DRPLA: An unusual disease or an underestimated cause of ataxia in Brazil?

BACKGROUND: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant spinocerebellar ataxia caused by pathological expansion of CAG trinucleotide repeats in the ATN1 gene. Most cases were described in patients from Japanese ancestry who presented with adult-onset progressive cerebellar ataxia associated with cognitive impairment, choreoathetosis and other movement disorders. DRPLA has been rarely described in Brazilian patients. METHODS: We performed a retrospective observational multicentric study including six different Neurology Centers in Brazil. All patients with genetically confirmed diagnosis of DRPLA had their medical records evaluated and clinical, genetic and neuroimaging features were analyzed. RESULTS: We describe of eight Brazilian patients (5 male, 3 female) from four nuclear families with genetically confirmed DRPLA. The most common neurological features included cerebellar ataxia (n = 7), dementia (n = 3), chorea (n = 2), psychiatric disturbances (n = 2), progressive myoclonic epilepsy (n = 2) and severe bulbar signs (n = 1). Progressive myoclonic epilepsy was observed in two juvenile-onset cases before 20-year. A large CAG trinucleotide length was observed in the two juvenile-onset cases and genetic anticipation was observed in all cases. Neuroimaging studies disclosed cerebellar atrophy (n = 6), as well as brainstem and cerebellar atrophy (n = 2) and leukoencephalopathy (n = 1). CONCLUSION: The patients described herein reinforce that clinical features of DRPLA are highly influenced by age of onset, genetic anticipation and CAG repetition lengths. There is a large complex spectrum of neurological features associated with DRPLA, varying from pure cerebellar ataxia to dementia associated with other movement disorders (myoclonus, choreoathetosis). DRPLA is an unusual cause of cerebellar ataxia and neurodegeneration in Brazilian patients.

Embolic Stroke of Undetermined Source (ESUS) and Stroke in Atrial Fibrillation Patients: not so Different after all?

Abstract Background: Stroke related to atrial fibrillation (AF) is associated with high recurrence and mortality rates. Embolic Stroke of Undetermined Source (ESUS) is associated with fewer vascular risk factors, less disability, and a high recurrence rate. Objective: To compare risk factors, functional outcomes and the occurrence of primary endpoint (a composite of recurrent stroke, cardiovascular death, and myocardial infarction) between AF stroke and ESUS patients. Method: A retrospective analysis was conducted including all consecutive patients with first-ever ischemic stroke admitted to the Hospital de Clinicas (Clinical Hospital) of the Federal University of Paraná from October 2012 to January 2017 (n=554). There were 61 patients with stroke due to AF and 43 due to ESUS. Both groups were compared for demographic characteristics and vascular risk factors. Logistic regression models were performed to assess the impact of each variable on the primary endpoint in a 12-month follow-up. Statistical significance was considered for p-values < 0.05. Results: ESUS patients, as compared to AF patients, were younger and more likely to be smokers. ESUS patients presented a mean CHADS2VASc score of 4, while the AF group presented a score of 5 (p <0.001). The primary endpoint was observed in 9 (20.9%) ESUS and 11 (18.0%) AF patients over a 12-month period (p=0.802). Higher glucose levels upon hospital admission (p=0.020) and a higher modified Rankin Scale upon hospital discharge (p=0.020) were predictors of the primary endpoint occurrence. Conclusion: AF and ESUS stroke patients presented very similar independence rates upon hospital discharge and outcomes after 12 months, despite some baseline differences, including stroke recurrence, vascular death, and myocardial infarction.

Stroke recurrence in the different subtypes of ischemic stroke. The importance of the intracranial disease.

The aim of the study was to analyze the long-term recurrence rate in patients with a first-ever ischemic stroke secondary to intracranial large artery atherosclerosis (LAA) in a Brazilian population. METHODS: All stroke patients admitted to the hospital between October 2012 and September 2015 were evaluated. The stroke mechanism subtypes were classified as cardioembolism, LAA, small-vessel occlusion, other determined etiologies, and stroke of undetermined etiology. RESULTS: The 359 first-ever ischemic stroke patients were followed up for a mean time of 21.6 ± 15.1 months. The LAA intracranial (38.9%) and extracranial (24.6%) stroke patients presented with a higher stroke recurrence. Intracranial LAA [HR, 10.2 (3.6-29.1); p < 0.001] and extracranial LAA [HR, 5.05 (1.79-14.2); p = 0.002] were the only conditions to show positive correlation with the recurrence rate, after adjusting for risk factors, thrombolysis, and National Institutes of Health Stroke Scale score at admission. CONCLUSION: Intracranial LAA presents a higher incidence of recurrence of ischemic stroke when compared with other etiologies in a Southern Brazilian population.

