Tremor Rating Scale Research Articles

Automated analysis of pen-on-paper spirals for tremor detection, quantification, and differentiation

Objective: To develop an automated algorithm to detect, quantify, and differentiate between tremor using pen-on-paper spirals. Methods: Patients with essential tremor (n = 25), dystonic tremor (n = 25), Parkinson’s disease (n = 25), and healthy volunteers (HV, n = 25) drew free-hand spirals. The algorithm derived the mean deviation (MD) and tremor variability from scanned images. MD and tremor variability were compared with 1) the Bain and Findley scale, 2) the Fahn–Tolosa–Marin tremor rating scale (FTM–TRS), and 3) the peak power and total power of the accelerometer spectra. Inter and intra loop widths were computed to differentiate between the tremor. Results: MD was higher in the tremor group (48.9 ± 26.3) than in HV (26.4 ± 5.3; p < 0.001). The cut-off value of 30.3 had 80.9% sensitivity and 76.0% specificity for the detection of the tremor [area under the curve: 0.83; 95% confidence index (CI): 0.75, 0.91, p < 0.001]. MD correlated with the Bain and Findley ratings (rho = 0.491, p = 0 < 0.001), FTM–TRS part B (rho = 0.260, p = 0.032) and accelerometric measures of postural tremor (total power, rho = 0.366, p < 0.001; peak power, rho = 0.402, p < 0.001). Minimum Detectable Change was 19.9%. Inter loop width distinguished Parkinson’s disease spirals from dystonic tremor (p < 0.001, 95% CI: 54.6, 211.1), essential tremor (p = 0.003, 95% CI: 28.5, 184.9), or HV (p = 0.036, 95% CI: -160.4, -3.9). Conclusion: The automated analysis of pen-on-paper spirals generated robust variables to quantify the tremor and putative variables to distinguish them from each other. Significance: This technique maybe useful for epidemiological surveys and follow-up studies on tremor.

Stepwise Dual-Target Magnetic Resonance–Guided Focused Ultrasound in Tremor-Dominant Parkinson Disease: A Feasibility Study

Magnetic resonance-guided focused ultrasound (MRgFUS) has been applied successfully in treating refractory tremors in Parkinson disease (PD). It generates a precise thermal ablation in a specific nucleus or tract, such as ventral intermediate nucleus (VIM) or pallidothalamic tract (PTT). Despite a single lesion improving parts of the PD symptoms, the feasibility and efficacy of a stepwise dual-lesion in VIM and PTT are yet to be explored. Three patients with tremor-dominant PD (aged 60.7 ± 6.0 years) received dual-target MRgFUS treatment with a series of primary and secondary outcome measures. The VIM and PTT were navigated based on individual magnetic resonance imaging planning of the brain. The primary outcome measures were the off-status Clinical Rating Scale for Tremor and Unified Parkinson's Disease Rating Scale part III (UPDRS-III). The secondary outcome measures included UPDRS I, II, IV, Hohen and Yahr score, Neuropsychiatry Inventory, Quality of life in PD Rating Scale, Non-Motor Symptoms Scale, and Clinical Global Impression. The baseline data were compared with those acquired 1 day and 1 month following the treatment. The severity of tremor and motor deficits represented by Clinical Rating Scale for Tremor-part B and UPDRS III were significantly improved (P < 0.05 by nonparametric Mann-Whitney U tests) after dual-target ablations. The nonmotor symptoms investigated by UPDRS II and Non-Motor Symptoms Scale also showed significant improvement at the 1-day and 1-month follow-up. There was no adverse effect except temporary procedure-related headache and dizziness during the treatment. Stepwise dual-lesion targeting VIM and PTT is a safe and effective MRgFUS therapeutic strategy for patients with PD.

