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Predictive factors of seizure frequency and duration of antiepileptic treatment in rolandic epilepsy: A retrospective study
Predictive Factors of Seizure Frequency and Duration of Antiepileptic Treatment in Rolandic Epilepsy: A Retrospective Study Giovanni Ambrosetto, MD, Paola Giovanardi Rossi, MD and Carlo Alberto Tassinari, MD
Factors useful to predict seizure frequency and duration of antiepileptic treatment of children with benign partial epilepsy and rolandic spikes were retrospectively evaluated in 72 patients seizure-free for at least 5 years and off antiepileptic drugs for at least 2 years. Three groups were considered: Group I, 11 patients (15%) with a single seizure; GroupII, 40 patients (56%) with 2 to 6 seizures; Group III, 21 patients (29%) with over 6 seizures. Significant predictors of rare seizure frequency were: presence of convulsive generalized seizures as the sole ictal manifestation, found in 17 patients of Group II and in one patient of Group III (p < 0.001), and longer average interval between first and second seizure in Group II than in Group III (7.8 months versus 3.5 months, p
Benign epilepsy of children with rolandic spikes, also called rolandic epilepsy (RE) has a good medium- and long-term prognosis [1-3] . Seizures, usually simple partial or secondarily generalized [4, 5], generally cease at puberty. Adult relapse is rare [6,7]. Although patients almost always recover, seizure frequency may vary a great deal in different cases [8]. The severity of a given type of epilepsy may be related to seizure frequency and different degrees of recurrence have different psychosocial implications. It is therefore important to foresee the trend of seizures in individual patients. The first aim of this paper is to establish whether any useful parameters can be adopted to forecast seizure
From the Instituto di Neurologia, II Cattedra (GA, CAT), Cattedra di Neuropsichiatria Infantile (PGR), Universita di Bologna, Bologna. Received for publication: November 10,1986. Accepted for pUblication: February 20, 1987. Correspondence address: Dr. Giovanni Ambrosetto, Instituto di Neurologia, 40123 Via Ugo Foscolo 7, Bologna, Italy.
frequency. Further, as seizures finally cease, it is clinically useful to know when to suspend antiepileptic drugs. Hence we also evaluated the duration of treatment in RE. PATIENTS From among the outpatients at the Epilepsy Centre of the Neurology Clinic, University of Bologna, we selected 72 cases who had suffered from RE but were seizure-free for at least 5 years and off antiepileptic drugs for at least 2 years. The group comprised 47 males (65%) and 25 females (35%), average age 17 at the last visit (range 11.5 -23 years). All patients except 10 were examined by one of us after the first seizure. One patient was examined for the first time 6 months prior to the onset of seizures for a minor skull trauma leading to discovery of rolandic spikes on his EEG. By definition, neurological examination as well as CT scan was normal in all patients. EEGs were recorded every 8 months in addition to spontaneous sleep recordings during the afternoon or the whole night. The average length of observation was 8.2 years (range 5-12 years).
METHODS The patients were divided into 3 groups on the basis of the total number of seizures: Group I, 11 patients (I 5%) with a single seizure; Group II, 40 patients (56%) with 2-6 seizures; Group III, 21 patients (29%) with over 6 seizures. The three groups were compared for: 1) Sex. 2) Etiological factors. Febrile convulsions and/or epileptic seizures in the family were considered familial factors. Pre- or postmaturity, neonatal asphyxia and febrile convulsions were taken as personal factors . 3) Age of onset of seizures. 4) Type of seizures. 5) Time of seizures. 6) EEG features (Fig 1). Four features were considered: i) focal if the rolandic spikes were always located on one side only, ii) multifocal if at least one recording showed independent rolandic spikes in both hemispheres, iii) diffuse if the rolandic spikes spread over one or both hemispheres in over half the tracings, iv) generalized if the rolandic spikes were accompanied by generalized spike-wave discharges. 7) Associated complaints. These included enuresis, headache, behavioural disturbances, and difficulties at school. 8) Frequency of seizures. 9) Interval between first and second seizure. 10) Period between initial and last seizures. 11) Duration of antiepileptic therapy. Antiepileptic treatment was started, generally with carbamazepine (CBZ) or valproate (VPA), after the occurrence of the first seizure. Mean doses of CBZ were 27.5 mg/kg/die in Group I, 26.8 in Group II and 29.1 mg/kg/die in Group III. Mean doses of VP A were 25.0 mg/kg/die in Group II and 28.2 mg/kg/die in Group III. No patient of Group I received VPA. During the course of epilepsy, dosages were sometimes adjusted depending on persistence of seizures and/or patient's weight gain. Blood levels of antiepileptic drugs, when performed, were similar in the three groups and never exceeded the upper limits of the therapeutic range.
