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Wolf-Hirschhorn syndrome (WHS) is caused by deletion of the terminal region of chromosome 4 short arm and is frequently associated with intractable epilepsy. This article evaluates the clinical features of epileptic seizures in WHS and the therapeutic efficacy of oral antiseizure medications (ASMs). Patients with WHS who were treated for epilepsy at the Saitama Children's Medical Center under 5 years of age were included. WHS was diagnosed based on genetic tests and clinical symptoms. Medical records regarding the age of onset of epilepsy, seizure type, treatment of status epilepticus (SE), and effectiveness of ASMs were retrospectively reviewed. Oral ASMs were considered effective when seizures were reduced by at least 50% compared with the premedication level. Eleven patients were included in the study. The median age at the onset of epilepsy was 9 months (range: 5-32 months). Unknown-onset bilateral tonic-clonic seizure was the most common type of seizure, occurring in 10 patients. Focal clonic seizures occurred in four patients. Ten patients exhibited recurrent episodes of SE, and its frequency during infancy was monthly in eight patients and yearly in two. SE occurrence peaked at 1 year of age and decreased after 3 years of age. The most effective ASM was levetiracetam. Although WHS-associated epilepsy is intractable with frequent SE occurrence during infancy, improvement in seizure control is expected with age. Levetiracetam may be a novel ASM for WHS., Competing Interests: S.H. received funding for travel and speaker honoraria from UCB Japan Co. Ltd, Daiichi Sankyo Co. Ltd., and Eisai Co. Ltd., and received research funds from Syneos Health Clinical Co. Ltd for the clinical trial of Zogenix. K.K. received research funds from Syneos Health Clinical Co. Ltd. for the clinical trial of Zogenix. Atsuro Daida received grant funding to research abroad from SENSHIN Medical Research Foundation. The other authors have no conflicts of interest to declare., (Thieme. All rights reserved.)

Purpose: We aimed to evaluate choice and efficacy of intravenous antiepileptic drugs (AEDs) for status epilepticus (SE) in Dravet syndrome and to find predictable clinical features demonstrating the effectiveness of benzodiazepine (BZD) for SE., Methods: We retrospectively investigated the medical records in patients with Dravet syndrome and evaluated the effectiveness rate of intravenous AEDs and the rate of adverse effects. To find the clinical features of BZD-effective SE, we divided the SE episodes into the following two groups: BZD effective group and BZD non-effective group. The choice of treatment was dependent on physicians' discretion according to the protocol for SE in our institution., Results: Sixty-eight SE episodes in 10 patients were assessed. The median age at SE was 31 months. Of 68 episodes, 42 episodes (61.8%) were in the BZD effective group and 26 (38.2%) in the BZD non-effective group. There were no significant differences in clinical features. In the BZD non-effective group, the effective rates of continuous midazolam, phenobarbital, phenytoin/fosphenytoin were 9/9 episodes (100%), 14/17 (82.4%), and 2/5 (40.0%), respectively. Adverse effects were identified in 19/68 episodes (27.9%), including 11/42 episodes in the BZD effective group and 8/26 in the BZD non-effective group, which was no statistical difference between the two groups. Respiratory suppression was found in all 19 episodes and the incidence of endotracheal intubation in the BZD non-effective group (15.4%) was higher than that in the BZD effective group (2.4%) (p = 0.046)., Conclusion: BZD may be used as first choice, and phenobarbital prior to continuous midazolam as second choice for SE with Dravet syndrome. There might be no predictable clinical features showing that BZD will be effective., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate whether serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels predict response to adrenocorticotropic hormone (ACTH) therapy in patients with infantile spasms., Methods: We prospectively evaluated patients with infantile spasms who were referred to Saitama Children's Medical Center from January 2011 to December 2020. We measured Q-albumin and serum MMP-9 and TIMP-1 levels before ACTH therapy. Patients were divided into three groups based on the etiology of their infantile spasms: those with an unknown etiology and normal development (unknown-normal group); those with a structural and acquired etiology (structural-acquired group); and those with a structural and congenital, genetic, metabolic, or unknown etiology with developmental delay (combined-congenital group). Responders were defined as those having complete cessation of spasms for more than 3 months with the resolution of hypsarrhythmia on electroencephalography during ACTH therapy., Results: We collected serum from 36 patients with West syndrome and five patients with infantile spasms without hypsarrhythmia before ACTH therapy. Twenty-three of 41 patients (56.1%) were responders, including 8/8 (100%) in the unknown-normal group, 6/9 (66.7%) in the structural-acquired group, and 9/24 (37.5%) in the combined-congenital group. The serum MMP-9 level and MMP-9/TIMP-1 ratio were significantly higher in responders than in nonresponders (P = 0.001 for both)., Conclusion: A therapeutic response to ACTH was associated with a higher serum MMP-9 level and higher MMP-9/TIMP-1 ratio in patients with infantile spasms. Therefore, these biomarkers may predict responses to ACTH therapy in this patient population., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Telemedicine has spread rapidly during the coronavirus disease 2019 (COVID-19) pandemic and shown its usefulness, particularly for patients with epilepsy, compared to face-to-face visits. We sought to evaluate the clinical features of patients with childhood onset epilepsy associated with consultations by telephone call during the COVID-19 pandemic., Methods: We retrospectively investigated the medical records of patients with childhood onset epilepsy who visited an outpatient clinic in Saitama Children's Medical Center, Saitama, Japan, from 1 March 2020 to 30 September 2020. To find the clinical features of patients who utilized telemedicine consultation (by telephone call), we divided the patients into the telemedicine group and the face-to-face group. We then reviewed the clinical features. Telemedicine consultation was not implemented for new patients., Results: We enrolled 776 outpatients in total, and 294 patients (37.9%) utilized telemedicine consultations. The total number of visits was 2,299 and the total number of telemedicine consultations was 373 (16.2%). No clinical feature was associated with telemedicine consultations except for age at onset of epilepsy. The number of oral antiepileptic drugs prescriptions decreased in 23 of 776 (3.0%) of the patients who did not experience seizure deterioration, including status epilepticus, or who visited the emergency room., Conclusion: Telemedicine consultations were successfully utilized for epilepsy treatment at our outpatient clinic, regardless of epilepsy type, etiology, seizure frequency, comorbidities, and patients' residential areas. Thus, telemedicine by telephone call may be a useful resource in the management of patients with childhood onset epilepsy during the pandemic., (© 2021 Japan Pediatric Society.)

