It has been thought that the occurrence of multiple sclerosis (MS) could be associated with daily ultraviolet exposure. In this study we investigated the geospatial association between average daily ultraviolet B (UVB) irradiance and MS prevalence in Newfoundland and Labrador (NL), Canada.

A complete list of patients diagnosed with MS in the province of NL was constructed. Places of habitation from birth to diagnosis were ascertained by mailout survey.

A 74% rate of return on the survey results was obtained. A plot of the average daily erythemal UV over the available five years (1998-2002) shows that the distribution of MS follow a north-south gradient. Average daily UVB measurements are lower in the higher latitudes. A statistically significant negative correlation of MS incidence with erythemal UVB was found that is stronger than the correlation using latitude. This correlation appears to be strongest in the first year of life and declines when subsequent years are examined up to age ten. No significant correlation was found for the subjects' locale of habitation at the time of their first MS attack.

This study suggests that UVB radiation may contribute to the pathogenesis of MS.

Acute isolated optic neuritis is often the first manifestation of multiple sclerosis (MS), and its management remains controversial. Over the past decade, with the advent of new disease-modifying agents, management of isolated optic neuritis has become more complicated.

To evaluate the current practice patterns of Canadian ophthalmologists and neurologists in the management of acute optic neuritis, and to evaluate the impact of recently published randomized clinical trials.

Mail survey.

All practicing ophthalmologists and neurologists in Canada were mailed a survey evaluating the management of isolated acute optic neuritis and familiarity with recent clinical trials. Surveys for 1158 were mailed, and completed surveys were collected anonymously through a datafax system. Second and third mailings were sent to non-respondents 6 and 12 weeks later.

The final response rate was 34.5%. Although many acute optic neuritis patients initially present to ophthalmologists, neurologists are the physicians primarily managing these patients. Ordering magnetic resonance imaging, and treating with high dose intravenous steroids has become the standard of care. However, 15% of physicians (14% of ophthalmologists and 16% of neurologists) continue to prescribe low dose oral steroids, and steroids are being given for reasons other than to shorten the duration of visual symptoms by 73% of ophthalmologists and 50% of neurologists. More neurologists than ophthalmologists are familiar with recent clinical trials involving disease-modifying agents.

Although the management of acute optic neuritis has been evaluated in large clinical trials that were published in major international journals, some ophthalmologists and neurologists are not following evidence-based recommendations.

To quantify the prevalence of cerebral palsy (CP) in British Columbia within a four-year birth cohort.

The study was a population-based record linkage study of a birth cohort of British Columbian children born between April 1, 1991 and March 31, 1995. Cases were identified by the presence of International Classification of Diseases, Version 9 (ICD-9) diagnostic code “343” recorded at three years of age or older or by having the ICD-9 diagnostic code “343” recorded prior to the third birthday with two confirmatory diagnoses within the first three years of life through a record search of the BC Medical Services Plan billing files for the fiscal years 1991 to 1995.

This research has provided an estimate of the prevalence of CP in the four-year birth cohort 1991 to 1995 in British Columbia. An aggregate prevalence rate of CP was measured as 2.68 per 1000 live births, and a congenital rate was measured at 2.57 for the same population. Birth weight and gestational age demonstrated a significant relationship with the development of CP. This study should lend credence to the establishment of a CP register in British Columbia.

Parkinsonism (PD) is occasionally seen in several types of spinocerebellar ataxia (SCA). Mutations in SCA gene have been reported in the patients of parkinsonism without ataxia.

We examined spinocerebellar ataxia type 12 mutation in 877 PD and 199 multiple system atrophy (MSA) patients.

No patients showed abnormal SCA12 expansion. It suggests that PD and MSA are not associated with SCA12 and it is not necessary to screen SCA12 in PD and MSA patients.

