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Background Pediatric-onset multiple sclerosis (POMS) accounts for 3 to 10% of all MS diagnoses. POMS is usually characterized by prominent disease activity, and patients are at higher risk of developing physical disability and cognitive impairment. Objective This article characterizes a cohort of POMS patients followed at the pediatric neurology unit of a Portuguese tertiary hospital. Methods Retrospective observational study. Clinical records of all patients with POMS between 2011 and 2020 were revised. Results A total of 21 patients, with a female:male ratio of 11:10 and a mean age of onset of 14.8 years were included. Clinical manifestations at presentation included myelitis in eight patients (two with associated brainstem syndrome), optic neuritis in six (one with associated cerebellar syndrome), supratentorial symptoms in four, and isolated brainstem syndrome in two. Twenty patients had oligoclonal immunoglobulin G bands in cerebrospinal fluid. Supra- and infratentorial involvement was identified in the first brain magnetic resonance imaging of nine patients. Initial relapses were treated with intravenous steroids in 19 patients. The mean time for diagnosis was 2.8 months. Eleven patients were on first-line treatment (nine on β-interferon, two on teriflunomide) and 10 on second-line treatment (six on natalizumab, three on fingolimod, one on ocrelizumab). The mean annual relapse rate was 0.29 (range, 0.01–3), and the median Expanded Disability Status Scale was 1. Four patients reported learning disabilities and/or cognitive deficits. Conclusion About half of patients in this cohort were on second-line disease-modifying treatment, with 19% showing cognitive impairment. Efforts to establish an early diagnosis are crucial to improving these patients' outcomes.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly associated with early-onset stroke, migraine and vascular dementia. However, optic nerve involvement has been previously recognised. Results: We report a case of a 21-year-old female presenting with right inferior temporal scotoma, dyschromatopsia, relative pupillary afferent defect and bilateral disk oedema in the fundoscopic examination. Visual evoked potential latencies were bilaterally increased, suggesting optic neuropathy. Cerebrospinal fluid (CSF) evaluation showed 11 leukocytes, .45 mg/dL proteins, elevated IgG (4.55 mg/dL) and 2 oligoclonal bands (OCB) restricted to the CSF. ESR was 17 mm/h and CRP 5 mg/dL. Anti-Aquaporin4 anti-MOG antibodies were negative. The MRI showed right optic nerve hyperintensity, enhancing after the administration of contrast product, and multiple FLAIR focal lesions present throughout the white matter, with a noticeable confluence in the anterior temporal horns. She improved after IV high-dose methylprednisolone. Because the lesions of the white matter were highly atypical for an inflammatory disease and highly suggestive of CADASIL genetic testing was requested. A heterozygous pathogenic variant c994C>T p (Arg332Cys) in the exon 6 of the NOTCH3 gene, compatible with the diagnosis of CADASIL was found. Conclusions: This case highlights isolated optic nerve involvement as a presenting feature of CADASIL, possibly reflecting an inflammatory process associated with this hereditary vasculopathy.

Introduction There is a complex interplay between systemic autoimmunity, immunosuppression, and infections. Any or all of these can result in neurologic manifestations, requiring diligence on the part of neurologists. Case report We herein report a case of a patient on immunosuppressive treatment for a vasculitis that resulted in zoster meningoencephalitis. This was further complicated by the development of anti-NMDAr encephalitis, the etiology of which is undetermined and further discussed in this paper. The patient eventually developed COVID-19 during hospitalization, succumbing to the respiratory infection. Conclusion This case emphasizes that post-infectious autoimmune disorders are becoming increasingly recognized and that they should still be considered in patients who are on immunosuppression. Practitioners should be aware of the complex relationship between autoimmunity and immunosuppression and consider both throughout the disease course.

