Long-term analysis of adrenocorticotropic hormone monotherapy for infantile epileptic spasms syndrome with periventricular leukomalacia.

PURPOSE: Infantile epileptic spasms syndrome (IESS) with periventricular leukomalacia (PVL) has a poor neurological prognosis. Adrenocorticotropic hormone (ACTH) and vigabatrin therapies are the recommended first-line treatments for IESS. However, ACTH monotherapy for IESS with PVL has not been studied in detail. We analysed long-term outcomes of ACTH monotherapy for IESS with PVL. METHODS: We retrospectively examined 12 patients with IESS and PVL at Saitama Children's Medical Center between January 1993 and September 2022. We evaluated seizure outcomes 3 months post-ACTH therapy and at the last visit. We also assessed electroencephalography findings and developmental outcomes. A positive response was defined as complete remission of epileptic spasms, no other seizure types, and hypsarrhythmia resolution post-ACTH therapy. RESULTS: The median onset age of epileptic spasms was 7 (range: 3-14) months. The median age at initiation of ACTH therapy was 9 (7-17) months. Seven of 12 patients (58.3%) showed a positive response. The median age at the last visit was 5 years and 6 months (1 year and 5 months-22 years and 2 months). At the last visit, only 2 of 7 initial responders remained seizure-free who demonstrated normal electroencephalography findings within 1-month post-ACTH therapy. Patients with epileptic discharge in the parieto-occipital region within 1-month post-ACTH therapy showed relapse of epileptic spasms or other seizure types. CONCLUSION: Patients having epileptic discharge in the parietal or occipital regions on electroencephalography within 1-month post-ACTH therapy may be at a high risk of epileptic spasm recurrence or other seizure types in the long term.

Efficacy of Antiseizure Medications in Wolf-Hirschhorn Syndrome.

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.

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.

Quantitative pretreatment EEG predicts efficacy of ACTH therapy in infantile epileptic spasms syndrome.

OBJECTIVE: This study aimed to determine the correlation between outcomes following adrenocorticotrophic hormone (ACTH) therapy and measurements of relative power spectrum (rPS), weighted phase lag index (wPLI), and graph theoretical analysis on pretreatment electroencephalography (EEG) in infants with non-lesional infantile epileptic spasms syndrome (IESS). METHODS: Twenty-eight patients with non-lesional IESS were enrolled. Outcomes were classified based on seizure recurrence following ACTH therapy: seizure-free (F, n = 21) and seizure-recurrence (R, n = 7) groups. The rPS, wPLI, clustering coefficient, and betweenness centrality were calculated on pretreatment EEG and were statistically analyzed to determine the correlation with outcomes following ACTH therapy. RESULTS: The rPS value was significantly higher in the delta frequency band in group R than in group F (p < 0.001). The wPLI values were significantly higher in the delta, theta, and alpha frequency bands in group R than in group F (p = 0.007, <0.001, and <0.001, respectively). The clustering coefficient in the delta frequency band was significantly lower in group R than in group F (p < 0.001). CONCLUSIONS: Our findings demonstrate the significant differences in power and functional connectivity between outcome groups. SIGNIFICANCE: This study may contribute to an early prediction of ACTH therapy outcomes and thus help in the development of appropriate treatment strategies.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

The effectiveness of intravenous benzodiazepine for status epilepticus in Dravet syndrome.

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.

Telemedicine in epilepsy management during the coronavirus disease 2019 pandemic.

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.

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.

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.

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.

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.

Efficacy and serum concentrations of perampanel for treatment of drug-resistant epilepsy in children, adolescents, and young adults: comparison of patients younger and older than 12 years.

PURPOSE: Perampanel (PER) is a selective, non-competitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. In Japan, PER is approved for patients with epilepsy who are at least 12 years old for the adjunctive treatment of primary generalised tonic-clonic seizures and partial-onset seizures (with or without secondary generalization). We surveyed the efficacy, adverse effects, and serum concentrations of PER, focusing especially on patients younger than 12 years of age. METHODS: We retrospectively surveyed the clinical information of patients treated with PER and assessed the efficacy at 6 months after treatment initiation. We compared efficacy, adverse effects, and serum concentration in patients younger or older than 12 years of age. Responders were defined as those who experienced a ≥50% seizure reduction. RESULTS: Eighty-four patients were enrolled. The average age of the younger group was 7.1 ±â€¯3.3 (standard deviation) years compared to 16.4 ±â€¯3.7 years in the older group. The responder rate was 42.9% (36/84). The responder rate did not differ between the two age groups (<12 years, 20/44, 45.4%; >12 years, 16/40, 40.0%; p = 0.78). The younger age group had a significantly lower concentration-to-dose (CD) ratio than the older age group (<12 years, 1849.8 ±â€¯2209.3; >12 years, 3076.3 ±â€¯3352.2, p = 0.02). Treatment-emergent adverse events (TEAEs) were observed in 22.6% (19/84) of patients, with the most common being somnolence (8/84, 9.5%). CONCLUSION: PER may be an alternative to treat seizures in paediatric drug-resistant epilepsy. Serum concentrations of PER might be lower in patients younger than 12 years than in older patients.

