Outcomes of Focused Ultrasound Thalamotomy in Tremor Syndromes.

BACKGROUND: The current literature comparing outcomes after a unilateral magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy between tremor syndromes is limited and remains a possible preoperative factor that could help predict the long-term outcomes. OBJECTIVE: The aim was to report on the outcomes between different tremor syndromes after a unilateral MRgFUS thalamotomy. METHODS: A total of 66 patients underwent a unilateral MRgFUS thalamotomy for tremor between November 2018 and May 2020 at St Vincent's Hospital Sydney. Each patient's tremor syndrome was classified prior to treatment. Clinical assessments, including the hand tremor score (HTS) and Quality of Life in Essential Tremor Questionnaire (QUEST), were performed at baseline and predefined intervals to 36 months. RESULTS: A total of 63 patients, comprising 30 essential tremor (ET), 24 dystonic tremor (DT), and 9 Parkinson's disease tremor (PDT) patients, returned for at least one follow-up. In the ET patients, at 24 months there was a 61% improvement in HTS and 50% improvement in QUEST compared to baseline. This is in comparison to PDT patients, where an initial benefit in HTS and QUEST was observed, which waned at each follow-up, remaining significant only up until 12 months. In the DT patients, similar results were observed to the ET patients: at 24 months there was a 61% improvement in HTS and 43% improvement in QUEST compared to baseline. CONCLUSION: These results support the use of unilateral MRgFUS thalamotomy for the treatment of DT, which appears to have a similar expected outcome to patients diagnosed with ET. Patients with PDT should be warned that there is a risk of treatment failure. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

New Detection of Locally Acquired Japanese Encephalitis Virus Using Clinical Metagenomics, New South Wales, Australia.

In the context of an emerging Japanese encephalitis outbreak within Australia, we describe a novel locally acquired case in New South Wales. A man in his 70s had rapidly progressive, fatal meningoencephalitis, diagnosed as caused by Japanese encephalitis virus by RNA-based metagenomic next-generation sequencing performed on postmortem brain tissue.

Consistency is key: influence of skull density ratio distribution on the formation of clinically effective lesions and long-term tremor suppression following treatment with MR-guided focused ultrasound.

OBJECTIVE: Skull density ratio (SDR) influences the permeability of the skull to the ultrasound waves used in magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor. SDR values vary across the skull and the mean value is known to be predictive of sonication thermal increase. The aim of this investigation was to explore the effects of the SDR distribution on clinical outcomes following treatment with MRgFUS. METHODS: Data from 61 patients with essential or dystonic tremor treated with MRgFUS targeting the ventral intermediate nucleus (Vim) were retrospectively analyzed. Tremor suppression was assessed using the Clinical Rating Scale for Tremor (CRST) and hand tremor score (HTS). Vim ablation volume was measured on the T1-weighted MR image acquired both at 1 day and 12 months after treatment. The numerical distribution of SDR values measured for each element in the ultrasound transducer was quantified by calculating the mean, standard deviation, skewness, entropy, and kurtosis of the SDR histogram. The effect of the SDR metrics on change in CRST and HTS was examined using a linear mixed-effects model. Additionally, the effect of the regional distribution of SDR values was explored in an element-wise analysis between patients with above- and below-average tremor suppression. RESULTS: A significant positive effect was found between SDR kurtosis and improvement in CRST (ß = 0.33, p = 0.004) and HTS (ß = 0.38, p < 0.001). The effect was found to be significant at 1 month posttreatment (CRST: ß = 0.415, p = 0.008; HTS: ß = 0.369, p = 0.016), and at the most recent clinical follow-up (CRST: ß = 0.395, p < 0.001; HTS: ß = 0.386, p < 0.001). One hundred seventy-one significant elements were identified in the element-wise analysis. The mean percentage difference from the mean SDR in these elements was associated with improvement in CRST (ß = 0.27, p < 0.008) and HTS (ß = 0.27, p < 0.015). Higher SDR kurtosis was associated with increased lesion volume at 12 months (p = 0.040) and less reduction in volume relative to the day-1 lesion volume (p = 0.007). CONCLUSIONS: Greater SDR kurtosis was associated with larger, more stable lesions at 12 months posttreatment and increased tremor suppression at long-term follow-up. SDR kurtosis may provide a more meaningful prognostic factor than the mean SDR.

Magnetic Resonance-Guided Focused Ultrasound for Treatment of Essential Tremor: Ventral Intermediate Nucleus Ablation Alone or Additional Posterior Subthalamic Area Lesioning?

