Clinicians in the neurosciences need to interpret and apply a growing body of evidence about therapy.

Using a clinical scenario about painful diabetic neuropathy and evidence about one treatment option, we review the advantages, limitations, and the clinical interpretation of commonly reported measures of effectiveness, emphasizing their application to the care of individual patients.

Absolute differences between treatment and control groups (e.g., absolute risk difference) are clinically intuitive and preferable to relative measures (e.g., relative risk). The number needed to treat is particularly useful and clinically applicable. Continuous measures are best interpreted using thresholds of clinically important change, which provide information about the number of patients experiencing meaningful improvement or worsening.

Using simple principles of evidence based care, clinicians can correctly interpret the common measures of treatment effectiveness and apply them to the care of individual patients.

The incidence and prevalence of multiple sclerosis (MS) in Newfoundland and Labrador (NL) had been reported in 1984 and was considered to be relatively low at that time. This study revisits the incidence and prevalence of MS in NL for the year 2001.

Case searches through patient files of neurologists in NL were conducted. A complete list of patients billed for MS in NL between 1996 and 2003 was obtained and all cases were confirmed via chart review.

There were 493 living MS patients yielding a prevalence of 94.4/100,000 which is significantly higher than previously reported. Of the living patients, 330 had relapsing remitting (RRMS), 94 had secondary progressive, 66 had primary progressive (PPMS) and three had unspecified MS. The total female to male ratio was 2.7:1. There was no difference between the female to male ratios for RRMS vs PPMS. Patients with PPMS had a later onset compared to RRMS (p<0.00001). Yearly incidences were relatively constant from 1994 to 2001 (5.6/100,000). Significant delays between first symptoms and final diagnosis were common and the delay time has not changed over the past 15 years. A prevalence of 88.9/100,000 was estimated from survival and incidence trends and was not significantly different than the measured prevalence (p=0.38).

The increase in incidence and prevalence are accounted for through both better access to diagnostic facilities and more practicing neurologists. The revised prevalence and incidence are more in keeping with recently reported values throughout Canada.

L’augmentation de l’incidence et de la prÉvalence se justifient par une plus grande accessibilitÉ aux moyens diagnostiques et par la prÉsence d’un plus grand nombre de neurologues. La prÉvalence et l’incidence que nous rapportons sont plus conformes à celles rapportÉes rÉcemment à travers le Canada.

We present information regarding the standardization, reliability and clinical validity of two versions of the Behavioural Neurology Assessment (BNA). The BNA-Long Form consists of 24 subtests within separate domains: Attention, Memory, Language, Visuospatial Function, Executive Function, and Praxis. The BNA-Short Form consists of 13 subtests within the domains of Attention, Memory, Naming, Visuospatial Function and Executive Function. In addition to individual domain indices, a Grand Total score was calculated for both BNA versions.

To standardize the administration and scoring and validate the BNA for detection of dementia.

Standardized normative data were obtained on 115 healthy subjects ranging in age from 50 to 95. Test-retest stability was obtained on 19 subjects and clinical validity was investigated by administering the BNA and Mini-Mental Status Examination (MMSE) to 29 patients with dementia and 29 age-matched healthy subjects (controls).

Age had a significant effect on all but the Visuospatial and Praxis indices of the BNA-Long Form and an effect on Naming and Grand Total score of the Short-Form. Internal consistency (Cronbach's coefficient a) was .87 and .67 for the Long and Short Forms (.95 and .96 for dementia and control groups combined). Test-retest stability was acceptable. Grand Total indices of both BNA versions showed significant, positive correlations with the MMSE. Both BNA versions had superior sensitivity to dementia relative to the MMSE (.93 versus .79). Specificity was equivalent to the MMSE (.93 versus .97).

Positive predictive values of the BNA and MMSE are equivalent but the BNA provides superior negative predictive value.

The Canadian Neurological Society commissioned a manpower survey in 2002 to assess demographics, distribution, specialty interests, working conditions, job satisfaction and future plans of neurologists across the country.

A survey was mailed to all known Canadian neurologists (n = 694) on two separate occasions. Further encouragement by telephone contact was undertaken. The response rate was 54%.

