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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.

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

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.

Introdução: A demência frontotemporal corresponde a um conjunto de síndromas demenciais que têm em comum alterações de personalidade, comportamento e linguagem como características clínicas precoces; e a atrofia do córtex frontal e temporal como característica anátomo-patológica. Esta entidade parece estar subdiagnosticada, pelo que se pretende sensibilizar para as dificuldades na sua identificação e na gestão terapêutica. Descrição do caso: Homem de 74 anos sem antecedentes pessoais e familiares de relevo para a história da doença atual. Um ano após a idade normal de reforma começou a apresentar alteração progressiva dos padrões de conduta social, com ausência do controlo do impulso, associado a comportamentos alimentares desadequados e a rituais, bem como um discurso empobrecido. Algum tempo após o início dos sintomas e observação por outras especialidades médicas foi avaliado e orientado por neurologia. Comentário: O médico de família pode ter um papel importante na suspeição desta entidade clínica, devido à prestação de cuidados longitudinais que assegura um vasto conhecimento dos utentes. Nesse sentido possibilitará uma investigação e orientações adequadas e atempadas, evitando tratamentos desnecessários e potencialmente prejudiciais. Destaca-se, ainda, o seu papel de gestão da multimorbilidade associada e de suporte aos familiares/cuidadores. Introduction: Frontotemporal dementia is characterized by changes in personality, behavior, and language. Atrophy of the frontal and temporal cortex is the main pathological finding. As this entity is under-diagnosed, it is important to raise awareness of the difficulties in diagnosis and management. Case Description: A 74 year-old man had progressive changes in appropriate social behavior from age 66. This included a lack of impulse control, inadequate food behaviors and rituals, and reduced production of speech. Some time after the onset of symptoms and consultation with different medical specialists, he was referred to a neurologist who made the diagnosis of frontotemporal dementia. Commentary: The family physician can play an important role by suspecting this condition, through longitudinal care and personal knowledge of the patient. Proper investigation and appropriate and timely guidance can help avoid unnecessary and potentially harmful treatments. The family physician can also manage associated comorbidity and support the family and other caregivers.

ObjectiveTo develop and validate the evidence-based and consensus-based Behçet’s Syndrome Overall Damage Index (BODI).MethodsStarting from 120 literature-retrieved preliminary items, the BODI underwent multiple Delphi rounds with an international multidisciplinary panel consisting of rheumatologists, internists, ophthalmologists, neurologists, and patient delegates until consensus was reached on the final content. The BODI was validated in a cross-sectional multicentre cohort of 228 patients with Behçet’s syndrome (BS) through the study of (a) correlation between BODI and Vasculitis Damage Index (VDI) and (b) correlation between BODI and disease activity measures (ie, Behçet’s Disease Current Activity Form (BDCAF), Physician Global Assessment (PGA), Patient Global Assessment (PtGA)), c) content and face validity and (d) feasibility.ResultsThe final BODI consists of 4 overarching principles and 46 unweighted-items grouped into 9 organ domains. It showed good to excellent reliability, with a mean Cohen’s k of 0.84 (95% CI 0.78 to 0.90) and a mean intra-class correlation coefficient of 0.88 (95% CI 0.80 to 0.95). Overall, 128 (56.1%) patients had a BODI score ≥1, with a median score of 1.0 (range 0–14). The BODI significantly correlated with the VDI (r=0.693, pConclusionsPending further validation, the BODI may be used to assess organ damage in patients with BS in the context of observational and controlled trials.

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.

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.

