Brain connectivity in patients with dystonia during motor tasks.

OBJECTIVE: This study aims to investigate alterations of brain connectivity using multivariate electroencephalographic data to provide new insights of the brain connectivity dynamics of dystonia. APPROACH: We recorded electroencephalography (EEG) of patients with right upper limb idiopathic focal dystonia and paired controls during resting state, writing-from-memory, and finger-tapping tasks. We applied power spectrum analyses considering the mu, beta and gamma rhythms of the motor cortex and analyzed brain connectivity networks and microstates (MS). MAIN RESULTS: The power spectra results showed that patients had a loss of desynchronization of the beta rhythm during the writing task. We observed differences in the structure of the connective core in beta rhythm, as well as, in the intensity of the patient's hubs observed with basis in path length measures in mu and beta rhythms. Abnormalities were also identified in MS of default mode networks of patients associated with its performances during motor tasks. SIGNIFICANCE: The EEG connectivity analyses provided interesting insights about the cortical electrophysiological patterns in dystonia, such as loss of event-related desynchronization, changes in the effective connectivity with similar signature to other neurological diseases, indications of alterations in the default-mode-network. Our findings are consistent with previously described connectivity abnormalities in neuroimaging studies confirming that dystonia is a network disorder.

Genetic and environmental findings in early-onset Parkinson's disease Brazilian patients.

Parkinson's disease (PD) etiology has been attributed both to genetic and environmental factors. In this study, we investigated Brazilian early-onset PD (EOPD) patients for mutations in PARK2 and PARK8, exposure to environmental factors and possible correlations between PARK2 polymorphisms, environmental exposure, and disease age of onset. We enrolled 72 EOPD index patients and 81 healthy volunteers. Both groups were investigated for environmental exposure. EOPD patients were screened for PARK2 and PARK8 mutations. PARK2 coding polymorphisms Ser167Asn and Val380Leu were investigated in both groups. Mutations were present in 18% of the patients and in 32% of those with a positive family history. PARK2 mutations represented 12.5% and PARK8 mutations accounted for 5.5% of the mutations. A novel PARK2 mutation (D53X) was identified in 2 patients. A positive correlation was found between EOPD and well water drinking. In patients exposed to well water, a later age of onset was observed for those who carried at least one PARK2 380Leu allele. PARK2 mutations have an important role in EOPD Brazilian patients and PARK8 might be the second most important disease causing gene in this group. Well water drinking exposure represents a risk factor for EOPD and the PARK2 coding polymorphism Val380Leu might be interacting with environmental factors acting as a disease modifier.

Evaluation of patients with Clinically Unclear Parkinsonian Syndromes submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1.

Despite its relatively high prevalence Parkinson's Disease (PD) is still misdiagnosed in approximately 25% of cases. In this study our aim was to evaluate patients with Clinically Unclear Parkinsonian Syndromes (CUPS) submitted to brain SPECT imaging using the technetium-99m labeled Dopamine Transporter (DAT) tracer TRODAT-1. We recruited 15 subjects with CUPS and matched them with 13 patients with probable PD and 13 healthy control subjects (HCS). A SPECT with TRODAT-1 was performed at the baseline evaluation and patients from the CUPS were followed-up for 2-years to ensure or not PD diagnosis ("gold-standard"). The mean+/-SD results from Right and Left striatum Binding Potential (BP) were, respectively, 1.08+/-0.20 and 1.04+/-0.16 in the HCS group, 0.47+/-0.16 and 0.53+/-0.17 in the PD group, and 0.68+/-0.11 and 0.84+/-0.17 in the CUPS group. The rate of disagreement between baseline SPECT in the CUPS group as compared to the "gold standard" diagnosis (clinical diagnosis of PD on follow-up) was of 20%. The sensitivity of the SPECT with TRODAT-1 was 100%, while specificity was 70%. In conclusion, our data provided further information about the role of the technetium-99m labeled tracer TRODAT-1 as a biomarker of DAT reduction that can also be used in the diagnosis of patients with CUPS.

Degenerative parkinsonism in patients with psychogenic parkinsonism: A dopamine transporter imaging study.

OBJECTIVES: To evaluate patients with "clinically established" psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism. PATIENTS AND METHODS: Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n=5) and healthy control subjects (n=5). RESULTS: The mean age (years-old) at first evaluation in the PsyP group was 37.4+/-3.7, and the mean disease duration (years) was 3.9+/-1.2. DAT BPs (means+/-standard deviations) on right/left caudate were, respectively, 0.69+/-0.18 and 0.70+/-0.18 in the PD group versus 1.17+/-0.06 and 1.12+/-0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48+/-0.10 and 0.45+/-0.06 in the PD group versus 1.10+/-0.10 and 1.21+/-0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (< or =0.70) for controls, implying pre-synaptic dopaminergic deficit. CONCLUSIONS: Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.

Clinical and molecular neuroimaging characteristics of Brazilian patients with Parkinson's disease and mutations in PARK2 or PARK8 genes.

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1% and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.

Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the Amish-Mennonites.

The DYT6 gene for primary torsion dystonia (PTD) was mapped to chromosome 8p21-q22 in two Amish-Mennonite families who shared a haplotype of marker alleles across a 40 cM linked region. The objective of this study was to narrow the DYT6 region, clinically characterize DYT6 dystonia in a larger cohort, and to determine whether DYT6 is associated with dystonia in newly ascertained multiplex families. We systematically examined familial Amish-Mennonite dystonia cases, identifying five additional members from the original families, as well as three other multiplex Amish-Mennonite families, and evaluated the known DYT6 haplotype and recombination events. One of the three new families carried the shared haplotype, whereas the region was excluded in the two other families, suggesting genetic heterogeneity for PTD in the Amish-Mennonites. Clinical features in the five newly identified DYT6 carriers were similar to those initially described. In contrast, affected individuals from the excluded families had a later age of onset (46.9 years vs. 16.1 years in the DYT6), and the dystonia was both more likely to be of focal distribution and begin in the cervical muscles. Typing of additional markers in the DYT6-linked families revealed recombinations that now place the gene in a 23 cM region surrounding the centromere. In summary, the DYT6 gene is in a 23 cM region on chromosome 8q21-22 and does not account for all familial PTD in Amish-Mennonites.

Clinical and molecular neuroimaging characteristics of Brazilian patients with Parkinson's disease and mutations in PARK2 or PARK8 genes / Características clínicas e de neuroimagem molecular de pacientes brasileiros com doença de Parkinson e mutações nos genes PARK2 ou PARK8

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1 percent and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.

OBJETIVO: Descrever as características clínicas e de neuroimagem (SPECT) de pacientes brasileiros com doença de Parkinson e mutações PARK2 e PARK8. MÉTODO: Foram avaliados 119 pacientes com critérios clínicos para a doença de Parkinson. RESULTADO: Entre os pacientes avaliados foram encontrados 13 pacientes com mutação nos genes PARK2 (n=9) ou PARK8 (n=4). Não houve diferença significativa na avaliação das características clínicas entre os dois grupos. Os resultados de SPECT mostraram diferenças significativas quanto ao potencial de ligação do [99mTc] TRODAT-1 SPECT entre pacientes vs. controle, sendo a diferença mais pronunciada entre PARK2 e controle. CONCLUSÃO: A freqüência de mutação encontrada foi 10,1 por cento, sendo mais comum em mulheres. Estes pacientes apresentavam longo tempo de doença e alta prevalência de discinesias associadas ao uso da levodopa. Nossos pacientes com PARK8 não apresentaram uma história familiar relevante de doença de Parkinson.