A recurrent nova super-remnant in the Andromeda galaxy.

The accretion of hydrogen onto a white dwarf star ignites a classical nova eruption1,2-a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of insterstellar medium). Close to the upper mass limit of a white dwarf3 (1.4 solar masses), rapid accretion of hydrogen (about 10-7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years4,5 to decades6. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second7, must 'sweep up' the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known8-10, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually11, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions12, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years.

Neurological factors and Cesarean section in Australian women with epilepsy.

OBJECTIVES: To analyze the records of the pregnancies of 2283 Australian women with epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy database to identify neurological factors relevant to the Cesarean sections carried out in these pregnancies. RESULTS: The Cesarean section rate in Australian women overall increased by an average of 0.59% annually over 20 years, from 26.0% to its calculated 2020 value of 37.3%. For the operations in women with epilepsy, the corresponding figures were 0.71% annually, and 34.4% and 48.7%. The average annual rate of increase for pre-labor operations was 0.89% to a 2020 value of 39.1%, the annual rate for operations during labor showing no statistically significant change. Multivariate regression analysis identified a number of characteristics of women with epilepsy that were statistically significantly associated with an increased likelihood of Cesarean section, but of these only seizures continuing to occur in the third trimester and having chronic illness, in particular migraine, were neurological ones. In 70 migraine-affected women, the Cesarean section rate was 51.4%, compared with 39% in the remaining pregnancies (P < 0.05). CONCLUSIONS: Having seizures in the final trimester of pregnancy and having chronic neurological illness, especially migraine, favored Cesarean section being carried out in Australian women with epilepsy, but did not adequately account for the increasing rates of occurrence of the operation over the past 20 years.

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae.

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel about 10(-4) solar masses of material at velocities exceeding 1,000 kilometres per second. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of thermonuclear energy, prolonged optically thick winds or binary interaction with the nova envelope. Classical novae are now routinely detected at gigaelectronvolt γ-ray wavelengths, suggesting that relativistic particles are accelerated by strong shocks in the ejecta. Here we report high-resolution radio imaging of the γ-ray-emitting nova V959 Mon. We find that its ejecta were shaped by the motion of the binary system: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of γ-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are γ-ray emitters.

Antiepileptic drug polytherapy in pregnant women with epilepsy.

OBJECTIVE: To study seizure control and rates of foetal malformation in pregnancies of women with epilepsy treated with antiepileptic drug polytherapy. METHODS: The use of conventional statistical methods to analyse the Australian Pregnancy Register records of 1810 pregnancies in women with epilepsy, 508 treated with antiepileptic drug polytherapy. RESULTS: Polytherapy-treated pregnancies were less often seizure free than monotherapy-treated ones, for both focal (36.0% vs 51.9%: P < .05) and primary generalized epilepsies (41.1% vs 69.3%; P < .05). Drug combinations with dissimilar and similar mechanisms of action achieved similar rates of seizure freedom during pregnancy (36.3% vs 38.3%). The increased rate of malformed foetuses in polytherapy pregnancies depended on valproate or topiramate being in the drug combinations. The combinations of lamotrigine and levetiracetam offered the chance of seizure control and foetal safety. CONCLUSIONS: In pregnancy, the use of antiepileptic drug combinations is not necessarily disadvantageous to mother and foetus if valproate and topiramate are avoided.

Anti-epileptic drug exposure and risk of foetal death in utero.

OBJECTIVE: To clarify whether anti-epileptic drug exposure during pregnancy is associated with an increased risk of intrauterine foetal death. METHODS: Analysis of data from 2064 pregnancies with known outcomes included in the Australian Register of Antiepileptic Drugs in Pregnancy, 170 of the pregnancies being unexposed to the drugs in at least the first half of pregnancy. RESULTS: The relative risk (6.46; 95% C.I. 0.90, 46.22) of intrauterine death appeared higher, though not statistically significantly higher, in drug-exposed pregnancies compared with unexposed ones (3.44% vs 0.59%). There was no statistically significantly increased hazard associated with AED polytherapy as compared with monotherapy. Logistic regression analysis showed a statistically significantly increased and dose-related hazard of intrauterine death in relation to carbamazepine exposure. CONCLUSIONS: Intrauterine exposure to anti-epileptic drugs, particularly carbamazepine, may be associated with an increased risk of foetal death during pregnancy.

Predicting epileptic seizure control during pregnancy.

