The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects.

CSF amine related compound levels and thiamine results were compared in 40 FA, 44 OPCAand nine ARSAC patients with those of 94 sex- and age-matched subjects. Neuroimaging (CT scans and single photon emission computed tomographies i.e. SPECT) were carried out in all patients and controls. Genetic studies were conducted on OPCApatients. CSF amine related compounds were measured by high performance liquid chromatography, whereas CSF thiamine levels were measured by a microbiological method.

FA patients had significantly lower CSF HVA, 5HIAA and thiamine values than control patients and a trend for lower MHPG levels. In OPCA patients, CSF HVA, MHPG and thiamine values were markedly lower whereas CSF 5HIAA values showed only a trend towards lower levels; in ARSAC patients only thiamine and HVA CSF values were lower than those in control subjects.

After presenting the relationships between neurochemical findings on one side, the degree of ataxia, the degree of cerebellar atrophy and the SPECT findings on the other, the authors concluded that replacement and neuroprotective clinical trials in these patients would have to include two or three drugs because the neurotransmitter deficiencies are multiple.

Intravenous recombinant tissue plasminogen activator (tPA, alteplase) was conditionally licensed for the treatment of acute ischemic stroke (AIS) in Canada on February 17, 1999. As a condition of licensure, the Canadian Activase for Stroke Effectiveness Study (CASES) was established to monitor the use of alteplase for AIS in Canada. The study involves multiple stakeholders.

CASES is a prospective registry of patients treated with alteplase for AIS. The purposes of this registry are to ensure the safety of the drug in the Canadian context, to assess effectiveness of alteplase for AIS and to gather further information to try to establish which patients are most likely to benefit from treatment.

Both community (n=25) and tertiary centres (n=35) have enrolled a total of 944 patients to date. Early results suggest that thrombolytic stroke treatment is both safe and effective among these centres.

This paper outlines the development of and methods for the CASES study. The study is an example of a multi-stakeholder collaboration to advance the care of patients with acute stroke.

Unilateral audiovestibular symptoms are commonly seen in clinical practice and are rarely caused by retrocochlear pathology. However, clinicians are often required to rule out potentially serious causes of these unilateral symptoms. Gadolinium enhanced magnetic resonance imaging (GdMRI) is the most accurate test for detecting small cerebellopontine angle lesions and also screens the adjacent CNS structures. Its main disadvantage is the cost of the procedure.

We studied 100 consecutive patients with both GdMRI and a newer MRI screening study utilizing unenhanced T2-weighted fast spin echo (fse) MRI. Acquired images were randomly assessed by a panel of three neuro-radiologists.

We found that the screening (fse) MRI was as sensitive and specific when detecting cerebellopontine angle tumors.

We conclude that T2-weighted fse MRI is a safe and cost-effective alternative to GdMRI and offers better diagnostic utility when compared to auditory brain stem response (ABR) and CT scans.

We undertook a prospective study to investigate relationships between outcome measures of ulnar neuropathy at the elbow.

Thirty-one patients (mean age 52.6, range 20-80), with clinically and electrically verified ulnar neuropathy at the elbow, were seen independently by a neurosurgeon and a physiotherapist. All tests were administered to all patients on each visit. Data collected included measures of sensory (monofilament, two-point discrimination, vibration) and motor function (grip, key-pinch, muscle atrophy), pain (visual analogue scale (VAS)) and impact on lifestyle (Levine's questionnaires (function status score - FSS, symptom severity score - SSS)), disability of the arm, shoulder and hand module (DASH) and patient-specific measures (PSM). Parametric and non-parametric correlation and factor analysis were done.

Outcome analysis was available for 63 patient visits, with follow-up obtained for 20 patients (mean 8.5 months). Lifestyle and pain instruments (FSS, SSS, DASH, PSM and VAS) all correlated well with each other (r> 0.6, p< .01). DASH was moderately to highly correlated to nine of the 11 measures. Some tests correlated poorly, for example, Semmes-Weinstein monofilament with other sensory measures and muscle atrophy with almost all measures. Factor analysis revealed that there are two principal factors, accounting for 77% of the variance. Factor 1 relates to impact on lifestyle and pain while Factor 2 relates to strength and function.

