Effectiveness and Adverse Events of Use of Natalizumab in a Brazilian Cohort of Patients With Multiple Sclerosis.

PURPOSE: Natalizumab (NTZ) is a monoclonal antibody with confirmed efficacy in white populations with recurrent-remitting multiple sclerosis (RRMS); there are few studies, however, in mixed-race populations. Real-world studies of NTZ are needed to better understand the drug's effectiveness. This study evaluated the effectiveness and adverse events of NTZ in a cohort of Brazilian patients with MS, as well as the impact of clinical and demographic factors on patient response to treatment. METHODS: This multicenter, Brazilian observational study was conducted from January 2011 until December 2016 and included patients with RRMS (McDonald criteria 2005 and 2010) aged ≥18 years treated with NTZ for at least 3 months. Demographic, clinical, and radiologic data were obtained from medical records and during follow-up visits. The primary outcomes investigated were the absolute number of relapses and annualized rate of relapses, change in Expanded Disability Status Scale value, and presence of new lesions on magnetic resonance imaging after starting NTZ treatment; the occurrence and type of adverse events were also analyzed. In addition, the impact of demographic and clinical prognostic factors and radiologic activity on the effectiveness of NTZ was measured. Descriptive and univariate statistical analyses used a significance level of P < 0.05. RESULTS: The study enrolled 56 patients; 64% were women, and 36% were of African descent. There was a significant reduction in the mean absolute number (P = 0.001) and in the annualized rate (P = 0.001) of relapses and in the radiologic activity of the disease (P = 0.001). Furthermore, 71% of patients showed no increase in Expanded Disability Status Scale score after 1 year of treatment. The effectiveness of NTZ was not associated with the presence of clinical and demographic prognostic factors, and the most frequent adverse events during the use of NTZ were gastrointestinal symptoms; there were no cases of progressive multifocal leukoencephalopathy. IMPLICATIONS: According to patients' reports and clinicians' observations regarding clinical and radiologic benefits and tolerability to adverse events, the use of NTZ was favorable in this Brazilian MS cohort, regardless of the presence of unfavorable prognostic factors.

Guideline for multiple sclerosis treatment in Brazil: Consensus from the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology.

Multiple sclerosis has become an ever-increasing challenge to neurologists. With the release of the latest medications on the market, Brazilian neurologists feel divided between following their patients' evolution in accordance with the strict rules established by the Brazilian Ministry of Health regarding drug distribution, or following disease progression and worsening in accordance with the evidence in the literature. Therefore, a systematic review of the main published treatment guidelines was conducted and an escalating therapy proposed for guiding multiple sclerosis patient treatment in Brazil.

Guideline for multiple sclerosis treatment in Brazil: Consensus from the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology / Orientações para tratamento da esclerose múltipla no Brasil: Consenso do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia

ABSTRACT Multiple sclerosis has become an ever-increasing challenge to neurologists. With the release of the latest medications on the market, Brazilian neurologists feel divided between following their patients’ evolution in accordance with the strict rules established by the Brazilian Ministry of Health regarding drug distribution, or following disease progression and worsening in accordance with the evidence in the literature. Therefore, a systematic review of the main published treatment guidelines was conducted and an escalating therapy proposed for guiding multiple sclerosis patient treatment in Brazil.

RESUMO A esclerose múltipla vem se tornando um desafio crescente para os neurologistas. Com o lançamento de novos medicamentos no mercado, os neurologistas brasileiros se encontram divididos entre, apesar da evolução dos seus pacientes, seguir as regras restritas estabelecidas pelo Ministério da Saúde para distribuição de medicamentos, ou ao contrário, considerar a progressão e piora da doença, em concordância com as evidências da literatura. Devido a este impasse foi realizada uma revisão sistemática sobre as principais orientações de tratamento publicadas e foi proposto um escalonamento terapêutico para orientar o tratamento dos pacientes com esclerose múltipla no Brasil.

Familial forms of multiple sclerosis and neuromyelitis optica at an MS center in Rio de Janeiro State, Brazil.

