Impact of nusinersen on the health-related quality of life and caregiver burden of patients with spinal muscular atrophy with symptom onset after age 6 months.

INTRODUCTION/AIMS: Novel disease-modifying approaches for spinal muscular atrophy (SMA) have highlighted the patient's perspective on functional changes over time. In this study, we evaluated the impact of nusinersen on the health-related quality of life (HRQoL) of patients with later-onset SMA and the caregiver burden. METHODS: We assessed the changes in HRQoL using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL GCS) and the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM) during 26 months of treatment. Caregiver burden was assessed using the Assessment of Caregiver Experience with Neuromuscular Disease. We also assessed motor function using the Hammersmith Functional Motor Scale-Expanded (HFMSE) and the Revised Upper Limb Module score. RESULTS: Twenty-four patients and their caregivers were included. The median age of patients at treatment onset was 148.8 (6.8 to 269.4) months. A significant improvement was observed in psychosocial health in proxy-reported PedsQL (P = .023). However, the physical health scores of the PedsQL GCS and About my neuromuscular disorder subscores of the PedsQL NMM did not change, although there was a significant increase in HFMSE scores. Regarding the caregiver burden, the financial burden was reduced, whereas time burden increased. A higher HFMSE score was associated with better self-reported PedsQL GCS total scores (P < .001). DISCUSSION: Our results provide insights into the multifaceted implications of disease-modifying therapies for SMA through patient-reported outcome measures (PROMs). PROMs should be taken into consideration to assess the clinical significance of the functional changes identified by clinician-reported scales.

Evaluation of the neurofilament light chain as a biomarker in children with spinal muscular atrophy treated with nusinersen.

BACKGROUND: This study aimed to evaluate the neurofilament light chain (NfL) as a biomarker for treatment responses in children with a broad spectrum of spinal muscular atrophy (SMA) under nusinersen treatment. METHOD: We measured NfL levels in serum (sNfL) and cerebrospinal fluid (cNfL) in nusinersen-treated patients with SMA and children without neurologic disorders. Correlations between cNfL and sNfL levels and motor function scores were analyzed. RESULTS: sNfL and cNfL levels were measured in eight patients with SMA (SMA type 1, n = 3; SMA type 2, n = 5). sNfL levels were strongly correlated with cNfL levels regardless of the SMA subtype (r = 0.97, P < 0.001). Patients with SMA type 1 had higher baseline cNfL and sNfL levels before treatment initiation than those with SMA type 2 and neurologically healthy children. In patients with acute stage of SMA type 1 and 2, the NfL level rapidly decreased during the nusinersen treatment loading phase followed by stabilization at a lower plateau level. In contrast, in a patient with a chronic stage of SMA type 2, the NfL level remained within the normal range with no apparent downward trend. Motor function scores showed a tendency toward an inverse correlation with NfL levels in patients with acute stage although not in patients with chronic stage. CONCLUSIONS: cNfL and sNfL levels can be promising biomarkers for monitoring treatment response in patients within their acute stage, particularly in SMA type 1, although not in patients with a chronic stage of SMA type 2.

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.

Clinical Usefulness of Simultaneous Electroencephalography and Functional Magnetic Resonance Imaging in Children With Focal Epilepsy.

BACKGROUND AND PURPOSE: The current study analyzed the interictal epileptiform discharge (IED)-related hemodynamic response and aimed to determine the clinical usefulness of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) in defining the epileptogenic zone (EZ) in children with focal epilepsy. METHODS: Patients with focal epilepsy showing IEDs on conventional EEG were evaluated using EEG-fMRI. Statistical analyses were performed using the times of spike as events modeled with multiple hemodynamic response functions. The area showing the most significant t-value for blood-oxygen-level-dependent (BOLD) changes was compared with the presumed EZ. Moreover, BOLD responses between -9 and +9 s around the spike times were analyzed to track the hemodynamic response patterns over time. RESULTS: Half (n=13) of 26 EEG-fMRI investigations of 19 patients were successful. Two patients showed 2 different types of spikes, resulting in 15 analyses. The maximum BOLD response was concordant with the EZ in 11 (73.3%) of the 15 analyses. In 10 (66.7%) analyses, the BOLD response localized the EZs more specifically. Focal BOLD responses in the EZs occurred before IEDs in 11 analyses and were often widespread after IEDs. Hemodynamic response patterns were consistent in the same epilepsy syndrome or when repeating the investigation in the same patients. CONCLUSIONS: EEG-fMRI can provide additional information for localizing the EZ in children with focal epilepsy, and also reveal the pathogenesis of pediatric epilepsy by evaluating the patterns in the hemodynamic response across time windows of IEDs.

