Vitamin D and Parkinson's Disease.

Vitamin D is a fat-soluble secosteroid, traditionally considered a key regulator of bone metabolism, calcium and phosphorous homeostasis. Its action is made possible through the binding to the vitamin D receptor (VDR), after which it directly and indirectly modulates the expression of thousands of genes. Vitamin D is important for brain development, mature brain activity and associated with many neurological diseases, including Parkinson's disease (PD). High frequency of vitamin D deficiency in patients with Parkinson's disease compared to control population was noted nearly twenty years ago. This finding is of interest given vitamin D's neuroprotective effect, exerted by the action of neurotrophic factors, regulation of nerve growth or through protection against cytotoxicity. Vitamin D deficiency seems to be related to disease severity and disease progression, evaluated by Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale, but not with age of PD onset and duration of disease. Additionally, fall risk has been associated with lower vitamin D levels in PD. However, while the association between vitamin D and motor-symptoms seems to be possible, results of studies investigating the association with non-motor symptoms are conflicting. In addition, very little evidence exists regarding the possibility to use vitamin D supplementation to reduce clinical manifestations and disability in patients with PD. However, considering the positive balance between potential benefits against its limited risks, vitamin D supplementation for PD patients will probably be considered in the near future, if further confirmed in clinical studies.

Preoperative imaging findings in patients undergoing transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy.

The prevalence and impact of imaging findings detected during screening procedures in patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy for functional neurological disorders has not been assessed yet. This study included 90 patients who fully completed clinical and neuroradiological screenings for tcMRgFUS in a single-center. The presence and location of preoperative imaging findings that could impact the treatment were recorded and classified in three different groups according to their relevance for the eligibility and treatment planning. Furthermore, tcMRgFUS treatments were reviewed to evaluate the number of transducer elements turned off after marking as no pass regions the depicted imaging finding. A total of 146 preoperative imaging findings in 79 (87.8%) patients were detected in the screening population, with a significant correlation with patients' age (rho = 483, p < 0.001). With regard of the group classification, 119 (81.5%), 26 (17.8%) were classified as group 1 or 2, respectively. One patient had group 3 finding and was considered ineligible. No complications related to the preoperative imaging findings occurred in treated patients. Preoperative neuroradiological findings are frequent in candidates to tcMRgFUS and their identification may require the placement of additional no-pass regions to prevent harmful non-targeted heating.

Transcranial magnetic resonance-guided focused ultrasound thalamotomy as a safe treatment option in multiple sclerosis patients with essential tremor.

Transcranial magnetic resonance-guided focused ultrasound is a recently introduced incisionless treating option for essential tremor and tremor-dominant idiopathic Parkinson disease. There is preliminary evidence that it may result in a promising effective treatment option for other movement disorders too. Here, we report on two patients with multiple sclerosis with medication refractory debilitating essential tremor comorbidity who successfully underwent unilateral Vim tcMRgFUS thalamotomy for tremor control. Patients' clinical condition and expanded disability status scale scores showed no changes during the 1-year follow-up period with no evidence of multiple sclerosis activity or progression.

Intraoperative imaging findings in transcranial MR imaging-guided focused ultrasound treatment at 1.5T may accurately detect typical lesional findings correlated with sonication parameters.

