[Two siblings with eyelid myoclonia with absences].

We report two siblings with eyelid myoclonia with absences. Patient 1, a 7-year-old boy, visited us because of eyelid blinking resembling a tic. He had experienced the movements since 2 years old. The diagnosis of a simple motor tic was initially made, however, the episodes worsened gradually. Patient 2, a younger brother of patient 1, was a 5-year-old boy. His eyelid blinking also began at age of 2 years. Additionally, the mother's aunt and her cousin had a history of grand mal on awakening, and the patient's cousin has febrile seizures. Their clinical features were as follows; (i) eyelid myoclonia, described as rapid, rhythmic eyelid fluttering with upward jerking of the eyes and head, lasting for 1-2 seconds; (ii) it occurred frequently each day; (iii) when it lasted for more than 2-3 seconds, it was associated with absences; (iv) both hyperventilation and photic stimulation on 18 f/c induced clinical seizures; and (v) ictal EEG revealed 3-4 c/s generalized irregular spike-waves with a duration of 1-3 seconds. Based on these characteristics, a diagnosis of eyelid myoclonia with absences was made. The present cases are the first sibling cases reported in Japan and, according to their family history, a genetic predisposition should be considered.

[Relapse of seizure after withdrawal of antiepileptic drug treatment in childhood epilepsy: age-dependent factors].

In 556 epileptic children, clinical and encephalographic factors concerning the discontinuation of antiepileptic drugs (AED) were studied, with emphasis on age-related factors. Seizures relapsed in 80 patients (14.4%), the incidence being high in idiopathic generalized epilepsy with onsets in adolescence or adulthood (juvenile absence epilepsy, juvenile myoclonic epilepsy, grand mal on awakening), symptomatic partial epilepsy and symptomatic generalized epilepsy. The age distribution at the relapse showed two peaks; 9 to 11 and 17 to 19 years. The first peak represented patients with school-age onset epilepsies, and the second those with the adolescent or adult onset epilepsies. The age at discontinuation of AED depended on each epileptic syndrome, and the relapse rate was significantly higher when the AED was discontinued after adolescence. In 56 patients, seizure relapsed during the withdrawal phase or less than 1 year after the discontinuation. The type of the relapsing seizure was the same as the previous ones. On the other hand, in 16 out of 24 patients whose relapse occurred 1 year or more after the discontinuation, the seizure type was different from the previous ones. These results suggest the relevance of age-dependent factors to the discontinuation of therapy.

[Partial seizures during the course in patients with absence epilepsy].

We studied the incidence and clinicoelectrographic features of partial seizures in 46 patients with absence epilepsy. Ten patients (21.7%) showed obvious partial seizure symptoms during the course. Five patients had absence attacks with partial seizure symptoms, the ictal EEGs being a generalized 3 Hz spike-wave burst complex preceded by focal discharges. These absence attacks may be partial seizures with secondary bilateral synchronization, which originated from the frontal lobe. Three patients initially had partial seizures related to the frontal lobe, followed by absence attacks 8 months to 2.6 years after the start of CBZ therapy. The appearance of absence attacks may have been triggered by CBZ administration. Two patients had partial seizures at the relapse of epilepsy after the discontinuation of AED therapy for childhood absence epilepsy. This change of seizure types may be associated with the CNS maturation, or with localized cortical hyperexcitability subsequent to the foregoing generalized seizures. The prognosis of absence attacks in the all patients were excellent, and comparable to that of typical absence attacks. Our results suggest that localized cortical areas, especially the frontal lobe, are commonly involved in absence epilepsy. More detailed clinical observation is necessary to understand the pathogenesis of absence epilepsy.

Rotavirus encephalitis mimicking afebrile benign convulsions in infants.

A 2-year-old-boy had rotavirus gastroenteritis and demonstrated afebrile partial seizures with secondary generalization. The presence of rotavirus genome and anti-rotavirus IgG was detected in the cerebrospinal fluid. The genotype of VP4 was P8 and that of VP7 was G4. The imaging analysis by computed tomography and single photon emission computed tomography implied encephalitis. The seizures were well controlled by standard antiepileptic therapy, and the child experienced normal development with neither physical nor neurologic sequelae, which appeared to mimic benign infantile partial epilepsy.