Perampanel in lissencephaly-associated epilepsy.

We retrospectively investigated whether perampanel (PER) could serve as an alternative for treating drug-resistant seizures in lissencephaly. We investigated the following data: age at onset of epilepsy, age at start of PER, etiology, brain MRI findings, seizure type, seizure frequency, adverse effects, and concomitant anti-epileptic drugs. There were 5 patients with lissencephaly, including 2 with Miller-Dieker syndrome. Four out of five patients exhibited ≥ 50% seizure reduction. Myoclonic seizures disappeared in 1 patient. PER was an effective adjunctive anti-seizure drug in our series of patients with lissencephaly.

Efficacy and safety of pyridoxal in West syndrome: A retrospective study.

OBJECTIVE: To evaluate the efficacy and safety of pyridoxal for treating West syndrome. METHODS: We retrospectively investigated pyridoxal's efficacy and safety in 117 patients with West syndrome at Saitama Children's Medical Center from July 1993 to May 2016. Pyridoxal was administered at doses of 10-50 mg/kg/day. We evaluated seizure outcomes and electroencephalographic findings at 4 weeks after pyridoxal therapy. The responders were those with complete cessation of spasms for more than 4 weeks and those with resolution of hypsarrhythmia on EEG at 1-4 weeks after pyridoxal therapy. RESULTS: Five of the 117 patients (4.3%) were responders. The median duration between pyridoxal therapy to spasm cessation was 6 (5-13) days. Among the responders, four had hypsarrhythmia resolution, no spasm relapse, and no other seizure types more than 2 years after pyridoxal therapy. One responder had partial seizures and spasm relapse. No serious adverse effects occurred. There were no significant differences in sex, etiologies, complication, other seizure types preceding the spasms, onset age of spasms, age of pyridoxal therapy, treatment lag, initial and maintenance doses of pyridoxal, and adverse effects between pyridoxal responders and non-responders. CONCLUSIONS: The efficacy rate of pyridoxal monotherapy as first-line treatment for West syndrome was low. However, pyridoxal therapy showed a rapid response within 1 week and was safe. We consider pyridoxal therapy as a kind of challenge therapy during the evaluation period concerning differential diagnosis and etiologies of West syndrome and immunological risks before adrenocorticotrophic hormone therapy or vigabatrin therapy.

Quantitative evaluation of regional cerebral blood flow changes during childhood using 123I-N-isopropyl-iodoamphetamine single-photon emission computed tomography.

OBJECTIVE: To quantitatively evaluate regional cerebral blood flow (rCBF) and regional developmental changes during childhood using 123I-N-isopropyl-iodoamphetamine single-photon emission computed tomography (SPECT) and autoradiography. METHODS: We retrospectively analyzed quantitative values of rCBF in 75 children (29 girls) aged between 16 days and 178 months (median: 12 months), whose brain images, including magnetic resonance imaging and SPECT data, were normal under visual inspection at Saitama Children's Medical Center between 2005 and 2015. The subjects had normal psychomotor development, no focal neurological abnormalities, and neither respiratory nor cardiac disease at the time of examination. Regions of interest were placed automatically using a three-dimensional stereotactic template. RESULTS: rCBF was lowest in neonates, who had greater rCBF in the lenticular nucleus, thalamus, and cerebellum than the cerebral cortices. rCBF increased rapidly during the first year of life, reaching approximately twice the adult levels at 8 years, and then fell to approximately adult levels in the late teenage years. Cerebral cortex rCBF sequentially increased in the posterior, central, parietal, temporal, and callosomarginal regions during infancy and childhood. CONCLUSIONS: rCBF changed dramatically throughout childhood and ranged from lower than adult values to approximately two times higher than adult values. It had different trajectories in each region during brain development. Understanding this dynamic developmental change is necessary for SPECT image evaluation in children.