Primary Sjögren syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and tear glands, and autoantibody secretion, in the absence of other systemic autoimmune disorder. Among autoimmune diseases, it is a relatively common disease, but the burden of central nervous system (CNS) involvement is controversial. This retrospective study evaluates the prevalence, clinical patterns and outcomes of CNS involvement in a cohort of patients with primary Sjögren syndrome. We evaluated 93 patients with pSS diagnosed according to American-European Consensus Group criteria. Fourteen patients (15.1 %) had CNS involvement. All were women with an average age of onset of the disease of 42.1 ± 14.7 years (average ± SD) and an average age of onset of neurological involvement of 47.29 ± 16 years. Three had parkinsonian syndrome, two epilepsy, two motor and sensory deficits, two headache with brain magnetic resonance abnormalities, two neuromyelitis optica, two chronic progressive myelitis and one aseptic meningitis. Neurological involvement preceded Sjögren syndrome diagnosis in nine of the patients (64 %), and neurological outcome was good in 11 patients (78.6 %). Central nervous involvement was not as rare as expected, and the frequency was similar to the frequency of peripheral nervous system involvement. In half of the patients, this was the first symptom of the disease, emphasizing the importance of considering this diagnosis, especially in young female with neurological symptoms without other evident cause.

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.

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.

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

Objective Neuromyelitis Optica Spectrum Disorder (NMOSD) predominantly affects women and is often active during childbearing years. We investigated the association between NMOSD and pregnancy outcome. Methods Multivariate logistic regression was used to investigate whether pregnancies after NMOSD onset were at an increased risk of miscarriage or preeclampsia in an international cohort of 60 women with aquaporin-4 antibody-positive NMOSD and at least one pregnancy. Results Miscarriage and preeclampsia rates were 12.9% and 11.5%, respectively, increasing to 42.9% and 13.3% in pregnancies after NMOSD onset. Pregnancies after NMOSD onset had a significantly increased risk of miscarriage, independent of maternal age or maternal history of miscarriage (OR 7.28). Furthermore, the influence of NMOSD on miscarriage risk is present up to 3 years before disease onset (OR 9.85–11.6). Pregnancies after NMOSD ending in miscarriage were associated with higher pre-pregnancy and intra-pregnancy annualized relapse rates compared to viable pregnancies (mean ARR: 0.177 vs. 0.0250, respectively). The preeclampsia rate reported here is higher than reported in multiple sclerosis and population studies, however no association existed between NMOSD timing and preeclampsia. There was an increased risk of preeclampsia in women with multiple other autoimmune disorders and a miscarriage in the most recent previous pregnancy. Interpretation Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and women with more active disease in the peri-pregnancy period may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders are at an increased risk of preeclampsia.

Objective: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)–mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)–mediated myasthenia gravis (AChR-MG). Methods: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively. Results: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. Conclusions: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.

Objective: The Brief Smell Identification Test (B-SIT) was used to explore odour identification capacities in multiple sclerosis (MS). Methods: In total, 153 consecutive patients with MS and 165 healthy controls (HC) participated in the study. All participants were asked to answer the B-SIT and the Hospital Anxiety and Depression Scale (HADS). The Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Severity Scale (MSSS), and the Mini-Mental State Examination (MMSE) were used for patients’ clinical and cognitive characterization. Results: Patients with MS (11.1%) were more impaired on the B-SIT than HC participants (3%). The frequency of impairment was higher for patients with secondary progressive (SPMS; 11/16, 68.8%) than relapsing–remitting (RRMS; 4/121, 3.3%) or primary progressive (2/16, 12.5%) courses. A threshold score of ≤ 8 on the B-SIT provided a sensitivity of 69% and a specificity of 97% in the identification of SPMS among patients with relapsing onset. The association between SPMS and impaired B-SIT remained statistically significant after adjusting for demographic (i.e. age and education), clinical (i.e. disease duration, EDSS, and MSSS), psychopathological (i.e. HADS anxiety and depression scores), and cognitive (i.e. MMSE) variables. Conclusions: A brief odour identification measure provided a good discrimination between SPMS and RRMS courses. A systematic assessment of olfactory functions may contribute to the development of clinical markers of SPMS.

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.

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.To detect anxiety and depression in MS patients; and to investigate possible associations with clinical factors.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).Levels of anxiety and depression were significantly higher (p0.001) 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.The study findings support a close linkage between depressive mood and physical manifestations of MS.

