Probable Multiple Sclerosis Research Articles

A 50-year follow-up of the incidence of multiple sclerosis in Hordaland County, Norway

To assess longitudinal follow-up of the incidence of multiple sclerosis (MS) through five decades and estimate the prevalence rate in Hordaland County, Norway, on January 1, 2003. All patients with MS diagnosed from 1953 to 2003 were identified in the patient records of the Department of Neurology, Haukeland University Hospital, Bergen, Norway. The diagnostic criteria of Poser et al. were applied and only patients with definite and probable MS were included. The study comprises 912 patients, and 666 patients with MS were living in Hordaland on January 1, 2003. The annual incidence rates for the years 1953 to 2003 were calculated. The total crude prevalence rate on January 1, 2003, was 150.8 per 100,000 population: 191.3 per 100,000 among women and 109.8 per 100,000 among men. The annual incidence of MS increased from 1.8 per 100,000 in 1953 to 1957 to 6.0 per 100,000 in 1993 to 1997. Hordaland County, Norway, has changed from a low-risk to a high-risk area for multiple sclerosis (MS) during the last 50 years. During the last 25 years, the incidence of MS has been stable rather than increasing. Systematic longitudinal follow-up studies are essential to calculate reliable prevalence and incidence rates in MS. The results suggest that both methodologic and environmental factors are essential in determining the distribution of MS.

Clinical course, pathological correlations, and outcome of biopsy proved inflammatory demyelinating disease

Background: A pathological classification has been developed of early active multiple sclerosis (MS) lesions that reveals four patterns of tissue injury: I—T cell/macrophage associated; II—antibody/complement associated; III—distal oligodendrogliopathy, and IV—oligodendrocyte...

Possible increasing risk of multiple sclerosis in Catania, Sicily

To update prevalence and incidence rates of multiple sclerosis (MS) in Catania, Italy during 1990 to 1999 and evaluate their temporal profiles to assess a possible increase in the MS risk in our study population. We studied the frequency of MS in Catania, Italy (population of 313,110 as reported in the 2001 census). The primary sources for the case ascertainment were the neurologic and motor-rehabilitation departments, the MS centers, the Italian MS Association, private neurologists, and family doctors. We considered as prevalent and incident cases all patients who satisfied Poser's criteria for clinically definite MS (CDMS), laboratory-supported definite MS (LSDMS), clinically probable MS (CPMS), and laboratory-supported probable MS (LSPMS). We found 288 subjects with MS who had onset of disease before December 31, 1999 (prevalence day) in a population of 313,110 inhabitants. The prevalence rate was 92.0/100,000 (95% CI 81.8 to 103.2) and was higher in women (102.4/100,000) than in men (80.4/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 years (208.2/100,000). From 1990 to 1999, 155 patients with MS had the clinical onset of the disease. The mean annual incidence was 4.7/100,000 (95% CI 4.0 to 5.5). Age-specific incidence showed a peak in the group aged 25 to 34 years (11.7/100,000). Mean annual incidence for 5-year intervals increased from 3.9/100,000 during 1990 to 1994 to 5.5/100,000 during 1995 to 1999. Prevalence and incidence rates of multiple sclerosis have further increased during the last decade.

Unrecognised symptoms of depression in a community–based population with multiple sclerosis

The association between multiple sclerosis (MS) and depression has been well established but prevalence estimates have varied widely. The aims of this study were to assess the point prevalence of previously unrecognised symptoms of depression in a community-based population with MS and examine their relationship to other disease characteristics. Three hundred and seventy six patients with clinically definite or probable MS (Poser criteria) were ascertained during the course of an epidemiological study on two counties in Ireland. Of these 211 agreed to participate in the study. Subjects were examined and a Kurtzke Expanded Disability Status Scale Score and Multiple Sclerosis Functional Composite score rated. Participants also completed a Beck's Depression Inventory-II and a Multiple Sclerosis Impact Scale. In total 60 (28%) patients had moderate or severe symptoms of depression. Only thirty-five of the 211 patients had a history of depression as defined by a medical diagnosis of depression or prescription of an anti-depressant medication at any time prior to enrollment in the present study, of the remaining 176 patients, 41 (23.3%) had moderate or severe symptoms of depression as assessed by Beck's Depression Inventory-II. The only significant clinical difference between the 41 patients with pronounced depressive symptoms and the 135 less affected was shorter disease duration in the former. In this study one in four patients with MS had unrecognised and therefore untreated symptoms of depression. Disability alone is not a good indicator of the likelihood of coexistent depressive symptoms.

