University of GroningenThe Relevance of Intraoperative Clinical and Accelerometric Measurements for ThalamotomyOutcomeSmid, Annemarie; Oterdoom, D L Marinus; Pauwels, Rik W J; Tamasi, Katalin; Elting, JanWillem J; Absalom, Anthony R; van Laar, Teus; van Dijk, J Marc C; Drost, GeaPublished in:Journal of Clinical MedicineDOI:10.3390/jcm12185887IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2023Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Smid, A., Oterdoom, D. L. M., Pauwels, R. W. J., Tamasi, K., Elting, J. W. J., Absalom, A. R., van Laar, T.,van Dijk, J. M. C., & Drost, G. (2023). The Relevance of Intraoperative Clinical and AccelerometricMeasurements for Thalamotomy Outcome. 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For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Citation: Smid, A.; Oterdoom,D.L.M.; Pauwels, R.W.J.; Tamasi, K.;Elting, J.W.J.; Absalom, A.R.; vanLaar, T.; van Dijk, J.M.C.; Drost, G.The Relevance of IntraoperativeClinical and AccelerometricMeasurements for ThalamotomyOutcome. J. Clin. Med. 2023, 12, 5887.https://doi.org/10.3390/jcm12185887Academic Editor: Morgan BroggiReceived: 23 June 2023Revised: 30 August 2023Accepted: 8 September 2023Published: 10 September 2023Copyright: © 2023 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Journal ofClinical MedicineArticleThe Relevance of Intraoperative Clinical and AccelerometricMeasurements for Thalamotomy OutcomeAnnemarie Smid 1,* , D. L. Marinus Oterdoom 1, Rik W. J. Pauwels 1 , Katalin Tamasi 1,2 , Jan Willem J. Elting 3,Anthony R. Absalom 4, Teus van Laar 3, J. Marc C. van Dijk 1 and Gea Drost 1,31 Department of Neurosurgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1,9713 GZ Groningen, The Netherlands; d.l.m.oterdoom@umcg.nl (D.L.M.O.); r.w.j.pauwels@umcg.nl (R.W.J.P.);k.tamasi@umcg.nl (K.T.); j.m.c.van.dijk@umcg.nl (J.M.C.v.D.); g.drost@umcg.nl (G.D.)2 Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1,9713 GZ Groningen, The Netherlands3 Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1,9713 GZ Groningen, The Netherlands; j.w.j.elting@umcg.nl (J.W.J.E.); t.van.laar@umcg.nl (T.v.L.)4 Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1,9713 GZ Groningen, The Netherlands; a.r.absalom@umcg.nl* Correspondence: a.smid01@umcg.nlAbstract: Thalamotomy alleviates medication-refractory tremors in patients with movement disor-ders such as Parkinson’s Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However,limited data are available on tremor intensity during different thalamotomy stages. Also, the predic-tive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, weaimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered be-tween January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patientswith PD (n = 13), ET (n = 8), and HT (n = 3). MDS-UPDRS scores and tri-axial accelerometry datawere obtained during rest, postural, and intention tremor tests. Measurements were performed intra-operatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) duringcoagulation, (4) directly after coagulation, and (5) 4–6 months post-surgery. Accelerometric data wererecorded continuously during the coagulation process. Outcome measures included MDS-UPDRStremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area underthe curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1–2), duringcoagulation (3), post-coagulation effect (1–4), and postoperative effect (1–5). Following insertion andcoagulation, tremor intensity improved significantly compared to baseline (p < 0.001). The insertioneffect clearly correlated with the postoperative effect (ρ = 0.863, p < 0.001). Both tremor amplitudeand AUCP declined gradually during coagulation. Peak frequency did not change significantlyintraoperatively. In conclusion, the study data show that both the intraoperative insertion effect andthe post-coagulation effect are good predictors for thalamotomy outcomes.Keywords: thalamotomy; VIM; insertion effect; microlesion effect; intraoperative neurophysiologicalneuromonitoring; MDS-UPDRS; accelerometry; Parkinson’s Disease; essential tremor; Holmes tremor1. IntroductionThe most common movement disorders with disabling tremors are Parkinson’s Disease(PD), Essential tremor (ET), and Holmes tremor (HT) [1,2]. Tremor in PD is generallyobserved in the extremities at rest (4–7 Hz) [3–6]. ET is a monosymptomatic disease,predominated by bilateral action tremor (4–7 Hz) [2,6,7]. Patients with HT suffer fromrest, postural, and intention tremors due to low-frequency proximal and distal musclecontraction (<5 Hz) [2,8].If disabling tremor cannot be suppressed with medication, then a thalamotomy involv-ing a radiofrequency (RF) ablation of the thalamic ventral intermediate nucleus (VIM) is anJ. Clin. Med. 2023, 12, 5887. https://doi.org/10.3390/jcm12185887 https://www.mdpi.com/journal/jcmJ. Clin. Med. 2023, 12, 5887 2 of 14effective treatment option [9–21]. Thalamotomies are generally performed unilaterally sincebilateral procedures have increased the risk of speech and balance impairments [22,23].Surgery is generally performed under local anesthesia in awake conditions in order to judgethe intraoperative tremor improvement and to minimize side effects. The ever-changingenvironment in which newer methods of lesioning or ablating the VIM are performed,such as Magnetic Resonance Guided Focused Ultrasound (MRgFUS) [24,25] and GammaKnife thalamotomy [26], also poses a challenge for the intraoperative monitoring of tremor.Although there are few thalamotomy-related reports on the relevance of intraoperativetremor measurements, the effects measured intraoperatively are hypothesized to predictthalamotomy outcomes.After the insertion of an RF-lesioning probe in the target area and before heating orstimulation of the tip, immediate tremor alleviation can be observed during surgery: theinsertion effect or microlesion effect [27]. In this article, the term ‘insertion effect’ (IE) ismaintained. It is postulated that the occurrence of the IE indicates the accurate placementof the RF-lesioning probe within the VIM, underlining the need to adequately monitortremor intensity intraoperatively [27,28]. As soon as a permanent lesion is inflicted, tremorsuppression is immediately observed [21]. This is called the ‘post-coagulation effect’ (PCE).There are several methods to monitor tremor intensity [27–29]. Clinical scales (e.g.,Movement Disorder Society Unified PD Rating Scale [MDS-UPDRS]) are often used to as-sess surgical results [30,31]. However, although the MDS-UPDRS is a standardized scoringsystem, the results can vary based on the experience of the rater [31–35]. Sensor-basedmeasurements, like tri-axial accelerometry, allow for objective and continuous quantifica-tion of tremor intensity [34,36,37]. Several studies have demonstrated that accelerometrycan complement clinical assessment during neurosurgery, aiding clinicians in uniformlyassessing tremors [38–41].Although studies have focused on clinical results and side effects of thalamotomy,there is little data available on the neurophysiological aspects [21,22,42]. Also, there isno consensus on how the IE and PCE relate to the postoperative effect (PE) of unilateralthalamotomy. Therefore, this study focuses on accelerometry measurements during all sur-gical stages of RF-thalamotomy, including tremor severity in the postoperative phase. Thenovelty of this work lies in the quantification of tremor intensity during all surgical stagesof thalamotomy based on clinical assessment and