Impact of Seizures While Driving Prior to Diagnosis in People With Focal Epilepsy

Abstract

Objectives

To identify the type, frequency, and consequences of seizures while driving (SzWD) in people with epilepsy before diagnosis.

Methods

We performed a retrospective cohort study using the Human Epilepsy Project (HEP) to identify prediagnostic SzWD. Clinical descriptions from seizure diaries and medical records were used to classify seizure types and frequencies, time to diagnosis, and SzWD outcomes. Data were modeled using multiple logistic regression to assess for factors independently associated with SzWD.

Results

32 prediagnostic SzWD were reported among 23/447 (5.1%) participants. Of them, 7 (30.4%) had more than 1. Six participants (26.1%) experienced SzWD as their first lifetime seizure. Most SzWD were focal with impaired awareness (n = 27, 84.4%). Of participants who had motor vehicle accidents (MVAs), 6 (42.9%) had no recollection. SzWD led to hospitalization in 11 people. The median time from first seizure to first SzWD was 304 days (IQR = 0–4,056 days). The median time between first SzWD and diagnosis was 64 days (IQR = 10–176.5 days). Employment was associated with a 3.95-fold increased risk of SzWD (95% CI 1.2–13.2, p = 0.03), and nonmotor seizures were associated with a 4.79-fold increased risk (95% CI 1.3–17.6, p = 0.02).

Discussion

This study identifies the consequences of seizure-related MVAs and hospitalizations people experience before epilepsy diagnosis. This highlights the need for further research aimed at improving seizure awareness and improving time to diagnosis.

Introduction

Seizures while driving (SzWD) pose substantial risks for individuals and communities. Approximately 0.1%–1% of motor vehicle accidents (MVAs) per year are because of SzWD. These numbers reflect data after epilepsy diagnosis, and the contribution from people with as yet undiagnosed epilepsy is unclear.¹ Diagnostic and treatment delay has broad impact on quality of life and cognition and increases morbidity and mortality, which includes MVAs and hospitalizations.^2-10 Improving time to diagnosis and treatment may help reduce prediagnostic SzWD. In this study, we investigated the frequency and consequences of prediagnostic SzWD in people with focal epilepsy.

Methods

Study Design

The Human Epilepsy Project (HEP) is a multinational study that enrolled people with newly treated focal epilepsy. Information on seizure frequency, seizure characteristics, treatment initiation, and date of diagnosis was collected on enrollment. Information on prediagnostic SzWD including seizure descriptions and MVA descriptions were abstracted from medical records. All SzWD were included in analysis, including those in which patients did not report an accident or injury. The number of SzWD-associated hospitalizations, treatments, and diagnostic tests were identified in medical records. If a participant reported more than 1 SzWD but did not provide the number of times this occurred, it was counted as 2.

Seizures were classified as motor or nonmotor and aware or unaware based on participant/witness report. Seizures that were unwitnessed and/or undescribed were classified as unknown. Determination of whether the seizure semiology was motor or nonmotor was independently reviewed by 2 authors (J.P. and J.F.) and had full concordance.

Time from seizure onset to diagnosis was recorded in days from first reported seizure to date of diagnosis, from onset to SzWD, and from SzWD to diagnosis. When specific dates were not known, midpoint approximations were used as follows: 3rd day of a known week, 15th day of a known month, or July 1 of a known year. If a patient reported a SzWD during the year of their epilepsy diagnosis, and their diagnosis was before July 1, a midpoint between January 1 and the date of diagnosis was used. Hospitalizations, doctor visits, testing, and injuries due to SzWD were counted only if they were directly related to SzWD.

Standard Protocol Approvals, Registrations, and Patient Consents

This study was approved by the Institutional Review Board of participating institutions. Written informed consent was obtained from all participants.

Statistical Analysis

We used purposeful variable selection for creating a multivariable logistic regression model with SzWD as the outcome. Demographic variables included were sex, employment status, and family history of seizures. Seizure characteristics included were semiology, seizure awareness, age at onset, and time to diagnosis. Odds ratios and 95% CIs were reported, and p values of <0.05 were considered significant. Analyses were performed using JMP (version 16.2.0; SAS Institute Inc., Cary, NC; 2020).

Participants

HEP inclusion/exclusion criteria are available as supplemental material.

Data Availability

Data are available upon request from any qualified researcher.