Metanephrine Negative Pheochromocytoma: A rare case report of dopamine-secreting tumor in an adolescent patient with NF1.

Pheochromocytoma (PCC) occurs in 4% of pediatric neurofibromatosis type 1 (NF1) patients and is mostly characterized by epinephrine and norepinephrine secretion. Herein, we report the first case of a dopamine-secreting PCC in a 13-year-old patient with NF1, in whom a left adrenal mass was incidentally found on abdominal computed tomography (CT) during hypertension workup. Fractionated 24-h urine metanephrine excretion was normal but urine dopamine level was elevated. On 123I-metaiodobenzylguanidine (MIBG) single photon emission tomography/CT (SPECT/CT), focal MIBG uptake was observed. Our multidisciplinary team determined that surgery would be difficult to perform because the tumor was small and the symptoms were vague, with only increased dopamine level. After six months, the tumor increased in size on abdominal CT, with focal significant uptake of the lesion on 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET/CT. Laparoscopic resection was performed, and the mass was histologically confirmed as PCC. Currently, the vital signs of the patient are stable, urine dopamine levels are normal, and there is no abnormal uptake of 18F-FDOPA PET/CT. This study reports a case of a rare dopamine-secreting PCC. When metanephrine is negative in patients at high risk of PCC, focused examination and multidisciplinary approach are needed.

Association Between Antipsychotic Treatment and Neurological Adverse Events in Pediatric Patients: A Population-Based Cohort Study in Korea.

Background: Potential adverse effects might be caused by increasing the number of antipsychotic prescriptions. However, the empirical evidence regarding pediatric psychiatric patients is insufficient. Therefore, we explored the antipsychotic-induced adverse effects focusing on the neurological system. Method: Using the medical information of pediatric patients retrieved from the claims data of Health Insurance Review and Assessment in Korea, we identified those psychiatric patients who were started on antipsychotic treatment at age 2-18 years between 2010 and 2018 (n = 10,969). In this study, movement disorders and seizures were considered as major neurological adverse events. The extended Cox model with time-varying covariates was applied to explore the association between antipsychotic medication and adverse events. Findings: Total 1,894 and 1,267 cases of movement disorders and seizures occurred in 32,046 and 33,280 person-years, respectively. The hazard risks of neurological adverse events were 3-8 times higher in the exposed to antipsychotics period than in the non-exposure period. Among the exposure periods, the most dangerous period was within 30 days of cumulative exposure. High doses or polypharmacy of antipsychotics was associated with increased risks of neurological adverse events. Among individual antipsychotics, haloperidol showed the highest risk of developing movement disorders among the examined agents. Quetiapine showed a lower risk of developing movement disorders but a higher risk of developing seizures than risperidone. Conclusion: These findings suggest that antipsychotics should be used with caution in pediatric patients, especially regarding initial exposure, high dose, and polypharmacy.

Polymyoclonus aggravated by neck flexion as the isolated presenting symptom of Hirayama disease: case report.

BACKGROUND: We report a rare case of an 18-year-old male with unilateral hand tremor who was finally diagnosed with Hirayama disease (HD). CASE PRESENTATION: An 18-year-old male presented with unilateral polymyoclonus that aggravated with neck flexion. The patient did not complain of muscle weakness or muscle atrophy. The needle electromyography showed giant motor unit potentials in right cervical 7 and 8 innervated muscles. The cervical magnetic resonance imaging on supine and flexion state showed prominent forward effacement of posterior dural sac that was compatible with HD. CONCLUSIONS: HD usually presents with unilateral distal hand weakness, muscle atrophy and tremor. Although it is a benign and self-limiting disease, early diagnosis may lead to less clinical deterioration. Moreover, electromyography should be completed in the differentiation of young male patients who present with polymyoclonus without hand weakness or atrophy.

Factors associated with stigma and depressive symptoms in family members of patients with epilepsy.

