To re-evaluate practice patterns for methylprednisolone (MP) administration in patients with acute spinal cord injury (SCI) within the spinal surgery community across Canada five years after the publication of practice recommendations.

Canadian orthopedic and neurological spine surgeons were surveyed at their respective annual meetings about their practice of steroid administration for acute SCI by means of a questionnaire comprised of the same seven questions posed five years ago plus an additional question related to change of view.

Forty-two surgeons and twenty-one residents directly involved in the acute management of SCI completed the questionnaire. Seventy-six percent of spinal surgeons do not prescribe MP for SCI in sharp contrast to 76% who prescribed it five years ago. Of the 24% who use steroids, the NASCIS II dosing regimen is most commonly followed. One third of physicians continue to administer MP because of fear of litigation.

Over a five year period there has been a complete reversal in practice patterns of MP administration for SCI, along with an increased familiarity of the published literature. Attendance at meetings, participation in local group discussions, and peer-reviewed publications appear effective in altering practice preferences arising from peer pressure and even fear of litigation.

The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke.

7329 patients with AF and ≥1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0-3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype.

The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant.

In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.

Multidisciplinary treatment programs are seen as an effective way to treat patients with chronic illness. The purpose of this study was to describe a multidisciplinary headache program which was developed in the Canadian public healthcare setting, and to report on patient perceptions of the program and patient treatment outcomes.

The Calgary Headache Assessment and Management Program (CHAMP) was developed with initial funding from Alberta Health, and continued with function from the Calgary Health Region. Patient perceptions of the program were obtained with questionnaires. Outcome measures for a cohort of patients who completed the Self-Management Workshop were obtained using standard headache related disability measures.

Patient perceptions of the education session, the Lifestyle Assessment, and the Self-Management Workshop were very positive. Headache Disability Inventory scores fell from 56.2 to 46.3 from baseline to three months post Self-Management Workshop (p<.001). Corresponding scores for the HIT-6 were 63.6 and 58.2 (p <.001).

Multidisciplinary headache treatment programs can be developed in the Canadian public healthcare system. The program described here was well accepted by many patients and perceived to be useful by them. Headache related disability as measured by standard measures was significantly reduced after participation in the program.

1. To determine the awareness of the literature concerning therapeutic manoeuvres in severe closed head injury (CHI) among Canadian critical care clinicians and neurosurgeons, 2. To identify factors that affect utilization of these manoeuvres, and 3. To compare reported appropriateness and frequency of use with #1 and #2.

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

Fifty-nine of 99 neurosurgeons and 82 of 148 critical care physicians responded (57%). The majority of respondents were not able to identify the highest level of published evidence for most manoeuvres, except for the avoidance of corticosteroids (51%). The factor identified by most respondents as being most important in motivating use of any given manoeuvres was the level of published evidence (25%). Although reported appropriateness and frequency of use of most manoeuvres correlated well with each other, they did not correlate with awareness of evidence. In the case of corticosteroids, there was a strong correlation between non-use of steroids and awareness of evidence (R = - 0.30, p = 0.0003).

Respondents to this survey of Canadian physicians treating patients with severe head injury reported published evidence as being the most significant factor affecting use of a therapy. However, most respondents did not correctly identify the highest published level of evidence for most therapies. This study has identified difficulty with research translation that may have clinical implications.

Studies of the prevalence of multiple sclerosis (MS) in Canada have generally been isolated to specific regions. Given the importance of multiple sclerosis as a cause of disability in adults, a comprehensive review of Canadian MS prevalence examining current data, interregional variation, deficiencies in knowledge and frontiers for research is timely.

A systematic review of all studies addressing the prevalence of MS in Canada or regions within Canada, published in English or French since 1985, was conducted. Studies were identified using MEDLINE, EMBASE and bibliographic review. Ten studies were evaluated for methodological rigour and a test of heterogeneity across studies was performed and a measure of consistency (I2) estimated.

Studies were generally of high quality. Nine were restricted to regions within Canada and one provided an estimated national prevalence based on self-reported cases. All reported a high prevalence (>50 per 100 000). Latitude and longitude gradients were not striking while assessment of heterogeneity confirmed that regional differences were unlikely to be the result of sampling variability.

