Severe Neurological Manifestation Associated With Coronavirus Disease 2019 in Children During the Omicron Variant-Predominant Period.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be more infectious and less severe than the other variants. Despite the increasing number of symptomatic patients, severe neurological complications in children with the Omicron variant have been reported rarely, unlike with wild-type or Delta variants. This study aimed to investigate severe neurological complications in children with Omicron variant infection. METHODS: We conducted a retrospective study of 17 pediatric patients with severe neurological manifestations associated with coronavirus disease 2019 in Korea during the Omicron variant prevalence, from January 1 to April 30, 2022. RESULTS: Among the 17 patients, 11 had pre-existing neurological disabilities and nine met the criteria for multisystem inflammatory syndrome in children (MIS-C). Four of the five vaccine-eligible patients (12 years and older) were unvaccinated. Severe neurological manifestations included acute necrotizing encephalopathy, acute fulminant cerebral edema, acute disseminated encephalomyelitis, basal ganglia encephalitis, unclassified severe encephalopathy/encephalitis, and refractory status dystonicus. Patients with MIS-C and underlying neurological disabilities had longer median hospital and intensive care unit stays compared with those without these conditions. Five patients survived with new neurological deficits at the one-year follow-up, and three died, all of whom had underlying neurological disabilities. CONCLUSIONS: This study shows that severe neurological complications in pediatric patients with the Omicron variant of SARS-CoV-2 occur infrequently but may lead to significant morbidity and mortality, especially among those with pre-existing neurological disabilities and unvaccinated individuals. Continued efforts are necessary to prevent and manage such complications in these vulnerable populations.

The Korean undiagnosed diseases program phase I: expansion of the nationwide network and the development of long-term infrastructure.

BACKGROUND: Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system. RESULTS: During the program (2018-2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration. CONCLUSIONS: The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.

Multiple endocrine neoplasia type 2 and autoimmune polyendocrine syndromes (type 1 diabetes mellitus and Graves' disease) in a 16-year-old male with Kabuki syndrome.

Multiple endocrine neoplasia type 2A (MEN2A) is caused by germline pathogenic variants in the RET proto-oncogene and is characterized by medullary thyroid cancer (MTC), pheochromocytoma, and hyperparathyroidism. Autoimmune polyendocrine syndromes (APS) are defined as multiple endocrine gland insufficiency associated with loss of immune tolerance. APS type 2 (APS-2) consists of at least two of the following diseases: type 1 diabetes mellitus (T1DM), autoimmune thyroid disease, and Addison's disease. We describe the clinical, molecular, and biochemical findings of MEN2A, APS-2, and Kabuki syndrome (KS) in a 16-year-old male. Whole exome sequencing was performed to identify the genetic cause of the pheochromocytoma and syndromic features including facial dysmorphism, developmental delay, and epilepsy. RET pathogenic variant and KMT2D pathogenic variant were identified, and he was diagnosed with MEN2A and KS. This is the first case of association between MEN2 and APS in adolescence and the second proven case in humans. In addition, this is the first report of MEN2 and APS in KS.

Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene-Long-Term Follow-Up of a Sibling.

Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic variant in ACO2 gene (NM_001098.3) was found to be causative of this disease. To date, approximately 44 variants displaying various clinical features have been reported. Here, we report a case of two siblings with compound heterozygous variants in the ACO2 gene. Two siblings without perinatal problems were born to healthy non-consanguineous Korean parents. They showed GDD and seizures since infancy. Their first brain magnetic resonance imaging (MRI), electroencephalography, and metabolic workup revealed no abnormal findings. As they grew, they developed symptoms including ataxia, dysmetria, poor sitting balance, and myopia. Follow-up brain MRI findings revealed atrophy of the cerebellum and optic nerve. Through exome sequencing of both siblings and their parents, we identified the following compound heterozygous variants in the ACO2: c.85C > T (p.Arg29Trp) and c.2303C > A (p.Ala768Asp). These two variants were categorized as likely pathogenic based on ACMG/AMP guidelines. In conclusion, this case help to broaden the genetic and clinical spectrum of the ACO2 variants associated with ICRD. We have also documented the long-term clinical course and serial brain MRI findings for two patients with this extremely rare disease.

Update on benign convulsions with mild gastroenteritis.

