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Autologous haematopoietic stem cell transplantation is an emerging treatment option in refractory chronic inflammatory demyelinating polyradiculoneuropathy. We describe a case of a 46 year-old male, with history of IgG/lambda monoclonal gammopathy, who was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy at 27 years old. After an initial 10-year period of corticotherapy response, the patient experienced severe relapses and disease progression, evolving to a refractory state. First-line and escalating treatment could not achieve clinical stabilization, leading to severe disability. Pre-treatment with ibrutinib was initiated and autologous haematopoietic stem cell transplantation was performed without significant complications. Marked clinical improvement was observed in the following months, both subjective and objective. A significant proportion of the patients who respond to the first-line immunosuppressive therapy eventually become treatment-refractory. Autologous haematopoietic stem cell transplantation may be a treatment option, offering long-term remission with an overall acceptable side effect and risk profile.

The aim of this work was to study the prevalence of hypocalcemia in cancer patients based on ionized calcium and, as a secondary aim, the influence that hypocalcemia may have on survival. For this retrospective study, a representative sample of all the records of low and normal ionized calcium measured in 2014 was studied. Patients under 18 years and patients from the bone marrow transplantation service were excluded. The number of patients included in this study was 471. The median patient age was 63 years (18 to 91), and 247 (52%) were female. The most represented cancers were thyroid, colorectal, and breast. Ionized calcium was in the normal range in 331 (70%) patients and low in 140 (30%). In a univariable analysis, there were no significant differences in survival at 4 years between normal (47%) and low-level (42%) ionized calcium (p = 0.192), but there were differences in gender, age, the primary site, the number of metastatic sites, and the level of albumin. In the multivariable analysis, only the primary cancer, the number of metastatic sites, and the albumin levels were associated with survival. In a multivariable analysis excluding thyroid cancer, hypocalcemia remained not associated with survival. Hypocalcemia occurs in a variety of cancer types, and it does not have an influence on survival.

Background and purpose Literature regarding headache teleconsultation and patient satisfaction is scarce. The SARS‐CoV‐2 pandemic led to the restructuring of traditional clinical activity by adopting telemedicine. Our objectives were to evaluate patients' satisfaction with headache teleconsultation by telephone during the SARS‐CoV‐2 pandemic and assess patients' preferred model of appointment (face‐to‐face, teleconsultation by telephone, or both). Methods Patients with a previous diagnosis of primary headache or neuropathies and facial pain disorders, and at least one telephone headache visit during the first wave of COVID‐19, filled out an online questionnaire regarding sociodemographic parameters, satisfaction with teleconsultation, and preferred model of appointment. Results We included 83 patients (valid response rate of 64.3%); most had migraine (83.1%). Regarding teleconsultation, 81.9% considered this model adequate for follow‐up, 88.0% were satisfied with the information provided about the disease/treatment, and 73.5% were satisfied with the medication modification. Ninety percent would agree with a new tele‐evaluation if stable after the pandemic. The mixed model was the preferred medical consultation type for the postpandemic period (43.4%), followed by face‐to‐face visits (33.7%). Conclusions Patients were satisfied with the headache teleconsultation during the COVID‐19 era. However, an exclusive model of telemedicine does not seem suitable for monitoring all patients. A mixed approach could be integrated into clinical practice after the pandemic to optimize health care., Patients were satisfied with the headache teleconsultation during the COVID‐19 era. A mixed mode with teleconsultation could be integrated into clinical practice after the pandemic to optimize health care.

© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated., Background: Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality worldwide, often leading to hospital admissions. In Portugal, the factors associated with in-hospital mortality due to CAP are not fully documented. The aim of this study was to characterize the trends of CAP hospitalization in all age groups and the factors associated with their mortality between 2000 and 2014. Methods: We conducted a cross-sectional study using CAP hospitalization data in all age groups, in Portugal Mainland. Logistic regression was used to identify the factors associated with in-hospital mortality. Results: Between 2001 and 2011, CAP hospitalization rate increased from 2.8 to 4.3 per 1000 population. Hospitalization rates were higher in the extreme ages ( ≤ 4 and ≥ 75 years). However, a decrease in the hospitalization rate and its mortality was observed, in the younger ages. A total of 548,699 hospitalization CAP episodes, between 2000 and 2014, were analyzed, with male (56.2%) and elderly ≥65 years (91.7%) predominance, resulting in 101,740 deaths (18.5%). Men had a significantly lower mean age (64.3 ± 26.4 years versus 67.9 ± 27.5 years; p < 0.001). During the studied 15 years, there was an increase of 45.2% in the number of annual hospitalizations, concomitant with the admission increase of individuals aged over 75 years. Since 2012 a decrease in hospitalizations and associated deaths were detected. The increase in age represented a progressive and significant rise in the probability of death, except for the age group 1–4 years. The age group ≥85 years old (Adjusted OR = 124.256; 95%CI: 97.838–157.807) and males (Adjusted OR = 1.261; 95%CI: 1.243–1.280) were significantly associated with death risk for CAP hospitalization. After 2010, this risk decreased (Adjusted OR = 0.961; 95%CI: 0.940–0.982). The main factors affecting mortality were age, sex, unemployment rate, number of performed procedures and admission quinquennia. Conclusions: Despite a trend of decrease in CAP hospitalizations and associated death since 2012, the numbers of in-hospital mortality showed, in the 15 years under analysis, an overall increase over time, mainly associated with age, in particular very old people ( ≥ 75 years), males and a higher parish unemployment rate. Therefore, the implementation of CAP preventive measures should be reinforced in these vulnerable groups., This publication was funded by Fundação para a Ciência e a Tecnologia

