Adequate animal glioma models are mandatory for the pursuit of preclinical research in neuro-oncology. Many implantation models have been described, but none perfectly emulate human malignant gliomas. This work reports our experience in standardizing, optimizing and characterizing the Fischer/F98 glioma model on the clinical, pathological, radiological and metabolic aspects.

F98 cells were implanted in 70 Fischer rats, varying the quantity of cells and volume of implantation solution, and using a micro-infusion pump to minimize implantation trauma, after adequate coordinates were established. Pathological analysis consisted in hematoxylin and eosin (H&E) staining and immunohistochemistry for GFAP, vimentin, albumin, TGF-b1, TGF-b2, CD3 and CD45. Twelve animals were used for MR imaging at 5, 10, 15 and 20 days. Corresponding MR images were compared with pathological slides. Two animals underwent 18F-FDG and 11C-acetate PET studies for metabolic characterization of the tumors.

Implantation with 1x104 cells produced a median survival of 26 days and a tumor take of 100%. Large infiltrative neoplasms with a necrotic core were seen on H&E. Numerous mitosis, peritumoral infiltrative behavior, and neovascular proliferation were also obvious. GFAP and vimentin staining was positive inside the tumor cells. Albumin staining was observed in the extracellular space around the tumors. CD3 staining was negligible. The MR images correlated the pathologic findings. 18F-FDG uptake was strong in the tumors.

The standardized model described in this study behaves in a predictable and reproducible fashion, and could be considered for future pre-clinical studies. It adequately mimics the behavior of human malignant astrocytomas.

Memory impairment, usually impaired retrieval of information, has been described in HIV/AIDS, especially among those with severe illness. Neuro-cognitive disturbances in HIV/AIDS have been linked to poor quality of life and medication adherence. This prospective, case-control study was designed to assess the verbal and non-verbal memory as well as the attention abilities of Nigerian Africans with HIV/AIDS and correlate their performances with their CD4+ T lymphocytes (CD4+) counts.

A total of 288 randomly selected subjects, comprising 96 HIV-positive symptomatic patients, 96 HIV-positive asymptomatic patients and 96 HIV-negative controls, participated in the study. The subjects were age-, sex-, and level of education matched. The Recognition Memory Test and Choice Reaction Time tasks, components of the computer-assisted neuropsychological tests battery- the Iron Psychology ‘FePsy’ were used for cognitive assessments.

The mean memory scores of the HIV-positive asymptomatic subjects did not differ significantly from the controls (p>0.05) but the HIV-positive symptomatic subjects' scores were significantly lower than the controls (p<0.05). Both HIV-positive groups had psychomotor slowing and impaired attention (p<0.05). The HIV-positive subjects with CD4+ counts <200/μl and between 200 and 499/μl had significant memory impairment (p<0.001 and p<0.001 respectively) but there was no significant impairment among those with count ≥500/μl. Impaired ability for sustained attention was however present irrespective of the CD4+ level relative to controls (p<0.001).

We concluded that there was no significant memory disturbance among HIV-positive asymptomatic subjects despite the presence of impaired attention and psychomotor slowing, and that the severity of immune suppression (as indicated by the CD4+ T lymphocytes count) is a strong determinant of cognitive decline in HIV/AIDS.

The primary objective of this study is to evaluate clinician attitudes towards the treatment of cervical spondylotic myelopathy (CSM) in order to determine whether clinical equipoise exists for a segment of this patient population. The secondary objective is to examine the factors that influence treatment decisions.

Cross-sectional internet-based survey of neurologists, neurosurgeons and orthopedic surgeons.

Between 40-60% of respondents recommended surgery for (1) patients with minimal or no symptoms, but incidentally discovered increased T2 signal within the cervical cord on MRI, (2) patients with mild symptoms and indentation of the cervical cord but without increased T2 signal and (3) those with at least moderately severe clinical findings accompanied by MRI showing effacement of the thecal sac but without indentation of the cord or increased T2 signal. The severity of the radiological abnormalities most strongly influence treatment decisions.

