Publications by authors named "Shinsaku Yoshitomi"

17 Publications

  • Page 1 of 1

Methylprednisolone pulse therapy in 31 patients with refractory epilepsy: A single-center retrospective analysis.

Epilepsy Behav 2020 08 6;109:107116. Epub 2020 May 6.

National Epilepsy Center, NHO, Shizuoka Institute of Epilepsy and Neurological Disorders, Japan.

Purpose: We investigated the efficacy of methylprednisolone pulse therapy (MP) and responder characteristics in patients with refractory epilepsy.

Methods: We reviewed medical records of our center to identify patients with refractory epilepsy treated with MP other than continuous spikes and waves during slow sleep (CSWS), Landau-Kleffner syndrome (LKS), or Rasmussen's syndrome (RS) between 2004 and 2015. A course of MP consisted of intravenous methylprednisolone (30 mg/kg/day) on three consecutive days. Patients received multiple courses at intervals of four weeks. We examined seizure outcome, developmental outcome, antibodies to N-methyl-d-aspartate (NMDA)-type glutamate receptors (GluRs), cerebral spinal fluid (CSF)-albumin/serum-albumin ratio, and interictal electroencephalograms (EEGs). Responder to MP was defined as maintaining seizure reduction rate (SRR) ≥50% for three months after the first course of MP.

Results: Thirty-one consecutive patients treated with MP at our center were studied. Seizure types were focal onset impaired awareness seizure (FIAS) only (n = 23), FIAS with epileptic spasms (ES) (n = 7), and ES only (n = 1). Responder rate was 32.2% (10/31 patients), and seizure-free rate was 9.7% (3/31). Responders constituted 43.5% of patients without ES. No patient with ES was responder. Behavior and cognition also improved in 6 of 10 responders. History of seizure aggravation after inactivated vaccine before MP was found significantly higher rate in responder patients, comparing with nonresponder patients (p = 0.01).

Conclusion: Methylprednisolone pulse therapy may be considered for possible treatment in patients with focal epilepsy with drug-resistant seizures without ES, and it may improve cognitive function and behavioral comorbidities.
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http://dx.doi.org/10.1016/j.yebeh.2020.107116DOI Listing
August 2020

Verbal function recovery in a postoperative case with epileptic encephalopathy.

Pediatr Int 2020 Mar;62(3):412-414

NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka-shi, Shizuoka, Japan.

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http://dx.doi.org/10.1111/ped.14087DOI Listing
March 2020

Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizures or generalized tonic-clonic seizures.

Epilepsia 2020 01 7;61(1):125-137. Epub 2020 Jan 7.

Eisai Inc., Woodcliff Lake, NJ, USA.

Objective: Study 311 (NCT02849626) was a global, multicenter, open-label, single-arm study that assessed safety, tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics of once-daily adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with focal seizures (FS) (with/without focal to bilateral tonic-clonic seizures [FBTCS]) or generalized tonic-clonic seizures (GTCS).

Methods: In the 311 Core Study, a 4-week Pre-treatment Period (Screening/Baseline) preceded a 23-week Treatment Period (11-week Titration; 12-week Maintenance) and 4-week Follow-up. Endpoints included safety/tolerability (primary endpoint), median percent change in seizure frequency per 28 days from Baseline (Treatment Period), and 50% responder and seizure-freedom rates (Maintenance Period). Patients were stratified by age (4 to <7; 7 to <12 years) and concomitant enzyme-inducing anti-seizure drug (EIASD) use.

Results: One hundred eighty patients were enrolled (FS, n = 149; FBTCS, n = 54; GTCS, n = 31). The Core Study was completed by 146 patients (81%); the most common primary reason for discontinuation was adverse event (AE) (n = 14 [8%]). Mean (standard deviation) daily perampanel dose was 7.0 (2.6) mg/day and median (interquartile range) duration of exposure was 22.9 (2.0) weeks. The overall incidence of treatment-emergent AEs (TEAEs; 89%) was similar between patients with FS (with/without FBTCS) and GTCS. The most common TEAEs were somnolence (26%) and nasopharyngitis (19%). There were no clinically important changes observed for cognitive function, laboratory, or electrocardiogram (ECG) parameters or vital signs. Median percent reductions in seizure frequency per 28 days from Baseline were as follows: 40% (FS), 59% (FBTCS), and 69% (GTCS). Corresponding 50% responder and seizure-freedom rates were as follows: FS, 47% and 12%; FBTCS, 65% and 19%; and GTCS, 64% and 55%, respectively. Improvements in response/seizure frequency from Baseline were seen regardless of age or concomitant EIASD use.

