A severe tremor caused by a beta2 agonist in a patient with asthma-chronic obstructive pulmonary disease overlap.

A 46-year-old male developed respiratory distress due to asthma-chronic obstructive pulmonary disease overlap and experienced severe tremor caused by beta2 agonist inhalant. We present our successful experience with tizanidine administration.

Action tremor features discovery for essential tremor and Parkinson's disease with explainable multilayer BiLSTM.

The tremors of Parkinson's disease (PD) and essential tremor (ET) are known to have overlapping characteristics that make it complicated for clinicians to distinguish them. While deep learning is robust in detecting features unnoticeable to humans, an opaque trained model is impractical in clinical scenarios as coincidental correlations in the training data may be used by the model to make classifications, which may result in misdiagnosis. This work aims to overcome the aforementioned challenge of deep learning models by introducing a multilayer BiLSTM network with explainable AI (XAI) that can better explain tremulous characteristics and quantify the respective discovered important regions in tremor differentiation. The proposed network classifies PD, ET, and normal tremors during drinking actions and derives the contribution from tremor characteristics, (i.e., time, frequency, amplitude, and actions) utilized in the classification task. The analysis shows that the XAI-BiLSTM marks the regions with high tremor amplitude as important in classification, which is verified by a high correlation between relevance distribution and tremor displacement amplitude. The XAI-BiLSTM discovered that the transition phases from arm resting to lifting (during the drinking cycle) is the most important action to classify tremors. Additionally, the XAI-BiLSTM reveals frequency ranges that only contribute to the classification of one tremor class, which may be the potential distinctive feature to overcome the overlapping frequencies problem. By revealing critical timing and frequency patterns unique to PD and ET tremors, this proposed XAI-BiLSTM model enables clinicians to make more informed classifications, potentially reducing misclassification rates and improving treatment outcomes.

Tremor Estimation and Removal in Robot-Assisted Surgery Using Improved Enhanced Band-Limited Multiple Fourier Linear Combiner.

BACKGROUND: During a robot-assisted minimally invasive surgery, hand tremors in a surgeon's manipulation of the master manipulator can cause vibrations of the slave surgical instruments. METHODS: This letter addresses this problem by proposing an improved Enhanced Band-Limited Multiple Linear Fourier Combiner (E-BMFLC) algorithm for filtering the physiological tremor signals of a surgeon's hand. The proposed method uses the amplitude of the input signal to adapt the learning rate and a dense division of the combiner bands for the higher amplitude bands of the tremor signals. RESULTS: By using the proposed improved E-BMFLC algorithm, the compensation accuracy can be improved by 4.5%-8.9%, as well as a spatial position error of less than 1 mm. CONCLUSION: The results show that among all filtering methods, the improved E-BMFLC filtering method has the highest number of successful experiments and the lowest experimental time.

Frequency-Selective Suppression of Essential Tremor via Transcutaneous Spinal Cord Stimulation.

BACKGROUND: Essential tremor (ET) is a common debilitating condition, yet current treatments often fail to provide satisfactory relief. Transcutaneous spinal cord electrical stimulation (tSCS) has emerged as a potential noninvasive neuromodulation technique capable of disrupting the oscillatory activity underlying tremors. OBJECTIVE: This study aimed to investigate the potential of tSCS to disrupt tremor in a frequency-dependent manner in a cohort of patients with ET. METHODS: Eighteen patients with ET completed the study. The experiment consisted of 60-s postural tremor recording, during tSCS at tremor frequency, at 1 Hz, at 21 Hz, no stimulation, and trapezius stimulation. Tremor frequency and amplitude were analyzed and compared across the conditions. RESULTS: We found tremor amplitude reduction at tremor frequency stimulation significant only during the second half of the stimulation. The same stimulation resulted in the highest number of responders. tSCS at 1 Hz showed a trend toward decreased tremor amplitude in the latter half of stimulation. tSCS at 21 Hz did not produce any significant alterations in tremor, whereas trapezius stimulation exacerbated it. Notably, during tremor frequency stimulation, a subgroup of responders exhibited consistent synchronization between tremor phase and delivered stimulation, indicating tremor entrainment. CONCLUSIONS: Cervical tSCS holds promise for alleviating postural tremor in patients with ET when delivered at the subject's tremor frequency. The observed changes in tremor amplitude likely result from the modulation of spinal cord circuits by tSCS, which disrupts the oscillatory drive to muscles by affecting afferent pathways or spinal reflexes. However, the possibility of an interplay between spinal and supraspinal centers cannot be discounted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Psychiatric Manifestations in Early to Middle Stages of Fragile X-Associated Tremor-Ataxia Syndrome (FXTAS).

