A longitudinal study of the progression of Huntington's disease and oropharyngeal dysphagia: A four-case follow-up

ABSTRACT Huntington's disease (HD) is a neurodegenerative disorder, with dysphagia being a common symptom of the disease. Few studies established a relationship between neuromotor impairment and dysphagia. There is also a lack of described therapeutic approaches for dysphagia in HD. This study aimed to better understand the progression of neurological clinical aspects, instrumental swallowing and dysphagia management in four patients presented with HD in an outpatient follow-up setting. The longitudinal follow-up period was 36 to 43 months through neuroclinical assessments (Unified Huntington's Disease Rating Scale) and fiberoptic endoscopic swallowing evaluations. Case 1 - a moderate decline of independence with safe swallowing. Case 2 - a moderate motor impairment, safe swallowing and moderate dysphagia during follow-up. Case 3 - a longer disease duration and increased motor impairment associated with moderate/severe dysphagia. Case 4 - a longer disease duration, need of assistance to perform daily activities, severe dysphagia and palliative care, considering the family decision of exclusive oral feeding. This longitudinal study revealed that the progression of neuromotor damage was not directly related to dysphagia development. This case series demonstrates the importance of follow-up settings with instrumental swallowing evaluations and careful consideration of early palliative care for HD patients.

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 / Achados de ressonância magnética em criptococose do sistema nervoso central: comparação entre pacientes imunocompetentes e imunossuprimidos

Abstract 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.

Resumo 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.

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.

Differential Pattern of Cerebellar Atrophy in Tremor-Predominant and Akinetic/Rigidity-Predominant Parkinson's Disease.

Parkinson's disease (PD) is an akinetic-rigid disorder characterized by basal ganglia dysfunction and a possible cerebello-thalamo-cortical circuit involvement. This study aims to investigate the pattern of cerebellar involvement in PD and to assess whether it correlates with clinical parameters. MRI scans were acquired from 50 healthy controls (HC) and 63 patients; 44 were classified as tremor-predominant-PD (PDT) and 19 as akinetic/rigidity-predominant-PD (PDAR). We designed an analysis of covariance including the three groups and contrasted as follows: (1) all 63 PD vs HC, (2) PDT vs HC, (3) PDAR vs HC, and (4) PDT vs PDAR. For a precise evaluation of the cerebellum, we used the SUIT tool for voxel-based morphometry. Applying p = 0.001 and extent threshold = 20 voxels, the overall PD group vs HC showed decreased gray matter (GM) in the left lobules VI and crus I. The PDT group showed decreased cerebellar GM when compared with HC at left lobules VI, VIIb, and VIIIa; at right lobules Crus I, VIIb, and VIIIb; and vermal lobules VI and VIIIa. When compared with PDAR, PDT also showed a decrease in the left lobules VIIIa (p < 0.001). There were small clusters of both positive and negative correlation between disease duration and PDT group. The PDAR group showed no cerebellar changes. Our findings support the growing evidence of cerebellar involvement in the pathogenesis of the resting tremor.