Elsevier

Epilepsy & Behavior

Volume 112, November 2020, 107359
Epilepsy & Behavior

A prospective pilot study of cognitive impairment and mood in adults with first seizure, new-onset epilepsy, and newly diagnosed epilepsy at time of initial seizure presentation

https://doi.org/10.1016/j.yebeh.2020.107359Get rights and content

Highlights

  • Individuals with a first unprovoked seizure demonstrate cognitive impairment.

  • Domain-specific impairment may predict aspects of a patient's clinical course.

  • Findings support a shared mechanism for cognitive impairment, mood disorders and seizures.

Abstract

Introduction

This is an observational prospective cohort study of cognition and mood in individuals presenting to a tertiary neurology clinic with first unprovoked seizure (FS), new-onset epilepsy (NOE), and newly diagnosed epilepsy (NDE). Our aim was to understand the cognitive profile of these three diagnostic groups at the time of first presentation. Follow-up was obtained to evaluate any association between cognition at presentation and subsequent clinical course.

Methods

Forty-three participants (age: 18–60 years) were recruited with FS (n = 17), NOE (n = 16), and NDE (n = 10). Clinical details, neuropsychological testing, and screening for mood disorders were obtained at the time of presentation to clinic. Seizure recurrence was evaluated at clinic follow-up at least 6–12 months following the initial presentation.

Results

In all groups, general intelligence (intelligence quotient [IQ]) was consistent with population norms, but more than half of participants (55.8%) were impaired in at least one cognitive domain. The most commonly impaired domain in all diagnostic groups was visuospatial and visuoconstruction suggesting that it may be a sensitive marker of early cognitive impairment. Those with epilepsy (NOE and NDE) at initial presentation were more likely to be impaired than those with FS, particularly on tests of attention, working memory, and processing speed. Seven participants with FS converted to NOE (FSNOE) at follow-up. They were more likely to be impaired on tests of memory than those with FS who did not convert to NOE. On mood screening, 21% of participants scored moderate or severe for depressive symptoms, and 25.6% of participants scored moderate or severe for anxiety symptoms.

Discussion

Cognitive impairment and mood changes are common at first seizure presentation and mirror the pattern seen in chronic epilepsy. This cooccurrence of symptomatology at disease onset prior to prolonged antiepilepsy drug exposure suggests a shared underlying disease mechanism and carries important clinical implications for effective diagnosis and management of epilepsy. Furthermore, early cognitive testing may become a clinical biomarker and enable the prediction of an individual's clinical course.

Introduction

Cognitive impairment is common in people with epilepsy. Indeed, studies of people with longstanding epilepsy suggest that upwards of 80% have cognitive impairment in at least one domain [1]. Underlying causes are almost certainly multifactorial. Potential direct contributors include the underlying pathology and anatomical foci generating seizures, consequences of recurrent seizures, and the long-term effects of antiseizure medications [2,3]. Furthermore, there are likely contributions from high rates of comorbid mood disorders and indirect negative implications of epilepsy on socioeconomic status [[3], [4], [5]].

The prevalence of cognitive impairment and mood disorders suggests that epilepsy may be a ‘network disease’, whereby seizures, cognitive dysfunction, and psychiatric comorbidities are the result of a shared network dysfunction [6]. Further, cognitive impairment and mood likely have a tridirectional relationship with seizures and each other that only becomes more entwined with time [4,7]. As such, there have been efforts to study cognition and mood in the early stages of epilepsy without the confounding effects of prolonged impact of seizures and antiepilepsy medications in an attempt to better understand this complex relationship.

While many of these direct and indirect effects accrue over time [8,9], a growing literature suggests that cognitive impairment may appear early in the disease course [10]. Prospective studies of cognition in children demonstrate academic struggles prior to epilepsy diagnosis and neuropsychological difficulties at the time of diagnosis [11,12]. In adults, the Standard and New Antiepileptic Drugs (SANAD) study demonstrated that impairments in memory and psychomotor speed are present at the time of diagnosis with newly diagnosed epilepsy (NDE) [13]. Furthermore, a study of patients with new-onset epilepsy (NOE), with mean time to cognitive testing of three months, demonstrated impairment in attention, executive function, and memory [14]. This suggests that cognitive impairment may be prevalent at the time of diagnosis and potentially even before seizure onset. Studying individuals with a first unprovoked seizure (FS), even before diagnosis of epilepsy, and tracking their clinical progress over time may provide further insight into the relationship between cognitive impairment, mood, and seizures in individuals with epilepsy.

