Epilepsia, 42(12):1549–1552, 2001 Blackwell Science, Inc. © International League Against Epilepsy
Benign Partial Epilepsies of Adolescence: A Report of 37 New Cases *G. Capovilla, †A. Gambardella, ‡A. Romeo, *F. Beccaria, *A. Montagnini, †A. Labate, ‡M. Viri, §V. Sgro`, and 㛳P. Veggiotti *Department of Child Neuropsychiatry, “C. Poma” Hospital, Mantova; †Institute of Neurology, School Of Medicine, University Magna Graecia of Catanzaro; ‡Epilepsy Center, “Fatebenefratelli” Hospital, §Epilepsy Center, S. Paolo Hospital, Milan; and 㛳 Department of Child Neuropsychiatry, C. Mondino Institute, Pavia, Italy
Summary: Purpose: To delineate the electroclinical features of patients with partial seizures in adolescence with a benign outcome. Methods: Patients were recruited in five different Italian epilepsy centers. Patients were selected among those with partial seizures between ages 11 and 17 years. We excluded benign childhood epilepsies, those with neurologic or mental deficits, and those with neuroradiologically documented lesions. We also excluded patients with less than 3 years’ follow-up or who were still receiving antiepileptic therapy. Results: There were 37 (22 male, 15 female) patients. Seizures started at the mean age of 14.5 years (range, 11–16.11).
Two main electroclinical patterns emerged: 16 of 37 patients had somatomotor seizures frequently associated with focal theta discharges involving the centroparietal regions. Ten of 37 patients showed versive seizures and interictal spiking involving the posterior regions. A third group had clinical characteristics resembling the cases described by Loiseau. All had a favorable outcome. Conclusions: This relevant multicenter study further confirms the existence of benign partial epilepsies with onset during adolescence. Key Words: Epilepsy—Benign partial epilepsy—Idiopathic epilepsy—Partial seizure—Adolescence.
The classification of epileptic syndromes adopted by the International League against Epilepsy recognizes two main syndromes of idiopathic partial epilepsy: benign epilepsy with centrotemporal spikes (BECT) and benign epilepsy of childhood with occipital paroxysms (BEOP) (1). These two syndromes are described and accepted only in childhood, even if, in the past two decades, several authors have described other forms of benign partial epilepsy (BPE) outside childhood, mostly in infancy (2–6). Conversely, a later onset during adolescence has been usually considered to reflect a symptomatic or cryptogenic etiology with a less favorable prognosis, even though Loiseau et al. (7,8) described an “unrecognized syndrome of benign focal epileptic seizures of adolescence” (BPSA). More recently, very few articles focused on this topic (9,10), and the electroclinical features as
well as the boundaries of benign partial epilepsies of adolescence still must be better defined. The aim of our work was to present a group of 37 patients affected by partial seizures with a benign course and to study in detail their electroclinical characteristics. METHODS The patients were recruited between 1985 and 1997 in five different Italian epilepsy centers. This retrospective study was performed on patients with partial seizures starting during adolescence. The age cutoff of the first unprovoked seizure was from 11 to 17 years. To assess the long-term outcome, we excluded cases with less than 3 years’ follow-up. We considered only the cases observed at the time of their first seizures, to study their initial EEG picture. The total number of patients was 199. From the initial group, we excluded patients with neuroradiologically documented lesions (66 cases), or neurologic or mental deficits (23 cases). Some of the remaining cases, who matched the electroclinical picture of BECT or BEOP (35 cases), also were excluded from this study. We cannot draw any epidemiologic conclusions because of the different types of recruiting centers,
Abstract presented at the next International Epilepsy Congress of Buenos Aires. Accepted as platform presentation. Revision received September 13, 2001. Address correspondence and reprint requests to Dr. G. Capovilla at Department of Child Neuropsychiatry, “C. Poma” Hospital, Viale Albertoni 1, 46100 Mantova, Italy. E-mail:
[email protected]
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G. CAPOVILLA ET AL. TABLE 1. Clinical findings in 37 patients with BPSA Sex
Men
Women
Fam
Age at onset (yr)
Length of the seizures (s)
22 (60%)
15 (40%)
16/37 (44%)
11–16.11 (mean 14.5)
60–120
Occurrence W
S
Therapy
Follow-up (yr)
23/37 (62%)
17/37 (46%)
25/37 (67%)
3–13.6 (mean, 6.3)
Fam, familiarity; W, wakefulness, S, sleep.