Benign convulsions with mild gastroenteritis (CwG) are characterized by afebrile convulsions associated with viral gastroenteritis in previously healthy infants and children. The main causative pathogens are rotavirus and norovirus. CwG occurs frequently in both East Asian and Western countries. The prevalence of CwG was reportedly not decreased by the introduction of rotavirus vaccines, and the prevalence of norovirus-associated CwG has been increasing annually. Convulsions in CwG are usually clustered, do not last longer than 5 minutes, and are mostly generalized. Laboratory diagnostics, electroencephalography (EEG), and imaging findings are usually normal. There is a probability of mild, transient abnormal findings on EEG or imaging limited to the acute disease phase. Although several reports have suggested that pathogens that affect the central nervous system through direct or indirect mechanisms could be related to the pathophysiology of CwG, its mechanism is not fully understood. Several antiepileptic drugs are effective during convulsions; however, long-term antiepileptic treatment is not required as CwG usually has a good prognosis.

Benign Convulsions with Mild Rotavirus and Norovirus Gastroenteritis: Nationwide Data from the Health Insurance Review and Assessment Service in South Korea.

There have been no large-scale studies on the epidemiology of benign convulsions with mild gastroenteritis (CwG) since the introduction of the rotavirus vaccine in South Korea in 2007. This study aimed to analyze the trends in rotavirus gastroenteritis (RVGE) and rotavirus-associated CwG (RaCwG) after rotavirus vaccination. Further, we aimed to analyze changes in norovirus gastroenteritis (NVGE) and norovirus-associated CwG (NaCwG) using nationwide data from the Korean Health Insurance Review and Assessment Service. Between 2007 and 2019, this study analyzed children aged <6 years who were diagnosed with RVGE, NVGE, RaCwG and NaCwG. The changes in the prevalence of each disease and the ratio of CwG to enteritis were analyzed and the effects of age, sex and season were also analyzed. RVGE, RaCwG, NVGE and NaCwG were diagnosed in 273,898, 4246, 35,593 and 337 patients, respectively. The prevalence of RVGE was on a decreasing trend every year, but the prevalence of NaCwG and NVGE was on an increasing trend. There was a significant annual increase in the ratio of CwG to enteritis in both viruses. In order to control the prevalence of RaCwG, measures other than the rotavirus vaccine are required and measures to prevent norovirus are necessary.

Immunogenicity and safety of the third booster dose of the inactivated Japanese encephalitis vaccine in Korean children: A prospective multicenter study.

The immunization schedule for the inactivated Japanese encephalitis (JE) vaccine in Korea is a two-dose primary series at 12-24 months of age and three booster doses at 12 months after primary schedule and at 6 and 12 years of age. The aim of this study was to investigate immunogenicity and safety of the third booster dose of the inactivated JE vaccine, as well as the long-term immunogenicity of the second booster dose in Korean children. Healthy children aged 11-13 years, primed and given four doses of inactivated JE vaccines were included. All subjects received the third booster dose of the JE vaccine. Neutralizing antibody (NTAb) titers were assessed before and 4-6 weeks after vaccination using plaque reduction neutralization test (PRNT), and were considered to be protective at ≥ 1:10. Local and systemic adverse events were monitored for 4 weeks after vaccination. Before and after booster vaccination, all seroprotection rates were 100%. Geometric mean titer (GMT) showed a 6.05-fold increase, from 139.11 (95% CI: 110.76, 174.71) to 841.53 (95% CI, 714.25, 991.50). The local tolerability and systemic safety profiles were favorable, with no serious adverse events. In conclusion, the third booster dose of the inactivated JE vaccine was demonstrated to be safe and immunogenic in Korean children when administered according to the current immunization schedule.

Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review.

BACKGROUND: KBG syndrome (OMIM #148050) is a rare, autosomal dominant inherited genetic disorder caused by heterozygous mutations in the ankyrin repeat domain-containing protein 11 (ANKRD11) gene or by microdeletion of chromosome 16q24.3. It is characterized by macrodontia of the upper central incisors, distinctive facial dysmorphism, short stature, vertebral abnormalities, hand anomaly including clinodactyly, and various degrees of developmental delay. KBG syndrome presents with variable clinical feature and severity among individuals. Here, we report two KBG patients who have different novel heterozygous mutations of ANKRD11 gene with wide range of clinical manifestations. CASE PRESENTATION: Two novel heterozygous mutations of ANKRD11 gene were identified in two unrelated Korean patients with variable clinical presentations. The first patient presented with short stature and early puberty and was treated with growth hormone and gonadotropin-releasing hormone agonist without adverse effects. He had mild intellectual disability. In targeted exome sequencing, a novel de novo frameshift variant was identified in ANKRD11, c.5889del, and p. (Ile1963MetfsX9). The second patient had severe intellectual disability with epilepsy. He had normal height and prepubertal stage at the age of 11 years. He had behavioral problems such as autism-like features, anxiety, and stereotypical movements. Whole exome sequencing (WES) was performed, and the novel heterozygous mutation, c3310dup, p. (Glu110GlyfsTer5) in ANKRD11 was identified. CONCLUSION: KBG syndrome is often underdiagnosed because of its non-specific features and phenotypic variability. Performing a next-generation sequencing panel, including the ANKRD11 gene for cases of developmental delay with/without short stature may be helpful to identify hitherto undiagnosed KBG syndrome patients.

