1,721,032 research outputs found
Neurological paraneoplastic syndromes: An update
No full textPurpose of reviewTo describe recent advances in the diagnosis and treatment of paraneoplastic neurological syndromes (PNS).Recent findingsPNS are rare complications of cancer caused by an immune cross-reaction between antigens expressed by tumor cells and neurons. The target of the immune attack can be an intracellular antigen or a cell-surface antigen. Although both types of autoimmunity are 'paraneoplastic', as indirectly triggered by the presence of a tumor, they profoundly differ in terms of clinical profile, pathogenesis and outcome. PNS associated with antibodies to intracellular antigens (icPNS) are characterized by relentless progression and poor response to treatment, because of rapid and permanent neuronal loss. PNS associated with antibodies to cell-surface antigens (csPNS) generally show favorable response to immune therapy and good functional outcome, as they result from reversible neuronal dysfunction.SummaryThe spectrum of paraneoplastic autoimmunity has dramatically expanded following the discovery of cell-surface antibodies. Novel antibodies are incessantly discovered, some of which have a solid association with cancer. As csPNS usually respond to immune therapy, the optimization of current treatment strategies should have high priority to improve therapeutic results and prevent relapses
Neurological complications of chimeric antigen receptor T cells and immune-checkpoint inhibitors: ongoing challenges in daily practice
No full textPURPOSE OF REVIEW: The aim of this review is to summarize the most recent advances in the management of neurological toxicities associated with immune-checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cells. RECENT FINDINGS: The advent of cancer immunotherapies has dramatically improved the prognosis of several refractory and advanced neoplasms. Owing to their mechanism of action, cancer immunotherapies have been associated with a variety of immune-related adverse events (irAE). Neurological irAE are uncommon compared with other irAE, but they are associated with significant morbidity and mortality. Despite the efforts to draft common protocols and guidelines, the management of neurological irAE remains challenging. Our ability to predict the development of neurotoxicity is still limited, hampering to elaborate prevention strategies. Treatment heavily relies on the administration of high-dose corticosteroids that, however, have the potential to impair oncological efficacy. The experimentation of novel strategies to avoid resorting to corticosteroids is hindered by the lack of an adequate understanding of the pathogenetic mechanisms driving the development of irAE. SUMMARY: In this review, we will discuss the most recent advances on the diagnosis and management of neurological irAE associated with ICIs and CAR-T cells, focusing on the issues that remain most challenging in clinical practice
Gut microbiome alterations in anti-NMDA receptor encephalitis: caveats for result interpretation
No full textPsychiatric symptoms in anti glutamic acid decarboxylase associated limbic encephalitis in adults: a systematic review
No full textAutoimmune Limbic Encephalitis (LE) is a relatively new category of immune-mediated diseases with a wide range of neuropsychiatric symptoms. LE associated with Glutamic Acid Decarboxylase (GAD) antibodies is difficult to diagnose due to its possible atypical presentation with neuropsychiatric and behavioral features. We performed a systematic review of literature and retrieved 21 cases of anti GAD-associated LE with neuropsychiatric signs. Median age at onset was 27 years with a female predominance (81.0 %) and median diagnostic delay of 6 months. Clinical presentation included typical LE symptoms such as anterograde amnesia (95.2 %) and temporal lobe or tonico-clonic seizures (95.2 %). Psychiatric symptoms were described in 61.9 % of patients, presenting as anxiety, depressive symptoms, apathy and behavioral changes. Extra-limbic symptoms were present in 14.3 % of patients. No neoplasia associated was found. Some patients had poor epileptic, cognitive and psychiatric outcomes requiring prolonged immunosuppressive treatment. The description of the neuropsychiatric spectrum of anti-GAD LE and its specificities aims to improve our understanding of this entity, and may lead to earlier diagnosis as well as better outcome
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Anti-Interleukin-6 and Janus Kinase Inhibitors for Severe Neurologic Toxicity of Checkpoint Inhibitors
No full textBACKGROUND AND OBJECTIVES: To describe the marked clinical and biological responses of a targeted treatment with anti-interleukin-6 (IL-6)-receptor antibody and Janus kinase (JAK) inhibitors in a patient with a severe, corticoresistant CNS toxicity of immune-checkpoint inhibitor (ICI) therapy. METHODS: A 58-year-old man was admitted for subacute paraparesis, urinary retention, and ascending paresthesia. He was under treatment with ipilimumab and nivolumab for metastatic melanoma. Spine MRI disclosed multiple T2-hyperintense, contrast-enhancing longitudinally extensive lesions. A diagnosis of ICI-related acute transverse myelitis was made. RESULTS: ICIs were immediately discontinued, and the patient received high-dose glucocorticoids plus 1 session of plasma exchange, but he did not improve. Based on the marked elevation of CSF IL-6 (505 pg/mL), a second-line targeted therapy with anti-IL-6-receptor tocilizumab (8 mg/kg/mo for 3 infusions) plus JAK inhibitor ruxolitinib (50 mg/d) was administered. Patient neurologic status started to improve shortly after, with corresponding radiologic resolution. At 9 months, the patient was able to walk independently, presenting only slight residual disability while remaining in oncologic partial response. DISCUSSION: Our case suggests that some patients with severe, corticoresistant CNS immune-related toxicities of ICIs may benefit from cytokine blockade. Cytokine measurement in serum and CSF might help in selecting patients for personalized treatment strategies
CLIPPERS mimickers: relapsing brainstem encephalitis associated with anti-MOG antibodies
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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