Prevalence and Incidence of Multiple Sclerosis in Las Palmas, Canary Islands, Spain

Objectives: To determine the prevalence and incidence of multiple sclerosis (MS) in the city of Las Palmas (Canary Islands, Spain), geographically belonging to north-western Africa, but with European ancestry. Methods: This population-based survey was conducted for a period of 5 years (1998–2002) in a Sanitary District of Las Palmas city (28° 20’ N), with a population of 82,623 inhabitants. Multiple sources were periodically investigated for case ascertainment. Patients with definite and probable MS were included. Results: Sixty-four patients with MS were identified on prevalence day, December 31, 2002. According to Poser’s criteria the crude prevalence rate was 77.5 per 100,000 (95% CI: 59.7–98.9). This rate decreased to 73.8 (95% CI: 56.5–94.8) according to McDonald’s criteria. Age-adjusted rates for the world and European standard populations were 61.6 (95% CI: 47.1–78.9) and 70.6 (95% CI: 55–89), respectively. Prevalence was higher for women aged 25–44 years. In 17 patients onset of MS occurred within the study period. Average annual incidence was 4.1 per 100,000 (95% CI: 2.4–6.6). Conclusions: The prevalence and incidence rates in Las Palmas city are close to those reported from Continental Spain and other countries of southern Europe with similar social and ethnic background. These results highlight the role of racial-ethnic factors in the genesis of MS.

A Second-Generation Genomic Screen for Multiple Sclerosis

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disorder. Despite substantial evidence for polygenic inheritance of the disease, the major histocompatibility complex is the only region that clearly and consistently demonstrates linkage and association in MS studies. The goal of this study was to identify additional chromosomal regions that harbor susceptibility genes for MS. With a panel of 390 microsatellite markers genotyped in 245 U.S. and French multiplex families (456 affected relative pairs), this is the largest genomic screen for MS conducted to date. Four regions met both of our primary criteria for further interest (heterogeneity LOD [HLOD] and Z scores >2.0): 1q (HLOD=2.17; Z=3.38), 6p (HLOD=4.21; Z=2.26), 9q (HLOD; Z=2.71), and 16p (HLOD=2.64; Z=2.05). Two additional regions met only the Z score criterion: 3q (Z=2.39) and 5q (Z=2.17). Further examination of the data by country (United States vs. France) identified one additional region demonstrating suggestive linkage in the U.S. subset (18p [HLOD=2.39]) and two additional regions generating suggestive linkage in the French subset (1p [HLOD=2.08] and 22q [HLOD=2.06]). Examination of the data by human leukocyte antigen (HLA)-DR2 stratification identified four additional regions demonstrating suggestive linkage: 2q (HLOD=3.09 in the U.S. DR2- families), 6q (HLOD=3.10 in the French DR2- families), 13q (HLOD=2.32 in all DR2+ families and HLOD=2.17 in the U.S. DR2+ families), and 16q (HLOD=2.32 in all DR2+ families and HLOD=2.13 in the U.S. DR2+ families). These data suggest several regions that warrant further investigation in the search for MS susceptibility genes.

European validation of a standardized clinical description of multiple sclerosis

The EDMUS system is a clinical database specifically tailored to the description of multiple sclerosis (MS). The EVALUED (Evaluation of the EDMUS system) study is an European project with two objectives: 1) to assess the inter-examiner reliability of the whole EDMUS system; 2) to validate the EDMUS-Grading Scale (EGS),which is a simplified version of the Kurtzke Disability Status Scale (DSS). The protocol included 12 neurologists working in pairs within six European centres (Bari, Basel, Florence, London, Lyon, Würzburg). They assessed independently 30 MS patients in their centre, filling in the EDMUS forms. The reliability of the system was assessed on selected key items in the history of the MS onset, the clinical course and the disease course classification. The clinical examination of the patients permitted an assessment of the Kurtzke Expanded Disability Status Scale (EDSS) and the EGS. Level of agreement was measured in terms of kappa and weighted kappa indexes whenever appropriate. The study included 180 patients with definite or probable MS of whom 37% were males. Age was 35.8+/-9.6 years (mean +/- SD), disease duration 7.8+/-5.7 years, and mean EDSS score 4.1+/-2.2. The disease course was relapsing-remitting in 67%, secondary progressive in 22%, and progressive from disease onset in 11%. For key items of the history, the inter-examiner reliability level ranged from moderate to excellent. Concerning the disability scales, perfect agreement was reached in 59 % for EDSS and 78% for EGS. The close correlation and linear association (r=0.94, p<0.0001) between both scales demonstrated EGS's construct validity. The EDMUS system allows a consistent clinical description of MS using a common language. This standardized follow-up of MS patients is valuable especially in studies requiring a critical mass of informative patients.