accelerometry. The aim of this studyis to quantify the clinical changes in tremor during the different stages of thalamotomyusing both the MDS-UPDRS and tri-axial accelerometry. Secondly, we aim to investigatethe relationship between intraoperative findings and clinical outcomes. Lastly, our aimis to investigate the correlation between clinical assessments and accelerometric outcomemeasures.2. Materials and MethodsThis observational study was conducted at the neurosurgical department of the Uni-versity Medical Center Groningen (UMCG), the Netherlands. The local medical ethicsreview committee judged that this study does not fall within the remit of the Dutch ‘Re-search involving human subjects Act’. This study was performed in compliance with theHelsinki Declaration for research on human beings. All participants provided writteninformed consent for the use of their data.2.1. Study ParticipantsData were gathered between January 2020 and June 2023 from consecutive patientswith an indication for unilateral RF-thalamotomy. In patients with PD, diagnosis wasestablished according to the UK Brain Bank criteria [43]. For those with ET and HT, thediagnosis was made by movement disorders neurologists and confirmed with a video-assisted surface-EMG accelerometric tremor registration [6]. The treatment plan wasdiscussed and established in a multidisciplinary meeting before inclusion of this study forall participants.J. Clin. Med. 2023, 12, 5887 3 of 142.2. Surgical ProcedureParticipants were withheld tremor-suppressing medication for at least 12 h prior to thethalamotomy. Anesthesia administration, frame placement, and target identification wereperformed as described by Lange and Kremer et al. [28]. In short, the VIM was accessed bypenetrating the brain using a bipolar RF probe (TCB013 RF TC Brain Electrode 2 × 2 mm,Inomed Medizintechnik GmbH, Emmendingen, Germany) via a cranial burr hole. Priorto inserting the bipolar RF electrode, baseline tremor intensity of the contralateral arm(relative to the hemisphere being treated) was evaluated (see Section 2.4). Directly afterinsertion of the electrode in the target, the same evaluations were performed to assess theIE. When an acceptable position was found, the electrode tip was heated to 90 ◦C for 60 s byan Inomed Neuro N50 lesion generator. Directly after coagulation, the tremor evaluationswere performed once more. Until improvement in tremor was deemed satisfactory, theelectrode was repositioned, and the subsequent steps were repeated.2.3. MaterialsA tri-axial accelerometer (MMA8452Q tri-Axis, Freescale Semiconductor, Inc., Austin,TX, USA) with a sampling rate of 200 Hz and range of ±2 g was used. The sensor wassecured in a custom-built non-conductive plastic case and attached to the proximal phalanxof the contralateral index finger (relative to the treated hemisphere) with an adjustablesilicon strap (Figure 1) [38].J. Clin. Med. 2023, 12, x FOR PEER REVIEW 3 of 14 diagnosis was made by movement disorders neurologists and confirmed with a video-assisted surface-EMG accelerometric tremor registration [6]. The treatment plan was dis-cussed and established in a multidisciplinary meeting before inclusion of this study for all participants. 2.2. Surgical Procedure Participants were withheld tremor-suppressing medication for at least 12 h prior to the thalamotomy. Anesthesia administration, frame placement, and target identification were performed as described by Lange and Kremer et al. [28]. In short, the VIM was ac-cessed by penetrating the brain using a bipolar RF probe (TCB013 RF TC Brain Electrode 2 × 2 mm, Inomed Medizintechnik GmbH, Emmendingen, Germany) via a cranial burr hole. Prior to inserting the bipolar RF electrode, baseline tremor intensity of the contrala-teral arm (relative to the hemisphere being treated) was evaluated (see Section 2.4). Di-rectly after insertion of the electrode in the target, the same evaluations were performed to assess the IE. When an acceptable position was found, the electrode tip was heated to 90 °C for 60 s by an Inomed Neuro N50 lesion generator. Directly after coagulation, the tremor evaluations were performed once more. Until improvement in tremor was deemed satisfactory, the electrode was repositioned, and the subsequent steps were repeated. 2.3. Materials A tri-axial accelerometer (MMA8452Q tri-Axis, Freescale Semiconductor, Inc., Aus-tin, TX, USA) with a sampling rate of 200 Hz and range of ±2 g was used. The sensor was secured in a custom-built non-conductive plastic case and attached to the proximal phal-anx of the contralateral index finger (relative to the treated hemisphere) with an adjustable silicon strap (Figure 1) [38]. Figure 1. Accelerometer positioned on the left index finger. Accelerometric data were recorded in LabVIEW v. 2017 (National Instruments, Aus-tin, TX, USA) [38]. Signal analysis was performed in MATLAB v. 2022b (MathWorks, Na-tick, MA, USA). Statistical analysis was performed in IBM SPSS statistics v. 26 (Interna-tional Business Machines Corporation, Armonk, NY, USA). MDS-UPDRS items 3.15–3.17 were used for assessment of participants [44]. 2.4. Measurements All measurements were performed with the participant awake and in supine position [38]. Tremor severity was assessed with three tremor tests: postural (arm stretched out), intention (finger-to-nose maneuver), and at rest. Accelerometric data were recorded dur-ing these tremor tests, while a movement disorders neurologist simultaneously assessed MDS-UPDRS scores. Measurements were performed (1) before lesioning probe insertion, (2) after lesion-ing probe insertion, (3) during coagulation, (4) after coagulation, and (5) at 4–6 months follow-up (Figure 2). The three tremor tests were performed in steps 1, 2, 4, and 5. Steps 1 to 4 were repeated until improvement in tremor was deemed satisfactory. Accelerometric data were recorded continuously during coagulation (Figure 2). Figure 1. Accelerometer positioned on the left index finger.Ac elerometric data were recorded in LabVIEW v. 2017 (National Instruments, Austin,TX, USA) [38]. Signal analysis was performed in MATL B v. 2022b (MathWorks, Natick,MA, US ). Statistic l analysis was performed in IBM SPSS statistics v. 26 (InternationalBusiness Machines Corporation, Armonk, NY, USA). MDS-UP RS items 3.15–3.17 wereus d for assessment of partici nts [44].2.4. easurementsAll measurements were performed with the participant awake and in supine posi-tion [38]. Tremor severity was assessed with three tremor tests: postural (arm stretchedout), intention (finger-to-nose maneuver), and at rest. Accelerometric data were recordedduring these tremor tests, while a movement disorders neurologist simultaneously assessedMDS-UPDRS scores.Measurements were performed (1) before lesioning probe insertion, (2) after lesioningprobe insertion, (3) during coagulation, (4) after coagulation, and (5) at 4–6 months follow-up (Figure 2). The three tremor tests were performed in steps 1, 2, 4, and 5. Steps 1 to 4were repeated until improvement in tremor was deemed satisfactory. Accelerometric datawere recorded continuously during coagulation (Figure 2).For each outcome measure, the sum of the values of the three tremor tests at thatmeasurement moment was used for analysis. The three different effects that were calculatedfor each type of summed outcome measure (SOM) were defined as follows. The insertioneffect (IE) was defined as the SOM just prior to insertion of the lesioning probe (1) minusthe SOM immediately post-insertion (2). The