RESULTS Sex There were no significant differences between sexes in the three groups. Etiological factors (Table 1) The majority of patients presented no etiological factors. Familial factors were found more frequently in Group II than in Group III (not significant). Familial RE was found only in Groups I and II . Age of onset of seizures (Table 2) The age at the time of the first seizure was most often between 6 and 10 years in the three groups. Earlier onset occurred more frequently in Group III where there were no cases of last onset. The difference was statistically not significant. Type of seizures (Table 3) Simple partial seizures and/or secondarily generalized seizures (generalized fits with focal onset and/or focal postictal deficit, e.g. dysarthria or paresis) were the most frequent seizure type in the three groups. A significantly higher percentage of generalized seizures (generalized fits without apparent focal onset and/or focal postictal deficit) was found in Group II (p
Fig 1 EEG discharges of RE. F: focal, M: multifocal, D: diffuse, G: generalized. Zac. La.
9 yr.
Car. Mar. 9 yrs
Bus. lu. 11 yr.
Oem. Don. 12 yr.
Ambrosetto et al: Rolandic epilepsy
301
Table 4 Time of seizures
Table 1 Etiology I
Etiological factors
n (%)
Absent
7 ( 64)
Familial Personal
1 * ( 9) 3 ( 27)
17
11 (100)
n (%)
( 43)
11 ( 52)
6** ( 15) ( 20)
1 ( 5) 4 ( 19)
7**(17)
5 ( 24)
(100)
21 (100)
8
40
Time
I n (%)
Sleep
8 ( 73)
27 ( 68)
10 ( 48)
Wakefulness
3 ( 27)
6 ( 15)
4 ( 19)
7 ( 17)
7 ( 33)
40 (100)
21 (100)
III
n (%)
Familial and personal Total
Groups
Groups II
Sleep and wakefulness Total
11 (100)
Table 2 Onset of seizures Groups II n (%)
Age (years)
n (%)
III
n (%)
1-5
3 ( 27)
9 ( 22)
8 ( 38)
6 - 10
6 ( 55)
25 ( 63)
13 ( 62)
> 10
2 ( 18)
6 ( 15)
Total
11 (100)
40 (100)
n (%)
G
2 ( 18)
17
SP and/or SG
8 ( 73)
20
U Ass Total
(
9)
( 50) 2)
2* (
11 (100)
40
5)
(100)
III n (%)
Focal Multifocal
4 ( 36) 7 ( 64)
21 ( 53) 10 ( 25)
III
n (%) 12 ( 57) 7 ( 33)
Diffuse
4 ( 10)
(
Generalized
5 ( 12)
(
11 (100)
40 (100)
5) 5)
21 (100)
(
Interval between fIrst and second seizure 5)
( 71) 15 ( 14) 3 2** ( 10) 21
(100)
G: generalized, SP: simple partial, SG : secondary generalized, U: unilateral, Ass: association of two or more types of seizures, *: one patient with G and SP seizures, one patient with G and U seizures, ** : one patient with G and SP seizures, one patient with G and U seizures, t : significant versus Group III (p < 0.001) .
majority of patients. In a third of the cases in Group III, seizures arose both during wakefulness and sleep. EEG features (Table 5)
Multifocal abnormalities were more frequent in Group I than in the other groups (not significant). Generalized discharges were found more often in Group II than in Group III (not significant) . Four of the five patients in Group II with generalized discharges had generalized seizures . Three of them had a family history of epilepsy. Associated complaints There were no associated complaints in Group I, while
302 Brain & Development, Vol 9, No 3, 1987
n (%)
Groups II n (%)
they were reported in 10 patients in Group II (25%) and 8 patients in Group III (38%).
