Malar rash and hand tremor in early symptoms of cerebrotendinous xanthomatosis and the effect of chenodeoxycholic acid on them.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare but treatable lipid storage disease resulting from mutations in the CYP27A1 gene. PURPOSE: The study aims to evaluate patients diagnosed with CTX and reveal new information, especially about the signs of CTX and patients' response to the treatment. METHODS: The study was conducted retrospectively in 12 definitively diagnosed CTX patients. The patients' clinical, laboratory, imaging, genetic findings, and chenodeoxycholic acid (CDCA) treatment results were analyzed. RESULTS: The median age at diagnosis for the patients was 16.5 years (minimum-maximum: 7-32). Juvenile cataracts, detected in more than 90% (11/12) of the patients, were the most common clinical finding. Malar rash, not previously reported in the literature for CTX, was present in 75% (9/12) of the patients. Hand tremors, the first neurological symptom, occurred in adolescence and were the initial symptom of the disease in five patients. Hand tremors were present in 83.3% (10/12) of the patients. Hand tremors (in 5 patients) and malar rash (in 2 patients) were clinical findings with full recovery due to the CDCA treatment. CONCLUSION: The study defines the malar rash finding, which has not been reported in the literature before, as a possible new clinical finding in CTX disease, attributed to its partial or full recovery with CDCA treatment. Additionally, as a novelty in the literature, our study highlights the full recovery of neurological findings, such as hand tremors, in CTX. Patients presenting with hand tremors and malar rash, especially in adolescence, should undergo CTX investigation for early diagnosis and treatment.

Comparative Effectiveness of Transcutaneous Afferent Patterned Stimulation Therapy for Essential Tremor: A Randomized Pragmatic Clinical Trial.

Background: Transcutaneous afferent patterned stimulation (TAPS) is a wrist-worn, non-invasive therapy delivering calibrated stimulation to the median and radial nerves. Previous randomized controlled studies have demonstrated the efficacy and safety of TAPS therapy in some patients with essential tremor (ET), but evidence supporting therapeutic benefits of TAPS versus standard of care (SOC) is lacking. This randomized prospective study evaluated the clinical benefit of adding TAPS treatment to SOC versus SOC alone. Methods: This randomized pragmatic trial recruited patients from a large health plan's Commercially Insured and Medicare Advantage population. All 310 patients received a TAPS device and were randomized 1:1 to either one month adding TAPS therapy to usual care (TX arm) or usual care with tremor assessment only (SOC arm). The pre-specified endpoints were changes in tremor power measured by motion sensors on the device (primary) and improvement in Bain & Findley Activities of Daily Living (BF-ADL) upper limb scores (secondary) between TX and SOC in all patients who completed the one-month study. Results: 276 patients completed the one-month study (N = 133 TX, N = 143 SOC). The study met the primary and secondary endpoints, with significantly reduced tremor power in TX compared with SOC (0.017 (0.003) versus 0.08 (0.014) (m/s2)2; geometric mean (SE); p < 0.0001) and greater improvement in the BF-ADL score in TX than SOC (1.6 (0.43) vs 0.2 (0.37) points; mean (SE); p < 0.05). No serious device-related adverse events were reported. Discussion: This trial demonstrates that adding TAPS treatment to SOC significantly improves tremor power and BF-ADLs in patients with ET compared to SOC alone over one month of home use. Highlights: This study found that adding TAPS treatment to SOC significantly improves tremor power and BF-ADL scores in patients with ET compared to SOC alone over one month of home use. This real-world evidence study suggests that non-invasive TAPS therapy is a safe and valuable treatment option for patients with ET.

FiMec tremor stabilization spoon: design and active stabilization control of two DoF robotic eating devices for hand tremor patients.

This article is about vibration-damping robotic eating devices designed for use by people who have difficulty in eating due to hand tremors due to neuromuscular system disorder. The robotic eating device has two degrees of freedom (DoF). It contains an active controller structure to absorb vibrations in the y- and z-directions. In the handle part of the robotic eating device, there are two DC motors placed on the y- and z-axis, a three-axis IMU inertia sensor, an embedded system board, and a power unit. To absorb the vibration measured from the IMU sensor, the position control of the two motors to which the spoon is connected is provided by PID controllers. The part of the spoon (the pit surface) where the food is placed is tried to be kept constant. To test the vibration-damping performance of the control method, the dynamic model of the spoon along the eating kinematic trajectory was simulated in the SimMechanics environment using vibration data from ten tremor patients. The results show that the stabilization method can absorb the vibration in the hand of the person in the range of 84-99.409% and successfully provide the stabilization of the spoon tip. This damping rate is promising for providing a healthy diet for hand tremor patients.