Intraclass measures, particularly ones assessing lifestyle and pain instruments are strongly correlated. Factor analysis revealed two principal factors that account for the majority of the variance; future studies with a larger sample size are needed to validate this analysis.

Multiple sclerosis (MS) is a disease characterised by perivascular infiltrates and demyelination of the white matter in the central nervous system. Although the precise cause of MS remains unknown, some investigations have been carried out on antioxidant mechanisms in these patients.

In this study, malondialdehyde (MDA), as a lipid peroxidation marker, and ceruloplasmin (Cp) and transferrin (Trf), as antioxidant proteins, levels were determined in cerebrospinal fluid (CSF) and serum of 30 MS patients before and after corticosteroid therapy and in 20 control subjects. Transferrin and Cp levels were measured by the nephelometric method and MDAwas measured spectrophotometrically.

Mean MDAserum and MDACSF levels were found to be highest in the pretreatment group and lowest in the control group. Although there was no significant difference in terms of serum Trf level, serum Cp was found higher in pre- and posttreatment groups than in the control groups. Ceruloplasmin and Trf levels of CSF were not detectable using the nephelometric method. A significant correlation was found between MDACSF and MDAserum in the pretreatment group (r=0.58).

These data revealed that lipid peroxidation was increased in serum and particulary in CSF of MS patients and was reduced with corticosteroid therapy.

The ketogenic diet for children with refractory epilepsy requires a strict control of the amount of ingested carbohydrates. This can be altered by medication prescribed for the epileptic syndrome or for intercurrent illnesses. The goal of this paper is to compile the carbohydrate and caloric content of commonly used medications in this population.

We compiled a list of frequently used medications with the help of Canadian manufacturers and the Compendium of Pharmaceuticals and Specialties. We also tested a worst case scenario calculation based on the weight of the tablet.

We list the carbohydrate and caloric content of 790 medications studied. Our worst case scenario gives an over-estimate in all cases, making adjustments based on this calculation in an emergency setting safe.

We propose this list as a tool for physicians, dietitians, nurses and pharmacists. The list can easily be adjusted, based on local practices and reviewed periodically.

Family and friends play an important role in caring for individuals with dementia living in the community. In preparation for the Canadian Consensus Conference on Dementia held in Montreal, Canada in February 1998, the subject of dementia caregiving was reviewed in order to provide primary care physicians with some guidelines for their practice. The review was updated in June 2000 in preparation for this article.

Pertinent English-language publications and resources from the Alzheimer Society of Canada were reviewed from 1985 onwards. Findings related to the consequences of caregiving, services for caregivers and recommendations regarding the role of the primary care physician were reviewed.

Dementia caregivers experience many positive and negative consequences of caregiving. Some comprehensive services for caregivers have been shown to delay institutionalization and reduce negative consequences of caregiving. The primary care physician has a role to play in working with families and should address the following issues: 1) education about dementia; 2) psychological support for caregivers; 3) assistance mobilizing caregiver social support networks.

Primary care physicians have an important role to play in acknowledging and supporting the caregiving provided by family and friends to individuals with dementia.

The aim of the present study was to identify the mutations in the connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth disease (CMTX).

Molecular analysis was performed by nonisotopic single strand conformation polymorphism (SSCP) analysis and sequencing. Clinical evaluation was carried out according to the scale defined by the European Hereditary Motor and Sensory Neuropathy Consortium.

In one family, the mutation Arg142Trp was located in the transmembrane domain III whereas, in four other families we identified a novel mutation (Ser26Trp) located in the transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that these four families are related and suggests a founder mutation. Sixteen patients from these four families were studied. As expected, all the affected males were more clinically affected than the females and all affected patients exhibited some electrophysiological characteristics of demyelination.

Our study suggests that the Ser26Trp mutation may cause a primary demyelinating neuropathy that is not associated with a specific clinical phenotype. We also find evidence that the majority of kindreds share a common ancestor.

Zonisamide (ZNS) is an antiepileptic drug developed in Japan. Various experimental studies have investigated the effects of ZNS. However, the mechanism of action of ZNS against limbic seizures and secondary generalization is not well-known. We studied ictal regional accumulation of ZNS in the rat brain during kainic acid (KA)-induced limbic status epilepticus.