OBJECTIVE: The objective of the study was to assess whether the type of seizure disorder present in the prospective mother with epilepsy, her use of antiepileptic drugs (AEDs) in early pregnancy, and her seizure control before pregnancy help predict her prospects for seizure freedom throughout pregnancy. METHODS: This paper is based on data accumulated in the Australian Pregnancy Register (APR) between 1998 and late 2016. Information was analyzed concerning epileptic seizure occurrence and AED therapy taken before and during pregnancy, using simple statistical and confidence interval (C.I.) methods, mainly relative risk (R.R.) calculations. RESULTS: After excluding pregnancies lost to follow-up, and those that ended prematurely because of spontaneous abortion or stillbirth, 1939 pregnancies were available for study. Seizures had occurred during pregnancy in 829 (42.8%), and convulsive seizures in 385 (19.9%). Seizures of any type occurred in 78.4% of pregnancies where seizures had occurred in the previous year (active epilepsy) and in 22.3% of those associated with inactive epilepsy. Seizures of any type had occurred in 54.9% of pregnancies initially unexposed to AEDs and in 45.5% of those treated with AEDs throughout. The corresponding figures for convulsive seizures during pregnancy were 31.7% and 22.3%. There was statistically significant evidence that, in women with epilepsy (WWE), having a seizure disorder that was active in the prepregnancy year and one untreated in early pregnancy was associated with decreased prospects of seizure freedom during pregnancy. Decreased chances of seizure-free pregnancies in women with focal epilepsies and those treated with multiple AEDs were probably explained by greater frequencies of active seizure disorders in these patient categories. CONCLUSIONS: Women with epilepsy who experience seizures in the year prior to pregnancy appear 3 or 4 times more likely to continue to have seizures during pregnancy than women whose seizures are fully controlled prior to pregnancy. Not taking AEDs in early pregnancy also increases the hazard for seizure occurrence in pregnancy.

Bone loss with antiepileptic drug therapy: a twin and sibling study.

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility. INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031). CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Antiepileptic drugs, foetal malformations and spontaneous abortions.

BACKGROUND: Some recent studies have found an association between foetal malformations in earlier antiepileptic drug (AED)-exposed pregnancies and an increased hazard of such malformations in subsequent pregnancies. We investigated this matter further, and also considered the possible role of spontaneous abortions in previous pregnancies, in this situation. METHODS: Analysis of foetal malformation data for current and previous pregnancies in women taking AEDs and women with untreated epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy (APR) from 1999 to late 2014. RESULTS: Antiepileptic drug-treated women with either a malformed foetus or a spontaneous abortion in their previous pregnancy had a statistically significant twofold to threefold increased risk of foetal malformation in their next pregnancy, compared with similarly treated women with normal offspring in their previous pregnancy. This was not seen in the same circumstances in women with untreated epilepsy. On AED treatment, the women were more likely to have spontaneous abortions than in their previous untreated pregnancies. Possibly some of the increased abortion rate resulted from drug-related malformations that were incompatible with continuing intrauterine survival. CONCLUSIONS: In assessing the hazard of an AED-treated woman having a malformed foetus, it is important to know both the AEDs being taken and, if there had been a previous pregnancy, whether a foetal malformation or a spontaneous abortion occurred in it.

Does pregnancy per se make epilepsy worse?

OBJECTIVE: To determine whether being pregnant in its own right alters epileptic seizure control. MATERIALS/METHODS: Study of 148 pregnancies in women who took no antiepileptic drugs before pregnancy and in at least the earlier half of pregnancy, 69 taking none throughout pregnancy. RESULTS: More women (P < 0.01) had seizures of any type during pregnancy (45.9%) than in the prepregnancy year (34.5%), and also convulsive seizures (30.4% vs 12.3%). After excluding potential confounding factors, viz. late prepregnancy drug withdrawal, treatment resumption in pregnancy possibly preventing seizure recurrence, the figures became seizures of any type 56.6% during and 35.5% before pregnancy and convulsive seizures 39.4% during and 18.2% before pregnancy (both P < 0.01). There was a non-statistically significant greater tendency for seizure control to be lost during pregnancy in genetic generalized than in focal epilepsies (54.2% vs 35.5%). CONCLUSIONS: Irrespective of its effects on antiepileptic drug disposition, being pregnant per se seems to impair epileptic seizure control.

Sodium selenate treatment mitigates reduction of bone volume following traumatic brain injury in rats.