Background: Cognitive dysfunction as a predictor of clinical progression and mortality in multiple sclerosis (MS) is still a matter of debate. Objective: The aim of this study was to explore the long-term outcome associated with neuropsychological performance in a cohort of patients with MS. Methods: A series of 408 MS patients had previously undergone a comprehensive neuropsychological assessment and a contemporaneous neurological evaluation (T1). A retrospective review of the clinical records was conducted 102–192 months after T1. Demographic and clinical data regarding the last clinical appointment with EDSS measurement (T2) were collected and the date of the last clinical contact or death (TS) was recorded. Results: This review revealed that cognitive dysfunction (T1) was associated with higher odds of transitioning from relapsing–remitting course to a progressive disease course (adjusted odds ratio (OR) = 2.29, p = 0.043) and higher hazard of death in the total sample (adjusted hazard ratio (HR) = 3.07, p = 0.006) and the progressive disease course subgroup (adjusted HR = 3.68, p = 0.007), even when adjusting for other covariates. Discussion: The study results demonstrate that cognitive dysfunction in MS is predictive of poorer prognosis and mortality.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant condition which phenotype can be extremely variable considering its multisystem involvement, including the central nervous system. Neuromuscular findings are facial and distal extremities muscle weakness, muscle atrophy and myotonia. Standard diagnosis is obtained with molecular testing to detect CTG expansions in the myotonic dystrophy protein of the kinase gene. Brain magnetic resonance imaging typically shows characteristic subcortical white matter (WM) abnormalities located within anterior temporal lobes.We present a 39-year-old male patient with a progressive external ophthalmoplegia, facial and limb muscle weakness, percussion myotonia and atypical brain magnetic resonance imaging findings, showing confluent brainstem WM lesions, affecting the pons, a rare radiologic feature in this disorder. Genetic testing confirmed the diagnosis for DM1.This presentation with external ophthalmoplegia and brainstem WM loss in DM1 can show an important correlation with clinical findings and have an important diagnostic and prognostic value.

ObjectiveTo analyze the effects of pregnancy on neuromyelitis optica spectrum disorder (NMOSD) according to patients' serostatus and immunosuppressive therapy (IST).MethodsWe 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.ResultsWe 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.ConclusionWe 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.

Introduction: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. Objective: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). Methods: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. Results: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p

The impact of COVID-19 in patients with neuroimmunological disorders is not fully established. There is some evidence suggesting an increased risk of more severe infection associated with the use of immunosuppressors in this population.To characterize SARS-CoV-2 infection in patients followed in the neuroimmunology outpatient clinic of a tertiary centre from the north of Portugal.Retrospective analysis of neuroimmunological patients with PCR-proven SARS-CoV-2 infection during the observational period of 20 months.Ninety-one patients were infected, 68.1% female, with a mean age of 48.9±16.7 years. The median disease duration was 11.0 (IQR 6.0-19.0) years. Sixty-one patients (67.0%) had Multiple Sclerosis, of which 50 with relapsing-remitting course, 12 (13.2%) Myasthenia Gravis (MG), 6 (6.6%) Autoimmune Encephalitis and 6 (6.6%) Chronic Inflammatory Demyelinating Polyneuropathy. Seventy-six patients (83.5%) were taking disease-modifying therapy, 77.6% of which were on immunosuppressants, including anti-CD20 in 12 (13.2%). Most patients had mild COVID-19 (84.6%), with 3 cases (3.3%) of severe disease and, 7 cases (7.7%) of critical disease being reported. In total, 13 patients were hospitalized and 4 died. Patients with severe to critical disease were significantly older than patients with milder forms (69.4±21.0 versus 46.5±14.4 years, p0.01). MG was also associated with more severe disease (p=0.02). There was no association between comorbidities or use of immunosuppressors (including anti-CD20) and COVID-19 severity.Greater age and MG were associated with severe or critical COVID-19. We found no association between a specific DMT, including anti-CD20, and outcome. Clinical recovery was achieved by 93.4%.

