Validation of the International Classification of Diseases, Tenth Revision-Clinical Modification Diagnostic Code for Essential Tremor.

Background: The positive predictive value (PPV) of the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) code for "essential and other specified forms of tremor" in identifying essential tremor (ET) cases was found to be less than 50%. The ability of the ICD-10-CM G25.0 code for "essential tremor" to identify ET has not been determined. The study objective was to determine the PPV of the G25.0 code. Methods: Patients in a tertiary health system with a primary care encounter associated with ICD-10-CM code G25.0 in 2022 underwent medical record review to determine if the consensus criteria from the International Parkinson and Movement Disorder Society for an ET diagnosis were met. Results: 442 patients were included. The PPV of G25.0 in identifying probable ET cases was 74.7% (95% confidence interval (CI) 70.4-78.5%). Among patients prescribed propranolol, the PPV improved to 87.8% (95% CI 78.0-93.6%). Discussion: Compared to the ICD-9-CM code 333.1, G25.0 is superior for identifying ET cases. A potential limitation of this study is that the consensus criteria applied relies on nonspecific physical exam findings which may lead to an overestimation of the PPV of G25.0. Highlights: The ICD-10-CM diagnosis code for essential tremor has not been previously validated. The objective of this study was to determine the PPV of the G25.0 code. The PPV in identifying essential tremor cases was 74.7%. The PPV improved among patients prescribed propranolol.

An Eye on the First Surgical Side: Appreciating the Potential Impacts of a Second DBS Lead on Ipsilateral Symptoms.

Clinical Vignette: A 63-year-old man with severe essential tremor underwent staged bilateral ventralis intermedius (Vim) deep brain stimulation (DBS). Left Vim DBS resulted in improved right upper extremity tremor control. Months later, the addition of right Vim DBS to the other brain hemisphere was associated with acute worsening of the right upper extremity tremor. Clinical Dilemma: In staged bilateral Vim DBS, second lead implantation may possibly alter ipsilateral tremor control. While ipsilateral improvement is common, rarely, it can disrupt previously achieved benefit. Clinical Solution: DBS programming, including an increase in left Vim DBS amplitude, re-established and enhanced bilateral tremor control. Gap in Knowledge: The mechanisms underlying changes in ipsilateral tremor control following a second lead implantation are unknown. In this case, worsening and subsequent improvement after optimization highlight the potential impact of DBS implantation on the ipsilateral side. Expert Commentary: After staged bilateral Vim DBS, clinicians should keep an eye on the first or original DBS side and carefully monitor for emergent side effects or worsening in tremor. Ipsilateral effects resulting from DBS implantation present a reprogramming opportunity with a potential to further optimize clinical outcomes. Highlights: This case report highlights the potential for ipsilateral tremor worsening following staged bilateral DBS and provides valuable insights into troubleshooting and reprogramming strategies. The report emphasizes the importance of vigilant monitoring and individualized management in optimizing clinical outcomes for patients undergoing staged bilateral DBS for essential tremor.

Assessing ChatGPT Ability to Answer Frequently Asked Questions About Essential Tremor.

Background: Large-language models (LLMs) driven by artificial intelligence allow people to engage in direct conversations about their health. The accuracy and readability of the answers provided by ChatGPT, the most famous LLM, about Essential Tremor (ET), one of the commonest movement disorders, have not yet been evaluated. Methods: Answers given by ChatGPT to 10 questions about ET were evaluated by 5 professionals and 15 laypeople with a score ranging from 1 (poor) to 5 (excellent) in terms of clarity, relevance, accuracy (only for professionals), comprehensiveness, and overall value of the response. We further calculated the readability of the answers. Results: ChatGPT answers received relatively positive evaluations, with median scores ranging between 4 and 5, by both groups and independently from the type of question. However, there was only moderate agreement between raters, especially in the group of professionals. Moreover, readability levels were poor for all examined answers. Discussion: ChatGPT provided relatively accurate and relevant answers, with some variability as judged by the group of professionals suggesting that the degree of literacy about ET has influenced the ratings and, indirectly, that the quality of information provided in clinical practice is also variable. Moreover, the readability of the answer provided by ChatGPT was found to be poor. LLMs will likely play a significant role in the future; therefore, health-related content generated by these tools should be monitored.

