Treatment-Specific Network Modulation of MRI-Guided Focused Ultrasound Thalamotomy in Essential Tremor: Modulation of ET-Related Network by MRgFUS Thalamotomy

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01294-9.     

Comparison of Transcranial Focused Ultrasound and Transcranial Pulse Stimulation for Neuromodulation: A Computational Study

ObjectiveThe objective of the study was to investigate transcranial wave propagation through two low-intensity focused ultrasound (LIFU)–based brain stimulation techniques—transcranial focused ultrasound stimulation (tFUS) and transcranial pulse stimulation (TPS). Although tFUS involves delivering long trains of acoustic pulses, the newly introduced TPS delivers ultrashort (～3 μs) pulses repeated at 4 Hz. Accordingly, only a single simulation study with limited geometry currently exists for TPS. We considered a high-resolution three-dimensional (3D) whole human head model in addition to water bath simulations. We anticipate that the results of this study will help researchers investigating LIFU have a better understanding of the effects of the two different techniques.ApproachWith an objective to first reproduce previous computational results, we considered two spherical tFUS transducers that were previously modeled. We assumed identical parameters (geometry, position, and imaging data set) to demonstrate differences, purely because of the waveform considered. For simulations with a 3D head data set, we also considered a parabolic transducer that has been used for TPS delivery.ResultsOur initial results successfully verified previous modeling workflow. The tFUS distribution was characterized by the typical elliptical profile, with its major axis perpendicular to the face of the transducer. The TPS distribution resembled two mirrored meniscus profiles, with its widest diameter oriented parallel to the face of the transducer. The observed intensity value differences were theoretical because the two waveforms differ in both intensity and time. The consideration of a realistic 3D human head model resulted in only a minor distortion of the two waveforms.SignificanceThis study simulated TPS administration using a 3D realistic image-derived data set. Although our comparison results are strictly limited to the model parameters and assumptions made, we were able to elucidate some clear differences between the two approaches. We hope this initial study will pave the way for systematic comparison between the two approaches in the future.     

Bilateral Pallidotomy for Dystonia: A Systematic Review

Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2–180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Deep Brain Stimulation for Dystonia: A Meta‐Analysis

Objective. To use a meta‐analysis on all reported cases of deep brain stimulation (DBS) for dystonia to determine which factors significantly influence outcome. The Burke‐Fahn‐Marsden (BFM) movement scale, the most reported measure, was chosen as the primary outcome measure for this analysis. Methods. A MEDLINE search identified 137 patients who underwent DBS for dystonia in 24 studies that had individual BFM scores. Individual patient data, including age at onset of dystonia, age at surgery, gender, distribution of dystonia, etiology of dystonia, presence of associated features, abnormality of preoperative imaging, prior stereotactic surgeries, nucleus stimulated, type of anesthesia used, use of physiologic monitoring, type of imaging used for localization, stimulation parameters used, time of response to stimulation, and timing of outcome assessment were entered into an SPSS database for statistical analysis. Results. The mean BFM percentage change (improvement in postoperative score from baseline) was 51.8% (range ?34% to 100%). Significantly better outcomes were achieved with stimulation of the globus pallidus internus (GPi) than with stimulation of the posterior portion of the ventral lateral (VLp) nucleus of the thalamus (p = 0.0001). The etiology of the dystonia also had a significant effect on outcomes. Statistically significant improvements in outcomes were seen for all etiologic categories, except encephalitis. Dystonia due to birth injury and encephalitis had significantly worse outcomes when compared to other etiologies. However, there were no significant differences in the outcomes of patients who were DYT1 (DYT1 is the gene associated with the disorder Dystonia Musculorum Deformans) gene positive, DYT1 gene negative, or had pantothenate kinase‐associated neurodegeneration (PKAN), tardive dyskinesia, and idiopathic and posttraumatic dystonias. Longer duration of dystonia symptoms correlated negatively with surgical outcome. A regression model using the three variables—stimulation site, etiology of dystonia, and duration of dystonia symptoms—explained 51% of the variance in outcomes. Conclusion. Deep brain stimulation of the GPi provides significant improvement in BFM scores in a variety of dystonic conditions.     

