Polymorphisms of genes participating in iron transportation have been associated with Alzheimer's disease (AD) risk. The association between transferrin (TF) gene rs1049296 (P570S) polymorphism and AD is controversial.

We performed meta analysis on data from 19 studies with 6310 cases and 13661 controls to reexamine the association between the TF gene rs1049296 polymorphism and AD. We applied a fixed-effects model to combine the odds ratio (OR) and 95% confidence intervals (95% CI). Egger's test was carried out to evaluate the potential publication bias.

The overall ORs with 95% CIs showed statistical association between the TF gene rs1049296 polymorphism and the risk of AD in the allele contrast, the recessive model and the dominant model for allele C2 (fixed-effects pooled OR 1.11; 95% CI 1.05 to 1.17, pooled OR 1.13; 95% CI 1.06 to 1.21, and pooled OR 1.23; 95% CI 1.03 to 1.47, respectively). In the contrast of C2C2+C2C1 vs C1C1, large heterogeneity among the Asian subgroup (p=0.041, I2= 68.6%) was observed but not among the overall population (p = 0.184, I2= 22.4%). No publication bias was observed.

The present meta analysis demonstrated that TF gene rs1049296 polymorphism is a genetic determinant of AD.

Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery.

A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement.

Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008).

Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.

We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).

The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.

The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

The aim of the study is to explore the association of serum bilirubin levels with admission severity and short term clinical outcomes among acute ischemic stroke patients.

Data were collected from 2361 acute ischemic stroke patients in four hospitals of Shangdong Province during January 2006 and December 2008. National Institutes of Health Stroke Scale (NIHSS) was used to assess admission and discharge severity. NIHSS≥10 at discharge or in-hospital death was defined as short-term clinical outcomes. Logistic regression and trend test were used to examine the association of serum bilirubin levels with admission severity and short term clinical outcomes.

Serum bilirubin levels were significantly and positively associated with admission severity (P for trend <0.05). The age-sex adjusted odds ratios (95% confidential intervals) of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.245 (0.873, 1.777)/1.276 (0.895, 1.818), 1.484 (1.048, 2.102)/1.628 (1.158, 2.289) and 2.869 (2.076, 3.966)/2.765 (1.996, 3.828), respectively, compared with the lowest quartile; the multivariate adjusted odds ratios of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.088(0.711, 1.665)/1.436(0.94, 2.193), 1.328(0.877, 2.011)/1.647(1.092, 2.485) and 2.336(1.579, 3.458)/3.079 (2.049, 4.623), respectively, compared with the lowest quartile. However, no association between serum bilirubin levels and short-term clinical outcomes was observed in our study.

Serum bilirubin levels were associated with initial stroke severity closely. Nevertheless, there is no significant relationship between serum bilirubin levels and short-term clinical outcomes among acute ischemic stroke patients.

Discrimination between radiation necrosis and tumor progression after radiation therapy represents a radiologic challenge. The aim of our investigation is to identify patterns of radiation necrosis on brain magnetic resonance imaging (MRI) and positron emission tomography (PET) with Fluoroethyltyrosin (FET) after proton beam therapy (PBT) for skull base tumors.

Five consecutive patients with extra-axial neoplasms were included, presenting a total of eight radiation necrosis lesions (three clival chordomas; two petroclival chondrosarcomas; two women; mean age: 49 ± 18.2 years). Radiation necrosis was defined as the appearance of abnormal enhancement on MRI after PBT decreasing over time, and additional histopathologic confirmation in one patient. MRI and PET imaging were retrospectively analyzed by two experienced radiologists in consensus.

All lesions were localized close to the primary tumor in the field of irradiation. Three patients showed bilateral symmetrical lesions. All lesions showed T2 hyperintensity and T1 hypointensity. Cerebral blood volume (CBV) was reduced in all available studies. None of the lesions showed a restricted diffusion. FET-PET (three patients) showed a higher uptake in four out of five lesions; three of which had a mean tumor-to-background (TBRmean) uptake lower than 1.95 and FET uptake increasing over time and were correctly classified into radiation necrosis.

