Clinical safety of intracranial EEG electrodes in MRI at 1.5 T and 3 T: a single-center experience and literature review.

PURPOSE: Intracranial electroencephalography (EEG) can be a critical part of presurgical evaluation for drug resistant epilepsy. With the increasing use of intracranial EEG, the safety of these electrodes in the magnetic resonance imaging (MRI) environment remains a concern, particularly at higher field strengths. However, no studies have reported the MRI safety experience of intracranial electrodes at 3 T. We report an MRI safety review of patients with intracranial electrodes at 1.5 and 3 T. METHODS: One hundred and sixty-five consecutive admissions for intracranial EEG monitoring were reviewed. A total of 184 MRI scans were performed on 135 patients over 140 admissions. These included 118 structural MRI studies at 1.5 T and 66 functional MRI studies at 3 T. The magnetic resonance (MR) protocols avoided the use of high specific energy absorption rate sequences that could result in electrode heating. The intracranial implantations included 114 depth, 15 subdural, and 11 combined subdural and depth electrodes. Medical records were reviewed for patient-reported complications and radiologic complications related to these studies. Pre-implantation, post-implantation, and post-explantation imaging studies were reviewed for potential complications. RESULTS: No adverse events or complications were seen during or after MRI scanning at 1.5 or 3 T apart from those attributed to electrode implantation. There was also no clinical or imaging evidence of worsening of pre-existing implantation-related complications after MR imaging. CONCLUSION: No clinical or radiographic complications are seen when performing MRI scans at 1.5 or 3 T on patients with implanted intracranial EEG electrodes while avoiding high specific energy absorption rate sequences.

Establishing a Canadian registry of patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research. METHODS: We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset. RESULTS: We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS. CONCLUSIONS: The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Adult-onset epilepsy associated with dysembryoplastic neuroepithelial tumors.

RATIONALE: Dysembryoplastic neuroepithelial tumors (DNET) are benign, localized lesions that typically cause localization-related epilepsy of childhood onset. Although excellent seizure outcomes are expected following surgical resection of focal, benign lesions, reports in pediatric epilepsy series suggest that this may not be the case with DNETs, which may exhibit complex and often multifocal epileptogenesis. We report the characteristics and surgical outcome of an adult- and childhood-onset cohort with this condition. METHODS: Retrospective cohort of 23 patients seen at two major epilepsy centers, with localization-related epilepsy associated with histopathologically demonstrated DNETs. We assessed clinical, electrographic and surgical outcome features in patients with adult- and childhood-onset epilepsy. We were particularly interested in the level of congruence of EEG and MRI data and the need for intracranial recordings. We evaluated seizure outcomes at last follow-up. RESULTS: The mean age was 33.3 years (range: 5-56 years). Ten patients had adult-onset epilepsy. Thirteen patients (57%) had simple partial, 21 (91%) had complex partial, 16 (70%) had secondarily generalized seizures and 5 patients had only simple partial seizures. Status epilepticus did not occur. Non-enhancing lesions on MRI were located in the temporal lobe in 17 patients, the frontal lobe in 3 patients and the parietal/occipital region in 2 patients. One patient had a DNET that involved both frontal and temporal areas. Ictal scalp EEG and MRI were congruent in 17 patients (74%). Eleven patients (48%) underwent lesionectomies, while the rest required some resection of extralesional cortex as well. Five patients required intracranial EEG. There was no association with cortical dysplasia. Seventeen patients (74%) had an Engel class 1 outcome, in a follow-up period that ranging from 5 to 98 months. CONCLUSIONS: We found no difference in outcomes between adult- and childhood-onset cases. Although epileptogenicity was complex, congruence between electro-clinical and neuroimaging studies was high and allowed good surgical outcomes at 1 year of follow-up.

Therapeutic action of cannabinoid on axonal injury induced by peroxynitrite.

This study examined whether the potent cannabinoid HU210 ameliorates axonal injury through its indirect action to stimulate the secretion of corticosterone. We observed that HU210 dramatically reduced peroxynitrite-induced axonal injury in rats receiving adrenalectomy and corticosterone replacement treatment. These results suggest that the ameliorating effects of cannabinoids on axonal injury associated with multiple sclerosis are achieved by its direct action, but not by its indirect action to elevate the serum corticosterone levels.

Epidemiology of multiple sclerosis in London and Middlesex County, Ontario, Canada.

A case-controlled epidemiologic study of multiple sclerosis (MS) was carried out in London, Ontario, and its surrounding Middlesex County for the period 1974-1983. The prevalence rates for clinically definite/probable MS on January 1, 1984 were 94/100,000 for the city and 91/100,000 for the county. The estimated annual incidence rate for the decade 1974-83 was 3.4/100,000. The female-to-male sex ratio was 2.5:1. A familial history of MS was recorded in 14.4% of close relatives and a total of 17% when distant relatives are included. The MS group is predominantly of British (70%) and European (23%) origin. The urban-rural residence pattern analysis indicates no significant regional influence on the risk of developing MS.

The incidence of amyotrophic lateral sclerosis in southwestern Ontario, Canada.

The incidence, prevalence, and mortality rates of amyotrophic lateral sclerosis in southwestern Ontario, Canada, were determined for the years 1978 through 1982. The average annual incidence rate was 1.63 per 100,000 population. The prevalence rate was 4.9 per 100,000 on January 1, 1983. The average annual mortality rate was 1.52 per 100,000 population and increased with age, reaching a peak in the 70 to 79-year decade in both sexes. The male:female ratio was 1.2:1. The average age at diagnosis was 62.5 years, and the average duration from date of diagnosis was 2.5 years. The distribution of the disease was uneven in 12 counties, with the highest incidence in Perth (3.33) and Essex (2.43) counties. The city of Windsor, in an industrial region, had a high average annual incidence rate of 2.81.

The influence of pregnancy on disability from multiple sclerosis: a population-based study in Middlesex County, Ontario.

We analyzed the effect of pregnancy on long-term disability resulting from multiple sclerosis in 185 women ascertained through a retrospective population-based survey of MS in Middlesex County, Ontario, Canada. There was no association between disability and total number of term pregnancies, timing of pregnancy relative to onset of MS, or either onset or worsening of MS in relation to a pregnancy. The mean number of pregnancies both before and after onset of MS was no different among groups stratified according to disability. This study addresses some of the difficulties inherent in studying the effect of pregnancy on disability resulting from MS.

The Mayo Clinic-Canadian Cooperative trial of sulfasalazine in active multiple sclerosis.

OBJECTIVE: To determine whether sulfasalazine is better than placebo in slowing disability progression in MS. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 199 patients with active relapsing-remitting (n = 151) or progressive (n = 48) MS were evaluated at 3-month intervals for a minimum of 3 years (94% completed 3 years of follow-up; mean follow-up, 3.7 years). MRI studies were performed at 6-month intervals on a subset of 89 patients. RESULTS: Sulfasalazine failed to slow or prevent disability progression as measured by the primary outcome (confirmed worsening of the Expanded Disability Status Scale [EDSS] score by at least 1.0 point on two consecutive 3-month visits). Sulfasalazine influenced favorably a number of secondary outcomes during the first 18 months of the trial (e.g., annualized relapse rate, proportion of relapse-free patients; progressive subgroup only: rate of EDSS progression at 1 and 2 years, median time to EDSS progression) but these positive findings were not sustained into the second half of the trial. CONCLUSIONS: Sulfasalazine does not prevent EDSS score progression in the subset of MS patients studied by this protocol. Treatments may improve relapse-related outcomes in MS, at least temporarily, without providing sustained slowing of EDSS progression. Phase III MS trials should be of sufficient length to determine a meaningful impact on disease course.

Adherent cells suppress measles and herpes simplex I virus-induced blastogenesis of multiple sclerosis lymphocytes.

Viral antigen-induced blastogenesis of lymphocytes from multiple sclerosis (MS) patients was investigated to determine if the responses were actively suppressed. We found that depletion of adherent cells increased measles and herpes simplex I virus antigen-induced transformation of MS lymphocytes. Addition of indomethacin to cultures of unfractionated MS lymphocytes also caused an increase in viral antigen-induced responses. These two facts, plus finding that the cell type mediating the immunosuppression did not rosette with 2-aminoethylisothiouronium bromide hydrobromide-treated sheep red blood cells, indicate that the suppressed T-cell responsiveness of MS patients is caused by macrophages rather than T-cells. These results have a major implication for the divergent published data on blastogenesis induced in MS patient lymphocytes by specific antigens, viral or otherwise. We feel the inconsistencies may simply have arisen from the different lymphocyte isolation and washing procedures used giving variable levels of macrophages and, hence, variable levels of immune suppression. This clearly suggests that induction of blastogenesis in MS patient lymphocytes by a wider array of infectious agent antigens and by various neural antigens should now be undertaken using adherent cell-depleted lymphocytes.

The value of routine cultures of the cerebrospinal fluid in patients with external ventricular drains.

OBJECTIVE: The purpose of this study was to determine whether routine cerebrospinal fluid (CSF) bacteriological cultures in patients with external ventricular drains (EVDs) can identify infections early and prevent complications related to bacterial ventriculitis. METHODS: We retrospectively reviewed the microbiological reports and clinical data for all patients in whom an EVD was placed at a tertiary care pediatric neurosurgical center between 1984 and 1997. EVDs were inserted in the operating room or intensive care unit, and, in most patients whose EVD remained in place for more than 2 days, daily cultures of CSF were performed. RESULTS: One hundred fifty-seven patients in whom 160 EVDs had been placed were included in the study. Forty-eight positive cultures were identified, of which the majority were determined to be contaminants. Seven infections were identified on the basis of microbiological criteria (i.e., a gram-positive stain and positive culture) and a subsequent positive culture. In all patients in whom infections developed, routine daily cultures of CSF were performed, and, in each instance, these cultures failed to identify the infections before clinical changes occurred. All seven patients with infection had fever (>38.5 degrees C) and peripheral leukocytosis (>11 x 10(3)/mm3) on the day the infection was identified, and one had a change in CSF appearance. CONCLUSION: The results of this study suggest that routine culture of CSF in children with EVDs is not necessary, and that if CSF cultures are performed for new fever (>38.5 degrees C) or peripheral leukocytosis, neurological deterioration, or a change in CSF appearance, infections will be identified in a timely fashion. In situations in which these clinical indicators might be masked, routine cultures may be valuable.

Giant intraspinal pseudomeningoceles cause delayed neurological dysfunction after brachial plexus injury: report of three cases.

OBJECTIVE AND IMPORTANCE: Delayed neurological dysfunction after a brachial plexus injury is uncommon. We present the cases of three patients with a history of significant brachial plexus trauma and late neurological deterioration secondary to giant intraspinal extradural pseudomeningoceles. CLINICAL PRESENTATION: Three patients, each with a remote history of brachial plexus trauma, presented with slowly progressive upper-limb weakness. An examination revealed bilateral lower motor neuron weakness in the upper extremities in all patients and evidence of spastic paraparesis in one. Magnetic resonance imaging and postmyelogram computed tomographic scans demonstrated large anterior extradural cerebrospinal fluid collections extending from the upper cervical to lower thoracic and lumbar levels in each patient. Myelograms demonstrated a connection with the subarachnoid space in two patients. INTERVENTION: Direct obliteration of the connection between the cyst and the subarachnoid space was completed in two patients, and a cystoperitoneal shunt was placed in the third. Postoperative imaging demonstrated complete resolution of the extradural collections. Arrest of progression of upper-limb deterioration was observed in all patients, and dramatic improvement of long tract symptoms occurred in one. CONCLUSION: Giant intraspinal pseudomeningoceles are a rare complication of brachial plexus root injuries or avulsion, capable of causing significant morbidity. Early intervention can improve symptoms related to long tract involvement and prevent further deterioration of lower motor neuron disease. The pathophysiology of neurological dysfunction caused by these giant collections is unclear; however, vascular and mechanical factors thought to be important in the pathogenesis of cervical myelopathy also may have a role.

Head injuries in skiers and snowboarders in British Columbia.

BACKGROUND: At the Vancouver General Hospital Neurosurgical Service there have been a significant number of seriously brain injured snowboarders, seemingly out of proportion to the number of skiers. The purpose of this study was to determine whether snowboarders suffered more serious head injuries than skiers in the Vancouver catchment area. METHODS: The British Columbia Trauma Registry was searched for patients incurring head injuries while skiing or snowboarding on British Columbia mountains during the period from January 1992 to December 1997. Patients were included if they were admitted to hospital and underwent neurosurgical consultation. RESULTS: A total of 40 skiers and 14 snowboarders met the above criteria. Of the skiers, 15% sustained a severe head injury by Glasgow Coma Score, another 30% sustaining moderate head injuries, while 29% of snowboarders had a severe injury and 36% a moderate injury. A concussion was present in 60% of the skiers and 21% of the snowboarders. Snowboarders suffered an intracranial hemorrhage in 71% of the cases compared to 28% of the skiers. A craniotomy was performed acutely in 10% of skiers and in 29% of snowboarders. Three deaths occurred as a direct result of head injury, one while snowboarding. All but one of the surviving skiers were able to return home, whereas four of 13 surviving snowboarders required additional inpatient rehabilitation or transfer to another acute hospital for ongoing care. CONCLUSIONS: Snowboarders suffer more significant head injuries compared to skiers in this series and are much more likely than skiers to require an intracranial procedure. In our opinion, this indicates that additional safety measures, in particular the use of mandatory helmets, should be considered by ski areas and their patrons.

The concurrence of multiple sclerosis and amyotrophic lateral sclerosis.

We report the clinical and pathological findings of the unusual combination of two idiopathic central nervous system diseases, multiple sclerosis and amyotrophic lateral sclerosis in a 56 year old physician with a twenty-seven year history of a disease initially characterized by relapses and remissions, followed by an eight year quiescent period. During the last year of life there was rapid deterioration with development of generalized weakness, atrophy, weight loss and fasciculations of body and tongue, and associated difficulty with swallowing and sudden respiratory failure. The autopsy confirmed characteristic "burned out" plaques of multiple sclerosis and anterior horn cell and axonal degeneration of amyotrophic lateral sclerosis.

A cluster-focus of multiple sclerosis at Henribourg, Saskatchewan.

This study presents the clinical characteristics of 8 victims of multiple sclerosis from the hamlet of Henribourg, Saskatchewan with a population of less than 75 people. A diligent victim of the disease had observed that six female classmates from the early 1940's had later developed multiple sclerosis. Two male military personnel who had also resided briefly in close proximity, during the same common exposure time, also later developed multiple sclerosis. The mean onset time of developing the disease after leaving the area was 20 years. This cluster-focus suggests a common exposure to an environmental factor or a common infective agent in the etiology of multiple sclerosis.

The occurrence of multiple sclerosis in the Hutterites of North America.

OBJECTIVE: To report the occurrence, clinical characteristics and genealogical analysis of multiple sclerosis in the Hutterites of North-Western United States and Western Canada. BACKGROUND: The incidence of multiple sclerosis is reported to be lower or rare in certain ethnic groups and genetic isolates and was previously observed to be absent in the Hutterite population. METHODS: After long-term surveillance, six patients were identified and clinical examinations and laboratory investigations including VER and MRI were completed. RESULTS: The six cases included two brothers, two first cousins, male and female, another male and female, all representing two of the three endogamous groups of Hutterites, are linked to two common ancestors through lines of descent dating to 1723. The individual pedigrees were analyzed from extensive genealogical records covering eight generations. CONCLUSION: The incidence of multiple sclerosis in Hutterites is low in a high risk area of North America. A specific mode of inheritance pattern has not been established and a common founder effect may play a role in the development of multiple sclerosis. The genetic contribution of the Hutterites seems greater than previously recognized.

Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis.

Tizanidine (Sirdalud) was compared to baclofen (Lioresal) in a randomized, double-blind, cross-over trial. Each medication was introduced over a three week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one week drug withdrawal and a two week washout period. Sixty-six patients entered the trial and forty-eight completed both treatment phases. At the end of the trial, neurologists and physiotherapists thought that baclofen was superior on the basis of perceived efficacy and tolerance (p less than or equal to 0.05). Although the efficacy of tizanidine or baclofen was judged as good to excellent by 24 and 39% of patients respectively, this difference was not statistically significant. Muscle weakness was the most common adverse effect. This was significantly more troublesome in patients treated with baclofen. Somnolence and xerostomia were more common in patients treated with tizanidine. Both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity in patients with multiple sclerosis. Preference of either drug is tempered principally by side-effects.

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, cluster focus. II. The soil.

The childhood-related, geographically-linked factor which predisposes towards (or protects against) multiple sclerosis (MS) could be one or more chemicals in the environment. Chemical study of the environment or "focus" of an MS cluster may maximize the chances of detecting such an etiological link. The soil chemistry of an MS focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of soil from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. A combination of our present results with those reported in the literature suggests that an environment predisposing to MS may have a number of the following chemical characteristics: Calcareous; with soils (but not necessarily waters) generally low in copper, iron and vanadium; with excess lead, nickel and zinc in the upper soil layer; with waters relatively high in chloride, chromium, molybdenum, nitrate plus nitrite, and zinc; but low in selenium and sulfate. One possible causal pathway to explain the apparent link between the excess rate of MS and some of the curious geochemical findings at Henribourg is presented. Many other possible explanations could equally well be advanced, and methods for testing such alternative hypotheses are proposed.

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, Cluster Focus. I. The water.

Some childhood-related, geographically-linked factor predisposes towards (or protects against) multiple sclerosis (MS). It is quite plausible that this factor could be one or more chemicals in the environment, and that chemical study of the environment or "focus" of an MS cluster might maximize the chances of detecting such an etiological link. The water chemistry of such a focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of water from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. Overall, the results suggest that an environment predisposing to MS may have a number of water chemistry characteristics such as: relative deficiency of selenium and sulfate, but relative abundance of barium, calcium, chloride, chromium, magnesium, manganese, molybdenum, nitrate plus nitrite, strontium and zinc. Possible explanations for the apparent link between the excess rate of MS and the water geochemistry findings at Henribourg are discussed.

Deterioration in the health-related quality of life of persons with multiple sclerosis: the possible warning signs.

Baseline data from a population-based study examining the health-related quality of life (HRQL) of MS patients about to begin disease modifying therapy was used to determine the factors associated with the HRQL of Saskatchewan adults with relapsing-remitting MS. Participants completed a self-report questionnaire regarding demographic and socioeconomic status, fatigue, comorbid medical conditions, disability level (EDSS), number of attacks in past 6 months, illness intrusiveness (Illness Intrusiveness Ratings Scale), depression (Beck Depression Inventory), and HRQL (SF-36 Health Status Survey). Multiple linear regression models were used to identify the factors associated with the physical and mental health summary scores of the SF-36. We found poorer physical HRQL in those who are female; older; not working; have musculoskeletal or respiratory problems; greater fatigue, higher disability scores, and more MS attacks. High illness intrusiveness; digestive system problems; genitourinary problems; and headaches were associated with poorer mental HRQL. Interestingly, we found an interaction between sex and age in mental HRQL, with worse mental health in older men but better mental health in older women. These findings may assist health care providers in identifying patients who may be at risk for decline in their HRQL, permitting appropriate and timely interventions.