To provide a simple means of ”real time“ recognition of emergence from post-traumatic amnesia (PTA).

Ninety-one patients with traumatic brain injury (PBI); 53 minor (GCS 13-15), 19 moderate (GCS 9-12), 18 severe (GCS 3-8). Twenty-seven control subjects treated at two regional trauma units for their acute phase and followed in a hospital-based research institute were studied prospectively. Subjects were examined repeatedly following injury with the Galveston Orientation and Amnesia Test (GOAT) and tests of their ability to learn and retain new information. Word triplets balanced for concreteness and frequency were presented. Immediate and 24-hour recall were tested. If 24-hour recall was imperfect, recognition was tested by presenting the 3 target words and 6 distracters. The target words were then re-presented and recall was tested the next day. The time intervals to first perfect recognition and first free perfect recall were compared with the patients' first GOAT score of 75 or greater on 2 successive days. Simple line drawings of common objects were also presented to the subjects using an identical paradigm. The outcome measures were GOAT, 3-word recognition and recall, 3 picture recognition and recall.

For all categories of head injury severity, the median interval to perfect free recall of words followed the achievement GOAT criterion by a significant interval. The mean GOAT scores for perfect 3-word recall and recognition corresponding to minor, moderate and severe injuries were 97, 90 and 88, and 97, 76 and 68 respectively. The recognition and recall of pictures preceded the recognition and recall of words by approximately 1 day.

The orientation measures of the GOAT that contain material that the patient knew prior to injury obscure the determination of recovery of continuous memory and should be tested separately. Three-word recall which is simpler to administer than the GOAT is a more reliable measure of emergence from PTA. For patients who are dysphasic or who do not share a common language with the examiner, 3-picture recognition and recall may substitute for word recognition and recall.

To evaluate the safety and tolerability of subcutaneous (s.c.) cladribine therapy in patients with chronic progressive multiple sclerosis (CPMS), and to evaluate the effects on lymphocyte subsets.

Cladribine, a synthetic antineoplastic agent with immunosuppressive effects, may favourably affect the course of CPMS. However results of a previous reported clinical trial showed significant myelosuppression in some patients.

19 patients with severe (mean extended disability status score [EDSS] = 6.7) CPMS were treated on a compassionate basis with cladribine 0.07 mg/kg/ day s.c. for 5 days per cycle, repeated every 4 weeks for a total of 6 cycles. Patients underwent clinical evaluation, EDSS, and hematologic analysis before, during, and following therapy.

The treatment was very well tolerated with no clinically significant side effects observed. Between baseline and the end of cycle 6, mean decreases were noted in absolute lymphocyte count from 1697 to 463 (p = 0.000012), CD4 count from 865 to 187 (p = 0.0000008), CD8 from 418 to 165 (p = 0.005) and CD19 from 197 to 26 (p = 0.000002). Platelet, granulocyte and RBC counts were unaffected. Approximately one year after completion of therapy, some recovery of CD4 and CD8 counts had occurred although both counts remained suppressed compared to baseline (302 and 227 respectively); the CD19 count had recovered essentially to normal by one year. EDSS scores post-therapy revealed some deterioration in 8 patients and stable scores in the remaining 11. Global patient evaluations of the treatment were mixed.

Cladribine therapy, at lower doses than previously reported, was remarkably well tolerated in CPMS, with no significant myelosuppression. Profound effects occurred in total lymphocyte count and CD4, CD8 and CD19 subsets.

Long-term glioblastoma multiforme survivors (LTGBMS) are uncommon. The frequency which these occur in an unselected population and factors which produce these unusually long survivors are unknown.

To determine in a population- based study 1) the frequency of LTGBMS in a population and 2) identify which patient, treatment or tumor characteristics would predict which glioblastoma (GBM) patient would become a LTGBMS.

The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in southern Alberta between 1/1/75 - 12/31/91. Patient charts were reviewed and histology re-examined by a blinded neuropathologist. LTGBMS were defined as GBM patients surviving ≥ 3 years after diagnosis. Each LTGBMS was compared to three age-, gender-, and year of diagnosis-matched controls to compare patient, treatment, and tumor factors to GBM patients without long-term survival.

There were 279 GBMs diagnosed in the study period. Five (1.8%) survived ≥ three years (range, 3.2-15.8 years). Seven additional long-term survivors, who carried a diagnosis of GBM, were excluded after neuropathologic review; the most common revised diagnosis was malignant oligodendroglioma. LTGBMS (avg. age = 45 years) were significantly younger when compared to all GBM patients (avg. age = 59 years, p - 0.0001) diagnosed in the study period. LTGBMS had a higher KPS at diagnosis (p = 0.001) compared to controls. Tumors from LTGBMS tended to have fewer mitoses and a lower Ki-67 cellular proliferative index compared to controls. Radiation-induced dementia was common and disabling in LTGBMS.

