Epilepsio, 31(6):7%794, 1990 Raven Rcss, Ltd., New Yo& 0 International League Against Epilepsy
Some Genetic Aspects of Idiopathic and Symptomatic Absence Seizures: Waking and Sleep EEGs in Siblings R. Degen, H.-E. Degen, and Ch. Roth Epilepsy Centre, Bethel, F.R.G.
Sunmmry: Epileptic activity was recorded in the waking and sleep EEG of 62.5% of 80 siblings of 38 patients with absence seizures. Epileptic discharges were noted in waking only in 8.7%, in waking as well as sleep in 28.8%, and in sleep only in 25%. Generalized, partly irregular, and slow spike-wave complexes were found, twice with lateral emphasis. Spike-wave complexes were recorded in W o of 50 siblings of patients with idiopathic absence and in 46.7% of 30 siblings of patients with symptomatic absence. One epileptic discharge was observed every 108.6 s on the average, without striking differences between siblings of patients with idiopathic (99.7 s) and symptomatic absence (1 19.3 s). Without any differences between siblings of children with idiopathic and symptomatic absence, the most epileptic discharges were activated in sleep stages C and D, followed by stages A and B. The highest activation rate was observed in the 7-14year-old group (73.5%) and to a somewhat lesser degree in the group between 15 and 20 years of age (66.7%); fewer epileptic discharges were recorded in
younger (25%) and older patients (28.6%). The higher activation rates in the male sex were significant only in siblings of patients with idiopathic absence. Although only five patients (13.2%) were photosensitive, a photosensitivity was found in 24% of siblings of children with idiopathic absence and in 20% of siblings of patients with symptomatic absence. Three siblings of patients with idiopathic absence also had absence seizures; in one of them a febrile seizure occurred at an earlier age. All of them showed generalized spike wave discharges in waking as well as sleep. Occipital theta delta activity with generalization was observed more frequently in siblings of patients with idiopathic absence (82.2%) than in those of patients with symptomatic absence (63.6%). Our waking and sleep EEG recordings prove that concerning etiology-genetic factors play a striking role in idiopathic absence, but are also of considerable significance in the symptomatic types. Key Words Epilepsy-Absence seizures-Electroencephalography-Genetics.
Absence seizures characterize the idiopathic generalized epilepsies included in childhood absence epilepsy (pyknolepsy) or in juvenile absence epilepsy (Commission, 1985). In idiopathic epilepsies, brain damage is neither present nor expected and patients show no neurologic deficits, mental retardation, or behavior disturbances; frequently, however, there is a positive family history. Both simple and complex absence seizures may be observed. Symptomatic absence seizures are classified as cryptogenetic or symptomatic epilepsies within the generalized epilepsies or can belong to the symptomatic types of localized epilepsies. By definition, symptomatic absence seizures are predominantly the consequence of known or supposed brain damage. Patients with those absence seizures often
have neurologic deficits, mental retardation, and behavior disturbances. Family history is less frequently positive for seizures. Symptomatic absence seizures are best known as one of the three seizure types of the Lennox-Gastaut syndrome, but are also found with generalized tonic-clonic seizures or complex partial seizures. The clinical diagnosis is often more difficult in the symptomatic than in the idiopathic types because the seizures often start and finish less abruptly and consciousness is less affected. Eyelid and perioral myoclonias and atonic facial and neck components (with dropping of the head and the trunk) and salivation are occasionally observed. Often asynchronous, irregular and slow, partly abortive 2-2.5-Hz spike-wave complexes and more rarely 3 4 H z spike-wave complexes are recorded in the EEG. Background EEG slowing is often present, sometimes with foci. The EEG findings of healthy siblings of patients with idiopathic absence seizures (Matthes and We-
Received June 1988; revision accepted November 1990. Address correspondence and reprint requests to Professor Dr. R. Degen at Epilepsy Centre Bethel, 4800 Bielefeld 13, F.R.G.