Background Mood disorders, as depression and anxiety, are frequent in Multiple Sclerosis (MS) patients. High pro-inflammatory cytokine levels (e.g. IL-1β) have been reported in depressed individuals. Objective We aimed to investigate the role of the rs16944 (IL-1β-511 C>T) polymorphism in the development of anxiety and depression symptoms in a Portuguese cohort of MS patients. Methods 393 MS patients answered the Hospital Anxiety and Depression Scale (HADS) at T1. This questionnaire was reapplied to a subgroup of 175 MS patients approximately three years later (T2). HADS cut-off scores for anxiety and depression were respectively ≥11 and ≥8. Results At T1, anxiety was found in 106 MS patients (27.0%) and 11 controls (16.7%); whereas depression was identified in 116 (29.5%) MS patients and 9 controls (13.6%). Persistent anxiety and depression were respectively recorded in 12% and 20% of MS patients. The rs16944TT genotype was found to be a susceptibility factor for the occurrence of depression at T1 (OR = 3.16, p=0.002) and the development of persistent depression (OR = 5.63, p=0.003) in MS. Conclusion Study results support the hypothesis that inflammation is a significant factor in psychopathology development.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. Objective: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. Methods: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. Results: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. Conclusion: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries. info:eu-repo/semantics/publishedVersion

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.

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.Description of pediatric NMOSD cases identified in a national multicentric NMOSD Portuguese registry.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.NMOSD may present in pediatric age. It is essential to establish the diagnosis and promptly start therapy to improve the prognosis.

Hereditary diffuse leukoencephalopathy with axonal spheroids demonstrates clinical and neuroimaging heterogeneity.

Introduction Neurosarcoidosis occurs in about 5% to 15% of patients with sarcoidosis. The purpose of this study was to identify and characterize a cohort of neurosarcoidosis patients and to review the largest previously reported neurosarcoidosis case series. Methods This retrospective study enrolled all patients with the diagnosis of probable or definitive neurosarcoidosis according to Zajicek and Scolding criteria, followed at the neurology department of a tertiary center in Portugal from January 1989 to December 2015. Results A total of 15 patients presented a diagnosis of probable or definitive neurosarcoidosis, with a mean age at time of diagnosis of 38.5 years. The presenting neurologic syndrome was isolated cranial neuropathy, aseptic meningitis, myelitis, brain parenchymal lesion, myelorradiculitis and meningomyelorradiculitis. MRI study most often presented different enhancing lesions and the CSF analysis commonly revealed a lymphocytic pleocytosis and raised proteins. Thirteen patients had histopathology confirmation of systemic sarcoidosis and one preformed a spinal cord biopsy. Corticosteroids was the most often used treatment alone or in combination with immunosuppressive drugs. After a mean follow-up of 86.1 months, the majority of patients fully recovered to a mRankin 0. Discussion Fully comprehension of neurosarcoidosis is still a challenge due to its rarity and limited number of large published series, which renders the epidemiological study of this disease very difficult. In this study, the thoroughly medical records review and the summarize of previous published cohorts allow to add some information in the epidemiological and clinical knowledge of this entity.

In February 2017, a 52-year-old woman was brought to our clinic after abrupt right vision loss. Four days later, both eyes were affected, bilateral optic neuritis (ON) was diagnosed, and the patient was treated with a short course of corticosteroids. Her medical history revealed she was admitted at the age of 18 years with severe paraparesis, followed 4 weeks later by right vision loss. With a short course of corticosteroids, the patient achieved full recovery, but no etiology was found. Myelin oligodendrocyte glycoprotein (MOG)-IgG positivity and aquaporine-4 antibodies (AQP4-IgG) absence (cell-based immunoassay, analysed by microscopy) were confirmed in the present attack (figure for case description).