Latitudinal variation in the prevalence of multiple sclerosis in Ireland, an effect of genetic diversity

Background: Northern Ireland has a high and rising prevalence rate of multiple sclerosis (MS). The most recent survey in 1996 found a rate of 168.7/100 000. Recorded prevalence rates for...

The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study

Background:Studies have suggested that T2 lesion activity is prominent in early relapsing-remitting multiple sclerosis, whereas brain atrophy, while seen early, appears more evident in later progressive disease. The temporal relation...

Cognitive impairment in probable multiple sclerosis

Objectives: To evaluate and characterise cognitive impairment in the very early stage of multiple sclerosis (MS), in which patients are still diagnosed as suffering from probable MS. Methods: The Brief...

Infection with Chlamydia pneumoniae and risk of multiple sclerosis.

Chlamydia pneumoniae (Cpn) has been proposed as a possible etiologic agent for multiple sclerosis (MS), but results of previous studies are conflicting. Using a nested case-control design, we examined the association between Cpn infection and MS in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II) cohorts. Among 32,826 women in the NHS and 29,722 women in the NHS II with blood samples, 141 incident cases of definite or probable MS were documented. Each case was matched to two healthy controls on year of birth and NHS cohort. Serum samples were tested for the presence of Cpn-specific immunoglobin G antibodies using microimmunofluorescence. Cpn immunoglobin G seropositivity was positively associated with risk of MS (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.1-2.7). This association did not change after adjusting for age at blood collection, ancestry, latitude of residence at birth, and smoking (OR = 1.9; CI = 1.1-3.1). Seropositivity for Cpn was only moderately associated with risk of relapsing-remitting MS (OR = 1.7; CI = 0.9-3.2), but it was strongly associated with risk of progressive MS (OR = 7.3; CI = 1.4-37.2). Geometric mean titers of Cpn-specific immunoglobin G antibody were similar in women with relapsing-remitting MS as compared with matched controls (44 vs 39), but they were elevated in women with progressive MS (99 vs 40). These results support a positive association between Cpn infection and progressive MS.

Cognitive Symptoms in Very Early MS

The early cognitive symptoms of multiple sclerosis (MS) are often not apparent unless they are specifically evaluated. These Israeli researchers used a neuropsychological test battery to evaluate the cognition of 67 patients (mean age, 32; 45 women) with probable MS who presented to an MS center for initial interviews. …

Epidemiology of multiple sclerosis in the Canary Islands (Spain): a study on the island of La Palma.

To determine the prevalence of multiple sclerosis (MS) on the Island of La Palma, Canary Islands, Spain. A population-based transverse study was carried out on the Island of La Palma (population: 81,507), from 1995 to 1998. The 15 December 1998 was established as prevalence day. Sources of information were periodically obtained from case records from public primary care centres, private hospitals, private centres, magnetic resonance units and others. In accordance with the Poser criteria all cases of definite or probable MS were included. 34 cases of MS were found on prevalence day (9 male and 25 female): 32 cases were clinically definite and 2 were clinically probable MS. Crude prevalence was 42/100,000. Incidence during time of study was 2.25/100,000. The island of La Palma could be considered as an area of medium-high risk, the risk being higher than that expected because of the geographical latitude of the island. This study confirms the hypothesis of the high prevalence of MS in Spain. We have not found significant clinical differences in MS patients from those in other studies.

Multiple sclerosis in Malta in 1999: an update

Objectives: To ascertain the prevalence of multiple sclerosis (MS) in the islands of Malta and compare it with a previous study undertaken 21 years earlier, when a remarkably low prevalence...

