452
Selected Papers: Medical Therapy
Medical Therapy Intravenous Administration of Anticonvulsants under EEG Monitoring in ESES: Rapid Prediction of the Efficacy of Oral Administration of Drugs Kenji Sugai, M.D., Norio Sakuragawa M.D.* and Masataka Arima, M.D.*
Department of Pediatrics, National Nishi-Kofu Hospital, Kofu *National Center Hospital for Mental, Nervous and Muscular Disorders, NCNP, Kodaira
EEG tracing at 15, 30 and 45 minutes after IV, and 75% or more reduction of SW index was estimated as markedly effective, 50-74% reduction as effective and less than 50% reduction as ineffective. Then, AZA, 10-18 mg/kg, V.B6, 20 mg/kg, PHT, 3.9-5.0 mg/kg or, in case of IV of DZP, nitrazepam, 0.2-0.35 mg/kg, or clonazepam, 0.05-0.1 mg/kg or DZP, 0.25-0.3 mg/kg, were orally given to the patient for 1-12 weeks, and the efficacy was evaluated with the same criteria from a 30-minute or
Table 1: Efficacy of Anticonvulsants by IV and PO
Introduction Electrical status epilepticus during slow sleep (ESES) is a self-limited and agerelated condition, but it is intractable and long lasting ESES inevitably causes intellectual and behavioral impairrnenh2 Prompt and proper treatment is thus important, but efficacious therapy has not been e~tablished.~ We studied whether the efficacy of oral administration (PO) of antiepileptic drugs (AEDs) can be predicted or not by intravenous administration (IV) of the drugs under EEG monitoring. Subjects and Methods Six patients with ESES, aged 4 to 10, who had 90-9896 of a spike and wave index (SW index) during non-REM sleep on all-night polygraphic EEG recordings, were selected for this study. One to four AEDs of acetazolamide (AZA), 10-14 mg/ kg, vitamin B6 (V.B6), 11-25 mg/kg, phenytoin (PHT), 10-11 mg/kg, and diazepam (DZP), 0.26-0.3 mg/kg, were individually given intravenously to a patient under EEG monitoring at one-hour or more intervals when the EEG tracing returned nearly to a base line level. SW indices were calculated every 10 minutes of
Patients
AZA
PHT
V.B6
DZP
~
1
+/++’
2
-/-
-/X
3 4
-/x
- /X
-/+c
-/x
~~
+ +/N:+ C:+ + +/N:++
+b
++/++b
C:+/D:+ ++/D:+‘ +/D:+
-/-
+
5
+
+/N:+
-/-
6
C:-
’
+
Eficacy of IV of the drug/PO of the drug: +, markedly effective; +, effective; - , ineffective; x, not studied because of ineffectiveness by IV. b, ’: efficacy by combined administration. N, NZP; C, CZP; D. DZP.
Table 2: Correlation of Efficacies of IV and PO of “Anticonvulsants” PO
IV
++ + -
Subtotal
++
+
4
2 2
!
I
7
j
1
4
0
1
1
5
5
1
-
________________ 1-----!
Subtotal
3
4
5
15
‘p=0.077 when the table is classified into the four cells shown by broken lines (Fisher’s exact probability test). “Efficacy o f anticonvulsants: + + , markedly effective; , effective; - , ineffective.
+
The Japanese Journal of Psychiatry and Neurology, Vol. 46, No. 2, 1992
-
C z , ESM ( 4 0)
r" ,
2 .
RIC' , NREY
Fig. 1 : tion (IV) shown by spike and
~
.
L
,
-3
-
A*,
453
-__ -Czp, ESM
( 31
d 7
-
Case 1. Continuous spike-wave discharges reduced markedly by intravenous administraof antiepileptic drugs. The drugs were also effective by oral administration (PO) as routine EEG and all-night polygraphic EEG recording. Figures in parentheses indicate wave indices.
