Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor of the central nervous system. Its pathogenesis remains unknown. Like glioblastomas, AT/RTs contain brain cancer stem cells (CSCs) that suppress the immunity of patients and are resistant to conventional chemotherapy and radiation therapy. Considerable infiltration of immune cells, including macrophages/microglia, dendritic cells and T-cells, has been noted in glioblastomas, which correlates with poor prognosis. The present study examines the significance of infiltrating immune cells in four cases of AT/RT; including one associated with an autoimmune disease, Henoch-Schonlein purpura.

Tumor tissues from four patients with AT/RT were analyzed and compared with those from four patients with glioblastomas. The frequency of immune cells, including CD68+, CD4+, and CD8+ cells, was assessed by scoring for statistical analysis.

The infiltration of immune cells was identified in the case of AT/RT associated with HSP and three other cases of infratentorial AT/RTs. Moderate infiltration of CD68+ macrophages/microglia and CD4+ cells was noted in AT/RTs with no significant difference from that in glioblastomas (p > 0.05). However, the infiltration of CD8+ T-cells was significantly higher in AT/RTs than that in glioblastomas (p < 0.05); CD4+/CD8+ ratio was significantly lower in AT/RTs than that in glioblastomas (p < 0.05). In addition, eosinophils were found in all AT/RTs, but not in glioblastomas.

These findings suggest an immune microenvironment of AT/RTs with more immune effectors than glioblastomas. Our observation contributes to understanding the growth environment of AT/RTs for which adjuvant immunotherapy may be potentially beneficial.

The neuropeptide oxytocin, produced in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, is now understood to function as a neurotransmitter critical for various aspects of social cognition and pro-social behaviour. While patients with Frontotemporal dementia (FTD) display prominent and progressive deficits in such social behaviours, the integrity of these nuclei in FTD is not known.

We conducted a quantitative neuropathologic examination of the SON and PVN from patients with FTLD with TDP-43 proteinopathy, Alzheimer's disease, Lewy body disease and controls to determine whether significant pathologic changes or neuronal loss may contribute to the striking behavioural symptoms of FTD.

Contrary to predictions, we found both nuclei to be free of significant pathologic change (TDP-43) in FTLD. In contrast, tau related pathology was found in the PVN in Alzheimer's disease, and alpha-synuclein pathology in the SON in patients with Lewy body dementia.

These results indicate that the SON and PVN are resistant to FTLD TDP-43 pathology. They also support prior suggestions that the SON is resistant to Alzheimer's disease (AD) related pathology, and extend this to demonstrate SON susceptibility to alpha-synuclein pathology in patients with Lewy body dementia.

To compare North American Symptomatic Carotid Endarterectomy Trial (NASCET) stenosis values and NASCET grade categorization (mild, moderate, severe) of semi-automated vessel analysis software versus manual measurements on computed tomography angiography (CTA).

There were four observers. Two independently analyzed 81 carotid artery CTAs using semi-automated vessel analysis software according to a blinded protocol. The software measured the narrowest stenosis in millimeters (mm), distal internal carotid artery (ICA) in mm, and calculated percent stenosis based on NASCET criteria. One of these two observers performed this task twice on each carotid, the second analysis was delayed two months in order to mitigate recall bias. Two other observers manually measured the narrowest stenosis in mm, distal ICA in mm, and calculated NASCET percent stenosis in a blinded fashion. The calculated NASCET stenoses were categorized into mild, moderate, or severe. Chi square and analysis of variance (ANOVA) were used to test for statistical differences.

ANOVA did not find a statistically significant difference in the mean percent stenosis when comparing the two manual measurements, the two semi-automated measurements, and the repeat semi-automated. Chi square demonstrated that the distribution of grades of stenosis were statistically different (p<0.05) between the manual and semiautomated grades. Semi-automated vessel analysis tended to underestimate the degree of stenosis compared to manual measurement.

The mean percentage stenosis determined by semi-automated vessel analysis is not significantly different from manual measurement. However, when the data is categorized into mild, moderate and severe stenosis, there is a significant difference between semi-automated and manual measurements. The semi-automated software tends to underestimate the stenosis grade compared to manual measurement.

The benefits of intravenous recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke is time dependent. Guidelines recommend a door-to-needle (DTN) time of less than 60 minutes.