Hepatitis B Vaccination and First Central Nervous System Demyelinating Event: A Case-Control Study

Objective: To investigate the relationship between hepatitis B (HB) vaccination and a first central nervous system (CNS) demyelinating event in adults. Methods: In 1998, we conducted a multicentre, hospital-based case-control study which enrolled 402 cases of first CNS demyelinating event occurring between 1994 and 1995 and 722 controls matched for centre, age, sex and date of admission. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from a standardized phone interview. Forty percent of eligible cases and 50% of eligible controls could not be localized or were excluded because they did not satisfy inclusion or matching criteria. Results: Conditional logistic regression performed on 236 and 355 matched controls showed that adjusted odds ratios for the first CNS demyelinating event within 2 months following an injection of HB vaccine were 1.8 [95% confidence interval (CI), 0.7–4.6] in the whole group and 1.4 (95% CI, 0.4–4.5) in the subgroup of cases (n = 152) and controls (n = 253) referring to vaccination certificates during the phone interview. Restricting the analyses to the cases with definite or probable multiple sclerosis, these odds ratios were 2.0 (95% CI, 0.8–5.4) and 1.6 (95% CI, 0.4–5.6), respectively. Odds ratios tend towards 1 for a longer interval between HB vaccine and demyelinating event. Conclusions: This study was sufficiently powerful to rule out a strong association between HB vaccine exposure and a subsequent demyelinating event. However, it could not provide a clear indication of a moderately increased risk of a CNS demyelinating event shortly after HB vaccination in adults.

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis: Brex PA, Ciccarelli O, O’Riordan J, Sailer M, Thompson AJ, Miller DH. N Engl J Med 2002;346:158–164

In patients with optic neuritis and other isolated syndromes clinically suggestive of demyelinating disease, the presence of white matter lesions on magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis (MS) will develop months or years later. This study sought to determine the relation between early lesion volume, changes in volume, and long-term disability in this group of patients. Seventy-one patients with isolated syndromes (36 with optic neuritis) were followed in a serial MRI study for a mean of 14.1 years. Clinically definite MS developed in 48 patients (68%) and probable MS in a further five (7%). Clinically definite MS developed in 44 of the 50 patients (88%) with abnormal results on MRI at presentation and in four of 21 patients (19%) with normal results on MRI. Overall, 49 of 50 patients with abnormal MRIs (98%) had clinical or radiologic evidence of multiphasic disease consistent with MS. The median Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability) score at follow-up for those with MS was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to MS). The EDSS score at 14 years correlated moderately with lesion volume on MRI at five years and with the increase in lesion volume over the first five years. The authors conclude that in patients who first present with isolated syndromes suggestive of MS, the increases in the volume of the lesions seen on MRI of the brain in the first five years may correlate with the degree of long-term disability from MS. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment.—Nancy J. Newman

Remitting REM sleep behavior disorder as the initial sign of multiple sclerosis

We report a case of a 25-year-old woman presenting with a 6 month history of REM sleep behavior disorder (RBD), confirmed by video-polysomnography. A brain MRI disclosed multiple cerebral periventricular and pontine non-gadolinium-enhancing hyperintensities and CSF isoelectric focusing showed oligoclonal bands, consistent with a diagnosis of probable multiple sclerosis (MS). RBD episodes disappeared after ACTH treatment, but clinical relapses and MRI follow-up confirmed the diagnosis of MS. Although RBD has been described in association with MS, it has not been reported as a heralding sign, nor related to MS brainstem lesion. Our case emphasizes the value of RBD as a clinical tell-tale sign: when isolated RBD appears in a young subject, brain-imaging studies and long-term follow-up are warranted.

HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis

Background: The association between multiple sclerosis and class II alleles of the major histocompatibiliy complex, in particular the DRB1*1501-DQB1*0602 haplotype, is well established but their role in determining specific features...

Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis

Objectives: Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology...

Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study.

Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2), and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. Prospective, nested case-control study. Of 62 439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 1989-1990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P =.03), EBNA-2 (GMT, 91 vs 40; P =.01), and EA-D (15.9 vs 5.9; P =.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.7-3.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8 (95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. Our results support a role of EBV in the etiology of MS.