Alzheimer’s disease (AD) is the most common cause of dementia in older adults. Acceptance of the cholinergic hypothesis led to a search for medications which could enhance central cholinergic activity in this condition. There are now three cholinesterase inhibitors available for the treatment of AD in Canada.

To review the currently available cholinesterase inhibitors approved for the treatment of AD in Canada and to provide guidance on who and how to treat with these agents.

Donepezil, rivastigmine, and galantamine are approved for the treatment of AD in Canada. In clinical trails, patients with mild to moderate AD treated with these agents experienced modest improvements in cognition, function, behaviour, and/or global clinical state. The magnitude of benefits seen with each agent appeared to be similar. While to date, there is no convincing evidence that one is more efficacious or effective, they do differ in their pharmacokinetics, additional mechanisms of action, and side effect profiles. Therefore, the selection of agent will be based on considerations such as side effect profiles, ease of administration, personal familiarity/experience, and beliefs about the importance of the noted differences in their pharmacokinetics and additional mechanisms of action.

We believe that these agents should be offered to all individuals with a mild to moderate dementia where Alzheimer’s pathology is felt to be a contributing factor. We view all three available cholinesterase inhibitors as first-line drugs.

This report summarizes an invitational symposium on epilepsy and Canadian laws governing motor vehicle driving held in Québec City in November 1998.

Invited neurological experts from Canada, the USA, and Europe; and representatives of provincial and territorial licensing bodies, the Canadian Council of Motor Transport Administrators, the Canadian Medical Protective Association, and the Canadian Medical Association participated. An edited version of transcribed audiotapes was prepared. Specific issues discussed were whether or not a physician should be required to report a patient with epilepsy to the licensing authority (mandatory reporting), the nature and quantification of the risks posed by epileptic drivers, and what would be a reasonable law regulating driving by people with epilepsy in Canada.

The consensus among medical experts was that mandatory reporting should be abolished in Canada and that a 6-12 month seizure-free period was appropriate before most patients could return to driving private cars. Experts also believed that these standards should be uniform across Canada. There was strong disagreement with the recommendation of the Canadian Medical Association that all such drivers be reported to provincial licensing authorities even in provinces without mandatory reporting rules.

Physicians should be familiar with and follow the rules regarding epilepsy and driving in the provinces where they practice. Nevertheless, current evidence is against mandatory physician reporting of drivers with epilepsy and the neurologists recommended that this be abolished throughout Canada. Shorter seizure-free intervals should also be considered before resuming driving of private cars.

Proof from randomized controlled trials that carotid endarterectomy (CEA) is efficacious in stroke prevention has resulted in a large resurgence of its use in recent years. We wished to determine if patients in our region were being selected and treated with complication rates consistent with the randomized trials.

We have completed four audits of CEAs performed in our region since 1994, each followed by feed-back of results to the participating surgeons. Operations for > 70% symptomatic stenosis were considered appropriate, those for 50%-69% symptomatic and > 60% asymptomatic stenosis were considered uncertain and all others, including those in medically or neurologically unstable patients, were designated inappropriate. In part 4, the referral source and nature of the patients was also determined.

Part 1 (April 1994 - September 1995) found that of 291 CEAs performed 33% were appropriate, 48% were uncertain and 18% were inappropriate, and 40% of patients who underwent CEA were asymptomatic. In part 2 (September 1996 - September 1997) appropriate indications significantly improved to 49% of 184 CEAs (P=0.005), uncertain indications remained nearly the same at 47%, inappropriate indications fell to 4% (P=0.00002), and asymptomatic patients remained at 40%. The results of part 3 (October 1997 - October 1998) remained nearly the same as part 2 (249 CEAs, 47% appropriate, 51% uncertain, 2% inappropriate, 45% asymptomatic). Part 4 (October 1999 - October 2000) results were significantly better than part 3, appropriate indications increasing from 47% to 58% of 222 CEAs (P=0.02), and an elimination of inappropriate operations (P=0.03). Stroke and death complications declined over the study period from an overall rate of 5.2% in part 1 to 2.3% in part 4. In part 4 the majority of patients (69%) were referred to surgeons directly from general practitioners, including 58 (73%) of the 80 asymptomatic patients who underwent CEA.

Regular auditing and feedback of results and information to surgeons has resulted in significant and continued improvements in the surgical performance of CEAin our region. Since the majority of patients are referred directly to surgeons by general practitioners, it is important that this group of physicians be familiar with current CEA guidelines.

Outcomes must be measured as a first step toward improving performance. We sought to measure the national and provincial outcomes from carotid endarterectomy (CE) and explain provincial differences.

