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  • Wiley  (6)
  • Lee, Han Sang  (6)
  • 1
    Online Resource
    Online Resource
    Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy
    Wiley ; 2022
    In:  Epilepsia Vol. 63, No. 11 ( 2022-11), p. 2958-2969
    Details
    In: Epilepsia, Wiley, Vol. 63, No. 11 ( 2022-11), p. 2958-2969
    Abstract: Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large‐scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity. Methods Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 ( CYP )2C9 and CYP2C19 genes. In addition, clinical information—including efficacy, toxicity, and concomitant drugs—was collected. Results The serum LCM concentration showed a linear correlation with the daily dose ( r  = .66, p   〈  .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups ( p  = .01 and p   〈  .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p  = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p   〈  .001). Based on this, we suggest a reference range for LCM in the Korean population (6–9 μg/ml). Significance Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Issue
    URL: Article
    DOI: 10.1111/epi.v63.11
    DOI: 10.1111/epi.17399
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2002194-X
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  • 2
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    Mega‐dose phenobarbital therapy for super‐refractory status epilepticus
    Wiley ; 2015
    In:  Epileptic Disorders Vol. 17, No. 4 ( 2015-12), p. 444-452
    Details
    In: Epileptic Disorders, Wiley, Vol. 17, No. 4 ( 2015-12), p. 444-452
    Abstract: Aims . To evaluate the efficacy and safety of mega‐dose phenobarbital (MDPB; enteral or parenteral phenobarbital 〉 10 mg/kg/day) for treating super‐refractory status epilepticus (SRSE; continuous or recurrent status epilepticus for ≥24 hours after the onset of continuous anaesthetic treatment) in adult patients. Methods . Adult patients with SRSE who were treated with MDPB in our institution from March 2005 to September 2014 were reviewed. We collected data on basic demographics, clinical features, functional status, anticonvulsant treatment, and possible adverse events. SRSE outcome was divided into six categories: successful therapy, initial failure, breakthrough seizures, withdrawal seizures, intolerable side effects, and death during treatment. Results . Ten adult patients with SRSE received MDPB. Median age at seizure onset was 38 years (range: 18‐59), and half were male. All patients had no history of seizures and had symptoms suggestive of viral encephalitis. Median duration of status epilepticus was 17.5 days (range: 6–60) and anaesthetics were used for a median of 14.0 days (range: 2–54) before MDPB. Successful control of SRSE was achieved in half of the patients, however, only one of ten patients was able to fully recover at discharge. Median duration of the MDPB was 45.5 days and the maximum serum phenobarbital level reached a median of 151.5 μg/ml. Patients with successful MDPB therapy had normal brain imaging (80% vs. 0%; p =0.048) and better functional outcome at discharge and after three months of follow‐up. Infection was the most critical complication, along with cardiorespiratory depression. Conclusion . MDPB is a therapeutic option for control of SRSE when other choices are exhausted.
    Type of Medium: Online Resource
    ISSN: 1294-9361 , 1950-6945
    URL: Issue
    URL: Article
    DOI: 10.1684/epd2.2015.17.issue-4
    DOI: 10.1684/epd.2015.0778
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2118181-0
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  • 3
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    Anti‐LGI1 encephalitis is associated with unique HLA subtypes
    Wiley ; 2017
    In:  Annals of Neurology Vol. 81, No. 2 ( 2017-02), p. 183-192
    Details
    In: Annals of Neurology, Wiley, Vol. 81, No. 2 ( 2017-02), p. 183-192
    Abstract: Autoimmune encephalitis (AE), represented by anti–leucine‐rich glioma‐inactivated 1 (anti‐LGI1) and anti–N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis, has increasing clinical significance based on recent discoveries of neuronal autoantibodies. However, its immunopathogenesis is not fully understood. Here, we investigated whether AE is associated with the human leukocyte antigen (HLA) subtypes. Methods We compared the HLA genotypes of 11 anti‐LGI1 and 17 anti‐NMDAR encephalitis patients to the control groups, which consisted of 210 epilepsy patients and 485 healthy Koreans. Results Anti‐LGI1 encephalitis was associated with the DRB1*07:01–DQB1*02:02 haplotype (10 patients; 91%) in HLA class II genes, as well as with B*44:03 (8 patients; 73%) and C*07:06 (7 patients; 64%) in the HLA class I region. The prevalence of these alleles in anti‐LGI1 encephalitis was significantly higher than that in the epilepsy controls or healthy controls. By contrast, anti‐NMDAR encephalitis was not associated with HLA genotypes. Additional analysis using HLA‐peptide binding prediction algorithms and computational docking underpinned the close relationship. Interpretation This finding suggests that most anti‐LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183–192
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v81.2
    DOI: 10.1002/ana.24860
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2037912-2
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  • 4
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    Anakinra treatment for refractory cerebral autoinflammatory responses
