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Background: Development of inhibitors is the most serious complication in haemophilia A treatment. The assessment of risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). However, evidence on risk factors for and natural history of inhibitors has been generated mostly in previously untreated patients (PUPs). The purpose of this study was to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) programme, and explore determinants and course of inhibitor development., Methods: We used a case series study design and developed a case report form to collect patient level data; including detection, inhibitor course, treatment, factor VIII products used and events that may trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch)., Results: We identified 19 publications that reported 38 inhibitor cases and 45 cases from 31 EUHASS centres. Individual patient data were collected for 55/83 (66%) inhibitor cases out of 12 330 patients. The median (range) peak inhibitor titre was 4.4 (0.5-135.0), the proportion of transient inhibitors was 33% and only two cases of 12 undergoing immune tolerance induction failed this treatment. In the two months before inhibitor development, surgery was reported in nine (22%) cases, and high intensity treatment periods reported in seven (17%) cases., Conclusions: By studying the largest cohort of inhibitor development in PTPs assembled to date, we showed that inhibitor development in PTPs, is on average, a milder event than in PUPs., (© 2017 John Wiley & Sons Ltd.)

Brain magnetic resonance imaging (MRI) studies in patients with Dravet syndrome and SCN1A mutations have shown abnormal findings in a small minority of patients. The origin of the structural abnormalities--such focal brain atrophy, cortical dysplasia, and hippocampal sclerosis--observed in some children remains unclear. There seems to be no correlation between the presence of MRI abnormalities and duration of epilepsy, age at seizure onset, or the frequency of episodes of status epilepticus having occurred early in life. Recent descriptions of Rasmussen syndrome and of the hemiconvulsion-hemiplegia syndrome in isolated patients with SCN1A mutations are of uncertain meaning but might indicate that co-occurring immunomediated or seizure-induced structural changes can, in turn, become a substrate for the severe epileptic encephalopathy. The few available neuropathologic studies of Dravet syndrome have provided inconsistent findings, including evidence of subtle brain malformation. However, the underlying dysfunction of the SCN1A gene might confer to the brain a unique profile of vulnerability whose consequences are not easily disclosed by neuropathology and require specific experimental settings to be fully appreciated. There would seem to be value in studies in animal models of these aspects, as well as prospective studies in humans, with a particular view to establishing if earlier diagnosis and efforts at seizure control may influence the development of any clinical, imaging, or pathologic deterioration., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: One possible cause for surgical failure following temporal lobectomy for the treatment of epilepsy due to classical hippocampal sclerosis (CHS) is the presence of more widespread cortical changes. Neocortical changes in CHS shown by quantitative neuroimaging studies may involve hippocampal projection pathways. Our aim was to quantitate neocortical pathology using a postmortem series of brains from patients with epilepsy and CHS., Methods: Sections from 13 cortical regions from both left and right hemispheres, including hippocampal projection pathways, were examined from nine epilepsy patients with unilateral CHS (4), bilateral CHS (2), non-CHS (3), and non-epilepsy controls (4). Using GFAP, CD68, and NPY immunohistochemistry as markers of acquired neocortical pathology, quantitative analysis of the staining fractions in the cortex and white matter was carried out., Key Findings: Higher staining fractions were observed for all markers in both cortex and white matter in CHS patients, which was significantly different for CD68 and NPY compared to controls (p < 0.05) but not to non-CHS epilepsy cases. There was no significant difference between staining fractions in left and right hemispheres for unilateral CHS cases. Regional analysis showed preferential gliosis and microgliosis of temporal poles, frontal poles, and orbitofrontal cortex in epilepsy cases., Significance: This study supports acquired neocortical pathology in epilepsy patients both with and without CHS. Cortical pathology does not show lateralization to the side of CHS. Preferential involvement of the temporal and frontal poles may relate to other factors, such as cortical injury associated with seizures, rather than involvement through hippocampal pathways., (Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.)