[Diagnosis and Treatment of Neuro-Behçet: A Clinical Update]. / Diagnóstico e Tratamento do Neuro-Behçet: Uma Actualização Clínica.

Behçet's disease is a relapsing multisystemic inflammatory syndrome characterized by recurrent oral and/or genital ulcers, uveitis, arthritis, skin lesions, and gastrointestinal and neurological involvement. Neuro-Behçet corresponds to nervous system involvement and is one of the most severe complications of Behçet disease. It occurs in 3% to 30% of cases and is categorized into parenchymal (most common) or non-parenchymal disease. The most common manifestation of parenchymal neuro-Behçet is meningoencephalitis with involvement of the brainstem, where patients present with cranial neuropathies, encephalopathy, sensory-motor syndromes, epilepsy, or myelitis. The main non-parenchymal manifestation is cerebral venous thrombosis. Neuro-Behçet has a predominantly subacute course, with remission within weeks, or clinical progression in one third of the cases. The diagnosis is essentially clinical and diagnostic tests help to corroborate the suspicion, distinguish from differential diagnoses, and exclude complications. Brain magnetic resonance imaging allows the identification of acute lesions (hypointense or isointense on T2-weighted and hypointense on T1-weighted sequences) contrast-enhanced, and chronic lesions characterized by non-contrast enhanced small lesions and brainstem atrophy. If non-parenchymal involvement is suspected, cerebral veno-magnetic resonance imaging /computed tomography should be performed. Cerebrospinal fluid shows elevated proteinorachia and pleocytosis in parenchymal and no changes in non-parenchymal neuro-Behçet (except increased opening pressure). Outbursts of parenchymal disease should be treated with high dose intravenous corticosteroid therapy, with subsequent switch to oral corticoids, followed by biologic therapy, usually an anti-TNF. The treatment of cerebral venous thrombosis is controversial and may consist of a combination of corticosteroids and anticoagulation.

A doença de Behçet é uma síndrome inflamatória multissistémica recidivante, caraterizada por úlceras orais e/ou genitais recorrentes, uveítes, artrite, lesões cutâneas e envolvimento gastrointestinal e neurológico. O neuro-Behçet corresponde ao envolvimento do sistema nervoso e é uma das complicações mais graves da doença de Behçet. Ocorre em 3% a 30% dos casos e categoriza-se em doença parenquimatosa (mais frequente) ou não-parenquimatosa. A manifestação mais comum do neuro-Behçet parenquimatoso é a meningoencefalite com acometimento do tronco cerebral, sendo que os doentes se apresentam com neuropatias cranianas, encefalopatia, síndromes sensitivo-motoras, epilepsia ou mielite. A principal manifestação não-parenquimatosa é a trombose venosa cerebral. O neuro-Behçet apresenta uma evolução maioritariamente subaguda, com remissão em semanas, ou com progressão clínica, em um terço dos casos. O diagnóstico é essencialmente clínico e os exames complementares auxiliam a corroborar a suspeita, a diferenciar de diagnósticos diferenciais e a excluir complicações. A ressonância magnética cerebral permite observar lesões agudas (hipo ou isointensas em T2 e hipointensas em T1) que captam contraste, e lesões crónicas caraterizadas por pequenas lesões que não captam contraste e atrofia do tronco cerebral. Na suspeita de envolvimento não-parenquimatoso deve ser realizada venoressonância magnética/tomografia computorizada cerebral. O líquido cefalorraquidiano apresenta elevação da proteinorraquia e da pleocitose no neuro-Behçet parenquimatoso e não tem alterações no não-parenquimatoso (exceto aumento da pressão de abertura). Os surtos de doença parenquimatosa devem ser tratados com corticoterapia endovenosa em alta dose, com posterior desmame para corticoterapia oral, seguida de terapêutica biológica, habitualmente anti-TNF. O tratamento da trombose venosa cerebral é controverso, podendo consistir na associação de corticoterapia e anticoagulação.

Predictors of cognitive dysfunction one-year post COVID-19.

OBJECTIVES: (a) To characterize the frequency of objective cognitive deficits and self-perceived cognitive difficulties and (b) to explore demographic and clinical predictors of cognitive dysfunction and cognitive complaints. METHOD: One hundred and ten adults diagnosed with COVID-19 between March and November 2020, aged ≤ 74 years underwent a brief neuropsychological evaluation 12 months after infection, which included: Brief Visuospatial Memory Test-Revised, California Verbal Learning Test, and Symbol Digit Modalities Test. T scores < 38 were considered abnormal performance; cognitive dysfunction was defined as ≥ 2 abnormal tests. Participants also completed Broadbent's Cognitive Failure Questionnaires (CFQ), Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, and Short-Form Health Survey. CFQ ≥ 43 was considered indicative of cognitive complaints. RESULTS: Twenty participants (18.2%) had cognitive dysfunction and 36 (33.3%) had cognitive complaints. Cognitive dysfunction was related to lower education, preinfection history of headache/migraine, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were more likely to occur in women, those with fewer years of education, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were also significantly related to symptoms of anxiety, depression, and fatigue. Sex and psychopathology were not significant predictors of cognitive dysfunction. Modest associations were found between CFQ total score and cognitive test performance. DISCUSSION: A subset of individuals develops cognitive difficulties in the context of post-COVID syndrome. Results may support the protective effect of education, a known proxy of cognitive reserve. COVID-19 infection symptoms of headache and sleep disturbance appear to be risk factors for long-term cognitive difficulties. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Fluid biomarkers in stroke: From animal models to clinical care.

