Refractory myasthenia gravis: Characteristics of a portuguese cohort.

INTRODUCTION: Some myasthenia gravis (MG) patients are refractory to conventional treatments. METHODS: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. RESULTS: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). DISCUSSION: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019.

Idiopathic inflammatory myopathies - The burden of disease: Cohort analysis focusing on damage and comorbidities.

INTRODUCTION/BACKGROUND: Idiopathic Inflammatory Myopathies (IIM) continue to be a major clinical challenge worldwide. The exact aetiopathogenesis of this chronic and disabling disease remains elusive, preventing the development of novel and effective therapeutic strategies and leading to a high incidence of damage. The complexity of treating these diseases is even greater due to the numerous comorbidities that affect these patients. METHODS: Retrospective review of the cohort of patients diagnosed with IIM and followed in a dedicated unit of a tertiary hospital between 1971 and December 2022, with particular attention to damage and comorbidities. Damage was assessed using the Myositis Damage Index. Comorbidities were recorded and analysed as a whole and also assessed using the Charlson Comorbidity Index. Health Assessment Questionnaire (HAQ) Disability Index (DI) was performed by phone call in December 2022, to all patients actively followed-up in the Unit. RESULTS: Analysis of 149 patients with a mean follow-up of 9 years (range 0-51) revealed >90% with damage and comorbidities. Most comorbidities were a consequence of the damage and were particularly related to prolonged steroid therapy. Cardiovascular damage, which occurred either as cardiovascular risk factors or as end-organ sequelae (cardiovascular disease and chronic kidney disease), was the main cause and a major contributor to death. Depression was also high on the list of associated comorbidities. Median HAQ was 2.09 representing high negative impact in quality of life. CONCLUSIONS: Although survival rates have increased in recent decades, patients with IIM carry a high burden of disease with poor quality of life, mainly caused by damage and comorbidities. While comorbidities accumulation is the major factor for poor quality of life, damage severity is the main predictor for mortality. Improved therapeutic strategies are needed to reduce the need for steroids and to introduce routine screening and management of comorbidities as an essential partner of immunosuppressive therapy, leading to comprehensive care of myositis patients and effective improvement of their quality of life.

Teriflunomide treatment outcomes in multiple sclerosis: A Portuguese real-life experience.

Teriflunomide is an oral disease-modifying therapy for relapsing-remitting multiple sclerosis patients. A decline in physical and cognitive functions, which negatively impacts their quality of life (QoL), is observed in relapsing-remitting multiple sclerosis patients. The aim of this study was to characterise adult Portuguese relapsing-remitting multiple sclerosis patients treated with teriflunomide in routine clinical practice concerning their quality of life, comorbidities, treatment effectiveness, satisfaction, compliance and safety. TeriLIVE-QoL was a multicentre, non-interventional, prospective cohort study that collected demographic and clinical characteristics, patient-reported outcomes and adverse events from patients treated with teriflunomide of 14 mg over 2 years. Notably, around 18 months of this period occurred during the COVID-19 pandemic. Of the 99 participants, 25% were treatment-naïve. Annualised relapse rate and the score for the Hospital Anxiety and Depression Scale decreased after 1 (p = 0.01) and 2 years of treatment (p < 0.001), respectively. Convenience (p = 0.001), effectiveness (p = 0.002) and global satisfaction scores (p < 0.001) presented high values (up to 95.6) and continued to improve along the study. Treatment persistence was 77%, and compliance reached 82% 2 years after initiation. Three patients experienced serious adverse events. TeriLIVE-QoL provides real-world evidence of clinical effectiveness, high treatment satisfaction, consistent safety and improved psychiatric outcomes, associated with elevated treatment persistence and compliance in patients treated with teriflunomide.iance reached 82% 2 years after initiation. Three patients experienced serious adverse events.

Autoimmune encephalitis: suspicion in clinical practice and mimics.

Despite the existence of well-established diagnostic criteria for autoimmune encephalitis, there are diseases capable of mimicking it. This study sought to retrospectively evaluate the reasons for testing and the final diagnosis of patients admitted to a Neurology ward tested for anti-NMDAR antibodies and estimate sensitivity and specificity of current diagnostic criteria. The threshold for testing was lower than that of the prevailing diagnostic criteria, and the proportion of autoimmune encephalitis mimics was high. Searching for alternative diagnoses is of pivotal importance in cases of autoimmune encephalitis suspicion, and diagnostic criteria may need expanding so that no autoimmune encephalitis is missed.

