Tremor Rating Research Articles

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.

P 23 The overlap of lesions placed by MRIgFUS with the cerebellothalamic tract does not adequately explain symptom control in ET

Background: The thalamic ventral intermediate (Vim) nucleus is part of a network that appears to be disrupted in essential tremor (ET) and is the most relevant target of functional neurosurgery to alleviate ET symptoms. As the most important afferent of the VIM, the cerebellothalamic tract (CTT) transmits information from cerebellar nuclei. Disruption of this tract - in the past via subthalatomies and in the present via deep brain stimulation is considered the best option of tremor treatment, partly because of the high anatomical density of CTT fibers before entering the VIM, and partly because of the greater distance to sensory thalamic nuclei. Recently, initial pilot studies have also documented transcranial MRI-guided high-intensity focused ultrasound (MRIgFUS) as an effective treatment modality. Unilateral MRIgFUS lesioning was highly efficacious in reducing contralateral hand tremor in ET with mild and transient adverse effects. However, targeting of MRIgFUS has so far been based on MRI imaging without dedicated evidence of the underlying connectome. Here, we test a method for quantitative analysis of the involved fiber tracts and test whether the measured clinical effect correlates with overlap of the set lesion with individual fiber tracts, such as CTT. Materials and Methods: We revisited pre- and post-procedural MRIs of 6 ET patients (Øage 70,7 (± 8,5) years , Ø Tremor rating (TR) (pre): 43,8 (± 9,8)) who underwent unilateral ablation of the CTT by MRIgFUS. The images, obtained 48 hours (48H) and 3-6 months (3M+) after the procedure, were used to create 3D-models of the lesions which were localized within MNI-space with the pre-procedural MRI and atlas registration using Suretune®. The models were subsequently used to calculate interferences with fiber tracts. A linear model was employed to assess the correlation between the quantitative interference and improvement of the clinical score at two timepoints after the procedure (48H, n=6: TR: 16,7 (±5,5) ; 3M+, n= 5: TR: 19,2 (±7,2)). Results: The lesions volume differed between the 48H (Ø 281.78mm3(±77.77), n=6) and 3M+(Ø 53.82mm3(±22), n=5) conditions (p<0.01). After 48H primarily the CTT (Ø72,4 % (±34)) but also the M1 (Ø36,05 % (±43)) interfered, while after 3M+ the overlap reduced tremendously for the CTT (Ø1% (±1,6), p=0.017) and slightly for the M1(Ø26,7% (±28,4), p=0.67). Preliminary results could not show a correlation between the observed clinical improvement with the interference of the lesions with a specific tract. Discussion: Interestingly, there is no clear correlation between clinical outcome and the overlap between the lesion placed by MRIgFUS and the fibers of the CTT. This might indicate that the observed clinical effect would have to be explained only partially by the targeted CTT but also by other fiber tracts. The data set was too small for a meaningful multivariate regression analysis, but pooling data sets from different centers may mean a solution to this problem in the future.

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.

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.

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

Patients' self-assessment of essential tremor severity by a validated scale: A useful tool in telemedicine?

IntroductionThere are some validated rating scales to assess severity of Essential tremor (ET), the most common cause of action tremor. Clinical evaluation through telematic consultations has been expanding in the last decade. Patients' self-assessment of tremor severity at home could constitute a useful tool in telemedicine. This paper aims to assess intrarater and interrater reliability of ET severity using Fahn-Tolosa Marin Tremor Rating Scale (FTMTRS) for patients' and neurologists' ratings. Material and methodsPatients were instructed on how to perform and rate the FTMTRS tasks. Supervised by neurologists, each patient performed one FTMTRS self-assessment at the hospital, which was rated in a blinded way by two neurologists, and six more self-assessments at home afterwards. Postural, intention and specific-tasks tremor were rated. A cumulative linked mixed model was used to assess intrarater and interrater reliability. ResultsA total of 161 self-assessments from 19 patients were analyzed. Intrarater reliability of patients' self-ratings at home showed ICCs between 0.843 and 0.962. Interrater ICCs of neurologists' ratings were also excellent for all tremor types (0.903–0.987). Concordance between neurologists' and patients' assessments showed ICCs ranging from 0.407 to 0.824, with the higher agreement for writing/drawing-related tremor (0.824; CI 95% 0.634–0.989). ConclusionsThe rating of ET severity from FTMTRS self-assessments performed by well-trained patients at home could be a suitable clinical measure to assess tremor in non-face-to-face medical consultations. The assessment of tremor during specific tasks could be the most efficient measure for the patient self-assessment at home. These results could be useful in telemedicine.