Careful Phenotypic Characterization of Tremor Phenomenology in a Patient with Spinocerebellar Ataxia Type 12-Tremor Features Do Not Match Those of Essential Tremor.

Background: The tremor characteristics of patients with spinocerebellar ataxia 12 (SCA12) are often likened to those in patients with essential tremor (ET); however, data are sparse, and videotaped tremor examinations are rare. Case Report: A 37-year-old woman with progressive hand and head tremors underwent genetic testing after conventional diagnostics failed to explain her symptoms. A PPP2R2B variation confirmed spinocerebellar ataxia type 12 (SCA12), a condition not previously considered because classical cerebellar signs were absent. The tremor characteristics of this patient differed in numerous respects from those seen in patients with ET. Discussion: Although often likened to ET, under careful scrutiny, the tremor characteristics observed in this patient with SCA12 were inconsistent with those typically seen in ET. Such discrepancies highlight the necessity of careful phenotyping for tremor disorders, particularly in familial cases. Recognizing the specific tremor phenomenology of SCA12 and distinguishing it from ET is crucial to avoid misdiagnosis and to guide appropriate management and familial counseling. Highlights: This report characterizes in detail an early-stage SCA12 patient initially misdiagnosed as essential tremor, underscoring the importance of nuanced clinical assessment and genetic testing in atypical tremor cases. Similar patients should be meticulously phenotyped to prevent misclassification and enhance our understanding of tremor pathophysiology.

Ventral intermediate nucleus of the thalamus, dentatorubrothalamic tract, and caudal zona incerta: stimulation of which structure provides ongoing tremor control in patients with essential tremor?

OBJECTIVE: Essential tremor (ET) is the most common movement disorder. Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) is known to improve symptoms in patients with medication-resistant ET. However, the clinical effectiveness of VIM-DBS may vary, and other targets have been proposed. The authors aimed to investigate whether the same anatomical structure is responsible for tremor control both immediately after VIM-DBS and at later follow-up evaluations. METHODS: Of 68 electrodes from 41 patients with ET, the authors mapped the distances of the active contact from the VIM, the dentatorubrothalamic tract (DRTT), and the caudal zona incerta (cZI) and compared them using Friedman's ANOVA and the Wilcoxon signed-rank follow-up test. The same distances were also compared between the initially planned target and the final implantation site after intraoperative macrostimulation. Finally, the comparison among the three structures was repeated for 16 electrodes whose active contact was changed after a mean 37.5 months follow-up to improve tremor control. RESULTS: After lead implantation, the VIM was statistically significantly closer to the active contact than both the DRTT (p = 0.008) and cZI (p < 0.001). This result did not change if the target was moved based on intraoperative macrostimulation. At the last follow-up, the active contact distance from the VIM was always significantly less than that of the cZI (p < 0.001), but the distance from the DRTT was reduced and even less than the distance from the VIM. CONCLUSIONS: In patients receiving VIM-DBS, the VIM itself is the structure driving the anti-tremor effect and remains more effective than the cZI, even years after implantation. Nevertheless, the role of the DRTT may become more important over time and may help sustain the clinical efficacy when the habituation from the VIM stimulation ensues.

Testing for Alcohol Responsiveness in Familial Essential Tremor.

Background: Essential tremor (ET) is the most common movement disorder in adults and is considered to be highly heritable. A reduction of the tremor amplitude after alcohol consumption is reported in approximately half of the patients. In this study, we describe the alcohol response in our familial ET cohort by employing an alcohol responsivity test designed by Knudsen et al. outside its original research group for the first time. Methods: We recruited families with at least three trembling family members and confirmed ET diagnoses. During the in-hospital alcohol responsivity test, tremor was measured using Archimedes spirals before alcohol consumption (T0), one hour after alcohol intake (T1), and the next morning (T2). The spirals were rated by two independent raters using the Bain Findley scale. The average of these two scores was calculated as the Archimedes Spiral Rating (ASR) for each time point. Results: Twenty-four confirmed ET patients were included for analysis. The median ASR at T0 (5.0) and T2 (4.75) were significantly higher than the median ASR at T1 (3.25) (both p < 0.001). In 67% of patients, a difference in ASR between T0 and T1 (dASR) ≥ 2 pointed towards an improvement of tremor after consuming alcohol. Discussion: We confirmed that the alcohol responsiveness test of Knudsen et al. is useful in determining objective alcohol responsivity. We established a significantly reduced ASR after alcohol consumption in 67% of familial ET patients in our cohort. In the future, a larger population is needed to establish whether familial aggregation of alcohol responsivity occurs in essential tremor patients. Highlights: The test designed by Knudsen et al. effectively established objective alcohol responsiveness outside its original research group.We found an objective alcohol response in 67% of our familial ET cohort.Subjective VAS scores were significantly lower after alcohol consumption.There was no correlation between the objective and subjective alcohol responsiveness.Familial aggregation of alcohol responsiveness in ET should be studied in a larger cohort.