OBJECTIVES: Administration of sodium selenate to rats given traumatic brain injury (TBI) attenuates brain damage and improves long-term behavioural outcomes. We have previously provided evidence that TBI causes bone loss in rats, however the effect of sodium selenate treatment on bone quantity following TBI is unknown. METHODS: Rats were randomly assigned into sham injury or fluid percussion injury (FPI) groups and administered saline or sodium selenate for 12 weeks post-injury. Femora were analysed using histomorphometry, peripheral quantitative computed tomography (pQCT) and biomechanical testing. RESULTS: Distal metaphyseal trabecular bone volume fraction of FPI-selenate rats was higher than FPI-vehicle rats (41.8%; p<0.01), however, femora from selenate-treated groups were shorter in length (4.3%; p<0.01) and had increased growth plate width (22.1%; p<0.01), indicating that selenate impaired long bone growth. pQCT analysis demonstrated that distal metaphyseal cortical thickness was decreased in TBI rats compared to shams (11.7%; p<0.05), however selenate treatment to TBI animals offset this reduction (p<0.05). At the midshaft we observed no differences in biomechanical measures. CONCLUSION: These are the first findings to indicate that mitigating TBI-induced neuropathology may have the added benefit of preventing osteoporosis and associated fracture risk following TBI.

Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans.

Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R(2)=0.27) than the IWPC pharmacogenomics (R(2)=0.15) or clinical (R(2)=0.16) algorithms. Among high-dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC pharmacogenomics and clinical algorithms, respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry was observed for the IWPC pharmacogenomics algorithm among patients requiring ⩾60 mg per week (ß=-2.04, P=0.02).

Glutamate quantification in patients with supratentorial gliomas using chemical shift imaging.

This study aimed to evaluate and validate chemical shift imaging (CSI) for in vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If validated, CSI could become an extremely useful tool to investigate metabolic dysfunction of Glu in excitotoxic neuropathologies. Quantitative CSI estimates of Glu concentrations were compared with known concentrations of Glu in aqueous phantom solutions. Forty-one patients with known or likely supratentorial gliomas underwent preoperative CSI. The spectra obtained were analyzed for Glu concentrations and Glu to creatine (Cr) ratios. These in vivo measurements were correlated against ex vivo Glu content quantified by high performance liquid chromatography (HPLC) measured in 65 resected brain tumor and peritumoral brain specimens. For the phantom solutions the CSI estimates of Glu concentration and the Glu/Cr ratios were highly correlated with known Glu concentration (r² = 0.95, p = 0.002, and r² = 0.97, p < 0.0001, respectively). There was a modest, but statistically significant, correlation between the ex vivo measured Glu and in vivo spectroscopic Glu concentration (r² = 0.22, p = 0.04) and ratios of Glu to Cr (r² = 0.30, p = 0.002). Quantitative measurement of Glu content is feasible in patients with supratentorial gliomas using CSI. The in vitro and in vivo results suggest that this has the potential to be a reliable quantitative imaging assay for brain tumor patients. This may have wide clinical research applications in a number of neurological disorders where Glu excitotoxicity and metabolic dysfunction are known to play a role in pathogenesis, including tumor associated epilepsy, epilepsy, stroke and neurotrauma.

The teratogenicity of the newer antiepileptic drugs - an update.

OBJECTIVE: To assess the risk of teratogenicity from maternal intake of the more widely used newer antiepileptic drugs, especially lamotrigine, levetiracetam and topiramate. MATERIALS AND METHODS: Use of confidence interval and regression methods to compare risks of foetal malformation in pregnancies in women exposed (n = 1572) and in women with epilepsy not exposed (n = 153) to antiepileptic drugs in the first trimester. RESULTS: Compared with the foetal malformation rate in women with epilepsy who were untreated in the first trimester (3.3%), the malformation rates for lamotrigine (4.6%), levetiracetam (2.4%) and topiramate (2.4%), all in monotherapy, were not statistically significantly different. However, the malformation rates for topiramate as part of polytherapy (14.1%) and for valproate in both monotherapy (13.8%) and polytherapy (10.2%) were statistically significantly higher. Regression analysis of combined monotherapy and polytherapy data showed no statistically significant increased risk of teratogenesis associated with lamotrigine or levetiracetam, but a statistically significant and dose-related risk for first trimester topiramate (P = 0.01) and valproate (P < 0.0001) exposure. CONCLUSIONS: Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.

