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1 Seizure 20 (2011) Contents lists available at ScienceDirect Seizure journal homepage: Electroclinical features of idiopathic generalized epilepsies in the elderly: A geriatric hospital-based study Vi Huong Nguyen Michel a,f, Claude Sebban a, Sylvie Debray-Meignan b, Zohra Ourabah c, Marie-Claude Rousseau-Lavallard d, François Piette e, Claude Adam f,g,h, * a Service d Explorations fonctionnelles, Hôpital Charles Foix, 7 avenue de la République, Ivry sur Seine, France b Service de Gériatrie, La Collégiale, 33 Rue du Fer à Moulin, Paris, France c Service de Gériatrie, Hôpital Charles Foix, 7 avenue de la République, Ivry sur Seine, France d Service de Neurophysiologie, Hôpital Sainte Antoine, 184 Rue Faubourg Sainte Antoine, Paris, France e Service de Médecine Interne Gériatrique, Hôpital Charles Foix, 7 avenue de la République, Ivry sur Seine, France f Unité d Epileptologie, Service de Neurologie 1, Hôpital de La Pitié-Salpêtrière, Bd de L Hôpital, Paris Cedex 13, France g Laboratoire de Neurosciences Cognitives et Imagerie Cérébrale, CNRS UPR640, Hôpital de La Pitié-Salpêtrière, Paris, France h Université Pierre et Marie Curie, Paris 6, France ARTICLE INFO ABSTRACT Article history: Received 17 June 2010 Received in revised form 19 December 2010 Accepted 27 December 2010 Keywords: Aged Generalized seizures Status epilepticus EEG Antiepileptic drugs Purpose: Idiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly described in children and adolescence. Our aim is to describe their electroclinical features in the elderly. Methods: Patients aged 70 years or more were prospectively selected in a geriatric EEG laboratory on the basis of rhythmic generalized spikes and waves discharges. Their clinical data were then examined to ascertain the syndromic diagnosis. Results: Among 1181 geriatric patients referred for EEG over a 30-month period, IGE were identified in 10 cases. Eight patients began seizures in childhood or adulthood (3 childhood absence epilepsies, 2 juvenile/adult myoclonic epilepsies and 3 epilepsies with-generalized-tonic clonic-seizures alone (EGTCS)) and 2 very late in life with EGTCS. The early-onset IGE cases had usually experienced a quiescent long period in adulthood before relapsing late in life. This relapse, mostly severe, consisted of absence status, myoclonic status or repeated generalized tonic clonic seizures and was often notsituation related. Absence status and myoclonic status were stopped by Clonazepam. The two late-onset IGE cases had familial history of epilepsy. Inappropriate antiepileptic drugs (AED) previously given in four patients with two worsenings were corrected. Conclusions: In this study, the non-negligible number of elderly cases observed over a short period of time suggests that IGE are frequent in the elderly but underestimated until recently. IGE may be lifelong with late severe exacerbations. A few very late-onset IGE cases exist. EEG remains useful in contributing to diagnose IGE and AED adjustment continues to be beneficial at extreme age. ß 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. 1. Introduction Idiopathic generalized epilepsies (IGE) are presumably genetic in nature and characterized by initially generalized seizures and generalized discharges on EEG. They affect approximately 30% of all patients with epilepsy 1,2 and have been typically described in childhood or adolescence 3 with an excellent prognosis with time. 4,5 Gastaut 4 found less than 1% of patients with IGE after the age of 65 and Loiseau et al. 6 failed to identify late-onset IGE cases and found only five cases in the literature. Recent studies * Corresponding author at: Unité d Epileptologie, Service de Neurologie 1, Clinique P. Castaigne, Hôpital de La Pitié-Salpêtrière, Bd de L Hôpital, Paris Cedex 13, France. Tel.: ; fax: address: claude.adam@psl.aphp.fr (C. Adam). indicate however a less favourable prognosis of absence epilepsies 7 9 and of epilepsies with generalized-tonic clonic seizures 10 or a much more prolonged evolution of juvenile myoclonic epilepsies (JME) IGE might be thus prolonged into adulthood and, presumably, lifelong, 9,12 might exacerbate at an advanced age or might even appear after the age of ,19 28 These previous reports however are few, scattered and concern relatively young older patients. Long-term follow-up studies of IGE did not go beyond the age of and cannot predict the frequency and the evolution of IGE at an extreme age. So it seems interesting to report IGE cases in older patients and their clinical features. Here we describe the characteristics of 10 cases, collected over a 30-month period, to illustrate their age of onset, their evolution with time, their seizure types, their diagnostic and therapeutic history up to a very advanced age (mean age of 79.4 years) /$ see front matter ß 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi: /j.seizure