Significance: Results from the 311 Core Study suggest that daily oral doses of adjunctive perampanel are generally safe, well tolerated, and efficacious in children age 4 to <12 years with FS (with/without FBTCS) or GTCS.
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http://dx.doi.org/10.1111/epi.16413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004020PMC
January 2020

Corrigendum to "Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome" [Epilepsy Res. 154 (2019) 34-38].

Epilepsy Res 2019 Oct 27;156:106158. Epub 2019 Jun 27.

NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka-shi, Shizuoka 420-8688, Japan.

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http://dx.doi.org/10.1016/j.eplepsyres.2019.106158DOI Listing
October 2019

Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy.

Nat Commun 2019 06 7;10(1):2506. Epub 2019 Jun 7.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10) enrichment of damaging de novo mutations in NF1, a gene primarily linked to neurofibromatosis, in infantile spasm. Together with accumulating evidence for roles of oligogenic or modifier variants in severe neurodevelopmental disorders, our results highlight genetic complexity in EE/DEE, and indicate that EE/DEE is not an aggregate of simple Mendelian disorders.
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http://dx.doi.org/10.1038/s41467-019-10482-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555845PMC
June 2019

Efficacy and tolerability of perampanel in pediatric patients with Dravet syndrome.

Epilepsy Res 2019 08 21;154:34-38. Epub 2019 Apr 21.

NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka-shi, Shizuoka 420-8688, Japan.

Purpose: In the present study, we aimed to investigate the efficacy and tolerability of perampanel in patients with Dravet syndrome.

Methods: We retrospectively reviewed data regarding seizure frequency and adverse effects in 10 patients (four boys, six girls) with Dravet syndrome following treatment with perampanel. Perampanel treatment was considered effective when seizure frequency had been reduced by more than 50%.

Results: The mean age of patients at perampanel introduction was 11.5 ± 2.2 years. Seizure types were as follows: generalized tonic-clonic seizure (n = 8), unilateral clonic seizure (n = 6), myoclonic seizure (n = 3), atypical absence seizure (n = 3), and focal impaired awareness seizure (n = 1). The average number of concomitant anti-epileptic drugs (AEDs) was 3 ± 0.9. The mean duration of perampanel use was 11.1 ± 3.8 months. Seizure frequency was reduced by more than 50% in five patients (50%). The efficacy of perampanel for each seizure type was as follows: generalized tonic-clonic seizure: 50% (4/8), unilateral clonic seizure: 50% (3/6), myoclonic seizure: 33% (1/3), atypical absence seizure: 33% (1/3), and focal impaired awareness seizure: 100% (1/1). The effects of perampanel in each patient occurred between 3 and 6 months following the initiation of treatment. Seizure reduction was observed beginning at perampanel doses of 0.1 ± 0.07 mg/kg/day. Adverse events were observed in seven of 10 patients. Although somnolence was noted in 50% of patients, most events were mild.

Conclusions: The results of this retrospective observational study indicate that perampanel treatment may be promising in some patients with Dravet syndrome. Additional studies are necessary to verify the actual efficacy of perampanel for Dravet syndrome.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.02.014DOI Listing
August 2019

Quinidine therapy and therapeutic drug monitoring in four patients with KCNT1 mutations.

Epileptic Disord 2019 Feb;21(1):48-54

National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka.

