Symptomatic treatments of N-methyl-D-aspartate receptor encephalitis

Lee, Sang Kun

doi:10.47936/encephalitis.2020.00045

Cited by 6 publications

(8 citation statements)

References 15 publications

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“…In recent years, the utilization of topiramate monotherapy has become less common in South Korea due to the development of next‐generation ASMs. 31 , 32 However, topiramate remains a highly effective option when used as an add‐on therapy. Our study highlights the importance of using lower doses than previously suggested.…”

Section: Discussionmentioning

confidence: 99%

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling

Lee,

Kim,

Jang

et al. 2023

Ann Clin Transl Neurol

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ObjectiveDespite the suggested topiramate serum level of 5–20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range.MethodsWe retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as “insufficient” or “sufficient” by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values.ResultsA total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L.InterpretationThis study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia‐related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

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Section: Discussionmentioning

confidence: 99%

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling

Lee,

Kim,

Jang

et al. 2023

Ann Clin Transl Neurol

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“…Chronic environmental stress, including social stress, is known to induce inflammation in the brain, which is closely related to the psychiatric or psychosocial behaviors shown in brain disorders such as schizophrenia, dementia, encephalitis, autism, and psychopathy [ 1 - 27 ]. In humans, early-life stress (child and adolescent abuse and neglect) can induce structural or functional alterations in the brain, and chronically, repetitively abused or maltreated children often develop antisocial behavior, such as aggressive or violent and sadistic behaviors, in adulthood.…”

Section: Introductionmentioning

confidence: 99%

Chronic social stress in early life can predispose mice to antisocial maltreating behavior

Jeon,

Kim,

Lee

et al. 2024

encephalitis

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PurposeIn our previous study, we developed an assay system to evaluate antisocial maltreating behavior of conspecific mice using a perpetrator–victim paradigm. We also generated a mouse model for the maltreating behavior by mimicking child maltreatment or abuse. Here, we further investigate the antisocial behavior using anti-aggressive and antipsychotic drugs. MethodsModel mice sequentially subjected to maternal separation (MS), social defeat (SD), and social isolation (SI) in that order (MS/SD/SI model) were subjected to a maltreating behavioral task. The MS/SD/SI mice were treated with oxytocin (OXY), clozapine (CLZ), haloperidol (HAL), and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Western blotting and enzyme-linked immunosorbent assay were used for protein analysis. ResultsA substantial portion of the MS/SD/SI model mice (46% of males and 40% of females) showed a higher number of nose pokes than the control. OXY or 8-OH-DPAT treatment reduced the high number of nose pokes by the MS/SD/SI mice, whereas HAL increased it. CLZ did not affect the number of nose pokes by the MS/SD/SI mice. Interestingly, although the OXY level in the MS/SD/SI mice was similar to that in the control, the amount of OXY receptor was lower in the MS/SD/SI mice. The amount of 5-HT1A receptor was also decreased in the MS/SD/SI mice. ConclusionChronic social stress in childhood might predispose a mouse to antisocial behavior. Our maltreating behavior assay system, including the MS/SD/SI model, is a good animal system for research on and drug screening for brain disorders associated with antisocial or psychotic behavior.

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“…Ovarian teratoma is found in approximately 40% of patients, 2 in which the teratoma has NR1 expression and a germinal center leading to B‐cell activation and antibody production 3,4 . Accordingly, rapid removal of the ovarian teratoma, in addition to early adjuvant immunotherapy, is essential for patients' recovery 2,5,6 . However, in the majority of NMDARe patients without teratoma, other than the fact that B cells in cervical lymph nodes are NR1‐reactive in some patients, 3 the immunogenic cause is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“… 3 , 4 Accordingly, rapid removal of the ovarian teratoma, in addition to early adjuvant immunotherapy, is essential for patients' recovery. 2 , 5 , 6 However, in the majority of NMDARe patients without teratoma, other than the fact that B cells in cervical lymph nodes are NR1‐reactive in some patients, 3 the immunogenic cause is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Teratoma pathology and genomics in anti‐NMDA receptor encephalitis

Jang,

Lee,

Lee

et al. 2023

Ann Clin Transl Neurol

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IntroductionOvarian teratoma is a common occurrence in patients with anti‐NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to investigate the genomic landscape and microscopic findings by comparing NMDARe‐associated teratomas and non‐encephalitic control teratomas.Materials and MethodsA prospective consecutive cohort of 84 patients with NMDARe was recruited from January 2014 to April 2020, and among them, patients who received teratoma removal surgery at Seoul National University Hospital were enrolled. We conducted a comparison of whole‐exome sequencing data and pathologic findings between NMDARe‐associated teratomas and control teratomas.ResultsWe found 18 NMDARe‐associated teratomas from 15 patients and compared them with 17 non‐encephalitic control teratomas. Interestingly, the genomic analysis revealed no significant differences in mutations between encephalitic and non‐encephalitic teratomas. Pathologic analysis showed no discrepancies in terms of the presence of neuronal tissue and lymphocytic infiltration between the encephalitic teratomas (n = 14) and non‐encephalitic teratomas (n = 18). However, rituximab‐naïve encephalitic teratomas exhibited a higher frequency of germinal center formation compared to non‐encephalitic teratomas (80% vs. 16.7%, P = 0.017). Additionally, rituximab‐treated encephalitic teratomas demonstrated a reduced number of CD20+ cells and germinal centers in comparison to rituximab‐naïve encephalitic teratomas (P = 0.048 and 0.023, respectively).DiscussionThese results suggest that the initiation of immunopathogenesis in NMDARe‐associated teratoma is not primarily attributed to intrinsic tumor mutations, but rather to immune factors present in the encephalitic patient group, ultimately leading to germinal center formation within the teratoma.

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Symptomatic treatments of N-methyl-D-aspartate receptor encephalitis

Cited by 6 publications

References 15 publications

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling

Chronic social stress in early life can predispose mice to antisocial maltreating behavior

Teratoma pathology and genomics in anti‐NMDA receptor encephalitis

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