The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Yukitoshi Takahashi - One of the best experts on this subject based on the ideXlab platform.
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Functional neuroimaging in Rasmussen Syndrome.
Epilepsy research, 2018Co-Authors: Ichiro Kuki, Yukitoshi Takahashi, Yushi Inoue, Kazumi Matsuda, Yuko Kubota, Tetsuhiro Fukuyama, Haruo ShintakuAbstract:Abstract Purpose For a diagnosis of Rasmussen Syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. Methods Twenty-three patients diagnosed with RS according to Bien’s (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. Results Hypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. Conclusion In RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.
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semi quantitative analyses of antibodies to n methyl d aspartate type glutamate receptor subunits glun2b glun1 in the clinical course of Rasmussen Syndrome
Epilepsy Research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen Syndrome.
Epilepsy research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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Genetic variations of immunoregulatory genes associated with Rasmussen Syndrome.
Epilepsy research, 2013Co-Authors: Yukitoshi Takahashi, Noriyuki Akasaka, Kazumi Matsuda, Atsushi Imamura, Katsumi Imai, Yukiko Mogami, June Mine, Yasumichi Koide, Takashi Konishi, Yushi InoueAbstract:Summary Objective To elucidate the genetic predisposition of Rasmussen Syndrome (RS). Methods In 29 Japanese patients, we examined the genome sequences of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed cell-death 1 (PDCD1) , and T-bet (TBX21) genes by direct sequencing, and evaluated the significance of SNPs (single nucleotide polymorphism) by comparison with Hap Map data. Results In all patients, no disease-causative mutations were found in CTLA4 , PDCD1 , and T-bet . However, rs231775 SNP in exon 1 of CTLA4 showed significant positive genotypic ( p =0.0363) and allelic associations ( p =0.0137) with onset of RS compared with Japanese controls, as did rs231779 SNP in intron 1 of CTLA4 ( p =0.0467 and 0.0188, respectively). Also, rs2227982 SNP in exon 5 of PDCD1 showed significant positive genotypic and allelic associations with RS ( p =0.0145 and 0.0114, respectively). Poor cognitive outcome (IQ below 50) was found in 0% of wild type (C/C), 9% of heterologous (C/T) and 25% of homologous (T/T) genotype of rs2227982. Quadriplegia was found only in homologous (T/T) genotype, and hemiplegia was in heterologous (C/T) and homologous (T/T) genotype of rs2227982. No association between SNPs of T-bet and RS onset was found. Regarding SNPs in promoter regions (rs4794067 and rs17250932) of T-bet , however, IQ below 50 was found in 19% of wild type (T/T) and 0% of heterologous (T/C) genotype of rs4794067, and in 19% of wild type (T/T) and 0% of heterologous (T/C) genotype of rs17250932. Quadriplegic patients were found only in wild-type patients (rs4794067 and rs17250932). Conclusions We identified three SNPs (rs231775, rs231779, rs2227982) as some of the SNPs associated with onset of Japanese RS. We need further studies in other populations to confirm these genetic predispositions in RS.
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immunomodulatory therapy versus surgery for Rasmussen Syndrome in early childhood
Brain & Development, 2013Co-Authors: Yukitoshi Takahashi, Etsuko Yamazaki, Hirokazu Oguni, Kazumi Matsuda, Yuko Kubota, Jun Mine, Katsumi Imai, Yuki Mogami, Koichi Baba, Kenji SugaiAbstract:Abstract We examined seizure, cognitive, and motor outcomes in patients with Rasmussen Syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100 mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30 mg/kg/day (children) or 1000 mg/day (adults) for 3 days. Tacrolimus was given at an initial dose of 0.1 mg/kg/day (children). Mean onset age was 8.7 ± 10.5 years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.
Yuko Kubota - One of the best experts on this subject based on the ideXlab platform.
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Functional neuroimaging in Rasmussen Syndrome.
Epilepsy research, 2018Co-Authors: Ichiro Kuki, Yukitoshi Takahashi, Yushi Inoue, Kazumi Matsuda, Yuko Kubota, Tetsuhiro Fukuyama, Haruo ShintakuAbstract:Abstract Purpose For a diagnosis of Rasmussen Syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. Methods Twenty-three patients diagnosed with RS according to Bien’s (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. Results Hypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. Conclusion In RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.
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semi quantitative analyses of antibodies to n methyl d aspartate type glutamate receptor subunits glun2b glun1 in the clinical course of Rasmussen Syndrome
Epilepsy Research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen Syndrome.