Several recent studies have reported potassium sodium-activated channel subfamily T member 1 (KCNT1) mutations in epilepsy patients on quinidine therapy. The efficacy and safety of quinidine for epilepsy treatment, however, remains controversial. We herein report the cases of four patients with KCNT1 mutations treated with quinidine. A reduction in seizures of more than 50% after quinidine treatment was observed in one patient with epilepsy of infancy with migrating focal seizures (EIMFS), whereas two patients with EIMFS and one with focal epilepsy did not achieve apparent seizure reduction. The relationship between quinidine dose and serum quinidine concentration was inconsistent, particularly at high quinidine doses. One patient with EIMFS developed ventricular tachycardia the day after an increase in quinidine dose from 114 to 126 mg/kg/day. The serum trough quinidine concentration and the corrected QT interval (QTc) before arrhythmia onset were 2.4 μg/ml and 420 ms, respectively, and peak serum quinidine concentration after arrhythmia onset was 9.4 μg/ml. Another patient with EIMFS showed aberrant intraventricular conduction with a quinidine dose of 74.5 mg/kg/day and a serum trough concentration of 3.2 μg/ml. Given that serum quinidine levels may elevate sharply after a dose increase, careful monitoring of electrocardiographs and serum concentrations is required. Based on a review of previous reports and our experience with this case, quinidine should be considered as a promising drug for patients with EIMFS harbouring KCNT1 mutations, however, its efficacy remains controversial due to the limited number of cases, and more information on optimal serum concentrations and appropriate titration methods is required.
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http://dx.doi.org/10.1684/epd.2019.1026DOI Listing
February 2019

Different types of suppression-burst patterns in patients with epilepsy of infancy with migrating focal seizures (EIMFS).

Seizure 2019 Feb 18;65:118-123. Epub 2019 Jan 18.

National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka-shi, Shizuoka, 420-8688, Japan.

Purpose: In rare cases, patients with epilepsy of infancy withmigrating focal seizures (EIMFS) exhibit suppression-burst (SB) patterns on electroencephalography (EEG), similar to the findings observed in patients with Ohtahara syndrome and early myoclonic encephalopathy. In this report, we discuss six cases of EIMFS in which patients exhibited two types of SB patterns.

Methods: We evaluated six patients with EIMFS who had been admitted to the NHO Shizuoka Institute of Epilepsy and Neurological Disorders between 2011 and 2018. We retrospectively examined clinical characteristics and EEG findings for each patient. In all patients, the first EEG was performed within 1 month after seizure onset. Afterwards, EEG examinations were performed at irregular intervals (ranging from 1 to 5 months).

Results: Age at seizure onset ranged from 2 days to 3 months. SB was first detected within 1 month of age in two patients, and within the range of 3-14 months in the remaining four patients. Among the latter four patients, SB patterns persisted at the final EEG recording in three patients (34-54 months). In all patients, SB patterns were observed during sleep only. Interhemispheric asynchrony in SB was observed in the two patients who exhibited SB within 1 month of age, while synchronous SB patterns were observed in the remaining four patients.

Conclusions: Our findings indicate that EIMFS may be associated with two types of SB patterns (early-onset and late-onset), which can be distinguished based on the stage of emergence and level of synchrony.
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http://dx.doi.org/10.1016/j.seizure.2019.01.009DOI Listing
February 2019

Chronic dysfunction of blood-brain barrier in patients with post-encephalitic/encephalopathic epilepsy.

Seizure 2018 Dec 13;63:85-90. Epub 2018 Nov 13.

Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan.

Purpose: This study aimed to elucidate the characteristics and effects of chronic blood-brain barrier (BBB) dysfunction in patients with post-encephalitic/encephalopathic epilepsy (PEE), using brain images and the cerebral spinal fluid (CSF)/serum albumin ratio (albumin quotient, QAlb) as a marker of BBB function.

Methods: We examined the albumin levels in CSF and serum samples from 312 patients with refractory epilepsy in our center between 2004 and 2015. Sixty samples from patients with PEE and 97 samples from age- and sex-matched disease controls (DC) were evaluated. We classified PEE patients into a widespread lesion group and a focal lesion group by severity on brain magnetic resonance images in the chronic phase after acute encephalitis/encephalopathy.