This review confirms Canada as a country of very high MS prevalence and it is the first study to demonstrate that variation in regional estimates represents true differences in prevalence within Canada. Avenues for future MS prevalence research, including adoption of a national MS registry, are proposed.

To determine whether clinical data obtained by history and physical examination can predict eventual progression to dementia in a cohort of elderly people with mild cognitive impairment.

A prospective, longitudinal study of a cohort of elderly subjects with amnestic Mild Cognitive Impairment (MCI). Ninety subjects meeting the criteria for amnestic MCI were recruited and followed annually for an average of 3.3 years. Main outcome measure was the development of dementia determined by clinical assessment with confirmatory neuropsychological evaluation.

Fifty patients (56%) developed dementia on follow-up. They were older, had lower Mini-mental status exam (MMSE) scores and a shorter duration of symptoms at the time of first assessment. Multivariate logistic regression analysis identified age at symptom onset as the only clinical parameter which distinguished the group that deteriorated to dementia from the group that did not. The odds ratio for age was 1.1 (confidence interval 1.04 - 1.18).

Patients presenting with amnestic MCI insufficient for the diagnosis of dementia are at high risk of developing dementia on follow-up. In our cohort, 56% were diagnosed with dementia over an average period of 5.9 years from symptom onset. The only clinical predictor for the eventual development of dementia was older age at symptom onset. Clinical features alone were insufficient to predict development of dementia.

In the province of Quebec, a population-based study of Guillain-Barré syndrome (GBS) was conducted at the time of a mass immunization campaign against meningococcal disease, in 2001.

The study population included residents aged 2 months to 20 years observed from November 1st, 2000 to December 31, 2002, representing 4 075 465 person-years of observation. GBS cases were identified in the provincial hospital database Med-Echo and medical records were reviewed.

Thirty-three incident GBS cases were identified, including 27 cases of acute inflammatory demyelinating polyradiculopathy. The overall GBS incidence rate was 0.8/100 000 person-years, higher in persons aged 1 to 4 years (2.1/100 000) than in those 5 years or more (0.6/100 000). There was a female preponderance and no significant seasonal variation. All patients survived.

Results could be used to interpret reports of adverse events associated with the introduction of new vaccines in this age-group in Canada.

To determine the maximum tolerated dose of 3D conformal radiotherapy in combination with Cisplatin for patients with recurrent malignant gliomas.

From 1999-2003, nine patients with recurrent malignant glioma received fractionated radiotherapy and Cisplatin (20 mg/m2/d IV on days 1-5) in a Phase I radiation dose escalation trial. Three sequential dose levels were evaluated: 25 Gy, 30 Gy, and 35 Gy, using 5 Gy fractions. All patients received prior external beam radiation (median dose 59.4 (20-60) Gy) and five patients received prior chemotherapy.

Six male and three female patients were enrolled with a median age of 52 years, and a median Karnofsky performance status score of 70. The median re-irradiated tumor volume was 18.9 (0.1-78.5) cm3 and the median follow-up was 8.8 (3.2-31.2) months. One patient (30 Gy/ 6 fractions) experienced medically reversible acute grade 3 toxicity. A second patient (35 Gy/ 7 fractions) experienced acute grade 2 toxicity and histology showed tumor and radiation effect. A third patient (25 Gy/ 5 fractions) experienced late grade 3 toxicity from radiation necrosis. The radiological responses consisted of complete response (1 patient), partial response (1 patient), and stable disease (2 patients). The median overall survival was 8.8 months (95% CI 8.0-9.9), and the median disease free interval was 2.0 months (95% CI 1.4-4.4). Seven patients received chemotherapy following re-irradiation and Cisplatin.

The maximum tolerated dose of 3D conformal fractionated radiotherapy was 30 Gy in 6 fractions with low dose Cisplatin, which was well tolerated in terms of acute toxicity for our patient population. This regimen demonstrated only modest efficacy in the treatment of recurrent malignant glioma. Combinations of conformal re-irradiation and other systemic agents may merit investigation. Currently our recommended dose is 30 Gy in 6 fractions for selected patients.

