Liliana Patrucco

Epidemiological characteristics of pregnancy, delivery, and birth outcome in women with multiple sclerosis in Argentina (EMEMAR study)

Background The influence of pregnancy on Multiple Sclerosis (MS) has been extensively studied but such influence on Latin American women with MS has not been characterized. Our objective was to describe the course of pregnancy and birth outcome in Argentinean MS patients and the evolution of MS during pregnancy and after delivery. Method We used a retrospective design in eight MS centers in Argentina and administered a survey to women with definite MS (Mc Donald) with pregnancies during or after MS onset. We contacted 355 women of which 81 met inclusion criteria. We recorded 141 pregnancies. Results Involuntary abortion was observed in 16% of pregnancies (95% CI = 10–23). Thirty five women received immunomodulatory therapy (IMT) before 42 pregnancies. Twenty three (55%) out of 42 pregnancies were exposed to IMT. The mean time of IMT discontinuation before conception in 19 (45.2%) pregnancies without exposure, was 104 days (95% CI = 61.0–147.0). There were 103 deliveries: 79% full term. Birth defects were detected in 19% of pregnancies exposed to IMT (95% CI = 4–46) and in 2% of non-exposed (95% CI = 0.3–8.0). The mean relapse rate was: pre-pregnancy year: 0.22 (95% CI = 0.12–0.32); pregnancy: 0.31 in 1st (95% CI = 0.10–0.52), 0.19 (95% CI = 0.03–0.36) in 2nd, and 0.04 in 3rd trimester (95% CI = –0.04–0.12); 1st trimester post delivery: 0.82 (95% CI = 0.42–1.22). Conclusion We observed a higher rate of birth defects among infants exposed to immunomodulators in utero than those not exposed. The reduction in MS relapses during 2nd and 3rd trimester of pregnancy and its increase during postpartum is consistent with previous reports.

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.

CD24 as a genetic modifier of disease progression in multiple sclerosis in Argentinean patients

INTRODUCTION Previous reports have shown that CD24 gene polymorphisms have an important role in the risk of development and progression of multiple sclerosis (MS). OBJECTIVE To investigate the association between P226 polymorphisms (T/C), P1056 (A/G), P1527 (TG/del) and P1626 (A/G) of the CD24 gene and MS, comparing allele and genotype frequencies of patients versus controls. MATERIALS AND METHODS We analyzed DNA samples from 102 MS patients and from 205 unrelated healthy individuals. DNA was extracted from peripheral blood and polymorphic regions were amplified by nested PCR. Genotyping was performed by restriction fragments length polymorphisms. Time from disease onset to reach EDSS 6 and time to conversion to secondary progressive phase (SP) were used as variables of survival as well as percentage of patients that reached those endpoints. We used the log Rank test for data comparison (significant p≤0.05). RESULTS We found no differences between cases and controls in frequency of polymorphisms at the CD24 gene. 44.6% of patients with the AA genotype (P1626) reached an EDSS 6 vs 16% of patients with other genotypes (p<0.001, HR 3.2, 95% CI 1.4 to 7.4). 45.8% of patients with the AA genotype reached SPMS vs 16.7% without this genotype (p<0.001, HR 3.4, 95% CI 1.5 to 7.8). CONCLUSIONS This study showed a strong association between the presence of AA genotype in the 1626 polymorphism of the CD24 gene and the risk of disease progression in MS patients.

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.

Oligoclonal bands in multiple sclerosis patients: worse prognosis?

