Few data exist on the frequency and burden of epilepsy in Canada and on the impact of self-reported epilepsy in the general population. We assess the frequency, general health, psychosocial function, and health care resource use among self-identified epileptic persons in the general population.

The 1990 Ontario Health Survey is an omnibus, extensive health survey of 61,239 subjects representing the Ontario population. Self-reported epileptic subjects are compared with three groups, ie., those with ≥1 other chronic illnesses, the general population, and those with no health problems.

The point prevalence of self-reported epilepsy was 5.8 per 1,000 population, a figure similar to that of active epilepsy in other studies. Quality of life, family function and social support were worse in epileptic than in other chronically ill subjects. Similarly, the epilepsy population had more disability days and limitations in activities, and lower annual income than all other groups, including the chronically ill. Accidents were no more common among epileptic subjects than among controls. Epileptic persons were high users of health care resources, including hospitalization, emergency room, psychological/social work, nursing services and telephone contact with health professionals. Barriers to health care were experienced infrequently. Small area variations in health status and care are explored.

The health profile of self-reported epileptic subjects is similar to that obtained in studies involving defined epilepsy patients. In the general population, self-identification as having epilepsy carries a significant burden of illness, reflected in poorer health, psychosocial function, and quality of life, and higher health care resource use.

To study the effectiveness and safety of topiramate in clinical practice, for a group of patients with childhood onset epilepsy.

All patients treated with topiramate at the three study centers between November 1995 and December 31, 1997 were analyzed retrospectively, using a standardized study protocol. Data were gathered on demographic features, seizure response and medication related adverse events.

Eighty-seven patients were treated with topiramate. Over 90% seizure reduction was achieved in 8 (9%) patients, 50%-90% in 21 (24%), <50% in 54 (62%) patients. Four patients (5%) had a deterioration in seizure control. Adverse events required topiramate discontinuation in 36 (41%). Of these 27 (31%) complained of unacceptable cognitive dulling. The rate of dose escalation and final dose in mg/kg were similar in those who remained on topiramate and those who were intolerant because of cognitive side effects.

Although topiramate resulted in >50% seizure reduction in 29 (33%) of this group of patients with difficult epilepsy, its usefulness was limited by a high incidence of adverse effects. Adverse events prevented ongoing therapy for 36 (41%) and cognitive dulling resulted in topiramate discontinuation by 27 (31%) of the group.

The Canadian Burden of Illness Study Group reported that the quality of life (QoL) of multiple sclerosis (MS) patients falls drastically, early in the disease. With disability progression, the physical functioning scales of the Short Form 36 (SF-36) showed further decreases in QoL. The objective of this study is to describe the QoL of MS patients treated with interferon beta-1b (IFNB-1b) and to compare it to the QoL observed in a group of patients who had not been treated with IFNB-1b.

Treated patients were prospectively recruited and were seen at their regular visit to the MS clinic. They self-completed the SF-36 questionnaire and their QoL was described and retrospectively compared to that of historical controls.

When IFNB-1b treated patients were compared to historical control patients with the same relapsing forms of MS, the treated patients with an Expanded Disability Status Scale (EDSS) score lower than 3.0 had a significantly better QoL. This was significant for four of the eight SF-36 domains: Physical Function (+22%, p=0.0102), Role-Physical (+100%, p=0.0022), General Health (+27%, p=0.0070) and Social Function (+19%, p=0.0287). The average QoL difference was 8% in the EDSS 3.0-6.0 group and 10% in the EDSS >6 group.

Patients with relapsing forms of MS treated with IFNB-1b have better QoL than patients who are not treated, especially those with an EDSS < 3.0.

The Scripps neurologic rating scale (SNRS) is a summary measure of individual components comprising a neurological examination, designed for use in multiple sclerosis (MS). Our objective is to evaluate the responsiveness of the SNRS, within the context of a 2-year, randomized, double-blind crossover study of the efficacy of cladribine for treatment of secondary progressive MS.

Effect sizes were determined for the SNRS and its components, separately for each treatment group (initial placebo, and initial cladribine) over both years of the clinical trial, using a standard random effects model.

Individual components tended to show positive effect sizes (improvement) during periods of active therapy in both treatment groups, and negative effect sizes (deterioration) during periods of no active therapy. Summation indices derived from the individual components of the SNRS seemed somewhat more stable than the individual components. The two components mentation and mood, and bladder, bowel, or sexual dysfunction, were rather unresponsive in our clinical trial.

Changes in the components of the SNRS over the course of our clinical trial were consistent between the two treatment groups. Most components were moderately responsive; and, the summary SNRS score appropriately summarized the moderate magnitudes of change evinced in the individual components.

Malignant spinal cord astrocytomas are rare tumors and their specific MR characteristics have not been previously described. We present a detailed MR analysis of four children with malignant astrocytoma.

