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
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)
- et al.
Clinical neuropsychology in epilepsy: theoretical and practical issues
Handb Clin Neurol
(2012) - et al.
Chronic epilepsy and cognition
Lancet Neurol
(2004) - et al.
Neuropsychological effects of epilepsy and antiepileptic drugs
Lancet
(2001) - et al.
Disentangling the relationship between epilepsy and its behavioral comorbidities - the need for prospective studies in new-onset epilepsies
Epilepsy Behav
(2014) Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms and treatment
Biol Psychiatry
(2003)- et al.
The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - current knowledge and understanding
Epilepsy Behav
(2015) - et al.
Epilepsy and cognition – a bidirectional relationship?
Seizure
(2017) - et al.
Cognition in the early stages of adult epilepsy
Seizure
(2015) - et al.
The relationship between memory performance, perceived cognitive function, and mood in patients with epilepsy
Epilepsy Res
(1999) - et al.
Biomarkers for epileptogenesis and its treatment
Neuropharmacology
(2020)
Newly diagnosed epilepsy: cognitive outcome after 12 months
Epilepsia
Cognitive prognosis in chronic temporal lobe epilepsy
Ann Neurol
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
Children with new-onset epilepsy: neuropsychological status and brain structure
Brain
Patients with epilepsy: cognitively compromised before the start of antiepileptic drug treatment?
Epilepsia
Should cognition be screened in new-onset epilepsies? A study
J Neurol
Definition of new-onset epilepsy versus newly diagnosed epilepsy: role of time domain
Epilepsia
A practical clinical definition of epilepsy
Epilepsia
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