Low-temperature redox activity and alcohol ammoxidation performance on Cu- and Ru-incorporated ceria catalysts.

Transition-metal-incorporated cerium oxides with Cu and a small amount of Ru (Cu0.18Ru0.05CeOz) were prepared, and their low-temperature redox performance (<423 K) and catalytic alcohol ammoxidation performance were investigated. Temperature-programmed reduction/oxidation under H2/O2 and in situ X-ray absorption fine structure revealed the reversible redox behavior of the three metals, Cu, Ru, and Ce, in the low-temperature redox processes. The initially reduced Ru species decreased the reduction temperature of Cu oxides and promoted the activation of Ce species. Cu0.18Ru0.05CeOz selectively catalyzed the production of benzonitrile in the ammoxidation of benzyl alcohol. H2-treated Cu0.18Ru0.05CeOz showed a slightly larger initial conversion of benzyl alcohol than O2-treated Cu0.18Ru0.05CeOz, suggesting that the reduced structure of Cu0.18Ru0.05CeOz was active for the ammoxidation. The integration of both Cu and Ru resulted in the efficient promotion of ammoxidation, in which the Ru species were involved in the conversion of benzyl alcohol and Cu species were required for selective production of benzonitrile.

Electroencephalography-functional magnetic resonance imaging for clinical evaluation in focal epilepsy.

OBJECTIVE: We aimed to evaluate the contribution of simultaneous recording of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in the diagnosis of epilepsy syndrome, localization of the epileptogenic zone (EZ), and decision-making regarding surgical treatment. METHODS: We performed a retrospective study to evaluate patients with focal epilepsy who underwent EEG-fMRI. Two evaluators assessed epilepsy syndrome, presumed focus, and surgical candidacy and defined confidence levels. They assessed these clinical characteristics first without EEG-fMRI and then including EEG-fMRI to assess how the results of EEG-fMRI changed the evaluations. We also determined how the clinical evaluation was affected by the concordance level between the blood oxygen level-dependent (BOLD) response and the presumed focus location, and by the confidence level of the BOLD response itself based on the t-value of the primary and secondary clusters. RESULTS: Fifty-one scans from 48 patients were included. The BOLD map affected 66.7% of the evaluations by altering evaluation items (epilepsy syndrome, presumed focus, or surgical candidacy) or their confidence levels. EEG-fMRI results increased the confidence levels of epilepsy syndrome, presumed focus, or surgical candidacy in 47.1% of patients but reduced clinical confidence in these features in 11.8%. More specifically, the confidence levels increased for epilepsy syndrome in 28.5%, identification of presumed focus in 33.9%, and determination of surgical candidacy in 29.4%. The BOLD signal confidence level, whether high or low, did not influence these clinical factors. SIGNIFICANCE: Previous studies have emphasized the utility of EEG-fMRI for the localization of the epileptogenic zone. This study demonstrated the potential of EEG-fMRI to influence clinical confidence when determining epilepsy syndrome, the presumed epileptic focus, and surgical candidacy.

Mechanochemical Synthesis of Non-Solvated Dialkylalumanyl Anion and XPS Characterization of Al(I) and Al(II) Species.

A non-solvated alkyl-substituted Al(I) anion dimer was synthesized by a reduction of haloalumane precursor using a mechanochemical method. The crystallographic and theoretical analysis revealed its structure and electronic properties. Experimental XPS analysis of the Al(I) anions with reference compounds revealed the lower Al 2p binding energy corresponds to the lower oxidation state of Al species. It should be emphasized that the experimentally obtained XPS binding energies were reproduced by delta SCF calculations and were linearly correlated with NPA charges and 2p orbital energies.

Estimation of fMRI responses related to epileptic discharges using Bayesian hierarchical modeling.