Results

Of the 447 HEP participants, 23 reported SzWD before diagnosis. Demographic characteristics are summarized in Table 1.

Table 1.

Demographic Characteristics of Participants Who Experienced Prediagnostic SzWD

SzWD in Relation to Seizure Diagnosis

Of the 23 participants who experienced SzWD, 6 (26.1%) experienced their first lifetime seizure while driving, 14 (60.9%) had seizures before their first SzWD, and 3 (13%) did not report or recall whether the SzWD was their first lifetime seizure. 16 (69.6%) had 1 SzWD before diagnosis and 7 (30.4%) had more than 1. A total of 19 MVAs were reported. 14 participants (60.9%) had 1 and 4 had more than 1 prediagnosis SzWD-related MVA.

Time between seizure onset and first SzWD varied, with a median value of 304 days (IQR = 0–4,056 days, Figure). The median time to diagnosis from first SzWD for all participants was 46 days (IQR = 2–176.5 days), for those who had an SzWD-related MVA, it was 55 days (IQR = 12–223.5 days), and for those who did not, it was 479.5 days (IQR = 15–1,296). For those who experienced focal to bilateral tonic-clonic SzWD, time to diagnosis from SzWD was 4 days (IQR = 0–122 days). For those who experienced nonmotor SzWD, the median time from first SzWD to diagnosis was 163 days (IQR = 46–190 days). The time between SzWD for patients who experienced more than 1 before diagnosis varied from 37.5 days to 574.5 days, with a median time of 163 days (IQR = 43–795.5 days). Of all participants, 6 were diagnosed within a week of SzWD and 20 (87%) were diagnosed within a year (Figure).

Figure. Time (Days) From Seizure Onset to First Seizure While Driving (SzWD) (A) and Time (Days) From First SzWD to Diagnosis (B).

Seizure Types

Of 32 prediagnosis SzWD, 4 (12.5%) were focal aware seizures, 27 (84.4%) were focal impaired awareness, and 1 (3.1%) was unknown. 15 (65.2%) participants experienced unwitnessed SzWD. 22 (68.8%) SzWD were unknown as to whether motor or nonmotor. Five (15.6%) were witnessed nonmotor, and 5 (15.6%) were witnessed motor.

Motor Vehicle Accidents

Of the 19 SzWD-related MVAs, 11 (57.9%) resulted in hospitalizations, which led to 5 MRIs, 2 CT scans, and 5 EEGs. Injuries included 1 tongue bite, 1 dislocated thumb, 1 fractured sternum, 1 cerebral hemorrhage, and 1 near-drowning requiring 3-day hospitalization (Table 2). Six participants (26.1%) reported no recollection of their MVAs.

Table 2.

Consequences of Prediagnostic SzWD

Predictors of Prediagnostic SzWD

After adjusting for sex, family history, seizure semiology, seizure awareness, onset age, and time to diagnosis, employment was a significant predictor of prediagnostic SzWD, being associated with a 3.95-fold increased risk of experiencing a prediagnostic SzWD (95% CI 1.2–13.2, p = 0.03). After controlling for the same factors, seizure semiology was a significant predictor of prediagnosis SzWD, with nonmotor seizures being associated with a 4.79-fold increased risk (95% CI 1.3–17.6, p = 0.02).

Discussion

This study investigated seizures while driving experienced by people with epilepsy before diagnosis. It provides details on the relationship between SzWD and seizure types, time to diagnosis, and adverse outcomes. Other studies have examined the dangers of driving in people with known epilepsy or have looked at first lifetime seizures but have not analyzed the frequency and consequences of all prediagnostic SzWD.^11,12

In our study, 5% of participants reported experiencing SzWD before diagnosis, and several experienced multiple. By relying on self-reporting of historical events, this likely underestimates the true incidence and cannot account for mortality related to SzWD.

Considering a population in the United States of just more than 200 million between ages 16 and 64 years,¹³ and the annual incidence of epilepsy,¹⁴ there are roughly 126,180 driving-age people in the United States diagnosed with epilepsy each year. Extrapolating from our study, nearly 6,500 people per year experience prediagnosis SzWD in the United States alone, leading nearly 4,000 MVAs and over 2,200 hospitalizations. Much of this may be preventable with earlier diagnosis.