Abstract Introduction: Cerebrospinal fluid (CSF) oligoclonal bands (OB) imply intrathecal immunoglobulin synthesis and B-cell immune process. There is scarce evidence of OB having a role in disease prognosis. The objective of the present study was to determine OB’s prognostic value regarding disease progression. Methods: Between January 1994 and January 2007, relapsing–remitting MS (RRMS) patients in which OB were determined were included. Demographic, clinical aspects and presence of OB were analyzed. We compared OB+ versus OB− patients regarding progression to expanded disability status scale (EDSS) of 6·0 and to secondary progressive MS (SPMS). Cox proportional hazard models were used to compare the outcome between groups. P values <0·05 were considered significant. Results: One hundred and ninety-six patients were included. In 176 patients (90%), the CSF showed type II OB, 20 (10%) patients were OB negative. There were no differences between age, clinical presentation and EDSS at onset or in the immunomodulatory treatment received between OB+ and OB− patients. Sixty-two (31·6%) patients converted to SPMS during the follow-up, 59 (33·5%) were OB+ and 3 (15%) were OB−. EDSS of 6 was recorded in 56 (28·5%) patients during the follow-up; 54 (31%) were OB+ while only 2 (10%) OB- patients reached this outcome (reach SP phase, P = 0·032; HR: 2·2; 95% CI: 1·3–7·5 and EDSS of 6, P = 0·037; HR: 1·9; 95% CI: 1·3–8·5). Conclusion: We observed during the follow-up that OB− patients had a better prognosis and milder disability compared to OB+ patients.

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.

Embolic stroke secondary to cardiac papillary fibroelastoma.

Introduction:Papillary fibroelastoma is the most common primary cardiac valvular tumor. Historically, papillary fibroelastoma was an incidental autopsy finding, deemed to have no clinical significance. More recently, reports of symptomatic cases of papillary fibroelastoma with complications such as myocardial infarction and stroke suggest it should be considered a potentially dangerous lesion. In this report, we describe the clinical and echocardiographic findings of 3 patients with cardiac papillary fibroelastoma who presented with cerebral vascular events. Objective:To describe the clinical and echocardiographic findings of 3 patients with cardiac papillary fibroelastoma (CPF) who presented cerebral vascular events. Methods:Describe the findings of 3 patients and review of the literature. Results:We report 3 cases with cerebral ischemic events associated with the presence of CPF that were confirmed by histopathological examination. Conclusions:Cardiogenic embolism is recognized increasingly as an important cause of stroke, accounting of 20% of ischemic strokes. Cardioembolic stroke is largely preventable. The likelihood of recurrence is relatively high for most cardioembolic sources and therefore secondary stroke prevention is fundamental. TEE allowed to characterize well-established sources of embolism, and it was the best diagnostic approach in our patients. Magnetic resonance imaging was used in 1 of these patients, while it confirmed the presumptive diagnosis of cardiac tumor. The first-choice treatment of symptomatic CPF is surgical excision which must be performed as early as possible to reduce the risk of early recurrences of embolic events. The use of TEE in the evaluation of cerebral vascular events is not routinely performed, this method must be considered in patients for whom the cause of cerebrovascular ischemia is unclear, after noninvasive neurovascular studies.

Brain atrophy in clinically isolated syndrome

INTRODUCTION Previous reports have shown that brain atrophy appears early in the course of multiple sclerosis (MS). The aim of the present study was to evaluate whether brain atrophy already exists in clinically isolated syndrome (CIS) by comparing with a control sample. METHODS Patients with CIS were included prospectively from June 2008 to June 2009. A control group of healthy persons, matched by age and gender with CIS, was also included during the same period of time. An automated analysis tool, SIENAX, was used to obtain total brain volume (TBV), gray matter volume (GMV) and white matter volume (WMV). Mann-Whitney U test was used to analyze the data. RESULTS Twenty CIS patients and 30 healthy controls were included (8 vs. 17 females, p=0.11). Mean age for CIS was 35 ± 6 years vs. 34.4±5 in controls (p=0.61). Mean EDSS in CIS was 1.1 ± 0.5. Eighteen patients with CIS (90%) had abnormal baseline MRI. The TBV in CIS was 1.6.l ± 0.22.l × 106 vs.1.65 ± 0.15 × 106 in controls (p=0.005), the GMV in CIS was 0.58 ± 0.05 × 106 vs. 0.67 ± 0.03 × 106 in controls (p ≤ 0.001) and the WMV in CIS was 1 ± 0.1 × 106 vs. 1.12 ± 0.02 × 106 in controls (p=0.03). CONCLUSIONS This is the first study dealing with brain atrophy in a CIS sample from Latin America in which brain atrophy, mainly grey matter atrophy, was shown in early stages of the disease compared with healthy individuals.