Exploring the heterogeneous morphometric data in essential tremor with probabilistic modelling.

Essential tremor (ET) is a prevalent movement disorder characterized by marked clinical heterogeneity. Here, we explored the morphometric underpinnings of this cross-subject variability on a cohort of 34 patients with right-dominant drug-resistant ET and 29 matched healthy controls (HCs). For each brain region, group-wise morphometric data was modelled by a multivariate Gaussian to account for morphometric features' (co)variance. No group differences were found in terms of mean values, highlighting the limits of more basic group comparison approaches. Variance in surface area was higher in ET in the left lingual and caudal anterior cingulate cortices, while variance in mean curvature was lower in the right superior temporal cortex and pars triangularis, left supramarginal gyrus and bilateral paracentral gyrus. Heterogeneity further extended to the right putamen, for which a mixture of two Gaussians fitted the ET data better than a single one. Partial Least Squares analysis revealed the rich clinical relevance of the ET population's heterogeneity: first, increased head tremor and longer symptoms' duration were accompanied by broadly lower cortical gyrification. Second, more severe upper limb tremor and impairments in daily life activities characterized the patients whose morphometric profiles were more atypical compared to the average ET population, irrespective of the exact nature of the alterations. Our results provide candidate morphometric substrates for two different types of clinical variability in ET. They also demonstrate the importance of relying on analytical approaches that can efficiently handle multivariate data and enable to test more sophisticated hypotheses regarding its organization.

Computational study and validation of a novel passive hand tremor attenuator.

Tremors are a prevalent movement disorder due to a nervous system condition that leads to involuntary muscle movements observed in patients. This paper converts the tremorous anatomical human arm model to a single degree of freedom (SDOF) forced vibration problem. The mathematical modelling with Euler-Lagrange's equation is performed for the SDOF human arm model with two different potential vibration absorbers. A computational study is conducted on MATLAB Simulink by MathWorks Inc. (Natick, MA) to compare two absorbers, and the results are verified on the multibody dynamics simulation solution software, MSC Adams by Hexagon AB. It is concluded that the T beam-shaped vibration absorber represented a higher amplitude reduction, up to 80%, compared to the inertial mass absorber, which had an amplitude reduction of 65% over the range of frequencies. Experiments conducted with the T beam absorber prototype also support the computational findings. Future research focuses on designing an ergonomic wearable device with a proposed T-beam absorber that can passively attenuate the tremor at various frequencies.

Osmotic Demyelination Syndrome in a Patient With Tremors.

Osmotic demyelination syndrome is a neurological disorder caused by damage to the myelin sheath of brain cells secondary to rapid correction of hyponatremia. Clinical features are variable depending on the location of demyelination, with diagnosis confirmed by MRI. Once diagnosed, treatment is supportive. We present a 49-year-old female recently discharged from an outside hospital who presented with symptoms of tremors, ataxia, slurred speech, and confusion. The patient was diagnosed with osmotic demyelination syndrome based on the classic trident sign on MRI imaging. A review of her records showed rapid correction of serum sodium during her initial hospital visit.

Association of Diet With Essential Tremor: A Narrative Review.

Essential tremor is a neurological disorder categorized by the rhythmic shaking of the upper limbs, lower limbs, neck, or head. The etiology of essential tremor is believed to be genetic variations, environmental factors, lifestyle, etc. Poor lifestyle and diet are important factors contributing to the onset of various disorders. Environment and lifestyle play a significant part in the dietary habits of an individual. Some diet components may probably be associated with the etiopathogenesis or progression of the essential tremor. Dietary habits may be a key influence on the commencement of tremors in healthy individuals. Typically, the diet of essential tremor patients is not supervised. It may also intensify the tremors in essential tremor patients. Association of the diet with the essential tremor can shed light on the root of tremor aggravating aspect and aid in diet modification in essential tremor patients. The aim of the review is to establish a relation between the diet with etiopathogenesis and the progression of essential tremor. The review includes studies providing information about essential tremor and correlating essential tremor with diet, lifestyle, environment, and genetic factors. Studies that did not provide a link to the association of essential tremor were excluded. The interpretation of the research indicated that genetic variations might be triggered due to enzymatic changes triggered by dietary patterns. Dietary components showed ambiguous, weak, strong, or no association. Essential tremor may be influenced by diet. Further research must be carried out on essential tremor patients in the nutritional domain. Physicians may monitor the diet of the essential tremor patients and record the progress of the disorder on its basis to manage the patients with essential tremor and provide better services.

