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On November 8, 1923, William John Adie described an unusual disorder to the Section of Neurology of the Royal Society of Medicine. The condition comprised frequent momentary stereotyped impairments of consciousness that occurred in children, did not respond to antiseizure medications, and did not develop into epilepsy, as that term was then commonly understood, since no convulsive seizures occurred. After some time, the episodes terminated spontaneously, leaving the sufferer unhandicapped and neurologically intact. Almost certainly, Adie had described the present-day entity of childhood absence epilepsy. He termed it "pyknolepsy," knowing that the name "pyknolepsie" had been used for a similar disorder in Germany from 1916 onwards, though not reported elsewhere. Following Adie's account, published in 1924, reports of the disorder appeared in the English and French-language literature and continued to be published in German. It became increasingly accepted that pyknolepsy was a form of epilepsy that was part of Lennox's petit mal triad. The word pyknolepsy itself never became widely used and is now largely forgotten. Adie never took up the topic in print again. However, he had awakened English-language readers to one component in a broadening of the concept of what constituted epilepsy.

Purpose: To investigate the risk of teratogenesis occurring in relation to intrauterine exposure to infrequently used antiseizure medications in Australia., Methods: Analysis of data contained in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs., Results: There was statistically significant evidence that zonisamide, but not any other of nine infrequently used antiseizure medications in Australia, was associated with a risk of teratogenesis related to the maternal dose of the drug taken in at least the earlier half of pregnancy., Conclusions: The teratogenesis associated with zonisamide, like that associated with topiramate and possibly acetazolamide, may be an expression of a class effect shared among sulphonamide-derived carbonic anhydrase inhibitors that possess anti-seizure activity., Competing Interests: Declaration of competing interest FJE Vajda has received research support for the Australian Pregnancy Register from Epilepsy Action Australia, the Epilepsy Society of Australia, NHMRC, RMH Neuroscience Foundation, Sanofi-Aventis, Eisai, UCB Pharma, and Sci-Gen. T O'Brien has received research support from the Epilepsy Society of Australia, NHMRC, RMH Neuroscience Foundation, Sanofi-Aventis, UCB Pharma, and Sci-Gen and Eisai. P Perucca is supported by the Australian National Health and Medical Research Council (APP1163708), the Epilepsy Foundation, The University of Melbourne, Monash University, Brain Australia, and the Weary Dunlop Medical Research Foundation. He has also received speaker honoraria or consultancy fees provided to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. JE Graham, AA Hitchcock, CM Lander, and MJ Eadie have no relevant conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To assess the role of antiseizure medication (ASM) regimens and other factors in relation to the occurrence of intrauterine foetal death (IUFD) in pregnant women with epilepsy (WWE) enrolled in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR)., Results: IUFDs occurred in 70 (3.01 %) of 2,323 prospective pregnancies from WWE with known outcomes in the APR. Factors associated with IUFD occurrence included older maternal age, enrolment in the APR at an earlier stage of pregnancy, history of pregnancies which did not result in livebirths, parental history of foetal malformations, and maternal use of carbamazepine, lamotrigine or ethosuximide. Individual ASM dosages were not associated with IUFD occurrence. Relative to no exposure, the risk of IUFD increased with the increasing number of ASMs used in combination (2 ASMs: relative risk, RR = 5.45 [95 % CI: 0.73-41.80]; 3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), >3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), but this finding was attenuated after adjusting for other factors implicated in IUFD occurrence. Several ASM pairs were associated with an increased risk of IUFD relative to no exposure, but these associations were lost after accounting for confounders., Conclusions: Although it is possible that prenatal ASM exposure may increase the risk of IUFD, other non-pharmacological factors are more relevant to the occurrence to IUFD in pregnant WWE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [FJE Vajda has received research support for the Australian Pregnancy Register from Epilepsy Action Australia, the Epilepsy Society of Australia, the NHMRC, the RMH Neuroscience Foundation, Sanofi-Aventis, Eisai, UCB Pharma, and Sci-Gen. T O’Brien has received research support from the Epilepsy Society of Australia, the NHMRC, the RMH Neuroscience Foundation, Sanofi-Aventis, UCB Pharma, and Sci-Gen and Eisai. P Perucca is supported by an Emerging Leadership 2 Investigator Grant from the NHMRC (APP1163708), the Epilepsy Foundation, The University of Melbourne, Monash University, Brain Australia, and the Weary Dunlop Medical Research Foundation. He has also received speaker honoraria or consultancy fees provided to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. JE Graham, AA Hitchcock, CM Lander, and MJ Eadie have no relevant conflicts of interest to declare]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate rates of occurrence of pregnancies associated with a foetal malformation (FM pregnancy rates) following simultaneous intrauterine exposure to two antiseizure medications in 524 pregnancies in women with epilepsy from the Australian Pregnancy Register who were treated simultaneously with various combinations and dosages of two antiseizure medications (duotherapy)., Results: FM pregnancy rates tended to be higher in those exposed simultaneously to two antiseizure medications, each of which was a statistically significant teratogen (valproate, topiramate, or carbamazepine), than when there was exposure to only one such teratogen. When there was exposure to only one such teratogen together with clonazepam or levetiracetam, for neither of which there was statistically significant evidence of heightened teratogenicity, the FM pregnancy rates also tended to be higher, but less so. When lamotrigine was the other component of the duotherapy with an established teratogen, FM pregnancy rates tended to be lower than that for the teratogen used as monotherapy., Conclusion: Leaving aside issues in relation to seizure control, our data suggest that it would be best to avoid using established teratogenic antiseizure medications (carbamazepine, valproate and topiramate) in combination with each other due to the increased FM risks. When combining an established teratogenic medication with a less teratogenic one, i.e. lamotrigine, levetiracetam or clonazepam, lamotrigine appears to be the safer option., Competing Interests: Conflicts of Interest FJE Vajda has received research support for the Australian Pregnancy Register from the Epilepsy Society of Australia, NHMRC, RMH Neuroscience Foundation, Epilepsy Action, Sanofi-Aventis, Eisai, UCB Pharma, and Sci-Gen. T O’Brien has received research support from the Epilepsy Society of Australia, NHMRC, RMH Neuroscience Foundation, Sanofi-Aventis, UCB Pharma, and Sci-Gen and Eisai. P Perucca is supported by the Australian National Health and Medical Research Council (APP1163708), the Epilepsy Foundation, The University of Melbourne, Monash University, Brain Australia, and the Weary Dunlop Medical Research Foundation. He has also received speaker honoraria or consultancy fees given to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. JE Graham, AA Hitchcock, CM Lander, and MJ Eadie have no relevant conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)