784
WAKING AND SLEEP EEG IN SIBLINGS IN ABSENCE SEIZURES
ber, 1968; Doose et al., 1973) and idiopathic absence as well as primary generalized tonic-clonic seizures with generalized spike-wave complexes (Metrakos and Metrakos, 1961) have been reported. Methods included hyperventilation and photic stimulation as activation methods; sleep studies have been reported only by Bray and Wiser (1964, 1965) and Heijbel et al. (1975) in siblings of children with rolandic epilepsy. The EEG findings in relatives of patients with symptomatic absence seizures have not been reported. Such studies are of interest because whether genetics also play a role in this seizure type and whether and to what degree it is different from idiopathic absence seizures is unknown. PATIENTS AND SIBLINGS The 80 siblings of 38 patients with absence seizures were examined: 50 siblings of 22 patients with idiopathic and 30 siblings of 16 patients with symptomatic absence seizures. At the time of study, 39 siblings (48.75%) were ages 13-18 years, 24 (30%) were ages 7-12 years, 4 (5.0%) were 18 years old. Neurologic deficits (p < O.l), retarded infantile development (p < 0.05), mental retardation (p < 0.01), and behavior disturbances (p < 0.01) were, as expected, far more common in patients with symptomatic absence seizures (Fig. 1). Slightly abnormal or borderline findings were noted in the patients with idiopathic absence seizures; the more serious
785
abnormalities were observed in the symptomatic absence seizures. In both types, the percentage of males was higher than that of females (p > 0.1). Patients with idiopathic absence had a family history of epilepsy more often than did patients with symptomatic absence (Fig. 1) (p > 0.1). Among patients with idiopathic absence, 2 patients each had two and 1 had three epileptic relatives. The type of seizures of the relatives could not be ascertained exactly (Table 1). Patients with idiopathic absence far more often had a single seizure type (p < 0.05), whereas patients with symptomatic absence more often also had generalized tonic-clonic seizures (p > 0.1); a combination of three seizure types was observed exclusively in patients with symptomatic absence (p < 0.05) (Fig. 2). The first seizure in patients with idiopathic absence was most frequently observed between age 6 and 10 years; in patients with symptomaticabsence, it occurred between age 1 and 5 years (Fig. 3). Five of 38 patients were photosensitive. Photosensitivity alone was never observed, epileptic discharges were always recorded in the waking or sleep EEG. The waking and sleep EEGs of the siblings were recorded in our sleep laboratory, which has three soundproof rooms that can be darkened. The EEG recorders were located outside the rooms, but the patients could be observed through a window. A waking EEG was recorded immediately before each sleep EEG; sleep was induced with 1 mgkg body weight protactyl (promazine-hydrochloride) given as syrup. The average recording time was 20 min
= idiopathic
62.5
46.7 77.5
3
FIG. 1. Clinical findings in patients with idiopathic and symptomatic absence seizures: path., pathologic; neurol., neurologic; ret. inf. develop., retarded childhood development; fam., family; epilep., epilepsy.
~yt.inf. bduwior dovolop. d i e findings msrrtal farm hisbry ratardatiarr withrpilrp.
path. -1.
Epilepsia, Vd.31, No. 6, 1990
R . DEGEN ET AL.