We conclude that clinical equipoise does exist for certain groups of patients with CSM, suggesting that a randomized controlled trial could be performed in this population.

Visual processing deficits involving temporal characteristics are typically not captured by the widely used outcome measures (i.e., Expanded Disability Status Scale, Multiple Sclerosis Functional Composite) in multiple sclerosis (MS). Visual temporal thresholds (i.e., measurements of the temporal aspects in visual processing) are typically significantly higher (i.e., prolonged) in MS patients when compared to controls. The test-retest reliability of these thresholds was examined in patients with MS.

Visual temporal thresholds were measured in 21 stable MS patients during two separate test sessions. Test-retest reliability and the standard error of measurement were calculated. The threshold of change in visual temporal thresholds in MS patients that would correspond to real change beyond measurement error with 95% certainty was also calculated. For comparisons, a control group (n = 10) was included.

The test-retest reliability of this measure of visual temporal thresholds was 0.97. The threshold indicating change beyond chance or measurement error with 95% certainty was 11 ms. Higher thresholds were significantly correlated with longer durations of disease.

This measure of visual temporal thresholds has excellent test-retest reliability and a change of greater than 11 ms is highly likely to represent real change in MS patients. The findings indicate that these measurements may provide useful clinical information about functional changes regarding the temporal aspects of the visual system, which is currently not captured by the Extended Disability Status Scale.

A number of causative mutations such as a-synuclein, parkin, UCHL1, Pink-1, DJ-1 have been identified in Parkinson's disease (PD). They are usually found in the familial cases. One mutation of great interest is the G2019S mutation in the LRRK2 gene, which has been reported in both familial and sporadic PD. Its prevalence has been reported to vary markedly among different races. We examined the prevalence of the G2019S mutation in the Korean PD population for genetic study planning.

We conducted a genetic analysis of the G2019S mutation by standard PCR and restriction digestion method. 453 PD patients were studied, 34% of whom had an age at onset of <50 years and 3.8% had a positive family history.

None of the 453 study subjects carried the G2019S mutation.

Our result confirms previous reports that the G2019S mutation is rare among PD patients in the Asian population. This result supports the notion that the prevalence of this LRRK2 mutation is population specific, and that there may be a founder effect within western populations.

Current Health Canada instructions for use of the dopamine agonists (DA), pramipexole and ropinirole, state that Parkinson's disease (PD) patients should be told not to drive. The objective was to assess neurologists' actual clinical practice concerning driving advice they give to PD patients starting a DA.

An online survey was created consisting of 4 items regarding demographics, 5 regarding PD and driving, and 9 regarding DA use and driving. The survey was distributed to 563 neurologists.

In total 96 neurologists (17.9%) responded. 4.4% tell patients with PD not to drive, solely because they are taking a DA. Respondents assess the patient's tendency for excessive daytime sleepiness and sleep attacks after starting a DA more frequently than after starting other dopaminergic drugs (p<0.001).

A minor proportion of the clinicians responding to our survey advise PD patients not to drive, solely because they use a DA. Such being the case, we propose that current Health Canada guidelines need revision.

To determine: 1. the degrees of consensus and disagreement among Canadian critical care clinicians regarding the appropriateness (benefit exceeding risk) of common therapeutic manoeuvres in patients with severe closed head injury (CHI), and 2. the frequency with which clinicians employed these manoeuvres.

The study design was a systematic scenario-based survey of all neurosurgeons and critical care physicians treating patients with severe CHI in Canada.

