This article is available at e-publications@RCSI: http://epubs.rcsi.ie/gerstrmedart/1 -Use LicenceThis work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.This article is available at e-publications@RCSI: http://epubs.rcsi.ie/gerstrmedart/1T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med nejm.org

Cortical dysplastic lesions (CDyLs) are often associated with severe partial epilepsies. We describe the electrographic counterpart of this high degree of epileptogenicity, manifested by continuous or frequent rhythmic epileptogenic discharges recorded directly from CDyLs during intraoperative electrocorticography (ECoG). These ictal or continuous epileptogenic discharges (I/CEDs) assumed one of the following three patterns: (1) repetitive electrographic seizures, (2) repetitive bursting discharges, or (3) continuous or quasicontinuous rhythmic spiking. One or more of these patterns were present in 23 of 34 patients (67%) with intractable partial epilepsy associated with CDyLs, and in only 1 of 40 patients (2.5%) with intractable partial epilepsy associated with other types of structural lesions. I/CEDs were usually spatially restricted, thus contrasting with the more widespread interictal ECoG epileptic activity, and tended to colocalize with the magnetic resonance imaging-defined lesion. Completeness of excision of cortical tissue displaying I/CEDs correlated positively with surgical outcome in patients with medically intractable seizures; i.e., three-fourths of the patients in whom it was entirely excised had favorable surgical outcome; in contrast, uniformly poor outcome was observed in those patients in whom areas containing I/CEDs remained in situ. We conclude that CDyLs are highly and intrinsically epileptogenic, and that intraoperative ECoG identification of this intrinsically epileptogenic dysplastic cortical tissue is crucial to decide the extent of excision for best seizure control.

Background Amyloid-related imaging abnormalities (ARIA) have been reported in Alzheimer’s disease (AD) patients treated with bapineuzumab, a humanized monoclonal antibody to amyloid-β. ARIA includes MRI signal abnormalities suggestive of vasogenic edema and sulcal effusions (ARIA-E) and hemosiderin deposits (ARIA-H). A better understanding of the incidence and risk factors for ARIA may further the development of amyloid-modifying treatments for AD. Methods Two neuroradiologists independently reviewed (kappa=0.76) and then reached consensus reads on over 2500 FLAIR-MRIs from 262 participants in three phase 2 studies of bapineuzumab. Subjects (n=210) were included in risk analyses if they had no evidence of ARIA-E on pre-treatment MRI, received bapineuzumab, and had at least one post-treatment MRI. Findings 36/210 (17%) subjects developed ARIA-E during treatment; 28 of these 36 (78%) did not report associated symptoms. Adverse events reported in 8 symptomatic patients included headache, confusion, neuropsychiatric and gastrointestinal symptoms. 15/36 of the ARIA-E cases (42%) were detected only on central review. 13/15 received additional infusions while ARIA-E was present, without any associated symptoms reported. ARIA-E incidence increased with bapineuzumab dose (Hazard Ratio [HR] 2.24 per mg/kg increase in dose; p<0·001) and with APOE ε4 allele number (HR 2.55 per allele; p<0·001). Interpretation ARIA appears to represent a spectrum of imaging findings with variable clinical correlates, with some cases remaining asymptomatic even when treated through ARIA-E. The increased risk of ARIA with APOE ε4 and bapineuzumab dose, and the time course in relation to dosing, is consistent with alterations in vascular amyloid burden.

The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider's recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.

Campbell, B. C.V. et al. (2019) Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.ABSTRACT Background: CT-perfusion (CTP) and MRI may assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of ischaemic core and penumbra volumes were associated with functional outcomes and treatment effect.