A Pilot Study to Investigate the Effects of Electrical Stimulation on Recovery of Hand Function and Sensation in Subacute Stroke Patients

Objectives. 1) To compare the effect of cyclic neuromuscular electrical stimulation (NMES) of the forearm and elbow extensor muscles with passive stretching exercises on hand function and sensation following stroke. 2) To inform sample size for a larger randomized controlled trial (RCT). Materials and Methods. Twenty‐two subjects with hemiplegia resulting from a stroke during the previous 12 months were randomly allocated into stimulation (treatment) and exercise (control) groups. Stimulation was applied to the elbow, and forearm extensor muscle groups of the hemiplegic arm for 12 weeks. Subjects in the control group were taught passive stretching exercises for the same period. The primary outcome measure was the Action Research Arm test (ARAT). Sensation was tested using two‐point discrimination. Statistical analysis applied nonparametric analysis of covariance (ancova ). Results. Statistically significant between‐group differences in change in ARAT scores were shown between the two groups after 12 weeks of treatment (p = 0.003) and following 12 further weeks without intervention (p = 0.012). There were no significant differences in sensation. Conclusions. 1) A significant treatment effect of electrical stimulation over passive exercise has been demonstrated in a group of 22 subacute stroke patients, randomized into two equal groups and further work identified which may help to improve recovery of hand function and sensation following stroke. 2) A sample size of 24 subjects in each group has been estimated assuming a two‐sided test significance level of 5% with 80% power, primary outcome variability SD = 6.75, a minimum difference of ten ARAT score units, and a 10% dropout rate.     

Effect of Subthalamic Nucleus Stimulation on Severe Striatal Hand Deformity in Parkinson's Disease: A Case Report

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa‐induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN‐DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN‐DBS on the hand deformity was a secondary effect on muscular rigidity. STN‐DBS is assumed to represent a useful treatment option for striatal hand deformity.     

MRI‐Guided High‐Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A Review

Stroke, either ischemic or hemorrhagic, accounts for significantly high morbidity and mortality rates around the globe effecting millions of lives annually. For the past few decades, ultrasound has been extensively investigated to promote clot lysis for the treatment of stroke, myocardial infarction, and acute peripheral arterial occlusions, with or without the use of tPA or contrast agents. In the age of modern minimal invasive techniques, magnetic resonance imaging‐guided high‐intensity focused ultrasound is a new emerging modality that seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke. High‐intensity focused ultrasound causes thermal heating as the tissue absorbs the mechanical energy transmitted by the ultrasonic waves leading to tissue denaturation and coagulation. Several in‐vitro and in‐vivo studies have demonstrated the viability of this technology for sonothrombolysis in both types of stroke and have warranted clinical trials. Apart from safety and efficacy, initiation of trials would further enable answers regarding its practical application in a clinical setup. Though this technology has been under study for treatment of various brain diseases for some decades now, relatively very few neurologists and even neurosurgeons seem to be acquainted with it. The aim of this review is to provide basic understanding of this powerful technology and discuss its clinical application and potential role as an emerging viable therapeutic option for the future management of stroke.     

Ultrasound in EMG‐Guided Biopsies: A Prospective,Randomized Pilot Trial

Introduction: At our institution, core muscle biopsies are performed on muscles selected using electromyography (EMG). Ultrasound (US) guidance is not used routinely. The aim of this study was to determine if US guidance of EMG selected muscles would increase the diagnostic yield of the biopsy as compared to the current practice standards. Methods: Two trained physicians performed 40 randomized biopsies (US guided or traditional approach). The amount of tissue obtained in each biopsy was recorded (volume and mass), along with the final pathologic diagnosis in each case and incidence of complications. Results: Forty patients were studied. Sixteen muscle biopsies were done with US guidance; 50% had a definitive diagnosis, and 38% did not. In the non‐US guidance group, 58% had a definitive diagnosis, and 33% did not. Conclusions: US did not provide any additive advantage when used to guide biopsy in a muscle previously selected for biopsy with EMG. Muscle Nerve 54 : 786–788, 2016