Epidemiology of Rotavirus Gastroenteritis and Rotavirus-Associated Benign Convulsions with Mild Gastroenteritis after the Introduction of Rotavirus Vaccines in South Korea: Nationwide Data from the Health Insurance Review and Assessment Service.

Using nationwide data from the Health Insurance Review and Assessment service, we assessed the impact of rotavirus vaccines, introduced in South Korea, in 2007, on changes in the prevalence of factors (age, sex, and geographic location) associated with rotavirus gastroenteritis (RVGE) and rotavirus-associated benign convulsions with mild gastroenteritis (RaCwG). We analyzed health records of children younger than 3 years who visited clinical facilities and were diagnosed with RVGE or RaCwG between 2007 and 2019. The annual mid-year population (MYP) was obtained from the Korean Statistical Information Service. The annual prevalence of RVGE, RaCwG and associated factors were statistically analyzed. Overall, 219,686, and 4032, children were confirmed to have RVGE and RaCwG, respectively. Although the annual prevalence of RVGE decreased significantly, that of RaCwG did not. The annual ratio of RaCwG to RVGE was significantly high. Compared to the prevalence of RVGE, the prevalence of RaCwG was significantly lower in rural areas. The age of RaCwG patients was significantly lower than that of the MYP and that of RVGE patients. The decrease in the number of RaCwG patients after rotavirus vaccination was not as pronounced as the decrease in the number of RVGE patients.

Seroprevalence of Neutralizing Antibodies against Japanese Encephalitis Virus among Adolescents and Adults in Korea: A Prospective Multicenter Study.

The immunization schedule for the Japanese encephalitis (JE) vaccine in Korea is a two-dose primary series at 12-24 months of age, followed by booster doses 12 months after the second dose and at the ages of 6 and 12 years. Although the number of JE cases has markedly decreased after the universal vaccination program, JE predominantly occurs in adults. The aim of this study was to assess the age-specific prevalence of the JE-neutralizing antibody (NTAb) among adolescents and adults in Korea. A total of 1603 specimens were collected from a healthy Korean population above 15 years old in five provinces. The JE-NTAb titers were measured with the pseudotyped virus assay and considered to be positive at ≥ 1:50. The seropositivity of JE-NTAb was the highest in the 15-29 years category (>95%) and gradually began to decrease in the age group of 30-44 years (89.42%). The lowest and second lowest JE-NTAb seropositive rates were observed among those aged 70 years or older (59.77%) and those aged 55-59 years (75.24%), respectively. Subjects from Seoul exhibited the highest JE-NTAb titer in all age groups compared to other provinces. In conclusion, the JE-NTAb seropositive rates and titers have maintained appropriate levels in the general Korean population. We propose that adult immunization and boosters at 12 years of age against JE are not strongly recommended in Korea.

The Korean undiagnosed diseases program: lessons from a one-year pilot project.

BACKGROUND: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea. RESULTS: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficient clinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinically diagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex, atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 in group II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (< 18 years old) and 59 (60.8%) were male. The primary symptoms for 80 patients (82.5%) were neurologic. During the one-year pilot study, 72 patients completed a diagnostic assessment including clinical and molecular genetic analyses; some patients also underwent pathological or biochemical analysis. Twenty-eight of these patients (28/72, 38.9%) achieved molecular genetic diagnosis. Thirteen patients were diagnosed based on traditional tests, including biochemical assay, single or targeted genetic analysis, and chromosomal microarray. We performed whole exome sequencing on 52 patients, among whom 15 (28.8%, 15/52) reached a final diagnosis. One new disorder was identified via international collaboration. CONCLUSIONS: Using an efficient clinical diagnostic workflow, this KUDP pilot study resulted in a fair diagnostic success rate, improving the potential for additional diagnoses and new scientific discovery of complex and rare diseases. KUDP also satisfied unmet needs for rare diseases with multisystem involvement, highlighting the value of emerging genomic technologies for further research into rare and still-undiagnosed conditions.