Epilepsy research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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immunomodulatory therapy versus surgery for Rasmussen Syndrome in early childhood
Brain & Development, 2013Co-Authors: Yukitoshi Takahashi, Etsuko Yamazaki, Hirokazu Oguni, Kazumi Matsuda, Yuko Kubota, Jun Mine, Katsumi Imai, Yuki Mogami, Koichi Baba, Kenji SugaiAbstract:Abstract We examined seizure, cognitive, and motor outcomes in patients with Rasmussen Syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100 mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30 mg/kg/day (children) or 1000 mg/day (adults) for 3 days. Tacrolimus was given at an initial dose of 0.1 mg/kg/day (children). Mean onset age was 8.7 ± 10.5 years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.
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a substantial number of Rasmussen Syndrome patients have increased igg cd4 t cells tnfα and granzyme b in csf
Epilepsia, 2009Co-Authors: Yukitoshi Takahashi, Etsuko Yamazaki, Yuko Kubota, Jyun Mine, Tateki FujiwaraAbstract:PURPOSE We studied the immunologic molecules in cerebrospinal fluid (CSF) and discussed their evolutional changes in pediatric patients with Rasmussen Syndrome (RS). METHODS CSF samples collected from 27 patients with RS (average onset age, 7.5 +/- 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride, and immunoglobulin G (IgG) levels were measured by conventional methods. Surface markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B, interferon gamma (IFNgamma), interleukin 4 (IL-4), tumor necrosis factor alpha (TNFalpha), and IL-12 in CSF were quantitated by enzyme-linked immunosorbent assay (ELISA). Autoantibodies against GluR epsilon2 (NR2B) were examined by immunoblot. RESULTS The data of the first CSF examination showed that IgG levels (Mann-Whitney U test, p < 0.01), CD4(+) T cells (p = 0.02), TNFalpha levels (p < 0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease controls. White blood cell count, IFNgamma level, IL-12 level, and Granzyme B level were elevated, especially in the early stage of disease. CD4(+) T cells, CD8(+) cells, CD3(+) T cells, IgG levels, and TNFalpha levels were elevated at all stages of disease evolution. Protein levels and albumin levels were elevated in the progressed stage. Autoantibodies against GluR epsilon2 (NR2B) (IgG) were found in 50% of patients in the early stage, and the positive rate was low at the progressed stage. DISCUSSION The present findings suggest that complex pathophysiologic mechanisms involving CD4(+) T cells and CD8(+) T cells change evolutionally during the progression of RS. A crucial cytotoxic process occurs in the early stage, and declines in the progressed stage.
Shigeko Nishimura - One of the best experts on this subject based on the ideXlab platform.
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semi quantitative analyses of antibodies to n methyl d aspartate type glutamate receptor subunits glun2b glun1 in the clinical course of Rasmussen Syndrome
Epilepsy Research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen Syndrome.
Epilepsy research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
Tetsuhiro Fukuyama - One of the best experts on this subject based on the ideXlab platform.
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Functional neuroimaging in Rasmussen Syndrome.
Epilepsy research, 2018Co-Authors: Ichiro Kuki, Yukitoshi Takahashi, Yushi Inoue, Kazumi Matsuda, Yuko Kubota, Tetsuhiro Fukuyama, Haruo ShintakuAbstract:Abstract Purpose For a diagnosis of Rasmussen Syndrome (RS), clinical course together with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings are considered important, but there are few reports on functional neuroimaging. This study investigated cerebral blood flow (CBF)-single photon emission computed tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18 fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and correlated neuroimaging results with MRI and pathological findings. Methods Twenty-three patients diagnosed with RS according to Bien’s (2005) diagnostic criteria (including 12 patients with a histological diagnosis) were studied. CBF-SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings correlated with MRI and histological findings. Results Hypoperfusion areas were observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine patients, lowered uptake was detected in all nine patients, including two with no MRI abnormalities. Lowered glucose metabolism was observed in affected areas in all five patients by FDG-PET. Histological examination revealed findings of chronic encephalitis in all 12 patients examined, concomitant with focal cortical dysplasia in five patients. Conclusion In RS patients, functional neuroimaging reveals clear abnormal findings, even before the appearance of MRI abnormalities. BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may suggest possible impairment of inhibitory neurons.
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semi quantitative analyses of antibodies to n methyl d aspartate type glutamate receptor subunits glun2b glun1 in the clinical course of Rasmussen Syndrome
Epilepsy Research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen Syndrome.
Epilepsy research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
Hirokazu Oguni - One of the best experts on this subject based on the ideXlab platform.
