Publications by authors named "Mervyn J Eadie"

38 Publications

Disease modifying therapies for relapsing-remitting multiple sclerosis: Use and costs in Australia (1996-2019).

Mult Scler Relat Disord 2021 Feb 10;50:102835. Epub 2021 Feb 10.

School of Pharmacy, The University of Queensland, Australia. Electronic address:

Background: New disease modifying therapies (DMT) to control relapsing-remitting multiple sclerosis (RRMS) have been introduced to the market in the past few years and are now widely used in Australia.

Objective: To analyse the dispensed use of government subsidised RRMS DMTs in Australia from 1996 to 2019.

Methods: We obtained data of dispensed use of DMTs from the Australian Government's Pharmaceutical Benefits Scheme (PBS) administered by Medicare Australia. We measured use as defined daily dose (DDD) per 100,000 population per day. We obtained jurisdictional population data from the Australian Bureau of Statistics.

Results: Total DMT use increased by an average of 18% annually, from 2.4 (in 1996) to 69.9 DDD/100,000/day in 2019. Interferon β1B was the most commonly used medicine between 1996 and 2000, Interferon β1A between 2001 and 2014, and fingolimod subsequently. Among Australian states, Tasmania (the southernmost state) had the highest dispensed DMT use of 94.6 DDD/100,000/day in 2019. Concession beneficiaries under the Government's PBS had both lower use and cost per patient than general beneficiaries did. Fingolimod and ocrelizumab accounted for 55% of total expenditure on MS drug therapy in 2019.

Conclusion: The use of oral DMTs might increasingly replace parenteral treatments in the near future. Given the current substantial government expenditure on oral DMTs, it will be imperative to examine the real world effectiveness of DMTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.102835DOI Listing
February 2021

Antiepileptic drugs and depression during pregnancy in women with epilepsy.

Acta Neurol Scand 2020 Oct 29;142(4):350-355. Epub 2020 Jul 29.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Qld, Australia.

Objectives: To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient-recognized depression during pregnancy in women with epilepsy.

Materials And Methods: Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end.

Results: Patient-recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure-affected than in seizure-free pregnancies (5.67% vs 6.41%), though higher in AED-treated than AED-untreated pregnancies (6.24% vs 5.26%; RR = 1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient-recognized depression occurring during pregnancy and topiramate dosage with an increasing rate.

Conclusions: Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13315DOI Listing
October 2020

Folic acid dose, valproate, and fetal malformations.

Epilepsy Behav 2021 Jan 1;114(Pt A):107569. Epub 2020 Dec 1.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Queensland 4027, Australia.

Objective: To determine whether there is a relationship between folic acid dose and the degree of protection against valproate-associated and other antiepileptic drug (AED)-associated fetal structural malformations in women with AED-treated epilepsy.

Methods: Statistical analysis of data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy involving 2104 folic acid-treated pregnancies in women with epilepsy.

Results: Multiple variable logistic regression failed to demonstrate any statistically significant effect of folic acid dosage in reducing overall fetal malformation rates in women taking folic acid either before and during pregnancy (P = 0.640) or during early pregnancy only (P = 0.801), and in reducing spina bifida occurrence rates (P = 0.409).

Conclusions: In the present state of knowledge, it would seem misguided to hope that a folic acid dose of 5 mg/day taken before and during pregnancy would protect against the occurrence of valproate-associated and other AED-associated fetal structural malformations. Future studies are required to determine whether high-dose periconceptional folate use may decrease the risk of other valproate-associated adverse fetal outcomes, including impaired post-natal neurobehavioral development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107569DOI Listing
January 2021

Twin pregnancy in women with epilepsy.

Epilepsia 2020 12 2;61(12):2748-2753. Epub 2020 Nov 2.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Qld, Australia.

Objective: We report data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) to see if there are significant differences in relation to the courses and outcomes of the twin pregnancies contained in the register, as compared with the singleton ones.

Methods: The APR has been under the oversight of Melbourne institutional Human Ethics Research Committees; all women enrolled in the APR have provided written informed consent. Data from the APR were transferred to a spreadsheet and then analyzed using simple statistical techniques including logistic regression.

Results: The population studied comprised 44 twin and 2261 singleton pregnancies; thus, twin pregnancies accounted for 1.91% of all pregnancies studied. The women carrying twins tended to be older than the women with singleton pregnancies to a statistically significant extent, their pregnancies more often originated from assisted fertilization techniques, and their babies were more often delivered by cesarean section. There were no statistically significant differences in relation to antiepileptic drug (AED) therapy. Individual twins had statistically significantly lower mean birthweights than singleton babies and they were statistically significantly more often involved structurally malformed foetuses. In the first year of life, the twin pregnancies statistically significantly more often produced offspring that were affected by seizures in infancy.

