The neurological complications of chikungunya virus: A systematic review.

We performed a systematic review on the neurological complications of chikungunya virus. Such complications are being reported increasingly, owing primarily to the scale of recent epidemics but also to a growing understanding of the virus' neurovirulence. We performed a thorough literature search using PubMed and Scopus databases, summating the data on all published reports of neurological disease associated with chikungunya virus. We appraised the data for each major condition in adults, children, and neonates, as well as evaluating the latest evidence on disease pathogenesis and management strategies. The review provides a comprehensive summary for clinicians, public health officials, and researchers tackling the challenges associated with this important emerging pathogen.

Zika virus infection in the returning traveller: what every neurologist should know.

Zika virus has been associated with a wide range of neurological complications. Neurologists in areas without current active transmission of the virus may be confronted with Zika-associated neurological disease, as a large number of returning travellers with Zika virus infection have been reported and the virus continues to spread to previously unaffected regions. This review provides an overview of Zika virus-associated neurological disease and aims to support neurologists who may encounter patients returning from endemic areas.

SARS-CoV-2 Infection and Guillain-Barré Syndrome: A Review on Potential Pathogenic Mechanisms.

Since December 2019, the world has been facing an outbreak of a new disease called coronavirus disease 2019 (COVID-19). The COVID-19 pandemic is caused by a novel beta-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 infection mainly affects the respiratory system. Recently, there have been some reports of extra-respiratory symptoms such as neurological manifestations in COVID-19. According to the increasing reports of Guillain-Barré syndrome following COVID-19, we mainly focused on SARS-CoV-2 infection and Guillain-Barré syndrome in this review. We tried to explain the possibility of a relationship between SARS-CoV-2 infection and Guillain-Barré syndrome and potential pathogenic mechanisms based on current and past knowledge.

Peripheral spectrum neurological disorder after arbovirus infection is associated with HLA-F variants among Northeastern Brazilians.

INTRODUCTION: Non-classical class I human leukocyte antigens (HLA) molecules are known to modulate the function of cytotoxic cells (NK and T CD8+) during viral infection by interacting with inhibitory/activating receptors. However, little is known about the HLA-E/-F genetic variability on arbovirus infections. METHODS: We evaluated by massive parallel sequencing the full HLA-E/-F genetic diversity among patients infected during the arbovirus (ZIKV, DENV, and CHIKV) outbreak leading to a broad range of neurological complications in the Brazilian State of Pernambuco. In parallel, healthy blood donors from the same area were also studied. Plink and R software were used for genetic association study. To limit the false-positive results and enhance the reliability of the results, we adopted P-values <0.01 as significant levels. RESULTS: Compared to controls, the HLA-F alleles: -1610 C (rs17875375), +1383 G (rs17178385), and +3537 A (rs17875384), all in complete linkage disequilibrium with each other (r2 = 1), were overrepresented in patients presenting peripheral spectrum disorders (PSD). The HLA-F*Distal-D haplotype that harbored the -1610 C allele exhibited a trend increase in PSD group. No associations were found for HLA-E. CONCLUSIONS: Our findings showed that the HLA-F genetic background seems to be more important than HLA-E on the susceptibility to PSD complications.

Cytokines and Soluble HLA-G Levels in the Acute and Recovery Phases of Arbovirus-Infected Brazilian Patients Exhibiting Neurological Complications.

Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1ß, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (P<0.0001), MCP-1 (P<0.0001), HGF (P= 0.0001), and VEGF (P<0.0001) in the acute phase. Fourteen molecules (IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.

The legacy of ZikaPLAN: a transnational research consortium addressing Zika.

Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases.

ZikaPLAN: addressing the knowledge gaps and working towards a research preparedness network in the Americas.