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Background Readmission rate is an important healthcare quality metric and remains a problem in Multiple Sclerosis (MS) patients, nonetheless information about this issue is scarce. We present the first study to estimate hospital readmissions in a MS hospital-based European cohort. Methods Retrospective cohort study of patients with at least one hospitalization with a primary discharge of MS from August 1, 2009 and July 31, 2015. The primary outcome was hospitalization within 30 days post-discharge (30-DR). The secondary outcomes included length of stay during index and readmission, total hospital readmissions during the study period, predictors and causes of readmission. Results Forty-four (41.5%) patients had a hospital readmission during the six years of this study, 11.3% of them 30-DR, mainly due to infections (58.5%). The two most common comorbidities in these patients were neurogenic bladder (47.7%) and ischemic heart disease (18.1%). Progressive MS subtype was the main predictor of 30-DR, even after adjustment for therapy (OR: 6.29; p = 0.016), with an area under the curve of 0.73. Conclusion Progressive MS subtypes and “second-line drugs” carry a higher risk of hospital readmission soon after discharge. The impact and cost-effectiveness of strategies to lower readmission rates in MS should be the focus of upcoming studies.

BackgroundPatients with high-grade glioma (HGG) are at increased risk of venous thromboembolism (VTE), throughout the course of disease. Prophylactic anticoagulation is not established among patients with HGG, outside of perioperative context, due to potential for intracranial hemorrhage (ICH) and the limited data available for predictive VTE scores in primary brain tumors. The aim of this study was to characterize VTE prevalence in adult patients with HGG and assess ICH risk during therapeutic anticoagulation.MethodsRetrospective analysis of patients diagnosed with HGG at our institution, between 2009 and 2018. All adult patients proposed to systemic treatment were included into this study. Exclusion criteria was anticoagulation previous to diagnosis. VTE was defined as any radiographic-confirmed thrombus in the venous system. Risk factors of interest for VTE and bleeding risk scores were analyzed by chi-squared test and multivariate logistic regression. Survival analysis was performed using Kaplan-Meier method.ResultsA total of 410 patients were included of whom 31 (7,8%) developed a VTE, including 22 deep vein, 6 pulmonary and 3 central venous thrombosis. Twenty-nine patients with VTE had a WHO grade 4 glioma and 2 patients had grade 3 (anaplastic astrocytoma and oligodendroglioma).In 22 cases, the VTE occurred during systemic treatment, more frequently during Temozolomide (n=15), followed by Irinotecan+Bevacizumab (n=6), Lomustine+Bevacizumab (n=1) and PCV (n=1). The median time between diagnosis and VTE was 10,11 months (95CI 6,46-14,79). Khorana score, age, ECOG performance status, smoking and obesity did not significantly differ in the VTE population. All VTE were initially treated with low molecular weight heparin (LMWH), of which 64.5% maintained LMWH, and the remainder switched to warfarin (19.4%) or to direct oral anticoagulant (16.1%). Six patients (19,4%) had spontaneous ICH under anticoagulation. Patients with grade 3 glioma (p=0,032) had significantly higher rates of ICH than grade 4. Patients with higher ECOG had significantly higher risk of ICH (OR 3,23 (95CI 1,18-8,81), p=0,022). HAS-BLED and ACCP bleeding scores were not associated with ICH. There was no significant difference in overall survival for TVE or ICH.ConclusionAccording to our data, ICH occurred in nearly 20% anticoagulated patients with HGG, as described in literature, and did not correlate with poorer prognosis. High ECOG performance status was an independent risk factor for ICH. Further effort towards better prediction models for VTE and ICH in HGG is warranted.

Background Previous studies in multiple sclerosis (MS) showed that therapeutic inertia (TI) affects 60–90% of neurologists and up to 25% of daily treatment decisions. The objective of this study was to determine the most common factors and attribute levels associated with decisions to treatment escalation in an international study in MS care. Methods 300 neurologists with MS expertise from 20 countries were invited to participate. Participants were presented with 12 pairs of simulated MS patient profiles described by 13 clinically relevant factors. We used disaggregated discrete choice experiments to estimate the weight of factors and attributes affecting physicians’ decisions when considering treatment selection. Participants were asked to select the ideal candidate for treatment escalation from modest to higher-efficacy therapies. Results Overall, 229 neurologists completed the study (completion rate: 76.3%). The top 3 weighted factors associated with treatment escalation were: previous relapses (20%), baseline expanded disability status scale [EDSS] (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (≤ 3%). We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-MS specialists. Conclusions Our results provide critical information on factors influencing neurologists’ treatment decisions and should be applied to continuing medical education strategies.