Manganese-enhanced MRI reflects seizure outcome in a model for mesial temporal lobe epilepsy.

The neurobiological processes resulting in epilepsy, known as epileptogenesis, are incompletely understood. Manganese-enhanced MRI (MEMRI) can potentially aide in this quest as it provides superior tissue contrast, particularly of the hippocampal subregions. This longitudinal study aims to characterise the changes in the hippocampus of the post kainic acid-induced status epilepticus (KASE) rat model of mesial temporal lobe epilepsy using MEMRI in vivo. Serial acquisition of T(1)-weighted MEMRI images were taken before, 2 days and 6 weeks after KASE (10-30 mg/kg, i.p.) in 14 rats and in 11 control rats, while a second cohort of control (N=6) and epileptic animals (N=10) was imaged at 2 months post KASE only. MnCl(2) (50 mM, 10 µl) was administered in the right lateral ventricle 1 day before scanning. Regions of interest were drawn around the hippocampus and several subregions of the hippocampus (CA1, CA3 and dentate gyrus). Markers of epilepsy such as spontaneous recurrent seizures, hippocampal neuronal loss and mossy fiber sprouting were quantified. A persistent increase in MEMRI signal intensity was found in the hippocampus, CA1 and dentate gyrus in the KASE group compared to the control group (ANOVA P<0.05). The intensity signal in the hippocampus and subregions correlated inversely with the frequency of spontaneous recurrent seizures in the chronic epileptic phase, however there was no relationship observed between histopathological changes such as cell loss and mossy fiber sprouting with seizures. This study demonstrates that MEMRI is able to detect imaging changes in the hippocampus during the course of epileptogenesis relevant for seizure expression. These data strongly indicate a relationship between manganese enhancement and spontaneous seizure outcome, suggesting that MEMRI could provide a preclinical biomarker for the severity of epileptogenesis in vivo in animal models.

Associations between particular types of fetal malformation and antiepileptic drug exposure in utero.

OBJECTIVE: To study associations between patterns of fetal malformation and individual antiepileptic drugs taken during pregnancy. METHODS: Multiple variable logistic regression and other statistical analyses of data relating to 1733 fetuses from 1703 pregnancies (147 of which were not exposed to antiepileptic drugs during pregnancy). RESULTS: There were statistically significant (P < 0.05) associations between (i) valproate exposure and spina bifida, malformations of the heart and great vessels, digits, skull bones, and brain, but not hypospadias, cleft palate/lip and mouth abnormalities, (ii) topiramate exposure and hypospadias and brain maldevelopments, and (iii) carbamazepine (CBZ) exposure and renal tract abnormalities. CONCLUSIONS: The valproate findings are mostly in keeping with the published literature, but the topiramate finding regarding hypospadias and the association between CBZ exposure and various renal tract abnormalities raise questions of organ specific teratogenesis. More extensive data are desirable, particularly in relation to topiramate, which is being used increasingly as a migraine prophylactic in women of childbearing potential.

Ictal face perception disturbance, tattoos, and reclaiming the self.

We present a case of a young man with frightening ictal disturbance of face perception, or prosopometamorphopsia, arising from the left temporo-occipital region, leading to significant psychosocial impairment. A vivid forearm tattoo of the ictal experience conveyed its nature to the treating team and facilitated a psychotherapeutic process leading to significant psychosocial recovery. This case highlights the marked psychosocial and developmental impacts of epilepsy and the benefit of incorporating these into assessment and treatment.

Automated Interictal Epileptiform Discharge Detection from Scalp EEG Using Scalable Time-series Classification Approaches.

Deep learning for automated interictal epileptiform discharge (IED) detection has been topical with many published papers in recent years. All existing works viewed EEG signals as time-series and developed specific models for IED classification; however, general time-series classification (TSC) methods were not considered. Moreover, none of these methods were evaluated on any public datasets, making direct comparisons challenging. This paper explored two state-of-the-art convolutional-based TSC algorithms, InceptionTime and Minirocket, on IED detection. We fine-tuned and cross-evaluated them on a public (Temple University Events - TUEV) and two private datasets and provided ready metrics for benchmarking future work. We observed that the optimal parameters correlated with the clinical duration of an IED and achieved the best area under precision-recall curve (AUPRC) of 0.98 and F1 of 0.80 on the private datasets, respectively. The AUPRC and F1 on the TUEV dataset were 0.99 and 0.97, respectively. While algorithms trained on the private sets maintained their performance when tested on the TUEV data, those trained on TUEV could not generalize well to the private data. These results emerge from differences in the class distributions across datasets and indicate a need for public datasets with a better diversity of IED waveforms, background activities and artifacts to facilitate standardization and benchmarking of algorithms.