Myasthenia gravis is an autoimmune neuromuscular disease, usually affecting women in the second and third decades. The course is unpredictable during pregnancy and puerperium. Myasthenia gravis can cause major interference in labour and partum and exacerbations of the disease frequently occur. The aim of this series of cases is to analyse retrospectively the anaesthetic management of myasthenia gravis patients and complications during the peripartum period.Retrospective, single centre study from clinical files of female myasthenia gravis patients who delivered between 1985 and 2007 at Hospital de Santo António, Porto, Portugal.Seventeen myasthenia gravis patients delivered between 1985 and 2007 in Hospital Santo António. Two women were not included in the study as they had a spontaneous abortion in the first trimester. Four patients presented exacerbations of the disease during pregnancy, no exacerbation occurred in eight patients and three patients presented their first symptoms of myasthenia gravis during pregnancy (without diagnosis at time of delivery). Concerning the eight patients without exacerbations of the disease during pregnancy, pregnancy was brought to term in 87.5% of the cases; five women were submitted to nonurgent caesarean section (62.5%); and epidural block was performed in six patients (75%). No complications related to anaesthesia occurred in the peripartum period. Concerning the four patients with exacerbations of the disease, pregnancy was brought to term in three cases (75%); three women were submitted to nonurgent caesarean section (75%); and epidural block was performed in three patients (75%). One patient underwent an uncomplicated thymectomy under general anaesthesia during pregnancy and, in the postpartum period, there was a myasthenic crisis in another patient. Concerning the three patients without a myasthenia gravis diagnosis at partum, one woman already being followed for presenting muscular weakness had a vaginal delivery under epidural block, without complications; another patient, presenting discrete supine dyspnoea, was submitted to elective caesarean section under spinal block and developed severe dyspnoea that required mechanical ventilation and ICU admission; and in the remaining case, a woman presenting mild blurred vision was submitted to general anaesthesia, which resulted in delayed emergence, muscular weakness and respiratory failure. Pregnancy went full term in all cases (100%). No newborn had a myasthenic crisis.Myasthenia gravis can interfere slightly with pregnancy and partum, although exacerbations of the disease occur frequently. Strict surveillance and therapeutic optimisation are crucial. In women with controlled disease, caesarean section should be carried out only if there are obstetric reasons. Locoregional anaesthesia is preferred, mainly epidural block. A good multidisciplinary cooperation, specific precautions and surveillance can certainly contribute to an improved outcome in myasthenia gravis patients during the peripartum period.

Background Multiple sclerosis (MS) is associated with human leukocyte antigen (HLA) HLA–DRB1*15. Recent evidence that CD8 T cells are implicated in MS suggests that HLA class I may also contribute. An association of HLA–A*02 and A*03 alleles has been described. Objectives We examined the influence of HLA–A*02 and HLA–A*03 in Portuguese patients with MS, independently of HLA–DRB1*15 using a logistic regression model. Conclusions DRB1*15 increased the risk of developing MS and HLA–A*02 decreased the risk. A*03 had no effect. To analyze if HLA–A*02 association was independent from DRB1*15, an interaction between these two alleles was introduced in the model; no significant interaction was found.

Hypnic headache is regarded by most authors as a primary headache, but in some cases it was considered secondary to hypophysis, brain stem, or posterior fossa lesions.We report a case of a 69-year-old woman with a history of a headache that fulfils all International Classification of Headache Disorders-II criteria for hypnic headache, with 2 years of evolution, whose complementary investigation with magnetic resonance and magnetic resonance angiography revealed a dolichoectasia of the basilary artery. She was treated with verapamil with excellent response.To the best of our knowledge, this is the first described case of a patient with hypnic headache and a dolichoectasic basilar artery. The relation between these 2 entities is questionable, but we raise some possible explanations for this relationship.

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB115 (OR = 2.17) and HLA-DRB103 (OR = 1.81) alleles with MS, HLA-DRB103 with SLE (OR = 2.49), HLA-DRB101 (OR = 1.79) and HLA-DRB104 (OR = 2.81) with RA, HLA-DRB107 with Ps + PsA (OR = 1.79), HLA-DRB101 (OR = 2.28) and HLA-DRB108 (OR = 3.01) with SSc, and HLA-DRB103 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB113 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB113 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB113, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB113 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