Cognitive outcomes after focused ultrasound thalamotomy for tremor: Results from the COGNIFUS (COGNitive in Focused UltraSound) study

IntroductionMagnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an innovative method for the unilateral treatment of essential tremor (ET) and Parkinson's disease (PD) related tremor. Our aim was to assess cognitive changes following MRgFUS thalamotomy to better investigate its safety profile. MethodsWe prospectively investigated the cognitive and neurobehavioral profile of patients consecutively undergoing MRgFUS within a 2-year period. Patients had a comprehensive clinical and neuropsychological assessment before and six months after MRgFUS thalamotomy. ResultsThe final sample consisted of 40 patients (males 38; mean age±SD 67.7 ± 10.7; mean disease duration±SD 9.3 ± 5.6; ET 22, PD 18 patients). For the whole sample, improvements were detected in tremor (Fahn-Tolosa-Marin Clinical Rating Scale for tremor 35.79 ± 14.39 vs 23.03 ± 10.95; p < 0.001), anxiety feelings (Hamilton Anxiety rating scale 5.36 ± 3.80 vs 2.54 ± 3.28, p < 0.001), in the overall cognitive status (MMSE 25.93 ± 3.76 vs 27.54 ± 2.46, p 0.003; MOCA 22.80 ± 4.08 vs 24.48 ± 3.13, p < 0.001), and in quality of life (Quality of life in Essential Tremor Questionnaire 36.14 ± 12.91 vs 5.14 ± 6.90, p < 0.001 and PD Questionnaire-8 5.61 ± 4.65 vs 1.39 ± 2.33, p 0.001). No changes were detected in frontal and executive functions, verbal fluency and memory, abstract reasoning and problem-solving abilities. ConclusionOur study moves a step forward in establishing the cognitive sequelae of MRgFUS thalamotomy and in endorsing effectiveness and safety.

Gamma Knife Radiosurgery for Tremor Movement Disorder: A Systematic Review

AIM: The goal of this systematic review is to know how outcome of GKRS for tremor movement disorder. METHODS: Literature searching was conducted in database online that is PubMed, Science Direct, Cochrane Library, Google Scholar and hand searching with keyword “gamma knife,” “parkinson,” “tremor,” “success rate,” “good outcome,” and “free tremor.” Articles included were full-text and observational study and written in Bahasa or English. RESULTS: This systematic review used only six articles, which five of them examined ET and the other PD. Majority of studies used Fahn-Tolosa-Marin clinical tremor rating scale (TRS) for evaluation pre- and post-GKRS. However, the duration of follow-up is varies from &lt;1 year until 76 months. The doses are also varies from 110 until 150 Gy (Median 120–130 Gy). A study report that 1 year after GKRS, ET patients could have 58% improvement in writing and 51% in drawing. Other study, which of median follow-up was 36 months, had 69% of samples showed improvement in both action tremor and writing scores. Ohye et al. in 2008 reported that since 1992, they have 80% successful in GK thalamotomy for tremor, either ET or PD. Similar author has been done multivariate study in six Japanese institution which of result was GKRS thalamotomy could be alternative treatment for intractable tremor, either ET or PD until 24 months. All of the study about ET have improvement results with GKRS in ventralis intermedius (VIM) of the thalamus. However, one study about PD evaluated GKRS in subthalamic nucleus (STN) of thalamus and got neurological complication with higher-risk of GKRS hyper response. CONCLUSION: GKRS, especially VIM thalamotomy, offers effective and safe alternative for ET and PD. We need more studies with approved method to answer this clinical question accurately. However, the study comparing GKRS and open surgical is still needed.

Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial

Introductionand objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo. MethodsThis was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes. ResultsThere was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89–23.86] vs drug: 26.14 [-35.58 to −16.07], p-value: 0.164, CI: 0.157–0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001). ConclusionZonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding.

Pretherapeutic functional connectivity of tractography-based targeting of the ventral intermediate nucleus for predicting tremor response in patients with Parkinson's disease after thalamotomy with MRI-guided focused ultrasound.

