Different endovascular techniques can be employed to achieve vessel recanalization in acute stroke. We assessed whether an endovascular strategy that included angioplasty was safe and effectively recanalized acutely occluded intracranial vessels.

We retrospectively reviewed 70 patients that received intra-arterial therapy for acute stroke. Patients were divided into two groups depending on whether they had received angioplasty as part of their endovascular treatment.

Angioplasty was used in the treatment of 35/70 patients (50%). Median baseline NIHSS was 15. The site of occlusion was at the M1 in 11 patients, M1/M2 in 3, ICA/M1 in 13 and vertebrobasilar in 8 patients. Intravenous thrombolysis was administered to 16/35 patients (46%). Angioplasty was used alone in 4 patients, in combination with intra-arterial thrombolysis in 27 and with a mechanical retrieval device or stent in 13 patients. Recanalization (TICI 2-3) was achieved in 23/35 patients (66%). Median time from symptom onset to recanalization was six hours. In patients where angioplasty was employed, symptomatic intracranial hemorrhage occurred in 2/35 (6%), which was similar to patients that were not treated with angioplasty. A favorable functional outcome (mRS=2) was achieved in 20% (7/35) at 24 hour and 34% (12/35) at one month. All patients that had a favorable outcome had recanalized.

In this small cohort, an endovascular treatment strategy that employed angioplasty was safe and effectively recanalized acutely occluded intracranial vessels. Angioplasty should be considered as a potential treatment option in interventional acute stroke trials.

In parallel with robust efforts world-wide to develop effective neuroprotection for established disease, resources are being mobilized to delineate risk factors and implement preventive measures in a concerted effort to forestall the anticipated Alzheimer disease (AD) epidemic. A review of heritable and ‘acquired’ dementia risk factors, many operating at midlife, is presented in a companion paper.

In 2009, an Alzheimer Risk Assessment Clinic (ARAC) was established at the Jewish General Hospital (Montreal) to address the concerns increasingly being voiced by active middle-aged individuals at risk for AD. A positive family history of AD and/or perceived changes in personal cognitive function (predominantly short-term memory) are main reasons for referral. The primary objectives of ARAC are to (i) ascertain, inform and mitigate the risks of developing AD in cognitively-healthy persons aged 40-65 based on best available medical and epidemiological evidence, (ii) conduct scientific research on midlife dementia risk and prevention in this population and (iii) provide instruction in dementia risk assessment and management to health professionals, clinical/research fellows, medical residents and students. ARAC infrastructure, evaluation protocol, risk profile classification scheme, interventions, knowledge dissemination program, case vignettes, and seminal research projects are described.

It is hoped that ARAC and similar initiatives will help prevent or delay dementia by innovating effective interventions based on increasingly nuanced estimation of modifiable AD risk in presymptomatic persons.

Intracranial hypertension can cause secondary damage after a traumatic brain injury. Aggressive medical management might not be sufficient to alleviate the increasing intracranial pressure (ICP), and decompressive craniectomy (DC) can be considered. Decompressive craniectomy can be divided into categories, according to the timing and rationale for performing the procedure: primary (done at the time of mass lesion evacuation) and secondary craniectomy (done to treat refractory ICP). Most studies analyze primary and secondary DC together. Our hypothesis is that these two groups are distinct and the aim of this retrospective study is to evaluate the differences in order to better predict outcome after DC.

Seventy patients had DC over a period of four years at our center. They were divided into two groups based on the timing of the DC. Primary DC (44 patients) was done within 24 hours of the injury for mass lesion evacuation. Secondary DC (26 patients) was done after 24 hours and purely for the treatment of refractory ICP. Pre-op characteristics and post-op outcomes were compared between the two groups.

There was a significant difference in the mechanism of injury, the pupil abnormalities and Marshall grade between primary and secondary DC. There was also a significant difference in outcome with primary DC showing 45.5% good outcome and 40.9% mortality and secondary DC showing 73.1% good outcome and 15.4% mortality.

Primary and secondary DC have different indications and patients characteristics. Outcome prediction following DC should be adjusted according to the surgical indication.

It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.

We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.

58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).

The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.

Amyloid-β (Aβ) related angiitis (ABRA) is a recently described clinicopathological entity characterized by cerebrovascular Aβ deposition and arteritis. Cerebral Aβ deposition is commonly present in cerebal amyloid angiopathy (CAA) and Alzheimer's disease (AD) but is rarely associated with inflammatory infiltration of vessel walls. Our objective is to help clarify the clinical spectrum, radiographic findings, response to treatment, and outcomes of ABRA. The neuropathological relationship between ABRA, cerebral amyloid angiopathy, and Alzheimer's disease is discussed.

We present three cases of ABRA managed at a tertiary care centre.

All three patients presented with seizures and cognitive dysfunction; one had multifocal neurologic findings. Brain biopsies revealed inflammatory arteritis with Aβ deposits in the vessel walls. All were treated with steroids and cyclophosphamide. Two had favorable outcomes and one stabilized but with severe residual neurologic disability.

ABRA is an unusual but likely under-recognized and potentially treatable disorder. As in other reported cases, our findings suggest that many patients respond favorably to immunosuppressive therapy. We believe that all biopsy specimens consistent with primary angiitis of the central nervous system (CNS) should be further examined for vascular Aβ deposition.

Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy.

Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections.

The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury.

This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.

Alzheimer's Disease (AD) is characterized in part by the increased presence of neurofibrillary tangles and amyloid beta (Aβ) plaques. Alzheimer's Disease is considered an inflammatory disease and, as such, nuclear factor-kappaB (NFκB) plays an important role in the pathophysiology of AD. Insulin acts as a neurotrophic factor. Yet, in the context of insulin resistance, concomitant hyperinsulinemia may contribute to the pathogenesis of AD.

Rat Primmary Hippocampal Neurons (RPHN) were treated with insulin in the absence and presence of Wortmannin and ERK5 small inhibitory RNA and assayed for downstream effectors of activated ERK5.

Here we demonstrate that genetic inhibition of ERK5 blocks insulin stimulated (1) activation and translocation of ERK5 and NFκB, (2) phosphorylation of IKKα via association with ERK5, (3) increases in Aβ1-40 and Aβ1-42 soluble proteins 3-fold and 2.2-fold, respectively, and (4) increases in tau phosphorylation in RPHN.

ERK5 plays an active role in insulin signaling in neurons and may be a potential therapeutic target for neurodegenerative diseases.