To establish baseline data, using a quantitative motor evaluation protocol, prior to a prospective longitudinal study of the natural history of muscular involvement in myotonic dystrophy (DM).

We conducted a cross-sectional study using a protocol consisting of manual muscle testing (MMT), quantitative muscle testing (QMT), and timed functional testing (TFT) on 50 definite DM patients (27 men, 23 women), aged 16 to 67 years. The relationships between MMT, QMT and TFT scores and disease duration were examined using linear regression analysis.

The muscle weakness was symmetric and the neck flexors and the distal muscles of upper and lower extremities were weaker than proximal muscles. Using MMT scores, the average strength decline was 0.95% per year and was similar for men and women. The strength decline was significantly more rapid for distal muscles than for proximal muscles. Quantitative muscle testing scores documented a strength decline per year of disease duration of 1.2-1.6% for the hip flexors and of 2.0-3.0% for the hand grip flexors.

We observed significant linear relationships between the scores generated by this protocol and disease duration. These data illustrate the distal to proximal progression of muscular involvement in DM, a pattern of progression well-recognized by the clinicians. The follow-up assessment of a large DM cohort in a longitudinal study will establish whether this quantitative protocol provides sensitive measures of the disease progression.

To explore the somatosensory cortical responses to natural moving tactile stimulation in adult subjects using magnetoencephalography.

We measured cortical somatosensory magnetic evoked fields (SEFs) to moving tactile stimuli by a brush over the right thumb once every 1.5 s in seven subjects. Electric SEFs with various intensity or simulated jitter were used for comparison.

Tactile SEFs in primary somatosensory cortex (SI) consisted of two deflections: N24mT and P55mT. Electric SEFs consisted of N24mE, P30mE, P40mE, and P55mE. The amplitude of N24mT was only 34% ± 12% of N24mE, whereas P55mT and P55mE were of about the same size. With increased jitter or decreased intensity, attenuation of electric SEFs was more clearly found in early deflection than late deflection.

Natural moving tactile stimulation produced simpler cortical somatosensory waveforms in comparison with electric SEFs, partly related to less sharp intensity and stimulation jitter with moving tactile stimulation. We propose that of all the afferent fibers conveying the early deflection, the low threshold components participate the generation of the late deflection.

In this study, we investigated the feasibility of using a 1.5 Tesla (T) clinical magnetic resonance imaging (MRI) system for in vivo assessment of three histopathologically different brain tumor models in mice.

We selected mouse models in which tumor growth was observed in different intracranial compartments: Patched+/- heterozygous knock-out mice for tumor growth in the cerebellum (n = 5); U87 MG human astrocytoma cells xenografted to the frontal lobe of athymic mice (n =15); and F5 (n = 15) or IOMM-Lee (n = 15) human malignant meningioma cells xenotransplanted to the athymic mouse skull base or convexity. Mice were imaged using a small receiver surface coil and a clinical 1.5 T MRI system. T1- and fast spin echo T2-weighted image sequences were obtained in all animals. Gadolinium was injected via tail vein to better delineate the intracranial tumors. Twenty mice were followed by serial MRI to study tumor growth over time. In these mice, images were typically performed after tumor implantation, and at two week intervals. Mice were euthanized following their last imaging procedure, and their tumors were examined by histopathology. The histopathological preparations were then compared to the last MR images to correlate the imaging features with the pathology.

Magnetic resonance imaging delineated the tumors in the cerebellum, frontal lobes and skull base in all mouse models. The detection of intracranial tumors was enhanced with prior administration of gadolinium, and the limit of resolution of brain tumors in the mice was 1-2 mm3. Sequential images performed at different time intervals showed progressive tumor growth in all animals. The MR images of tumor size and location correlated accurately with the results of the histopathological analysis.

Magnetic resonance imaging of murine brain tumors in different intracranial compartments is feasible with a 1.5 T clinical MR system and a specially designed surface coil. Tumors as small as 1-2 mm3 can be detected with good image resolution. Mice harbouring nascent brain tumors can be followed sequentially by serial MR imaging. This may allow for a noninvasive means by which tumor growth can be measured, and novel therapies tested without resorting to sacrifice of the mice.

To describe the clinical and laboratory findings in cases of neonatal herpes simplex virus (HSV) encephalitis.

Neonatal HSV encephalitis is a devastating infection which requires a high degree of clinical suspicion and rapid initiation of antiviral therapy.

We performed a retrospective search for all cases of HSV encephalitis within the two Saskatchewan pediatric tertiary care centers for the period of 1985-2001. Only those patients with consistent clinical presentations along with direct evidence of presence of HSV, such as positive cerebrospinal fluid (CSF) viral cultures, positive polymerase chain reaction (PCR) for HSV from CSF, or positive immunoglobulin G against HSV from neonatal blood, were selected.