[Unilateral thalamotomy with high intensity focal ultrasound in patients with refractory essential tremor: a comparative study between patients under and over 70 years of age]. / Talamotomía unilateral con ultrasonidos focales de alta intensidad en pacientes con temblor esencial refractario: un estudio comparativo entre pacientes menores y mayores de 70 años.

INTRODUCTION: High intensity focal ultrasound (HIFU) thalamotomy is a novel treatment for refractory tremor. This study aims to compare the reduction in tremor intensity and adverse effects of treatment between patients younger and older than 70 years of age. PATIENTS AND METHODS: All the patients with refractory essential tremor treated with HIFU between March 2021 and March 2023 were included consecutively. Various demographic and clinical variables were analysed, including age and the items on the Clinical Rating Scale for Tremor (CRST). Cerebral vascular pathology was quantified using the Fazekas scale. Outcomes and adverse effects were compared between the patients aged 70 years or younger, and those older than 70 years. RESULTS: Ninety patients were included, and 50 of them were over 70 years old. Prior to treatment, the CRST A + B score was 20.4 ± 5.7 among those under 70 years of age, and 23.3 ± 5.1 in those older (p = 0.013). At six months after treatment, the mean was 3.8 ± 5.1 and 4.8 ± 4.5, respectively (p = 0.314). We found no significant differences in the CRST C score (2.8 ± 4.1 and 3.5 ± 4.8, p = 0.442). There were also no significant differences between the patients with vascular pathology (Fazekas = 1) and those without (4.6 ± 7.3 and 4.3 ± 4, p = 0.832). There were no differences in the presence of adverse effects between the groups based on age and vascular pathology. CONCLUSIONS: Contrary to traditional opinion, older patients do not have a poorer response or a higher rate of adverse effects after HIFU treatment.

TITLE: Talamotomía unilateral con ultrasonidos focales de alta intensidad en pacientes con temblor esencial refractario: un estudio comparativo entre pacientes menores y mayores de 70 años.Introducción. La talamotomía con ultrasonidos focales de alta intensidad (HIFU) es un tratamiento novedoso para el temblor refractario. El objetivo de este estudio es comparar la reducción en la intensidad del temblor y los efectos adversos del tratamiento entre pacientes menores y mayores de 70 años. Pacientes y métodos. Se incluyó consecutivamente a todos los pacientes con temblor esencial refractario tratados con HIFU entre marzo de 2021 y marzo de 2023. Se analizaron diferentes variables demográficas y clínicas, incluyendo la edad y los apartados de la Clinical Rating Scale for Tremor (CRST). Se cuantificó la patología vascular cerebral mediante la escala de Fazekas. Se compararon los resultados y los efectos adversos entre los grupos de edad de 70 años o menos y de más de 70 años. Resultados. Se incluyó a 90 pacientes, 50 de ellos de más de 70 años. Previamente al tratamiento, la CRST A + B era de 20,4 ± 5,7 en los menores de 70 años y de 23,3 ± 5,1 en los mayores (p = 0,013). A los seis meses tras el tratamiento, la media fue de 3,8 ± 5,1 y 4,8 ± 4,5, respectivamente (p = 0,314). No hallamos diferencias significativas en la CRST C (2,8 ± 4,1 y 3,5 ± 4,8, p = 0,442). Tampoco hubo diferencias significativas entre pacientes con patología vascular (Fazekas = 1) y sin ella (4,6 ± 7,3 y 4,3 ± 4, p = 0,832). No hubo diferencias en la presencia de efectos adversos entre los grupos de edad y de patología vascular. Conclusiones. En contra de lo tradicionalmente concebido, los pacientes de mayor edad no tienen una peor respuesta ni una mayor tasa de efectos adversos tras el tratamiento con HIFU.