A retrospective audit of 730 stroke charts from 2008 - 2011 was conducted at Health Sciences Centre. 158 patients treated with IV rt-PA were identified. The time intervals between Emergency Department (ED) arrival, administration of rt-PA and uninfused brain computed axial tomographic scan (CT) were recorded. From this, CT to needle times were calculated. During November 2010 to January 2011 feedback was given to neurologists, ED physicians, ED nurses, and CT technologists. This raised awareness and emphasized the importance of this time driven protocol.

The median DTN times for 2008, 2009, and 2010 were 69, 71 and 76 minutes respectively. The median CT-to-needle time for this time period was 47 minutes. In 2011 (n =58) the median DTN time was 49 minutes and the median CT-to-needle was 18 minutes, which were marked improvements (p<0.00005 and p<0.005, respectively). In 2008-2010 only 31% of treated patients (n=100) received rt-PA within 60 minutes, whereas in 2011 this increased to 64%.

Dramatic improvements in DTN times and in the percentage of patients receiving rt-PA treatment within 60 minutes were observed in 2011 after feedback was provided regarding the suboptimal performance. Prior to receiving feedback, DTN times were similar to national median DTN times. All centres administering rt-PA for acute ischemic stroke should monitor their clinical performance and give feedback on a regular basis.

Lack of additional utility over non-contract computed tomography (NCCT) in decision making and delay in door to needle time are arguments used against routine computed tomographic angiography (CTA) use in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center.

We reviewed 850 stroke thrombolysis patients in a university hospital in Canada from April 1996 to December 2009. Time to treatment was divided into the following interval times: onset-to-door, door-to-needle and onset-to-needle. Patients were categorized into: Group 1 (April 1996-Dec 2002) (Non-contrast CT Scan based thrombolysis) n=297, Group 2 (Jan 2004-Dec 2009) (CTA based thrombolysis) n=504. The period from Jan to Dec 2003 (n=49) was considered a washout period as we had started the CTA protocol that year. Interval times were compared between the two groups.

Interval times in Group 1 and Group 2 were: median onset-to-door times in Group 1 [55 minutes (IQR 48),] and Group 2 [61 minutes (IQR 57)] (p=0.019); median door-to-needle times in Group 1 [67 minutes(IQR 43)] and Group 2 [62.5 minutes (IQR 52)] (p=0.519); median onset-to-needle times in Group 1 (139 minutes (IQR 73)] and Group 2 (141.5 min (IQR 109.5) (p=0.468). In multivariable linear regression analysis, age and onset-to-door time influenced the door-to-needle time. For every decade of age, door-to-needle times were 5.4 minutes faster.

CTA based thrombolytic approach for acute ischemic stroke does not significantly delay thrombolysis in routine clinical practice.

To assess the relationship between carotid flow velocity and cognitive impairment in patients with mild-moderate (<50%) carotid artery disease.

We studied 407 participants with available carotid ultrasound and cognitive measures. We related peak systolic velocity (PSV) and end diastolic velocity (EDV) of internal carotid artery (ICA) and common carotid artery (CCA) and intimal medial thickness (IMT) to Mini Mental State Examination (MMSE), Clock Draw Test (CDT), Activities of Daily Living Scale (ADL)and Montreal Cognitive Assessment (MoCA).

EDV of CCA was significantly different in higher and lower MoCA (MMSE) groups. Multiple regression analysis demonstrated that lower EDV was significantly associated with lower MoCA (+0.459 per standard deviation (SD), p<0. 01 for the left; +0.539 per SD, p<0. 01 for the right) and CDT (odds ratio (OR) 0.093, p< 0.05 for the left; OR) 0.120, p<0. 01 for the right) scores. PSV of left CCA (-0.205 per SD, p<0.05) and IMT (+42.536 per SD, p< 0.001) were associated with ADL. PSV of right CCA was associated with MMSE (+0.081 per SD, p<0.001). No significant relationship between ICA flow velocity and cognitive performance was observed.

Our preliminary data show that common carotid artery flow velocity was associated with cognitive performance.

To characterize at clinical and molecular levels a family presenting with X-linked recessive Hereditary Spastic Paraplegia (HSP).

HSPs are a large group of genetically heterogeneous neurodegenerative disorders characterized by progressive upper motor neuron signs. Mutations in the proteolipid protein (PLP1) gene have been identified in families linked to the SPG2 locus on chromosome Xq22. However, Pelizaeus-Merzbacher disease (PMD) is also an X-linked recessive neurological disorder caused by PLP1 mutations.

