Publications by authors named "Yukitoshi Takahashi"

269 Publications

Psychiatric outcome of temporal lobe epilepsy surgery: A prospective, 2-year follow-up study.

Epilepsy Behav 2021 Jul 26;122:108216. Epub 2021 Jul 26.

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

Objective: We performed a prospective, longitudinal, 2-year follow-up study to clarify psychiatric courses and outcomes after temporal lobe epilepsy surgery.

Methods: We assessed 141 patients (68 men, 73 women) aged 16 or older with structured interviews and psychiatric rating scales before surgery and 3 months, 1 year, and 2 years afterward.

Results: Fifty-two patients (36.9%) had a psychiatric condition before surgery or during the follow-up period or both. The number of patients with a psychiatric condition decreased from 31 (22.0%) before surgery to 14 (9.9%) at 2 years. On the basis of our results, we defined 5 courses of psychiatric conditions: course 0, no psychopathology (n = 89, 63.1%); course 1, remission or resolution of a presurgical psychiatric condition after surgery (n = 19, 13.5%); course 2, new onset, transient psychiatric condition after surgery (n = 19, 13.5%); course 3, new onset, persistent psychiatric condition after surgery (n = 2, 1.4%); and course 4, chronic psychiatric condition before and after surgery (n = 12, 8.5%). In 14/25 (56.0%) patients with a mood or anxiety disorder before surgery, the condition remitted or resolved after surgery (course 1). Eighteen of 110 patients (16.4%) without any psychopathology before surgery developed mood or anxiety disorders afterward, including major depressive disorder in 13 patients (courses 2 and 3); in more than half of these patients, the disorder manifested within 1 year. More patients with a past history of psychiatric conditions were found in course 2 than in course 0. The duration of epilepsy was longer in course 4 than in course 0, and age at epilepsy onset was lower in course 4 than in course 0.

Significance: Most patients with a psychiatric condition show a favorable outcome 2 years after surgery; however, some show a transient worsening or new onset of psychiatric conditions, in particular depression.
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http://dx.doi.org/10.1016/j.yebeh.2021.108216DOI Listing
July 2021

Current medico-psycho-social conditions of patients with West syndrome in Japan.

Epileptic Disord 2021 Jul 13. Epub 2021 Jul 13.

Department of Pediatrics, School of Medicine, Shinshu University, Matsumoto, Japan.

Objective: To unveil current medical and psychosocial conditions of patients with West syndrome in Japan.

Methods: A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset.

Results: For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%.

Significance: The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.
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http://dx.doi.org/10.1684/epd.2021.1301DOI Listing
July 2021

Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA).

Orphanet J Rare Dis 2021 Jul 6;16(1):301. Epub 2021 Jul 6.

Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St Georges University of London, London, UK.

Background: Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients.

Methods: TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2).

Results: Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.2% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%).

Conclusion: Rare manifestations were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.
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http://dx.doi.org/10.1186/s13023-021-01917-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259106PMC
July 2021

A Single-Arm Open-Label Clinical Trial on the Efficacy and Safety of Sirolimus for Epileptic Seizures Associated with Focal Cortical Dysplasia Type II: A Study Protocol.

Kurume Med J 2021 Jul 15;66(2):115-120. Epub 2021 Jun 15.

Department of Pediatrics, Showa University School of Medicine.

Epileptic seizures are core symptoms in focal cortical dysplasia (FCD), a disease that often develops in infancy. Such seizures are refractory to conventional antiepileptic drugs (AED) and temporarily disappear in response to AED in only 17% of patients. Currently, surgical resection is an important option for the treatment of epileptic seizures in FCD. In 2015, Korean and Japanese groups independently reported that FCD is caused by somatic mosaic mutation of the MTOR gene in the brain tissue. Based on these results we decided to test a novel treatment using sirolimus, an mTOR inhibitor, for epileptic seizures in patients with FCD type II. A single arm open-label clinical trial for FCD type II patients is being conducted in order to evaluate the efficacy and safety of sirolimus. The dose of sirolimus is fixed for the first 4 weeks and dose adjustment is achieved to maintain a blood level of 5 to 15 ng/mL during 8 to 24 weeks after initiation of administration, and it is kept within this level during a maintenance therapy period of 12 weeks. Primary endpoint is a reduction in the rate of incidence of focal seizures (including focal to bilateral tonic-clonic seizures) per 28 days during the maintenance therapy period from the observation period. To evaluate the frequency of epileptic seizures, registry data will be used as an external control group. We hope that the results of this trial will lead to future innovative treatments for FCD type II patients.
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http://dx.doi.org/10.2739/kurumemedj.MS662007DOI Listing
July 2021

Case Report: Rituximab Improved Epileptic Spasms and EEG Abnormalities in an Infant With West Syndrome and Anti-NMDAR Encephalitis Associated With APECED.