In the scenario of acute epidural hematoma with mass effect, respondents agreed very strongly that surgery was appropriate. Clinicians reported mannitol and hypertonic saline as appropriate. Beyond these two interventions, agreement was less strong, and the use of the extraventricular drain (EVD), phenytoin, cooling, hyperventilation, nimodipine, and jugular venous oximetry (JVO) were of uncertain appropriateness. Steroids were considered inappropriate. In a scenario of diffuse axonal injury (DAI), clinicians agreed strongly that fever reduction, early enteral feeding, intensive glucose control, and cerebral perfusion pressure (CPP)-directed management were appropriate. The use of mannitol, hypertonic saline, EVD, JVO, narcotics and propofol were also appropriate. Neuromuscular blockade, surgery, and hyperventilation were of uncertain appropriateness. The appropriateness ratings of the interventions considered in the scenario of an intracranial contusion mirrored the DAI scenario. In general, correlations between the reported appropriateness and frequency of use of each intervention were very high. An exception noted was the use of the JVO. The correlation between CPP-guided therapy and the use of the EVD was weak.

This survey has described current practice with regard to treatment of patients with severe CHI. Areas of variation in perceived appropriateness were identified that may benefit from further evaluation. Suggested priorities for evaluation include the use of osmotic diuretics, anticonvulsants, and intracranial manometry.

Much research has gone into the assessment of function and health-related quality of life (HRQOL) in those with multiple sclerosis (MS). The Medical Outcomes Study 36-item short form (SF-36) has been widely used in this population but current recommendations are that it be supplemented with condition-specific measures such as the MS Quality of Life Inventory (MSQLI) and the MS Functional Composite (MSFC). The goal of the baseline component of this study was the measurement of generic and condition-specific HRQOL, and the identification of factors associated with these outcomes.

HRQOL was assessed at the baseline phase of a longitudinal study. Participants completed the assessment during their regularly scheduled clinic visit.

300 of 387 eligible patients agreed to participate, for a response rate of 77.5%. Age ranged from 22 to 77 years, while duration of MS ranged from 1 to 47 years. Mean SF-36 scores were well below age- and sex-adjusted normative data. Only 240 completed the MSFC component. Higher EDSS, use of support services, pain medications, clinical depression and antidepressant use were associated with poorer HRQOL, while higher income and education were associated with better HRQOL.

There is a substantial burden of illness associated with MS when compared to normative HRQOL data. This was more pronounced in physically- than in mentally-oriented domains. Assessment of HRQOL provides a valuable complement to the EDSS by providing information about the patient perception of function and HRQOL beyond that which can be obtained by physical assessment alone.

We reviewed our experience in 96 consecutive patients exhibiting periodic lateralized epileptiform discharges (PLEDs) on EEG.

EEG reports from January 1, 1999 to September 30, 2006 were screened for the term ‘PLEDs’ and its variants. A retrospective chart review, including examination of neuroimaging and other investigations, was conducted on each patient identified.

Acute stroke, tumor and central nervous system infection were the most common etiologies, accounting for 26%, 12% and 12% of cases respectively. Acute hemorrhage and traumatic brain injury combined accounted for another 12%. Previously unreported etiologies included posterior reversible encephalopathy syndrome (PRES), familial hemiplegic migraine and cerebral amyloidosis. There were 9 cases of chronic PLEDs attributable to underlying cortical dysplasia or severe remote cerebral injury, all with an accompanying partial seizure disorder. A prominent role for alcohol withdrawal was noted, and in 6 cases was the sole etiological factor. Fever was present as a potential contributing factor in 40% of cases, and significant metabolic abnormalities in 35%. Seizure activity occurred in 85% of patients overall, but in 100% of patients with PLEDs Plus and BiPLEDs Plus. The overall mortality rate was 27%. Mortality among patients with BiPLEDs however was almost twice that, at 52%.

This case series demonstrates the wide variety of potential PLED etiologies. It also emphasizes that despite advances in neurocritical care, the morbidity and mortality associated with PLEDs has changed little since their recognition four decades ago.

