Brain : a journal of neurology
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Multicenter Study
Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene.
Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase gamma (POLG1) have recently been described in patients with diverse clinical presentations, revealing a complex relationship between genotype and phenotype in patients and their families. POLG1 was sequenced in patients from different European diagnostic and research centres to define the phenotypic spectrum and advance understanding of the recurrence risks. Mutations were identified in 38 cases, with the majority being sporadic compound heterozygotes. ⋯ The clinical presentation ranged from the neonatal period to late adult life, with an overlapping phenotypic spectrum from severe encephalopathy and liver failure to late-onset external ophthalmoplegia, ataxia, myopathy and isolated muscle pain or epilepsy. There was a strong gender bias in children, with evidence of an environmental interaction with sodium valproate. POLG1 mutations cause an overlapping clinical spectrum of disease with both dominant and recessive modes of inheritance. 1399G-->A (A467T) is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counselling.
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Deep brain stimulation (DBS) has an increasing role in the treatment of idiopathic Parkinson's disease. Although, the subthalamic nucleus (STN) is the commonly chosen target, a number of groups have reported that the most effective contact lies dorsal/dorsomedial to the STN (region of the pallidofugal fibres and the rostral zona incerta) or at the junction between the dorsal border of the STN and the latter. We analysed our outcome data from Parkinson's disease patients treated with DBS between April 2002 and June 2004. ⋯ Stimulation related complications were seen in some group 2 patients. High frequency stimulation of the cZI results in greater improvement in contralateral motor scores in Parkinson's disease patients than stimulation of the STN. We discuss the implications of this finding and the potential role played by the ZI in Parkinson's disease.
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We investigated whether previously reported differences between Alzheimer's disease and dementia with Lewy bodies (DLB) in resting occipital activity lead to activation differences within functionally specialized visual cortical areas and deactivation differences in the default network. Patients with Alzheimer's disease (n = 10; 5 male), DLB (n = 9; 4 male) and controls (n = 13; 5 male) performed three functional MRI (fMRI) scanning experiments involving visual colour, face or motion stimuli. Reaction time or accuracy in DLB and Alzheimer's disease differed significantly from controls but not between patient groups, with the exception of accuracy in the face task (DLB < Alzheimer's disease; P = 0.038). ⋯ However, these differences could be explained by behavioural performance, failing to reach significance in the ANCOVA analysis. In the default network, group deactivation differences between controls and both patient groups were found for the colour and motion task (colour: control < Alzheimer's disease P = 0.02; control < DLB P = 0.019; motion: control < Alzheimer's disease P = 0.118; control < DLB P = 0.118) but could be accounted for by behavioural performance. The results suggest that cognitive fMRI can be used to detect both performance-dependent and performance-independent differences between Alzheimer's disease and DLB, reflecting the distribution of functional pathology in the two conditions.
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The goal of probabilistic tractography is to obtain a connectivity index along a white matter pathway that reflects fibre organization and is sensitive to pathological abnormalities contributing to disability. Here, we present the development of voxel-based connectivity measures along the tractography-derived corticospinal tract (CST). We investigated whether these connectivity measures are different in patients with amyotrophic lateral sclerosis (ALS) and correlate with the rate of disease progression. ⋯ However, there was no evidence of an association between disease progression rate and any of the FA measures in the bilateral CST. Our findings suggest that FA and connectivity provide complementary information, since FA is sensitive to the detection of all the group differences, whereas the summary connectivity measures correlate with disease progression rate. The development of such connectivity measures raises their potential as markers of disease progression in ALS, and provides guidance for their use in other neurological diseases.