( 43)t (
EEG discharges
Total
Groups II n (%)
Seizures
I
21 (100)
Table 3 Type of seizures I
III n (%)
Table 5 EEG features
*: RE in the family , ** : two cases of RE in the family .
I
II n (%)
Two patients in Group II had only 2 seizures in 24 hours and were not considered from this point of view. The average interval between first and second seizures was 7.8 months in Group II (range 0.3-36 months) and 3.5 months in Group III (range 0.5-24 months). This difference was statistically significant (p<0.0001) . The intervals between subsequent seizures were generally longer and more irregular in Group II than in Group III (Fig 2). Frequency of seizures
Mean frequency of seizures was one seizure/5.8 months in Group II and one seizure/3.1 months in Group III, and this difference reached statistical Significance (p < 0.05). Period between fust and last seizures (Table 6) On average, seizures ceased earlier in Group II than in Group III. The average period between the first and the last seizures was significantly shorter in Group II than in Group III (p
Table 6 Period between first and last seizures
GROUP II (2-6 SEIZURES) SEIZURES
I
-L---'---L.---L_~-L----'----'_..L..-.....I---I.L.L.J. 0,6
0,9
4
0,3
0,6
0,9
5
0,3
0,6
0,9
6 8
0,3
Age vrs
SEIZURES
II I 6
0,6
0,9
0,3
7
0,6
8
0,9
0,50,6 Age vrs
GROUP
m
(>6 SEIZURES)
I 0,6
0.9
7
SEIZURES
U I I IH I
H
I 0,3
0,6
0,9
8
0.3
0.6
0,9
9
I
I •
0,20,3 Age vrs
IIIU
SEIZURES
IIU
I
First seizure (age, yrs)
Age yrs
Fig 2 Seizure recurrence ofpatients in Groups II and III.
respectively. The patient in Group III had 8 seizures hetween the ages of 7 and 13 years. All remaining patients in Groups I and II and 15 patients in Group III received an initial therapy consisting of VP A or CBZ. Three patients in Group III were treated with a combination of CBZ and phenobarbital (PB), and two received a combination of phenytoin (PHT) and PB. The average duration of global treatment was similar in Groups II and III. The average duration of treatment after the last seizure was longer, even if not significantly, in Group II than in Group III.
DISCUSSION When a patient has a first epileptic seizure, the problem is to establish whether it will remain an isolated event or whether it is the first sign of an epilepsy defmed as a state of recurrent chronic seizures. If the single seizure is not followed by others, the patient should not be con-
Groups II
7.5
III
7.4
5.6
Last seizure (age, yrs)
8.9
10.1
Duration
1.5*
(yrs)
4.5
*: significant versus Group III (p < 0.00001).
Table 7 Duration of antiepileptic therapy Mean duration (yrs)
I!
0,3
Epilepsy
1*
Groups II**
III***
Total
3
6
7
After last seizure
3
4.6
3
*: five patients received no antiepileptic drugs, **: two patients received no antiepileptic drugs. Nine patients had undetermined onset of therapy, ***: one patient received no antiepileptic drugs. One patient had undetermined onset of therapy.