Low Memory T Cells Blood Counts and High Naïve Regulatory T Cells Percentage at Relapsing Remitting Multiple Sclerosis Diagnosis.

Objective: The aim of this study is to assess the peripheral immune system of newly diagnosed patients with relapsing remitting multiple sclerosis (RRMS) and compare it to healthy controls (HC). Methods: This cross-sectional study involves 30 treatment-naïve newly diagnosed patients with RRMS and 33 sex- and age-matched HC. Peripheral blood mononuclear cells were analyzed regarding: i) thymic function surrogates [T cell receptor excision circles (TRECs) and recent thymic emigrants (RTEs)]; ii) naïve and memory CD4+ and CD8+ T cells subsets; iii) T helper (Th) phenotype and chemokine receptors expression on CD8+ T cells subsets; iv) regulatory T cell (Tregs) phenotype; and exclude expression of activating/inhibitory receptors by natural killer (NK) and NKT cells. Analyses were controlled for age, sex, and human cytomegalovirus (HCMV) IgG seroprevalence. Results: Newly diagnosed patients with RRMS and HC have equivalent thymic function as determined by similar numbers of RTEs and levels of sjTRECs, DJßTRECs, and sj/DJßTREC ratio. In the CD8+ T cells compartment, patients with RRMS have a higher naive to memory ratio and lower memory cell counts in blood, specifically of effector memory and TemRA CD8+ T cells. Interestingly, higher numbers and percentages of central memory CD8+ T cells are associated with increasing time from the relapse. Among CD4+ T cells, lower blood counts of effector memory cells are found in patients upon controlling for sex, age, and anti-HCMV IgG seroprevalence. Higher numbers of CD4+ T cells (both naïve and memory) and of Th2 cells are associated with increasing time from the relapse; lower numbers of Th17 cells are associated with higher MS severity scores (MSSS). Patients with RRMS have a higher percentage of naïve Tregs compared with HC, and lower percentages of these cells are associated with higher MSSS. Percentages of immature CD56bright NK cells expressing the inhibitory receptor KLRG1 and of mature CD56dimCD57+ NK cells expressing NKp30 are higher in patients. No major alterations are observed on NKT cells. Conclusion: Characterization of the peripheral immune system of treatment-naïve newly diagnosed patients with RRMS unveiled immune features present at clinical onset including lower memory T cells blood counts, particularly among CD8+ T cells, higher percentage of naïve Tregs and altered percentages of NK cells subsets expressing inhibitory or activating receptors. These findings might set the basis to better understand disease pathogenesis.

Pediatric neuromyelitis optica spectrum disorders in Portugal: A multicentre retrospective study.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are more prevalent in adulthood, with few cases reported in pediatric age (<18 years). In this group, anti-aquaporin 4 (AQP4) antibodies are less frequent, while antibodies against myelin oligodendrocyte glycoprotein (MOG) are more commonly detectable than in adults. OBJECTIVE AND METHODS: Description of pediatric NMOSD cases identified in a national multicentric NMOSD Portuguese registry. RESULTS: Twenty (11.1%) NMOSD cases were diagnosed in pediatric age. Twelve (60%) were female, with a median age of onset of 12.5 (6.8-16.5) years. The presenting feature was transverse myelitis in 10 (50%), 4 of which with simultaneous optic neuritis and 2 with concomitant brainstem syndrome. Nine patients (45%) had pleocytosis in the CSF. Six (30.0%) exhibited anti-AQP4 antibodies, 13 (65.0%) anti-MOG antibodies, and one was seronegative for both. Four anti-AQP4 antibodies-positive patients had ≥1 relapse. Most anti-MOG-positive cases were monophasic (53.8%). In the acute phase, all patients received IV methylprednisolone, nine received IVIg and four plasma exchange. One anti-AQP4-positive patient died. Ten patients (5 anti-AQP4-positive/5 anti-MOG-positive) were on maintenance immunosuppressive therapy at the time of data collection. CONCLUSION: NMOSD may present in pediatric age. It is essential to establish the diagnosis and promptly start therapy to improve the prognosis.