Zika Preparedness Latin American Network (ZikaPLAN) is a research consortium funded by the European Commission to address the research gaps in combating Zika and to establish a sustainable network with research capacity building in the Americas. Here we present a report on ZikaPLAN`s mid-term achievements since its initiation in October 2016 to June 2019, illustrating the research objectives of the 15 work packages ranging from virology, diagnostics, entomology and vector control, modelling to clinical cohort studies in pregnant women and neonates, as well as studies on the neurological complications of Zika infections in adolescents and adults. For example, the Neuroviruses Emerging in the Americas Study (NEAS) has set up more than 10 clinical sites in Colombia. Through the Butantan Phase 3 dengue vaccine trial, we have access to samples of 17,000 subjects in 14 different geographic locations in Brazil. To address the lack of access to clinical samples for diagnostic evaluation, ZikaPLAN set up a network of quality sites with access to well-characterized clinical specimens and capacity for independent evaluations. The International Committee for Congenital Anomaly Surveillance Tools was formed with global representation from regional networks conducting birth defects surveillance. We have collated a comprehensive inventory of resources and tools for birth defects surveillance, and developed an App for low resource regions facilitating the coding and description of all major externally visible congenital anomalies including congenital Zika syndrome. Research Capacity Network (REDe) is a shared and open resource centre where researchers and health workers can access tools, resources and support, enabling better and more research in the region. Addressing the gap in research capacity in LMICs is pivotal in ensuring broad-based systems to be prepared for the next outbreak. Our shared and open research space through REDe will be used to maximize the transfer of research into practice by summarizing the research output and by hosting the tools, resources, guidance and recommendations generated by these studies. Leveraging on the research from this consortium, we are working towards a research preparedness network.

Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis.

The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

[Electromyografic patterns predictive of motor evolution in neuroschistosomiasis]. / Aspectos eletromiográficos preditores da evolução motora de pacientes com neuroesquistossomose.

Neuroschistosomiasis in myeloradicular pattern is frequently observed in patients from Northeast of Brazil. Despite of this, the evolution of neurologic and electromyographic patterns is not well studied in this group of patients. The aims of this study were to describe and compare the clinic and electromyographic abnormalities of patients with neuroschistosomiasis and radicular involvement. We analyzed 21 electromyographic exams of the lower limbs carried out in the initial presentation of the disease. Electromyographic pattern of 95.2% of patients was compatible to axonal lumbosacral multirradiculopathy, with variable denervation extension, but predominantly from levels L2 to S2. There was variable degree of deficit in the lower limbs, and the follow-up of motor disturbances was better more frequently when the roots were involved in smaller number. Electromyography should permit to know the motor prognosis of patients with myeloradiculitis due schistosomiasis.

Guillain-Barré syndrome associated with the Zika virus outbreak in Brazil.

Zika virus (ZIKV) is now considered an emerging flavivirosis, with a first large outbreak registered in the Yap Islands in 2007. In 2013, a new outbreak was reported in the French Polynesia, with associated cases of neurological complications including Guillain-Barré syndrome (GBS). The incidence of GBS has increased in Brazil since 2015, what is speculated to be secondary to the ZIKV infection outbreak. The gold-standard test for detection of acute ZIKV infection is the polymerase-chain reaction technique, an essay largely unavailable in Brazil. The diagnosis of GBS is feasible even in resource-limited areas using the criteria proposed by the GBS Classification Group, which is based solely on clinical grounds. Further understanding on the relationship of ZIKV with neurological complications is a research urgency.

Depression and anxiety in individuals with amyotrophic lateral sclerosis: a systematic review.

INTRODUCTION: Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature. METHODS: We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria. RESULTS: The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms. CONCLUSIONS: Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it.

Real-life experience with fampridine (Fampyra®) for patients with multiple sclerosis and gait disorders.

