Marcos Papais Alvarenga

Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, Rio de Janeiro, Brazil

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Publications (14)34.95 Total impact

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    ABSTRACT: The anti-aquaporin4 (anti-AQP4) antibody is specific for neuromyelitis optica (NMO), but is also found in limited forms. The presence of this antibody in acute transverse myelitis (ATM) has been associated with recurrence and conversion to NMO, but the influence on disability has not yet been described. To describe the frequency of anti-AQP4 in ATM and analyze the influence in long-term prognosis. Cross-sectional and retrospective study. Consecutive ATM cases in a multiple sclerosis center in Rio de Janeiro, Brazil, from 2000 through 2009 were reviewed. Recurrent cases tested for anti-AQP4 were selected. ATM with magnetic resonance imaging spinal cord lesions extending over three or more vertebral segments was classified as longitudinally extensive transverse myelitis (LETM); Kurtzke scale was applied at last evaluation. Frequency of anti-AQP4; severity of spinal cord dysfunction at last follow-up. Twenty six patients (21 female:5 male; 17 white:9 African descent) were studied. The first ATM occurred at 38.04 ± 12.7 years. The interval between the first and the second ATM was eight months (1-150) and the number of ATM varied from two to seven. After 40.5 months (12-192) of disease, the median Expanded Disability Status Scale (EDSS) score was three (0-9). Anti-AQP4 antibody was positive in 26.9%. LETM was found in 65.4%. LETM presented later onset, higher disability and higher positivity to anti-AQP4 (LETM 41.2% versus no-LETM 0%, P = 0.024). Dysfunction at long-term follow-up was similar in anti-AQP4 positive and negative cases. The frequency of anti-AQP4 in recurrent ATM was 26.9%, increasing to 41.2% among LETM. Presence of the antibody had no influence on morbidity.
    The journal of spinal cord medicine 07/2012; 35(4):251-5. · 1.54 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Women with multiple sclerosis (MS) who intend to get pregnant are often advised to discontinue disease modifying therapy (DMT) prior to conception. This recommendation is not based on medical evidence and may interfere with disease control by immunomodulatory drugs. The present study was designed to help discuss the effect of DMT for MS on pregnancy and on disease course. PATIENTS AND METHODS: Retrospective data from 152 pregnancies of 132 women with MS were collected by the physician in charge of the case. All data were entered into a specific file for qualitative and quantitative statistical analysis. RESULTS: From the total group of patients, 89 pregnancies occurred without any exposure to MS drugs, while 61 pregnancies occurred with at least eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and neonatal complications was similar in both groups, except for the newborn weight and height which was smaller for mothers receiving medications. Mothers' post-delivery relapse rate and EDSS scores in the follow-up period were significantly higher in the absence of treatment. CONCLUSION: It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised.
    Clinical neurology and neurosurgery 05/2012; · 1.30 Impact Factor
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    ABSTRACT: Natalizumab is a monoclonal antibody shown to be highly effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Patients treated with natalizumab can develop antibodies directed against this agent that may affect the efficacy and safety of the drug. In this observational study, the kinetics of the appearance and the incidence of anti-natalizumab antibodies were followed prospectively for 18 months in a cohort of 64 consecutive patients treated with natalizumab for relapsing MS. Blood samples were drawn immediately before starting natalizumab therapy and each month afterwards. The presence of antibodies against natalizumab was assessed by enzyme-linked immunosorbent assay (ELISA) in all patients. Anti-natalizumab antibodies were detected in nine (14.1%) natalizumab-treated patients, three (4.68%) of whom were transiently positive while six (9.37%) were persistently positive (these patients discontinued natalizumab). All positive titres were observed during the first 4 months of treatment. One patient with a hypersensitivity reaction also had persistent antibodies. We conclude that antibodies against natalizumab develop early, within the first 6 months of therapy with natalizumab. Although no antibodies were detected after 4 months of therapy in this particular study, this does not rule out their development later on in exceptional cases.