Background Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the CNS. There have been few epidemiologic studies on NMO, none in Portugal. Objective To analyze the clinical, biological and MRI characteristics from a cohort of Portuguese patients who fulfilled the Wingerchuk 2006 NMO/NMOSD criteria. To identify and characterize those who had concomitant autoimmune disease or circulating autoantibodies. Methods We performed an observational, retrospective, multicenter study in 5 Hospital Centers in Portugal. Results Sixty-seven patients fulfilled the inclusion criteria. They were mainly Caucasian, 55 female. Median age at onset was 32.0 years and mean follow-up 7.4 ± 6.0 years. Twenty-one patients were definite NMO and optic neuritis (ON) the most frequent initial presentation. Forty-six were classified as NMO spectrum disorders. The main subtypes were recurrent ON and single longitudinally extensive transverse myelitis. Twenty-four patients had positive AQP4-IgG. Twenty-three had other circulating autoantibodies. Fifteen out of 67 patients had concomitant autoimmune disease. There was a significant correlation between the presence of autoimmune disease and the positivity for AQP4-IgG. Five patients died, all definite NMO. Conclusion This is the first study about this rare disease in Portugal. Demographic features were similar to other studies. The existence of concomitant autoimmune disease was significantly associated with seropositivity for AQP4-IgG.

Muscle specific kinase (MuSK) myasthenia gravis (MG, MuSK-MG) is a rare subgroup of MG affecting mainly women during childbearing years. We investigated the influence of pregnancy in the course of MuSK-MG and pregnancy outcomes in females with MuSK-MG. A multicentre cohort of 17 women with MuSK-MG was studied retrospectively; 13 of them with ≥1 pregnancy. MuSK-MG onset age was 35,4 years; 23,0% had other autoimmune disorder; 46,2% were treatment refractory. Thirteen women experienced 27 pregnancies, either after MG onset (group I) (n = 4; maternal age at conception = 29.8 years) or before MG onset (group II) (n = 23; maternal age at conception = 26.2 years). In group I pregnancy occurred in average 9.8 years after the MG onset; it occurred in average 17.0 years before MG in group II. In group I, all were on steroids at time of conception, one on azathioprine and another receiving IVIG regularly. There were mild exacerbations that responded to treatment adjustments. There were no relapses in the 12 months following the delivery. There was no pre-eclampsia, birth defects or stillbirths in either group; 3 miscarriages in group II. One case of neonatal MG was recorded. In this small series, pregnancy did not seem to precipitate MuSK-MG or to have a major influence in the MuSK-MG course, and there was no apparent negative impact in pregnancy outcomes in those where pregnancy followed the MG onset. The weight was lower in the newborn of the group I mothers, although none had low birth weight.

Background: Recent data suggest that cognitive reserve modulates the adverse effects of multiple sclerosis (MS) pathology on cognitive functioning; however, the protective effects of education in MS are still unclear. Objective: To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features. Methods: A total of 419 MS patients and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MS patients’ NP scores were adjusted for sex, age and education; and the estimated 5th percentile (or 95th percentile, when appropriate) was used to identify any deficits. Patients also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E ( ApoE) genotypes were investigated. Results: Patients with higher education were less likely ( p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles. Conclusions: These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS.

Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. Weobserved a negative association between the activating KIR2DS1 gene and MS (adjusted OR = 0.450, p = 0.030)independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells. This work was partially supported by Merck Serono Portugal.

Objective: To investigate the influence of pregnancy on patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: A total of 190 women with NMOSD were enrolled from 7 referral hospitals in 4 countries. We reviewed medical records and used a structured questionnaire to investigate gravidity, parity, and the number of relapses during the 2 years before pregnancy, during each trimester of pregnancy, during the first and second trimesters after delivery, and for 6 months thereafter. The annualized relapse rate (ARR) was calculated for each period. Results: Of the 190 women with NMOSD, 40 patients experienced 54 informative pregnancies, and all of them were seropositive for aquaporin-4 antibody. Fourteen patients developed the first symptoms of NMOSD either during the pregnancy (3 patients) or within a year after delivery or abortion (8 and 3 patients, respectively). Twenty-six patients experienced 40 pregnancies after the onset of NMOSD (26 deliveries and 14 abortions [1 spontaneous and 13 elective]). There was one preterm delivery with birth defects and no stillbirths. The ARR during pregnancy did not differ from that before pregnancy, but it increased significantly during the first and second trimesters after delivery (5.3 and 3.7 times, respectively). Moreover, 77% of the deliveries were associated with postpartum relapses. Conclusion: The significantly increased relapse rate and numerous cases of NMOSD onset after pregnancy suggest that delivery adversely affects the course of NMOSD. Prospective studies are needed to confirm our findings.