Results: Median QAlb was higher in PEE than in DC [median (range) ×10: PEE 3.6 (1.0-10.3) versus DC 2.7 (1.0-6.7), p = 0.007]. In a linear regression analysis of the relationship between QAlb and patient's age at CSF examination or duration of epilepsy, the slope of the regression line was greater in PEE than in DC. Furthermore, in patients under ten years of age, linear regression analysis of QAlb versus seizure frequency showed a weak but positive correlation. Among PEE patients, seizure frequency was higher in the widespread lesion group than in the focal lesion group [300 (4-3000) versus 30 (1-1500) seizures/month, p <  0.001].

Conclusion: Our study suggests that patients with PEE have more severe BBB dysfunction, and that the BBB dysfunction is associated with refractory epilepsy.
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http://dx.doi.org/10.1016/j.seizure.2018.11.005DOI Listing
December 2018

A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy.

Brain Dev 2017 Mar 12;39(3):256-260. Epub 2016 Oct 12.

Department of Pediatrics, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Japan.

Introduction: Mutations of SLC35A2 that encodes Golgi-localized Uridine diphosphate (UDP)-galactose transporter at Xp11.23 lead to congenital disorders of glycosylation (CDG). Although patients with CDG generally have diverse systemic symptoms, patients with a SLC35A2 mutation manifest predominantly disorders of the central nervous system (CNS).

Case Report: A female infant aged 12months was referred to our center because of intractable seizures. The patient was born with birth weight of 3228g after 40weeks of unremarkable gestation. At the age of 2months, she had partial seizures evolving to epileptic spasms. Her electroencephalogram showed hypsarrhythmia. Her seizures were refractory to antiepileptic drugs. At referral to our center at 12months, she had developmental delay (no head control), widely spaced inverted nipples, external strabismus, and bilateral heterochromia of irises. Blood examinations were normal. Brain magnetic resonance imaging findings included cerebral and cerebellar atrophy, thinning of the corpus callosum, and arachnoid pouch. Whole-exome sequencing detected a de novo frameshift mutation c.950delG (p.Gly317Alafs*32) at exon 4 in SLC35A2. Seizures subsided after the second adrenocorticotropic hormones (ACTH) therapy at 18months. At the age of 36months, although she had intellectual disability with no meaningful words, she was seizure-free and was able to sit without support and showed smiling face a lot.

Conclusion: This report reviewed the clinical features of patients with a SLC35A2 mutation. ACTH therapy may be effective for refractory epilepsy in these patients.
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http://dx.doi.org/10.1016/j.braindev.2016.09.009DOI Listing
March 2017

Antibodies against peptides of NMDA-type GluR in cerebrospinal fluid of patients with epileptic spasms.

Eur J Paediatr Neurol 2016 Nov 13;20(6):865-873. Epub 2016 Jul 13.

National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, 886 Urushiyama, Aoi-ku, Shizuoka 420-8688, Japan.

Objective: We investigated the contribution of antibodies against N-methyl-d-aspartate (NMDA)-type glutamate receptor (GluR) in cerebrospinal fluid (CSF) to the clinical features of patients with epileptic spasms (ES).

Methods: CSF samples were collected from 33 patients with ES with median (range) age 1.8 (0.2-8.5) years. Thirty patients without ES with 3.5 (0.5-7.0) years were also studied as disease controls. The CSF levels of antibodies against peptides of NMDA-type GluR subunits (GluN2B & GluN1) were measured by enzyme-linked immunosorbent assay.

Results: The levels of antibodies against the n-terminal of GluN2B (GluN2B-NT2), c-terminal of GluN2B (GluN2B-CT) and n-terminal of GluN1 (GluN1-NT), were significantly higher in patients with ES than in disease controls (p < 0.01, p < 0.01 & p = 0.03). Levels of antibodies to GluN2B-NT2 & CT were not related with ACTH therapy nor conventional CSF factors (cell counts, protein level, etc). Levels of antibodies to GluN2B-NT2 & CT showed evidence of correlation within a linear regression model with intervals from the onset to the examination of CSF until 25 months (p = 0.01 & p = 0.01). The correlation was significant in patients with unknown cause (p = 0.01). Five of 33 patients (four unknown cause & one chromosomal anomaly) had higher level of antibodies to GluN2B-NT2 exceeding mean + 1 SD of all ES patients, and they had poor motor (score 0) and cognitive outcomes (score 0 or 1).