Pregnancy in Patients With AQP4-Ab, MOG-Ab, or Double-Negative Neuromyelitis Optica Disorder.

OBJECTIVE: To analyze the effects of pregnancy on neuromyelitis optica spectrum disorder (NMOSD) according to patients' serostatus and immunosuppressive therapy (IST). METHODS: We performed a retrospective multicenter international study on patients with NMOSD. Patients were tested for aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). Informative pregnancies were reported when NMOSD onset occurred before or during pregnancy or up to 12 months postpartum. The mean annualized relapse rate (ARR) was calculated for the 12 months before conception, for each trimester of pregnancy, and postpartum. Events such as miscarriage, abortion, and preeclampsia were reported. IST was considered if taken in the 3 months before or during pregnancy. RESULTS: We included 89 pregnancies (46 with AQP4-Ab, 30 with MOG-Ab, and 13 without either Ab) in 58 patients with NMOSD. Compared to the prepregnancy period, the ARR was lower during pregnancy in each serostatus group and higher during the postpartum period in patients with AQP4-Ab (p < 0.01). Forty-eight percent (n = 31) of pregnancies occurred during IST and these patients presented fewer relapses during pregnancy and the 12 months postpartum than untreated patients (26% vs 53%, p = 0.04). Miscarriages occurred in 10 (11%) pregnancies, and were mainly in patients with AQP4-Ab (with or without IST) and a previous history of miscarriage. Preeclampsia was reported in 2 (2%) patients who were AQP4-Ab-positive. CONCLUSION: We found a rebound in the ARR during the first postpartum trimester that was higher than the prepregnancy period only in AQP4-Ab-positive patients. Taking IST just before or during pregnancy reduces the risk of relapses in these conditions.

Prognostic value of odor identification impairment in multiple sclerosis: 10-Years follow-up.

BACKGROUND: Olfactory dysfunction has been linked to clinical severity variables in multiple MS populations. Though, its prognostic value is still unknown. OBJECTIVE: The aim of this study was to explore the long-term outcome associated with Brief-Smell Identification Test (B-SIT) performance in a cohort of MS patients. METHODS: A retrospective review of the clinical records was conducted in 149 patients who participated in a previous study, with a median follow-up of 121 months. Demographic and clinical data regarding the last clinical appointment with EDSS measurement were collected. Multiple Sclerosis Severity Scale (MSSS) and Age-Related Multiple Sclerosis Severity (ARMSS) scores were calculated. Date of the last clinical contact or death was recorded. RESULTS: Among MS patients with progressive clinical course (n = 33), those with impaired B-SIT at baseline had greater change per month during follow-up (as measured by increases in MSSS and ARMSS scores) and a higher hazard of death. No significant associations were found among patients with relapsing and remitting MS (n = 116). CONCLUSIONS: The study results demonstrate that odor identification impairment has prognostic value in progressive MS, suggesting that a brief odor identification measure can be a marker of neurodegeneration in progressive MS.

JC virus antibodies in Portuguese multiple sclerosis patients: JUSTIFY study results.

OBJECTIVE: To confirm anti-JC virus (JCV) antibody seroprevalence in Portuguese patients with relapsing-remitting multiple sclerosis (RRMS) and to determine their anti-JCV antibody index. METHODS: JUSTIFY was a retrospective, multicentre study that included 655 RRMS patients tested at least once with the anti-JCV antibody assay STRATIFY JCV DxSelect. Demographic data, multiple sclerosis history and results of the anti-JCV antibody test were collected, along with physicians' reasons for requesting the test and the impact of the results. RESULTS: Overall anti-JCV antibody seroprevalence was 60.8% (95% confidence interval, 56.9-64.5). Seroprevalence was associated with higher age (P = .030) and was lower in natalizumab-treated patients (P < .001). The mean anti-JCV antibody index of immunosuppressant-naive patients was 1.5 ±â€¯1.3 (n = 378). The main reasons for performing the test were clinical characterization (35.5%) and medication change (26.2%). In patients who switched treatments (n = 109), fingolimod (47.7%) and natalizumab (26.6%) were the most commonly chosen new treatments. CONCLUSIONS: The study confirmed the high anti-JCV antibody prevalence in Portuguese RRMS patients and its association with age. These data can be used to better understand the benefit-risk profile of natalizumab treatment in Portuguese patients and to support progressive multifocal leukoencephalopathy risk management strategies.