The SPG2 locus was investigated by linkage analysis in the family. The PLP1 gene was screened by sequencing. We present findings in a large French-Canadian family with an X-linked recessive HSP. The proband presented early with developmental delay and developed progressive spastic paraplegia. He has been wheelchair-bound since the age of three years. At the latest follow-up, he was 20 years-old and had severe spasticity predominantly affecting the lower extremities, moderate cerebellar dysfunction, and optic atrophy.

Linkage to SPG2 was established and a G to A mutation (M1R) in the initiation codon of the PLP1 gene was identified, likely resulting in the complete absence of proteolipid protein.

We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome.

Longitudinal, patient-level data on resource use and costs after an ischemic stroke are lacking in Canada. The objectives of this analysis were to calculate costs for the first year post-stroke and determine the impact of disability on costs.

The Economic Burden of Ischemic Stroke (BURST) Study was a one-year prospective study with a cohort of ischemic stroke patients recruited at 12 Canadian stroke centres. Clinical history, disability, health preference and resource utilization information was collected at discharge, three months, six months and one year. Resources included direct medical costs (2009 CAN$) such as emergency services, hospitalizations, rehabilitation, physician services, diagnostics, medications, allied health professional services, homecare, medical/assistive devices, changes to residence and paid caregivers, as well as indirect costs. Results were stratified by disability measured at discharge using the modified Rankin Score (mRS): non-disabling stroke (mRS 0-2) and disabling stroke (mRS 3-5).

We enrolled 232 ischemic stroke patients (age 69.4 ± 15.4 years; 51.3% male) and 113 (48.7%) were disabled at hospital discharge. The average annual cost was $74,353; $107,883 for disabling strokes and $48,339 for non-disabling strokes.

An average annual cost for ischemic stroke was calculated in which a disabling stroke was associated with a two-fold increase in costs compared to NDS. Costs during the hospitalization to three months phase were the highest contributor to the annual cost. A “back of the envelope” calculation using 38,000 stroke admissions and the average annual cost yields $2.8 billion as the burden of ischemic stroke.

The aim of this retrospective study was to investigate if elevated C reactive protein (CRP) was related to the stroke severity, and to analyze its different distribution in stroke subtypes.

316 patients with acute ischemic stroke (AIS) were enrolled and had CRP determinations; they were dichotomized as<7 or ≥7mg/L according to the previous report. 128 patients with transient ischemic attack who also had CRP measurements were selected as controls. A possible level-risk relationship between elevated CRP and NIHSS, which considered relatively severe illness as a value≥8, was studied within the AIS group.

CRP was elevated in 21% of the AIS compared to 4% in the control group (p = 0.000). Within the AIS group, patients with CRP levels ≥7mg/L had a significantly increased risk of severe stroke (OR 3.33, 95% CI 1.84-6.00, p =0.00). In subtype stroke, the highest rate of elevated CRP and NIHSS were in those with cardioembolic stroke (CE) using TOAST classification, total anterior circulation infarction (TACI) of OCSP classification and large volume infarction (LVI) of Adams classification; the odds ratio(OR) between elevated CRP and NIHSS was 6.14 (95% CI 1.43-26.44) in CE, 1.714 (95% CI 1.30-2.26) in TACI, 2.32 (95% CI 1.08-4.99) in LVI, and the p value were all below 0.05.

Elevated CRP level can reflect the severity of AIS, which was association with stroke subtype.

Conus medullaris syndrome (CMS) is a clinical neurologic syndrome caused by a conus medullaris lesion. CMS is a heterogeneous entity with various etiologies such as trauma or a space-occupying lesion. Multiple cases of CMS following spinal anesthesia have been reported, but CMS after radioisotope (RI) cisternography has not yet been reported.

We present four patients who developed CMS after RI cisternography.

All experienced neurological deficits such as paraparesis, sensory loss, and urinary incontinence three to four days after RI cisternography. Two showed abnormalities on lumbar magnetic resonance imaging, and three had complete symptom resolution within ten weeks.

The pathomechanism of the CMS is unclear, but we hypothesize that RI neurotoxicity might be responsible. It is possible that the use of low-dose 99mTc-DTPA or an alternative diagnostic tool such as magnetic resonance cisternography could help to prevent this complication.