Tractography-based direct targeting of the ventral intermediate nucleus (T-VIM) is a novel method that provides patient-specific VIM coordinates. This study aimed to explore the accuracy and predictive value of using T-VIM in combination with tractography and resting-state functional connectivity techniques to perform magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment of Parkinson's disease (PD). PD patients underwent MRgFUS thalamotomy and were recruited for functional MRI scanning. A subscore of the Clinical Rating Scale for Tremor was used to evaluate tremor improvement. T-VIM and surgical VIM (S-VIM) were defined on preoperative diffusion tensor MRI and 24-hour postoperative T1-weighted imaging, respectively. The overlapping volume and center distance between S-VIM and T-VIM were measured to determine their correlations with 12-month postoperative tremor improvement. Moreover, pretherapeutic functional connectivity of T-VIM or S-VIM, based on region-of-interest connectivity and whole-brain seed-to-voxel connectivity, was measured with the resting-state functional connectivity technique to investigate their correlations with tremor improvement. All patients had excellent tremor improvement (mean [range] tremor improvement 74.82% [50.00%-94.44%]). The authors found that both overlapping volume and center distance between T-VIM and S-VIM were significantly correlated with tremor improvement (r = 0.788 and p = 0.012 for overlapping volume; r = -0.696 and p = 0.037 for center distance). Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex (r = 0.876 and p = 0.002), subthalamic nucleus (r = 0.700 and p = 0.036), and visual area (r = 0.911 and p = 0.001) was significantly and positively correlated with tremor improvement. T-VIM may improve the clinical application of MRgFUS thalamotomy as a treatment of PD. Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex, subthalamic nucleus, and visual area may predict PD tremor responses after MRgFUS thalamotomy.

The effect of a mobile-based self-care program on tremor of people with multiple sclerosis

Background and aims: Multiple sclerosis (MS) is one of the most common progressive neurological diseases in young people. Tremor is a common and debilitating symptom in people with MS, significantly affecting their quality of life. This study aimed to evaluate the effect of a self-care program based on a mobile application on tremors in people with MS. Methods: This semi-experimental study was conducted on 72 patients with MS in Chaharmahal and Bakhtiari province in 2019. Samples were selected by convenience sampling and randomly assigned to intervention and control groups (36 people in each group). For the intervention group, a self-care program in the form of a mobile application was installed on their mobile phones and, for two months, used by patients. The use of the program was measured using self-report checklists and telephone tracking. The control group receives routine intervention only. Data were collected before and two months after the intervention using the Fahn-Tolosa-Marin Tremor Rating Scale and analyzed using SPSS software version 21 and descriptive and inferential statistics (chi-square, independent t test, and paired t test). Results: There was no statistically significant difference between the two groups in the mean tremor score before the intervention (P=0.768). However, after the intervention, this difference was significant (P=0.022). Conclusion: According to the findings, teaching a self-care program through a mobile application effectively improves the tremor of patients with MS and can be considered an effective intervention method.

Continuous Monitoring of Essential Tremor: Standards and Challenges.

The value of continuous symptom monitoring in people with essential tremor is uncertain. To determine the relationship between tremor amplitude measured with wearable inertial sensors and clinician- and patient-rated measures. For 14 days, patients (1) wore inertial sensors on both wrists, (2) self-rated their tremor using a diary, (3) drew spirals, and (4) completed an activities of daily living scale once daily. Patients were also scored using The Essential Tremor Rating Scale (TETRAS) performance in the clinic by a clinician. We found strong correlations in patient-reported metrics of tremor, but weak correlations between these data and both the inertial sensor data and the in-clinic TETRAS scores. The patient experience of tremor during normal daily activities may differ from the transducer-based measures of tremor amplitude and rating scales of tremor severity. Future studies should consider how to record features of tremor that are important to patients.

