Multiple Sclerosis: Metz LM

Polman CH, Reingold SC, Barkhof F, Calabresi PA, Clanet M, Cohen JA, Cutter GR, Freedman MS, Kappos L, Lublin FD, McFarland HF, Metz LM, Miller AE, Montalban X, O'Connor PW, Panitch H, Richert JR, Petkau J, Schwid SR, Sormani MP, Thompson AJ, Weinshenker BG, Wolinsky JS. · Department of Neurology, Free University Medical Center in Amsterdam, PO Box 4075, 1007 MB Amsterdam, The Netherlands. · Neurology. · Pubmed #18362273 No free full text.

Abstract: The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.

Yong VW, Giuliani F, Xue M, Bar-Or A, Metz LM. · Hotchkiss Brain Institute and the Department of Clinical Neurosciences, University of Calgary, Alberta, Canada. · Neurology. · Pubmed #17548566 No free full text.

Abstract: Activated T cells, particularly those of the T-helper (Th) 1 subset, have the capacity to kill neurons. Strategies for preventing such damage may include deviation of activated T cells into the Th2 subset (e.g., via use of glatiramer acetate), alteration of functional properties of Th1 cells (e.g., through use of interferon [INF]-beta or IV immunoglobulin), and inhibition of activated cell migration into the CNS (e.g., by employing INF-beta or natalizumab). Matrix metalloproteinase-9 (MMP-9) also causes neuron death in neurotoxicity models, and examination of medications with MMP inhibitory activity indicates that minocycline is capable of preventing such damage. Minocycline also has other properties relevant to conferring neuroprotection, such as inhibition of microglial activity and apoptosis pathways. In a small pilot study in patients with relapsing-remitting multiple sclerosis, minocycline treatment produced favorable outcomes in terms of gadolinium-enhancing lesions and clinical course. Further studies are needed to establish whether experimental neuroprotection strategies involving these mechanisms may be translated into preventing neurodegeneration in multiple sclerosis.

Yong VW, Zabad RK, Agrawal S, Goncalves Dasilva A, Metz LM. · Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. · J Neurol Sci. · Pubmed #17382965 No free full text.

Abstract: The matrix metalloproteinases (MMPs) are implicated in the pathology of multiple sclerosis (MS). This review summarizes the consequences of upregulation of MMP members in MS as well as in an animal model of the disease, experimental autoimmune encephalomyelitis (EAE). The pathogenic roles of MMPs are considered, especially in the transmigration of leukocytes into the CNS. We review the evidence that interferon-beta, an immunomodulator that is commonly used in MS, affects MMP expression in the disease. The potential of minocycline as a therapy in MS, based on its activity as an MMP inhibitor, is discussed. Besides affecting MMPs, minocycline may have other actions that help account for its possible utility in MS.

Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. · VU Medical Center Amsterdam, Free University, PO Box 7057, 1007 MB Amsterdam, the Netherlands. · Ann Neurol. · Pubmed #16283615 No free full text.

Abstract: New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.

Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. · Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. · Lancet Neurol. · Pubmed #15556807 No free full text.

Abstract: The capacity of minocycline to alleviate disease for several neurological disorders in animals is increasingly being recognised. Indeed, that one drug alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is astounding. In this review, we describe the evidence for the efficacy of minocycline in several animal models of neurological disease, discuss the mechanisms by which minocycline affects a range of neurological diseases with diverse causes, and introduce the emerging investigation of minocycline in clinical neurology. The encouraging results of minocycline in experimental neurology bode well for its therapeutic use in human neurological diseases.

Metz LM, Patten SB, McGowan D. · Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Alberta, Canada. · Biomed Pharmacother. · Pubmed #10554671 No free full text.

Abstract: Symptom management is the assessment and treatment of the manifestations of multiple sclerosis (MS). Optimal treatment includes patient education, rehabilitation, counseling, and sometimes medical or surgical therapy. A multi-disciplinary treatment team is usually required to provide the wide range of services necessary to manage MS symptoms. This article will review the medical and surgical options used in the management of primary MS symptoms.

Zhang Y, Metz LM, Yong VW, Bell RB, Yeung M, Patry DG, Mitchell JR. · Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. · Can J Neurol Sci. · Pubmed #18574932 No free full text.

