Jimena Miguez

Brain atrophy in radiologically isolated syndromes.

The aim of this study was to compare brain atrophy in radiologically isolated syndrome (RIS), in clinically isolated syndrome (CIS), and in individuals with subjective complaints (ISC).

Application of the McDonald 2010 criteria for the diagnosis of multiple sclerosis in an Argentinean cohort of patients with clinically isolated syndromes.

Background: The International Panel on Diagnosis of Multiple Sclerosis has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS). We aimed to evaluate these new criteria in a cohort of patients from Buenos Aires, Argentina. Methods: Patients with CIS, in whom MRI was performed within three months of onset of symptoms, were included between January 2005–June 2010. Poser or McDonald 2005 criteria were used as gold standard diagnostic criteria for MS. MRI was assessed by a blind evaluator identifying recently diagnostic MS criteria. New criteria sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were determined. Results: Altogether 101 patients were included. Of these, 86 patients converted to MS (McDonald 2005/Poser) during the follow-up. The mean follow-up time was 7.3±3.2 years (range 1.8–11 years). Sensitivity was 84%, specificity 80%, PPV 96%, NPV 46% and accuracy 82%. The sub-analysis applied only to non-European descendants (mestizos, natives and zambos) showed a high level of accuracy for these new diagnostic criteria in this local ethnic/genetic population (sensitivity 77%, specificity 72%, PPV 94%, NPV 38%). Conclusions: This study assessing McDonald 2010 criteria in a Latin-American population may contribute to its international validation.

Brain atrophy as a non-response predictor to interferon-beta in relapsing-remitting multiple sclerosis.

Abstract Background: Several predictors for treatment failure to interferon-beta (IFN-beta) have been proposed; however, brain atrophy has not been well studied. Methods: In this prospective and longitudinal study, all consecutive relapsing–remitting multiple sclerosis (RRMS) patients treated with sc IFN-beta-1a were included. Confirmed disability progression or a new relapse between weeks 48 and 144 after beginning with IFN-beta was considered as treatment non-response. EDSS progression, relapses, number of active lesions at 1 year (new or enlarging T2-weighted plus gadolinium-enhancing lesions, categorized in > 2 or ≤ 2), and brain parenchymal fraction (%BVC) volume change within the initial year of treatment were used as predictive factors. Cox regression model was adjusted for age, gender, and disease duration. Results: Seventy-one patients were included (71·8% female) with a follow-up of 144 weeks. Thirty-four (48%) fulfilled criteria of non-response to IFN-beta treatment. The model showed: (1) relapses+disability progression: HR  =  4·6, 95% IC: 3·1–6·7 (P < 0·001); (2) relapses+BVC decrease: HR  =  4·1, 95% IC: 3·2–7·3 (P  =  0·001); (3) relapses+disability progression+new active lesions: HR  =  10·1, 95% IC: 7·1–15·2 (P < 0·001); and (4) relapses+disability progression+new active lesions+BVC decrease: HR  =  14·4, 95% IC: 11·4–21·2 (P < 0·001). Conclusions: Adding BVC measures to previously described predictive failure factors may increase sensitivity to early identify non-responder patients to IFN-beta-1a in the second and third years of therapy.

Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

Multiple sclerosis (MS) was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

Increasing prevalence of multiple sclerosis in Buenos Aires, Argentina.

UNLABELLED In 1996, the prevalence of multiple sclerosis (MS) for the metropolitan area of Buenos Aires using the capture-recapture method was estimated to be between 14 and 19.8 cases per 100,000 inhabitants. The aim of this study was to update the prevalence to 2014 following the same methodology. METHODS Gran Buenos Aires is the denomination that refers to the megalopolis comprised by the autonomous city of Buenos Aires and the surrounding conurbation of the province of Buenos Aires. The study was carried out taking December 2014 as the prevalence month. We used the capture-recapture method to estimate the prevalence of MS cross-matching registries from 6 MS Centers from the metropolitan area of Buenos Aires. Log-linear model Poisson regression was used to estimate the number of affected MS patients not detected by any of the 6 sources considered. RESULTS 1035 registries were obtained from the 6 lists from 910 different patients detected. The population of the area based on 2010 census was 12,806,866, the number of MS cases estimated amongst source interactions were 4901. The estimated prevalence was 38.2 per 100,000 inhabitants (95% CI 36.1-41.2). CONCLUSION The study is an update almost 20 years after the first one in the area showing a significant increase in the previous reported prevalence. Our findings are in line with previous studies performed in other regions of the world.

Disease onset in familial and sporadic multiple sclerosis in Argentina

UNLABELLED The present study was carried out to assess if there is an anticipation of age at onset in younger generations of familial multiple sclerosis (FMS) vs. sporadic MS (SMS) in Argentina. METHODS multicenter study that included patients from 14 MS Centers of Argentina. Patients were considered as FMS if they had in their family at least one relative of first or second degree diagnosed with MS; otherwise, patients were considered to have SMS. We compared the age at onset between familial and sporadic cases as well as the age at onset between relatives from different generations in FMS vs. SMS. RESULTS 1333 patients were included, 97 of them were FMS (7.3%). A lower age at onset in the younger generations of FMS cases was found compared with older generations of FMS as well as. SMS cases (24.1±3.7 years vs. 30.3±5.7 years, and 32.4±9.4 respectively; p<0.001). No differences were observed between older generations of FMS vs. SMS cases (p=0.12). CONCLUSION we observed an anticipation of age at onset of MS in younger generations of patients with FMS vs. older generations of FMS and SMS.