Purpose: We aimed to study the efficacy of adrenocorticotropic hormone (ACTH) treatment on infantile spasms with different aetiologies. In particular, we were interested in patients with structural-acquired aetiology., Methods: Patients with infantile spasms, who were treated with ACTH, were divided into three groups based on the aetiologies: unknown aetiology with normal development (unknown-normal), structural-acquired, and combined-congenital aetiologies that included genetic, metabolic, structural-congenital, or unknown aetiology with developmental delay., Results: Of the 107 patients included (58 males, 49 females), 25 patients had unknown-normal aetiology [median age at onset 5 months, standard deviation (SD) 3.12, range 2-16 months]; 20 patients had structural-acquired aetiology (median age at onset 6.5 months, SD 3.85 months, range 4-17 months); and 62 patients had combined-congenital aetiologies (median age at onset 5 months, SD 2.73 months, range 2-16 months). The efficacy of ACTH was 64.0 %, 65 %, and 30.6 % in the unknown-normal aetiology, structural-acquired aetiology, and combined-congenital aetiologies, respectively (p < 0.01). Multivariate analysis showed a statistically significant higher efficacy in the unknown-normal aetiology [Odds ratio (OR) 4.63, 95 % confidence interval (CI) 1.60-13.30] and structural-acquired aetiology (OR 3.41, 95 % CI 1.01-11.50) compared to that in the combined-congenital aetiologies., Conclusion: Infantile spasms with structural-acquired aetiology had greater response to ACTH treatment than those with combined-congenital aetiologies. The efficacy of standard therapy of infantile spasms should be considered based on aetiology., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Some pediatric patients with autoimmune encephalitis (AE) experience sequelae in spite of immunotherapy. In this study, we aimed to evaluate the association of serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels with the neurological prognosis of AE., Methods: We retrospectively included 13 patients with AE who had been referred to Saitama Children's Medical Center from February 2011 to May 2019. We compared serum MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio in the acute period (within 30 days from the onset of AE) and subacute period (30-day period following the acute period). We also compared these biomarker levels between patients with (group A) and without sequelae (group B). Sequelae were evaluated at discharge or the last visit., Results: Group A (median age, 7.8 years; range, 5.3-10.7 years) and group B (median age, 13.3 years; range, 11.1-15.4 years) had 6 patients each; 1 patient was excluded because the time of AE onset was unknown. In the acute period, there were no significant differences in MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio between groups A and B. In the subacute period, serum MMP-9/TIMP-1 ratio was higher in group A than in group B (p < 0.01). There were no significant differences in MMP-9 and TIMP-1 levels between groups A and B., Conclusions: Patients with sequelae of AE showed a high MMP-9/TIMP-1 ratio in the subacute period. Our study demonstrates that elevation of serum MMP-9/TIMP-1 ratio in the subacute period may be a predictive factor of sequelae of AE., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the general presentation of epileptic spasms without hypsarrhythmia (ESwoH) and retrospectively determine whether there are differences in treatment effects related to ACTH therapy, long-term seizure outcome, and evolution of EEG features according to pre-treatment EEG patterns. According to the pattern of background activity, we divided our cohort into two groups: Group 1: normal background activity or with localized intermittent slow waves; Group 2: intermittent slow waves appearing generalized or in two or more lobes. Subjects included 22 children (Group 1: n=10; Group 2: n=12) diagnosed with ESwoH who received treatment from 2007 to 2017. The median age at onset of epileptic spasms was 5.5 months and the follow-up period lasted for 40.5 months. ACTH therapy was performed for seven patients from Group 1 and eight patients from Group 2. Only one patient from Group 2 responded to ACTH. Patients receiving effective treatments at early stages had excellent seizure outcome. Refractory cases included six patients in Group 1 and eight patients in Group 2; subsequent follow-up EEGs indicated hypsarrhythmia in one patient in Group 1 (17%) and six patients (75%) in Group 2, including one patient whose EEG pattern indicated progression to Lennox-Gastaut syndrome. Overall, ACTH is ineffective for patients with epileptic spasms without hypsarrhythmia. The EEG may indicate possible future development of hypsarrhythmia if epileptic spasms are resistant to treatment, especially in patients with diffuse slow waves on pre-treatment EEG. The efficacy of treatment introduced at early stages from onset may predict long-term seizure outcome.