Abstract: BACKGROUND: Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients. METHODS: Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months. RESULTS: Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p < 0.001) and during the extension (8.7%, p = 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment. CONCLUSIONS: This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.

Zhang Y, Zabad RK, Wei X, Metz LM, Hill MD, Mitchell JR. · Department of Radiology, University of Calgary, Calgary, Canada. · Mult Scler. · Pubmed #17468444 No free full text.

Abstract: T2 hypointensity (black T2, BT2) in the deep grey matter of multiple sclerosis (MS) patients correlate weakly with disability at 1.5 T. BT2 is likely to be caused by abnormal iron deposition. We compared the correlation between disability and deep grey matter BT2 measured on 3 T MRI and on 1.5 T MRI in 17 MS patients. We observed a significant correlation between expanded disability status scale and signal intensity on 3 T MRI in the globus pallidus and the caudate nucleus (r = -0.5, P < 0.05). BT2 at 3 T may be a useful MRI measure associated with disability in MS and warrants further study.

Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB, Yong VW. · Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. · Mult Scler. · Pubmed #17463074 No free full text.

Abstract: Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.

Brown LN, Metz LM. · Department of Clinical Neurosciences, University of Calgary, Alberta, Canada. · Mult Scler. · Pubmed #16320735 No free full text.

Abstract: BACKGROUND: Tactile temporal thresholds, which represent the time separating the onset of two tactile stimuli when they are judged as simultaneous, can differentiate a group of people with multiple sclerosis (MS) from normal controls. Demyelination, axonal injury and loss, and altered information processing all occur in MS and may cause these increased thresholds. Thus, tactile temporal thresholds may be a useful outcome measure in MS. Our objective was to assess whether tactile temporal thresholds reflect change during a MS relapse. METHODS: During a study to evaluate the stability of tactile temporal thresholds in people with MS, two participants suffered relapses. Both events were associated with prolonged thresholds (i.e., significantly increased thresholds). CONCLUSIONS: Tactile temporal thresholds can detect neurologic worsening and thus warrant further evaluation as a useful method to facilitate in the monitoring of disease change in people with MS.

Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. · Department of Clinical Neurosciences, University of Western Ontario, London, Ontario, Canada. · Neurology. · Pubmed #15452302 No free full text.

Abstract: Oral prednisone (1)might be a convenient, inexpensive alternative to IV methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the concentration-time curve (AUC), the main component of bioavailability, did not differ between groups (p = 0.122). This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses.

Metz LM, Patten SB, Archibald CJ, Bakker JI, Harris CJ, Patry DG, Bell RB, Yeung M, Murphy WF, Stoian CA, Billesberger K, Tillotson L, Peters S, McGowan D. · Department of Clinical Neurosciences, University of Calgary, Alberta, Canada. · J Neurol Neurosurg Psychiatry. · Pubmed #15201369 links to  free full text

Abstract: OBJECTIVE: To assess the effects of glatiramer acetate and beta interferon on fatigue in multiple sclerosis. METHODS: Fatigue was measured at baseline and six months using the fatigue impact scale (FIS). Groups (glatiramer acetate and beta interferon) were evaluated for the proportion improved, using Fisher's exact test. Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables. RESULTS: Six month paired FIS assessments were available for 218 patients (76% female). Ages ranged between 19 and 61 years, with 86% having relapsing-remitting disease. Glatiramer acetate was used by 61% and beta interferon by 39%. At baseline, total FIS and subscale scores were comparable in the two groups. More patients improved on glatiramer acetate than on beta interferon on total FIS (24.8% v 12.9%, p = 0.033; adjusted odds ratio = 2.36, 95% confidence interval 1.03 to 5.42), and on physical (28.6% v 14.1%, p = 0.013) and cognitive subscales (21.1% v 10.6%, p = 0.045). Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue, after accounting for baseline group differences. CONCLUSIONS: The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with beta interferon. Confirmation of this result is required.

Patten SB, Metz LM. · Department of Community Health Sciences, University of Calgary MS Clinic, Alberta, Canada. · Int J Psychiatry Med. · Pubmed #12269596 No free full text.