The effect of low-dose intravenous bisphosphonate treatment on osteoporosis in children with quadriplegic cerebral palsy.

PURPOSE: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. METHODS: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, 10.9±5.76 years), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5-1.0 mg/kg/day, 2 consecutive days) every 3-4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. RESULTS: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was 4.49±2.22 mg/kg/yr, and the mean treatment period was 10.8±3.32 months. The BMD z score of the lumbar spine showed a significant increase from -4.22±1.24 before treatment to -2.61±1.69 during treatment (P=0.008). Alkaline phosphatase decreased during treatmentn (P=0.037). Significant adverse drug reactions and new fractures were not reported. CONCLUSION: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

Complete occlusion of the right middle cerebral artery associated with Mycoplasma pneumoniae pneumonia.

We report a case of a 5-year-old girl who developed left hemiparesis and left facial palsy, 6 days after the initiation of fever and respiratory symptoms due to pneumonia. Chest radiography, conducted upon admission, showed pneumonic infiltration and pleural effusion in the left lung field. Brain magnetic resonance imaging showed acute ischemic infarction in the right middle cerebral artery territory. Brain magnetic resonance angiography and transfemoral cerebral angiography revealed complete occlusion of the right middle cerebral artery. Mycoplasma pneumoniae infection was identified by a 4-fold increase in IgG antibodies to M. pneumoniae between acute and convalescent sera by enzyme-linked immunosorbent assay. Fibrinogen and D-dimer levels were elevated, while laboratory exams in order to identify other predisposing factors of pediatric stroke were all negative. This is the first reported pediatric case in English literature of a M. pneumoniae-associated cerebral infarction involving complete occlusion of the right middle cerebral artery.

Peripheral facial palsy, the only presentation of a primitive neuroectodermal tumor of the skull base.

INTRODUCTION: Peripheral facial palsy is rarely caused by primary neoplasms, which are mostly constituted of tumors of the central nervous system, head and neck, and leukemia. PRESENTATION OF CASE: A 2-month-old male infant presented with asymmetric facial expression for 3 weeks. Physical examination revealed suspicious findings of right peripheral facial palsy. Computed tomography of the temporal bone revealed a suspicious bone tumor centered in the right petrous bone involving surrounding bones with extension into the middle ear cavity and inner ear. Subtotal resection of the tumor was performed due to crucial structures adjacent the mass. Histopathology and immunohistochemistry of the resected tumor was consistent with primitive neuroectodermal tumor. CONCLUSION: We report a rare case of a primitive neuroectodermal tumor located at the skull base presenting with only peripheral facial palsy.

Development of multifocal nodular lesions of a liver mimicking hepatic metastasis, following resection of an insulinoma in a child.

Insulinoma, which arises from insulin-producing pancreatic beta cells, is a rare tumor in children. Only 5%-10% of insulinomas are malignant and undergo metastasis. We report a case of an 11-year-old girl who experienced hypoglycemia-related seizures induced by an insulinoma; after resection of the primary tumor, she developed hepatic focal nodular hyperplasia (FNH). Laboratory test results indicated marked hypoglycemia with hyperinsulinemia. Abdominal ultrasonography (US) and computed tomography results were normal; however, magnetic resonance imaging (MRI) showed a solid mass in the pancreatic tail. Therefore, laparoscopic distal pancreatectomy was performed. Two months after the surgery, an abdominal MRI revealed multiple nodular lesions in the liver. An US-guided liver biopsy was then performed, and histological examination revealed FNH without necrosis or mitotic activity. The patient has been free of hypoglycemia for 2 years, and recent MRI studies showed a decrease in the size of FNH lesions, without any evidence of metastasis. Even though no metastatic lesions are noted on imaging, close observation and follow-up imaging studies are required in a child with insulinoma that has malignant potential on histopathologic findings.

Benign convulsion with mild gastroenteritis.