Background Irreversible organ damage is considered a core outcome by the OMERACT working group. However, no specific tools are currently available to detect and measure damage accrual in Behcet’s syndrome (BS). Objectives To develop and preliminarily validate the Behcet’s syndrome Overall Damage Index (BODI). NCT03803462. Methods A preliminary version of the instrument (p-BODI) was developed by reviewing pre-existing tools [e.g. Vasculitis damage index (VDI)] and through an extensive literature review. p-BODI was then reviewed and implemented by a multi-rounds Delphi process, involving an international and multidisciplinary (5 rheumatologists, 4 internist, 1 ophthalmologist, 1 neurologist) panel of experts in BS management and a patients’ delegate. A group of clinicians (CG), not involved in the BODI development, was asked to independently score a set of clinical vignettes, in order to test the instrument reliability, after a training process consisting of a user manual and a video-tutorial. Then, Cohen’s K and Intra-class correlation coefficient (ICC) between assessors and gold standard were calculated. Afterwards, BODI validation was conducted according to the OMERACT Filter 2.0 in a multicenter BS cohort. Results Starting from a list of 120 candidate items, the final version of BODI consisted of 4 overarching principles, 30 items and 12 sub-items (each of them scores one point) grouped in 8 domains (figure). In terms of reliability, the mean K coefficient was 0.84 (95%CI 0.78 to 0.90) and the ICC was 0.88 (95%CI 0.80-0.95). Validation cohort consisted of 228 BS patients (49.1% males), with a median (IQR) age and disease duration of 46.9 (35.5-55.0) and 11.7 (5.8-20.7) years, respectively. Overall, prevalence of any BODI damage (BODI ≥1) was 56.1% with a median score of 1.0 (0-2.0). In regard of construct validity, BODI score significantly correlated with VDI (Spearman’s rho 0.693, p Full agreement among the CG was reached in judging BODI as a credible, comprehensive, easy to use, timesaving and acceptable instrument. Conclusion BODI is the first tool specifically developed to assess damage in BS. Preliminary data encourage further validation of BODI in more extended and multi-ethnic BS cohorts before being applied in clinical practice and as a therapeutic outcome. Disclosure of Interests Matteo Piga: None declared, Alberto Floris: None declared, Gerard Espinosa: None declared, Nikolaos Kougkas: None declared, Andrea Lo Monaco: None declared, Giuseppe Lopalco Speakers bureau: SOBI, BMS, Ida Orlando: None declared, Vittorio Pirani: None declared, Ernestina Santos: None declared, Luisa Serpa Pinto: None declared, George Bertsias: None declared, Luca Cantarini: None declared, Alberto Cauli: None declared, Ricard Cervera: None declared, Joao Correia: None declared, Marcello Govoni: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Ana Martins da Silva: None declared, Piergiorgio Neri: None declared, Carlos Vasconcelos: None declared, Monica Muntoni: None declared, Alessandro Mathieu: None declared

Background Disease activity evaluation is mandatory according to the OMERACT Core Set of Domains for Behcet’s Syndrome (BS). Poor data are available on Patient (PtGA) and physician (PGA) global assessment of disease activity in BS. Objectives To assess PtGA performance in patients with BS and how different disease manifestations influence the patient and physician’s perception of disease activity. Methods A multicenter cross-sectional cohort of consecutive BS patients was enrolled. Disease activity was evaluated by PtGA, PGA and the Behcet’s disease current activity form (BDCAF). PtGA and PGA were assessed trough a single question (“How active was BS during the last week?”) in a 10-cm visual analogic scale. Health related quality of life (HRQoL) perception was evaluated by the Physical Component Summary (PCS) and the Mental Component summary (MCS) of the SF36v2 questionnaire. Correlation between PtGA, PGA, BDCAF and between them and SF36v2 component summaries was assessed trough the Spearman’s correlation coefficient (rho). Two separated multiple regression models were built to measure the independent effect (β regression) of each active clinical manifestation on PtGA and PGA. Results Overall, 226 BS patients from 5 Mediterranean Countries were enrolled. Out of them, 111 (49.1%) were males and the median (IQR) age and disease duration were 46.9 (35.6-55.2) and 11.7 (5.9-20.8) years, respectively. The median (IQR) value of PtGA, PGA and BDCAF were 2.0 (0.3-5.0), 1.0 (0.0-3.0) and 3.0 (0.0-5.0), respectively. PtGA significantly correlated (Figure) with both PGA (rho 0.759. p 0.001) and MCS (rho -451. p > 0.001). Conclusion PtGA seems to be a valid outcome measure in BS and should be considered as a separate outcome measure or better be included in composite index for overall disease activity evaluation. Disclosure of Interests Alberto Floris: None declared, Matteo Piga: None declared, Gerard Espinosa: None declared, Nikolaos Kougkas: None declared, Andrea Lo Monaco: None declared, Giuseppe Lopalco Speakers bureau: SOBI, BMS, Ida Orlando: None declared, Vittorio Pirani: None declared, Ernestina Santos: None declared, Luisa Serpa Pinto: None declared, George Bertsias: None declared, Luca Cantarini: None declared, Alberto Cauli: None declared, Ricard Cervera: None declared, Joao Correia: None declared, Marcello Govoni: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Ana Martins da Silva: None declared, Piergiorgio Neri: None declared, Carlos Vasconcelos: None declared, Alessandro Mathieu: None declared

