Oral Colonization by Candida Species in Patients with Multiple Sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease that affects the central nervous system. Since immune system plays a key role in this disease, patients with MS can present higher risk of infections. PURPOSE: This study aimed to investigate the prevalence of Candida spp. in the oral cavity of MS patients in relation to a control group METHODS: In total, 100 individuals were selected: 55 diagnosed with MS and 45 healthy individuals (control group). Saliva samples were collected and seeded in culture media selecting for Candida. Following an incubation period of 48 h, colony-forming units (CFU mL-1) were counted and colonies were isolated for Candida species identification by multiplex PCR. The results were analysed by chi-squared and Mann-Whitney U statistical tests considering a significance level of 5%. RESULTS: Candida spp. were confirmed in the oral cavity of 50.09% patients in the MS group and 35.55% individuals in the control group. In individuals positive for the growth of Candida spp., the median values of Candida colonies were 220 CFU mL-1 for the MS group and 120 CFU mL-1 for the control group. However, no statistically significant differences were observed between groups for both prevalence and CFU mL-1 count. Of the Candida species identified, 73.91% were C. albicans, 21.73% C. glabrata, 2.17% C. tropicalis, and 2.17% C. krusei. CONCLUSIONS: The colonization of Candida spp. in the oral cavity of individuals with multiple sclerosis was higher than in the control group; however these findings were not proven to be statistically significant.

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding.

Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or ß-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.

Cost analysis of multiple sclerosis in Brazil: a cross-sectional multicenter study.

BACKGROUND: Multiple sclerosis (MS) is a central nervous system disease associated with irreversible progression of disability, which imposes a substantial socioeconomic onus. The objective of this study was to determine the economic impact of multiple sclerosis from the Brazilian household and healthcare system perspectives. Secondary objectives were to assess the impact of fatigue on daily living and health-related quality of life (HRQL) of MS patients. METHODS: This is a cross-sectional study in which Brazilian eligible patients attending eight major MS specialized sites answered an interview capturing data on demographics, disease characteristics and severity, comorbidities, resource utilization, fatigue, utilities and health-related quality of life from November/2011 to May/2012 . Costs were assessed considering a prevalence-based approach within 1 year of resource consumption and were estimated by multiplying the amount used by the corresponding unit cost. Patients were classified as having mild, moderate or severe disability according to the Expanded Disability Status Scale (EDSS). RESULTS: In total, 210 patients who met eligibility criteria were included, 40 % had mild, 43 % moderate and 16 % severe disability; disability level was missing for 1 %. The average total direct cost per year was USD 19,012.32 (SD = 10,465.96), and no statistically significant differences were not observed according to MS disability level (p = 0.398). The use of disease modifying therapies (DMTs) corresponded to the majority of direct expenditures, especially among those patients with lower levels of disability, representing around 90 % of total costs for mild and moderate MS patients. It was also observed that expenses with medical (except DMTs) and non-medical resources are higher among patients with more severe disease. Worsening disability also had an important influence on health-related quality of life and self-perceived impact of fatigue on daily living. CONCLUSION: Our data demonstrates the significant economic impact of MS on both Brazilian household and health system, in terms of DMTs and other disease management costs. When patients move upwards on the disease severity scale, costs with health resources other than drugs are significantly increased.

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.

Decreased Neurofilament L Chain Levels in Cerebrospinal Fluid and Tolerogenic Plasmacytoid Dendritic Cells in Natalizumab-Treated Multiple Sclerosis Patients - Brief Research Report.

BACKGROUND: Neurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients. OBJECTIVE: To evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment. METHODS: CSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2+) were accessed through flow cytometry analyses. RESULTS: CSF levels of NfL were significantly reduced during NTZ treatment, while the serum levels of sHLA-G were increased. Moreover, NTZ treatment enhanced tolerogenic (HLA-G+, CD274+, and HLA-DR+) molecules and migratory (CCR7+) functions of pDCs in the peripheral blood. CONCLUSION: These findings suggest that NTZ stimulates the production of molecules with immunoregulatory function such as HLA-G and CD274 programmed death-ligand 1 (PD-L1) which may contribute to the reduction of axonal damage represented by the decrease of NfL levels in patients with MS.

