BackgroundEpilepsy is a major complication of stroke. We aimed to establish whether there is an association between intravenous thrombolysis, intra-arterial thrombolysis and post stroke seizure (PSS) development. Improved understanding of the relationship between reperfusion therapies and seizure development may improve post-stroke monitoring and follow-up.MethodsThis was a retrospective, multicentre cohort study conducted at the Royal Melbourne Hospital and Jingling Hospital Nanjing. We included patients with anterior circulation ischemic stroke admitted 2008–2015. Patients were divided into four treatment groups 1. IV-tPA only, 2. Intra-arterial therapies (IAT) only, 3. IAT + IV-tPA and 4. stroke unit care only (i.e. no IV-tPA or IAT). To assess the association between type of reperfusion treatment and seizure incidence we used multivariable logistic regression models adjusted for age, stroke severity, 3-month functional outcome and prognostic factors.ResultsThere were 1375 stroke unit care-only patients, of whom 28 (2%) developed PSS. There were 363 patients who received only IV-tPA, of whom 21 (5.8%) developed PSS. There were 93 patients who received IAT only, of whom 12 (12.9%) developed PSS and 112 that received both IV-tPA + IAT, of which 5 (4.5%) developed PSS. All reperfusion treatments were associated with seizure development compared to stroke unit care-only patients: IV-tPA only adjusted odds ratio (aOR) 3.7, 95%CI 1.8–7.4, p < 0.0001; IAT aOR 5.5, 95%CI 2.1–14.3, p < 0.0001, IAT + IV-tPA aOR 3.4, 95% CI 0.98–11.8, p = 0.05. These aORs did not differ significantly between treatment groups (IV-tPA + IAT versus IV-tPA p = 0.89, IV-tPA + IAT versus IAT, p = 0.44).ConclusionsPatients receiving thrombolytic or intra-arterial reperfusion therapies for acute ischemic stroke are at higher risk of epilepsy and may benefit from longer follow-up. No evidence for an additive or synergistic effect of treatment modality on seizure development was found.Electronic supplementary materialThe online version of this article (10.1186/s12883-018-1064-x) contains supplementary material, which is available to authorized users.

Key pointsr Mothers at risk of preterm delivery are routinely given synthetic glucocorticoids such as dexamethasone to help mature fetal lungs and improve survival after birth.r We have previously shown that dexamethasone given after an acute episode of asphyxia in preterm fetal sheep is associated with greater brain injury.r In this study we found that fetal exposure to dexamethasone after asphyxia in preterm fetal sheep was associated with reduced intracerebral oxygenation during the critical latent phase of recovery.r In the secondary phase, maternal dexamethasone was associated with increased epileptiform transient activity and evidence of greater mitochondrial oxidation.r These findings suggest that fetal exposure to the synthetic glucocorticoid dexamethasone is associated with a critical mismatch between the brain's demand for oxygenation and the supply of oxygen that may contribute to greater brain injury.Abstract Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml -1 ) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia.

Background and PurposeMaternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain.MethodsChronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10) or saline (n = 10). Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach.ResultsMaternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290±76 vs 484±98 neurons/mm2, mean±SEM, P<0.05) and basal ganglia (putamen, 538±112 vs 814±34 neurons/mm2, P<0.05) compared to asphyxia-saline, and with greater loss of both total (913±77 vs 1201±75/mm2, P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66±8 vs 114±12/mm2, P<0.05, vs sham controls 165±10/mm2, P<0.001). This was associated with transient hyperglycemia (peak 3.5±0.2 vs. 1.4±0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum −1.5±1.2 dB vs. −5.0±1.4 dB in saline controls, P<0.01), but later onset and fewer overt seizures.ConclusionsIn preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage.

Background: Alberta Stroke Program Early CT Score (ASPECTS) assesses early ischemic change on non-contrast CT (NCCT). We hypothesised that assessing ASPECTS regions on CT Perfusion (CTP) rather than NCCT would improve inter-rater agreement and prognostic accuracy, particularly in patients presenting early after stroke onset. Methods: Ischemic stroke patients treated with intravenous alteplase from 2009 to 2014 at our institution were included in this study. Inter-rater agreement and prognostic accuracy of ASPECTS across modalities were analysed by the time between stroke onset and initial NCCT, dichotomized 1st quartile versus quartiles 2-4, referred to as epochs. ASPECTS was assessed by 2 independent raters, blinded to stroke onset time, with agreement determined by weighted kappa (κ_w). Prognostic accuracy for favourable outcome (modified Rankin Scale 0-2) was assessed using the receiver-operating characteristic analysis. Results: A total of 227 participants were included. There was significant time-by-CT modality interaction for ASPECTS, p < 0.0001. The inter-rater agreement of ASPECTS on NCCT significantly increased as onset to CT time increased (κ_w epoch 1 = 0.76 vs. κ_w epoch 2-4 = 0.89, p = 0.04), whereas agreement using CTP parameters was stable across epochs. Inter-rater agreement for CTP-ASPECTS was significantly higher than NCCT in early epoch: Tmax κ_w = 0.96, p = 0.002; cerebral blood volume (CBV) κ_w = 0.95, p = 0.003; cerebral blood flow (CBF) κ_w = 0.94, p = 0.006, with no differences in the later epochs. Prognostic accuracy of ASPECTS on NCCT in epoch 1 were (area under the ROC curves [AUC] = 0.52, 95% CI 0.48-0.56), CBV (AUC = 0.55, 95% CI 0.42-0.69, CBF (AUC = 0.58, 95% CI 0.46-0.71) and Tmax (AUC = 0.62, 95% CI 0.49-0.75), p = 0.46 between modalities. Conclusions: CTP can improve reliability when assessing the extent of ischemic changes, particularly in patients imaged early after stroke onset.