Abstract: OBJECTIVE: Two recent randomized double-blind placebo controlled clinical trials of interferon beta-1a in multiple sclerosis have obtained hopelessness ratings using the Beck Hopelessness Scale (BHS). One of these studies, the PRISMS trial, evaluated interferon beta-1a in relapsing remitting multiple sclerosis (RRMS). Another, the SPECTRIMS trial, evaluated the same medication in secondary progressive (SP) MS. The objective of this analysis was to compare levels of hopelessness in persons with RRMS and SPMS, and to describe changes over time in the clinical trial participants. METHOD: Raw data from each clinical trial was obtained from the sponsor of the trials (Serono). Median BHS ratings, and the proportions at or above the BHS cut-point of 10 were calculated over a two (PRISMS) or three (SPECTRIMS) year period. RESULTS: The analysis included n = 532 clinical trial participants. Ratings of hopelessness were higher in SPMS clinical trial participants (SPECTRIMS) than in the RRMS group (PRISMS) at baseline (Fisher's exact test, p = 0.0035). Furthermore, ratings of hopelessness were higher during follow-up than at baseline, in the SPMS group (McNemar's exact probability,p = 0.0015), but not in the RRMS group (McNemar's exact probability,p = 0.65). Depression was strongly associated with hopelessness in both RRMS (z = 4.13, p < 0.001) and SPMS (z = 5.24, p < 0.001). CONCLUSIONS: Hopelessness is associated with SPMS, and may increase over time in this group. Hopelessness may influence suicide risk in people with MS and may potentially have an impact on coping and quality of life. Additional research is necessary to define the clinical implications of hopelessness in persons with this condition.

Patten SB, Metz LM, Anonymous00072. · Department of Community Health Sciences and Psychiatry, University of Calgary, Alberta, Canada. · Neurology. · Pubmed #12221168 No free full text.

Abstract: Depression is a suspected side effect of treatment with interferon beta1a in MS. However, an association with depression has not been confirmed by rigorous studies. During the SPECTRIMS clinical trial of interferon beta1a (Rebif) in secondary progressive MS, depression ratings were obtained from 365 subjects treated either with interferon beta1a or with placebo. No significant differences between groups emerged during 36 months of follow-up. These data suggest that depression is not a side effect of interferon beta1a.

Patten SB, Metz LM. · Department of Community Health Sciences, University of Calgary, Alberta, Canada. · Mult Scler. · Pubmed #11548984 No free full text.

Abstract: Depression is a suspected side effect of multiple sclerosis (MS) treatment with interferon beta-1a. However, this has not been confirmed by rigorous studies. Several psychological symptom rating scales were completed during the PRISMS clinical trial of subcutaneous interferon beta-1a (Rebif) for relapsing-remitting MS. We conducted an analysis of these data in order to determine whether symptom elevations were associated with treatment. The PRISMS clinical trial included 560 subjects from 22 centres in nine countries. There were two active treatment arms (44 mcg x 3 and 22 mcg x 3 subcutaneously three times per week) and a placebo group. Two hundred and sixty-seven of these subjects were enrolled at English speaking study centres, where psychiatric symptom ratings were obtained at baseline, 6, 12, 18 and 24 months using the Center for Epidemiological Studies Depression Rating Scale (CES-D), the General Health Questionnaire (GHQ) and the Beck Hopelessness Scale (BHS). After randomization, the groups completing these scales were similar in terms of age, gender, EDSS, duration of illness and employment status. Median CES-D scores in the high dose, low dose and placebo groups at baseline were also similar: 8.0, 7.0 and 8.0, respectively. After 6 months of treatment the median change in CES-D score was zero in all three groups. The proportion of subjects exceeding the traditional CES-D cut-point for clinically significant depression (> 15) after 6 months of treatment was strongly associated with pre-treatment depression (RR 2.9, 95% C.I.: 1.8-4.7), but not with treatment group (chi-square=1.64, d.f.=2, P=0.44). The results were comparable at 12, 18 and 24 months and when ratings from the other scales were evaluated. This analysis confirms that depression is common in persons with MS: the incidence of CES-D depression in the first 6 months of follow-up was 15.6%. However, no evidence of increased depressive symptomatology was observed in association with interferon beta-1a (Rebif).

Thannhauser JE, Mah JK, Metz LM. · Division of Applied Psychology, Faculty of Education, University of Calgary, Calgary, Alberta, Canada. · Pediatr Neurol. · Pubmed #19589460 No free full text.