PURPOSE: Literature regarding family stigma related to epilepsy is scarce. This study investigated the prevalence of family stigma and depressive symptoms and the associated factors among the family members of patients with epilepsy. METHODS: In a cross-sectional study, Stigma Scale-Revised score ≥ 4 and Patient Health Questionnaire-9 score ≥ 10 were considered indicative of moderate-to-severe stigma and depressive symptoms, respectively. Stepwise logistic regression analyses were performed. RESULTS: Of the 482 family members, a mean age was 47.1 ±â€¯9.4 years, and 73.4% were female. Of the patients, a mean age was 25.5 ±â€¯16.7 years, and 45.0% were female. Idiopathic generalized epilepsy and focal epilepsy were noted in 22.4% and 65.6% of patients, respectively. Family stigma and depressive symptoms were noted in 10.0% and 11.2% of family members, respectively. Family stigma was significantly associated with high seizure frequency and being a sibling or offspring of a patient independent of their depressive symptoms. By contrast, depressive symptoms in family members were significantly associated with polytherapy, being parents of a patient, and neurological comorbidities independent of family stigma. In a subset of patients and their family, patients had higher proportion of stigma and depressive symptoms than their family. Depressive symptoms and stigma among patients were significantly correlated with those among parents, but not spouse. CONCLUSION: Family stigma is common in families with epilepsy and is closely related to depressive symptoms. Frequent seizures, polytherapy, neurological comorbidities, and the relationship to a patient may be factors that are independently associated with family stigma and depressive symptoms in family members.

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study.

BACKGROUND AND PURPOSE: The US Food and Drug Administration approval for perampanel has only recently been expanded to patients as young as 4 years, and so there have been few real-life studies of the effects of perampanel in pediatric patients. The aim of this study was to determine the long-term efficacy, factors affecting treatment response, and tolerability of perampanel as an add-on therapy in pediatric patients aged 4 years or older with epilepsy. METHODS: This multicenter retrospective observational study collected data from pediatric epilepsy centers of four Korean national universities. Changes in the seizure frequency from baseline, adverse events, and retention rates were obtained at 3, 6, and 12 months. Adverse events and discontinuation profiles were obtained to assess tolerability. RESULTS: This study included 220 children and adolescents (117 males and 103 females) aged 4 to 20 years. The overall response rate was 43.6%, and the seizure-freedom rate was 17.7%. Factors affecting a good treatment response were the absence of intellectual disability, small number of concomitant antiepileptic drugs, and low baseline seizure frequency. Eighty-eight patients (40%) experienced adverse events, but they mostly were of mild severity and resolved after the dose reduction or discontinuation of perampanel. The retention rates at 3, 6, and 12 months were 85.0%, 71.8%, and 50.5%, respectively. CONCLUSIONS: Adjunctive treatment with perampanel was efficacious and tolerated in pediatric patients aged 4 years or older with epilepsy. Early perampanel treatment may help to reduce the burden of their seizures and improve their quality of life.

Clinical Experience of Nusinersen in a Broad Spectrum of Spinal Muscular Atrophy: A Retrospective Study.

BACKGROUND: Nusinersen has recently been approved and more widely used as first-line treatment of spinal muscular atrophy (SMA). This study aimed to evaluate the real-world experience of nusinersen use for patients with a broad spectrum of SMA. METHODS: We reviewed consecutive patients with SMA treated with nusinersen from April 2018 to April 2020. Data collected included clinical and diagnostic characteristics, molecular genetics, functional motor outcomes, and adverse events. RESULTS: Seven patients including four with SMA type 1 and three with SMA type 2 were treated with nusinersen. The median disease duration at the time of the first dose and the median follow-up duration were 37 months (range: 0.5-254 months) and 6.1 months (range: 2.1-22.1 months), respectively. Of the 41 lumbar punctures (LPs), seven fluoroscopy-guided LPs were successfully performed for two patients without sedation. All patients showed improvement in motor function even though the current tools for motor assessment seemed unable to detect subtle subjective improvement. All patients maintained a stable respiratory status. No patient has experienced a severe adverse event or discontinued treatment so far. CONCLUSION: Although the number of patients in this study was small, our results suggest that nusinersen is effective even in patients with a later stage of the disease. Additional long-term prospective studies with more number of patients having a broad spectrum of diseases are needed to identify meaningful improvement in the motor function and quality of life after nusinersen treatment.

Does the new Korean term for epilepsy reduce the stigma for Korean adults with epilepsy?

