Patrícia Maria de Carvalho Aguiar

Acoustic voice assessment in Parkinson's disease patients submitted to posteroventral pallidotomy

UNLABELLED Long-term complications in levodopa treated Parkinsons disease (PD) patients caused a resurgence of interest in pallidotomy as an option of treatment. However, postoperative complications such as speech disorders can occur. PURPOSE The aim of this study is to evaluate the acoustic voice in PD patients, before and after posteroventral pallidotomy. METHOD Twelve patients with PD were submitted to neurological and voice assessments during the off and on phases, in the pre-operative, 1st and 3rd post-operative months. The patients were evaluated with the UPDRS and the vocal acoustic parameters -- f0, NHR, jitter, PPQ, Shimmer, APQ (using the software MultiSpeech-Kay Elemetrics-3700). RESULTS The off phase UPDRS scores revealed a tendency to improvement at the 1st month and the off phase worsened. The shimmer and APQ improved. CONCLUSION This study shows that pallidotomy has little improvement on functional use of communication of PD patients.

Clinical features of dystonia in atypical parkinsonism

BACKGROUND The association between Dystonia and Parkinsons disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn &Yahr -scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS The overall frequency of dystonia in our sample was 50% with 30.4% (n=7) in the MSA group, 62.5% (n=5) in the PSP group, and 100% (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50%) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.INTRODUCAO: A associacao de distonia e doenca de Parkinson (DP) ja foi bem estabelecida, principalmente para distonia focal em pe ou mao. Entretanto, ha poucos dados quanto a distonia em pacientes com parkinsonismo atipico. OBJETIVO: Avaliar a frequencia e o padrao da distonia em um grupo de pacientes com parkisnonismo atipico (atrofia de multiplos sistemas - AMS; paralisia supranuclear progressiva - PSP; degeneracao corticobasal - DCB) e investigar se a distonia pode ser a manifestacao inicial neste grupo. METODO: Um total de 38 prontuarios medicos foi revisado (n=23/grupo AMS; n=8/grupo PSP; n=7/grupo PSP) e os dados foram apresentados em medias/desvios padroes. As variaveis avaliadas foram: sexo, idade de inicio, duracao da doenca, primeiro sintoma, caracteristicas clinicas da distonia e outros sinais neurologicos, resposta ao tratamento com levodopa, escala de Hoehn & Yahr >3 em 3 anos de doenca, e achados de ressonância magnetica. RESULTADOS: A frequencia total de distonia em nosso grupo foi 50%, sendo 30,4% (n=7) no grupo AMS, 62.5% (n=5) no grupo PSP e 100% (n=8) no grupo DCB. Em nenhum dos pacientes, distonia foi o primeiro sintoma. Varias apresentacoes de distonia foram observadas: camptocormia, anterocolis, retrocolis, distonia oromandibular, em pe e mao. CONCLUSAO: Em nossa serie, distonia foi uma caracteristica comum em pacientes com parkinsonismo atipico (frequencia de 50%) e fez parte da historia natural em todos os grupos, embora nao tenha sido o sintoma inicial em nenhum deles. Anormalidades no exame de neuroimagem nao necessariamente estao relacionadas a distonia focal, e o tratamento com levodopa nao influenciou o padrao da distonia em nosso grupo de pacientes.

PINK1 polymorphism IVS1−7 A → G, exposure to environmental risk factors and anticipation of disease onset in Brazilian patients with early-onset Parkinson's Disease

Parkinsons disease (PD) etiology has been attributed both to genetic and environmental factors, although the exact mechanisms of its pathogenesis remains elusive. We investigated Brazilian early-onset PD (EOPD) patients with PINK1 polymorphisms (SNPs) in order to find possible correlations between SNPs, environmental exposure, and disease age of onset. We enrolled 48 patients and 61 controls. PINK1 SNPs and environmental exposure (living in rural areas, well-water drinking, exposure to pesticides, herbicides and organic solvents and smoking) were investigated in both groups. We divided our group of patients into four subgroups, according to the presence/absence of PINK1 SNP IVS1-7 A-->G and the presence/absence of environmental factors exposure. We found a significant decrease (ANOVA test: p=0.02) of age at disease onset in those patients that had the IVS1-7 A-->G SNP and were exposed to environmental risk factors. Our data suggest that the interaction of PINK1 SNP IVS1-7 A-->G and environmental risk factors together have an important role in EOPD: each of them individually has a minor influence, whereas their interaction is associated with a significant effect in anticipating the disease clinical onset.

Head tremor in patients with cervical dystonia: different outcome?

