- Email: [email protected]
Convulsions in epileptic women after administration of prostaglandin E2 derivative
1138
normal, revealed
no lesions that would be expected to precipitate infarction. The clinical features seem to argue against a fortuitous association even though the man had received an equivalent dose of desmopressin many times before without adverse effects. A handful of case studies need not imply causality or establish mechanism. However, this and the previous reports raise an important safety issue about desmopressin and until the matter is resolved desmopressin will be a less attractive agent for use in blood donors. Our centre and several others that administer desmopressin to plasma exchange donors have now chosen to restrict its use to highly motivated younger donors without risk factors for vascular disease such as hypertension, diabetes, smoking, hyperlipidaemia, and family history of premature vascular disease.
Department of Medicine, Rush-Presbyterian-St Luke’s Medical Center, Chicago, Illinois 60612, USA
combined with a pregnancy-related decrease in matemal plasma concentrations of anti-epileptic drugs3 may have caused reduced valproate levels. Another possible explanation is psychological stress and sleep deprivation before the scheduled termination, adding to the risk of a convulsion. The risk of a grand-mal seizure during normal labour is only 1-3%,9 which makes the occurrence of convulsions in 3 out of 4 pregnant epileptic women injected with sulproston unacceptably high. We have stopped using sulproston for pregnancy terminations in epileptic patients, until substantial evidence on its safety is provided. Department of Obstetrics and Gynaecology and Clinical Genetics, Academic Hospital Dijkzigt, Erasmus University Rotterdam, 3015GD Rotterdam, Netherlands
H. BRANDENBURG M. G. J. JAHODA
J. W. WLADIMIROFF F. J. Los D. LINDHOUT
BRUCE C. MCLEOD D, Schmidt D. In-utero exposure to valproate and neural tube defects Lancet 1986, i: 1392-93. Saunders M Epilepsy in women of childbearing age. Br Med J 1989; 299: 581. Anderson GG, Steege JF. Clinical experience using intra-amniotic prostaglandins F2&agr; for midtrimester abortion in 600 patients. Obsiet Gynecol 1975; 46: 591-95. La Ferla JJ. Midtrimester abortion. techniques and complications Clin Perinatol 1983; 10: 305-20. Lauersen NH, Wilson KH Termination of midtrimester pregnancy by serial intramuscular injections of 15(s)-15-methyl-prostaglandin F2. Am J Obstet
1 Lindhout
1. Mannucci PM. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988; 72: 1449-55. 2. Nilsson IM, Walter H, Mikaelsson M, Vilhardt H. Factor VIII concentrate prepared from DDAVP stimulated blood donor plasma. Scand J Haematol 1979; 22: 42-46. 3. McLeod BC, Sassetti RJ, Cole ER, Scott JP. A high potency, single donor cryoprecipitate of known factor VIII content dispensed in vials. Ann Intern Med
1987; 106: 35-40. BC, McKenna R, Sassetti RJ. Treatment of von Willebrand’s disease and
4. McLeod
hypofibrinogenemia with single donor cryoprecipitate from plasma exchange donation. Am Hemarol 1989; 32: 112-16 J 5. Richardson DW, Robinson AG. Desmopressin. Ann Intern Med 1985; 103: 228-39. 6. Mannucci PM, Lusher JM. Desmopressin and thrombosis. Lancet 1989; ii: 675-76 BC, Sassetti RJ, Cole ER, Scott JP. Long term, frequent plasma exchange donation of cryoprecipitate. Transfusion 1988; 28: 307-10.
