Does fatigue occur in MS patients without disability?

BACKGROUND: Motor dysfunction and fatigue are the most common impairments that are associated with multiple sclerosis (MS). Walk tests and scales demonstrate the presence of fatigue in patients with MS with different levels of disability. OBJECTIVE: To evaluate objective and subjective fatigue in MS patients without disability. METHODS: Were selected MS patients with relapsing remitting clinical course, from 18 to 55 years old and EDSS 0 to 1.5; controls were paired for age, gender, body mass index, and physical activity level. Fatigue caused by pulmonary diseases, anemia, diabetes, thyroid disease, psychiatry diseases (except depression), and orthopedic and rheumatologic diseases are excluded. All participants performed the 6-minute walk test (6MWT), the MS Functional Composite (MSFC), and completed the Modified Fatigue Impact Scale (MFIS) and the Beck Depression Inventory. A multivariate model was applied to identify the variables associated with fatigue. RESULTS: 54 individuals were selected (31 patients; 23 controls). In the MSFC and 6MWT, no significant difference was observed between the groups. A MFIS total score indicated fatigue in 35% of the patients, 42% in the physical domain, 25.8% in the cognitive domain, and 29% in the psychosocial domain, which differed from the controls in all comparisons. Fatigue was associated with MS, low-physical activity, and mood disorders. CONCLUSIONS: Fatigue occurs in patients with MS in the absence of motor dysfunction and is associated with the disease itself, the sedentary lifestyle, and mood disorders. The 6MWT is not useful to demonstrate motor fatigue in subjects without neurological disability.

Postpartum Treatment With Immunoglobulin Does Not Prevent Relapses of Multiple Sclerosis in the Mother.

Multiple sclerosis (MS) is a chronic, neurological, immune-mediated disease that can worsen in the postpartum period. There is no consensus on the use of immunoglobulin for prevention of disease relapses after delivery. We have shown that the controversial beneficial effect of immunoglobulin given immediately after birth could not be observed in patients with MS.

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.

Is it useful to perform carbon monoxide diffusion capacity and respiratory muscle function tests in patients with multiple sclerosis without disability?

BACKGROUND AND OBJECTIVE: Impairment of respiratory function has been described in end-stage multiple sclerosis (MS), as well as in patients with mild to severe disability. No data are available regarding the respiratory function of MS patients without disability. The objective of this study was to assess the pulmonary function, respiratory muscle strength and carbon monoxide diffusion capacity of the lungs (DL(CO)) in patients with relapsing-remitting multiple sclerosis (RRMS) without disability. METHODS: Twenty-seven RRMS patients and 25 healthy control subjects were recruited. All subjects underwent clinical and neurological examination, and spirometry; lung volumes, DL(CO) and maximal respiratory pressures were measured. All subjects were rated on the Modified Fatigue Impact Scale and Fatigue Severity Scale scales. RESULTS: There were no significant differences in age, gender, height, weight or body mass index between the groups. The mean duration of illness in the MS group was 5.44 ± 3.74 years, and the mean Expanded Disability Status Scale was 0.62 ± 0.65. The mean values for total lung capacity, forced expiratory volume in 1 s (FEV(1)) and FEV(1) /FVC were normal in both groups. Fifteen RRMS patients exhibited a reduction in maximal expiratory pressure (MEP), but only one patient exhibited a reduction in maximal inspiratory pressure. The mean values for DL(CO) were lower in RRMS patients (P = 0.0004) than in the control group. DL(CO) was decreased in 15 (55.55%), out of 27 RRMS patients. The fatigue scale results were not correlated with pulmonary function test results CONCLUSIONS: DL(CO) and MEP may be impaired in RRMS patients without disability.

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.

Differences in the progression of primary progressive multiple sclerosis in Brazilians of African descent versus white Brazilian patients.

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.

Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice.