Multiphasic disseminated encephalomyelitis associated with herpes virus infection in a patient with TLR3 deficiency.

We report a case of a 14-year-old girl that presented headache, amaurosis, drowsiness, fever, vomiting and diffuse reduction of muscle strength. She had been diagnosed with ADEM one year before and had a previous diagnosis of Toll-Like 3 receptor deficiency. Cerebrospinal fluid analysis revealed pleocytosis (28/mm3, 12/mm3 red blood cells, 70% lymphocytes cells, 2% monocytes cells, 28% neutrophils), normal total protein (38 pg/mL) and normal glucose level (53/mm3). Studies for CSF oligoclonal bands and serum anti-MOG were negative but polymerase chain reaction (PCR) testing was positive for herpes virus 1. In the first ADEM episode, PCR for herpes virus was also positive. Magnetic resonance imaging (MRI) of the brain revealed disseminated hyperintense lesions on T2-weighted and FLAIR images in the white matter of frontal, parietal and temporal lobes, corresponding to extensive asymmetric areas of demyelination that produced mass effect and gadolinium enhancement. Electroencephalography demonstrated irregular diffuse and generalized slow-wave activity with predominance in frontal region. The diagnosis of multiphasic disseminated encephalomyelitis (MDEM) triggered by herpes simplex virus was made. Herpes virus is a neurotropic virus that can cause a wide variety of neurological infection-triggered autoimmune disorders and that is particularly damaging to the central nervous system in situations of impaired immune system. TLR3 is expressed in astrocytes and dendritic cells of the central nervous system and is essential for natural immunity to herpes simplex. TLR3-deficient patients have already been described with herpes simplex encephalitis. TLR3 deficiency may predispose and explain autoimmune and demyelinating manifestations induced by herpes virus. The association of multiphasic disseminated encephalomyelitis triggered by herpes virus in a patient with TLR3 deficiency has not been previously reported in the literature.

Immunomodulator therapy migration in relapsing remitting multiple sclerosis: a study of 152 cases.

BACKGROUND: Since 1997, immunological modulators have been used for treatment of Relapsing Remitting Multiple Sclerosis (RRMS) in the Multiple Sclerosis Attendance and Treatment Center (CATEM) with significant alterations in this disease natural history. AIM: To add data on the experience of CATEM for the treatment of RRMS patients that had immunomodulators. METHOD: RRMS patients that received continuously immunomodulator drugs were evaluated on adherence, migration, withdrawal and progression rates. The patients were divided in three groups by the period of immunomodulators intake. RESULTS: There were registered in Group 1 withdrawal in 98 patients (25%) and adherence in 292 cases (74%); Group 2 interruption of therapy in 140 patients, 92 (31%) due to progression for PSMS, 14 (5%) for pregnancy, withdrawal in 34 (11%), adherence in 88%; Group 3 progression in 41 (26%), pregnancy in 3 (2%) withdrawal in 42 (27%) and adherence in 72%. The migration rate was about one third (31.57%) and the principal cause was therapeutic failure; the mean migrating time was 0.5-2.5 years in group 3. CONCLUSION: Immunomodulatory treatment for RRMS patients may have significant levels of failure and side effects; the adherence was compatible with the international literature.

Suicidal ideation, anxiety, and depression in patients with multiple sclerosis.

