Objectives: To report the characteristics of a population of patients with idiopathic generalised epilepsy (IGE) with age of onset over 20 years, and compare them with patients with “classical” IGE.
Methods: Data were collected from a computerised database of all patients with IGE attending a regional adult epilepsy clinic. Demographic data, epilepsy characteristics, and treatment outcomes were recorded.
Results: 72 patients with IGE of a total population of 844 had an age of onset over 20 years (8.5%). There was similar incidence of family history of epilepsy, EEG findings, and remission rates between those with a younger and older age of onset of IGE. There was a lower incidence of previous febrile convulsions in patients with adult onset. There were fewer patients with absence seizures in the adult onset group (15.3% v 46.4% in the “classical” group).
Conclusions: IGE with onset later than the third decade was rare in the population studied. Prolonged EEG in selected patients may be helpful in diagnosing adult onset IGE, but the diagnosis of epilepsy remains clinical. Adult onset IGE shares many features with “classical” IGE, including EEG findings and prognosis, and is likely to represent a genetic epilepsy.
- adult onset idiopathic epilepsy
Statistics from Altmetric.com
Idiopathic generalised epilepsy (IGE) is characterised by the combination of one or more of the triad of seizure types of absence, myoclonus, and tonic–clonic seizures, and the EEG hallmark of paroxysms of generalised spike–wave. The IGEs account for approximately a third of all cases of epilepsy,1 with the onset in the majority during childhood and adolescence. However, IGE with an onset in adulthood has been recognised for many years23 but until recently has been thought to be rare. Some recent reports have suggested that adult onset IGE may be more common than originally thought,4–8 with some cases starting as late as the eighth decade.8
In this study we report the characteristics of a series of 72 patients with IGE beginning over the age of 20 years, in comparison with the rest of a large IGE population in a tertiary United Kingdom centre.
Data from the patients attending the Mersey regional epilepsy clinic have been computerised since 1989, with demographic data as well as diagnostic and treatment details. Patients with IGE were identified from this database at the Walton Centre. At a satellite clinic (run by DS) the patients were identified from a manually recorded patient data file. An epilepsy syndrome diagnosis was made for each patient, based on the clinical and EEG features according to the International League Against Epilepsy (ILAE) classification where possible.9 All patients who were felt either clinically or with EEG support to have IGE were included.
The following data were recorded from the case notes for each patient: basic demographics, family history of epilepsy in a first degree relative, history of febrile convulsions, seizure types and dates of onset, EEG results, antiepileptic drug treatment history, and longest seizure-free period on each antiepileptic drug regimen. Remission was defined as a period of 12 months of seizure freedom.
We identified 844 patients with IGE. The age of onset in the majority was less than 20 years (772 patients (91.5%)), and 72 patients (8.5%) had an onset over the age of 20 years, with only nine patients (1.2%) over the age of 30 years.
The characteristics of the patients with an age of onset of over 20 years are summarised in tables 1 and 2. The mean age of onset was similar in each diagnostic group (table 1), but with a wider age range in myoclonic epilepsies and tonic–clonic seizures only. No patients with an absence epilepsy beginning over the age of 25 years were identified. All patients with an absence epilepsy also had tonic–clonic seizures, compared with 85.2% (75/88) of those with childhood absence epilepsy and 85.9% (79/92) with juvenile absence epilepsy. Absences were more uncommon in patients with adult onset myoclonic epilepsy (13.3%) than in those with onset at a younger age (31.8%).
There was a higher proportion of male patients in the adult onset group. There were similar proportions in each group with photosensitivity and focal abnormalities on EEG, but slightly more in the “classical” group with generalised spike wave activity. There was no significant difference in the proportions with a family history of epilepsy, but febrile convulsions were less common in the group with later onset IGE (table 2).
Thirty four of the adult onset patients (47.2%) were currently on valproate monotherapy, 12 (16.7%) on lamotrigine, and four (5.6%) on topiramate. Six patients (8.3%) were on valproate and lamotrigine in combination, and the remainder were taking a variety of antiepileptic drug combinations. Three (4.2%) had never taken antiepileptic drugs, and two (2.8%) were in remission after successful drug withdrawal. Thirty patients (41.7%) were currently in remission, the antiepileptic drug regimen most likely to induce remission being valproate monotherapy (58.8% of the patients on this regimen). There was a very similar remission rate in each diagnostic subgroup, and overall between the two groups.
