Over the past four years, West Nile virus (WNV) has become a significant health issue in North America. In 2002, WNV infection made its first appearance in the human population in Canada.

Patients who presented to the University Health Network and Mount Sinai Hospital in Toronto with neurological disease attributed to WNV infection were identified and followed by the neurology service. Clinical features and results of laboratory, electrodiagnostic, radiological and pathological studies are presented.

In August and September 2002, 26 patients were admitted with WNV infection; 14 presented with neurological illness. Encephalitis was the most common presentation (11 patients). Eleven patients developed neuromuscular disease; two at presentation and nine after encephalitis. While the majority had a motor process that localized to the anterior horn cell and/or motor neuron, two patients had evidence of a demyelinating neuropathy and one a sensorimotor axonal neuropathy. Less common manifestations included rhombencephalitis, ataxia, myelopathy and parkinsonism. Death occurred in four patients; two > 75 years of age, and two who were immunocompromised.

The most common neurological manifestation of WNV infection was encephalitis with subsequent neuromuscular involvement. The diversity of clinical and pathological findings, however, suggests widespread involvement of the central and peripheral nervous system. A poorer prognosis for neurological recovery and overall survival was seen in older and immunocompromised patients.

Between August 25 and September 25, 2003 seven patients with West Nile virus neurological manifestations were identified through the hospital neurology consultation services in Calgary, Alberta, Canada. Three of the seven patients were treated with interferon alpha-2b (IFN alpha-2b). In this report we document the clinical characteristics of these seven cases.

Clinical and laboratory information was obtained from a retrospective review of patient hospital and clinic charts. Patients were included if they had serological evidence of West Nile virus infection and had clinical evidence of aseptic meningitis, encephalomyelitis, cerebellar syndrome or motor neuronopathy. Three patients received a treatment course of three million units IFN alpha-2b, administered by subcutaneous injection once per day for 14 days.

Four patients had cerebellar signs without change in consciousness, two had both encephalitis and neuromuscular weakness, and one patient had focal lower motor neuron arm weakness. The mean age was 52 (range 24 - 73). All patients had flu-like illness and fever as presenting symptoms and six had severe headaches. Two patients were immunocompromised prior to infection. Two patients with cerebellar signs (one with opsoclonus-myoclonus) improved spontaneously and exhibited only mild residual deficits on discharge. The other two patients with cerebellar findings developed brainstem involvement, one coinciding with and one subsequent to the cerebellar symptoms. Within one week of treatment with IFN alpha-2b these latter two patients showed marked improvement. One patient with encephalitis and neuromuscular weakness, was treated with IFN alpha-2b and subsequently recovered.

In this case review of seven patients, multiple neurological symptoms occurred in each patient and the neurological presentation was varied. Four patients had predominant cerebellar findings and one patient had opsoclonus-myoclonus, not previously reported. The marked improvement in three patients who received IFN alpha-2b raises preliminary optimism towards this potential treatment.

The growing science and technology of various neurosurgical areas fosters subspecialization. The transmission of this expanding knowledge base to the neurosurgical resident becomes an increasing challenge. A survey of neurosurgical residency program directors was undertaken to evaluate their response to the budding subspecialization of spine surgery within general neurosurgery.

A survey requesting background data, educational infrastructure and prevailing opinion was distributed to all 13 neurosurgical program directors in Canada. The responses were tabulated and results recorded. It is upon these results that conclusions and proposed directions are based.

The current practice of the overwhelming majority of Canadian academic neurosurgical centers is to have neurosurgical spinal subspecialists working under the umbrella of the general neurosurgical division. A large percentage of neurosurgical program directors in Canada believe that the management of spinal disease, including both intradural procedures and instrumentation, is and should remain an integral part of general neurosurgical training. A consensus statement regarding the requirements of neurosurgical training in spinal disorders is the expressed desire of almost all program directors. A proposed direction and resolution is discussed.

Medical error is an extremely important component of patient safety and requires intense study. The present investigation undertook to examine patients' perceptions and attitudes regarding medical error.

Qualitative case study methodology was used. We conducted 30 face-to-face interviews with patients within one week of undergoing a neurosurgical operation for a brain tumour. Interviews were audiotaped and transcribed and the data subjected to thematic analysis.

Three overarching themes emerged from the data: 1) trust in the patient's surgeon was of paramount importance; 2) patients'views toward medical error varied between fear and vulnerability to no concern; and 3) discussion of error was felt to be beneficial as it could help the medical profession decrease future errors and could help dispel the patient's fear and anxiety about the upcoming surgery.

Patients'trust in their physician/surgeon is of paramount importance in allaying their fears about the possible occurrence and impact of medical error during their treatment. The level of concern about error varies among patients, but most felt that discussion of error was a good thing.