The prevalence and demographic distribution of treated epilepsy: a community-based study in Tasmania, Australia.

OBJECTIVES: To estimate the prevalence and demographic distribution of treated epilepsy in a community-based population. MATERIALS & METHODS: We surveyed all residents in Tasmania, Australia, who were supplied at least one antiepileptic drug prescription between July 1, 2001 and June 30, 2002, recorded on the national prescription database. We adjusted for the effect of disease-related non-response bias by imputation methods. RESULTS: After three mail contacts, 54.0% (4072/7541) responded, with 1774 (43.6%) indicating treatment for epilepsy, representing 86.0% of the estimated total possible cases in Tasmania. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39); lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00)); greater with increasing age (P < 0.001); similar in the three main geographic regions; and similar with socioeconomic status of postcode of residence. CONCLUSIONS: Although our estimates are likely to be affected by access to health services, overall treated epilepsy prevalence of 4.4 per 1000 is similar to previous studies. Our finding of high elderly prevalence has been reported in a few recent studies in developed countries and has important clinical and public health implications in populations with similar aging demographics.

An asymmetric shock wave in the 2006 outburst of the recurrent nova RS Ophiuchi.

Nova outbursts take place in binary star systems comprising a white dwarf and either a low-mass Sun-like star or, as in the case of the recurrent nova RS Ophiuchi, a red giant. Although the cause of these outbursts is known to be thermonuclear explosion of matter transferred from the companion onto the surface of the white dwarf, models of the previous (1985) outburst of RS Ophiuchi failed to adequately fit the X-ray evolution and there was controversy over a single-epoch high-resolution radio image, which suggested that the remnant was bipolar rather than spherical as modelled. Here we report the detection of spatially resolved structure in RS Ophiuchi from two weeks after its 12 February 2006 outburst. We track an expanding shock wave as it sweeps through the red giant wind, producing a remnant similar to that of a type II supernova but evolving over months rather than millennia. As in supernova remnants, the radio emission is non-thermal (synchrotron emission), but asymmetries and multiple emission components clearly demonstrate that contrary to the assumptions of spherical symmetry in models of the 1985 explosion, the ejection is jet-like, collimated by the central binary whose orientation on the sky can be determined from these observations.

Changes in hippocampal GABAA/cBZR density during limbic epileptogenesis: relationship to cell loss and mossy fibre sprouting.

Reduced GABA(A)/central benzodiazepine receptor (GABA(A)/cBZR) density, mossy fibre sprouting (MFS) and hippocampal cell loss are well described pathological features of human temporal lobe epilepsy (TLE), and animal models thereof. However, the temporal relationship of their development, and their roles in the emergence of the epilepsy, are uncertain. This was investigated in the kainic acid (KA)-induced post-status epilepticus (SE) model of TLE. Male Wistar rats (7 weeks, n=53) were randomised into control and KA groups. At 24h, 2, 4 or 6 weeks sham and KA post-SE animals were euthanised, brains extracted and GABA(A)/cBZR density, neuronal loss and MFS measured in hippocampal sub-regions. GABA(A)/cBZR density (B(max)) was measured by saturation-binding analysis using [(3)H]-flumazenil. At 24h post-SE GABA(A)/cBZR density was increased in almost all hippocampal subregions, but was decreased at the later time points with the exception of the dentate gyrus. There was significant neuronal loss in the CA3 SPc region (-24 ± 9.3%, p<0.05) at 24h, which remained stable at the later time points associated with an elevated GABA(A)/cBZR density per surviving neuron at 24h post-SE (+56.4%; p<0.05) which returned to control levels by 6 weeks post-SE. MFS in the dentate gyrus progressively increased over the 6 weeks following SE (+70.6% at 6 weeks), at which time there was a significant inverse relationship with GABA(A)/cBZR binding (r(2)=0.87; p=0.02). The temporal evolution of GABA(A)/cBZR density changes post-KA-induced SE, and the relationship with decreases in hippocampal pyramidal cell numbers and MFS, may point to a key role for these changes in the pathogenesis of acquired limbic epileptogenesis.