    Multiple Sclerosis 12/2010; 17(3):368-71. · 4.47 Impact Factor
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    ABSTRACT: Little is known about how the level of disability at the start of treatment with natalizumab affects its efficacy. Objectives: The aim of this study was to investigate the effect of natalizumab on relapses in patients with different levels of baseline disability associated with MS. This single-centre observational study collected demographic data for patients followed prospectively and who were scheduled to start natalizumab therapy due to the presence of disease activity. The annualized relapse rate (ARR) and Kurtzke Expanded Disability Status Scale scores were analysed for the previous year, on starting treatment (baseline) and 1 year after starting therapy. Seventy-seven patients (mean age: 39.0 years, mean disease duration: 12.4 years) were included. The difference between ARR before and after starting treatment was 0.92 for baseline Expanded Disability Status Scale ≤ 3.5 (p < 0.0005), 0.70 for Expanded Disability Status Scale 4.0-6.0 (p < 0.007) and 0.57 for Expanded Disability Status Scale ≥ 6 (p = 0.386). Expanded Disability Status Scale did not vary during the study. One patient discontinued treatment due to an adverse event and nine patients discontinued due to positive anti-natalizumab antibodies. The findings support the efficacy of natalizumab in reducing ARR in the year after starting treatment in patients with baseline Expanded Disability Status Scale ≤ 6.
    Multiple Sclerosis 11/2010; 17(2):192-7. · 4.47 Impact Factor
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    ABSTRACT: The aim of this study was to describe the demographic, clinical and laboratory features of idiopathic acute transverse myelitis (IATM). Patients with non-compressive ATM receiving care at Hospital da Lagoa, Rio de Janeiro (Brazil) between 2000 and 2008 were selected. Of the 70 cases of acute myelopathies, the idiopathic form was identified in 41 following exclusion of the cases associated with systemic lupus erythematosus (n = 1), Sjogren's syndrome (n = 1), herpes zoster (n = 1), cytomegalovirus in an HIV-positive patient (n = 1), Schistosoma mansoni (n = 1), actinic myelitis (n = 1), infectious myelitis of unknown etiology (n = 2) and those that, following the first attack of myelitis, converted to NMO (n = 19) or to clinically defined MS (n = 2). Of the 41 cases of IATM, the majority of patients were female (68.3%) and white (65.9%). Median age at first myelitis was 37.0 +/- 11.8 years. Over a median observation time of 36 months, 39.0% of patients remained monophasic, while recurrences occurred in 61.0% of cases. The number of ATM/patient ranged from one to seven. Among the recurrent cases the median time between the first and the second ATM was 12 months (range 1-150 months).The first myelitis was characterized mainly by partial myelitis with motor and sensorial dysfunction (63.4%). Complete and severe myelitis occurred more frequently among monophasic patients and partial myelitis with moderate dysfunction at onset in recurrent cases; however, over the long-term, dysfunction and disability were mild in both groups. Serial spine MRI confirmed spinal cord inflammation in 92.0% of cases and extensive spinal cord lesion was identified in 61.0%. Brain MRI was normal or not suggestive of MS in 94.4% of cases. CSF showed pleocytosis in 41.2%, increased IgG index in 24.0% and oligoclonal bands in 38.0% of 34 patients tested. Abnormal visual evoked potentials occurred in 11.5% of 26 patients. Positivity for anti-AQP4 was found in 23.5% of the 17 cases tested, suggesting limited forms of NMO. This study suggests some new aspects of the clinical course of IATM such as the high conversion rate to NMO, the predominance of women and a higher frequency of recurrent forms.
    Journal of Neurology 06/2010; 257(6):992-8. · 3.58 Impact Factor
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    ABSTRACT: Recent studies have suggested faster clinical progression and greater disability in multiple sclerosis patients of African descent. This study analysed the effect of ethnicity on progression and disability. Sixty-five patients with primary progressive multiple sclerosis were selected and classified as being of African descent or white. Time from onset of the disease until reaching Expanded Disability Status Scale grades 3, 6, and 8 was assessed, as well as irreversible disability (Expanded Disability Status Scale grade maintained for >or=6 months). In the African descent group, the median time to reach Expanded Disability Status Scale 3 was 1 year shorter (1 year vs 2 years, p= 0.02), and to reach Expanded Disability Status Scale 6 was 2 years shorter (3 years vs 5 years, p= 0.01) than in the group of white patients. According to the Kaplan-Meier survival curves, patients of African descent reached every disability stage faster than white patients (p= 0.03, p = 0.04, and p = 0.03, respectively, for Expanded Disability Status Scale grades 3, 6, and 8). As in United States and European patients of African descent, the more severe and faster progression of multiple sclerosis seen in Brazilian primary progressive multiple sclerosis patients of African descent suggests a possibly greater effect of ethnicity rather than environment on the progression of multiple sclerosis.
    Multiple Sclerosis 02/2010; 16(5):597-603. · 4.47 Impact Factor
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    ABSTRACT: We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4%) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3% were male and follow-up range was 8.5 to 16 years. Two cases (13.3%) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3%) presented MRI with multiple large lesions. CSF was normal in 73.3%. The severe disability observed at EDSS onset improved in 86.66% patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.