To assess the impact of the disease stage and therapy on motor cortical excitability in Parkinson’s disease (PD).

Twenty newly diagnosed and medication-free, early stage patients, 20 late stage patients under antiparkinsonian therapy and 20 normal healthy controls were included. Motor threshold (MT), amplitudes of motor evoked potential (MEP), motor evoked potential amplitude/compound muscle action potential amplitude (MEP/CMAP) ratio, central motor conduction time (CMCT) and cortical silent period (CSP) were measured by stimulation of the motor cortex using a 13.5 cm circular coil and recordings from abductor digiti minimi muscle. Following the first study protocol, early stage patients were given therapy and the same protocol was repeated three months later.

Motor threshold was lower; and the MEP/CMAP ratio was higher in early and late stage patients than normals. In early stage patients after proper therapy, the MTs became higher than before therapy, but still remained lower than normals. In late stage patients, the CMCTs were shorter than the early stage patients before therapy and normals, but there was no difference between the early stage patients and normals. In early stage patients after therapy, the CMCT became longer than before therapy and this difference was significant in both late stage patients and normals. Although more prominent in late stage patients, the CSP duration in both PD groups was found shorter than normals. In early stage patients, after therapy, the CSP durations became significantly longer compared with before therapy.

These findings suggest that the motor cortical excitability increases in PD because of the impairment of the corticomotoneuronal inhibitory system.

Objective clinical evaluation of memory frequently requires serial testing but the issue of whether multiformed tests are equivalent and can be used interchangeably is seldom examined. An added problem in bilingual Canadian settings is the extent to which it is appropriate to measure French speakers’ performance on translations of English tests. The present work used the Rey Auditory Verbal Learning Test (RAVLT) and a nonverbal analog, the Aggie Figures Learning Test (AFLT), to examine whether a) different forms of the same test are equivalent, b) performance on the two tests is comparable, c) two language groups perform similarly, and d) the RAVLT can detect dysfunction in patients with temporal lobe epilepsy (TLE).

We compared three French versions of the RAVLT and three forms of the AFLT in 114 healthy francophone adults. We subsequently compared the performance of the same francophone subjects to a previously obtained sample of anglophones on both tests, and then administered the RAVLT to anglophone or francophone patients with TLE.

For both tasks the three forms were equivalent and performance on the RAVLT was comparable to that on the AFLT. Francophone subjects performed slightly worse on the RAVLT compared to anglophones but performance of the two language groups did not differ on the AFLT. Finally, left TLE patients were impaired compared to right on the RAVLT, but no performance differences were observed across the two language groups in the patient sample.

The RAVLT and AFLT are useful tools for examination of learning and memory in French and English speaking populations. On the RAVLT, the lesion effect in patients is not affected by differences in performance between language groups.

The neuropathological findings of 32 progressive supranuclear palsy (PSP) cases over a period of 17 years were reviewed.

Of the 26 cases with adequate clinical data, 20 patients either presented with cognitive dysfunction or developed a cognitive impairment subsequently during the course of the disease. Co-existing changes of argyrophilic grains and corticobasal degeneration (CBD) were found in 28% and 32% of the cases respectively. Alzheimer-related pathology was found in 69% of cases but only 18.75% of cases fulfilled the consortium to establish a registry for Alzheimer's disease (CERAD) criteria for either definite or probable Alzheimer's disease. Lewy bodies were noted in four cases (12.5%), all in the subcortical regions. Only seven cases of PSP showed no pathological evidence of other co-existing neurodegenerative diseases. The severity of the cerebrovascular pathology in this cohort was insufficient to explain any clinical symptomatology.

As in previous studies, this study has demonstrated the frequent co-existence of pathological changes usually noted in other neurodegenerative diseases in PSP. Whether these coexisting pathological changes contribute to the cognitive impairment in PSP remains uncertain.

Limb girdle muscular dystrophy type 1B is an autosomal dominant disease characterized by late onset proximal muscle involvement associated with cardiac complications such as atrioventricular conduction blocks, dilated cardiomyopathy, and sudden death.