Background Therapeutic inertia (TI) is a worldwide phenomenon that affects 60 to 90% of neurologists and up to 25% of daily treatment decisions during management of multiple sclerosis (MS) patients. A large volume of MS patients are women of childbearing age, and desire for pregnancy is a complex variable often affecting MS care. The objective of this study was to determine the effect of desire for pregnancy on decisions to escalate treatment during management of MS patients. Methods 300 neurologists with expertise in MS from 20 countries were invited to participate in the study. Participants were presented with 12 pairs of simulated MS patient profiles reflective of case scenarios encountered in clinical practice. Participants were asked to select the ideal candidate for treatment escalation from modest to higher-efficacy therapies. Disaggregated discrete choice experiments were used to estimate the weight of factors and attributes affecting physicians’ decisions when considering treatment selection. An excel calculator that provides estimates as the percentage of participants that would escalate treatment for a simulated case-scenario was constructed. Results 229 (76.3%) completed the study. The mean age (SD) of study participants was 44 (±10) years. The mean (SD) number of MS patients seen per month by each neurologist was 18 (±16). Non-MS specialists were significantly less likely to escalate treatment than MS specialists across mild, moderate, and severe patient cases. These differences were accentuated when case scenarios introduced a desire for pregnancy. The findings were consistent when MRI-lesions, severity of symptoms, and number of relapses were included. Conclusions Desire for pregnancy differentially influences decisions to escalate treatment, suggesting knowledge-to-action gaps between MS and non-MS specialists. Our findings indicate the need for educational strategies to overcome these gaps and improve clinical outcomes for MS patients who desire pregnancy.

Systemic lupus erythematosus is a heterogeneous and unpredictable autoimmune disease which can be complicated to approach and treat. Hemophagocytic lymphohistiocytosis and diffuse alveolar hemorrhage are rare disease complications. The authors describe a clinical case of a 32-year-old woman with lupus and fever of unknown origin. From the investigations performed, the myelogram revealed hemophagocytosis and Leishmania parasites, therefore liposomal amphotericin B was then started. In addition to directed therapy, she maintained fever that evolved with diffuse alveolar hemorrhage. The myelogram was repeated and showed that she still had hemophagocytosis but now without parasites. Corticotherapy was increased and intravenous Immunoglobulin was started, with improvement. Rituximab was started as a result of macrophage activation syndrome and diffuse alveolar hemorrhage. Months after discharge, she began once again to have sustained fever and Leishmania parasites were found again, therefore liposomal amphotericin B was started once more associated with miltefosine. She continues being followed-up as she is asymptomatic and using steroidsin weaning scheme.O lúpus eritematoso sistémico é uma doença autoimune heterogénea e imprevisível, o que pode complicar a sua abordagem e tratamento. A linfohistiocitose hemofagocítica e a hemorragia alveolar difusa são complicações raras da doença. Os autores descrevem o caso de uma mulher de 32 anos, com lúpus e febre de origem indeterminada. Da investigação realizada, o mielograma revelou hemofagocitose e parasitas de Leishmania, pelo que iniciou anfotericina B lipossomal. Manteve febre apesar da terapêutica dirigida e evoluiu com hemorragia alveolar difusa. Repetiu mielograma, mantendo hemofagocitose já sem parasitas, tendo aumentado corticoterapia e iniciado imunoglobulina com melhoria. Dada a presença de síndrome de activação macrofágica e hemorragia alveolar difusa iniciou rituximab. Meses após a alta hospitalar, iniciou novamente febre sustentada e foram novamente identificados parasitas de Leishmania, pelo que reiniciou anfotericina B lipossomal associada a miltefosina. Mantém follow-up, encontrando-se assintomática e com corticóides em esquema de desmame.

Sports activities associated with repetitive cranial trauma have become a fad and are popular in gyms and even among children. It is important to consistently characterize the consequences of such sports activities in order to better advise society on the real risks to the central nervous system. We present the case of a former boxer reporting cognitive and behavioral symptoms that began six years after his retirement as a boxer, evolving progressively with parkinsonian and cerebellar features suggestive of probable chronic traumatic encephalopathy (CTE). Using our case as a paradigm, we extended the range of differential diagnosis of CTE, including corticobasal degeneration, multiple system atrophy, vitamin B12 deficiency, neurosyphilis, frontotemporal dementia and Alzheimer’s disease.

Neurological complications are frequently reported in an intensive care unit (ICU), as a manifestation of a critical systemic illness or of its treatment. On the specific setting of COVID-19 patients, peripheral nerve lesions can have a multiplicity of causes, such as post-infectious neuropathy, positioning-related neuropathy or iatrogeny. An unusual but potentially disabling complication of any peripheral nerve lesion is Complex Regional Pain Syndrome (CRPS). Although there have been no mechanistic studies assessing how SARS-CoV-2 might directly impact nociception, it is hypothesized that the systemic hyperinflammation seen in severe COVID-19 may contribute to peripheral and central neuronal sensitization, possibly increasing the risk of developing CRPS. This case report highlights the potential hazards and consequences of peripheral nerve injuries on an ICU setting in COVID-19 patients, as well as the importance of a multidisciplinary approach for an early diagnosis and treatment, which are directly related to a better prognosis., COVID-19; Critical care; Complex regional pain syndrome; Peripheral nerve injury; Case report.