Abstract: In this mixed-methods study, utilization data for disease-modifying therapies were reviewed to determine the adherence rate among our pediatric multiple sclerosis cohort. Adolescents were interviewed to explore their experiences with multiple sclerosis and the impact of peer relationships on adherence to treatment. Seventeen adolescents (6 male, 11 female) started interferon beta or glatiramer acetate before age 18. The mean age at first drug start date was 15.8 years. Eight of the adolescents (47%) discontinued treatment after a median duration of 20 months. Many of the adolescents struggled to integrate the injections into their daily lives, with peers either facilitating or impeding this transition. In conclusion, adolescents in this cohort had difficulty adhering to disease-modifying therapies, and peers played an important role in mediating their adjustment to multiple sclerosis. Specific strategies are required to improve adolescents' adherence to treatment, including less intrusive options and enhancing peer support.

Morrow SA, Metz LM, Kremenchutzky M. · Department of Clinical Neurosciences, University of Western Ontario, London, Ontario, Canada. · Can J Neurol Sci. · Pubmed #19378717 No free full text.

Abstract: BACKGROUND: Glucocorticoid treatment improves the speed of functional recovery of acute multiple sclerosis (MS) relapses but has not been shown to provide any long-term functional benefit. There is currently no convincing evidence that the clinical benefit is influenced by the route of administration or the dosage of glucocorticoid, or the particular glucocorticoid prescribed. Recent studies support similarities in the bioequivalence and in the clinical effect of high dose oral corticosteroids for MS relapses. OBJECTIVE: This survey aimed to determine the relapse treatment preferences of clinicians in Canadian MS clinics. METHODS: Members of the Canadian Network of MS Clinics are linked by an email server. A one page survey was distributed to the group to determine and report use of corticosteroids to manage MS relapses amongst Canadian MS specialists. RESULTS: Fifty-one clinicians from 17 MS clinics were surveyed. 32 (63%) surveys were returned representing 16 clinics. Five doses are most commonly prescribed, usually without a taper. Three or four doses and the use of a corticosteroid taper, however, are not uncommon. Gastric cytoprotection and sedatives are often prescribed for use as needed. CONCLUSION: This survey illustrates that when Canadian clinicians with expertise in managing MS treat MS relapses they choose high dose corticosteroids, either oral or i.v. The results therefore represent Canadian practice as these clinicians provide direct patient care and influence care by community neurologists. Until evidence clearly identifies a superior practice all options should be available to clinicians and their patients.

Zhang Y, Zhu H, Mitchell JR, Costello F, Metz LM. · Department of Clinical Neurosciences, University of Calgary, Foothills Medical Centre, 1403-29th Street NW, Calgary, AB, Canada T2N 2T9. · Neuroimage. · Pubmed #19361563 No free full text.

Abstract: T2 hyperintensity is pathologically non-specific in multiple sclerosis (MS) yet lesion analysis remains an important disease outcome. Texture analysis based on the polar Stockwell Transform (PST) was performed on twelve acute T2 lesions before, during, and after the development of gadolinium-enhancement. When regular myelin structure is disrupted coarse texture increases because tissue becomes disorganized. Coarse texture was quantified as the sum of low frequency energy (sumLFE). Matching regions of contralateral and general normal appearing white matter (NAWM) and chronic T2 lesions were analyzed in parallel as controls. Coarse texture increased in acute lesions during enhancement (p<0.05) then variably recovered. It remained stable in NAWM and tended to increase in chronic T2 lesions. Seven of twelve acute lesions persisted visually at 8 months and the sumLFE was higher in these visually persistent lesions (p<0.05) than in resolved lesions. The sumLFE at month 8 correlated with that in pre-lesional NAWM and in acute lesions (p<0.05) and was independent of lesion volume, signal intensity (SI), and location. This study suggests that PST texture analysis extracts more information about tissue integrity than conventional MRI analysis that relies on lesion size and SI. Texture analysis also appears to identify abnormalities in pre-lesional NAWM, to measure tissue injury in acute lesions, predict poor recovery, and detect mild ongoing tissue injury in chronic T2 lesions. PST texture analysis using conventional MRI may therefore provide valuable new insights into lesion pathology by measuring tissue integrity. This small longitudinal study supports further validation of the PST technique.

Brown LN, Eliasziw M, Metz LM. · Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. · Can J Neurol Sci. · Pubmed #18062451 No free full text.

