Brain : a journal of neurology
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Cognitive dysfunction (affecting particularly attention and working memory) occurs early in patients with multiple sclerosis. Previous studies have focused on identifying potentially adaptive functional reorganization through recruitment of new brain regions that could limit expression of these deficits. However, lesion studies remind us that functional specializations in the brain make certain brain regions necessary for a given task. ⋯ We interpret these results as showing that, while cognitive processing in the task appears to be performed using similar brain regions in patients and controls, the patients have reduced functional reserve for cognition relevant to memory. Functional connectivity analysis suggests that altered inter-hemispheric interactions between dorsal and lateral prefrontal regions may provide an adaptive mechanism that could limit clinical expression of the disease distinct from recruitment of novel processing regions. Together, these results suggest that therapeutic enhancement of the coherence of interactions between brain regions normally recruited (functional enhancement), as well as recruitment of alternative areas or use of complementary cognitive strategies (both forms of adaptive functional change), may limit expression of cognitive impairments in multiple sclerosis.
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Spasticity is most commonly defined as an inappropriate, velocity dependent, increase in muscle tonic stretch reflexes, due to the amplified reactivity of motor segments to sensory input. It forms one component of the upper motor neuron syndrome and often leads to muscle stiffness and disability. Spasticity can, therefore, be measured through electrophysiological, biomechanical and clinical evaluation, the last most commonly using the Ashworth scale. ⋯ Correlations with other measures were consistent with predictions. The 88-item Multiple Sclerosis Spasticity Scale (MSSS-88) is a reliable and valid, patient-based, interval-level measure of the impact of spasticity in multiple sclerosis. It has the potential to advance outcomes measurement in clinical trials and clinical practice, and provides a new perspective in the clinical evaluation of spasticity.
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Mental rotation of body parts determines activation of cortical and subcortical systems involved in motor planning and execution, such as motor and premotor areas and basal ganglia. These structures are severely impaired in several movement disorders, including dystonia. Writer's cramp is the most common form of focal hand dystonia. ⋯ In particular, increased difficulty in rotating right-sided stimuli at 120 degrees and left-sided stimuli at 240 degrees would suggest that mental rotation of body parts reflects the anatomical constraints of real hand movements. In conclusion, patients with writer's cramp presented mental rotation deficits specific to the hand. Importantly, deficits were present during mental rotation of both the right (affected) and the left (unaffected) hand, thus suggesting that the observed alterations may be independent and even exist prior to overt manifestations of dystonia.
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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.