BACKGROUND: During the last two decades, neuromyelitis optica spectrum disorder (NMOSD) has undergone important changes, with new diagnostic markers and criteria, better recognition of clinical phenotypes, better disease prognosis and new therapeutic approaches. Consequently, management of NMOSD patients in Latin American (LATAM) has become more complex and challenging in clinical practice. In making these consensus recommendations, the aim was to review how the disease should be managed and treated among LATAM patients, in order to improve long-term outcomes in these populations. METHODS: A panel of LATAM neurologists who are experts in demyelinating diseases and dedicated to management and care of NMOSD patients gathered virtually during 2019 and 2020 to make consensus recommendations on management and treatment of NMOSD patients in LATAM. To achieve this consensus, the RAND/UCLA methodology for reaching formal consensus was used. RESULTS: The recommendations focused on diagnosis and differential diagnoses, disease prognosis, tailored treatment, identification of suboptimal treatment response and special circumstances management. They were based on published evidence and expert opinions. CONCLUSIONS: The recommendations of these consensus guidelines seek to optimize management and specific treatment of NMOSD patients in LATAM.

State of the Art and Future Challenges in Multiple Sclerosis Research and Medical Management: An Insight into the 5th International Porto Congress of Multiple Sclerosis.

The 5th International Porto Congress of Multiple Sclerosis took place between the 14th and 16th of February 2019 in Porto, Portugal. Its intensive programme covered a wide-range of themes-including many of the hot topics, challenges, pitfalls and yet unmet needs in the field of multiple sclerosis (MS)-led by a number of well-acknowledged world experts. This meeting review summarizes the talks that took place during the congress, which focussed on issues in MS as diverse as the development and challenges of progressive MS, epidemiology, differential diagnosis, medical management, molecular research and imaging tools.

Is Asian type MS an MS phenotype, an NMO spectrum disorder, or a MOG-IgG related disease?

BACKGROUND: A specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease. METHODS: We selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment "at nadir" and "at recovery" of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied. RESULTS: Forty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown). CONCLUSION: In Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype.

Prevalence of multiple sclerosis in Goiânia, Goiás, Brazil.

OBJECTIVE: Multiple sclerosis (MS) prevalence, in some cities in Brazil, was estimated and was found to range from 0.75 to 30.7/100,000. The reasons for such a large variation in rates of prevalence are not clear, but environment and genetics help to explain this phenomenon. METHODS: A cross-sectional study using three sources of case ascertainment to estimate the prevalence of MS in the city of Goiânia in December, 2015. RESULTS: A total of 318 MS patients was found after removing overlapping sources. The prevalence of MS was 22.4/100,000 population. CONCLUSION: Our study was the first in Goiás and the third in the midwest region, and we found a great increase in the prevalence of MS in the region. It is necessary to perform other studies using the same methodology for a more accurate evaluation of the true prevalence of MS in Brazil.

Familial multiple sclerosis in a Brazilian sample: Is HLA-DR15 involved in susceptibility to the disease?

BACKGROUND: The HLA-DR15 extended haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 comprises the strongest genetic risk factor for multiple sclerosis (MS). The aim of this work was to investigate whether HLA-DR15 alleles were significantly associated with the susceptibility to MS familial forms (MSf) in an admixed Brazilian population. METHODS: Association analyses between DR15 and the clinical and demographic variables were made. RESULTS: We have genotyped 25 familial cases. The DR15 was detected in 11/25 (44%) of them and in none of controls (P < .00001). DR15 was significantly associated to a foreign ancestor background (P = .029) and later age of onset (P = .018).

Clinical course of optic neuritis in patients with relapsing neuromyelitis optica.

OBJECTIVE: To describe the clinical characteristics, course, and prognosis of optic neuritis in recurrent neuromyelitis optica. METHODS: 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). RESULTS: 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%). CONCLUSIONS: 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.

The reliability of specific primary progressive MS criteria in an ethnically diverse population.

UNLABELLED: Three different diagnostic criteria for primary progressive MS were recently proposed for Caucasian population of Western European region. OBJECTIVE: 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. METHODS: 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). CONCLUSION: 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.

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.

Lower frequency of antibodies to MOG in Brazilian patients with demyelinating diseases: An ethnicity influence?

