Carbapenem-Resistant Pseudomonas aeruginosa Spondylodiscitis Treated with Ceftazidime-Avibactam: A Case Report with Literature Review.

Pyogenic spondylodiscitis (PS) is a highly morbid and potentially fatal bacterial infection with an increasing incidence in recent decades. Its diagnosis and treatment are challenging, especially with the expansion of multidrug- or extensively drug-resistant bacteria. We report a rare case of PS caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) that was treated with ceftazidime-avibactam (C/A). The choice of C/A therapy was based on the patient's bacterial sensitivity profile and intolerance to the initial therapeutic regimen (polymyxin B and meropenem). The total antimicrobial treatment time was seven weeks. The evolution of the clinical course met the cure criteria, which was characterized by remission of signs and symptoms, normalization of inflammatory markers, and radiological improvement over 18 months of clinical follow-up. This is a rare case of CRPA spondylodiscitis that responded to C/A treatment.

Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil. METHODS: We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation. RESULTS: We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively. CONCLUSION: The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.

ANTECEDENTES: Arteriopatia cerebral autossômica dominante com enfartes subcorticais e leucoencefalopatia (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, em inglês) é uma causa genética de acidente vascular cerebral (AVC) isquêmico e a forma mais comum de acidente vascular cerebral não aterosclerótico. Apesar de ser a doença vascular hereditária mais prevalente que há, os dados clínicos para a população brasileira são escassos. Considerando que o Brasil tem uma das constituições genéticas mais heterogêneas do mundo, o conhecimento sobre perfis genéticos e epidemiológicos é obrigatório. Este estudo teve como objetivo elucidar as características clínicas e epidemiológicas de pacientes com CADASIL no Brasil. MéTODOS: Apresentamos uma série de casos envolvendo 6 hospitais de reabilitação no Brasil, e relatamos dados clínicos e epidemiológicos de prontuários de pacientes admitidos entre 2002 e 2019 com confirmação genética. RESULTADOS: incluímos 26 pacientes (16 mulheres) em que as mutações nos éxons 4 e 19 eram as mais comuns. A idade média de início da doença foi de 45 anos. O AVC isquêmico foi o primeiro sintoma cardinal em 19 pacientes. Comprometimento cognitivo, demência e manifestações psiquiátricas foram detectados em 17, seis e 16 pacientes, respectivamente. Ao todo, 8 pacientes apresentavam enxaqueca, sendo com aura em 6 (75%) pacientes. Hiperintensidades de substância branca no polo temporal e na cápsula externa foram encontradas em 20 (91%) e 15 pacientes (68%), respectivamente. A pontuação mediana na escala de Fazekas foi de 2. Infartos lacunares, microssangramentos e macro-hemorragias foram observadas em 18 (82%), 9 (41%) e 2 (9%) pacientes, respectivamente. CONCLUSãO: O presente estudo representa a mais extensa série de pacientes brasileiros com CADASIL publicada até o momento, e relatamos o primeiro caso de micro-hemorragia na medula espinhal de um paciente com CADASIL. A maior parte dos nossos dados clínicos e epidemiológicos está de acordo com as coortes europeias, exceto para micro-hemorragias e macro-hemorragias, para as quais as taxas se enquadram entre as das coortes europeias e asiáticas.

Clinical and epidemiological profiles from a case series of 26 Brazilian CADASIL patients / Perfil clínico e epidemiológico de uma série de casos de 26 pacientes com diagnóstico de CADASIL

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic cause of ischemic stroke and the most common form of non-atherosclerotic stroke. Despite being the most prevalent vascular hereditary disease, clinical data regarding the Brazilian population are scarce. Considering that the Brazilian population has one of the most heterogeneous genetic constitutions in the world, knowledge about genetic and epidemiological profiles is mandatory. The present study aimed to elucidate the epidemiological and clinical features of CADASIL in Brazil. Methods We performed a case series study comprising 6 rehabilitation hospitals in Brazil and reported the clinical and epidemiological data from the medical records of patients admitted from 2002 to 2019 with genetic confirmation. Results We enrolled 26 (16 female) patients in whom mutations in exons 4 and 19 were the most common. The mean age at the onset of the disease was of 45 years. Ischemic stroke was the first cardinal symptom in 19 patients. Cognitive impairment, dementia, and psychiatric manifestations were detected in 17, 6, and 16 patients respectively. In total, 8 patients had recurrent migraines, with aura in 6 (75%) of them. White matter hyperintensities in the temporal lobe and the external capsule were found in 20 (91%) and 15 patients (68%) respectively. The median Fazekas score was of 2. Lacunar infarcts, microbleeds, and larger hemorrhages were observed in 18 (82%), 9, and 2 patients respectively. Conclusion The present is the most extensive series of Brazilian CADASIL patients published to date, and we have reported the first case of microbleeds in the spinal cord of a CADASIL patient. Most of our clinical and epidemiological data are in accordance with European cohorts, except for microbleeds and hemorrhagic strokes, for which rates fall in between those of European and Asian cohorts.