Focused ultrasound and deep brain stimulation for Parkinsonism – Review of literature to investigate tradeoff between safety and efficacy

Parkinsonism is a movement disorder, mostly caused by the neurodegenerative Parkinson's disease (PD), the second most common movement disorder. Its symptoms include rigidity, slow movement, tremor, and disruption of balance. First treatment line is dopamine replacement drugs, and surgery is due when medication fails. Surgery options include deep brain stimulation (DBS), which revolves around implanting impulse generator in the target structure, and magnetic resonance-guided focused ultrasound (MRgFUS), where transcranial sonication ablates certain structures to counter the excitotoxic circuitopathy. This review aims to compare results described in peer-reviewed publications describing DBS and MRgFUS in Parkinsonism in terms of improvement in symptoms and side effects. This study was carried out by searching prominent computerized biomedical databases (PubMed, Web of Science, Cochrane, and EMBASE) to assess and compare the safety and efficacy of MRgFUS and DBS procedures done for the treatment of PD. Most of the published results for each of the two operations are comparable, in tremor and Unified Parkinson's Disease Rating Scale scores, though minimal superiority is shown in the DBS results. The neurological adverse effects are similar between the two types, including mild-to-moderate transient instances of dysarthria and gait disturbances, which are the most common two adverse events, among others. However, DBS has a more severe or significant adverse event profile that includes hemorrhage and infection. Long-term improvement is observed more with DBS which can sustain improvement for up to 5 years. DBS, therefore, tends to better improve Parkinsonism prognosis at the cost of safety. Postoperative complications are less severe in MRgFUS, which can be a safe, efficient alternative procedure for medication-refractory Parkinsonism.

A standardized accelerometry method for characterizing tremor: Application and validation in an ageing population with postural and action tremor.

BackgroundOrdinal scales based on qualitative observation are the mainstay in the clinical assessment of tremor, but are limited by inter-rater reliability, measurement precision, range, and ceiling effects. Quantitative tremor evaluation is well-developed in research, but clinical application has lagged, in part due to cumbersome mathematical application and lack of established standards.ObjectivesTo develop a novel method for evaluating tremor that integrates a standardized clinical exam, wrist-watch accelerometers, and a software framework for data analysis that does not require advanced mathematical or computing skills. The utility of the method was tested in a sequential cohort of patients with predominant postural and action tremor presenting to a specialized surgical clinic with the presumptive diagnosis of Essential Tremor (ET).MethodsWristwatch accelerometry was integrated with a standardized clinical exam. A MATLAB application was developed for automated data analysis and graphical representation of tremor. Measures from the power spectrum of acceleration of tremor in different upper limb postures were derived in 25 consecutive patients. The linear results from accelerometry were correlated with the commonly used non-linear Clinical Rating Scale for Tremor (CRST).ResultsThe acceleration power spectrum was reliably produced in all consecutive patients. Tremor frequency was stable in different postures and across patients. Both total and peak power of acceleration during postural conditions correlated well with the CRST. The standardized clinical examination with integrated accelerometry measures was therefore effective at characterizing tremor in a population with predominant postural and action tremor. The protocol is also illustrated on repeated measures in an ET patient who underwent Magnetic Resonance-Guided Focused Ultrasound thalamotomy.ConclusionQuantitative assessment of tremor as a continuous variable using wristwatch accelerometry is readily applicable as a clinical tool when integrated with a standardized clinical exam and a user-friendly software framework for analysis. The method is validated for patients with predominant postural and action tremor, and can be adopted for characterizing tremor of different etiologies with dissemination in a wide variety of clinical and research contexts in ageing populations.

Comparison of Motor Scores between OFF and ON States in Tremor-Dominant Parkinson's Disease after MRgFUS Treatment.