some of which are general hospitals, whereas others are high specialized epilepsy centers, so that a recruiting bias certainly occurs. Among the remaining 75 patients, we excluded cases who had seizure recurrence after drug discontinuation (27 cases) or who were taking antiepileptic medications (AEDs; 11 cases). The remaining 37 patients are the object of this study. All these patients underwent a comprehensive clinical, neuropsychological, electroencephalographic, and magnetic resonance imaging (MRI) evaluation. Most of them also had brain computed tomography (CT) scans. Awake and sleep-deprived video-EEG recordings were obtained in all subjects. Repeated EEG recordings every 3–12 months also were obtained in all patients. RESULTS Of 22 (60%) men and 15 (40%) women, a family history of epilepsy (13 cases) or febrile convulsion (three cases) was present in 16 cases (44%). Pre-, peri-, and postnatal personal history was unremarkable in all. Psychomotor development and neurologic examinations were normal, both before and after the onset of the seizures. Table 1 shows the main clinical characteristics of our cases. Seizure manifestations The majority (26 of 37, 70%) of our patients had either somatomotor or versive seizures. Sixteen patients had somatomotor fits characterized by sensory symptoms involving an upper extremity or one side of the face. In some cases, the tongue was first affected. A progression of sensory symptoms was reported by all these 16 patients. Usually, at the end of the seizure, the patients were able to report their symptoms. Occasionally, together with the seizure progression, loss of consciousness or secondary generalization occurred. Versive motor attacks occurred in ten of 37 patients and were initially characterized by eyes and/or head deviation, often followed by loss of consciousness with or without second-
ary generalization. Interestingly, the age at onset of these versive attacks was always older than 13 years, with a peak between 14 and 15 years. In the whole group, secondarily generalized seizures occurred in 21 (57%) of 37 cases. Five (16%) of 37 patients had other types of simple partial seizures without a secondarily generalized phase. Eleven (27%) of 37 cases had complex partial seizures without secondary generalization. Table 2 summarizes the seizure types of our patients. Seizures occurred a little more frequently during the awake state (23 of 37, 62%) than during sleep (17 of 37, 46%). In three cases, seizures were present during both awake and sleeping states. Seizure length ranged between 1 and 3 min. Seizures were often followed by postictal sleep. The frequency of seizures was usually very low. Eleven of 37 patients had only a single attack, and seven of them never had any therapy. In 11 patients, seizures recurred at short intervals, within 1 or 2 days. None of our patients had more than three seizures. EEG findings Table 3 summarizes the EEG findings of our patients. A normal EEG, during both wakefulness and sleep, was observed in 17 (46%) of 37 patients. In 13 of 37 patients, the EEG abnormalities appeared only during sleep stages I–II. The remaining seven of 37 patients showed EEG abnormalities during both wakefulness and sleep. We observed three main types of EEG abnormalities: focal spikes, sharp waves, and theta discharges. Focal spikes were present in nine cases and appeared more often during sleep (seven patients). Sometimes spikes appeared in the same patients who had, during wakefulness, focal theta discharges. Importantly, these EEG abnormalities were encountered mostly in subjects who had versive seizures (seven of 10 patients) and were localized in the occipital or parietooccipital regions. Morphologically, they were quite different from focal spikes characterizing childhood BPEs (Fig. 1). Focal sharp waves in six patients occurred more frequently during sleep (four of six). Finally, focal theta discharges were present in eight
TABLE 2. Type of seizure in 37 patients with BPSA Somatomotor (16/37) Sec gen 9
CP 4
SP
Versive (10/37) Sec gen
3
5
CP 4
TABLE 3. EEG findings in 37 patients with BPSA
Others (11/37)
SP 1
Sec gen 7
CP 3
1
Sec gen, secondarily generalized; CP, complex partial; SP, simple partial.