INTRODUCTION: Psychiatric disorders frequently occur in patients with multiple sclerosis (MS); however, limited reports are available on these comorbidities. We aimed to investigate the relationships among MS, anxiety, depression, and suicidal ideation. METHODS: One hundred and thirty two patients with relapsing-remitting MS were evaluated using the Expanded Disability Status Scale, Beck Depression Inventory-II (BDI-II), Beck Scale for Suicide Ideation (BSI), and Hospital Anxiety and Depression Scale. RESULTS: A hierarchical regression analysis was performed to evaluate the variables. The regression equation significantly predicted the BSI score (R2 = 0.306; adjusted R2 = 0.273; F (9, 125) = 9.18; p < 0.0005), and the BDI-II score was the only variable that contributed significantly to this model (p < 0.0005). CONCLUSIONS: A high prevalence of depression and anxiety, and a higher rate of suicidal ideation were identified in MS patients compared to the general population. The presence of depressive symptoms appeared to have a direct influence on the risk of suicide.

Attention impairment associated with relapsing-remitting multiple sclerosis patients with mild incapacity.

Neuropsychological studies have consistently reported cognitive dysfunctions associated with multiple sclerosis. One-hundred fifteen subjects with relapsing-remitting multiple sclerosis (RRMS) were compared with forty health controls according to a neuropsychological test battery, which included digit span, trail making, cancellation and stroop test. Both groups were matched for age, sex and educational level. Subjects with RRMS had a worse performance the speed of response. Subjects with RRMS spent more time to complete the test in either sections A (p=0.001) or B (p=0.001), although there was no significant difference in terms of number of errors. The total time required to finish the Stroop test was higher for subjects with RRMS (p<0.001), being the time difference between groups significant at trial 4 (p<0.001). Attention impairment in subjects with RRMS is related to slowed central processing, which may be affected in all stages, including impairment of automatic and controlled processing of information and in the motor program.

[Relation between fatigue and autonomic disturbances in multiple sclerosis]. / Relação entre fadiga e distúrbios autonômicos na esclerose múltipla.

Fatigue is a common symptom in multiple sclerosis (MS). The objective of this study was to relate fatigue and autonomic disturbances in MS. Fifty patients with MS relapsing remitting clinical form participated in this study. Thirty three (66%) were women and 17 (34%) men. Score less or equal to 3.5 in the EDSS. Five non invasive cardiovascular tests were applied in all patients for the sympathetic and parasympathetic evaluation. The results obtained in the hand grip test were increased in the blood pressure of 14.62 +/- 9.13 mmHg for the group with fatigue and of 21.68 +/- 7.18 mmHg for the non fatigue group. This difference was statistically significant (p<0.05). Conclusion is that there is a loss in the capacity to increase blood pressure in patients with fatigue suggesting a sympathetic dysfunction.

[Multiple sclerosis: cross-cultural adaptation and validation of the modified fatigue impact scale]. / Esclerose múltipla: adaptação transcultural e validação da escala modificada de impacto de fadiga.

OBJECTIVE: The aim of this study is a cross-cultural adaptation and validation of the modified fatigue impact scale for Portuguese (MFIS-BR). METHOD: The MFIS was translated to Portuguese and re-translated to English. Two pilot studies had been carried through to obtain the MFIS-BR, which was applied to 57 consecutive stable MS patients and 45 healthy controls. The retest was applied 30 days later. RESULTS: In analyzing the statistics the internal consistency reability was similar to the original scale (0.74-0.86). The MFIS-BR showed ability to identify the different groups. Concerning the reliability the interclass correlation coefficient showed an excellent agreement (0.264-1.0). CONCLUSION: The MFIS-BR fills the criteria of applicability, sensibility which are similar to the original version.

[Vestibular rehabilitation in patients with relapsing-remitting multiple sclerosis]. / Reabilitação vestibular em pacientes com esclerose múltipla remitente-recorrente.