BACKGROUND: Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). OBJECTIVE: To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. METHODS: Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. RESULTS: The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. CONCLUSION: Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

Recommendations by the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and the Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) on vaccination in general and specifically against SARS-CoV-2 for patients with demyelinating diseases of the central nervous system / Recomendações do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia (DCNI/ABN) e do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e Doenças Neuroimunológicas (BCTRIMS) sobre vacinação em geral e contra a SARS-CoV-2 para pacientes com doenças desmielinizantes do sistema nervoso central

ABSTRACT The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

RESUMO O DC de Neuroimunologia da ABN e o BCTRIMS trazem, nesse documento, as recomendações sobre vacinação da população com doenças desmielinizantes do sistema nervoso central (SNC) contra infecções em geral e contra o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2), causador da COVID-19. Destaca-se a gravidade do atual momento frente ao avanço da COVID-19 em nosso País, o que torna mais evidente e importante a criação de guia de referência para orientação aos médicos, pacientes e autoridades de saúde pública quanto à vacinação, meio efetivo e seguro no controle de determinadas doenças infecciosa. O DCNI/ABN e o BCTRIMS recomendam que os pacientes com doenças desmielinizantes do SNC (ex., EM e NMOSD) sejam constantemente monitorados, quanto a atualização do seu calendário vacinal, especialmente, no início ou antes da mudança do tratamento com uma droga modificadora de doença (DMD). É importante também salientar que as vacinas são seguras e os médicos devem estimular o seu uso em todos os pacientes. Evidentemente, deve ser dada especial atenção às vacinas com vírus vivos atenuados. Por fim, é importante que os médicos verifiquem qual DMD o paciente está em uso e quando foi feita a sua última dose, pois cada fármaco pode interagir de forma diferente com a indução da resposta imune.

[Neurological manifestations of dengue: study of 41 cases]. / Manifestações neurológicas de dengue: estudo de 41 casos.

UNLABELLED: The increase of encephalitis and meningoencephalitis in patients with dengue, diagnosed at a public hospital, Neurology State reference, we adopted systematic data collection. OBJECTIVE: The objective was to present 41 cases of neurological manifestations of dengue and to compare data with literature. METHOD: This is a descriptive study, retrospective from March to July 1997 and, prospective, from February to May 2002, analyzing damaged neurological regions and diagnostic of 41 patients. RESULTS: Involved regions were brain (5/7 cases - 71.4%, in 1997, and 20/34 cases - 58.8%, in 2002), spinal cord (2/34 cases - 5.9% in 2002) and peripheral nerves (2/7 cases - 28.6% in 1997 and 12/34 cases - 35.3% in 2002). There was no meningeal involvement. According to topography, there was encephalic and peripheral nerves diagnosis in both periods and, exclusively in 2002, spinal cord damage. Cerebral hemorrhage and acute disseminated encephalomyelitis were diagnosed for the first time, as well as hemifacial spasm worsening as possible neurological manifestation of dengue. CONCLUSION: This is the third casuistics in dengue and nervous system. Three dengue complications were diagnosed, for the first time registered on the literature.

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study.

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients' demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in 200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found with gender, age at onset, ethnicity, early or late onset forms, disease course, or long-term severe disability. The relative frequency of NMO among relapsing-remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of miscegenation found in SA, MS affects three quarters of all patients with IIDD, mainly white young women who share similar clinical characteristics to those in Western populations in the northern hemisphere, with the exception of ethnicity; approximately one-third of all cases occur among non-white individuals. At the last assessment, the majority of RRMS patients showed mild disability, and the risk for secondary progression was significantly superior among those of African ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young African-Brazilian women, evolving with a recurrent course and causing moderate or severe disability in both ethnic groups. The South-North gradient with increasing NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela confirmed previous studies showing a higher frequency of NMO among non-white populations.

[Epidemiology of 118 cases of multiple sclerosis after 15 years of follow-up on the reference center of Hospital da Restauração, Recife, Pernambuco, Brazil]. / Epidemiologia de 118 casos de esclerose múltipla com seguimento de 15 anos no centro de referência do Hospital da Restauração de Pernambuco.