OBJECTIVES: To assess the intraoperative neuroimaging findings in patients treated with transcranial MR-guided focused ultrasound (tcMRgFUS) thalamotomy using 1.5T equipment in comparison with the 48-h follow-up. METHODS: Fifty prospectively enrolled patients undergoing unilateral tcMRgFUS thalamotomy for either medication-refractory essential tremor (n = 39) or Parkinson tremor (n = 11) were included. Two radiologists evaluated the presence and size of concentric lesional zones (zone I, zone II, and zone III) on 2D T2-weighted sequences acquired intraoperatively after the last high-energy sonication and at 48 h. Sonication parameters including number of sonications, delivered energy, and treatment temperatures were also recorded. Differences in lesion pattern and size were assessed using the McNemar test and paired t test, respectively. RESULTS: Zones I, II, and III were visualized in 34 (68%), 50 (100%), and 44 (88%) patients, and 31 (62%), 50 (100%), and 45 (90%) patients after the last high-energy sonication for R1 and R2, respectively. All three concentric zones were visualized intraoperatively in 56-58% of cases. Zone I was significantly more commonly visualized at 48 h (p < 0.001). Diameter of zones I and II and the thickness of zone III significantly increased at 48 h (p < 0.001). Diameters of zones I and II measured intraoperatively demonstrated significant correlation with thermal map temperatures (p ≤ 0.001). Maximum temperature significantly correlated with zone III thickness at 48 h. A threshold of 60.5° had a sensitivity of 56.5-66.7% and a specificity of 70.5-75.5% for thickness > 6 mm at 48 h. CONCLUSIONS: Intraoperative imaging may accurately detect typical lesional findings, before completing the treatment. These imaging characteristics significantly correlate with sonication parameters and 48-h follow-up. KEY POINTS: • Intraoperative T2-weighted images allow the visualization of the zone I (coagulation necrosis) in most of the treated patients, while zone II (cytotoxic edema) is always detected. • Lesion size depicted with intraoperative transcranial MRgFUS imaging correlates well with procedure parameters. • Intraoperative transcranial MRgFUS imaging may have a significant added value for treating physicians.

Preliminary experience with a transcranial magnetic resonance-guided focused ultrasound surgery system integrated with a 1.5-T MRI unit in a series of patients with essential tremor and Parkinson's disease.

OBJECTIVE Transcranial magnetic resonance-guided focused ultrasound surgery (tcMRgFUS) is one of the emerging noninvasive technologies for the treatment of neurological disorders such as essential tremor (ET), idiopathic asymmetrical tremor-dominant Parkinson's disease (PD), and neuropathic pain. In this clinical series the authors present the preliminary results achieved with the world's first tcMRgFUS system integrated with a 1.5-T MRI unit. METHODS The authors describe the results of tcMRgFUS in a sample of patients with ET and with PD who underwent the procedure during the period from January 2015 to September 2017. A monolateral ventralis intermedius nucleus (VIM) thalamic ablation was performed in both ET and PD patients. In all the tcMRgFUS treatments, a 1.5-T MRI scanner was used for both planning and monitoring the procedure. RESULTS During the study period, a total of 26 patients underwent tcMRgFUS thalamic ablation for different movement disorders. Among these patients, 18 were diagnosed with ET and 4 were affected by PD. All patients with PD were treated using tcMRgFUS thalamic ablation and all completed the procedure. Among the 18 patients with ET, 13 successfully underwent tcMRgFUS, 4 aborted the procedure during ultrasound delivery, and 1 did not undergo the tcMRgFUS procedure after stereotactic frame placement. Two patients with ET were not included in the results because of the short follow-up duration at the time of this study. A monolateral VIM thalamic ablation in both ET and PD patients was performed. All the enrolled patients were evaluated before the treatment and 2 days after, with a clinical control of the treatment effectiveness using the graphic items of the Fahn-Tolosa-Marin tremor rating scale. A global reevaluation was performed 3 months (17/22 patients) and 6 months (11/22 patients) after the treatment; the reevaluation consisted of clinical questionnaires, neurological tests, and video recordings of the tests. All the ET and PD treated patients who completed the procedure showed an immediate amelioration of tremor severity, with no intra- or posttreatment severe permanent side effects. CONCLUSIONS Although this study reports on a small number of patients with a short follow-up duration, the tcMRgFUS procedure using a 1.5-T MRI unit resulted in a safe and effective treatment option for motor symptoms in patients with ET and PD. To the best of the authors' knowledge, this is the first clinical series in which thalamotomy was performed using tcMRgFUS integrated with a 1.5-T magnet.