Stroke recurrence in the different subtypes of ischemic stroke. The importance of the intracranial disease / Recorrência nos diferentes subtipos de acidente vascular cerebral isquêmico. A importância da doença intracraniana

ABSTRACT The aim of the study was to analyze the long-term recurrence rate in patients with a first-ever ischemic stroke secondary to intracranial large artery atherosclerosis (LAA) in a Brazilian population. Methods: All stroke patients admitted to the hospital between October 2012 and September 2015 were evaluated. The stroke mechanism subtypes were classified as cardioembolism, LAA, small-vessel occlusion, other determined etiologies, and stroke of undetermined etiology. Results: The 359 first-ever ischemic stroke patients were followed up for a mean time of 21.6 ± 15.1 months. The LAA intracranial (38.9%) and extracranial (24.6%) stroke patients presented with a higher stroke recurrence. Intracranial LAA [HR, 10.2 (3.6-29.1); p < 0.001] and extracranial LAA [HR, 5.05 (1.79-14.2); p = 0.002] were the only conditions to show positive correlation with the recurrence rate, after adjusting for risk factors, thrombolysis, and National Institutes of Health Stroke Scale score at admission. Conclusion: Intracranial LAA presents a higher incidence of recurrence of ischemic stroke when compared with other etiologies in a Southern Brazilian population.

RESUMO O objetivo do presente estudo é analisar a taxa de recorrência a longo prazo em pacientes com o primeiro AVCi secundário à aterosclerose de grande artéria intracraniana em uma amostra brasileira. Métodos: Pacientes admitidos entre outubro de 2012 e setembro de 2015 foram analisados. Os subtipos do mecanismo de AVC foram classificados como cardioembolismo, aterosclerose de grandes artérias, oclusão de pequenos vasos, outras etiologias determinadas e AVCi de causa indeterminada. Resultados: Foram avaliados 359 pacientes com primeiro AVCi. O tempo médio de seguimento foi de 21,6 ± 15,1 meses. A aterosclerose de grande artéria, intracraniana (38,9%) e extracraniana (24,6%), apresentou a maior taxa de recorrência. A aterosclerose de grande artéria intracraniana [HR, 10,2 (3,6-29,1); p < 0,001] e extracraniana [HR, 5,05 (1,79-14,2); p = 0,002] demonstraram correlação positiva com a taxa de recorrência, após o ajuste para fatores de risco, trombólise e gravidade dos sintomas na admissão. Conclusão: A aterosclerose de grande artéria, tanto intracraniana como extracraniana, apresenta maior recorrência comparado aos outros mecanismos de AVCi em uma amostra do Sul do Brasil.

Dystonia in Patients with Spinocerebellar Ataxia 3 - Machado-Joseph disease: An Underestimated Diagnosis?

BACKGROUND: Spinocerebellar Ataxia type 3 (SCA3) or Machado-Joseph Disease (MJD) is characterized by cerebellar, central and peripheral symptoms, including movement disorders. Dystonia can be classified as hereditary and neurodegenerative when present in SCA3. OBJECTIVE: The objective of this study was to evaluate the dystonia characteristics in patients with MJD. METHOD: We identified all SCA3 patients with dystonia from the SCA3 HC-UFPR database, between December 2015 and December 2016.Their medical records were reviewed to verify the diagnosis of dystonia and obtain demographic and clinical data. Standardized evaluation was carried out through the classification of Movement Disorders Society of 2013 and Burke Fahn-Marsden scale (BFM). RESULTS: Amongst the presenting some common characteristics, 381 patients with SCA3, 14 (3.7%) subjects presented dystonia: 5 blepharospasm, 1 cervical dystonia, 3 oromandibular, 3 multifocal and 2 generalized dystonia. Regarding dystonia's subtypes, 71.4% had SCA3 subtype I and 28.6% SCA3 subtype II. The average age of the disease onset was 40±10.7 years; the SCA3 disease duration was 11.86± 6.13 years; the CAG repeat lengths ranged from 75 to 78, and the BFM scores ranged from 1.0 to 40. There was no correlation between the dystonia severity and CAG repeat lengths or the SCA3 clinical evolution. CONCLUSION: Dystonia in SCA3 is frequent and displays highly variable clinical profiles and severity grades. Dystonia is therefore a present symptom in SCA3, which may precede the SCA3 classic symptoms. Dystonia diagnosis is yet to be properly recognized within SCA3 patient.