2 Table 1 Summary of patients electrical and clinical characteristics. Pts Sex/age (yrs) Familial atcd of epilepsy Age at onset of seizures Seizures types and seizures frequency EEG data Subsyndromes Treatment and outcome 1 F/85 No Adolescence GTCSs in adolescence treated by PB. No recurrence during decades. Relapse of repeated GTCSs followed by one AS from age 80 under PB. Ictal EEG: continuous Hz generalized SW and PSW discharges during absence status which were suppressed by intravenous Clonazepam. Interictal epileptic discharges presented on 24 hours EEG without activation during sleep. EGTCS Good control with VPA. Follow-up of 7 months. 2 F/77 No Adolescence Myoclonic jerks in adolescence. One GTCS at the age of 20. No recurrence during decades without treatment. Severe relapse with myoclonic status, at age 76 under no AED. 3 F/81 Yes (sister) 8 yrs GTCS at age 8. Rare recurrences under PB and no seizure during the last 20 yrs. Relapse of repeated GTCSs at age 80 under no AED. 4 F/75 Yes (little daughter) 40 yrs GTCSs, myoclonic jerks at age 40. No recurrence without treatment. Relapse of repeated GTCSs and myoclonic jerks at age 75 under no AED. 5 F/74 No Childhood Absence seizures in childhood, then GTCSs. Persistence of absence seizures with 2 AS, GTCSs under GBP and PHT at age M/81 No 35 yrs GTGSs at age 35. No recurrence without treatment. Relapse of seizures at age 81 under no AED. 7 F/97 No Childhood Absence seizures, GTCSs at age 27 treated with PB. Absences and several GTCSs per yrs under PB. Last GTCS at age 93. No seizure during the last 4 yrs. 8 F/70 No 9 yrs Absence seizures, GTCSs. 2 GTCSs per year, daily absences seizures under CBZ, PHT and PB. Repeated GTCSs at age 69 without modification of treatment. Ictal EEG: sub continuous generalized PSW discharges accompanied with myoclonias which were suppressed by intravenous Clonazepam. Interictal epileptic discharges persisted, accompanied by myoclonic jerks on IPS at 15Hz on standard EEG. 3 Hz generalized SW discharges on standard EEG. SW, PSW were activated on drowsiness and on awakenings during 24 h EEG. 4 Hz interictal generalized SW discharges on standard EEG. Ictal EEG: sub continuous, irregular 3 Hz-generalized SW during absence status which were stopped by Clonazepam per os. Interictal epileptic discharges persisted on standard EEG. Interictal 3.5 Hz generalized SW discharges activated by drowsiness. PSW presented during sleep on 24 h EEG. Interictal generalized SW, PSW discharges on standard EEG, activated by drowsiness. Ictal EEG: brief absence seizure with stopping of counting accompanied by a 3 Hz generalized SW discharge during hyperventilation. Interictal epileptic discharges were activated by drowsiness, PS discharges presented during sleep on 24 h EEG. JME EGTCS JME CAE EGTCS CAE CAE Good control with VPA but side effects. Worsening of seizures under CBZ, Myoclonus exacerbated by LTG, Complete control under LEV at age 77. Follow-up of 1 year. Good control with VPA. Follow-up 15 months. Persistence of myoclonias under PHT (prescribed before admission) which was replaced by LEV. Lost to follow-up. Good control with VPA but side effects. Rare seizures under LTG and LEV. Follow up of 2 yrs. Good control with LEV. Follow-up 12 months. Refused to change her PB. Lost to follow up. CBZ, PHT were replaced by LEV, Lost to follow-up. V.H. Nguyen Michel et al. / Seizure 20 (2011)

3 294 V.H. Nguyen Michel et al. / Seizure 20 (2011) Table 1 (Continued ) EEG data Subsyndromes Treatment and outcome Seizures types and seizures frequency Age at onset of seizures Familial atcd of epilepsy Pts Sex/age (yrs) EGTCS Good control with VPA. Follow up 2 yrs. 61 yrs At least 2 GTCSs. 