PURPOSE: The purpose of this study was to evaluate differences in stigma, disclosure management of epilepsy, and knowledge about epilepsy between patients with epilepsy who recognized and did not recognize the new Korean term for epilepsy. METHODS: This was a cross-sectional, multicenter study. The Stigma Scale-Revised, the Disclosure Management Scale, the Patient Health Questionnaire-9, and a questionnaire assessing knowledge about epilepsy were used. The set of questionnaires had two versions, using either the old or new name for epilepsy. Multivariate logistic regression analyses were used. RESULTS: A total of 341 patients with epilepsy and 509 family members were recruited. Approximately 62% of patients felt some degree of epilepsy-related stigma. Mild stigma, severe concealment of epilepsy diagnosis, and increased knowledge about epilepsy were independently identified as factors associated with recognition of the new term in patients. Recognition of the new term was more prevalent in patients and family members with higher education, female family members, and family members having patients with younger age at seizure onset and shorter duration of epilepsy. There were no significant differences between the two types of questionnaires. About 81% of patients and 93% of family members had a positive attitude about renaming epilepsy. CONCLUSION: The use of the new Korean term for epilepsy (cerebroelectric disorder) increased knowledge about epilepsy but did not reduce stigma and concealment of epilepsy diagnosis in Korean adults with epilepsy. Higher education may be an important factor for knowing the new term in patients and family members.

Extremely Early Onset Transthyretin Familial Amyloid Polyneuropathy with a Leu55Pro Mutation: A Pediatric Case Report and Literature Review.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant disease caused by the deposition of amyloid fibrils composed of TTR proteins. Symptoms of this disease include progressive sensorimotor neuropathy, cardiomyopathy, and involvement of other organs. We described a pediatric case of extremely early onset TTR-FAP with a TTR Leu55Pro mutation. A 17-year-old boy began to suffer from lower limb weakness, gait disturbance, and decreased sensation from 14 years of age onward. He presented with hypertrophic cardiomyopathy, periorbital and scleral ecchymosis, anhidrosis, orthostatic intolerance, and gastrointestinal autonomic dysfunction including nausea, vomiting, and diarrhea alternating with constipation. The patient's older sister had developed similar gastrointestinal symptoms from 20 years of age onward and was diagnosed as having hypertrophic cardiomyopathy. The boy's biopsy results showed infiltrated amyloid deposition on subcutaneous fat tissue and endocardium. Genetic analysis of the TTR gene demonstrated that both the patient and his sister had a pathogenic mutation, c.224T > C (Leu55Pro). Both patients were prescribed tafamidis, a TTR stabilizing agent. Although a majority of TTR-FAPs occur during adulthood, it should be suspected, even in pediatric populations, when symmetric length dependent neuropathy occurs in conjunction with a family history of neuropathy, autonomic neuropathy, and/or cardiomyopathy.

Central nervous system vasculitis from Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children: A case report.

BACKGROUND: Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders (EBV-T/NK-LPD) is a group of rare disorders resulting from EBV-infected T/NK-cells. It manifests as a broad spectrum of clinical symptoms according to immunologic status and viral load of an infected patient. Here, we report a boy who developed central nervous system (CNS) vasculitis and myelopathy as possible neurologic manifestations of EBV-T/NK-LPD. CASE REPORT: A 16-year-old boy came to our hospital with a necrotic skin lesion on his right shoulder. He suffered from local skin reactions with high fevers after mosquito bites since he was 10 years old. During the evaluation of his skin lesion, he suddenly developed left facial palsy. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) showed acute infarctions of the pons and middle cerebellar peduncle and irregularities of both anterior inferior cerebellar arteries. Serologic testing showed an elevation of total Ig E levels, anti-VCA IgG levels, and anti-EA IgG titers. EBV DNA copy numbers of the whole blood and cerebrospinal fluid (CSF) were elevated. Biopsy of the right shoulder skin showed extranodal NK/T-cell lymphoma. According to clinical features and laboratory findings, he was diagnosed with EBV-T/NK-LPD. He was treated with chemotherapy and hematopoietic stem cell transplantation but developed recurrent infarctions during treatment. CONCLUSION: This case showed the diagnostic challenge of neurologic manifestations of EBV-T/NK-LPD. EBV-T/NK-LPD-associated CNS vasculitis needs to be considered as a differential diagnosis of CNS vasculitis, when it is accompanied by the typical clinical spectrum of EBV-T/NK-LPD such as severe mosquito bite allergy, extranodal NK/T-cell lymphoma.