more sleep EEG tracing or an all-night polygraphic EEG recording. The correlation of the efficacy of IV of AED with that of PO of the drug was discussed. Results Sixteen IVs and 15 POs of AEDs were carried out, and AZA, V.B6 and DZP were effective but PHT was ineffective by both IV and PO (Table 1). Their efficacies were considerably correlated with each other, though not significantly by Fisher's exact probability test (Table 2, Fig. 1). The efficacies by IV were grossly inconsistent with those by PO in three cases. In two of them, IV of DZP was effective or markedly effective but PO of CZP was ineffective, and PO of NZP was effective or markedly effective. In the third case, AZA was ineffective by IV but effective by combined PO with DZP. With these AEDs,
continuous spike-wave discharges during sleep disappeared or significantly reduced in all cases, and clinical seizures ceased promptly except in one case. Though the SW index increased to 50-90% again in four cases and clinical seizures reappeared in two cases in 7-60 months of follow-up observation, relapses of ESES were well controlled by replacement with or addition of other AEDs, and intellectual or behavioral disturbances did not develop during this follow-up period. Discussion
The present method has not been reported, but IV of benzodiazepine during slow sleep arrested the continuous spikes and waves in ESES for one hour3, and a rapid prediction of the efficacy of PO of AEDs by IV of the drugs under EEG monitoring was suggested in other refractory epi-
454
Selected Papers: Medical Therapy
lepsies'. Though limited AEDs are available for IV, this study suggests that IV of AED under EEG monitoring can be a useful method to find efficacious AEDs rapidly in the treatment of ESES. References
1. Sugai, K., Sakuragawa, N. and Arima, M.: Rapid estimation of the efficacy of orally administered antiepileptic drugs by intravenous administration of the drugs under EEG monitoring. Brain Dev 12: 732, 1990. 2. Tassinari, C.A., Bureau, M., Dravet, C.,
Roger, 3. and Daniele-Natale, 0.: Electrical status epilepticus during sleep in children (ESES). In: Sterman, M.B., Shouse, M.N. and Passouant, P. (Eds.), Sleep and epilepsy. Academic Press, London, New York, pp 465-479, 1982. 3. Tassinari, C.A., Bureau, M., Dravet, C., Dalla Bernardina, B. and Roger, J.: Epilepsy with continuous spikes and waves during slow sleep. In: Roger, J., Dravet, C., Bureau, M., Dreifuss, F.E. and Wolf, P. (Eds.), Epileptic syndromes in infancy, childhood and adolescence. John Libbey Eurotext, London, Paris, pp 194-204, 1985.
Selected Papers: Medical Therapy
Medical Therapy Intravenous Administration of Anticonvulsants under EEG Monitoring in ESES: Rapid Prediction of the Efficacy of Oral Administration of Drugs Kenji Sugai, M.D., Norio Sakuragawa M.D.* and Masataka Arima, M.D.*
Department of Pediatrics, National Nishi-Kofu Hospital, Kofu *National Center Hospital for Mental, Nervous and Muscular Disorders, NCNP, Kodaira
EEG tracing at 15, 30 and 45 minutes after IV, and 75% or more reduction of SW index was estimated as markedly effective, 50-74% reduction as effective and less than 50% reduction as ineffective. Then, AZA, 10-18 mg/kg, V.B6, 20 mg/kg, PHT, 3.9-5.0 mg/kg or, in case of IV of DZP, nitrazepam, 0.2-0.35 mg/kg, or clonazepam, 0.05-0.1 mg/kg or DZP, 0.25-0.3 mg/kg, were orally given to the patient for 1-12 weeks, and the efficacy was evaluated with the same criteria from a 30-minute or
Table 1: Efficacy of Anticonvulsants by IV and PO
Introduction Electrical status epilepticus during slow sleep (ESES) is a self-limited and agerelated condition, but it is intractable and long lasting ESES inevitably causes intellectual and behavioral impairrnenh2 Prompt and proper treatment is thus important, but efficacious therapy has not been e~tablished.~ We studied whether the efficacy of oral administration (PO) of antiepileptic drugs (AEDs) can be predicted or not by intravenous administration (IV) of the drugs under EEG monitoring. Subjects and Methods Six patients with ESES, aged 4 to 10, who had 90-9896 of a spike and wave index (SW index) during non-REM sleep on all-night polygraphic EEG recordings, were selected for this study. One to four AEDs of acetazolamide (AZA), 10-14 mg/ kg, vitamin B6 (V.B6), 11-25 mg/kg, phenytoin (PHT), 10-11 mg/kg, and diazepam (DZP), 0.26-0.3 mg/kg, were individually given intravenously to a patient under EEG monitoring at one-hour or more intervals when the EEG tracing returned nearly to a base line level. SW indices were calculated every 10 minutes of
Patients
AZA
PHT
V.B6
DZP
~
1
+/++’
2
-/-
-/X
3 4
-/x
- /X
-/+c
-/x
~~
+ +/N:+ C:+ + +/N:++
+b
++/++b
C:+/D:+ ++/D:+‘ +/D:+
-/-
+
5
+
+/N:+
-/-
6
C:-
’
+
Eficacy of IV of the drug/PO of the drug: +, markedly effective; +, effective; - , ineffective; x, not studied because of ineffectiveness by IV. b, ’: efficacy by combined administration. N, NZP; C, CZP; D. DZP.