Abstract: BACKGROUND: Visual processing deficits involving temporal characteristics are typically not captured by the widely used outcome measures (i.e., Expanded Disability Status Scale, Multiple Sclerosis Functional Composite) in multiple sclerosis (MS). Visual temporal thresholds (i.e., measurements of the temporal aspects in visual processing) are typically significantly higher (i.e., prolonged) in MS patients when compared to controls. The test-retest reliability of these thresholds was examined in patients with MS. METHODS: Visual temporal thresholds were measured in 21 stable MS patients during two separate test sessions. Test-retest reliability and the standard error of measurement were calculated. The threshold of change in visual temporal thresholds in MS patients that would correspond to real change beyond measurement error with 95% certainty was also calculated. For comparisons, a control group (n = 10) was included. RESULTS: The test-retest reliability of this measure of visual temporal thresholds was 0.97. The threshold indicating change beyond chance or measurement error with 95% certainty was 11 ms. Higher thresholds were significantly correlated with longer durations of disease. CONCLUSIONS: This measure of visual temporal thresholds has excellent test-retest reliability and a change of greater than 11 ms is highly likely to represent real change in MS patients. The findings indicate that these measurements may provide useful clinical information about functional changes regarding the temporal aspects of the visual system, which is currently not captured by the Extended Disability Status Scale.

Patten SB, Williams JV, Metz LM. · Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada T2N 4N1. · Mult Scler. · Pubmed #17986504 No free full text.

Abstract: BACKGROUND: Randomized controlled trials incorporating validated depression scales have failed to identify an association between interferon beta treatment and depression in MS. This is surprising since interferons used in other clinical contexts are considered capable of causing depression. The negative results in MS could be due inadequate power in the published trials. METHODS: In this study, longitudinal data from an IMS Health Canada database called the Therapy Dynamics database were analyzed. The database contains information about prescriptions filled at outpatient pharmacies in Canada, linked at the individual level over time periods as long as 36 months. Antidepressant prescriptions were used as a proxy indicator for depressive disorders. The frequency of antidepressant use was compared in cohorts treated with glatiramer acetate and interferon beta. RESULTS: No differences in the frequency of antidepressant treatment were observed. A large proportion (approximately 40%) in all treatment cohorts were treated with antidepressants at some time over the study interval. The proportions remained comparable after adjustment for age and sex and in a time-to-event analysis of new antidepressant prescriptions. Among patients receiving prescriptions exclusively from Neurologists, the frequency of exposure to antidepressants was much lower (2.4%). CONCLUSIONS: This analysis uncovered no evidence that antidepressant treatment occurs more often in people treated with interferon beta than in those treated with glatiramer acetate. These results help to confirm that depression is not associated with interferon beta treatment in MS.

Svenson LW, Warren S, Warren KG, Metz LM, Patten SB, Schopflocher DP. · Alberta Health and Wellness, Department of Public Health Sciences, University of Alberta, Edmonton, Canada. · Can J Neurol Sci. · Pubmed #17598594 No free full text.

Abstract: BACKGROUND: Multiple Sclerosis (MS) is reported to be uncommon among North American aboriginals despite frequent intermarriage with people of European ancestry, but few population-based studies have been conducted. The purpose of this study was to determine the prevalence of MS among First Nations aboriginal people in Alberta, Canada compared to the general population. METHODS: All hospital in-patient and physician fee-for-service records between 1994 and 2002 where a diagnosis of MS was mentioned were extracted from government health databases in the province of Alberta. First Nations people can be identified since the federal government (Health Canada) pays health care insurance premiums on their behalf. Multiple Sclerosis prevalence per 100,000 population for both First Nations people and the general population of Alberta were calculated for each year during this time span. RESULTS: Among First Nations in Alberta, MS prevalence was 56.3 per 100,000 in 1994 and 99.9 per 100,000 in 2002, an increase of 43.6%. In 2002 prevalence was 158.1 and 38.0 for females and males respectively, a female to male ratio of 4.2:1. Multiple Sclerosis prevalence among the general population of Alberta was 262.6 per 100,000 in 1994 and 335.0 per 100,000 in 2002, an increase of 21.6%. In 2002 prevalence was 481.5 and 187.5 for females and males respectively, a female to male ratio of 2.6:1. Peak prevalence for both First Nations and general population females in 2002 was age 50-59, also 50-59 for both First Nations and general population males. CONCLUSION: While MS prevalence in First Nations people is lower than in the general population of Alberta, it is not rare by worldwide standards.

