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 findings of previous studies remain controversial on the optimal management required for effective seizure control after surgical excision of arteriovenous malformations (AVMs). We evaluated the efficacy of additional bipolar electrocoagulation on the electrically positive cortex guided by intraoperative electrocorticography (ECoG) for controlling cerebral AVMs-related epilepsy.

Sixty consecutive patients with seizure due to cerebral AVMs, who underwent surgical excision of cerebral AVMs and intraoperative ECoG, were assessed. The AVMs and surrounding hemosiderin stained tissue were completely removed, and bipolar electrocoagulation was applied on the surrounding cerebral cortex where epileptic discharges were monitored via intraoperative ECoG. Patients were followed up at three to six months after the surgery and then annually. We evaluated seizure outcome by using Engel's classification and postoperative complications.

Forty-nine patients (81.6%) were detected of epileptic discharges before and after AVMs excision. These patients underwent the removal of AVMs plus bipolar electrocoagulation on spike-positive site cortex. After electrocoagulation, 45 patients' epileptic discharges disappeared, while four obviously diminished. Fifty-five of 60 patients (91.7%) had follow-up lasting at least 22 months (mean 51.1 months; range 22-93 months). Determined by the Engel Seizure Outcome Scale, 39 patients (70.9%) were Class I, seven (12.7%) Class II, five (9.0%) Class III, and four (7.2%) Class IV.

Even alter the complete removal of AVM and sunwinding gliolic and hemosiderin stained tissue, a high-frequency residual spike remained on the surrounding cerebral cortex. Effective surgical seizure control can be achieved by carrying on I additional bipolar electrocoagulation on the cortex guided by the intraoperative ECoG.

The objective of this study was to investigate whether medical television dramas portray proper seizure first aid.

Episodes of the four highest-rated US medical dramas (“Grey's Anatomy,” “House M.D.”, “Private Practice,” and “ER”) were screened for the presence of seizures. “Patient” age, sex, semiology, and etiology were recorded. The appropriateness of seizure first aid management was determined by comparison to the Epilepsy Foundation of America (EFA) guidelines.

Among 364 television programs, 65 seizures (in 59 individuals) were identified (30 males; 29 females). Seizures were primary or secondarily generalized tonic-clonic in 53 (81.5%) cases. Other seizure types included complex partial (5, 7.7%), simple partial (1, 1.5%), myoclonic (1, 1.5%), absence (1,1.5%), and psychogenic (1, 1.5%). On 63 occasions (96.9%), first aid was performed by a health care professional. First aid management was judged appropriate in 21 (32.3%) seizures, inappropriate in 28 (43.1%), and indeterminate in 16 (24.6%). Inappropriate practices included holding the person down (17, 26.2%), trying to stop the involuntary movements (10, 15.4%) and putting something in the person's mouth (11, 16.9%).

The first aid management of seizures performed by actors portraying health care professionals was inappropriate in nearly half of all cases. Inaccurate depiction of seizure first aid management may contribute to misinformation of the general public. The television industry could easily incorporate the simple first aid EFA seizure guidelines as a public service without sacrificing dramatic impact.

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.

A meta-analysis of randomized controlled trials (RCTs) was conducted to update the available evidence on the safety and efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) in the treatment of carotid artery stenosis.

A comprehensive search was performed of MEDLINE, EMBASE, CENTRAL, bibliographies of included articles and past systematic reviews, and abstract lists of recent scientific conferences. For each reported outcome, a Mantel-Haenszel random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). The I2 statistic was used as a measure of heterogeneity.

Twelve RCTs enrolling 6,973 patients were included in the meta-analysis. Carotid artery stenting was associated with a significantly greater odds of periprocedural stroke (OR 1.72, 95% CI 1.20 to 2.47) and a significantly lower odds of periprocedural myocardial infarction (OR 0.47, 95% CI 0.29 to 0.78) and cranial neuropathy (OR 0.08, 95% CI, 0.04 to 0.16). The odds of periprocedural death (OR 1.11, 95% CI 0.56 to 2.18), target vessel restenosis (OR 1.95, 95% CI 0.63 to 6.06), and access-related hematoma were similar following either intervention (OR 0.60, 95% CI 0.30 to 1.21).

In comparison with CEA, CAS is associated with a greater odds of stroke and a lower odds of myocardial infarction. While the results our meta-analysis support the continued use of CEA as the standard of care in the treatment of carotid artery stenosis, CAS is a viable alternative in patients at elevated risk of cardiac complications.

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.

Despite the evidence of cognitive deficits in Multiple Sclerosis (MS) patients, evaluation of their cognitive integrity is often limited to the use of clinical interviews and questionnaires. However, the consensus in the literature is that these patients under- or overestimate their deficits and repercussions. The objective of this study was to clarify why some patients overestimate while others underestimate their memory deficits.

Fifty-four participants (30 MS, 24 controls) completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and were tested on a battery of neuropsychological tests. Based on the test results, MS patients were categorized as having either mild or moderate/severe cognitive deficits.

The moderate/severe MS group differed from the two other groups on the Rey Auditory Verbal Learning Test (RAVLT) but did not differ from the control group on the PRMQ. Conversely, the mild MS group did not differ from the control group on the RAVLT but did report significantly more problems than this group on the PRMQ. There was no difference between the two clinical groups on the Depression Index (Beck) but there was a significant correlation (r=.409) between the depression scores and the overestimation of prospective memory problems (PRMQ).