OBJECTIVE: The purpose of the present study was to assess the psychiatric manifestations of early to middle stages of fragile X-associated tremor-ataxia syndrome (FXTAS) and their relationship with executive function and FMR1 cytosine-guanine-guanine (CGG) repeat numbers across genders. METHODS: Cross-sectional data from 100 participants (62 men, 38 women; mean±SD age=67.11±7.90 years) with FXTAS stage 1, 2, or 3 were analyzed, including demographic information, cognitive measures, psychiatric assessments (Symptom Checklist-90-Revised and Behavioral Dyscontrol Scale-II [BDS-II]), and CGG repeat number. RESULTS: Participants with FXTAS stage 3 exhibited significantly worse psychiatric outcomes compared with participants with either stage 1 or 2, with distinct gender-related differences. Men showed differences in anxiety and hostility between stage 3 and combined stages 1 and 2, whereas women exhibited differences in anxiety, depression, interpersonal sensitivity, obsessive-compulsive symptoms, and somatization, as well as in the Global Severity Index, the Positive Symptom Distress Index, and the Positive Symptom Total. Among male participants, negative correlations were observed between BDS-II total scores and obsessive-compulsive symptoms, as well as between anxiety and CGG repeat number. CONCLUSIONS: These findings suggest that even at early FXTAS stages, patients have significant cognitive and other psychiatric symptoms, with notable gender-specific differences. This study underscores the clinical and prognostic relevance of comorbid psychiatric conditions in FXTAS, highlighting the need for early intervention and targeted support for individuals with relatively mild motor deficits.

Microinterventional system for robot-assisted gonioscopic surgery- technical feasibility and preclinical evaluation in synthetic eye models.

BACKGROUND: Preclinical technical feasibility study of robot-assisted microinvasive glaucoma surgery using a novel ophthalmic robot-assisted surgery system. METHODS: Feasibility was assessed in synthetic eye models in two stages: Stage I, nonimplantable robot-assisted goniotomy; and Stage II, robot-assisted stent implantation using a trabecular bypass stent. Robot-assisted interventions were subsequently compared to the manual approach. RESULTS: Stage I: Two surgeons completed 10 trials each of ab-interno sectoral goniotomy with and without robotic assistance for at least 3 clock hours using a standard goniotomy knife and more than 10 clock hours of extended goniotomy using a flexible, guided goniotomy instrument. Stage II: Trabecular bypass stent deployment was successfully achieved in 100% of the attempts with and without robotic assistance. Surgical time was recorded and compared between the robotic-assisted and the manual approach. CONCLUSIONS: A system for robot-assisted microinvasive glaucoma surgery can successfully achieve implantable and nonimplantable interventions in the anterior segment. This is the first known demonstration of the feasibility of robot-assisted glaucoma surgery.

Subjective and Objective Day-to-Day Performance Measures of People with Essential Tremor.