OBJECTIVE The association of cervical dystonia (CD) with other movement disorders have been already described, but data on clinical outcome regarding these patients are scant. The aim of this paper was to investigate whether patients with CD and head tremor (HT) would have a different outcome regarding to botulinum toxin type-A (BTX-A) treatment response and clinical and demographic parameters. METHOD We retrospectively evaluated 118 medical charts of patients with CD and divided them into two groups: with (HT+) and without (HT-) head tremor. We compared the following clinical and demographic parameters: age at onset, disease duration, progression of symptoms, etiology, familial history, presence of hand tremor. We also analyzed the response to BTX-A according to Tsui score in both groups. RESULTS The occurrence of head tremor in our sample was of 38.2%. The occurrence of postural hand tremor in the patients from the HT+ group was higher than in the HT- one (p=0.015) and if we compare BTX-A response in each group, we observe that patients with HT present a better outcome in a setting of longer follow-up. In HT+ group, Tsui score pre treatment was 10 (6-12.5) and after follow-up was 8 (5.5-10.5); p<0.001. In HT- group there was no significant difference 9 (7-12) in pre treatment and after follow-up; p=0.07. CONCLUSION According to our data it seems that head tremor may influence the clinical outcome or treatment response with BTX-A in patients with CD.

Talamotomia e palidotomia estereotáxica com planejamento computadorizado no tratamento da doença de Parkinson: avaliação do desempenho motor a curto prazo de 50 pacientes

Estudamos o desempenho motor de 50 pacientes com doenca de Parkinson submetidos a cirurgia estereotaxica com planejamento computadorizado, sem ventriculografia (talamotomia ventro-lateral e/ou palidotomia postero-ventral) antes e 1 mes apos o procedimento cirurgico. Foram realizadas 27 talamotomias ventro-laterais (TVL) unilaterais, 10 palidotomias postero-ventrais (PPV) unilaterais, 6 PPV bilaterais, e 7 TVL associadas a PPV. A avaliacao motora foi feita com a Escala Unificada para Doenca de Parkinson, escore motor, nos periodos on e off. No total, houve melhora do escore motor em todos os grupos. A melhora das discinesias foi observada predominantemente no hemicorpo contralateral a cirurgia, no grupo das palidotomias. Dos 50 pacientes, 16 (32 por cento) apresentaram complicacoes pos-operatorias, 9 destes (56,25 por cento) se recuperaram totalmente, 6 (37,25 por cento) mostraram melhora parcial, e 1 (6,25 por cento) nao apresentou melhora dentro do primeiro mes. Os resultados foram considerados satisfatorios, e a analise desses dados a longo prazo indicara se os beneficios sao duradouros.We evaluated the motor function of 50 patients with Parkinsons disease, who underwent stereotaxic surgery with computerized planning, without ventriculography (ventrolateral thalamotomy- VLT- and/or posteroventral pallidotomy- PVP) before and one month after surgery. 27 unilateral TVL, 10 unilateral PVP, 6 bilateral PVP, and 7 TVL with PVP were performed. The motor evaluation was performed with the Unified Parkinsons Disease Rating Scale, motor score, during on and off periods. We observed a global motor improvement in all groups. The improvement of dyskinesias was obtained in the contralateral side of the body, in the PVP groups. From the 50 patients, 16 (32%) presented post-operative complications, 9 of these (56.25%) improved completely, 6 (37.25%) improved partially, and 1 (6.25%) did not improve during the first month. These results were considered satisfactory, and a long term analysis will show whether these benefits are long lasting or not.

Biomarkers in Parkinson Disease: global gene expression analysis in peripheral blood from patients with and without mutations in PARK2 and PARK8

OBJECTIVE To evaluate the performance of gene expression analysis in the peripheral blood of Parkinson disease patients with different genetic profiles using microarray as a tool to identify possible diseases related biomarkers which could contribute to the elucidation of the pathological process, as well as be useful in diagnosis. METHODS Global gene expression analysis by means of DNA microarrays was performed in peripheral blood of Parkinson disease patients with previously identified mutations in PARK2 or PARK8 genes, Parkinson disease patients without known mutations in these genes and normal controls. Each group consisted of five individuals. RESULTS Global gene expression profiles were heterogeneous among patients and controls, and it was not possible to detect a consistent pattern between groups. However, analyzing genes with differential expression of p < 0.005 and fold change ≥ 1.2, we were able to identify a small group of well-annotated genes. CONCLUSIONS Despite the small sample size, the identification of differentially expressed genes suggests that the microarray technique may be useful in identifying potential biomarkers in the peripheral blood of Parkinson disease patients or in people at risk of developing the disease. This will be important once neuroprotective therapies become available, and may contribute to the identification of new pathways involved in the disease physiopathology. Results presented here should be further validated in larger groups of patients.