Simultaneous electroencephalography-functional MRI (EEG-fMRI) is a unique and noninvasive method for epilepsy presurgical evaluation. When selecting voxels by null-hypothesis tests, the conventional analysis may overestimate fMRI response amplitudes related to interictal epileptic discharges (IEDs), especially when IEDs are rare. We aimed to estimate fMRI response amplitudes represented by blood oxygen level dependent (BOLD) percentage changes related to IEDs using a hierarchical model. It involves the local and distributed hemodynamic response homogeneity to regularize estimations. Bayesian inference was applied to fit the model. Eighty-two epilepsy patients who underwent EEG-fMRI and subsequent surgery were included in this study. A conventional voxel-wise general linear model was compared to the hierarchical model on estimated fMRI response amplitudes and on the concordance between the highest response cluster and the surgical cavity. The voxel-wise model overestimated fMRI responses compared to the hierarchical model, evidenced by a practically and statistically significant difference between the estimated BOLD percentage changes. Only the hierarchical model differentiated brief and long-lasting IEDs with significantly different BOLD percentage changes. Overall, the hierarchical model outperformed the voxel-wise model on presurgical evaluation, measured by higher prediction performance. When compared with a previous study, the hierarchical model showed higher performance metric values, but the same or lower sensitivity. Our results demonstrated the capability of the hierarchical model of providing more physiologically reasonable and more accurate estimations of fMRI response amplitudes induced by IEDs. To enhance the sensitivity of EEG-fMRI for presurgical evaluation, it may be necessary to incorporate more appropriate spatial priors and bespoke decision strategies.

Coordination-Induced Trigger for Activity: N-Heterocyclic Carbene-Decorated Ceria Catalysts Incorporating Cr and Rh with Activity Induction by Surface Adsorption Site Control.

A coordination-induced trigger for catalytic activity is proposed on an N-heterocyclic carbene (NHC)-decorated ceria catalyst incorporating Cr and Rh (ICy-r-Cr0.19Rh0.06CeOz). ICy-r-Cr0.19Rh0.06CeOz was prepared by grafting 1,3-dicyclohexylimidazol-2-ylidene (ICy) onto H2-reduced Cr0.19Rh0.06CeOz (r-Cr0.19Rh0.06CeOz) surfaces, which went on to exhibit substantial catalytic activity for the 1,4-arylation of cyclohexenone with phenylboronic acid, whereas r-Cr0.19Rh0.06CeOz without ICy was inactive. FT-IR, Rh K-edge XAFS, XPS, and photoluminescence spectroscopy showed that the ICy carbene-coordinated Rh nanoclusters were the key active species. The coordination-induced trigger for catalytic activity on the ICy-bearing Rh nanoclusters could not be attributed to electronic donation from ICy to the Rh nanoclusters. DFT calculations suggested that ICy controlled the adsorption sites of the phenyl group on the Rh nanocluster to promote the C-C bond formation of the phenyl group and cyclohexenone.

Adjunctive perampanel therapy for patients with epileptic spasms.

BACKGROUND: Perampanel is an antiepileptic drug. Some studies have documented the efficacy of perampanel in epileptic spasms. We aimed to evaluate the efficacy and safety of adjunctive perampanel therapy (PT) in patients with epileptic spasms. METHODS: We retrospectively surveyed the efficacy and safety of adjunctive PT in 14 patients with epileptic spasms at the Saitama Children's Medical Center between June 2016 and September 2021. Seizure outcomes and safety were evaluated 12 months after commencing PT. Response to perampanel was defined as complete remission of epileptic spasms for more than 3 months. RESULTS: The median age at onset of epileptic spasms was 0.4 years (range, 0.1-1.3 years). The etiology was structural in 11 patients, genetic in two, and unknown in one. The median age at the commencement of PT was 3.2 years (1.5-10.3 years). The initial and maintenance doses of perampanel were administered at 0.04 (range, 0.02-0.05) mg/kg/day and 0.12 (range, 0.03-0.24) mg/kg/day, respectively. Five of the 14 patients (35.7%) showed remission of epileptic spasms for more than 3 months at 12 months after PT; these patients had a structural etiology. The median duration between commencement of perampanel and spasm remission was 2 months (range, 1-6 months). No serious adverse effects occurred. CONCLUSIONS: This is the first case series evaluating adjunctive PT for epileptic spasms. PT is worth investigating to treat epileptic spasms in patients with structural etiologies. As our study population primarily comprised children aged 2 years and older, PT may be useful for epileptic spasms beyond infancy.