Front Neurol 2021 20;12:679164. Epub 2021 May 20.

Department of Paediatrics, St Mary's Hospital, Kurume, Fukuoka, Japan.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder caused by a mutation in the autoimmune regulator gene. Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy typically exhibit hypoparathyroidism, adrenocortical failure, and chronic mucocutaneous candidiasis. There are only a few case reports of autoimmune encephalitis during autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, but not as an initial manifestation. Furthermore, there are no reports of patients with infantile spasms/West syndrome with autoimmune encephalitis, partly because the median age for paediatric patients with anti-N-methyl-D-aspartate receptor encephalitis, which is the most frequent and best characterised in paediatric autoimmune encephalitides, is 13-14 years. Herein, we present a case of a 3-month-old infant with autoimmune encephalitis as an initial manifestation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy who later developed infantile spasms/West syndrome. A 3-month-old girl was admitted to our hospital with a fever, involuntary movements in all four limbs, and right-side facial palsy. Acute central nervous system demyelination diseases were suspected from neuroimaging findings and the presence of the cerebrospinal fluid oligoclonal band. She did not respond to multiple methylprednisolone pulse therapies and later developed infantile spasms/West syndrome and diabetes mellitus. Rituximab, a chimeric mouse/human monoclonal antibody directed against human CD20 which depletes B cells, was initially administered as a treatment for autoimmune encephalitis. Unexpectedly, this treatment resulted in complete spasm cessation and resolution of hypsarrhythmia. The patient eventually showed severely delayed developmental milestones, and her electroencephalography findings showed periodic generalised slow spike-and-wave pattern. Despite the limited ability to extrapolate findings from a single case, rituximab's effects may suggest that B cells play a crucial role in infantile spasms/West syndrome mechanisms; use of rituximab as an aetiology-specific treatment for infantile spasms/West syndrome patients with autoimmune encephalitis or its effectiveness for infantile spasms/West syndrome patients with other underlying mechanisms warrants further investigation.
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http://dx.doi.org/10.3389/fneur.2021.679164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176955PMC
May 2021

Two cases of DYNC1H1 mutations with intractable epilepsy.

Brain Dev 2021 Jun 3. Epub 2021 Jun 3.

Department of Pediatrics, Jichi Medical University, Tochigi, Japan. Electronic address:

Background: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot-Marie-Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria.

Case Reports: Patient 1 had severe ID. At the age of 2 months, she presented myoclonic seizures and tonic seizures, and later experienced atonic seizures and focal impaired-awareness seizures (FIAS). EEG showed slow waves in right central areas during myoclonic seizures. Brain MRI revealed pachygyria, predominantly in the occipital lobe. After callosal transection her atonic seizures disappeared, but FIAS remained. Patient 2 was diagnosed with autism spectrum disorder (ASD) and severe ID. At the age of 7 years, he presented generalized tonic-clonic seizures, myoclonic seizures, and FIAS. Interictal EEG showed generalized spike-and-wave complexes, predominantly in the left frontal area. Brain MRI was unremarkable. Exome sequencing revealed novel de novo mutations in DYNC1H1: c.4691A > T, p.(Glu1564Val) in Patient 1 and c.12536 T > C, p.(Leu4179Ser) in Patient 2.

Conclusions: DYNC1H1 comprises a stem, stalk, and six AAA domains. Patient 2 is the second report of an AAA6 domain mutation without malformations of cortical development. The p.(Gly4072Ser) mutation in the AAA6 domain was also reported in a patient with ASD. It may be that the AAA6 domain has little effect on neuronal movement of DYNC1H1 along microtubules.
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http://dx.doi.org/10.1016/j.braindev.2021.05.005DOI Listing
June 2021

TuberOus SClerosis registry to increAse disease awareness (TOSCA) Post-Authorisation Safety Study of Everolimus in Patients With Tuberous Sclerosis Complex.