Five male and four female infant patients were identified. At a mean age of presentation of 24±20 days, seizures occurred in six neonates, lethargy in six neonates, temperature changes in five neonates, and apnea in three neonates. Examination of CSF demonstrated an initial monocytosis or lymphocytosis, elevated CSF protein and depressed CSF glucose in 100% of patients. Electroencephalography (EEG) was abnormal in 100% of patients. Initial computerized tomography was abnormal in 55% of patients. Clinical follow-up over an average of two years demonstrated developmental delay in four patients and upper motor neuron findings in four patients. No patients suffered from postencephalitic epilepsy or mortality.

Neonatal HSV encephalitis most commonly presents with seizures, lethargy, and dysthermia. Cerebrospinal fluid testing and EEG have 100% sensitivity in cases with laboratory confirmation of HSV presence. Improvements in morbidity and mortality as compared to previous reports may relate to better recognition of this illness and acyclovir therapy. The lack of postinfection epilepsy in our series may also relate to better recognition and acyclovir therapy within this series of patients.

Seroepidemiological studies have shown an association between raised antibody titres against Chlamydia pneumoniae, and carotid atherosclerosis or stroke. However, direct evidence for a causal link between arterial infection with C. pneumoniae and carotid disease remains weak. We hypothesized that long-term follow-up of patients with pathologically-proven arterial C. pneumoniae infection might provide further insight into the role of C. pneumoniae in carotid atherosclerosis.

We followed a cohort of 70 carotid endarterectomy patients for ipsilateral restenosis, contralateral progression, and all-cause mortality (four year median follow-up period). All patients had presence or absence of C. pneumoniae in their carotid plaques documented by immunohistochemistry after endarterectomy. A survival function was generated and the log-rank test was used to assess the difference in survival between subjects with and without documented chlamydial infection in their plaque.

Baseline demographic and cardiovascular risk factors were similar between the two groups, and survival analysis demonstrated no difference (p>0.05) in all-cause mortality, or all-cause mortality combined with restenosis and progression.

Our data finds no causal role for C. pneumoniae in restenosis or progression of carotid disease or mortality in this patient population with advanced carotid atherosclerosis.

Trigeminal neuralgia (TN) has a higher incidence among patients with multiple sclerosis (MS) than in the general population. This cohort of MS patients with TN presents a series of management challenges including poor tolerance of antineuralgic medications and occasional bilateral presentation. We analyzed our surgical series of MS patients presenting with TN who were treated with percutaneous radiofrequency rhizotomy to estimate the success, failure and recurrence rate of this procedure for those patients.

Surgical reports were retrospectively reviewed between the years 1996-2000. Patients with MS and TN who received a percutaneous rhizotomy during that time were included in the study and followed until the end of 2002. Data regarding age, sex, duration of MS and pain, response to medical treatment, pain distribution and surgical outcome were evaluated.

There were thirteen patients with MS and medically refractory TN treated with percutaneous radiofrequency rhizotomy. The average age at diagnosis for MS was 41 with TN beginning an average of eight years later. Following rhizotomy, complete pain relief without the need for any medication was achieved in 81% of the patients. The addition of medications resulted in pain control in the remaining patients. During a mean follow-up period of 52 months, there was a 50% recurrence rate. There were no complications related to the procedure and the associated facial numbness was well-tolerated.

Percutaneous radiofrequency rhizotomy is a safe and effective method for the treatment of TN in patients with MS. The unique susceptibility of this cohort to the side effects of antineuralgic medications may require early consideration of rhizotomy.

Unemployment is common in people with multiple sclerosis (MS) and is associated with loss of income and impaired health related quality of life. This study determined variables associated with unemployment and risk factors for the development of unemployment in people with MS.

Ninety-six patients who were under age 65 and participated in two previous studies to measure economic costs and health related quality of life in MS were included. The baseline employment rate and variables associated with unemployment at baseline were determined. The ability of these variables to predict unemployment over the next two and a half years was then evaluated.

At baseline 50.1% (50/96) of participants were employed. Two and a half years later only 40.6% (39/96) remained employed. This represents loss of employment for 22.0% (11/50) of those originally employed. Factors associated with unemployment at baseline included greater disability, progressive disease course, longer disease duration, and older age. Risk factors for loss of employment over the next 2.5 years included greater disability and older age.

This study confirms the low employment rate among people with MS and confirms the association of several previously-reported factors with greater risk of unemployment. It is also the first study to confirm that some of these factors also increase the risk of future unemployment. People with MS who are over age 39 or have moderate disability and are still employed can now be identified as at risk for becoming unemployed over the next 2.5 years. They should be considered for interventions to maintain employment or to lessen the impact of unemployment.

Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in British Columbian Coastal Natives has, to date, been a clinical and laboratory diagnosis. However, magnetic resonance imaging (MRI) abnormalities have been well-described in other populations in which HAM/TSP is endemic.

In order to assess the usefulness of MRI as a diagnostic tool in this population, we compared scans of HAM/TSP patients with those of HTLV-I positive non-HAM/TSP British Columbian Coastal Natives (carriers) and multiple sclerosis patients presenting with progressive paraparesis.

The typical nonspecific findings of thoracic cord atrophy and increased signal in the periventricular and subcortical white matter on T2-weighted images were confirmed in the HAM/TSP patients. Despite a lack of specificity of the MRI findings between HAM/TSP patients and HTLV-I carriers, criteria that could effectively differentiate HAM/TSP patients from multiple sclerosis patients with similar clinical presentations were determined.

Clinical and radiological correlations suggest that longitudinal MRI investigations charting the course of HAM/TSP may reveal the clinical significance of these lesions and further define the role of MRI in the diagnosis of this entity. Magnetic resonance imaging is an important supplement to immunological and clinical data in differentiating multiple sclerosis from HAM/TSP.

The aim of the present study was to determine the potential therapeutic value of the lazaroid U-83836E on blood brain barrier (BBB) breakdown and edema with respect to the changes in the synaptosomal Na+/K+ and Mg2+/Ca2+- adenosinetriphosphatase (ATPase) activities, tissue malondialdehyde levels and the neuronal viability in the rat brain subjected to cerebral trauma.

Traumatic brain injury (TBI) was introduced by applying a 75 gm. cm force to the right parietal cortex using the weight-drop method. The first set of animals was used for determining time course changes of the synaptosomal Na+/K+ and Mg2++/Ca2+-ATPase and the malondialdehyde levels and were sacrificed 2, 6 and 24h after lesion production. A group of the animals was treated with U-83836E proir to TBI and sacrificed 24h after cerebral injury. A second set of animals was used for evaluating the alterations in BBB disruption and tissue water content and were sacrificed 2, 6 and 24h after lesion production. Two groups of animals were treated with U-83836E and sacrificed after 2 and 24h following TBI. U-83836E was given intraperitoneally thirty minutes before trauma at a dose of 10 mg/kg. Neuronal necrosis was also evaluated in the groups of U-83836E and physiological saline-treated animals.

Extravasation of Evans blue into the traumatized hemisphere was maximum at 2h (p<0.001) and returned close to the control levels at 24h after TBI (p>0.05). Edema had developed progressively over time and reached the maximum degree of 2.1 % (p<0.001) at 24 h. U-83836E showed no effect on the BBB breakdown and the tissue water content at 2h and still had no effect on the BBB breakdown after 24h following the trauma (p>0.05), although it reduced edema after 24h (p<0.01). The losses of Na+/K+ and Mg2+/Ca2+-ATPase activities were found as 39.5 % (p<0.001) and 29.4 % (p<0.01) of the control value, respectively, and remained at the decreased levels throughout the experiment. Malondialdehyde level continued to increase over time reaching up to 209 % (p<0.001) of the control value 24h after TBI. Both ATPase activities were improved to near control values (p>0.05) by the effect of U-83836E. U-83836E inhibited the increase of lipid peroxidation (p<0.001) and also salvaged neuronal necrosis (p<0.05).

U-83836E given prophylactically after cerebral trauma appears to reduce edema, possibly by inhibiting increases in lipid peroxidation and by stabilizing ATPase. Further studies are recommended to verify the similar effects of the brain penetrating lazaroids when they are given after trauma.

An altered breathing pattern in sleep, over two to three weeks, reported by the parents of a child on Vagal Nerve Stimulation (VNS) therapy for refractory epilepsy, prompted a sleep study in him. His polysomnography (PSG) revealed respiratory irregularity concordant with VNS activation. Dyspnoea is a well recognised and reported side effect of the VNS. However there are only a few studies looking at respiration in sleep with VNS. We therefore undertook PSGs in seven other children on VNS.

Sleep studies were undertaken, in accordance with standard clinical practice. Sleep and apnoeas and hypopneas were scored in accordance with conventional criteria. Respiratory pattern changes in sleep (RPCS) with VNS were looked for.

Respiratory pattern changes in sleep were seen during PSG in seven of eight children on VNS for refractory epilepsy. Decreased effort and tidal volume occurred in seven children, concordant with VNS activation. In one child, this was associated with a fall in respiratory rate, in the other six children with an increase. No study showed an apnoea/hypopnoea index in the abnormal range. The RPCS were not associated with significant hypoxia or hypercapnoea.

Our results suggest that RPCS occur in most children with VNS. This is not surprising in view of the significant influence vagal afferents have on respiratory control centres. The RPCS did not appear to have a clinical impact in our group. However further investigations are suggested to explore this phenomenon, especially in patients with sleep apnoea syndromes or compromised respiratory function.

Invasive monitoring with subdural electrodes (SDE) for investigation of medically intractable epilepsy may be associated with undesirable immediate postoperative morbidity such as headache, nausea, vomiting, fever, and meningism. We undertook to evaluate the potential beneficial role of perioperative dexamethasone in reducing these symptoms.

In a double-blind placebo controlled clinical trial 30 patients undergoing SDE insertion were randomized to receive either placebo or a course of dexamethasone beginning one hour prior to surgery and tapering to discontinue over 72 hours postoperatively. Pain, pain relief, nausea, nausea relief, temperature, and meningism were assessed regularly in the postoperative period, and analgesic, antipyretic, and antiemetic drug requirements were tabulated.

One patient was withdrawn from the dexamethasone group due to lack of data. With regards to postoperative pain, the direction of benefit favoured dexamethasone but a significant treatment by time interaction prevented further analysis of treatment effect. The dexamethasone group did have significantly lower temperatures and higher nausea relief scores. There was no statistically significant difference between the groups with regards to pain relief, nausea, and meningism scores. The beneficial effects of dexamethasone were delayed in onset, of limited duration, and not uniform over the observation period.

Dexamethasone appears to have a role in reducing immediate morbidity following SDE insertion but its effect is not uniform in the postoperative period; it appears to be delayed in onset, and of limited duration. Further study is necessary to determine the ideal dosing schedule.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a key rate-limiting enzyme in the mevalonate pathway, which generates precursors both for cholesterol biosynthesis and for the production of nonsteroidal 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 mechanism of this phenomenon is unclear. Possible involvement of changes in expression of certain cell-cycle related genes led us to study some of them in more detail.

Medulloblastoma cell lines were exposed in vitro to lovastatin, and the effects of gene expression changes were studied using RT-PCR, antisense oligonucleotide, DNA electrophoresis and Western blotting analysis.

1) Levels of total Ras gene mRNA and individual Ras gene mRNA are stable in lovastatin treatment in all examined medulloblastoma cell lines. 2) Blocking c-myc gene over-expression does not enhance medulloblastoma cell sensitivity to lovastatin. 3) Following lovastatin treatment, p16 expression exhibits no change, but pronounced increases of p27KIP1 protein are observed in all examined cell lines. Lovastatin induces pronounced increases of p21WAF1 protein only in Daoy and UW228, but not in D283 Med and D341 Med. 4) Following lovastatin treatment, increased p53 protein is detected only in D341 Med, and bax protein is unchanged in all cell lines.

Lovastatin-induced growth inhibition and apoptosis in medulloblastoma are not dependent on the regulation of Ras and c-myc gene expression, but may be mediated by p27KIP1 gene expression. Lovastatin-induced apoptosis in medulloblastoma is probably p53 independent, but p53 and p21WAF1 gene expression may also mediate anti-proliferative effects of lovastatin on specific medulloblastoma cell lines.

To describe a novel therapeutic strategy for the treatment of “blister-like” aneurysms of the distal internal carotid artery (ICA). Direct surgical treatments of these fragile lesions have been associated with generally poor outcomes.

Two consecutive patients presenting with acute subarachnoid hemorrhage from “blister-like” aneurysms were treated with preliminary balloon occlusion of the ICA, followed by surgical trapping of the ICA beyond the aneurysm.

The treatment resulted in complete thrombosis of both aneurysms with no clinical complications.

This combined endovascular-neurosurgical approach offers a controlled, safer alternative to primary surgical therapy of “blister-like” aneurysms.

To report on five patients with temporal lobe epilepsy (TLE) as the unique manifestation of multiple sclerosis (MS).

Among 350 consecutive MS patients, we identified 16/350 (4.6%) who also had epileptic seizures. Here, we review their electrophysiological and clinical features.

Five of these 16 patients (four female, one male; mean age 34.2 years; range 31 to 38) with MS and epileptic seizures had an extremely homogeneous clinical picture characterized by TLE as the unique manifestation of MS, even at long follow-up (mean: five years; range 4 to 10). In all patients, seizures started in the second or third decade. Brain MRI revealed at least one juxta-cortical lesion within the temporal region. Antiepileptic medication was always effective.

The present study provides the first evidence of a peculiar form of MS characterized by TLE as the unique manifestation of the disease with no disability or MS relapses at long-term follow-up.