Clinical and etiological characteristics of new-onset epilepsy in the elderly

INTRODUCTION

Epilepsy is one of the most common chronic neurological conditions in the world, representing a major public health problem. Its global prevalence, estimated at 8%, is higher in developing countries where it varies from 10% to 40% in some regions of sub-Saharan Africa (SSA).^[1] In Burkina Faso, the prevalence of epilepsy is estimated at between 10% and 16%, with limited access to medical care and adequate treatment.^[2] The elderly population, which includes people over the age of 60–65 years, is the fastest growing in the world.^[3] In people aged >60, epilepsy is the 3^rd most common neurological pathology after stroke and Alzheimer’s disease,^[4] with prevalence increasing with age due to the continuing aging of the world’s population and the increase in risk factors for epileptogenicity, particularly stroke and dementia.^[3,5] Today, in SSA, there is a trend toward an increase in life expectancy at birth and a gradual rise in the proportion of elderly people, linked to the significant improvement in socioeconomic and health conditions. The consequences are a rise in cardiovascular, cerebrovascular, and neurodegenerative diseases and neoplasms, which could increase the incidence of epilepsy in the elderly. While in developed countries, the incidence of epilepsy increases sharply after the age of 60 or 65 years, this phenomenon has not yet been clearly reported in series from low-income countries.^[6] However, a few studies have been published on epilepsy in the elderly in SAA.^[7-9] Epilepsy in the elderly has specific features that make it a special clinical entity: crude and atypical clinical symptomatology with risks of diagnostic errors and delays, etiologies dominated by cerebrovascular and neurodegenerative pathologies, therapeutic difficulties linked to polypathology, polymedication, and organ aging, and finally a negative impact on the functional and vital prognosis of patients.^[10]

In Burkina Faso, there are no epidemiological data on epilepsy in the elderly. The objectives of this study were to describe the clinical and etiological characteristics of new-onset epilepsy in the elderly in tertiary hospitals in Ouagadougou, Burkina Faso. This study would provide us with a database for understanding epilepsy in the elderly and contribute to better management of epilepsy.

MATERIALS AND METHODS

This was a descriptive cross-sectional study conducted from January 1, 2022, to June 30, 2024, for 30 months. The period from January 2022 to December 2023 was devoted to enrolling and monitoring the patients included, while the period from January 2024 to June 2024 was devoted solely to monitoring the evolutionary follow-up of the patients included. Patients aged 60 and over, seen in consultation or hospitalized, for epilepsy, in the neurology departments of the 3 UH of Ouagadougou (UH Tengandogo, HU Bogodogo, UH Yalgado Ouédraogo) during the study, having given their verbal consent to participate in the study. The diagnosis of epilepsy was made by a senior neurologist based on the occurrence of 2 or more unprovoked epileptic seizures at least 24 h apart, occurring after the age of 60 years, between January 2022 and December 2023. Follow-up of the patients’ evolutionary profile after diagnosis and management was spread out until June 30, 2023, i.e., at least 6 months for each patient. Patients in whom epilepsy had appeared before the age of 60 years, patients who had not given verbal consent to participate in the study, patients with a follow-up of <6 months, and patients with one or more epileptic seizures symptomatic of acute cerebral disorders were excluded from the study. Patients with atypical clinical seizure patterns and no obvious paroxysmal epileptic abnormalities with electroclinical correlation were excluded from the study. Patients who presented with both focal and generalized seizures and/or with both focal and generalized epileptic abnormalities on electroencephalography (EEG) were considered to have unclassifiable epileptic seizures.

In Burkina Faso, an elderly person is defined as any person older than 60 years according to the 2019 general population census.^[11]

Before starting the study, we contacted the neurologists at the 3 Ouagadougou teaching hospitals (Tengandogo, Bogodogo, and Yalgado Ouédraogo) and obtained their agreement to take part in the study before explaining the methodology. Data collection procedure consisted of deploying one interviewer (a 7^th year medical student) per university hospital, i.e., 3 interviewers in all, with ourselves supervising the survey. Data collection was summarized on an anonymous individual data collection form for each patient included, using Kobocollect software. It was based on direct interaction with the patients included, with questioning, a clinical examination, and taking into account any data from complementary examinations carried out. Data collection also took into account clinical information from health diaries, outpatient registers, and hospital clinical records. EEG recordings were made during the inter-critical period on digital EEG equipment using 21 electrodes according to the international 10–20 system, and interpretations were made by 3 EEG neurologists certified in clinical neurophysiology and epileptology.

The diagnosis of epilepsy or epileptic syndrome was made by a certified epileptologist based on clinical arguments, including the history of the disease, the results of the neurological physical examination, the results of the EEG recorded on the scalp in the inter-critical state, and the results of the cerebral computed tomography (CT) scan.