Acute Necrotizing Encephalopathy in Children: a Long Way to Go.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare, but potentially life threatening neurological condition in children. This study aimed to investigate its clinical spectrum, diagnostic and therapeutic dilemma, and prognosis. METHODS: Twelve children with ANE were included in the study. The diagnosis was made by clinical and radiological characteristics from January 1999 to December 2017 and their clinical data were retrospectively analyzed. RESULTS: A total of 12 children aged 6 to 93 months at onset (5 male: 7 female) were evaluated. The etiology was found in 4 of them (influenza A, H1N1; coxsackie A 16; herpes simplex virus; and RANBP2 gene/mycoplasma). The most common initial presentations were seizures (67%) and altered mental status (58%). The majority of the subjects showed elevation of aspartate aminotransferase/alanine aminotransferase with normal ammonia and increased cerebrospinal fluid protein without pleocytosis. Magnetic resonance imaging revealed increased T2 signal density in bilateral thalami in all patients, but the majority of the subjects (67%) also had lesions in other areas including tegmentum and white matter. Despite the aggressive immunomodulatory treatments, the long-term outcome was variable. One child and two sisters with genetic predisposition passed away. CONCLUSION: ANE is a distinctive type of acute encephalopathy with diverse clinical spectrum. Even though the diagnostic criteria are available, they might not be watertight. In addition, treatment options are still limited. Further studies for better outcome are needed.

Diagnostic usefulness of arterial spin labeling in MR negative children with new onset seizures.

PURPOSE: Arterial spine labeling (ASL) magnetic resonance imaging (MRI) is the non-invasive measurement of cerebral blood flow that can localize the seizure focus in patients with epilepsy. The aim of this study was to identify its utility for localizing the seizure focus in children with no structural lesion on MRI. METHODS: Forty-three consecutive children who underwent electroencephalography (EEG) and structural MRI, along with ASL for evaluation of newly developed seizures, were included. ASL abnormalities were classified as hypo/hyperperfusion, based on visual assessment, and compared with the seizure focus determined by clinical information and EEG. RESULTS: Among the 43 patients (M 17: F 26, mean age, 6.3 ± 3.3 years), the seizure type was focal in 36 patients and generalized in seven patients. Twenty-five (58.1%) patients showed perfusion change. Out of 36 patients with focal seizure, 24 (66.7%) showed ASL abnormalities, and 19 (52.8%) showed concordance between ASL and clinical focus. Out of seven patients with generalized seizure, only one patient showed ASL abnormalities. The overall concordance revealed moderate agreement (k = 0.542). ASL acquisition within one day from seizure onset was the only significant associating factor with the concordance between the two (p = 0. 014). CONCLUSION: To our knowledge, this is the first study to assess the usefulness of ASL MRI to assist in localizing the seizure focus in MR-negative children with new onset seizures. The combined use of ASL with EEG and structural MRI may play an important role in the evaluation of pediatric epilepsy.

Efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy.

PURPOSE: There is limited data on the use of perampanel in children under 12 years of age. We evaluated the efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy. METHODS: This retrospective observational study was performed in Kyungpook National University Hospital from July 2016 to March 2018. A responder was defined as a patient with ≥50% reduction in monthly seizure frequency compared with the baseline. Adverse events and discontinuation data were obtained to evaluate tolerability. RESULTS: Twenty-two patients (8 males, 14 females) aged 3.1-11.4 years (mean, 8.0±2.5 years) were included in this study. After an average of 9.2 months (range, 0.5-19 months) of follow-up, 15 patients (68%) showed a reduction in seizure frequency, including 5 patients (23%) with seizure freedom. The age at epilepsy onset was significantly lower (P=0.048), and the duration of epilepsy was significantly longer (P=0.019) in responders than in nonresponders. Nine patients (41%) experienced adverse events, including somnolence (23%), respiratory depression (9%), violence (4.5%), and seizure aggravation (4.5%). The most serious adverse event was respiratory depression, which required mechanical ventilation in 2 patients (9%). Eight patients (36%) discontinued perampanel due to lack of efficacy or adverse events. Three out of 4 patients (75%) who discontinued perampanel due to adverse events had an underlying medical condition. CONCLUSION: Perampanel offers a treatment option for refractory epilepsy in children. Adjunctive treatment with perampanel requires special consideration in those with underlying medical conditions to prevent serious adverse events.