post-coagulation effect (PCE) was defined asthe pre-insertion SOM (1) minus the SOM directly after coagulation (4). The postoperativeeffect (PE) was defined as the pre-insertion SOM (1) minus the SOM at follow-up (5), seeFigure 2.J. Clin. Med. 2023, 12, 5887 4 of 14J. lin. ed. 2023, 12, x FOR PEER REVIEW 4 of 14 Figure 2. Tremor severity was measured at five time points to assess the IE, the PCE, and the PE: (1) pre-insertion and (2) post-insertion of the lesioning probe, (3) during coagulation, (4) directly after coagulation during surgery, and (5) 4–6 months follow-up. For each outcome measure, the sum of the values of the three tremor tests at that measurement moment was used for analysis. The three different effects that were calcu-lated for each type of summed outcome measure (SOM) were defined as follows. The in-sertion effect (IE) was defined as the SOM just prior to insertion of the lesioning probe (1) minus the SOM immediately post-insertion (2). The post-coagulation effect (PCE) was de-fined as the pre-insertion SOM (1) minus the SOM directly after coagulation (4). The post-operative effect (PE) was defined as the pre-insertion SOM (1) minus the SOM at follow-up (5), see Figure 2. It is hypothesized that both IE and PCE correlate with PE for both MDS-UPDRS and accelerometric SOM. Second, it is hypothesized that MDS-UPDRS tremor scores correlate with accelerometric outcome measures. 2.5. Accelerometric Measures Accelerometric data pre-processing was performed as described previously [38]. To assess postural, intention, and rest tremor, three outcome measures were calculated from the accelerometry data per respective test: (1) dominant frequency; (2) maximal ampli-tude; (3) area under the curve of power within the tremor frequency band (AUCP) [38]. The tremor frequency band was defined as 4–7 Hz for PD and ET and 2–5 Hz for HT, based on the frequencies found during preoperative recordings. To determine the power of the acceleration norm (cm/s2), the periodogram power spectral density (PSD) estimate was calculated [45]. Via trapezoidal numerical integration, the AUCP in the 2–5 Hz and 4–7 Hz frequency bands was calculated from this periodo-gram. The dominant or peak frequency was defined as the frequency with the highest power value. For the calculation of the mean tremor amplitude, the mean of all peaks in the absolute amplitude vector was determined. This mean was multiplied by two in order to calculate the mean tremor amplitude [38]. 2.6. Statistical Analysis The main outcome measures used for the statistical analyses were MDS-UPDRS sum score, summed amplitude, and summed AUCP. Based on visual inspection of the histo-grams of the outcome variables, nonparametric tests were used for all analyses. The alpha level was determined to be 5%. Wilcoxon signed-rank test was used to analyze the IE, PCE, and PE (Figure 2). Spearman’s rank correlation coefficient (Spearman’s ρ) was used to calculate the strength of association between the IE and PE and between the PCE and PE. Spearman’s ρ was also applied to calculate the correlation between the MDS-UPDRS scores and accelerometric amplitude and between the MDS-UPDRS scores and AUCP of each tremor test. Figure 2. Tremor severity was measured at five time points to assess the IE, the PCE, and the PE:(1) pre-insertion and (2) post-insertion of the lesioning probe, (3) during coagulation, (4) directly aftercoagulation during surgery, and (5) 4–6 months follow-up.It is hypothesized that both IE and PCE correlate with PE for both MDS-UPDRS andaccelero etric SOM. Second, it is hypothesized that MDS-UPDRS tremor scores correlatewith accelerometric outcome measures.2.5. Accel rometr c MeasuresAccelerometric data pre-processing was performed as described previously [38]. Toassess postural, intention, and rest tremor, three outcome measures were calculated fromthe accel rometry data per respective test: (1) dominant frequency; (2) maximal amplitude;(3) area under the curve of p wer within the t emor frequency band (AUCP) [38]. Thetremo frequency band was defined as 4–7 Hz for PD and ET and 2–5 Hz for HT, based onthe frequencies found during pr operative recordings.To determine the power of the acceleration norm (cm/s2), the periodogram powerspectral density (PSD) estimate was calculated [45]. Via trapezoidal numerical integration,the AUCP in the 2–5 Hz and 4–7 Hz frequency bands was calculated from this periodogram.The dominant or peak frequency was defined as the frequency with the highest powervalue. For the calculation of the mean tremor amplitude, the mean of all peaks in theabsolute amplitude vector was determined. This mean was multiplied by two in order tocalculate the mean tremor amplitude [38].2.6. Statistical AnalysisThe main outcome measures used for the statistical analyses were MDS-UPDRSsum score, summed amplitude, and summed AUCP. Based on visual inspection of thehistograms of the outcome variables, nonparametric tests were used for all analyses. Thealpha level was determined to be 5%. Wilcoxon signed-rank test was used to analyze the IE,PCE, and PE (Figure 2). Spearman’s rank correlation coefficient (Spearman’s ρ) was usedto calculate the strength of association between the IE and PE and between the PCE andPE. Spearman’s ρ was also applied to calculate the correlation between the MDS-UPDRSscores and accelerometric amplitude and between the MDS-UPDRS scores and AUCP ofeach tremor test.3. R sultsA group of 22 patients (15 men, 7 women; age (69.9 ± 11.3 years) were included. Datawere gathered from 13 surgeries in 13 patients with PD, eight surgeries in seven patientswith ET (one re-operation after 11 months), and three surgeries in two patients with HT(one re-operation after 14 months). In 17 out of 24 procedures, a single coagulation attemptwas sufficient for a satisfactory effect on tremor severity (Table 1).J. Clin. Med. 2023, 12, 5887 5 of 14Table 1. Demographics.Demographic Total Population PD ET HTGender (percentage) Male: 15 (68.2%)Female: 7 (31.8%)Male: 9 (69.2%)Female: 4 (30.8%)Male: 4 (57.1%)Female: 3 (42.9%)Male: 2 (100.0%)Female: 0 (0.0%)Mean (SD) age (years) 69.9 (11.3) 70.8 (8.4) 76.0 (5.2) 49.0 (10.4)Mean (SD) disease duration (years) 8.4 (5.0) 7.9 (4.1) 11.4 (6.4) 4.4 (0.7)Mean (SD) follow-up (months) 5.4 (1.1) 5.5 (0.9) 4.9 (1.1) 6.4 (1.2)Treated hemisphere(percentage)Right: 10 (45.5%)Left: 12 (54.5%)Right: 5 (38.5%)Left: 8 (61.5%)Right: 3 (42.9%)Left: 4 (57.1%)Right: 2 (100.0%)Left: 0 (0.0%)Number of coagulationattempts (SD) 1.4 (0.7) 1.1 (0.3) 1.6 (0.9) 2.3 (0.6)3.1. Quantification of Changes in Tremor during Defined Thalamotomy StagesPost-insertion MDS-UPDRS sum scores were significantly lower when compared topre-insertion: 5 (1–11) vs. 2 (0–8) [p < 0.001]. The pre-insertion MDS-UPDRS sum scoreswere significantly higher than the post-coagulation sum scores, from 5 (1–11) to 0 (0–6)[p < 0.001]. A significant decrease was found in the postoperative MDS-UPDRS sum scorescompared to the pre-insertion sum scores, from 5 (1–11) to 0 (0–6) [p < 0.001] (Figure 3a).J. Clin. Med. 2023, 12, x FOR PEER REVIEW 5 of 14 3. Results A group of 22 patients (15 men, 7 women; age (69.9 ± 11.3 years) were included. Data were gathered from 13 surgeries in 13 patients with PD, eight surgeries in seven patients with ET (one re-operation after 11 months), and three surgeries in two patients with HT (one re-operation after 14 months). In 17 out of 24 procedures, a single coagulation attempt was sufficient for a satisfactory effect on tremor severity (Table 1). Table 1. Demographics. Demographic Total Population PD ET HT Gender (percentage) Male: 15 (68.2%) Female: 7 (31.8%) Male: 9 (69.2%) Female: 4 (30.8%) Male: 4 (57.1%) Female: 3 (42.9%) Male: 2 (100.0%) Female: 0 (0.0%) Mean (SD) age (years) 69.9 (11.3) 70.8 (8.4) 76.0 (5.2) 49.0 (10.4) Mean (SD) disease duration (years) 8.4 (5.0) 7.9 (4.1) 11.4 (6.4) 4.4 (0.7) Mean (S ) follow-up (months) 5.4 (1.1) 5.5 (0.9) 4.9 (1.1) 6.4 (1.2) Treated hemisphere (percentage) Right: 10 (45.5%) Left: 12 (54.5%) Right: 5 (38.5%) Left: 8 (61.5%) Right: 3 (42.9%) Left: 4 (57.1%) Right: 2 (1 .0%) Left: 0 (0.0%) Number of coagulation attempts (SD) 1.4 (0.7) 1.1 (0.3) 1.6 (0.9) 2.3 (0.6) 3.1. Quantification of Changes in Tremor during Defined Thalamotomy Stages Post-insertion MDS-UPDRS sum scores were significantly lower when compared to pre-insertion: 5 (1–11) vs. 2 (0–8) [p < 0.001]. The pre-insertion MDS-UPDRS sum scores were significantly higher than the post-coagulation sum scores, from 5 (1–11) to 0 (0–6) [p < 0.001]. A significant decrease was found in the postoperative MDS-UPDRS sum scores compared to the pre-insertion sum scores, from 5 (1–11) to 0 (0–6) [p < 0.001] (Figure 3a). The summed tremor amplitude at pre-ins tion was significantly higher when com-ared to p st-insertion: 5 (0–61) cm vs. 1 (0–58) cm [p < 0.001]. The pre-insertion summ d amplitude w s also significantly higher than at post-coagulation, fr 5 (0–6 ) cm to 0 (0–30) cm [p < 0.001]. A significant decrease was found in th postoperative summed ampli-tude compared to pre-insertion, from 5 (0–61) cm to (0–9) cm [p < 0.0 1] (Figure 3b). (a) (b) Figure 3. Boxplots with median and interquartile range for (a) MDS-UPDRS sum scores and (b) summed tremor amplitude at pre-insertion, post-insertion, post-coagulation, and follow-up for all participants. The MDS-UPDRS sum score data per measurement moment in Figure 3a are given separately for each patient group in Figure 4a. Figure 3. Boxplots with median and interquartile range for (a) MDS-UPDRS sum scores and(b) summed tremor amplitude at pre-insertion, post-insertion, post-coagulation, and follow-upfor all participants.The summed tremor amplitude at pre-insertion was significantly higher when com-pared to post-insertion: 5 (0–61) cm vs. 1 (0–58) cm [p < 0.001]. The pre-insertion summedamplitude was also significantly higher than at post-coagulation, from 5 (0–61) cm to 0(0–30) cm [p < 0.001]. A significant decrease was found in the postoperative summedamplitude compared to pre-insertion, from 5 (0–61) cm to 1 (0–9) cm [p < 0.001] (Figure 3b).The MDS-UPDRS sum score data per measurement moment in Figure 3a are givenseparately for each patient group in Figure 4a.For the PD group, post-insertion MDS-UPDRS sum scores were significantly lowerwhen compared to pre-insertion: 6 (1–10) vs. 0 (0–2) [p < 0.001]. The pre-insertion MDS-UPDRS sum scores of the PD group were significantly higher than the post-coagulationsum scores, from 6 (1–10) to 0 (0–1) [p < 0.001]. A significant decrease was found in thepostoperative MDS-UPDRS sum scores compared to the pre-insertion sum scores of the PDgroup, from 6 (1–10) to 0 (0–3) [p < 0.001] (Figure 4a).J. Clin. Med. 2023, 12, 5887 6 of 14J. Clin. Med. 2023, 12, x FOR PEER REVIEW 6 of 14 (a) (b) Figure 4. Boxplots with median and interquartile range for (a) MDS-UPDRS sum scores and (b) summed tremor amplitude at pre-insertion, post-insertion, post-coagulation, and follow-up for each group (PD group in black, ET group in red, HT group in blue). For the PD group, post-insertion MDS-UPDRS sum scores were significantly lower when compared to pre-insertion: 6 (1–10) vs. 0 (0–2) [p < 0.001]. The pre-insertion MDS-UPDRS sum scores of the PD group were significantly higher than the post-coagulation sum scores, from 6 (1–10) to 0 (0–1) [p < 0.001]. A significant decrease was found in the postoperative MDS-UPDRS sum scores compared to the pre-insertion sum scores of the PD group, from 6 (1–10) to 0 (0–3) [p < 0.001] (Figure 4a). In the ET group, MDS-UPDRS sum scores significantly decreased from 3 (2–11) pre-insertion to 2 (0–7) post-insertion [p = 0.018]. The pre-insertion MDS-UPDRS sum scores of the ET group were also significantly higher than the post-coagulation sum scores, from 3 (2–11) to 0 (0–4) [p = 0.003]. The pre-insertion summed amplitude of the ET group de-creased from 3 (2–11) to 0 (0–6) postoperatively, although this decrease was not significant [p = 0.387] (Figure 4a). The post-insertion MDS-UPDRS sum scores of the HT group were lower than at pre-insertion: 6 (2–11) vs. 6 (2–8) [p = 0.109]. The pre-insertion MDS-UPDRS sum scores de-creased significantly from 6 (2–11) to 4 (0–6) [p = 0.024] post-coagulation. The decrease in MDS-UPDRS sum scores at pre-insertion from 6 (2–11) to 5 (5–6) [p = 0.288] postopera-tively was not significant (Figure 4a). In Figure 4b, the summed tremor amplitude data per measurement moment of Figure 3b are given separately for each patient group. The summed tremor amplitude of the PD group at pre-insertion was significantly higher when compared to post-insertion: 6 (0–28) cm vs. 0 (0–2) cm [p < 0.001]. The pre-insertion summed amplitude was also significantly higher than at post-coagulation, from 6 (0–28) cm to 0 (0–1) cm [p < 0.001]. A significant decrease was found in the postoperative summed amplitude compared to pre-insertion, from 6 (0–28) cm to 0 (0–1) cm [p < 0.001]. Figure 4. Boxplots with median and interquartile range for (a) MDS-UPDRS sum scores and(b) summed tremor amplitude at pre-insertion, post-insertion, post-coagulation, and follow-upfor each group (PD group in black, ET group in red, HT group in blue).In the ET group, MDS-UPDRS sum scores significantly decreased from 3 (2–11) pre-insertion to 2 (0–7) post-insertion [p = 0.018]. The pre-insertion MDS-UPDRS sum scoresof the ET group were also significantly higher than the post-coagulation sum scores,from 3 (2–11) to 0 (0–4) [p = 0.003]. The pre-insertion summed amplitude of the ET groupdecreased from 3 (2–11) to 0 (0–6) postoperatively, although this decrease was not significant[p = 0.387] (Figure 4a).The post-insertion MDS-UPDRS sum scores of the HT group were lower than atpre-insertion: 6 (2–11) vs. 6 (2–8) [p = 0.109]. The pre-insertion MDS-UPDRS sum scoresdecreased significantly from 6 (2–11) to 4 (0–6) [p = 0.024] post-coagulation. The decrease inMDS-UPDRS sum scores at pre-insertion from 6 (2–11) to 5 (5–6) [p = 0.288] postoperativelywas not significant (Figure 4a).In Figure 4b, the summed tremor amplitude data per measurement moment ofFigure 3b are given separately for each patient group.The summed tremor amplitude of the PD group at pre-insertion was significantlyhigher whe compared to post-insertion: 6 (0–28) cm vs. 0 (0–2) cm [p < 0.001]. The pre-insertion summed amplitude was also sig ificantly higher than at post-coagulation, from 6(0–28) cm to 0 (0–1) cm [p < 0.001]. A significant decrease was found in the postoperativesummed amplitude compar o pre-insert on, from 6 (0–28) cm to 0 (0–1) c [p < 0.001].In th ET group, the summed amplitude significantly decreased from 3 (0–33) cmpre-insertion to 1 (0–23) cm post- nserti n [p = 0.002]. The pre-insertion summed amplitudeof t ET group was also significantly higher than the post-coagulation amplitude, from 3(0–33) cm to 1 (0–4) cm [p = 0.002]. The pre-insertion summed amplitude of the ET groupJ. Clin. Med. 2023, 12, 5887 7 of 14decreased from 3 (0–33) cm to 1 (0–5) cm postoperatively, although this decrease was