Front Neurol 2021 23;12:630378. Epub 2021 Mar 23.

Pediatric Neurology Unit, Department of Paediatrics, UZ Brussel VUB, Brussels, Belgium.

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.
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http://dx.doi.org/10.3389/fneur.2021.630378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021912PMC
March 2021

Change in the pharmacokinetics of lacosamide before, during, and after pregnancy.

Seizure 2021 May 15;88:12-14. Epub 2021 Mar 15.

Department of Clinical Research, NHO, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka, 420-8688, Japan; Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422-8526, Japan.

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http://dx.doi.org/10.1016/j.seizure.2021.03.011DOI Listing
May 2021

Semiological differences of focal onset bilateral motor (convulsive) seizure between mesial temporal lobe epilepsy and neocortical epilepsy.

Epilepsy Res 2021 Feb 7;170:106553. Epub 2021 Jan 7.

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

Objective: We investigated the semiology of focal onset bilateral motor (convulsive) seizure (FBMS) in patients with intractable focal epilepsy who underwent epilepsy surgery to understand its value in localizing the origin of the seizure.

Methods: The study included 20 patients who underwent resective surgery after intracranial video-EEG monitoring (iEEG) with a favorable seizure outcome (Engel class I), and had at least one FBMS during iEEG. The diagnosis was mesial temporal lobe epilepsy (MTLE) for 7 patients and neocortical epilepsy (NE) for 13 patients (lateral temporal lobe, 3; posterior cortex, 6; frontal lobe, 3; perirolandic, 1). Videotaped FBMSs were carefully analyzed.

Results: A generalized tonic phase appeared in all 7 patients with MTLE, but was absent in 6 of the 13 patients with NE (P = .044). Tonic cry was more frequently observed in MTLE than in NE (P = .012). Facial tonicity preceding limb tonicity was more frequently seen in patients with MTLE (P = .001).

Conclusion: Notably, patients with MTLE and those with NE showed semiological differences during bilateralization. FBMS includes not only focal to bilateral tonic-clonic seizure but also focal to bilateral clonic seizure.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106553DOI Listing
February 2021

Limbic encephalitis in a patient with systemic lupus erythematosus successfully treated with high-dose glucocorticoids and intravenous cyclophosphamide therapy: the potential pathogenicity of anti-glutamate receptor antibodies.

Mod Rheumatol Case Rep 2021 Jul 9;5(2):250-253. Epub 2021 Feb 9.

Department of Allergy and Rheumatology, The University of Tokyo Hospital, Tokyo, Japan.

Limbic encephalitis (LE) is a clinically defined syndrome characterised by an acute or subacute impairment of short-term memory, seizures and psychiatric symptoms (i.e. depression, anxiety and hallucination). LE could come from certain conditions where the neuropsychiatric systemic lupus erythematosus (NPSLE) of the multiple central nervous system is layered. In this report, we describe a 46-year-old Japanese female with SLE that suddenly presented with seizures, sensory aphasia and pseudobulbar affect. She was diagnosed with severe NPSLE presenting clinical LE (LE-SLE) by excluding malignancies, infectious encephalitis and symptomatic epilepsy using diffusion-weighted magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). The patient showed a rapid response to treatment with methylprednisolone pulses followed by high-dose prednisolone and intravenous cyclophosphamide. She had elevated anti-glutamate receptor antibodies (anti-GluRs) in her serum and cerebrospinal fluid (CSF) on admission, and the titres decreased to a normal range at a one-year follow up. Our case highlights the importance of measuring anti-neuron antibodies including anti-GluRs in NPSLE patients, and suggests that the reduction of these pathogenic autoantibodies in serum or CSF could be a prognostic marker.
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http://dx.doi.org/10.1080/24725625.2021.1876340DOI Listing
July 2021

Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants.

Brain Dev 2021 Apr 9;43(4):505-514. Epub 2021 Jan 9.

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

Objective: Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments.

Methods: We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information.

Results: We identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI.

Conclusion: Our patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.
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http://dx.doi.org/10.1016/j.braindev.2020.12.006DOI Listing
April 2021

Exploratory investigation on antibodies to GluN1 and cognitive dysfunction in patients with chronic autoimmune psychosis.

Neurosci Lett 2021 01 25;743:135588. Epub 2020 Dec 25.