Sporadic Creutzfeldt-Jakob disease (CJD) is a fatal, transmissible spongiform encephalopathy characterized by rapidly progressive dementia, myoclonus, ataxia and akinetic mutism. The underlying mechanism is believed to be a conformational change of a native prion protein which characteristically fails to provoke an immune response. Commensurate with the latter, cerebrospinal fluid (CSF) classically exhibits a non-inflammatory profile.

We report two patients with pathologically-proven sporadic CJD presenting with a significant CSF pleocytosis.

Although uncommon, the presence of an inflammatory CSF profile should not exclude the diagnosis of sporadic CJD.

The safe integration into practice of a new surgical technique requires an appreciation of the learning curve. The object of this study was to assess the learning curve for minimally invasive microdiscectomy (MIM) utilizing a tubular retractor system.

A prospective evaluation of a single surgeon's first 52 consecutive MIM cases for radiculopathy secondary to single-level posterolateral lumbar disc herniation was performed. The learning curve was assessed using operative time, conversion to open rate, complications, and length of hospitalization.

The duration of operative time decreased over the course of the study (range, 49-151 min). By case 15, operative time was typically 60 min or less. There was only one conversion to an open procedure (Case 2). Complications occurred in three cases. All but nine patients were discharged home on the day of surgery.

The learning curve for MIM was demonstrated. Further assessment of this curve for a large group of surgeons is necessary before a randomized controlled trial comparing standard microdiscectomy to MIM can be conducted.

Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients.

Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months.

Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p<0.001) and during the extension (8.7%, p= 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment.

This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.

This study is aimed to explore the frequency characteristics of pain-evoked neuromagnetic responses in the secondary somatosensory (SII) cortices.

Thulium-laser nociceptive stimuli to the left hand dorsum of 10 right-handed healthy adults. The pain stimuli were rated as mild, moderate, and severe levels according to subjects' reports on a 10-point visual analog scale. We analyzed their cortical responses with wavelet-based frequency analyses and equivalent current dipole (ECD) modeling.

For each pain level, we found an increase of theta (4-8 Hz) and alpha (8-13 Hz) power in bilateral SII areas at 180-210 ms after stimulus onset. The power was larger for the moderate than for the mild pain level (p < 0.05), but there was no statistical power difference of these oscillations between moderate and severe pain stimulus conditions (p = 0.7). Within the SII area, we did not observe particular difference in theta and alpha ECD locations between varying pain level conditions.

The 4-13 Hz activities, peaking from 180 to 210 ms, are oscillatory correlates of SII activation in response to nociceptive stimulation, but their power may code the magnitude of pain stimuli only up to moderate level, as rated subjectively. This measure could be potentially used to evaluate SII activation in further pain studies.

In the emergency department, portable point-of-care testing (POCT) coagulation devices may facilitate stroke patient care by providing rapid International Normalized Ratio (INR) measurement. The objective of this study was to evaluate the reliability, validity, and impact on clinical decision-making of a POCT device for INR testing in the setting of acute ischemic stroke (AIS).

A total of 150 patients (50 healthy volunteers, 51 anticoagulated patients, 49 AIS patients) were assessed in a tertiary care facility. The INR’s were measured using the Roche Coaguchek S and the standard laboratory technique.

The interclass correlation coefficient and 95% confidence interval between overall POCT device and standard laboratory value INRs was high (0.932 (0.69 - 0.78). In the AIS group alone, the correlation coefficient and 95% CI was also high 0.937 (0.59 - 0.74) and diagnostic accuracy of the POCT device was 94%.

When used by a trained health professional in the emergency department to assess INR in acute ischemic stroke patients, the CoaguChek S is reliable and provides rapid results. However, as concordance with laboratory INR values decreases with higher INR values, it is recommended that with CoaguChek S INRs in the > 1.5 range, a standard laboratory measurement be used to confirm the results.

Frame-based stereotactic brain biopsy has played an important role in the management of patients with suspected neoplastic intracranial lesions over the last three decades. We reviewed the surgical experience of one surgeon to determine the nature and frequency of complications associated with this procedure.