Using Deep Learning for Task and Tremor Type Classification in People with Parkinson's Disease.

Hand tremor is one of the dominating symptoms of Parkinson's disease (PD), which significantly limits activities of daily living. Along with medications, wearable devices have been proposed to suppress tremor. However, suppressing tremor without interfering with voluntary motion remains challenging and improvements are needed. The main goal of this work was to design algorithms for the automatic identification of the tremor type and voluntary motions, using only surface electromyography (sEMG) data. Towards this goal, a bidirectional long short-term memory (BiLSTM) algorithm was implemented that uses sEMG data to identify the motion and tremor type of people living with PD when performing a task. Moreover, in order to automate the training process, hyperparamter selection was performed using a regularized evolutionary algorithm. The results show that the accuracy of task classification among 15 people living with PD was 84±8%, and the accuracy of tremor classification was 88±5%. Both models performed significantly above chance levels (20% and 33% for task and tremor classification, respectively). Thus, it was concluded that the trained models, based on using purely sEMG signals, could successfully identify the task and tremor types.

Hand tremor detection in videos with cluttered background using neural network based approaches.

With the increasing prevalence of neurodegenerative diseases, including Parkinson's disease, hand tremor detection has become a popular research topic because it helps with the diagnosis and tracking of disease progression. Conventional hand tremor detection algorithms involved wearable sensors. A non-invasive hand tremor detection algorithm using videos as input is desirable but the existing video-based algorithms are sensitive to environmental conditions. An algorithm, with the capability of detecting hand tremor from videos with a cluttered background, would allow the videos recorded in a non-research environment to be used. Clinicians and researchers could use videos collected from patients and participants in their own home environment or standard clinical settings. Neural network based machine learning architectures provide high accuracy classification results in related fields including hand gesture recognition and body movement detection systems. We thus investigated the accuracy of advanced neural network architectures to automatically detect hand tremor in videos with a cluttered background. We examined configurations with different sets of features and neural network based classification models. We compared the performance of different combinations of features and classification models and then selected the combination which provided the highest accuracy of hand tremor detection. We used cross validation to test the accuracy of the trained model predictions. The highest classification accuracy for automatically detecting tremor (vs non tremor) was 80.6% and this was obtained using Convolutional Neural Network-Long Short-Term Memory and features based on measures of frequency and amplitude change.

Different effects of essential tremor and Parkinsonian tremor on multiscale dynamics of hand tremor.

OBJECTIVE: Essential tremor (ET) and Parkinsonian tremor (PT) are often clinically misdiagnosed due to the overlapping characteristics of their hand tremor. We aim to examine if ET and PT influence the multiscale dynamics of hand tremor, as quantified using complexity, differently, and if such complexity metric is of promise to help identify ET from PT. METHODS: Forty-eight participants with PT and 48 with ET performed two 30-second tests within each of the following conditions: sitting while resting arms or outstretching arms horizontally. The hand tremor was captured by accelerometers secured to the dorsum of each hand. The complexity was quantified using multiscale entropy. RESULTS: Compared to PT group, ET group had lower complexity of both hands across conditions (F > 34.2, p < 0.001). Lower complexity was associated with longer disease duration (r2 > 0.15, p < 0.009) in both PT and ET, and within PT, greater Unified Parkinson's Disease Rating Scale-III UPDRS-III scores (r2 > 0.18, p < 0.009). Receiver-operating-characteristic curves revealed that the complexity metric can distinguish ET from PT (area-under-the-curve > 0.77, cut-off value = 48 (postural), 49 (resting)), which was confirmed in a separate dataset with ET and PT that were clearly diagnosed in prior work. CONCLUSIONS: The PT and ET have different effects on hand tremor complexity, and this metric is promising to help the identification of ET and PT, which still needs to be confirmed in future studies. SIGNIFICANCE: The characteristics of multiscale dynamics of the hand tremor, as quantified by complexity, provides novel insights into the different pathophysiology between ET and PT.

Reputation-Aware Data Fusion for Quantifying Hand Tremor Severity Form Interaction with a Smartphone.