The central and peripheral nervous systems are often affected in intensive care unit (ICU) patients, especially those with prolonged assisted ventilation and sepsis or systemic inflammatory response syndrome (SIRS). The autonomic nervous system, however, has been under-investigated in such patients. We evaluated autonomic nervous system (ANS) function in 29 ICU patients with various neurological disorders.

Testing involved cardiac R-R variation (CRRV) as an index of parasympathetic function and the sympathetic skin response (SSR) for sympathetic assessment.

Only those 8 patients with sepsis-related neuropathy or encephalopathy had abnormal CRRV, while the SSR was absent in all but 2 patients.

Our preliminary study revealed a high incidence of autonomic dysfunction in ICU patients with various neurological disorders.

Persons with multiple sclerosis (MS) represent a small segment of the population, but given the progression of the disease, they experience substantial physical, psychosocial and economic burdens.

The primary aim was to compare demographic characteristics, health status, health behaviours, health care resource utilization and access to health care of the community dwelling populations with and without MS.

Cross-sectional survey using data from the Canadian Community Health Survey (CCHS 1.1). Adjusted analyses were performed to assess differences between persons with MS and the general population, after controlling for age and sex. Normalized sampling weights and bootstrap variance estimates were used.

Respondents with MS were 7.6 times (95% CI: 5.4, 10.7) more likely to have health-related quality of life scores that reflected severe impairment than respondents without MS. Respondents with MS were 12.2 times (95% CI: 8.6, 17.2) to rate their health as ‘poor’ or ‘fair’ than the general population. Urinary incontinence and chronic fatigue syndrome were 18.7 times (95% CI: 12.5, 28.2) and 21.9 times (95% CI: 11.9, 40.3), more likely to be reported by respondents with MS than those without. Differences between the two populations also existed in terms of health care resource utilization and access and health behaviours.

Large discrepancies in health status and health care utilization existed between persons with MS who reside in the community and the general population according to all indicators used. Health care needs of persons with MS were also not met.

Age-related brain changes may contribute to axial features in Parkinson's disease (PD).

To determine if ventricular volume and white matter high signal changes (WMC) are related to motor signs in PD and controls independent of age.

Patients were rated with the Unified Parkinson's Disease Rating Scale (subscore A: tremor, rigidity, bradykinesia, and facial expression; subscore B: speech and axial impairment). Steps and time taken to walk 9.144 meters were measured. Total ventricular volume (TVV) and intracranial volume (ICV) were measured on T1-weighted MRI using manual tracing software. WMC were rated on axial T2-weighted, dual-echo or FLAIR MR images using a visual scale.

TVV (cm3) (PD: 36.48 ± 15.93; controls: 32.16 ± 14.20, p = 0.21) and WMC did not differ between groups (PD: 3.7 ± 4.2; controls: 3.2 ± 3.1, p = 0.55). Age correlated positively with ICV-corrected TVV and WMC in PD (cTVV: r = 0.48, p = 0.003; WMC: r=0.42, p=0.01) and controls (cTVV: r = 0.31, p = 0.04; WMC: r=0.44, p=0.003). Subscore B (r = 0.42, p = 0.01) but not subscore A (r = 0.25, p = 0.14) correlated with cTVV in PD. Steps and walking time correlated with cTVV and WMC in PD; cadence correlated with cTVV and steps with WMC in controls. Age-adjustment eliminated correlations.

Subscore B, but not subscore A correlated positively with ventricular volume in PD, though this association was accounted for by age. Age-related brain change super-imposed on PD may contribute to axial features.

Multiple Sclerosis (MS) is reported to be uncommon among North American aboriginals despite frequent intermarriage with people of European ancestry, but few population-based studies have been conducted. The purpose of this study was to determine the prevalence of MS among First Nations aboriginal people in Alberta, Canada compared to the general population.