OBJECTIVE: To describe familial forms of demyelinating diseases from an MS referral center in Río de Janeiro State, Brazil. METHODS: A descriptive, cross-sectional study was done to identify familial IIDD cases in Hospital da Lagoa, a public hospital where 75% of patients with IIDD who live in Rio de Janeiro state, located in the Southeast region of Brazil, are referred. The diagnoses of all consecutive patients followed in 2011 were reviewed to apply new diagnostic criteria (Wingerchuk et al., 2008). The diagnosis of IIDD was confirmed based on clinical history, neurological examination, MRI of the skull and spinal cord, CSF analysis and investigation of IgG NMO antibodies. The cases that had at least one other relative with IIDD were selected for the study. RESULTS: Familial forms were found only in the multiple sclerosis (MS) and neuromyelitis optica syndrome (NMOSD) categories. 23 MS families were identified, 60.86% with first degree kinship. It has a Caucasian preponderance, 90% of whom were white. The frequency of early onset was 15% and 20% of the MSf cases have progressive primary course. CONCLUSION: The frequency of familial cases of IIDD was 6.12% among MS patients and 2.8% in NMO spectrum syndromes.

The impact of diagnostic criteria for neuromyelitis optica in patients with MS: a 10-year follow-up of the South Atlantic Project.

BACKGROUND: It is recognized that there is a particular geographic and ethnic distribution of neuromyelitis optica (NMO) among Caucasian and non-Caucasian populations. OBJECTIVE: To review the diagnoses of patients whom were enrolled in the South Atlantic Project, a Brazilian multiple sclerosis (MS) survey performed from 1995-1998, and to identify NMO and MS case frequencies. METHODS: We reviewed the data from a 10-year follow-up of MS patients. To apply the current diagnostic criteria, the neurologists were asked to collect clinical and laboratory data from the medical records of study patients treated from 1999-2009. RESULTS: The spectrum of inflammatory demyelinating disease in 322 patients (67% white; 33% African-Brazilian) was: 49 (15%) with NMO; 14 (4%) with NMO syndromes; 10 (3%) with acute disseminated encephalomyelitis (ADEM); one isolated tumefactive brain lesion; 249 (77%) with MS (151 with relapsing-remitting MS (RRMS), 70 with secondary progressive MS (SPMS) and 27 with primary progressive MS (PPMS)). Disability was more severe in NMO and PPMS. One-third of the NMO patients had died. CONCLUSIONS: The frequency of NMO was 6.8% in São Paulo and 20.5% in Rio de Janeiro, and mainly seen in persons of African descent, which strengthens the hypothesis of there being an ethnic association of this disease. We recommend that epidemiological studies on MS that were performed previously be reviewed again, to ensure more accurate diagnoses.

Evaluation of pattern-reversal visual evoked potential in patients with neuromyelitis optica.

BACKGROUND: The visual evoked potential (VEP) is used in the evaluation of multiple sclerosis (MS) patients, showing a delay in P100 wave latency with no changes in amplitude in 60-100% of cases. In the last decade, the recurrent form of neuromyelitis optica (NMO) has been recognized, and clinically characterized by acute events of transverse myelitis (TM) and optic neuritis (ON), differing from MS in clinical and laboratory criteria. Despite these differences, so far, the VEP parameters described in MS have been used in the evaluation of patients with NMO. The objective of this study was to investigate VEP responses in NMO. METHODS: Patients with NMO underwent pattern-reversal visual stimulation. Nineteen patients were selected for the study. RESULTS: Among the 38 eyes examined, 18 (47.4%) had no visual evoked responses and 13 (34.2%) had a reduction of P100 wave amplitude with normal latency. Only two (5.3%) had the pattern described in MS and five (13.2%) were normal. CONCLUSION: Evaluation of VEP in patients with definite NMO revealed a pattern that is different from that of MS in 81.6% of eyes examined, characterized by the absence of responses, or decreased amplitude with normal latency.

Diffusion tensor MR imaging evaluation of the corpus callosum of patients with multiple sclerosis.

OBJECTIVE: To evaluate the fractional anisotropy (FA) values of the normal-appearing white matter of the corpus callosum (CC) in patients with relapsing-remitting multiple sclerosis (MS). METHOD: Fifty-seven patients with diagnosis of relapsing-remitting MS and 47 age- and gender-matched controls were studied. A conventional MR imaging protocol and a DTI sequence were performed. One neuroradiologist placed the regions of interest (ROIs) in the FA maps in five different portions of the normal-appearing CC (rostrum, genu, anterior and posterior portion of the body and splenium) in all cases. The statistical analysis was performed with the Mann-Whitney U test and p<0.05 was considered statistically significant. RESULTS: The FA values were lower in the MS patients compared with the controls (p<0.05) in the following CC regions: rostrum (0.720 vs 0.819), anterior body (0.698 vs 0.752), posterior body (0.711 vs 0.759) and splenium (0.720 vs 0.880). CONCLUSION: In this series, there was a robust decrease in the FA in all regions of the normal-appearing CC, being significant in the rostrum, body and splenium. This finding suggests that there is a subtle and diffuse abnormality in the CC, which could be probably related to myelin content loss, axonal damage and gliosis.