Objective.Depressed mood and cognitive impairments are common findings in systemic lupus erythematosus (SLE) and frequently coexist. We assessed the neuropsychological functioning of patients with SLE and investigated its association with psychopathological symptoms.Methods.A total of 85 patients with SLE (28 with neuropsychiatric syndromes: NPSLE) and 85 healthy control subjects with similar demographic characteristics were asked to perform a series of neuropsychological tests. A self-report questionnaire (the Hospital Anxiety and Depression Scale) was used to screen for psychopathology symptoms. Patients with SLE underwent a neurological examination.Results.Patients with NPSLE were more depressed and were more frequently impaired in cognitive and olfactory functions than controls or non-NPSLE patients. The NPSLE group remained statistically different from the other 2 groups on a series of neuropsychological measures (the Auditory Verbal Learning Test, Trail Making Test – Part A, Nine-Hole Peg Test, and Brief Smell Identification Test) even after control for elevated anxiety and depressed mood. Non-NPSLE and control groups were not significantly different regarding either psychopathological symptoms or neuropsychological functioning.Conclusion.Verbal memory, psychomotor speed, and olfaction are particularly vulnerable to dysfunction in NPSLE; impairment in these neuropsychological domains is not completely explained by psychopathology symptoms.

Background: Vanishing white matter is an inherited leukoencephalopathy with typical childhood onset. Late onset forms are rare and may present with an extended range of phenotypes. Case report We present a patient born to consanguineous parents who developed learning disabilities by the age of 16 years. At the age of 25 she had a focal motor seizure with subsequent hemiparesis. After an extensive investigation she was diagnosed and treated as multiple sclerosis. There was progressive memory and planning impairment and, six years later, Sjögren syndrome with central nervous system involvement was diagnosed. For six months she was treated with cyclophosphamide, without any improvement. The next two years she had major clinical deterioration following infections. A homozygous mutation was identified in the EIF2B5 gene at the age of 33, and she died a year later. Conclusions: VWM leukoencephalopathy is still largely recognized as a pediatric disorder, with many adult neurologists being unfamiliar with the late onset presentations. We wish to draw attention into these forms, avoiding submitting these patients to extensive workup and unnecessary treatments. © 2011 Elsevier B.V. All rights reserved.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events, miscarriages and thrombocytopenia with persistently positive antiphospholipid antibodies. 1 , 2 APS may be isolated (primary APS) or associated to a connective tissue disease, most often systemic lupus erythematosus (SLE). 1 , 2 APS usually affects young patients before the fifth decade 3 with stroke being the commonest neurological manifestation. 4 Various other neurological manifestations are being recognized in patients with APS including migraine, epilepsy, multi-infarct dementia and chorea. 2 The pathological process underlying the neurological manifestations remains obscure. 1 , 2 Herein we report a case of primary APSpresenting with a group of unusual neurological manifestations in a 68-year-old woman.

Introduction Pseudotumor cerebri is an entity characterized by elevated intracranial pressure with normal cerebrospinal fluid and no structural abnormalities detected on brain MRI scans. Common secondary causes include endocrine pathologies. Hyperthyroidism is very rarely associated and only three case reports have been published so far. Case presentation We report the case of a 31-year-old Luso-African woman with clinical symptoms and laboratory confirmation of Graves' disease that presented as pseudotumor cerebri. Conclusion This is a rare form of presentation of Graves' disease and a rare cause of pseudotumor cerebri. It should be remembered that hyperthyroidism is a potential cause of pseudotumor cerebri.