The current study explored the effects of treadmill exercise intensity on functional recovery and hippocampal phospho-NR2B (p-NR2B) expression in cerebral ischemic rats, induced by permanent middle cerebral artery occlusion (MCAO) surgery.

Adult male Sprague-Dawley rats were randomly divided into four groups, including sham, no exercise (NE), low intensity training (LIT, v = 15 m/min), and moderate intensity training groups (MIT, v = 20 m/min). At different time points, the hippocampal expressions of p-NR2B and total NR2B were examined. In addition, neurological deficit score (NDS), body weight, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate brain infarct volume as assessments of post-stroke functional recovery. In order to investigate the effect of exercise on survival, the mortality rate was also recorded.

The results showed that treadmill exercise significantly decreased hippocampal expression of p-NR2B but didn't change the total NR2B, compared to the NE group on the 3rd, 7th, and 14th days following MCAO surgery. The effect on changes in p-NR2B levels, body weight, and brain infarct volume were more significant in the LIT compared to the MIT group.

The current findings demonstrate that physical exercise can produce neuroprotective effects, in part by down-regulating p-NR2B expression. Furthermore, the appropriate intensity of physical exercise is critical for post-stroke rehabilitation.

Fatigue affects 33-77% of stroke survivors. There is no consensus concerning risk factors for fatigue post-stroke, perhaps reflecting the multifaceted nature of fatigue. We characterized post-stroke fatigue using the Fatigue Impact Scale (FIS), a validated questionnaire capturing physical, cognitive, and psychosocial aspects of fatigue.

The Stroke Outcomes Study (SOS) prospectively enrolled ischemic stroke patients from 2001-2002. Measures collected included basic demographics, pre-morbid function (Oxford Handicap Scale, OHS), stroke severity (Stroke Severity Scale, SSS), stroke subtype (Oxfordshire Community Stroke Project Classification, OCSP), and discharge function (OHS; Barthel Index, BI). An interview was performed at 12 months evaluating function (BI; Modified Rankin Score, mRS), quality of life (Reintegration into Normal living Scale, RNL), depression (Geriatric Depression Scale, GDS), and fatigue (FIS).

We enrolled 522 ischemic stroke patients and 228 (57.6%) survivors completed one-year follow-up. In total, 36.8% endorsed fatigue (59.5% rated one of worst post-stroke symptoms). Linear regression demonstrated younger age was associated with increased fatigue frequency (β=-0.20;p=0.01), duration (β=-0.22;p<0.01), and disability (β=-0.24;p<0.01). Younger patients were more likely to describe fatigue as one of the worst symptoms post-stroke (β=-0.24;p=0.001). Younger patients experienced greater impact on cognitive (β=-0.27;p<0.05) and psychosocial (β=-0.27;p<0.05) function due to fatigue. Fatigue was correlated with depressive symptoms and diminished quality of life. Fatigue occurred without depression as 49.0% of respondents with fatigue as one of their worst symptoms did not have an elevated GDS.

Age was the only consistent predictor of fatigue severity at one year. Younger participants experienced increased cognitive and psychosocial fatigue.

The FRG1-transgenic mouse displays muscle dysfunction and atrophy reminiscent of fascioscapulohumeral muscular dystrophy (FSHD) and could provide a model to determine potential therapeutic interventions.

To determine if FRG1 mice benefit from treatments that improve muscle mass and function, mice were treated with creatine alone (Cr) or in combination with treadmill exercise (CrEX).

The CrEx treatment increased quadriceps weight, mitochondrial content (cytochome c oxidase (COX) activity, COX subunit one and four protein), and induced greater improvements in grip strength and rotarod fall speed. While Cr increased COX subunits one and four protein, no effect on muscle mass or performance was found. Since Cr resulted in no functional improvements, the benefits of CrEx may be mediated by exercise; however, the potential synergistic action of the combined treatment cannot be excluded.

Treatment with CrEx attenuates atrophy and muscle dysfunction associated with FRG1 overexpression. These data suggest exercise and creatine supplementation may benefit individuals with FSHD.

This study aims to assess current practices of Canadian physicians providing botulinum toxin-A (BoNT-A) treatments for children with hypertonia and to contrast these with international “best practice” recommendations, in order to identify practice variability and opportunities for knowledge translation.