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

Introduction: Mild cognitive dysfunction has been implicated in a number of psychiatric diseases and affects social functioning. Although clinical criteria were recently proposed for autoimmune psychosis (AP), biomarkers have not yet been established for the severity and prognosis of cognitive dysfunction. We herein investigated the relationships between 3 types of serum antibodies and cognitive dysfunction in chronic psychiatric patients suspected of AP.

Methods: We included 31 patients suspected of AP and obtained information on their clinical characteristics. Three types of autoantibodies (the anti-N-methyl--aspartate receptor (anti-NMDAR Ab), anti-N-terminal of GluN1 (anti-GluN1-NT Ab), and anti-thyroid antibodies) were evaluated in serum. Cognitive function was assessed using Wechsler Adult Intelligence Scale-III. We examined the relationships between serum autoantibodies and cognitive dysfunction in patients using multiple regression models.

Results: Serum titers of anti-GluN1-NT Ab significantly contributed to the estimated score of working memory (B= -55.85, β= -0.46, p= 0.01), while no correlation was observed between the other 2 types of antibodies and cognitive function.

Conclusions: The present results indicate the potential of serum anti-GluN1-NT Ab as a biomarker for the severity and prognosis of cognitive dysfunction underlying various psychiatric symptoms in patients with AP. The pathological significance of anti-GluN1-NT Ab needs to be verified in future studies.
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http://dx.doi.org/10.1016/j.neulet.2020.135588DOI Listing
January 2021

An exploratory investigation of antibodies to NMDA-type glutamate receptor subunits in serum and cerebrospinal fluid among psychiatric patients with anti-thyroid antibodies.

Heliyon 2020 Dec 8;6(12):e05677. Epub 2020 Dec 8.

Department of Psychiatry, Yokohama City University School of Medicine, Japan.

Introduction: Hashimoto's thyroiditis, which is characterized by anti-thyroid antibodies such as the anti-thyroglobulin (Tg) antibody and anti-thyroid peroxidase (TPO) antibody, is one of the autoimmune diseases associated with psychiatric illnesses. We previously reported a high prevalence of antibodies to N-terminals of N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN1-NT and GluN2B-NT2) among psychiatric patients with anti-thyroid antibodies. However, it remains unclear whether the presence of anti-thyroid antibodies influences antibodies to GluN1-NT or GluN2B-NT2 among psychiatric patients. The present study aims to examine antibodies to GluN1-NT and GluN2B-NT2 in psychiatric patients with anti-thyroid antibodies (PPATs) and in those without (non-PPATs).

Material And Methods: We recruited psychiatric inpatients aged 20-60 years. Patients were excluded if they had a history of neurological diseases, dementia, developmental disorders, tumors, or autoimmune diseases except autoimmune thyroiditis. The rest of the participants were divided into two groups according to the presence of serum anti-Tg and anti-TPO antibodies. We investigated serum and cerebrospinal fluid (CSF) antibodies to GluN1-NT and GluN2B-NT2 using an enzyme-linked immunosorbent assay (ELISA).

Results: We initially recruited seventy-three psychiatric inpatients. Forty-six patients were excluded because of the exclusion criteria. Eighteen PPATs and nine non-PPATs were ultimately enrolled. We also collected stored sera of eighteen healthy controls (HCs) who were age- and sex-matched with PPATs. The optical densities (ODs) of serum antibodies to GluN1-NT (p = 0.0020) and GluN2B-NT2 (p = 0.039) were significantly higher in PPATs than in HCs. The ODs of CSF antibodies to GluN1-NT (p = 0.030) and GluN2B-NT2 (p = 0.017) as well as the positive ratios of those antibodies were significantly higher in PPATs than in non-PPATs.

Conclusion: Our finding indicates that detecting anti-thyroid antibodies in psychiatric patients would be a clue to consider psychiatric conditions related to antibodies to GluN1-NT/GluN2B-NT2. Further studies focusing on the relationship between PPATs and antibodies to GluN1-NT/GluN2B-NT2 are needed.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725722PMC
December 2020

Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy.

Seizure 2020 Dec 29;83:181-186. Epub 2020 Oct 29.

Department of Clinical Research, NHO, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka, 420-8688, Japan; Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422-8526, Japan.

Objective: We aimed to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum perampanel concentration and to correlate the concentration with clinical response and tolerability.