Twenty-six patients with focal or lateralized neuronal migration disorders and intractable partial epilepsy were treated surgically. Twenty-four had reliable follow-up ranging from 1 to 15 years (mean, 5.0). Pathologically, they fell into two categories: focal cortical dysplasia (12 patients) and forme fruste of tuberous sclerosis (8 patients). In the remaining 4 patients, the material was inadequate for histological analysis. Outcome regarding seizure control was assessed according to a classification most sensitive to variations in frequency of major attacks. Ten (42%) of the 24 patients achieved good or excellent outcome, 6 (25%) had a worthwhile decrease in seizure frequency, and 8 (33%) had only discrete improvement. The variable most strongly correlated with surgical outcome was the amount of lesion removed. Seventy-seven percent of patients in whom a complete excision or excision of 50% or more of the lesion was accomplished achieved excellent or good surgical outcome. Conversely, no patient with less than 50% of the lesion removed attained the same result. There was no correlation between other clinical, radiological, or electrographic variables and outcome regarding seizure control. Specifically there was no significant correlation between the amount of excision of the epileptogenic area as judged by scalp electroencephalography and electrocorticography studies, and surgical outcome. In patients with neuronal migration disorders and intractable partial epilepsy, removal of the structural abnormality takes precedence over removal of epileptogenic tissue as the main surgical strategy to achieve seizure control.

We studied 30 patients with partial epilepsy and a radiological or pathological diagnosis of localized neuronal migration disorders, with a view to surgical treatment. Eight patients had identifiable prenatal etiological factors. The frequency of complex partial, partial motor, and secondarily generalized seizures was approximately 70% each. Drop attacks were present in 27%: Their presence usually correlated with a lesion involving the central region. Partial motor or generalized convulsive status epilepticus occurred in 30%, and was most frequently associated with extensive structural abnormalities involving two or more lobes. A full-scale intelligence quotient of less than 80 was found in 44%. Magnetic resonance imaging (MRI) was superior to computed tomography for identification of the dysplastic cortical lesions. In one third, MRI showed only subcortical abnormalities. It did not allow distinction between true pachygyria, focal cortical dysplasia, or the forme fruste of tuberous sclerosis. The epileptogenic area was usually more extensive than the lesion; it was multilobar in more than 70% of patients. Of 26 surgically treated patients, a histological diagnosis of the type of neuronal migration disorder was possible in 22: 12 had focal cortical dysplasia and 10 the forme fruste of tuberous sclerosis. In the remaining 4, no definite histological diagnosis was made, since the maximally abnormal tissue could not be examined. In the latter, and in the 4 nonoperated patients, the diagnosis of neuronal migration disorder was based on imaging findings. The presence of the forme fruste of tuberous sclerosis correlated with delayed psychomotor development and more extensive epileptogenic areas.

Grey matter heterotopias, demonstrated by MRI, may present with a broad spectrum of clinical severity. We have studied 33 patients with periventricular nodular heterotopias (PNH); 19 (58%) had unilateral and 14 (42%) bilateral lesions. Thirteen of the 19 patients (68%) with unilateral subependymal nodules of grey matter had, in addition, unilateral focal subcortical heterotopias (SNH), comprising 39% of the entire group. Most had normal intellectual and motor function but some presented with mild mental retardation and neurological deficits. Recurrent seizures were described in 82%, mainly partial attacks with temporo-parieto-occipital auras. Nodular heterotopias led to unilateral or bilateral independent temporal epileptic discharges in 47% of epileptic patients with PNH alone and in 61% of those who had SNH in addition. Extratemporal or multilobar, unilateral or bilateral interictal spiking was present in 10 other patients (36%). Two first degree relatives of patients with seizures were affected but had no seizures, three were investigated for other apparently unrelated neurological symptoms: memory impairment, vertigo or transient ischaemic attacks in one person each. Contiguous ovoid nodules of grey matter, symmetrically lining both lateral ventricles, were described in nine patients. Seven of them were female, including four with familial incidence of PNH. Such lesions may explain the familial occurrence of epilepsy in some families. Seven patients underwent anterior temporal resection: two patients with unilateral subependymal and focal subcortical heterotopias were seizure free or significantly improved. Four patients, three with PNH alone and one with additional subcortical nodules, did not improve significantly after surgery. The remaining patient was followed for less than 6 months.