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.

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.

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.

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.

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.

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.

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.

Evaluation of development-specific targets for antiepileptogenic therapy using rapid kindling.

We used the method of rapid hippocampal kindling to assess the potential antiepileptogenic efficacy of a number of anticonvulsant medications. This method afforded a higher throughput than methods based on traditional kindling or post-status epilepticus models of epileptogenesis. This "compressed epileptogenesis" model also permitted the study of age-dependent pharmacologic targets, and distinguished among antiepileptic drugs (AEDs) on the basis of their age-specific antiepileptogenic efficacy. We found retigabine to be the most effective anticonvulsant therapy during early development. Topiramate seemed most effective further along development, whereas some drugs did not demonstrate an age-specific effect. The method also reproduced some of the paradoxical pharmacologic findings previously shown with lamotrigine. Although the utility of this model for screening the antiepileptogenic therapies requires further validation, it introduces the ability to undertake development-specific testing and a more rapid throughput than conventional methods.

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.

Elevated plasma corticosterone level and depressive behavior in experimental temporal lobe epilepsy.

Depression is frequently reported in epilepsy patients; however, mechanisms of co-morbidity between epilepsy and depression are poorly understood. An important mechanism of depression is disinhibition within the hypothalamo-pituitary-adrenocortical (HPA) axis. We examined the functional state of the HPA axis in a rat model of co-morbidity between temporal lobe epilepsy and depression. Epilepsy was accompanied by the interictal elevation of plasma corticosterone, and by the positively combined dexamethasone/corticotropin releasing hormone test. The extent of the HPA hyperactivity was independent of recurrent seizures, but positively correlated with the severity of depressive behavior. We suggest that the observed hyperactivity of the HPA axis may underlie co-morbidity between epilepsy and depression.

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.

Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: an ontogenic study.

PURPOSE: To examine antiepileptogenic and antiictogenic potential of retigabine (RTG) under conditions of rapid kindling epileptogenesis during different stages of development. METHODS: The experiments were performed in postnatal day 14 (P14), P21, and P35 male Wistar rats. After stereotaxic implantation of hippocampal stimulating and recording electrodes, the effects of RTG on baseline afterdischarge (AD) properties were studied. Next, the animals underwent rapid kindling (sixty 10 s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of seizures (kindling acquisition), and responses to test stimulations after kindling (retention) were compared between RTG and vehicle-treated rats. Additionally, the effects of RTG on the severity of seizures in previously kindled animals were examined. RESULTS: When administered intraperitoneally in doses that induced only mild, or no motor deficits, RTG significantly dampened brain excitability, evident as the increase of AD threshold and shortening of AD duration. During kindling, RTG delayed the development of focal seizures in P14 rats, and prevented the occurrence of full limbic seizures at all three ages. At P14 and P21, but not at P35, pretreatment with RTG prevented the establishment of kindling-induced enhanced seizure susceptibility. Administration of RTG to kindled animals decreased the severity of seizures induced by test stimulation. The effect was most prominent at P14. DISCUSSION: RTG exerted both antiepileptogenic and antiictogenic effects under conditions of rapid kindling model. These effects were apparent during postneonatal, early childhood, and adolescent stages of development.

Effects of the ketogenic diet on neurogenesis after kainic acid-induced seizures in mice.

The ketogenic diet (KD) remains a therapy in search of explanation although it is an established treatment of intractable epilepsy. Recent studies suggest that the KD may be both anticonvulsant and antiepileptogenic. Epileptic seizures have been shown to stimulate the proliferation rate of neuronal progenitor cells in adult animals, which may be related to epileptogenesis. It is known that calorie restriction (CR) increases neurogenesis. The KD was originally formulated to reproduce the biochemical changes seen upon fasting (extreme CR). Thus, we investigated the effects of the KD on neurogenesis after kainic acid (KA)-induced seizures in mice. In the present study, quantitative analysis of BrdU labeling revealed a significant increase in the proliferation rate of neuronal progenitor cells after KA-induced seizures in the KD-fed mice. This finding may provide a clue to explain how the KD exerts antiepileptogenic effects although further studies are mandatory to elucidate the relationship between seizure-induced neurogenesis augmented by the KD and its antiepileptogenic properties. In conclusion, our results suggest that the KD enhances neurogenesis, which may be related to its beneficial effects on epilepsy.

A case of acute hepatitis with Mycoplasma pneumoniae infection and transient depression of multiple coagulation factors.

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection.

MR imaging in a child with scurvy: a case report.

Scurvy is very rare disease in industrialized societies. Nevertheless, it still exists in higher risk groups including economically disadvantaged populations with poor nutrition, such as the elderly and chronic alcoholics. The incidence of scurvy in the pediatric population is very low. This study reports a case of scurvy in a 5-year-old girl with cerebral palsy and developmental delay based on MRI findings.

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.

Topiramate monotherapy in infantile spasm.

Infantile spasm is an age-related refractory epilepsy. Topiramate is a new anticonvulsant with multiple mechanisms of action, and it may be effective for treating pediatric epilepsies. To evaluate the efficacy and tolerability of first-line topiramate treatment for infantile spasm, 20 patients received topiramate monotherapy during this study. They were treated with an initial dose of 1mg/kg/day, with a progressive titration of 1 mg/kg a week until their spasms were controlled and a maximum dose of 12 mg/kg/day was achieved. The evaluation of the treatment efficacy was based on the spasm frequency data that was obtained by the scalp and video-EEG, and by the parental count of spasm. Thirty percent of the subjects became spasm-free during the study. Six of 20 subjects (30%) had cessation of spasm and disappearance of hypsarrhythmia as seen via the video EEG; four (50%) of eight idiopathic patients had a response, whereas two (17%) of 12 patients with symptomatic infantile spasm responded. Seventy of the patients, including the spasm-free patients, had a reduction in their seizure frequency of more than 50%, and 10% of the patients had a reduction in their seizure frequency of less than 50%. The clusters of spasm frequency decreased from 10.6 +/- 8.5 to 3.5 +/- 1.4 clusters/day. Topiramate is effective and tolerated in those patients suffering from infantile spasm. Our results suggest that this drug should be considered as a new first-line drug for treating infantile spasm.