Tremor Severity Research Articles

Tremor detection Transformer: An automatic symptom assessment framework based on refined whole-body pose estimation

Essential tremor (ET) is a prevalent neurological disorder that necessitates using objective and non-invasive methods for assessing symptom severity. Traditional visual assessments are often limited by subjectivity, while other wearable sensors or visual markers may result in unnatural movements. This study presents a novel contact-free visual-based pipeline for ET assessment that integrates refined whole-body pose estimation with Transformer-based tremor detection to quantify tremor severity at a fine-grained level. The proposed pose estimation method combines the Transformer with HRNet, effectively capturing spatial-temporal complementary information from multiple body parts and enabling highly accurate tremor detection. The Transformer-based tremor detection is well-suited for modeling long-range dependencies and sequential tremor data extracted by the pose estimation model, further improving the performance of our proposed method. Our study collected data from 61 patients with ET, achieving an average accuracy, recall, and F1 score of 95.6%/95.6%, 89.2%/95.0%, and 83.0%/92.4% for classifying ET severity both during rest and postural tasks, respectively. Our proposed method outperforms the temporal convolutional network baseline, increasing F1 scores by 21.17% and 14.22% for rest and postural tasks, respectively. This high level of accuracy makes our method highly useful for clinical applications such as remote monitoring, diagnosis, and treatment evaluation. Our proposed technique has many advantages over traditional ET assessment techniques, including non-invasiveness, contact-free operation, and not requiring any wearable sensors or visual markers. Moreover, our method can be applied to other movement disorders requiring objective measurements of symptom severity. In summary, our contact-free visual-based pipeline for ET assessment represents a significant improvement over traditional ET assessment techniques, and our quantification results demonstrate its potential for use in clinical settings.

Regional white matter hyperintensity volume in Parkinson's disease and associations with the motor signs.

To determine whether white matter hyperintensity (WMH) volumes in specific regions are associated with Parkinson's disease (PD) compared to non-PD controls, and to assess their impact on motor signs through cross-sectional and longitudinal analyses. A total of 50 PD participants and 47 age- and gender-matched controls were enrolled. All PD participants were followed up for at least 2 years. To detect regions of greater WMH in the PD, the WMH volume of each region was compared with the corresponding region in the control group. Linear regression and linear mixed effects models were respectively used for cross-sectional and longitudinal analyses of the impact of increases in WMH volume on motor signs. The PD group had greater WMH volume in the occipital region compared with the control group. Cross-sectional analyses only detected a significant correlation between occipital WMH volume and motor function in PD. Occipital WMH volume positively correlated with the severity of tremor, and gait and posture impairments, in the PD group. During the follow-up period, the participants' motor signs progressed and the WMH volumes remained stable, no longitudinal association was detected between them. The baseline occipital WMH volume cannot predict the progression of signs after adjustment for baseline disease duration and the presence of vascular risk factors. PD participants in this study were characterized by greater WMH at the occipital region, and greater occipital WMH volume had cross-sectional associations with worse motor signs, while its longitudinal impact on motor signs progression was limited.

A Novel Accelerometry Method to Perioperatively Quantify Essential Tremor Based on Fahn–Tolosa–Marin Criteria

The disease status, progression, and treatment effect of essential tremor (ET) patients are currently assessed with clinical scores, such as the Fahn–Tolosa–Marin Clinical Rating Scale for Tremor (FTM). The use of objective and rater-independent monitoring of tremors may improve clinical care for patients with ET. Therefore, the focus of this study is to develop an objective accelerometry-based method to quantify ET, based on FTM criteria. Thirteen patients with ET and thirteen matched healthy participants underwent FTM tests to rate tremor severity, paired with tri-axial accelerometric measurements at the index fingers. Analogue FTM assessments were performed by four independent raters based on video recordings. Quantitative measures were derived from the accelerometric data, e.g., the area under the curve of power in the 4–8 Hz frequency band (AUCP) and maximal tremor amplitude. As such, accelerometric tremor scores were computed, using thresholds based on healthy measurements and FTM criteria. Agreement between accelerometric and clinical FTM scores was analyzed with Cohen’s kappa coefficient. It was assessed whether there was a relationship between mean FTM scores and the natural logarithm (ln) of the accelerometric outcome measures using linear regression. The agreement between accelerometric and FTM scores was substantial for resting and intention tremor tests (≥72.7%). However, the agreement between accelerometric postural tremor data and clinical FTM ratings (κ = 0.459) was low, although their logarithmic (ln) relationship was substantial (R2 ≥ 0.724). Accelerometric test–retest reliability was good to excellent (ICC ≥ 0.753). This pilot study shows that tremors can be quantified with accelerometry, using healthy thresholds and FTM criteria. The test–retest reliability of the accelerometric tremor scoring algorithm indicates that our low-cost accelerometry-based approach is a promising one. The proposed easy-to-use technology could diminish the rater dependency of FTM scores and enable physicians to monitor ET patients more objectively in clinical, intraoperative, and home settings.

