Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group

Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre-KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow-up, side events, and KDT discontinuation. It has been helpful in outlining a state-of-the-art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.ope

Generation of an Induced Pluripotent Stem Cell (iPSC) Line From a 42-year-old Adult Cerebral Type X-linked Adrenoleukodystrophy (X-ALD) Patient

X-linked Adrenoleukodystrophy (X-ALD) is a neuro-metabolic disorder that is caused by malfunction of a peroxisomal transporter protein, adenosine ATP-binding cassette transporter superfamily D member 1 (ABCD1). We established an induced pluripotent stem cell (iPSC) line from a 42-year-old male X-ALD patient-derived dermal fibroblasts with Sendai virus-mediated reprogramming. Established iPSCs stably expanded, expressed genes of pluripotency, and maintained normal karyotype. In vitro differentiation assay revealed the characteristics of all three germ layers.ope

Neurological Symptoms of SARS-CoV-2 Infection in Pediatric Patients

Purpose Coronavirus disease 2019 (COVID-19) causes various neurological symptoms in children, as well as respiratory symptoms, and the number of reported cases is increasing with the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. This study aimed to investigate the neurological symptoms and incidence in pediatric patients hospitalized with COVID-19. Methods We retrospectively analyzed the medical records of patients under the age of 18 diagnosed with COVID-19 and admitted to National Health Insurance Service Ilsan Hospital using real-time reverse transcription-polymerase chain reaction from December 2020 to March 2022. We reviewed data on the age of confirmed COVID-19 patients, fever, and respiratory, gastrointestinal, and neurological symptoms. We evaluated the chief complaints of hospitalization and classified them as non-neurological or neurological, according to the chief complaints that caused the most discomfort. Results Among 376 patients, 63 (16.8%) and 313 (83.2%) patients were classified as having neurological and non-neurological symptoms, respectively. The most common neurological symptoms were headache (49, 13.0%), followed by seizures (39, 10.4%), myalgia (24, 6.4%), and dizziness (14, 3.7%). Additionally, there were patients with anosmia (nine, 2.4%), ageusia (four, 1.1%), and visual disturbance (two, 0.5%). Of the 39 patients who experienced seizures, 15 (15/39, 51.7%) had no symptoms except fever, and seizures were the only main presenting symptom of SARS-CoV-2 infection. Conclusion Neurological symptoms are common in pediatric COVID-19 patients. Seizures can be an early symptom of SARS-CoV-2 infection and should not be underestimated during the COVID-19 pandemic.ope

Generation of two induced pluripotent stem cell (iPSC) lines from X-linked adrenoleukodystrophy (X-ALD) patients with adrenomyeloneuropathy (AMN)

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by a mutation in the ATP-binding cassette transporter subfamily D member 1 (ABCD1) gene. We generated two induced pluripotent stem cell (iPSC) lines from X-ALD patients with adrenomyeloneuropathy (AMN) by Sendai virus containing OCT4, SOX2, KLF4 and c-MYC. Established iPSC lines expressed various pluripotency markers, had differentiation potential of three germ layers in vitro, had normal karyotype and retained ABCD1 mutation.ope

Could Cannabidiol be a Treatment Option for Intractable Childhood and Adolescent Epilepsy?

Epilepsy is an important disease that affects brain function, particularly in those under 3 years old. Uncontrolled seizures can affect cognitive function and quality of life. For these reasons, many trials have been conducted to investigate treatments for pediatric epilepsy. Currently, many antiepileptic drugs are available for the treatment of epilepsy, but cases of intractable epilepsy continue to exist. In the past, cannabis has been tested as a potential treatment of intractable epilepsy. Since 2013, 10 epilepsy centers in America have conducted research regarding the efficacy of cannabis to treat epilepsy. Cannabis has many components, including cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). THC has psychoactive properties exerted through its binding of the cannabinoid receptor (CBR) whereas CBD is a CBR antagonist. The inhibition of epilepsy by CBD may therefore be caused by various mechanisms, although the detailed mechanisms of CBD actions have not yet been well defined. In most studies, trial doses of CBD were 2-5 mg/kg/day. Several such studies have shown that CBD does have efficacy for treatment of epilepsy. Reported adverse effects of CBD were mostly mild, including drowsiness, diarrhea, and decreased appetite. Severe adverse reactions requiring treatment, such as status epilepticus, have also been reported but it is not clear that this is related to CBD. Furthermore, many previous studies have been limited by an open-label or survey design. In future, double-blind, controlled trials are required and the use of CBD to treat other neurological problems should also be investigated.ope

Multicenter clinical study of childhood periodic syndromes that are common precursors to migraine using new criteria of the International Classification of Headache Disorders (ICHD-II).

