Adult-onset Alexander disease with brainstem and cervical cord enhancing lesions.

Leukodystrophies are a group of genetic diseases with diverse clinical features and prominent involvement of the central nervous system white matter. We describe a 27-year-old man who presented with a progressive neurological disease, and striking involvement of the brainstem and symmetrical white matter lesions on MR scanning. Having excluded several other causes of leukodystrophy, we confirmed Alexander disease when a genetic panel showed a probable pathogenic variant in GFAP: p.Leu359Pro. Clinicians should suspect Alexander disease in people with a progressive neurological motor decline who has pyramidal and bulbar signs and compatible neuroimaging.

Arginase 1 deficiency presenting as complicated hereditary spastic paraplegia.

INTRODUCTION: Argininemia or arginase deficiency is a metabolic disorder caused by pathogenic variants in ARG1 and consists of a variable association of progressive spastic paraplegia, intellectual disability, and seizures. Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder characterized by lower limb spasticity. This study presents 7 patients with arginase 1 deficiency from 6 different families, all with an initial diagnosis of complicated HSP. METHODS: We evaluated the clinical data of 7 patients belonging to six independent families who were diagnosed with hyperargininemia in a neurogenetics outpatient clinic. RESULTS: All patients had lower limb spasticity and six had global developmental delay. Five individuals had intellectual disability and two had epilepsy. Psychiatric abnormalities were seen in two patients. In two participants of this study, MRI disclosed thinning of the corpus callosum. Molecular diagnosis was made by whole exome sequencing. All variants were present in homozygosis; we identified two novel missense variants, one novel frameshift variant, and one previously published missense variant. DISCUSSION: Clinical diagnosis of early onset complicated hereditary spastic paraplegia was made in all patients. Two patients were initially suspected of having SPG11 due to thinning of the corpus callosum. As argininemia may present with a highly penetrant phenotype of spastic paraplegia associated with additional symptoms, this disease may represent a specific entity amongst the complicated HSPs.

Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era.

Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. There are a number of important and treatable acquired causes for this imaging and clinical presentation. There are also a very large number of genetic causes which due to their relative rarity and sometimes variable and overlapping presentations can be difficult to diagnose. In this review, we provide a structured approach to the diagnosis of inherited disorders of white matter in adults. We describe clinical and radiological clues to aid diagnosis, and we present an overview of both common and rare genetic white matter disorders. We provide advice on testing for acquired causes, on excluding small vessel disease mimics, and detailed advice on metabolic and genetic testing available to the practising neurologist. Common genetic leukoencephalopathies discussed in detail include CSF1R, AARS2, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and mitochondrial and metabolic disorders.

A novel complex neurological phenotype due to a homozygous mutation in FDX2.

Defects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leukoencephalopathy. Muscle biopsy demonstrated an unusual pattern of regional succinate dehydrogenase and cytochrome c oxidase deficiency with iron accumulation. The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c.431C > T, p.P144L). The deleterious effect of the mutation was validated by real-time reverse transcription polymerase chain reaction and western blot analysis, which demonstrated normal expression of FDX2 mRNA but severely reduced expression of FDX2 protein in muscle tissue. This study describes a novel complex neurological phenotype with unusual MRI and muscle biopsy features, conclusively mapped to a mutation in FDX2, which encodes a ubiquitously expressed mitochondrial ferredoxin essential for early [Fe-S] cluster biogenesis.

Você excluiu neurossífilis? / Did you rule out neurosyphilis?

Neurosyphilis, formerly a frequent cause of dementia, is now a rare condition in developed countries. However, syphilis remains common in many developing countries, where adequate diagnosis and treatment of early syphilis may be lacking, increasing the chances of neurosyphilis and prevalence of syphilitic dementia. Objectives: To present cases of syphilitic dementia seen in a cognitive and behavioral neurology unit in Brazil, emphasizing their first symptoms and the challenges they posed in diagnosis. Methods: At our unit of the Hospital das Clínicas of the University of São Paulo, all patients are submitted to blood treponemal tests. When the test is positive, a lumbar puncture is performed. We retrospectivelly reviewed all cases of neurosyphilis seen in our unit from January 1991 to November 2009. Results: Nine cases of neurosyphilis (0.77% of the 1160 cases in our files) were identified over the period. Patients with neurosyphilis were all men, had a mean age of 47.8 (±13.0) years (median of 43 years), and presented with various neuropsychiatric syndromes and elusive diagnoses. The median time from onset of symptoms to diagnosis was 24 months and only one patient made a full recovery after treatment. Conclusions: Neurosyphilis is not frequent but remains present, causing several types of neuropsychiatric syndromes. As it is very simple to rule out neurosyphilis by performing a blood treponemal test, this test should be performed in all patients with neuropsychiatric symptoms, particularly in regions of the world where syphilis is still a commonly occurring disease.