Therapeutic inertia (TI) is defined as a failure to initiate or intensify treatments despite evidence of disease activity. Its prevalence and determining factors in Relapsing-Remitting Multiple Sclerosis (RRMS) patients in Portugal are not known. The main objective of this work was to ascertain the prevalence of TI in RRMS and its determining factors.We conducted a multicentre retrospective observational study of RRMS patients followed in MS Clinics of six Portuguese hospitals with at least one medical appointment in 2018. TI was defined as the absence of treatment initiation or intensification when therapeutic goals were unmet, that is when there was evidence of disease activity based on the definition of "no evidence of disease activity" (NEDA) which refers to absence of clinical relapses, absence of disease progression measured by expanded disability status scale (EDSS) and absence of new disease activity (new T2 lesions/enhancing lesion) on magnetic resonance imaging (MRI) over the period of observation.We included 427 patients with RRMS meeting inclusion criteria, 69.6% females, with a mean age of 41.66 years old. The mean age at diagnosis was 33.17 years old and the average number of years since diagnosis was 8.72. MS relapses were reported on 54 patients. Moderate to severe relapses were reported in 59.3%. Median EDSS score was 1.5. Intention to get pregnant was explicit in 39 patients, representing 18.8% of the women at childbearing age. Among the 365 patients who had an MRI, 23.8% had new T2 lesions and 7.4% had enhancing lesions. Regarding DMT, 72.8% were treated with interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate, 20.6% were under fingolimod, natalizumab, rituximab, and cladribine, and the remaining 6.6% were without treatment. Adverse events were reported in 12.9% of patients, and 10.1% mentioned preferences regarding the treatment. TI was present in 80 (18.7%) patients, representing 54.8% of those with potential to inertia. Patients with a radiologically less active disease, who were already on a DMT and who had no adverse events from their current treatment were more likely to have TI (p0,05). Also, patients followed in centers classified as higher level of care (level 1) had more TI compared with patients followed in centers of levels 2 and 3.TI was present in 1 in 5 patients, exceeding half of the sample with the potential to inertia, corroborating the high prevalence of TI in other studies. The determining factors of TI were the absence of relapses or the occurrence of mild relapses, being already on DMT, absence of adverse events, and follow-up in higher care level centers. TI is a topic rarely addressed in MS and this work highlights the importance of therapeutic optimization in these patients. Further studies should be held to explore the factors that influence TI once they have a great impact on therapeutic decisions.

O penfigoide bolhoso é uma doença autoimune caracterizada pela formação de bolhas subepidérmicas. Pode ser autolimitada mas quando necessário o tratamento passa pelo uso de corticoides, imunossupressores, e em última linha agentes biológicos. Apresenta-se o caso de um doente de 37 anos com penfigoide bolhoso com uma forma de apresentação grave e refratária. Após cerca de um mês de tratamento com vários fármacos de primeira linha, por ausência de resposta, optou-se por iniciar rituximab com franca melhoria das lesões. Os autores pretendem realçar a utilidade e eficácia deste fármaco nesta patologia.

Less than 10% of Alzheimer’s disease (AD) cases are familial. Presenilin-1 (PSEN1) mutations are the most frequent aetiology and may be associated to atypical neurological manifestations. We report the case of a 27-year-old right-handed man, ensuing with mild cognitive impairment, motor discoordination and axial myoclonus after a parachute accident. At age 32 he was referred to our neurology clinic, presenting cognitive impairment, cerebellar syndrome, axial myoclonus and hypomimia, without other signs of parkinsonism. Because of absence of family history, he was worked up along the line of spinal ataxic disorders. Later, he developed pseudobulbar affect, cognitive deterioration, right upper limb paresis and spastic paraparesis. Subsequent investigation identified a PSEN1 P117L mutation and the diagnosis of autosomal dominant AD was made. This case illustrates the diagnostic challenge imposed by atypical presentation of de novo PSEN1 mutation, leading to unnecessary investigation. Genetic study might be essential for defining the diagnosis.

The diagnosis of giant cell arteritis (GCA) is based on the presence of clinical and laboratory features. Color-duplex sonography (CDS) may supplant the limited sensitivity of temporal artery biopsy. The aim of our work was to characterize clinical and laboratory findings in patients with positive CDS for GCA.Retrospective study of all consecutive patients of our center fulfilling American College of Rheumatology criteria for GCA who performed CDS study between 2009-2019. Data on clinical and laboratory features were compared in two groups: with and without halo sign.Ninety-one patients were included. Temporal halo sign was identified in 46% of patients. Halo sign was more often present in older patients (77 ± 8 vs 73 ± 8 years, p = 0.022), associated with systemic features (58% vs 42%, p = 0.011), higher erythrocyte sedimentation rate (84 ± 26 vs 74 ± 34 mm/hour, p = 0.020), and lower hemoglobin values (10.9 ± 1.5 vs 12.1 ± 1.6 g/dL, p 0.001). The number of patients under corticosteroids before CDS was higher in the group without halo (62% vs 33%, p = 0.005). Ischemic stroke occurred in 17 patients (19%), 76% in the vertebrobasilar territory, and stroke was associated with vertebral halo sign (p 0.001).Halo sign was present in half of our patients. Previous corticosteroids treatment decreased positive CDS findings. Systemic symptoms and laboratory findings are more notorious in halo sign subgroup of patients. Stroke cases in GCA patients disproportionally affected the posterior circulation. Ultrasonography provides information about a more pronounced systemic involvement and a higher risk of major complications.