Multiple sclerosis (MS) is a demyelinating, inflammatory illness, that attack the white matter of the central nervous system, and abnormal vestibular sensations (vertigo, disequilibrium) are frequent. The vestibular rehabilitation (VR) is determined by mechanisms of adaptations, neural substitutions and compensations. This study evaluated the improvement of the central or peripheral vertigo in patients with relapsing-remitting MS submitted to the VR (exercises of Cawthorne-Cooksey), through the scale of Berg and Dizziness Handicap Inventory (DHI). In this sample of 4 cases the VR, carried through in a period of 2 months, demonstrated the improvement in 3 patients according to the Berg scale and in 2 patients considering that of the DHI.

Characterization of the first symptoms of multiple sclerosis in a Brazilian center: cross-sectional study.

CONTEXT AND OBJECTIVE:: Multiple sclerosis (MS) is a chronic, immune-mediated and degenerative central nervous system (CNS) disease with well-established diagnostic criteria. Treatment can modify the course of the disease. The objective of this study was to describe the initial symptoms of multiple sclerosis in a Brazilian medical center. DESIGN AND SETTING:: Descriptive study, conducted in a Brazilian reference center for multiple sclerosis treatment. METHODS:: Data on 299 patients with confirmed diagnoses of MS were included in the study. Their medical files were evaluated and the data were analyzed. RESULTS:: The most common symptom involved the cranial nerves (50.83%) and unifocal manifestation was presented by the majority of this population (73.91%). The mean time between the first symptom and the diagnosis was 2.84 years. Unifocal symptoms correlated with longer time taken to establish the diagnosis, with an average of 3.20 years, while for multifocal symptoms the average time taken for the diagnosis was 1.85 years. Unifocal onset was related to greater diagnostic difficulty. CONCLUSIONS:: MS is a heterogeneous disease and its initial clinical manifestation is very variable.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands.

The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions. RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

Immunomodulatory treatment in multiple sclerosis: experience at a Brazilian center with 390 patients.

UNLABELLED: Since 1993 the Federal Drug Administration approved the use of immunomodulatory therapy in multiple sclerosis (MS), modifying the natural course of disease, as demonstrate our experience in treatment of MS patients at the MS Treatment Center (CATEM). OBJECTIVE: To evaluate patient behavior using immunomodulatory therapy for a period of five years treatment. METHOD: We selected 390 patients in CATEM with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. RESULTS: At initial treatment 292 (61.5%) patients presented RRMS, 98 (20.6%) SPMS with relapses, 27 SPMS (5.6%) and 58 (12.1%) primary progressive MS (PPMS). In RRMS 182 (62.5%) used the interferon beta 1a SC, 15 (5.2%) interferon beta 1a IM, 85 (29%) interferon beta 1b and 10 (3.3%) glatiramer acetate. In SPMS 63 (64.3%) used interferon beta 1a SC, 4 (4.1%) interferon beta 1a IM and 31 (31.4%) interferon beta 1b. We observed that in this period 195 (50%) migrated between drugs, 35 (9%) gave up therapy and 160 (41%) continued the initial therapy. CONCLUSION: Stopping the immunomodulatory therapy emerges as a problem in the second year of treatment and it can be a subset of interferon non responsive or development of neutralizing antibodies.

[Fatigability evaluation on multiple sclerosis patients by using a hand held dynamometer]. / Avaliação da fatigabilidade em pacientes com esclerose múltipla através do dinamômetro manual.

Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS). The aim of this study was to evaluate the fatigability on patients with MS by the application of hand grip isotonic and isometric exercises with dynamometer. As results the fatigability, the isometric strength and time were statistically similar in the control group and in MS. We conclude that although fatigue is a frequent subjective complaint on MS, the fatigability and the recover after exercises seems to be normal.

Olfactory alterations in patients with multiple sclerosis.

OBJECTIVE: To assess olfactory function using the Connecticut test and verify correlations between olfactory alteration, disease duration and the Expanded Disability Status Scale (EDSS). METHODS: One hundred MS patients and 100 healthy control patients responded to a questionnaire. Those with olfactory alteration underwent a facial CT to exclude other causes. RESULTS: Thirty-two percent of patients showed alterations, compared with 3% in the healthy control group. Patients having EDSS above 4, showed a 5.2-times increased risk of dysfunction. Patients over 38 years of age have a 2.2-times increased risk over younger patients. CONCLUSIONS: Because MS patients are likely to experience olfactory alterations, this study is a useful tool in follow-up care, although more studies are necessary to evaluate the correlations in MS evolution.