Antithrombotic effects of 3-([1:1',2':1"]-3'-terphenyl)propanol in animals.

3-([1:1',2':1"]-3'-Terphenyl)propanol (CAS 186835-06-3, F050) and acetylsalicylic acid (ASA) inhibited platelet aggregation induced by CaCl2, arachidonic acid, collagen, adenosine diphosphate (ADP) and thrombin in guinea pigs, rabbits and rats in vitro. However, F050 had a wider spectrum of actions than ASA. Orally administered F050 inhibited platelet aggregation ex vivo. F050 significantly reduced the thrombus formation in the extracorporeal circulation thrombosis model in guinea pigs. It inhibited erythrocyte hemolysis induced by hypotonic NaCl, while ASA did not. F050, but not ASA, inhibited increases in platelet [CA2+]i caused by thrombin in guinea pigs. F050 is a parent compound that will facilitate the development of an orally active drug for the treatment of thrombotic diseases.

Epileptic seizures and event-related potentials (P300) in childhood partial epilepsies.

To clarify the relationship between cognitive function and clinical seizures, auditory event-related potentials (P300) were examined in 72 patients (185 trials) with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). In this study, to rule out the effects of epileptogenesis and other factors, we only examined patients with partial epilepsies undergoing carbamazepine (CBZ) monotherapy at doses of less than 16 mg/kg/day. The results were: 1) the mean age-corrected P300 latency in the patients with SPE (394 +/- 38 msec) was significantly prolonged compared with that in the patients with IPE (378 +/- 28). 2) The prolongation of the P300 latency had no relationship to the seizure frequency, seizure type or seizure duration. 3) In both epileptic groups, there was no significant correlation between the seizure-free period and the age-corrected P300 latency. Our results suggest that the effect of clinical seizures on the cognitive function may be relatively little, and that the cognitive dysfunction in partial epilepsies may mainly originate from epileptogenesis or other factors.

Event-related potentials (P300) and EEG activity in childhood partial epilepsy.

To clarify the relationship between the cognitive function and EEG activity, auditory event-related potentials (P300) were examined in 72 patients with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). For this study, patients undergoing carbamazepine monotherapy with a dose of less than 16 mg/kg/day were selected to rule out the effects of anti-epileptic drugs. The results were as follows: (1) The P300 latency tended to be prolonged in association with the EEG slowing in both epileptic groups. (2) There was no clear relationship between the frequency of paroxysmal discharges and the P300 latency. (3) The P300 latency was slightly prolonged in the patients with temporal foci compared with that in ones with extra-temporal foci. (4) There was no significant relationship between the generalization of focal paroxysmal discharges and the P300 latency. These results suggested that the influence of EEG abnormalities (particularly paroxysmal discharges) on the P300 latency is relatively little, and the cognitive dysfunction in partial epilepsies mainly originates from other factors such as the epileptogenic lesion itself.

Withdrawal of antiepileptic drug treatment in childhood epilepsy: factors related to age.

The clinical and electroencephalographic changes with age were evaluated in 304 patients with childhood epilepsies, whose antiepileptic treatment had been discontinued after a seizure free period of more than three years. The withdrawal rate differed significantly between epileptic syndromes, being higher in idiopathic epilepsy and lower in symptomatic epilepsy. The age at withdrawal was characteristic for each epileptic syndrome, and generally showed two peaks: at preadolescence and early school age. Forty one (13.5%) of the 304 patients experienced relapses. The relapse rate differed between epileptic syndromes. Relapses occurred at a unique age in each epileptic syndrome, and were frequent in preadolescence and early adulthood. Electroencephalography that still showed paroxysmal discharges at withdrawal did not necessarily predict the occurrence of a relapse, but the changes in background activity with age, which may indicate maturation of the CNS, were significantly different between the patients with and those without relapses. The results suggest that age related to each epileptic syndrome should be considered when deciding on withdrawal of antiepileptic drugs.

Effects of antiepileptic drugs on EEG background activity in children with epilepsy: initial phase of therapy.

