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Objective: The ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a subset of patients with drug-resistant epilepsy, although the mechanisms of the KD have not been fully elucidated. The aims of this observational study were to investigate comprehensive short-term metabolic changes induced by the KD and to explore candidate metabolites or pathways for potential new therapeutic targets., Methods: Subjects included patients with intractable epilepsy who had undergone the KD therapy (the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil). Plasma and urine samples were obtained before and at 2-4 weeks after initiation of the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS)., Results: Samples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively. The KD increased ketone bodies, various fatty acids, lipids, and their conjugates. In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA, including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric acid and lactic acid, were elevated., Conclusions: The metabolites that were significantly changed after the initiation of the KD and related metabolites may be candidates for further studies for neuronal actions to develop new anti-seizure medications., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mari Akiyama reports financial support was provided by Public Interest Incorporated Foundation Japan Epilepsy Research Foundation. Daisuke Saigusa reports financial support was provided by Government of Japan Ministry of Education, Culture, Sports, Science, and Technology. Daisuke Saigusa reports financial support was provided by Japan Agency for Medical Research and Development. Daisuke Saigusa reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Accurate estimation of the epileptogenic zone (EZ) is essential for favorable outcomes in epilepsy surgery. Conventional ictal electrocorticography (ECoG) onset is generally used to detect the EZ but is insufficient in achieving seizure-free outcomes. By contrast, high-frequency oscillations (HFOs) could be useful markers of the EZ. Hence, we aimed to detect the EZ using interictal spikes and investigated whether the onset area of interictal spike-related HFOs was within the EZ. Methods: The EZ is considered to be included in the resection area among patients with seizure-free outcomes after surgery. Using a complex demodulation technique, we developed a method to determine the onset channels of interictal spike-related ripples (HFOs of 80-200 Hz) and investigated whether they are within the resection area. Results: We retrospectively examined 12 serial patients who achieved seizure-free status after focal resection surgery. Using the method that we developed, we determined the onset channels of interictal spike-related ripples and found that for all 12 patients, they were among the resection channels. The onset frequencies of ripples were in the range of 80-150 Hz. However, the ictal onset channels (evaluated based on ictal ECoG patterns) and ripple onset channels coincided in only 3 of 12 patients. Conclusions: Determining the onset area of interictal spike-related ripples could facilitate EZ estimation. This simple method that utilizes interictal ECoG may aid in preoperative evaluation and improve epilepsy surgery outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Numata-Uematsu, Uematsu, Sakuraba, Iwasaki, Osawa, Jin, Nakasato and Kure.)

Biallelic 4-hydroxyphenylpyruvate dioxygenase-like protein ( HPDL ) variants were recently reported as a cause of progressive and incurable neurodegenerative diseases ranging from neonatal-onset leukoencephalopathy with severe neurodevelopmental delay to spastic paraplegia. Although the physiological function of HPDL remains unknown, its subcellular localization in the mitochondria has been reported. Here, we report a case of HPDL -related neurological disease that was clinically and neuroimaging compatible with Leigh syndrome, previously unreported, and was treated with a ketogenic diet., Competing Interests: None., (© 2021 The Authors.)

Objective: Cerebral palsy is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested genetic diseases can be misdiagnosed as cerebral palsy. We hypothesized that two simple criteria, that is, full-term births and nonspecific brain MRI findings, are keys to extracting masqueraders among cerebral palsy cases due to the following: (1) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of cerebral palsy and (2) brain MRI assessment is essential for excluding environmental causes and other particular disorders., Methods: A total of 107 patients-all full-term births-without specific findings on brain MRI were identified among 897 patients diagnosed with cerebral palsy who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole-exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines., Results: Pathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1 , CYP2U1 , SPAST , GNAO1 , CACNA1A , AMPD2 , STXBP1 , and SCN2A . Five identified variants had previously been reported. No pathogenic copy number variations were identified. The AMPD2 missense variant and the splice-site variants in CTNNB1 and AMPD2 were validated by in vitro functional experiments., Interpretation: The high rate of detecting causative genetic variants (52.9%) suggests that patients diagnosed with cerebral palsy in full-term births without specific MRI findings may include genetic diseases masquerading as cerebral palsy.

Many studies have reported many adverse effects of children's use of media. These effects include reduced cognitive development and hyperactivity and attention disorders. Although it has been recommended that child be kept away from the media during the early developmental period, many modern parents use the media as a way to calm their children. Consequently, these children lack the opportunity to form selective attachments by reduced social engagement. These children's symptoms occasionally mimic autism spectrum disorder (ASD). However, few studies have examined the symptoms children develop with early media exposure. Here, we present a boy exposed to the media during his early development who was diagnosed with attachment disorder. He was unable to make eye contact and was hyperactive and had delayed language development, like children with ASD. His symptoms improved dramatically after he was prevented from using all media and encouraged to play in other ways. After this treatment, he would make eye contact, and talked about playing with their parents. Simply avoiding the media and playing with others can change the behavior of a child with ASD-like symptoms. It is important to understand the symptoms caused by attachment disorder and early media exposure. J. Med. Invest. 65:280-282, August, 2018.