Distal Upper Limb Tremor during Walking in Parkinson's Disease.

Distal upper limb tremor during walking (TW) is frequently observed in Parkinson's disease (PD) but its clinical features are unknown. To characterize the occurrence and the clinical features of TW in comparison to the other types of tremors in PD. Fifty-one PD patients with rest tremor were evaluated off- and on-treatment. Occurrence, body distribution, severity and latency of TW and of other tremor types were assessed. TW was present in 78% of the PD patients examined. TW body distribution and severity were similar to those of rest and re-emergent tremor but different from the postural tremor presented by the same patients. TW latency, observed in 85% of patients, was on average 5.8 s. Dopaminergic treatment significantly improved TW, rest, and re-emergent tremor severity but left TW latency unaffected. TW is a frequent motor sign in PD and is likely a clinical variant of rest tremor.

Stigma and Social Avoidance in Adults with Essential Tremor.

People with essential tremor (ET) can be subject to stigma, and some adopt avoidance behaviors. Characteristics associated with ET stigma and the relationship between perceived stigma and social dysfunction have not been studied. To discern predictors of perceived stigma and social dysfunction in ET, and to identify potentially treatable psychological factors associated with social dysfunction. We surveyed ET patients (n = 158) on recalled stigma incidents and social dysfunction related to tremor, as well as clinical and demographic characteristics including tremor severity, and psychological constructs including anxiety, depression, mindfulness, resilience, and narcissism. Worse tremor severity (Standardized beta [SB] 1.4, P < 0.001) especially among younger participants (interaction of age and tremor severity SB -0.9, P < 0.001) and presence of vocal tremor (SB 0.7, P = 0.002) predict perceived stigma. 53/157 (33.8%) participants met criteria for social dysfunction, employing maladaptive avoidance strategies. Scores for perceived stigma (Odds Ratio [OR] 1.2, P = 0.002), depression (OR 1.5, P = 0.004) and stigma psychological distress (OR 1.2, P = 0.001) as well as sex (OR 4.3 for females, P = 0.045) predicted social dysfunction. Depression and stigma psychological distress contribute to social dysfunction related to ET stigma. Treating these psychological factors may mitigate social avoidance behaviors prevalent among susceptible individuals: those who most perceive ET stigma, i.e. relatively younger patients with worse tremor or with vocal tremor, and in particular females who are more prone to social dysfunction than males with the same degree of perceived stigma.

Using histogram analysis of the intrinsic brain activity mapping to identify essential tremor.

Essential tremor (ET) is one of the most common movement disorders. Histogram analysis based on brain intrinsic activity imaging is a promising way to identify ET patients from healthy controls (HCs) and further explore the spontaneous brain activity change mechanisms and build the potential diagnostic biomarker in ET patients. The histogram features based on the Resting-state functional magnetic resonance imaging (Rs-fMRI) data were extracted from 133 ET patients and 135 well-matched HCs as the input features. Then, a two-sample t-test, the mutual information, and the least absolute shrinkage and selection operator methods were applied to reduce the feature dimensionality. Support vector machine (SVM), logistic regression (LR), random forest (RF), and k-nearest neighbor (KNN) were used to differentiate ET and HCs, and classification performance of the established models was evaluated by the mean area under the curve (AUC). Moreover, correlation analysis was carried out between the selected histogram features and clinical tremor characteristics. Each classifier achieved a good classification performance in training and testing sets. The mean accuracy and area under the curve (AUC) of SVM, LR, RF, and KNN in the testing set were 92.62%, 0.948; 92.01%, 0.942; 93.88%, 0.941; and 92.27%, 0.939, respectively. The most power-discriminative features were mainly located in the cerebello-thalamo-motor and non-motor cortical pathways. Correlation analysis showed that there were two histogram features negatively and one positively correlated with tremor severity. Our findings demonstrated that the histogram analysis of the amplitude of low-frequency fluctuation (ALFF) images with multiple machine learning algorithms could identify ET patients from HCs and help to understand the spontaneous brain activity pathogenesis mechanisms in ET patients.