Background Multiple sclerosis treatment has changed in the last years with the emergence of new disease-modifying therapies (DMTs). Despite a better efficacy profile, these drugs raise concerns about infectious risk, which needs to be mitigated. Objective To analyze the results of a systematic collaborative approach between Neurology and Infectious Diseases (ID) Departments in the management of infectious risk and complications in MS patients treated with DMT. Methods Retrospective collection of MS patients’ demographic and clinical data from clinical records of MS and ID outpatient clinics (2011–2017). Results We included 149 patients: most had evidence of previous contact with Herpesviridae, and half of them were not immune to hepatitis A and B viruses (HAV and HBV). Vaccines for HAV, HBV, and Streptococcus pneumoniae were administered in 91%, 78%, and 88% of non-immune patients, respectively. JC virus serology monitoring prevented natalizumab (NTZ) initiation or prompted its switch in 34/122 patients. Forty patients had latent tuberculosis, in which 88% were treated. Infectious events occurred in 33 patients, mostly mild urinary, respiratory, and herpes virus group infections. Only three patients required inpatient care. Conclusion Facing the expansion of the new DMT, we highlight the benefits of an interdisciplinary approach for safer use of the chosen treatment.

Background Spectral-domain optical coherence tomography has been used in several neurological conditions, and peripapillary and macular measurements have been proposed as potential biomarkers in these disorders. The aim of this study was to investigate retinal and choroidal changes in Huntington's disease and to evaluate any potential correlation with the stage of the disease. Methods A cross-sectional observational study compared patients with Huntington's disease and controls. Patients were evaluated using the Unified Huntington's Disease Rating Scale. Spectral-domain optical coherence tomography with enhanced depth imaging was used, and peripapillary choroidal and retinal nerve fiber layer thickness and macular retinal and choroidal thickness were evaluated. Results Fifteen eyes of 8 patients and 16 eyes of 8 sex-, age-, and mean refractive error–matched healthy controls were included. Average (231.3 ± 52.8 vs 296.2 ± 57.1, P = 0.033), central (341.8 ± 70.5 vs 252.0 ± 57.9, P = 0.015), and inferior (225.3 ± 57.9 vs 313.8 ± 55.2, P = 0.007) macular choroidal thickness were significantly reduced in patients, in comparison with controls. No differences were observed in macular retina or peripapillary retinal and choroidal measurements. However, there was a negative correlation between Total Motor Score of the Unified Huntington's Disease Rating Scale and average (r2 = 0.585, P = 0.027), superior (r2 = 0.653, P = 0.015), nasal (r2 = 0.642, P = 0.017), and inferior (r2 = 0.574, P = 0.029) macular retinal thickness. Conclusions Our results suggest that both the choroidal and retinal macula are altered in Huntington's disease and may become useful biomarkers for monitoring neurodegeneration in this disease. The involvement of the choroid may also support the recent findings of vascular involvement in Huntington's disease. © 2016 Movement Disorder Society

Cavernous angiomas are central nervous system malformations. Most common manifestations are seizures and acute focal neurological deficits. We present a case report of a seventy-one year-old man with a two-month history of behavior changes, attention deficit and indifference followed by gait unsteadiness. Neuropsychological evaluation showed severe cognitive impairment and executive dysfunction. Head computed tomography depicted a supraventricular hydrocephaly. Magnetic resonance imaging revealed a small hemorrhage, contiguous to a mesencephalic cavernous angioma, obstructing the Sylvius aqueduct, causing secondary hydrocephalus. Four months after endoscopic ventriculocisternostomy, neuropsychological evaluation showed improvement and the patient regained autonomy. Parenchyma cavernous angiomas causing direct hemorrhage and subsequent obstruction of the Sylvian aqueduct are uncommon. Sub-acute behavior and mental state abnormalities are rare first manifestations of cavernous angioma and requires high clinical suspicion for its correct diagnosis. Magnetic resonance imaging evaluation is crucial in the detection of such patients as prompt neurosurgical intervention may substantially improve cognitive function.Os angiomas cavernosos são malformações do sistema nervoso central cujas manifestações mais comuns são crises epiléticas e défices neurológicos agudos. Apresentamos o caso clínico de um doente de 71 anos com uma história com dois meses de evolução de alteração do comportamento, défice de atenção e apatia, sucedidas por marcada instabilidade da marcha. A avaliação neuropsicológica revelava alterações cognitivas e disfunção executiva marcadas. Na Tomografia Computorizada Cerebral observava-se hidrocefalia supraventricular enquanto na Ressonância Magnética cerebral era possível observar uma pequena hemorragia que obstruía o aqueduto de Sylvius localizada contiguamente a um angioma cavernoso mesencefálico. Quatro meses após o tratamento com ventriculocisternostomia endoscópica, o doente apresentava melhoria significativa na avaliação neuropsicológica tendo voltado a adquirir a autonomia prévia. A apresentação de um angioma cavernoso parenquimatoso como uma obstrução do aqueduto de Sylvius secundária a hemorragia é invulgar. Rara é também a sua apresentação como alterações do comportamento e do estado mental subagudas. Uma avaliação neuroimagiológica e uma intervenção neurocirúrgica precoces foram essenciais para a melhoria cognitiva observada.