Define the full phenotypic spectrum of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type 1B.

We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac conduction disease phenotype that carried a new mutation in the LMNA gene and sought to define its full phenotypic spectrum by performing complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA studies.

The proband and 12 living at risk relatives were tested. In total, we identified seven carriers of a new (IVS9-3C>G) LMNA gene mutation. Of the three symptomatic patients, all had cardiac involvement, but only two presented proximal limb weakness. The one available muscle biopsy demonstrated a normally expressed lamin A/C protein, localized at the nuclear envelope. RNA study revealed a loss of exon 10 transcription caused by the IVS9-3C to G splicing mutation.

We have identified a new mutations in the LMNA gene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.

Cognitive dysfunction is one of the common clinical symptoms in multiple sclerosis (MS), but there is no effective treatment for it.

The aim of this study was to evaluate the effect of rivastigmine in treating memory and cognitive dysfunction in MS.

A single-center double-blind placebo-controlled randomized clinical trial conducted from October 2005 to February 2007. Sixty definite MS patients with cognitive impairment age 16 to 54 years were randomly allocated to receive a 12-week treatment course of either rivastigmine (1.5 mg once a day increment over 4 weeks to 3 mg twice daily) or placebo. Response to treatment was assessed by the Wechsler Memory Scale (WMS) at baseline and 12 weeks after start of therapy.

A slight, but significant memory improvement occurred in both groups. Of the 30 patients treated with rivastigmine, the mean (SD) WMS general memory score increased from 60.3 (4.2) at baseline to 64.9 (5.3) at the end of study period (P<0.001). Correspondingly, in the 30 patients treated with placebo, the mean (SD) WMS general memory score increased from 60.5 (4.9) to 64.5 (3.7) (P < 0.001). The average WMS general memory score at the end of trial did not changed between rivastigmine and placebo group (mean difference, 0.4; 95% CI, -2.0, 2.8).

No significant differences were seen between rivastigmine and placebo on the mean (SD) WMS general memory score. A larger multicenter study of rivastigmine in MS is warranted in order to more definitely assess the efficacy of this intervention.

Neurenteric cysts are rare congenital epithelium-lined cysts of the central nervous system. They are found predominantly in the spinal cord, with lower incidence in the intracranial compartment, and may be associated with various other congenital spinal anomalies. Seven patients with symptomatic intraspinal neurenteric cysts are presented.

Seven patients with intraspinal neurenteric cysts aged from nine months to ten years treated at this hospital from May 2000 to July 2006 were reviewed. The clinical manifestations, imaging and surgical findings of patients were analyzed retrospectively. All patients underwent operation. One patient's cervical neurenteric cyst was resected using the lateral cervical approach, and the other six resections were performed with posterior approach.

All seven patients presented with neurological involvement. One patient had an intramedullary cyst, while the other six cysts were situated ventrally. Three patients' cysts occurred in the cervical region, two in the cervicothoracic region, one in the thoracic region and one in the lumbar region. One patient had bony anomalies, and one had a lumbar posterior occult spinal dysraphism. Five patients' symptoms improved rapidly after surgery.

Intraspinal neurenteric cysts in children are rare and most occur ventral to the spinal cord. Magnetic resonance imaging (MRI) is the most effective imaging modality. Earlier diagnosis and surgical resection of spinal neurenteric cysts improves prognosis.

To characterize postural stability control and levodopa responsiveness in early Parkinson's disease (PD).

Postural sway was studied during quiet stance in ten patients within six years of PD onset, both before (OFF) and after (ON) regular oral levodopa dosing. Postural sway was recorded using a force platform during 30 sec with eyes open, and six dependent variables were examined.

Mild baseline subclinical changes in postural sway were recorded in our patients. Clear benefit was observed in five out of six characteristics (mean sway, transversal sway, sagittal sway, sway intensity, and sway area) in the ON condition.

Postural control mechanisms are affected early in PD and modulated by dopamine.

Pergolide is an ergot derived dopamine agonist that is widely used for the treatment of Parkinson’s disease. Studies have found an association between pergolide and valvular heart abnormalities although there is still much to be learned about the clinical significance of the valvular changes, who is at risk, and whether there is duration of exposure effect.