Records were reviewed for 858 patients undergoing frame-based stereotactic procedures from January 1986 to May 2006. Data on each case were prospectively collected by the senior author. Procedures for Ommaya reservoir placement, brachytherapy, stereotactic craniotomy flap localization, shunt placement, or treatment of previously-diagnosed intracranial cystic lesions were excluded, leaving 614 patients in whom a total of 622 procedures were performed for purely diagnostic purposes. Complication rates and their association with clinical variables were sought.

Morbidity and mortality rates were 6.9% (43/622) and 1.3% (8/622), respectively. The risk of symptomatic hemorrhage (intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH], intraventricular hemorrhage [IVH]) was 4.8%. The risks of transient or permanent neurological deficits were 2.9% (18/622) and 1.5% (9/622), respectively. Biopsy of deep-seated lesions was associated with increased overall complication rate, while biopsy of Glioblastoma Multiforme (GBM) was associated with perioperative mortality.

Overall, complication rates were comparable with those in previous reports. The subgroup of patients with deep-seated lesions or a histologic diagnosis of GBM may possess an elevated risk of overall complications or mortality, respectively, compared to other patients undergoing frame-based stereotactic brain biopsy.

Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.

Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.

Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.

The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

Since temozolomide (TMZ) entry into routine practice in the first-line management of glial tumors, post-TMZ recurrences present a growing challenge. Without standard chemotherapy for TMZ failure, care in such palliative settings requires consideration not only of efficacy but of toxicity and convenience.

At our institution, a combination regimen has been used: oral alkylating agents procarbazine (PCB) (100-150 mg/m2/day) and TMZ (150-200 mg/m2/day) administered on days 1-5 of a 28-day cycle. This treatment has been initiated upon radiological and/or clinical disease progression, and continued until evidence of further progression or toxicity. We retrospectively reviewed our experence with this regimen.

Since November 2004, 17 patients (median age 53) were treated for histologically confirmed glioma (glioblastoma multiforme (GBM), N=12; Grade 3 glioma, N=3; Grade 2 glioma, N=2) after a median of 2 recurrences. TMZ was previously given either as adjuvant therapy (post-chemoradiotherapy maintenance in 8 of 13 cases) or as salvage monotherapy (4 cases). Of 16 evaluable cases, 14 (13 high grade tumors) showed O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Two patients achieved partial response and one had complete response by RECIST criteria. Disease progressed after a median of 4 cycles (range 1 to 11+), with an actuarial progression-free survival of 42% after 6 cycles. Grade 3/4 toxicity was rare, and no dose reductions were needed. One patient discontinued treatment due to procarbazine hypersensitivity.

Combination PCB-TMZ is well-tolerated, with modest activity in TMZ-exposed glioma.

: The purpose of this retrospective review of all operated cases of pituitary adenomas in the last decade, is to define the demographic patterns and characteristics of such tumors and to assess surgical outcomes with regards to safety and efficacy of trans–sphenoidal tumor removal in our institution.

Surgically treated pituitary adenomas presenting from 1995 till 2005 were reviewed for different variables. Results were expressed as mean, standard deviation and median for continuous and number with percentage for categorical data. Chi square test was applied to measure differences and significance was taken at p value < 0.05.

One hundred and twenty–five patients were operated for pituitary adenoma. Sixty–three percent were male and mean age was 37 years. Sixty percent of the patients presented with headache and/or visual symptoms. Twelve percent presented with pituitary apoplexy and 28% presented with symptoms due to pituitary hyperfunction. Fifty–five percent of patients had functioning and 44% had nonfunctioning adenomas. Mean pre operative tumor diameter from 86 pre op MRI scans was 26.76 mm (3–78 mm). Eighty–four percent of patients underwent trans–sphenoidal tumor resection and three percent had craniotomy. Mean size of post op residual tumor as calculated from 76 available post operative scans was 5.3 mm (range 0–31 mm). 17.6% of the patients required hormone replacement beyond three months and 10% were re–operated. Overall mortality was 1.6%.

