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Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus

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Abstract

Background

The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient).

Methods

This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L).

Results

A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19–99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection.

Conclusions

Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

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Source of support

None.

Data availability

Data sets are available from the corresponding author for any qualified investigator.

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Acknowledgements

We acknowledge the editorial assistance of the North Carolina Translational and Clinical Sciences Institute and i2b2 software, which was used in conducting the study; both are supported by the National Center for Advancing Translational Sciences of the National Institutes of Health through grant award UL1TR002489.

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Authors and Affiliations

  1. Department of Neurology, Division of Critical Care Neurology and Division of Epilepsy, University of North Carolina at Chapel Hill, 170 Manning Drive, Physician Office, Chapel Hill, NC, USA

    Clio Rubinos, Courtney Blodgett, Carolyn Tsai, Susan E. Wilson, Casey Olm-Shipman & Rick Meeker

  2. Department of Neurology, University of Florida, Gainesville, FL, CB 7025, USA

    Maria Jose Bruzzone

  3. School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Puja Patel & Rachel Hianik

  4. Department of Neurology, Yale University School of Medicine, New Haven, CT, USA

    Rakesh Jadav & Lawrence J. Hirsch

  5. Instituto de Investigación Científica, Universidad de Lima, Lima, Peru

    Jordane Boudesseul

  6. Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA

    Chuning Liu & Hongtu Zhu

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  1. Clio Rubinos
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Contributions

Dr. Rubinos, Bruzzone and Hirsch conceptualized and designed the study, oversaw data acquisition, and intellectually revised the manuscript. Dr. Rubinos drafted the manuscript and intellectually revised it. Mr. Boudesseul provided initial data analysis and revision of manuscript. Drs. Tsai and Jadav and Mrs. Patel, Mrs. Hainik, and Mrs. Blodgett were responsible for data acquisition and critically revised the manuscript. Drs. Wilson, Meeker, Bruzzone, Olm-Shipman, and Hirsch revised the manuscript for intellectual content. Dr Zhu and Mrs Liu performed the final statistical analysis.

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Correspondence to Clio Rubinos.

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Conflict of interest

No author declared any conflict of interest pertaining to this article, and all reported items pertain to outside of this work. Drs. Tsai, Jadav, Bruzzone, Olm-Shipman, Wilson, and Meeker and Mrs. Patel, Mrs. Hainik, and Mrs. Blodgett did not report any disclosures. Dr. Rubinos receives funding from the Physician in Training Program (UNC School of Medicine). Dr. Hirsch reports research support to Yale University for investigator-initiated studies from the Daniel Raymond Wong Neurology Research Fund at Yale; royalties from Wiley and Wolters-Kluwer; personal fees from Ceribell, Monteris, Neuropace, Aquestive, Medtronic, UCB, Marinus, Accure, Natus, Neurelis, and Eisai; and speaking honoraria from Neuropace, Natus, and UCB.

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This study adheres to ethical guidelines and has approval from the local institutional review board (UNC, IRB20-3089; Yale, IRB HIC#111109342), including waiver of consent.

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Rubinos, C., Bruzzone, M.J., Blodgett, C. et al. Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus. Neurocrit Care 38, 41–51 (2023). https://doi.org/10.1007/s12028-022-01579-z

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