The mean age of neurologists who responded was 51 years, with 14% being women. Approximately 55% of neurologists were community-based. Seventy-six percent designated a sub-specialty interest. On average, neurologists worked 57 hours per week and the majority had significant “on-call” commitments. Job satisfaction was higher among academic neurologists when compared with community-based neurologists, and greater among men than women. A greater percentage of older neurologists were satisfied with their work than their younger colleagues. Significant attrition in the neurological work force is a major concern, since up to 20% of neurologists reported that they are likely to retire in the next five years and about 15% are likely to reduce their practice.

This survey suggests that substantial concerns are facing Canadian neurology over the next five years. Major efforts to retain existing expertise and enhance residency training will be required to simply maintain the present quality of neurological care in Canada.

Newfoundland and Labrador, Canada, have been almost exclusively populated by immigrants from southwest England and southeast Ireland. The province’s population grew largely by natural increase from 20,000 people in 1835 to half a million at present. Very little interregional migration occurred within the province. This uniquely-populated region and its subsequent founder effect provide the basis to develop models of disease prevalence.

To develop a model for the regional prevalence of multiple sclerosis (MS), accounting for settlement patterns and geographic location (latitude).

All living MS patients with confirmed addresses (438 patients) in the province were mailed a survey requesting their place of birth. Regional prevalences were calculated from a 75% rate of return of the survey. Theoretical regional prevalences were proportionally calculated from the source prevalences of southwest England, southeast Ireland, Scotland and the Channel Islands based on settlement patterns. These theoretical regional prevalences were corrected for geographical variations of latitude based on observations in the United Kingdom. Theoretical and actual regional prevalences were compared.

When actual regional prevalences were compared with theoretical prevalences, very little variation was noted, especially after correcting for variation in latitude.

A regional variation in MS prevalence is noted in the island portion of Newfoundland and Labrador. This regional variation can be modeled by using both migration patterns and latitudinal position. This model demonstrates that the prevalence of MS is influenced by both genetic and environmental contributions.

Pulmonary edema (PE) can occur in the early or late period following subarachnoid hemorrhage (SAH). The incidence of each type of PE is unknown and the association with ventricular dysfunction, both systolic and diastolic, has not been described.

Retrospective chart review of 178 consecutive patients with SAH surgically treated over a three-year period. Patients with pulmonary edema diagnosed by a radiologist were included. Early onset SAH was defined as occurring within 12 hours. Cardiac function at the time of the PE was analyzed using hemodynamic and echocardiographic criteria of systolic and diastolic dysfunction. Pulmonary edema was observed in 42 patients (28.8%) and was more often delayed (89.4%). Evidence of cardiac involvement during PE varied between 40 to 100%.

Pulmonary edema occurs in 28.8% of patients after SAH, and is most commonly delayed. Cardiac dysfunction, both systolic and diastolic, is commonly observed during SAH and could contribute to the genesis of PE after SAH.

The goal of this study was to provide a general descriptive and cognitive portrait of a population with traumatic brain injury (TBI) at the time of their acute care stay.

Three hundred and forty-eight TBI patients were assessed. The following data were collected for each patient: age, level of education, duration of post-traumatic amnesia, Galveston Orientation Amnesia Test score, Glasgow Coma Scale score, results of cerebral imaging, Neurobehavioral Rating Scale score, the Functional Independence Measure cognitive score and the Glasgow Outcome Scale score.

The clinical profile of the population revealed a mean age of 40.2 (±18.7) and a mean of 11.5 (±3.6) years of education. Most patients presented with frontal (57.6%) and temporal (40%) lesions. Sixty-two percent had post-traumatic amnesia of less than 24 hours. Seventy percent presented with mild TBI, 14% with moderate and 15% with severe TBI. The cognitive deficits most frequently observed on the Neurobehavioral Rating Scale were in the areas of attention, memory and mental flexibility as well as slowness and mental fatigability. Most patients had good cognitive outcome on the Functional Independence Measure and scores of 2 and 3 were frequent on the GOS. Forty-five percent of the patients returned home after discharge, 51.7% were referred to in or out patient rehabilitation and 3.2% were transferred to long-term care facilities.

Because of the specialized mandate of acute care institutions, the information provided here concerning characteristics of our TBI population is essential for more efficient decision-making and planning/programming with regards to care and service delivery.

