Focused ultrasound as an evolving therapy for Parkinson's disease

2019 ◽  
Vol 34 (9) ◽  
pp. 1241-1242 ◽  
Author(s):  
Paul Fishman ◽  
Nir Lipsman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Focused Ultrasound

scholarly journals Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Focused Ultrasound ◽  
Temporal Cortex ◽  
Clinical State ◽  
Cognitive Improvement ◽  
Bbb Opening

AbstractMR-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.

scholarly journals Radiofrequency Lesioning for Movement and Psychiatric Disorders-Experience of 107 Cases

2021 ◽  
Vol 15 ◽  
Author(s):  
Paresh K. Doshi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scales ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Paper Analysis ◽  
Complication Rates ◽  
Obsessive Compulsive ◽  
Select Group ◽  
Obsessive Compulsive Disorders

BackgroundRadiofrequency lesioning (RFL) though used since the 1950s, had been replaced by DBS in the 1990s. The availability of magnetic resonance-guided focused ultrasound for lesioning has renewed the interest in RFL.ObjectiveThis paper analysis RFL in contemporary Functional Neurosurgery for various indications and its outcome. Complication rates of RFL are compared with the same author’s experience of DBS.MethodsOne hundred and seven patients underwent RFL between 1998 and 2019. Indications included Parkinson’s Disease (PD), tremors, dystonia, and obsessive-compulsive disorders (OCD). The surgeries performed include thalamotomy (29), pallidotomy (49), subthalamotomy (23), and anterior capsulotomy/nucleus accumbens lesioning (6). Appropriate rating scales were used for preoperative and postoperative evaluations.ResultsThere was a 25% recurrence rate of tremors for PD after thalamotomy. Writer’s cramp rating scale improved from a mean of 10.54–1.6 in task specific dystonia (TSD) patients, after thalamotomy. In PD patients, after pallidotomy, contralateral motor Unified Parkinson’s Disease Rating Scale (UPDRS) and dyskinesia scores, improved by 41 and 57%, respectively, at 1-year. Burke-Fahn-Marsden Dystonia Rating Scale in hemidystonia patients improved from 18.04 to 6.91, at 1-year. There was 32 and 31% improvement in total and motor UPDRS, respectively, in the subthalamotomy patients, at 2-year. All patients of OCD were in remission. There were three deaths in the pallidotomy group. Postoperative, dysarthria, confusion, hemiparesis, dyskinesia, and paraesthesia occurred in 12 patients, of which, 7 were transient.ConclusionRFL is a useful option in a select group of patients with tremors and dystonia. It is our preferred treatment option for TSD and OCD.

scholarly journals A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies

2018 ◽  
Vol 44 (2) ◽  
pp. E13 ◽  
Author(s):  
Goutam Ghoshal ◽  
Lucy Gee ◽  
Tamas Heffter ◽  
Emery Williams ◽  
Corinne Bromfield ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Minimally Invasive ◽  
Focused Ultrasound ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Rodent Model ◽  
Therapeutic Interventions ◽  
Porcine Liver

OBJECTIVEMinimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator.METHODSUsing an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson’s disease to investigate the feasibility of its application in brain.RESULTSThermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson’s disease.CONCLUSIONSThe authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

Magnetic resonance–guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson's disease and essential tremor cases

2018 ◽  
Vol 128 (1) ◽  
pp. 202-210 ◽  
Author(s):  
Menashe Zaaroor ◽  
Alon Sinai ◽  
Dorith Goldsher ◽  
Ayelet Eran ◽  
Maria Nassar ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Rating Scale ◽  
Innovative Technology ◽  
The Mean

OBJECTIVEThalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation.METHODSPatients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39).RESULTSThirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46–87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2–30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6–24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14–45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13–24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850–23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°–60°C).CONCLUSIONSMRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse events profile of MRgFUS over other surgical approaches for treating tremor with similar efficacy. Large randomized studies are needed to assess prolonged efficacy and safety.

scholarly journals Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland

2021 ◽  
Vol 12 ◽  
Author(s):  
Lennart H. Stieglitz ◽  
Markus F. Oertel ◽  
Ettore A. Accolla ◽  
Julien Bally ◽  
Roland Bauer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Patient Selection ◽  
Movement Disorders ◽  
High Intensity ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Brain Disorders ◽  
Functional Neurosurgery ◽  
Consensus Paper

