1 gene of the 12 Korean strains clustered most closely to the Japan strain (AB759192) and the 3D gene of the Korean strains also clustered to the Japan strain, which showed no evidence of recombination. CONCLUSIONS: To our knowledge, this is the first report on the detection of HPeV-3 from CSF samples in Korea, which suggests the necessity of routine screening for this virus in young infants with sepsis-like illness and meningitis.

Magnetic resonance imaging and spectroscopic analysis in 5 cases of Pelizaeus-Merzbacher disease: metabolic abnormalities as diagnostic tools.

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.

A multicenter trial of oxcarbazepine oral suspension monotherapy in children newly diagnosed with partial seizures: a clinical and cognitive evaluation.

PURPOSE: We conducted a prospective, multicenter, open label trial to evaluate the effectiveness of oxcarbazepine (OXC) oral suspension as monotherapy for children newly diagnosed with partial seizures. METHODS: This trial included a two- to eight-week titration and stabilization period to achieve effective target doses and a 24-week maintenance phase. The primary outcome measure was the seizure-free rate over six months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase. The effectiveness of OXC was compared in intellectually normal versus intellectually impaired children (intelligence quotient <70). RESULTS: We enrolled 171 patients and analyzed 168 as the per-protocol (PP) group (3 patients had protocol violations). The mean age of the PP group was 8.4±2.7 years. The maintenance dose of OXC was 24.9±8.0mg/kg/day. Of the 168 patients included in the efficacy analysis, 122 (72.6%) completed the study and 94 (56.0%) became seizure-free after the OXC treatment. Comparing the efficacy of OXC for intellectually normal and intellectually impaired patients, 79 (56.8%) of the 139 intellectually normal patients and 15 (51.7%) of the 29 intellectually impaired patients became seizure-free (P=0.61). After treatment, intelligence scale scores improved in intellectually normal patients compared to the intellectually impaired children (P<0.05). Social problems quantified by behavior scales improved in intellectually impaired patients compared to intellectually normal children (P<0.05). CONCLUSIONS: OXC is effective and well-tolerated as monotherapy in children with partial seizures. There was no difference in the effectiveness of OXC between intellectually normal and intellectually impaired children.

Cognitive function of idiopathic childhood epilepsy.

Most children with epilepsy are of normal intelligence. However, a significant subset will have temporary or permanent cognitive impairment. Factors that affect cognitive function are myriad and include the underlying neuropathology of the epilepsy, seizures, epileptiform discharges, psychosocial problems, age at seizure onset, duration of epilepsy, and side effects associated with antiepileptic drugs. This review article discusses cognitive function in children with idiopathic epilepsy and the effects of antiepileptic drugs on cognitive function in children.

A case of acute necrotizing encephalopathy associated with parainfluenza virus infection.

Acute necrotizing encephalopathy (ANE) may be suspected when a young child presents with abrupt onset of altered mental status, seizures, or both. Definitive clinical diagnosis is based on magnetic resonance imaging (MRI) results. ANE is associated with influenza virus infections. Preliminary data suggests that up to 25% of ANE patients die, and up to 25% of ANE survivors develop substantial neurologic sequelae. Here, we describe a case of a comatose 22-month-old girl who was admitted to our hospital because of febrile illness and seizures. On day 13 of her illness, she died from ANE associated with infection from parainfluenza virus. Brain MRI results indicated diffuse bilateral symmetric signal changes in both basal ganglia, thalami, periventricular white matter, pons, and cerebral white matter, as well as generalized swelling of the brain.

A case of midgut malrotation presenting as multiple afebrile seizures.

Provoked seizures are a common pediatric problem and can be caused by multiple etiologies. However, there have been few reports of benign infantile seizures associated with gastrointestinal tract abnormality. We report on a 3-month-old male infant who presented with multiple afebrile seizures, EEG abnormalities and a midgut malrotation. Surgical treatment of the malrotation resulted in seizure resolution and EEG normalization. This case emphasizes that patients presenting with multiple seizures and symptoms of gastroenteritis should be evaluated for abnormalities of the gastrointestinal tract.

Comparison of short- versus long-term ketogenic diet for intractable infantile spasms.

PURPOSE: To compare the prognoses between short-term (8 months) and conventional long-term (> 2 years) trials involving patients with refractory infantile spasms who successfully completed the ketogenic diet (KD). METHODS: Of 40 patients who achieved seizure-free outcomes and showed improvement in hypsarrhythmic patterns within 6 months of the KD, with a 3:1 fat to nonfat ratio as an add-on treatment, 16 patients were randomized into the short-term trial group and the diet was tapered throughout two additional months. Twenty-four patients were randomized into a long-term trial group, and 19 patients could successfully discontinue the diet after 2 years. Primary outcome measures included seizure relapse and frequency of 35 patients for > 12 months after successful completion of the KD. KEY FINDINGS: Of 16 patients in the short-term trial group, two patients relapsed with clusters of spasms, and one patient had recurrence of occasional focal seizures. Of 19 patients in the long-term trial group, two patients progressed to Lennox-Gastaut syndrome and one patient experienced recurrence of occasional focal seizures with secondary generalization. An early response to the KD, evidenced by short latency before seizure freedom and disappearance of hypsarrythmia and cryptogenic etiology, may indicate a successful early discontinuation of the KD. Significant growth failure was complicated only in conventional long-term trial group. SIGNIFICANCE: Use of the KD for only 8 months in children who become spasm-free appears to be justified, with similar outcomes, recurrence rate, and less growth disturbance than a longer-term, traditional use.