Stroke is a leading cause of death and disability worldwide. Stroke prevention, early diagnosis, and efficient acute treatment are priorities to successfully impact stroke death and disability. Fluid biomarkers may improve stroke differential diagnostic, patient stratification for acute treatment, and post-stroke individualized rehabilitation. In the present work, we characterized the use of stroke animal models in fluid biomarker research through a systematic review of PubMed and Scopus databases, followed by a literature review on the translation to the human stroke care setting and future perspectives in the field. We found increasing numbers of publications but with limited translation to the clinic. Animal studies are very heterogeneous, do not account for several human features present in stroke, and, importantly, only a minority of such studies used human cohorts to validate biomarker findings. Clinical studies have found appealing candidates, both protein and circulating nucleic acids, to contribute to a more personalized stroke care pathway. Still, brain tissue complexity and the fact that different brain pathologies share lesion biomarkers make this task challenging due to biomarker low specificity. Moreover, the study design and lack of validation cohorts may have precluded a formal integration of biomarkers in different steps of stroke diagnosis and treatment. To overcome such issues, recent pivotal studies on biomarker dynamics in individual patients are providing added value to diagnosis and anticipating patients' early prognosis. Presently, the most consistent protein biomarkers for stroke diagnosis and short- and long-term prognosis are associated with tissue damage at neuronal (TAU), axonal (NFL), or astroglial (GFAP and S100ß) levels. Most promising nucleic acids are microRNAs (miR), due to their stability in plasma and ease of access. Still, clinical validation and standardized quantitation place them a step behind compared protein as stroke biomarkers. Ultimately, the definition of clinically relevant biomarker panels and optimization of fast and sensitive biomarker measurements in the blood, together with their combination with clinical and neuroimaging data, will pave the way toward personalized stroke care.

Red Cell Distribution Width is Associated with 30-day Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Red cell distribution width (RDW) has been associated with mortality and outcome in a wide variety of non-neurological and neurological diseases, namely in myocardial infarction and acute ischemic stroke, and the reason for this is not completely understood. We aimed to investigate RDW as a potential prognostic marker in patients with intracerebral hemorrhage (ICH). METHODS: This is a retrospective study of consecutive patients with acute non-traumatic ICH admitted to a single center during a 4-year period. We reviewed individual clinical records to collect demographic and baseline information, including RDW at admission, 3-month functional status, and incidence of death during follow-up. Baseline computed tomography imaging was reviewed to classify the location of ICH, and to measure ICH volume and perihematomal edema volume. Patients were divided according to quartile distribution of RDW (RDW-Q1-4). RESULTS: The final study population consisted of 358 patients, median age 71 years (interquartile range [IQR] 60-80), 55% were male, and median Glasgow Coma Scale was 14 (IQR 10-15), with a mean follow-up of 17.6 months. Patients with higher RDW values were older (p = 0.003), more frequently presented with an active malignancy (p = 0.005), atrial fibrillation (p < 0.001), intraventricular hemorrhage (p = 0.048), and were anticoagulated (p < 0.001). Three-month functional independence was similar throughout RDW quartiles. RDW-Q4 was independently associated with increased 30-day mortality (adjusted odds ratio = 3.36, 95%CI = 1.48-7.62, p = 0.004), but not independently associated with increased mortality after 30 days (adjusted hazards ratio = 0.71, 95%CI = 0.29-1.73, p = 0.448). CONCLUSIONS: RDW is a robust and independent predictor of 30-day mortality in non-traumatic ICH patients, and further studies to understand this association are warranted.

Noncontrast computed tomography markers of outcome in intracerebral hemorrhage patients.

Objectives: The characterization of markers capable of predicting clinically significant hematoma growth (HG) in patients with intracerebral hemorrhage (ICH) may be useful for the selection of patients for clinical trials. The use of several noncontrast computed tomography (NCCT) markers has been suggested to stratify the risk of HG. The aim of this study was to analyze HG prediction using different NCCT markers in patients with spontaneous ICH. Methods: Single-hospital retrospective study of patients with spontaneous ICH, who underwent initial NCCT <24 hours after symptom onset. Clinical characteristics were collected and two independent observers analyzed hemorrhage characteristics, volumes and 8 NCCT markers. HG was defined as a growth of ≥33% or ≥6mL in follow-up CT and 30-day survival was collected. Results: 328 patients were included. The most frequent NCCT marker was 'any hypodensity' (68.0%) and the less frequent was the blend sign (11.6%). HG occurred in 22.1% of patients and the only independent predictors for HG were 'any hypodensity' (OR=3.32, 95%CI=1.18-9.34, p=0.023) and the swirl sign (OR=3.98, 95%CI=1.41-11.21, p=0.009). Although all NCCT markers were more frequent in patients who died within 30 days, the only independent predictors were 'irregular margins' (OR=4.54, 95%CI=1.63-12.66, p=0.004) and the satellite sign (OR=2.49, 95%CI=1.07-5.75, p=0.034). NCCT markers with greater sensitivity for HG were 'any hypodensity' and the swirl sign, although with poor positive predictive values and poor areas under the curve. Conclusion: Even though some NCCT markers are independent predictors of HG and 30-day survival, they have suboptimal diagnostic test performances for such outcomes. Abbreviation: OR: odds ratio; 95%CI: 95% confidence interval.