Resumo Antecedentes Arteriopatia cerebral autossômica dominante com enfartes subcorticais e leucoencefalopatia (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, em inglês) é uma causa genética de acidente vascular cerebral (AVC) isquêmico e a forma mais comum de acidente vascular cerebral não aterosclerótico. Apesar de ser a doença vascular hereditária mais prevalente que há, os dados clínicos para a população brasileira são escassos. Considerando que o Brasil tem uma das constituições genéticas mais heterogêneas do mundo, o conhecimento sobre perfis genéticos e epidemiológicos é obrigatório. Este estudo teve como objetivo elucidar as características clínicas e epidemiológicas de pacientes com CADASIL no Brasil. Métodos Apresentamos uma série de casos envolvendo 6 hospitais de reabilitação no Brasil, e relatamos dados clínicos e epidemiológicos de prontuários de pacientes admitidos entre 2002 e 2019 com confirmação genética. Resultados incluímos 26 pacientes (16 mulheres) em que as mutações nos éxons 4 e 19 eram as mais comuns. A idade média de início da doença foi de 45 anos. O AVC isquêmico foi o primeiro sintoma cardinal em 19 pacientes. Comprometimento cognitivo, demência e manifestações psiquiátricas foram detectados em 17, seis e 16 pacientes, respectivamente. Ao todo, 8 pacientes apresentavam enxaqueca, sendo com aura em 6 (75%) pacientes. Hiperintensidades de substância branca no polo temporal e na cápsula externa foram encontradas em 20 (91%) e 15 pacientes (68%), respectivamente. A pontuação mediana na escala de Fazekas foi de 2. Infartos lacunares, microssangramentos e macro-hemorragias foram observadas em 18 (82%), 9 (41%) e 2 (9%) pacientes, respectivamente. Conclusão O presente estudo representa a mais extensa série de pacientes brasileiros com CADASIL publicada até o momento, e relatamos o primeiro caso de micro-hemorragia na medula espinhal de um paciente com CADASIL. A maior parte dos nossos dados clínicos e epidemiológicos está de acordo com as coortes europeias, exceto para micro-hemorragias e macro-hemorragias, para as quais as taxas se enquadram entre as das coortes europeias e asiáticas.

Neuromuscular Choristoma: Report of Five Cases With CTNNB1 Sequencing.

Neuromuscular choristoma (NMC) are lesions of the peripheral nervous system characterized by an admixture of skeletal muscle fibers and nerves fascicles that are frequently associated with desmoid fibromatosis (DF). Mutations in CTNNB1, the gene for ß-catenin protein, are common in DF and related to its pathogenesis. They are restricted to exon 3, with 3 point mutations: T41A, S45F, and S45P. To understand the pathogenesis of NMC, we tested CTNNB1 status in 5 cases of NMC whether or not they were associated with DF. The screening of mutations in CTNNB1 gene was based on amplicon deep sequencing using the ION Proton platform. Three patients had the S45F mutation; in 2 the mutation was common to both lesions and in one the DF was wild type while the NMC had the S45F mutation. One patient had a T41A mutation in the NMC and no associated DF. In the last patient, the DF lesion had a T41A mutation; there was no lesion with the S45P mutation. The presence of similar CTNNB1 mutations in NMC/DF-associated lesions and sporadic DF reinforces the relationship between both lesions and points to a common pathogenic mechanism.