Our aim was to better understand the nature of cognitive impairment in early epilepsy by obtaining and comparing cognitive profiles of individuals from the following three diagnostic groups: FS, NOE defined as seizure onset and diagnosis within the last year, and NDE defined as diagnosis within the past year but seizure onset greater than one year ago [15]. By including FS and NOE, it was our aim to study individuals at an early time point and to afford a cross section of cognition across multiple clinical time points. Given the high prevalence and interplay of comorbid mood disorders, all participants were screened for depression and anxiety. A second aim was to understand if baseline cognitive deficits were associated with seizure recurrence at follow-up.

Section snippets

Study design

This prospective observational cohort study recruited participants from the Halifax First Seizure Clinic (HFSC) who presented between November 28, 2016 and July 5, 2018. This is an academic tertiary neurology clinic located in Halifax, Nova Scotia, Canada and is staffed by epileptologists, neurologists with special interest in seizures, and specialist nurse practitioners.

Participants

Inclusion criteria were as follows: (I) diagnosis of FS, NOE (seizure onset and diagnosis within the past year), or NDE

Demographics

Forty-three participants (Table 2) were recruited over the study period. Overall, there were more men (67.4%) than women, but this did not differ between diagnostic groups (χ2 (2, N = 43) = 2.89, p = 0.24). Cannabis use was common, with 18.6% of participants identifying as daily users, but there were no differences in use between diagnostic groups (p = 0.54). At least one follow-up visit to monitor for seizure recurrence was obtained on every participant with a mean follow-up duration of

Discussion

By recruiting individuals at the time of first presentation to a comprehensive epilepsy clinic, we were successful in obtaining an early cognitive profile in three separate diagnostic groups. In all groups, including those with a single unprovoked seizure, we found high rates of cognitive impairment. There were important differences between diagnostic groups which require more study but may ultimately shed light on the pathophysiology and development of cognitive impairment in epilepsy. The

Conclusions

Cognitive impairment and mood symptoms are prevalent in adults presenting with their first unprovoked seizure and early epilepsy. The pattern of cognitive impairment mirrors that found in later stages of epilepsy. This suggests that there is likely a shared underlying disease mechanism generating seizures, cognitive impairment, and neuropsychiatric disorders. Early recognition of cognitive impairment and mood disorders may allow for prompt intervention and treatment of these two comorbidities.

Declaration of competing interest

The authors declare no conflicts of interest.

Acknowledgments

We would like to thank our participants, our referring physicians (S.W.; K.I.; K.L.; M.S.), and our psychometrists (D.B.-T.; J.I.) for making this study possible.

Funding

This work was supported by the Nova Scotia Health Authority (NSHA) Research Fund.

References (37)

  • G.A. Baker et al.

    Newly diagnosed epilepsy: cognitive outcome after 12 months

    Epilepsia

    (2011)
  • B.P. Hermann et al.

    Cognitive prognosis in chronic temporal lobe epilepsy

    Ann Neurol

    (2006)
  • K.J. Oostrom et al.

    Not only a matter of epilepsy: early problems of cognition and behavior in children with “epilepsy only” – a prospective, longitudinal, controlled study starting at diagnosis

    Pediatrics

    (2003)
  • B. Hermann et al.

    Children with new-onset epilepsy: neuropsychological status and brain structure

    Brain

    (2006)
  • J. Taylor et al.

    Patients with epilepsy: cognitively compromised before the start of antiepileptic drug treatment?

    Epilepsia

    (2010)
  • J.A. Witt et al.

    Should cognition be screened in new-onset epilepsies? A study

    J Neurol

    (2012)
  • B. Pohlmann-Eden et al.

    Definition of new-onset epilepsy versus newly diagnosed epilepsy: role of time domain

    Epilepsia

    (2012)
  • R.S. Fisher et al.

    A practical clinical definition of epilepsy

    Epilepsia

    (2014)
  • Cited by (12)

    • Efficacy of a specialized inpatient rehabilitation program in patients with early versus chronic epilepsy

      2023, Epilepsy and Behavior
      Citation Excerpt :

      Other issues are fear of stigma affecting employment and difficulties to accept the diagnosis, found in > 60%, respectively [6]. Several studies have shown impaired quality of life (QOL) and emotional well-being already early in the course of the epilepsy [7–9]. At the same time, both employment rate and income of persons with a recent epilepsy diagnosis are lower than in the general population or in matched controls without seizures [10,11].

    View all citing articles on Scopus
    View full text