Background: Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements.Objective: To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper.Methods: Eighteen experienced neurosurgeons and neurologists practicing in Switzerland in the field of movement disorders and one health physicist representing 15 departments of 12 Swiss clinical centers and 5 medical societies participated in the workshop and contributed to the consensus paper. All experts have experience with current treatment modalities or with MRgHiFUS. They were invited to participate in two workshops and consensus meetings and one online meeting. As part of workshop preparations, a thorough literature review was undertaken and distributed among participants together with a list of relevant discussion topics. Special emphasis was put on current experience and practice, and areas of controversy regarding clinical application of MRgHiFUS for functional neurosurgery.Results: The recommendations addressed lesioning for treatment of brain disorders in general, and with respect to MRgHiFUS indications, stereotactic targets, treatment alternatives, patient selection and management, standardization of reporting and follow-up, and initialization of a national registry for interventional therapies of movement disorders. Good clinical evidence is presently only available for unilateral thalamic lesioning in treating essential tremor or tremor-dominant Parkinson's disease and, to a minor extent, for unilateral subthalamotomy for Parkinson's disease motor features. However, the workgroup unequivocally recommends further exploration and adaptation of MRgHiFUS-based functional lesioning interventions and confirms the need for outcome-based evaluation of these approaches based on a unified registry. MRgHiFUS and DBS should be evaluated by experts familiar with both methods, as they are mutually complementing therapy options to be appreciated for their distinct advantages and potential.Conclusion: This multidisciplinary consensus paper is a representative current recommendation for safe implementation and standardized practice of MRgHiFUS treatments for functional neurosurgery in Switzerland.

scholarly journals Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson’s disease

2020 ◽  
pp. 1-8 ◽  
Author(s):  
Timothy R. Miller ◽  
Sijia Guo ◽  
Elias R. Melhem ◽  
Howard M. Eisenberg ◽  
Jiachen Zhuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Temperature Rise ◽  
Focused Ultrasound ◽  
Threshold Model ◽  
Average Energy ◽  
Lesion Size ◽  
Temperature Threshold ◽  
Treatment Efficiency ◽  
Mr Thermometry

OBJECTIVEMagnetic resonance–guided focused ultrasound (MRgFUS) ablation of the globus pallidus interna (GPi) is being investigated for the treatment of advanced Parkinson’s disease symptoms. However, GPi lesioning presents unique challenges due to the off-midline location of the target. Furthermore, it remains uncertain whether intraprocedural MR thermometry data can predict final lesion characteristics.METHODSThe authors first performed temperature simulations of GPi pallidotomy and compared the results with those of actual cases and the results of ventral intermediate nucleus (VIM) thalamotomy performed for essential tremor treatment. Next, thermometry data from 13 MRgFUS pallidotomy procedures performed at their institution were analyzed using 46°C, 48°C, 50°C, and 52°C temperature thresholds. The resulting thermal models were compared with resulting GPi lesions noted on postprocedure days 1 and 30. Finally, the treatment efficiency (energy per temperature rise) of pallidotomy was evaluated.RESULTSThe authors’ modeled acoustic intensity maps correctly demonstrate the elongated, ellipsoid lesions noted during GPi pallidotomy. In treated patients, the 48°C temperature threshold maps most accurately predicted postprocedure day 1 lesion size, while no correlation was found for day 30 lesions. The average energy/temperature rise of pallidotomy was higher (612 J/°C) than what had been noted for VIM thalamotomy and varied with the patients’ skull density ratios (SDRs).CONCLUSIONSThe authors’ acoustic simulations accurately depicted the characteristics of thermal lesions encountered following MRgFUS pallidotomy. MR thermometry data can predict postprocedure day 1 GPi lesion characteristics using a 48°C threshold model. Finally, the lower treatment efficiency of pallidotomy may make GPi lesioning challenging in patients with a low SDR.

scholarly journals Focused Ultrasound Thalamotomy for Tremor-dominant Parkinson’s Disease: A Prospective 1-year Follow-up Study

2021 ◽  
Author(s):  
Kazuaki YAMAMOTO ◽  
Hisashi ITO ◽  
Shigeru FUKUTAKE ◽  
Takashi ODO ◽  
Tetsumasa KAMEI ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Focused Ultrasound ◽  
Follow Up Study
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