These data highlight the dismal prognosis for GBM patients who have both a short median survival and very small chance (1.8%) of long-term survival. The LTGBMS were younger, had a higher performance status, and their tumors tended to proliferate less rapidly than control GBM patients. When long-term survival does occur it is often accompanied by severe treatment-induced dementia.

The management of women with epilepsy involves a number of important issues including conception control, sexual dysfunction and fertility, the effect of seizures on the fetus, possible changes in seizure frequency during pregnancy, potential teratogenic effects of antiepileptic drugs and management issues during pregnancy. The primary goal in the treatment of women with epilepsy remains optimal seizure control in the absence of unacceptable adverse effects. The advantages and disadvantages of the new antiepileptic drugs in women remain to be fully established but these new agents allow a wider choice for improved seizure control

In spite of scattered reports to the contrary, concern is continually expressed that the frequency of cerebral palsy has not decreased with modern perinatal/neonatal care. Overall, epidemiological information on cerebral palsy is scant. The generally accepted prevalence is 2 to 2.5 per thousand school-age children.

A population-based record linkage study of a presently living cohort of 96,359 children born from April, 1985 through March, 1988 and followed over an eight-year tracking period captured the diagnostic codes for all fee-for-service physician claims, all hospital separations and individual birth data from the Department of Vital Statistics of the Government of Alberta. The ICD-9 code "343" was used to identify subjects. The childhood prevalence and frequency by birthweight- specific sub-groups of cerebral palsy were determined.

Two hundred and forty-eight living children with confirmed cerebral palsy after age three years (congenital, 229 [92.3%]; probable acquired 19 [7.7%]) were identified giving an overall prevalence of 2.57 per 1000. Seventy percent were diagnosed before their third birthday. Cohort prevalence of cerebral palsy for low birthweight children (< 2500 grams) was 17.7, very low birthweight (< 1500 grams), 78.5; and extremely low birthweight (< 1000 grams), 98.4. Low birthweight children made up just over one-third of cases in this study.

Cerebral palsy continues to affect a significant number of children suggesting the prevalence of cerebral palsy has not decreased. The proportion of affected children with low birthweight in this study is less than that reported in the literature.

Multiple sclerosis (MS) is a common neurologic disease in young and middle-aged adults affecting approximately 35,000 Canadians. The objectives of this study were to estimate the annual and lifetime costs of MS from the Canadian societal perspective.

Patients were consecutively recruited by neurologists in 14 MS outpatient clinics across Canada. They were classified according to the Expanded Disability Status Scale (EDSS) into three groups: mild (EDSS ≤ 2.5), moderate (EDSS = 3.0-6.0) and severe (EDSS ≥ 6.5). Sociodemographic, clinical and resource utilization data were collected retrospectively for the three months prior to patient inclusion. Costing of resources was performed from Ministry of Health, private third party payers, patient and societal perspectives. Average Canadian costs ($CDN 1995) were valued from available provincial data.

A total of 198 patients were included in the analysis (mild: n = 62, moderate: n = 68 and severe: n = 68). Costs increased with increasing EDSS scores, from all perspectives. The annualized societal costs per patient were $CDN 14,523, $CDN21,698 and $CDN37,024 for the mild, moderate and severe groups, respectively. In all severity groups, most of the financial burden is borne by patients, from 74% to 88%. Indirect costs, namely lost daily activity/leisure time and lost productivity, were the major societal cost drivers. The lifetime cost of MS, including patient institutionalization, was estimated to be $CDN 1,608,000 per patient.

In Canada, MS is associated with enormous direct and indirect costs. Patients carry most of the economic burden of this disease. The results of this burden of illness study provide a basis for cost-effectiveness analyses of new therapeutic interventions for MS.

Electroencephalography (EEG) is playing an increasingly important role in the management of comatose patients in the intensive care unit.

The techniques of EEG monitoring are reviewed. Initially, standard, discontinuous recordings were performed in intensive care units (ICUs). Later, continuous displays of “raw EEG” (CEEG) were used. More recently, the addition of quantitative techniques allowed for more effective reading.

Applications of continuous EEG to clinical problems are discussed. The most useful role of CEEG appears to be the detection and management of nonconvulsive seizures. There is a need for controlled studies to assess the role for CEEG in neuro-ICUs and general ICUs.