Significance: The data suggest that there may be an increased hazard of fetal malformation in the offspring of twin pregnancy in women with epilepsy, but that with contemporary standards of management of epilepsy and pregnancy, there is unlikely to be an increased hazard of seizure-affected pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16727DOI Listing
December 2020

The outcome of altering antiepileptic drug therapy before pregnancy.

Epilepsy Behav 2020 10 22;111:107263. Epub 2020 Jul 22.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Queensland 4027, Australia.

We investigated the outcome of altering antiepileptic drug (AED) therapy in the year before pregnancy on 2233 occasions in Australian women in the 20-year period of functioning of the Raoul Wallenberg Australian Pregnancy Register (APR). Therapy had been altered in 358 instances (16%) in the months prior to the pregnancy (median interval: 18 weeks). Antiepileptic drug doses had been changed in 141 pregnancies (39.4%), being decreased in 94; drugs changed in 151 (42.2%); drugs withdrawn without replacement in 66 (18.4%) but resumed in 40 before pregnancy ended. The main drugs involved were valproate (34%), phenytoin (16.5%), topiramate (12.6%), and carbamazepine (11.4%). Antiepileptic drug doses were increased significantly more often (16.9% vs. 6.4%) when epilepsy before pregnancy was not controlled, and AED treatment ceased significantly less often (13.6% vs. 24.0%). The alterations were more often made in women with generalized epilepsies and in those whose seizure disorders were not fully controlled in the prepregnancy year, suggesting that avoidance of teratogenicity and achieving improved seizure control often motivated the changes. Overall, the alterations did not result in improved rates of seizure freedom during pregnancy, as compared with pregnancies where therapy was unchanged; however, fetal malformation rates were lower 3.6% vs. 5.4%, but this difference did not attain statistical significance. The same trends regarding seizure control and malformations persisted after pregnancies involving valproate exposure were excluded. In conclusion, this analysis of the APR cohort did not demonstrate that altering AEDs before pregnancy produced a significant improvement in seizure control and the reduction in fetal malformation rate that occurred was not statistically significant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107263DOI Listing
October 2020

Pregnancy after valproate withdrawal-Fetal malformations and seizure control.

Epilepsia 2020 05 21;61(5):944-950. Epub 2020 Apr 21.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Queensland, Australia.

Objective: To assess the outcomes in women with epilepsy in relation to fetal malformation and epileptic seizure control during pregnancy when valproate (VPA) intake was ceased, or the drug's dose was reduced before pregnancy.

Methods: Statistical analysis of data collected in the Australian Pregnancy Register between 1999 and 2018 concerning 580 pregnancies previously treated with VPA, with the VPA dose reduced or the drug withdrawn prior to pregnancy in 158 cases.

Results: Although the available data have limitations, fetal malformation rates in the pregnancies studied were lower in the VPA changed pregnancies (4.5%) than in the VPA unchanged comparator pregnancies (10.9%, hazard ratio [HR] 0.412, 95% confidence interval [CI] 0.190-0.892), and were only 2.7% where VPA intake was ceased before pregnancy (HR 0.262, 95% CI 0.083-0.826). Seizure-affected pregnancies were more frequent in the VPA changed pregnancies than in the VPA unchanged ones (46.2% vs 30.8%, HR 1.500, 95% CI 1.203-1.870). Convulsive seizure-affected pregnancies also were increased, but the difference was not statistically significant.

Significance: Prepregnancy reduction in VPA dosage reduced the hazard of fetal malformations, whereas ceasing intake of the drug decreased the hazard to one similar to that which applies in the general population, but at a cost of decreased control of epileptic seizures during the pregnancies studied. Further investigations are needed to see whether such findings apply more widely in women with epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16505DOI Listing
May 2020

Seizures in infancy in the offspring of women with epilepsy.

Acta Neurol Scand 2020 Jan 22;141(1):33-37. Epub 2019 Oct 22.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD, Australia.

Objectives: To assess (a) the incidence of seizures in the first year of life in infants born to mothers with epilepsy and (b) factors that might contribute to the seizure incidence.

Materials & Methods: Analysis of data collected in the Australian Register of Antiepileptic Drugs in Pregnancy during and at the end of the year after pregnancy.

Results: By the end of a year following pregnancy, seizures had occurred in the progeny of 47 pregnancies (2.40%), including febrile seizures in 18 (0.92%), the latter rate being higher than the 0.40% and 0.59% rates for the same situation in the general population reported in the recent literature. Seizures in infancy were more likely in the offspring of mothers with generalized as compared with focal epilepsies (3.65% vs 1.56%; RR = 2.332; P < .05) and within the generalized epilepsy mothers in those who were not seizure free during pregnancy (4.83% vs 2.89%). Seizures were also more likely in infants with foetal malformations, especially ones not discovered until after the first post-natal month.

Conclusions: These findings may help in advising mothers with epilepsy regarding the chance of their offspring experiencing seizures in the first year of life; they also suggest the desirability of achieving maternal seizure control throughout pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13170DOI Listing
January 2020

Valproate-associated foetal malformations-Rates of occurrence, risks in attempted avoidance.