notsignificant [p = 0.209] (Figure 4b).The summed tremor amplitude of the HT group at pre-insertion was higher than atpost-insertion: 11 (1–61) cm vs. 8 (1–58) cm [p = 0.075]. The post-coagulation summedamplitude of the HT group was significantly lower than that at pre-insertion: 11 (1–61)cm vs. 2 (0–30) cm [p = 0.018]. The decrease in summed amplitude from 11 (1–61) cm atpre-insertion to 8 (2–9) cm postoperative was not significant [p = 0.237] (Figure 4b).During CoagulationTremor amplitude and AUCP declined gradually during coagulation in all patients(Figure 5). The amplitudes at t = 10 s were significantly higher compared to t = 60 s, from 2(0–13) cm to 0 (0–6) cm [p < 0.001]. AUCP at t = 60 s decreased significantly compared toAUCP at t = 10 s, from 5182 (cm/s2)2 (55–484,986) to 173 (cm/s2)2 (10–30,474) [p < 0.001].Peak frequency did not change significantly during the coagulation process, from 3 (1–6)Hz to 3 (1–7) Hz [p > 0.05].J. Clin. Med. 2023, 12, x FOR PEER REVIEW 7 of 14 In the ET group, the summed amplitude significantly decreased from 3 (0–33) cm pre-insertion to 1 (0–23) cm post-insertion [p = 0.002]. The pre-insertion summed ampli-tude of the ET group was also significantly higher than the post-coagulation amplitude, from 3 (0–33) cm to 1 (0–4) cm [p = 0.002]. The pre-insertion summed amplitude of the ET group decreased from 3 (0–33) cm to 1 (0–5) cm postoperatively, although this decrease was not significant [p = 0.209] (Figure 4b). The summed tremor amplitude of the HT group at pre-insertion was higher than at post-insertion: 11 (1–61) cm vs. 8 (1–58) cm [p = 0.075]. The post-coagulation summed am-plitude of the HT group was significantly lower than that at pre-insertion: 11 (1–61) cm vs. 2 (0–30) cm [p = 0.018]. The decrease in summed amplitude from 11 (1–61) cm at pre-insertion to 8 (2–9) cm postoperative was not significant [p = 0.237] (Figure 4b). During Coagulation Tremor amplitude and AUCP declined gradually during coagulation in all patients (Figure 5). The a plitudes at t = 10 s were significantly higher compared to t = 60 s, from 2 (0–13) cm to 0 (0–6) cm [p < 0.001]. AUCP at t = 60 s decreased significantly co pared to P at t = 10 s, from 5182 (cm/s2)2 (55–484,986) to 173 (cm/s2)2 (10–30,474) [p < 0.001]. eak freq ency i not change signi cantly ring the coag lation rocess, fro 3 (1–6) z t 3 (1–7) z [p > 0.05]. (a) (b) (c) (d) (e) (f) Figure 5. The mean amplitude per 10 s (a,c,e) and AUCP per 10 s (b,d,f) during the 60-s coagulation process, given for the PD group (a,b), ET group (c,d) and HT group (e,f). Figure 5. The mean amplitude per 10 s (a,c,e) and AUCP per 10 s (b,d,f) during the 60-s coagulationprocess, given for the PD group (a,b), ET group (c,d) and HT group (e,f).J. Clin. Med. 2023, 12, 5887 8 of 14For the PD group, the amplitudes at t = 10 s were significantly higher compared tot = 60 s, from 1 (0–2) cm to 0 (0–0) cm [p < 0.001]. AUCP at t = 60 s decreased significantlycompared to AUCP at t = 10 s in the PD group, from 705 (cm/s2)2 (55–6719) to 51 (cm/s2)2(10–173) [p < 0.001].The amplitudes in the ET group at t = 10 s were significantly higher compared tot = 60 s, from 2 (0–11) cm to 0 (0–4) cm [p < 0.001]. The AUCP of the ET group at t = 60 sdecreased significantly compared to the AUCP at t = 10 s, from 11,382 (cm/s2)2 (329–484,986)to 295 (cm/s2)2 (101–9513) [p < 0.001].For the HT group, the amplitudes at t = 10 s were significantly higher compared tot = 60 s, from 5 (2–13) cm to 0 (0–2) cm [p < 0.001]. AUCP at t = 60 s decreased significantlycompared to AUCP at t = 10 s in the HT group, from 33,360 (cm/s2)2 (867–263,567) to772 (cm/s2)2 (172–5301) [p < 0.001].3.2. Relation between Intraoperative Findings and Clinical OutcomeThe IE was found to be significantly associated with PE for all outcome measures[Spearman’s ρ > 0.690; p < 0.001] (Table 2). This was also the case for a correlation betweenthe PCE and PE [Spearman’s ρ > 0.918; p < 0.001] (Table 3). The MDS-UPDRS sum scoresand summed amplitude of the IE and PE were plotted per patient group and number ofcoagulation attempts in Figure 6. The MDS-UPDRS sum scores and summed amplitudeof the PCE and PE per patient group and number of coagulation attempts are shown inFigure 7.Table 2. Spearman’s correlation between insertion effect and postoperative effect.CoagulationAttempt Outcome Measure Spearman’s ρ R2 95% CI pOnly first attemptsMDS-UPDRS sum scores 0.863 0.745 0.693, 0.942 <0.001Summed AUCP 0.975 0.951 0.940, 0.990 <0.001Summed Amplitude 0.690 0.476 0.377, 0.861 <0.001Only final attemptsMDS-UPDRS sum scores 0.967 0.934 0.920, 0.986 <0.001Summed AUCP 0.898 0.807 0.766, 0.957 <0.001Summed Amplitude 0.783 0.612 0.538, 0.906 <0.001Table 3. Spearman’s correlation between post-coagulation effect and postoperative effect.CoagulationAttempt Outcome Measure Spearman’s ρ R2 95% CI pOnly first attemptsMDS-UPDRS sum scores 0.950 0.903 0.882, 0.980 <0.001Summed AUCP 0.936 0.876 0.849, 0.973 <0.001Summed Amplitude 0.982 0.965 0.957, 0.993 <0.001Only final attemptsMDS-UPDRS sum scores 0.934 0.873 0.846, 0.973 <0.001Summed AUCP 0.955 0.911 0.892, 0.981 <0.001Summed Amplitude 0.918 0.843 0.809, 0.966 <0.001J. Clin. Med. 2023, 12, 5887 9 of 14J. Clin. Med. 2023, 12, x FOR PEER REVIEW 8 of 14 For the PD group, the amplitudes at t = 10 s were significantly higher compared to t = 60 s, from 1 (0–2) cm to 0 (0–0) cm [p < 0.001]. AUCP at t = 60 s decreased significantly compared to AUCP at t = 10 s in the PD group, from 705 (cm/s2)2 (55–6719) to 51 (cm/s2)2 (10–173) [p < 0.001]. The amplitudes in the ET group at t = 10 s were significantly higher compared to t = 60 s, from 2 (0–11) cm to 0 (0–4) cm [p < 0.001]. The AUCP of the ET group at t = 60 s decreased significantly compared to the AUCP at t = 10 s, from 11,382 (cm/s2)2 (329–484,986) to 295 (cm/s2)2 (101–9513) [p < 0.001]. For the HT group, the amplitudes at t = 10 s were significantly higher compared to t = 60 s, from 5 (2–13) cm to 0 (0–2) cm [p < 0.001]. AUCP at t = 60 s decreased significantly compared to AUCP at t = 10 s in the HT group, from 33,360 (cm/s2)2 (867–263,567) to 772 (cm/s2)2 (172–5301) [p < 0.001]. 3.2. Relation between Intraoperative Findings and Clinical Outcome The IE was found to be significantly associated with PE for all outcome measures [Spearman’s ρ > 0.690; p < 0.001] (Table 2). This was also the case for a correlation between the PCE and PE [Spearman’s ρ > 0.918; p < 0.001] (Table 3). The MDS-UPDRS sum scores and summed amplitude of the IE and PE were plotted per patient group and number of coagulation attempts in Figure 6. The MDS-UPDRS sum scores and summed amplitude of the PCE and PE per patient group and number of coagulation attempts are shown in Figure 7. (a) (b) Figure 6. The correlation between insertion effect and postoperative effect for the MDS-UPDRS sum scores (a) and summed tremor amplitude (b), given for each group (PD group in black, ET group in red, and HT group in blue). Figure 6. The correlation between insertion effect and postoperative effect for the MDS-UPDRS sumscores (a) and summed tremor amplitude (b), given for each group (PD group in black, ET group inred, and HT group in blue).J. Clin. Med. 2023, 12, x FOR PEER REVIEW 9 of 14 (a) (b) Figure 7. The correlation between post-coagulation effect and postoperative effect for the MDS-UP-DRS sum scores (a) and summed tremor amplitude (b), given for each group (PD group in black, ET group in red, and HT group in blue). Table 2. Spearman’s correlation between insertion effect and