Neuropathic Tremor in Guillain-Barré Syndrome.

Neuropathic Tremor (NT) is a postural/kinetic tremor of the upper extremity, often encountered in patients with chronic neuropathies such as paraprotein-associated and hereditary neuropathies. To describe the clinical and electrophysiological features of NT in a previously underrecognized setting- during recovery from Guillain-Barré Syndrome (GBS). Patients with a documented diagnosis of GBS in the past, presenting with tremor were identified from review of clinical records. Participants underwent structured, videotaped neurological examination, and electrophysiological analysis using tri-axial accelerometry-surface electromyography. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. We describe the clinical and electrophysiological features of 5 patients with GBS associated NT. Our cohort had a fine, fast, and slightly jerky postural tremor of frequency ranging from 8 to 10 Hz. Dystonic posturing and overflow movements were noted in 4/5 patients. Tremor appeared 3 months-5 years after the onset of GBS, when patients had regained near normal muscle strength and deep tendon jerks were well elicitable. Electrophysiological analysis of tremor strongly suggested the presence of a central oscillator in all patients. NT is not limited to chronic inflammatory or hereditary neuropathies and may occur in the recovery phase of GBS. The tremor is characterized by a high frequency, jerky postural tremor with dystonic posturing. Electrophysiological evaluation suggests the presence of a central oscillator, hypothetically the cerebellum driven by impaired sensorimotor feedback.

Added forearm weights for gait pattern normalization in patients with Parkinson’s disease

Patients with Parkinson’s Disease presented gait impairment. Applying additional weights to enhancing sensory input may improve gait impairment. We assumed that gait impairment could be improved when patients walked with additional forearm weights, and the gait improvement was associated with clinical characteristic of Parkinson’s Disease. Thirty patients with Parkinson’s Disease and 30 age-sex matched controls were recruited. Spatiotemporal and joint kinematics parameters were evaluated by a three-dimensional motion capture system in normal walking and walking with sandbags, respectively. The comparisons of spatiotemporal parameters were analyzed using t-test or nonparametric tests. The comparison of joint kinematic data was analyzed using statistical parametric mapping. The correlation between motor symptom and gait parameters changes was analyzed using Pearson’s correlation analysis. During normal walking, patients showed deteriorated gait compared with controls. After applying weights to forearms patients increased cadence (p = 0.004), speed (p < 0.001) and step length (p = 0.048), and decreased stride time (p = 0.003). The hip angles significantly increased during 5%–23% and 87%–100% of gait cycle, while knee angles during 9%–25% and 88%–98% of the gait cycle, and ankle angles in 92%-100% of gait cycle. The gait parameters of patients with forearm-loading showed no significant difference compared with healthy subjects walking normally. The change of gait parameters correlated positively with the axial and tremor severity while correlated negatively with the rigidity sub-score. Patients with tremor dominant subtype also showed greater improvement of speed and step time compared with patients with postural instability/gait difficulty subtype. Applying added weights bilaterally to the forearms of patients can normalize gait patterns. Notably, patients with higher scores on axial and tremor and lower rigidity scores gained more benefits.

A severe tremor associated with Klinefelter syndrome: A case report

A severe tremor associated with Klinefelter syndrome: A case report

Opportunistic screening for atrial fibrillation using a photoplethysmography technique in geriatric patients, a preliminary analysis of the Dutch-GERAF Study

