Brain : a journal of neurology
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Randomized Controlled Trial Comparative Study
Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38.
Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the first time, we present a head-to-head comparison study of the immediate and long-lasting observations of the migraine-inducing, arterial, physiological and biochemical responses comparing PACAP38 and vasoactive intestinal polypeptide. ⋯ Blood levels of vasoactive intestinal polypeptide and tryptase were unchanged after PACAP38 infusion. In conclusion, PACAP38-induced migraine was associated with sustained dilatation of extracranial arteries and elevated plasma PACAP38 before onset of migraine-like attacks. PACAP38 has a much higher affinity for the PAC1 receptor and we therefore suggest that migraine induction by PACAP38 may be because of activation of the PAC1 receptor, which may be a future anti-migraine drug target.
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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.
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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.
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Randomized Controlled Trial
Theta burst stimulation reduces disability during the activities of daily living in spatial neglect.
Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. ⋯ The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.
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Randomized Controlled Trial
Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model.
This study was designed to determine whether an intervention proven effective in the laboratory to ameliorate the effects of experimental spinal cord injury could provide sufficient benefit to be of value to clinical cases. Intraspinal olfactory ensheathing cell transplantation improves locomotor outcome after spinal cord injury in 'proof of principle' experiments in rodents, suggesting the possibility of efficacy in human patients. However, laboratory animal spinal cord injury cannot accurately model the inherent heterogeneity of clinical patient cohorts, nor are all aspects of their spinal cord function readily amenable to objective evaluation. ⋯ There were no significant differences in outcome between treatment groups in measures of long tract functionality. We conclude that intraspinal olfactory mucosal cell transplantation improves communication across the damaged region of the injured spinal cord, even in chronically injured individuals. However, we find no evidence for concomitant improvement in long tract function.