Thirteen Canadian physicians assembled to develop and analyze results of a cross-sectional electronic survey, sent to 50 physicians across Canada.

Seventy-eight percent (39/50) of physicians completed the survey. The most frequently identified assessment tools were Gross Motor Function Classification System, Modified Tardieu Scale and neurological examination. Goal-setting tools were infrequently utilized. Common indications for BoNT-A injections and the muscles injected were identified. Significant variability was identified in using BoNT-A for hip displacement associated with hypertonia. The most frequent adverse event reported was localized weakness; 54% reporting this “occasionally“ and 15% “frequently”. Generalized weakness, fatigue, ptosis, diplopia, dysphagia, aspiration, respiratory distress, dysphonia and urinary incontinence were reported rarely or never. For dosage, 52% identified 16 Units/kg body weight of Botox® as maximum. A majority (64%) reported a maximum 400 Units for injection at one time. For localization, electrical stimulation and ultrasound were used infrequently (38% and 19% respectively). Distraction was the most frequently used pain-management technique (64%).

Canadian physicians generally adhere to international best practices when using BoNT-A to treat paediatric hypertonia. Two knowledge-translation opportunities were identified: use of individualized goal setting prior to BoNT-A and enhancing localization techniques. Physicians reported a good safety profile of BoNT-A in children.

Multiple Sclerosis is characterized by relapses separated by periods of relative quiescence. High dose intravenous corticosteroid pulses for three to five days is the current standard for the treatment of acute relapses, but recent evidence supports the use of equivalent doses of oral therapy as an alternative. The highest single dose preparation of oral prednisone is a 50mg tablet, requiring patients to take 25 tablets a day. Questions regarding compliance with this oral regimen have been raised.

To determine whether MS patients are complaint with 1250mg of oral prednisone daily for acute relapses.

Between November 2008 and December 2009, all patients diagnosed with an acute relapse in the London (Ontario) MS clinic were prospectively identified. If treatment with oral prednisone was initiated, subjects were given a survey to be mailed anonymously to the clinic.

Sixtyeight MS relapses were diagnosed and treated with corticosteroids in 66 patients of which 60 (58 subjects) were treated with 1250mg prednisone. Fifty-three (91.4%) surveys were returned. The reported compliance rate was high at 94.3% (50/53) with only one patient reporting being unable to take all the required pills due to intolerance. Most subjects (43, 86.0%) encountered at least one side effect, most commonly insomnia, mood changes and increased appetite. Two thirds of subjects (69.8%) indicated a preference for oral medication for future relapses.

High dose (1250mg) oral prednisone is an acceptable therapy to MS patients for the treatment of acute relapses with a high rate of compliance.

Sex differences in the risk factors, presentation and outcome of cerebral venous sinus thrombosis (CVST) are poorly defined, despite a discrepant prevalence between males and females. The proportion of patients on hormonal therapy who develop CVST varies widely. We describe the clinical features, risk factors and outcome by sex and by hormone-related risk factors among a large cohort of patients.

We reviewed records of 108 consecutive patients with CVST at a tertiary hospital in Calgary between 1999 and 2009. Descriptive statistics were used for between group comparisons (men, women with hormone-related risk factors and women without hormone-related risk factors).

Females made up 62% of patients, half of whom were on systemic hormonal therapy. Men and women without hormonal risk factors were older at onset. Oral contraceptive use was the major risk factor in women (45%) while concurrent mastoiditis was the most common predisposing factor in men (27%). Complications were frequent and overall mortality was 6%. Persisting deficits at discharge were more common in men (54% vs. 35% and 32%, p = 0.036). There was a trend for women with hormone-related risk factors to have less residual focal neurologic deficit than the other groups (5% vs. 15% and 17%, p=0.051).

There are differences between sexes in the presentation, risk factors and outcome of patients with CVST.

Symptomatic intracranial atherosclerosis (ICAS) is a dynamic disease that frequently progresses. Statins have been shown to have anti-atherosclerotic activity. We therefore investigated whether statins could prevent progression of ICAS.