Acta Neurol Scand 2019 Jan 14;139(1):42-48. Epub 2018 Aug 14.

Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, Queensland, Australia.

Objectives: To gain insight into the main advantages and disadvantages that might result from valproate being unavailable for women who intend to become pregnant.

Materials And Methods: Analysis of data from the Australian Pregnancy Register concerning pregnancies exposed to valproate (N = 501) and pregnancies where previous valproate intake had been ceased before pregnancy (N = 101).

Results: The risk of foetal malformation associated with valproate exposure during pregnancy was dose-related, and there was a tendency for the more major malformations, including those often managed by therapeutic abortion, for example spina bifida, to occur at higher valproate doses. Had there been no exposure to valproate during pregnancy, some 80% of the foetal malformations that occurred might have been avoided. Cessation of previous valproate therapy before pregnancy was associated with an increased hazard of seizure-affected pregnancy. This was particularly the case for women with generalized epilepsies, in whom the incidence of seizure-affected pregnancy was increased by 50% to nearly 100%.

Conclusions: Avoiding valproate intake during pregnancy is likely to reduce the incidence of foetal malformation, but at a cost of worsened maternal epilepsy control. Individualization of treatment is particularly important in considering withdrawal of valproate in the light of the fact that it is much more widely used in generalized epilepsy, there being fewer alternative drugs than for focal epilepsy and withdrawal is not without risk for both mother and baby. This study may provide a quantitative basis for assessing the balance between benefit and disadvantage for individual women with valproate-treated epilepsy who are considering pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13005DOI Listing
January 2019

A career in epilepsy.

Authors:
Mervyn J Eadie

Epilepsy Behav 2017 05 13;70(Pt A):265-268. Epub 2017 Jan 13.

Emeritus Professor of Clinical Neurology and Neuropharmacology, University of Queensland, Brisbane, Australia; Faculty of Medicine, University of Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane 4027, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2016.12.002DOI Listing
May 2017

Dopamine Agonists: Time Pattern of Adverse Effects Reporting in Australia.

Drugs Real World Outcomes 2015 Sep;2(3):199-203

School of Medicine, The University of Queensland, 288 Herston Rd, Herston, QLD, 4006, Australia.

Background: In Australia, there is voluntary reporting of suspected adverse events (AEs) of therapeutic medicines. Some dopamine agonists (DAs) have serious AEs.

Objective: We aimed to explore the pattern of DA AE reporting over two decades.

Methods: We analysed AE case line listings obtained from the Australian Committee on the Safety of Medicines (ACSOM) for bromocriptine, cabergoline, pergolide, pramipexole and ropinirole, and related these to drug utilisation data (1992-2012). We noted the AE nature, frequency, onset, novelty, severity and outcome.

Results: The 220 suspected AEs fell into five categories: (i) syncopal/pre-syncopal, (ii) fibrotic, (iii) psychotic, (iv) obsessive-compulsive behaviours (OCB) and (v) increased sleep. There were differential lag times between initial individual drug registration and reporting of suspected AEs, with a lag of at least one year for fibrotic reactions and OCB compared to more contemporaneous reporting of other AEs. Consistent with the published literature, ACSOM data showed that ergot DAs share fibrotic reactions as a class AE, whereas symptomatic hypotensive reactions, psychosis and OCB occurred in both ergot and non-ergot DAs, cabergoline and pramipexole, respectively. Reports of syncopal and pre-syncopal reactions seemed to diminish as ergot-based DA use declined. Levodopa was taken simultaneously with DAs in 87 instances. Of those treated, 92 % were 50 years or older. Parkinson's disease accounted for 89 % of use (119 reports).

Conclusions: Exploring the temporal relationship between post-marketing AE reporting and utilisation data, as exemplified by DAs, can be a valuable pharmacovigilance tool to encourage targeted adverse event monitoring and reporting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40801-015-0028-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883210PMC
September 2015

Epilepsy, Ammon's horn sclerosis, and Camille Bouchet.

Authors:
Mervyn J Eadie

J Hist Neurosci 2017 Jul-Sep;26(3):231-237. Epub 2016 Sep 7.

a Faculty of Medicine and Biomedical Sciences , University of Queensland , Brisbane , Australia.

Increasing interest into the relationship between Ammon's horn sclerosis (hippocampal sclerosis) and epilepsy seems to have developed after 1880 when Sommer's paper appeared. Bouchet and Cazauvieilh had published the original description of the hippocampal anatomical abnormality in 1825 while attempting to locate the cerebral sites of origin of epilepsy and insanity. However, they offered no interpretation of the significance of the structural change. What has sometimes not been noticed in the subsequent literature is that, after a further investigation, in 1853, Bouchet described the change in 18 of 43 additional brains from persons with epilepsy. Despite this frequency of occurrence of the hippocampal abnormality, he concluded that epileptic seizures had no single site of origin in the brain. Before most of his contemporaries and their successors, he began to propose the idea that all epileptic seizures were symptoms of various, though mostly cerebral, disorders. In doing this, he tended to be reluctant to accept the view that epilepsy was a disease in its own right.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0964704X.2016.1224141DOI Listing
April 2018

Antiepileptic drug combinations not involving valproate and the risk of fetal malformations.