Thrombolytic therapy with recombinant tissue plasminogen activator (tPA) has been shown to be cost-effective and safe. Thrombolysis for stroke with tPA is now a standard of care in North America. However, it is only used on a small percentage of patients.

The Registry of the Canadian Stroke Network was a consent-based stroke registry from 21 hospital sites across Canada. Using the thrombolysis data in phase 1 and 2 of the Registry, we sought to describe the use of stroke thrombolysis and its outcomes.

A total of 4107 patients were diagnosed with ischemic stroke in phase 1 and 2 of the Registry, of which 8.9% were treated with tPA. In consented tPA patients, the method of tPA administration was 85.8% IV only, 9.0% IA only, and 5.2% IV/IA combined. Patients had a median onset-to-treatment time of 167 minutes [IQR 140-188]. One quarter (25.5%) of eligible candidates (time from onset <150 minutes) were treated with tPA. Protocol violations occurred in 27.7% (67/242) of patients with 14.9% (10/67) mortality. Overall, in-hospital mortality was 11.6%. Lower Canadian Neurological Scale score and higher glucose level were predictive of mortality The symptomatic intracerebral hemorrhage (ICH) rate (phase 2 only) was 4.3%. The mean Stroke Impact Scale-16 score at six months was 73.2, approximately equivalent to a modified Rankin scale score of 2.

At selected hospitals in Canada, thrombolysis use is higher than previously reported rates. Thrombolysis continues to be safe and effective in Canada.

To review the demographics and workload characteristics of pediatric neurology in Canada.

A standardized survey questionnaire was mailed out to practicing pediatric neurologists in Canada in 2001. Variables examined were age, gender, hours on call, regular hours worked per week, type of practice and projected changes in practice over next five to ten years. Results were compared to the 1994 Pediatric Neurology Manpower Survey which had used the same survey instrument.

Fifty-six (70%) pediatric neurologists practicing in Canada returned the survey. As was the case in 1994, no significant differences in workload were found based on age or gender. The average age of the practicing pediatric neurologist in 2001 was 51 years compared to 45 years in 1994. The proportion of physicians over 55 years in 2001 was 35% compared to 25% in 1994.

Pediatric neurology in Canada is an aging specialty needing a significant recruitment of new members.

We compared the functional status and survival time of patients with malignant gliomas.

This retrospective review included 143 patients diagnosed with malignant gliomas. Patients were grouped according to histopathological diagnosis. To measure functional status, patients were assigned a Karnofksy performance status (KPS) score at the time of presentation and at one, three, six, nine, 12 months and yearly intervals thereafter. Data were analyzed using descriptive methods as well as Kruskal-Wallis tests, Chi-square tests, Log-Rank tests and Cox’s proportional hazards modeling.

Eighty-four patients were male. The median age of patients was 63 years. One hundred and seven patients had a histopathological diagnosis of glioblastoma multiforme, 23 of anaplastic astrocytoma and 13 of anaplastic oligodendroglioma. Twenty-nine patients received aggressive multimodal treatment, 83 received intermediate treatment and the remaining 31 patients received conservative therapy. Significant treatment complications occurred in 33% of patients including four post-operative deaths. The anaplastic oligodendroglioma group had lower mortality and maintained better KPS scores over time, as did patients receiving full treatment. The most significant prognostic factors for functional status included age, pretreatment KPS, and type of treatment received. The most significant factors associated with time until death included age, severity of comorbidities, pretreatment KPS, presence of confusion, histopathological diagnosis and type of treatment received.

In patients with malignant gliomas, younger age, better functional status at presentation and aggressive multimodal treatment were associated with improved longer-term functional status and survival. Confirmation of the effect of multimodal treatment on patient functional status would require a randomised controlled clinical trial.

Deep brain stimulation (DBS) is used increasingly worldwide for the treatment of Parkinson's disease, dystonia, tremor and pain. As with any implanted system, however, DBS introduces a new series of problems related to its hardware. Infection, malfunction and lead migration or fracture may increase patient morbidity and should be considered when evaluating the risk/benefit ratio of this therapy. This work highlights several factors felt to increase DBS hardware complications.