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Happitech. Provided the mobile photoplethysmography application Background Undiagnosed atrial fibrillation (AF) poses a great risk for stroke in high-risk patients. Different screening strategies have been developed to identify these patients. Geriatric patients often have multimorbidity, and are to be considered a population at very high risk for development of AF and cardiovascular events, but may have less access to wearable screening devices. Purpose The Dutch multicentre study into opportunistically screening of Geriatric patients for Atrial Fibrillation using a PPG smartphone App (the Dutch-GERAF Study) applies opportunistic screening to ambulatory geriatric patients, to identify new cases of AF and optimize stroke prevention. This preliminary analysis describes the feasibility and willingness to use of a smart phone photoplethysmography (PPG) application in an ambulatory cohort. Method Analysis of participation data and PPG use, of all included patients aged 70 years or older within the GERAF study. The GERAF study is a multicentre study on opportunistic screening for AF using a PPG application among patients visiting a geriatric outpatient clinic. All patients without a pacemaker/ICD, severe tremor, or severe dementia were invited to participate, during a 6 months screening period. Patients were stimulated to use the application at home on their own mobile device at least 3 times within 6 months following inclusion. If preferred by the patient, the application was installed on the mobile device of a spouse or other family member. The PPG signals were analysed using the commercially available algorithm. Results Data on PPG use for patients was available for 568 patients. Of these, 122 (21.5%) had a history of AF, and therefore not included in this analysis. Data on PPG use was analysed of 446 patients, 240 were female (54%), average age was 79 ± 5.5 years, the oldest patient was 95 years old. In total, patients performed 2232 PPG recordings within 6 months, in which a sufficient signal was acquired in 1874 (84%) recordings. The signal appeared sufficient at the first attempt in 79.3% of the recordings. In case of a failed first attempt, 60.5% of the patients immediately performed at least one extra recording until sufficient signal quality was achieved, and overall 61.2% of the patients performed at least 2 PPG recordings. Only 69 (15.5%) patients who consented to participation, did not perform any recordings. Conclusion This analysis of preliminary GERAF PPG data shows that very old subjects (with a mean age of almost 80 years) are willing and able to use eHealth applications on a mobile device. Most PPG recordings were of sufficient signal quality, and more than half of the patients were willing to perform repeated recordings.

Grey matter correlates of dystonic soft signs in essential tremor

BackgroundQuestionable signs of dystonia are a common finding in patients with essential tremor (ET). Brain structural alterations in ET patients plus dystonic soft signs (ET + ds) in comparison to ET patients without dystonic soft signs (ET-ds) or patients with tremor associated with manifest dystonia (TAWD) have not been examined yet. Therefore, our study aims to explore alterations of brain grey matter in patients with ET + ds. MethodsA total of 68 elderly patients with ET-ds (n = 32), ET + ds (n = 20) or idiopathic cervical dystonia with dystonia associated action tremor of the upper limbs (TAWD, n = 16) and 42 age-matched healthy controls underwent a clinical and electrophysiological assessment and 3T MRI. For grey matter alterations T1 MRI images were analysed by voxel-based morphometry. Additionally, regression analyses with clinical parameters (tremor frequency, severity and disease duration) were performed. ResultsVBM showed a significant increase of grey matter in the right lentiform nucleus in ET + ds and TAWD compared to HC and ET-ds. Further, an increase of cortical grey matter in the middle frontal gyrus in ET + ds was shown. The hypertrophy of the lentiform nucleus in ET + ds was correlated with disease severity and duration. ConclusionPatients with ET + ds showed grey matter brain structural alterations similar to TAWD. Our findings suggest an involvement of the basal ganglia-cortical loop in ET + ds which may indicate a pathophysiological similarity with TAWD rather than ET.

Cortical mean diffusivity is reliable in measuring brain abnormalities in drug-naïve essential tremor patients

ObjectiveEssential tremor (ET) is a common movement disorder, but the pathogenesis is poorly understood. Several associated brain areas were reported with inconsistent results due to heterogeneous populations. It is necessary to analyze a more homogeneous patient group. MethodsWe recruited 25 drug-naïve ET patients and 36 age- and sex-matched controls. All participants were right-handed. ET. ET was defined according to diagnostic criteria of the Consensus Statement of the Movement Disorder Society on Tremor. ET patients were divided into sporadic (SET) and familial ET (FET). We assessed tremor severity in ET. The cortical microstructural changes were compared between ET patients and controls using mean diffusivity (MD) of diffusion tensor imaging, and cortical thickness. The correlation of tremor severity with the cortical MD and thickness were respectively analyzed. ResultsMD values were increased in the insular, precuneus, medial orbitofrontal, posterior, and isthmus cingulate and temporo-occipital areas in ET. In comparison between SET and FET, MD values were higher in the superior and caudal middle frontal, postcentral, and temporo-occipital regions in FET. The cortical thickness of ET patients was more increased in the left lingual gyrus and lower in the right bankssts gyrus. We could not find any correlation of tremor severity with the MD values in ET patients. Still, there was a positive correlation with the cortical thickness of the frontal and parietal areas. ConclusionsOur results support the idea that ET is a disorder that disrupts widespread brain regions and indicates that cortical MD may be more sensitive to measure brain abnormalities than cortical thickness.