Epilepsia 2016 07 5;57(7):1048-52. Epub 2016 Jun 5.

Faculties of Medicine and Biomedical Science, University of Queensland, Brisbane, Queensland, Australia.

Objective: To investigate the relationship between antiepileptic drug (AED) polytherapy in pregnant women and the risk of fetal malformations as prescribing practice changed, with valproate being used less often and at lower doses. Specifically, the risks associated with two of the most common AEDs included in polytherapy over recent years, levetiracetam and topiramate, were examined.

Methods: An observational cohort study in which malformation rates were analyzed in 1,461 pregnancies exposed to AED monotherapy, and in 484 exposed to antiepileptic drug combinations, from the Australian Register of Antiepileptic Drugs in Pregnancy over a 15-year period (1999-2014).

Results: Fetal malformation rates had fallen over time in monotherapy pregnancies, but increased in polytherapy pregnancies, despite decreasing use and lower dosages of valproate. The rise in polytherapy malformation rates began around 2005 when levetiracetam and topiramate use began to increase. Excluding pregnancies involving valproate exposure, malformation rates were higher in the remaining polytherapy pregnancies as compared with the monotherapy ones (6.90% vs. 3.64%; odds ratio [OR] 1.96, 95% confidence interval [CI] 1.14-3.39). Malformation rates were similar in polytherapy pregnancies whether or not levetiracetam was included (7.14% vs. 8.38%), but were higher in polytherapy pregnancies involving topiramate (14.94% vs. 6.55%: OR 2.507, 95% CI 1.23-5.10). Logistic regression showed that topiramate in polytherapy had a positive dose relationship with teratogenicity risk (p = 0.025).

Significance: The malformation risk associated with AED polytherapy depends on the specific drugs involved. Topiramate, when used as part of AED polytherapy that did not include valproate, was associated with a dose-related increased risk of fetal malformations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.13415DOI Listing
July 2016

The clinical pharmacology of traditional antiepileptic drugs.

Epileptic Disord 2014 Dec;16(4):395-408

School of Health, Biomedical Science, University of Queensland, Brisbane, Australia.

Despite the availability of newer agents, a number of antiepileptic drugs have continued to be employed reasonably widely, many years after their introduction to human therapeutics. These drugs comprise phenobarbitone and some of its congeners, phenytoin, ethosuximide, carbamazepine, valproate, and certain benzodiazepines. Details of their pharmacological profiles are outlined in the following account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2014.0704DOI Listing
December 2014

Treating epilepsy in pregnant women.

Authors:
Mervyn J Eadie

Expert Opin Pharmacother 2014 Apr 10;15(6):841-50. Epub 2014 Mar 10.

University of Queensland, Honorary Consultant Neurologist, School of Medicine and Biomedical Science , 4th Floor, Ladhope Chambers, 131 Wickham Terrace, 4000 Brisbane , Australia +61 7 38311704 ; +61 7 33719886 ; M.Eadie@ uq.edu.au.

Introduction: The management of epilepsy during pregnancy involves achieving the best compromise between the sometimes competing aims of maintaining the well-being of the prospective mother and that of her foetus. Recently available knowledge helps achieve this by providing a better understanding of the hazards that intrauterine exposure to antiepileptic drugs holds for the development of the body structure and aspects of the intellect of the human foetus. The newer knowledge also helps explain why maternal seizure control may deteriorate during pregnancy, and how this risk may be avoided.

Areas Covered: A survey of the relevant English language literature concerning human epilepsy and pregnancy, foetal outcomes from pregnancy in women with epilepsy, and antiepileptic drug pharmacokinetics and clinical efficacy during pregnancy was carried out.

Expert Opinion: A mother's past history of foetal malformations, and the intake of valproate during a pregnancy, are significant factors in increasing the hazard of malformations during that pregnancy. Therefore, as far as reasonably possible, valproate use during pregnancy is better avoided. Full seizure control in the pre-pregnancy year, and adjusting antiepileptic drug doses to maintain plasma drug concentrations throughout pregnancy at values associated with seizure control before pregnancy, have major influences in preserving seizure control during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1517/14656566.2014.896902DOI Listing
April 2014

Dose dependence of fetal malformations associated with valproate.

Neurology 2013 Sep 2;81(11):999-1003. Epub 2013 Aug 2.

From the Department of Medicine and Neuroscience (F.J.V., T.J.O., J.E.G.), University of Melbourne, Royal Melbourne Hospital, Parkville; and University of Queensland (C.M.L., M.J.E.), Royal Brisbane Hospital, Brisbane, Australia.

Objective: To study the relationships between maternal valproate dose in pregnancy and the pattern of various fetal malformations.

