To investigate predictive factors of complete obliteration following treatment with linac-based stereotactic radiosurgery for intracerebral arteriovenous malformations.

Archived plans for 48 patients treated at the British Columbia Cancer Agency and who underwent post-treatment digital subtraction angiography to assess obliteration were studied. Actuarial estimates of obliteration were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of incidence of obliteration. Log-rank test was used to search for parameters associated with obliteration.

Complete nidus obliteration was achieved in 38/48 patients (79.2%). Actuarial rate of obliteration was 75.9% at 4 years (95% confidence interval 63.1%-88.6%). On univariate analysis, prescribed dose to the margin (p=0.002) and dose to isocentre (p=0.022) showed statistical significance. No parameters were significant in a multivariate model. According to the log-rank test, prescribed dose to the margin of >20 Gy (p=0.004) and dose to the isocentre of >25 Gy (p=0.004) were associated with obliteration.

Reported series in the literature suggest a number of different factors are predictive of complete obliteration of arteriovenous malformations following radiosurgery. However, differing definitions of volume and complete obliteration makes direct comparison between series difficult. This study demonstrates that complete obliteration of the nidus following linear accelerator-based stereotactic radiosurgery for arteriovenous malformations appears to be most closely related to the prescribed marginal dose. In particular, a marginal dose of >20Gy is strongly associated with obtaining complete obliteration of the nidus.

We report the results of a consecutive series of patients treated with Gamma Knife (GK) Surgery for cerebral arteriovenous malformations (AVMs).

We retrospectively reviewed 69 patients treated with GK for cerebral AVMs between November 2003 and April 2009, recording clinical data, treatment parameters, and AVM obliteration rates in order to assess our effectiveness with GK in treating these lesions.

Ten patients were lost to follow-up. Presentations included: seizure (24), hemorrhage (18), persistent headache (12), progressing neurological signs (10), and incidental (9). In 24 patients (34.8%) treatment planning consisted of digital subtraction angiography (DSA), magnetic resonance imaging (MRI), and computed tomogram (CT) angiography (CTA). Currently we rely predominantly on CTA and/or MRI scanning only. Fourty-one patients have been followed for a minimum of 3 years; average age 40.9yr., 58.5% males. Average dose at the 50% isodose line was 20.3 Gy (range 16 to 26.4 Gy). Obliteration was observed in 87.8% by MRI, CT, or DSA. Not all obliteration was confirmed by DSA. Complications occurred in 12 of 59 (20.3%) patients, and in 11 of 41 (26.8%) with 3 year follow-up. Major (temporary) complications for the 59 included symptomatic cerebral edema (7), seizure (2), and hemorrhage (1). Major permanent complications occurred in one patient suffering a cranial nerve V deafferentation, and in two patients suffering a hemorrhage.

GKS for cerebral AVM's offers an effective and safe method of treatment, with low permanent complication rate.

The purpose of the present study is to investigate the expression of inflammation factor endothelial-leukocyte adhesion molecule (E-selectin, CD62E) in cerebral aneurysm walls and its relationship with aneurysm rupture.

Cerebral aneurysm tissue samples were collected at the time of surgical clipping of nine patients with history of subarachnoid hemorrhage, and then compared with control artery tissues from the superficial temporal arteries (STA) of five patients with intracranial tumors. Immunohistochemistry (IHC) was performed to reveal and localize E-selectin expression in the aneurysms and artery tissues. Western blot analysis was used to relatively quantify the level of E-selectine protein expression in cerebral aneurysms when compared with normal arteries.

E-selectin was detected in the wall of all the aneurysm tissue samples and was rarely found in normal control arteries by IHC, and it was concentrated in proliferating and disorganized epithelia cells. Moreover, with the Western blot method, the E-selectin protein level increased significantly in aneurysm tissues compared to normal STA.

E-selectin might be an important factor involved in the process of cerebral aneurysm formation and rupture, by promoting inflammation and weakening cerebral artery walls.

The objective of the study was to determine the frequency of cerebral microbleeds (CMBs) by using phasesensitive imaging in patients with previous transient ischemic attack (TIA) or stroke who were receiving aspirin treatment.

We retrospectively analyzed 300 outpatients with ischemic cerebrovascular disease: 150 had been receiving aspirin treatment for >1 year (patients), and 150 controls had not previously received aspirin. Cerebral microbleeds were defined by a trained observer (blinded to clinical details) according to results of T2-weighted, T1-weighted, diffusion-weighted, and phase-sensitive magnetic resonance imaging (MRI). Numerous vascular risk factors including white matter hyperintensity (WMH), duration of aspirin treatment, age, hypertension or diabetes mellitus were investigated for a possible association with the presence of CMBs in the two groups.