Nonmotor seizures were independently associated with SzWD in our study. Because nonmotor seizures portend longer time to diagnosis than motor seizures,^2,4 this likely increases the odds of SzWD. Similarly, employment was independently associated with SzWD in our study, likely related to the fact 86% of employed individuals commute through automobile.¹⁵

Our study highlights substantial risks of delays in epilepsy diagnosis. A primary limitation was that HEP enrolled only at tertiary referral centers in high-income countries and excluded an older population (older than 60 years). There were also a small number of prediagnosis SzWD, likely leading to underestimating the true incidence.

This study analyzed the impact of prediagnostic SzWD and found substantial consequences for people with epilepsy, communities, and healthcare systems. This highlights a need to improve seizure recognition among both public and healthcare workers.

Appendix 1. Authors

Appendix 2. Coinvestigators

Study Funding

HEP is sponsored by the Epilepsy Study Consortium as well as by industry, philanthropy, and foundations. These include UCB Pharma, Eisai, Pfizer, Lundbeck, Sunovion, The Andrews Foundation, The Vogelstein Foundation, Finding a Cure for Epilepsy and Seizures (FACES), and Friends of Faces. The funders of HEP had no role in this study or decision to submit the manuscript for publication.

Disclosure

B. Bases and S. Barnard report no disclosures relevant to this article; J. French receives salary support from the Epilepsy Foundation and for consulting work and/or attending Scientific Advisory Boards on behalf of the Epilepsy Study Consortium for Aeonian/Aeovian, Alterity Therapeutics Limited, Anavex, Arkin Holdings, Angelini Pharma S.p.A, Arvelle Therapeutics, Inc., Athenen Therapeutics/Carnot Pharma, Autifony Therapeutics Limited, Baergic Bio, Biogen, Biohaven Pharmaceuticals, BioMarin Pharmaceutical Inc., BioXcel Therapeutics, Bloom Science Inc., BridgeBio Pharma Inc., Camp4 Therapeutics Corporation, Cerebral Therapeutics, Cerevel, Clinical Education Alliance, Coda Biotherapeutics, Corlieve Therapeutics, Crossject, Eisai, Eliem Therapeutics, Encoded Therapeutics, Engage Therapeutics, Engrail, Epalex, Epihunter, Epiminder, Epitel Inc, Equilibre BioPharmaceuticals, Greenwich Biosciences, Grin Therapeutics, GW Pharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Knopp Biosciences, Lipocine, LivaNova, Longboard Pharmaceuticals, Lundbeck, Marinus, Mend Neuroscience, Merck, NeuCyte Inc., Neumirna Therapeutics, Neurocrine, Neuroelectrics USA Corporation, Neuronetics Inc., Neuropace, NxGen Medicine Inc., Ono Pharmaceutical Co., Otsuka Pharmaceutical Development, Ovid Therapeutics Inc., Paladin Labs Inc., Passage Bio, Pfizer, Praxis, PureTech LTY Inc., Rafa Laboratories Ltd, SK Life Sciences, Sofinnova, Stoke, Supernus, Synergia Medical, Takeda, UCB Inc., Ventus Therapeutics, Xenon, Xeris, Zogenix, and Zynerba. J. French has also received research support from the Epilepsy Study Consortium (Funded by Andrews Foundation, Eisai, Engage, Lundbeck, Pfizer, SK Life Science, Sunovion, UCB, Vogelstein Foundation) Epilepsy Study Consortium/Epilepsy Foundation (funded by UCB), GW/FACES, and NINDS. J. French is on the editorial board of Lancet Neurology and Neurology Today. J. French is the Chief Medical/Innovation Officer for the Epilepsy Foundation. J. French has received travel reimbursement related to research, advisory meetings, or presentation of results at scientific meetings from the Epilepsy Study Consortium, the Epilepsy Foundation, Angelini Pharma S.p.A., Clinical Education Alliance, NeuCyte, Inc., Neurocrine, Praxis, and Xenon. J. Pellinen has received research support from the Department of Neurology at the University of Colorado School of Medicine, the Colorado Clinical and Translational Sciences Institute by way of NIH/NCATS Colorado CTSA Grant Number UL1 TR002535, NIH/NINDS in the form of a Clinical Research LRP, and the American Epilepsy Society. J. Pellinen serves as chair of the professional advisory board for the Epilepsy Foundation of Colorado and Wyoming (unpaid), serves as the Epilepsy Section Editor for Current Neurology and Neuroscience Reports, and has received compensation for advisory board work for SK Life Science. Go to Neurology.org/N for full disclosures.