Background Cytomegalovirus (CMV) reactivation with neurological involvement in patients with acquired immunodeficiency syndrome (AIDS) is increasingly rare since the introduction of antiretroviral therapy (ART). Manifestations include encephalitis, myelitis, polyradiculopathy and, less commonly, mononeuritis multiplex (MNM). We report a case of disseminated CMV disease with gastrointestinal and peripheral and central nervous system involvement in a patient with AIDS, manifesting primarily as MNM. Case presentation A 31-year old woman with AIDS presented with a clinical picture of MNM. Electromyography confirmed the clinical findings. CMV DNA was detected in cerebrospinal fluid (CSF) and blood. Gastrointestinal involvement was histologically documented. HIV RNA was also detected in CSF and brain MRI was consistent with HIV encephalopathy. A diagnosis of disseminated CMV disease (with esophagitis, colitis, encephalitis and MNM) and HIV encephalopathy was made. Treatment consisted of ganciclovir and foscarnet, followed by maintenance therapy with valganciclovir. Evolution was favorable and valganciclovir was stopped after sustained immune recovery following ART initiation. Conclusion We discuss the diagnostic approach to CMV neurological disease, with a focus on MNM and CMV encephalitis. Combination therapy with ganciclovir and foscarnet should be considered for all forms of neurological involvement, although available data are scarce. Since there is significant overlap between CMV encephalitis and HIV encephalopathy, ART drugs with higher CSF penetration may have to be considered. ART and immune recovery are essential to improve outcomes.

Large-cell neuroendocrine tumors (NETs) are poorly differentiated malignancies of rare incidence and aggressive nature. NETs mostly arise in the lung followed by the gastrointestinal tract, although they are potentially ubiquitous throughout the body. Primary unknown NET has a worse prognosis and shorter survival comparing with other NETs, with limited available data in the literature concerning this subgroup. The authors report the case of large-cell NET with supraclavicular lymph node presentation. Total excisional biopsy revealed an enlarged adenopathy 18 × 15 × 10 mm, which was extensively infiltrated by a solid malignant neoplasm composed of large cells with granular chromatin, nuclear pseudo-inclusions, high mitotic index, and focal necrosis, with a Ki 67 index 25-30% and positive immunohistochemical study for the expression of cytokeratin 8/18, chromogranin, synaptophysin, and thyroid transcriptional factor-1 (TTF-1). There was no evidence of primary location apart from two infracentimetric lung lesions that could not be accessed for biopsy and were negative at both somatostatin receptor scintigraphy and positron emission tomography. The NET relapsed with three mediastinal masses, so the patient was started on chemotherapy with carboplatin and etoposide with initial total response. Early progression showed no response to further chemotherapy regimens (temozolomide, oral etoposide); therefore, the patient was treated with local radiotherapy. This patient has an atypical long survival (54 months) compared to the literature data. In fact, there are few long-term survivors of large-cell NET and they are all related to complete surgical resection.

Background Patients with high-grade glioma (HGG) are at increased risk of venous thromboembolism (VTE), throughout the course of disease. Prophylactic anticoagulation is not established outside of perioperative context, due to potential for intracranial hemorrhage (ICH) and the limited data available for predictive VTE scores. Our study aims to characterize VTE risk and assess anticoagulation safety in HGG. Methods Retrospective analysis of adult patients with HGG diagnosis, proposed to systemic treatment between 2009 and 2018. Exclusion criteria was anticoagulation previous to diagnosis. VTE was defined as radiographic-confirmed thrombus in venous system. Risk factors for VTE and ICH were analyzed by chi-squared test and multivariate logistic regression; survival analysis by Kaplan-Meier method. Results Of 410 patients, 31 (7,8%) developed a VTE, including 22 deep, 6 pulmonary and 3 central vein thrombosis. Twenty-nine patients with VTE had WHO grade 4 glioma and 2 patients had grade 3 (anaplastic astrocytoma and oligodendroglioma). In 22 cases, the VTE occurred during systemic treatment, more frequently during Temozolomide (n = 15), followed by Irinotecan+Bevacizumab (n = 6). The median time to VTE was 10,11 months. Khorana score, age, ECOG performance status, smoking and obesity did not significantly differ in the VTE population. All VTE were initially treated with low molecular weight heparin (LMWH), of which 64.5% maintained LMWH, and the remainder switched to warfarin (19.4%) or to direct oral anticoagulant (16.1%). Six patients (19,4%) had spontaneous ICH under anticoagulation. Patients with grade 3 glioma (p = 0,032) had significantly higher rates of ICH. Patients with higher ECOG had significantly higher risk of ICH (OR 3,23 (95CI 1,18-8,81), p = 0,022). HAS-BLED and ACCP bleeding scores were not associated with ICH. There was no significant difference in overall survival for TVE or ICH. Conclusions According to our data, ICH occurred in nearly 20% anticoagulated patients with HGG, as described in literature, and did not correlate with poorer prognosis. High ECOG performance status was an independent risk factor for ICH. Further effort towards better prediction models for VTE and ICH in HGG is warranted. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

•APMPPE is a rare condition preferentially affecting young adults.•It presents as blurred vision, central or paracentral scotomas or metamorphopsia.•Diagnosis is based on fundoscopy evaluation and confirmed by fluorescein angiogram.•Spinal cord infarction may be a rare APMPPE neurological complication.

