Chronic epilepsy and cognition

doi:10.1016/S1474-4422(04)00906-8

The Lancet Neurology

Volume 3, Issue 11, November 2004, Pages 663-672

https://doi.org/10.1016/S1474-4422(04)00906-8 Get rights and content

Summary

Cognitive profiles in epilepsy are as heterogenous as the epileptic syndromes themselves; causes, topography of epileptogenic areas, pathogenetic mechanisms, and the diverse features characterising the clinical course all contribute to the effect on cognition. Chronic epilepsy generally impairs cognition, but it also induces processes of functional reorganisation and behavioural compensation. In most idiopathic epilepsies, cognition is only mildly deteriorated or even normal by clinical standards. Localisation-related cryptogenic and symptomatic epilepsy disorders are accompanied by focal deficits that mirror the specific functions of the respective areas. Poor cognitive outcome is generally associated with an early onset and a long duration of the disease and with poor seizure control. There is evidence that cognitive functions are already impaired at the onset of the disease, and that the maturation of cognitive functions in children is susceptible to the adverse influence of epilepsy. In adults, cognitive decline progresses very slowly over decades with an age regression similar to that of people without epilepsy. Successful epilepsy surgery can stop or partly reverse the unfavourable cognitive development, but left-temporal resections in particular have a high risk of additional postoperative verbal memory impairment. Cognitive recovery in the adult brain after successful surgery indicates functional compensation and, to some degree, functional reorganisation or a reactivation of functions previously suppressed by influence from distant but connected epileptogenic areas.

Section snippets

Cognitive status at disease onset

Is cognition already affected at or even before the onset of epilepsy? It is difficult to obtain conclusive data about this question. In patients with lesions or, more generally, in those with symptomatic epilepsy, it is difficult to disentangle the effects of epilepsy as a symptom from those of the underlying disease. In these patients, however, negative effects of a disease (eg, developmental disorders, trauma, ischaemia, tumour, encephalitis) obviously precede the onset of symptomatic

Idiopathic epilepsies

Although idiopathic syndromes are diverse with respect to severity, clinical appearance, and pathogenetic mechanisms, they share the absence of an identifiable underlying cerebral disease or lesion and the presence of a genetic predisposition, at least in most syndromes. Some of these syndromes are “generalised”, which means that ictal and interictal EEG correlates of these epilepsies cover the whole neocortex. Others are focal with a clear preference for a certain region like the

Cognitive plasticity and long-term development

Besides adverse effects, chronic epilepsy can activate processes of functional compensation and plasticity, particularly in early-onset epilepsies. It is generally assumed that cognitive plasticity decreases with ageing, although the exact time windows for significant functional compensation of the various cognitive capacities are not well known. From lesion studies focusing on language areas independent of the issue of epilepsy, researchers conclude that the earlier a circumscribed lesion in

Conclusion, summary, and outlook

Cognitive profiles in epilepsy are as heterogenous as the epileptic syndromes themselves: aspects of aetiology, topography of epileptogenic areas, pathomechanisms, and the diverse features characterising the clinical course of the disease all contribute to the respective effects on cognition. Patients with localised epilepsies generally have deficits in the cognitive functions controlled by the respective areas, as exemplified by memory impairment in TLE and executive deficits in frontal-lobe

Search strategy and selection criteria

References for this review were identified by searches of MEDLINE up to and including August 2004 with the search terms “epilepsy”, “cognition” or “cognitive”, “memory”, “language”, “attention”, and “neuropsychological”. References were also identified from relevant original and review articles and through searches of the authors' files as well as comprehensive textbooks as cited in the references.

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Cited by (589)