Fourteen male Wistar rats underwent a stereotactic operation. For recording the electroencephalogram (EEG), electrodes were placed in the left amygdala (LA), left dorsal hippocampus, and over the left sensorimotor cortex. For microinjection, a stainless steel cannula was also inserted into the LA. Seven days after surgery, rats were anesthetized and a catheter was inserted into the femoral vein. The animals were immobilized and allowed to recover from anesthesia for at least two hours. In eight rats, 1.0μL (1.0μg) of KA was injected into the LA, and 1.0 μL of phosphate buffer solution was injected into the LA in six control rats. Sixty minutes after injection, 14C-ZNS was administered intravenously, and an autoradiographic study was done.

During limbic status epilepticus, only seizures in the sensorimotor cortex were markedly attenuated a few minutes after 14C-ZNS administration. Additionally, high uptake of 14C-ZNS was noted ipsilaterally in the sensorimotor cortex, parietal cortex and thalamus (lateral portion). In control rats, no EEG change was seen, and distribution of 14C-ZNS was rather homogeneous.

These results suggested that ZNS suppresses secondary generalization of limbic seizures by a direct effect on the cerebral cortex.

The identification of the earliest indication of rhythmical oscillations and paroxysmal events associated with an epileptic seizure is paramount in identifying the location of the seizure onset in the scalp EEG. In this work, data-dependent filters are designed that can help reveal obscure activity at the onset of seizures in problematic EEGs.

Data-dependent filters were designed using temporal patterns common to selected segments from pre-ictal and ictal portions of the scalp EEG. Temporal patterns that accounted for more variance in the ictal segment than in the pre-ictal segment of the scalp EEG were used to form the filters.

Application of the filters to the scalp EEG revealed temporal components in the seizure onset in the scalp recording that were not obvious in the unfiltered EEG. Examination of the filtered EEG enabled the onset of the seizure to be recognized earlier in the recording. The utility of the filters was confirmed qualitatively by comparing the scalp recording to the intracranial recording and quantitatively by calculating correlation coefficients between the scalp and intracranial recordings before and after filtering.

The data-dependent approach to EEG filter design allows automatic detection of the basic frequencies present in the seizure onset. This approach is more effective than narrow band-pass filtering for eliminating artifactual and other interference that can obscure the onset of a seizure. Therefore, temporal-pattern filtering facilitates the identification of seizure onsets in challenging scalp EEGs.

In recent years, an increased prevalence of Parkinson's disease (PD) in southern Israel was observed. The aim of this study was to determine which exposures are associated with PD in the urban population of this region.

Ninety-three PD patients living in towns were compared to 93 age and sex matched controls. A previously validated questionnaire, including demographic data, education, data on exposures, previous diseases, family history and habits, was administered.

In multivariate logistic regression analysis, it was found that history of work in construction sites was the strongest predictor of PD risk, followed by exposure to pesticides. In contrast, there was a negative association with smoking and history of mechanical factory employment. When the same statistical analysis was limited to association of PD with smoking, pesticides and construction work, the latter was found to be the strongest risk factor.

The risk factors for PD in this population are work on a construction site and exposure to pesticides.

Ventricular catheter placement is a common neurosurgical procedure often resulting in inaccurate intraventricular positioning. We conducted a comparison of the accuracy of endoscopic and conventional ventricular catheter placement in adults.

A retrospective analysis of data was performed on 37 consecutive patients undergoing ventriculo-peritoneal shunt (VPS) insertion with endoscopy and 40 randomly selected, unmatched patients undergoing VPS insertion without endoscopy, for the treatment of hydrocephalus of varied etiology. A grading system for catheter tip position was developed consisting of five intraventricular zones, V1-V5, and three intraparenchymal zones, A, B, C. Zones V1 for the frontal approaches and V1 or V2 for the occipital approaches were the optimal catheter tip locations. Postoperative scans of each patient were used to grade the accuracy of ventricular catheter placement.

Seventy-six percent of all endoscopic ventricular catheters were in zone V1 and 100% were within zones V1-V3. No endoscopically inserted catheters were observed in zones V4, V5 or intraparenchymally. Thirty-eight percent of the conventionally placed catheters were in zone V1, 53% in zones V1-3 and 15% intraparenchymally. There was a statistically significant difference in the percentage of catheters in optimal location versus in any other location, favoring endoscopic guidance (p<0.001).