This paper aims to map the daily functional characteristics of people diagnosed with essential tremor (ET) based on their subjective self-reports. In addition, we provide objective measurements of a cup-drinking task. This study involved 20 participants diagnosed with ET who completed the Columbia University Assessment of Disability in Essential Tremor (CADET) questionnaire that included five additional tasks related to digital equipment operation we wrote. Participants also described task-performance modifications they implemented. To create objective personal performance profiles, they performed a cup-drinking task while being monitored using a sensor measurement system. The CADET's subjective self-report results indicate that the most prevalent tasks participants reported as having difficulty with or requiring modifications were writing, threading a needle, carrying a cup, using a spoon, pouring, and taking a photo or video on a mobile phone. Analysis of participants' modifications revealed that holding the object with two hands or with one hand supporting the other were the most prevalent types. No significant correlation was found between the CADET total scores and the cup drinking objective measures. Capturing patients' perspectives on their functional disability, alongside objective performance measures, is envisioned to contribute to the development of custom-tailored interventions aligned with individual profiles, i.e., patient-based/smart healthcare.

Development of a Tremor Detection Algorithm for Use in an Academic Movement Disorders Center.

Tremor, defined as an "involuntary, rhythmic, oscillatory movement of a body part", is a key feature of many neurological conditions including Parkinson's disease and essential tremor. Clinical assessment continues to be performed by visual observation with quantification on clinical scales. Methodologies for objectively quantifying tremor are promising but remain non-standardized across centers. Our center performs full-body behavioral testing with 3D motion capture for clinical and research purposes in patients with Parkinson's disease, essential tremor, and other conditions. The objective of this study was to assess the ability of several candidate processing pipelines to identify the presence or absence of tremor in kinematic data from patients with confirmed movement disorders and compare them to expert ratings from movement disorders specialists. We curated a database of 2272 separate kinematic data recordings from our center, each of which was contemporaneously annotated as tremor present or absent by a movement physician. We compared the ability of six separate processing pipelines to recreate clinician ratings based on F1 score, in addition to accuracy, precision, and recall. The performance across algorithms was generally comparable. The average F1 score was 0.84±0.02 (mean ± SD; range 0.81-0.87). The second highest performing algorithm (cross-validated F1=0.87) was a hybrid that used engineered features adapted from an algorithm in longstanding clinical use with a modern Support Vector Machine classifier. Taken together, our results suggest the potential to update legacy clinical decision support systems to incorporate modern machine learning classifiers to create better-performing tools.

Thalamic ventral-Oralis complex/rostral zona incerta deep brain stimulation for midline tremor.

BACKGROUND: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies. OBJECTIVE: To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor. METHODS: Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported. RESULTS: Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients. All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred. CONCLUSION: In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.

REM sleep behavior disorder and Prodromal Parkinson's Disease in patients with Essential Tremor.

Several studies suggested the presence of non-motor symptoms in Essential Tremor (ET), including REM sleep behavioral disorder (RBD). RBD is an essential criterion for Prodromal Parkinson's Disease (PPD), suggesting a link between ET and PD. Our objective was to assess the prevalence and features of ET patients with RBD and PDD. RBD was diagnosed by questionnaire screening, followed by polysomnography. PPD risk factors and prodromic markers were assessed with a structured protocol. Patients were characterized regarding tremor features. ET patients with RBD (ET-RBD) and PPD (ET-PPD) were compared to patients without RBD (ET-nonRBD) and without PPD (ET-nonPPD), respectively. ET-RBD patients were also compared with a group of isolated RBD (iRBD) regarding PPD features. We assessed a total of 64 ET patients. Five (8.3 %) and 4 (6.3 %) had criteria for RBD and PPD, respectively. ET-RBD patients did not differ from ET-nonRBD except for a higher prevalence of PPD. There were no significant differences between ET-RBD and iRBD (n = 12) groups. ET-PPD had a higher prevalence of positive DaT-Scans and RBD compared to ET-nonPPD. Three ET-RBD patients had PPD and 3 ET-PPD had RBD. Both RBD and PPD are more frequent in ET patients than in general aged population but not related with specific tremor features. ET-RBD patients did not differ significantly from iRBD patients, a group prone to develop PD. These data suggest a link between ET and PD and are in accordance with studies showing an increase incidence of lewy-body pathology and PD in ET populations.

