Vitamin B6 in acute encephalopathy with biphasic seizures and late reduced diffusion

Background The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures (FS), which poses a great diagnostic challenge for clinicians. Excitotoxicity is speculated to be the pathogenesis of AESD. Vitamin B6 (VB6) is essential for the biosynthesis of gamma-aminobutyric acid, an inhibitory neurotransmitter. The aim of this study is to investigate our hypothesis that VB6 deficiency in the brain may play a role in AESD. Methods We obtained cerebrospinal fluid (CSF) samples from pediatric patients with AESD after early seizures and those with FS. We measured pyridoxal 5′-phosphate (PLP) and pyridoxal (PL) concentrations in the CSF samples using high-performance liquid chromatography with fluorescence detection. Results The subjects were 5 patients with AESD and 17 patients with FS. Age did not differ significantly between AESD and FS. In AESD, CSF PLP concentration was marginally lower (p = 0.0999) and the PLP-to-PL ratio was significantly (p = 0.0417) reduced compared to those in FS. Conclusions Although it is impossible to conclude that low PLP concentration and PLP-to-PL ratio are causative of AESD, this may be a risk factor for developing AESD. When combined with other markers, this finding may be useful in distinguishing AESD from FS upon initial presentation

Effect of adrenocorticotropic hormone therapy for epileptic spasms developing after the age of 1 year

AbstractPurposeEpileptic spasms sometimes begin after the first year of life, and such seizures are recognized as late-onset spasms (LOS). The prognosis of LOS is poor, and a treatment strategy has not been established. This study aimed to assess the short- and long-term effects of adrenocorticotropic hormone (ACTH) therapy for LOS.MethodsWe investigated the rate of LOS in 22 patients (14 boys and 8 girls) treated with ACTH therapy. The age at onset of LOS and at the start of ACTH therapy ranged from 12 to 94 months (median, 31.6±22.1 months) and from 12.5 to 116 months (median, 37.5±23.7 months), respectively. We investigated the response rate of LOS treated with ACTH therapy, and compared the clinical features between responders (short-term) and nonresponders.ResultsNine (41%) of the 22 patients showed cessation of epileptic spasms within 3 months. The epileptic spasms ceased in four of these nine patients for more than 1 year. The age at onset of LOS was significantly associated with short-term seizure cessation (p<0.05). Patients who achieved short-term cessation of seizures received ACTH therapy within 6 months from the onset of LOS.ConclusionACTH therapy is a potentially effective treatment when started within 6 months from the onset of LOS. A younger age at onset of LOS is associated with a favorable outcome

Ictal Tc-Ethyl Cysteinate Dimer SPECT Findings of a Girl With Refractory Localization-Related Epilepsy Who Developed Transient Ictal Bradycardia

Ictal bradycardia, which is considered to be one of the causes of sudden unexplained death in epilepsy, is rare. A 10-year-old girl with focal cortical dysplasia in her right centroparietal region developed transient ictal bradycardia during cluster seizures. Brain magnetic resonance imaging demonstrated a high signal intensity lesion adjacent to the focal cortical dysplasia lesion. Ictal 99m Tc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) detected hyperperfusion in an area containing the high signal intensity lesion, which was located close to the insular cortex. Since the hyperperfusion zone observed on SPECT was considered to reflect seizure propagation, it is possible that the ictal bradycardia experienced in the present case was caused by the following mechanism: The repetitive seizure activity caused the high-intensity lesion seen on MRI to expand into the right insular cortex, which controls cardiac rhythm, resulting in ictal bradycardia

Nonacidic Chemotype Possessing <i>N</i>‑Acylated Piperidine Moiety as Potent Farnesoid X Receptor (FXR) Antagonists

Farnesoid X receptor (FXR) plays a major role in the control of cholesterol metabolism. Antagonizing transcriptional activity of FXR is an effective means to treat the relevant metabolic syndrome. Some of antagonists so far have the charged functions; however, they may negatively affect the pharmacokinetics. We describe herein a structure–activity relationship (SAR) exploration of nonacidic FXR antagonist <b>6</b> focusing on two regions in the structure and biological evaluation of nonacidic <b>10</b> with the characteristic <i>N</i>-acylated piperidine group obtained from SAR studies. As the robust affinity to FXR is feasible with our nonacidic analogue, <b>10</b> is among the most promising candidates for <i>in vivo</i> testing

Comprehensive study of metabolic changes induced by a ketogenic diet therapy using GC/MS- and LC/MS-based metabolomics

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