The effects of antiepileptic drugs (AED) on EEG background activity were evaluated in 37 newly treated children with epilepsy, compared with 46 age-matched healthy controls. Before AED therapy, the children with epilepsy, both partial (treated with carbamazepine, CBZ group) and generalized seizures (treated with valproic acid, VPA group), already exhibited significant slowing of EEG with increased delta and decreased alpha power. Following 3 to 6 months of AED therapy, this EEG slowing was enhanced in the CBZ group and reduced in the VPA group. Following 1 year of AED therapy, an increase in frequency was recognized in the CBZ group. These results suggest that 1) most children with epilepsy already exhibit slowing of the EEG at the onset of seizures, which may reflect CNS developmental deficit, 2) the short-term effects on EEG are different between CBZ and VPA, and 3) EEG development with age continues under continuous AED administration. The EEG background activity in children with epilepsy is affected by many factors, which include the underlying CNS dysfunction of the epilepsy itself and also AED therapy (type of AEDs, duration of therapy, etc).

Changes of P300 latency with age in childhood epilepsy.

Auditory event-related potentials (P300 latency; odd-ball paradigm) were examined in 129 patients with childhood epilepsies and 53 controls. The P300 latency in the patients with epilepsies (373 +/- 39.4 ms) was significantly longer than in controls (356 +/- 38.4), and the prolongation was greatest in the patients with symptomatic partial epilepsies (390 +/- 40.5), mild in those with idiopathic generalized epilepsies (370 +/- 24.3), and minimum in those with idiopathic partial epilepsies (363 +/- 28.9). Abnormal P300 latency occurred at all ages during childhood in patients with symptomatic partial epilepsies, and at older ages in patients with idiopathic generalized epilepsies. The shortening of latency with age was relatively small in patients with epilepsies compared with controls. These results suggest that the prolongation of P300 latency (i.e., existence of cognitive disturbance) displays characteristic changes with age in each epileptic syndrome.

Flunitrazepam for sleep disturbance in children with intractable epilepsy.

Add-on therapy with flunitrazepam (FNZ) was performed in 5 children with marked sleep disturbance and intractable seizures. Correction of the sleep disturbance was attained immediately after the start of FNZ administration in all patients. Furthermore, a significant decrease in the seizure frequency (3 patients) and improved quality of life (4 patients) were concomitantly observed. There was no adverse effect or interaction with conventional AEDs on long-term use.

Changes in EEG foci with age in childhood partial epilepsies.

The age changes of epileptic foci on EEG were evaluated in 208 patients with childhood partial epilepsies, who were followed for more than 3 years. 1) The incidence of EEG foci in each region apparently differed with age. Frontal and central foci were frequent before school age and after adolescence. Temporal foci showed a peak around adolescence, and occipital foci a peak from 3 to 7 years, respectively. Parietal foci were rare at all ages. 2) The migration of EEG foci was recognized 171 times in 81 of the 208 patients (38.9%) during the clinical course. The migration was frequently seen at early school age and preadolescence, and the direction of migration was predominantly anterior to posterior at early school age, and posterior to anterior at preadolescence. These results suggest that EEG foci show characteristic changes with age during the clinical course, which may be related to maturation of the central nervous system.

Auditory event-related potentials in benign childhood epilepsy with centrotemporal spike: the effects of carbamazepine.

To clarify the relationship between cognitive function and CBZ therapy, auditory event-related potentials (P300) were examined in 23 patients with Benign Childhood Epilepsy with Centrotemporal Spike (BCECT) compared with 54 normal controls. The results were 1) the mean P300 latency in BCECT (368 +/- 29 msec) was significantly prolonged compared with that in normal controls (349 +/- 30 msec), but most individual patients showed normal values. 2) The prolongation of P300 latency was greatest during the course of therapy. 3) On repeated examination of P300, P300 latency was found to gradually become shorter with age in spite of continuous CBZ therapy. At initiation of CBZ therapy, the P300 latency became shorter; on the other hand, P300 latency became shorter with the discontinuation of CBZ. 4) The age-corrected P300 latency showed a significant positive correlation with the serum concentration of CBZ. Our results suggest that CBZ therapy has both an undesirable effect (chronic impairment) and a desirable effect (improvement of underlying dysfunction caused by epileptogenesis) on cognitive function.

