S ince the time that Spiegel and colleagues introduced stereotactic devices for the treatment of humans, there have been many advances in stereotactic procedures for treating neurological diseases, including Parkinson's disease (PD), essential tremor (ET), chronic neuropathic pain, and obsessive-compulsive disorder (OCD). 21Radiofrequency (RF) thermal ablation can create lesions in deep brain structures more easily than earlier modalities such as chemical ablation using alcohol. RF was widely applied to treat movement and psychiatric disorders until deep brain stimulation surgery was introduced. 8,11,15 However, RF lesioning procedures were found to be associated with a relatively high rate of permanent complications, especially when performed in both hemispheres. 19 As an alternative to RF thermal lesioning, bilateral deep brain stimulation has been shown to have a high success rate and an acceptable risk of complications. 23Although the risks associated with current neurosurgical procedures for movement and psychiatric disorders are considered acceptable, there are many potential procedure-, hardware-, and anesthesia-related complications that must be considered by both physicians and patients. To overcome these shortcomings, a less invasive technique using ultrasonic energy was developed. Magnetic resoabbreviatioNs Emax = maximal energy required to achieve Tmax; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound surgery; OCD = obsessive-compulsive disorder; PD = Parkinson's disease; RF = radiofrequency; SDR = skull density ratio; Tmax = maximum temperature. obJective Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson's disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS. methods The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive-compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined. results Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r 2 = 0.206, y = 64.156 − 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r 2 = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate...

Our results demonstrate that MRgFUS thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory ET. However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment.

MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.