The Clinical Spectrum of Benign Epilepsy with Centro-Temporal Spikes: a Challenge in Categorization and Predictability.

Benign epilepsy with centro-temporal spikes (BECTS) is the most common type of focal epilepsy in children; it is age-dependent and presumably genetic. Traditionally, children with BECTS have a very good prognosis, even without medical treatment, and are thought to show no neurological symptoms or cognitive deficits. However, many previous studies have shown that BECTS can present with various clinical and electroencephalographic characteristics that are commonly associated with neuropsychological deficits, including linguistic, cognitive, and behavioral impairment. The degree of the neuropsychological deficits appears to depend on the sleep cycle and the localization of epileptiform discharges. Furthermore, based on neurobiological studies, a complex interplay between the processes of brain maturation and the involvement of genes that confer susceptibility may contribute to a variety of different childhood epileptic syndromes with various neuropsychological deficits. Thus, BECTS, atypical benign focal epilepsy during childhood, status epilepticus of BECTS, Landau-Kleffner syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep are all considered different entities, but are part of a single spectrum of disorders. In clinical practice, we have to consider BECTS as benign only when there are no or only mild neuropsychological deficits before medical treatment.

Familial acute necrotizing encephalopathy with RANBP2 mutation: The first report in Northeast Asia.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare but rapidly progressing encephalopathy following a febrile illness, commonly a viral infection. It is characterized by the features of acute encephalopathy such as seizure, alteration of consciousness, and symmetric involvement of the bilateral thalamus on neuroimaging tests. Although most ANE cases have occurred sporadically, familial or recurrent ANE has been reported in Caucasian patients, with genetic susceptibility to ANE noted in some patients due to a RANBP2 mutation. We report the cases of two Korean siblings with typical ANE and RANBP2 mutation. CASE REPORT: A 2year-old Korean girl presented with prolonged seizures and encephalopathy after two days of febrile illness. Brain computed tomography (CT) showed diffuse brain swelling and low attenuation in the bilateral thalamus. Two months later, her younger sister presented with lethargy and flurries of seizures after a Mycoplasma pneumoniae infection. Brain magnetic resonance imaging scan (MRI) showed a characteristic involvement of the bilateral thalamus, suggesting ANE. Although they received intravenous steroids and immunoglobulin, the older child died; her sister remained in a coma. Both were diagnosed with familial ANE after identifying a common missense mutation in RANBP2 (c.1754C>T: p.Thr585Met) in the younger sister and their father. CONCLUSIONS: This report is the first case of familial ANE in Northeast Asia identifying a RANBP2 mutation with poor outcome. Due to rapidly deterioration and recurrent nature of familial ANE, genetic test of RANBP2 mutation should be considered for early diagnosis. Further studies are needed to elucidate the nature of ANE.

Clinical importance of F-waves as a prognostic factor in Guillain-Barré syndrome in children.

PURPOSE: A limited number of studies have examined the link between F-wave abnormalities and clinical presentation in pediatric Guillain-Barré syndrome (GBS). Therefore, this study examined the importance of F-wave abnormalities as a prognostic factor in pediatric GBS patients. METHODS: The records and electrodiagnostic studies (EDS) of 70 GBS patients were retrospectively evaluated, and divided into 2 groups according to the results of EDS. Group A (n=33) presented with F-wave abnormalities, and group B (n=26) exhibited normal findings. We compared laboratory reports, clinical features, response to treatment, and prognosis between the 2 groups. RESULTS: Motor weakness was the most frequently observed symptom for either group. Clinically, the incidence of fever and upper respiratory symptoms differed between the 2 groups, while the prevalence of abnormal deep tendon reflex (DTR) was significantly higher in group A than B (P<0.05). Patients diagnosed with GBS had received intravenous immunoglobulin treatment: 94% in group A and 58% in group B. Furthermore, significantly greater numbers of patients in group A showed H-reflex abnormalities and poor prognosis compared with group B (P<0.05). CONCLUSION: This study demonstrated that F-waves are a clinically important prognostic factor in GBS. F-wave abnormalities were associated with abnormal DTR and poor prognosis in patients. Limited studies have examined the link between F-wave abnormalities and clinical results; therefore, further randomized controlled studies are needed to confirm the clinical characteristics and efficacy of treatments.