786
TABLE 1. Occurrence of epileptic seizures in relatives of patients with seizures Siblings
Parents
Grandparents
Uncles, aunts
Cousins
Others
Total
IdioDathic
4 1
1 1
Total
5
-
-
2 1 3
6 1 7
13 4 17
Type of
seizure
S~tdptomatiC
2
sence had more epileptic activity (Fig. 6) (waking only p < 0.1 ;waking and sleep p < 0.1;sleep only p > 0.05). Three siblings (3.8%) had epileptic seizures, and all were siblings of patients with idiopathic absence. All had idiopathic absence; in one, a febrile seizure was observed at an earlier age, and in one patient absence status was observed. One sibling attended a school for learning-disabled children. In all three siblings, generalized bilateral synchronous 3-4 Hz spike wave discharges were noted in waking and sleep (Table 3). By counting single discharges of epileptic activity without considering photostimulation, we observed one epileptic discharge every 108.6 s on the average without striking differences between siblings of patients with idiopathic (99.7 s) or symptomatic absence (119.3 s). Eighteen siblings (22.5%) had photosensitivity (Fig. 7). Photosensitivity alone was observed three times. Epileptic activity was observed in sleep in nine patients and in waking and sleep in six. Twelve (24%) were siblings of patients with idiopathic absence, and six were siblings (20%) of patients with symptomatic absence (p > 0.1). Of the 18 photosensitive siblings, only two were siblings of patients
for waking; and 40 min for sleep EEG. Bipolar montages were used (time constant, 0.3; low-pass fdters, 70 Hz;paper speed 30 mmls). Tracings were visually evaluated with the sleep stages classified according to the method of Loomis et al. (1937). The chi-square and Fisher’s test were used for statistical calculations. RESULTS Epileptic activity was activated in 50 siblings (62.5%) (p < 0.01); 7 in waking only (8.7%), 23 in waking and sleep (28.8%), and 20 (25%) in sleep only (waking-sleep only: p < 0.05). Generalized, partly abortive, irregular, sometimes slow spikewave, or sharp slow-wave complexes were recorded (Fig. 4); a l a t e d emphasis was observed twice (Fig. 5 ) , true foci were never found. If siblings of patients with idiopathic and symptomatic absence seizures were considered separately, epileptic activity was observed in 36 (72%) siblings of idiopathic patients and in only 14 (46.7%) (p < 0.05) siblings of symptomatic patients (Table 2). When waking and sleep EEGs were considered separately, siblings of patients with idiopathic ab-
x FtQ. 2. Combination of idiopathic and symptomatic absences with other seizure types: comb., combination; ton-clon., tonic-clonic; seiz.. seizure.
58
-a
only
Epikpsia. Vol. 31. No. 6,1990
c0mb.wit.h toh-clon,
comb. of 3 a d z . typos
WAKING AND SLEEP EEG IN SIBLINGS IN ABSENCE SEIZURES
787
= idiopathic = symptomatic
FIG. 3. Age at first seizure of patients with idiopathic and symptomatic absences.
43.8
05
6-18
>iey-
who were also photosensitive. OII the other hand, photosensitivity was observed in the siblings of only two of the five photosensitive patients. Examination of the photosensitive patients according to sex and sex of the patients showed some differences, but they were not significant (p > 0.05). Without striking differences (p > 0.1) between siblings of patients with idiopathic or symptomatic absence, most epileptic activity was recorded in sleep stages C and D and least was recorded in stages A and B (Fig. 8 sleep stages A + B - C + D; p < 0.1). Epileptic activity was activated most frequently between the ages of 7 and 14 years (25 of 34 = 73.5%), and less frequently between the ages of 15
and 20 years (22 of 33 = 66.7%), and in patients aged 13 years (2 of 7 = 28.6%) (p > 0.1). In the group 14 years): p > 0.11. When male and female siblings were compared, the activation rates were higher in males (p > 0.05)
FIG. 4. A boy 9 years 8 months of age, had generalized irregular 3-4442 spike-wave dis-
&iksia. Vd. 31, No. 6, 1990
I
U 0'9&
x
WAKING AND SLEEP EEG IN SIBLINGS IN ABSENCE SEIZURES TABLE 2. Stage of epileptic activity in siblings of patients with various seizure types Waking or waking and sleep (%) Primarily generalized tonicclonic seizures Absences Idiopathic Symptomatic Rolandic epilepsy Lennox-Gastaut syndrome
22 37.5 46 23.4 20.3
20 25 26 23.3 17.4
42 62.5 72 46.7 37.7
21.3
12.8
34.1