sidered epileptic and hence should not be treated with antiepileptic drugs. Of our patients, 15% had had only one seizure and 5 of these did not receive anyantiepileptic therapy. Prognostic studies on isolated seizures are rare and the opinions expressed in the literature are somewhat contro· versial [9-14]. Our data from Group I patients indicate that, if an otherwise normal child has a rolandic seizure and rolandic spikes on EEG recording, antiepileptic treatment can be delayed until the second seizure without undue risk and independently of existing prognostic factors. If the seizures recur, then antiepileptic treatment may be considered. RE was given a good prognosis as soon as the condition was identified [15-17] and this has been confirmed in recent studies [1-3]. The seizures usually cease at puberty but may occur more or less frequently in different patients. About a third of the patients in Group II had only 2 seizures. Seizure recurrence in the two untreated patients in Group II was similar, if not less than that of treated patients. Five patients , not included in this study, had two seizures off antiepileptic drugs and were seizurefree for four years. Other patients in Group II might well have remained untreated without seizure recurrence. We consequently suggest that it is reasonable to wait for the treatment not only after the first seizure but also after the second seizure. The best predictive factors for seizure frequency was the interval between the first and second seizure. A long interval more often indicated a low frequency of subsequent seizures. In partial epilepsies of childhood, other than RE, the rare initial recurrence of seizures has also been considered a factor favouring a good prognosis [18,
19] . Ambrosetto et al: Rolandic epilepsy 303
The presence of generalized convulsive seizures alone was another significant indicator of rare seizures. Sex, etiological factors , age of epilepsy onset and time of seizures were not Significant. As in childhood epilepsies other than RE, EEG also proved of little prognostic value [20] . In the patients in Group III whose average seizure frequency was significantly higher, the average duration of the disease was longer than in Group II patients. Although the average duration of the disease was significantly different in Groups II and III, the average duration of antiepileptic treatment was similar in both groups and the average duration of treatment after the last seizure was even longer in Group II than in Group III . This contradiction was probably due to the fact that the risk of relapse correlated to untimely withdrawal of therapy was higher in patients with rare seizures recurring at long, irregular intervals than in patients with frequent seizures recurring at short, regular intervals. Relapse correlated with untimely withdrawal of treatment occurred in 5 patients in Group II and one patient in Group III. In the relapsed patients in Group II, therapy was suspended by the physician three times after a year free of seizures and twice after two seizure-free years. The patient of Group III relapsed when the family decided to withdraw treatment after 4 months free of seizures. None of the patients in Group III had a relapse following withdrawal of antiepileptic drugs after two years free of seizures . A higher risk of relapse after early withdrawal of antiepileptic therapy correlated with a low frequency of seizures seems to be a peculiar feature of RE since the percentage of relapse in partial epilepsy of childhood usually increases when seizures are frequent [21] . Antiepileptic drugs, doses, and blood levels were similar in Groups II and III. This is another contradiction in terms since seizure frequency was signiilcantly different in the two groups. It may be that higher doses of a single drug or combination of drugs were better able to control the seizures [22] . In conclusion, when RE has been diagnosed, the physician should adopt the following therapeutic approach: when the first seizure occurs, antiepileptic treatment should be delayed as the seizure may well remain an isolated event. Psychosocial implications permitting, onset of the treatment should be delayed also if a second seizure occurs, as the second seizure is often the last seizure. Patients with a third seizure should be pharmacolOgically treated if no significant predictor of low seizure frequency is present. CBZ is generally considered the drug of choice in the treatment of RE, but the control of the seizures may not be obtained in about 20% of affected children [23] . Then, antiepileptic drugs should be administered at the maximum dose tolerated if frequent seizures persist.
304 Brain & Development, Vol 9, No 3, 1987