Cerebellar degeneration and progressive ataxia associated with HIV-virus infection.

INTRODUCTION: The spectrum of neurologic disorders associated with HIV infection is very broad, resulting from direct virus invasion, opportunistic infections, malignancies and toxic effects of drugs. METHODS: Among a large cohort of ataxia patients (N = 1050) evaluated between 2008 and 2017, we detected four patients with HIV-infection who developed a pure progressive cerebellar ataxia syndrome combined with cerebellar atrophy. RESULTS: Adverse drug effects, opportunistic infections and malignancies as well as immune-reconstitution syndrome were ruled out based on history and laboratory data. The exact pathophysiological mechanisms of ataxia in HIV patients is not very clear, but seems to be immune-mediated or a direct neurotoxic virus effect leading to apoptosis of Purkinje and granular cells. CONCLUSION: HIV infection should be investigated in adult patients with undetermined sporadic progressive pure ataxia with cerebellar atrophy.

Tumor neuroectodérmico primitivo: relato de caso / Primitive neuroectodermal tumor: case report

JUSTIFICATIVA E OBJETIVOS: O tumor neuroectodérmico primitivo (PNET) pertence a um grupo de tumores de pequenas células redondas e, devido a sua semelhança biológica com os sarcomas de Ewing, tem sido incluído nesta família. O objetivo deste estudo foi descrever o quadro clínico, características de imagem e evolução de um caso de processo expansivo em coxa direita, com histologia consistente com sarcoma de Ewing extraesquelético. RELATO DO CASO: Paciente do sexo feminino, 21 anos, branca, apresentava queixa de dificuldade para deambular e dor na perna direita há aproximadamente seis meses. Ao exame físico foi detectada massa sólida na raiz da coxa direita. Exames de imagens identificaram formação expansiva sólida, sendo o estudo histopatológico/imuno-histoquímico compatível com PNET/sarcoma de Ewing extraesquelético. Foi instituído tratamento quimioterápico, que nãofoi suspenso mesmo após diagnóstico de gestação. A gravidez evoluiu com oligodramnia e óbito fetal. Dois meses após o diagnóstico, a paciente apresentou depressão, piora do estado geral e óbito. CONCLUSÃO: O estudo relatado reflete a agressividade desta doença apesar da possibilidade de multimodalidade terapêutica. A aplicação da genética molecular em estudos recentes correlaciona o rearranjo genético da translocação entre os cromossomas 11e 22 com o prognóstico.

BACKGROUND AND OBJECTIVES: Primitive neuroectodermal tumor (PNET) belongs to a family of small round cell tumors, and because of their biological similarity has been includedin the family of Ewing's sarcomas. The objective of this case was to describe the clinical, imaging characteristics and outcome of a case of an expansive process in the right thigh, with histology consistent with extraskeletal Ewing's sarcoma. CASE REPORT: Female patient, 21 years, white, featured a complaint of difficulty in walking and pain in his right leg for about six months. On examination a solid mass was detected at the root of the right thigh. Imaging techniques identified an expansive solid mass and histopathology was compatible with PNET/extra-skeletal Ewing's sarcoma. Chemotherapy was instituted, which was not suspended even after pregnancy diagnosis. It progressed with oligohydramnios and fetal death. In two months, the patient had depression, poor general condition and death. CONCLUSION: The study reported reflects the aggressive nessof this disease despite multimodality therapy. The application of molecular genetics in recent studies correlating the genetic rearrangement of the translocation between chromosomes 11:22 prognosis.

Thrombotic thrombocytopenic purpura associated with mixed connective tissue disease: a case report.

Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD) is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

Desafios operacionais persistentes determinam a não redução da transmissão materno-infantil do HIV / Persistent operational challenges lead to non-reduction in maternal-infant transmission of HIV