Associations between cognitive function and a range of significant life events in an elderly essential tremor cohort study

BackgroundAlthough essential tremor (ET) is associated with cognitive decline, we know little about how specific cognitive changes predict significant events in patients' lives. We examined the relations of attention, executive function, language, memory, and visuospatial performance to the occurrence of near falls, falls, walking aid use, home health aide use, non-independent living and hospitalizations within a prospective, longitudinal study of ET cases. We expected executive function and memory to be most strongly associated with these events. Methods131 ET cases (mean age at baseline = 76.4 ± 9.4 years; 109 normal cognition; 17 mild cognitive impairment, 5 demented) completed questionnaires (clinical history and occurrence of life events) and a battery of neuropsychological tests at baseline and at 18, 36, and 54 months. We assessed associations between cognitive functioning and outcomes via regression equations. ResultsCases with lower baseline levels of executive function reported more near falls, p < 0.006, and were more likely to use a walking aid, p < 0.03, odds ratio (OR) = 2.89 during the follow-up period, than were other cases. Decline in executive function was associated with home health aide use during follow-up, p < 0.04, OR = 3.34. Baseline visuospatial performance also bore a marginally significant association with non-independent living arrangements during follow-up, p < 0.06, OR = 2.13. These effects were independent of age and tremor severity. ConclusionThese data establish the important role that cognitive decline, and executive function specifically, play in the experiences of ET patients. Moreover, these associations are of sufficient magnitude to have significant clinical implications.

An Unobtrusive Method for Remote Quantification of Parkinson’s and Essential Tremor Using mm-Wave Sensing

Tremor is a primary symptom of common movement disorders such as Essential tremor and Parkinson’s disease. People experiencing tremors face difficulty in performing everyday tasks which negatively impacts their independence. Tremor quantification helps clinicians in evaluating disease progression and treatment response. Majority of the existing methods include cameras or motion sensors embedded in wearables and hand-held devices. The continuous wearing of contact sensors can be uneasy for the patients while the cameras cause privacy concerns. This paper proposes a novel method for tremor quantification using a Frequency Modulated Continuous Wave (FMCW) radar sensor. In this paper, an off-the shelf, low-cost FMCW radar has been configured to capture vibrations induced in distal limbs, a representative feature of Essential and Parkinson’s Tremors. Moreover, a signal processing chain is developed to extract characteristic tremor frequency and amplitude by reconstructing the tremor signal from the radar return signals. For robustness and increased accuracy, static clutter and voluntary body motion are eliminated. Extensive experiments were performed and results were compared to the state-of-the-art methods that use accelerometers and gyroscopes. A strong correlation ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</i> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> >0.97) is found between the reference sensor readings and predicted values for both quantified parameters. The mean error for the frequency and amplitude is 0.14Hz and 0.03cm, respectively. Results demonstrate a superior accuracy as compared to the existing non-contact techniques, with the added advantage of privacy and integrity preserving for the end-user. Hence, the proposed system can provide reliable long-term objective assessment, aiding clinicians in the evaluation of tremor severity and treatment effectiveness.

Novel Pathways Correlating with MS-Related Tremor, A Case-Control Study (P10-3.001)