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. info:eu-repo/semantics/publishedVersion

Background: Autoimmune hepatitis (AIH) is a rare and chronic inflammatory disorder associated with extrahepatic autoimmune diseases, including, infrequently, multiple sclerosis (MS). Short Reports: We report five cases of MS and AIH association. One patient developed AIH while under interferon beta-1b and the remaining while off disease-modifying therapy, although after methylprednisolone bolus in three. All presented a liver biopsy compatible with AIH. Hepatitis resolution was achieved with immunosuppressive treatment, but one patient died after a fulminant hepatitis requiring liver transplant. Discussion: A thorough review of published cases supports this clear, although rare, association and a liver biopsy should be considered in AIH suspected cases.

BACKGROUND In multiple sclerosis (MS), even in the absence of a clinical episode of optic neuritis (ON), the optic nerve and retinal nerve fiber layer (RNFL) may be damaged leading to dyschromatopsia. Subclinical dyschromatopsia has been described in MS associated with lower motor and cognitive performances. OBJECTIVES To set the prevalence of dyschromatopsia in eyes of MS patients without a history of ON, to compare its prevalence in patients with and without ON history, and to explore the association between dyschromatopsia and disease duration, average peripapillary RNFL thickness, macular volume, and cognitive and motor performances. METHODS An observational cross-sectional study was conducted at multiple medical centers. Data were collected after single neurological and ophthalmological evaluations. Dyschromatopsia was defined by the presence of at least 1 error using Hardy-Rand-Rittler plates. RESULTS In our population of 125 patients, 79 patients (63.2%) never had ON and 35 (28.8%) had unilateral ON. The prevalence of dyschromatopsia in eyes of patients without ON was 25.7%. Patients with dyschromatopsia had a statistically significant lower RNFL thickness (P = 0.004 and P = 0.040, right and left eyes, respectively) and worse performance in symbol digit modalities test (P = 0.012). No differences were found in macular volume or motor function tasks. CONCLUSIONS Dyschromatopsia occurs frequently in MS patients. It may be associated with a worse disease status and possibly serve as a marker for the detection of subclinical disease progression since it was detected even in the absence of ON. It correlated with thinner peripapillary RNFL thickness and inferior cognitive performance.

Introduction We evaluated the clinical course during pregnancy and neonatal outcomes of a cohort of Portuguese women with myasthenia gravis (MG). Methods Retrospective study. Results Twenty-five patients with 30 pregnancies were included. Mean maternal age was 32.4 ± 4.1 years. Miscarriage rate was 6.7%, with delivery of 28 newborns. Deterioration in MG during pregnancy occurred in 43.3%, and 46.4% occurred at postpartum. Eighty percent were medicated with pyridostigmine, 43.3% with corticosteroids, and 40% with intravenous immunoglobulin. There were no maternal or neonatal deaths. Mean gestational time at delivery was 38.2 weeks. No cases of fetal growth restriction, preeclampsia, preterm delivery, or fetal demise were observed. Global cesarean rate was 64.3%. Two newborns developed transient neonatal myasthenia. Conclusions A high rate of clinical worsening of MG in the mother was observed in this retrospective study, which highlights the importance of a multidisciplinary approach for avoiding maternal adverse outcomes. Muscle Nerve 54: 715-720, 2016.