Table 2: Correlation of Efficacies of IV and PO of “Anticonvulsants” PO
IV
++ + -
Subtotal
++
+
4
2 2
!
I
7
j
1
4
0
1
1
5
5
1
-
________________ 1-----!
Subtotal
3
4
5
15
‘p=0.077 when the table is classified into the four cells shown by broken lines (Fisher’s exact probability test). “Efficacy o f anticonvulsants: + + , markedly effective; , effective; - , ineffective.
+
The Japanese Journal of Psychiatry and Neurology, Vol. 46, No. 2, 1992
-
C z , ESM ( 4 0)
r" ,
2 .
RIC' , NREY
Fig. 1 : tion (IV) shown by spike and
~
.
L
,
-3
-
A*,
453
-__ -Czp, ESM
( 31
d 7
-
Case 1. Continuous spike-wave discharges reduced markedly by intravenous administraof antiepileptic drugs. The drugs were also effective by oral administration (PO) as routine EEG and all-night polygraphic EEG recording. Figures in parentheses indicate wave indices.
more sleep EEG tracing or an all-night polygraphic EEG recording. The correlation of the efficacy of IV of AED with that of PO of the drug was discussed. Results Sixteen IVs and 15 POs of AEDs were carried out, and AZA, V.B6 and DZP were effective but PHT was ineffective by both IV and PO (Table 1). Their efficacies were considerably correlated with each other, though not significantly by Fisher's exact probability test (Table 2, Fig. 1). The efficacies by IV were grossly inconsistent with those by PO in three cases. In two of them, IV of DZP was effective or markedly effective but PO of CZP was ineffective, and PO of NZP was effective or markedly effective. In the third case, AZA was ineffective by IV but effective by combined PO with DZP. With these AEDs,
continuous spike-wave discharges during sleep disappeared or significantly reduced in all cases, and clinical seizures ceased promptly except in one case. Though the SW index increased to 50-90% again in four cases and clinical seizures reappeared in two cases in 7-60 months of follow-up observation, relapses of ESES were well controlled by replacement with or addition of other AEDs, and intellectual or behavioral disturbances did not develop during this follow-up period. Discussion
The present method has not been reported, but IV of benzodiazepine during slow sleep arrested the continuous spikes and waves in ESES for one hour3, and a rapid prediction of the efficacy of PO of AEDs by IV of the drugs under EEG monitoring was suggested in other refractory epi-
454
Selected Papers: Medical Therapy
lepsies'. Though limited AEDs are available for IV, this study suggests that IV of AED under EEG monitoring can be a useful method to find efficacious AEDs rapidly in the treatment of ESES. References
1. Sugai, K., Sakuragawa, N. and Arima, M.: Rapid estimation of the efficacy of orally administered antiepileptic drugs by intravenous administration of the drugs under EEG monitoring. Brain Dev 12: 732, 1990. 2. Tassinari, C.A., Bureau, M., Dravet, C.,
Roger, 3. and Daniele-Natale, 0.: Electrical status epilepticus during sleep in children (ESES). In: Sterman, M.B., Shouse, M.N. and Passouant, P. (Eds.), Sleep and epilepsy. Academic Press, London, New York, pp 465-479, 1982. 3. Tassinari, C.A., Bureau, M., Dravet, C., Dalla Bernardina, B. and Roger, J.: Epilepsy with continuous spikes and waves during slow sleep. In: Roger, J., Dravet, C., Bureau, M., Dreifuss, F.E. and Wolf, P. (Eds.), Epileptic syndromes in infancy, childhood and adolescence. John Libbey Eurotext, London, Paris, pp 194-204, 1985.