Aquaporin-4 inhibition attenuates Pentylenetetrazole-induced behavioral seizures and cognitive impairments in kindled rats
2024, Physiology and Behavior
Epilepsy is a neurological condition distinguished by recurrent and unexpected seizures. Astrocytic channels and transporters are essential for maintaining normal neuronal functionality. The astrocytic water channel, aquaporin-4 (AQP4), which plays a pivotal role in regulating water homeostasis, is a potential target for epileptogenesis. In present study, we examined the effect of different doses (10, 50, 100 μM and 5 mM) of AQP4 inhibitor, 2-nicotinamide-1, 3, 4-thiadiazole (TGN-020), during kindling acquisition, on seizure parameters and seizure-induced cognitive impairments. Animals were kindled by injection of pentylenetetrazole (PTZ: 37.5 mg/kg, i.p.). TGN-020 was administered into the right lateral cerebral ventricle 30 min before PTZ every alternate day. Seizure parameters were assessed 20 min after PTZ administration. One day following the last PTZ injection, memory performance was investigated using spontaneous alternation in Y-maze and novel object recognition (NOR) tests. The inhibition of AQP4 during the kindling process significantly decreased the maximal seizure stage and seizure duration (two-way ANOVA, P = 0.0001) and increased the latency of seizure onset and the number of PTZ injections required to induce different seizure stages (one-way ANOVA, P = 0.0001). Compared to kindled rats, the results of the NOR tests showed that AQP4 inhibition during PTZ-kindling prevented recognition memory impairment. Based on these results, AQP4 could be involved in seizure development and seizure-induced cognitive impairment. More investigation is required to fully understand the complex interactions between seizure activity, water homeostasis, and cognitive dysfunction, which may help identify potential therapeutic targets for these conditions.
Efficacy, tolerability and safety of add-on third-generation antiseizure medications in treating focal seizures worldwide: a network meta-analysis of randomised, placebo-controlled trials
2024, eClinicalMedicine
Adjunctive newer antiseizure medications (ASMs) are being used in patients with treatment-resistant focal-onset seizures (FOS). An updated network meta-analysis (NMA) was necessary to compile evidence in this critical area.
We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus from their inception until 17 January 2024, evaluating the efficacy, tolerability, and safety of rufinamide (RUF), brivaracetam (BRV), cenobamate (CNB), eslicarbazepine (ESL), lacosamide (LCM), retigabine (RTG), and perampanel (PER) as adjunctive treatments for FOS. Efficacy outcomes included seizure response and seizure freedom. Tolerability was assessed by discontinuation due to adverse events (AEs). Safety outcomes were evaluated based on the number of patients experiencing at least one AE and serious adverse events (SAEs). This review is registered with PROSPERO (CRD42023485130).
A total of 29 studies involving 11,750 participants were included. For seizure response, all ASMs were significantly superior to placebo, with RTG ranking highest, followed by CNB. Considering dosage, CNB 400 mg/d was top-ranked, followed by RTG 1200 mg/d. For seizure freedom, BRV was highest-ranked, followed by CNB, with BRV 100 mg/d leading, followed by CNB 400 mg/d. Regarding tolerability, LCM 600 mg/d had the lowest ranking, followed by CNB 400 mg/d. For the safety outcome of AEs, ESL 1200 mg/d was ranked lowest, followed by CNB 400 mg/d. Regarding SAEs, LCM 400 mg/d was ranked lowest, followed by RTG 1200 mg/d.
ASMs at different dosages have varying efficacy and tolerability profiles. We have provided hierarchical rankings of ASMs for efficacy and safety outcomes. Our findings offer the most comprehensive evidence available to inform patients, families, physicians, guideline developers, and policymakers about the choice of ASMs in patients with treatment-resistant FOS.
None.
Neuropsychology of late-onset epilepsies
2024, Seizure
In an increasingly ageing society, patients ageing with epilepsy and those with late-onset epilepsies (LOE) represent a challenge for epilepsy care and treatment. Senescence itself bears risks of pathologies which in the form of acute focal damage (e.g. stroke) or slowly progressive degenerative damage can cause seizures and substantial cognitive impairment. There is converging evidence from studies in LOE that cognitive impairments are present from epilepsy onset before treatment is initiated and may even precede the emergence of seizures. This suggests that these impairments (like the seizures) are expressions of the underlying disease. Indeed, both seizures and cognitive impairments can be early indicators of disease conditions which lead to mental decline. Cognitive decline over time poses the challenge of disentangling the interrelation between seizures, treatment effects and underlying disease. This issue must be considered as some of the etiologies for causing neuropsychological decline can be addressed. Medication and active epilepsy can contribute to impairments and their impact may be reversible. Dementia is rare if seizures are what has brought the person to attention, and if this is not accompanied by other slowly developing features (such as cognitive of psychiatric changes). From a neuropsychological point of view choosing the right screening tools or assessments, obtaining the history and timeline of impairments in relation to epilepsy, and most importantly longitudinally following the patients regardless of whether epilepsy is ultimately controlled or not appear essential.
Neuromorphometric associations with mood, cognition, and self-reported exercise levels in epilepsy and healthy individuals
2024, Epilepsy and Behavior Reports
Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p < 0.001), poorer mood (p = 0.029), and lower MoCA scores (p = 0.027) than HCs. These group differences were associated with reduced volume, decreased gyrification, and altered surface topology (IGEs < HCs) in frontal, temporal and cerebellar regions involved in executive function, memory retrieval, and emotional regulation, respectively.
These preliminary results support the notion that increased PEL may promote neuroplasticity in IGEs, thus emphasizing the role of physical activity in promoting brain health in people with epilepsy.
German questionnaires assessing quality of life and psycho-social status in people with epilepsy: Reliable change and intercorrelations
2024, Epilepsy and Behavior
People with epilepsy (PWE) not only suffer from seizures but also from various psycho-social issues containing facets such as social functioning, anxiety, depression or stigmatization, and consequently quality of life. (1) Assessing reliable change of these issues is crucial to evaluate their course and potential treatment effects. As most psycho-social self-report questionnaires have been validated in separate samples, their clinical-socio-demographic differences may limit the comparability and generalizability of the scales’ internal consistency, which is important for the reliable change index (RCI). Using a co-normalized approach, we provide the internal consistency and RCIs for a large set of questionnaires targeting quality of life (QOLIE-31-P), depressive symptoms (NDDI-E), anxiety (GAD-7), seizure severity (LSSS), subjective antiseizure medication adverse events (LAEP), stigma, epilepsy-related fear, and restrictions in daily life (PESOS), and subjective cognition (FLei). As for some German versions of these measures, psychometric data is still missing, we also add important information for the German language area.
(2) In addition, knowledge about intercorrelations of these constructs is needed to shape questionnaire usage and treatment approaches. We thus investigate associations of these scales and compare weighted and unweighted subscales of the QOLIE-31-P.
In our prospective study, 202 adult in-patients of the Epilepsy-Center Berlin-Brandenburg with a reliable diagnosis of epilepsy filled out a set of self-report questionnaires between 03/2018 and 03/2021. We calculated Cronbach’s α, RCIs, and bivariate intercorrelations and compared the respective correlations of weighted and unweighted scales of the QOLIE-31-P.
For most of the scales, good to excellent internal consistency was identified. Furthermore, we found intercorrelations in the expected directions with strong links between scales assessing similar constructs (e.g., QOLIE-31-P Cognition and FLei), but weak relationships between measures for different constructs (e.g., QOLIE-31-P Seizure worry and FLei). The QOLIE-31-P Total score was highly correlated with most of the other scales. Some differences regarding their correlational patterns for weighted and unweighted QOLIE-31-P scales were identified.
Psycho-social constructs share a large amount of common variance, but still can be separated from each other. The QOLIE-31-P Total score represents an adequate measure of general psycho-social burden.
A single-center survey on physical activity barriers, behaviors and preferences in adults with epilepsy
2023, Epilepsy and Behavior
Improved understanding of physical activity barriers and preferences in people with epilepsy is needed to successfully design and perform larger, more robust effectiveness trials.
Adult patients at a single tertiary epilepsy center between January and April 2020 were surveyed. The survey included a validated physical activity questionnaire (Physical Activity Scale for the Elderly) plus 15 items aimed to address 1) perceptions and beliefs regarding physical activity, 2) barriers to routine physical activity, and 3) willingness and ability to participate in a physical activity intervention and 4) current physical abilities, activities, and preferences.
95 participants with epilepsy (age 42 ± 16.2, 59 % female) completed the survey. Sixty-five participants (68.4 %) reported that they believe that physical activity could improve their seizure frequency. However, 40 % of those surveyed said their neurologist had never talked to them about physical activity. The most commonly reported barriers to physical activity were lack of time (24.7 %) and fear of having a seizure (19.7 %), while barriers to intervention participation included being unable to come to in-person sessions (53 % of those willing to participate),living far away (39.3 %), time constraints (28.6 %), and lack of transportation (21.4 %).
Future physical activity studies in people with epilepsy should focus on using tailored interventions that accommodate their unique beliefs and barriers.