Gender ratio trends over time in multiple sclerosis patients from Argentina

Several studies in multiple sclerosis (MS) suggest a trend of increasing disease frequency in women during the last decades. A direct comparison of gender ratio trends among MS populations from Argentina remains to be carried out. The objective of the study was to compare gender ratio trends, over a 50-year span in MS populations from Argentina. METHODS multicenter study that included patients from 14 MS Centers of Argentina. Patients with definite MS with birth years ranging from 1940 to 1989 were included. Gender ratios were calculated by five decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the Argentinean national registry of births. The F/M ratios were calculated using a multivariate logistic regression per five decades by the year of birth approach. Analyses were performed using Stata 10.1. RESULTS 1069 patients were included. Gender ratios showed a significant increase from the first to the last decade in the whole MS sample (from 1.8 to 2.7; p value for trend=0.023). The Gender ratio did not show differences considering MS subtype. CONCLUSION our study showed a modest increase of the F/M ratio (from 1.8 to 2.7) over time among patients affected by MS in Argentina.

Brain structural changes in patients in the early stages of multiple sclerosis with depression

Abstract Some studies suggest an inflammatory mechanism associated with the presence of depression in multiple sclerosis (MS); however, there is little data concerning these findings. The purpose of this study was to investigate the presence of brain structural changes in patients with MS and depression and to compare them with patients suffering from MS without depression and healthy controls. Methods: A case-control study that included patients with relapsing-remitting MS (RRMS) defined by validated criteria, over 18 years of age, with less than three years from disease onset, EDSS ≤ 3, with no history of previous depression and under immunomodulatory treatment with interferon beta, if any. A control group paired by age and gender was also included. Patients were clinically assessed to determine the presence of depression. Demographic clinical and structural aspects of parameters from the scan, such as lesion volume, total brain volume (TBV), white matter volume (WMV), neocortical gray matter volume (NGMV), and fractional anisotropy (FA) were analyzed. Results: Sixty-five individuals were enrolled: 20 healthy controls, 22 patients with MS without depression, and 23 patients with MS with depression. Patients with MS and depression showed a lower TBV (P = 0.01), NGMV (0.01) together with an increase in lesion burden in T2 (P < 0.01) but not in T1 (P = 0.09) and no differences in global FA among groups (P = 0.23) and in WMV (P = 0.12). Conclusion: Patients with RRMS and depression had a reduced total brain volume and a significantly increased lesion burden at T2 MR than patients with RRMS without depression.

Structural sex differences at disease onset in multiple sclerosis patients.

Background Male sex is associated with worsening disability and a more rapid progression of multiple sclerosis (MS). This study analysed structural sex differences in magnetic resonance images of the brain, comparing women whose disease started before and after the menopause with a control group of men. Methods This was a case control study in which female patients whose MS started before (Group 1) and after (Group 2) the menopause were included. The control group was matched by age, disease duration, Expanded Disability Status Scale and disease-modifying treatment. Patients were analysed according to demographic and clinical variables, as well as in terms of radiological measurements at disease onset and during the first 12 months of follow-up. These measurements included normalised total brain volume (NTBV), normalised cortical volume (NCV), normalised white matter volume, left and right hippocampus, the thalamus, brain stem volume, lesion load and percentage brain volume change. A linear regression model was used to analyse the data. Results A total of 97 patients were included: 53 in Group 1 (27 females) and 44 in Group 2 (22 females). In Group 1, we observed a reduction in brain volume in males compared with females at disease onset in NTBV (p = 0.01), NCV (p = 0.001) and brain stem volume (p = 0.01). We did not observe differences in Group 2 at disease onset in the brain volumes analysed. Conclusion We observed structural sex differences in brain volume at disease onset in the pre-menopausal group. However, no structural differences were observed at disease onset between the sexes after the menopause had started.

Thalamus volume change and cognitive impairment in early relapsing–remitting multiple sclerosis patients

Aims The objective of the study was to assess whether changes in the volume of the thalamus during the onset of multiple sclerosis predict cognitive impairment after accounting for the effects of brain volume loss. Methods A prospective study included patients with relapsing–remitting multiple sclerosis less than 3 years after disease onset (defined as the first demyelinating symptom), Expanded Disability Status Scale of 3 or less, no history of cognitive impairment and at least 2 years of follow-up. Patients were clinically followed up with annual brain magnetic resonance imaging and neuropsychological evaluations for 2 years. Measures of memory, information processing speed and executive function were evaluated at baseline and follow-up with a comprehensive neuropsychological test battery. After 2 years, the patients were classified into two groups, one with and the other without cognitive impairment. Brain dual-echo, high-resolution three-dimensional T1-weighted magnetic resonance imaging scans were acquired at baseline and every 12 months for 2 years. Between-group differences in thalamus volume, total and neocortical grey matter and white matter volumes were assessed using FIRST, SIENA, SIENAXr, FIRST software (logistic regression analysis P < 0.05 significant). Results Sixty-one patients, mean age 38.4 years, 35 (57%) women were included. At 2 years of follow-up, 17 (28%) had cognitive impairment. Cognitive impairment patients exhibited significantly slower information processing speed and attentional deficits compared with patients without cognitive impairment (P < 0.001 and P = 0.02, respectively). In the cognitive impairment group a significant reduction in the percentage of thalamus volume (P < 0.001) was observed compared with the group without cognitive impairment. Conclusion We observed a significant decrease in thalamus volume in multiple sclerosis-related cognitive impairment.