We analyzed a large Canada-wide administrative hospital discharge database of all patients, except those in Québec, receiving CE in 1994-1997 and used logistic regression for risk adjustment to measure adverse outcomes nationally and by province. Our main outcome measures were in-hospital stroke and/or death.

A total of 14,268 patients underwent CE in the years 1994-1997. The overall death rate was 1.3% and the combined stroke and/or death rate was 4.1%. There was a trend towards improvement over the four years. The provinces of Saskatchewan and Newfoundland had significantly higher adverse event rates for the risk-adjusted combined outcome measure.

The outcome of CE in Canada is good and showed improvement over four years. However, significant differences in provincial outcomes were found. This suggests that regionalization across provincial boundaries may be needed to promote higher surgeon and hospital case volumes and thus improve outcomes.

Though various textbooks describe clinical manoeuvres that help detect subtle motor deficits, their sensitivity, specificity and predictive values have not been determined. We investigated the sensitivity, specificity and predictive values of various manoeuvres in order to determine the most sensitive and reliable test or combination thereof.

Straight arm raising (Barré), pronator drift, Mingazzini’s manoeuvre, finger tap, forearm roll, segmental strength and deep tendon reflexes were tested in 170 patients with (86) and without (84) a proven lesion in the motor areas confirmed by computed tomography.

Segmental motor strength had good specificity (97.5%) but poor sensitivity (38.9%) and negative predictive value (NPV) (58.7%). The forearm roll had a similar profile. Finger tap had a sensitivity of 73.3% and a specificity of 87.5%. Barré and pronator testing had a sensitivity and specificity of 92.2% and 90.0% respectively. Hyperreflexia had a sensitivity of 68.9% and a specificity of 87.5%. An abnormality of pronator, reflexes or finger tap had a sensitivity of 97%, and when these three tests were positive, specificity was 97%. When all six tests were positive, the positive predictive value was 100%, when all six tests were negative the NPV was 100%.

The detailed segmental examination has very good specificity for detecting motor deficits, but the sensitivity and NPV are unacceptably low. Pronator drift with finger tap and reflexes is the most reliable and time-effective combination of tests for the detection of subtle motor lesions, and could replace the segmental motor examination as a screening for motor lesions.

We describe nine females with Rett Syndrome (RS), aged 14 to 26 years. All had had developmental delay before the end of their first year and had subsequently regressed to profound dementia with apraxia, ataxia, irregular respirations and often also seizures.

The Revised Gesell developmental assessment and Alpern-Boll Developmental Profile were used in modified form. Volumetric measurements of basal ganglia using MRI were compared with the findings in nine age-matched volunteer females. Positron emission scans with [18F]-6-fluorodopa and [11C]-raclopride were performed under light anesthesia with intravenous Propofol, and the findings were compared with those in healthy control girls. Bidirectional sequencing of the coding regions of the MECP2 gene was investigated in blood samples for mutational analyses.

The RS females functioned at a mental age level ranging from about 4 to 15 months. The scores correlated with height, weight and head circumference. Magnetic resonance scans of basal ganglia showed a significant reduction in the size of the caudate heads and thalami in the Rett cases. Positron emission scans demonstrated that the mean uptake of fluorodopa in RS was reduced by 13.1% in caudate and by 12.5% in putamen as compared to the controls, while dopamine D2 receptor binding was increased significantly by 9.7% in caudate and 9.6% in putamen. Mutations in the coding regions of the MECP2 gene were present in all nine patients. No significant correlation between type and location of mutation and volumetric changes or isotope uptake was demonstrable.

Our findings suggest a mild presynaptic deficit of nigrostriatal activity in Rett syndrome.

To evaluate the investigation and treatment of patients with a diagnosis of transient ischemic attacks (TIA) in the emergency department (ED) a tertiary care teaching hospital with a neuroscience referral program.

A chart review was conducted in the hospital. Consecutive ED charts with a diagnosis of TIA were included; each was reviewed by independent coders using a standardized data form.

Two hundred and ninety-three TIAcharts were reviewed; the gender ratio was 1:1 with a mean age of 66 years. Most patients (75%; 95% CI: 70, 80) were evaluated by ED physicians; the remaining patients were seen directly by referral services. The median time from symptom onset to ED arrival was 2.9 hours and the duration of symptoms was 4.6 hours. Most patients received CT scans (81%; 95% CI: 73, 85), complete blood counts (74%; 95% CI: 68, 79), and electrocardiograms (75%; 95% CI: 70, 80) in the ED. In 16% (95% CI: 13, 22) a carotid doppler was performed and in 26% (95% CI: 21, 31) an outpatient doppler was booked. Among those who were discharged (75%; 95% CI: 70, 80), antithrombotic medications were not prescribed to 28% (95% CI: 22, 34).