OBJETIVO: Determinar os obstáculos à efetiva redução da transmissão materno-infantil do HIV em Campos dos Goytacazes (RJ). MÉTODOS: Estudo de coorte, com acompanhamento médico de gestantes com diagnóstico confirmado de infecção pelo HIV e de seus bebês, atendidos no Serviço Municipal de Atendimento Especializado de Doenças Sexualmente Transmissíveis e AIDS, no período de janeiro de 2004 a abril de 2007; coleta de informações relativas às variáveis de exposição e desfecho a partir dos prontuários; determinação de frequências das variáveis e análise bivariada entre os fatores de exposição e o desfecho; cálculo de riscos relativos de transmissão materno-infantil do HIV associados às variáveis de exposição, com intervalo de confiança de 95 por cento; e avaliação de significância estatística de associações de risco. RESULTADOS: Foram acompanhados 78 binômios, sendo de 7,7 por cento a taxa de transmissão materno-infantil do HIV. As variáveis que mostraram associações estatisticamente significantes com a transmissão materno-infantil do HIV foram: a não utilização de antirretrovirais para profilaxia ou tratamento na gestação (RR = 21,00; IC95 por cento 2,64-166,74, p = 0,001); e o diagnóstico materno após a gestação (RR = 6,80; IC95 por cento 1,59-29,17, p = 0,025). Novas gestações em mulheres com outros filhos já expostos ao HIV ocorreram em 19,12 por cento dos casos. CONCLUSÕES: Não houve redução da taxa de transmissão materno-infantil do HIV no período de 2004-2007 em relação ao triênio anterior. Foram caracterizados como obstáculos determinantes desta não redução: a baixa cobertura pela testagem anti-HIV no pré-natal, impossibilitando tratamento ou profilaxia materna eficiente; e o uso incorreto do teste rápido na admissão para o parto.

OBJECTIVE: To determine impediments to the effective reduction of maternal-infant transmission of HIV in the municipality of Campos dos Goytacazes, RJ, Brazil. METHODS: This is a cohort study, with medical follow-up, of pregnant women with confirmed diagnosis of HIV infection, and their infant children, assisted at the Municipal Specialized Service of Sexually Transmitted Diseases/AIDS from January 2004 to April 2007. Information regarding exposure and outcome variables was collected from their medical records. Frequencies of variables were determined and bivariate analysis performed for exposure factors and transmission of HIV. Relative risks of HIV transmission associated with exposure variables were calculated using 95 percent confidence intervals. Statistical significance of risk associations was evaluated. RESULTS: Seventy-eight mother-child pairs were studied; the rate of maternal-infant transmission of HIV was 7.7 percent. Variables showing significant association with maternal-infant transmission of HIV were the non-utilization of antiretrovirals for prophylaxis or treatment during pregnancy (RR = 21.00; 95 percentCI 2.64-166.74, p = 0.001) and diagnosis of maternal disease after pregnancy (RR = 6.80; 95 percentCI 1.59-29.17, p = 0.025). New pregnancies in women with other children also exposed to HIV occurred in 19.12 percent (15/78) of cases. CONCLUSIONS: There was no reduction in the rate of maternal-infant transmission of HIV in the period 2004-2007 in relation to the preceding triennium. The following were recognized as impediments to the effective reduction of maternal-infant transmission of HIV: low prenatal screening coverage of maternal HIV infection, impairing maternal treatment or prophylaxis; and the incorrect use of the rapid screening test at admission for delivery.

Persistent operational challenges lead to non-reduction in maternal-infant transmission of HIV.

OBJECTIVE: To determine impediments to the effective reduction of maternal-infant transmission of HIV in the municipality of Campos dos Goytacazes, RJ, Brazil. METHODS: This is a cohort study, with medical follow-up, of pregnant women with confirmed diagnosis of HIV infection, and their infant children, assisted at the Municipal Specialized Service of Sexually Transmitted Diseases/AIDS from January 2004 to April 2007. Information regarding exposure and outcome variables was collected from their medical records. Frequencies of variables were determined and bivariate analysis performed for exposure factors and transmission of HIV. Relative risks of HIV transmission associated with exposure variables were calculated using 95% confidence intervals. Statistical significance of risk associations was evaluated. RESULTS: Seventy-eight mother-child pairs were studied; the rate of maternal-infant transmission of HIV was 7.7%. Variables showing significant association with maternal-infant transmission of HIV were the non-utilization of antiretrovirals for prophylaxis or treatment during pregnancy (RR = 21.00; 95%CI 2.64-166.74, p = 0.001) and diagnosis of maternal disease after pregnancy (RR = 6.80; 95%CI 1.59-29.17, p = 0.025). New pregnancies in women with other children also exposed to HIV occurred in 19.12% (15/78) of cases. CONCLUSIONS: There was no reduction in the rate of maternal-infant transmission of HIV in the period 2004-2007 in relation to the preceding triennium. The following were recognized as impediments to the effective reduction of maternal-infant transmission of HIV: low prenatal screening coverage of maternal HIV infection, impairing maternal treatment or prophylaxis; and the incorrect use of the rapid screening test at admission for delivery.