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semi quantitative analyses of antibodies to n methyl d aspartate type glutamate receptor subunits glun2b glun1 in the clinical course of Rasmussen Syndrome
Epilepsy Research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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Semi-quantitative analyses of antibodies to N-methyl-d-aspartate type glutamate receptor subunits (GluN2B & GluN1) in the clinical course of Rasmussen Syndrome.
Epilepsy research, 2015Co-Authors: Tetsuhiro Fukuyama, Yukitoshi Takahashi, Hirokazu Oguni, Yuko Kubota, Katsumi Imai, Yukiko Mogami, Yoshiyuki Kondo, Hiroshi Sakuma, Koji Tominaga, Shigeko NishimuraAbstract:Summary Objective In Rasmussen Syndrome (RS), in addition to the predominant involvement of cytotoxic T cells, heterogeneous autoantibodies against neural molecules are also found, but their function has not been elucidated. We examined antibodies to N -methyl-d-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN2B & GluN1) semi-quantitatively in cerebrospinal fluid (CSF) samples from RS patients, and evaluated their changes over time and their roles in immunopathogenesis. Methods Autoantibodies against N-terminal and C-terminal of GluN2B and GluN1 were examined in 40 CSF samples collected from 18 RS patients 5 to 180 months after the onset of RS. Epileptic patients without infectious etiology or progressive clinical course served as disease controls ( n =23). Synthesized peptides encoding the extracellular and intracellular domains of human GluN2B and GluN1 subunits were used as antigens in ELISA. We defined the cut-off for these antibodies as mean +2 standard deviations (optimal density) of the disease controls. MRI were evaluated according to the MRI staging proposed by Bien et al. (2002b, Neurology 58, 250). Results CSF levels of antibodies against N-terminal and C-terminal of GluN2B were higher in RS patients than in disease controls ( p p p p Conclusions Broad epitope recognition spectrum and delayed production of autoantibodies to NMDA type GluR in CSF of RS patients suggest that the autoantibodies are produced against NMDA type GluR antigens derived from cytotoxic T cell-mediated neuronal damages. These antibodies may impact the pathophysiology of RS in the most active stage, and could be a marker for active inflammation in the clinical course of RS. Further studies including passive transfer of the antibodies to mice may reveal the pivotal roles of the antibodies in RS.
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immunomodulatory therapy versus surgery for Rasmussen Syndrome in early childhood
Brain & Development, 2013Co-Authors: Yukitoshi Takahashi, Etsuko Yamazaki, Hirokazu Oguni, Kazumi Matsuda, Yuko Kubota, Jun Mine, Katsumi Imai, Yuki Mogami, Koichi Baba, Kenji SugaiAbstract:Abstract We examined seizure, cognitive, and motor outcomes in patients with Rasmussen Syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100 mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30 mg/kg/day (children) or 1000 mg/day (adults) for 3 days. Tacrolimus was given at an initial dose of 0.1 mg/kg/day (children). Mean onset age was 8.7 ± 10.5 years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months.
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Rasmussen Syndrome: multifocal spread of inflammation suggested from MRI and PET findings.
Epilepsia, 2003Co-Authors: Yumi Maeda, Hirokazu Oguni, Yoshiaki Saitou, Ayako Mutoh, Kaoru Imai, Makiko Osawa, Yukio Fukuyama, Tomokatsu Hori, Fumitaka Yamane, Osamu KuboAbstract:Summary: Background: A 6-year-old girl with Rasmussen Syndrome (RS) showed multiple small high-signal-intensity areas independently in the right hemisphere by fluid-attenuated inversion recovery (FLAIR) imaging on magnetic resonance imaging (MRI) 1 year after the onset of epilepsy. Methods: MRI performed 4 months later demonstrated a further increase in the number of these foci and enlargement in the size of the previous FLAIR lesions. Results: An [ 18 F]-fluorodeoxyglucose‐positron emission tomography (FDG-PET) study showed a strong, spotty uptake in the right temporooccipital regions, corresponding to the sites of continuous EEG seizure discharges. In contrast, [ 11 C]methionine PET demonstrated multifocal uptake regions, which corresponded anatomically to the FLAIR lesions, suggesting sites of underlying chronic inflammation. Conclusions: These neuroimaging findings suggested that the inflammatory process in RS spreads either multifocally at the same time, as seen in this case, or from one discrete area to the adjacent region, as reported previously. Key Words: Rasmussen Syndrome—FLAIR image—[ 11 C]methionine PET—Multifocal spread.
