Brain : a journal of neurology
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Randomized Controlled Trial Clinical Trial
Subthalamic nucleus stimulation and somatosensory temporal discrimination in Parkinson's disease.
Whereas numerous studies document the effects of dopamine medication and deep brain stimulation on motor function in patients with Parkinson's disease, few have investigated deep brain stimulation-induced changes in sensory functions. In this study of 13 patients with Parkinson's disease, we tested the effects of deep brain stimulation on the somatosensory temporal discrimination threshold. To investigate whether deep brain stimulation and dopaminergic medication induce similar changes in somatosensory discrimination, somatosensory temporal discrimination threshold values were acquired under four experimental conditions: (i) medication ON/deep brain stimulation on; (ii) medication ON/deep brain stimulation off; (iii) medication OFF/deep brain stimulation on; and (iv) medication OFF/deep brain stimulation off. ⋯ Somatosensory temporal discrimination threshold values differed significantly between deep brain stimulation on and deep brain stimulation off conditions only when the patients were studied in the medication ON condition and were higher in the deep brain stimulation on/medication ON than in the deep brain stimulation off/medication ON condition. Dopamine but not subthalamic nucleus deep brain stimulation restores the altered somatosensory temporal discrimination in patients with Parkinson's disease. Deep brain stimulation degrades somatosensory temporal discrimination by modifying central somatosensory processing whereas dopamine restores the interplay between cortical and subcortical structures.
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Randomized Controlled Trial
Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy.
This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy (n=372) or progressive supranuclear palsy (n=311) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort. The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction. For the Dementia Rating Scale impairment was observed in approximately 57% of the progressive supranuclear palsy group and 20% of the multiple system atrophy group. ⋯ These results demonstrate, in the largest prospectively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date, the existence of a cognitive profile similar to that previously reported in idiopathic Parkinson's disease. The results indicate a high level of cognitive impairment associated with progressive supranuclear palsy, but also point to comparable dysfunction in a substantial proportion of the patients with multiple system atrophy. Significant cognitive impairment appears consistent with a diagnosis of multiple system atrophy, even early in the disease, with important implications for diagnosis, research and management.
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Randomized Controlled Trial
Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity.
Treatment of early relapsing-remitting multiple sclerosis with the lymphocyte-depleting humanized monoclonal antibody alemtuzumab (Campath [registered trade mark]) significantly reduced the risk of relapse and accumulation of disability compared with interferon β-1a in a phase 2 trial [Coles et al., (Alemtuzumab vs. interferon β-1a in early multiple sclerosis. N Engl J Med 2008; 359: 1786-801)]. Patients treated with alemtuzumab experienced an improvement in disability at 6 months that was sustained for at least 3 years. ⋯ Media from these post-alemtuzumab peripheral blood mononuclear cell cultures promoted survival of rat neurones and increased axonal length in vitro, effects that were partially reversed by neutralizing antibodies against brain-derived nerve growth factor and ciliary neurotrophic factor. This conditioned media also enhanced oligodendrocyte precursor cell survival, maturation and myelination. Taken together, the clinical analyses and laboratory findings support the interpretation that improvement in disability after alemtuzumab may result, in part, from neuroprotection associated with increased lymphocytic delivery of neurotrophins to the central nervous system.
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Randomized Controlled Trial
Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain.
Epidural motor cortex stimulation (MCS) has been proposed as a treatment for chronic, drug-resistant neuropathic pain of various origins. Regarding pain syndromes due to peripheral nerve lesion, only case series have previously been reported. We present the results of the first randomized controlled trial using chronic MCS in this indication. ⋯ Although the results of the crossover trial were slightly negative, which may have been due to carry-over effects from the operative and immediate postoperative phases, observations made during the open trial were in favour of a real efficacy of MCS in peripheral neuropathic pain. Analgesic effects were obtained on the sensory-discriminative rather than on the affective aspect of pain. These results suggest that the indication of MCS might be extended to various types of refractory, chronic peripheral pain beyond trigeminal neuropathic pain.
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Randomized Controlled Trial
PACAP38 induces migraine-like attacks in patients with migraine without aura.
Experimental studies have shown that infusion of vasoactive neurotransmitters may trigger headache or migraine-like attacks in man. Pituitary adenylate cyclase activating peptide-38 (PACAP38) is a strong vasodilator found in trigeminal sensory and parasympathetic perivascular nerve fibers. We therefore hypothesized that infusion of PACAP38 would cause headache in healthy subjects and migraine-like attacks in migraine patients. ⋯ In conclusion, PACAP38 infusion caused headache and vasodilatation in both healthy subjects and migraine patients. In migraine sufferers, PACAP38 caused delayed migraine-like attacks. The findings stimulate further investigation of the neuronal and vascular mechanisms of PACAP38.