postoperative effect. Coagulation Attempt Outcome Measure Spearman’s ρ R2 95% CI p Only first attempts MDS-UPDRS sum scores 0.863 0.745 0.693, 0.942 <0.001 Summed AUCP 0.975 0.951 0.940, 0.990 <0.001 Summed Amplitude 0.690 0.476 0.377, 0.861 <0.001 Only final attempts MDS-UPDRS sum scores 0.967 0.934 0.920, 0.986 <0.001 Summed AUCP 0.898 0.807 0.766, 0.957 <0.001 Summed Amplitude 0.783 0.612 0.538, 0.906 <0.001 Table 3. Spearman’s correlation between post-coagulation effect and postoperative effect. Coagulation Attempt Outcome Measure Spearman’s ρ R2 95% CI p Only first attempts MDS-UPDRS sum scores 0.950 0.903 0.882, 0.980 <0.001 Summed AUCP 0.936 0.876 0.849, 0.973 <0.001 Summed Amplitude 0.982 0.965 0.957, 0.993 <0.001 Only final attempts MDS-UPDRS sum scores 0.934 0.873 0.846, 0.973 <0.001 Summed AUCP 0.955 0.911 0.892, 0.981 <0.001 Summed Amplitude 0.918 0.843 0.809, 0.966 <0.001 Table 4. Spearman’s correlation between the MDS-UPDRS scores and the accelerometric outcome measures for each type of tremor test. Outcome Measure Tremor Condition Spearman’s ρ R2 95% CI p Mean amplitude Rest tremor 0.706 0.498 0.605, 0.784 <0.001 Postural tremor 0.867 0.751 0.815, 0.905 <0.001 Intention tremor 0.811 0.657 0.740, 0.863 <0.001 All combined 0.815 0.664 0.775, 0.848 <0.001 AUCP Rest tremor 0.714 0.510 0.616, 0.791 <0.001 Postural tremor 0.903 0.815 0.864, 0.931 <0.001 Intention tremor 0.731 0.535 0.638, 0.804 <0.001 All combined 0.812 0.659 0.772, 0.845 <0.001 Figure 7. The correlation between post-coagulation effect and postoperative effect for the MDS-UPDRS sum scores (a) and summed tremor amplitude (b), given for each group (PD group in black,ET group in red, and HT group in blue).3.3. Correlation between Clinical Assessments and Accelerometric Outcome MeasuresThe MDS-UPDRS scores of the individual tremo tests correlated significantly withaccelerometric amplitude [ pearman’ ρ > 0.706; p < 0.001]. These results were also signifi-cant for the correlation between MDS-UPDRS scores and AUCP for the individual tremortests [Spearman’s ρ > 0.714; p < 0.001] (Table 4).J. Clin. Med. 2023, 12, 5887 10 of 14Table 4. Spearman’s correlation between the MDS-UPDRS scores and the accelerometric outcomemeasures for each type of tremor test.Outcome Measure Tremor Condition Spearman’s ρ R2 95% CI pMean amplitudeRest tremor 0.706 0.498 0.605, 0.784 <0.001Postural tremor 0.867 0.751 0.815, 0.905 <0.001Intention tremor 0.811 0.657 0.740, 0.863 <0.001All combined 0.815 0.664 0.775, 0.848 <0.001AUCPRest tremor 0.714 0.510 0.616, 0.791 <0.001Postural tremor 0.903 0.815 0.864, 0.931 <0.001Intention tremor 0.731 0.535 0.638, 0.804 <0.001All combined 0.812 0.659 0.772, 0.845 <0.0014. DiscussionIn this study, accelerometric and clinical tremor assessments were performed duringvarious stages of unilateral RF-thalamotomy in patients with PD, ET, and HT. Postoperativetremor intensity after unilateral thalamotomy was also studied. The aim of this researchwas to quantify changes in tremor intensity during surgery and to evaluate the relationshipbetween intraoperative findings and clinical outcomes.This study shows that tri-axial accelerometry can objectively quantify intraoperativetreatment effects during RF-thalamotomy. Tri-axial accelerometry showed that tremoramplitude and AUCP declined gradually during the coagulation process and that peakfrequency did not change significantly during the surgical procedure. Also, IE and PCEsignificantly correlated with PE at follow-up, as shown in both MDS-UPDRS ratings andaccelerometric assessment. The main contribution of this study is that accelerometricmeasurements can provide standardized and objective input for clinical decision-makingduring thalamotomy. Moreover, accelerometry can be performed in real time during thecoagulation process to show the change in tremor intensity.Both tremor amplitude and AUCP declined gradually during the coagulation process,but peak frequency did not change significantly. These findings suggest that the activity ofthe fundamental tremor generator changes with lesioning, and probably not the generatoritself. Previously, Earhart et al. reported that tremor frequency did not change with changesin Deep Brain Stimulation (DBS) of the VIM [46]. Other studies have shown that neuronalfiring is inhibited during VIM-DBS [47,48], which might explain why tremor amplitudeand not tremor frequency are reduced.The IE and PCE evaluated in this study were consistent with previously reportedfindings [10–12,27,28,38,39,49]. It is generally thought that IE can predict the outcomeof stereotactic surgery [27,28,50,51]. The results of this study suggest that a strong IEpredicts successful tremor suppression postoperatively. Concurrently, these data indicatethat the absence of both the IE and PCE predicts no change in tremor intensity after surgery.Therefore, these results suggest that the IE and PCE should be taken into account duringintraoperative clinical decision-making for the replacement of the lesioning probe.The high correlation between the IE and the PE in this study can be explained bythe use of accelerometry-based outcome measures. For example, a Spearman’s ρ up to0.975 was found in the AUCP outcome measure. Accelerometric measurements allow forcontinuous outcome measures, in contrast to discrete ordinal scales like the MDS-UPDRS.Another explanation for differences in correlation between IE and PE might be that earlierresearch was performed in patients undergoing DBS [27,28,50,51].The strength of the correlations between IE and PE and between PCE and PE differedamongst the three patient groups and the number of coagulation attempts, as seen inFigures 6 and 7. The relationship between IE and PE and between PCE and PE seemed tobe stronger for the PD group, compared to the ET group and HT group, as seen in Figures 6and 7. No conclusions can be based on these findings as this study was not designed orpowered to investigate these differences, and the small sizes of the subgroups precludedfurther testing of the statistical significance of these differences.J. Clin. Med. 2023, 12, 5887 11 of 14The results of this study suggest that RF-thalamotomy is an effective treatment inpatients with unilateral tremors. At the same time, the medical field is evolving with alter-native procedures like MRgFUS [24,25] and Gamma Knife thalamotomy [26]. These newinterventions require an operative setting (e.g., MRI scanner, radioactive environment) thatdoes not allow real-time intraoperative clinical assessment by a neurologist. Accelerometryoffers a solution, providing reliable and objective measures for clinical decision-makingduring surgery [38,39,52]. This is supported by Baek et al., who found that accelerometrycan be used for determining the location and number of MRgFUS targets to achieve optimaltremor reduction [53].Apart from the fact that accelerometry provides rater-independent measurements,standardized accelerometric measures can settle the current uncertainty on the outcome oftremor treatment. Other benefits of this technique are that it is widely available and inexpen-sive (purchase costs 10 USD~30 USD), and analysis is easy and straightforward [37,38,52,54].Also, this low-power technology does not involve disposable parts and has an estimatedlifespan of at least ten years, making it a sustainable measurement method [55,56].LimitationsDue to the surgical setting with restricted freedom of movement for the patient, it wasnot possible to perform a full MDS-UPDRS assessment. Instead, only