REFERENCES 1. Beaussart M, Faou R. Evolution of epilepsy with rolandic paroxysmal foci: a study of 324 cases. Epilepsia 1978; 19: 337-42. 2. Blom S, Heijbel 1. Benign epilepsy of children with centrotemporal EEG foci: a follow-up study in adulthood of patients initially studied as children . Epilepsia 1982;23: 629-32. 3. Loiseau P, Pestre M, Dartigues JF,Commenges D, BarbergerGateau C, Cohadon S. Long-term prognosis in two forms of childhood epilepsy: typical absence seizures and epilepsy with rolandic (centrotemporal) EEG foci. Ann Neurol 1983; 13:642-8. 4. Dalla Bernardina B, Tassinari CA. EEG of a nocturnal seizure in a patient with benign epilepsy of childhood with rolandic spikes. Epilepsia 1975;16:497-501. 5 . Ambrosetto G, Gobbi G. Benign epilepsy of childhood with rolandic spikes, or a lesion? EEG during a seizure. Epilepsia 1975;16:793-6. 6. Beaussart M. Crises epileptiques apres guerison d'une EPR (epilepsie paroxysmes rolandiques) . Rev EEG Neurophysiol 1981; 11 :489-92. 7 . Ambrosetto G, Tinuper P, Baruzzi A. Relapse of benign partial epilepsy of children in adulthood: report of a case. 1 Neurol Neurosurg Psychiatry 1985;48:90. 8. Nayrac P, Beaussart M. Les pointes ondes pre-rolandiques: expression EEG tres particuliere. Etude electroclinique de 21 cas. Rev Neurol 1958;99:201-6. 9. Thomas MH. The single seizure. It's study and management. lAMA 1959;169:457-9. 10. Johnson LC, De Bolt WL, Long MT, et al. Diagnostic factors in adult males following initial seizures. Arch Neurol 1972; 27 :193-7. 11. Saunders M, Marshall C. Isolated seizures: an EEG and clinical assessment. Epi/epsia 1975;16 :731-3. 12. Loiseau P, Orgogozo 1M. An unrecognized syndrome of benign focal epileptic seizures in teenagers. Lancet 1978;2: 1070-1. 13. Cleland PG, Mosquera I, Steward WP , Fosier lB. Prognosis of isolated seizures in adult life. Br Med 1 1981;283:1364. 14 . Annegers IF, Shirts SB, Hauser WA, Kurland LT. Risk of recurrence after an initial unprovoked seizure. Epilepsia 1986;27:43-50. 15 . Gibbs EL, Gibbs FA. Good prognosis of mid temporal epilepsy. Epilepsia 1960; 1 :448-5 3. 16. Lombroso C. Sylvian seizures and midtemporal spike foci in children. Arch Neurol 1967; 17:52-9. 17. Blom S, Heijbel I, Bergfors PG. Benign epilepsy of children with centro-temporal EEG foci. Prevalence and follow-up study of 40 patients. Epi/epsia 1972;13:609-19. 18. Roger 1, Dravet C, Menendez P, Bureau M. Les epilepsies partielles de I'enfant. Evolution et facteurs de prognostic. Rev EEG Neurophysiol 1981; 11:431-7. 19. Scarpa P, Carassini B. Partial epilepsy in childhood: clinical andEEG study of261 cases. Epilepsia 1982;23:333-41. 20. Sofijanov NG. Clinical evolution and prognosis of childhood epilepsies. Epilepsia 1982 ;23:61-9. 21. Todt H. The late prognosis of epilepsy in childhood : re sults ofa prospective follow-up study. Epilepsia 1984;25:137-44. 22. Lesser RP, Pippenger CE, Liiders H, Dinners DS. High dose rnonotherapy in treatment of intractable seizures. Neurology (Cleveland) 1984;34:707-11. 23. Aicardi J. Epilepsy in children. New York: Raven Press, 1986: 124.
a
Factors useful to predict seizure frequency and duration of antiepileptic treatment of children with benign partial epilepsy and rolandic spikes were retrospectively evaluated in 72 patients seizure-free for at least 5 years and off antiepileptic drugs for at least 2 years. Three groups were considered: Group I, 11 patients (15%) with a single seizure; GroupII, 40 patients (56%) with 2 to 6 seizures; Group III, 21 patients (29%) with over 6 seizures. Significant predictors of rare seizure frequency were: presence of convulsive generalized seizures as the sole ictal manifestation, found in 17 patients of Group II and in one patient of Group III (p < 0.001), and longer average interval between first and second seizure in Group II than in Group III (7.8 months versus 3.5 months, p
Benign epilepsy of children with rolandic spikes, also called rolandic epilepsy (RE) has a good medium- and long-term prognosis [1-3] . Seizures, usually simple partial or secondarily generalized [4, 5], generally cease at puberty. Adult relapse is rare [6,7]. Although patients almost always recover, seizure frequency may vary a great deal in different cases [8]. The severity of a given type of epilepsy may be related to seizure frequency and different degrees of recurrence have different psychosocial implications. It is therefore important to foresee the trend of seizures in individual patients. The first aim of this paper is to establish whether any useful parameters can be adopted to forecast seizure
From the Instituto di Neurologia, II Cattedra (GA, CAT), Cattedra di Neuropsichiatria Infantile (PGR), Universita di Bologna, Bologna. Received for publication: November 10,1986. Accepted for pUblication: February 20, 1987. Correspondence address: Dr. Giovanni Ambrosetto, Instituto di Neurologia, 40123 Via Ugo Foscolo 7, Bologna, Italy.
frequency. Further, as seizures finally cease, it is clinically useful to know when to suspend antiepileptic drugs. Hence we also evaluated the duration of treatment in RE. PATIENTS From among the outpatients at the Epilepsy Centre of the Neurology Clinic, University of Bologna, we selected 72 cases who had suffered from RE but were seizure-free for at least 5 years and off antiepileptic drugs for at least 2 years. The group comprised 47 males (65%) and 25 females (35%), average age 17 at the last visit (range 11.5 -23 years). All patients except 10 were examined by one of us after the first seizure. One patient was examined for the first time 6 months prior to the onset of seizures for a minor skull trauma leading to discovery of rolandic spikes on his EEG. By definition, neurological examination as well as CT scan was normal in all patients. EEGs were recorded every 8 months in addition to spontaneous sleep recordings during the afternoon or the whole night. The average length of observation was 8.2 years (range 5-12 years).