7. McLeod
Convulsions in epileptic women after administration of prostaglandin E2 derivative SIR,-Between January, 1989, and April, 1990, five fetuses with
spina bifida were detected in four pregnancies, all at increased risk of neural-tube defects because the mother was taking the anti-epileptic drug valproate.’,’ Termination was requested, and the four women were given intramuscular injections of the prostaglandin E2 derivative sulproston. All the patients had been without convulsions for at least 1years, but three had convulsions after administration of this agent. Case 1 (26, primigravida, 1700 mg valproate daily). Sulproston 500 ug was injected 4-hourly, and shortly after the third injection she had a seizure. On the next day, after two more injections of sulproston combined with diazepam and valproate, she aborted without further complications a male fetus with spina bifida. Case 2 (28, second pregnancy, 1800 mg valproate daily). In this twin pregnancy a spina bifida was found in both fetuses. Sulproston 500 ug was given every 4 h and after the third injection the patient had a seizure. It then emerged that she had not taken her morning dose of valproate. On the next day intra-amniotic instillation of hypertonic saline resulted, without any further seizures, in the abortion of two male fetuses with a spina bifida. Case 3 (29, third pregnancy, 1000 mg valproate daily). She had an uneventful termination after two injections of sulproston 500 ltg. Case 4 (24, primigravida, 1200 mg valproate daily). Convulsions occurred 1 h after administration of 500 ltg sulproston. Intraamniotic instillation of hypertonic saline resulted in an abortion the next day with no further seizures. Prostaglandins are widely used for second-trimester terminations. The main side-effects are nausea, vomiting, diarrhoea, and bronchial spasm. 3-6 A cautionary note was put on the product leaflet following the observation of convulsions in one case. In one study 5 out of 320 non-epileptic women had a convulsion after intra-amniotic instillation of prostaglandin F2"/ but little has been published about the risks of convulsions from sulproston. In rats, prostaglandin levels rise during convulsions but the role of prostaglandin in the induction of seizures is unclear.8 A vasoconstrictive effect on the central nervous system from sulproston may have been responsible for the epileptic insult in the above cases. Alternatively, in the first two patients, vomiting
2. 3. 4.
5.
Gynecol 1976, 124: 169-76. U, Kubli F. Klinische Nebenwirkungen und Komplikationen der Prostaglandme bei Abortinductionen. Gynakologie 1978; 11: 39-44, 7. Lyneham RC, McLeod JG, Smith ID, et al. Convulsions and electroencephalogram abnormalities after intra-amniotic prostaglandin F2&agr;. Lancet 1973; ii: 1003-05 8. Hiilesma VK. A prospective study on maternal and fetal outcome in 139 women with epilepsy. Academic dissertation. University of Helsinki, 1982: 35-38 9 Wallenstein MC. Differential effect of prostaglandin synthetase inhibitor pretreatment on pentylenetetrazol-induced seizures in rat Arch Int Pharmacodyn Ther 6. Haller
1985, 275: 93-104
21-year follow-up of myokymia with impaired muscle relaxation SIR,-Gardner-Medwin and Waited described a case of myokymia with impaired muscle relaxation, referred to them by the department of neurology, Cardiff. This report prompted Isaacs2 to suggest that his original name, syndrome of continuous muscle fibre activity, for the condition was more appropriate. In his original description of the condition Isaacs3 had also suggested the name armadillo disease, comparing the patient’s movements to those of this slow moving armour-plated quadruped. One of us (A. W.) came across the original report while looking for a case fulfilling the diagnostic criteria for the syndrome of continuous muscle fibre activity. A search of other reports of similar cases revealed little information on the long-term natural history of the disease. Gardner-Medwin and Walton’s patient was therefore traced via her medical records at Newcastle and Cardiff, and was reviewed. In 1967, at age 21, she was started on phenytoin 100 mg thrice daily, with symptomatic improvement. She had been lost to follow-up in 1971. When reviewed in November, 1989, she was symptom-free and taking no drugs. Phenytoin had been discontinued 13 years earlier when she had a 2-week holiday without the drug and had no ill effects. She had had two children, one before and one after stopping phenytoin, without complications. General examination revealed no abnormality. Cranial nerves were normal. She had a mild fixed flexion deformity of the fingers and evidence of previous bilateral Achilles tendon surgery. Muscle tone was generally mildly increased and power was normal. Sensation was preserved. The tendon reflexes in the arms were brisk and symmetrical, as were the knee jerks. The ankle jerks could not be elicited. Abdominal reflexes were normal and plantar responses were feebly flexor. Coordination and gait were normal. Fear of lifts had led her to ascend the nine floors to the clinic on foot, which suggested a normal level of fitness. The finding of brisk tendon reflexes led to a review of her notes, with attention to comments on tendon reflexes, which showed that when disease activity was high the reflexes were unobtainable, but when disease was low, the reflexes were present and brisk. Thus the disease pattern seemed to be loss or decrease in tendon reflexes with
normal, revealed
no lesions that would be expected to precipitate infarction. The clinical features seem to argue against a fortuitous association even though the man had received an equivalent dose of desmopressin many times before without adverse effects. A handful of case studies need not imply causality or establish mechanism. However, this and the previous reports raise an important safety issue about desmopressin and until the matter is resolved desmopressin will be a less attractive agent for use in blood donors. Our centre and several others that administer desmopressin to plasma exchange donors have now chosen to restrict its use to highly motivated younger donors without risk factors for vascular disease such as hypertension, diabetes, smoking, hyperlipidaemia, and family history of premature vascular disease.