The aim of this study was to investigate the association between RDW values and the prognosis of patients with Bell palsy in an effort to find a prognostic biomarker that predicts recovery from Bell palsy. We measured RDW and evaluated facial movement in 61 patients with Bell palsy aged 50 years and less. All patients were treated with a steroid plus an antiviral agent. Seven patients underwent surgery for facial nerve decompression. During the post-treatment period, patients with a Yanagihara grading score of 36 or more were regarded as having a satisfactory recovery. Patients were divided into two groups (recovered and unrecovered) according to their response to treatment, and several parameters, including the RDW, were measured for further analysis. RDW values were significantly higher in the unrecovered group than in the recovered group (13.5 ± 1.7 vs. 12.7 ± 0.7%, p = 0.046). In the multiple logistic regression model, RDW was the only factor associated with recovery from Bell palsy (odds ratio 1.93, 95% confidence interval 1.02-4.65, p = 0.042). Our preliminary study provides the first evidence that the red cell distribution width (RDW) can predict recovery from Bell palsy in patients aged 50 years and less. Further studies are necessary to elucidate the potential pathophysiological mechanisms for our findings.

Conclusion: Red cell distribution width (RDW) can predict outcome in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Further studies are required to clarify the potential pathophysiological explanations for these findings., Objectives: RDW is one of the parameters reported in a complete blood count, and is elevated in direct proportion to variation in red cell size (anisocytosis). High RDW values are strongly associated with poor clinical outcomes in various diseases, including inflammatory and thrombotic diseases. To identify a prognostic biomarker that better predicts outcomes after ISSNHL, the association between RDW values at hospitalization and prognosis in patients with ISSNHL was assessed., Method: This study measured RDW and performed hearing assessments in 89 consecutive patients with ISSNHL. Patients were then divided into two groups ('recovered' and 'unrecovered'), according to their response to the treatment, and further analysis undertaken., Results: Mean RDW was significantly higher in the unrecovered group (13.2% ± 1.0% compared with 12.7% ± 0.7% in the recovered group, p = 0.031). After adjusting for potentially confounding factors in a binary logistic regression model, only RDW was associated with recovery from ISSNHL (odds ratio = 2.33, 95% confidence interval = 1.20-4.51, p = 0.012).