Most radiation necroses were in direct continuity with the primary tumor mimicking tumor progression. The most consistent imaging findings for PBT radiation necrosis are low CBV without restricted diffusion and FET-PET TBRmean lower than 1.95 or increasing uptake over time. Bilateral symmetric involvement may be another indicator of radiation necrosis.

To review our institutional experience with Gamma Knife (GK) stereotactic radiosurgery in treating large vestibular schwannomas (VS) of 3 to 4 cm diameter.

We conducted a retrospective cohort review of all patients treated with GK for VS at our institution between November 2003 and March 2012. Data on age, sex, VS volume, location and maximal diameter, House-Brackmann (HB) facial nerve scores pre and post-GK, Gardner-Robertson (GR) hearing score pre and post-GK, GK treatment parameters, VS response time, complications and clinical outcome was recorded.

A total of 28 patients during the defined time period were identified. Three patients were lost to follow-up. Mean follow-up was 34.5 months. Tumor control occurred in 92%, and was maintained in 85.7% at two years. Facial nerve or hearing preservation occurred in all treated compared to pre-GK status, as per HB and GR grading. Transient complications occurred in 80%. Temporary vestibular dysfunction occurred in seven patients (28%). One patient (4%) had the permanent complication of worsening pre-GK hemifacial spasm. Four patients (16%) developed hydrocephalus post-GK.

GK stereotactic radiosurgery as a primary treatment modality for large VS can provide acceptable tumor control rates with good facial nerve and hearing preservation, and low complication rates.

To evaluate the prevalence of nonlesional focal epilepsy in an adult epilepsy clinic and its refractoriness to antiepileptic drug therapy.

Focal epilepsy is frequently, but not always, associated with structural epileptogenic lesions identifiable on magnetic resonance imaging (MRI).

We analyzed the data from all patients evaluated at an adult epilepsy clinic from January 2002 to December 2011. Clinical and paraclinical findings were used to diagnose focal epilepsy. Magnetic resonance imaging were reviewed and classified as normal, with an epileptogenic lesion, or with a lesion of unclear epileptogenicity. Epileptogenic lesions were further categorized as tumours, vascular malformations, gliosis (including hippocampal atrophy/sclerosis), and malformations of cortical development. Our study group included patients with no lesions on MRI. Pharmacoresistance of patients with nonlesional focal epilepsy was assessed using the ILAE and Perucca's criterias.

Out of 1521 patients evaluated (mean age 44 years; range 14-93 years), 843 had focal epilepsy. Magnetic resonance imaging data, available for 806 (96%) subjects, showed epileptogenic lesions in 65%, no obvious epileptogenic lesions in 31% and lesions of unclear epileptogenicity in 4%. Magnetic resonance imaging-identified lesions included gliosis due to an acquired insult (52% including 17% of hippocampal atrophy or sclerosis), tumours (29%), vascular malformations (16%) and malformations of cortical development (10%). Fifty-two percent of nonlesional focal epileptic patients were drug-refractory.

In a tertiary epilepsy clinic, close to a third of patients with focal epilepsy were found to be nonlesional, half of which were drug-resistant.

Many of the falls among people with Parkinson's disease (PD) occur during sudden, on-the-spot turning which requires systematic reorientation of axial segments towards the new direction. We examined whether a disturbance in the coordination of segmental reorientation is an important cause of turning difficulty in individuals with PD and is altered by dopaminergic medication.

The sequence and timing of segmental reorientation during 45° and 90° on-the-spot turns was examined in fourteen individuals with PD while “off” and “on” medication and nineteen healthy controls (HC).

Regardless of the magnitude of the turn, HC reoriented their head, shoulder, and pelvis simultaneously followed by mediolateral foot displacement. PD patients displayed temporal coordination patterns similar to the HC. PD however, reduced the velocity and early magnitude of reorientation of each body segment which were both slightly improved by dopaminergic medication.