Electroencephalography-functional magnetic resonance imaging of epileptiform discharges: Noninvasive investigation of the whole brain.

Simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) is a unique and noninvasive method for investigating epileptic activity. Interictal epileptiform discharge-related EEG-fMRI provides cortical and subcortical blood oxygen level-dependent (BOLD) signal changes specific to epileptic discharges. As a result, EEG-fMRI has revealed insights into generators and networks involved in epileptic activity in different types of epilepsy, demonstrating-for instance-the implication of the thalamus in human generalized spike and wave discharges and the role of the default mode network in absences and focal epilepsy, and has suggested a mechanism for the cortico-subcortical interactions in Lennox-Gastaut syndrome discharges. EEG-fMRI can find deep sources of epileptic activity not available to scalp EEG or magnetoencephalography, and provides critical new information to delineate the epileptic focus when considering surgical treatment or electrode implantation. In recent years, methodological advances, such as artifact removal and automatic detection of events, have rendered this method easier to implement, and its clinical potential has since been established by evidence of the impact of BOLD response on clinical decision-making and of the relationship between concordance of BOLD responses with extent of resection and surgical outcome. This review presents the recent developments in EEG-fMRI methodology and EEG-fMRI studies in different types of epileptic disorders as follows: EEG-fMRI acquisition, gradient and pulse artifact removal, statistical analysis, clinical applications, presurgical evaluation, altered physiological state in generalized genetic epilepsy, and pediatric EEG-fMRI studies.

Serum matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-1 levels may predict response to adrenocorticotropic hormone therapy in patients with infantile spasms.

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.

Ultrahigh Proton Conduction via Extended Hydrogen-Bonding Network in a Preyssler-Type Polyoxometalate-Based Framework Functionalized with a Lanthanide Ion.

The exploration of composition-structure-function relationship in proton-conducting solids remains a challenge in materials chemistry. Polyoxometalate-based compounds have been long considered as candidates for proton conductors; however, their low structural stability and a large decrease in conductivity under reduced relative humidity (RH) have limited their applications. To overcome such limitations, the hybridization of polyoxometalates with proton-conducting polymers has emerged as a promising method. Besides, 4f lanthanide ions possess a high coordination number, which can be utilized to attract water molecules and to build robust frameworks. Herein, a Preyssler-type polyoxometalate functionalized with a 9-coordinate Eu3+ (Eu[P5W30O110K]11-) is newly synthesized and combined with poly(allylamine) with amine moieties as protonation sites. The resulting robust crystalline composite exhibits an ultrahigh proton conductivity >10-2 S cm-1 at 368 K and 90% RH, which is still >10-3 S cm-1 at 50% RH, due to the strengthened and extended hydrogen-bonding network.

Comparison of adrenocorticotropic hormone efficacy between aetiologies of infantile spasms.

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.

Efficient detection of copy-number variations using exome data: Batch- and sex-based analyses.

Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.

Zonisamide Therapy for Patients With Paroxysmal Kinesigenic Dyskinesia.