Head injury is an important cause of morbidity and mortality in pediatrics. Comprehensive studies on outcome are scarce despite significant clinical concern that multiple areas of functioning may be impaired following moderate to severe head injury. The literature suggests that sequelae include not only medical problems but also impairments in cognitive functioning.

Aretrospective medical and psychology chart review of patients, age 1-18 years, admitted to the Children's Hospital of Eastern Ontario with moderate (Glasgow Coma Scale [GCS] 9-12) or severe head injury (GCS ≤ 8) from November 1, 1993 until December 31, 1998 was conducted. Correlations were performed between medical variables (i.e., GCS, Pediatric Risk of Mortality [PRISM] III score, duration of ICU and hospital stay) and measures of intelligence and memory functioning.

Eighty-three children age 1 to 18 were included. Seventy percent of the children were classified as having a severe head injury. There was a mortality rate of thirteen percent. Younger age at injury, lower GCS, and higher PRISM III scores predicted higher mortality. Medical complications were documented systematically. Forty-four patients underwent at least one cognitive assessment and 17 of these children had intelligence testing at three points in time: baseline (< four months), early recovery (five to 15 months) and follow-up (16 to 38 months). The mean intelligence and memory scores fell within the average range at the latest point in follow-up. For those children who underwent three serial assessments, the mean verbal and performance IQ fell within the low average range at baseline improving significantly to fall within the average range by early recovery. Continued improvements were apparent in verbal memory beyond early recovery, with the mean obtained at follow-up falling within 1 SD of the normative mean. Despite the return to normal ranges for the group means the proportion of scores falling below 1.5 standard deviations from the mean was greater than population norms for verbal IQ, performance IQ and verbal memory. Lower GCS scores and longer duration of stay in ICU or hospital were predictive of lower nonverbal intelligence. Lower GCS was also predictive of lower visual memory scores.

This study describes a population of Canadian children who suffered moderate or severe traumatic brain injury. Initial GCS was the best predictor of mortality and cognitive outcome. These children demonstrated a temporal improvement in intelligence and memory functioning, with their mean performance on these cognitive measures falling within the average range at 16 to 38 months postinjury, although there was considerable variability in the outcomes between individuals.

To conduct active surveillance of the Canadian paediatric population for children who have a progressive intellectual and neurological deterioration to detect the occurrence of cases of Creutzfeldt-Jakob disease or variant Creutzfeldt-Jakob disease.

Any child who is less than or equal to 18 years of age, who had a progressive loss of already attained intellectual/ developmental abilities and development of abnormal neurological signs of greater than three months duration was eligible for inclusion.

July 1999 to July 2001.

Enhanced active surveillance system for progressive intellectual and neurological deterioration was implemented to detect, prospectively, among the Canadian paediatric population. Each month, all paediatricians and paediatric neurologists in Canada were mailed a reporting form. All reported cases were reviewed by the principal investigator who classified the cases into one of four predetermined categories. Cases where there was evidence of neurological and intellectual regression without known cause were reviewed by a panel. Reported cases were reviewed for the possibility of classic or variant Creutzfeldt-Jakob disease.

Over 2200 physicians took part in this program. There was more than an 80% monthly return rate of the initial report form. Ninety-nine possible cases of progressive neurological and intellectual deterioration were reported. Sixty cases were classified as having a progressive neurological syndrome associated with intellectual deterioration. Fourteen cases were duplicates. One case of Creutzfeldt-Jacob disorder was found but no cases of the variant form of Creutzfeldt-Jacob disorder. Fifteen cases were felt not to meet the above-mentioned entry criteria.

The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear.

We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients.

The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy.

The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

Long latency reflexes (LLR) include afferent sensory, efferent motor and central transcortical pathways. It is supposed that the cortical relay time (CRT) reflects the conduction of central transcortical loop of LLR. Recently, evidence related to the cortical involvement in multiple sclerosis (MS) has been reported in some studies. Our aim was to investigate the CRT alterations in patients with MS.

Upper extremity motor evoked potentials (MEP), somatosensory evoked potentials (SEP) and LLR were tested in 28 patients with MS and control subjects (n=22). The patients with MS were classified according to the clinical form (relapsing-remitting [R-R] and progressive groups). The MS patients with secondary progressive and primary progressive forms were considered as the “progressive” group. CRT for LLR was calculated by subtracting the peak latency of somatosensory evoked potentials (SEP) and that of motor evoked potentials (MEP) by transcranial magnetic stimulation from the onset latency of the second component of LLR (LLR2) (CRT = LLR2 – [MEP latency + N20 latency])

Cortical relay time was calculated as 7.4 ± 0.9 ms in control subjects. Cortical relay time was prolonged in patients with MS (11.2 ± 2.9 ms) (p<0.0001). The latencies of LLR, MEP and SEP were also prolonged in patients with MS. Cortical relay time was not correlated with disease severity and clinical form in contrast to other tests.