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Focal EEG abnormalities
SP Abnormal EEG (wakefulness)
Abnormal EEG (NREM sleep)
Spikes
Sharp waves
Theta discharge
7/37 (19%)
20/37 (54%)
9
6
8
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FIG. 1. Top: Typical occipital abnormalities in a patient with benign childhood occipital epilepsy. Bottom: Clear morphologic differences in a case with versive seizure of adolescence.
patients. Frequently (six cases), they were localized over the centroparietal areas and occurred in patients who showed somatomotor seizures. A peculiar phenomenon was the “vanishing” of the EEG abnormalities, particularly of the focal theta discharge, which often occurred for a limited period during the initial phase of the illness. A photoparoxysmal response was present only in two patients, whereas generalized epileptiform discharges were never found. Therapy Twelve patients never had any therapy, and seven of them had only one seizure. In all other cases, seizures were always easily controlled. Recurrence of seizures, during the treatment, occurred only in five cases. The most frequently used drug was carbamazepine (CBZ; 16 cases), followed by sodium valproate (VPA). In the more recent observed cases, the treatment was withheld. All our patients had stopped their medication before the study began. In all these patients, the follow-up without therapy was >1 year with a mean value of 3 years and 9 months. Follow-up All of our 37 patients had >3 years’ follow-up, and 29 of 37 >5. The follow-up extremes were 3 and 13 years 6 months (mean, 6 years 3 months). Among the 25 cases who had been pharmacologically treated, follow-up was >5 years in 15 cases and >8 years in 10 cases. DISCUSSION Epileptologists have always considered with suspicion the occurrence of a first unprovoked seizure during ado-
lescence. In these cases, a poor prognosis is currently suspected because of the possible presence of an underlying brain lesion. Usually there is also a high expectation of recurrence of seizures, even if neuroradiologic studies are negative, and a diagnosis of cryptogenic partial epilepsy is made when no lesion is detected. In this study, we have illustrated that a benign course can be observed in patients whose partial seizures start during adolescence, if there is a clinical context of neurologic and neuroradiologic normality, regardless of the occurrence of paroxysmal epileptiform abnormalities. On this basis, as already addressed by other authors (7–10), we further confirm the existence of a form of partial epilepsy with benign evolution that starts during adolescence. It is important to recognize these conditions and to avoid giving a poor prognosis at a first seizure only because of its occurrence during adolescence. Furthermore, in such conditions, starting a pharmacologic treatment should be questioned, both for the benign course and the low frequency of the seizures. It is of interest that two main electroclinical patterns have emerged from this large multicenter study. The first, which resembles the one reported by other authors (9,10), is characterized by the occurrence of rare somatomotor seizures and the presence of focal theta discharges over the centroparietal regions. It should be noted, however, that in our patients, the somatomotor seizures rarely had a jacksonian progression. The second type of electroclinical pattern consists of versive seizures and focal spikes or sharp waves over the posterior regions. It is reasonable to hypothesize that these two groups of patients were identified because of the large number of cases we collected. King et al. (10) also claimed the Epilepsia, Vol. 42, No. 12, 2001
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existence of some BPSA patients whose EEGs evidenced the presence of epileptiform abnormalities, but they did not share any distinctive morphology or distribution, presumably because the number of patients was too small to draw any conclusions (10). Probably a proportion of our cases are similar to those of Loiseau et al. (7,8), particularly those patients with a short seizure period (as Loiseau et al. described, “no more than 36 hours”) and a normal EEG picture. Loiseau et al. stated that interictal EEGs were always normal, even if they did not specify whether EEG recordings were obtained during wakefulness or sleep (7,8). Many of our cases had a normal awake EEG, and paroxysmal abnormalities appeared only during sleep. In accordance with our findings, King et al. (10) also reported that some of their patients had EEG abnormalities. The absence of family history was another finding in BPSA (10). On the contrary, in our cases, we found a high rate of family history of epilepsy, and this further supports the probable idiopathic nature. Differential diagnosis of benign forms includes mainly cryptogenic partial epilepsy, in which a neurologic, neuroradiologic, and intellectual normality is often found. Moreover, the ictal semiology of cryptogenic partial epilepsies is different from that of our benign cases. Seizures are more polymorphous in the entire group and, often, complex partial seizures without secondary generalization are encountered. Furthermore, the very long follow-up further supports the benign nature of our cases. Finally, older cases of benign partial epilepsy of childhood, like BECT or BEOP, might enter into differential diagnosis with our cases, particularly for those with occipital spikes. The electroclinical features observed in the present series are substantially different from those re-
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ported in benign partial epilepsies of childhood (1). In particular, both seizure semiology and spike morphology evidence clear differences from BECT or BEOP. Another important feature to underline is the onset age of our cases with occipital spikes and versive attacks, older than those in childhood benign forms. To conclude, our opinion is that benign partial idiopathic epilepsies of adolescence do exist. Even if the diagnosis is difficult and necessarily retrospective, AED treatment could be avoided, even after a second seizure. Acknowledgment: We thank Andrea Dalporto for his technical support.
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