tremor items thatthe treatment aimed to improve were used for the measurements. Also, the results of theintraoperative measurements could have been influenced by stress, fatigue, or sedativemedication effects during the surgery.Second, all consecutive patients undergoing thalamotomy between January 2020 andJune 2023 were included, even patients in whom multiple lesions were made. This mighthave caused discrepancies in our results, as the IE of the first attempt may have influencedthe effect of the subsequent attempt. For this reason, the outcomes of the first and finalattempts have been reported separately. This provides insight into how both results relateto the clinical outcome.5. ConclusionsThis study shows that tremor amplitude and AUCP both declined gradually duringthe coagulation process and that peak frequency did not change significantly during theprocedures. It was also shown that both the insertion effect and the post-coagulationeffect are good predictors for thalamotomy outcome. The MDS-UPDRS scores of the in-dividual tremor tests correlated significantly with the accelerometric outcome measures.Accelerometric monitoring of tremors allows the objective quantification of these intraop-erative parameters, reducing the dependency on experienced raters for reliable clinicalassessments.Author Contributions: Conceptualization, A.S. and G.D.; methodology, A.S., K.T. and G.D.; software,J.W.J.E.; formal analysis, A.S.; investigation, A.S., R.W.J.P., G.D. and T.v.L.; resources, J.W.J.E. and G.D.;data curation, A.S. and G.D.; writing—original draft preparation, A.S.; writing—review and editing,D.L.M.O., R.W.J.P., K.T., J.W.J.E., A.R.A., T.v.L., J.M.C.v.D. and G.D.; visualization, A.S.; supervision,T.v.L., J.M.C.v.D. and G.D.; project administration, A.S. and G.D. All authors have read and agreed tothe published version of the manuscript.Funding: This research received no external funding.Institutional Review Board Statement: Exemption from the act on research involving human sub-jects was granted by the local medical ethics review committee (METc UMC Groningen). This studywas conducted in compliance with the Helsinki Declaration for research on human beings.Informed Consent Statement: All participants provided written informed consent.Data Availability Statement: The data may be available at a reasonable request.Conflicts of Interest: The authors declare no conflict of interest.J. Clin. Med. 2023, 12, 5887 12 of 14References1. Jankovic, J.; Fahn, S. Physiologic and Pathologic Tremors-Diagnosis, Mechanism, and Management. Ann. Intern. Med. 1980, 93,460–465. [CrossRef]2. Bhatia, K.P.; Bain, P.; Bajaj, N.; Elble, R.J.; Hallett, M.; Louis, E.D.; Raethjen, J.; Stamelou, M.; Testa, C.M.; Deuschl, G. ConsensusStatement on the Classification of Tremors. from the Task Force on Tremor of the International Parkinson and Movement DisorderSociety. Mov. Disord. 2018, 33, 75–87. [CrossRef]3. Jankovic, J. Parkinson’s Disease: Clinical Features and Diagnosis. J. Neurol. Neurosurg. Psychiatry 2008, 79, 368–376. [CrossRef]4. Vaillancourt, D.E.; Newell, K.M. The Dynamics of Resting and Postural Tremor in Parkinson’s Disease. Clin. Neurophysiol. 2000,111, 2046–2056. [CrossRef]5. Kalia, L.; Lang, A.E. Parkinson’s Disease. Lancet 2015, 386, 896–912. [CrossRef]6. van der Stouwe, A.M.M.; Elting, J.W.; van der Hoeven, J.H.; van Laar, T.; Leenders, K.L.; Maurits, N.M.; Tijssen, M.A.J. HowTypical Are ‘Typical’ Tremor Characteristics? Sensitivity and Specificity of Five Tremor Phenomena. Park. Relat. Disord. 2016, 30,23–28. [CrossRef]7. van de Wardt, J.; van der Stouwe, A.M.M.; Dirkx, M.; Elting, J.W.J.; Post, B.; Tijssen, M.A.J.; Helmich, R.C. Systematic ClinicalApproach for Diagnosing Upper Limb Tremor. J. Neurol. Neurosurg. Psychiatry 2020, 91, 822–830. [CrossRef]8. Kim, M.C.; Son, B.C.W.; Miyagi, Y.; Kang, J.K. Vim Thalamotomy for Holmes’ Tremor Secondary to Midbrain Tumour. J. Neurol.Neurosurg. Psychiatry 2002, 73, 453–455. [CrossRef]9. Pauwels, R.W.J.; Oterdoom, D.L.M.; Drost, G.; van Laar, T.; van Dijk, J.M.C. Long-Term Patient-Reported Outcome of Radiofre-quency Thalamotomy for Tremor. Stereotact. Funct. Neurosurg. 2020, 98, 187–192. [CrossRef]10. Jankovic, J.; Cardoso, F.; Grossman, R.G.; Hamilton, W.J. Outcome after Stereotactic Thalamotomy for Parkinsonian, Essential,and Other Types of Tremor. Neurosurgery 1995, 37, 680–687. [CrossRef] [PubMed]11. Fox, M.W.; Ahlskog, J.E.; Kelly, P.J. Stereotactic Ventrolateralis Thalamotomy for Medically Refractory Tremor in Post-LevodopaEra Parkinson’s Disease Patients. J. Neurosurg. 1991, 75, 723–730. [CrossRef]12. Akbostanci, M.C.; Slavin, K.v.; Burchiel, K.J. Stereotactic Ventral Intermedial Thalamotomy for the Treatment of Essential Tremor:Results of a Series of 37 Patients. Stereotact. Funct. Neurosurg. 1999, 72, 174–177. [CrossRef] [PubMed]13. Hassler, R.; Riechert, T. Indikationen Und Lokalisationsmethode Der Gezielten Hiernoperationen. Nervenarzt 1954, 25, 441–447.[PubMed]14. Tripathi, M.; Mehta, S.; Singla, R.; Ahuja, C.K.; Tandalya, N.; Tuleasca, C.; Batish, A.; Mohindra, S.; Agrahari, A.; Kaur, R. VimStereotactic Radiosurgical Thalamotomy for Drug-Resistant Idiopathic Holmes Tremor: A Case Report. Acta Neurochir. 2021, 163,1867–1871. [CrossRef]15. Hopfner, F.; Deuschl, G. Managing Essential Tremor. Neurotherapeutics 2020, 17, 1603–1621. [CrossRef] [PubMed]16. Ferreira, J.J.; Mestre, T.A.; Lyons, K.E.; Benito-León, J.; Tan, E.K.; Abbruzzese, G.; Hallett, M.; Haubenberger, D.; Elble, R.; Deuschl,G. MDS Evidence-Based Review of Treatments for Essential Tremor. Mov. Disord. 2019, 34, 950–958. [CrossRef]17. Martínez-Moreno, N.E.; Sahgal, A.; de Salles, A.; Hayashi, M.; Levivier, M.; Ma, L.; Paddick, I.; Régis, J.; Ryu, S.; Slotman, B.J.;et al. Stereotactic Radiosurgery for Tremor: Systematic Review. J. Neurosurg. 2019, 130, 589–600. [CrossRef]18. Espay, A.J.; Mandybur, G.T.; Revilla, F.J. Surgical Treatment of Movement Disorders. Clin. Geriatr. Med. 2006, 22, 813–825.[CrossRef]19. Shahzadi, S.; Tasker, R.R.; Lozano, A. Thalamotomy for Essential and Cerebellar Tremor. Stereotact. Funct. Neurosurg. 1995, 65,11–17. [CrossRef]20. Schuurman, P.R.; Bosch, D.A.; Bossuyt, P.M.M.; Bonsel, G.J.; van Someren, E.J.W.; de Bie, R.M.A.; Merkus, M.P.; Speelman, J.D. AComparison of Continuous Thalamic Stimulation and Thalamotomy for Suppression of Severe Tremor. N. Engl. J. Med. 2000, 342,461–468. [CrossRef]21. Dallapiazza, R.F.; Lee, D.J.; de Vloo, P.; Fomenko, A.; Hamani, C.; Hodaie, M.; Kalia, S.K.; Fasano, A.; Lozano, A.M. Outcomesfrom Stereotactic Surgery for Essential Tremor. J. Neurol. Neurosurg. Psychiatry 2019, 90, 474–482. [CrossRef] [PubMed]22. Bruce, B.B.; Foote, K.D.; Rosenbek, J.; Sapienza, C.; Romrell, J.; Crucian, G.; Okun, M.S. Aphasia and Thalamotomy: ImportantIssues. Stereotact. Funct. Neurosurg. 2004, 82, 186–190. [CrossRef] [PubMed]23. Alshaikh, J.; Fishman, P.S. Revisiting Bilateral Thalamotomy for Tremor. Clin. Neurol. Neurosurg. 2017, 158, 103–107. [CrossRef]24. Pooja, N.A.; Pahuja, S.K.; Veer, K. Significance of MRI Guided Focused Ultrasound Thalamotomy for Parkinson’s Disease: AReview. Curr. Med. Imaging Former. Curr. Med. Imaging Rev. 2021, 17, 714–719. [CrossRef]25. Elias, W.J.; Lipsman, N.; Ondo, W.G.; Ghanouni, P.; Kim, Y.G.; Lee, W.; Schwartz, M.; Hynynen, K.; Lozano, A.M.; Shah, B.B.; et al.A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N. Engl. J. Med. 2016, 375, 730–739. [CrossRef][PubMed]26. Ohye, C.; Shibazaki, T.; Sato, S. Gamma Knife Thalamotomy for Movement Disorders: Evaluation of the Thalamic Lesion andClinical Results. J. Neurosurg. 