Supraclinoid carotid aneurysms have traditionally been classified according to their relation to the major carotid branches, but considerable variation exists with respect to site of origin, projection, and relationship to the skull base. Distal internal carotid aneurysms with a superior or medial projection are uncommon vascular lesions, with an unusually high incidence of operative complications.

Surgical experience with five patients suffering from subarachnoid hemorrhage due to ruptured aneurysms of the dorsomedial wall of the distal internal carotid artery is presented, with emphasis on their angiographic appearance, anatomical features, and operative management.

All five patients underwent surgical clipping. Intra-operative rupture occurred in two cases, with avulsion of the aneurysm from the internal carotid artery in both. A third patient experienced recurrent subarachnoid hemorrhage three days after uneventful surgery, due to the clip shearing off of the parent vessel.

Distal internal carotid aneurysms do not conform to the usual principles of aneurysm formation and are unique in their dorsomedial location unrelated to an arterial bifurcation. Although their anatomy is straightforward and exposure is not restricted by bone or dural structures of the skull base, they possess extremely fragile necks which make surgical management particularly hazardous.

In the absence of a biological marker for Alzheimer's disease (AD), diagnosis has to be achieved using clinical criteria sets such as those outlined in DSM-IV, NINCDS-ADRDA, or ICD-10. As these criteria are quite broadly defined, there may be inter-rater variability in interpretation.

Using a previously published CT scan measuring technique which correlates well with diagnoses achieved using the NINCDS-ADRDA criteria as interpreted at our clinic, we chose to independently examine and reach a diagnosis in patients selected for participation in clinical trials of therapeutic agents for the treatment of AD. Forty-four CT scans from six investigators across Canada were examined using this model. All patients had been diagnosed as having AD by NINCDS-ADRDA criteria and were deemed acceptable to participate in a clinical trial.

The diagnostic concordance achieved in the original published model was 91.5%. The diagnostic concordance in the population currently being studied was 77.3%. However when examined by site, results ranged from 57.1% to 100%. Using the model, an index of atrophy and a probability of diagnosis of AD can be determined. Across sites, there were statistically significant differences in these measures (p ≤ 0.035). The mean probability of diagnosis of AD across sites ranged from 0.56 to 0.94. Although the sites with lower probabilities had slightly lower mean ages and slightly less atrophy, there was no overall correlation of the atrophy measures with age.

Current results raise the possibility that the selection of patients for AD clinical trials using current diagnostic criteria sets may not be adequate and conclusions with respect to agent efficacy could be flawed.

To evaluate, in a double-blind fashion, the efficacy of deep brain stimulation of the internal segment of the globus pallidus (GPi) contralateral to a previous unilateral medial pallidotomy (MP).

This pilot study involved 4 patients with a previous MP and one previously unoperated patient unable to tolerate any antiparkinsonian drugs. One of the patients with a prior unilateral MP had two electrodes implanted in the contralateral side, one in GPi and one in Vim thalamus. Detailed neurologic assessments were performed after overnight drug withdrawal and in the drug “on” state at baseline, 1 week and 3 months (in all), and 9 and 12 months (one) with patients and evaluators blinded to the status of stimulation.

GPi stimulation resulted in improvements in “off-period” contralateral bradykinesia, rigidity and tremor in all patients. Dyskinesias and freezing episodes were ameliorated in one patient each but dyskinesias were transiently induced in another. The patient with GPi+Vim electrodes had complete resolution of contralateral tremor with thalamic stimulation but less benefit from acute GPi stimulation. One patient experienced a single seizure one week post-op and no other surgical complications were observed.

Deep brain stimulation can be applied safely and effectively in patients who have already had a pallidotomy on the contralateral side. The effect of stimulation at different sites on different symptom profiles and levodopa-induced dyskinesias requires further evaluation.

The cost of care for hydrocephalic patients is not well established.

This retrospective study for the years 1990-1996 analyzed the cost of surgical intervention and hospitalization of hydrocephalic patients in the community-based setting of Manitoba, Canada, with a stable population of 1.138 million.

The number of discharges with a primary diagnosis of hydrocephalus was greater than 200 annually. The mean duration of hospital stay was 12.4 to 21.9 days, depending on the etiology of hydrocephalus. Approximately 80 shunt procedures were performed annually. The total annual cost of care, excluding outpatient costs and chronic non-hospital based costs which could not be determined accurately, was estimated to be CDN$ 3.5 million in this community.

Hydrocephalus is a chronic condition which puts substantial monetary demands on society and therefore deserves greater attention.