PURPOSE: To evaluate the clinical features and characteristics of childhood periodic syndromes (CPS) in Korea using the new criteria of the International Classification of Headache Disorders (ICHD)-II. METHODS: The study was conducted at pediatric neurology clinics of five urban tertiary-care medical centers in Korea from January 2006 to December 2007. Patients (44 consecutive children and adolescents) were divided into three groups (cyclic vomiting syndrome [CVS], abdominal migraine [AM], and benign paroxysmal vertigo of childhood [BPVC]) by recurrent paroxysmal episodes of vomiting, abdominal pain, dizziness, and/or vertigo using the ICHD-II criteria and their characteristics were compared. RESULTS: Totally, 16 boys (36.4%) and 28 girls (63.6%) were examined (aged 4-18 yr), with 20 CVS (45.5%), 8 AM (18.2%), and 16 BPVC (36.4%) patients. The mean age at symptom onset was 6.3+/-3.6 yr, 8.5+/-2.7 yr, and 8.5+/-2.9 yr in the CVS, AM, and BPVC groups, respectively, showing that symptoms appeared earliest in the CVS group. The mean age at diagnosis was 8.0+/-3.4 yr, 10.5+/-2.6 yr, and 10.1+/-3.2 yr the CVS, AM, and BPVC groups, respectively. Of the 44 patients, 17 (38.6%) had a history of recurrent headaches and 11 (25.0%) showed typical symptoms of migraine headache, with 5 CVS (25.0%), 2 AM (25.0%), and 4 BPVC (25.0%) patients. Family history of migraine was found in 9 patients (20.4%): 4 in the CVS group (20.0%), 2 in the AM group (25.0%), and 3 in the BPVC group (18.8%). CONCLUSION: The significant time lag between the age at symptom onset and final diagnosis possibly indicates poor knowledge of CPS among pediatric practitioners, especially in Korea. A high index of suspicion may be the first step toward caring for these patients. Furthermore, a population-based longitudinal study is necessary to determine the incidence and natural course of these syndromesope

Real-Time Seizure Detection using EEG: A Comprehensive Comparison of Recent Approaches under a Realistic Setting

Electroencephalogram (EEG) is an important diagnostic test that physicians use to record brain activity and detect seizures by monitoring the signals. There have been several attempts to detect seizures and abnormalities in EEG sig nals with modern deep learning models to re duce the clinical burden. However, they cannot be fairly compared against each other as they were tested in distinct experimental settings. Also, some of them are not trained in real-time seizure detection tasks, making it hard for on device applications. In this work, for the first time, we extensively compare multiple state-of the-art models and signal feature extractors in a real-time seizure detection framework suitable for real-world application, using various evalu ation metrics including a new one we propose to evaluate more practical aspects of seizure de tection models.ope

Automatic Identification of Interictal Epileptiform Discharges in Secondary Generalized Epilepsy

Ictal epileptiform discharges (EDs) are characteristic signal patterns of scalp electroencephalogram (EEG) or intracranial EEG (iEEG) recorded from patients with epilepsy, which assist with the diagnosis and characterization of various types of epilepsy. The EEG signal, however, is often recorded from patients with epilepsy for a long period of time, and thus detection and identification of EDs have been a burden on medical doctors. This paper proposes a new method for automatic identification of two types of EDs, repeated sharp-waves (sharps), and runs of sharp-and-slow-waves (SSWs), which helps to pinpoint epileptogenic foci in secondary generalized epilepsy such as Lennox-Gastaut syndrome (LGS). In the experiments with iEEG data acquired from a patient with LGS, our proposed method detected EDs with an accuracy of 93.76% and classified three different signal patterns with a mean classification accuracy of 87.69%, which was significantly higher than that of a conventional wavelet-based method. Our study shows that it is possible to successfully detect and discriminate sharps and SSWs from background EEG activity using our proposed method.ope

Functional recovery after transplantation of mouse bone marrow-derived mesenchymal stem cells for hypoxic-ischemic brain injury in immature rats

PURPOSE: We aimed to investigate the efficacy of and functional recovery after intracerebral transplantation of different doses of mouse mesenchymal stem cells (mMSCs) in immature rat brain with hypoxic-ischemic encephalopathy (HIE). METHODS: Postnatal 7-days-old Sprague-Dawley rats, which had undergone unilateral HI operation, were given stereotaxic intracerebral injections of either vehicle or mMSCs and then tested for locomotory activity in the 2nd, 4th, 6th, and 8th week of the stem cell injection. In the 8th week, Morris water maze test was performed to evaluate the learning and memory dysfunction for a week. RESULTS: In the open field test, no differences were observed in the total distance/the total duration (F=0.412, P=0.745) among the 4 study groups. In the invisible-platform Morris water maze test, significant differences were observed in escape latency (F=380.319, P<0.01) among the 4 groups. The escape latency in the control group significantly differed from that in the high-dose mMSC and/or sham group on training days 2-5 (Scheffe's test, P<0.05) and became prominent with time progression (F=6.034, P<0.01). In spatial probe trial and visible-platform Morris water maze test, no significant improvement was observed in the rats that had undergone transplantation. CONCLUSION: Although the rats that received a high dose of mMSCs showed significant recovery in the learning-related behavioral test only, our data support that mMSCs may be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal dose that shows maximal efficacy for HIE treatment.ope

Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.ope