To examine how the introduction of amplitude-integrated electroencephalography (aEEG) to our neonatal intensive care unit (NICU) influenced clinical practice.

This was a retrospective study examining clinical practice three years before and three years after the introduction of aEEG monitors to our NICU. A time series analysis was performed to explore whether aEEG introduction was associated with changes in the rates of conventional EEGs performed, neurology consultations and neonates diagnosed with seizures.

Following aEEG introduction, the total number of conventional EEGs performed remained constant; however, there was significant shift in conventional EEG utilization towards neonates receiving fewer multiple EEGs and more single EEGs. There was no change in the rate of neurology consultations or the number of neonates diagnosed with seizures.

Introduction of aEEG monitors to our NICU has led to less reliance on conventional EEG as a tool for the serial evaluation of brain function. Since the number of neonates diagnosed with seizures did not increase, aEEG monitoring did not appear to uncover a significant subgroup of patients with subclinical seizures that would previously have gone undetected. Conventional EEG and aEEG are complementary tools for the assessment of newborn cerebral function.

Chronic migraine is a significant cause of disability world-wide and occipital region stimulation (OS) has been proposed to treat it. While participating in an industry-sponsored pilot trial of OS, we aimed to collect data regarding our surgical complications and long term usage of OS in our chronic migraine patients.

Ten patients (8 female, median age 46.5 years) were enrolled based on criteria established by the sponsoring company, screened in the headache clinic, and followed for a median of 33 months. We did not access data collected by industry for this report and instead collected our own data prospectively, including predominant location of headache, location of paresthesia evoked by OS, and complications.

Adverse events included three possible early infections requiring antibiotics but not hardware removal, one late implantable pulse generator erosion requiring removal, one generator malfunction requiring revision, and loss of paresthetic coverage requiring four revisions in four patients. Two patients experienced new symptoms requiring psychiatric intervention. Five patients had no benefit and have been explanted. Of those who remain using their device, the proportion of their pre-operative pain located in the occipital region was 0.62 ± 0.14, whereas in those patients who have been explanted, the proportion was 0.31 ± 0.18 (t = 3.15, p=0.01).

Complication rates with OS are higher than those seen with other stimulation techniques, despite identical hardware and similar surgery. The location of migraine pain did predict outcome, and suggests that only those with primarily occipital region headache are candidates for this therapy.

To compare the clinical features of our sero-negative and sero-positive neuromyelitis optica (NMO) patients.

Thirty-nine patients with NMO were recruited and analyzed retrospectively. Serum aquaporin 4 (AQP4) antibody status was determined by a cell-based assay. For the sero-negative patients, cerebrospinal fluid (CSF) and serum samples were re-tested using the cell-based assay and an indirect immunofluorescence assay.

By the cell-based assay, 30 patients (76.92%, 30/39), were positive for AQP4 antibodies in serum and 37 patients (94.9%, 37/39), had a CSF-positive antibody status. Seven NMO patients (17.9%, 7/39) were sero-negative by the cell-based assay but demonstrated positive CSF results. By indirect immunofluorescence, the remaining two patients, who had no AQP4 antibodies in serum or CSF by the cell-based assay, were positive for IgG antibodies in serum, which selectively targeted the central nervous system microvessels, pia, subpia, Virchow-Robin space, kidney, and stomach. There were no significant differences between the sero-positive and sero-negative NMO groups among their demographic and clinical data.

Repeating the test using a different assay or CSF is helpful to clarify whether sero-negative NMO patients do in fact carry AQP4 antibodies.

Progressive external ophthalmoplegia (PEO) is a mitochondrial myopathy of ocular muscles. Diagnostic investigation usually involves limb skeletal muscle biopsy and molecular genetic studies, although diagnostic yield tends to be low. The purpose of this study was to evaluate the diagnostic yield obtained by analysis of levator palpebrae (LP) muscle tissue.

This is a clinicopathologic study of 8 patients with a diagnosis of PEO, who had LP muscle biopsies as part of oculoplastic procedures. Six of these patients also had limb muscle biopsies. Histopathology, electron microscopy and genetic studies were performed.

Diagnostic histopathologic findings were present in 4/6 quadriceps biopsies, and 7/8 LP biopsies. Genetic testing on DNA extracted from LP muscle revealed abnormalities in 4 patients.

In patients whose LP muscle demonstrate both genetic defects and histopathological abnormalities, the diagnosis of PEO can be confirmed without limb muscle biopsy. Patients having LP resection during oculoplastics procedures for treatment of ptosis may therefore be able to avoid a separate procedure for limb muscle biopsy. Further study is required to determine the specificity of these findings.