Methods: Analysis of data in the Australian Register of Antiepileptic Drugs in Pregnancy collected from 1999 to 2012. The specific type of fetal malformation in offspring exposed to valproate in utero was correlated with the dose of valproate taken by the mother in the first trimester.

Results: Compared with other malformations, the mean dose of valproate taken during the first trimester was higher in mothers whose offspring had spina bifida (2,000 ± 707 vs 1,257 ± 918 mg/d) and hypospadias (2,417 ± 1,320 vs 1,235 ± 715 mg/d) (both p < 0.05). The overall mean maternal valproate dosage taken by women in the Register decreased over the last 5 years of the study period. This was paralleled by a statistically significant decrease in the rate of occurrence of spina bifida and hypospadias, but not other malformations.

Conclusions: Human fetal malformations associated with valproate exposure during pregnancy do not all seem to bear the same quantitative relationship to drug dose, and reduction in valproate dose in earlier pregnancy is likely to offer greater dividends in protecting against spina bifida and hypospadias than against other types of fetal malformations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0b013e3182a43e81DOI Listing
September 2013

Shortcomings in the current treatment of epilepsy.

Authors:
Mervyn J Eadie

Expert Rev Neurother 2012 Dec;12(12):1419-27

Faculty of Health Sciences, University of Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD 4027, Australia.

Contemporary drug therapy fails to control epileptic seizures in some 30% of patients, resulting in the need to employ other measures when they appear practicable. A good deal of potentially relevant statistical detail is available regarding the outcomes of the available antiepileptic therapies, but its interpretation is sometimes difficult because of uncertainty about the types of epilepsy to which it applies, and because of deficiencies in knowledge of the natural histories of the various epileptic syndromes, if untreated. The actual shortcomings in the contemporary treatment of epilepsy appear to arise not only from the limited curative capacities of the available therapies, but from a number of deficiencies in knowledge concerning the significant aspects of what should determine treatment policy and the optimal employment of antiepileptic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1586/ern.12.129DOI Listing
December 2012

William Gowers: the never completed third edition of the 'Bible of Neurology'.

Brain 2012 Oct 3;135(Pt 10):3178-88. Epub 2012 Sep 3.

Faculty of Health Sciences, University of Queensland, Brisbane 4027, Australia.

William Gowers' classic single-authored two-volume A manual of diseases of the nervous system appeared in a first edition in 1886 and 1888, and in a second edition in 1892 and 1893, with a third edition of Volume 1 in 1899. No third edition of Volume 2 ever appeared. However, in 1949 Critchley stated that he had seen part of a revision of this volume. Subsequent writers could not find this material, but it recently came to light at Gowers' old hospital at Queen Square, London. The present paper describes the rediscovered material, containing Gowers' handwritten alterations for a further edition of Volume 2, and substantial new material, at least in relation to nystagmus and myasthenia. Gowers' declining health, or a conflict between his planned new text and his contributions to the neurology segments (1899) of Allbutt's System of medicine, may explain why a third edition of Volume 2 of the Manual of diseases of the nervous system never appeared.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/aws181DOI Listing
October 2012

Teratogenesis in repeated pregnancies in antiepileptic drug-treated women.

Epilepsia 2013 Jan 6;54(1):181-6. Epub 2012 Aug 6.

Departments of Medicine and Neurology, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Purpose: Considerable information is now available concerning the risk of teratogenesis in the individual pregnancy exposed to antiepileptic drugs (AEDs). However, there is comparatively little information available concerning the risk in the subsequent pregnancies of women who continue to take the AED associated with a fetal malformation in a previous pregnancy. This article addresses this matter.

Methods: Analysis of data concerning fetal abnormalities in 1,243 women who had 2,637 pregnancies between mid-1999 and 2010 recorded in the Australian Register of Antiepileptic Drugs in Pregnancy. Of the 2,637 pregnancies, 1,114 had been completed before initial enrolment in the Register.

Key Findings: Women taking any AED who had given birth to a malformed baby in their first enrolled pregnancy and who continue taking the same drug were at increased risk of having a malformed offspring in their next pregnancy (35.7% vs. 3.1%; odds ratio [OR] 17.6; 95% confidence interval [95% CI] 4.5-68.7). Among these women, those taking valproate (VPA) were more likely to have malformed fetuses in their next pregnancies than those who had taken VPA without fetal abnormalities (57.2% vs. 7.0%, OR 17.8; 95% CI 2.7, 119.1). There were similar although not statistically significant trends in those who had taken AEDs other than VPA. Similar, although again not statistically significant, trends were found, when considering the pairings of the most recent preenrollment pregnancy and the following one. If a woman had two or more pregnancies that resulted in AED-associated fetal malformation, the types of malformation were often different.