2005, 102, 234–240. [CrossRef] [PubMed]27. Tykocki, T.; Nauman, P.; Koziara, H.; Mandat, T. Microlesion Effect as a Predictor of the Effectiveness of Subthalamic Deep BrainStimulation for Parkinson’s Disease. Stereotact. Funct. Neurosurg. 2013, 91, 12–17. [CrossRef]28. Lange, S.F.; Kremer, N.I.; van Laar, T.; Lange, F.; Steendam-Oldekamp, T.E.; Oterdoom, D.L.M.; Absalom, A.R.; van Dijk, J.M.C.;Drost, G. The Intraoperative Microlesion Effect Positively Correlates with the Short-Term Clinical Effect of Deep Brain Stimulationin Parkinson’s Disease. Neuromodulation 2021, 26, 459–465. [CrossRef]J. Clin. Med. 2023, 12, 5887 13 of 1429. Cersosimo, M.G.; Raina, G.B.; Benarroch, E.E.; Piedimonte, F.; Alemán, G.G.; Micheli, F.E. Micro Lesion Effect of the GlobusPallidus Internus and Outcome with Deep Brain Stimulation in Patients with Parkinson’s Disease and Dystonia. Mov. Disord.2009, 24, 1488–1493. [CrossRef]30. Goetz, C.G.; Tilley, B.C.; Shaftman, S.R.; Stebbins, G.T.; Fahn, S.; Martinez-Martin, P.; Poewe, W.; Sampaio, C.; Stern, M.B.; Dodel,R.; et al. Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): ScalePresentation and Clinimetric Testing Results. Mov. Disord. 2008, 23, 2129–2170. [CrossRef]31. Kremer, N.I.; Smid, A.; Lange, S.F.; Mateus Marçal, I.; Tamasi, K.; Van Dijk, J.M.C.; Van Laar, T.; Drost, G. Supine MDS-UPDRS-IIIAssessment: An Explorative Study. J. Clin. Med. 2023, 12, 3108. [CrossRef]32. Post, B.; Merkus, M.P.; de Bie, R.M.A.; de Haan, R.J.; Speelman, J.D. Unified Parkinson’s Disease Rating Scale Motor Examination:Are Ratings of Nurses, Residents in Neurology, and Movement Disorders Specialists Interchangeable? Mov. Disord. 2005, 20,1577–1584. [CrossRef] [PubMed]33. Evers, L.J.W.; Krijthe, J.H.; Meinders, M.J.; Bloem, B.R.; Heskes, T.M. Measuring Parkinson’s Disease over Time: The Real-Worldwithin-Subject Reliability of the MDS-UPDRS. Mov. Disord. 2019, 34, 1480–1487. [CrossRef]34. Lukšys, D.; Jonaitis, G.; Griškevičius, J. Quantitative Analysis of Parkinsonian Tremor in a Clinical Setting Using InertialMeasurement Units. Park. Dis. 2018, 2018, 1683831. [CrossRef]35. Rodríguez-Molinero, A.; Samà, A.; Pérez-López, C.; Rodríguez-Martín, D.; Alcaine, S.; Mestre, B.; Quispe, P.; Giuliani, B.;Vainstein, G.; Browne, P.; et al. Analysis of Correlation between an Accelerometer-Based Algorithm for Detecting ParkinsonianGait and UPDRS Subscales. Front. Neurol. 2017, 8, 431. [CrossRef]36. Espay, A.J.; Bonato, P.; Nahab, F.B.; Maetzler, W.; Dean, J.M.; Klucken, J.; Eskofier, B.M.; Merola, A.; Horak, F.; Lang, A.E.; et al.Technology in Parkinson’s Disease: Challenges and Opportunities. Mov. Disord. 2016, 31, 1272–1282. [CrossRef] [PubMed]37. Lieber, B.; Taylor, B.E.S.; Appelboom, G.; Mckhann, G.; Connolly, E.S. Motion Sensors to Assess and Monitor Medical and SurgicalManagement of Parkinson Disease. World Neurosurg. 2015, 84, 561–566. [CrossRef]38. Smid, A.; Elting, J.W.J.; van Dijk, J.M.C.; Otten, B.; Oterdoom, D.L.M.; Tamasi, K.; Heida, T.; van Laar, T.; Drost, G. IntraoperativeQuantification of MDS-UPDRS Tremor Measurements Using 3D Accelerometry: A Pilot Study. J. Clin. Med. 2022, 11, 2275.[CrossRef]39. Shah, A.; Coste, J.; Lemaire, J.J.; Taub, E.; Schüpbach, W.M.M.; Pollo, C.; Schkommodau, E.; Guzman, R.; Hemm-Ode, S.Intraoperative Acceleration Measurements to Quantify Improvement in Tremor during Deep Brain Stimulation Surgery. Med.Biol. Eng. Comput. 2017, 55, 845–858. [CrossRef] [PubMed]40. Papapetropoulos, S.; Gallo, B.v.; Guevara, A.; Singer, C.; Mitsi, G.; Lyssikatos, C.; Jagid, J.R. Objective Tremor Registration duringDBS Surgery for Essential Tremor. Clin. Neurol. Neurosurg. 2009, 111, 376–379. [CrossRef]41. Smid, A.; Elting, J.W.J.; van Dijk, J.M.C.; Otten, E.; Oterdoom, D.; Tamasi, K.; Heida, T.; van Laar, T.; Drost, G. Intraoperativequantification of MDS-UPDRS tremor measurements using 3D accelerometry. Mov. Disord. 2023, 13 (Suppl. S1), 2275. [CrossRef]42. Iacono, R.P.; Henderson, J.M.; Lonser, R.R. Combined Stereotactic Thalamotomy and Posteroventral Pallidotomy for Parkinson’sDisease. J. Image Guid. Surg. 1995, 1, 133–140. [CrossRef]43. Hughes, A.J.; Daniel, S.E.; Kilford, L.; Lees, A.J. Accuracy of Clinical Diagnosis of Idiopathic Parkinson’s Disease: A Clinico-Pathological Study of 100 Cases. J. Neurol. Neurosurg. Psychiatry 1992, 55, 181–184. [CrossRef] [PubMed]44. Goetz, C.G.; Fahn, S.; Martinez-Martin, P.; Poewe, W.; Sampaio, C.; Stebbins, G.T.; Stern, M.B.; Tilley, B.C.; Dodel, R.; Dubois, B.;et al. The MDS-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale. Available online: www.movementdisorders.org (accessed on 21 June 2022).45. Salarian, A.; Russmann, H.; Wider, C.; Burkhard, P.R.; Vingerhoets, F.J.G.; Aminian, K. Quantification of Tremor and Bradykinesiain Parkinson’s Disease Using a Novel Ambulatory Monitoring System. IEEE Trans. Biomed. Eng. 2007, 54, 313–322. [CrossRef]46. Earhart, G.M.; Hong, M.; Tabbal, S.D.; Perlmutter, J.S. Effects of Thalamic Stimulation Frequency on Intention and PosturalTremor. Exp. Neurol. 2007, 208, 257–263. [CrossRef]47. Milosevic, L.; Kalia, S.K.; Hodaie, M.; Lozano, A.M.; Popovic, M.R.; Hutchison, W.D. Physiological Mechanisms of ThalamicVentral Intermediate Nucleus Stimulation for Tremor Suppression. Brain 2018, 141, 2142–2155. [CrossRef]48. Elble, R.J. Mechanisms of Deep Brain Stimulation for Essential Tremor. Brain 2014, 137, 4–6. [CrossRef]49. Nagaseki, Y.; Shibazaki, T.; Hirai, T.; Kawashima, Y.; Wada, H.; Ohye, C. Long-Term Follow-up Results of Selective VIM-Thalamotomy. J. Neurosurg. 1986, 65, 296–302. [CrossRef]50. Maltête, D.; Derrey, S.; Chastan, N.; Debono, B.; Gérardin, E.; Fréger, P.; Mihout, B.; Menard, J.F.; Hannequin, D. Microsubthalam-otomy: An Immediate Predictor of Long-Term Subthalamic Stimulation Efficacy in Parkinson Disease. Mov. Disord. 2008, 23,1047–1050. [CrossRef]51. Mann, J.M.; Foote, K.D.; Garvan, C.W.; Fernandez, H.H.; Jacobson IV, C.E.; Rodriguez, R.L.; Haq, I.U.; Siddiqui, M.S.; Malaty, I.A.;Morishita, T.; et al. Brain Penetration Effects of Microelectrodes and DBS Leads in STN or GPi. J. Neurol. Neurosurg. Psychiatry2009, 80, 794–797. [CrossRef]52. Smid, A.; Pauwels, R.W.J.; Elting, J.W.J.; Everlo, C.S.J.; van Dijk, J.M.C.; Oterdoom, D.L.M.; van Laar, T.; Tamasi, K.; van der Stouwe,A.M.M.; Drost, G. A Novel Accelerometry Method to Perioperatively Quantify Essential Tremor Based on Fahn–Tolosa–MarinCriteria. J. Clin. Med. 2023, 12, 4235. [CrossRef]J. Clin. Med. 2023, 12, 5887 14 of 1453. Baek, H.; Chen, J.; Lockwood, D.; Obusez, E.; Poturalski, M.; Nagel, S.J.; Jones, S.E. Feasibility of Magnetic Resonance–CompatibleAccelerometers to Monitor Tremor Fluctuations during Magnetic Resonance–Guided Focused Ultrasound Thalamotomy: Techni-cal Note. Oper. Neurosurg. 2023, 24, 641–650. [CrossRef] [PubMed]54. Sievänen, H.; Kujala, U.M. Accelerometry-Simple, but Challenging. Scand. J. Med. Sci. Sports 2017, 27, 574–578. [CrossRef][PubMed]55. Bâzu, M.; Gălăţeanu, L.; Ilian, V.; Loicq, J.; Habraken, S.; Collette, J.-P. Quantitative Accelerated Life Testing of MEMS Accelerome-ters. Sensors 2007, 7, 2846–2859. [CrossRef] [PubMed]56. Semiconductor, F. Data Sheet: Technical Data Xtrinsic MMA8452Q 3-Axis, 12-Bit/8-Bit Digital Accelerometer, 2010.Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individualauthor(s) and contributor(s) and not of MDPI and/or the editor(s). 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