METHODS The patients were divided into 3 groups on the basis of the total number of seizures: Group I, 11 patients (I 5%) with a single seizure; Group II, 40 patients (56%) with 2-6 seizures; Group III, 21 patients (29%) with over 6 seizures. The three groups were compared for: 1) Sex. 2) Etiological factors. Febrile convulsions and/or epileptic seizures in the family were considered familial factors. Pre- or postmaturity, neonatal asphyxia and febrile convulsions were taken as personal factors . 3) Age of onset of seizures. 4) Type of seizures. 5) Time of seizures. 6) EEG features (Fig 1). Four features were considered: i) focal if the rolandic spikes were always located on one side only, ii) multifocal if at least one recording showed independent rolandic spikes in both hemispheres, iii) diffuse if the rolandic spikes spread over one or both hemispheres in over half the tracings, iv) generalized if the rolandic spikes were accompanied by generalized spike-wave discharges. 7) Associated complaints. These included enuresis, headache, behavioural disturbances, and difficulties at school. 8) Frequency of seizures. 9) Interval between first and second seizure. 10) Period between initial and last seizures. 11) Duration of antiepileptic therapy. Antiepileptic treatment was started, generally with carbamazepine (CBZ) or valproate (VPA), after the occurrence of the first seizure. Mean doses of CBZ were 27.5 mg/kg/die in Group I, 26.8 in Group II and 29.1 mg/kg/die in Group III. Mean doses of VP A were 25.0 mg/kg/die in Group II and 28.2 mg/kg/die in Group III. No patient of Group I received VPA. During the course of epilepsy, dosages were sometimes adjusted depending on persistence of seizures and/or patient's weight gain. Blood levels of antiepileptic drugs, when performed, were similar in the three groups and never exceeded the upper limits of the therapeutic range.
RESULTS Sex There were no significant differences between sexes in the three groups. Etiological factors (Table 1) The majority of patients presented no etiological factors. Familial factors were found more frequently in Group II than in Group III (not significant). Familial RE was found only in Groups I and II . Age of onset of seizures (Table 2) The age at the time of the first seizure was most often between 6 and 10 years in the three groups. Earlier onset occurred more frequently in Group III where there were no cases of last onset. The difference was statistically not significant. Type of seizures (Table 3) Simple partial seizures and/or secondarily generalized seizures (generalized fits with focal onset and/or focal postictal deficit, e.g. dysarthria or paresis) were the most frequent seizure type in the three groups. A significantly higher percentage of generalized seizures (generalized fits without apparent focal onset and/or focal postictal deficit) was found in Group II (p
Fig 1 EEG discharges of RE. F: focal, M: multifocal, D: diffuse, G: generalized. Zac. La.
9 yr.
Car. Mar. 9 yrs
Bus. lu. 11 yr.
Oem. Don. 12 yr.
