Brain : a journal of neurology
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Comparative Study
PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation.
Parkinson's disease may arise from multiple aetiologies, including genetic mutations that are for the most part uncommon. We describe here the positron emission tomography (PET) findings in clinically affected and asymptomatic, high-risk members of two autosomal dominantly inherited Parkinson's disease kindreds with recently described mutations at the PARK8 locus, in a novel gene encoding a leucine-rich repeat kinase (LRRK2). Affected family members have L-dopa-responsive parkinsonism with loss of dopaminergic nigral neurons and pleomorphic subcellular pathology. ⋯ In these individuals, 18F-dopa uptake remained normal, although two of them also displayed abnormal 11C-DTBZ binding. Our study demonstrates that the in vivo neurochemical phenotype of LRRK2 mutations is indistinguishable from that of sPD, despite the pathological heterogeneity of the condition. Furthermore, we suggest that compensatory changes including downregulation of the DAT and upregulation of decarboxylase activity may delay the onset of parkinsonian symptoms.
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Olfactory ensheathing cells transplanted into the injured spinal cord in animals promote regeneration and remyelination of descending motor pathways through the site of injury and the return of motor functions. In a single-blind, Phase I clinical trial, we aimed to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. Participants were three male paraplegics, 18-55 years of age, with stable, complete thoracic injuries 6-32 months previously, with stable spinal column, no implanted prostheses, and no syrinx. ⋯ There was no neuropathic pain reported by the participants, no change in psychosocial status and no evidence of deterioration in neurological status. Participants will be followed for 3 years to confirm long-term safety and to compare neurological, functional and psychosocial outcomes with the control group. We conclude transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to one year post-implantation.
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Our objective was to investigate axonal dysfunction in patients with systemic lupus erythematosus (SLE) using proton magnetic resonance spectroscopy (1H-MRS). We studied prospectively 90 SLE patients (mean age of 32.5 years) and 23 normal volunteers (mean age of 33.8 years). We performed single voxel proton MRS using point resolved spectroscopy sequence over the superior-posterior region of the corpus callosum. ⋯ By contrast, there was a significant reduction of NAA/Cr ratio in 15 patients who had inactive SLE at initial MRS and active SLE at follow-up (P = 0.001). In 10 patients with inactive SLE both at initial and at follow-up MRS NAA/Cr ratio did not change (P = 0.2). This study shows evidence of axonal dysfunction in patients with active SLE, independently of CNS manifestations that may be reversible, at least in part, during periods of inactivity of disease.
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Most therapies under development to restore motor function after spinal cord injury (SCI) assume intact brain motor functions. To examine this assumption, 12 patients with chronic, complete SCI and 12 controls underwent functional MRI during attempted, and during imagined, right foot movement, each at two force levels. In patients with SCI, many features of normal motor system function were preserved, however, several departures from normal were apparent: (i) volume of activation was generally much reduced, e.g. 4-8% of normal in primary sensorimotor cortex, in the setting of twice normal variance in signal change; (ii) abnormal activation patterns were present, e.g. increased pallido-thalamocortical loop activity during attempted movement and abnormal processing in primary sensorimotor cortex during imagined movement; and (iii) modulation of function with change in task or in force level did not conform to patterns seen in controls, e.g. in controls, attempted movement activated more than imagined movement did within left primary sensorimotor cortex and right dorsal cerebellum, while imagined movement activated more than attempted movement did in dorsolateral prefrontal cortex and right precentral gyrus. ⋯ Many features of brain motor system function during foot movement persist after chronic complete SCI. However, substantial derangements of brain activation, poor modulation of function with change in task demands and emergence of pathological brain events were present in patients. Because brain function is central to voluntary movement, interventions that aim to improve motor function after chronic SCI likely also need to attend to these abnormalities of brain function.