Methods: A total of 4224 serum samples were obtained from 763 pediatric, adolescent, and adult patients for routine therapeutic drug monitoring. We compared the extent of enzyme induction between cytochrome P450 3A4 (CYP3A4) inducer regimens and built a statistical model to estimate the serum perampanel concentration that considered use of CYP3A4 inducers and inhibitors. To assess the tolerability and clinical effectiveness of perampanel therapy, we used the nested case-control approach. The case group was matched with the control group for age, sex, epilepsy type, and perampanel exposure periods.

Results: Concomitant use of the inducers phenytoin, carbamazepine, and phenobarbital dose-dependently reduced the perampanel concentration by 51 %, 67 %, and 37 %, respectively. The estimate model showed a good correlation between the predicted and measured concentrations (r = 0.62, p < 0.001). In 206 patients, the seizure reduction from baseline was > 50 % and the median perampanel concentration was 351 ng/mL (interquartile range, 191-603 ng/mL). Adverse events, such as somnolence, dizziness, and irritability, were experienced by 185 patients. The responder odds ratio was 5.1-fold higher in patients with a serum concentration > 600 ng/mL than in those with a serum concentration < 200 ng/mL; however, the former group had a 7.9-fold higher incidence of adverse events.

Conclusion: Therapeutic drug monitoring is clinically useful to assess drug interactions between perampanel and CYP3A4 inducers and inhibitors. We recommend that the target concentration of perampanel is initially set at 200-600 ng/mL. Serum concentrations > 600 ng/mL were associated with greater anti-seizure effects but had an increased risk of adverse events.
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http://dx.doi.org/10.1016/j.seizure.2020.10.017DOI Listing
December 2020

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

Hum Mutat 2021 Jan 11;42(1):50-65. Epub 2020 Nov 11.

Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.

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.
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http://dx.doi.org/10.1002/humu.24129DOI Listing
January 2021

Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B.

J Neuroimmunol 2020 12 15;349:577427. Epub 2020 Oct 15.

Department of Molecular Neuroscience, Graduate Schools of Innovative Life Science and Medicine, University of Toyama, Toyama, Japan. Electronic address:

To characterize internalization of NMDA-type glutamate receptors (GluRs) by antibodies to NMDA-type GluRs, we produced rabbit antibodies to N-terminals of human GluN1 and GluN2B, and examined internalization of NMDA-type GluRs in HEK293T cells using confocal microscopy. Internalization of NMDA-type GluRs occurred from at least 10 min after incubation with antibodies to GluN1 and or GluN2B and was temperature-dependent. These findings confirm that antibodies to N-terminals of GluN1 and GluN2B present in the cerebrospinal fluid of patients with NMDAR encephalitis can mediate prompt internalization of NMDA-type GluR complexes.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577427DOI Listing
December 2020

Renal Manifestations of Tuberous Sclerosis Complex: Key Findings From the Final Analysis of the TOSCA Study Focussing Mainly on Renal Angiomyolipomas.

Front Neurol 2020 16;11:972. Epub 2020 Sep 16.

Klinikverbund Allgäu gGmbH, Kempten, Germany.