Quantifying the impact of upper limb tremor on the quality of life of people with multiple sclerosis: a comparison between the QUEST and MSIS-29 scales

BackgroundUpper limb tremor is common in people with multiple sclerosis (pwMS) and can affect day to day function, impacting on their tremor related quality of life (tremor-QOL). The Quality of Life in Essential Tremor Questionnaire (QUEST) is a tremor-QOL scale, however it has not been validated for use in pwMS. This is in contrast to the Multiple Sclerosis Impact Scale (MSIS-29), a MS health related QOL (MS-QOL) scale validated in pwMS. The aim of this study was to quantify tremor-QOL in pwMS using both the QUEST and MSIS-29 and establish the convergent validity of the QUEST scale with the MSIS-29. MethodsData were derived from an existing registered clinical trial studying the efficacy of Botox (onabotulinumtoxinA) compared to placebo in pwMS-related upper limb tremor (ACTRN12617000379314). We determined MS-related disability (Expanded Disability status scale score (EDSS)), tremor severity (Bain and Findley Clinical Tremor Rating Scale (Bain)), cerebellar function (Scale for the Assessment and rating of Ataxia (SARA)), and upper limb manual dexterity (9 Hole Peg Test (9-HPT)). The QUEST and MSIS-29 were used to quantify tremor-QOL and MS-QOL respectively. Convergent validity was investigated by examining the correlation between QUEST and MSIS-29, and the pattern of correlation of the two scales compared to the EDSS, SARA, BAIN and 9-HPT. ResultsOur cohort of 57 patients (16 male; 41 female), mean age of 47.6, had moderate MS-related disability with median EDSS score of 5 (IQR = 3.5). Median Bain score was 8, indicating mild tremor severity, which corresponded to mild to moderately poor tremor-QOL given mean Quest Summary Index (QSI) of 45.7. QSI correlated to tremor severity as measured by Bain total score (rs(55) = 0.339, p < 0.01), manual dexterity as measured by 9-HPT (rs(55) = 0.304, p < 0.05), and MS disease activity measured by EDSS (rs(55) = 0.347, p < 0.01). MSIS-29 also showed correlations to EDSS, and 9-HPT, but did not correlate to Bain total score. There was a strong relationship between QSI and MSIS-29 in pwMS (r(55) = 0.709, p < 0.01). ConclusionIn this cross-sectional study, we found that both the MS-QOL and tremor-QOL of pwMS with upper limb tremor was reduced. We were also the first to demonstrate that tremor-QOL in pwMS with upper limb tremor can be measured using the QUEST, which may be better suited for use in pwMS affected by arm-tremor than the MSIS-29. There is a lack of literature to specifically address tremor-QOL in pwMS, and more research is warranted.

Volcanic tremor associated with the Surtsey eruption of 1963–1967

The formation of the island of Surtsey over 3.5 years, remains one of the best-documented volcanic, island-forming eruptions to date. The basaltic submarine volcanic activity was detected on November 14, 1963, where ocean depth was 130 m prior to the eruption at the southern end of the Vestmannaeyjar archipelago. The eruptions occurred in several phases involving explosive and effusive activity, including the initial submarine phase on November 12–13, 1963. Separate phases of subaerial volcanic activity occurred during November 14, 1963–January 1964, January–April 1964, April 1964–May 1965, May–October 1965, December 1965–August 1966, and August 1966–June 1967. Seismic data quality from this period is inferior compared to that of modern monitoring systems. Four permanent seismic stations were operated in Iceland at the time, whereof only two, located at 115 and 140 km distance, had the sensitivity to record tremor from Surtsey. Nevertheless, the scanned analog seismograms (http://seismis.hi.is/) show that the eruptive activity was accompanied by considerable seismic activity, both earthquakes, and volcanic tremor. Earthquakes were primarily associated with changes in vent location. Both spasmodic and harmonic tremor was identified, both with low (&lt;3 Hz) and higher (3–5 Hz) characteristic frequencies. The results indicate a complicated relationship between tremor and magma flow rate or style of activity. During the explosive eruption, the highest magma flow rates occurred in the first 10–20 days, a period with little observed tremor. The highest tremor is observed in December 1963–March 1964, after the discharge rates had dropped substantially, and on a timescale of hours-to-days, no clear relationship between tremor and eruption style is observed. The same applies to the effusive activity, where no seismic tremor was observed during most of the effusive eruption of Surtungur, despite the fact that magma flow rates were ~3 times higher than during later phases where some tremor was observed. Keywords: Submarine volcanism, eruption precursors, volcanic tremor, precursory tremor, continuous uprush eruptions

Age and Sex Affect Essential Tremor (ET) Plus: Clinical Heterogeneity in ET Based on the National Survey in China.