In Pakistan, patients are more likely to present either with apoplexy or with a giant pituitary adenoma than patients reported from developed countries. Overall, our results have been satisfactory and comparable with the literature.

Vascular endothelial cell (VEC) injury represents a major initiating step in the process of atherosclerosis, which may lead to cerebral infarction. “Circulating endothelial cell” (CEC) is an index of ongoing endothelial injury, while intimal-medial thickness (IMT) detected by sounography was used to evaluate the severity of atherosclerosis. However, to our knowledge, there is no study that investigated the relationship of these two determinations. Our study was designed to address correlate CEC with IMT.

The study population consisted of 30 patients with acute cerebral infarction (ACI) and 30 age-and sex-matched volunteers as controls. The CEC counts were determined using Hladovec's method. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries to measure IMT. CEC counts in ACI group were significantly increased compared with control group (4.88±2.14 cells /0.9μl vs 2.73±1.95/0.9μl, P0.01); IMT in ACI patients was also significantly thicker compared with volunteers (2.72±1.07 mm vs 1.73±0.99 mm, P<0.01). There was positive correlation between CEC counts and maximal carotid artery IMT in both groups (r=0.522, P<0.01 in ACI patients and r=0.395, P<0.05 in healthy volunteers).

Circulating endothelial cell counts can directly reflect the vascular injury. CEC counts parallel IMT. The CEC may be an independent predictor of cerebral infarction.

To evaluate the prevalence of restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD) and the relationship between RLS and clinical/laboratory findings of COPD.

One hundred and thirty-four COPD patients without secondary causes of RLS were included. Thirty-nine (29.1%) patients were diagnosed with RLS and classified as Group 1. The control group consisted of 65 age-matched COPD patients without RLS. Group 1 was divided into subgroups according to the Johns Hopkins Severity (JHS) scale. Patients with a score of 0, 1, or 2 were classified as JHS 0-2 and those with a score of 3 as JHS 3. Group 1 and the control group and subgroups were compared for clinical and laboratory characteristics.

We found that the duration of COPD was longer and that airway obstruction, hypercapnia, and hypoxia were more evident in patients with RLS than those without. Similar differences were also detected between JHS subgroups 3 (more severe) and 0-2. Polyneuropathy frequency was significantly higher in Group 1 compared to controls. However, Group 1 subgroups showed a similar frequency of polyneuropathy. In a multivariate analysis, hypercapnia made a significant independent contribution to both JHS 0-2 and JHS 3 patients when RLS severity was set as the dependent variable. Polyneuropathy and the duration of COPD were significant independent variables for patients in the JHS 3 subgroup. Polyneuropathy was the strongest predictor for the JHS 3 patients.

We conclude that RLS is frequent in COPD, particularly in patients with severe hypoxemia/hypercapnia and in late stages of the disease.

Injury to the brain and spinal cord is one of the most catastrophic and costly occurrences in the Ontario health system. The objective of the present study was to evaluate the impact of past Ontario Neurotrauma Foundation (ONF) studentships and fellowships in terms of capacity building in the neurotrauma field in Ontario.

An online, cross sectional survey amongst past recipients of studentships and fellowships that terminated prior to July 2005. Explicit data were collected on various aspects of career development including current activity, awards and publications.

Thirty-six out of 42 (86%) eligible past trainees responded; 12 (33%) were Masters students, 12 (33%) were PhD students and 12 (33%) were Post-Doctoral students. A majority of the recipients (61%) are currently involved in neurotrauma-related activities (clinical, research and teaching) in more than 20% of their time, with no substantial differences between the degree groups. Half the recipients are currently involved in neurotrauma-related research in more than 20% of their time. The awardees published 1.5 peer-review manuscripts/person-year and received multiple awards. A high majority of our recipients (86%) feel that the ONF award had a substantial impact on their career.

A high proportion of past award recipients remain involved in neurotrauma activities, especially in research. These results may lead to a cautious conclusion of the positive impact of the ONF studentships and fellowships on neurotrauma capacity building. These results should be considered in strategic planning of funding agencies similar to ONF.