To assess the long term risk of hospital admissions for valvular heart disease (VHD) or congestive heart failure (CHF, a clinically overt outcome of VHD) in new users of pergolide compared to new users of levodopa. The secondary objective was to assess whether there are any characteristics that can predict who is at higher risk of developing this outcome.

Retrospective, population-based cohort study.

Ontario, Canada.

Ontario residents aged 66 and older, newly started on treatment with either pergolide or levodopa.

Admission to hospital with the most responsible diagnosis of congestive heart failure or valvular heart disease.

The risk for admission for valvular heart disease or congestive heart failure were higher in those with 1-4 years exposure to pergolide compared with no exposure to pergolide (VHD: hazard ratio 2.4, p = 0.04; CHF: hazard ratio 1.6, p =0.02). No such pattern was found with exposure to levodopa.

Our study demonstrates that treatment with pergolide is associated with a higher risk of hospital admission for valvular heart disease or congestive heart failure and that this risk is greater in those with 1-4 years exposure than in those with less exposure. We did not find an increased risk beyond four years.

Previous studies describe significant rates of misdiagnosis of stroke, seizure and other neurological problems, but there are few studies examining diagnostic accuracy of all emergency referrals to a neurology service. This information could be useful in focusing the neurological education of physicians who assess and refer patients with neurological complaints in emergency departments.

All neurological consultations in the emergency department at a tertiary-care teaching hospital were recorded for six months. The initial diagnosis of the requesting physician was recorded for each patient. This was compared to the initial diagnosis of the consulting neurologist and to the final diagnosis, as determined by retrospective chart review.

Over a six-month period, 493 neurological consultations were requested. The initial diagnosis of the requesting physician agreed with the final diagnosis in 60.4% (298/493) of cases, and disagreed or was uncertain in 35.7% of cases (19.1% and 16.6% respectively). In 3.9% of cases, the initial diagnosis of both the referring physician and the neurologist disagreed with the final diagnosis. Common misdiagnoses included neurocardiogenic syncope, peripheral vertigo, primary headache and psychogenic syndromes. Often, these were initially diagnosed as stroke or seizure.

Our data indicate that misdiagnosis or diagnostic uncertainty occurred in over one-third of all neurological consultations in the emergency department setting. Benign neurological conditions, such as migraine, syncope and peripheral vertigo are frequently mislabeled as seizure or stroke. Educational strategies that emphasize emergent evaluation of these common conditions could improve diagnostic accuracy, and may result in better patient care.

Current cognitive models propose that multiple processes are involved in reading and writing.

Our goal was to use linguistic analyses to clarify the cognitive dysfunction behind two classic alexic syndromes.

We report four experiments on two patients, one with alexia without agraphia following occipitotemporal lesions, and one with alexia with agraphia from a left angular gyral lesion.

The patient with occipital lesions had trouble discriminating real letters from foils and his reading varied with word-length but not with linguistic variables such as part of speech, word frequency or imageability. He read pseudo-words and words with regular spelling better, indicating preserved use of grapheme-to-phoneme pronunciation rules. His writing showed errors that reflected reliance on ‘phoneme-to-grapheme’ spelling rules. In contrast, the patient with a left angular gyral lesion showed better recognition of letters, words and their meanings. His reading was better for words with high imageability but displayed semantic errors and an inability to use ‘grapheme-to-phoneme’ rules, features consistent with deep dyslexia. His agraphia showed impaired access to both an internal lexicon and ‘phoneme-to-grapheme’ rules.

Some cases of pure alexia may be a perceptual word-form agnosia, with loss of internal representations of letters and words, while the angular gyral syndrome of alexia with agraphia is a linguistic deep dyslexia. The presence or absence of agraphia does not always distinguish between the two; rather, writing can mirror the reading deficits, being more obvious and profound in the case of an angular gyral syndrome.

Optical coherence tomography (OCT) - measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS).

Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON.

Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically - affected eyes of non - MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non - MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302).

Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non - MS patients over time.