Gait Variability as a Potential Motor Marker of Cerebellar Disease-Relationship between Variability of Stride, Arm Swing and Trunk Movements, and Walking Speed.

Excessive stride variability is a characteristic feature of cerebellar ataxias, even in pre-ataxic or prodromal disease stages. This study explores the relation of variability of arm swing and trunk deflection in relationship to stride length and gait speed in previously described cohorts of cerebellar disease and healthy elderly: we examined 10 patients with spinocerebellar ataxia type 14 (SCA), 12 patients with essential tremor (ET), and 67 healthy elderly (HE). Using inertial sensors, recordings of gait performance were conducted at different subjective walking speeds to delineate gait parameters and respective coefficients of variability (CoV). Comparisons across cohorts and walking speed categories revealed slower stride velocities in SCA and ET patients compared to HE, which was paralleled by reduced arm swing range of motion (RoM), peak velocity, and increased CoV of stride length, while no group differences were found for trunk deflections and their variability. Larger arm swing RoM, peak velocity, and stride length were predicted by higher gait velocity in all cohorts. Lower gait velocity predicted higher CoV values of trunk sagittal and horizontal deflections, as well as arm swing and stride length in ET and SCA patients, but not in HE. These findings highlight the role of arm movements in ataxic gait and the impact of gait velocity on variability, which are essential for defining disease manifestation and disease-related changes in longitudinal observations.

Speech, voice, and language outcomes following deep brain stimulation: A systematic review.

BACKGROUND: Deep brain stimulation (DBS) reliably ameliorates cardinal motor symptoms in Parkinson's disease (PD) and essential tremor (ET). However, the effects of DBS on speech, voice and language have been inconsistent and have not been examined comprehensively in a single study. OBJECTIVE: We conducted a systematic analysis of literature by reviewing studies that examined the effects of DBS on speech, voice and language in PD and ET. METHODS: A total of 675 publications were retrieved from PubMed, Embase, CINHAL, Web of Science, Cochrane Library and Scopus databases. Based on our selection criteria, 90 papers were included in our analysis. The selected publications were categorized into four subcategories: Fluency, Word production, Articulation and phonology and Voice quality. RESULTS: The results suggested a long-term decline in verbal fluency, with more studies reporting deficits in phonemic fluency than semantic fluency following DBS. Additionally, high frequency stimulation, left-sided and bilateral DBS were associated with worse verbal fluency outcomes. Naming improved in the short-term following DBS-ON compared to DBS-OFF, with no long-term differences between the two conditions. Bilateral and low-frequency DBS demonstrated a relative improvement for phonation and articulation. Nonetheless, long-term DBS exacerbated phonation and articulation deficits. The effect of DBS on voice was highly variable, with both improvements and deterioration in different measures of voice. CONCLUSION: This was the first study that aimed to combine the outcome of speech, voice, and language following DBS in a single systematic review. The findings revealed a heterogeneous pattern of results for speech, voice, and language across DBS studies, and provided directions for future studies.

Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.

Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.

Validation of a New Patient-Reported Outcome Measure of the Functional Impact of Essential Tremor on Activities of Daily Living.

Background: The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines. Objective: Develop and validate a TETRAS PRO subscale. Methods: Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for 67 adults with ET or ET plus. Test-retest reliability was computed at intervals of 1 and 30 days. The influence of mood (Hospital Anxiety and Depression Scale, HADS) and coping behaviors (Essen Coping Questionnaire, ECQ) was examined with multiple linear regression. Results: TETRAS PRO was strongly correlated (r > 0.7) with TETRAS ADL, TETRAS-P, and QUEST and exhibited good to excellent reliability (Cronbach alpha 95%CI = 0.853-0.926; 30-day test-retest intraclass correlation 95%CI = 0.814-0.921). The 30-day estimate of minimum detectable change (MDC) was 6.6 (95%CI 5.2-8.0). TETRAS-P (rsemipartial = 0.607), HADS depression (rsemipartial = 0.384), and the coping strategy of information seeking and exchange of experiences (rsemipartial = 0.176) contributed statistically to TETRAS PRO in a multiple linear regression (R2 = 0.67). Conclusions: TETRAS PRO is a valid and reliable scale that is influenced strongly by tremor severity, moderately by mood (depression), and minimally by coping skills. The MDC for TETRAS PRO is probably sufficient to detect clinically important change.

