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The foetal outcomes of 2,635 pregnancies recorded in the Australian Pregnancy Register were studied. In at least the initial 4months of 515 pregnancies, there had been no intrauterine exposure to antiepileptic drugs, though the women involved in 264 of these pregnancies took antiepileptic drugs in later pregnancies. Compared with these 515 drug-unexposed pregnancies, foetal malformations risks were increased more than five-fold in association with valproate monotherapy, and more than doubled in association with carbamazepine monotherapy (p<0.05). There were no statistically significant increases in malformation rates associated with other more commonly used antiepileptic drugs, while the malformation risk in relation to levetiracetam exposure was lower than that in the drug-unexposed pregnancies. The published literature has rather consistently shown raised malformation rates associated with carbamazepine monotherapy, though only once was it statistically significant. There now appears to be enough evidence to make it likely that carbamazepine possesses some teratogenic capacity. This makes it unwise to employ the malformation rate associated with carbamazepine monotherapy as a comparator when assessing the foetal hazards from exposure to newer antiepileptic drugs. Levetiracetam may prove a better comparator if adequate untreated control material is unobtainable., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The demographic characteristics, details of pregnancies, epilepsies, and treatment of 855 pregnant women with epilepsy enrolled in the Australian Antiepileptic Drugs in Pregnancy Register during 1999-2005 were compared with the corresponding data for the 801 women enrolled from 2006-2012. We estimate that the Register captures approximately 1 in 12 of all pregnancies in Australian women with epilepsy. A number of statistically significant changes were found, with nearly all explained by factors such as re-enrolment of women who had enrolled earlier pregnancies, changes in general population behaviour, altered attitudes to prescribing valproate and using it in lower doses, and the advent of newer antiepileptic drugs which have displaced the use of older agents. It appears that the Register has continued to capture a reasonably representative sample of pregnant Australian women with epilepsy as time has passed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Data on the use in pregnancy of the new antiepileptic drugs (AED) are limited. We analysed data collected by the Australian Pregnancy Register to provide information on their relative teratogenicity. The database containing pregnancy outcomes from 1317 women with epilepsy (WWE) was examined for three widely used new AED in monotherapy in the first trimester--lamotrigine, levetiracetam and topiramate. This was compared with outcomes of pregnant WWE on monotherapy with three traditional AED, and with untreated women. The incidence of malformations associated with lamotrigine monotherapy was 12/231 (5.2%), with topiramate 1/31 (3.2%) and with levetiracetam 0/22 (0%). This compares with rates of 1/35 (2.9%) for phenytoin, 35/215 (16.3%) for valproate (VPA), 19/301 (6.3%) for carbamazepine and 6/116 (5.2%) for untreated women. There was no evidence of dose-dependent risks of foetal malformation, except with VPA monotherapy. We conclude that the new AED appear no more teratogenic than traditional drugs in monotherapy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine how valid 68 first-trimester pregnancies of untreated epileptic women would prove as an internal control group for investigating foetal malformation rates in 709 simultaneously collected antiepileptic drug-exposed pregnancies in an Australian register of pregnancies in epileptic women. We carried out comparisons of values for parameters relating to personal details, obstetric aspects, and epilepsies prior to and during pregnancy in the drug-exposed and drug-unexposed pregnancies, with observations on subpopulations within the drug-unexposed group. Statistically significant (p<0.05) differences existed for only seven of more than 50 parameters compared. None of these seven parameters had a statistically significant influence on foetal malformation rates in the whole dataset. In 23 of the 65 epileptic pregnancies unexposed to antiepileptic drugs, therapy had been ceased shortly prior to pregnancy and was often resumed after the first trimester. In the remaining 42, therapy had been ceased earlier, often despite continuing seizures. Planned withdrawal of therapy did not appear to produce additional hazards for mothers and foetuses in the former subgroup. In the data collection studied, there did not appear to be evidence of statistically significant differences between untreated pregnancies and treated epileptic pregnancies that would be likely to invalidate the former group as an internal control for the latter, at least when assessing foetal malformation rates.

Internal comparisons using the data of the Australian Register of Antiepileptic Drugs in Pregnancy as of November 2005, and comparisons with Australian population data, were carried out. It was found that (i) except for under-representation of mothers of Asian origin, the demography of the register population was reasonably representative of the Australian situation; (ii) except for more pregnancies terminated for foetal malformation, malformation rates were similar in retrospectively and non-retrospectively enrolled pregnancies; (iii) some 21% of foetal malformations would have been excluded by not including malformations first recognised after the neonatal period; and (iv) in practice, the comparator against which malformation rates were expressed made little difference to the rates found. It is desirable to have available such analyses of pregnancy register data before comparing the findings of different registers.

We report progress in the accumulation of data by the Australian Pregnancy Register over 64 months, confirming the rise in enrollment and the predominantly epileptic indication for taking antiepileptic drugs. Eighty percent of the enrollment was prospective. The focus of the current report is the observation that as a possible result of education and dissemination of information about the risks of exposure to high-dose valproate, there has been a decline in the drug's doses prescribed in Australia, as well as a decline in the proportion of patients prescribed this drug in pregnancy. The risk of teratogenicity associated with valproate in doses in excess of 1100 mg/day was confirmed, and the incidence of lamotrigine-related malformations was comparable to that associated with exposure to phenytoin and carbamazepine. Reporting of data for this paper took into account the 12 months follow-up period for each pregnancy outcome, thus in effect making the evaluation period 21 months for each pregnancy and its outcome.