    Arquivos de neuro-psiquiatria 09/2009; 67(3A):643-51. · 0.55 Impact Factor
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    ABSTRACT: Three different diagnostic criteria for primary progressive MS were recently proposed for Caucasian population of Western European region. The objective of the study was to apply these criteria to a series of Brazilian patients with high ethnic diversity background to evaluate reproducibility and reliability. 52 patients classified as form of the disease that is progressive from onset and followed between 2000 and 2006 were included. Thompson, McDonald and Polman criteria were applied based in clinical date and complementary exams. Results: 72% fulfilled all three criteria with moderate agreement (p<0.001). Ten patients fulfilled at least one criterion and four failed to fulfill any of the three criteria. Strong agreement was found between Thompson and McDonald criteria (p<0.001), agreement was moderate between Thompson and Polman criteria (p<0.001) and weak agreement occurred between McDonald and Polman criteria (p=0.042). The main difference between these criteria is the change in the role of CSF, previously a prerequisite for diagnosis. Rigid diagnostic criteria as Thompson have higher specificity, should be used in clinical research protocols, while more flexible criteria as Polman facilitate the diagnosis of PPMS in neurological practice, particularly in initial stages of the disease, because of their potentially higher sensitivity.
    Journal of the Neurological Sciences 08/2008; 270(1-2):159-64. · 2.24 Impact Factor
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    ABSTRACT: To describe the clinical characteristics, course, and prognosis of optic neuritis in recurrent neuromyelitis optica. We analyzed 60 patients diagnosed using 1999 Mayo Clinic criteria who were seen between 1985 and 2004 at Hospital da Lagoa (Rio de Janeiro, Brazil). Optic neuritis was the initial feature in 53.3% of patients, most with unilateral disease. Recurrent optic neuritis before myelitis occurred in 18.3%. The visual impairment was severe at nadir of the visual index event in 78.3%, with a high remission rate. In the median disease duration of 8 years (range, 0.5-30 years), 380 relapses (118 optic neuritis, 223 myelitis, 39 optic neuritis and myelitis) occurred. At the last follow-up, 53.3% of patients had bilateral visual impairment and 63.3% were blind in at least 1 eye. A high mortality rate (23.3%) was due to cervical myelitis. Mortality rates were significantly higher among Afro Brazilian patients (58.3%). Optic neuritis in patients with recurrent neuromyelitis optica has a severe and acute onset, with predominantly unilateral lesions followed by improvement of clinical symptoms. In the long-term, the disease leads to severe bilateral visual impairment. Mortality rates are higher among patients of Afro Brazilian descent.
    Archives of Ophthalmology 02/2008; 126(1):12-6. · 3.83 Impact Factor
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    ABSTRACT: Background: Brazil is a continental South American country with a great ethnic diversity and is located in tropical-equatorial areas with a low prevalence of multiple sclerosis (MS). The Grupo de Neuro Imunologia da Academia Brasiileira de Neurologia (1994–1998) organized the first MS population survey (South Atlantic project) analyzing 602 MS patients, most of them from the southeast region, classified by the criteria of Poser et al. (1983). In the last decade, new diagnostic criteria for MS (McDonald et al., 2001), neuromyelitis optica (NMO) (Wingerchuk et al., 1999) and primary progressive MS (PPMS) (Thompson et al., 2000) have been proposed based on clinical, radiological and laboratory data. Objective: To review the diagnosis of patients included in SIAPEM (Brazilian MS data base) from 1995 to 1998, treated at three MS referral centers in Rio de Janeiro (Hospital da Lagoa, UNI-RIO and Clinica Bambina). Methods: The medical records of 208 patients were analyzed. The patients were classified into the different diseases of the group of demyelinating inflammatory demyelinating diseases (DDII) of the central nervous system (Weisnhenker, 2005). Clinical and laboratory data were used for the application of the new criteria. Results: Loss of follow-up occurred in 19 out of 208 (9%) patients. Of the remaining 189 patients (62, 5% white Brazilian and 37, 5% African Brazilian) in the MS centers, DDII was confirmed in 182 (96%). The patients were classified as: MS (102 relapsing-remitting MS, 24 PPMS), NMO (28 with a relapsingremitting clinical course and three monophasic), transverse myelitis (2), optic neuritis (2), acute disseminated encephalomyelitis (6), MDEM (3) and cases with large cerebral lesions (2). The diagnosis was changed in seven cases (3%): Arnold Chiari (1), tropical spastic paraparesis (2), lacunar stroke (1), vasculitis by cocaine (1), CMS ischemic spinal cord syndrome (1) and psychiatric syndrome (1). Conclusions: The Poser criteria did not allow a differential diagnosis between MS and other DDII. Nowadays, the diagnosis of MS, although still based on clinical data, has stronger support from magnetic resonance imaging. Two out of three of the Brazilian patients remained with the MS diagnosis. The second most frequent disease was NMO (16.4%). The estimated prevalence of NMO in Caucasians is 1%. MS epidemiological studies in tropical areas need to apply both criteria (MS and NMO).