Introduction In this study we estimated the prevalence, incidence, and mortality of myasthenia gravis (MG) in northern Portugal and characterized the clinical features of the patients identified. Methods We used 2 data sources: clinical records from the hospitals and pyridostigmine prescription registers. Results On December 31, 2013, we estimated a point prevalence of 111.7 patients per million population. The highest prevalence was observed in the group >65 years of age, especially in men (288.1 per million). During 2013, we estimated an incidence rate of 6.3 per million per year. Among women, the incidence rate was highest in the 15-49-year age group; in men, incidence increased with age up to 22.1 per million in those >65 years old. The MG-related mortality rate was 0.5 per million. Conclusions These figures are in keeping with similar studies and emphasize the importance of diagnosis and management of MG in elderly populations. Muscle Nerve 54: 413-421, 2016.

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.

Introduction Paraneoplastic neurological syndromes (PNS) are immune-mediated diseases that occur in patients with tumors and can be associated with onconeural antibodies. Our aim was to describe our cohort of patients with PNS. Methods Retrospective analysis of a cohort of patients followed in a Portuguese tertiary center, with autoantibodies against intracellular antigens from our PNS panel, between 2012 and 2017. Results Among the 882 patients with suspected PNS (1029 samples), 37 (4.2%) had positive and 27 (3.1%) weak positive antibodies. A total of 17 (29.3%) PNS were diagnosed, 5 were classic syndromes. Autoantibodies found were anti-Yo, anti-Hu, anti-titin, anti-Ma2, anti-SOX1, anti-Ri and anti-CV2/CRMP5. They were associated with thymoma, breast, colon, parotid gland and lung (small-cell, neuroendocrine or carcinoid) cancer. Among the 17 PNS patients, no tumor was found in 4 (mean follow-up of 46 months); no patients improved with tumor treatment, while 8 improved with immunotherapy; ten patients (59%) died during follow-up. Twenty (60.6%) patients with positive antibodies and 21 (84.0%) with weak positive were not diagnosed with a PNS. Conclusions PNS had highly heterogenous clinical presentations. Response to tumor treatment was overall poor, with an unfavorable prognosis. In our cohort, only 29.3% of the patients with positive antibodies were diagnosed with a PNS.

Purpose of reviewThymomas appear very rarely after extended thymectomy for early-onset myasthenia gravis (EOMG). We describe 2 such cases that highlight potential early warning signs.Recent findingsIn their 20s, one woman and one man developed EOMG (AChR antibody-positive), requiring extended transsternal removal of hyperplastic thymi at ages 35 and 27, respectively. Their myasthenia gravis was readily controlled for the next 10 and 7 years before deteriorating in both, with appearance of late clinical features and anticytokine autoantibodies suggesting underlying thymomas, namely respiratory infections, genital herpes, chronic candidiasis, and alopecia in the woman and erythroderma and lichen planus in the man, followed by Pseudomonas, Klebsiella, and cytomegalovirus infections plus chronic hepatitis during intensifying immunosuppressive therapy. Type B thymomas were then detected. Despite surgery or radiotherapy, and intensive drug therapy, the patients died 7 and 1 years later.SummaryCertain infections/dermatologic manifestations that associate with long-standing thymomas may herald their late appearance, despite previous thymectomy.