Conclusion: In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea., Objectives: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of gadoteridol and gadodiamide., Method: In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range = 8-32 kHz), the test solution (gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status., Results: At 14 days following gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32 kHz. Gadodiamide application caused a significant change in the ABR threshold at 8 kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after gadoteridol or gadodiamide application.

Aim: To examine the effects of patient age, canalicular obstruction, mode of anesthesia, and duration of nasolacrimal intubation on the outcomes of endoscopic endonasal dacryocystorhinostomy (DCR)., Methods: Totally 56 eyes of 46 patients with prolonged epiphora underwent minimally invasive endoscopic endonasal DCR. A successful surgical outcome was defined as a significant improvement in symptoms, adequate water passage from the puncta to the nasal cavity, and patency of the DCR ostium. All outcomes were assessed at least 6mo after extubation. Fisher's exact test was used to discuss the factors, and then the logistic regression analysis was made by SAS 9.4 software., Results: The overall success rate was 75.0%, and complete resolution was observed in 27 eyes. The success rate was higher for patients with ≥6mo intubation than for those with <6mo intubation. However, there were no significant differences in outcomes between groups stratified by age (<65 or ≥65y), presence or absence of canalicular obstruction, mode of anesthesia (local or general), and use or nonuse of a radiowave unit. One patient developed subcutaneous emphysema around the eye and nose and one developed subcutaneous hemorrhage after surgery., Conclusion: Endoscopic endonasal DCR can be considered safe and minimally invasive with reasonable success rates, particularly when the duration of nasolacrimal intubation is ≥6mo.

Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

Conclusion: After the administration of a standard dose of gadodiamide, an intravenous gadolinium-based contrast agent (GBCA), magnetic resonance imaging (MRI) evaluation of endolymphatic hydrops (EH) became possible in patients with ipsilateral delayed endolymphatic hydrops (DEH). We found that patients with ipsilateral DEH may also have bilateral EH., Objective: MRI evaluation contributes to understanding of the pathological conditions in patients with EH. However, double or triple the standard dose of GBCA is often required to obtain images of high quality. We attempted to examine EH bilaterally in patients with ipsilateral DEH after routine administration of an intravenous GBCA., Methods: GBCA (gadodiamide, 0.2 ml/kg) was administered intravenously to five patients with ipsilateral DEH. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR) MRI was performed with a 3-T MRI scanner 4 h after GBCA administration., Results: In all five patients, EH was observed in the affected vestibules. Moreover, EH was observed bilaterally in four (80%) of five patients with ipsilateral DEH. The region of the deaf ear affected by EH was considerably larger compared with the normal ear in three patients. However, observed regions of EH were of approximately the same size in both ears in patients 4 and 5.

Acute epiglottitis may trigger death because of serious airway obstruction. It is necessary to perform emergency and accurate airway intervention. In this retrospective study we present 216 cases of acute epiglottitis in adults. Airway management was done in 39 cases (18.1%), but most cases were treated conservatively. The mean patient age was 53 years and the male-to-female ratio was 1.9 to 1.0. The most frequent symptoms were sore throat (88%). The mean duration from symptom onset to consultation to our hospital was 1.9 days in the airway management group and 2.9 days in the conservatively treated group, which was statistically significant (p<0.05). Focusing on epiglottal swelling seen under the flexible laryngoscope, the percentage of airway management was 52.6% for swelling of the unilateral false vocal cords and 12.9% for swelling of the aryepiglottic fold. A statistically significant difference was also seen in complaints of respiratory difficulties (p<0.01), the rise of WBC (p<0.01), the rise of CRP (p<0.01), and diabetes mellitus (p<0.01).