We conclude that endoscopic ventricular catheter placement provides improved positioning accuracy than conventional techniques.

Depressive syndromes in dementia are common, treatment is challenging and controlled intervention studies are small in number. The goal of this paper is to review known information about the etiology, epidemiology and treatment of these syndromes, as summarized at the recent Canadian Consensus Conference on Dementia.

A number of Medline searches were performed (most recently updated in October 2000) using the subject categories dementia and depression, or apathy or emotional lability and other relevant articles were also reviewed. The background article was edited and amended at the Consensus Conference on Dementia. Final recommendations appearing in the summary article by Patterson et al were accepted by the group consensus process. Clinical discussion and informational updates were added for the current text by the authors.

Depressive syndromes, ranging in severity from isolated symptoms to full depressive disorders, increase in dementia. While clear-cut depressive disorder is increased in this population, sub-syndromal disorders are even more common and cause considerable distress. Antidepressant treatment may improve the quality of life in depressed, demented people, although it is less successful than in those without cognitive impairment and carries more risk of iatrogenic effects.

Physicians should be alert to the presence of depressive syndromes in dementia. Depressive illness should be treated and, when necessary, referral should be made to an appropriate specialist. Treatment must minimize iatrogenic effects. Although there is some support for treatment of syndromes that do not meet criteria for depressive disorder or dysthymia, the first line of intervention in these situations should involve nonpharmacological approaches.

Glioblastoma Multiforme (GBM) is the most common and malignant brain tumor in adults. The median survival in patients harboring this neoplasm is 12 months irrespective of any form of therapy. Health care costs of illnesses with high mortality rates, such as GBM, are of particular interest in times of constrained health care resources. No information regarding costs for the treatment of patients with GBM is available in Canada. The aim of this study was to conduct an analysis of the costs of treatment of GBM in Nova Scotia.

Patients with histologically proven GBM during a three year period (1996-1998) in Nova Scotia were included in the study. Analysis was based on hospital costs supplemented by data on additional medical services received following discharge for the primary intervention.

The mean cost of medical care per patient from the time of diagnosis to death was $ 17,149. The highest costs were related to hospitalization with ward costs alone accounting for 48% of all costs. Radiotherapy costs were 25%, surgery costs were 16% and chemotherapy costs were 7% of all costs. Costs for diagnostic procedures were 6% of the total costs.

Our data reflect the costs and practice pattern in the treatment of GBM in Nova Scotia and may be of value as an initial attempt to analyze costs of treatment of GBM in Canada.

Neurological involvement occurs in 5-15% of patients with sarcoidosis and isolated “neurosarcoidosis” occurs in less than 1% of all cases. Classical clinical presentations have been described, such as bilateral facial palsy, but often the disease presents insidiously with varied signs and symptoms. We present a patient who required biopsy of a lumbar nerve root for diagnosis of chronic, progressive neurosarcoidosis and review the literature with an emphasis on diagnosis.

We have reviewed a patient who presented with signs and symptoms related to infiltration of her meninges and nerve roots by sarcoidosis. All pertinent history and physical information was taken from interviews with the patient and review of her chart. Laboratory, radiographic, and pathological investigations are presented.

A high index of suspicion is required for the diagnosis of neurosarcoidosis. Gadolinium-enhanced MRI is useful but the findings are often nonspecific, and there should be a low threshold for biopsy whenever the diagnosis is considered.

Aneurysms arising from lenticulostriate artery branches in moyamoya-type disease are challenging lesions to treat, due to their fragility and deep location. Surgery is difficult and endovascular options may be limited.

A 57-year-old woman presented with a right ganglionic parenchymal hemorrhage due to a ruptured lenticulostriate artery aneurysm associated with ipsilateral middle cerebral artery occlusion. The aneurysm and parent feeding artery were occluded using endovascular injection of N-butyl cyanoacrylate.

The aneurysm was successfully obliterated and although some glue did enter the more distal middle cerebral artery, there was no change in the patient's neurologic status.

In highly selected cases where lenticulostriate aneurysms cannot be directly accessed for surgery or endovascular coiling, obliteration with liquid acrylic glue may be considered as a therapeutic option.