Ambrosetto et al: Rolandic epilepsy
301
Table 4 Time of seizures
Table 1 Etiology I
Etiological factors
n (%)
Absent
7 ( 64)
Familial Personal
1 * ( 9) 3 ( 27)
17
11 (100)
n (%)
( 43)
11 ( 52)
6** ( 15) ( 20)
1 ( 5) 4 ( 19)
7**(17)
5 ( 24)
(100)
21 (100)
8
40
Time
I n (%)
Sleep
8 ( 73)
27 ( 68)
10 ( 48)
Wakefulness
3 ( 27)
6 ( 15)
4 ( 19)
7 ( 17)
7 ( 33)
40 (100)
21 (100)
III
n (%)
Familial and personal Total
Groups
Groups II
Sleep and wakefulness Total
11 (100)
Table 2 Onset of seizures Groups II n (%)
Age (years)
n (%)
III
n (%)
1-5
3 ( 27)
9 ( 22)
8 ( 38)
6 - 10
6 ( 55)
25 ( 63)
13 ( 62)
> 10
2 ( 18)
6 ( 15)
Total
11 (100)
40 (100)
n (%)
G
2 ( 18)
17
SP and/or SG
8 ( 73)
20
U Ass Total
(
9)
( 50) 2)
2* (
11 (100)
40
5)
(100)
III n (%)
Focal Multifocal
4 ( 36) 7 ( 64)
21 ( 53) 10 ( 25)
III
n (%) 12 ( 57) 7 ( 33)
Diffuse
4 ( 10)
(
Generalized
5 ( 12)
(
11 (100)
40 (100)
5) 5)
21 (100)
(
Interval between fIrst and second seizure 5)
( 71) 15 ( 14) 3 2** ( 10) 21
(100)
G: generalized, SP: simple partial, SG : secondary generalized, U: unilateral, Ass: association of two or more types of seizures, *: one patient with G and SP seizures, one patient with G and U seizures, ** : one patient with G and SP seizures, one patient with G and U seizures, t : significant versus Group III (p < 0.001) .
majority of patients. In a third of the cases in Group III, seizures arose both during wakefulness and sleep. EEG features (Table 5)
Multifocal abnormalities were more frequent in Group I than in the other groups (not significant). Generalized discharges were found more often in Group II than in Group III (not significant) . Four of the five patients in Group II with generalized discharges had generalized seizures . Three of them had a family history of epilepsy. Associated complaints There were no associated complaints in Group I, while
302 Brain & Development, Vol 9, No 3, 1987
n (%)
Groups II n (%)
they were reported in 10 patients in Group II (25%) and 8 patients in Group III (38%).
( 43)t (
EEG discharges
Total
Groups II n (%)
Seizures
I
21 (100)
Table 3 Type of seizures I
III n (%)
Table 5 EEG features
*: RE in the family , ** : two cases of RE in the family .
I
II n (%)
Two patients in Group II had only 2 seizures in 24 hours and were not considered from this point of view. The average interval between first and second seizures was 7.8 months in Group II (range 0.3-36 months) and 3.5 months in Group III (range 0.5-24 months). This difference was statistically significant (p<0.0001) . The intervals between subsequent seizures were generally longer and more irregular in Group II than in Group III (Fig 2). Frequency of seizures
Mean frequency of seizures was one seizure/5.8 months in Group II and one seizure/3.1 months in Group III, and this difference reached statistical Significance (p < 0.05). Period between fust and last seizures (Table 6) On average, seizures ceased earlier in Group II than in Group III. The average period between the first and the last seizures was significantly shorter in Group II than in Group III (p
Table 6 Period between first and last seizures
GROUP II (2-6 SEIZURES) SEIZURES
I
-L---'---L.---L_~-L----'----'_..L..-.....I---I.L.L.J. 0,6
0,9
4
0,3
0,6
0,9
5
0,3
0,6
0,9
6 8
0,3
Age vrs
SEIZURES
II I 6
0,6
0,9
0,3
7
0,6
8
0,9
0,50,6 Age vrs
GROUP
m
(>6 SEIZURES)
I 0,6
0.9
7
SEIZURES
U I I IH I
H
I 0,3
0,6
0,9
8
0.3
0.6
0,9
9
I
I •
0,20,3 Age vrs
IIIU
SEIZURES
IIU
I
First seizure (age, yrs)
Age yrs
Fig 2 Seizure recurrence ofpatients in Groups II and III.
respectively. The patient in Group III had 8 seizures hetween the ages of 7 and 13 years. All remaining patients in Groups I and II and 15 patients in Group III received an initial therapy consisting of VP A or CBZ. Three patients in Group III were treated with a combination of CBZ and phenobarbital (PB), and two received a combination of phenytoin (PHT) and PB. The average duration of global treatment was similar in Groups II and III. The average duration of treatment after the last seizure was longer, even if not significantly, in Group II than in Group III.
DISCUSSION When a patient has a first epileptic seizure, the problem is to establish whether it will remain an isolated event or whether it is the first sign of an epilepsy defmed as a state of recurrent chronic seizures. If the single seizure is not followed by others, the patient should not be con-
Groups II
7.5
III
7.4
5.6
Last seizure (age, yrs)
8.9
10.1
Duration
1.5*
(yrs)
4.5
*: significant versus Group III (p < 0.00001).