A review of the clinical database at the Hospital for Sick Children, Toronto revealed four patients with histologically-verified malignant spinal cord astrocytomas (WHO Grade 3 or 4) with pre-operative MR available for retrospective review.

There were three boys and one girl with a mean age at presentation of four years (range 7 months - 12 years). Mean duration of symptoms prior to presentation was six weeks (range 3 days - 5 months). Pre-operative MR analysis revealed that all tumors were located in the cervical or cervico-thoracic regions and expanded the cord over an average of 6.5 vertebral levels. The signal was usually hypointense on T1-weighted and hyperintense or mixed intensity on T2-weighted images. In the three cases where gadolinium was given, all demonstrated enhancement (one rim enhancement with a discrete border and two with inhomogeneous central enhancement). One tumor appeared to be exophytic, one had a significant cystic component, and none showed evidence of hemorrhage. Pre-operative leptomeningeal spread of tumor was documented in two of four cases and involved intracranial spread in both cases.

There did not appear to be any specific MR characteristics to help differentiate a malignant astrocytoma from a low-grade tumor, except for the high rate of leptomeningeal spread at presentation. It is recommended that full neuraxis MR imaging be performed pre-operatively in children in whom a rapidly progressive clinical course suggests a malignant lesion. This will likely have a high positive yield and provide valuable information prior to surgical intervention.

Electromyography (EMG) is a useful test, but unfortunately also painful. We frequently encounter patients who worry about its painful nature, but tolerate it very well. Objectives: We evaluated anxiety levels of patients referred for EMG to explore the possible correlating and contributing factors to high anxiety.

A structured questionnaire, including the State-Trait Anxiety Inventory was completed by patients immediately before EMG testing. Emergency, hospitalized, and seriously ill patients were excluded.

Seventy-nine cases with ages ranging from 19-72 years (mean 43) were included. Thirty-five (44%) patients had a high pre-test anxiety level. The likelihood of high anxiety was increased if the patient was worried about the test (p<0.001) or about other issues unrelated to the test or underlying diagnosis (p<0.001), or was taking an anti-psychotic or anxiolytic drug (p=0.008). The degree or source of knowledge regarding the test procedure, did not affect the pre-test anxiety level.

The information about EMG testing received by patients in this group did not affect pre-test anxiety levels. The patient's expectations regarding the test did influence anxiety levels and this may reflect generalized anxiety regarding testing procedures or misinformation regarding the nature of the test, as patients in general reported a better than anticipated experience following the test.

Tracer constants (Ki) for blood-to-brain diffusion of sucrose were measured in the rat to profile the time course of blood-brain barrier injury after temporary focal ischemia, and to determine the influence of post-ischemic hypothermia.

Spontaneously hypertensive rats were subjected to transient (2 hours) clip occlusion of the right middle cerebral artery. Reperfusion times ranged from 1.5 min to 46 hours, and i.v. 3H-sucrose was circulated for 30 min prior to each time point (1h, 4h, 22h, and 46h; n=5-7 per time point). Ki was calculated from the ratio of parenchymal tracer uptake and the time-integrated plasma concentration. Additional groups of rats (n=7-8) were maintained either normothermic (37.5oC) or hypothermic (32.5oC or 28.5oC) for the first 6 hours of reperfusion, and Ki was measured at 46 hours.

Rats injected after 1.5 - 2 min exhibited a 10-fold increase in Ki for cortical regions supplied by the right middle cerebral artery (p<0.01). This barrier opening had closed within 1 to 4 hours post-reperfusion. By 22 hours, the blood-brain barrier had re-opened, with further opening 22 and 46 hours (p<0.01), resulting in edema. Whole body hypothermia (28oC-29oC) during the first six hours of reperfusion prevented opening, reducing Ki by over 50% (p<0.05).

Transient middle cerebral artery occlusion evokes a marked biphasic opening of the cortical blood-brain barrier, the second phase of which causes vasogenic edema. Hypothermic treatment reduced infarct volume and the late opening of the blood-brain barrier. This opening of the blood-brain barrier may enhance delivery of low permeability neuroprotective agents.

3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is a key rate-limiting enzyme in the mevalonate pathway, which generates precursors for cholesterol biosynthesis and the production of non-steroidal mevalonate derivatives that are involved in a number of growth-regulatory processes. We have reported that lovastatin, a competitive inhibitor of HMG-CoA reductase, not only inhibits medulloblastoma proliferation in vitro, but also induces near-complete cell death via apoptosis. The present study explores some of the pathways which may be involved in lovastatin-induced apoptosis.

Medulloblastoma cell lines were exposed in vitro to lovastatin with or without mevalonate, and document the effects using morphology, flow cytometry, DNA electrophoresis and Northern analysis.