All hospital in-patient and physician fee-for-service records between 1994 and 2002 where a diagnosis of MS was mentioned were extracted from government health databases in the province of Alberta. First Nations people can be identified since the federal government (Health Canada) pays health care insurance premiums on their behalf. Multiple Sclerosis prevalence per 100,000 population for both First Nations people and the general population of Alberta were calculated for each year during this time span.

Among First Nations in Alberta, MS prevalence was 56.3 per 100,000 in 1994 and 99.9 per 100,000 in 2002, an increase of 43.6%. In 2002 prevalence was 158.1 and 38.0 for females and males respectively, a female to male ratio of 4.2:1. Multiple Sclerosis prevalence among the general population of Alberta was 262.6 per 100,000 in 1994 and 335.0 per 100,000 in 2002, an increase of 21.6%. In 2002 prevalence was 481.5 and 187.5 for females and males respectively, a female to male ratio of 2.6:1. Peak prevalence for both First Nations and general population females in 2002 was age 50-59, also 50-59 for both First Nations and general population males.

While MS prevalence in First Nations people is lower than in the general population of Alberta, it is not rare by worldwide standards.

Routine histopathological examination of intervertebral disc specimens is commonly performed in North American hospitals, but recent studies have questioned the utility of this practice in cases where the indication for surgery is a benign process such as degenerative disc disease. In this study, we have performed a cost-benefit analysis of this practice.

We performed a cost-benefit analysis of routine histopathological examination of 1775 routine (non-neoplastic and non-infectious indications for surgery) and 70 non-routine (suspected neoplastic or infectious indications for surgery) discectomy specimens obtained over an eight-year period (1996 and 2004). Chart reviews were used to determine if any histopathology findings were clinically significant (i.e., affected subsequent patient care). Total costs were calculated. A literature review was conducted to compare our results with other published series.

We found four unexpected histopathology results among 1775 specimens obtained from routine cases, one of which was clinically significant. We calculated costs of $42,165.25 per unexpected histopathological finding and $168,625 per clinically significant histopathological finding. For non-routine surgeries, the cost per abnormal pathological finding was $116.67.

In routine cases, histopathological examination of disc specimens is not justified. The decision to send specimens for pathological examination should be based on the surgeon's judgment.

Posterior reversible encephalopathy syndrome (PRES) occurs most commonly in the setting of known hypertension or use of immunosuppressive agents.

We report four previously-well children who presented acutely with altered mentation, seizures and visual disturbances and were diagnosed with PRES.

Only one child had a history of gross hematuria prior to the seizure. All four were discovered to be hypertensive only after onset of their neurological symptoms, and were subsequently diagnosed with glomerulonephritis. All four had rapid resolution of neurological symptoms with adequate treatment of hypertension.

Blood pressure must be measured promptly in all children presenting with these symptoms. If elevated, the diagnosis of PRES should be strongly considered and a workup for renal disease pursued.

Diffusion tensor MRI fiber tractography (DTT) is the first non-invasive in vivo technique for delineating specific white matter (WM) tracts. In cerebral neoplasm, DTT can be used to illustrate the relationship of the tumor with respect to adjacent WM trajectories.

Fiber tractography was used in this study to assess tumor-induced changes in WM trajectories in three cases of cerebral neoplasm: glioblastoma multiforme, meningioma, and anaplastic astrocytoma.

Three patterns of WM alteration were identified: 1) disruption, 2) displacement, and 3) infiltration. Tumor disruption of WM tracts was observed in glioblastoma multiforme, which terminated fibers crossing the corpus callosum. In meningioma, DTT illustrated bulk displacement of the corticospinal tract in the affected hemisphere as well as preservation of the deviated axons. In anaplastic astrocytoma, fiber tracking demonstrated disruption of WM tracts at the tumor origin as well as intact axons through areas of tumor infiltration.

Fiber tracking results correlated with the clinical and histopathological features of the tumor. Larger case series will be required to determine if fiber tracking can add accuracy to existing imaging methods for grading tumors.