Brain : a journal of neurology
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Clinical Trial
Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection.
Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. ⋯ In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.
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Changes in health policy have underlined the importance of evidence-based clinical practice and rigorous evaluation of patient-based outcomes. As patient-based outcome measurement is particularly important in treatment trials of multiple sclerosis, a number of disease-specific instruments have been developed recently. One limitation of these instruments is that none was developed using the standard psychometric approach of reducing a large item pool generated from people with multiple sclerosis. ⋯ Correlations with other measures and the analysis of group differences provided evidence that the MSIS-29 measures the physical and psychological impact of multiple sclerosis. Effect sizes (physical scale = 0.82, psychological scale = 0.66) demonstrated preliminary evidence of good responsiveness. These results indicate the MSIS-29 is a clinically useful and scientifically sound patient-based outcome measure of the impact of multiple sclerosis suitable for clinical trials and epidemiological studies.
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Clinical Trial Controlled Clinical Trial
Modulation of presynaptic inhibition and disynaptic reciprocal Ia inhibition during voluntary movement in spasticity.
The aim of the study was to investigate whether impaired control of transmission in spinal inhibitory pathways contributes to the functional disability of patients with spasticity. To this end, transmission in the pathways mediating disynaptic reciprocal Ia inhibition and presynaptic inhibition was investigated in 23 healthy subjects and 20 patients with spastic multiple sclerosis during ankle dorsiflexion and plantar flexion. In healthy subjects, but not in spastic patients, the soleus H reflex was depressed at the onset of dorsiflexion (300 ms rise time, 20% of maximal voluntary effort). ⋯ There was no difference between the two populations in the modulation of presynaptic inhibition during tonic plantar flexion and dorsiflexion. It is suggested that the abnormal regulation of disynaptic reciprocal inhibition and presynaptic inhibition in patients with spasticity is responsible for the abnormal modulation of stretch reflexes in relation to voluntary movement in these patients. Lack of an increase in reciprocal inhibition and presynaptic inhibition at the onset of dorsiflexion may be responsible for the tendency to elicitation of unwanted stretch reflex activity and co-contraction of antagonistic muscles in patients with spasticity.
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Clinical Trial
Prospective study of selective peripheral denervation for botulinum-toxin resistant patients with cervical dystonia.
We have carried out a prospective study of selective peripheral denervation (SPD) in cervical dystonia (CD) patients with primary or secondary botulinum toxin (BT) treatment failure using independent standardized assessment. Patients referred for surgery had a standardized clinical examination, neck muscle EMG, videofluoroscopic swallow and CT of the cervical spine, and were selected for surgery on the basis of the results of these investigations. CD severity, disability and pain were assessed preoperatively and at 3, 6, 9, 12 and 18 months postoperatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). ⋯ We conclude that SPD is an effective treatment for patients with secondary, but probably not for those with primary, BT treatment failure. Reinnervation is not infrequent and can compromise outcome. Postoperative morbidity is low, but there is a risk of dysphagia.
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Complex regional pain syndrome type I (CRPS I, formerly known as reflex sympathetic dystrophy) is a painful neuropathic disorder that develops after trauma affecting the limbs without overt nerve injury. Clinical features are spontaneous pain, hyperalgesia, impairment of motor function, swelling, changes in sweating, and vascular abnormalities. In this study, the pathophysiological mechanisms of vascular abnormalities were investigated. ⋯ Secondary changes in neurovascular transmission may lead to vasoconstriction and cold skin in chronic CRPS I, whereas sympathetic activity is still depressed. Vascular abnormalities are dynamic. The maximal skin temperature difference that occurs during the thermoregulatory cycle distinguishes CRPS I from other extremity pain syndromes with high sensitivity and specificity.