4 Hz interictal generalized SW discharges were activated by drowsiness. PS discharges presented during sleep on 24 h EEG. 9 F/74 Yes (brother, daughter) EGTCS Good control with LTG. Follow-up 1 year. 10 M/80 Yes (father) 80 yrs 2 GTCSs Hz interictal generalized SW discharges were activated by sleep. PS discharges presented during sleep on 24 h EEG. Abbreviations: CAE, childhood absence epilepsy; AS, absence status; atcd, antecedent; AED, antiepileptic drug; CBZ, carbamazepine; EGTCS, epilepsy with generalized tonic clonic seizures alone; GTCS, generalized tonic clonic seizures; IPS, intermittent photic stimulation; JME, juvenile myoclonic epilepsy; LTG, lamotrigine; LEV, levetiracetam; Pts, patients; PB, phenobarbital; PHT, phenytoine; PS, polyspikes; PSW, polyspikes and waves; SW, spikes and waves; VPA, valproate; yrs, years. 2. Methods We performed this study in an EEG laboratory which is situated in a university geriatric hospital (Charles-Foix Hospital). It was the only neurophysiologic laboratory which served exclusively the elderly population in the south of Paris. Among all the patients having an EEG recording from January 2006 to June 2008, we prospectively selected those aged 70 years or over and with discharges of rhythmic (around 3 Hz) generalized spikes or polyspikes and waves on EEG recording. We then examined them, interrogated them or their family or friends about their history, and collected the results of their ancillary exams (brain imaging, previous EEG, biological tests). We finally retained or not the diagnosis of IGE according to the international classification criteria, 3 except for the age criteria, i.e. we did not rule out the diagnosis because of an old age at onset if all other EEG-clinical criteria were fulfilled. 29 The standard EEG recordings were performed with 30 electrodes placed according to the modified system 30 for a minimum 20 min and the 24-h EEG with at least 8 electrodes. Intermittent photic stimulation (IPS) was systematically done. Hyperventilations were proposed depending on patient s cooperation. 3. Results 3.1. Clinical and EEG data (Table 1) Among 1181 patients aged 70 years or over and recorded in the EEG laboratory, 12 patients had generalized spikes or polyspikes and waves on EEG recording. Of these, IGE was not proved in two women: the first one had generalized polyspikes triggered by IPS and followed by a generalized tonic clonic seizure (GTCS), but no obvious diagnosis was established because of the lack of precise clinical history and follow-up; the other woman had a myoclonic status with generalized polyspikes which was probably in relation to the introduction of an antidepressant drug (Citalopram). The diagnosis of IGE was retained in the remaining 10 patients (8 women, mean age 79.4 years, range 70 97). They all presented GTCS, absences or massive myoclonia (see Table 1 for more details). All the following descriptions concern only the 10 latter patients. A total of 25 EEG recordings were performed: at least one standard EEG for each patient, and a 24-h EEG in 6 (only Patient 4 had one EEG and the others from 2 to 4 EEG recordings). Ictal discharges were recorded in 4/10 patients (two absence status, one myoclonic status, one absence seizure); interictal discharges persisted on repeated EEG recordings in all patients except for Patient 4 who had only one EEG recording. Three patients (Patients 1, 2, 5) had previous EEGs on which we retrieved the same interictal abnormalities. The diagnosis was: in 5 cases an epilepsy with generalized tonic clonic seizures alone (EGTCS) 31 which occurred at various times of the day 32 ; in 2 cases either a JME or an adult myoclonic epilepsy resembling JME except for the age of onset 33 and in 3 cases a childhood absence epilepsy (CAE). Eight patients began seizures in childhood or in adulthood at 35 and 40 years (early-onset IGE group) and the 2 other patients in their old age at 61 or 80 (lateonset IGE group: Patients 9, 10). The diagnosis of IGE was recognized in our institution. In Patient 2, a JME had been previously suggested but then misdiagnosed as partial epilepsy. Neurological exams showed no focal signs and biologic tests showed no relevant abnormalities in all patients. Cognitive function, evaluated during the hospitalisation, was unaltered in 3 (Patients 4, 8, 10), mildly or moderately impaired in 5 patients (17 < mini mental state (MMS) < 26/30) and severely impaired in 2 patients (MMS < 10/30) (Patients 1, 9). All patients had had an