The perception of multiple sclerosis (MS) severity and risk associated with therapies might influence shared decision making in different countries. We investigated the perception of MS severity and factors associated with risk acceptance in Brazil in 96 patients with relapsing-remitting MS using a standardized questionnaire and compared this with two European cohorts. Multiple sclerosis was perceived as a very severe disease and the risk of developing progressive multifocal leukoencephalopathy due to natalizumab was seen as moderate to high. Seventy-six percent considered a risk of 1:1,000, or higher, an impediment for natalizumab use. Older age was the only variable associated with higher risk acceptance and our patients showed a more conservative profile than German and Spanish patients. Our patients perceived MS severity and progressive multifocal leukoencephalopathy risk similarly to elsewhere, but their willingness to take risks was more conservative. This should be considered when discussing therapeutic options and it might have an impact on guideline adaptations.

Central nervous system (CNS) vasculopathy associated with Varicella Zoster Virus (VZV) infection, usually manifesting as stroke due to ischemic lesions by involvement of small arteries, is frequently misdiagnosed. Immunocompromised patients have a particularly higher risk of severe disease and also CNS involvement during or following VZV presentations. We report a case of an 84-year-old man, with myelodysplastic syndrome, who presented with herpes zoster ophthalmicus complicated with left periocular cellulitis and an abnormal neurological exam. Intravenous treatment with acyclovir and amoxicillin/clavulanic acid was began. VZV DNA was detected in the cerebrospinal fluid (CSF) and brain magnetic resonance imaging revealed three acute ischemic lesions in the left frontal and both cerebellar lobes. A VZV CNS multifocal vasculopathy was diagnosed and treatment with intravenous acyclovir continued for 21 days.Immunocompromised patients with VZV infection can have a more severe course of disease with disseminated involvement and multifocal vasculopathy. In these patients the CSF detection of anti-VZV IgG as well as VZV DNA can be helpful in the diagnosis of CNS VZV vasculopathy. The antiviral treatment can improve the outcome and should be adjusted taking in consideration the degree of immunosuppression. This clinical case and review of the literature highlights the challenges in the diagnosis and management of VZV CNS vasculopathy in immunocompromised patients. Keywords: Varicella Zoster Virus, Vasculopathy, Stroke, Immunocompromised, Acyclovir

Currently, targeted anti-epidermal growth factor receptor (EGFR) agents have an important role in the treatment of various cancers. These drugs, particularly anti-EGFR monoclonal antibodies, may induce electrolyte disorders, such as hypomagnesaemia and hypocalcaemia. Early symptoms of magnesium deficiency can easily go unrecognized. However, hypomagnesaemia can in rare cases lead to serious clinical manifestations, including cardiac arrhythmias or convulsions. The elective tubular expression of renal EGF/EGFR explains the mechanism of this class-related drug side effect. Inhibition of the EGFR induces a mutated-like transient receptor potential cation channel, subfamily M, member 6 (TRPM6) syndrome, characterized by urinary magnesium and calcium wasting. The risk of hypomagnesaemia is associated with treatment duration. It is a reversible toxicity; the recovery of magnesium serum levels is usually seen 4-6 weeks of stopping the anti-EGFR antibody. Using literature from peer-reviewed journals, this review reports the clinical trials findings and discusses the mechanisms and the treatment of hypomagnesaemia induced by anti-EGFR targeted agents.

Objective Among the behaviors associated with food intake, exposure to television is particularly important given the number of adolescents exposed. Also, increased time spent watching television has been associated with physical inactivity and with less desirable dietary intake among adolescents. The aim of this study was to examine the association between television viewing and dietary intake among 13-y-old adolescents. Methods A cross-sectional evaluation was carried out in the 2003–2004 school year, including adolescents born in 1990 and enrolled in the schools of Porto, Portugal. Time spent watching TV was collected by self-administered questionnaires and dietary intake was evaluated using a food frequency questionnaire. Included in the analysis were 1436 adolescents. Results Spending more than 120 min per day watching TV was significantly associated with higher intake of total fat and polyunsaturated fat and with lower intake of magnesium, in both sexes. Additionally, in girls, spending more than 120 min per day watching TV was associated with lower intake of complex carbohydrates, fiber, total vitamin A, folate, vitamin C, calcium, iron, phosphorus, and potassium. In boys, higher intake of saturated fat and cholesterol was found among those spending more time watching TV. Conclusions We found that television viewing is associated with higher consumption of foods containing more fats and sugars and a lower consumption of fruits and vegetables. Consequently, adolescents who watched more television had a higher intake of total fat and polyunsaturated fat and a lower intake of minerals and vitamins. This dietary behavior among adolescents may have long-term health implications, not only limited to obesity.