pathic absence. Sleep recordings were reported by Bray and Wiser (1964, 1965) and Heijbel et al. (1975) in siblings of patients with rolandic epilepsy. The activation rate of the waking EEG was 37.5%, which can be compared with the data of Metrakos and Metrakos (l%l), who reported epileptic activity in 36.8% of patients’ siblings. Our data and theirs differ because they recorded EEGs of siblings of patients with generalized regular and irregular spike-wave discharges who had primary absence, primary tonic-clonic seizures, or both seizure types. Therefore, we compared their results with the activation rates of siblings of our patients with idiopathic absence; the comparison is not exact because we considered only idiopathic absence whereas they also included patients with primary tonic-clonic seizures. In an earlier investigation, we recorded EEGs of siblings of patients with primary generalized tonic-clonic seizures; epileptic discharges were activated in the waking and sleep EEG in 42% and in the waking EEG alone in 22% (Degen and Degen, 1983a). Doose et al. (1973) (7.6%) and Matthes and Weber (1968) (9.2%) reported low activation rates of generalized epileptic activity in siblings of patients with idiopathic absence. Our findings may differ for the following reasons. First, we administered 1 mg/ kg promazine-hydrochloride for sleep induction,
789
waited 45 min to 1 h for maximum effect, and then recorded a waking EEG with the subject in a sitting position, followed by the sleep EEG. Signs of drowsiness that led to activation of epileptic activity were noted clinically and on the waking EEG in many patients. Even if no signs of drowsiness were present, microfluctuationsof vigilance probably occurred to activate epileptic discharges. Second, tension, which often prevents activation of epileptic discharges, disappeared for the most part in our patients because of the sedative effect of promazinehydrochloride. Third, inclusion of siblings of photosensitive patients may have resulted in a higher activation rate, but because no epileptic discharges were recorded in three siblings of the five photosensitive patients, this factor probably does not play a role. Fourth, the assumption that promazine hydrochloride, administered for sleep induction, could have had an activating effect as reported in the literature was excluded by the results of our earlier study (Degen and Degen, 1984). The difference between our findings and those of other investigators may also have been due to a difference in patients or siblings (age, sex). The highest activation rate occurred in siblings between ages 7 and 14 years (73,5%). Metrakos and Metrakos (1961) found a peak in patients from age 4 years 3 months to 16 years 6 months. Matthes and Weber (1968) reported that 65% of siblings with spike-wave complexes were
Some Genetic Aspects of Idiopathic and Symptomatic Absence Seizures: Waking and Sleep EEGs in Siblings R. Degen, H.-E. Degen, and Ch. Roth Epilepsy Centre, Bethel, F.R.G.
Sunmmry: Epileptic activity was recorded in the waking and sleep EEG of 62.5% of 80 siblings of 38 patients with absence seizures. Epileptic discharges were noted in waking only in 8.7%, in waking as well as sleep in 28.8%, and in sleep only in 25%. Generalized, partly irregular, and slow spike-wave complexes were found, twice with lateral emphasis. Spike-wave complexes were recorded in W o of 50 siblings of patients with idiopathic absence and in 46.7% of 30 siblings of patients with symptomatic absence. One epileptic discharge was observed every 108.6 s on the average, without striking differences between siblings of patients with idiopathic (99.7 s) and symptomatic absence (1 19.3 s). Without any differences between siblings of children with idiopathic and symptomatic absence, the most epileptic discharges were activated in sleep stages C and D, followed by stages A and B. The highest activation rate was observed in the 7-14year-old group (73.5%) and to a somewhat lesser degree in the group between 15 and 20 years of age (66.7%); fewer epileptic discharges were recorded in
younger (25%) and older patients (28.6%). The higher activation rates in the male sex were significant only in siblings of patients with idiopathic absence. Although only five patients (13.2%) were photosensitive, a photosensitivity was found in 24% of siblings of children with idiopathic absence and in 20% of siblings of patients with symptomatic absence. Three siblings of patients with idiopathic absence also had absence seizures; in one of them a febrile seizure occurred at an earlier age. All of them showed generalized spike wave discharges in waking as well as sleep. Occipital theta delta activity with generalization was observed more frequently in siblings of patients with idiopathic absence (82.2%) than in those of patients with symptomatic absence (63.6%). Our waking and sleep EEG recordings prove that concerning etiology-genetic factors play a striking role in idiopathic absence, but are also of considerable significance in the symptomatic types. Key Words Epilepsy-Absence seizures-Electroencephalography-Genetics.