    Multiple Sclerosis 01/2008; 14:S195-S195. · 4.47 Impact Factor
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    ABSTRACT: The present study focused on human leukocyte antigen (HLA) DQB1, DQA1 and DRB1 allelic variation according to ethnicity and analyzed whether susceptibility to multiple sclerosis (MS) depends on population characteristics. Eighty-eight healthy African-Brazilians and 92 healthy white Brazilians living in Rio de Janeiro City were selected and the HLA phenotype between the two ethnic groups was compared with 44 MS patients of African descent and 40 patients of European descent. HLA class II genes were performed using polymerase chain reaction (PCR) and PCR-sequence-specific primer amplification. DQA1*0201-0301 alleles were associated with the white Brazilian population (P < 0.001). The DRB*1501 allele was present in White Brazilians (P=0.003), and DRB1*03-1503 in African-Brazilians. The DRB1*1501 allele confers an ethnicity-dependent MS susceptibility in White patients and the DQB1*0602 allele confers genetic susceptibility regardless of ethnicity. Heterogeneous phenotypes occur in both Brazilian ethnic groups. Taking into account that the response to immunomodulator drugs for MS treatment changes according to the DRB1*1501 allele and African-American MS patients presented poor response to the interferons, phenotype heterogeneity of HLA loci found in this study could influence therapeutic decisions in the Brazilian MS population.
    Acta Neurologica Scandinavica 05/2007; 115(5):306-11. · 2.47 Impact Factor
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    ABSTRACT: Brazil has a high mixed ethnic background and is a low Multiple sclerosis prevalence region. In our population the clinical course and outcome of progressive MS since onset were much alike to the MS high prevalence areas, demonstrating that once the disease manifests, factors that affect frequency do not influence the clinical features and course Objectives: to describe clinical and laboratorial features of primary progressive multiple sclerosis (PPMS) in Brazilian patients and to apply the specific diagnostic criteria: Thompson criteria (2000), McDonald (2001) and Polman criteria (2005). Methods: Fifty MS patients with progressive disease at onset assisted at Rio de Janeiro, Brazil were analyzed. Results: Caucasian/Non-Caucasian ratio was 2.3:1 and women/men ratio was 1.2:1. The main affected Functional Systems (FS) were pyramidal and cerebellar. 80% reached EDSS 6 after a mean time of 5.2 years and 46% reached EDSS 8 after a mean time of 9 years. Cranial MR was abnormal to PPMS in 90% (45/50) and vertebral MR abnormal in 97% (31/32); CSF IgG intrathecal synthesis was detected in 81% (38/47), and abnormal VEP in 87% (20/23). The majority of patients met Polmann criteria-88% (44/50), followed by McDonald criteria-76% (38/50), and by Thompson criteria- 72%(36/50) classified as defined and 28% (14/50) as probable. Agreement index between three criteria was good (Kappa value=0.63, p<0.001).Interpretation: We concluded that the specific criteria for PPMS were met with high frequency and agreement in our population with mixed ethnicity, living in a tropical environment.
    23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS); 01/2007
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    ABSTRACT: Monophasic neuromyelitis optica (NMO) is a rare form of post-infection acute disseminated encephalomyelitis (ADEM). Cases occurring after dengue virus infection are rare, despite the high prevalence of this disease in tropical and subtropical countries. We report a female patient, 11 years old, of Japanese ancestry and living in North Brazil, who developed NMO 1 week after having had a benign form of dengue fever. The disease was confirmed by the detection of dengue IgM antibodies in serum and cerebrospinal fluid (CSF). Restricted distribution of the lesions in the optic nerve and spinal cord was confirmed by ophthalmological evaluation and magnetic resonance imaging of the brain and spinal cord. Therapeutic intervention with corticotherapy resulted in benign evolution. This is the second report of optic spinal syndrome following dengue virus infection in patients of Japanese ancestry, suggesting an influence of the genetic background in the susceptibility to post-dengue NMO.
    Journal of Infection and Chemotherapy 01/2007; 12(6):396-8. · 1.55 Impact Factor
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