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- Apolipoprotein E Polymorphism Interacts with Cigarette Smoking in Progression of Multiple SclerosisPublication . Sena, A; Couderc, R; Ferret-Sena, V; Pedrosa, R; Andrade, ML; Araujo, C; Roque, R; Cascais, MJ; Morais, MGBACKGROUND AND PURPOSE: The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients. METHODS: Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated. RESULTS: There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS (P = 0.033) and MSSS (P = 0.023) in comparison with non-smokers. CONCLUSION: Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.
- Catatonia in Anti-N-Methyl-D-Aspartate (NMDA) Receptor Encephalitis Misdiagnosed as SchizophreniaPublication . Ponte, A; Brito, A; Nóbrega, C; Pinheiro, S; Gama Marques, JAnti-N-Mmethyl-D-aspartate receptor encephalitis is an autoimmune disease of the central nervous system with prominent neurologic and psychiatric features. Symptoms appear progressively and sometimes with an exclusively psychiatric initial presentation. The patient's evaluation should be meticulous, and we should use all the diagnostic tests required for the exclusion of entities that can mimic this disease. We report the diagnostic investigation of a case of anti-N-methyl-D-aspartate receptor encephalitis in a patient with a previous diagnosis of schizophrenia with poor response to antipsychotics. The aim of this case report is to highlight the importance of close surveillance for neuropsychiatric symptoms, especially catatonia, and to recognize autoimmune encephalitis in the differential diagnosis of psychotic disorders with neurological symptoms and resistance or intolerance to antipsychotics. A prompt diagnosis will contribute to a faster onset of therapy and an overall improvement in prognosis.
- Cerebrospinal Fluid Sex Steroid Hormones in Bacterial MeningitisPublication . Dias, S; Brouwer, M; Boelen, A; van de Beek, DUnfavorable outcome in bacterial meningitis is related to excessive inflammation and higher inflammatory markers have been reported in female than in male patients. Sex steroid hormones have immunomodulatory properties and can be found in the cerebrospinal fluid (CSF); however, their actions have not been studied in bacterial meningitis. We investigated the association between CSF sex steroid hormone levels and inflammatory parameters, disease severity, and outcome in pneumococcal meningitis. We identified adults with culture-proven pneumococcal meningitis in a prospective cohort study (2006-2014). We measured estradiol and testosterone in CSF using liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin (SHBG) using an enzyme-linked immunoassay. Hormone levels were compared according to outcome, which was graded using the Glasgow Outcome Scale (a score of 5 indicating favorable, 1-4 unfavorable outcome). Correlation analysis was used to measure the association between hormone levels and inflammatory cytokines, chemokines, and complement factors as well as severity of illness, as measured by the Glasgow Coma Scale and the Dutch Meningitis Risk Score. We included 60 patients: 20 men, 20 premenopausal (<50 years), and 20 postmenopausal (>50 years) women. Twenty-one (35%) patients had an unfavorable outcome and 11 (18%) died. Cases with an unfavorable outcome exhibited higher estradiol (median 14.0 vs 5.0 pmol/L, P = .04) and lower SHBG (0.40 vs 1.0 nmol/L, P = .03) levels compared with those with a favorable outcome. Estradiol was positively correlated with C-reactive protein (R = 0.42, P = .001), CSF protein (R = 0.33, P = .01), and proinflammatory cytokine levels. CSF concentrations of the sex steroid hormone estradiol were associated with outcome and CSF inflammation. Understanding the dose and time-dependent interaction between sex steroid hormones and the inflammatory response in bacterial meningitis represents an important and understudied topic.
- Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine–Induced Immune Thrombotic ThrombocytopeniaPublication . Sánchez van Kammen, M; Aguiar de Sousa, D; Poli, S; Cordonnier, C; Heldner, M; van de Munckhof, A; Krzywicka, K; van Haaps, T; Ciccone, A; Middeldorp, S; Levi, M; Kremer Hovinga, J; Silvis, S; Hiltunen, S; Mansour, M; Arauz, A; Barboza, M; Field, T; Tsivgoulis, G; Nagel, S; Lindgren, E; Tatlisumak, T; Jood, K; Putaala, J; Ferro, J; Arnold, M; Coutinho, J; Sharma, A; Elkady, A; Negro, A; Günther, A; Gutschalk, A; Schönenberger, S; Buture, A; Murphy, S; Paiva Nunes, A; Tiede, A; Puthuppallil Philip, A; Mengel, A; Medina, A; Hellström Vogel, Å; Tawa, A; Aujayeb, A; Casolla, B; Buck, B; Zanferrari, C; Garcia-Esperon, C; Vayne, C; Legault, C; Pfrepper, C; Tracol, C; Soriano, C; Guisado-Alonso, D; Bougon, D; Zimatore, D; Michalski, D; Blacquiere, D; Johansson, E; Cuadrado-Godia, E; De Maistre, E; Carrera, E; Vuillier, F; Bonneville, F; Giammello, F; Bode, F; Zimmerman, J; d’Onofrio, F; Grillo, F; Cotton, F; Caparros, F; Puy, L; Maier, F; Gulli, G; Frisullo, G; Polkinghorne, G; Franchineau, G; Cangür, H; Katzberg, H; Sibon, I; Baharoglu, I; Brar, J; Payen, JF; Burrow, J; Fernandes, J; Schouten, J; Althaus, K; Garambois, K; Derex, L; Humbertjean, L; Lebrato Hernandez, L; Kellermair, L; Morin Martin, M; Petruzzellis, M; Cotelli, M; Dubois, MC; Carvalho, M; Wittstock, M; Miranda, M; Skjelland, M; Bandettini di Poggio, M; Scholz, M; Raposo, N; Kahnis, R; Kruyt, N; Huet, O; Sharma, P; Candelaresi, P; Reiner, P; Vieira, R; Acampora, R; Kern, R; Leker, R; Coutts, S; Bal, S; Sharma, S; Susen, S; Cox, T; Geeraerts, T; Gattringer, T; Bartsch, T; Kleinig, T; Dizonno, V; Arslan, YImportance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, setting, and participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main outcomes and measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.
- Cognitive Impairment and Magnetic Resonance Imaging Correlates in Primary Progressive Multiple SclerosisPublication . Gouveia, A; Dias, S; Santos, T; Rocha, H; Coelho, C; Ruano, L; Galego, O; Diogo, M; Seixas, D; Sá, MJ; Batista, SObjectives: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. Materials and methods: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. Results: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=-.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. Conclusion: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction.
- Contralateral Upper Limb Weakness Following Botulinum Toxin A Injection for Poststroke SpasticityPublication . Camões- Barbosa, A; Mendes Ribeiro, I; Medeiros, LBotulinum toxin type A has been approved for spasticity management in poststroke patients. The adverse effects are generally of two types: those related to local injection; and those related to the systemic effects from spread of the toxin. Contralateral weakness after botulinum toxin A treatment is a rarely reported adverse effect. We report the case of a 33-year-old female who had been receiving regular injections of incobotulinum toxin A due to spasticity of the right limbs after a hemorrhagic stroke. A switch was made to abobotulinum toxin A with an overall conversion ratio of 1:3.83. The patient presented contralateral upper limb paresis, especially of the deltoid muscle, in the second week post-injection. The electroneuromyography showed neuromuscular block due to botulinum toxin A. She recovered completely after eight months. A switch between different formulations of botulinum toxin type A should prompt caution when carrying out unit conversions. Distant side effects may appear, including paresis in the contralateral limbs.