Absence seizures characterize the idiopathic generalized epilepsies included in childhood absence epilepsy (pyknolepsy) or in juvenile absence epilepsy (Commission, 1985). In idiopathic epilepsies, brain damage is neither present nor expected and patients show no neurologic deficits, mental retardation, or behavior disturbances; frequently, however, there is a positive family history. Both simple and complex absence seizures may be observed. Symptomatic absence seizures are classified as cryptogenetic or symptomatic epilepsies within the generalized epilepsies or can belong to the symptomatic types of localized epilepsies. By definition, symptomatic absence seizures are predominantly the consequence of known or supposed brain damage. Patients with those absence seizures often
have neurologic deficits, mental retardation, and behavior disturbances. Family history is less frequently positive for seizures. Symptomatic absence seizures are best known as one of the three seizure types of the Lennox-Gastaut syndrome, but are also found with generalized tonic-clonic seizures or complex partial seizures. The clinical diagnosis is often more difficult in the symptomatic than in the idiopathic types because the seizures often start and finish less abruptly and consciousness is less affected. Eyelid and perioral myoclonias and atonic facial and neck components (with dropping of the head and the trunk) and salivation are occasionally observed. Often asynchronous, irregular and slow, partly abortive 2-2.5-Hz spike-wave complexes and more rarely 3 4 H z spike-wave complexes are recorded in the EEG. Background EEG slowing is often present, sometimes with foci. The EEG findings of healthy siblings of patients with idiopathic absence seizures (Matthes and We-
Received June 1988; revision accepted November 1990. Address correspondence and reprint requests to Professor Dr. R. Degen at Epilepsy Centre Bethel, 4800 Bielefeld 13, F.R.G.
784
WAKING AND SLEEP EEG IN SIBLINGS IN ABSENCE SEIZURES
ber, 1968; Doose et al., 1973) and idiopathic absence as well as primary generalized tonic-clonic seizures with generalized spike-wave complexes (Metrakos and Metrakos, 1961) have been reported. Methods included hyperventilation and photic stimulation as activation methods; sleep studies have been reported only by Bray and Wiser (1964, 1965) and Heijbel et al. (1975) in siblings of children with rolandic epilepsy. The EEG findings in relatives of patients with symptomatic absence seizures have not been reported. Such studies are of interest because whether genetics also play a role in this seizure type and whether and to what degree it is different from idiopathic absence seizures is unknown. PATIENTS AND SIBLINGS The 80 siblings of 38 patients with absence seizures were examined: 50 siblings of 22 patients with idiopathic and 30 siblings of 16 patients with symptomatic absence seizures. At the time of study, 39 siblings (48.75%) were ages 13-18 years, 24 (30%) were ages 7-12 years, 4 (5.0%) were 18 years old. Neurologic deficits (p < O.l), retarded infantile development (p < 0.05), mental retardation (p < 0.01), and behavior disturbances (p < 0.01) were, as expected, far more common in patients with symptomatic absence seizures (Fig. 1). Slightly abnormal or borderline findings were noted in the patients with idiopathic absence seizures; the more serious
785
abnormalities were observed in the symptomatic absence seizures. In both types, the percentage of males was higher than that of females (p > 0.1). Patients with idiopathic absence had a family history of epilepsy more often than did patients with symptomatic absence (Fig. 1) (p > 0.1). Among patients with idiopathic absence, 2 patients each had two and 1 had three epileptic relatives. The type of seizures of the relatives could not be ascertained exactly (Table 1). Patients with idiopathic absence far more often had a single seizure type (p < 0.05), whereas patients with symptomatic absence more often also had generalized tonic-clonic seizures (p > 0.1); a combination of three seizure types was observed exclusively in patients with symptomatic absence (p < 0.05) (Fig. 2). The first seizure in patients with idiopathic absence was most frequently observed between age 6 and 10 years; in patients with symptomaticabsence, it occurred between age 1 and 5 years (Fig. 3). Five of 38 patients were photosensitive. Photosensitivity alone was never observed, epileptic discharges were always recorded in the waking or sleep EEG. The waking and sleep EEGs of the siblings were recorded in our sleep laboratory, which has three soundproof rooms that can be darkened. The EEG recorders were located outside the rooms, but the patients could be observed through a window. A waking EEG was recorded immediately before each sleep EEG; sleep was induced with 1 mgkg body weight protactyl (promazine-hydrochloride) given as syrup. The average recording time was 20 min
= idiopathic
62.5
46.7 77.5
3
FIG. 1. Clinical findings in patients with idiopathic and symptomatic absence seizures: path., pathologic; neurol., neurologic; ret. inf. develop., retarded childhood development; fam., family; epilep., epilepsy.