[The relationship between P300 latencies, and WISC-R and Wechsler memory scale results in epileptic children].

Auditory event-related potentials (ERPs) were recorded in 35 epileptic children of 9 to 13 years of age, and compared with conventional test batteries of cognitive functions. ERPs were elicited with the auditory oddball paradigm. Corrected P300 latencies showed an inverse correlation with the total score (IQ) of WISC-R and that of the Wechsler memory scale (WMS). A strong inverse correlation was also observed with specific items of these test batteries, as follows; "comprehension", "picture completion" and "coding" in WISC-R, and "associated learning", "digit span", "visual reproduction", "mental control", "orientation" and "information" in WMS. These findings suggested that the prolongation of P300 latencies in epileptic children are related with the impairment of cognitive functions. The P300 latency is correlated with a characteristic kind of cognitive function; "simple recognition", "short term memory" and "easy judgement".

[The EEG background activity in children with epilepsy--effects of the removal of anticonvulsants on the EEG].

The development of the EEG background activity is generally impaired in children with epilepsy. Antiepileptic drugs (AEDs) are one of the important factor which influence the EEG background activity. We studied the effect of AEDs on the EEG. Subjects were 46 normal children and 48 children with epilepsy aged 5 to 15, who had not any organic brain damage and showed normal psychomotor development. Forty children with epilepsy (CBZ; 30 cases, VPA; 10 cases) had been on monopharmacy and 8 cases on polypharmacy. All of them have outgrown their epilepsy. The serial EEGs were recorded during withdrawal and after discontinuation of AED in each patient. These records were evaluated using computerized power spectral analysis. CBZ reduction associated with a decrease in delta and theta powers and an increase in alpha-2 power, which were also observed at VPA reduction in concomitant AEDs (VPA+CBZ). No parameter changed by VPA reduction in monopharmacy. The slowing of the EEG background activity was noticed even after discontinuation of CBZ. It required more time after discontinuation of CBZ in younger children than older before the EEG background activity became normal controls. These findings suggested that CBZ had a adverse effect, which was more remarkable in younger children than older children, on the development of EEG background activity and that the effect of CBZ on EEG was different from that of VPA.

[Development of the background activity of EEG in children with epilepsy; comparison with normal children].

We investigated the development of the background activity of EEGs in 150 children with epilepsy by means of computerized power spectral analysis, using Fourier transformation by O1 Twenty-seven cases with idiopathic generalized epilepsy (IGE), 30 cases with idiopathic partial epilepsy (IPE), 60 cases with symptomatic partial epilepsy (SPE), 33 cases with cryptogenic partial epilepsy (CPE) and 48 normal children were studied. The records with paroxysmal activity at 01 were excluded in this study. In normal children, total, delta and theta powers showed a significant inverse correlation with age, but alpha-2 and beta-2 powers showed a significant positive correlation with age. In children with epilepsy, there were significant increases of delta and theta powers and a decrease of alpha-2 power compared with normal children. The development of the EEGs was different among the patients with various types of the epileptic syndrome. It was suggested that age, prognosis and anticonvulsants were important factors which influence the EEGs background activity.

[Factors affecting P300 latencies in epileptic children].

Auditory event-related potentials (ERPs) were recorded from 131 epileptic children of 4 to 20 years of age, and the related factors affecting P300 latencies were evaluated using multiple regression analysis. The examined factors were as follows: (1) age at P300 recording and duration of illness, (2) seizure types and epileptic syndromes, (3) anti-epileptic drugs (AEDs), (4) seizure prognosis, (5) organic brain dysfunctions, (6) x-ray CT and (7) EEG background activity and frequency of paroxysms. ERPs were elicited with the oddball paradigm. Five factors of them had significant correlations with P300 latencies. 1) P300 latencies were gradually shortened with age. 2) P300 latencies were prolonged in the patients before and during AED medication compared with those during the period of off-therapy. 3) Symptomatic partial epilepsy showed obviously prolonged P300 latencies. 4) P300 latencies were shortened with increasing alpha 2 power of EEG. 5) P300 latencies became prolonged with the length of illness.