Objective: To compare the motor function improvements in ON and OFF states in tremor-dominant Parkinson’s disease (TDPD) patients within one year of follow-up after ablation of the unilateral ventral intermediate nucleus of the thalamus (Vim) by magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS). Methods: A total of nine consecutive patients confirmed with TDPD who underwent unilateral Vim ablation by MRgFUS between April 2019 and September 2019 were included. The Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRSIII) and Clinical Rating Scale for Tremor (CRST) were performed in the ON and OFF stages to distinguish the surgical effects from drug therapy effects. The adverse events and adjustment of drug doses were also recorded. Results: The preoperative MDS-UPDRSIII score in OFF and ON states was 55.0 (48.0, 65.5) and 26.0 (17.0, 27.0), while the CRST score was 46.0 (39.5, 53.5) and 20.0 (13.0, 23.5), respectively; the Levodopa equivalent dose was 600 (456, 600) mg/d. At 1 year after operation, the total MDS-UPDRSIII score and CRST score were 40.0 (30.0, 60.5) and 16.0 (10.0, 29.5) in the OFF state, and 21.0 (17.5, 27.0) and 2.0 (1.5, 7.0) in the ON state, respectively. Compared with the preoperative levels, follow-up at the two-time points (three months and one year after operation) showed the total MDS-UPDRSIII score, as well as MDS-UPDRSIII tremor, bradykinesia, and rigidity scores of contralateral limbs all significantly improved in OFF state. However, in the ON state, only the total MDS-UPDRSIII score and tremor score of contralateral limbs significantly improved. The total CRST score and the CRST (A + B) score of contralateral limbs significantly improved at three months and one year after the operation compared with before the operation in both ON and OFF states. The Levodopa equivalent dose at one and three months were not significantly different from the preoperative dose (p > 0.05). No serious adverse responses were observed. Conclusion: Treating TDPD with unilateral Vim ablation by MRgFUS could improve the symptoms of limb tremor and the other core symptoms, such as bradykinesia and rigidity, as well as some non-motor symptoms and the symptoms of ipsilateral limbs.

Changes in the Cerebello-Thalamo-Cortical Network After Magnetic Resonance-Guided Focused Ultrasound Thalamotomy.

Objective: In recent years, transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor (ET). So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in ET patients treated with tcMRgFUS thalamotomy. Methods: Eleven patients diagnosed with ET were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3 Tesla magnetic resonance imaging (3T MRI) including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed before the procedure as well as 1 year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus, and the corticospinal tract in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results: The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p < 0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r = -0.54, p = 0.04; MD: r = 0.57, p = 0.04); RD: r = 0.67, p = 0.036). Further, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r = 0.58; p = 0.062; MD: r = -0.52, p = 0.64; RD: r = -0.61 p = 0.090). Conclusions: Microstructural changes were detected within the CTCT after tcMRgFUS, and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism, and ultimately to improve targeting prospectively. Impact statement The results of this study demonstrate microstructural changes within the cerebello-thalamo-cortical pathways 1 year after MR-guided focused ultrasound thalamotomy. Even more, microstructural changes within the cerebello-thalamo-cortical pathways correlated significantly with clinical outcome. These findings do not only highly emphasize the need of new targeting strategies for MR-guided focused ultrasound thalamotomy but also help to elucidate the treatment mechanism of it.

First use of MRI-guided focused ultrasound to treat patients with essential tremor in Russia

Introduction. Treatment with MRI-guided focused ultrasound (MRgFUS) is a new, non-invasive surgical technique for treating extrapyramidal movement disorders. This article presents the first use of MRgFUS in Russia for treating patients with essential tremor (ET).&#x0D; Materials and methods. Patients (n = 26; 17 men and 9 women) aged 2182 years (median age 46.0 years) and with severe and refractory ET, underwent MRgFUS thalamotomy (ExAblate 4000, Insightec). One side was treated in 22 patients (left thalamus in 18 and right thalamus in 6), both sides were treated concurrently in two patients, and both sides were treated consecutively in two patients. Tremor was assessed using the Clinical Rating Scale for Tremor (CRST). Because international clinical specialists could not visit Russia due to the COVID-19 pandemic, MRgFUS was performed via telehealth on May 5, 2020, in a world first.&#x0D; Results. A satisfactory result was achieved in 25 (96%) out of 26 patients. CRST scores improved by 64.7% on the side of the operation, by 10.2% on the control side, and by 37.5% overall. Intraoperative side effects included headache during sonication (42.3%), vertigo (15.4%), nausea (11.5%), vomiting (7.7%), numbness (3.8%), ataxia (3.8%), and pathological response to cold exposure (3.8%). The symptoms resolved immediately after surgery. Unstable gait was noted in five patients, which completely resolved two weeks after surgery. Median postoperative follow-up duration was 109 days [53; 231], with a maximum of 625 days. No relapses (if the hyperkinesia had completely disappeared) or increased tremor (if reduced after surgery) were observed.&#x0D; Conclusion. The efficacy of MRgFUS for ET was 96%, with no long-term complications. Both bilateral concurrent and bilateral consecutive MRgFUS thalamotomy is possible, but its efficacy and safety should be assessed in a randomized study. In a world first, MRgFUS was successfully implemented using telehealth.