The authors undertook a prospective analysis of their patients receiving this therapy in two Canadian centres, over a four-year period.

One hundred and forty-four patients received 204 permanent electrode implants. The average follow-up duration was 24 months. Complications related to the DBS hardware were seen in 11 patients (7.6%). There were two lead fractures (1.4%) and nine infections (6.2%) including two erosions (1.4%). There was a significantly greater risk of infection in patients who underwent staged procedures with externalization. In patients with straight scalp incisions, the rate of infection was higher than that seen with curved incisions.

Hardware complications were not common. A period of externalization of the electrodes for a stimulation trial was associated with an increased infection rate. It is also possible that a straight scalp incision instead of curvilinear incision may lead to an increase in the rate of infection. With a clear understanding of the accepted DBS device indications and their potential complications, patients may make a truly informed decision about DBS technology.

To reduce postoperative hydrocephalus following surgery in the region of the fourth ventricle.

We describe the use of a conventionally placed lateral ventricular catheter to facilitate anterograde ventricular irrigation during surgery in the region of the fourth ventricle. This technique offers a safe alternative to more conventional approaches to fourth ventricular irrigation and obviates the need for placement of a third or fourth ventricular catheter and/or serial lumbar punctures by thoroughly flushing blood and tissue debris from the operative field at the time of surgery.

Preliminary results spanning a five-year period show a lower incidence in the need for early ventriculo-peritoneal shunts (5%) and delayed ventriculo-peritoneal shunts (10%).

This technique represents a safe method of reducing hydrocephalus following operative procedures in the region of the fourth ventricle.

Numerous therapeutic interventions have been developed in the neurosciences. Clinicians need summary measures about efficacy of therapies that derive from the best available evidence, and that can be readily extrapolated to clinical practice. The number needed to treat (NNT) is intuitive and clinically applicable. We provide clinicians with a single source that summarizes important therapies in the main neurological and neurosurgical areas.

Critically appraised evidence about therapies in the neurosciences was obtained from meta-analyses in all neurosciences groups in the Cochrane library, and from critically appraised topics at the University of Western Ontario. Therapies were included if they were deemed relevant and if outcomes were dichotomous. For each therapy, we obtained absolute risk differences and their 95% confidence intervals (CI), the corresponding NNTs, control and experimental event rates, and the time-frame of the outcome assessment.

We assembled a table of NNTs for 87 interventions in ten disease categories, deriving from meta-analyses (70%) or randomized controlled trials (30%), and assessing surgical interventions (7%), procedures (9%) or pharmacological treatments (84%). The NNTs varied widely, ranging from 1 in the use of epidural blood patch for post-dural puncture headache to 4608 for meningococcal vaccination. Preventative interventions had substantially larger NNTs. Time-frames were inappropriately short for many chronic conditions.

Large collections of NNTs provide useful, updateable summaries of therapeutic effects in the neurosciences, an increasingly interventional clinical field.

Prevention of bilirubin encephalopathy relies on the detection of newborns who are at risk of developing serious hyperbilirubinemia. The objective of this study was to reassess the clinical syndrome of kernicterus as neurodiagnostic studies have become more readily available and can be used to evaluate these infants.

The study population was neonates born at term or near term admitted to The Hospital for Sick Children in Toronto, Ontario, Canada, between January 1990 and May 2000. During the study period, there were 9776 admissions (average number of admissions per year – 888 infants). The inclusion criteria were that patients had total serum bilirubin levels of > 400μmol/L at the time of diagnosis and no evidence of hypoxic ischemic encephalopathy. Records were reviewed to establish neurodevelopment outcomes.

Twelve neonates (nine males) were identified. Bilirubin levels at the time of diagnosis ranged from 405 to 825μmol/L. Causes of these elevated levels included glucose-6-phosphate dehydrogenase deficiency (seven patients), dehydration (three patients), sepsis (one patient), and was undetermined in one patient. Abnormal visual evoked potentials were found in three of nine patients and abnormal brainstem auditory evoked potentials in seven of ten patients. Abnormal electroencephalograms were documented in five patients studied. Brain magnetic resonance imaging results were abnormal in three of four patients.