The etiological diagnosis of epilepsy was based on a range of clinical arguments (history of the disease, search for risk factors for epilepsy in the history, clinical neurological and neuropsychological examination), EEG (focal, diffuse or generalized nature of epileptic paroxysms, existence or absence of a slowdown in background activity), and cerebral CT (potentially epileptogenic cerebral lesions), with evidence of clinico-electro-radiological correlations. Due to the unavailability and/or inaccessibility of magnetic resonance imaging (MRI) in our context, we used brain CT rather than MRI, which certainly reduced the accuracy of the diagnosis. None of the patients underwent serum anti-neuronal antibody assays or autoimmunity tests, limiting the study’s ability to explore autoimmune or rare causes. Response to antiepileptic treatment was assessed during outpatient follow-up visits.

Sociodemographic, clinical (epilepsy risk factors, comorbidities, seizure and epilepsy characteristics, inter-critical neurological signs, etc.), paraclinical (EEG data, brain CT results, biological data), therapeutic (anti-epileptic drugs used), and treatment outcome at 6 months were assessed. The classifications of epileptic seizures and epilepsy were those of the ILAE 2017.^[12]

The data collected were analyzed by ourselves, using Epi-Info software version 7.2.4.0. This was a descriptive analysis that involved calculating percentages for qualitative variables and measures of central tendency (mean, median) and dispersion (standard deviation, minimum, maximum) for quantitative variables.

Beforehand, we provided patients with detailed information about the aims and conduct of the study, and we particularly emphasized its safety and the anonymity of the data that would be collected. We then reassured patients that their participation in the study was free and voluntary.

After obtaining a favorable verbal opinion from the institutional ethics committee, followed by authorization from the administration of each of the 3 university hospitals involved, we finally proceeded with the study.

Each patient’s data were collected on an anonymous data collection form; each patient was identified by a unique number, and no first or last name was included in this study.

RESULTS

We consecutively collected 67 cases, of which 41 patients (61.2%) were male, giving a sex ratio (M/F) of 1.5. The average age at onset of seizures in our patients was 68.5 years ± 6.3 (60–82 years); patients in the age group of 60–69 years, with 48.5%, were the most represented [Figure 1].

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Figure 1:

Distribution of patients with epilepsy in the elderly by age.

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Comorbidities were found in 53 patients (79.1%): hypertension, a history of stroke, type 2 diabetes, and a history of COVID 19 infection, in 32 cases (47.8%), 31 cases (46.3%), 17 cases (25.4%), and 11 cases (16.4%), respectively [Table 1].

Focal seizures, observed in 38 patients (56.7%), were the most frequently encountered type of seizure, followed by seizures which appeared to be generalized from the outset and unclassifiable seizures, with 18 cases (26.9%) and 11 cases (16.4%), respectively. Among the focal seizures, those with altered consciousness (break in contact) with or without psychomotor automatisms, with 26 cases (38.7%), were the most frequent. Cognitive disorders, focal sensory-motor deficit, and behavioral disorders, with 31 cases (46.3%), 7 cases (10.4%), and 3 cases (4.5%) respectively, were the inter-critical neurological and neuropsychological signs associated [Table 2].

In terms of seizure frequency, rare epileptic seizures were the most frequent, with 42 cases (63%) [Figure 2].

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Figure 2:

Distribution of patients with epilepsy in the elderly according to seizure frequency.

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All our patients had a waking EEG during the inter-critical period. Intercritical epileptic paroxysms were detected in 56 patients (84.8%). Focal epileptic paroxysms observed in 33 patients (49.2%) were the most common; they were dominated by frontal and temporal locations with 32.8% and 25.4% of cases, respectively.

A total of 65 patients (97%) underwent brain scans, which revealed potentially epileptogenic brain lesions in 49 patients (75.4%), dominated by circumscribed cortico-subcortical hypodensity and circumscribed cortical and/or corticosubcortical atrophy in 26 patients (40%) and 10 patients (15.4%), respectively. Intercritical EEG and CT scan abnormalities are summarized in Table 3.

Frontal lobe epilepsy and temporal lobe epilepsy, with 30 cases (44.8%) and 17 cases (25.4%) respectively, were the most frequently encountered epilepsy diagnoses [Figure 3].

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Figure 3:

Distribution of patients with epilepsy in the elderly according to epilepsy classification.

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Epilepsies of structural causes diagnosed in 36 patients (53.7%) were the most common, followed by epilepsies of undetermined causes in 27 patients (40.3%) and epilepsies presumed to be genetic in 4 patients (6%). Among the epilepsies with structural causes, post-stroke epilepsies with 21 cases (31.3%) and epilepsies secondary to infection of the central nervous system (CNS) with 6 cases (8.9%) were the most common. Among the infectious causes, neurocysticercosis was the most frequent, with 4 cases (6%) [Table 4].