Renal angiomyolipomas are one of the most common renal manifestations in patients with tuberous sclerosis complex (TSC), with potentially life-threatening complications and a poor prognosis. Despite the considerable progress in understanding TSC-associated renal angiomyolipomas, there are no large scale real-world data. The aim of our present study was to describe in detail the prevalence and outcome of renal angiomyolipomas in patients with TSC, enrolled into the TuberOus SClerosis registry to increase disease Awareness (TOSCA) from 170 sites across 31 countries worldwide. We also sought to evaluate the relationship of TSC-associated renal angiomyolipomas with age, gender and genotype. The potential risk factors for renal angiomyolipoma-related bleeding and chronic kidney disease (CKD) were studied in patients who participated in the TOSCA renal angiomyolipoma substudy. Of the 2,211 eligible patients, 1,062 (48%) reported a history of renal angiomyolipomas. The median age of TSC diagnosis for the all subjects ( = 2,211) was 1 year. The median age of diagnosis of renal angiomyolipoma in the 1,062 patients was 13 years. Renal angiomyolipomas were significantly more prevalent in female patients ( < 0.0001). Rates of angiomyolipomas >3 cm ( = 0.0119), growing lesions ( = 0.0439), and interventions for angiomyolipomas ( = 0.0058) were also higher in females than males. Pre-emptive intervention for renal angiomyolipomas with embolisation, surgery, or mammalian target of rapamycin (mTOR) inhibitor may have abolished the gender difference in impaired renal function, hypertension, and other complications. The rate of interventions for angiomyolipomas was less common in children than in adults, but interventions were reported in all age groups. In the substudy of 76 patients the complication rate was too low to be useful in predicting risk for more severe CKD. In addition, in this substudy no patient had a renal hemorrhage after commencing on an mTOR inhibitor. Our findings confirmed that renal angiomyolipomas in subjects with mutations develop on average at the later age, are relatively smaller in size and less likely to be growing; however, by age 40 years, no difference was observed in the percentage of patients with and mutations needing intervention. The peak of appearance of new renal angiomyolipomas was observed in patients aged between 18 and 40 years, but, given that angiomyolipomas can occur later, lifelong surveillance is necessary. We found that pre-emptive intervention was dramatically successful in altering the outcome compared to historical controls; with high pre-emptive intervention rates but low rates of bleeding and other complications. This validates the policy of surveillance and pre-emptive intervention recommended by clinical guidelines.
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http://dx.doi.org/10.3389/fneur.2020.00972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526256PMC
September 2020

Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study.

Front Neurol 2020 28;11:904. Epub 2020 Aug 28.

Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St Georges University of London, London, United Kingdom.

Research on tuberous sclerosis complex (TSC) to date has focused mainly on the physical manifestations of the disease. In contrast, the psychosocial impact of TSC has received far less attention. The aim of this study was therefore to examine the impact of TSC on health, quality of life (QoL), and psychosocial well-being of individuals with TSC and their families. Questionnaires with disease-specific questions on burden of illness (BOI) and validated QoL questionnaires were used. After completion of additional informed consent, we included 143 individuals who participated in the TOSCA (TuberOus SClerosis registry to increase disease Awareness) study. Our results highlighted the substantial burden of TSC on the personal lives of individuals with TSC and their families. Nearly half of the patients experienced negative progress in their education or career due to TSC (42.1%), as well as many of their caregivers (17.6% employed; 58.8% unemployed). Most caregivers (76.5%) indicated that TSC affected family life, and social and working relationships. Further, well-coordinated care was lacking: a smooth transition from pediatric to adult care was mentioned by only 36.8% of adult patients, and financial, social, and psychological support in 21.1, 0, and 7.9%, respectively. In addition, the moderate rates of pain/discomfort (35%) and anxiety/depression (43.4%) reported across all ages and levels of disease demonstrate the high BOI and low QoL in this vulnerable population.
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http://dx.doi.org/10.3389/fneur.2020.00904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485558PMC
August 2020

Discrimination between ictal EEG and EMG activity based on digital EEG.

Epileptic Disord 2020 Oct;22(5):689-690

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

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http://dx.doi.org/10.1684/epd.2020.1194DOI Listing
October 2020

Therapeutic Monitoring of Lacosamide in Japanese Patients With Epilepsy: Clinical Response, Tolerability, and Optimal Therapeutic Range.

Ther Drug Monit 2020 10;42(5):754-759

Department of Clinical Research, NHO, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama.

Background: Lacosamide is a novel anticonvulsant that acts by enhancing sodium channel slow inactivation. The aims of this study were to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum lacosamide concentration and explore the relationship between lacosamide serum concentration and both clinical response and adverse effects.

Methods: The authors analyzed 649 serum samples from 426 Japanese patients with epilepsy. The concentration-to-dose (CD) ratio of lacosamide was compared among patients on various AED regimens. Clinical information about seizure frequency and adverse events was obtained from clinical records.

Results: In patients who did not receive enzyme-inducing AEDs, the CD ratio (mean ± SD) of lacosamide was 1.84 ± 0.68. By contrast, the CD ratio in patients who received phenytoin, carbamazepine, and phenobarbital was 1.42 ± 0.66 (22.8% lower), 1.46 ± 0.40 (20.7% lower), and 1.36 ± 0.38 (26.1% lower), respectively. Seventy-four patients (17.3%) achieved >50% seizure reduction. The median lacosamide concentration in patients who received and did not receive a sodium channel blocker was 6.6 mcg/mL (26.4 μmol/L) and 8.4 mcg/mL (33.6 μmol/L), respectively. Adverse events, including dizziness, somnolence, diplopia, and anorexia, were reported by 70 patients (16.4%). The incidence rate in patients treated with sodium channel blockers was significantly higher than that in patients not treated with these drugs (21.1% vs. 10.3%; P < 0.005), and the median lacosamide concentration in these patient groups was 5.1 (20.4 μmol/L) and 7.5 mcg/mL (30 μmol/L), respectively.