Our findings suggested that CRT can be a valuable electrophysiological tool in patients with MS. Involvement of extracortical neural circuits between sensory and motor cortices or cortical involvement due to MS may cause these findings.

The nervous system is a major target of HIV-1 infection and site of many complications of AIDS. Most of our knowledge pertaining to the range and frequency of neuropathology in HIV-1/AIDS is from large centres outside Canada in different social and health care settings. The goal of the present study was to describe HIV-1/AIDS-associated neuropathology before and during the era of highly active antiretroviral therapy at a Canadian teaching centre.

The records of the Department of Pathology, London Health Sciences Centre were electronically searched for cases of HIV-1/AIDS that came to postmortem examination since 1985. The clinical records and pathological materials were reviewed.

Sixteen autopsies of HIV-1/AIDS were identified. All patients were male. Fourteen contracted HIV-1 through high risk homosexual activity, one through the transfusion of blood products and one through intravenous drug use. Three patients (19%) had pre-mortem evidence of HIV-1 associated dementia. At autopsy, 12 of the 16 cases had neuropathological findings and the most common diagnoses were HIV-1 encephalitis, progressive multifocal leukoencephalopathy, toxoplasmosis, and primary CNS lymphoma.

High risk homosexual activity was a more prominent factor in acquiring AIDS in cases coming to postmortem examination compared with previous reports from most larger urban centres outside Canada where injection drug use and high risk heterosexual activity factored prominently. The incidence of HIV-1 associated dementia was similar to that reported previously. This study confirms the heavy burden and wide spectrum of disease experienced by the nervous system in HIV-1/AIDS.

Periventricular white matter disease (PVWD) is associated with abnormalities on tests that involve complex cognitive processes, along with an increased risk of cerebrovascular events which are associated with significant morbidity in older patients. This study investigates whether the neurological examination can predict the presence of PVWD on magnetic resonance imaging (MRI). No prior studies have assessed whether the neurological examination can predict the presence of PVWD on MRI.

A focused neurological examination was performed on a random selection of patients referred for a MRI of the brain. Staff neuroradiologists who were blinded to the results of the physical examination independently read the MRI scans. The MRI interpretations were divided into four categories based on the degree of PVWD: none, mild, moderate, severe.

Twenty-three subjects had some degree of PVWD, while 25 subjects had none. The total number of neurologic signs correlated significantly with the severity of PVWD even when adjusting for the effect of age (rho=0.67, p<0.001). Ninety-one percent of subjects with PVWD had three or more abnormal signs, while 76% of subjects without PVWD had fewer than three. Abnormalities with the three step motor sequencing and horizontal visual tracking tests were maximally predictive of PVWD. One or both of these tests were abnormal in 96% of subjects with PVWD, while 64% of subjects without PVWD had no problems with either test.

Simple neurologic tests can predict the presence or absence of PVWD on MRI.

We propose a simple modification to an established blood-brain barrier disruption (BBBD) animal model that allows us to use ketamine/xylazine as the anaesthetic agent, therefore decreasing the complexity and the cost of the model, while maintaining similar efficiency.

Sixty-two Long Evans rats were anaesthetized by intraperitoneal injection of ketamine/ xylazine. Osmotic BBBD was performed by administering 25% mannitol into the internal carotid artery in a retrograde fashion from the external carotid. The infusion rate of mannitol, as well as the duration was adjusted in a stepwise fashion to identify optimal parameters for BBBD and minimize complications. As a supplementary step to previously reported models, a vascular clip was applied to the common carotid artery prior to the infusion of mannitol, therefore isolating our model system from the depressant hemodynamic effects of ketamine/xylazine. Evans blue dye was used to control for BBBD intensity.

Using this model at an initial infusion rate of 0.15 ml/sec, a significant incidence of brain hemorrhage (75%) and a death rate of 62.5% were observed. Decreasing the infusion rate in a stepwise fashion, 0.08 ml/sec was found to produce optimal BBBD, as demonstrated by Evans blue staining. At this rate, 6/7 animals depicted grade II staining, whereas one animal depicted grade IV.

The application of a clip to the common carotid artery prior to mannitol infusion allowed us to isolate the cerebral circulation from the depressant hemodynamic effects of ketamine/xylazine. This supplementary step produced consistent and efficient BBBD in our animal model.