The frequency of CMBs (60/150 (40%) vs 18/150 (12%); odds ratio 4.899, p <0.0001) and intracerebral hemorrhage (ICH)(42/150 (28%) vs 2/150 (1%); odds ratio 28.778, p <0.0001) were significantly higher in the patients than in the controls. Among patients, those using aspirin for >5 years(42/68 (62%) showed a higher frequency of CMBs than those receiving aspirin for ≤ 5 years(18/82 (22%); odds ratio 5.744, p<0.0001). WMH (p=0.020/0.030, 0.007/0.000) age (p=0.007/0.000) and hypertension (p=0.000/0.033), in patients and controls respectively, were each associated with CMBs.

There was a clear impact of aspirin treatment on CMBs associated with intracerebral hemorrhage in Chinese patients. The frequency of CMBs and hemorrhagic complications was higher in patients treated with long-term aspirin.

To clarify the role of inflammation in the pathogenesis of cerebral small vessel disease (SVD), we investigated whether the gene encoding transforming growth factor-beta 1(TGF-beta 1) is a risk factor for cerebral SVD as a whole, and for two different SVD subtypes.

TGF-beta 1 codon10 (T+29C) genotype was determined in 441 Chinese patients (313 male and 128 female) with cerebral SVD and 450 control subjects (326 male and 124 female). Cerebral SVD patients were retrospectively classified into two groups based on neuroimaging findings: lacunar infarction group with 112 patients and ischaemic leukoaraiosis group with 329 patients.

Subjects carrying TT homozygote were susceptible to cerebral SVD [adjusted odds ratio (OR) =1.44, 95% confidence interval (CI), 1.05-1.98; P=0.026]. Further analysis of SVD subtypes revealed a moderate association with the ischaemic leukoaraiosis group [OR= 1.60, 95% CI, 1.14-2.25; P=0.007].

Codon 10 of TGF-beta 1 might be a risk factor for SVD, specifically in ischaemic leukoaraiosis phenotype.

Free fatty acids (FFAs), an important energy substrate, have an association with cardiovascular diseases, such as atherosclerosis, myocardial dysfunction and abnormal cardiac rhythm. However, limited reports are available on the association between FFAs and ischemic stroke. We hypothesized that plasma FFA concentration could be associated with an ischemic stroke, emphasizing the relationship between FFA and subtypes of ischemic stroke.

A cross-sectional study examined the association between FFA concentration and subtypes of stroke and cerebral atherosclerosis from a hospital-based acute stroke registry.

Data of 715 stroke patients were analyzed. The concentration of FFA was highest in the cardioembolic stroke subtype compared with the other stroke subtypes. Logistic regression analysis revealed that an increase in FFA concentration was significantly associated with the cardioembolic subtype after the adjustment of covariates. FFA concentration was also higher in patients with atrial fibrillation (AF) than those without AF. According to the presence of atherosclerotic stenosis, no significantly difference of FFA concentration was found for intracranial and extracranial cerebral arterial atherosclerosis.

Here we report a significant association between fasting FFA concentration and the cardioembolic stroke subtype. AF is suggested as the mediating factor between FFA and the cardioembolic stroke subtype.

Cytosol Ca2+ overload plays a vital role in ischemic neuronal damage, which is largely contributed by the Ca2+ influx through L-type voltage-gated calcium channels (L-VGCCs) and N-methyl-D-aspartate (NMDA) type glutamate receptors. In this article, L-VGCCs were activated by depolarization to investigate the cross-talk between NMDA receptors and L-VGCCs.

Depolarization was induced by 20 minutes incubation of 75 mM KCl in cultured rat cortical neuron. Apoptosis-like neuronal death was detected by DAPI staining. Tyrosine phosphorylation of NMDA receptor subunit 2A (NR2A), interactions of Src and NR2A were detected by immunoblot and immunoprecipitation.

Depolarization induced cortical neuron apoptosis-like cell death after 24 hours of restoration. The apoptosis was partially inhibited by 5 mM EGTA, 100 μM Cd2+, 10 μM nimodipine, 100 μM genistein, 20 μM MK-801, 2 μM PP2 and combined treatment of nimodipine and MK-801. NR2A tyrosine phosphorylation increased after depolarization, and the increase was inhibited by the drugs listed above. Moreover, non-receptor tyrosine kinase Src bound with NR2A after depolarization and restoration. The binding was also inhibited by the drugs listed above.

The results indicated that depolarization-induced neuronal death might be due to extracellular Ca2+ influx through L-VGCCs and subsequently Src activationmediated NR2A tyrosine phosphorylation.

Optic Neuritis (ON) is one of the most common clinically isolated syndromes which develops into clinically diagnosed Multiple Sclerosis (CDMS) over time.

To assess the conversion rate of Iranian patients presenting with idiopathic ON to CDMS as well as monitoring potential demographic and clinical risk factors.

Atotal of 219 patients' medical records of idiopathic ON from March 2001 to May 2009 were reviewed. Demographic findings, ophthalmologic characteristics on admission and discharge, diagnostic approaches, type and dosage of therapy were retrospectively reviewed. A structured telephone interview was then conducted to identify patients who had subsequently been diagnosed with MS. Survival analysis was used to evaluate the cumulative probability of MS conversion and contributory risk factors.