Our finding that the HC and PD patients turn en bloc when the turn is predictable and there are no time constraints shows that the strategy of en bloc turning is not wrong if the movement parameters are unconstrained. However, in real life situations, which usually require quick and unpredictable turns, the en bloc strategy may be unsafe and more likely to result in falls. While in such situations HC are able to change the strategy from en bloc to sequential segmental turning, PD patients may not be able to do so and continue to turn en bloc.

The Neuromuscular Registry of Saguenay-Lac-Saint-Jean (SLSJ), Québec, Canada was established for epidemiological surveillance of neuromuscular disorders including amyotrophic lateral sclerosis (ALS). The objectives of this study are to analyze the ALS clinical characteristics of the SLSJ population and to determine the incidence rate over time by five year periods since 1985.

The Registry was validated by a review of the medical records maintained at the CSSS de Chicoutimi, the regional university hospital and, by the estimation of the number of hospitalizations for ALS patients using the Quebec Hospital inpatient database (MED-ECHO).

A total of 109 patients were included. Overall, the clinical features of ALS observed in SLSJ population are similar to those described in the literature. We observed a significant increase in the incidence rate of ALS during the 2005-2009 period compared with the previous periods. This is due to a significant increase in the incidence rate among the ≥65 years old group, from 4.68 per 100,000 persons/year (CI 95% 2.88-6.48) during 1985-2004 period to 12.22 (CI 95% 7.43-17.02) during 2005-2009 period.

Given the small size of the SLSJ population, a longer observation period will be needed to confirm a new steady state incidence of ALS in this region.

It is estimated that some hundreds of Canadian patients with multiple sclerosis (MS) have journeyed abroad to avail themselves of ‘liberation therapy’ (venoplasty) following the initial report by Zamboni et al in 2009. That study also led to public pressure upon Departments of Health in Canadian Provinces to fund the procedure. The present study was done in order to advise the Government of Newfoundland and Labrador as to whether or not it should do so.

We conducted an observational study of 30 MS subjects who had submitted to venoplasty, using objective, semi-objective and subjective measures.

Significant subjective improvement was reported by half of the subjects at three months, although the degree of perceived improvement was less at 12 months. The objective and semi-objective tests employed did not indicate improvement in any area over the one-year follow-up period. Seven of the 29 subjects in whom CT venography was performed at the end of the study year were found to have uni- or bilateral occlusion or >50% stenosis of at least one cervical draining vein, but they showed no deterioration in their clinical status compared to those in whom no venous occlusion nor stenosis was found.

No objective improvement was found at one year in thirty MS subjects who had undergone venoplasty, although many reported a degree of subjective benefit.

To identify the predictors of symptomatic post-radiation T2 signal change in patients with arteriovenous malformations (AVM) treated with radiosurgery.

The charts of 211 consecutive patients with arteriovenous malformations treated with either gamma knife radisurgery or linear accelerator radiosurgery between 2000-2009 were retrospectively reviewed. 168 patients had a minimum of 12 months of clinical and radiologic follow-up following the procedure and complete dosage data. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects.

141 patients had no clinical symptomatic complications. 21 patients had global or focal neurological deficits attributed to symptomatic edema. Variables associated with development of symptomatic edema included a non-hemorrhagic symptomatic presentation compared to presentation with hemorrhage, p=0.001; OR (95%CI) = 6.26 (1.99, 19.69); the presence of venous rerouting compared to the lack of venous rerouting, p=0.031; OR (95% CI) = 3.25 (1.20, 8.80); radiosurgery with GKS compared to linear accelerator radiosurgery p = 0.012; OR (95% CI) = 4.58 (1.28, 16.32); and the presence of more than one draining vein compared to a single draining vein p = 0.032; OR (95% CI) = 2.82 (1.06, 7.50).

We postulated that the higher maximal doses used with gamma knife radiosurgery may be responsible for the greater number of adverse radiation effects with this modality compared to linear accelerator radiosurgery. We found that AVMs with greater venous complexity and therefore instability resulted in more adverse treatment outcomes, suggesting that AVM angioarchitecture should be considered when making treatment decisions.

