Temporal lobe dysfunction in late-onset epilepsy of unknown origin

Highlights

• Late-Onset Epilepsy of Unknown origin (LOEU) presents both focal- and focal to bilateral tonic-clonic seizures.

• Late-Onset Epilepsy of Unknown origin presents a mild phenotype with a good response to single antiepileptic treatment.

• The cognitive profile of LOEU patients can be normal, with focal deficits or multidomain impairment.

• In these patients, the application of neurophysiology and metabolic imaging techniques reveals the dysfunction of the temporal lobe.

Abstract

Objective

Epilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU.

Methods

We selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment.

Results

Twenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%).

Significance

Late-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.

Introduction

Epilepsy has a peak of incidence in late adulthood, with a progressive increase in the number of affected individuals with aging [1]. Since the average age of the world population grows constantly, thanks to the overall improvement of living conditions, medical diagnostics, and treatments, epilepsy with onset in advanced adulthood is a progressively relevant problem and, as a consequence, an increasing source of expenditure for the Health Systems [2], [3].

The most common causes of late-onset epilepsy (LOE) are structural: cerebrovascular or infectious diseases, brain tumors, trauma, and metabolic or toxic conditions [4]. Furthermore, in the last few years, several studies showed a link between epilepsy with onset in adulthood and neurodegenerative diseases, particularly Alzheimer’s disease (AD) [5], [6]. In fact, the prevalence of epilepsy is increased in the years preceding the cognitive decline [7], [8] and some elderly patients with new-onset epilepsy demonstrated clinical and biological markers of AD [9], [10], with conversion to dementia at follow-up [11]. Recent data also show that in more than half of patients with LOE, it is possible to detect mild cognitive impairment (MCI) at the neuropsychological assessment [10].

Despite advances in the etiology of epilepsy in aged people, in many patients the cause of seizures remain unclear. These cases are referred to as NonLesional Late-Onset Epilepsy (NLLOE) [12] or Late-Onset Epilepsy of Unknown origin (LOEU) [9]. By now, only little is known about this condition, in particular regarding the clinical and neuropsychological features, and the underlying brain structural and functional abnormalities [13].

¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) of the brain has a key role in the diagnostic process of epilepsy. Especially for temporal lobe epilepsy (TLE), but also for nonlesional extratemporal and MRI-negative temporal lobe epilepsies, brain FDG-PET can in fact help localizing the epileptogenic lesion, discriminating between discordant neurophysiologic and imaging findings, and predicting the prognosis for post-surgical procedures [14], [15], [16]. Moreover, the assessment of brain glucose metabolism helps clinicians for the better definition of the epileptogenic ictal onset and functional deficit in refractory focal epilepsy [17].

The neuropsychological assessment of patients with epilepsy is routinely performed, especially for those with surgical indication [18]. The evaluation of the neuropsychological aspects of patients provides important data about the localization of the epileptic focus, adverse drugs effects, and postoperative monitoring. Moreover, the main domains affected, such as memory, attention, executive functions, language, visuospatial skills, logical reasoning, depression, anxiety and quality of life are important elements to evaluate during the diagnostic process [19].

In the present study, we describe a cohort of patients with LOEU who underwent an in-depth clinical and metabolic neuroimaging (FDG-PET) characterization, and an extensive neuropsychological assessment.