Serum 25-hydroxyvitamin D levels in multiple sclerosis patients from the north of Portugal.

Increasing evidence has shown that individuals with Multiple Sclerosis (MS) have lower 25-hydroxyvitamin D [25(OH)D] levels compared to healthy controls. There is no information regarding 25(OH)D levels and MS in Portugal. Therefore the aim of the current study was to examine the levels of 25(OH)D in a group of patients with MS and in healthy matched controls, as well as the association of 25(OH)D levels with disease course, disability and severity. A group of 244 unrelated Portuguese patients, with a definitive diagnosis of MS, and 198 ethnically matched healthy controls were included in the study. A sub-group of patients with recent disease onset was included. Serum 25(OH)D was measured using an electrochemiluminescence binding assay. The mean serum level of 25(OH)D in patients with MS was 39.9±22.0 nmol/L, which was significantly lower (p<0.0001) than those in healthy controls, 55.4±23.4 nmol/L. There was a negative correlation between 25(OH)D levels and EDSS (r=-0.293, p<0.0001) and MSSS scores (r=-0.293, p<0.0001). In multiple logistic regression analysis adjusted for age, gender, disease form, EDSS, disease duration and MSSS, 25(OH)D levels were independently associated with EDSS (p=0.004) and disease duration (p=0.016), and with MSSS (p=0.001). In accordance with the majority of the literature, low serum 25(OH)D levels were associated with susceptibility and disability in MS patients from Portugal. Lower serum 25(OH)D levels were also found in patients with a recent disease onset, supporting vitamin D levels as a risk factor for MS.

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1.

INTRODUCTION: Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. MATERIAL AND METHODS: The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. RESULTS: We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. CONCLUSION: We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.

Introdução: A esclerose múltipla caracteriza-se pela presença de lesões inflamatórias a nível do encéfalo e medula espinhal. A ressonância magnética é atualmente um exame indispensável no diagnóstico, na avaliação da atividade da doença e na resposta ao tratamento. Embora na nossa prática as vantagens da ressonância magnética estejam bem estabelecidas, continuam a existir dificuldades técnicas (uso de sequências e protocolos não padronizados) e clínicas (frequência de exames não adequada) que podem dificultar o diagnóstico e o seguimento dos doentes. Neste contexto, o Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão conjunta, designaram um comité de peritos para a criação de recomendações adaptadas à realidade nacional sobre a utilização da ressonância magnética na esclerose múltipla. O objetivo deste documento é publicar as primeiras recomendações de consenso portuguesas sobre a utilização da ressonância magnética na esclerose múltiplana prática clínica.Material e Métodos: O Grupo de Estudos de Esclerose Múltipla e a Sociedade Portuguesa de Neurorradiologia, após discussão do tema em reuniões de âmbito nacional e de uma reunião do grupo de trabalho que teve lugar na Figueira da Foz em maio de 2017, designaram um comité de peritos que elaboraram por método de consenso vários protocolos padronizados sobre o uso da ressonância magnética no diagnóstico e seguimento da esclerose múltipla. O documento teve como base a melhor evidência científica e a opinião dos peritos. Posteriormente, o documento foi enviado para escrutínio à maioria dos responsáveis de consulta de esclerose múltipla e dos departamentos de neurorradiologia; os comentários e sugestões foram considerados. Os protocolos técnicos referentes à aquisição de imagem e a informação que deverá constar no relatório destes exames serão publicados numa publicação separada.Resultados: Neste artigo são propostas várias orientações práticas para promover estratégias padronizadas para serem aplicadas na prática clínica dos profissionais de saúde portugueses no que se refere ao uso da ressonância magnética na esclerose múltipla.Conclusão: Os autores esperam que estas primeiras orientações portuguesas, sobre a utilização da ressonância magnética na esclerose múltipla na prática clínica, baseadas nas melhores evidências e práticas clínicas disponíveis, sirvam para otimizar a gestão da esclerose múltipla e melhorar o tratamento destes doentes em Portugal.

The vitamin D receptor gene FokI polymorphism and Multiple Sclerosis in a Northern Portuguese population.