Individuals with Parkinson's disease (PD) show poorer balance and greater incidence of falls while turning. We investigated whether a disturbance in timing and sequence of reorientation of body segments is a potential cause of turning difficulty in PD and is altered by levodopa.

The sequence and timing of segmental reorientation during 45° and 90° walking turns were recorded in nineteen healthy controls and fourteen individuals with PD “off” and “on” medication.

Both healthy elderly and PD patients “off” medication displayed a top-down sequence of segment reorientation, but differed with respect to the delay time between segments: PD “off” medication displayed a shorter delay between the onset of head and shoulder reorientation and longer delays for pelvis and foot reorientation. Furthermore, for all segments the peak angular velocities were lower for PD patients than healthy controls, with greater difference between the two groups during larger turns. While for both groups the velocity and magnitude of rotation of all segments were greater during larger turns, the relative timing of reorientation of segments remained the same during small and large turns. Medication had no significant effect on the timing and sequence of reorientation of segments and caused only a small and non-significant increase to segment velocities.

This study further characterized the turning performance of individuals with PD. Our findings have clinical applications and therapeutic value for PD patients with difficulty turning. Understanding the specific deficiencies of turning performance of PD patients allows the therapists to opt for the most effective rehabilitation techniques.

In most studies, treatment decisions of brainstem glioma are based solely on MRI features and do not incorporate a histopathological diagnosis. In the current study, we sought to compare MRI characteristics with histopathological findings of bainstem glioma.

From April 2003 through April 2012, 150 patients were diagnosed with brainstem gliomas by MRI and microsurgically treated in Tiantan Hospital, Beijing, China. All the MRI and histopathological findings of these patients were respectively reviewed.

Of the 150 patients, 65 were female and 85 were male, 120 were adults and 30 were children (age < 18 years), 108 were low-grade glioma (72.0%), 35 were high-grade glioma (23.3%). The accuracy of the MRI diagnosis for brainstem glioma was 95.3%. Data analysis of the MRI findings revealed that a focal lesion was associated with a more favorable histopathological diagnosis in intrinsic (P=0.005) and exophytic (P=0.001) brainstem glioma patients. In the intrinsic diffuse type, tumors without enhancement had more favorable pathological findings (P=0.009).

To our knowledge, this is the largest case series of this nature reported in the literature to date. The results of this study suggest that MRI features of brainstem gliomas could predict some pathological features and guide prognosis, choice of biopsy and treatment modalities. The pathology of tumors with a focal appearance on MRI was associated with a prognosis that was significantly better than their diffuse counterparts. For the intrinsic diffuse gliomas, non-enhancing tumors had pathology suggestive of a favorable prognosis.

To compare neurologist and patient perceptions of multiple sclerosis (MS)-related health status.

MS patients (n=99) were recruited from six sites in Canada. Following a consultation with their neurologist, patients estimated their relapse frequency, rated their general health and quality of life (QoL), reviewed descriptions of eight health domains and selected the three most important, and completed a utility assessment using the standard gamble (SG). Concurrently, neurologists independently used the same instruments to rate their patients' health status. Assessments were compared on the basis of paired mean values of both groups and the degree of exact agreement quantified by intraclass coefficient (ICC) and kappa analyses, which yield values of 1.0 with 100% agreement.

There were significant differences (p<0.001) between patient and neurologist ratings for relapses in the last year (0.86 vs. 0.4, respectively), QoL (61.2 vs. 69.7 (maximum score = 100) and utility (0.864 vs. 0.971); ICC analysis revealed moderate to poor levels of agreement (0.56 for QoL to 0.03 for SG). There was little concordance in identification of important health domain and the only significant associations were in bodily pain and social functioning (kappa statistic = 0.24, p = 0.026 for both). Neurologists identified physical functioning domains as important, while patients placed more emphasis on mental health domains.

Discrepancies between neurologist and patient perceptions of MS were observed. The study identifies a need to educate neurologists on the recognition of MS health domains that are important in the definition of patient QoL.