    Wiley ; 2022
    In:  Annals of Clinical and Translational Neurology Vol. 9, No. 1 ( 2022-01), p. 91-97
    Details
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 9, No. 1 ( 2022-01), p. 91-97
    Abstract: Refractory cerebral autoinflammatory–autoimmune diseases are often associated with dysregulated innate immunity and are targeted by anakinra, an interleukin‐1 receptor antagonist. We analyzed the therapeutic effect of anakinra in refractory cerebral autoinflammatory response (CAIR) at a single institution from January 2017 to May 2021. In total, 12 patients with various etiologies were sympathetically treated with anakinra (100 mg/day subcutaneously). Four patients showed good responses, and among these patients, three patients had pathologically demonstrated CAIR. The other eight patients were nonresponsive. No patient had a serious adverse effect. Thus, anakinra may be a therapeutic option for refractory cerebral autoinflammatory diseases.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    URL: Article
    DOI: 10.1002/acn3.v9.1
    DOI: 10.1002/acn3.51500
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2740696-9
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  • 5
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    The safety and efficacy of intravenous immunoglobulin in autoimmune encephalitis
    Wiley ; 2022
    In:  Annals of Clinical and Translational Neurology Vol. 9, No. 5 ( 2022-05), p. 610-621
    Details
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 9, No. 5 ( 2022-05), p. 610-621
    Abstract: Although intravenous immunoglobulin (IVIG) is the first‐line immunotherapy in autoimmune encephalitis, all supporting evidence comes from retrospective case series. Here, we performed a prospective clinical trial of IVIG for functional recovery in autoimmune encephalitis. Methods This single‐arm, open‐label study assessed the efficacy and safety of 10% intravenous IVIG treatment in newly diagnosed patients with possible autoimmune encephalitis. Patients received IVIG (0.4 g/kg/day) for 5 days. Rescue immunotherapy was permitted when the patient deteriorated before day 8 or showed no improvement at day 8. The primary outcome was the change in the modified Rankin Scale (mRS) score at day 8 and 29. The secondary outcomes were the mRS score improvement and the score changes and improvements on four other clinical scales. Results Overall, 23 patients received IVIG (intension‐to‐treat, ITT), and 18 patients completed the study according to the protocol (per‐protocol, PP). mRS improved significantly at days 8 and 29 compared to baseline in both the ITT and PP populations. Other secondary outcomes also improved significantly at day 8, 15, and 29 versus baseline. In the PP population, 6/18 patients achieved favorable outcomes with IVIG alone (mRS = 0~2 at day 8), and 12/18 patients received rescue immunotherapy. Five adverse events were reported in relation to IVIG, all of which were mild. Interpretation IVIG improved neurological functional outcomes, and the improvement was evident by day 8. Adverse effects were tolerable. These data provide the prospective evidence regarding the efficacy of IVIG in improving the functional outcomes of autoimmune encephalitis.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    URL: Article
    DOI: 10.1002/acn3.v9.5
    DOI: 10.1002/acn3.51540
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2740696-9
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  • 6
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    Tofacitinib treatment for refractory autoimmune encephalitis
    Wiley ; 2021
    In:  Epilepsia Vol. 62, No. 4 ( 2021-04)
    Details
    In: Epilepsia, Wiley, Vol. 62, No. 4 ( 2021-04)
    Abstract: To treat intractable cases of autoimmune encephalitis, the need for novel immunotherapy that penetrates the blood‐brain barrier (BBB) is increasing. Tofacitinib is a Janus kinase (JAK) inhibitor used to treat refractory immune‐mediated diseases that effectively penetrates the BBB. Accordingly, tofacitinib could be a new option for patients with refractory autoimmune encephalitis. Patients treated with tofacitinib were selected from Seoul National University Hospital cohort for autoimmune encephalitis from April 2019 until July 2020. We retrospectively analyzed the efficacy of tofacitinib in patients with autoimmune encephalitis who showed insufficient responses to multimodal conventional immunotherapies. Tofacitinib was administered orally at a dose of 5 mg twice daily. A total of eight patients were treated with tofacitinib; two had good responses (clinical global impression‐improvement score [CGI‐I] = 1 or 2), three had partial responses (CGI‐I = 3), and three showed no significant improvements (CGI‐I = 4) in response to tofacitinib. The two good responders showed the improvement of chronic autoimmune meningoencephalitis and the cessation of the new‐onset refractory status epilepticus in anti‐myelin oligodendrocyte glycoprotein (MOG)–associated disorder, which was previously intractable to anesthetics and the other immunotherapies. No patients had serious side effects. Our findings suggest the potential of tofacitinib as a therapeutic option for central nervous system autoimmune diseases.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Issue
    URL: Article
    DOI: 10.1111/epi.v62.4
    DOI: 10.1111/epi.16848
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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