Brain : a journal of neurology
-
Although magnetic resonance imaging is a standard investigation in neurodegenerative disease, sensitive and specific markers for the underlying histopathological diagnosis are largely lacking. This report presents evidence to indicate that corticobasal degeneration and progressive supranuclear palsy, in particular, might be identifiable at a single subject level with diffusion tensor imaging. Patients with clinical diagnoses of Alzheimer's disease, semantic dementia and non-fluent primary progressive aphasia (n = 9 each) were contrasted with control subjects (n = 26) with the diffusion tensor imaging measures: fractional anisotropy, axial and radial diffusivity. ⋯ Further underscoring the hypothesis that this finding relates specifically to a diffuse pathological process in the white matter of the tauopathies, and is not merely a function of disease severity, a grey matter analysis consisting of group level voxel-based morphometry revealed only focal areas of atrophy in all three groups. Consistent with past reports for the respective clinical syndromes, these were centred on the left frontal operculum and caudate nucleus in non-fluent primary progressive aphasia (the corticobasal degeneration/progressive supranuclear palsy set), anterior temporal lobes in semantic dementia, and hippocampus and posterior cingulate gyrus in Alzheimer's disease. Detection of this extensive white matter lesion in corticobasal degeneration and progressive supranuclear palsy-a pathologically proven feature of these conditions--in single subjects with diffusion tensor imaging appears to have strong diagnostic marker potential for these diseases.
-
Randomized Controlled Trial
Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial.
Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. ⋯ The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.
-
Randomized Controlled Trial
Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson's disease: results from a randomized trial.
Deep brain stimulation of the subthalamic nucleus improves motor functions in patients suffering from advanced Parkinson's disease but in some patients, it is also associated with a mild decline in cognitive functioning about one standard deviation from the preoperative state. We assessed the impact of the cortical lead entry point, the subcortical electrode path and the position of the active electrode contacts on neuropsychological changes after subthalamic nucleus-deep brain stimulation compared to a control group of patients receiving best medical treatment. Sixty-eight patients with advanced Parkinson's disease were randomly assigned to have subthalamic nucleus-deep brain stimulation or best medical treatment for Parkinson's disease. ⋯ Passage of the chronic stimulation lead through the head of the caudate increases the risk of global cognitive decline and working memory performance after subthalamic nucleus-deep brain stimulation in Parkinson's disease. Therefore the electrode path should be planned outside the caudate nuclei, whenever possible. This study also stresses the importance of precise positioning of the active stimulating contact within the subthalamic volume to avoid adverse effects on semantic verbal fluency and response inhibition.
-
Neuroaxonal loss is a major substrate of irreversible disability in multiple sclerosis, however, its cause is not understood. In multiple sclerosis there may be intracellular sodium accumulation due to neuroaxonal metabolic dysfunction, and increased extracellular sodium due to expansion of the extracellular space secondary to neuroaxonal loss. Sodium magnetic resonance imaging measures total sodium concentration in the brain, and could investigate this neuroaxonal dysfunction and loss in vivo. ⋯ Independent association was seen of deep grey matter sodium concentration with expanded disability status score (coefficient = 0.24, P = 0.003) and timed 25 ft walk speed (coefficient = -0.24, P = 0.01), and of T1 lesion sodium concentration with the z-scores of the nine hole peg test (coefficient = -0.12, P < 0.001) and paced auditory serial addition test (coefficient = -0.081, P < 0.001). Sodium concentration is increased within lesions, normal appearing white matter and cortical and deep grey matter in multiple sclerosis, with higher concentrations seen in secondary-progressive multiple sclerosis and in patients with greater disability. Increased total sodium concentration is likely to reflect neuroaxonal pathophysiology leading to clinical progression and increased disability.
-
Machado-Joseph disease or spinocerebellar ataxia type 3, the most common dominantly-inherited spinocerebellar ataxia, results from translation of the polyglutamine-expanded and aggregation prone ataxin 3 protein. Clinical manifestations include cerebellar ataxia and pyramidal signs and there is no therapy to delay disease progression. Beclin 1, an autophagy-related protein and essential gene for cell survival, is decreased in several neurodegenerative disorders. ⋯ Beclin 1-mediated significant improvements in motor coordination, balance and gait with beclin 1-treated mice equilibrating longer periods in the Rotarod and presenting longer and narrower footprints. Furthermore, in agreement with the improvements observed in motor function beclin 1 overexpression prevented neuronal dysfunction and neurodegeneration, decreasing formation of polyglutamine-expanded aggregates, preserving Purkinje cell arborization and immunoreactivity for neuronal markers. These data show that overexpression of beclin 1 in the mouse cerebellum is able to rescue and hinder the progression of motor deficits when administered to pre- and post-symptomatic stages of the disease.