Transcranial high-intensity Magnetic Resonance-guided focused ultrasound (tcMRgFUS) – safety and impacts on tremor severity and quality of life

IntroductionTranscranial high-intensity Magnetic Resonance-guided Focused Ultrasound (tcMRgFUS) is a technique for treatment of severe, medication-refractory Essential Tremor (ET). We summarize 1-year follow-up results focusing on clinical and safety parameters and impacts on quality of life. MethodsA total of 45 patients with severe, medication-refractory ET were treated with tcMRgFUS thalamotomy. 37 patients completed the clinical follow-up of 12 months. Tremor severity, disability and quality of life were measured using the Clinical Rating Scale for Tremor (CRST), surface electromyography, the Quality of Life in Essential Tremor Questionnaire (QUEST) and the Short-Form-36 questionnaire (SF-36). Depressive symptoms and cognitive function were assessed using standardized questionnaires. Electrophysiological measurements were conducted to evaluate possible effects on central motor and sensory pathways. Results1 year after tcMRgFUS the mean tremor improvement on a hand-specific subscore of the CRST was 82%. The QUEST and SF-36 revealed an improvement of mental quality of life, especially in activities of daily living and psychosocial function; depressive symptoms decreased significantly. There was no worsening of cognitive function overt within the self-rating questionnaire; no prolongation of sensory evoked potentials or central motor conduction time occurred. Side effects were mostly classified as mild (78%) and transient (62%). ConclusionsTcMRgFUS for severe tremor has a distinct impact on quality of life and neuropsychological symptoms. Self-assessments of cognitive function revealed stable outcomes 1 year after tcMRgFUS. No prolongation of sensory or motor conduction time were found in neurophysiology measures. Side effects occurred in 78% of treated patients but were mostly transient and mild.

Cutoff values for the best management strategy for magnetic resonance-guided focused ultrasound ablation for essential tremor.

The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor. Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics. Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not. MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network). ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.

Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality

BackgroundSleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET.MethodWe enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted.ResultsGlobal network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (r = −0.354, p =0.027).ConclusionOur findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.