Warren S, Svenson LW, Warren KG, Metz LM, Patten SB, Schopflocher DP. · Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada. · Neuroepidemiology. · Pubmed #17164566 No free full text.

Abstract: Multiple sclerosis (MS) is thought to be rare among North American aboriginals, although few population-based frequency studies have been conducted. Data from government health databases were used to describe the incidence of MS among First Nations aboriginal people in the province of Alberta compared to the general population from 1994 to 2002. The general population rates were consistently higher than First Nations rates, but were essentially stable across this time span for both groups. For First Nations the MS incidence was 7.6 per 100,000 and 20.6 per 100,000 for the general population in 2002. During 2000-2002 for First Nations the incidence was 12.7 for females and 7.6 for males, with a female-to-male ratio of 1.7:1. During the same period the general population incidence was 32.2 for females and 12.7 for males, with a female-to-male ratio of 2.5:1. The peak incidence for both First Nations and the general population of Alberta was in the age group 30-39 years in 2002. The high incidence rates are consistent with high prevalence rates reported for both groups in 2002: 99.9 per 100,000 for First Nations and 335.0 per 100,000 for the general population. While the MS incidence in First Nations people is lower than in the general population of Alberta, it is not rare by worldwide standards.

Brown LN, Metz LM, Eliasziw M. · Department of Psychology, University of Calgary, Calgary, Alberta, Canada. · Mult Scler. · Pubmed #17086902 No free full text.

Abstract: BACKGROUND: Tactile temporal thresholds are typically significantly higher (ie, prolonged) in multiple sclerosis (MS) patients when compared to controls and increase significantly during relapses, probably reflecting integrity of conduction across a portion of the corpus callosum. As part of an ongoing validation study of tactile temporal thresholds, the test-retest reliability of these thresholds was examined in patients with MS. METHODS: Tactile temporal thresholds were measured in 61 MS patients during two separate test sessions within three weeks. Test-retest reliability and the standard error of measurement were calculated. The threshold of change in tactile temporal thresholds in MS patients that would correspond to real change beyond measurement error with 95% certainty was also calculated. RESULTS: The test-retest reliability of this measure of tactile temporal thresholds was 0.93. The threshold indicating change beyond chance or measurement error with 95% certainty was 19 ms. CONCLUSIONS: This measure of tactile temporal thresholds has excellent test-retest reliability and a change of greater than 19 ms is highly likely to represent real change. This measure is promising as a precise, reliable outcome measure in MS.

Patten SB, Lavorato DH, Metz LM. · Department of Community Health Sciences, University of Calgary, AB, Canada. · Gen Hosp Psychiatry. · Pubmed #16271659 No free full text.

Abstract: OBJECTIVE: In multiple sclerosis (MS), depression rating scales may be used as case-finding instruments for depressive disorders, but depressive symptom ratings may have clinical implications beyond their case-finding role. The objective of this analysis was to explore this possibility by carrying out descriptive analyses of symptom ratings obtained using the Center for Epidemiological Studies Depression Rating Scale (CES-D) in an MS clinic population. METHOD: The analysis used cross-sectional baseline data collected from 589 subjects enrolled in a prospective cohort study. Data collection included demographic and clinical information including Extended Disability Status Scale ratings, a 54-item MS Quality of Life Scale and the Fatigue Impact Scale. RESULTS: Across a spectrum of CES-D scores, correlations with other health indicators were observed. Depressive symptoms were higher in more disabled subjects. CES-D scores were correlated with the emotional well-being dimension of quality of life and with a social fatigue impact dimension. Alternative scoring of the CES-D had a negligible impact on the pattern of correlation. CONCLUSIONS: CES-D ratings appear to be interpretable beyond the traditional yes/no categorization used in case finding. CES-D ratings are predictive of other clinical parameters in domains relevant to mental health.

Patten SB, Svenson LW, Metz LM. · Department of Community Health Sciences, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. · Neurology. · Pubmed #16217073 No free full text.

Abstract: Administrative data from a Canadian province were accessed to assess the association of psychotic disorders with multiple sclerosis (MS). Physician-assigned ICD-9-CM codes were used to classify MS and psychotic disorder status. A significant association was observed. Additional research is needed to determine the clinical importance and treatment needs of this population.