The new term essential tremor (ET) plus was proposed in the 2018 tremor consensus criteria. The National Survey of Essential Tremor Plus in China, a large multicenter registry study, aimed to evaluate the clinical features of pure ET and ET plus and explore possible factors related to ET plus. All patients with ET underwent neurological examination and neuropsychological assessment at 17 clinical sites. The diagnosis was made according to the 2018 consensus criteria. Clinicodemographic characteristics were analyzed. A total of 1160 patients were included, including 546 patients with pure ET and 614 patients with ET plus. The proportion of females was significantly higher in the ET plus than that in the pure ET (P = 0.001). The age at onset (AAO) of pure ET showed a bimodal distribution, with peaks in the 2nd and 5th decades. However, the AAO of the ET plus group demonstrated a skewed distribution, with a single peak in the 6th decade. Female sex (OR=1.645, P<0.001), older age (OR=1.023, P<0.001), lower educational level (OR=0.934, P<0.001), head tremor (OR=1.457, P<0.001), and higher the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS)-II scores (OR=1.134, P<0.001) were significantly associated with ET plus. Old age and female sex may contribute to ET plus development. Pure ET showed a bimodal distribution for AAO, whereas ET plus showed a unimodal distribution. It remains unclear whether pure ET and ET plus are merely different stages of a single disease or represent distinct disease entities.

Loss of long-term benefit from VIM-DBS in essential tremor: Asecondary analysis of repeated measurements.

AimsDeep brain stimulation (DBS) in the ventral intermediate nucleus (Vim‐DBS) is the preferred surgical therapy for essential tremor (ET). Tolerance and disease progression are considered to be the two main reasons underlying the loss of long‐term efficacy of Vim‐DBS. This study aimed to explore whether Vim‐DBS shows long‐term loss of efficacy and to evaluate the reasons for this diminished efficacy from different aspects.MethodsIn a repeated‐measures meta‐analysis of 533 patients from 18 studies, Vim‐DBS efficacy was evaluated at ≤6 months, 7–12 months, 1–3 years, and ≥4 years. The primary outcomes were the score changes in different components of the Fahn‐Tolosa‐Marin Tremor Rating Scale (TRS; total score, motor score, hand‐function score, and activities of daily living [ADL] score). Secondary outcomes were the long‐term predictive factors.ResultsThe TRS total, motor, and ADL scores showed significant deterioration with disease progression (p = 0.002, p = 0.047, and p < 0.001, respectively), while the TRS total (p < 0.001), hand‐function (p = 0.036), and ADL (p = 0.004) scores indicated a significant long‐term reduction in DBS efficacy, although the motor subscore indicated no loss of efficacy. Hand‐function (p < 0.001) and ADL (p = 0.028) scores indicated DBS tolerance, while the TRS total and motor scores did not. Stimulation frequency and preoperative score were predictive factors for long‐term results.ConclusionThis study provides level 3a evidence that long‐term Vim‐DBS is effective in controlling motor symptoms without waning benefits. The efficacy reduction for hand function was caused by DBS tolerance, while that for ADL was caused by DBS tolerance and disease progression. More attention should be given to actual functional recovery rather than changes in motor scores in patients with ET.

Computerised analysis of writing and drawing by essential tremor phenotype

We investigated whether computerised analysis of writing and drawing could discriminate essential tremor (ET) phenotypes according to the 2018 Consensus Statement on the Classification of Tremors. The Consensus scheme emphasises...

Response to Thalamic Ventralis Intermedius Nucleus Deep Brain Stimulation in Essential Tremor vs. Essential Tremor-Plus.