<h3>Objective:</h3> Identifying the white matter fiber pathways responsible for tremor in Multiple Sclerosis (MS). <h3>Background:</h3> MS-related tremor is characteristically resistant to treatment, affecting 25% and 58% of the patients with MS. <h3>Design/Methods:</h3> Patients with MS-related tremor (n=36) had 3.0 T MRI scans with T1-weighted, FLAIR, and diffusion-weighted (DWI) sequences. Subjects were gender and age-matched with a control MS group (n = 36) without tremor. Using regional brain diffusivity measures obtained from MRICloud and diffusion connectometry findings from DSI Studio, we identified 53 tracts-of-interest associated with MS-related tremor. Tractography of the identified tracts was performed in DSI Studio. The diffusion data were reconstructed using generalized q-sampling. A supervised atlas-based tractography method was used to segment the pathways using tract-specific parameters set based on neuroanatomical topology and standardized across subjects. We obtained the partial spearman correlation coefficients (r_s) for tremor severity with mean tract diffusivity measures adjusting for possible confounders. <h3>Results:</h3> Of the 53 tracts, 5 showed negative correlation between mean tract fractional anisotropy (FA) and tremor severity: the left medial lemniscus (r_{s =} −0.55, p = &lt; .001), the forceps minor of the corpus callusom (r_{s =} −0.45, p = 0.009), the right anterior corticostriatal tract (r_{s =} −0.413, p = 0.017), the forceps major of the corpus callusom (r_s = −0.376, p = 0.031), and the fornix (r_s = −0.367, p = 0.035). Of these tracts 3 had radial diffusivity (RD) values significantly correlating with tremor severity, namely the left medial lemniscus (r_s = 0.429, p = 0.013), the right anterior corticostriatal tract (r_s = 0.379, p = 0.029), and the forceps minor of corpus callosum (r_s = 0.369, p = 0.034). <h3>Conclusions:</h3> Using two independent techniques, we identified pathways associated with MS-related tremor. For the first time, we show that commissural, medial lemniscus, and striatal tracts correlate with tremor severity. <b>Disclosure:</b> Mr. Bayoumi has nothing to disclose. Khader Hasan has nothing to disclose. The institution of Dr. Lincoln has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Lincoln has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Lincoln has received research support from Deaprtment of Defense. The institution of Dr. Lincoln has received research support from National Institutes of Health. The institution of Dr. Lincoln has received research support from EMD-Serono. Dr. Lincoln has received intellectual property interests from a discovery or technology relating to health care.

Cerebellar Transcranial Alternating Current Stimulation in Essential Tremor Patients with Thalamic Stimulation: A Proof-of-Concept Study.

Essential tremor (ET) is a disabling condition resulting from a dysfunction of cerebello-thalamo-cortical circuitry. Deep brain stimulation (DBS) or lesion of the ventral-intermediate thalamic nucleus (VIM) is an effective treatment for severe ET. Transcranial cerebellar brain stimulation has recently emerged as a non-invasive potential therapeutic option. Here, we aim to investigate the effects of high-frequency non-invasive cerebellar transcranial alternating current stimulation (tACS) in severe ET patients already operated for VIM-DBS. Eleven ET patients with VIM-DBS, and 10 ET patients without VIM-DBS and matched for tremor severity, were included in this double-blind proof-of-concept controlled study. All patients received unilateral cerebellar sham-tACS and active-tACS for 10min. Tremor severity was blindly assessed at baseline, without VIM-DBS, during sham-tACS, during and at 0, 20, 40min after active-tACS, using kinetic recordings during holding posture and action ('nose-to-target') task and videorecorded Fahn-Tolosa-Marin (FTM) clinical scales. In the VIM-DBS group, active-tACS significantly improved both postural and action tremor amplitude and clinical (FTM scales) severity, relative to baseline, whereas sham-tACS did not, with a predominant effect for the ipsilateral arm. Tremor amplitude and clinical severity were also not significantly different between ON VIM-DBS and active-tACS conditions. In the non-VIM-DBS group, we also observed significant improvements in ipsilateral action tremor amplitude, and clinical severity after cerebellar active-tACS, with a trend for improved postural tremor amplitude. In non-VIM-DBS group, sham- active-tACS also decreased clinical scores. These data support the safety and potential efficacy of high-frequency cerebellar-tACS to reduce ET amplitude and severity.

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

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

Blepharoclonus as a Potential Novel Clinical Marker in Parkinson’s Disease (P3-11.009)

Blepharoclonus as a Potential Novel Clinical Marker in Parkinson’s Disease (P3-11.009)

The Impact of Deep Brain Stimulation on the Embarrassment and Self-Esteem of Patients with Essential Tremor (P7-11.008)