Escore de Cálcio Coronário e Estratificação do Risco de Doença Arterial Coronariana em Pacientes com Acidente Vascular Encefálico Isquêmico Aterosclerótico e não-Aterosclerótico / Coronary Calcium Score and Stratification of Coronary Artery Disease Risk in Patients with Atherosclerotic and Non-Atherosclerotic Ischemic Stroke

Resumo Fundamento O acidente vascular encefálico isquêmico (AVEi) e a doença arterial coronariana (DAC) coexistem frequentemente e compartilham fatores de risco para doença aterosclerótica. Segundo a American Heart Association , os subtipos de AVEi podem ser considerados equivalentes de risco para DAC, mas a evidência para o AVEi não-aterosclerótico não está bem definida. Além disso, o escore de cálcio coronário (CAC) é um marcador preciso para estimar o risco de DAC. Entretanto, a distribuição do CAC pelos subtipos de AVEi ainda não foi bem caracterizada. Objetivos Comparar o CAC entre os grupos de AVEi ateroscleróticos e não ateroscleróticos, e determinar quais covariáveis estão associadas a CAC alto no AVEi Métodos Em um estudo transversal, incluímos todos os pacientes com AVEi, com idades entre 45 a 70 anos no momento do acidente vascular, consecutivamente admitidos em um hospital de reabilitação entre agosto de 2014 e dezembro de 2016, sem DAC prevalente. Todos os pacientes passaram por tomografia computadorizada (TC), para medir o CAC. CAC≥100 foi considerado alto risco de DAC. O nível de significância foi p<0,05. Resultados Dos 244 pacientes estudados (média de idade de 58,4±6,8 anos; 49% do sexo feminino), 164 (67%) apresentavam etiologia não-aterosclerótica. As proporções de CAC≥100 foram semelhantes entre os grupos ateroscleróticos e não-ateroscleróticos (33% [n=26] x 29% [n=47]; p= 0,54). Entre todos os pacientes com AVEi, apenas os de idade ≥60 anos foram associados independentemente a CAC≥100 (RC 3,5; 95% IC 1,7-7,1), ajustado para hipertensão, dislipidemia, diabetes, sedentarismo, e histórico familiar de DAC. Conclusão O AVEi aterosclerótico não apresentou risco maior de DAC quando comparado ao AVEi não-aterosclerótico de acordo com o CAC. Apenas a faixa etária ≥60 anos - mas não a etiologia - foi associada independentemente a CAC≥100. (Arq Bras Cardiol. 2020; 115(6):1144-1151)

Abstract Background Ischemic Stroke (IS) and Coronary Artery Disease (CAD) frequently coexist and share atherosclerotic disease risk factors. According to the American Heart Association, IS subtypes may be considered CAD risk equivalents, but the evidence for non-atherosclerotic IS is uncertain. Additionally, the Coronary Calcium Score (CCS) is an accurate marker to address CAD risk; however, CCS distribution between IS subtypes is not well characterized. Objectives To compare the CCS between atherosclerotic and non-atherosclerotic IS groups; and to determine which covariates were associated with high CCS in IS. Methods This cross-sectional design included all patients with IS, 45 to 70 years of age at the time of the stroke, consecutively admitted to a rehabilitation hospital between August 2014 and December 2016, without prevalent CAD. All patients underwent CT scanning for CCS measurement. CCS≥100 was considered a high risk for CAD, with a significance level of p<0.05. Results From the 244 studied patients (mean age 58.4±6.8 years; 49% female), 164 (67%) had non-atherosclerotic etiology. The proportions of CCS≥100 were similar between the atherosclerotic and the non-atherosclerotic groups (33% [n=26] x 29% [n=47]; p= 0.54). Among all IS patients, only age ≥60 years was independently associated with CCS≥100 (OR 3.5; 95%CI 1.7-7.1), accounting for hypertension, dyslipidemia, diabetes, sedentarism, and family history of CAD. Conclusion Atherosclerotic IS did not present a greater risk of CAD when compared to non-atherosclerotic IS according to CCS. Only age ≥60 years, but not etiology, was independently associated with CCS≥100.

Coronary Calcium Score and Stratification of Coronary Artery Disease Risk in Patients with Atherosclerotic and Non-Atherosclerotic Ischemic Stroke. / Escore de Cálcio Coronário e Estratificação do Risco de Doença Arterial Coronariana em Pacientes com Acidente Vascular Encefálico Isquêmico Aterosclerótico e não-Aterosclerótico.

