To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.

We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.

Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).

While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.

Computed tomogram (CT) imaging is often used for immediate postoperative assessment of transsphenoidal pituitary adenoma resection while magnetic resonance imaging (MRI) is used for follow-up. The residual mass is known to decrease in size over time but the difference between the two imaging modalities has not been quantified. Our objective was to quantify the size difference of the residual mass on immediate postoperative CT compared with delayed MRI.

Retrospective analysis of 69 patients who had undergone pituitary adenoma resection at our institution between 2004-2010. Sellar and suprasellar diameter, along with the overall volume of the residual mass were measured on both the immediate postoperative CT and delayed MRI.

Average preoperative sellar and suprasellar diameter was 22.2 ± 4.6mm and 20.9 ± 5.9mm, respectively. Average sellar residual diameter on immediate postoperative CT (16.5 ± 5.4 mm, 25% reduction) was significantly larger than delayed MRI (10.6 ± 6.2mm, 52% reduction). The average suprasellar component on CT (15.5±6.5mm, 26% reduction) was also significantly larger than that on MRI (3.3 ± 5.4 mm, 84% reduction). The postoperative CT showed a 46% reduction in volume while a 71% reduction was noted on the delayed MRI.

A significant reduction in residual mass is noted on delayed MR imaging compared with immediate postoperative CT. Therefore, from a resource management and prognostication point of view, CT should be used for immediate postoperative assessment while delayed MRI should be used to assess operative success and for communication with patients.

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 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.

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.

The impact of malignant glioma resection on survival is still a matter of controversy. The lack of well-designed prospective studies as well as control of all factors in retrospective studies plays an important role in this debate. Amongst some of these uncontrolled factors, are the inclusion of different histological grades, the lack of objective methods to estimate the extent of resection and unspecified delays in post-operative imaging.

We retrospectively reviewed 126 consecutive patients with glioblastoma, operated on by the senior authors at the Centre Hospitalier Universitaire de Sherbrooke, who met the following criteria: >18 years of age, newly diagnosed glioblastoma, pre-operative magnetic resonance imaging (MRI) within 2 weeks prior to surgery, and a post-operative MRI within 72 hours after surgery. Extent of tumour resection was calculated using pre and post-operative tumour delimitation on gadolinium-enhanced T1 MRI in a volumetric analysis.

Applying stringent specific inclusion criteria, 126 patients were retained in the analysis. The median overall survival was 271 days and the median extent of resection was 65%. Patients with more than 90% of tumour resection had a significantly better outcome, improving median survival from 225 to 519 days (P=0.006). Other factors that significantly improved survival were the use of radiotherapy, the number of regimens and type of chemotherapy used.

A more aggressive approach combining maximal safe resection and use of salvage chemotherapy seems to confer a survival advantage for glioblastoma patients.

Previously all subarachnoid hemorrhage (SAH) patients were admitted, whereas now patients with angiography may be discharged.

To survey neurosurgeons to determine current practice and what constitutes a clinically significant subarachnoid hemorrhage.

We surveyed all neurosurgeons listed in the Canadian Medical Directory. We used a modified Dillman technique with up to five mailed surveys plus a pre-notification letter. Neurosurgeons rated the significance of 13 scenarios of subarachnoid hemorrhage. Scenarios varied from aneurysmal subarachnoid hemorrhage to patients with isolated xanthochromia in cerebrospinal fluid. Each scenario was rated for clinical significance using a 5-point scale [1(always) to 5(never)].

Of the 224 surveyed, 115 neurosurgeons responded. Scenarios with aneurysms requiring intervention, arteriovenous malformations, death or any surgical intervention all had median responses of 1 (IQR 1, 1). Scenarios having xanthochromia and few red blood cells in cerebrospinal fluid with negative computerized tomogram (CT) and angiography had median responses of 3 (IQR 1, 4). Scenarios with perimesencephalic pattern on CT with negative angiography had median of 3 (IQR 2, 4). Scenarios where patient is discharged from the emergency department had median of 4 (IQR 3, 5).

Subarachnoid hemorrhages due to aneurysms or arteriovenous malformations causing death or requiring surgical intervention are always clinically significant. Other types of nonaneurysmal subarachnoid hemorrhages had inconsistent ratings for clinical significance. These survey results highlight the need for further discussions to standardize the diagnosis of what constitutes a clinically significant subarachnoid hemorrhage and what care should be afforded to these patients.

Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE.

Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined.

Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%).

Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.