Neuropathological findings in essential tremor.

Essential tremor (ET) is one of the most common neurological conditions and the most common movement disorder. The pathophysiological mechanisms that underlie this entity have not yet been described. However, recent post-mortem brain studies have provided useful insight into the underlying pathology of ET. Two brain areas have been consistently found to present neuropathological alterations in patients with ET: the brainstem, for presence of Lewy bodies or neuronal depletion, and the cerebellum, regarding Purkinje cells' morphology and density. In the present study we aim to review the literature on the main neuropathological findings in ET brains.

Effectiveness of physiotherapy rehabilitation approaches for Parkinson's disease: A Durrës case study.

BACKGROUND AND PURPOSE: The article's significance lies in the substantial rise in the risk of developing Parkinson's disease (PD), necessitating the exploration of various approaches to rehabilitation and medical treatment. The purpose of the article is to detect the direct effect of physiotherapy for patients with PD and to identify how it helps in slowing down cardio-pulmonary failure, improving the posture, balance, bradykinesia and tremor. METHODS: The research utilised clinical data from 407 PD patients aged 30-100 years at the Central Polyclinic of Durrës, spanning 2011-2022, and included a systematic literature review and statistical analysis comparing physiotherapy outcomes with European Union standards. RESULTS: The research demonstrates the efficiency of physiotherapy in the short and long term in the treatment of PD for patients and medical personnel. All information can be used to increase the functional abilities of patients and minimise complications after physiotherapy and to estimate the effectiveness of different exercises in delaying PD. Older adults, particularly those aged 71-80, are most affected by PD, with males more likely to be diagnosed. Physiotherapy rehabilitation improves motor symptoms, posture, and balance in 30-80-year-olds, but its effectiveness declines with age. Advanced rehabilitation methods in Italy lead to better outcomes, suggesting the potential for improvement in Durres disease. CONCLUSIONS: The study emphasises the need for improved rehabilitation strategies for older patients by recommending tailored programs, advanced methods, standardisation, training, and long-term monitoring. Further research should concentrate on the long-term sustainability of physiotherapy benefits, the development of targeted interventions for older patients, and the integration of innovative therapeutic approaches.

Effects on Gait and Balance of VIM Gamma Knife Radiosurgery in Essential Tremor.

INTRODUCTION: Essential tremor (ET) is the most common movement disorder, characterized by an action tremor in the upper limbs. Neurosurgical techniques targeting the thalamic ventrointermediate nucleus (VIM) including thermocoagulation demonstrated a potential risk for gait and posture worsening. This study evaluates the potential effect of VIM Gamma Knife radiosurgery (GKR) in ET on gait and posture performances. METHODS: We conducted a prospective study to quantitatively assess gait and balance in severe ET patients before and 1 year after unilateral GKR. Seventy-three patients were included in this series. RESULTS: First, we confirmed the unilateral GKR efficacy in severe ET patients: global tremor score and impairments in activities of daily living improved, respectively, by 67% and 71.7%. The global gait and posture analysis found no significant differences before and 1 year after GKR. Three patients (4.1%) developed mild to moderate gait and posture impairment with proprioceptive ataxia. All of these AEs were induced by a hyper-response to radiosurgery. CONCLUSIONS: Gait and posture performances were not statistically significant at the population. Nevertheless, gait and posture worsened in 4% of patients after GKR, all in the setting of hyper-response. This study shows that GKR may be a safe neurosurgical alternative to improve ADL in a population of patients with TE.

Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor.