BACKGROUND: We evaluated zonisamide therapy in patients with paroxysmal kinesigenic dyskinesia (PKD). METHODS: We analyzed zonisamide therapy in 17 patients with PKD at Saitama Children's Medical Center between November 1994 and April 2020. We collected information regarding family history, previous history, age at onset, age at zonisamide commencement, dyskinesia characteristics, brain magnetic resonance imaging, interictal electroencephalography, treatment lag, zonisamide efficacy, zonisamide dose, serum zonisamide concentration, and adverse effects. We evaluated PKD frequency at six months after zonisamide therapy commencement. RESULTS: Fourteen patients met the inclusion criteria. The median age at zonisamide therapy commencement was 12.8 (9.4 to 16.3) years. Zonisamide therapy was effective in 13 of 14 (92.9%) patients: complete remission for more than three months after zonisamide therapy (n = 7), decreased dyskinesia frequency by more than 90% (n = 4), dyskinesia frequency by 75% to 90% (n = 2), and no change of dyskinesia frequency (n = 1). The initial and maintenance zonisamide doses were 2.0 (1.4 to 3.8) and 2.0 (1.5 to 5.9) mg/kg/day, respectively. The median duration between zonisamide therapy commencement and dyskinesia decrease or cessation was 4 (1 to 60) days: 10 of 14 (71.4%) patients responded to zonisamide within one week after zonisamide therapy commencement. Regarding adverse effects, two patients experienced somnolence and one developed reduced perspiration. CONCLUSIONS: We suggest that zonisamide monotherapy is effective for patients with PKD as a first-line treatment. We can evaluate the efficacy of zonisamide therapy within one week. Because zonisamide lacks the enzyme-inducing effects of carbamazepine and phenytoin, it may be useful for PKD treatment.

Mechanistic Understanding of the Heterogeneous, Rhodium-Cyclic (Alkyl)(Amino)Carbene-Catalyzed (Fluoro-)Arene Hydrogenation.

Recently, chemoselective methods for the hydrogenation of fluorinated, silylated, and borylated arenes have been developed providing direct access to previously unattainable, valuable products. Herein, a comprehensive study on the employed rhodium-cyclic (alkyl)(amino)carbene (CAAC) catalyst precursor is disclosed. Mechanistic experiments, kinetic studies, and surface-spectroscopic methods revealed supported rhodium(0) nanoparticles (NP) as the active catalytic species. Further studies suggest that CAAC-derived modifiers play a key role in determining the chemoselectivity of the hydrogenation of fluorinated arenes, thus offering an avenue for further tuning of the catalytic properties.

A recurrent TMEM106B mutation in hypomyelinating leukodystrophy: A rapid diagnostic assay.

INTRODUCTION: Hypomyelinating leukodystrophies (HLDs) are genetically heterogeneous syndromes, presenting abnormalities in myelin development in the central nervous system. Recently, a recurrent de novo mutation in TMEM106B was identified to be responsible for five cases of HLD. We report the first Japanese case of TMEM106B gene mutation. CASE STUDY: A 3-year-old patient presented with nystagmus and muscle hypotonia in his neonatal period, followed by delayed psychomotor development. Brain magnetic resonance images showed delayed myelination. Wave III and subsequent components were not presented by his auditory brainstem response. These features were similar to those observed in Pelizaeus-Merzbacher disease (PMD). METHODS: Proteolipid protein 1 (PLP1) gene screening, Mendelian disease panel exome, and whole-exome sequencing (WES) were sequentially performed. RESULTS: After excluding mutations in either PLP1 or other known HLD genes, WES identified a mutation c.754G > A, p.(Asp252Asn) in TMEM106B, which appeared to occur de novo, as shown by Sanger sequencing and SalI restriction enzyme digestion of PCR products. DISCUSSION: This is the sixth case of HLD with a TMEM106B mutation. All six cases harbored the same variant. This specific TMEM106B mutation should be investigated when a patient shows PMD-like features without PLP1 mutation. Our PCR-SalI digestion assay may serve as a tool for rapid HLD diagnosis.

High-power, frontal-dominant ripples in absence status epilepticus during childhood.