Diffusion tensor MR imaging evaluation of the corpus callosum of patients with multiple sclerosis / Avaliação do corpo caloso em pacientes com esclerose múltipla através de imagens de RM por tensor de difusão

OBJECTIVE: To evaluate the fractional anisotropy (FA) values of the normal-appearing white matter of the corpus callosum (CC) in patients with relapsing-remitting multiple sclerosis (MS). METHOD: Fifty-seven patients with diagnosis of relapsing-remitting MS and 47 age- and gender-matched controls were studied. A conventional MR imaging protocol and a DTI sequence were performed. One neuroradiologist placed the regions of interest (ROIs) in the FA maps in five different portions of the normal-apearing CC (rostrum, genu, anterior and posterior portion of the body and splenium) in all cases. The statistical analysis was performed with the Mann-Whitney U test and p<0.05 was considered statistically significant. RESULTS: The FA values were lower in the MS patients compared with the controls (p<0.05) in the following CC regions: rostrum (0.720 vs 0.819), anterior body (0.698 vs 0.752), posterior body (0.711 vs 0.759) and splenium (0.720 vs 0.880). CONCLUSION: In this series, there was a robust decrease in the FA in all regions of the normal-appearing CC, being significant in the rostrum, body and splenium. This finding suggests that there is a subtle and diffuse abnormality in the CC, which could be probably related to myelin content loss, axonal damage and gliosis.

OBJETIVO: Avaliar os valores da anisotropia fracionada (FA) da substância branca aparentemente normal do corpo caloso (CC) em pacientes com esclerose múltipla (EM) remitente recorrente. MÉTODO: 57 pacientes com diagnóstico de EM remitente recorrente e 47 controles pareados por sexo e idade foram estudados. O protocolo convencional de RM e imagens de tensor de difusão foram adquiridas. Um neurorradiologista posicionou as regiões de interesse nos mapas de FA em seis porções do CC aparentemente normal (rostro, joelho, anterior e posterior porções do corpo e esplênio) em todos os casos. A análise estatística foi realizada com o teste Mann-Whitney U e p<0,05 foi considerado estatisticamente significativo. RESULTADOS: Os valores de FA foram menores nos pacientes com EM comparados com os controles (p<0,05) nas seguintes porções do CC: rostro (0,720 vs 0,819), corpo anterior (0,698 vs 0,752), corpo posterior (0,711 vs 0,759) e esplênio (0,720 vs 0,880). CONCLUSÃO: Na presente série houve redução robusta na FA em todas as regiões aparentemente normais do CC, sendo significativa no rostro, corpo e esplênio. Este achado sugere que há alteração difusa no corpo caloso de pacientes com EM, provavelmente relacionada a perda da mielina, lesão axonal e gliose.

Variantes da síndrome de Guillain-Barré. Forma faringo-cérvico-braquial e forma paraparética. Apresentaçåo de casos clínicos e revisåo de literatura / Variants of Guillian-Barré syndrome. Faringo-cervico-brachial form and par-peretic form. Present clinical cases and review literature

Os autores apresentam casos raros de variantes da Síndrome de Guillain-Barré (SGB) descritas na literatura como forma faringo-cérvico-braquial e forma parapética cujos diagnósticos só foram confirmados após exaustiva investigaçåo e longo acompanhamento evolutivo. É feiro uma revisåo atualizada do assunto, abordando, em especial, as diferentes formas de apresentaçåo da doença e os critérios diagnósticos para SBG adotados pelo Institute of Neurological and Communicative Disorders and Stroke (NINDS)

Variantes da sindrome de Guillain-Barre. Forma faringo-cervico-branquial e forma paraparetica. Apresentacao de casos clinicos e revisao da literatura

Os autores apresentam casos raros de variantes da Sindrome de Guillain-Barre (SGB) descritos na literatura como forma faringo-cervico-branquial e forma paraparetica cujos diagnosticos so foram confirmados apos exaustiva investigacao e longo acompanhamento evolutivo. E feita uma revisao atualizada do assunto, abordando, em especial, as diferentes formas de apresentacao da doenca e os criterios diagnosticos para SGB adotados pelo Institute of Neurological and Communicative Disorders and Stroke (N.I.N.D.S.).