Carbamyl phosphate synthase deficiency (CPS) is a rare urea cycle defect. We present a case of a 41-year-old woman diagnosed with CPS deficiency during pregnancy. She is the oldest CPS-deficient patient, at diagnosis, reported to date and the first to be diagnosed during pregnancy. This case highlights the need for consideration of inborn errors of metabolism in adults presenting with unusual neurological and psychiatric conditions.

Unlabelled: To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study., Methods: A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes., Results: 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (16.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1%, [Formula: see text] ). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (1,975 vs. 1,128 mg, P < 0.01). The incidence of FM with VPA doses >or= 1,100 mg was 30.2% vs. 3.2% with doses <1,100 mg (P <0.01)., Conclusions: There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy.

Background: Most women with epilepsy need to take antiepileptic drugs (AEDs) in pregnancy to prevent the potentially harmful effects of seizures. Retrospective studies have demonstrated an increased chance of having a child with a birth defect (BD) in women with epilepsy taking AEDs. It is uncertain how much of this risk is directly caused by the AEDs and whether certain drugs or combinations are associated with a greater risk., Aims: To establish a register to evaluate prospectively the incidence of adverse pregnancy outcomes in women exposed to specific AEDs; to determine whether certain AEDs or combinations were associated with a greater risk; and to determine whether other factors influenced the risk., Methods: An Australia-wide, prospective, voluntary, telephone-interview based, observational register. Three groups of pregnant women were enrolled: those with epilepsy taking AEDs, those with epilepsy not taking AEDs, and those taking AEDs for a non-epileptic indication. The pregnancy outcomes were evaluated by follow-up interviews and by reference to hospital and treating doctors' records., Results: Over the first 30 months of the study (till December 2001) 334 eligible women were enrolled, with all states and territories being represented. Two hundred and ninety two pregnancies had been completed, of which 256 (88%) resulted in a healthy live birth, 19 (6.5%) a live birth with a birth defect, four an induced abortion because of a detected malformation on ultrasound, one premature labour with a stillbirth and 12 (4%) spontaneous abortions. Of the completed pregnancies, 269 were exposed to at least one AED during the first trimester. The incidence of birth defects in relation to specific AEDs was: valproate (16.7%), phenytoin (10.5%), lamotrigine (7.7%) and carbamazepine (3.3%), none of which was significantly different from that in women with epilepsy not taking an AED (4.3%, n.s.). The dose of valproate taken was higher in pregnancies with BD compared to those without (mean 2081 mg vs. 1149 mg, p<0.0001). The incidence of folate supplementation being taken prior to conception did not differ for pregnancy outcomes with or without BD (70% vs. 66%, n.s.)., Conclusions: The model for the Australian Pregnancy Register appears to be successful, with strong enrolment from all regions over the first 30 months. The study is prospective and includes reference to all new AEDs approved in Australia over the past decade. Analysis of the pregnancy outcomes to date may reveal early trends, but numbers are still to small for any definitive conclusions to be made regarding the relative risk in pregnancy of individual AEDs.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke-like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We sought to demonstrate mutations of the Notch3 gene in Australian patients suspected of having CADASIL. Patients from several families were referred to the study. A diagnosis was determined clinically and by neuroimaging. Those suspected of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight patients, two of whom were siblings, were suspected of having CADASIL. Five patients (including the siblings) had mutations. Because of strong clustering of Notch3 mutations in CADASIL, this has potential as a reliable test for the disease in Australian patients., (Copyright 2001 Harcourt Publishers Ltd.)

Inflammatory demyelinating neuropathies have been associated with membranous and focal sclerosing glomerulonephritis. Here we describe a 58 year old man with a clinical history, physical examination and laboratory investigations consistent with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), who also had severe lower limb and sacral oedema resistant to medical therapy. Mild proteinuria was present and a renal biopsy showed features consistent with focal sclerosing glomerulonephritis (FSGN). The patient's weakness and oedema did not respond to i.v. immunoglobulin or plasmapheresis but responded to high dose oral prednisone. The oedema was not explained by immobility, hypoproteinaemia or local factors. The occurrence of the oedema in a person with CIDP and FSGN and its improvement with prednisone, together with improvement in CIDP and FSGN, suggests that it was immune mediated, possibly due to increased capillary permeability. The presence of renal disease in patients with inflammatory demyelinating neuropathies may be more common than currently realised., (Copyright 2000 Harcourt Publishers Ltd.)

The efficacy and side effects of pergolide, a D(1) and D(2) dopamine agonist, were assessed in an open label study in 39 patients with long standing Parkinson's disease complicated by end of dose failure and/or dyskinesia. 27 patients completed 28 weeks of the study. The mean dose of pergolide was 2.26 mg/day (0.15-5.0mg/day). Levodopa was reduced by a mean of 273 mg/day (range 0-1950mg/day) from the initial mean dose of 920 mg/day (range 150-2950mg/day). Hours in which the drug was efficacious significantly increased. Dyskinesia and dystonia were significantly reduced. The scores on an abbreviated Parkinson's disease rating scale significantly improved in both the 'on' and 'off' periods. 11 patients withdrew due to early side effects but the majority of patients tolerated pergolide well. In these patients pergolide was an effective adjunct to levodopa.