1) Mevalonate prevents apoptosis when co-incubated with lovastatin, or when administered to lovastatin-pretreated cells. 2) Mevalonate restores the lovastatin-arrested cell cycle, allowing S phase entry. 3) Mevalonate does not prevent lovastatin-induced apoptosis after a critical duration of lovastatin pretreatment. For cell lines Daoy and UW228 this was 24 hours, and for D283 Med and D341 Med it was 48 hours. 4) Increases in HMG-CoA reductase mRNA levels induced by lovastatin are abrogated by co-incubation with lovastatin and mevalonate.

These results confirm that lovastatin inhibition of this enzyme results in blockage of the mevalonate pathway, and that such a block is a critical step in the mechanism of lovastatin-induced apoptosis.

This study demonstrates the utility of a newly-developed moveable 1.5 Tesla intraoperative MR imaging system using a case report of a multi-lobulated parafalx meningioma.

A 43-year-old female presented with progression of a multi-lobulated anterior parafalx meningioma several years following resection of a large left frontal convexity meningioma.

Surgical excision of the lesion was undertaken. Following apparent total resection, intraoperative MR imaging revealed two residual dumbell shaped lobules. Using these updated MR images, the tumour was readily identified and removed.

The moveable 1.5 Tesla intraoperative MR system used in the present case provides rapid, high resolution MR images during neurosurgical procedures. Moving the magnet out of the surgical field during surgery permits the use of all standard neurosurgical instruments. The ease of use and quality of images combined with minimal interference on well-established surgical techniques makes this system a valuable adjunct in the neurosurgical treatment of intracranial disease.

Paraneoplastic encephalomyelitis (PEM) is a well characterized, and typically irreversible, paraneoplastic syndrome, usually associated with small cell lung cancer or other malignancy. We describe a case of a young woman with a benign ovarian teratoma who presented with a reversible PEM.

A 24-year-old woman presented with a three week history of memory impairment, unusual behavior, personality changes, auditory hallucinations, hypersomnolence and binocular diplopia. On admission she was disoriented and inattentive with impaired short term memory. Small doses of lorazepam (1 mg), given for episodic agitation, repeatedly induced multidirectional bilateral nystagmus and a skew deviation, but her neurological examination was otherwise normal. A left-sided pelvic mass was palpable. Brain MRI pre- and post-gadolinium was normal. There was a mild CSF pleocytosis and an EEG showed minimal bilateral background activity irregularities. There were no other laboratory abnormalities. Two weeks after admission, she clinically deteriorated developing central respiratory failure and a flaccid paraplegia. Repeat MRI showed an area of increased T2 weighted signal in the medulla and three similar areas in the spinal cord. Following removal of her tumor, treatment with high dose corticosteroids and intravenous immunoglobulin, she ultimately made a full recovery. Pathology revealed the tumor to be a benign ovarian cystic teratoma.

This is the first report of a reversible PEM seen in association with a benign tumor, in this case a mature ovarian teratoma. Presumably, an immune response directed against neural elements of the teratoma cross-reacted with normal brain, brainstem and spinal cord antigens to cause neurologic symptoms. Tumor removal was followed by neurologic recovery.

Cranial dermal sinuses are rare and occur most frequently in the posterior fossa and along the midline. Likewise, supratentorial dermoid cysts are very uncommon.

We report a unique case of an adult female patient with both a supratentorial dermoid cyst and an incomplete dermal sinus tract.

The patient is a 31-year-old female, who presented with a new onset complex partial seizure. Neuroimaging and surgery revealed a right superior temporal dermoid cyst with an associated dermal sinus tract. Furthermore, the dermal sinus tract was incomplete and had no cutaneous manifestations.

We present a rare patient with an off midline supratentorial dermoid cyst associated with a uniquely incomplete cranial dermal sinus tract. The dermal sinus tract involved the bone, dura and intradural compartment, without involving the overlying skin. This represents a novel variant in the spectrum of cranial dermal sinus abnormalities.

Quadriplegic myopathy (QM) and its variants generally are described in critically ill patients who are exposed to steroids and nondepolarizing muscle blocking agents (NDMBAs).

A patient with sepsis who was not exposed to steroids or an NDMBA infusion developed QM and was studied using serial quantitative electromyography.

Clinical and electrophysiological studies identified evidence of a severe myopathy and muscle biopsy showed necrosis, calcifications and selective loss of myosin filaments in non-necrotic fibers. Her clinical recovery paralleled rises in motor unit action potential (MUAP) amplitudes studied by serial automatic decomposition electromyography (ADEMG).

QM can develop with sepsis and without significant exposure to steroids and NDMBAs. ADEMG can be a useful tool in electrophysiological evaluation of critically ill patients with weakness.