Unilateral gamma knife thalamotomy for tremor safety and efficacy in multimodal assessment: a prospective case-control study with two-year follow-up.

INTRODUCTION: Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). MATERIAL AND METHODS: 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT. Patients were assessed with psychological tests and acoustic voice analysis. Tremor assessment was performed with a digitising table using the Fahn-Tolosa-Marin rating scale (FTMRS). The Unified Parkinson's Disease rating scale part III (UPDRS-III) was also used in the PD group. Gait and balance was assessed using clinical tests, stabilometric platform, and treadmill. RESULTS: No side effects were observed in a two-year follow-up. There was no notable deterioration observed in the patients' psychological evaluation, speech, or assessment of gait and balance. The scores were significantly lower (p = 0.01) in parts A and B of FTMRS one year after GKT. In post hoc analysis, the scores did not differ significantly between V0 and V24. In FTMRS part C (activities of daily living), no significant change was observed. There was no significant difference in total UPDRS part III score or in score of UPDRS part III domains 3 and 4 ('tremor at rest' and 'action and postural tremor of hands') between measurements. CONCLUSIONS: UGKT may be a safe treatment modality if performed in an experienced centre. Tremor reduction may diminish over time, and UGKT did not lead to cognitive, gait or speech deterioration in a long-term observation.

Erroneous Compensation for Long-Latency Feedback Delays as Origin of Essential Tremor.

Essential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with 24 ET patients (14 female; 10 male) and 28 neurologically intact (NI) human volunteers (17 female; 11 male) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients' early muscular responses (short and long-latency responses, 20-50 and 50-100 ms, respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.

Machine learning models for diagnosis of essential tremor and dystonic tremor using grey matter morphological networks.

BACKGROUND: Essential tremor (ET) and dystonic tremor (DT) are the two most common tremor disorders, and misdiagnoses are very common due to similar tremor symptoms. In this study, we explore the structural network mechanisms of ET and DT using brain grey matter (GM) morphological networks and combine those with machine learning models. METHODS: 3D-T1 structural images of 75 ET patients, 71 DT patients, and 79 healthy controls (HCs) were acquired. We used voxel-based morphometry to obtain GM images and constructed GM morphological networks based on the Kullback-Leibler divergence-based similarity (KLS) method. We used the GM volumes, morphological relations, and global topological properties of GM-KLS morphological networks as input features. We employed three classifiers to perform the classification tasks. Moreover, we conducted correlation analysis between discriminative features and clinical characteristics. RESULTS: 16 morphological relations features and 1 global topological metric were identified as the discriminative features, and mainly involved the cerebello-thalamo-cortical circuits and the basal ganglia area. The Random Forest (RF) classifier achieved the best classification performance in the three-classification task, achieving a mean accuracy (mACC) of 78.7%, and was subsequently used for binary classification tasks. Specifically, the RF classifier demonstrated strong classification performance in distinguishing ET vs. HCs, ET vs. DT, and DT vs. HCs, with mACCs of 83.0 %, 95.2 %, and 89.3 %, respectively. Correlation analysis demonstrated that four discriminative features were significantly associated with the clinical characteristics. CONCLUSION: This study offers new insights into the structural network mechanisms of ET and DT. It demonstrates the effectiveness of combining GM-KLS morphological networks with machine learning models in distinguishing between ET, DT, and HCs.