BACKGROUND: The cause of Multiple Sclerosis (MS) remains poorly understood, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals after exposure to as-yet undefined environmental factors. One of these environmental factors is vitamin D, a well-known immune modulator. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3, has been shown to exert its immune modulatory properties through its nuclear receptor (VDR) namely by inhibiting the proliferation of Th cells. The purpose of this study was to evaluate the influence of FokI VDR polymorphism in MS development and progression. METHODS: A group of 533 unrelated Portuguese patients with a definitive diagnosis of MS and 446 ethnically matched healthy controls were included in the study. FokI was genotyped using a PCR-based TaqMan Genotyping Assay and serum 25-hydroxyvitamin D [25(OH)D] was also assessed. RESULTS: A statistically significant higher frequency of the ff genotype was observed in MS patients (15.6% vs. 10.1%, p=0.012, OR (95% CI)=1.687(1.120-2.541)). No differences were observed in the frequencies of the FokI polymorphism according to disease course or with progression of disability. None of the genotypes was significantly associated with 25(OH)D serum levels. CONCLUSIONS: An association between FokI ff genotype and MS susceptibility was found, but not with disease form or progression. Additional clinical and experimental studies should take the FokI VDR polymorphism into account, and further clarify the role of vitamin D, its metabolites and its receptor in MS.

HLA and age of onset in myasthenia gravis.

The aetiology of MG is unknown, but both genetic and environmental factors are important. Over the years association of MG with Human Leucocyte Antigens (HLA) has been described in different populations. We investigated a possible association between HLA-DRB1 alleles and age of onset in MG. One hundred and fourteen MG patients (82 females) and 282 control individuals (CP) were studied. Patients were classified according to the age of onset (early-onset <50, n = 74 and late-onset ≥ 50, n = 20). Patients with thymoma (n = 20) were analyzed separately. HLA-DRB1 and HLA-B*08 genotyping was performed using PCR-SSP methodology. HLA-DRB1*03 allele was overrepresented in the global MG. When the early-onset subgroup was considered, this association became even stronger. Regarding the late-onset subgroup, the frequency of HLA-DRB1*01 allele was higher than in the CP. For the thymoma subgroup, the HLA-DRB1*10 allele frequency was significantly higher when compared to the CP. These results have shown a strong association of HLA-DRB1*03 with MG, especially for EOMG also in our population. HLA-DRB1*01 was associated to LOMG suggesting that is a susceptibility factor for this subgroup of the disease. This study confirms a different genetic background of MG subgroups regarding age of onset.

JCV epidemiology in MS (JEMS)--epidemiology of anti-JCV antibody prevalence in multiple sclerosis patients--Portuguese data.

BACKGROUND: Progressive multifocal leukoencephalopathy, caused by oligodendrocyte lytic infection by JCVirus, is a growing concern for patients undergoing immune modulatory therapies for treatment of autoimmune diseases, such as multiple sclerosis (MS). The objective of JEMS was to describe the prevalence of anti-JCV antibodies in MS patients and to assess the various factors associated to it. METHODS: Serum samples were collected and tested for anti-JCV antibody using the STRATIFY JCV™ assay in 131 Portuguese MS patients. Factors potentially associated with prevalence were also evaluated, as well as the effect of established risk factors. RESULTS: In the population of 131 Portuguese patients included in the JEMS, the overall anti-JCV antibody prevalence was 69.5% (95% CI, 61.6-77.4). The anti-JCV antibody prevalence did not seem to be influenced by demographic characteristics, although results demonstrate a non-significant trend for increased prevalence with age. Disease characteristics, treatment duration, treatment history, prior immunosuppressive therapy use and natalizumab exposure duration did not seem to be associated with anti-JCV prevalence. CONCLUSION: The results of Portuguese MS patients participating in the JEMS study present some differences when compared with the global population and literature results. An overall prevalence higher than expected raises awareness for data confirmation with greater sample size studies.

Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.

Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo. Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic function and nutritional status. We quantified the monthly rates of change in efficacy measures, and TTR stabilization, and monitored adverse events (AEs). Patients who continued on tafamidis had stable rates of change in NIS-LL (from 0.08 to 0.11/month; p = 0.60) and TQOL (from -0.03 to 0.25; p = 0.16). In patients switched from placebo, the monthly rate of change in NIS-LL declined (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to -0.16; p < 0.001). Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months. AEs were similar between groups; no patients discontinued because of an AE. Long-term tafamidis was well tolerated, with the reduced rate of neurologic deterioration sustained over 30 months. Tafamidis also slowed neurologic impairment in patients previously given placebo, but treatment benefits were greater when tafamidis was begun earlier.

Systemic lupus erythematosus, progressive multifocal leukoencephalopathy, and T-CD4+ lymphopenia.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T-CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections.

A coincidental case of young-onset Parkinson disease and multiple sclerosis.

BACKGROUND: Parkinsonism in patients with multiple sclerosis is rare. Some patients have 2 coincidental diseases, whereas others have a Parkinsonian syndrome symptomatic to demyelinating lesions. CASE REPORT: We describe a 42-year-old female patient who developed left akinetic-rigid Parkinsonian syndrome at the age of 38 years. Brain magnetic resonance imaging revealed multiple white matter hyperintense T2-weighted lesions. DaTSCAN revealed reduced uptake of dopamine transporter in the right striatum. Intravenous corticosteroids were inefficacious. She had major clinical improvement with levodopa and 6 months later developed peak-dose dyskinesias. At the age of 41 years, she presented with a brainstem attack, with complete symptom resolution after intravenous corticosteroids. Subsequent brain magnetic resonance imagings disclosed new inflammatory lesions. Immunomodulatory treatment was started with ß-interferon. COMMENTS: In this patient, the presence of an asymmetrical Parkinsonian syndrome, with good response to levodopa, peak-dose dyskinesias, and abnormal DaTSCAN, supports the diagnosis of young-onset Parkinson disease. The multiple sclerosis diagnosis was established based on clinical evidence of time and space dissemination of demyelinating lesions.

Gliomatosis cerebri diagnostic challenge: two case reports.

BACKGROUND: Gliomatosis cerebri is a specific entity defined as a diffuse neoplastic glial cell infiltration of the brain, preserving the architecture of the normal surrounding tissues, involving more than 2 cerebral lobes. Clinical symptoms or radiologic features are nonspecific, and patients are often misdiagnosed with other neurologic diseases. REVIEW SUMMARY: Here, we report the diagnostic workup of 2 patients with gliomatosis cerebri, discussing the clinical, radiologic, and pathologic findings. Case 1: a 64-year-old woman who presented with an intracranial hypertension syndrome and had symmetrical white matter T2-weighted and fluid-attenuated inversion recovery hyperintensities pattern on magnetic resonance imaging; and case 2: a 54-year-old man with the diagnosis of multiple sclerosis for 8 years who presented with de novo cognitive impairment and focal deficits. CONCLUSIONS: This report highlights the difficulty of this differential diagnosis and the need of considering it also in the presence of a symmetrical pattern of white matter involvement. Cerebral biopsy remains crucial for the correct diagnosis and treatment approach.

Depression and anxiety in a Portuguese MS population: associations with physical disability and severity of disease.

BACKGROUND: Mood disorders, namely depression and anxiety, have been well documented in patients with Multiple Sclerosis (MS). However, the putative associations between clinical features and mood disorders have not been well established. OBJECTIVES: To detect anxiety and depression in MS patients; and to investigate possible associations with clinical factors. SUBJECTS AND METHODS: 325 consecutive patients with MS and 183 healthy subjects answered the Hospital Anxiety and Depression Scale (HADS), a self-rating questionnaire. Multiple Regression Analysis and Multivariate Analysis of Covariance were applied to assess the effect of demographic and clinical factors on HADS' anxiety and depression scores, using age and disease duration as covariates. Logistic Regression Analysis was used to study the influence of these factors on anxiety and depression, as defined by two different cut-off scores (i.e., 8 and 11). RESULTS: Levels of anxiety and depression were significantly higher (p<0.001) for MS patients group than healthy subjects. Age, disease duration, age at onset, Kurtzke Expanded Disability Status Scale, and Multiple Sclerosis Severity Scale were positively associated with depression scores. Low education (i.e., <9 years) in MS was significantly associated with more anxiety and depression symptoms. CONCLUSIONS: The study findings support a close linkage between depressive mood and physical manifestations of MS.