GUILHERME DIOGO SILVA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
20 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 20
- Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis(2022) SILVA, Guilherme Diogo; CASTRILLO, Bruno Batitucci; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, DagobertoOcrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS.
- Characteristics and management of Susac syndrome in an emergent country: a multi-center case series from Brazil(2022) SANTIAGO, Igor Bessa; ARAUJO, Abraao Lazaro Meneses; NOBREGA, Ivna Lacerda Pereira; SILVA, Walisson Grangeiro Bringel; MENDES, Lucas Silvestre; PONTE, Jose Israel Araujo; DIAS, Daniel Aguiar; CASTRO, Jose Daniel Vieira de; CUNHA, Francisco Marcos Bezerra; SOBREIRA-NETO, Manoel Alves; BRAGA-NETO, Pedro; MARTINS, Gabriela Joca; ARAGAO, Ricardo Evangelista Marrocos de; SILVA, Guilherme Diogo; NOBREGA, Paulo RibeiroBackground Susac syndrome (SS) is a rare endotheliopathy with an estimated prevalence of 0.14-0.024 per 100,000. It is an important differential diagnosis in demyelinating disorders. There are few case series and no large randomized controlled trials, and most reports come from developed countries. We report six cases of SS in three centers in Brazil and discuss management challenges in emergent countries. Methods This is a retrospective case series of patients diagnosed with SS in three medical centers in Brazil between April 2018 and July 2021. The European Susac consortium (EuSaC) criteria were used for diagnosis of SS. Demographic data and clinical interventions were described and outcomes were assessed subjectively and by applying the modified Rankin Scale (mRS) on last follow-up. Results Six patients were diagnosed with SS (3 males, 3 females). Mean age at presentation was 36 years (range 17 to 54). The most common initial symptom was confusion, followed by visual impairment and hearing loss. Characteristic snowball lesions on magnetic resonance imaging (MRI) were present in four patients (66%). Retinal artery abnormalities were present in half (3/6) of patients, and sensorineural hearing loss was present in four patients (66%). Outcome was favorable (mRS <= 2) in five patients (86%). Patients treated early had a more favorable outcome. Conclusion Emergent countries face challenges in the diagnosis and management of patients with SS, such as access to advanced tests (fluorescein angiography, serial MRI) and treatment drugs (rituximab, mycophenolate). Further research should consider particularities of patients with SS in emergent countries.
- Challenges and insights in immunization in patients with demyelinating diseases: a bench-to-bedside and evidence-based review(2022) SILVA, Guilherme Diogo; OLIVEIRA, Vitor Falcao de; MENDONCA, Leonardo OliveiraBackground: Infections are among the main causes of death in patients with demyelinating diseases of the central nervous system (CNSDD). Vaccines are effective methods in reducing hospitalization and death from infectious diseases, but they are challenging in patients with CNSDD because of autoimmunity and immunosuppression. Objectives: To summarize the pathophysiological rationale and main evidence for vaccine recommendations in patients with CNSDD. Methods: Specialists with different backgrounds on the subject: a neurologist specialized in demyelinating diseases, an infectious diseases specialist and an immunologist, presented a critical narrative review of vaccination literature in patients with CNSDD, highlighting which vaccines should or should not be administered and the best time for it. Results: Patients with DDSNC are at increased risk of vaccine-preventable viral and bacterial infections.Vaccines can prevent herpes zoster, hepatitis B reactivation, HPV-associated warts and tumors, viral and bacterial pneumonia, and meningitis. Live attenuated virus vaccines should not be used when the patient is on immunosuppression. Vaccines should be avoided during relapses. The greatest vaccine efficacy is given before treatment or at the end of medication. Conclusion: Patients with DDSNC need differentiated immunization in relation to additional vaccines, contraindicated vaccines and timing of vaccination.
- Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach(2022) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; FEO, Lucas Bueno; SILVA, Guilherme Diogo; DISSEROL, Caio Cesar Diniz; PAOLILO, Renata Barbosa; LARA, Amanda Nazareth; TONACIO, Adriana Coracini; MENDES, Maria Fernanda; PEREIRA, Samira Luisa Apostolos; CALLEGARO, DagobertoBackground Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. Objective To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. Methods Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. Conclusion We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD.
conferenceObject Exploring the association between iron rims in MS lesions, mood disorders, fatigue and cognition(2022) NUNES, D.; PEREIRA, S.; CALLEGARO, D.; AVOLIO, I.; MENDES, M.; SILVA, G.; SILVA, T. da; TIEPPO, E.; ARAUJO, R. de; UCHOA, L.; SILVA, C. da; RIMKUS, C. de Medeiros- Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review(2022) SILVA, Guilherme Diogo; GUEDES, Bruno Fukelmann; JUNQUEIRA, Iori Rodrigues; GOMES, Helio Rodrigues; VIDAL, Jose ErnestoBackground Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce.Objective To critically review the literature on CM and propose a rational approach in the Brazilian scenario.Methods Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil.Results In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data.Conclusion We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.
