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Research ArticleOriginal Article
Open Access

Altered plasma glutamate and glutamine levels in patients with drug-resistant and drug-responsive symptomatic focal epilepsy

Wei Wang, Yanchuan Wu, Xiaoling Li, Lin Li, Ke Sun and Suying Yan
Neurosciences Journal October 2021, 26 (4) 315-322; DOI: https://doi.org/10.17712/nsj.2021.4.20210041
Wei Wang
From the Department of Pharmacy (Wang, Li, Lin Li, Yan); from the Department of Central Laboratory (Wu); from the Department of Functional Neurosurgery (Sun); from the Beijing Institute of Functional Neurosurgery (Sun), Xuanwu Hospital, Capital Medical University, and from the Beijing Municipal Geriatric Medical Research Center (Wu), Beijing, China.
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Yanchuan Wu
From the Department of Pharmacy (Wang, Li, Lin Li, Yan); from the Department of Central Laboratory (Wu); from the Department of Functional Neurosurgery (Sun); from the Beijing Institute of Functional Neurosurgery (Sun), Xuanwu Hospital, Capital Medical University, and from the Beijing Municipal Geriatric Medical Research Center (Wu), Beijing, China.
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Xiaoling Li
From the Department of Pharmacy (Wang, Li, Lin Li, Yan); from the Department of Central Laboratory (Wu); from the Department of Functional Neurosurgery (Sun); from the Beijing Institute of Functional Neurosurgery (Sun), Xuanwu Hospital, Capital Medical University, and from the Beijing Municipal Geriatric Medical Research Center (Wu), Beijing, China.
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Lin Li
From the Department of Pharmacy (Wang, Li, Lin Li, Yan); from the Department of Central Laboratory (Wu); from the Department of Functional Neurosurgery (Sun); from the Beijing Institute of Functional Neurosurgery (Sun), Xuanwu Hospital, Capital Medical University, and from the Beijing Municipal Geriatric Medical Research Center (Wu), Beijing, China.
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Ke Sun
From the Department of Pharmacy (Wang, Li, Lin Li, Yan); from the Department of Central Laboratory (Wu); from the Department of Functional Neurosurgery (Sun); from the Beijing Institute of Functional Neurosurgery (Sun), Xuanwu Hospital, Capital Medical University, and from the Beijing Municipal Geriatric Medical Research Center (Wu), Beijing, China.
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Suying Yan
From the Department of Pharmacy (Wang, Li, Lin Li, Yan); from the Department of Central Laboratory (Wu); from the Department of Functional Neurosurgery (Sun); from the Beijing Institute of Functional Neurosurgery (Sun), Xuanwu Hospital, Capital Medical University, and from the Beijing Municipal Geriatric Medical Research Center (Wu), Beijing, China.
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  • For correspondence: [email protected]
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    Figure 1

    - Receiver operating characteristic (ROC) curve analysis of the ability of the plasma glutamate level to distinguish drug-resistant epilepsy (DRE) patients from healthy controls (A). Receiver operating characteristic curve analysis of the ability of the plasma glutamine level to distinguish drug-responsive epilepsy (DSE) patients from healthy controls (B).

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    Table 1

    - Characteristics of the healthy control participants as well as the patients with drug-resistant epilepsy (DRE) and drug-responsive epilepsy (DSE).

    CharacteristicsHealthy controls (n=132)DRE patients (n=80)P-valueDSE patients (n=46)P-value
    Gender
    Male77490.675260.83
    Female5531 20 
    Age (years)29 (26, 34)27 (23.25, 33.75)0.00927 (22, 34.25)0.056
    BMI (kg/m2)23.65 (21.8, 25.70)22.69 (19.99, 26.92)0.25422.67 (20.90, 25.51)0.27
    Duration of epilepsy (years)N/A13 (10, 21.75)N/A9 (4.75, 20)N/A
    Seizure frequency in the day prior to blood draw n (%)
    DailyN/A28 (35)N/AN/AN/A
    WeeklyN/A20 (26)N/AN/AN/A
    MonthlyN/A32 (40)N/AN/AN/A
    AED utilization profile at the last clinic visit n (%)
    MonotherapyN/A13 (16.3)N/A16 (34.8)N/A
    PolytherapyN/A67 (83.8)N/A30 (65.2)N/A
    Glutamate (μM)111.358 (99.088, 131.814)187.68 (152.505, 215.515)<0.001115.074 (91.71, 152.072)0.523
    Glutamine (μM)762.65 (709.775, 820.926)784.142 (726.821, 864.685)0.111880.132 (760.29, 954.172)<0.001
    • BMI - body mass index, AED - antiepileptic drug, N/A - not applicable. Data for age, BMI, duration of eplilepsy, and levels of glutamate and glutamine are presented as median (25% percentile, 75% percentile)

    • View popup
    Table 2

    - Plasma glutamate and glutamine levels in the DRE, DSE, and control groups (adjusted for age as a covariate).