We have presented a large series of patients with IGE of adult onset and compared them with classical cases to provide insight into the IGEs as a diagnostic group. There has been controversy over the existence or otherwise of adult onset IGE, partly because a variable age of onset was used in previous studies. For example, significant numbers of patients with adult onset IGE were reported in studies stating a “cut off” age group of 18 years7 or 20 years.8 However, a study that found little evidence for IGE with an onset in adulthood was examining patients with their first seizure over the age of 60 years.10 Clearly the entity of IGE beginning in the early 20s exists, as is confirmed by this study. There is increasing evidence now for the existence of IGE beginning beyond the third decade.4–811 Two of the largest studies of adult onset IGE found that 13.4%7 and 28%8 of the IGE population attending adult clinics had an onset in adult life. Our study had a lower proportion, with only 72 patients (8.5%) with an onset over the age of 20 years, and only nine (1.2%) over 30 years. This will in part reflect the fact that our study included all patients attending the clinic with IGE, including those diagnosed in childhood.
Marini et al concluded that EEGs and sleep deprived EEGs are an important tool in the investigation of all patients who present with seizures, and that failure to carry out these studies in older patients will inevitably lead to misdiagnosis as a partial epilepsy in some.8 This is not generally accepted in the United Kingdom as “best practice,”12 and therefore it is possible that in our centre some older cases have been misdiagnosed. However, it is still most likely that in patients with onset of seizures over the age of 25 years the epilepsy has a focal onset. If there are focal clinical features, a clear aetiology, or focal abnormalities on imaging, the value of EEG is questionable unless surgical treatment is to be considered. In the absence of such features, the EEG is a useful investigation to diagnose a possible adult onset IGE, but when interpreting EEGs in this population one needs to take into account that frontal lobe epilepsies, which are more common in this age group, may have EEG features resembling IGE.13
Another factor of relevance when considering the existence of adult onset IGE is the possibility of previously unrecognised seizures. It is well recognised that apparent late onset IGE occurs in individuals who, in retrospect, had experienced myoclonus earlier in life.11 It may be that such patients have a mild genetic epilepsy which only manifests as tonic–clonic seizure later in life when certain seizure precipitants are encountered. It is possible that some of the patients either previously reported or in this study may have had other seizure types earlier in life and so the true age of onset would be difficult to determine.
The fact that so few cases of adult onset absence epilepsy have been identified and that there are no cases beginning over the age of 25 years suggests that either this syndrome is exceedingly rare or has been under-recognised in our population. Also, the proportion of patients with a myoclonic epilepsy who had absences was lower than may be expected. There is convincing evidence for absences starting in adult life5 and it is possible that some patients with tonic–clonic seizures only have been misdiagnosed as having a partial epilepsy if absences have not been recognised. Absences may be so brief as to go undetected in some adult patients, and so have been termed “phantom absences,” and may only be discovered with a hyperventilation EEG.5 Although it is stated that this syndrome has distinct features such as a high incidence of absence status and only infrequent tonic–clonic seizures,5 it is possible that some of our patients with tonic–clonic seizures only may have had unrecognised absences.
The mean age of onset of adult patients in this study was the early to mid-20s, with a slightly later onset of myoclonus if this occurred. Features of the younger and older onset patients can be compared but it should be borne in mind that, because of the clinic population studied, the younger population is likely to represent the more severe cases that have persisted into or relapsed in adulthood. The overall characteristics of the two groups were largely similar in terms of EEG findings, remission rates, and incidence of family history of epilepsy in a first degree relative. The similarity of the incidence of a family history suggests that these patients also have a genetic form of epilepsy. The reports of families with adult onset IGE,614 and the discovery of a possible genetic locus for familial adult myoclonic epilepsy,15 confirm that adult onset IGE is likely to be a genetic epilepsy. IGE with onset in adulthood was more likely to occur in men, which may suggest a male genetic predisposition, but this needs further study.
One factor that was different between patients with a younger or older onset in our study was a previous history of febrile convulsions. These were more common in patients with “classical” IGE than in those with onset in adulthood (10.5% v 5.6%). There is good evidence that febrile convulsions have a strong genetic component1617 and it seems likely that the febrile convulsions in patients who later develop IGE are a manifestation of a genetic susceptibility to seizures. It may be that the genetic susceptibility to febrile convulsions confers a risk for a particular type of epilepsy18 which is more likely to occur earlier in life.
A potential limitation of this study is the inclusion of patients without the typical EEG changes of IGE. However, patients were only included if the clinical diagnosis, based on seizure semiology and demographics, was secure, thereby keeping the study relevant to clinical practice.
IGE with an onset in the third decade is undoubtedly common, but onset in later age groups was rare in the population studied. Some patients with an adult onset epilepsy may have unrecognised IGE, particularly as absences can go unnoticed in this age group. Prolonged EEG in selected patients without focal clinical or imaging features may be helpful in diagnosing adult onset IGE, but the epilepsy in the majority of patients with onset in adult life will be focal in nature. The diagnosis of epilepsy remains reliant upon clinical acumen, but the EEG is a useful tool to aid with accurate syndromic classification. Adult onset IGE shares many features with “classical” IGE, including EEG findings and prognosis, and is likely to represent a genetic epilepsy. When the genetics of the IGEs are further elucidated we will be able to define and classify this group of patients more accurately.
Competing interests: none declared
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.