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.

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.

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.

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.

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.

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.