All our epileptic patients received antiepileptic treatment; the treatment regimen was monotherapy in 63 patients (94%) and dual therapy in 4 patients (6%). Sodium valproate and carbamazepine were the antiepileptic drugs most frequently prescribed, in 25 cases (39%) and 16 cases (25%), respectively [Figure 4].

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Figure 4:

Distribution of patients with epilepsy in the elderly according to anti-epileptic drugs used.

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At the end of an average treatment period of 9.7 months ± 7.6 (6–24 months), 45 patients (67.2%) were seizure free, whereas 22 patients (32.8%) still had recurrent epileptic seizures despite treatment.

DISCUSSION

In the present study, we enrolled 67 patients with epilepsy onset after the age of 60 years, diagnosed between January 2022 and December 2023 (24 months), and followed for an average of 9 months until June 2024. These results are consistent with the literature, which indicates that the incidence of epilepsy is significantly higher in the elderly than in any other age group.^[3,10]

Patients in SSA had a mean age of onset of seizures <70 years^[7-9] compared with a mean age >70 years reported in high- and middle-income countries.^[3,13,14] The mean age of onset of epilepsy of 68.5 years reported in our patients is in line with data from most SSA series. This difference in the age of onset of epilepsy in the elderly between patients from high- and middle-income countries and those from SSA could be explained by a longer life expectancy in developed countries, but could also reflect differences in etiology, recording methods, or age distribution.^[6] In our series, focal seizures were the type of seizure most frequently encountered (64.2%), and focal seizures with altered consciousness (rupture of contact) with or without psychomotor automatisms (formerly complex focal seizures) (38.7%) were also the most frequent. Tonic–clonic or myoclonic generalized seizures (26.9%) and secondarily generalized focal seizures (16.4%) were in the minority. Our results corroborate the data in the literature, the vast majority of which report a predominance of focal seizures, in particular focal seizures with altered consciousness without secondary generalization, reflecting the importance of focal cerebral lesions in elderly subjects. These studies are fairly unanimous on the exceptional nature of immediately generalized seizures, which almost always follow a forgotten childhood epilepsy.^{[3,5,7,10,13,15]} However, in SSA, Kuate-Tegueu et al. in Cameroon^[8] and Assadeck et al. in Niger^[9] reported a predominance of generalized tonic–clonic seizures. This discrepancy could be explained by the difficulty in recognizing the focal onset of seizures, often in the absence of reliable witnesses, or by the high frequency of memory disorders at this age. The positive diagnosis of epileptic seizures in the elderly is difficult because of numerous semiological atypia, including a less frequent or a specific aura, seizures reduced to an isolated break in contact with little or no automatism, prolonged post-critical confusion, and, finally, the absence of witnesses among family members or friends.^[5,10,14]

The type of epilepsy varies between series. In some series, temporal lobe epilepsy is the most frequently diagnosed type of epilepsy in the elderly^,[3] whereas in other series, such as Ramsay et al.,^[16] Acharya and Acharya^[17] and our own, extratemporal lobe epilepsy, particularly frontal epilepsy, is the most common type of epilepsy in the elderly. The extratemporal lobar location is all the more frequent as post-stroke causes represent the most common etiology.^[17]

In the literature, the diagnostic yield of intercritical scalp EEG is >50%. In our series, all our patients (100%) underwent an intercritical scalp EEG, with paroxysmal epileptic abnormalities detected in 84.8%; our data are therefore in line with the literature, which reports a diagnostic yield of EEG of over 50%.^[17] Approximately 97% of patients in our study underwent brain imaging, mainly brain CT, due to the limited accessibility and availability of MRI. Cerebral MRI is the most useful neuroimaging examination and the most helpful in the etiological diagnosis of epilepsy in the elderly, even though cerebral CT can be performed in various situations, such as in an acute or emergency context.^[18]

In our series, various structural abnormalities, potentially epileptogenic, were observed on brain CT, possibly contributing to the etiological diagnosis, which is in line with the literature.^[17] However, the most frequent finding in the brain CT scan were cerebral atrophy, non-pathological most often related to aging.

The reported prevalence of specific causes of epilepsy in the elderly depends on a number of factors, including the definitions used, the populations studied, and the investigative methods used.^[17] However, certain general trends emerge, and secondary etiologies are the most common. In all regions of the world, stroke sequelae (30– 50%) are the most frequently reported causes.^{[3,7,8,9,19-23]} Studies have shown that people with a history of stroke have a higher risk of developing epilepsy^[24] and that age >60 years is a risk factor for developing post-stroke epilepsy.^[25] Mechanisms of post-stroke epilepsy include structural changes, including reactive gliosis, meningocerebral scarring, selective neuronal loss, deafferentation, and collateral proliferation.^[25]