~yt.inf. bduwior dovolop. d i e findings msrrtal farm hisbry ratardatiarr withrpilrp.
path. -1.
Epilepsia, Vd.31, No. 6, 1990
R . DEGEN ET AL.
786
TABLE 1. Occurrence of epileptic seizures in relatives of patients with seizures Siblings
Parents
Grandparents
Uncles, aunts
Cousins
Others
Total
IdioDathic
4 1
1 1
Total
5
-
-
2 1 3
6 1 7
13 4 17
Type of
seizure
S~tdptomatiC
2
sence had more epileptic activity (Fig. 6) (waking only p < 0.1 ;waking and sleep p < 0.1;sleep only p > 0.05). Three siblings (3.8%) had epileptic seizures, and all were siblings of patients with idiopathic absence. All had idiopathic absence; in one, a febrile seizure was observed at an earlier age, and in one patient absence status was observed. One sibling attended a school for learning-disabled children. In all three siblings, generalized bilateral synchronous 3-4 Hz spike wave discharges were noted in waking and sleep (Table 3). By counting single discharges of epileptic activity without considering photostimulation, we observed one epileptic discharge every 108.6 s on the average without striking differences between siblings of patients with idiopathic (99.7 s) or symptomatic absence (119.3 s). Eighteen siblings (22.5%) had photosensitivity (Fig. 7). Photosensitivity alone was observed three times. Epileptic activity was observed in sleep in nine patients and in waking and sleep in six. Twelve (24%) were siblings of patients with idiopathic absence, and six were siblings (20%) of patients with symptomatic absence (p > 0.1). Of the 18 photosensitive siblings, only two were siblings of patients
for waking; and 40 min for sleep EEG. Bipolar montages were used (time constant, 0.3; low-pass fdters, 70 Hz;paper speed 30 mmls). Tracings were visually evaluated with the sleep stages classified according to the method of Loomis et al. (1937). The chi-square and Fisher’s test were used for statistical calculations. RESULTS Epileptic activity was activated in 50 siblings (62.5%) (p < 0.01); 7 in waking only (8.7%), 23 in waking and sleep (28.8%), and 20 (25%) in sleep only (waking-sleep only: p < 0.05). Generalized, partly abortive, irregular, sometimes slow spikewave, or sharp slow-wave complexes were recorded (Fig. 4); a l a t e d emphasis was observed twice (Fig. 5 ) , true foci were never found. If siblings of patients with idiopathic and symptomatic absence seizures were considered separately, epileptic activity was observed in 36 (72%) siblings of idiopathic patients and in only 14 (46.7%) (p < 0.05) siblings of symptomatic patients (Table 2). When waking and sleep EEGs were considered separately, siblings of patients with idiopathic ab-
x FtQ. 2. Combination of idiopathic and symptomatic absences with other seizure types: comb., combination; ton-clon., tonic-clonic; seiz.. seizure.
58
-a
only
Epikpsia. Vol. 31. No. 6,1990
c0mb.wit.h toh-clon,
comb. of 3 a d z . typos
WAKING AND SLEEP EEG IN SIBLINGS IN ABSENCE SEIZURES
787
= idiopathic = symptomatic
FIG. 3. Age at first seizure of patients with idiopathic and symptomatic absences.