    VariablesMean95% [CI]Test statisticsP-value
    Glutamate (μM)
    Control112.618[106.687-118.549]F=233.749<0.001
    DRE187.483[179.838-195.129]
    Glutamine (μM)
    Control767.876[751.039-784.713]F=0.9550.33
    DRE781.459[759.757-803.162]
    Glutamate (μM)
    Control113.167[108.175-118.16]F=3.120.079
    DSE121.886[113.487-130.284]
    Glutamine (μM)
    Control766.568[749.486-783.649]F=30.118<0.001
    DSE859.253[830.517-887.989]
    • DRE - drug-resistant epilepsy, DSE - drug-response epilepsy, CI - confidence interval

    • View popup
    Table 3

    - Univariate and multivariate logistic regression analyses of variables able to discriminate between DRE patients and controls.

    VariablesCrude OR [95% CI]P-valueAdjusted OR [95% CI]P-value
    Gender
    FemaleRef.   
    Male1.129 [0.64-1.991]0.675  
    Age0.947 [0.906-0.990]0.0170.963 [0.899-1.03]0.273
    BMI0.989 [0.911-1.073]0.786  
    Glutamate1.071 [1.051-1.093]<0.0011.071 [1.051-1.093]<0.001
    Glutamine1.002 [0.999-1.005]0.176  
    • DRE - drug-resistant epilepsy, OR - odds ratio, CI - confidence interval

    • View popup
    Table 4

    - Univariate logistic regression analysis of factors able to discriminate between DSE patients and controls.

    VariablesCrude OR [95% CI]P-value
    Gender
    FemaleRef. 
    Male0.929 [0.471-1.829]0.83
    Age0.974 [0.928-1.022]0.282
    BMI0.982 [0.873-1.106]0.769
    Glutamate1.01 [0.999-1.021]0.083
    Glutamine1.009 [1.005-1.012]<0.001
    • DSE - drug-response epilepsy, OR - odds ratio, CI - confidence interval

    • View popup
    Table 5

    - Univariate and multivariate ordinal logistic regression analyses for association between tertile glutamate levels and factors in the DRE group.

    VariableCrude OR [95% CI]P-valueAdjusted OR [95% CI]P-value
    Gender
    Female1 1 
    Male6.526 [2.571-16.567]<0.0016.021 [2.344-15.468]<0.001
    Age0.987 [0.932-1.046]0.665  
    BMI1.124 [1.024-1.233]0.0141.109 [1.006-1.222]0.037
    Duration of epilepsy1.011 [0.966-1.058]0.645  
    Seizure frequency
    Daily1   
    Weekly0.874 [0.304-2.514]0.803
    Monthly1.253 [0.493-3.187]0.635
    AED utilization profile at the last clinic visit
    Monotherapy1   
    Polytherapy0.967 [0.325-2.879]0.951
    • DRE - drug-resistant epilepsy, OR - odds ratio, CI - confidence interval, BMI - body mass index, AED - antiepileptic drug. Glutamate levels were sorted into a 3-level ordinal scale based on tertiles

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Altered plasma glutamate and glutamine levels in patients with drug-resistant and drug-responsive symptomatic focal epilepsy
Wei Wang, Yanchuan Wu, Xiaoling Li, Lin Li, Ke Sun, Suying Yan
Neurosciences Journal Oct 2021, 26 (4) 315-322; DOI: 10.17712/nsj.2021.4.20210041

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Altered plasma glutamate and glutamine levels in patients with drug-resistant and drug-responsive symptomatic focal epilepsy
Wei Wang, Yanchuan Wu, Xiaoling Li, Lin Li, Ke Sun, Suying Yan
Neurosciences Journal Oct 2021, 26 (4) 315-322; DOI: 10.17712/nsj.2021.4.20210041
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