Allergic contact dermatitis (ACD) is a type IV, delayed-type reaction caused by skin contact with low-molecular-weight organic chemicals and metal ions that activate antigen-specific T cells, primarily T-helper 1 (Th1), in a sensitized individual, leading to skin eczema.First-line treatments are based on avoidance of causal agents and topical corticosteroids/immunomodulators. In recalcitrant cases, chronic oral immunosuppressive agents may be used, but they may have serious adverse effects and do not address the immunological disfunction. We report a case of severe ACD, unresponsive to topical or oral immunosuppressive therapy, which resolved itself after treatment with teriflunomide (TF) 14 mg/daily used for multiple sclerosis. TF is a once-daily, oral selective and reversible dihydroorotate dehydrogenase inhibitor, revealing a new treatment option for ACD.

Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1β, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1β). To the best of our knowledge, this is the first study reporting a "protective" role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine "rebalancing" of the immune system represents a new target in AD therapeutic approach., The work at ICVS/3B's has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE, 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and funded by FEDER funds through the Competitiveness Factors Operational Program (COMPETE) and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The work at Centro Hospitalar do Porto (CHP) work was funded by "Bolsa para Investigacao" of Departamento de Ensino Formacao e Investigacao (DEFI) do CHP. S.P. das Neves is a recipient of a PhD fellowship with the reference PD/BD/114120/2015, from POCH through FCT National Funds.

We report a patient with congenital myasthenic syndrome (CMS) due to mutation in CHRNE with symptoms since the age of 4; mild to moderate fatigable weakness involved mainly ocular, bulbar and limb muscles; functional impact of the disease in their development and physical activity was modest. By the age of 34, the patient experienced gradual worsening of fatigue with dyspnoea and pronounced limb weakness, requiring significant increase of pyridostigmine. Further, a remarkable and sustained clinical improvement followed thymectomy with hyperplastic thymus. Despite of the absence of detectable antibodies to acetyl-choline receptor (AChR) (including clustered-AChR), muscle-specific kinase and low-density lipoprotein receptor-related protein-4 antibodies in the serum obtained nine years after thymectomy, the clinical, genetic and histological features are in keeping with the extremely rare association of two rare neuromuscular junction disorders - CMS and myasthenia gravis (MG). The inexistence of other conditions that could potentially associate with thymic hyperplasia also supports the diagnosis of MG.

Introduction: Behçet's disease (BD) is a multisystem inflammatory disease of unknown etiology that may affect the CNS - Neuro-Behçet (NB). Our aim was to evaluate the frequency of neurological involvement and characterize a cohort of our NB patients. Methods: We retrospectively revised the clinical, laboratory and imaging data of a cohort of BD patients, followed in our hospital outpatient clinic. Results: We identified 138 BD patients. Twenty-five out of 138 had NB (15 female). Four patients presented with neurological symptoms. We identified a total of 37 attacks. Twenty-one attacks were classified as parenchymatous, four non-parenchymatous and 12 as other syndromes. Seventeen patients had CSF analysis performed (20 samples). Five samples were normal, 15 showed CSF pleocytosis. The most frequent finding on MRI performed in the acute phase was extensive lesions involving the brainstem. Two patients died due to the neurological involvement of BD. Conclusion: We found 18.1% prevalence of NB and a higher female-to-male ratio in our group than in other series. Gastrointestinal and vascular involvement was more frequent in the NB group. The fact that neurological involvement may be the first manifestation of BD with therapeutic implications and associated morbidity points out the relevance of an early diagnosis.

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

• Of 214 patients with myasthenia gravis 17% have another autoimmune disease and 5% have another autoimmune neurological disease.

Introduction The association of myasthenia gravis (MG) and inflammatory myopathy is rare and often only one of the diseases is diagnosed. Thymus pathology may be in the origin of such disease association. Methods We described four patients with both MG and inflammatory myopathy. Results These cases correspond to 2.3% of our MG cohort. Case 1: MG, polymyositis and thymolipoma; case 2: MG and necrotizing myopathy without thymic pathology on a background of scleroderma, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia (CREST); case 3: MG and dermatomyositis without thymic pathology; case 4: MG and dermatomyositis with type C thymoma. Discussion The recognition of these neuromuscular co-morbidities contributes to (i) understanding their pathogenic mechanisms, (ii) developing better management approaches and (iii) further improving disease outcomes.