View all citing articles on Scopus

View full text

ReviewChronic epilepsy and cognition

Summary

Section snippets

Cognitive status at disease onset

Idiopathic epilepsies

Cognitive plasticity and long-term development

Conclusion, summary, and outlook

Search strategy and selection criteria

Prog Brain Res

Epilepsy Behav

Lancet Neurol

Epilepsy Behav

Epilepsy Behav

Brain Res Bull

Brain Cogn

Neuropsychologia

Epilepsy Behav

Neuropsychologia

Neuropsychologia

Seizure

Epilepsy Res

Neuropsychologia

Epilepsy Behav

Neuropsychologia

Neuropsychologia

Lancet Neurol

Seizure

Epilepsy Res

Epilepsy Behav

Epilepsy Behav

Brain Cogn

Neuropsychologia

Brain Lang

Epilepsy Behav

Neuropsychologia

Neuropsychologia

Neuropsychologia

Epilepsy and cognition

Epilepsy Behav

Memory and epilepsy: characteristics, course, and influence of drugs and surgery

Curr Opin Neurol

The role of early left-brain injury in determining lateralization of cerebral speech functions

Ann N Y Acad Sci

Epileptic activity influences the speech organization in medial temporal lobe epilepsy

Brain

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

Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study

Epilepsia

Motor and cognitive functions in newly diagnosed adult seizure patients before antiepileptic medication

Acta Neurol Scand

Cognitive function in Nigerians with newly diagnosed epilepsy

Can J Neural Sci

Neuropsychological functioning among 32 patients with temporal lobe epilepsy and their discordant siblings

Epilepsia

Frontal functions in juvenile myoclonic epilepsy

Neuropsychiatry Neuropsychol Behav Neurol

Visual working memory in primary generalized epilepsy: an 18FDG-PET study

Neurology

MR spectroscopy shows reduced frontal lobe concentrations of N-acetyl-aspartate in patients with juvenile myoclonic epilepsy

Epilepsia

Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures

Dev Med Child Neurol

Neuropsychological findings in children with benign childhood epilepsy with centroteniporal spikes

Dev Med Child Neurol

Cognitive consequences of rolandic epilepsy

Epileptic Disord

Neuropsychological functions in idiopathic occipital lobe epilepsy

Epilepsia

Magnetic resonance spectroscopy and imaging of the thalamus in idiopathic generalized epilepsy

Brain

Review
Chronic epilepsy and cognition