Benign convulsion with mild gastroenteritis (CwG) is a type of afebrile seizure that occurs in children. CwG is defined as a convulsion in a previously healthy child with no known central nervous system infection or encephalopathy, accompanying mild diarrhea without fever, electrolyte imbalance, or moderate to severe dehydration. Convulsions in CwG are characterized by multiple brief episodes of generalized or focal seizures. Although the etiology and pathophysiology have yet to be fully explained, many pathogenic mechanisms have been proposed including the possibility of direct invasion of the central nervous system by a gastrointestinal virus such as rotavirus or the possibility of indirect influence by the production and effects of certain mediators. The electroencephalogram findings are benign and long-term antiepileptic treatment is typically not required. Long-term prognosis has been favorable with normal psychomotor development. This review provides a general overview of CwG with the goal of allowing physicians practicing in the field of pediatrics to better recognize this unique entity and, ultimately, to minimize unnecessary evaluation and treatment.

Epileptic nystagmus and vertigo associated with bilateral temporal and frontal lobe epilepsy.

Epileptic nystagmus is defined as a quick, repetitive jerky movement of the eyeball associated with seizure activity. In cases of epileptic nystagmus associated with ictal discharge from multiple brain areas, localization of the exact epileptogenic zone could be extremely difficult. In a nine-year-old patient with epileptic nystagmus and vertigo associated with bilateral temporal and frontal lobe epilepsy, we could infer the epileptic focus by interpreting the patient's clinical picture, characteristics of nystagmus, and findings of electroencephalography.

Is It Possible to Predict the Iron Status from an Infant's Diet History?

PURPOSE: Iron deficiency remains a very common nutritional problem despite the improvement in nutrition and increased understanding of methods for its prevention. Thus, we try to create a new method for screening iron nutrition through infant nutrition history. METHODS: Among the children who visited Inha University Hospital from March 2006 to July 2012, 181 children with iron deficiency anemia (IDA) and 52 children without IDA ranging from 6 to 36 months of age were reviewed in this study. We used the age when they began to wean food, the type of sort weaning foods, the time required for successful weaning, iron content in weaning foods, and the duration of breastfeeding for scoring infant nutrition history based on a questionnaire. RESULTS: The mean score of the IDA group was 7.8±2.6 points, which was significantly higher than that of the control group (5.6±2.1) (p=0.000). If we set up the cutoff value at 6 points, this screening has 86.8% sensitivity and 36% specificity. In addition, as the IDA score increased, there was a falling trend of hemoglobin. CONCLUSION: The IDA score does not have high specificity or high sensitivity. However, this study conveys that those patients who record a high score have low hemoglobin. Therefore, we suggest this score system for screening more IDA patients via nonpainful techniques.

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis.

PURPOSE: We aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population. METHOD: Medical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; 'no seizure' (NS: patients without seizure), 'febrile seizure' (FS: patients with fever during seizure), 'afebrile seizure' (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis. RESULTS: Among the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3±0.8 vs. 2.8±1.0 days; p<0.0001). A single seizure attack was significantly higher in the AFS group (3.0±1.6 vs. 1.7±1.0 episodes; p=0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p=0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period. CONCLUSION: Despite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis.

Neuroprotective and antiepileptogenic effects of combination of anti-inflammatory drugs in the immature brain.

BACKGROUND: Inflammatory signaling elicited by prolonged seizures can be contributory to neuronal injury as well as adverse plasticity leading to the development of spontaneous recurrent seizures (epilepsy) and associated co-morbidities. In this study, developing rat pups were subjected to lithium-pilocarpine status epilepticus (SE) at 2 and 3 weeks of age to study the effect of anti-inflammatory drugs (AID) on SE-induced hippocampal injury and the development of spontaneous seizures. FINDINGS: We selected AIDs directed against interleukin-1 receptors (IL-1ra), a cyclooxygenase-2 (COX-2) inhibitor (CAY 10404), and an antagonist of microglia activation of caspase-1 (minocycline). Acute injury after SE was studied in the 2-week-old rats 24 h after SE. Development of recurrent spontaneous seizures was studied in 3-week-old rats subjected to SE 4 months after the initial insult.None of those AIDs were effective in attenuating CA1 injury in the 2-week-old pups or in limiting the development of spontaneous seizures in 3-week-old pups when administered individually. When empiric binary combinations of these drugs were tried, the combined targeting of IL-1r and COX-2 resulted in attenuation of acute CA1 injury, as determined 24 h after SE, in those animals. The same combination administered for 10 days following SE in 3-week-old rats, reduced the development of spontaneous recurrent seizures and limited the extent of mossy fiber sprouting. CONCLUSIONS: Deployment of an empirically designed 'drug cocktail' targeting multiple inflammatory signaling pathways for a limited duration after an initial insult like SE may provide a practical approach to neuroprotection and anti-epileptogenic therapy.