Table 7 Duration of antiepileptic therapy Mean duration (yrs)
I!
0,3
Epilepsy
1*
Groups II**
III***
Total
3
6
7
After last seizure
3
4.6
3
*: five patients received no antiepileptic drugs, **: two patients received no antiepileptic drugs. Nine patients had undetermined onset of therapy, ***: one patient received no antiepileptic drugs. One patient had undetermined onset of therapy.
sidered epileptic and hence should not be treated with antiepileptic drugs. Of our patients, 15% had had only one seizure and 5 of these did not receive anyantiepileptic therapy. Prognostic studies on isolated seizures are rare and the opinions expressed in the literature are somewhat contro· versial [9-14]. Our data from Group I patients indicate that, if an otherwise normal child has a rolandic seizure and rolandic spikes on EEG recording, antiepileptic treatment can be delayed until the second seizure without undue risk and independently of existing prognostic factors. If the seizures recur, then antiepileptic treatment may be considered. RE was given a good prognosis as soon as the condition was identified [15-17] and this has been confirmed in recent studies [1-3]. The seizures usually cease at puberty but may occur more or less frequently in different patients. About a third of the patients in Group II had only 2 seizures. Seizure recurrence in the two untreated patients in Group II was similar, if not less than that of treated patients. Five patients , not included in this study, had two seizures off antiepileptic drugs and were seizurefree for four years. Other patients in Group II might well have remained untreated without seizure recurrence. We consequently suggest that it is reasonable to wait for the treatment not only after the first seizure but also after the second seizure. The best predictive factors for seizure frequency was the interval between the first and second seizure. A long interval more often indicated a low frequency of subsequent seizures. In partial epilepsies of childhood, other than RE, the rare initial recurrence of seizures has also been considered a factor favouring a good prognosis [18,
19] . Ambrosetto et al: Rolandic epilepsy 303
The presence of generalized convulsive seizures alone was another significant indicator of rare seizures. Sex, etiological factors , age of epilepsy onset and time of seizures were not Significant. As in childhood epilepsies other than RE, EEG also proved of little prognostic value [20] . In the patients in Group III whose average seizure frequency was significantly higher, the average duration of the disease was longer than in Group II patients. Although the average duration of the disease was significantly different in Groups II and III, the average duration of antiepileptic treatment was similar in both groups and the average duration of treatment after the last seizure was even longer in Group II than in Group III . This contradiction was probably due to the fact that the risk of relapse correlated to untimely withdrawal of therapy was higher in patients with rare seizures recurring at long, irregular intervals than in patients with frequent seizures recurring at short, regular intervals. Relapse correlated with untimely withdrawal of treatment occurred in 5 patients in Group II and one patient in Group III. In the relapsed patients in Group II, therapy was suspended by the physician three times after a year free of seizures and twice after two seizure-free years. The patient of Group III relapsed when the family decided to withdraw treatment after 4 months free of seizures. None of the patients in Group III had a relapse following withdrawal of antiepileptic drugs after two years free of seizures . A higher risk of relapse after early withdrawal of antiepileptic therapy correlated with a low frequency of seizures seems to be a peculiar feature of RE since the percentage of relapse in partial epilepsy of childhood usually increases when seizures are frequent [21] . Antiepileptic drugs, doses, and blood levels were similar in Groups II and III. This is another contradiction in terms since seizure frequency was signiilcantly different in the two groups. It may be that higher doses of a single drug or combination of drugs were better able to control the seizures [22] . In conclusion, when RE has been diagnosed, the physician should adopt the following therapeutic approach: when the first seizure occurs, antiepileptic treatment should be delayed as the seizure may well remain an isolated event. Psychosocial implications permitting, onset of the treatment should be delayed also if a second seizure occurs, as the second seizure is often the last seizure. Patients with a third seizure should be pharmacolOgically treated if no significant predictor of low seizure frequency is present. CBZ is generally considered the drug of choice in the treatment of RE, but the control of the seizures may not be obtained in about 20% of affected children [23] . Then, antiepileptic drugs should be administered at the maximum dose tolerated if frequent seizures persist.
304 Brain & Development, Vol 9, No 3, 1987
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