Introduction: Essential tremor (ET) is a tremor syndrome characterized by bilateral, upper limb action tremor. Essential tremor-plus (ET-plus) describes ET patients with additional neurologic signs. It is unknown whether there is a difference in response to treatment with ventralis intermedius nucleus deep brain stimulation (VIM DBS) in patients with ET and ET-plus. Due to potential variability in underlying etiology in ET-plus, there is a concern that ET-plus patients may have worse outcomes. The aim of this study was to identify whether patients with ET-plus have worse tremor outcomes after VIM DBS than patients with ET.Methods: This is a retrospective chart and video review evaluating VIM DBS outcomes by comparing changes from baseline in the Fahn-Tolosa-Marin Tremor Rating Scale Part B (FTM-B) for the treated limb between patients with ET and ET-plus at follow-up examinations. Patients were re-classified as having ET or ET-plus using pre-operative examination videos by two independent movement disorders neurologists blinded to patient characteristics. As a secondary outcome, we evaluated for correlations and potential predictors of treatment response.Results: Twenty-six patients were included: 13 with ET, 13 with ET-plus. There were no significant differences in the change in FTM-B scores between the ET and ET-plus patients at each follow-up examination. None of the included patients developed new symptoms compatible with dystonia, parkinsonism or gait disturbances.Conclusions: Patients with ET-plus had tremor improvement from VIM DBS, with no differences when compared to those with ET, without emergence of postoperative neurological issues. Patients with ET-plus should still be considered good candidates for VIM DBS for treatment of tremor.

Prospective analysis of gross and fine electrode position and motor manifestations after STN-DBS and their correlation with electrode position.

Deep brain stimulation (DBS) has been proven to be a safe, reversible, cost-effective procedure for treatment of Parkinson's disease. Final electrode position remains a significant factor determining the outcomes of subthalamic nucleus DBS (STN-DBS). This study aims to analyze the final lead position in three-dimensional plane and its effect on gross and fine motor outcomes in cases of advanced Parkinson's disease operated for STN-DBS. Patients who underwent bilateral STN-DBS were prospectively followed for improvement in gross motor outcomes at 6 months. Improvement in dysgraphia was analyzed by Fahn-Tolosa-Marin Tremor Rating Scale Part B Score. Postoperative outcomes were correlated with final electrode position. A total of 64 Patients (128 leads) were analyzed. Patients who were less than 65 years of age at time of surgery had more significant reduction in UPDRS III (P=0.02). Cases with deviation of left x less than 3 mm had significant reduction in UPDRS III (P=0.05) and speech sub-scores (P=0.05). Deviation less than 2 mm in left x was associated with reduction in gait sub-scores (P=0.04). Optimal placement of right y electrode was associated with reduction in UPDRS III (P=0.02). Significant reduction in Fahn-Tolosa-Marin Tremor Rating Scale Part B Score was noted after DBS (P=0.001). Subthalamic nucleus DBS thus results in significantly improved functional outcome particularly in patients with age less than 65 years. Accurate final electrode position is associated with maximum clinical benefit and improvement in dysgraphia.

Safety and Outcomes of Dentate Nucleus Deep Brain Stimulation for Cerebellar Ataxia.

Cerebellar symptoms remain orphan of treatment options despite being prevalent and incapacitating. Investigate whether dentate nucleus deep brain stimulation (DN DBS) is safe and leads to improvements in cerebellar symptoms when compared to sham stimulation. This randomized double-blind crossover pilot trial enrolled five patients with spinocerebellar ataxia type 3 or post-lesion ataxia. Active or sham phases were randomly performed three months apart. The primary outcome was ataxia improvement as measured by the Scale for the Assessment and Rating of Ataxia (SARA) after the active compared to the sham period. Secondary outcome measures included safety and tolerability, the Fahn-Tolosa-Marin Tremor Rating Scale (FTMRS), quality of life measurements, and patients' global impression of change. The effects on ataxia were numerically better in four out of five patients after active versus sham stimulation. The composite SARA score did not change after comparing active to sham stimulation (8.6 ± 3.6 versus 10.1 ± 4.1; p = 0.223). The FTMRS showed significant improvement after active stimulation versus sham (18.0 ± 17.2 versus 22.2 ± 19.5; p = 0.039) as did patients' global impression of change (p = 0.038). The quality of life was not modified by stimulation (p = 0.337). DN DBS was well tolerated without serious adverse events. One patient had the electrode repositioned. DN DBS is a safe and well tolerated procedure that is effective in alleviating cerebellar tremor. In this small cohort of ataxic patients, DN DBS did not achieve statistical significance for ataxia improvement.

