ABSTRACT
Objective: Although the populations of patients with functional seizures (FS) and epileptic seizures (ES) are extremely heterogeneous with multiple etiologies and phenotypes, patients with FS have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (ROSQs). We evaluated if data-driven clustering and projection analysis could identify symptom phenotypes that could differentiate between patients with FS and ES.
Methods: The dataset included all adult patients admitted from January 2006 to March 2020 for video-electroencephalography with available ROSQs (N = 877). Latent clusters and axes of variation in ROSQ responses were evaluated using multiple well-established methods. Leave-one-out cross-validation was used to evaluate if logistic regression using information could differentiate patients with FS from ES.
Results: When evaluating individual symptom response and proportion of positive responses, the area under the receiver operating curve (AUC) was 62% (95% CI, 53%–69%) and 72% (CI, 65%–78%), respectively. The best AUC achieved by phenotyping methods was 74%. The patterns of clusters and components reflected properties of each analysis and did not correlate with assigned “system” from the ROSQ or other interpretations.
Discussion: The overall proportion of positive responses was the most informative metric to differentiate patients with FS compared to ES. While both FS and ES are heterogeneous populations with multiple subgroups, these subgroups were not meaningfully identified based on ROSQ symptoms. The limited overall predictive accuracy and AUC suggests that, in absence of other supporting data, ROSQ responses in patients with FS and ES were not clinically useful for screening.
Free Access: Please Log In
This content is completely free—but you need to be logged in to read the full article. If you already have an account, please log in below. Otherwise, register for free to unlock instant access.
References (38)
- Asadi-Pooya AA, Brigo F, Mildon B, et al. Terminology for psychogenic nonepileptic seizures: making the case for “functional seizures”. Epilepsy Behav. 2020;104(Pt A):106895. PubMed CrossRef
- Kerr WT, Stern JM. We need a functioning name for PNES: consider dissociative seizures. Epilepsy Behav. 2020;105:107002. PubMed CrossRef
- Beghi M, Peroni F, Cornaggia CM. Reply to: we need a functioning name for PNES: considering dissociative seizures. Epilepsy Behav. 2020;109:107084. PubMed CrossRef
- Dickinson P, Looper KJ. Psychogenic nonepileptic seizures: a current overview. Epilepsia. 2012;53(10):1679–1689. PubMed CrossRef
- Alessi R, Valente KD. Psychogenic nonepileptic seizures: should we use response to AEDS as a red flag for the diagnosis? Seizure. 2014;23(10):906–908. PubMed CrossRef
- Goldstein LH, Robinson EJ, Mellers JDC, et al; CODES study group. Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial. Lancet Psychiatry. 2020;7(6):491–505. PubMed CrossRef
- LaFrance WC Jr, Baird GL, Barry JJ, et al; NES Treatment Trial (NEST-T) Consortium. Multicenter pilot treatment trial for psychogenic nonepileptic seizures: a randomized clinical trial. JAMA Psychiatry. 2014;71(9):997–1005. PubMed CrossRef
- Libbon R, Gadbaw J, Watson M, et al. The feasibility of a multidisciplinary group therapy clinic for the treatment of nonepileptic seizures. Epilepsy Behav. 2019;98(Pt A):117–123. PubMed CrossRef
- Robles L, Chiang S, Haneef Z. Review-of-systems questionnaire as a predictive tool for psychogenic nonepileptic seizures. Epilepsy Behav. 2015;45:151–154. PubMed CrossRef
- Asadi-Pooya AA, Rabiei AH, Tinker J, et al. Review of systems questionnaire helps differentiate psychogenic nonepileptic seizures from epilepsy. J Clin Neurosci. 2016;34:105–107. PubMed CrossRef
- Kerr WT, Janio EA, Braesch CT, et al. Diagnostic implications of review-of-systems questionnaires to differentiate epileptic seizures from psychogenic seizures. Epilepsy Behav. 2017;69:69–74. PubMed CrossRef
- LaFrance WC Jr, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005–2018. PubMed CrossRef
- LaFrance WC Jr, Devinsky O. The treatment of nonepileptic seizures: historical perspectives and future directions. Epilepsia. 2004;45(suppl 2):15–21. PubMed CrossRef
- Iturria-Medina Y, Pérez Fernández A, Morris DM, et al. Brain hemispheric structural efficiency and interconnectivity rightward asymmetry in human and nonhuman primates. Cereb Cortex. 2011;21(1):56–67. PubMed CrossRef
- Perez DL, LaFrance WC Jr. Nonepileptic seizures: an updated review. CNS Spectr. 2016;21(3):239–246. PubMed CrossRef
- Sansone RA, Lam C, Wiederman MW. Responses to the medical review of systems: borderline versus nonborderline patients in an internal medicine outpatient clinic. Prim Care Companion CNS Disord. 2011;13(3):13. PubMed CrossRef
- Kerr WT, Janio EA, Braesch CT, et al. An objective score to identify psychogenic seizures based on age of onset and history. Epilepsy Behav. 2018;80:75–83. PubMed CrossRef
- Reuber M. Trauma, traumatisation, and functional neurological symptom disorder-what are the links? Lancet Psychiatry. 2018;5(4):288–289. PubMed CrossRef
- Baroni G, Piccinini V, Martins WA, et al. Variables associated with co-existing epileptic and psychogenic nonepileptic seizures: a systematic review. Seizure. 2016;37:35–40. PubMed CrossRef
- van der Maaten LJP, Hinton GE. Visualizing data using t-SNE. J Mach Learn Res. 2008;9:2579–2605.