Introduction Both neurosarcoidosis and central nervous system lymphoma can be very difficult to diagnose. We describe the case of a patient in whom neurosarcoidosis was strongly suspected, but who was eventually found to have lymphoma. We believe the case to be of interest and practical value to neurologists, oncologists and internists with an interest in inflammatory diseases. Case presentation A diagnosis of neurosarcoidosis was considered in a 49-year-old Caucasian man on the basis of the following symptoms and indications: a cough, bilateral hilar lymphadenopathy confirmed by thoracic computed tomography, the development of an S1 radiculopathy, cerebrospinal fluid abnormalities (raised protein level), bilateral lung hilar and lachrymal gland uptake on a gallium scan, and erythema nodosum confirmed with skin biopsy. These were followed by the development of multiple cranial neuropathies, including seventh nerve palsy. Exhaustive further investigations yielded no evidence for an alternative diagnosis. Treatments with steroids, cyclophosphamide, intravenous immunoglobulin and finally infliximab were of no benefit. He eventually developed cutaneous nodules, a biopsy of which revealed lymphoma that proved resistant to therapy. Conclusion Constant diagnostic vigilance is required in disorders such as neurosarcoidosis.

The impact of Behcet's disease on higher cognitive functions is still poorly understood. We proposed (1) to characterize the neuropsychological profile of Behcet's disease patients with (Neuro-BD) and without (BD) neurological manifestations; (2) to identify which clinical, psychopathological, and genetic variables are related to neuropsychological performance; and (3) to explore the association between cognitive functioning and neuroimaging findings in BD patients. Fifteen Neuro-BD and 35 BD patients in the nonactive phase of their illness underwent a neurological examination, performed a comprehensive battery of neuropsychological tests, and answered the hospital anxiety and depression scale. Human leukocyte antigen (HLA)-B*51 genotyping was also performed. Patients' neuropsychological performances were compared to those of healthy demographically matched subjects. Within one month from the testing date, a subset of 20-BD patients underwent a magnetic resonance imaging (MRI) scan. Fifty-three percent of Neuro-BD and 40% of BD patients were impaired at least on one neuropsychological measure (i.e., digit span-forward). Poorer cognitive functioning in Neuro-BD was associated with parenchymal involvement, whereas in BD it was related to presence of white matter changes in the frontal lobes, history of headache complaints, or higher levels of anxiety and depression. Current prednisone intake had a positive impact on neuropsychological performance. Disease duration, time since onset of neurological manifestations, or presence of HLA-B*51 allele had no significant influence. Our results indicate that Behcet's disease may affect cognitive abilities in the absence of overt neurological symptoms. These findings point to an insidious course of neurological involvement.

Background Neurological involvement in sarcoidosis is serious and often aggressive. Many patients respond to steroids but some show a progressive course despite treatment with steroids and even more potent immunosuppressive drugs. Objective The aim of this study was to describe our experience in the treatment of refractory neurosarcoidosis with Infliximab—its effect on the course of the disease and side effects. Methods A series of four patients are reported with neurosarcoidosis refractory to treatment with steroids combined with various immunosuppressive drugs in whom Infliximab was used. Results A good response, with improvement or stabilisation of the neurological condition, was seen in all cases, without significant side effects. Infliximab is a chimeric monoclonal antibody that neutralises the biological activity of tumour necrosis factor α, a cytokine thought to play an important role in the pathophysiology of sarcoidosis. Conclusion Our experience using Infliximab adds to the growing evidence that it may fulfil a useful role in cases of refractory neurosarcoidosis.

Reversible cerebral vasoconstriction syndromes are characterized by prolonged but reversible vasoconstriction of the cerebral arteries, presenting typically with thunderclap headache, with or without focal neurological signs or symptoms. They resemble primary central nervous system vasculitis but it is critical to differentiate these two entities. Here we draw attention to intracranial haemorrhage as an important and not uncommon clinical feature in reversible cerebral vasoconstriction syndrome. Four patients with reversible cerebral vasoconstriction syndrome, each presenting to a single unit with intracranial haemorrhage, are described. These descriptions of haemorrhage at presentation of RCVS extend the recognised clinical phenotype and so help to enhance recognition and diagnosis of this often unconsidered disorder.