BACKGROUND: There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD). OBJECTIVE: Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET. METHODS: We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients. RESULTS: The post-MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (ppermute < 0.05), with peak TDPD improvement (87%) at x = -13.5; y = -15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder-specific voxel-wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R2 = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R2 = 0.53; P = 0.025-voxel analysis). CONCLUSION: We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep brain stimulation for essential tremor in patients with ventriculomegaly.

Background: Deep brain stimulation of the nucleus ventralis intermedius (VIM-DBS) is considered a safe and effective treatment for medically intractable essential tremor (ET). However, ventriculomegaly can provide a surgical challenge, as there is an increased risk of breaching the ventricle during the procedure, with potential risk of intraventricular hemorrhage and target displacement. Case Description: In this case series, we report successful bilateral VIM-DBS in a 72-year-old and 69-year-old female ET patient with significant ventriculomegaly. VIM-DBS therapy provided an excellent tremor response. After 5 years, a ventriculoperitoneal shunt was implanted in the first patient due to an incomplete Hakim-Adams triad, with significant improvement in gait and cognition. Conclusion: To the best of our knowledge, we present the first report on VIM-DBS in ET patients with ventriculomegaly and illustrate that VIM-DBS can provide an excellent tremor response in patients with medically intractable ET, even in the context of marked ventriculomegaly.

Research hotspots and frontiers of essential tremor from 2013 to 2023: a visualization analysis based on CiteSpace.

Background: ET, one of the most prevalent neurological disorders, presents a significant challenge in terms of disability. Despite the growing focus on ET in recent years, comprehensive bibliometric analysis has been lacking. Methods: This study delves into essential tremor research covering the period from 2013 to 2023, utilizing the Web of Science (WOS) database. Employing CiteSpace for quantitative analysis, it examines an array of metrics including annual publication trends, contributions from countries and institutions, authorship patterns, key terminologies, and patterns of reference co-citation. The primary objective is to use CiteSpace for a detailed visual exploration of the literature over the last decade, pinpointing the evolving landscape and key areas of focus in essential tremor research, and thus providing a foundation for future investigative endeavors. Results: There were 2,224 literary works included in all. The amount of published works has been steadily rising in recent years. Of them, the majority originate from the United States, Louis, Elan D. is the publisher of the most publications (161 articles), and Movement Disorders is the journal that receives the most citations. The key words contribution and co-cited literatures suggest that the main research hotspots in recent years are the physiological and pathological mechanism of essential tremor, the determination of optimal targets for deep brain stimulation (DBS) and surgery transcranial magnetic resonance-guided focused ultrasound (MRgFUS) in the surgical management of essential tremor and the innovative research of botulinum toxin administration method.

Enhancing the understanding of coinfection outcomes: Impact of natural atypical porcine pestivirus infection on porcine reproductive and respiratory syndrome in pigs.

Atypical porcine pestivirus (APPV) is a novel member of the Pestivirus genus detected in association with congenital tremor (CT) type A-II outbreaks and from apparently healthy pigs, both as singular infection and as part of multi-pathogen infections. 'Classical' pestiviruses are known to cause immunosuppression of their host, which can increase susceptibility to secondary infections, severely impacting health, welfare, and production. To investigate APPV's effect on the host's immune system and characterise disease outcomes, 12 piglets from a natural APPV CT type A-II outbreak were experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV), a significant porcine pathogen. Rectal temperatures indicating febrile responses, viremia and viral-specific humoral and cellular responses were assessed throughout the study. Pathological assessment of the lungs and APPV-PRRSV co-localisation within the lungs was performed at necropsy. Viral co-localisation and pathological assessment of the lungs (Immunohistochemistry, BaseScope in situ hybridisation) were performed post-mortem. APPV status did not impact virological or immunological differences in PRRSV-infected groups. However, significantly higher rectal temperatures were observed in the APPV+ve/PRRSV+ve group over four days, indicating APPV increased the febrile response. Significant differences in the lung consolidation of the apical and intermediate lobes were also present, suggesting that APPV co-infection may augment lung pathology.