Magnetic resonance imaging typically showed an increased signal in the posteromedial aspect of the globus pallidus and was, therefore, useful in the assessment of the structural changes of chronic bilirubin encephalopathy after kernicterus.

Repinotan is a potent, serotonin (5-HT1A) full receptor agonist that interferes with ischemia-mediated neuronal cell death in animal models. This double-blind, placebo-controlled phase II study examined the safety, tolerability, and dose of repinotan in patients with acute ischemic stroke.

Patients with acute hemispheric ischemia and a National Institutes of Health Stroke Scale of 4 to 25 were randomized to placebo or repinotan 0.5, 1.25, or 2.5 mg/day (d) given by continuous intravenous infusion for 72 hours. Treatment was started within six hours of symptom onset. Evaluations were performed at four weeks and three months.

Among 240 patients in the safety analysis, repinotan was well-tolerated, with adverse events appearing more frequently in the highest dose group (2.5 mg/d). The most common adverse event was headache (21.3% to 35% with repinotan and 24.1% with placebo). Most (75%) adverse events were of mild or moderate severity. The most common severe adverse events were neurological worsening, cerebral hemorrhage, and brain edema. The number of deaths and serious adverse events were similar among placebo and repinotan groups. Compared to the placebo group, the proportion of patients with good outcomes at three months was greatest in the group receiving repinotan 1.25 mg/d, although the difference was not statistically significant.

This study indicates that the incidence of adverse events was comparable with all doses of repinotan and placebo, and no safety issues were observed. A trend toward better tolerability with evidence of efficacy was observed with the repinotan 1.25 mg/d dose.

Dans cette Étude, l’incidence des incidents thÉrapeutiques Était comparable quelle que soit la dose de repinotan par rapport au placebo et aucun problème reliÉ à la sÉcuritÉ du produit n’a ÉtÉ observÉ. On a observÉ l’efficacitÉ du repinotan à la dose de 1,25 mg/j. et une tendance à une meilleure tolÉrance du mÉdicament.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder which presents with recurrent myoglobinuria. Heterozygotes are usually asymptomatic.

We correlate the clinical, biochemical and molecular features of a family in which the proband is homozygous for CPT II deficiency, due to the common Ser 113 Leu mutation.

The 20-year-old female proband presented at age three years with episodic myalgia and myoglobinuria, elevated creatine kinase (CK) of 3600 IU/L and had a 33% residual CPT II activity in cultured skin fibroblasts. Her 25-year-old dizygotic twin brothers presented with muscle stiffness following prolonged exercise but no overt pigmenturia and had interictal CKs up to 662 IU/L. Her parents and a 13-year-old brother are asymptomatic. An elder sister, not investigated, had recurrent pigmenturia and died at eight years with myoglobinuria. Molecular analysis revealed that the proband is homozygous for the Ser 113 Leu mutation. Her parents are heterozygotes with CPT II activities of 55% to 70%. Her younger brother is normal with 83% activity. The symptomatic twin brothers are heterozygous but demonstrated unexpectedly low CPT II activities of 40%, which may explain their phenotype.

We postulate that there may be genetic, environmental and sex hormonal factors accounting for this manifesting heterozygosity and biochemical heterogeneity in CPT II deficiency.

Human immunodeficiency virus (HIV) infection frequently results in neurological complications but the impact of different neurological syndromes on patients' quality of life remains unknown.

We investigated health-related quality of life (HRQoL) parameters among HIV/Acquired Immune Deficiency Syndrome (AIDS) patients with and without neurological disease, including 11 dimensions of HRQoL within the Medical Outcomes Short-form Health Survey-HIV.

Comparisons of sociodemographic and systemic clinical variables did not differ between HIV/AIDS patients with (n=94) and without (n=75) neurological disease. However, patients with neurological diseases exhibited significantly lower HRQoL scores compared to matched controls, which was most evident among HIV/AIDS patients with cognitive impairment and sensory neuropathy. Prospective analysis revealed diminishing HRQoL scores prior to neurological diagnosis followed by a progressive and sustained improvement in HRQoL scores after intervention over a 96-week period.

These studies indicate that while HIV-related neurological diseases are associated with reduced HRQoL scores, enhanced neurological care has a positive impact on HIV/AIDS patients' overall well-being.