Neurodegenerative diseases, dominated by Alzheimer’s disease, account for 10–20% of the causes of geriatric epilepsy. It has been established that patients with all types of dementia have a 5–10-fold increased risk of epilepsy compared with an age-matched population without dementia; the frequency of epilepsy increases with the severity of the dementia, in line with increasing age and worsening of the neurodegenerative process. The mechanisms of epileptogenesis in dementia involve deposits of β-amyloid protein, selective neuronal loss (inhibitory neurons) and reactive gliosis, and chemical changes (alterations in acetylcholine, dopamine, gamma-aminobutyric acid and other neurotransmitters), or changes in cellular excitotoxicity and sodium and calcium channel functions, the effects of anti-dementia drugs and comorbidities.^{[10,17,19,25]} Dementia is rarely reported as a cause of epilepsy in the elderly in SSA, probably due to under-diagnosis, with families rarely consulting doctors about cognitive disorders in the elderly, which are often wrongly considered to be a “normal” consequence of aging, and to the difficulties in diagnosing psychobehavioral epileptic seizures in patients with dementia.^[10,17] In our series, dementia was reported in 1.5% of epilepsy etiologies in the elderly.

Primary or metastatic brain tumors are responsible for 10– 30% of epilepsies in the elderly. The following characteristics increase the epileptogenic risk of brain tumors in the elderly: primary nature, poor differentiation, temporal, frontal, or parietal location. Gliomas, meningiomas, and cerebral metastases are the epileptogenic brain tumors most frequently reported in the elderly.^{[10,17,19,25,26]} In our series, brain tumors represented only 4.5% of the causes of epilepsy in the elderly, essentially meningiomas (3%) and brain metastases of breast cancer (1.5%).

Sequelae of cranioencephalic trauma account for 5–20% of the causes of epilepsy in the elderly worldwide. This relatively high frequency is explained by the greater risk of falls and potentially serious cranioencephalic trauma and potentially epileptogenic brain lesions in the elderly.^{[10,17,19,26]} In our series, trichloroethylene sequelae accounted for 7.5% of the causes of epilepsy, which is in line with the literature.

Sequelae of CNS infections, mainly cerebral toxoplasmosis, which are rarely found in developed countries,^[10,19] are reported in SSA at rates of 2–5%,^[7-9] due to the higher prevalence of human immunodeficiency virus infection in this region. In our series, the fairly high prevalence of infectious causes of epilepsy in the elderly (8.9%) is due to the sequelae of neurocysticercosis (6%). Indeed, in Burkina Faso, an endemic area of cysticercosis, the sequelae of neurocysticercosis are a major cause of epilepsy, unlike other countries in Sub-Saharan Africa.^[27]

Between 33% and 50% of geriatric epilepsies have no detected cause, despite current technological advances.^[3,19] Paraneoplastic limbic encephalitis, autoimmune encephalitis, and posterior reversible encephalopathy syndrome are probably among the rare causes of geriatric epilepsies; some authors recommend that these rare factors should be investigated as part of the second-line etiological diagnosis of geriatric epilepsy, in the absence of an identified cause.^[19]

In our study, the proportion of undetermined causes, which was 40.3%, corroborates the data in the literature. However, it must be recognized that the use of brain CT rather than MRI and the absence of explorations of autoimmune or paraneoplastic diseases in our context of SSA, have certainly contributed to reducing diagnostic accuracy. It should be noted that some SSA studies report even higher rates of undetermined causes of around 66%.^[9]

In our series, as in other previous SSA series, first-generation antiepileptic drugs (sodium valproate, carbamazepine, phenobarbital) are the most frequently, if not almost exclusively, used for epilepsy in the elderly.^[7-9] However, series from developed countries report a preferential prescription of new-generation anti-epileptic drugs (AEDs) (lamotrigine, levetiracetam, oxcarbazepine, gabapentin).^[13,15] These prescriptions are in line with the results of a meta-analysis of clinical trials, which concluded that the efficacy profile of carbamazepine, levetiracetam, and lamotrigine was similar, although carbamazepine was poorly tolerated.^[28] The unavailability and/or unaffordability of MAEs for epilepsy patients in SSA explains this difference.

CONCLUSION

New-onset epilepsy was consecutively diagnosed in 67 elderly patients in the neurology departments of the university hospitals of Ouagadougou, over 2 years and 6 months. Clinical, EEG, and cerebral CT correlations revealed a predominance of focal seizures with altered consciousness and a predominance of focal lobar, frontal, or temporal epilepsies. Potentially epileptogenic brain lesions were found in 3/5 of the patients. Post-stroke sequelae and CNS infections were the most common causes. However, the causes remained undetermined in 2/5 of the patients. Sodium valproate and carbamazepine are the most commonly used MAEs. A national multicenter prospective study and improved access to brain MRI and paraclinical investigations would refine data on epilepsy in elderly populations in Burkina Faso.