Practice variation exists with respect to the investigation and treatment of TIAs in this tertiary-care teaching hospital. Carotid doppler investigation and use of anti-platelet therapy for patients with TIAare suboptimal. Clinical practice guidelines and rapid assessment TIAclinics may change these results.

Symptomatic brain metastases from prostatic carcinoma are rare (0.05% to 0.5%).

A 70-year-old man presented with a homonymous hemianopsia due to brain metastatic prostatic carcinoma shortly before becoming symptomatic of prostatic disease. CT and MRI of the brain showed a tumour deep in the right hemisphere near the thalamus and involving the optic radiation.

Routine haematological and biochemical tests were normal. The prostate specific antigen level was low on two separate occasions. The prostatic and brain tumours showed identical appearances, namely of a poorly differentiated adenocarcinoma with neuroendocrine differentiation (small cell carcinoma).

A literature review suggests that small cell carcinoma of the prostate is more likely to spread to the brain compared to adenocarcinoma and that brain metastases indicate a poor prognosis. The prostate gland should be remembered as a possible cause of brain metastases and that a normal serum prostate specific antigen does not exclude this diagnosis.

Carotid artery dissection resulting in occlusion or severe narrowing and massive intracranial embolism can result in life-threatening hemispheric ischemia. Aggressive endovascular and microsurgical measures may be necessary to salvage life and minimize stroke morbidity in this extreme situation.

We have treated two middle-aged women who presented within an hour of spontaneous cervical internal carotid artery (ICA) dissection causing hemiplegia, forced head and eye deviation, and declining consciousness. The first patient had a carotid occlusion through which a catheter could not be passed, so intracranial thrombolysis was achieved through a microcatheter navigated through the posterior circulation. Surgical intimectomy and thrombectomy of the dissected ICA was then carried out using an intraoperative Fogarty arterial embolectomy catheter passed up the dissected ICA, followed by endovascular stenting of the reopened cervical ICA. The second patient underwent intracranial microsurgical embolectomy and, after an unsuccessful attempt of stenting the dissected and severely narrowed cervical ICA, surgical reopening again with a Fogarty catheter. Both patients suffered basal ganglionic infarcts but most of the middle cerebral artery territories were preserved and the patients made satisfactory recoveries.

“Malignant” carotid artery dissection causing occlusion or near occlusion with intracranial embolism is an important cause of severe and life-threatening hemispheric ischemia. Treatment should include aggressive endovascular and microsurgical interventions when the hemisphere is at risk.

Tarsal tunnel syndrome is a rare form of entrapment neuropathy. In athletes, it is usually the result of repetitive activity, local injury or a space-occupying lesion. Rarely, athletic footwear has been described as the primary cause of this syndrome.

A 37-year-old male recreational hockey player was examined clinically and electrophysiologically because of spreading numbness in the toes of his left foot while playing hockey and wearing inflatable ice hockey skates designed to promote a better fit.

Clinical and electrophysiological studies revealed evidence of left medial and lateral plantar nerve involvement. Reduced amplitudes of mixed and motor plantar nerve responses with fibrillation potentials and positive sharp waves and no evidence of conduction block suggest that the primary pathology was axonal loss. Follow-up examination showed significant clinical and electrophysiological improvement after the patient stopped wearing his inflatable ice hockey skates.

We report an unusual case of tarsal tunnel syndrome caused by an inflatable ice hockey skate. The patient improved clinically and electrophysiologically when he stopped wearing the boot.

This paper discusses the association between inflammatory and mitochondrial pathologies in patients with HIV-1/AIDS treated with zidovudine (AZT).

We present the clinical and pathological details of a 52-year-old HIV-1 positive male who presented with progressive muscle weakness. We also review the current literature and address the debated pathogenesis of the inflammatory pathology.

Muscle biopsy revealed evidence of both HIV-1 polymyositis and AZT myopathy. Six months after initiation of corticosteroid therapy and discontinuation of AZT, the patient’s symptoms had greatly improved. The biopsy was repeated to show that both pathologies had resolved.

The perceived overlap in the pathological spectra of HIV-1 polymyositis and AZT myopathy has produced some debate on causation and treatment. Unfortunately, there have been very few reports where a repeat biopsy following a drug washout period confirmed resolution of the pathology. Furthermore, affected patients have not been treated in a uniform fashion. Whether this represents one disease or two remains uncertain. The clinical relevance of this issue lies in the potential for harm from the unnecessary use of corticosteroids. This question may be best addressed by a randomized clinical trial.