The results explain the contradiction in the literature. It is the mild group who overestimates, maybe because they are overly concerned by their deficits, whereas the cognitive impairments of the moderate/severe group lead them to underestimate and may make their self-assessment unreliable. Formal testing or information from a significant other would be advisable.

Spontaneous intracranial hypotension (SIH) is an increasingly described entity, with over 70 cases reported in the literature. The classic triad includes orthostatic headache, diffuse pachymeningeal enhancement on magnetic resonance imaging (MRI) with gadolinium, and low cerebrospinal fluid pressure (CSF) in the lateral decubitus (<60 mm H2O) and sitting positions.

We present four rare clinical presentations of SIH, two of which have not been previously described in the literature, to the best of our knowledge.

Patient 1 presented with dyspnea, dysphagia, bilateral ptosis, diplopia and seizures. Patient 2 presented with a paradoxical positional pattern of orthostatic hypotension. In Patient 3, bilateral subdural hematomas (SDH) were encountered; while in Patient 4, a recurrent unilateral SDH requiring multiple surgical interventions was demonstrated.

Although uncommon clinical presentations, all four cases of intracranial hypotension were spontaneous, demonstrated diagnostic MRI findings, and responded favorably to blood patches or saline injections.

Once a decision has been made to treat an intact aneurysm, the best treatment remains uncertain. Both surgical and endovascular management strategies are commonly performed for these lesions. Surgical clipping, for years the standard treatment, is gradually becoming supplanted by endovascular treatment. However, there is no randomized data available to compare the results of surgery versus endovascular treatment of unruptured aneurysms (UIAs).

We report the design of the Canadian UnRuptured Endovascular versus Surgery (CURES) trial to compare angiographic and clinical outcomes following treatment of UIAs.

The Canadian pilot phase will serve two purposes: i) to determine feasibility of the pivotal international study, and ii) to determine the incidence of treatment failure, a composite primary end-point comprising the occurrence of either: failure to accomplish aneurysm obliteration with the initial treatment modality, a major saccular aneurysm remnant or recurrence, or intracranial hemorrhage following treatment at one year. The pivotal international study will address which strategy leads to the best overall clinical outcomes in terms of mortality, morbidity, and clinical efficacy. CURES is designed to be a pragmatic management trial with loose inclusion criteria. The pilot study plans to enroll 260 patients, a size sufficient (at 80% power and 0.05 significance) to detect a decrease in the incidence of treatment failure from 13% to 4%. The formulation of specific hypotheses for the pivotal phase awaits the preliminary CURES morbidity and mortality results.

The CURES trial intends to test surgical versus endovascular management strategies for the treatment of unruptured intracranial aneurysms.

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.

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.

Stereotactically-focused radiosurgery (SRS) for the treatment of arteriovenous malformations (AVM) has been in widespread use for over two decades. Over this timeframe the indications for treatment, standardization of radiation dosage, and the results expected from treatment have been elaborated. Less well known are the long-term complications associated with SRS. We report three patients who had SRS for the treatment of AVM who developed a cyst at the site of treatment as a late complication.

From 201 patients treated by SRS for an AVM, three developed a cyst at the treatment site. Their clinical presentation, the characteristics of the AVMs and the treatment were reviewed, as well as similar cases gleaned from the literature.

Three women, aged 28-43 years, had an AVM treated by: craniotomy and clipping of arterial feeders followed by SRS, by craniotomy for resection followed by SRS or by endo vascular embolization and SRS. The patients did well following treatment but two of them developed a symptomatic and the other an asymptomatic cyst at the treatment site 3-19 years later. The symptomatic patients underwent marsupialization of the cyst and the other is under observation.

Stereotactic radiosurgery is an established and safe treatment for patients with AVMs. Delayed cyst formation can occur many years after treatment and long term follow-up is indicated in patients whose AVM has been treated with SRS.

Hyperostosis of the bone overlying meningiomas has been reported in up to 50% of cases. The skull becomes infiltrated by meningothelial tumor cells, necessitating removal of the hypertrophied bone to achieve a complete tumor resection. Unfortunately, aesthetic reconstruction of large bony defects can pose a significant challenge intra-operatively. Custom cranioplasty implants are very expensive and can only be fabricated after the bony defect exists, requiring a second surgery for implantation. Although numerous composite materials exist to repair the defects at the time of tumor resection, the challenge is to create an implant that fits appropriately without shifting and approximates the natural curvature of the skull. We have developed a technique for an “in situ cranioplasty” using a composite construct with strength in compression and tension.

After the skull is reshaped by shaving down part of the hyperostotic bone, titanium mesh is molded to the surface of the skull and screwed into the surrounding normal bone. The bone flap is then removed by drilling a trough at the outer margin of the tumor-involved skull and removing a ring of normal surrounding bone. The central portion of tumor involved skull is then craniectomized. The mesh can be reapplied and the full thickness of the central bone can be reconstructed with polymethylmethacrylate, yielding a solid construct perfectly matched to the patient's natural head shape.

This novel technique yields a sturdy, aesthetic, and cost-effective result which can be used to address any cranial vault defect at the time of tumor resection.

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.

Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time.

The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity.

Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity.

The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.

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.