- Endovascular Treatment of Pediatric Ischemic Stroke: a Single Center Experience and Review of the LiteraturePublication . Fragata, I; Morais, T; Silva, R; Paiva Nunes, A; Loureiro, P; Martins, JD; Pamplona, J; Carvalho, R; Baptista, M; Reis, JIntroduction: Mechanical thrombectomy is standard treatment for large vessel occlusion (LVO) in adults. There are no randomized controlled trials for the pediatric population. We report our single-center experience with thrombectomy of LVO in a series of pediatric patients, and perform a review of the literature. Methods: Retrospective review of consecutive pediatric thrombectomy cases between 2011 and 2018. Demographic variables, imaging data, technical aspects and clinical outcome were recorded. Results: In a period of 7 years, 7 children were treated for LVO at our center. Median age was 13 (2-17), and median Ped-NIHSS was 15 (3-24), and the median ASPECTS was 8 (2-10). Five patients had cardiac disease, and 2 of them were under external cardiac assistance. Median time from onset of symptoms to beginning of treatment was 7h06m (2h58m-21h38m). Five patients had middle cerebral artery occlusions. Thrombectomy was performed using a stentriever in 3 patients, aspiration in 3 patients, and combined technique in 1 patient. Six patients had good recanalization (TICI 2 b/3). There were no immediate periprocedural complications. At 3 months, 4 patients (57%) were independent (mRS score <3). Two patients died, one after haemorrhagic transformation of an extensive MCA infarct, and one due to extensive brainstem ischemia in the setting of varicella vasculitis. Discussion: Selected pediatric patients with LVO may be treated with mechanical thrombectomy safely. In patients under external cardiac assistance and under anticoagulation, thrombectomy is the only alternative for treatment of LVO. A multidisciplinary approach in specialized pediatric stroke centers with trained neurointerventionalists are essential for good results.
- Influence of Physicians’ Risk Perception on Switching Treatments Between High- Efficacy and Non–High-Efficacy Disease‑Modifying Therapies in Multiple SclerosisPublication . Seifer, G; Arun, T; Capela, C; Laureys, G; Jones, E; Dominguez-Castro, P; Sanchez-de la Rosa, R; Hiltl, S; Iaffaldano, PBackground: The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or non-high-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. Objective: Investigate the influence of physicians' risk perception on decision-making when switching treatments for MS and the reasons for switching. Methods: Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017- 2021. Results: Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). Conclusions: Physicians' risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs.
- Influence of Weather on Seizure Frequency - Clinical Experience in the Emergency Room of a Tertiary HospitalPublication . Brás, P; Barros, A; Vaz, S; Sequeira, J; Melancia, D; Fernandes, A; de Sousa, A; Dias, S; Menezes Cordeiro, I; Manita, M
- Language Improvement One Week After Thrombolysis in Acute StrokePublication . Martins, IP; Fonseca, J; Morgado, J; Leal, G; Farrajota, L; Fonseca, AC; Melo, TPOBJECTIVES: Language recovery following acute stroke is difficult to predict due to several evaluation factors and time constraints. We aimed to investigate the predictors of aphasia recovery and to identify the National Institute of Health and Stroke Scale (NIHSS) items that best reflect linguistic performance, 1 week after thrombolysis. MATERIALS AND METHODS: We retrieved data from a prospective registry of patients with aphasia secondary to left middle cerebral artery (MCA) stroke treated with intravenous thrombolysis. Complete recovery at day 7 (D7) was measured in a composite verbal score (CVS) (Σ Language+Questions+Commands NIHSS scores). Lesion size was categorized by the Alberta Stroke Program Early CT score (ASPECTS) and vascular patency by ultrasound. CVS was correlated with standardized aphasia testing if both were performed within a two-day interval. RESULTS: Of 228 patients included (age average 67.32 years, 131 men), 72% presented some language improvement that was complete in 31%. Total recovery was predicted by ASPECTS (OR=1.65; 95% CI, 1.295-2.108; P < 0.00) and baseline aphasia severity (OR=0.439; 95% CI, 0.242-0.796; P < 0.007). CVS correlated better with standardized aphasia measures (aphasia quotient, severity, comprehension) than NIHSS_Language item. CONCLUSIONS: Lesion size and initial aphasia severity are the main predictors of aphasia recovery one week after thrombolysis. A NIHSS composite verbal score seems to capture the global linguistic performance better than the language item alone.
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