4 [()TD$FIG] V.H. Nguyen Michel et al. / Seizure 20 (2011) at admission (cases 2, 5, 8). The 24-h EEG recorded in 6 patients (cases 1, 3, 6, 8, 9, 10) showed EEG discharges often activated by sleep except for case 1. Rhythmic generalized spikes and waves discharges were mostly present during the day while polyspikes and waves and/or polyspikes appeared preferentially during sleep in all of them (see examples in supplementary data). These patients had either EGTCS (cases 1, 3, 6, 9, 10) or CAE (case 8). IPS (15 Hz) provoked EEG discharges accompanied by myoclonic jerks in Patient 2 with JME and hyperventilations a brief absence in Patient 8 with CAE (see Table 1) Early-onset IGE In this group, an exacerbation of seizures between the age of 69 and 81 years (mean age 76) was observed in 7/8 patients suffering from IGE which began either in childhood or in adulthood. In 5 of them it occurred spontaneously after a long quiescent period during which 4 patients did not take any AED. This seizure exacerbation consisted of: absence status being preceded by repeated GTCS (Patient 1), sub continuous myoclonic seizures (Patient 2), repeated GTCS (Patients 3, 4, 6). Patient 2 had two types of exacerbation: first spontaneously before treatment at the age of 76 and later due to inappropriate AED at 77. Patient 8 had been having rare GTCS (i.e. whose seizures remained present during adulthood) under carbamazepine (CBZ), phenytoine (PHT) and phenobarbital (PB) for years, and had at the age of 69 a spontaneous exacerbation of GTCS without irregular intake of medication or inappropriate lifestyle. Patient 5 worsened under gabapentine (GBP), PHT and psychotropic drugs (drug-related exacerbation) Late-onset IGE Seizures occurred at the age of 61 (case 9) and of 80 (case 10) without precipitating factor. Both had familial history of epilepsy: the brother and the daughter of Patient 9, the father of Patient 10. They presented rare GTCSs which occurred during daytime. Brain imaging was normal. Cognitive functions were unaltered in Patient 10, and became impaired but a long time after the onset of epilepsy in Patient 9. Interictal generalized epileptic discharges were repeatedly observed on serial EEGs in both patients (4 and 2 for Patient 9 and 10, respectively). Fig. 1. (Patient 2): Standard EEG recording showing discharges of rhythmic generalized spikes and waves, prominent over the anterior regions, with a normal background activity (bipolar montage; HF 35 Hz; LF 0.3 Hz; calibration: vertical bar: 100 mv; horizontal bar: 1 s). active life and had worked except for one who was a housewife. Nine patients were married with children. Cerebral CT scan (six patients) or both CT scan and MRI (Patients 4, 5, 6, 10) showed normal results in 6 patients, some abnormal changes such as leukoaraiosis, cerebral atrophy or lacunes in 4 patients (Patients 1, 3, 6, 7) but an evident epileptogenic lesion in none of the cases. The EEG signs of some patients are depicted in Figs. 1, 2a, b and 3, and in supplementary data (supplementary figures 1a, b and 2a, b). For Patients 1, 2, 3 and 4, EEGs are also shown elsewhere. 18 Standard EEG recordings of interictal activity were performed in the morning (8 patients) or in the afternoon (cases 1, 3). These showed discharges of rhythmic (around 3 Hz) generalized spikes or polyspikes and waves prominent over the anterior regions on normal back ground activity without focal abnormalities. These characteristics were observed in both average reference and bipolar montages in all patients (one example in Fig. 2a and b). Interictal epileptic EEG discharges were more frequent when patients were treated with inappropriate antiepileptic drugs (AED) 3.4. Outcome The correct diagnosis of IGE permitted to stop inappropriate AED in 4 patients (CBZ in Patient 2; PHT in Patient 4; GBP and PHT in Patient 5, CBZ and PHT in Patient 8) and to introduce appropriate drugs in the two drug-worsened patients leading to either a complete seizure control (Patient 2) or to a marked improvement (Patient 5) (Table 1). Patient 2 with JME later interrupted vaproate acid (VPA) because of excessive somnolence, then began lamotrigine (LTG) that exacerbated myoclonia and finally was controlled by levetiracetam (LEV) (follow-up = 1 year). In Patient 5, efficient treatment by VPA was not well tolerated and interrupted because of side effects (excessive somnolence and digestive intolerance) and was replaced by LTG combined later to LEV (follow-up = 2 years) with rare persistent GTCS. The two others were lost to follow-up. Among the remaining patients, seizures were stable during the last four years under PB in Patient 7 who did not want to change her treatment. Patients 1, 3, 6, 9, 10 took already appropriate treatment (VPA in Patients 1, 3, 9, LEV in Patient 6, LTG in Patient 10) which were maintained at the same dosage after the diagnosis of IGE with an excellent control of seizures (mean followup = months).