Conclusions: Therapeutic drug monitoring of lacosamide is clinically useful because it allows physicians to estimate the extent of drug interactions and adjust the dose in individual AED regimens.
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http://dx.doi.org/10.1097/FTD.0000000000000764DOI Listing
October 2020

Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project.

J Neurodev Disord 2020 09 1;12(1):24. Epub 2020 Sep 1.

Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel VUB, Brussels, Belgium.

Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study.

Methods: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.

Results: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions.

Conclusions: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters.
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http://dx.doi.org/10.1186/s11689-020-09327-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465404PMC
September 2020

Changes in serum perampanel concentration profile after discontinuation of carbamazepine.

Epileptic Disord 2020 Aug;22(4):455-461

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

To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247 ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.
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http://dx.doi.org/10.1684/epd.2020.1182DOI Listing
August 2020

Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): New Findings on Age, Sex, and Genotype in Relation to Intellectual Phenotype.

Front Neurol 2020 7;11:603. Epub 2020 Jul 7.

Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel VUB, Brussels, Belgium.

Knowledge is increasing about TSC-Associated Neuropsychiatric Disorders (TAND), but little is known about the potentially confounding effects of intellectual ability (IA) on the rates of TAND across age, sex, and genotype. We evaluated TAND in (a) children vs. adults, (b) males vs. females, and (c) vs. mutations, after stratification for levels of IA, in a large, international cohort. Individuals of any age with a documented visit for TSC in the 12 months prior to enrolment were included. Frequency and percentages of baseline TAND manifestations were presented by categories of IA (no intellectual disability [ID, intelligence quotient (IQ)>70]; mild ID [IQ 50-70]; moderate-to-profound ID [IQ<50]). Chi-square tests were used to test associations between ID and TAND manifestations. The association between TAND and age (children vs. adults), sex (male vs. female), and genotype ( vs. ) stratified by IA levels were examined using the Cochran-Mantel-Haenszel tests. Eight hundred and ninety four of the 2,211 participants had formal IQ assessments. There was a significant association ( < 0.05) between levels of IA and the majority of TAND manifestations, except impulsivity ( = 0.12), overactivity ( = 0.26), mood swings ( = 0.08), hallucinations ( = 0.20), psychosis ( = 0.06), depressive disorder ( = 0.23), and anxiety disorder ( = 0.65). Once controlled for IA, children had higher rates of overactivity, but most behavioral difficulties were higher in adults. At the psychiatric level, attention deficit hyperactivity disorder (ADHD) was seen at higher rates in children while anxiety and depressive disorders were observed at higher rates in adults. Compared to females, males showed significantly higher rates of impulsivity and overactivity, as well as autism spectrum disorder (ASD) and ADHD. No significant age or sex differences were observed for academic difficulties or neuropsychological deficits. After controlling for IA no genotype-TAND associations were observed, except for higher rates of self-injury in individuals with mutations. Findings suggest IA as risk marker for most TAND manifestations. We provide the first evidence of male preponderance of ASD and ADHD in individuals with TSC. The study also confirms the association between and IA but, once controlling for IA, disproves the previously reported association with ASD and with most other TAND manifestations.
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http://dx.doi.org/10.3389/fneur.2020.00603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358578PMC
July 2020

Glucose transporter type 1 deficiency syndrome associated with autoantibodies to glutamate receptors.

Brain Dev 2020 Oct 24;42(9):686-690. Epub 2020 Jun 24.

Department of Pediatrics, Toho University, Sakura Medical Center, 564-1, Shimoshizu, Sakura, Chiba 285-0841, Japan. Electronic address:

Background: The clinical spectrum of glucose transporter type 1 deficiency syndrome (GLUT1DS) has broadened, with increasing recognition of a milder phenotype. Antibodies targeting the subunits of glutamate receptors (GluRs), including GluN1, GluN2B, and GluD2, have been detected in various neurological disorders. Anti-GluD2 antibodies in particular may be associated with cerebellar symptoms.