Biomarcadores na doença de Parkinson: avaliação da expressão gênica no sangue periférico de pacientes com e sem mutações nos genes PARK2 e PARK8

RESUMOObjetivo:Avaliar a viabilidade da analise da expressao genica por microarray no sangue periferico de pacientes com doenca de Parkinson com diferentes perfis geneticos, para a identificacao de marcadores que possam estar relacionados ao desenvolvimento da doenca ou que possam se tornar uteis para o seu o diagnostico.Metodos:Foram selecionados pacientes portadores de mutacoes nos genes PARK2 ou PARK8, alem de parkinsonianos nao-portadores dessas mutacoes e controles sadios, sendo cinco pessoas em cada grupo. A expressao genica global foi analisada por microarray [...]

Retrocollis, anterocollis or head tremor may predict the spreading of dystonic movements in primary cervical dystonia

BACKGROUND AND PURPOSE Few studies have attempted to develop clinical predictors for cervical dystonia (CD) aiming at progression of the dystonic movement. METHOD We retrospectively evaluated 73 patients with primary CD who underwent treatment with Botulinum toxin type-A (BTX-A). The patients were assembled in two groups according to the spread of dystonia during follow-up: spreading and non-spreading CD. We performed a binary logistic regression model using spreading of cervical dystonia as dependent variable aiming to find covariates which increase the risk of spreading. RESULTS Our logistic regression model found the following covariates and their respective risk ratios: time of disease >18.5 months=2.4, retrocollis=1.9, anterocollis=1.8, head tremor=1.6. CONCLUSION Time of disease >18.5 months, retrocollis, anterocollis and head tremor may predict spreading of dystonic movement to other regions of the body in CD patients.

Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia characterized by a combination of neurological involvement, cardiomyopathy, and skeletal and glucose metabolism disturbances. FRDA is caused by mutations in FXN gene that results in reduction of mRNA and protein levels of frataxin. Previous microarray and real-time quantitative PCR (qPCR) studies showed that the downregulation of FXN is associated with a complex gene expression profile. However, these studies showed a wide variability in the subset of genes with altered expression among tissues and models. Genes differentially expressed in peripheral blood cells (PBC) could potentially help in the understanding of FRDA pathophysiology and also function as reliable disease biomarkers obtained from an easily accessible tissue, which could have implications in clinical practice. This study aimed to validate by qPCR the expression of 26 genes, revealed as differentially expressed by other studies, using peripheral blood cells (PBC) of 11 FRDA patients compared to 11 healthy controls. We found a robust downregulation of FXN, but no statistically significant differences were found between FRDA and controls for the remaining genes. Except for FXN, our study did not find a differential gene expression profile in PBC of FRDA patients and a reliable gene expression profile biomarker in a clinical relevant and noninvasive tissue remains unclear.

Neuropsychological and clinical heterogeneity of cognitive impairment in patients with multiple system atrophy

OBJECTIVE We evaluated neuropsychological tests to compare cognitive impairment between two types of multiple system atrophy: predominant parkinsonism (MSA-P) and predominant cerebellar ataxia (MSA-C). PATIENTS AND METHODS This cross-sectional study included 14 patients diagnosed with MSA: four with MSA-C and ten with MSA-P. Presence of motor symptoms was determined by using the Unified Rating MSA Scale (URMSAS). Non-motor symptoms were evaluated by the Short Form Health Survey (SF-36), Scales for Outcomes in Parkinsons disease Autonomic (SCOPA-AUT), Hospital Anxiety and Depression Scale (HADS), and Beck Depression Inventory (BDI). Neuropsychological tests were used to evaluate general cognition, verbal and visual memory, working memory, constructional ability, visuospatial, language, and executive function. RESULTS The median age of the patients was 62 years, median disease duration was 3.5 years, and median education level was 10 years. The median Mini-Mental State Examination (MMSE) score was 26.5 points, and median Mattis Dementia Rating Scale (MDRS) score was 131.5. We compared the continuous data between the two MSA subtypes and observed that bodily pain reported in the quality of life questionnaire, SF-36, was worse in MSA-P (p<0.05), and attention function evaluated by MDRS was significantly lower in MSA-C than MSA-P (p<0.05). CONCLUSION Our comparative study of cognitive impairment in MSA-P and MSA-C showed that both groups had impaired executive and visuospatial functions, while the attention deficit was predominant only in MSA-C. These findings support the concept that cognitive deficit originates from striatofrontal dysfunction and cerebellar degeneration. Our study also suggests that cognitive impairment is relevant in MSA, and clinical neurologists should not neglect evaluation of these aspects in their daily clinical practice.