BACKGROUND: Ischemic Stroke (IS) and Coronary Artery Disease (CAD) frequently coexist and share atherosclerotic disease risk factors. According to the American Heart Association, IS subtypes may be considered CAD risk equivalents, but the evidence for non-atherosclerotic IS is uncertain. Additionally, the Coronary Calcium Score (CCS) is an accurate marker to address CAD risk; however, CCS distribution between IS subtypes is not well characterized. OBJECTIVES: To compare the CCS between atherosclerotic and non-atherosclerotic IS groups; and to determine which covariates were associated with high CCS in IS. METHODS: This cross-sectional design included all patients with IS, 45 to 70 years of age at the time of the stroke, consecutively admitted to a rehabilitation hospital between August 2014 and December 2016, without prevalent CAD. All patients underwent CT scanning for CCS measurement. CCS≥100 was considered a high risk for CAD, with a significance level of p<0.05. RESULTS: From the 244 studied patients (mean age 58.4±6.8 years; 49% female), 164 (67%) had non-atherosclerotic etiology. The proportions of CCS≥100 were similar between the atherosclerotic and the non-atherosclerotic groups (33% [n=26] x 29% [n=47]; p= 0.54). Among all IS patients, only age ≥60 years was independently associated with CCS≥100 (OR 3.5; 95%CI 1.7-7.1), accounting for hypertension, dyslipidemia, diabetes, sedentarism, and family history of CAD. CONCLUSION: Atherosclerotic IS did not present a greater risk of CAD when compared to non-atherosclerotic IS according to CCS. Only age ≥60 years, but not etiology, was independently associated with CCS≥100.

FUNDAMENTO: O acidente vascular encefálico isquêmico (AVEi) e a doença arterial coronariana (DAC) coexistem frequentemente e compartilham fatores de risco para doença aterosclerótica. Segundo a American Heart Association , os subtipos de AVEi podem ser considerados equivalentes de risco para DAC, mas a evidência para o AVEi não-aterosclerótico não está bem definida. Além disso, o escore de cálcio coronário (CAC) é um marcador preciso para estimar o risco de DAC. Entretanto, a distribuição do CAC pelos subtipos de AVEi ainda não foi bem caracterizada. OBJETIVOS: Comparar o CAC entre os grupos de AVEi ateroscleróticos e não ateroscleróticos, e determinar quais covariáveis estão associadas a CAC alto no AVEi. MÉTODOS: Em um estudo transversal, incluímos todos os pacientes com AVEi, com idades entre 45 a 70 anos no momento do acidente vascular, consecutivamente admitidos em um hospital de reabilitação entre agosto de 2014 e dezembro de 2016, sem DAC prevalente. Todos os pacientes passaram por tomografia computadorizada (TC), para medir o CAC. CAC≥100 foi considerado alto risco de DAC. O nível de significância foi p<0,05. RESULTADOS: Dos 244 pacientes estudados (média de idade de 58,4±6,8 anos; 49% do sexo feminino), 164 (67%) apresentavam etiologia não-aterosclerótica. As proporções de CAC≥100 foram semelhantes entre os grupos ateroscleróticos e não-ateroscleróticos (33% [n=26] x 29% [n=47]; p= 0,54). Entre todos os pacientes com AVEi, apenas os de idade ≥60 anos foram associados independentemente a CAC≥100 (RC 3,5; 95% IC 1,7-7,1), ajustado para hipertensão, dislipidemia, diabetes, sedentarismo, e histórico familiar de DAC. CONCLUSÃO: O AVEi aterosclerótico não apresentou risco maior de DAC quando comparado ao AVEi não-aterosclerótico de acordo com o CAC. Apenas a faixa etária ≥60 anos ­ mas não a etiologia - foi associada independentemente a CAC≥100. (Arq Bras Cardiol. 2020; 115(6):1144-1151).

Craniofacial findings in fibrodysplasia ossificans progressiva: computerized tomography evaluation.

OBJECTIVE: The aim of this study was the evaluation by using computerized tomography (CT) of craniofacial abnormalities in fibrodysplasia ossificans progressiva (FOP) patients regarding jaw restriction and retrognathia. STUDY DESIGN: Seven FOP patients were evaluated retrospectively in this observational study. Inclusion criteria were detection of ACVR1 gene mutation and complete craniofacial CT examination. The age of jaw restriction and presence of retrognathia were clinically determined. The features analyzed were skull base structures and heterotopic ossification (HO). RESULTS: Of this group (age range 4-23 years), the 3 oldest patients presented with jaw restriction and retrognathia as well as displayed elongation of the lateral pterygoid plate with HO of the pterygoid muscles that reached the medial surface of the right mandibular ramus. They had significant history of trauma or surgery. The other 4 patients did not have retrognathia or HO involving the facial or masticatory muscles, and the mouth opening was normal. CONCLUSIONS: CT evaluation can reveal HO of the pterygoid muscles that probably may cause jaw restriction and retrognathia in older FOP patients.