Chiari type II malformation (CII) is a developmental anomaly of the cerebellum and brainstem, which are important structures for processing the vestibulo-ocular reflex (VOR). We investigated the effects of the deformity of CII on the angular VOR during active head motion.

Eye and head movements were recorded using an infrared eye tracker and magnetic head tracker in 20 participants with CII [11 males, age range 8-19 years, mean (SD) 14.4 (3.2) years]. Thirty-eight age-matched healthy children and adolescents (21 males) constituted the control group. Participants were instructed to ‘look’ in darkness at the position of their thumb, placed 25 cm away, while they made horizontal and vertical sinusoidal head rotations at frequencies of about 0.5 Hz and 2 Hz. Parametric and non-parametric tests were used to compare the two groups.

The VOR gains, the ratio of eye to head velocities, were abnormally low in two participants with CII and abnormally high in one participant with CII.

The majority of participants with CII had normal VOR performance in this investigation. However, the deformity of CII can impair the active angular VOR in some patients with CII. Low gain is attributed to brainstem damage and high gain to cerebellar dysfunction.

Leptomeningeal disease (LMD) is a late complication of malignant glioma, mostly of glioblastoma, that usually responds poorly to treatment and is rapidly fatal. A long surviving case led us to review our experience with LMD in patients with oligodendrogliomas.

A 15-year retrospective chart review was performed. Patients with both oligodendroglial tumors and LMD were identified. A single neuro-pathologist reviewed all histological sections, a single neuro-radiologist reviewed all available images and lp/19q status was assessed.

Seven out of 145 patients with oligodendroglioma were diagnosed with LMD. Six were male. Median age at tumor diagnosis was 41 years (range, 28-50). None had radiographic or pathological evidence of leptomeningeal or subependymal tumor at initial diagnosis. Most patients had pure anaplastic oligodendrogliomas (4/7); 6/7 had 1p/19q co-deletion. The median time to first relapse was 41 months (range, 19-127). The median time to LMD was 76 months (range, 19-151) from initial diagnosis and 28 months (range, 0-36) from first relapse, respectively. Leptomeningeal disease treatments included spinal radiation and intrathecal and systemic chemotherapy. After progression, some patients with LMD remained stable clinically. The median survival from initial diagnosis was 104 months (range, 19-183) and from LMD diagnosis was 32 months (range, 2-43).

Leptomeningeal disease is a complication of oligodendroglioma that may occur preferentially in long surviving patients with 1p/19q co-deletion. Leptomeningeal disease in patients with oligodendrogliomas appears to be relatively indolent which may have implications for their treatment and be related to 1p/19q status.

The purpose of this study was to determine whether tasks involving effortful attention would cause augmentation of rigidity in patients with mild Parkinson disease.

In 17 subjects with mild Parkinson disease, rigidity in a single arm was assessed during various experimental conditions by a blinded movement disorders neurologist. Rigidity was scored separately at the wrist and the elbow using an ordinal scale. In three of the conditions, sustained attention was directed toward visual, auditory or movement-related stimuli. Two varieties of Froment maneuver served as positive controls: contralateral hand opening-closing or ipsilateral foot tapping. In addition, rigidity was assessed twice with subjects resting. The examiner was unaware of the sequence of experimental conditions and this was changed for each subject. Mean rigidity scores for the various experimental conditions were compared against the baseline state (an average of both trials with the patient resting) using a repeated measures ANOVA and post-hoc Tukey-Kramer multiple comparisons test.

Rigidity was significantly increased from baseline with each of the attentional tasks (p <0.01 to p <0.001) and also with the two Froment maneuvers (p <0.001). Rigidity augmentation with contralateral hand opening-closing was significantly greater than with any of the attentional tasks (p <0.05 to p <0.001).

Tasks of effortful attention did appear to augment rigidity in patients with mild Parkinson disease. We speculate that the greater augmentation seen with the Froment maneuver could have an anatomic basis.