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) for treatment of essential tremor (ET) traditionally targets the ventral intermediate (Vim) nucleus. Recent strategies include a secondary lesion to the posterior subthalamic area (PSA). OBJECTIVE: The aim was to compare lesion characteristics, tremor improvement, and adverse events (AE) between patients in whom satisfactory tremor suppression was achieved with lesioning of the Vim alone and patients who required additional lesioning of the PSA. METHODS: Retrospective analysis of data collected from ET patients treated with MRgFUS at St Vincent's Hospital Sydney was performed. Clinical Rating Scale for Tremor (CRST), hand tremor score (HTS), and Quality of Life in Essential Tremor Questionnaire (QUEST) were collected pre- and posttreatment in addition to the prevalence of AEs. The lesion coordinates and overlap with the dentatorubrothalamic tract (DRTT) were evaluated using magnetic resonance imaging. RESULTS: Twenty-one patients were treated in Vim only, and 14 were treated with dual Vim-PSA lesions. Clinical data were available for 29 of the 35 patients (19 single target and 10 dual target). At follow-up (mean: 18.80 months) HTS, CRST, and QUEST in single-target patients improved by 57.97% (P < 0.001), 36.71% (P < 0.001), and 58.26% (P < 0.001), whereas dual-target patients improved by 68.34% (P < 0.001), 35.37% (P < 0.003), and 46.97% (P < 0.005), respectively. The Vim lesion of dual-target patients was further anterior relative to the posterior commissure (PC) (7.84 mm), compared with single-target patients (6.92 mm), with less DRTT involvement (14.85% vs. 23.21%). Dual-target patients exhibited a greater proportion of patients with acute motor AEs (100% vs. 58%); however, motor AE prevalence was similar in both groups at long-term follow-up (33% vs. 38%). CONCLUSION: Posterior placement of lesions targeting the Vim may confer greater tremor suppression. The addition of a PSA lesion, in patients with inadequate tremor control despite Vim lesioning, had a trend toward better long-term tremor suppression; however, this approach was associated with greater prevalence of gait disturbance in the short term.

Effective Subthalamic Nucleus Deep Brain Stimulation Following MRgFUS for Tremor Dominant Parkinson's Disease.

Background: Whilst MRI guided Focused Ultrasound (MRgFUS) thalamotomy is an effective treatment option for tremor disorders, there are reports of tremor recurrence in patients with tremor dominant Parkinson's disease (PD). The mechanisms for tremor recurrence are unknown but likely relate to the duality of tremor network pathways with ramifications for subsequent treatment options. Cases: We report two cases of tremor dominant PD who experienced tremor recurrence following MRgFUS thalamotomy with subsequent successful subthalamic nucleus deep brain stimulation (DBS). Tremor scores were measured at baseline, 1- and 3-months post MRgFUS and at least 18 months post DBS in both patients. Both cases evidenced immediate improvement in tremor, after MRgFUS, followed by subsequent tremor recurrence. STN DBS resulted in almost complete long-term tremor alleviation in both cases. Conclusions: These cases demonstrate the efficacy and feasibility of STN DBS in patients with tremor dominant PD with tremor recurrence following MRgFUS thalamotomy. We discuss the dualism of tremor outflow pathways that may have implications for single target lesional therapies.

Evaluation of the efficacy and safety of MRI-guided focused ultrasound (MRgFUS) for focal hand dystonia: study protocol for an open-label non-randomised clinical trial.

Introduction: MRI-guided focused ultrasound (MRgFUS) thalamotomy provides an exciting development in the field of minimally invasive stereotactic neurosurgery. Current treatment options for focal hand dystonia are limited, with potentially more effective invasive stereotactic interventions, such as deep brain stimulation or lesional therapies, rarely used. The advent of minimally invasive brain lesioning provides a potentially safe and effective treatment approach with a recent pilot study establishing MRgFUS Vo-complex thalamotomy as an effective treatment option for focal hand dystonia. In this study, we undertake an open-label clinical trial to further establish MRgFUS Vo-complex thalamotomy as an effective treatment for focal hand dystonia with greater attention paid to potential motor costs associated with this treatment. To elucidate pathophysiology of dystonia and treatment mechanisms, neurophysiological and MRI analysis will be performed longitudinally to explore the hypothesis that neuroplastic and structural changes that may underlie this treatment benefit. Methods and analysis: A total of 10 participants will be recruited into this open-label clinical trial. All participants will undergo clinical, kinemetric, neurophysiological and radiological testing at baseline, followed by repeated measures at predesignated time points post MRgFUS Vo-complex thalamotomy. Further, to identify any underlying structural or neurophysiological abnormalities present in individuals with focal hand dystonia, 10 age and gender matched control participants will be recruited to undergo comparative investigation. These results will be compared with the intervention participants both at baseline and at 12 months to assess for normalisation of these abnormalities, if present. Ethics and dissemination: This trial was reviewed and approved by the St Vincent's Health Network Sydney Human Research Ethics Committee (2022/ETH00778). Study results will be published in peer-reviewed journals and presented at both national and international conferences. Trial registration number: CTRN12622000775718.

Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor.

Objectives: Magnetic resonance-guided focussed ultrasound (MRgFUS) is an incisionless ablative procedure, widely used for treatment of Parkinsonian and Essential Tremor (ET). Enhanced understanding of the patient- and treatment-specific factors that influence sustained long-term tremor suppression could help clinicians achieve superior outcomes via improved patient screening and treatment strategy. Methods: We retrospectively analysed data from 31 subjects with ET, treated with MRgFUS at a single centre. Tremor severity was assessed with parts A, B and C of the Clinical Rating Scale for Tremor (CRST) as well as the combined CRST. Tremor in the dominant and non-dominant hand was assessed with Hand Tremor Scores (HTS), derived from the CRST. Pre- and post-treatment imaging data were analysed to determine ablation volume overlap with automated thalamic segmentations, and the dentatorubrothalamic tract (DRTT) and compared with percentage change in CRST and HTS following treatment. Results: Tremor symptoms were significantly reduced following treatment. Combined pre-treatment CRST (mean: 60.7 ± 17.3) and HTS (mean: 19.2 ± 5.7) improved by an average of 45.5 and 62.6%, respectively. Percentage change in CRST was found to be significantly negatively associated with age (ß = -0.375, p = 0.015), and SDR standard deviation (SDRSD; ß = -0.324, p = 0.006), and positively associated with ablation overlap with the posterior DRTT (ß = 0.535, p < 0.001). Percentage HTS improvement in the dominant hand decreased significantly with older age (ß = -0.576, p < 0.01). Conclusion: Our results suggest that increased lesioning of the posterior region of the DRTT could result in greater improvements in combined CRST and non-dominant hand HTS, and that subjects with lower SDR standard deviation tended to experience greater improvement in combined CRST.

NMDA receptor antibody in teratoma-related opsoclonus-myoclonus syndrome.

Opsoclonus-myoclonus syndrome (OMS) is a brainstem/cerebellar syndrome producing disabling multi-directional saccadic oscillations with oscillopsia, with or without somatic myoclonus and cerebellar ataxia (Wong et al., 2001; Armangué et al., 2016). OMS is presumed to have an autoimmune basis and patients with it are tested for antineuronal antibodies and have imaging to locate any tumors. Here we report a unusual case of a young woman who had NMDAR antibody (NMDAR-ab) positive, teratoma-related, isolated OMS without encephalopathy. Removal of her ovarian teratoma, and immunotherapy with steroids, intravenous immunoglobulin (IVIg), plasma exchange (PLEX), and ultimately with B-cell depletion with rituximab resulted in total recovery after 3 months. Patients with teratoma-related OMS very rarely have NMDAR-ab which suggests that it is not the NMDAR-ab per se that causes the OMS.

Relationship Between Laryngeal Electromyography and Video Laryngostroboscopy in Vocal Fold Paralysis.

OBJECTIVES/HYPOTHESIS: The objective of this study was to better define the relationship of laryngeal electromyography and video laryngostroboscopy in the diagnosis of vocal fold paralysis. STUDY DESIGN: Retrospective diagnostic cohort study with cross-sectional data analysis METHODS: Data were obtained from 57 patients with unilateral vocal fold paralysis who attended a large tertiary voice referral center. Electromyographic findings were classified according to recurrent laryngeal nerve, superior laryngeal nerve, and high vagal/combined lesions. Video laryngostroboscopy recordings were classified according to the position of the immobile fold into median, paramedian, lateral, and a foreshortened/hooded vocal fold. The position of the paralyzed vocal fold was then analyzed according to the lesion as determined by electromyography. RESULTS: The recurrent laryngeal nerve was affected in the majority of cases with left-sided lesions more common than right. Vocal fold position differed between recurrent laryngeal and combined vagal lesions. Recurrent laryngeal nerve lesions were more commonly associated with a laterally displaced immobile fold. No fold position was suggestive of a combined vagal lesion. The inter-rater reliability for determining fold position was high. CONCLUSION: Laryngeal electromyography is useful in diagnosing neuromuscular dysfunction of the larynx and best practice recommends its continued implementation along with laryngostroboscopy. While recurrent laryngeal nerve lesions are more likely to present with a lateral vocal fold, this does not occur in all cases. Such findings indicate that further unknown mechanisms contribute to fold position in unilateral paralysis.