This retrospective cohort study assessed 55 patients with acute ischemic stroke and symptomatic ICAS in the middle cerebral or basilar arteries as shown on magnetic resonance angiography (MRA), with follow-up MRA performed more than 1 year after the index stroke. Change in ICAS was classified as progressive, regressive, or stable. Baseline clinical characteristics and risk factor control during follow-up were assessed, and laboratory tests were performed at the time of follow-up MRA. The statin group was defined as patients regularly treated with statins for more than 75% of the follow-up period; the remaining patients were defined as the non-statin group.

At a median follow-up time of 21.8 months (range, 11.8-66.1 months), the statin group consisted of 26 (47.3%) patients and the non-statin group of 29 (52.7%). During follow-up, 6 (10.9%) patients progressed, 14 (25.5%) regressed, and 35 (63.6%) remained stable. Statin treatment was significantly associated with non-progression of ICAS (p=0.024). Two patients in the non-statin group had recurrent strokes. Border-zone infarcts were associated with progression of ICAS (3/6, 50%; p=0.007), whereas risk factors and inflammatory biomarkers were not related to progression.

Treatment with statins may prevent progression of symptomatic ICAS. Prospective randomized controlled trials are required to confirm that statins protect against such progression.

Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. Recently an autosomal recessive deficiency in Antiquitin (ALDH7A1), a gene involved in the catabolism of lysine has been identified as the underlying cause.

In 21 and 23 year-old sisters, who had presented with neonatal / early infantile onset seizures, PDE was confirmed by elevated urinary alpha aminoadipic- 6- semialdehyde (α-AASA) excretion and compound heterozygosity for two known ALDH7A1 missense mutations. Although epilepsy was well controlled upon treatment with pyridoxine, thiamine, phenytoin and carbamazepine since early infancy, both had developmental delay with prominent speech delay as children. As adults, despite the same genetic background and early treatment with pyridoxine, their degree of intellectual disability (ID) differed widely. While the older sister's cognitive functions were in the moderate ID range and she was not able to live unattended, the younger sister had only mild ID and was able to live independently.

Although seizures are a defining feature of PDE, other disease manifestations can vary widely even within the same family. Adult neurologists should be aware that the diagnosis of PDE can be delayed and PDE should be considered in the differential diagnosis of adults with seizure disorders dating from childhood.

Transforming growth factor beta1 (TGFβ1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. The aim of the present study was to investigate the relationship between human TGFβ1 gene +869T>C (rs1800470), -509C>T (rs1800469) single nucleotide polymorphisms (SNPs) and haplotypes and cerebral infarction (CI) in a Chinese population.

The genetic association study was performed in 450 Chinese patients (306 male and 144 female) with CI and 450 control subjects (326 male and 124 female). TGFβ1 gene +869T>C and -509C>T polymorphisms were identified with amplification refractory mutation system polymerase chain reaction and DNA sequencing method.

The individual SNPs analysis showed the +869T and -509C in an additive model (+869T vs +869C; -509 C vs T), +869TT genotype in a recessive model (TT vs TC+CC) and 509CC genotype in a dominant model (CC+ CT vs TT) were identified to be related to CI (P<0.05). +869T>C and -509C>T SNPs were in strong linkage disequilibrium (d'=0.87, R2=0.75). Haplotype analysis showed that +869C/-509T haplotype was associated with a significant decreased risk of CI (OR= 0.86, 95%CI, 0.70-0.92; P=0.007). Furthermore,+869T/-509C haplotype was associated with a significant increased risk of CI (OR=1.31, 95%CI, 1.10-2.03; P=0.019).

The results of this study indicate that polymorphisms and the haplotypes in the TGFβ1 gene might be genetic markers for CI in the Chinese population.

Awake brain surgery is useful for the treatment of a number of conditions such as epilepsy and brain tumor, as well as in functional neurosurgery. Several studies have been published regarding clinical results and outcomes of patients who have undergone awake craniotomy but few have dealt with related ethical issues.

The authors undertake to explore broadly the ethical issues surrounding awake brain surgery for tumor resection to encourage further consideration and discussion.

Based on a review of the literature related to awake craniotomy and in part from the personal experience of the senior author, we conducted an assessment of the ethical issues associated with awake brain tumor surgery.

The major ethical issues identified relate to: (1) lack of data; (2) utilization; (3) conflict of interest; (4) informed consent; (5) surgical innovation; and (6) surgical training.

The authors respectfully suggest that the selection of patients for awake craniotomy needs to be monitored according to more consistent, objective standards in order to avoid conflicts of interest and potential harm to patients.