Significance: Women whose last pregnancy resulted in a fetal malformation have a substantially increased risk of having further malformed fetuses if they become pregnant again while taking the same AED, particularly VPA. This suggests that maternal factors, perhaps genomic, predispose to at least VPA-associated malformations. This knowledge, together with information about the outcome of any previous pregnancy, should help in advising women with AED-treated epilepsy who plan further pregnancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2012.03625.xDOI Listing
January 2013

W R Gowers 1895: two unpublished post-graduate lectures.

Brain 2012 Oct 6;135(Pt 10):3165-77. Epub 2012 Mar 6.

The National Hospital for Neurology and Neurosurgery Queen Square London and the Reta Lila Weston Institute for Neurological Studies, University College London, UK.

On 10 May 1893, William Gowers began a series of weekly clinical demonstrations at the National Hospital for the Relief and Cure of the Paralysed and Epileptic at Queen Square, London. The contents of some of these demonstrations were published as 'Post-graduate Clinical Lectures' in the Clinical Journal, and in other learned periodicals. Some were also later included in his book Clinical Lectures on Diseases of the Nervous System. Recently, the manuscripts of what appear to be verbatim transcripts of two further but unpublished demonstrations from Gowers' course in 1895 came to light, one containing alterations made in Gowers' handwriting. The first concerned a case of disseminated sclerosis and its differentiation from hysterical paraplegia, the second transverse myelitis and its consequences for bladder function. Why these lectures were never published remains uncertain, but their relatively unedited contents reveal something of the neurological knowledge, diagnostic reasoning, clinical examination and teaching methods employed by one of the great pioneers of clinical neurology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/aws029DOI Listing
October 2012

The prescribing of antiepileptic drugs for pregnant Australian women.

Aust N Z J Obstet Gynaecol 2012 Feb 12;52(1):49-53. Epub 2011 Sep 12.

Department of Medicine and Neurosciences, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Background: It is not clear how widely it is appreciated in Australia that certain antiepileptic drugs, particularly valproate, are teratogenic.

Aim: The aim of the study is to assess trends in the pattern of antiepileptic drug prescribing for pregnant women in Australia to determine whether drug use is optimal, particularly from the fetal viewpoint.

Methods: Analysis of data contained in the Australian Register of Antiepileptic Drugs, assessing trends in antiepileptic drug use correlated with pregnancy outcomes.

Results: Valproate was the only significant teratogen among the antiepileptic drugs in common use. There was a fetal malformation rate of 14.5% associated with its use in monotherapy, as compared with a rate of 3.15% in antiepileptic drug-unexposed pregnancies in women with epilepsy (OR = 5.23, 95% CI = 1.81, 15.09). The highest malformation rate associated with any other antiepileptic drug used in monotherapy was 5.0%, for carbamazepine. Neurologists had progressively prescribed valproate less frequently and in lower dosage than other classes of practitioner over the 10-year study period, with a parallel decrease in occurrence of fetal malformations in pregnancies referred to the Register. Other prescribers of valproate did not seem to have adopted these practices to the same extent and had not obtained similar degrees of reduction in the occurrence of fetal malformations.

Conclusions: Contemporary Australian obstetricians, even though they may not be valproate prescribers, when managing pregnancies in women taking valproate, need to be alert to the possibility that it may not be being used optimally from the fetal point of view, especially when not prescribed by neurologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1479-828X.2011.01359.xDOI Listing
February 2012

William Gowers' interpretation of epileptogenic mechanisms: 1880-1906.

Authors:
Mervyn J Eadie

Epilepsia 2011 Jun 22;52(6):1045-51. Epub 2011 Mar 22.

Central Clinical School, University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

In the 1870s, early in his neurologic career, William Gowers (1845-1911) was exposed to three main schools of thought concerning epileptogenesis, namely, that seizures resulted from (1) excessive neural activity in the medulla oblongata or pons (Marshall Hall, John Russell Reynolds, and Brown-Séquard), (2) excessive local cerebral cortical activity (Hughlings Jackson), or (3) suddenly decreased cerebral activity that released the intrinsic contractibility of skeletal muscle (Radcliffe). By 1881, Gowers had reasoned his way to the idea that epileptogenesis was best accounted for by local cortical overactivity. This overactivity might at times be initiated by local loss of inhibition. The overactivity in turn then might inhibit other parts of the central nervous system to explain loss of consciousness in seizures and postseizure temporary hemiparesis. The possibilities of the idea of inhibition, at first often called "resistance," continued to interest Gowers over the following 25 years. He settled on the synaptic gap as its likely site. However, the inhibition mechanism that he proposed, namely, retraction of dendrites, was rather extraordinary in the light of subsequent knowledge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2011.02983.xDOI Listing
June 2011

Utilization of anti-Parkinson drugs in Australia: 1995-2009.

Pharmacoepidemiol Drug Saf 2011 May 15;20(5):450-6. Epub 2011 Feb 15.

The University of Queensland, School of Population Health, Herston, Australia.

Purpose: To examine trends in the prescribing of anti-Parkinsonian drugs (APD) in Australia from 1995 to 2009.

