Benserazide as a potential novel fetal hemoglobin inducer: an observational study in non-carriers of hemoglobin disorders.

Induction of fetal hemoglobin production with hydroxyurea is an effective strategy in sickle cell disease and beta thalassemias, but up to 20% of patients do not respond to or cannot tolerate it. Benserazide is used in the treatment of Parkinson's disease and was noticed to induce gamma globin in preclinical models. We hypothesized that chronic treatment with benserazide-containing medication may be associated with increase in HbF production and in circulating F-cells. Blood samples were collected from 50 subjects including 35 patients on benserazide for Parkinson's disease, 10 healthy controls, and 5 patients with sickle cell anemia as positive controls for high fetal hemoglobin. We found a strong correlation between HbF and circulating F-cells in the entire population, but we found no significant increase in HbF and F-cell percentage in patients taking benserazide up to 700 mg daily. No hematologic abnormalities attributable to benserazide use after up to 22 years were detected. Our data support long-term safety and tolerability of benserazide at doses ten times higher than used in preclinical models to induce fetal hemoglobin. Further clinical trials enrolling patients with sickle cell disease and thalassemia are warranted to provide insight into its efficacy to treat those populations.

Is Ataxia an Underestimated Symptom of Huntington's Disease?

Background: Huntington's disease (HD) is a progressive disorder characterized by motor, cognitive and psychiatric features. Cerebellar ataxia is classically considered as uncommon in HD clinical spectrum. Objective: To determine the prevalence of cerebellar ataxia in patients with HD, both in the early and in the late stages of HD. Methods: Seventy-two individuals considered eligible were assessed by two trained doctors, applying the Scale for Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS) for ataxia, the Unified Huntington's Disease Rating Scale (UHDRS) and also, Barthel Index (BI), in order to evaluate functional capacity. Results: Fifty-one patients (70.8%) presented with clinical ataxia at the time of examination (mean time of disease was 9.1 years). Six (8.33%) patients presented with cerebellar ataxia as first symptom. When stratified according to time of disease, a decline in the presence of chorea (p = 0.032) and an increase in cognitive deficit (p = 0.023) were observed in the patients as the disease progressed. The presence of ataxia was associated with longer duration of illness and severity of illness (UHDRS) (p < 0.0001), and shorter Barthel (less functionality) (p = 0.001). Conclusions: Cerebellar involvement may play an important role in natural history of brain degeneration in HD. The presence of cerebellar ataxia in HD is relevant and it may occur even in early stages, and should be included as part of the motor features of the disease.

Magnetic resonance imaging findings in central nervous system cryptococcosis: comparison between immunocompetent and immunocompromised patients.

OBJECTIVE: To assess the magnetic resonance imaging (MRI) patterns associated with central nervous system infection with Cryptococcus sp. in relation to patient immune status. MATERIALS AND METHODS: This was a retrospective study of MRI data for 19 patients with neurocryptococcosis who underwent the examination between January 2000 and March 2014. The MRI characteristics examined included lesion topography, aspects of diffusion, T1-weighted images, T2-weighted images, and contrast enhancement patterns. RESULTS: In all cases, cryptococcal infection was confirmed by cerebrospinal fluid analysis. Of the 19 patients, 10 were immunocompromised and 9 were immunocompetent. Abnormal imaging patterns occurred alone or in conjunction with other manifestations. The imaging patterns found in immunocompromised patients included the following: leptomeningeal enhancement, in 6; pachymeningeal enhancement, in 3 (due to intracranial hypotension in 2); perivascular space involvement, in 4; granulomas, in 2; hydrocephalus, in 2; miliary nodules, in 1; and plexitis, in 1. In immunocompetent patients, the following imaging patterns were observed: leptomeningeal enhancement, in 5; perivascular space involvement, in 3; granulomas, in 3; cryptococcoma, in 1; ventriculitis, in 1; and hydrocephalus, in 1. In 2 immunocompetent patients, diffusion-weighted imaging showed diffusion restriction in cerebral cryptococcal granuloma. CONCLUSION: In both groups, the most common imaging finding was leptomeningeal enhancement, followed by dilatation of perivascular spaces with the presence of mucoid material. Rare presentations, such as miliary nodules, plexitis, ventriculitis, and pachymeningeal enhancement, were also observed. None of the imaging patterns common to immunocompetent and immunocompromised patients differed significantly in frequency between them.

OBJETIVO: Avaliar os padrões de ressonância magnética (RM) associados à infecção do sistema nervoso central por Cryptococcus sp. em relação ao status imunológico dos pacientes. MATERIAIS E MÉTODOS: Dados de RM de 19 casos de neurocriptococose foram analisados retrospectivamente de janeiro de 2000 a março de 2014. As características de RM examinadas incluíram: sítio da lesão, aspectos em difusão, imagens ponderadas em T1 e T2 e padrões de realce pelo contraste. RESULTADOS: A infecção por Cryptococcus sp. foi confirmada pela análise do liquor em todos os casos. Dos 19 pacientes, 10 eram imunossuprimidos e 9 eram imunocompetentes. Os padrões de imagem anormais ocorreram isoladamente ou em associação com outras manifestações. Os padrões de imagem encontrados nos pacientes imunossuprimidos incluíram: realce leptomeníngeo (n = 6), realce paquimeníngeo (n = 3; 2 devidos a hipotensão intracraniana), envolvimento do espaço perivascular (n = 4), granulomas (n = 2), hidrocefalia (n = 2), nódulos miliares (n = 1) e plexite (n = 1). Em pacientes imunocompetentes, os padrões de imagem incluíram: realce leptomeníngeo (n = 5), envolvimento do espaço perivascular (n = 3), granulomas (n = 3), criptococoma (n = 1), ventriculite (n = 1) e hidrocefalia (n = 1). As sequências ponderadas em difusão mostraram restrição em 2 pacientes imunocompetentes com granulomas intracerebrais por criptococose. CONCLUSÃO: O achado mais comum de imagem em ambos os grupos foi realce leptomeníngeo, seguido de dilatação dos espaços perivasculares pela presença do material mucoide. Apresentações raras como nódulos miliares, plexite, ventriculite e realce paquimeníngeo foram também observadas. Nenhum dos padrões de imagem comuns aos pacientes imunocompetentes e imunossuprimidos diferiu significativamente em frequência entre eles.