Concussion is a prevalent brain injury in the community. While primary prevention strategies need to be enhanced, it is also important to diagnose and treat concussions expertly and expeditiously to prevent serious complications that may be life-threatening or long lasting. Therefore, physicians should be knowledgeable about the diagnosis and management of concussions. The present study assesses Ontario medical students’ and residents’ knowledge of concussion management.

A survey to assess the knowledge and awareness of the diagnosis and treatment of concussions was developed and administered to graduating medical students (n= 222) and neurology and neurosurgery residents (n = 80) at the University of Toronto.

Residents answered correctly significantly more of the questions regarding the diagnosis and management of concussions than the medical students (mean = 5.8 vs 4.1, t= 4.48, p<0.01). Gender, participation in sports, and personal concussion history were not predictive of the number of questions answered correctly. Several knowledge gaps were identified in the sample population as a whole. Approximately half of the medical students and residents did not recognize chronic traumatic encephalopathy (n = 36) or the second impact syndrome (n = 44) as possible consequences of repetitive concussions. Twenty-four percent of the medical students (n = 18) did not think that “every concussed individual should see a physician” as part of management.

A significant number of medical students and residents have incomplete knowledge about concussion diagnosis and management. This should be addressed by targeting this population during undergraduate medical education.

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown.

To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity.

CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16).

CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027).

The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.

Determine if distributed practice of neurological exam (NE) skills in first year medical school produces sustained improvements in the skills of second year students.

A prospective, controlled, non-blinded study conducted at McGill University (class size = 180 students). Expanded teaching of muscle stretch reflexes was provided to first year medical students. A structured examination of muscle stretch reflexes (max score = 100) was administered in second year medical school after a required two week rotation in Neurology. Results for class A (received the intervention in first year) were compared to the results for the preceding class B (had not received the intervention).

77 of 177 (44%) eligible students in class A and 69 of 166 (42%) eligible students in class B participated. Results were analyzed separately for each of two examiners. Mean (SD) scores were 95.2 (5.6) for class A (intervention) and 81.7 (11.1) for class B (control) for the first examiner and 90.4 (8.2) for class A and 83.8 (11.7) for class B for the second examiner. Results were statistically significant (Mann-Whitney test z = 5.27, p < 0.0001 first examiner and z = 2.67, p < 0.0038 second examiner).

Distributed practice of muscle stretch reflexes during first year medical school results in improved performance by second year medical students after their mandatory clinical rotation in neurology, even when examined up to 14 months after the intervention. This finding has implications for the teaching of the NE.

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

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

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

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

Hemangioblastomas are benign vascular tumors of the central nervous system that occur sporadically or in association with von Hippel-Lindau disease. These tumors are characteristically composed of a dense capillary network with intervening stromal/interstitial cells. To date, the histogenesis of hemangioblastoma remains unclear. We hypothesize that hemangioblastomas arise from a defective mesodermal stem cell, which gives rise to the atypical vasculature.

To test our hypothesis, we have characterized the cellular composition of hemangioblastomas by immunophenotyping pluripotent and committed stem cells and vascular endothelial cells.

Our findings show that hemangioblastoma endothelial cells are positive for CD133, a stem and progenitor cell marker. Vascular endothelial cells also expressed nuclear Oct4. In addition to the endothelium, both CD133 and Oct4 were present in stromal and perivascular cells. Interestingly, neither the endothelium nor the stromal cells expressed Sox2 or Nanog suggesting a committed stem cell phenotype.

From these findings, we believe that hemangioblastoma stromal cells are committed stem cells producing both vascular cell types. The findings also show an unusual CD133-positive endothelial phenotype in hemangioblastoma.

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

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

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

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

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

Child neurology training in Canada has changed considerably over time, with increasing requirements for standardized teaching of the fundamentals of child neurology and the CanMEDS competencies. We sought to determine the current status of child neurology training in Canada as well future directions for training.

A web-based survey was sent to program directors (PD's) of active pediatric neurology training programs. General questions about the programs were asked, as well as about success at the Royal College of Physicians and Surgeons of Canada (RCPSC) exam, breakdown of rotations, views on CanMEDS roles and questions on the future of pediatric neurology.

9/9 PD's completed the survey. 96.5% of all trainees successfully passed their RCPSC exam from 2001-2006. Breakdowns of the number and type of rotations for each year of training were provided. All CanMEDS roles were deemed to be important by PD's and programs have developed unique strategies to teach and assess these roles. 92.6% of trainees chose to go into academic practice, with the most popular subspecialty being epilepsy. All PD's favour joint training sessions particularly for neurogenetics and neuromuscular disease. Overall, PD's suggest recruitment for future child neurologists at the medical student level but are divided as to whether we are currently training too few or too many child neurologists.

This survey provides a view of the current state of pediatric neurology training in Canada and suggestions for further development of postgraduate training. In particular, attention should be given to joint educational programs as well as urgently assessing the manpower needs of child neurologists.

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

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

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

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