5 [()TD$FIG] 296 V.H. Nguyen Michel et al. / Seizure 20 (2011) Fig. 2. (a) and (b) (Patient 8): Standard EEG recording (bipolar montage, a) showing rhythmic generalized spikes and waves and polyspikes and waves during wakefulness and 24-h EEG (Average reference, b) shows an activation of spikes and waves with long discharges in drowsiness (HF 35 Hz; LF 0.3 Hz; vertical bar: 100 mv; horizontal bar: 1 s). 4. Discussion Our cases allowed us to stress some salient features of IGE at an advanced age: the wide range of syndromic types; the long quiescent period without treatment before the late exacerbation without precipitating factors; the possible very late onset; the persistent sensitivity of seizures to AEDs, and the role of EEG. Recent publications of long-term follow-up studies in IGE (mean duration of 12.4 years 12 or 25.8 years 9 ) have indicated a high rate of seizure recurrence when medications are stopped 12 and a high percentage of patients continuing seizures despite AED treatment 9,12 suggesting that IGE may persist in their evolution; but they have not provided data beyond the age of 60. Information concerning IGE in the older patients is mainly given by scattered case reports in the literature with a mean age of 66 years (n = 39, range 51 84). 6,14,16,17,22,23,25,34 45 Our series from a geriatric population consisted of patients much older (mean age 79.4, range 70 97, see Table 1) with an age of 80 or over in four individuals. One of them was the oldest reported IGE case who had her last seizure at the age of 93 and EEG abnormalities still at the age of 97 (Fig. 3, Patient 7). Furthermore, we gathered 10 cases with early-onset or lateonset IGE cases among 1181 older patients over a short period of time (30 months). A previous study carried out in a Japanese tertiary epilepsy centre reported a rate of IGE reaching 15% of all patients with epilepsy and aged over 60 years (n = 190). 14 Along with this latter study, we thus strongly suspect that IGE are more common in geriatric patients than previously believed. 4,6 This underestimation of IGE in the elderly parallels with the difficulties of recognizing them in current practice. In our study, some patients were treated with unsuitable AEDs suggesting they were misclassified. Many reasons have been put forward for this in the literature: the unexpected character of the diagnosis at this age, 23 the predominance of new-onset partial epilepsies or situation-related seizures in the elderly, 46 the existence of a long period of quiescence (seizure reduction or apparent remission) in adulthood before relapse, 14,17,18,37 the frequent atypical EEG features or normal EEG results in some IGE, 41,47,48 the existence

6 [()TD$FIG] V.H. Nguyen Michel et al. / Seizure 20 (2011) Fig. 3. (Patient 7): Standard EEG recording showing persistence of EEG abnormalities with brief generalized spike-wave discharges in this oldest patient of the series (97 years). The background activity remains normal (bipolar montage; HF 35 Hz; LF 0.3 Hz; vertical bar: 100 mv; horizontal bar: 1 s). of inconspicuous and imperceptible late-onset absence epilepsies, 25 forgetting diagnosis with time, 38 the denial of past epilepsy by the patient himself, etc. 17 In addition, in older patients living alone, having cognitive impairment, reducing their daily activity and social contact, the medical history may be very difficult to reconstitute. Co-morbidity may also mask the diagnosis of IGE. Hiyoshi and Yagi 14 also indicated that IGE in the elderly were divided into persistent (13%) and late-onset (2%) cases. This latter entity after the age of 50 has been described until now in at least 24 individual cases. 4,14,19 28,33,49 We add two new IGE cases having begun at 61 and 80. In our geriatric patients, IGE were often identified at the occasion of seizure exacerbation. We observed all types of late seizure exacerbation already reported: repeated GTCS, subcontinuous myoclonic seizures or absence status. 