Department of Medicine, Rush-Presbyterian-St Luke’s Medical Center, Chicago, Illinois 60612, USA
combined with a pregnancy-related decrease in matemal plasma concentrations of anti-epileptic drugs3 may have caused reduced valproate levels. Another possible explanation is psychological stress and sleep deprivation before the scheduled termination, adding to the risk of a convulsion. The risk of a grand-mal seizure during normal labour is only 1-3%,9 which makes the occurrence of convulsions in 3 out of 4 pregnant epileptic women injected with sulproston unacceptably high. We have stopped using sulproston for pregnancy terminations in epileptic patients, until substantial evidence on its safety is provided. Department of Obstetrics and Gynaecology and Clinical Genetics, Academic Hospital Dijkzigt, Erasmus University Rotterdam, 3015GD Rotterdam, Netherlands
H. BRANDENBURG M. G. J. JAHODA
J. W. WLADIMIROFF F. J. Los D. LINDHOUT
BRUCE C. MCLEOD D, Schmidt D. In-utero exposure to valproate and neural tube defects Lancet 1986, i: 1392-93. Saunders M Epilepsy in women of childbearing age. Br Med J 1989; 299: 581. Anderson GG, Steege JF. Clinical experience using intra-amniotic prostaglandins F2&agr; for midtrimester abortion in 600 patients. Obsiet Gynecol 1975; 46: 591-95. La Ferla JJ. Midtrimester abortion. techniques and complications Clin Perinatol 1983; 10: 305-20. Lauersen NH, Wilson KH Termination of midtrimester pregnancy by serial intramuscular injections of 15(s)-15-methyl-prostaglandin F2. Am J Obstet
1 Lindhout
1. Mannucci PM. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988; 72: 1449-55. 2. Nilsson IM, Walter H, Mikaelsson M, Vilhardt H. Factor VIII concentrate prepared from DDAVP stimulated blood donor plasma. Scand J Haematol 1979; 22: 42-46. 3. McLeod BC, Sassetti RJ, Cole ER, Scott JP. A high potency, single donor cryoprecipitate of known factor VIII content dispensed in vials. Ann Intern Med
1987; 106: 35-40. BC, McKenna R, Sassetti RJ. Treatment of von Willebrand’s disease and
4. McLeod
hypofibrinogenemia with single donor cryoprecipitate from plasma exchange donation. Am Hemarol 1989; 32: 112-16 J 5. Richardson DW, Robinson AG. Desmopressin. Ann Intern Med 1985; 103: 228-39. 6. Mannucci PM, Lusher JM. Desmopressin and thrombosis. Lancet 1989; ii: 675-76 BC, Sassetti RJ, Cole ER, Scott JP. Long term, frequent plasma exchange donation of cryoprecipitate. Transfusion 1988; 28: 307-10.