Conclusion: Administration of diluted solutions of gadoteridol might cause considerably less toxic effects on cochlear outer hair cells (OHCs)., Objectives: Visualization of endolymphatic hydrops is done by intratympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. Here, we investigated the physiological and morphological responses of guinea pig cochlear cells to gadoteridol., Methods: Distortion product otoacoustic emission (DPOAE) levels were measured before and 1, 2, and 4 weeks after intratympanic injection of 1/8 or 1/16 dilution of gadoteridol in guinea pigs. Morphological changes in isolated cochlear OHCs were observed after application of gadoteridol and GdCl3., Results: At the highest frequency (F2 = 12 000 Hz), DPOAE level was significantly (p < 0.05) lower in the 1/8 diluted gadoteridol group than in the control group. Cell shape changes were observed in 24% (6/25) and 3% (1/33) of OHCs after application of 1/8 and 1/16 diluted gadoteridol, respectively. The occurrence of morphological damage was significantly lower after application of saline compared with 1/8 diluted gadoteridol. Morphological damage was significantly lower after application of 1/16 diluted gadoteridol compared with 1/8 diluted gadoteridol (p < 0.05). Morphological damage was observed at a high rate (8/10 cells, 80%) after application of GdCl3.

Conclusion: Even after the administration of a standard dose of an intravenous gadolinium-based contrast agent (GBCA), visualization of endolymphatic hydrops (ELH) became possible in patients with Meniere's disease. The next step would be to consistently visualize ELH in the upper part of the cochlea., Objective: To visualize ELH after routine administration of an intravenous GBCA., Methods: An intravenous GBCA (gadodiamide; 0.2 ml/kg) was administered to three patients with unilateral Meniere's disease and two healthy volunteers. Three-dimensional fluid attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) was performed with a 3 T MRI scanner 4 h later., Results: In all three patients, ELH was observed in the affected vestibules. In contrast, the endolymphatic space of both vestibules was the same size in healthy volunteers. ELH of the cochlea was not observed in any of the subjects. Gadolinium enhancement was insufficient in the upper turns of both cochleae in patients 1 and 3.

Conclusion: The findings suggest that alterations in the composition of inner ear fluid play important roles in the development of low-tone sudden deafness (LTSD). High-intensity signals on three-dimensional fluid attenuated inversion recovery (3D-FLAIR) may reflect an increased concentration of protein in the inner ear due to the increased permeability of blood vessels. Disordered blood flow in the inner ear is associated with an increased permeability of the blood-labyrinth barrier. Therefore, the disordered blood flow in the cochlea may be closely related to the pathophysiological mechanisms of LTSD., Objectives: The 3D-FLAIR sequence has been used to detect alterations in the composition of inner ear fluid. The purpose of this study was to report imaging findings in cases of LTSD., Methods: 3D-FLAIR magnetic resonance imaging was performed in five women with nonrecurrent-type LTSD., Results: Three of the five patients (60%) showed high-intensity signals in the cochlear basal turn on precontrast 3D-FLAIR. Postcontrast enhancement was not prominent in any patient. In patient 1, the cochlea of the unaffected side showed high-intensity signals. No patients had such signals in the vestibulae or the semicircular canals.

At the present time, the origin of protein bound D-amino acid (AA) has been fairly well elucidated, but that of free D-AA is still not well understood. To gain greater understanding of this, intestinal absorption in rats of free D,L-AA enantiomers (arginine, alanine and aspartic acid as models for basic, neutral and acidic AAs, respectively, in this study) and the relationship between age and absorption were investigated. The degree of rat intestinal absorption of free D,L-AAs was evaluated using apparent membrane permeability coefficients (Papp) which were obtained from an in situ intestinal single-pass perfusion method with Krebs-Ringer bicarbonate buffer (pH 7.4) solution containing D,L-AA enantiomers. Determinations of D,L-AA enantiomers in perfusion (in- and outflow) solutions were carried out by the in-capillary derivatization high-performance capillary electrophoretic methods (ICD-HPCE methods) that were previously developed by our group. Collectively, our observations suggest: (1) that the Papp of L-AA is higher than that of the D-isomer; (2) that D-AA can be absorbed as well as L-AA using a sodium ion-dependent transporter that is located on the brush border membrane of rat intestinal epithelial cells; (3) that Papp reached a maximum at 8 weeks of age, but were measured at decreased amounts at 52 and 104 weeks of age. These results suggest that free D-AA in a mammalian body originates from 'exogenous sources'.