Complex Migration of Tremor Near Cholame, CA, Resolved by Seismic Array Analysis

AbstractTectonic tremor observed along the Cholame and Parkfield sections of the San Andreas Fault has previously been associated with transient slip beneath the seismogenic zone. To study tremor and associated Low Frequency Earthquakes (LFEs), we deployed three dense near‐fault seismic arrays for a period of 3 months in 2018. In early August 2018, the arrays recorded a strong 4‐day‐long deep transient that nucleated in Cholame and propagated toward the northwest. The initiation area is characterized by tremor that persists throughout the transient, while adjacent fault portions located to the northwest host more intermittent tremor. From the rate and location of tremor and LFEs, we infer a deep slip transient, whose along‐strike propagation velocity is ∼8 km/day. Secondary tremor fronts are observed to travel ahead of the main slow slip front at speeds that are times faster. These rapid migrations propagate in slow slip events (SSE) slip‐parallel direction, and are sometimes observed to back‐propagate into previously ruptured segments. High‐resolution images of secondary fronts obtained by using near‐fault borehole stations indicate the active tremor band takes the shape of a narrow strain pulse that is bounded from above by the lower edge of the seismogenic zone. We estimate the stress drops associated with the secondary slip fronts are of the order of a few kPa. Frequency‐dependent analysis suggests the tremor signal is coherent at frequencies as high as 16 Hz, and that the spatial distribution of high‐ and low‐frequency tremor radiators is sometimes complementary.

COMPARISON OF TREMOR RELATED ADVERSE DRUG REACTION BETWEEN INTRAVENOUS AMINOPHYLLINE AND NEBULIZED SALBUTAMOL FOR ASTHMA EXACERBATION TREATMENT

The Department of Health estimates that asthma including 10 major causes of morbidity and mortality in the hospital. Asthma is a chronic respiratory disease that is becoming a serious health problem in many countries around the world. Drugs used in the treatment of asthma exacerbations is salbutamol and aminophylline. Drugs such as salbutamol and aminophylline can cause ADR (Adverse Drug Reaction) in the form of tremor with a sign involuntary shaking part of the hand. This research was conducted at the RSAL Dr. Oepomo to sample Aminofilin and in hospitals Seowandi to sample Salbutamol. The method used was quasi experimental. This study was conducted to compare the incidence of tremor in both asthma drug that is often used for the treatment of asthma such as Salbutamol and Aminofilin. The results of this study indicate there are differences in the incidence rate of ADR-related tremor between salbutamol and Aminofilin. Knowing the difference in incidence rate of tremor between aminophylline and salbutamol can assist in the selection of treatment which safer to avoid the effects of tremors that can occur from the use of of drugs asthma exacerbations.

Comparative connectivity correlates of dystonic and essential tremor deep brain stimulation

The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

Disrupted brain gray matter networks in drug-naïve participants with essential tremor.

To use structural magnetic resonance imaging and graph theory approaches to investigate the topological organization of the brain morphological network based on gray matter in essential tremor, and its potential relation to disease severity. In this prospective study conducted from November 2018 to November 2019, 36 participants with essential tremor and 37 matched healthy controls underwent magnetic resonance imaging. Brain networks based on the morphological similarity of gray matter across regions were analyzed using graph theory. Nonparametric permutation testing was used to assess group differences in topological metrics. Support vector machine was applied to the gray matter morphological matrices to classify participants with essential tremor vs. healthy controls. Compared with healthy controls, participants with essential tremor showed increased global efficiency (p < 0.01) and decreased path length (p < 0.01); abnormal nodal properties in frontal, parietal, and cerebellar lobes; and disconnectivity in cerebello-thalamo-cortical network. The abnormal brain nodal centralities (left superior cerebellum gyrus; right caudate nucleus) correlated with clinical measures, both motor (Fahn-Tolosa-Marìn tremor rating, p = 0.017, r = - 0.41) and nonmotor (Hamilton depression scale, p = 0.040, r = - 0.36; Hamilton anxiety scale, p = 0.008, r = - 0.436). Gray matter morphological matrices classified individuals with high accuracy of 80.0%. Participants with essential tremor showed randomization in global properties and dysconnectivity in the cerebello-thalamo-cortical network. Participants with essential tremor could be distinguished from healthy controls by gray matter morphological matrices.

No evidence of iron deposition in essential tremor: a susceptibility-weighted imaging study

To evaluate the role of iron deposition in subcortical nuclei of patients with essential tremor (ET). Twenty-three patients with ET underwent a standardized 3T-MRI protocol. We specifically assessed iron deposition using susceptibility-weighted angiography (SWAN) images in seven specific regions of interest (ROIs): the thalamus, putamen, globus pallidus, caudate nucleus, substantia nigra, red nucleus, and dentate nucleus. Tremor in ET patients was clinically assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). ET patient data were compared with data obtained from 23 Parkinson's disease (PD) patients and 14 healthy subjects (HS). No differences in iron deposition in the seven ROIs were found between ET patients and HS. Conversely, PD patients showed increased iron deposition in the substantia nigra in comparison with both ET patients and HS. Our results indicate the absence of iron deposition in subcortical nuclei of ET patients, which is generally considered a marker of neurodegeneration.