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. 2023 Apr;64(4):1035-1045.
doi: 10.1111/epi.17532. Epub 2023 Feb 19.

Influence of comorbidity on mortality in patients with epilepsy and psychogenic nonepileptic seizures

Michael Tan  1 , Neil Pearce  2 , Aurelio Tobias  3   4 , Mark J Cook  1 , Wendyl J D'Souza  1   5
Affiliations

Influence of comorbidity on mortality in patients with epilepsy and psychogenic nonepileptic seizures

Michael Tan et al. Epilepsia. 2023 Apr.

Abstract

Objective: This study aims to determine the contribution of comorbidities to excess psychogenic nonepileptic seizures (PNES) mortality.

Methods: A retrospective cohort study was conducted of tertiary epilepsy outpatients from St. Vincent's Hospital Melbourne, Australia with an 8:1 comparison cohort, matched by age, sex, and socioeconomic status (SES) to national administrative databases between 2007 and 2017. Privacy-preserving data linkage was undertaken with the national prescription, National Death Index, and National Coronial Information System. Forty-five comorbid disease classes were derived by applying the Australian validated RxRisk-V to all dispensed prescriptions. We fitted Cox proportional hazard models controlling for age, sex, SES, comorbidity, disease duration, and number of concomitant antiseizure medications, as a marker of disease severity. We also performed a parallel forward-selection change in estimate strategy to explore which specific comorbidities contributed to the largest changes in the hazard ratio.

Results: A total of 13 488 participants were followed for a median 3.2 years (interquartile range = 2.4-4.0 years), including 1628 tertiary epilepsy outpatients, 1384 patients with epilepsy, 176 with PNES, and 59 with both. Eighty-two percent of epileptic seizures and 92% of typical PNES events were captured in an epilepsy monitoring unit. The age-/sex-/SES-adjusted hazard ratio was elevated for epilepsy (4.74, 95% confidence interval [CI] = 3.36-6.68) and PNES (3.46, 95% CI = 1.38-8.68) and remained elevated for epilepsy (3.21, 95% CI = 2.22-4.63) but not PNES (2.15, 95% CI = .77-6.04) after comorbidity adjustment. PNES had more pre-existing comorbidities (p = .0007), with a three times greater median weighted Rx-RiskV score. Psychotic illness, opioid analgesia, malignancies, and nonopioid analgesia had the greatest influence on PNES comorbid risk.

Significance: Higher comorbidity appears to explain the excess PNES mortality and may represent either a wider underrecognized somatoform disorder or a psychological response to physical illness. Better understanding and management of the bidirectional relationship of these wider somatic treatments in PNES could potentially reduce the risk of death.

Keywords: PNES; comorbidity; epidemiology; epilepsy; mortality.

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References

REFERENCES

    1. Nevalainen O, Ansakorpi H, Simola M, Raitanen J, Isojarvi J, Artama M, et al. Epilepsy-related clinical characteristics and mortality: a systematic review and meta-analysis. Neurology. 2014;83(21):1968-77.
    1. Callaghan B, Choi H, Schlesinger M, Rodemer W, Pollard J, Hesdorffer DC, et al. Increased mortality persists in an adult drug-resistant epilepsy prevalence cohort. J Neurol Neurosurg Psychiatry. 2014;85(10):1084-90.
    1. Giussani G, Bianchi E, Beretta S, Carone D, DiFrancesco JC, Stabile A, et al. Comorbidities in patients with epilepsy: frequency, mechanisms and effects on long-term outcome. Epilepsia. 2021;62(10):2395-404.
    1. Keezer MR, Bell GS, Neligan A, Novy J, Sander JW. Cause of death and predictors of mortality in a community-based cohort of people with epilepsy. Neurology. 2016;86(8):704-12.
    1. Nightscales R, McCartney L, Auvrez C, Tao G, Barnard S, Malpas CB, et al. Mortality in patients with psychogenic nonepileptic seizures. Neurology. 2020;95(6):e643-52.

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