Methods: We analyzed the Medicare Australia and Drug Utilisation Sub-Committee (DUSC) databases for prescription data for overall APD dispensed use from 1995. We were able to examine prescribing by gender, age, and type of prescriber between 2002 and 2009. Prescriptions were converted to defined daily doses (DDD)/1000 population/day using Australian Bureau of Statistics population data.

Results: Dispensed use of levodopa + carbidopa remained steady from 1995 to 2009 (0.76-0.82 DDD/1000 population/day); levodopa + benserazide use increased from 0.34 to 0.55 DDD/1000 population/day. Since 2005 dispensed use of levodopa + carbidopa + entacapone has steadily increased, from 0.03 to 0.10 DDD/1000 population/day. In July 2009 levodopa + carbidopa was the most widely used agent, followed by levodopa + benserazide, then benztropine. Cabergoline increased from 1999, peaked in 2006, and thereafter declined. APD use peaked in males and females aged 60-69 years. Age-adjusted utilization was slightly higher in males than females.

Conclusions: The amount of levodopa dispensed has slowly increased with levodopa + benserazide increasing faster than levodopa + carbidopa. Use of cabergoline fell when pramipexole became available and the risk of ergot-related serosal adverse effects was more widely appreciated. Use of centrally acting anti-cholinergics decreased over a period of time when use of atypical anti-psychotic agents increased.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pds.2114DOI Listing
May 2011

The idea of epilepsy as a disease per se.

J Hist Neurosci 2010 Jul;19(3):209-20

Central Clinical School (University of Queensland), Royal Brisbane and Women's Hospital, Herston, Australia 4027.

In the 1850s Delasiauve and Russell Reynolds independently introduced the idea that the previously more inclusive concept of "epilepsy" should be restricted to that of an idiopathic disease manifesting epileptic seizures not caused by detectable brain pathology. This idea was rather widely accepted, though with some modification, over much of the next century. However there was increasing opposition to the idea from those, including John Hughlings Jackson, who perceived that all epileptic seizures must be symptoms of underlying brain disease. With increasing identification of structural brain pathology in what had been regarded as instances of idiopathic epilepsy, the latter view has increasingly prevailed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09647040902802822DOI Listing
July 2010

The teratogenic risk of antiepileptic drug polytherapy.

Epilepsia 2010 May 8;51(5):805-10. Epub 2009 Oct 8.

Department of Medicine and Neurosciences, Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia.

Purpose: To compare the risks of fetal malformation during pregnancy associated with antiepileptic drug (AED) polytherapy and monotherapy.

Methods: Statistical analysis of malformation rate and antiepileptic drug exposure data from the Australian Register of Antiepileptic Drugs in Pregnancy, and from the literature.

Results: The calculated relative risk (RR) value for AED polytherapy compared with monotherapy was below 1.0 in only 3 of 14 literature publications. In the register, at 1 year postnatally there were fetal malformations in 5.32% of 282 AED polytherapy pregnancies, and in 7.84% of 791 AED monotherapy pregnancies, an RR of 0.68 [95% confidence interval (CI) 0.39-1.17). For pregnancies exposed to valproate, the RR of fetal malformation (0.39, 95% CI 0.20-0.89) was lower in polytherapy (7.26%) than in monotherapy (17.9%); the difference did not depend on valproate dosage. The RR values for fetal malformation were not significantly different for AED polytherapy and monotherapy when valproate was not involved. Logistic regression suggested that coadministration of lamotrigine may have reduced the malformation risk from valproate.

Discussion: The fetal hazard of AED polytherapy relative to monotherapy may depend more on the degree of exposure to valproate than on the fact of polytherapy per se. Coadministration with lamotrigine may lower the fetal risk of valproate therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2009.02336.xDOI Listing
May 2010

Antiepileptic drugs in Australia: 2002-2007.

Pharmacoepidemiol Drug Saf 2010 Jan;19(1):82-9

School of Population Health, University of Queensland, Herston, QLD 4006, Australia.

Purpose: With the marketing of a number of new antiepileptic drugs (AEDs) in recent years it seemed possible that the pattern of Australian prescribing for patients with epilepsy may have been changing. We examined the trends in the prescribing of subsidised AEDs in the Australian population from 2002 to 2007.

Methods: We analysed the Medicare Australia and Drug Utilisation Sub-Committee databases for script data for AEDs from 2002 to 2007 in 5-year age groups by gender and by class of prescriber. Scripts were converted to defined daily doses (DDDs)/1000/day using Australian Bureau of Statistics population data.

Results: Overall AED use (mainly valproate, lamotrigine and levetiracetam) increased progressively in 2002-2007 from 9.33 to 10.12 DDD/1000 population/day. Sodium valproate was the most widely used agent followed by carbamazepine then phenytoin. Amount of AED used increased in those aged in their 20s and 30s to plateau between 40 and 90 years. Use peaked in those aged 80-84 years and was slightly higher in males than females.