- Guyon I, Elisseeff A. An introduction to variable and feature selection. J Mach Learn Res. 2003;3:1157–1182.
- Pulini AA, Kerr WT, Loo SK, et al. Classification accuracy of neuroimaging biomarkers in attention-deficit/hyperactivity disorder: effects of sample size and circular analysis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4(2):108–120. PubMed CrossRef
- Kottas M, Kuss O, Zapf A. A modified Wald interval for the area under the ROC curve (AUC) in diagnostic case-control studies. BMC Med Res Methodol. 2014;14(1):26. PubMed CrossRef
- Kerr WT, Zhang X, Hill CE, et al. Factors associated with delay to video-EEG in dissociative seizures. Seizure. 2021;86:155–160. PubMed CrossRef
- Kerr WT, Janio EA, Chau AM, et al. Objective score from initial interview identifies patients with probable dissociative seizures. Epilepsy Behav. 2020;113:107525. PubMed CrossRef
- Kerr WT, Zhang X, Janio EA, et al. Reliability of additional reported seizure manifestations to identify dissociative seizures. Epilepsy Behav. 2021;115:107696. PubMed
- McKenzie PS, Oto M, Graham CD, et al. Medically unexplained symptoms in patients with PNES: do they explain poor employment outcome in patients with good seizure outcomes? Epilepsy Behav. 2016;59:9–12. PubMed CrossRef
- Rawlings GH, Brown I, Reuber M. Predictors of health-related quality of life in patients with epilepsy and psychogenic nonepileptic seizures. Epilepsy Behav. 2017;68:153–158. PubMed CrossRef
- Jennum P, Ibsen R, Kjellberg J. Welfare consequences for people diagnosed with nonepileptic seizures: a matched nationwide study in Denmark. Epilepsy Behav. 2019;98(Pt A):59–65. PubMed CrossRef
- Robson C, Drew P, Walker T, et al. Catastrophising and normalising in patient’s accounts of their seizure experiences. Seizure. 2012;21(10):795–801. PubMed CrossRef
- Kerr WT, Janio EA, Le JM, et al. Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials. Seizure. 2016;40:123–126. PubMed CrossRef
- Abe C, Denney D, Doyle A, et al. Comparison of psychiatric comorbidities and impact on quality of life in patients with epilepsy or psychogenic nonepileptic spells. Epilepsy Behav. 2020;102:106649. PubMed CrossRef
- Engelberts NH, Klein M, van der Ploeg HM, et al. Cognition and health-related quality of life in a well-defined subgroup of patients with partial epilepsy. J Neurol. 2002;249(3):294–299. PubMed CrossRef
- Patel AD, Baca C, Franklin G, et al. Quality improvement in neurology: Epilepsy Quality Measurement Set 2017 update. Neurology. 2018;91(18):829–836. PubMed CrossRef
- Wardrope A, Jamnadas-Khoda J, Broadhurst M, et al. Machine learning as a diagnostic decision aid for patients with transient loss of consciousness. Neurol Clin Pract. 2020;10(2):96–105. PubMed
- Trainor D, Foster E, Rychkova M, et al. Development and validation of a screening questionnaire for psychogenic nonepileptic seizures. Epilepsy Behav. 2020;112:107482. PubMed CrossRef
- Mwangi B, Tian TS, Soares JC. A review of feature reduction techniques in neuroimaging. Neuroinformatics. 2014;12(2):229–244. PubMed CrossRef
- Berdahl CT, Moran GJ, McBride O, et al. Concordance between electronic clinical documentation and physicians’ observed behavior. JAMA Netw Open. 2019;2(9):e1911390. PubMed CrossRef
Please sign in or purchase this PDF for $40.