FV 9 Deep Brain Stimulation for targeting tremor and ataxia in SCA 27

Introduction: Spinocerebellar ataxia 27 (SCA 27) is a rare cerebellar ataxia caused by mutations in the FGF14 gene. It is characterised by tremor manifesting in early adulthood and slowly progressive ataxia in later decades. Here, we report the case of a 51 years old male patient who was initially diagnosed with medication-refractory essential tremor and therefore received thalamic deep brain stimulation (DBS). After the patient developed signs of cerebellar ataxia exome sequencing led to the diagnosis of SCA 27. In our clinical practice, we tested stimulation paradigms to target tremor and ataxia inspired by model findings (Anderson et al. 2019) suggesting differential effects of low- and high-frequency stimulation. Methods: The patient was implanted with quadripolar electrodes (model 3389, Medtronic) in the nucleus ventralis intermedius of the thalamus (VIM) with the lowest contact reaching the subthalamic fibre tracts. Initially, stimulation-induced manifestation of cerebellar ataxia was ruled out by a wash-out of DBS for 96 h. Next, we established a high-frequency (180 Hz) programme located at the thalamic contacts achieving best tremor control and a low-frequency (30 Hz) programme located at the lowest contacts to interfere with subthalamic fibre tracts. Electrode placement was verified using Lead-DBS. The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and the Scale of the Assessment and Rating of Ataxia (SARA) were performed for clinical assessment. At baseline, we evaluated the condition without stimulation (StimOFF) vs. 180 Hz vs. subthalamic 30 Hz stimulation. Further follow-up examinations were scheduled after 5 and 10 weeks. In the meantime, the patient activated the 180 Hz programme at daytime and either StimOff or 30 Hz stimulation at night. The investigator and patient were blinded to the night setting of the previous interval. Results: At baseline, tremor severity was attenuated by 180Hz DBS compared to StimOFF (TRS 13 vs. 21). Tremor was also attenuated by 30 Hz stimulation of the subthalamus at 1 mA (TRS: 14) but was gradually entrained with higher stimulation amplitudes up to 7 mA (TRS: 27). Changes of the SARA where mainly driven by the tremor component. During the first interval period, the patient adopted the 30 Hz night stimulation programme with 4 mA. In the follow-up examination tremor in the StimOFF condition (TRS: 12) improved to a TRS of 7 using the 180 Hz programme. Eventually, after the second period during which the patient adopted StimOFF at night, the baseline TRS was higher in the StimOFF condition (TRS: 23) and slightly improved to a TRS of 17 when using 180 Hz stimulation. Conclusions: Here, we report the first case of a patient with SCA 27 successfully treated with VIM-DBS in terms of tremor attenuation. We observed that low-frequency stimulation at night led to a more sustained tremor response by stimulation which may be due to antidromic stimulation of cerebellar-thalamic fibre tracts in the subthalamic area.

P 57 Markerless, video-based kinematic Tremor Analysis: machine vision in movement disorders

Introduction: Clinimetrics of movement disorders relies on scales such as the Fahn-Tolosa-Marin Tremor Rating Scale for Essential Tremor (ET). However, these rating scales are prone to rater bias. Quantitative measurements of tremor kinematics, which are proxy measures of clinical outcome, can be achieved with gold standard tremor analyses using reflective markers and several special cameras. Due to their resource-intensiveness, broad availability is lacking. We therefore asked whether new developments in the field of machine vision can close the gap between granular clinimetrics and simplicity. Patients & Methods: Using the open-source software DeepLabCut (DLC), we tuned a recurrent convolutional neural network (RCNN) to track anatomic landmarks of the upper body by annotating a total of 1.878 frames from 234 videos of 51 ET patients who had undergone deep brain stimulation for ET and 10 healthy subjects. In a retrospective subcohort of 43 patients, tremor amplitudes were derived using the RCNN predictions. We probed the influence of DBS condition on tremor kinematics and expert annotated tremor rating scores (TRS) using repeated measures (rm-)ANOVA and Wilcoxon signed-ranked tests. Then, we assessed correlation of tremor metrics with TRS. To prospectively validate the method, we calculated the correlation of tremor metrics derived from both the video-based RCNN and the marker-based gold standard approach in 7 patients. The videos for validation were not used for training and were unknown to the network. To test for precision, we assessed relative errors and equivalence of both methods using two one sided T-Tests (TOST). Results: The RCNN achieved a mean Euclidean train/test error of 3.56/10.74 pixels corresponding to the average pixel size of a fingertip. In the retrospective analysis, DBS exerted a significant effect on the mean tremor amplitudes (Friedman test: χ2(3)=45.3, p<.001) and TRS (right: W=7.0, p<.001; left: W=37.5, p<.001). RCNN-derived maximum amplitudes correlated strongly with TRS (right: rs=.789, p<.001; left: rs=.640, p<.001). In the prospective analysis, mean amplitudes derived from both methods were strongly correlated (DBS off: rs=.982, p<.001; DBS on: rs=.824, p<.001). Relative errors of RCNN-derived mean amplitudes from goldstandard measurements did not significantly deviate from zero (p>.06). TOST revealed RCNN-derived measurements to be partially (DBS off: upper bound T(13)=0.5, p=.7; lower bound T(13)=3.9, p<.001) and fully (DBS on: T(13)=-15.2, p<.001; T(13)=14.52, p<.001) located within 90% CI equivalence bounds. Conclusion: We demonstrate the utility of video-based markerless tremor analysis using an RCNN for both retrospective and prospective settings. Our method allows sufficiently accurate measurements of tremor characteristics to assess the severity of the disease and to map individual disease progression.