Conclusions: The rate of increase in the prescribing of AEDs remained steady between 2002 and 2007. The gender differences in prescribing reflect the higher prevalence of epilepsy in men and higher individual dosages used when many AEDs are prescribed on a body weight basis. The high use of some of these drugs in elderly people (> or =80 years) warrants further exploration. There is growing use of lamotrigine and gabapentin for indications apart from epilepsy-most likely neuropathic pain and mood disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pds.1871DOI Listing
January 2010

Experimental epileptology before 1900.

Authors:
Mervyn J Eadie

Epilepsia 2009 Mar;50(3):377-386

Central Clinical School, University of Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia.

The available English and other major Western European language literature was reviewed to assess the stage of development of experimental epileptology prior to the end of the 19th Century. The relevant investigations had been carried out in animals of various species employing a number of methods of evoking convulsive seizures, mainly mechanical, electrical or chemical stimulation or surgical removal of parts of the cerebral cortex. The studies had produced some conflicting data but (i) allowed the development of a number of reasonably satisfactory experimental models of convulsive epileptic seizures (ii) confirmed that such epileptic seizures arose from the cerebral cortex, and (iii) suggested that for local onset epileptic seizures to become generalised tonic-clonic ones, the opposite motor cortex and probably a brain stem, possibly pontine, centre needed to be involved. No generally acceptable animal model of chronic epilepsy had been developed, and the non-motor manifestations of epileptic seizures were still largely unexplored experimentally. Nevertheless, the pre-1900 investigations not only laid the foundations for the 20th Century expansion of experimental studies on epileptogenesis but also advanced the understanding of epileptic seizure production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2008.01895.xDOI Listing
March 2009

Samuel Wilks (1824-1911): neurologist and generalist of the Mid-Victorian Era.

Authors:
Mervyn J Eadie

J Med Biogr 2008 Nov;16(4):215-20

Department of Medicine, Central Clinical School, University of Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia.

Sir Samuel Wilks, sometime Physician to Guy's Hospital and President of the Royal College of Physicians (1896-99), was regarded as the leading British scientific physician of his day. His contributions to gastroenterology, cardiology and clinical science in general have been emphasized in recent times. He also recognized that syphilis affected the internal organs as well as the skin. In 1866 he realised that epileptogenesis occurred in the cerebral cortex: independently of Sir Charles Locock (1799-1875), he discovered the antiepileptic properties of potassium bromide. He provided possibly the first account of alcoholic peripheral neuritis and published an early account of probable myasthenia gravis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1258/jmb.2007.007042DOI Listing
November 2008

Should valproate be taken during pregnancy?

Ther Clin Risk Manag 2005 Mar;1(1):21-6

The Australian Registry of Antiepileptic Drug Use in Pregnancy includes 172 instances in which women took sodium valproate, with or without other antiepileptic drugs, during pregnancy. These pregnancies resulted in a substantially higher (p < 0.05) rate of malformed offspring (15.1%) compared with 348 pregnant women who took antiepileptic drugs other than valproate (2.3%) and 40 pregnancies in epileptic women who took no antiepileptic drugs (2.5%). At valproate doses of 1400 mg and below per day, the mean rate of pregnancies with fetal malformations was 6.42% and did not seem to be dose-dependent. At higher valproate doses, the mean rate of pregnancy with fetal malformation was 33.9% and appeared to increase with increasing drug dosage. This finding suggests the need for reappraisal of the use of valproate in women who may become pregnant or are pregnant whilst the drug is taken. The therapeutic policy adopted may depend on whether valproate doses below 1400 mg per day are regarded as safe for the fetus. This study indicates that the risk of malformation associated with such doses was just statistically significantly (p < 0.05) higher than that associated with other antiepileptic drugs. Various possible clinical scenarios are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1661607PMC
http://dx.doi.org/10.2147/tcrm.1.1.21.53605DOI Listing
March 2005

Antiepileptic drugs as human teratogens.

Authors:
Mervyn J Eadie

Expert Opin Drug Saf 2008 Mar;7(2):195-209

University of Queensland, and Royal Brisbane and Women's Hospital, Herston, Brisbane, Australia 4029, Australia.

Background: There is still uncertainty concerning the risk of fetal malformation associated with the intake of various individual antiepileptic drugs in pregnant women.

Objective: To assess the better-quality available evidence concerning the fetal hazards from exposure to antiepileptic drug monotherapy during human pregnancy.

Method: Examination of the available English language literature, particularly that dealing with individual antiepileptic drugs used in monotherapy, in the larger case series with better-quality internal comparison data.

Conclusions: There is reasonable evidence that valproate is a significant teratogen during therapeutic use in women; the other older antiepileptic drugs (phenobarbitone, phenytoin, carbamazepine) probably have some teratogenic potential, but less than valproate; the situation regarding the more recently marketed antiepileptic drugs is not yet clear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1517/14740338.7.2.195DOI Listing
March 2008