Background: The assessment of ophthalmic artery flow direction by transcranial Doppler sonography has become part of the cerebrovascular routine examination in stroke patients. It provides helpful information for the investigation of collateral circulation and can evaluate the hemodynamic significance of high-grade internal carotid artery (ICA) stenosis. Our aim was to determine the value of assessing the direction of ophthalmic artery blood flow in the setting of routine color flow duplex ultrasonography examination of patients with ipsilateral carotid disease.

s / The Breast 20 (2011) S12–S55 S49 benefit rate (CR+PR+SD>6mos) ( 3-5yrs, 15.9%; >5yrs, 28.6%). The proportion of patients reporting stable disease was also similar ( 3-5yrs, 47.56%; >5yrs, 44.44%). Overall survival and independently-reviewed assessment of progressionfree survival demonstrated no clinical differences in survival rates (p1⁄40.56 and p1⁄40.73, respectively) between the stratified treatment groups. The incidence of adverse events was similar across all eribulin mesylate treatment groups, with no significant differences in the incidence of Grade 3/4 adverse events of leukopenia, lymphopenia, neutropenia, febrile neutropenia, and neuropathy. In this exploratory, post-hoc analysis, the clinical response to eribulin mesylate in patients with mBC appears independent of time to first metastatic event. Additional studies are required to confirm these findings in less heavily pretreated patients.

Objectives: Family history is a representative risk factor for ovary cancer (OC), frequently associated with BRCA1/2 mutations. The primary objective was to determine the prevalence of BRCA1/2 mutations (somatic and germline) in patients with non-mucinous ovarian cancer (NMOC), invasive fallopian tube neoplasia (IFTN) or primary peritoneal carcinoma (PPC). Methods: National, interventional, retrospective and analytical study, with an estimated sample size of 261 women aged ≥18 years, diagnosed with NMOC, IFTN or PPC between 01/01/2014 and 31/12/2016 in the nine selected centers. Results: From 165 women eligible for analysis, the prevalence of BRCA1/2 mutation was 20% (24.2% somatic, 75.8% germline). For patients with a mutation, 54.5% had a mutation in BRCA1 (27.8% somatic, 72.2% germline), while 45.5% in BRCA2 (20.0% somatic, 80.0% germline). Mean age of the sample was 61.1 years (mutated 60.3 years, non-mutated 61.3 years For patients with a mutation, the ages of the subgroups with somatic and germline were 70.5 and 57.0 years, respectively, with statistically significant difference. Furthermore, patients with somatic mutation were 68.1 years at diagnosis, whereas those with germline were 54.6 years, with statistically significant difference. In addition, 56.4% of patients with a mutation had disease in stage III and 18.8% in stage IV. Regarding family history, 20.6% of the total had confirmed family history of BRCA associated cancer, being that information unknown by 29.1%. In patients with BRCA1/2 germline mutation, 48.0% confirmed family history of BRCA-associated tumors, in opposition to 15.2% in the non-mutated group. From the patients with mutation who reported familial history, 75.0% reported breast cancer, 33.3% ovarian cancer and 15.0% other tumors. Conclusions: PADOC study evaluated for the first time the nationwide prevalence of BRCA1/2 germline and somatic mutations in ovarian cancer in Portugal, and the results suggest an estimated prevalence of 20.0%. These results highlight the importance of raising awareness for the disease in Portugal and the recommendation of broad genetic testing also bearing in mind the percentage of patients that have no information of BRCA-related cancers in family.

Objectives The aim of the study was to provide insights into the contributions of HIV infection stage, antiretroviral therapy (ART) and vascular risk factors to the occurrence of ischaemic stroke in HIV-infected patients. Methods We performed a case–control study of HIV-infected patients followed in our clinic. We compared patients hospitalized between January 2006 and June 2014 with an ischaemic stroke or transient ischaemic attack to age- and gender-matched controls without stroke. Results Of 2146 patients followed in our clinic, we included 23 cases (20 men and three women; mean age 51.3 years) and 23 controls. Eighty-three per cent of cases had had a stroke and 17% a transient ischaemic attack. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, small-vessel occlusion was the most frequent aetiology, followed by large-artery atherosclerosis and cardioembolism. Compared with controls, stroke was statistically significantly associated with diabetes, smoking and low concentrations of high-density lipoprotein (HDL) cholesterol. Illegal drug use, a low CD4 count and a high viral load were also associated with ischaemic cerebral events. There were no statistically significant differences between cases and controls in Centers for Disease Control and Prevention (CDC) HIV stage, CD4 count nadir and HIV infection time-to-event. No statistically significant differences were found concerning ART or treatment compliance. Conclusions In our single centre study, we found associations of illegal drug use, HIV replication and some traditional vascular risk factors with the occurrence of ischaemic cerebral events. The paradigm of the care of HIV-infected patients is changing. Concomitant diseases in the ageing patient with HIV infection, including cerebrovascular disease, must also be addressed in view of their impacts on morbidity and mortality. Apart from controlling the HIV infection and immunosuppression with ART, vascular risk factors must also be addressed.