UNLABELLED: The prevalence of multiple sclerosis (MS) has a considerable variability all over the world. According to Kurtzke, South America is considered to have low prevalence (minor than 5 cases: 100000 habitants). OBJECTIVE: To describe the MS epidemiology on a reference center, compared to eight Brazilian series. METHOD: according to a descriptive, prospective, longitudinal, prevalence study, we analyzed data of 118 patients, who attended at the Reference Center for Attention to Patients with Demielinizating Diseases of Hospital da Restauração (CRAPPDD-HR)-Recife-Pernambuco, Brazil, from January 1987 to March 2002, to have MS diagnosed according to Poser criteria. RESULTS: The patients were followed up by 1 to 15 years. Ninety five (80.5%) patients were in treatment with immune-modulators. The prevalence was 1,36:100000 habitants. We have identified: predominance of mulattoes (110,93.2%), 82 (82.2%) cases clinically defined, 15 (12.7%) cases laboratorial defined and 6 (5.1%) cases clinically probable; a number of maximum bouts equal to 46; more frequent mild EDSS for patients with 1 to 10 years of MS of remittent-recurrent (RR) form. Gender rate of 83 cases of RR form was equivalent to the general one, however on RR with secondary progressive form form, the rate was 2.5 times greater for females than for males, and on primary progressive form, 5.5 times greater for males. CONCLUSION: Although some results of this research had been similar to that of eight studies used as standards for comparison, the differences will require new approaches.

[The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: I. The evidences for the use of immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation]. / Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla: I. As evidências para o uso de imunossupressores, plasmaférese e transplante autólogo de células tronco.

Since the sixties immunosuppressive agents have been used in the treatment of multiple sclerosis as there was cumulating evidence of the inflammatory nature of the disease. Cyclophosphamide, azathioprine and methotrexate have been the most frequently employed drugs whereas other agents such as cyclosporine and cladribine have been recently tested for RRMS. Mithoxantrone, on the other hand, was approved by the FDA for treatment of aggressive forms of the disease. Other immunointerventions such as plasma exchange and autologous hematopoietic stem cell transplantation have recently been employed in some special circumstances. This paper analyses the most important published data on the use of the immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation according to the classes of evidences and types of recommendations of these drugs and immunointerventions. It provides sufficient information to support the guidelines expressed in the BCTRIMS Expanded Consensus on Treatment of MS.

[The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: III. Evidence and recommendation-based guidelines]. / Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla: III. Diretrizes baseadas em evidências e recomendações.

There has been unprecedented advances in knowledge of multiple sclerosis (MS) in the last few years. A new set of criteria for its diagnosis and a bunch of recent clinical trials with disease-modifying agents (DMA) have been published. All of that has made it necessary to update and expand the previous consensus for MS treatment as formulated by the Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS) two years ago. The BCTRIMS Expanded Consensus emphasizes the need to (1) consider MS treatment on an individual basis; (2) educate patients about the potential benefits and risks of treatment; (3) monitor drugs side effects; (4) have a signed Informed Consent Form; (5) consider the relative cost of the drug. The various clinical possibilities and the indications of the DMA and other immunointerventions are considered according to classes of evidences and types of recommendations. The BCTRIMS Expanded Consensus on Treatment of MS may turn out to be a model to other developing countries.

How do we manage and treat a patient with multiple sclerosis at risk of tuberculosis?

Tuberculosis continues to be a serious health problem worldwide. The disease continues to be underdiagnosed and not properly treated. In conditions that affect the immune system, such as multiple sclerosis (MS), latent tuberculosis may thrive and reactivate during the use of immunomodulatory and immunosuppressive drugs. Among the best treatment options for patients with latent or active tuberculosis who have MS are IFN-ß, glatiramer acetate and mitoxantrone. Drugs leading to a reduced number and/or function of lymphocytes should be avoided or used with caution. Tuberculosis must always be investigated in patients with MS and treated with rigor.