Case Report: A 3-year-5-month-old boy with normal development exhibited myoclonus refractory to antiepileptic drugs from one year ago. He developed tremor and ataxia. Cerebrospinal fluid (CSF) revealed fasting-state glucose 50 mg/dl (CSF/blood glucose ratio of 0.50). Single photon emission computed tomography with I-iodoamphetamine revealed hypoperfusion in the cerebellum. At age 4 years and 5 months, treatment with intravenous methylprednisolone (IVMP) relieved his symptoms and improved the cerebellar hypoperfusion. However, his symptoms reappeared at age 5 years and 1 month. Treatment with IVMP was repeated, resulting in transient disappearance of symptoms. At age 6 years and 9 months, he was diagnosed with GLUT1DS by genetic analysis, and treatment with modified Atkins diet was started with efficacy. Levels of anti-GluN1, -GluN2B, and -GluD2 antibodies in the serum and CSF were measured 4 times. All antibodies in the CSF were elevated over 2 standard deviations above controls, and the levels fluctuated along with the severity of his symptoms. The level of anti-GluD2 antibodies in CSF declined to the normal range only after starting the modified Atkins diet.

Conclusion: Treatment with IVMP transiently improved this patient's symptoms. Levels of anti-GluR antibodies may be associated with symptom severity.
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http://dx.doi.org/10.1016/j.braindev.2020.05.010DOI Listing
October 2020

Cryptococcus Meningitis Can Co-occur with Anti-NMDA Receptor Encephalitis.

Intern Med 2020 Sep 9;59(18):2301-2306. Epub 2020 Jun 9.

Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.

We herein report a 50-year-old man with alcoholic cirrhosis who developed loss of consciousness and tremor of the upper limbs. Magnetic resonance imaging findings were suggestive of limbic encephalitis with bilateral hippocampal damage, and a cerebrospinal fluid (CSF) examination confirmed anti-N-methyl-D-aspartate (NMDA) and anti-glutamate receptor antibodies. Despite initial corticosteroid therapy, meningeal irritation symptoms appeared, owing to the development of cryptococcal meningitis (CM), diagnosed by the detection of cryptococcal capsular polysaccharide antigen in the follow-up CSF analysis. Cerebral infarction with reversible stenosis of major cerebral arteries during the clinical course was also observed. Following administration of antifungals and corticosteroids, the number of cells in the CSF gradually declined, and NMDA receptor antibodies disappeared. Our study demonstrates the unique coexistence of CM with anti-NMDA receptor encephalitis in adults.
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http://dx.doi.org/10.2169/internalmedicine.4629-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578615PMC
September 2020

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

Alice in wonderland syndrome in an elderly patient with focal onset epilepsy.

J Clin Neurosci 2020 Jun 10;76:243-245. Epub 2020 Apr 10.

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

Alice in wonderland syndrome (AIWS) is a rare perceptual disorder characterized by subjective distortions of visual and somatosensory perception. Symptoms of AIWS are attributable to functional and structural changes of the visual and somatosensory perceptual system; however, few reports have investigated the pathophysiology of AIWS with regard to epilepsy, especially ictal electroencephalogram (EEG) changes. Herein, we describe the case of an 82-year-old woman with focal onset epilepsy presenting with AIWS, whose seizures were documented by video-EEG monitoring. Video-EEG revealed multiple focal impaired awareness seizures, and ictal EEG changes arose from the right occipital region with small periodic positive discharges with evolution towards the right centro-parietal regions. Our case highlights not only a relationship between epileptic seizures and AIWS but also provides pathological insight into AIWS.
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http://dx.doi.org/10.1016/j.jocn.2020.04.010DOI Listing
June 2020

Toxic epidermal necrolysis accompanied by several immune-related adverse events developed after discontinuation of nivolumab.

Eur J Cancer 2020 05 2;131:1-4. Epub 2020 Apr 2.

Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

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http://dx.doi.org/10.1016/j.ejca.2020.02.044DOI Listing
May 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

A case of Kleine-Levin syndrome with positive anti-NMDA-type glutamate receptor antibodies.

Pediatr Int 2020 Mar;62(3):409-410

Department of Pediatrics, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, Japan.

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http://dx.doi.org/10.1111/ped.14088DOI Listing
March 2020
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