OBJECTIVE: Antibodies against Myelin Oligodendrocyte glycoprotein (MOG-Ab) have been investigated as potential biological marker for neuromyelitis optica (NMO) and high-risk syndromes (HR) negative for AQP4-Ab in populations with different ethnic background. We tested AQP4 and MOG antibodies in a Brazilian population with high African ethnic background. METHOD: The study population was composed of adult patients from Rio de Janeiro with inflammatory demyelinating diseases (new and old cases). Blood samples were sent blindly to test the AQP4 and MOG antibodies by CBA. The frequency of positive MOG-Ab was estimated in the NMOHR and the NMO spectrum disorders (NMOSD). A systematic review with meta-analysis assessed the frequency of MOG-Ab in Caucasians and non-Caucasians. RESULTS: 200 adult patients (52% Afro-Brazilian) 115 of them with NMOHR were tested. MOG antibodies were found in 5/68 negative cases of AQP4-Ab negative (7%). The criteria for NMOSD were fulfilled by 70 patients with NMOHR and none of them was positive for MOG-Ab. A low prevalence of MOG antibodies and a predominant phenotype of bilateral Optic Neuritis were found in most non-Caucasian patients. CONCLUSION: The low frequency of MOG Ab in patients from Rio de Janeiro and in other non-Caucasian populations suggests a racial/ancestral influence.

Case Report: Acute Transverse Myelitis after Zika Virus Infection.

We report here one case of Zika virus (ZIKV) infection associated with auto-immunity directed against the central nervous system in a Brazilian woman who developed acute transverse myelitis 9 days after recovery from an acute episode of fever with generalized erythema. Imaging of the spinal cord showed an elongated area on the T1-T10 level with gadolinium uptake. The diagnostic of the ZIKV infection was confirmed by cerebrospinal fluid and serum analysis. This patient had serum positivity for autoantibodies against myelin oligodendrocyte glycoprotein (MOG), a specific antibody against the myelin sheath. We propose that a direct central nervous system infection by ZIKV could lead to a specific auto-immunity against MOG protein.

Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms.

Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

Neuromyelitis optica: phenotypic characteristics in a Brazilian case series.

OBJECTIVE: To describe the characteristics of 34 Brazilian NMO patients. To evaluate the contribution of the 2015 criteria to the diagnosis of NMO spectrum disorders (NMOSD) in 40 patients with longitudinal extensive transverse myelitis (LEMT). METHODS: This is a retrospective, descriptive and analytic study. RESULTS: Among NMO patients, there was a predominance of women, with onset in the fourth decade of life, and AQP4-IgG seropositivity in 73.5%. The diagnosis of NMOSD was established in 37.5% of LETM patients according to AQP4-IgG positivity and in 5% of LETM patients if the AQP4-IgG result was unknown. CONCLUSIONS: The characteristics of this series are similar to those of other Western populations. The AQP4-IgG testing assists in the diagnosis of NMOSD.

Risk factors for convertion to clinically defined multiple sclerosis after clinically isolated syndrome in a racially mixed Brazilian cohort.

UNLABELLED: Clinically isolated syndrome may reflect the first symptom of Multiple Sclerosis. Though more prevalent in Caucasians, MS can also affect Afrodescendts. Modifying disease drugs can delay convertion to clinically defined multiple sclerosis, therefore, identify patients at a higher risk of convertion is important. However data of risk factors in racially mixed population are scarce. OBJECTIVES: To analyze predictor factors to the conversion from CIS to CDMS in a mixed race Brazilian cohort. PATIENTS AND METHODS: It is a prognostic observational retrospective study, in 122 patients from MS referential center at Hospital da Lagoa, Rio de Janeiro-Brazil. Demographic and clinical features, as well as MRI and cerebrospinal fluid data were analyzed. RESULTS: After five years follow-up 87.3% converted to CDMS. Regarding to median time of conversion, there was no difference between gender, race, age at onset, mono or polysymptomatic presentation. Cerebellar CIS significantly reduced time to second event; likewise sphincter impairment. Considering DMD, patients without treatment converted earlier. CONCLUSION: Ancestry did not influence conversion risk. Cerebellar and shpincter impairment as well as MRI criteria both Barkhof/Tintoré and Swanton were important predictors. In future studies it should be also analysed the risk factors of progression in mixed race populations.