OBJECTIVE: Absence status epilepticus (ASE) is a form of non-convulsive status epilepticus characterized by ongoing or intermittent epileptic activity accompanied by behavioral and cognitive changes. Herein, we assessed high-frequency oscillations in the ripple band in patients with ASE and typical absence seizures. METHODS: We enrolled five patients with ASE, 26 patients with childhood absence epilepsy (CAE), and 15 patients with juvenile absence epilepsy (JAE). We performed time-frequency analysis of electroencephalogram data for ictal absence seizures at each electrode to assess the high frequency activity (HFA) rate, peak frequency, and peak power. RESULTS: The average HFA rates were 60.7%, 20.8%, and 12.9% in ASE, CAE, and JAE patients, respectively. The average peak frequencies were 126.4 Hz, 120.9 Hz, and 126.1 Hz in ASE, CAE, and JAE patients, respectively. The average peak power values were 2,388.8 µV2, 120.9 µV2, and 126.1 µV2 in ASE, CAE, and JAE patients, respectively, and all epilepsy groups exhibited frontal-dominant ripple distribution. CONCLUSION: ASE patients presented higher power and frontal dominant ripples of absence seizure, compared to CAE and JAE patients. SIGNIFICANCE: Future studies should utilize scalp-recorded ripples as a biomarker of absence epilepsy. This may aid in the development of novel treatment strategies for ASE.

Use of Perampanel and a Ketogenic Diet in Nonketotic Hyperglycinemia: A Case Report.

BACKGROUND: Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. CASE: The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. CONCLUSION: Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.

Clinical features and electroclinical evolution in 22 cases with epileptic spasms without hypsarrhythmia.

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.

Predictive factors of first dosage intravenous immunoglobulin-related adverse effects in children.

BACKGROUND: Intravenous immunoglobulin (IVIG) therapy is used in the treatment of various diseases, and IVIG-related adverse effects (IVIG-AEs) vary from mild to severe. However, the mechanisms underlying IVIG-AEs and the potential predictive factors are not clear. This study investigated whether certain IVIG-AEs can be predicted before IVIG administration. STUDY DESIGN AND METHODS: This retrospective cohort study at the Division of Neurology, Saitama Children's Medical Center included patients enrolled from 2008 to 2018 who were < 18 years old and received IVIG for the first time. IVIG-AEs were classified according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 104 patients fulfilled the inclusion criteria. The rate of IVIG-AEs was 37.5% (39/104). The most frequent IVIG-AEs were fever (41.0% [16/39]) and headache (38.5% [15/39]). AEs were below grade 2 in all except one patient and there were no grade 4 AEs. High serum total protein (TP) level was significantly related to the occurrence of IVIG-AEs (odds ratio, 14.8; 95% confidence interval, 2.4-90.5; P < 0.01). The optimal cutoff TP level was 6.7 g/dL. Although low WBC count and immunoglobulin G level may be predictive risk factors of IVIG-AEs, it was not confirmed in this study. CONCLUSION: IVIG-AEs occurred in 37.5% of cases, and most were mild. TP was the best predictive risk factor of IVIG-AEs before IVIG administration. These results may aid in elucidating the mechanism underlying IVIG-AEs.

Serum matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-1 levels in autoimmune encephalitis.

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.

Phenotype-genotype correlations in patients with GNB1 gene variants, including the first three reported Japanese patients to exhibit spastic diplegia, dyskinetic quadriplegia, and infantile spasms.

We report the first three Japanese patients with missense variants in the GNB1 gene. Patients exhibited severe dyskinetic quadriplegia with cortical blindness and epileptic spasms, West syndrome (but with good outcomes), and hypotonic quadriplegia that later developed into spastic diplegia. Whole-exome sequencing revealed two recurrent GNB1 variants (p.Leu95Pro and p.Ile80Thr) and one novel variant (p.Ser74Leu). A recent investigation revealed large numbers of patients with GNB1 variants. Functional studies of such variants and genotype-phenotype correlation are required to enable future precision medicine.