From the 219 ON patients, 109 [age 11-51, female: 81%] were followed up. Among the male gender the mean age of patients developing MS was significantly lower (P=0.01). In cox regression model, female sex (p=0.07), bilateral ON (p=0.003), MRI abnormalities (p <0.001) and high dose (5g) corticosteroid therapy (p<0.001) were identified as risk factors for the development of MS. The two and five year cumulative probability of developing MS were 27% and 45%, respectively.

Idiopathic ON in Iranian patients carries higher risk of progression to MS compared to other Asian countries. MRI lesions are the strongest independent risk factor of developing CDMS. Bilateral ON, female gender and high dose corticosteroid therapy are also important factors in predicting CDMS development.

The American Academy of Neurology recommended using phenytoin or carbamazepine to prevent early post-traumatic seizures (PTS) in severe traumatic brain injuries (TBI). In this study, we examined the effects of using phenytoin prophylaxis on mild, moderate, and severe TBIs. There have been no studies looking at compliance rate and side effects of systematic use of phenytoin at a large population scale. The goal of this study is to determine 1) the proportion of TBI patients receiving phenytoin prophylaxis; 2) which parameters decided when to decide administer phenytoin; 3) prophylaxis efficacy and complication rate.

We retrospectively studied all patients admitted with a TBI over a two year-period and collected the following information: age, GCS score, CT-scan Marshall grade, incidence of early PTS, incidence of phenytoin use and time delay, side effects, and incidence of over-dosage or under-dosage.

1008 patients were included. 5.4 % had early PTS, 2.3 % while on prophylaxis and 3.1% while not on prophylaxis, 1.9% before reaching the hospital and 1.2% prior to phenytoin administration while in hospital. Delay of administration was 5 hours. 64.8% received prophylaxis and physicians used positive CT scan as the primary decision-making parameter (p<.001). Compliance with guidelines was 99.7%. Adverse reactions occurred in 0.5%. Levels were drawn in 42.2% (52% therapeutic, 41% low, 7% high).

Phenytoin is used according to guidelines, with CT scan being the main decision factor for its use. The frequency of early PTS rate is low and side effects are rare. However, earlier administration of phenytoin and adequate levels could further prevent early PTS.

Retrospective study assessing the efficacy and tolerability of vagus nerve stimulation (VNS) for the treatment of refractory epilepsy at Notre-Dame Hospital.

Chart review of all adult epileptic patients treated by VNS with ≥ 1 year follow-up. Responders were defined as patients with ≥ 50% reduction of baseline seizure frequency.

Thirty-four patients (14M; mean age = 29.9 yrs) received a VNS. Sub-pectoralis implantation (n = 25) was more frequent than subcutaneous (n = 9). Most patients suffered from intractable partial epilepsy. After 6 months, 12 months, 24 months, and 36 months, 14/34 patients (41%), 16/34 patients (47%), 17/30 patients (57%) and 12/20 patients (60%) respectively were responders. Two patients (6%) became seizure-free. Complications related to implantation were minor: eight cases of limited cervical hypoesthesia, two minor scar infections and one Horner syndrome. Adverse events (voice hoarseness, throat paresthesia, coughing) related to stimulation were generally mild and tended to wane over time. However, a reduction in seizure frequency did not translate into a reduction in medication, as only 9% of responders had less antiepileptic medication at last follow-up compared to baseline.

VNS as practiced at Notre-Dame hospital is an efficacious and safe treatment for refractory epilepsy. Quotas allotted to epilepsy centers in the province of Quebec should be lifted or increased to allow more patients to benefit from this therapeutic device.

Repetitively discharging neurons in epileptic foci have a high energy requirement that might be demonstrated histochemically as increased mitochondrial enzymatic activity in brain resections for epilepsy in children.

Frozen sections were studied histochemically of 10 brain resections from 7 epileptic children, 2 months to 17 years of age. None had mitochondrial disease. Three patients had tuberous sclerosis (TS) or hemimegalencephy (HME). Tissues included hippocampus and neocortex. Oxidative enzymes were studied for respiratory chain complexes I, II, IV, using the muscle biopsy protocol. In addition, immunoreactivities of α-B-crystallin and transmission electron microscopy (EM) were performed.

Oxidative activities were variable in adjacent neurons within a field: a minority were intense, adjacent to neurons with weaker mitochondrial activity exhibiting poor contrast of the soma because of similar oxidative activity in surrounding neuropil. Endothelium of vessels uniformly exhibits strong activity. Alpha-B-crystallin reactivity was strong at these foci. EM confirmed an abundance of neuronal mitochondria with normal cristae. In TS and HME, many dysplastic neurons showed intense activity; balloon cells had sparse activity.

Histochemistry of mitochondrial oxidative enzymes reveals scattered and clustered neurons with stronger activities than others at epileptic foci. Such intensely staining neurons may be functionally “hypermetabolic” but they do not signify mitochondrial disease. Individual intensely stained neurons might be epileptogenic, but do not denote an epileptogenic field in the same manner as α-B-crystallin, which also was strongly reactive in these foci.