7. McLeod
Convulsions in epileptic women after administration of prostaglandin E2 derivative SIR,-Between January, 1989, and April, 1990, five fetuses with
spina bifida were detected in four pregnancies, all at increased risk of neural-tube defects because the mother was taking the anti-epileptic drug valproate.’,’ Termination was requested, and the four women were given intramuscular injections of the prostaglandin E2 derivative sulproston. All the patients had been without convulsions for at least 1years, but three had convulsions after administration of this agent. Case 1 (26, primigravida, 1700 mg valproate daily). Sulproston 500 ug was injected 4-hourly, and shortly after the third injection she had a seizure. On the next day, after two more injections of sulproston combined with diazepam and valproate, she aborted without further complications a male fetus with spina bifida. Case 2 (28, second pregnancy, 1800 mg valproate daily). In this twin pregnancy a spina bifida was found in both fetuses. Sulproston 500 ug was given every 4 h and after the third injection the patient had a seizure. It then emerged that she had not taken her morning dose of valproate. On the next day intra-amniotic instillation of hypertonic saline resulted, without any further seizures, in the abortion of two male fetuses with a spina bifida. Case 3 (29, third pregnancy, 1000 mg valproate daily). She had an uneventful termination after two injections of sulproston 500 ltg. Case 4 (24, primigravida, 1200 mg valproate daily). Convulsions occurred 1 h after administration of 500 ltg sulproston. Intraamniotic instillation of hypertonic saline resulted in an abortion the next day with no further seizures. Prostaglandins are widely used for second-trimester terminations. The main side-effects are nausea, vomiting, diarrhoea, and bronchial spasm. 3-6 A cautionary note was put on the product leaflet following the observation of convulsions in one case. In one study 5 out of 320 non-epileptic women had a convulsion after intra-amniotic instillation of prostaglandin F2"/ but little has been published about the risks of convulsions from sulproston. In rats, prostaglandin levels rise during convulsions but the role of prostaglandin in the induction of seizures is unclear.8 A vasoconstrictive effect on the central nervous system from sulproston may have been responsible for the epileptic insult in the above cases. Alternatively, in the first two patients, vomiting
2. 3. 4.
5.
Gynecol 1976, 124: 169-76. U, Kubli F. Klinische Nebenwirkungen und Komplikationen der Prostaglandme bei Abortinductionen. Gynakologie 1978; 11: 39-44, 7. Lyneham RC, McLeod JG, Smith ID, et al. Convulsions and electroencephalogram abnormalities after intra-amniotic prostaglandin F2&agr;. Lancet 1973; ii: 1003-05 8. Hiilesma VK. A prospective study on maternal and fetal outcome in 139 women with epilepsy. Academic dissertation. University of Helsinki, 1982: 35-38 9 Wallenstein MC. Differential effect of prostaglandin synthetase inhibitor pretreatment on pentylenetetrazol-induced seizures in rat Arch Int Pharmacodyn Ther 6. Haller
1985, 275: 93-104
21-year follow-up of myokymia with impaired muscle relaxation SIR,-Gardner-Medwin and Waited described a case of myokymia with impaired muscle relaxation, referred to them by the department of neurology, Cardiff. This report prompted Isaacs2 to suggest that his original name, syndrome of continuous muscle fibre activity, for the condition was more appropriate. In his original description of the condition Isaacs3 had also suggested the name armadillo disease, comparing the patient’s movements to those of this slow moving armour-plated quadruped. One of us (A. W.) came across the original report while looking for a case fulfilling the diagnostic criteria for the syndrome of continuous muscle fibre activity. A search of other reports of similar cases revealed little information on the long-term natural history of the disease. Gardner-Medwin and Walton’s patient was therefore traced via her medical records at Newcastle and Cardiff, and was reviewed. In 1967, at age 21, she was started on phenytoin 100 mg thrice daily, with symptomatic improvement. She had been lost to follow-up in 1971. When reviewed in November, 1989, she was symptom-free and taking no drugs. Phenytoin had been discontinued 13 years earlier when she had a 2-week holiday without the drug and had no ill effects. She had had two children, one before and one after stopping phenytoin, without complications. General examination revealed no abnormality. Cranial nerves were normal. She had a mild fixed flexion deformity of the fingers and evidence of previous bilateral Achilles tendon surgery. Muscle tone was generally mildly increased and power was normal. Sensation was preserved. The tendon reflexes in the arms were brisk and symmetrical, as were the knee jerks. The ankle jerks could not be elicited. Abdominal reflexes were normal and plantar responses were feebly flexor. Coordination and gait were normal. Fear of lifts had led her to ascend the nine floors to the clinic on foot, which suggested a normal level of fitness. The finding of brisk tendon reflexes led to a review of her notes, with attention to comments on tendon reflexes, which showed that when disease activity was high the reflexes were unobtainable, but when disease was low, the reflexes were present and brisk. Thus the disease pattern seemed to be loss or decrease in tendon reflexes with