Conclusion: The CSF level of antibodies against GluN2B in ES patients with unknown cause was estimated to increase after onset. We hypothesize that some ES patients may have immune process after the onset of ES.
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http://dx.doi.org/10.1016/j.ejpn.2016.07.006DOI Listing
November 2016

WDR45 mutations in three male patients with West syndrome.

J Hum Genet 2016 Jul 31;61(7):653-61. Epub 2016 Mar 31.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

West syndrome is an early-onset epileptic encephalopathy characterized by clustered spasms with hypsarrhythmia seen on electroencephalogram (EEG). West syndrome is genetically heterogeneous, and its genetic causes have not been fully elucidated. WD Repeat Domain 45 (WDR45) resides on Xp11.23, and encodes a member of the WD repeat protein interacting with phosphoinositides (WIPI) family, which is crucial in the macroautophagy pathway. De novo mutations in WDR45 cause beta-propeller protein-associated neurodegeneration characterized by iron accumulation in the basal ganglia. In this study, we performed whole exome sequencing of individuals with West syndrome and identified three WDR45 mutations in three independent males (patients 1, 2 and 3). Two novel mutations occurred de novo (patients 1 and 2) and the remaining mutation detected in a male patient (patient 3) and his affected sister was inherited from the mother, harboring the somatic mutation. The three male patients showed early-onset intractable seizures, profound intellectual disability and developmental delay. Their brain magnetic resonance imaging scans showed cerebral atrophy. We found no evidence of somatic mosaicism in the three male patients. Our findings indicate that hemizygous WDR45 mutations in males lead to severe epileptic encephalopathy.
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http://dx.doi.org/10.1038/jhg.2016.27DOI Listing
July 2016

Phenotypes of children with 20q13.3 microdeletion affecting KCNQ2 and CHRNA4.

Epileptic Disord 2015 Jun;17(2):165-71

Department of Pediatrics, Aichi Medical University, Nagakute.

In order to clarify the phenotypes of 20q13.33 microdeletion, clinical manifestations and genetic findings from four patients are discussed in relation to chromosomal microdeletions at 20q13.33. All patients had epileptic seizures mostly beginning within the neonatal period and disappearing by 4 months of age, similar to epilepsy phenotypes of benign familial neonatal seizures. We performed array comparative, genomic hybridization analysis in order to investigate the chromosomal aberration. Developmental outcome was good in two patients with deletion restricted to three genes (CHRNA4, KCNQ2, and COL20A1), whereas delay in developmental milestones was observed in the other two with a wider range of deletion. Information obtained from array comparative genomic hybridization may be useful to predict seizure and developmental outcome, however, there is no distinctive pattern of abnormalities that would arouse clinical suspicion of a 20q13.33 microdeletion. Deletion of KCNQ2 and CHRNA4 does not appear to affect seizure phenotype. Molecular cytogenetic techniques, such as array comparative genomic hybridization, will be necessary to clarify the relationship between phenotypes and individual genes within this region.
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http://dx.doi.org/10.1684/epd.2015.0746DOI Listing
June 2015

Three patients manifesting early infantile epileptic spasms associated with 2q24.3 microduplications.

Brain Dev 2015 Oct 3;37(9):874-9. Epub 2015 Apr 3.

Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan; Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.

Background: Recent development of genetic analyses enabled us to reveal underlying genetic causes of the patients with epileptic encephalopathy in infancy. Mutations of voltage-gated sodium channel type I alpha subunit gene (SCN1A) are to be causally related with several phenotypes of epilepsy, generalized epilepsy with febrile seizure plus (GEFS+), Dravet syndrome, and other infantile epileptic encephalopathies. In addition to SCN1A, contiguous genes such as SCN2A and SCN3A in 2q24.3 are also reported to have contribution to epileptic seizures. Therefore, gene abnormality involving this region is reasonable to contribute to epilepsy manifestation.