Neurossífilis, anteriormente uma causa freqüente de demência, é atualmente rara nos países desenvolvidos. A sífilis é ainda uma doença comum em muitos países em desenvolvimento, onde o diagnóstico e tratamento da sífilis precoce podem não ser adequados, o que aumenta a possibilidade de ocorrência de neurossífilis e de demência. Objetivos: apresentar casos de demência sifilítica atendidos em uma unidade de neurologia cognitiva e do comportamento no Brasil, enfatizando os primeiros sintomas e os desafios que impuseram ao diagnóstico. Métodos: Em nossa unidade do Hospital das Clínicas da Universidade de São Paulo, todos os pacientes são submetidos a teste treponêmico no sangue. Quando o teste é positivo, é realizada punção lombar. Avaliamos retrospectivamente todos os casos de neurossífilis atendidos em nossa unidade de janeiro de 1991 a novembro de 2009. Resultados: Nove casos de neurossífilis (0,77% dos 1.160 casos de nossos arquivos) foram identificados neste período. Os pacientes com neurossífilis eram todos homens, com idade média de 47,8 (±13,0) anos (mediana de 43 anos), e apresentaram-se com vários tipos de síndromes neuropsiquiátricas, de difícil diagnóstico. O tempo médio entre o início dos sintomas e o diagnóstico foi de 24 meses e apenas um paciente teve recuperação completa após o tratamento. Conclusões: Neurossífilis não é frequente, mas ainda está presente causando vários tipos de síndromes neuropsiquiátricas. Como é muito simples excluir o diagnóstico de neurossífilis mediante teste treponêmico no sangue, este teste deve ser realizado em todo paciente com sintomas neuropsiquiátricos, particularmente nas regiões do mundo onde a sífilis é ainda uma doença comum.

Insuficiência renal aguda dialítica: experiência em Hospital Universitário / Acute renal failure requiring dialytic treatment: experience of a School-Based Hospital

Introdução: Apesar dos avanços terapêuticos, a insuficiência renal aguda (IRA) persiste como uma complicação comum em pacientes hospitalizados, contribuindocom elevada mortalidade. Objetivo: Avaliar a incidência, etiologia, as características clínicas e evolução da população com IRA dialítica ocorrida na unidade de terapia intensiva (UTI) do Hospital Universitário da Universidade Federal de Juiz de Fora. Métodos: Das 8846 internações no período de março de 2001 a março de 2003, analisamos retrospectivamente 49 pacientes, que desenvolveram IRA dialítica na UTI, que resultou numa incidência de 0,7. Avaliamos idade, sexo, causa da internação, fatores de risco, etiologia, albumina, e evolução: oligúria, complicações, número de diálises, dias de internação, mortalidade e recuperação da função renal. Resultados: A idade média foi de 53,3±18,5 anos, e 59,2 eram do sexo masculino. Os fatores de risco para IRA estiveram presentes em 83,7 da amostra e 71,4 tiveram IRA isquêmica ou tóxica. 75,5 dos pacientes apresentaram oligúria e estes evoluíram com mortalidade mais elevada (75,6 vs. 41,6; p<0,05). As complicações avaliadas (sepse e/ou falência de múltiplos órgãos (FMO) ocorreram em 67,3 da amostra e a maioria apresentou FMO. Observamos elevada mortalidade (67,3), associada à FMO e oligúria. Dos sobreviventes, apenas 31,2 normalizaram a creatinina e 56,2 resistiram inclusive em diálise. Conclusões: Na população estudada, a IRA dialítica tem etiologia multifatorial e envolve fatores de risco conhecidos. A mortalidade é elevada e ocorre nos pacientes com marcadores de maior gravidade. Nos sobreviventes, houve predomínio de doença renal prévia e o prejuízo da função renal em longo prazo foi marcante.

Perfil dos alunos da Faculdade de Medicina da Universidade Federal de Juiz de Fora / Universidade Federal de Juiz de Fora medical course student's profile

Conhecer os alunos de um curso médico, mesmo que parcialmente, num contexto de grande diversidade, é uma tarefa no mínimo difícil. Porém, todos eles têm em comum o interesse de receber e realizar a melhor formaçäo possível. Desta forma, ao aprimorarmos nossos conhecimentos sobre os anseios, aspiraçöes e realidades destes alunos, estaremos capacitando os docentes a melhor atender às necessidades do curso. Assim, aplicamos um questionário a alunos do 1§ ao 9§ períodos da Faculdade de Medicina da Universidade Federal de Juiz de Fora (U. F. J. F), respondidos individualmente, contendo sete quesitos. Notamos o "ideal filantrópico" como principal motivo pela escolha da profissäo, conceito "regular" e "bom" sobre o curso, "eventual" ou "rara" orientaçäo sobre a prática médica, "desinformaçäo" sobre pós-graduaçäo e "acentuada" intençäo de cursar Residência Médica como alguns dos dados apurados. Concluímos que os resultados obtidos sinalizam para açöes que podem ser implementadas, de forma a aprimorar a prática docente e a orientaçäo aos alunos durante o curso médico.