Ventral Intermediate Nucleus of the Thalamus versus Posterior Subthalamic Area: Network Meta-Analysis of DBS Target Site Efficacy for Essential Tremor

Background: Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (Vim) of the thalamus or the posterior subthalamic area (PSA) are effective treatments for essential tremor (ET). However, their relative efficacy is unknown. Objective: Here, we present the first systematic review and network meta-analysis, examining the efficacy of Vim versus PSA DBS for treating medically refractory ET. Methods: We included all primary studies that reported validated Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores pre-/postimplantation or on-/off-stimulation postimplantation, for patients receiving either Vim or PSA DBS. The primary outcome was FTM-TRS score reduction; the secondary outcome was percent reduction in score. We categorized all outcomes as short-term (≤12 months) or long-term (>12 months). Results: For pre-/postimplantation comparisons, 19 and 11 studies met inclusion criteria for short- and long-term follow-ups, respectively. For on-/off-stimulation tremor score comparisons, 8 studies met inclusion criteria for short-term follow-up. Network meta-analysis of pre-/postimplantation tremor scores showed greater tremor reduction with PSA implantation short-term (absolute tremor reduction: PSA: −30.94 [95% confidence interval (CI): −34.93, −26.95]; Vim: −26.26 [95% CI: −33.39, −19.12]; relative tremor reduction: PSA: 63.3% [95% CI: 61.8%–64.8%]; Vim: 57.8% [95% CI: 56.5%–59.0%]). However, there was no difference in efficacy between PSA and Vim DBS when comparing tremor on-versus off-stimulation at short-term follow-up or pre- versus postimplantation tremor reduction long-term. Conclusion: Our systematic review highlighted both heterogeneity in scoring systems used and lack of transparency in reporting total scores, limiting direct comparison across studies. We found a modestly superior efficacy with PSA stimulation in the short term, but no difference in tremor reduction long-term.

Deep Brain Stimulation for Arm Tremor: A Randomized Trial Comparing Two Targets.

ObjectiveDeep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) effectively suppresses arm tremor. Uncontrolled studies suggest the posterior subthalamic area (PSA) may be superior. We compared the intra‐individual efficacy of VIM‐ versus PSA‐DBS on tremor suppression and arm function.MethodsWe performed a randomized, double‐blind, crossover trial at Oslo University Hospital in patients (18–80 years) with isolated or combined action tremor affecting at least one arm. Four‐contact DBS leads were implanted (bi‐ or unilaterally) with a trajectory to cover the VIM (upper two contacts) and PSA (lower two contacts). Patients were randomized (1:1 ratio) post‐surgery to: Group 1, VIM‐stimulation months 0–3 (period 1), then PSA‐stimulation months 4–6 (period 2); Group 2, PSA‐stimulation first, then VIM‐stimulation. Primary endpoint was the difference in improvement from baseline to the end of the VIM‐ versus PSA‐period in the sum of the dominant arm tremor scores of the Fahn‐Tolosa‐Marin Tremor Rating Scale (FTMTRS), items 5/6 + 10−14.ResultsForty‐five patients were randomized to Group 1 (n = 23) or 2 (n = 22). In the primary endpoint per‐protocol analysis (mixed model, n = 40), mean difference in the sum FTMTRS score improvement for the dominant arm was −2.65 points (95% CI −4.33 to −0.97; p = 0.002). The difference in favour of PSA stimulation was highly significant in period 2, but not period 1.InterpretationOur randomized trial demonstrated that PSA stimulation provided superior tremor suppression compared with VIM stimulation. A period effect reducing tremor for up to three months in both groups was most likely attributed to a post‐surgery stun effect. ANN NEUROL 2022;91:585–601