4,14 17 We add that they occurred frequently (7/8 patients) after a long quiescent period (5/7 patients) under AED (Patient 1) or not (Patients 2, 3, 4, 6). So a very long-lasting remission without treatment in adulthood does not mean recovery for ever as in four of our very old patients. There is also some evidence that continuing AED might protect patients against exacerbations since only one patient out of five relapsed under treatment. By contrast we did not observe any relapse caused by AED withdrawal among our patients as it happens in adulthood, 9,12 perhaps because of the limited size of our sample. We know that absence status can occur at any age during the course of IGE, 16,37,50 57 sometimes a long time after the epilepsy onset 17,22,55,56,58 but may intervene for the first time after the age of ,34,36,37,39,42,45,55,56,59 Absence status may lead to the discovery of phantom absences 25 or an early onset IGE which has been a long time inactive and forgotten. 17,18 Accordingly we have to distinguish late-onset absence status in the course of IGE from de novo late-onset absence status. The main characteristics allowing this differentiation could be the absence of precipitating factors, the tendency to recur and the persistence of interictal EEG abnormalities after the status in the course of a preexisting IGE. 39,60 We show that interictal generalized spikes or polyspikes and waves discharges of around 3 Hz remained indicative of IGE despite old age (in 10 out of 12 patients). So their presence in elderly patients having seizures pleads in favour of IGE and can contribute to the diagnosis along with the clinical data. However, we do not know the exact sensitivity of EEG in our population since the existence of EEG abnormalities was one of the criteria of selection (some IGE patients without suggestive EEG patterns might be missed). Four patients were treated with inappropriate AED (Patients 2, 4, 5, 8). Once replaced and correctly adapted to epilepsy type and patient s tolerance, the correct treatment resulted in a good control of seizures in two of them whose follow-up was known (Patients 2, 5). The other patients already under correct medication evolved well except for one who did not want to change her PB and was lost to follow-up. Inappropriate AED in IGE 14,21,23,25,28,38,40 are known to frequently result in the persistence 14,21,23,38 or in the worsening of seizures. 14,23,28,40 In the elderly, worsening of seizures in IGE was described with CBZ 28 or PHT. 14,23,40 LTG may aggravate myoclonia in elderly patients with JME or even provoke de novo myoclonic jerks in patients with IGE. 43 In conclusion, we found 10 cases of early-onset or late-onset IGE in seniors. This should incite us to become more aware of these patients and not to reject the diagnosis of IGE on the single criterion of age. We show that IGE in the elderly can be lifelong, with late exacerbations after a long quiescent period without treatment and may be aggravated by inappropriate medication. We support the view that they are more frequent than previously believed. In the challenging context of extreme age, or when clinical data are missing, EEG could be helpful for the diagnosis. Conflict of interest There is no conflict of interest. Acknowledgment We would like to thank Geraldine Vine for her contribution to the correction of the English language. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi: /j.seizure References 1. Gastaut H, Gastaut JL, Goncalves e Silva GE, Fernandez Sanchez GR. Relative frequency of different types of epilepsy: a study employing the classification of the International League Against Epilepsy. Epilepsia 1975;16: Loiseau P, Duche B, Loiseau J. Classification of epilepsies and epileptic syndromes in two different samples of patients. Epilepsia 1991;32:303 9.

