Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). OBJECTIVE: The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. METHODS: We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12 months after thalamotomy. RESULTS: We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. CONCLUSIONS: In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Improvement of secondary fixed dystonia of the upper limb after chronic extradural motor cortex stimulation in 10 patients: first reported series.

BACKGROUND: Fixed dystonic postures secondary to ischemic, traumatic, or postsurgical lesions located in the basal ganglia and brainstem constitute a major therapeutic challenge and limit motor rehabilitation efficacy. They are often refractory to conservative treatment. Aberrant cerebral plasticity developed after deep brain lesions is thought to lead to abnormal cortical representation of the affected part of the body and then to pathological fixed postures. OBJECTIVE: To assess the efficacy of motor cortex stimulation in patients with upper limb fixed dystonia. METHODS: Ten patients were submitted to computer-assisted and electromyography-monitored implantation of intracranial epidural electrodes over the central cortical sulcus contralateral to the affected limb. Patients were followed up from 1 to 9 years (9 patients), except for patient 10, whose follow-up was limited to 4 months. RESULTS: Seven of 7 patients showed > 30% improvement in the Disability of Shoulder, Arm, and Hand Scale and an overall 70% increase in the score of the Short Form-36 Physical Activity subscale with significant and stable improvement of quality of life during stimulation. The partial recovery of hand dexterity observed in most of the treated patients additionally contributed to a significant improvement of their quality of life. CONCLUSION: Although the pathophysiology of fixed dystonia is unknown, our results suggest a major role of the motor cortex in this condition and reinforce the hypothesis that postlesional delayed cortical rearrangements might take place in these forms and be the target of effective therapeutic neuromodulation.

Potential immunoregulatory role of heme oxygenase-1 in human milk: a combined biochemical and molecular modeling approach.

Human milk contains biological factors that are involved in a newborn's growth and immune system regulation. By integrating standard biochemical experimental protocols with computational methods, the present study investigates the presence of heme oxygenase-1 (HO-1), a cytoprotective enzyme, in human milk at different levels of maturation and in milk formulae. Furthermore, we evaluated cytokine and glutathione S-transferase (GSH) levels. Samples were collected from colostrum (on Day 1 after birth), from transition milk (on Postdelivery Days 7 and 14) and from mature milk (on Day 30 after delivery) in 14 healthy women. HO-1 protein, GSH and cytokines levels were measured using enzyme-linked immunosorbent assay and flow cytometry. HO-1 protein levels were significantly higher in colostrum (1.33 ng/ml; 5th centile 0.92; 95th centile 2.38) and in transition milk at 14 days (0.97 ng/ml; 5th centile 0.87; 95th centile 1.45) than in mature milk (0.9 ng/ml; 5th centile 0.8; 95th centile 1.38). Levels of HO-1 in milk formulae were similar to those in colostrum. No significant differences in GSH content were observed in mature milk, transition milk and colostrum, whereas significantly higher GSH levels were observed in milk formulae. No significant levels of cytokines, with the exception of interleukin-8, were found. Computational studies on the possible interactions between HO-1 and CD91 were carried out by a battery of softwares, namely, GRAMM (version 1.03), DALI, CLUSTALW (version 2.0), PatchDock and FireDock, mutually counterchecking and validating each other. The computational results, the strong convergence (to the same "solution") of which finally leads to an "experimental-like" character, showed that HO-1 may bind to CD91, thus suggesting its major role as a new chaperokine in immune response regulation. These findings, which connect and integrate biochemical data and computational data interpretation, represent a synergistic and powerful means of conducting biological research.

Protective effects of a standardised red orange extract on air pollution-induced oxidative damage in traffic police officers.

Several pathological conditions have all been associated with a higher release of atmospheric pollutants. There is growing evidence that oxidative stress may represent one of the agents involved in the initiation and/or progression of many of these pathologies. The aim of the present study was to evaluate the effects of short-term dietary supplementation with a standardised red orange extract (ROC) on a group of traffic police officers exposed to traffic exhaust pollution and cigarette smoking, by measuring some noninvasive biomarkers of oxidative stress. At the beginning of the study, all the groups showed similar serum lipid hydroperoxide levels, but traffic officers showed lower serum concentrations of thiol (SH) groups; furthermore, the frequency of spontaneous sister chromatide exchanges (SCEs) in peripheral lymphocytes was increased by smoking (but not by pollution exposure alone) at a higher degree in subjects exposed to traffic pollution. After 1 month of ROC administration, serum lipid hydroperoxide levels decreased only in all non-smoking subjects; furthermore, SH group levels measured in traffic officers appeared restored to normal values observed in the respective controls. Finally, the increase in SCE frequency induced by smoking was reduced by treatment with ROC especially in traffic officers. Our study suggests that ROC supplementation could be useful to minimise the detrimental effects caused by exposure to air pollution and smoking.