Results: We encountered three patients with 2q24.3 microduplication diagnosed by Array comparative genomic hybridization array (aCGH). They developed partial seizures and epileptic spasms in their early infantile periods and showed remarkable developmental delay, although their seizures disappeared from 11 to 14 months of age. One of three patients had 2q24.3 microduplication which excludes SCN1A. Therefore, characteristics of epilepsy with 2q24.3 microduplication do not necessarily need duplication of SCN1A. This study suggested that 2q24.3 microduplication is one of the causes for early infantile epileptic spasms. Epileptic spasms associated with 2q24.3 microduplications may have better seizure outcome comparing with other etiologies.
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http://dx.doi.org/10.1016/j.braindev.2015.03.001DOI Listing
October 2015

[Adverse effects of antiepileptic drugs].

Nihon Rinsho 2014 May;72(5):908-19

Adverse effects of antiepileptic drugs are classified into idiosyncratic adverse effects, pharmacology-related adverse effects and biological effect after modification of seizure frequencies. Pharmacology-related adverse effects include those by administered AED and those by mutual interactions. Stevens-Johnson syndrome, one of the idiosyncratic adverse effects, may be predicted by the intrinsic HLA type (e.g., A*31:01 for CBZ). In epileptic patients after acute encephalitis, cutaneous adverse reactions usually occur in a month after encephalitis, but some patients will tolerate the causative AED by the extremely slow re-introduction. Prevention of pharmacology-related adverse effects needs therapeutic drug monitoring, and slow introduction considering dose-response curves for AEDs. Genotype examination of CYP2C9 and 2C19 can contribute to the safe introduction of PHT.
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May 2014

Clinical impacts of genomic copy number gains at Xq28.

Hum Genome Var 2014 24;1:14001. Epub 2014 Jul 24.

Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health , Izumi, Japan .

Duplications of the Xq28 region are the most frequent chromosomal aberrations observed in patients with intellectual disability (ID), especially in males. These duplications occur by variable mechanisms, including interstitial duplications mediated by segmental duplications in this region and terminal duplications (functional disomy) derived from translocation with other chromosomes. The most commonly duplicated region includes methyl CpG-binding protein 2 gene (MECP2), which has a minimal duplicated size of 0.2 Mb. Patients with MECP2 duplications show severe ID, intractable seizures and recurrent infections. Duplications in the telomeric neighboring regions, which include GDP dissociation inhibitor 1 gene (GDI1) and ras-associated protein RAB39B gene (RAB39B), are independently associated with ID, and many segmental duplications located in this region could mediate these frequently observed interstitial duplications. In addition, large duplications, including MECP2 and GDI1, induce hypoplasia of the corpus callosum. Abnormalities observed in the white matter, revealed by brain magnetic resonance imaging, are a common finding in patients with MECP2 duplications. As primary sequence analysis cannot be used to determine the region responsible for chromosomal duplication syndrome, finding this region relies on the collection of genotype-phenotype data from patients.
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http://dx.doi.org/10.1038/hgv.2014.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785515PMC
April 2016

[A case of acute necrotizing encephalopathy and acute encephalopathy with biphasic seizures and late reduced diffusion].

No To Hattatsu 2012 Nov;44(6):487-91

Department of Pediatric Neurology, Nagano Children's Hospital, Azumino, Nagano.

Acute necrotizing encephalopathy (ANE) has a characteristic imagimg finding of bilateral symmetrical thalamic lesions. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic clinical course and high intensity of subcortical white matter in MRI diffusion images appearing around the late seizure. We herein report a case of an 8-month-old girl who presented with fever and status epilepticus associated with human herpes 6 infection. Although MRI first demonstrated images of ANE, typical AESD images were observed several days after the onset. We therefore concluded that this case had a combination of ANE and AESD. A proper therapeutic strategy should be established, and acute encephalopathy needs to be better clarified by identifying diagnostic markers and improving the genetical analysis.
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November 2012