7 298 V.H. Nguyen Michel et al. / Seizure 20 (2011) Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30: Gastaut H. Individualization of so-called benign and functional epilepsy at different ages. Appraisal of variations corresponding the predisposition for epilepsy at these ages. Rev Electroencéphalogr Neurophysiol Clin 1981;11: Loiseau P, Panayiotopoulos CP, Hirsch E. Epilepsie-absences de l enfance et syndromes apparentés. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, editors. Les syndromes épileptiques de l enfant et de l adolescent. Eastleigh: John Libbey; p Loiseau J, Crespel A, Picot MC, Duche B, Ayrivie N, Jallon P, et al. Idiopathic generalized epilepsy of late onset. Seizure 1998;7: Wirrell EC, Camfield CS, Camfield PR, Gordon KE, Dooley JM. Long-term prognosis of typical childhood absence epilepsy: remission or progression to juvenile myoclonic epilepsy. Neurology 1996;47: Bartolomei F, Roger J, Bureau M, Genton P, Dravet C, Viallat D, et al. Prognostic factors forchildhoodandjuvenileabsenceepilepsies. Eur Neurol 1997;37: Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, et al. Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol 2004;251: Wolf P. Epilepsie avec crises grand mal du réveil. In: Roger BM, Dravet Ch J, Genton P, Tassinari CA, Wolf P, editors. Les syndromes épileptiques de l enfant et de l adolescent. Eastleigh: John Libbey; p Delgado-Escueta AV, Enrile-Bacsal F. Juvenile myoclonic epilepsy of Janz. Neurology 1984;34: Martinez-Juarez IE, Alonso ME, Medina MT, Duron RM, Bailey JN, Lopez-Ruiz M, et al. Juvenile myoclonic epilepsy subsyndromes: family studies and long-term follow-up. Brain 2006;129: Thomas P, Genton P, Gelisse P, Wolf P. Epilepsie myoclonique juvénile. In: Roger BM, Dravet Ch J, Genton P, Tassinari CA, Wolf P, editors. Les syndromes épileptiques de l enfant et de l adolescent. Eastleigh: John Libbey; p Hiyoshi T, Yagi K. Epilepsy in the elderly. Epilepsia 2000;41(9): Dziewas R, Kellinghaus C, Ludemann P. Nonconvulsion status epilepticus in patients with juvenile myoclonic epilepsy: types and frequencies. Seizure 2002;11: Zambrelli E, Terzaghi M, Sinforiani E, Manni R. Non-convulsive status epilepticus and generalised tonic clonic seizures persisting in old age in a patient with idiopathic generalised epilepsy: a long-term observation. Neurol Sci 2006;27: Bauer G, Bauer R, Dobesberger J, Benke T, Walser G, Trinka E. Absence status in the elderly as a late complication of idiopathic generalized epilepsies. Epileptic Disord 2007;9: Nguyen-Michel VH, Ourabah Z, Sebban C, Lavallard-Rousseau MC, Adam C. Idiopathic generalised epilepsies in the elderly: the viewpoint of a geriatrician. Rev Neurol (Paris) 2009;165: Courjon J, Artru F, Zeskov P. Epileptic crises occurring after the age of 60 years observed in practice of neurology in a neuro-surgical department. La Semaine des hôpitaux 1970;46: Vercelletto P, Delobel R. Study of etiologic and prognostic factors in epilepsy with the onset after 60 years of age. La Semaine des hôpitaux 1970;46: Terzano MG, Gemignani F, Mancia D. Petit mal status with myoclonus: case report. Epilepsia 1978;19: Dunne JW, Summers QA, Stewart-Wynne EG. Non-convulsive status epilepticus: a prospective study in an adult general hospital. Q J Med 1987;62: Gram L, Alving J, Sagild JC, Dam M. Juvenile myoclonic epilepsy in unexpected age groups. Epilepsy Res 1988;2: Oller-Daurella L, Sorel L. Benign grand mal epilepsy in the adult. Acta Neurol Belg 1989;89: Panayiotopoulos CP, Koutroumanidis M, Giannakodimos S, Agathonikou A. Idiopathic generalised epilepsy in adults manifested by phantom absences, generalised tonic clonic seizures, and frequent absence status. J Neurol Neurosurg Psychiatry 1997;63: Marini C, King MA, Archer JS, Newton MR, Berkovic SF. Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics. J Neurol Neurosurg Psychiatry 2003;74: Yenjun S, Harvey AS, Marini C, Newton MR, King MA, Berkovic SF. EEG in adultonset idiopathic generalized epilepsy. Epilepsia 2003;44: Toth V, Rasonyi G, Fogarasi A, Kovacs N, Auer T, Janszky J. Juvenile myoclonic epilepsy starting in the eighth decade. Epileptic Disord 2007;9: Roger J, Bureau M, Oller Ferrer-Vidal L, Oller Daurella L, Saltarelli A, Genton P. Clinical and electroencephalographic characteristics of idiopathic generalized epilepsies. In: Malafosse PGA, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalized epilepsies. London: John Libbey; p Guideline thirteen: guidelines for standard electrode position, nomenclature, American Electroencephalographic Society. J Clin Neurophysiol 1994;11: Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, Epilepsia 2010;51: Unterberger I, Trinka E, Luef G, Bauer G. Idiopathic generalized epilepsies with pure grand mal: clinical data and genetics. Epilepsy Res 2001;44: Gilliam F, Steinhoff BJ, Bittermann HJ, Kuzniecky R, Faught E, Abou-Khalil B. Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy. Neurology 2000;55: Amand G. Absence states and prolonged states of confusion after the age of 60 years. Rev Electroencephalogr Neurophysiol Clin 1971;1: Gastaut H, Gastaut JL. Les epilepsies du troisième âge, dans le cadre des crises cérébrales propre à cet âge. In: Billé J, editor. Le cerveau du troisième âge. Paris: Dausse; p Bauer G, Aichner F, Mayr U. Nonconvulsive status epilepticus following generalized tonic clonic seizures. Eur Neurol 1982;21: Gastaut H, Zifkin BG, Mariani E, Puig JS. The long-term course of primary generalized epilepsy with persisting absences. Neurology 1986;36: Grunewald RA, Panayiotopoulos CP. Diagnosing juvenile myoclonic epilepsy in an elderly patient. Seizure 1994;3: Thomas P, Andermann F. Late-onset absence status epilepticus in most often situation-related. In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalized epilepsies. London: John Libbey; p Osorio I, Reed RC, Peltzer JN. Refractory idiopathic absence status epilepticus: a probable paradoxical effect of phenytoin and carbamazepine. Epilepsia 2000;41: Montalenti E, Imperiale D, Rovera A, Bergamasco B, Benna P. Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients. J Neurol Sci 2001;184: Fernandez-Torre JL, Diaz-Castroverde AG. Non-convulsive status epilepticus in elderly individuals: report of four representative cases. Age Ageing 2004;33: Crespel A, Genton P, Berramdane M, Coubes P, Monicard C, Baldy-Moulinier M, et al. Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies. Neurology 2005;65: Jacob S, Martin D, Rajabally YA. Juvenile myoclonic epilepsy in an elderly patient. Age Ageing 2006;35: Genton P, Ferlazzo E, Thomas P. Absence status epilepsy: delineation of a distinct idiopathic generalized epilepsy syndrome. Epilepsia 2008;49: Loiseau J, Loiseau P, Duche B, Guyot M, Dartigues JF, Aublet B. A survey of epileptic disorders in southwest France: seizures in elderly patients. Ann Neurol 1990;27: Genton P, Salas Puig X, Tunon A, Lahoz C, Del Socorro M, Sachez G. Juvenil myoclonic epilepsy and related syndromes: clinical and neuropsychological aspects. In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalized epilepsies. London: John Libbey; p Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994;35: Cutting S, Lauchheimer A, Barr W, Devinsky O. Adult-onset idiopathic generalized epilepsy: clinical and behavioral features. Epilepsia 2001;42: Lennox WG. The petit mal epilepsies: their treatment with Tridione. J Am Assoc 1945;129: Niedermeyer E, Khalifeh R. Petit mal status ( spike-wave stupor ). An electroclinical appraisal. Epilepsia 1965;6: Novak J, Corke P, Fairley N. Petit Mal Status in adults. Dis Nerv Syst 1971;32: Andermann F, Robb JP. Absence status. A reappraisal following review of thirtyeight patients. Epilepsia 1972;13: Gibberd FB. The prognosis of petit mal in adults. Epilepsia 1972;13: van Gall M, Scollo-Lavizzari G, Becker H. Absence status in the adult. New results including computerized transverse axial tomography. Eur Neurol 1978;17: Porter RJ, Penry JK. Petit mal status. Adv Neurol 1983;34: Baykan B, Gokyigit A, Gurses C, Eraksoy M. Recurrent absence status epilepticus: clinical and EEG characteristics. Seizure 2002;11: Courjon J, Fournier MH, Mauguiere F. Status epilepticus in adult epileptics followed in a neurologic hospital. Rev Electroencéphalogr Neurophysiol Clin 1984;14: Agathonikou A, Panayiotopoulos CP, Giannakodimos S, Koutroumanidis M. Typical absence status in adults: diagnostic and syndromic considerations. Epilepsia 1998;39: Thomas P, Beaumanoir A, Genton P, Dolisi C, Chatel M. De novo absence status of late onset: report of 11 cases. Neurology 1992;42: