An observational study of venoplasty in patients with multiple sclerosis.

RATIONALE: It is estimated that some hundreds of Canadian patients with multiple sclerosis (MS) have journeyed abroad to avail themselves of 'liberation therapy' (venoplasty) following the initial report by Zamboni et al in 2009. That study also led to public pressure upon Departments of Health in Canadian Provinces to fund the procedure. The present study was done in order to advise the Government of Newfoundland and Labrador as to whether or not it should do so. METHODS: We conducted an observational study of 30 MS subjects who had submitted to venoplasty, using objective, semi-objective and subjective measures. RESULTS: Significant subjective improvement was reported by half of the subjects at three months, although the degree of perceived improvement was less at 12 months. The objective and semi-objective tests employed did not indicate improvement in any area over the one-year follow-up period. Seven of the 29 subjects in whom CT venography was performed at the end of the study year were found to have uni- or bilateral occlusion or >50% stenosis of at least one cervical draining vein, but they showed no deterioration in their clinical status compared to those in whom no venous occlusion nor stenosis was found. CONCLUSION: No objective improvement was found at one year in thirty MS subjects who had undergone venoplasty, although many reported a degree of subjective benefit.

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.

The relation of ultraviolet radiation and multiple sclerosis in Newfoundland.

BACKGROUND: It has been thought that the occurrence of multiple sclerosis (MS) could be associated with daily ultraviolet exposure. In this study we investigated the geospatial association between average daily ultraviolet B (UVB) irradiance and MS prevalence in Newfoundland and Labrador (NL), Canada. METHODS: A complete list of patients diagnosed with MS in the province of NL was constructed. Places of habitation from birth to diagnosis were ascertained by mailout survey. RESULTS: A 74% rate of return on the survey results was obtained. A plot of the average daily erythemal UV over the available five years (1998-2002) shows that the distribution of MS follow a north-south gradient. Average daily UVB measurements are lower in the higher latitudes. A statistically significant negative correlation of MS incidence with erythemal UVB was found that is stronger than the correlation using latitude. This correlation appears to be strongest in the first year of life and declines when subsequent years are examined up to age ten. No significant correlation was found for the subjects' locale of habitation at the time of their first MS attack. CONCLUSIONS: This study suggests that UVB radiation may contribute to the pathogenesis of MS.

Incidence and prevalence of multiple sclerosis in Newfoundland and Labrador.

BACKGROUND: The incidence and prevalence of multiple sclerosis (MS) in Newfoundland and Labrador (NL) had been reported in 1984 and was considered to be relatively low at that time. This study revisits the incidence and prevalence of MS in NL for the year 2001. METHODS: Case searches through patient files of neurologists in NL were conducted. A complete list of patients billed for MS in NL between 1996 and 2003 was obtained and all cases were confirmed via chart review. RESULTS: There were 493 living MS patients yielding a prevalence of 94.4/100,000 which is significantly higher than previously reported. Of the living patients, 330 had relapsing remitting (RRMS), 94 had secondary progressive, 66 had primary progressive (PPMS) and three had unspecified MS. The total female to male ratio was 2.7:1. There was no difference between the female to male ratios for RRMS vs PPMS. Patients with PPMS had a later onset compared to RRMS (p<0.00001). Yearly incidences were relatively constant from 1994 to 2001 (5.6/100,000). Significant delays between first symptoms and final diagnosis were common and the delay time has not changed over the past 15 years. A prevalence of 88.9/100,000 was estimated from survival and incidence trends and was not significantly different than the measured prevalence (p=0.38). CONCLUSIONS: The increase in incidence and prevalence are accounted for through both better access to diagnostic facilities and more practicing neurologists. The revised prevalence and incidence are more in keeping with recently reported values throughout Canada.

Multiple sclerosis in Newfoundland and Labrador--a model for disease prevalence.

BACKGROUND: Newfoundland and Labrador, Canada, have been almost exclusively populated by immigrants from southwest England and southeast Ireland. The province's population grew largely by natural increase from 20,000 people in 1835 to half a million at present. Very little interregional migration occurred within the province. This uniquely-populated region and its subsequent founder effect provide the basis to develop models of disease prevalence. OBJECTIVES: To develop a model for the regional prevalence of multiple sclerosis (MS), accounting for settlement patterns and geographic location (latitude). METHODS: All living MS patients with confirmed addresses (438 patients) in the province were mailed a survey requesting their place of birth. Regional prevalences were calculated from a 75% rate of return of the survey. Theoretical regional prevalences were proportionally calculated from the source prevalences of southwest England, southeast Ireland, Scotland and the Channel Islands based on settlement patterns. These theoretical regional prevalences were corrected for geographical variations of latitude based on observations in the United Kingdom. Theoretical and actual regional prevalences were compared. RESULTS: When actual regional prevalences were compared with theoretical prevalences, very little variation was noted, especially after correcting for variation in latitude. CONCLUSION: A regional variation in MS prevalence is noted in the island portion of Newfoundland and Labrador. This regional variation can be modeled by using both migration patterns and latitudinal position. This model demonstrates that the prevalence of MS is influenced by both genetic and environmental contributions.

Anaphylactoid reaction to methylprednisolone pulsed therapy for multiple sclerosis.

A further case of anaphylactoid reaction to methylprednisolone is reported. The occurrence of allergic reactions to steroids is reviewed, and suggestions for management of pulsed IV methylprednisolone therapy are made.

Pilot study to improve health outcomes for medication-induced headache sufferers.

The objectives of this prospective cohort study were to identify and encourage individuals with symptoms consistent with medication-induced headache (MIH) to seek medical help, and to determine the health outcomes of these patients. All community pharmacists (approximately 150) on Newfoundland's Avalon Peninsula were provided with continuing education material on MIH and were asked to display a poster inviting individuals taking analgesics more than two days a week for headache to speak to their pharmacist. Pharmacists were asked to provide a patient information pamphlet to individuals with medication use and symptoms consistent with MIH, to request them to contact a study nurse and to log the number of potential MIH patients encountered. The study nurse supervised the completion of headache and quality of life questionnaires, and advised the subjects to seek help from their family physicians. Forty-six pharmacists returned logs identifying 142 potential MIH subjects: 21 contacted the study nurse, 17 completed the questionnaires and 11 were classified as MIH sufferers. MIH sufferers reported a reduction in headache frequency (P<0.02) and analgesic consumption (P<0.05) when re-interviewed after three months. A health care team approach can improve health outcomes for some MIH sufferers. Further work to evaluate strategies to encourage chronic headache sufferers to seek help is required.

Sudden death in multiple sclerosis associated with sun exposure: a report of two cases.

BACKGROUND: Two cases of sudden unexpected deaths in patients with multiple sclerosis were investigated by the Office of The Chief Forensic Pathologist. METHOD: Case studies. RESULTS: Marked similarities of the deaths, including circumstances, scene examination, and autopsy findings including a complete drug screen were recorded. CONCLUSIONS: Exposure to high ambient temperature may pose a danger to patients with multiple sclerosis. Mechanisms of death and the potential dangers to patients with clinically widespread disease are discussed.

Immunological associations in familial and non-familial Alzheimer patients and their families.

A number of autoimmune diseases and immune-related conditions were investigated in a series of 100 Alzheimer patients and their families. The group was divided into those who had familial dementia of the Alzheimer type and non-familial dementia of the Alzheimer type. HLA DR3 was associated with the familial dementia of the Alzheimer type patients. Adult exposure to tuberculosis appeared to be a risk factor for familial dementia of the Alzheimer type patients. Autoimmune diseases clustered among the non-familial dementia of the Alzheimer type patients, and also among their relatives. Asthma and infertility were also significantly increased among non-familial dementia of the Alzheimer type relatives. The analysis showed that (1) autoimmunity may be important in the sporadic form of Alzheimer disease; (2) it may be possible to confer a decreased risk for Alzheimer disease among relatives when many autoimmune diseases occur in the family; (3) it may be important to assess environmental risk factors for Alzheimer disease separately in patients with familial and sporadic disease; and (4) the efficacy of drug therapies may be dependent on whether the patients have a familial or sporadic form of Alzheimer disease.

The focal encephalopathies associated with mycoplasma pneumoniae.

Five patients with evidence of focal encephalopathy are reported. In each case, evidence of mycoplasma pneumoniae infection was detected. No patient improved with conventional antibiotic therapy, but in three subjects, rapid and complete recovery did occur contemporaneously with the administration of high dose steroid therapy. It is suggested that focal as well as diffuse cerebral or cerebellar lesions may occur as manifestations of auto-immune disease complicating mycoplasmal infections in young people and that this illness may be designated as acute mycoplasma-associated encephalopathy.

Numbness of half of the tongue.

We report a case of intermittent compression of he lingual nerve due to sialolithiasis and presenting with episodic unilateral numbness of the tongue. Removal of the obstruction has relieved the patient of symptoms over a 21 month period to date.

A Canadian population survey on the clinical, epidemiologic and societal impact of migraine and tension-type headache.

Trained telephone interviewers contacted 1,573 adults across Canada about the nature and frequency of headaches suffered by them or by others in their households. Using a table of pain symptoms and other characteristics abstracted from the International Headache Society (IHS) classification, the headaches were assigned to migraine headache, tension-type headache or other diagnostic groups. Of the households sampled, 59% had at least one headache sufferer in residence. The proportion of headache sufferers with migraine was 14%; with tension-type, 36%; and with both, 14%. Migraine headache caused more disability than tension-type headache, with nearly 20% of migraine sufferers taking time off work and disability lasting for a mean of 1 day. It is concluded that the current prevalences of migraine and tension-type headache in Canada fall around the mean of previous studies, that the IHS criteria can form a basis for diagnostic classification and that the functional impact of migraine has been seriously underestimated in the past.

The use of medications for cognitive enhancement.

OBJECTIVE: To provide Canadian physicians and allied health care professionals with the evidence they need to help them make treatment decisions in the management of patients with Alzheimer's disease or other dementias. OPTIONS: The full range and quality of diagnostic and therapeutic modalities available to Canadian physicians for the management of dementia. OUTCOMES: Improvement in the treatment of dementias, leading to reduced suffering, increased functional capacity and decreased economic burden. EVIDENCE AND VALUES: The creation of these evidence-based consensus statements involved literature reviews of the subject by the authors; comparison of alternative clinical pathways and description of the methods whereby published data were analyzed; definition of the level of evidence for data in each case; evaluation and revision in a conference setting (involving primary care physicians, neurologists, psychiatrists, geriatricians, psychologists, consumers and other interested parties); insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all authors. BENEFITS, HARMS, AND COSTS: A rational plan for the therapy of dementias is likely to lead to substantial benefits in both human and economic terms. RECOMMENDATIONS: Treatment decisions should be made taking into account the severity or stage of the disease, the availability of caregivers, the presence of disease affecting other bodily systems and the ability of the subject to pay the cost of the medications. Donepezil is considered to have positive effects upon certain tests of neuropsychological function and may produce some improvement in Alzheimer's disease of mild to moderate severity as measured by rating scales. Its ability to improve quality of life remains uncertain. No other drug treatments (apart from symptomatic therapies) are at present approved for the treatment of Alzheimer's disease*. VALIDATION: These recommendations were created by a writing committee, evaluated and revised at a consensus conference and further reviewed and revised by the writing committee prior to publication.

Impact of migraine and tension-type headache on life-style, consulting behaviour, and medication use: a Canadian population survey.

A large sample of Canadian adults was surveyed by telephone to determine the prevalence and characterization of headache, and the effects of headache on life-style, consulting behaviours and medication use. We reported prevalence and characterization in a previous issue; here, we detail the effects of headaches on sufferers. Sixteen and one-half percent of adult Canadians experience migraine and 29% tension-type headaches. In over 70% of headache sufferers interpersonal relationships are impaired. Regular activities are limited in 78% of migraine attacks and 38% of tension-type headaches. Despite this, only 64% of migraine and 45% of tension-type headache sufferers had ever sought medical attention, and of these only 32% returned for ongoing care. Fourteen percent of migraine and 8% of tension-type headache sufferers had used emergency departments. Most headache sufferers take medication, primarily over-the-counter varieties. Measures to reach the headache population are needed, as are safe effective treatment options that will encourage them to participate in their medical care.

Association between Alzheimer disease and amyotrophic lateral sclerosis?

We report two cases of Alzheimer disease (AD)--one of them familial--in which the patient also had amyotrophic lateral sclerosis (ALS), and one patient with familial AD who had a son with ALS. Three further cases of probable ALS were found in pedigrees of AD reported from the literature. It is proposed that this association is not coincidental, but may suggest an etiological factor in common.

A randomized, controlled trial of linopirdine in the treatment of Alzheimer's disease.

OBJECTIVES: We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease. METHODS: A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline. RESULTS: No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01. CONCLUSIONS: This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

Management of acute stroke. Ways to minimize damage and maximize recovery.

Brain infarctions due to atherothrombosis or cardiogenic emboli account for most cases of stroke. The remainder are caused by hemorrhages related to hypertension or subarachnoid bleeding. Management includes immediate measures to prevent further damage and rehabilitative measures by a multidisciplinary team. Efforts must also be directed toward preventing future strokes.