Sustained reduction of essential tremor with low-power non-thermal transcranial focused ultrasound stimulations in humans.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique; when skull aberrations are compensated for, this technique allows, with millimetric accuracy, circumvention of the invasive surgical procedure associated with deep brain stimulation (DBS) and the limited spatial specificity of transcranial magnetic stimulation. OBJECTIVE: /hypothesis: We hypothesize that MR-guided low-power TUS can induce a sustained decrease of tremor power in patients suffering from medically refractive essential tremor. METHODS: The dominant hand only was targeted, and two anatomical sites were sonicated in this exploratory study: the ventral intermediate nucleus of the thalamus (VIM) and the dentato-rubro-thalamic tract (DRT). Patients (N = 9) were equipped with MR-compatible accelerometers attached to their hands to monitor their tremor in real-time during TUS. RESULTS: VIM neurostimulations followed by a low-duty cycle (5 %) DRT stimulation induced a substantial decrease in the tremor power in four patients, with a minimum of 89.9 % reduction when compared with the baseline power a few minutes after the DRT stimulation. The only patient stimulated in the VIM only and with a low duty cycle (5 %) also experienced a sustained reduction of the tremor (up to 93.4 %). Four patients (N = 4) did not respond. The temperature at target was 37.2 ± 1.4 °C compared to 36.8 ± 1.4 °C for a 3 cm away control point. CONCLUSIONS: MR-guided low power TUS can induce a substantial and sustained decrease of tremor power. Follow-up studies need to be conducted to reproduce the effect and better to understand the variability of the response amongst patients. MR thermometry during neurostimulations showed no significant thermal rise, supporting a mechanical effect.

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

Evaluation and Management of Tremor.

Tremor is a commonly encountered condition in the primary care setting and can manifest at rest, with action, or both. Common causes include Parkinson disease, essential tremor, and drug-induced tremor. In this article, the authors discuss how to examine a patient with tremor and which features of the history and examination can help clue the provider in to the appropriate diagnosis. They also review treatments for varying types of tremor and when referral to a neurologist may be necessary.

Radiosurgical thalamotomy for essential tremor: state of the art, current challenges and future directions.

INTRODUCTION: Essential tremor (ET) is the most frequent movement disorder, affecting up to 5% of adults > 65 years old. In 30-50% of cases, optimal medical management provides insufficient tremor relief and surgical options are considered. Thalamotomy is a time-honored intervention, which can be performed using radiofrequency (RF), stereotactic radiosurgery (SRS), or magnetic resonance-guided focused ultrasounds (MRgFUS). While the latter has received considerable attention in the last decade, SRS has consistently been demonstrated as an effective and well-tolerated option. AREAS COVERED: This review discusses the evidence on SRS thalamotomy for ET. Modern workflows and emerging techniques are detailed. Current outcomes are analyzed, with a specific focus on tremor reduction, complications and radiological evolution of the lesions. Challenges for the field are highlighted. EXPERT OPINION: SRS thalamotomy improves tremor in > 80% patients. The efficacy appears comparable to other modalities, including DBS, RF and MRgFUS. Side effects result mostly from idiosyncratic hyper-responses to radiation, which occur in up to 10% of treatments, are usually self-resolving, and are symptomatic in < 4% of patients. Future research should focus on accumulating more data on bilateral treatments, collecting long-term outcomes, refining targeting, and improving lesion consistency.

Association Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson's Disease.

Background: Parkinson's disease (PD) and Essential tremor (ET) are the two most common tremor diseases with recognized genetic pathogenesis. The overlapping clinical features suggest they may share genetic predispositions. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and early-onset PD (EOPD), and found the suggestive association between teneurin transmembrane protein 4 (TENM4) and EOPD. In the current research, we explored the potential genetic interplay between ET-associated genetic loci/genes and sporadic late-onset PD (LOPD). Methods: We performed whole-genome sequencing in the 1962 sporadic LOPD cases and 1279 controls from mainland China. We first used logistic regression analysis to test the top 16 SNPs identified by the ET genome-wide association study for the association between ET and LOPD. Then we applied the optimized sequence kernel association testing to explore the rare variant burden of 33 ET-associated genes in this cohort. Results: We did not observe a significant association between the included SNPs with LOPD. We also did not discover a significant burden of rare deleterious variants of ET-associated genes in association with LOPD risk. Conclusion: Our results do not support the role of ET-associated genetic loci and variants in LOPD. Highlights: 1962 cases and 1279 controls were recruited to study the potential genetic interplay between ET-associated genetic loci/variants and sporadic LOPD.No significant association between the ET-associated SNPs and LOPD were observed.No significant burden of rare deleterious variants of ET-associated gene in LOPD risk were found.