<h3>Objective:</h3> To examine how Deep Brain Stimulation (DBS) influences embarrassment and self-esteem in patients with essential tremor (ET) and assess caregiver impressions. <h3>Background:</h3> Social embarrassment is one of the reasons that patients with ET choose to have DBS surgery. However, studies have not explicitly evaluated how DBS influences embarrassment and self-esteem following surgery. <h3>Design/Methods:</h3> This prospective survey-based cohort study assessed embarrassment and self-esteem in patients with ET (N=15) who were eligible to receive DBS. The Essential Tremor Embarrassment Assessment (ETEA), Rosenberg Self-Esteem Scale, and Bain and Findley Tremor Activities of Daily Living scale were administered at two time points: before DBS (T0) and 3 months following DBS surgery (T1). Semi-structured interviews were conducted at T0 and T1 and analyzed thematically. Clinical Global Impression (CGI) scales were administered at T0 and T1 to both patients and caregivers to assess how DBS influences perception of patient symptoms. <h3>Results:</h3> Demographically, the average age was 71.27 years and 8/15 were female. The average duration of ET was 34 years and 80% presented with bilateral onset. At T0, patients were most embarrassed with eating, drinking, and writing activities, only 1/15 patients reported low self-esteem, and caregiver perceptions of the patient’s quality of life were poorer than patient impressions. Females had higher embarrassment scores (M=13.9, F=26.4, p=0.15) and lower self-esteem scores (M=22.8, F=20.0, p=0.27) compared to males. Patients with unilateral onset had significantly lower self-esteem compared to patients with bilateral onset (unilateral=16.0, bilateral=22.6, p=0.011). Thematic analysis revealed activity modification contributes to feelings of embarrassment and patients with severe tremors were more likely to give up hobbies. <h3>Conclusions:</h3> These findings emphasize how embarrassment impacts quality of life and provide greater insight into which features of ET are associated with higher levels of embarrassment and lower self-esteem. Data collection and analysis at T1 is ongoing, with an expected enrollment of 40 total patients. <b>Disclosure:</b> Ms. Dave has nothing to disclose. The institution of Dr. Frey has received research support from Tourette Association of America. Dr. Yu has nothing to disclose. Janine Lemos Melo Lopes has nothing to disclose. The institution of Dr. Hess has received research support from Parkinson’s Foundation.

Does chromosome 16p12.1-p12.2 harbor a novel gene for essential tremor? (P5-11.012)

<h3>Objective:</h3> To describe a patient with de novo duplication of 16p12.1-p12.2 associated with severe action tremor and developmental delay, and genetic analysis of candidate genes within the duplicated chromosomal segment. <h3>Background:</h3> A family history of essential tremor (ET) can be found in 30–80% of all affected patients, suggesting a strong genetic contribution to its etiology. However, discovery of disease-causing genes has been largely elusive. Candidate genes can be identified using linkage analysis, whole exome or genome sequencing, and genetic association studies. Detection of genomic rearrangements with gene dosage changes in tremor patients provides another unique opportunity to identify additional candidate genes. <h3>Design/Methods:</h3> Case report and genetic analysis of the candidate chromosomal region. Chromosomal microarray analysis was performed in patient and both parents. We designed PCR primers for all coding exons of selected candidate genes. We included 75 unrelated probands from kindreds with familiar ET. Candidate genes were sequenced in all ET controls. <h3>Results:</h3> The proband is a 20-year-old female with significant developmental delay who developed progressive tremor at age of 15 years. Her tremor was a moderate to severe 4–5 Hz postural and action distal tremor, not present at rest, minimally responsive to propranolol. Additional examination revealed diffusely brisk reflexes with positive Hoffman and cross adductor sign, and upgoing toes. MRI brain did not show evidence of hypomyelination. She underwent chromosomal microarray analysis that identified duplications 12p13.33 and 16p12.2-p12.1. Chromosome 12p duplication was also detected in her father. Duplication of 12p was considered nonpathogenic and duplication 16p was <i>de novo</i>. The duplicated segment on chromosome 16p contained eight genes and six were considered possible candidate for tremor: <i>UQCRC2</i>, <i>CDR2</i>, <i>EEF2K</i>, <i>POLR3A</i>, <i>LOG23117</i>, and c16orf65. No putative deleterious mutations have been identified in ET controls. <h3>Conclusions:</h3> We report identification and genetic analysis of six novel candidate genes on chromosome 16p12.1-p12.2 that may be associated with ET. <b>Disclosure:</b> Dr. D’Aguiar Rosa has nothing to disclose. Dr. Yousaf has nothing to disclose. Dr. Hedera has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Hedera has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Hedera has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for University of Louisville.