MRZH reaction increases sensitivity for intrathecal IgG synthesis in IgG Oligoclonal band negative Multiple Sclerosis patients.

Given the low detection rates of CSF IgG-Oligoclonal bands (IgG-OCB) in non-European Multiple Sclerosis (MS) patients and higher specificity of the MRZH-reaction, we evaluated whether associating MRZH-reaction to CSF IgG-OCB detection improved investigation of suspected MS. Paired CSF and sera were analyzed for IgG-OCB and polyspecific viral antibodies. IgG-OCB were detected in 72% of MS patients and an MRZH-reaction in 67%. Combining IgG-OCB and MRZH raised detection of IgG abnormalities to 97% of studied MS patients. Detection of IgG-OCB and/or ≥2 MRZH antibodies showed sensitivity of 88% and specificity of 92% for MS, versus 72% and 96% for IgG-OCB alone.

[Ethical issues in multiple sclerosis under physicians and patients point of view]. / Questões éticas na esclerose múltipla sob o ponto de vista de médicos e pacientes.

UNLABELLED: Multiple sclerosis (MS) is a neurologic disorder that mostly affects young adults and can usually evolute to physical disability. Thus, caring patients with MS brings many ethic questions for the physician. OBJECTIVE: To identify physicians and patients' perceptions about the illness and so improve doctor-patient relationship. METHOD: It was made two different questionnaires, one for patients and another for physicians, 103 patients and 44 physicians answered them. RESULTS: 96.1% of patients knew their diagnosis, all others would like to know it. From those, 74.7% thought that that way it was disclosured was correct and 90.9% said that the doctor should tell us it. The worst symptoms described were fatigue (29.1%) and motor deficits (28.1%). By other side, 68% of patients told they suffered because of the illness. The most important reason for doctors to tell the diagnosis to the patients was to improve adherence to treatment (56.8%). A familiar present at this moment was demanded for 54.6% of doctors. When asked about orientations in a pregnancy, 50% of physicians did not answer correctly. Finally, 50% of physicians were against complementary and alternative therapies. CONCLUSION: Patients want to know their diagnosis and doctors should tell them in the most adequate moment and give more information. A debate about palliative care is also necessary.

[Signs and symptoms associated to otoneurologic alterations diagnosed on computerized vestibular exam of patients with multiple sclerosis]. / Sinais e sintomas associados a alterações otoneurológicas diagnoticadas ao exame vestibular computadorizado em pacientes com esclerose múltipla.

OBJECTIVE: To identify main symptoms and signs on computerized vestibular testing in patients diagnosed with multiple sclerosis. METHOD: Thirty patients with the diagnosis of multiple sclerosis were studied. We analyzed data related to presented symptoms and the findings from a computerized vestibular testing realized in the otoneurological ambulatory in Santa Casa de Misericórdia de São Paulo in 2003. RESULTS: Reported symptoms consisted mainly of disequilibrium (60%), tingling of limbs (43.3%), vertigo (40%), headache and anxiety (36.7%), tinnitus (30%), depression (26.7%). In vestibular testing we found alterations in positional nystagmus (6.7%), spontaneous nystagmus with the eyes shut (30%), directional nystagmus (13.3%) and caloric testing (63.3%). In the final conclusion of the exam, the diagnosis of irritative type peripheral vestibular syndrome (60%) and central syndrome (13.4%) prevailed. CONCLUSION: We conclude that the realization of an otoneurological exam has become indispensable in patients with multiple sclerosis. This is due to high prevalence of alterations at computerized vestibular exam and of otoneurological symptoms.