43.8
05
6-18
>iey-
who were also photosensitive. OII the other hand, photosensitivity was observed in the siblings of only two of the five photosensitive patients. Examination of the photosensitive patients according to sex and sex of the patients showed some differences, but they were not significant (p > 0.05). Without striking differences (p > 0.1) between siblings of patients with idiopathic or symptomatic absence, most epileptic activity was recorded in sleep stages C and D and least was recorded in stages A and B (Fig. 8 sleep stages A + B - C + D; p < 0.1). Epileptic activity was activated most frequently between the ages of 7 and 14 years (25 of 34 = 73.5%), and less frequently between the ages of 15
and 20 years (22 of 33 = 66.7%), and in patients aged 13 years (2 of 7 = 28.6%) (p > 0.1). In the group 14 years): p > 0.11. When male and female siblings were compared, the activation rates were higher in males (p > 0.05)
FIG. 4. A boy 9 years 8 months of age, had generalized irregular 3-4442 spike-wave dis-
&iksia. Vd. 31, No. 6, 1990
I
U 0'9&
x
WAKING AND SLEEP EEG IN SIBLINGS IN ABSENCE SEIZURES TABLE 2. Stage of epileptic activity in siblings of patients with various seizure types Waking or waking and sleep (%) Primarily generalized tonicclonic seizures Absences Idiopathic Symptomatic Rolandic epilepsy Lennox-Gastaut syndrome
22 37.5 46 23.4 20.3
20 25 26 23.3 17.4
42 62.5 72 46.7 37.7
21.3
12.8
34.1
pathic absence. Sleep recordings were reported by Bray and Wiser (1964, 1965) and Heijbel et al. (1975) in siblings of patients with rolandic epilepsy. The activation rate of the waking EEG was 37.5%, which can be compared with the data of Metrakos and Metrakos (l%l), who reported epileptic activity in 36.8% of patients’ siblings. Our data and theirs differ because they recorded EEGs of siblings of patients with generalized regular and irregular spike-wave discharges who had primary absence, primary tonic-clonic seizures, or both seizure types. Therefore, we compared their results with the activation rates of siblings of our patients with idiopathic absence; the comparison is not exact because we considered only idiopathic absence whereas they also included patients with primary tonic-clonic seizures. In an earlier investigation, we recorded EEGs of siblings of patients with primary generalized tonic-clonic seizures; epileptic discharges were activated in the waking and sleep EEG in 42% and in the waking EEG alone in 22% (Degen and Degen, 1983a). Doose et al. (1973) (7.6%) and Matthes and Weber (1968) (9.2%) reported low activation rates of generalized epileptic activity in siblings of patients with idiopathic absence. Our findings may differ for the following reasons. First, we administered 1 mg/ kg promazine-hydrochloride for sleep induction,
789
waited 45 min to 1 h for maximum effect, and then recorded a waking EEG with the subject in a sitting position, followed by the sleep EEG. Signs of drowsiness that led to activation of epileptic activity were noted clinically and on the waking EEG in many patients. Even if no signs of drowsiness were present, microfluctuationsof vigilance probably occurred to activate epileptic discharges. Second, tension, which often prevents activation of epileptic discharges, disappeared for the most part in our patients because of the sedative effect of promazinehydrochloride. Third, inclusion of siblings of photosensitive patients may have resulted in a higher activation rate, but because no epileptic discharges were recorded in three siblings of the five photosensitive patients, this factor probably does not play a role. Fourth, the assumption that promazine hydrochloride, administered for sleep induction, could have had an activating effect as reported in the literature was excluded by the results of our earlier study (Degen and Degen, 1984). The difference between our findings and those of other investigators may also have been due to a difference in patients or siblings (age, sex). The highest activation rate occurred in siblings between ages 7 and 14 years (73,5%). Metrakos and Metrakos (1961) found a peak in patients from age 4 years 3 months to 16 years 6 months. Matthes and Weber (1968) reported that 65% of siblings with spike-wave complexes were