- Primary angiitis of the central nervous system as a mimic of multiple sclerosis: A case report(2022) TIEPPO, Eduardo Macedo de Souza; SILVA, Tomas Fraga Ferreira da; ARAUJO, Roger Santana; SILVA, Guilherme Diogo; PAES, Vitor Ribeiro; RIMKUS, Carolina de Medeiros; TINONE, Gisela; PEREIRA, Samira Apostolos; CALLEGARO, DagobertoBackground: Primary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis. Case presentation: A 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization. Discussion: Our patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging. Conclusion: The presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis.
- Controversies and Clinical Applications of Non-Invasive Transspinal Magnetic Stimulation: A Critical Review and Exploratory Trial in Hereditary Spastic Paraplegia(2022) CARRA, Rafael Bernhart; SILVA, Guilherme Diogo; PARAGUAY, Isabela Bruzzi Bezerra; LIMA, Fabricio Diniz de; MENEZES, Janaina Reis; PINEDA, Aruane Mello; NUNES, Glaucia Aline; SIMOES, Juliana da Silva; JR, Marcondes Cavalcante Franca; CURY, Rubens GisbertMagnetic stimulation is a safe, non-invasive diagnostic tool and promising treatment strategy for neurological and psychiatric disorders. Although most studies address transcranial magnetic stimulation, transspinal magnetic stimulation (TsMS) has received recent attention since trials involving invasive spinal cord stimulation showed encouraging results for pain, spasticity, and Parkinson's disease. While the effects of TsMS on spinal roots is well understood, its mechanism of action on the spinal cord is still controversial. Despite unclear mechanisms of action, clinical benefits of TsMS have been reported, including improvements in scales of spasticity, hyperreflexia, and bladder and bowel symptoms, and even supraspinal gait disorders such as freezing and camptocormia. In the present study, a critical review on the application of TsMS in neurology was conducted, along with an exploratory trial involving TsMS in three patients with hereditary spastic paraplegia. The goal was to understand the mechanism of action of TsMS through H-reflex measurement at the unstimulated lumbosacral level. Although limited by studies with a small sample size and a low to moderate effect size, TsMS is safe and tolerable and presents consistent clinical and neurophysiological benefits that support its use in clinical practice.
- Case Report: Neurodegenerative Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Infection, a Report of Three Cases: Creutzfeldt-Jakob Disease, Rapidly Progressive Alzheimer's Disease, and Frontotemporal Dementia(2022) PIMENTEL, Gabriela Almeida; GUIMARAES, Thiago Goncalves; SILVA, Guilherme Diogo; SCAFF, MilbertoThe relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurodegenerative diseases is yet to be fully clarified. Rapid worsening and even new-onset cases of those disorders have been reported in association with coronavirus disease 2019 (COVID-19). We describe three cases of neurodegenerative diseases in patients with SARS-CoV-2: a case of Creutzfeldt-Jakob disease during the COVID-19 acute phase, to our knowledge, is the second one described in the literature; a rapidly progressive Alzheimer's Disease; and a patient with frontotemporal dementia, and a quick decline of both cognitive and behavioral domains. This report suggests an association between SARS-CoV-2 infection and a higher probability of developing or accelerating neurodegenerative chronic neurologic conditions. We reinforce the need for a close cognitive follow-up in the aftermath of Sars-Cov2 infection.
- Anti-Tr/DNER Antibody-Associated Cerebellar Ataxia: a Systematic Review(2022) CAMPANA, Igor Gusmao; SILVA, Guilherme DiogoRapidly progressive cerebellar ataxia is a classical paraneoplastic neurological syndrome associated with different autoantibodies and typical demographic characteristics, extracerebellar signs, tumor association, and prognosis. Anti-Tr/anti-Delta/Notch-like epidermal growth factor-related receptor (DNER) antibody is one of the associated antibodies. Given the rarity of this condition, our current knowledge is based on case reports and small case series. In order to improve our understanding of these conditions, we conducted a systematic review of the literature. Our study followed the PRISMA reporting guidelines. Studies of patients with the presence of anti-Tr/DNER antibodies in serum or cerebrospinal fluid (CSF) were included. We extract data information related to study characteristics, demographics, clinical symptoms, tumor association, neuroimaging, and cerebrospinal fluid analysis. Out of 131 records, we analyzed 17 papers, including a total of 85 patients with anti-Tr/DNER antibody-associated cerebellar ataxia. We confirmed that this disease occurred mostly in middle-aged males. Isolated cerebellar ataxia was the most common presentation. Extracerebellar features were rare (8%). Ninety-one percent of the patients presented an associated tumor, being Hodgkin lymphoma the most common. Abnormal neuroimaging patterns included cerebellar atrophy (19%) and cerebellar hypersignal (6%). Cerebrospinal fluid was inflammatory in 64% of the patients. Oncological response was complete in 88%, but neurological prognosis was poor with only 41% of the patients presenting significant neurological improvement at the last follow up. Anti-Tr/DNER antibodies should be tested in rapid progressive cerebellar ataxia. Oncological response is excellent; however, many patients do not improve from their cerebellar ataxia.