In this paper, we present an approach to improve the accuracy of hand tremor severity in Parkinson's patients in real-life unconstrained environments. The system leverages data achieved from daily interaction people with their smartphones and uses technologies for classifying and combining data. We describe the basic concept of data fusion and demonstrate how different combination techniques can improve the accuracy of tremor detection. The fusion enable to achieve the 23.5% improvement with respect to the average of individual classification models.

In Situ Tremor in Vitreoretinal Surgery.

OBJECTIVE: Surgeon tremor was measured during vitreoretinal microscopic surgeries under different hand support conditions. BACKGROUND: While the ophthalmic surgeon's forearm is supported using a standard symmetric wrist rest when operating on the patient's same side as the dominant hand (SSD), the surgeon's hand is placed directly on the patient's forehead when operating on the contralateral side of the dominant hand (CSD). It was hypothesized that more tremor is associated with CSD surgeries than SSD surgeries and that, using an experimental asymmetric wrist rest where the contralateral wrist bar gradually rises and curves toward the patient's operative eye, there is no difference in tremor associated with CSD and SSD surgeries. METHODS: Seventy-six microscope videos, recorded from three surgeons performing macular membrane peeling operations, were analyzed using marker-less motion tracking, and movement data (instrument path length and acceleration) were recorded. Tremor acceleration frequency and magnitude were measured using spectral analysis. Following 47 surgeries using a conventional symmetric wrist support, surgeons incorporated the experimental asymmetric wrist rest into their surgical routine. RESULTS: There was 0.11 mm/s2 (22%) greater (p = .05) average tremor acceleration magnitude for CSD surgeries (0.62 mm/s2, SD = 0.08) than SSD surgeries (0.51 mm/s2, SD = 0.09) for the symmetric wrist rest, while no significant (p > .05) differences were observed (0.57 mm, SD = 0.13 for SSD and 0.58 mm, SD = 0.11 for CSD surgeries) for the experimental asymmetric wrist rest. CONCLUSION: The asymmetric wrist support reduced the difference in tremor acceleration between CSD and SSD surgeries.

Smartphone-Based Monitoring of Parkinson Disease: Quasi-Experimental Study to Quantify Hand Tremor Severity and Medication Effectiveness.

BACKGROUND: Hand tremor typically has a negative impact on a person's ability to complete many common daily activities. Previous research has investigated how to quantify hand tremor with smartphones and wearable sensors, mainly under controlled data collection conditions. Solutions for daily real-life settings remain largely underexplored. OBJECTIVE: Our objective was to monitor and assess hand tremor severity in patients with Parkinson disease (PD), and to better understand the effects of PD medications in a naturalistic environment. METHODS: Using the Welch method, we generated periodograms of accelerometer data and computed signal features to compare patients with varying degrees of PD symptoms. RESULTS: We introduced and empirically evaluated the tremor intensity parameter (TIP), an accelerometer-based metric to quantify hand tremor severity in PD using smartphones. There was a statistically significant correlation between the TIP and self-assessed Unified Parkinson Disease Rating Scale (UPDRS) II tremor scores (Kendall rank correlation test: z=30.521, P<.001, τ=0.5367379; n=11). An analysis of the "before" and "after" medication intake conditions identified a significant difference in accelerometer signal characteristics among participants with different levels of rigidity and bradykinesia (Wilcoxon rank sum test, P<.05). CONCLUSIONS: Our work demonstrates the potential use of smartphone inertial sensors as a systematic symptom severity assessment mechanism to monitor PD symptoms and to assess medication effectiveness remotely. Our smartphone-based monitoring app may also be relevant for other conditions where hand tremor is a prevalent symptom.

Hand tremor suppression device for patients suffering from Parkinson's disease.

In this study, a wearable device is developed as a mechanical treatment to suppress hand tremors in people with Parkinson's disease (PwPD). The biodynamic modelling of the human hand was done by considering the hand as a primary mass-spring-damper system. Dual passive vibration absorbers have been designed to match the frequencies of tremors. The performance assessment of the device was performed using the temporal response of hand tremors. The results showed that the device reduced the amplitude of the angular movement of the wrist by 57.25%. The device fabricated in the form of a bracelet was easy to wear by PwPD when needed.

Rehabilitation of the Parkinson's tremor by using robust adaptive sliding mode controller: a simulation study.

One of the efficient methods in controlling the Parkinson's tremor is Deep Brain Stimulation (DBS) therapy. The stimulation of Basal Ganglia (BG) by DBS brings no feedback though the existence of feedback reduces the additional stimulatory signal delivered to the brain. So this study offers a new adaptive architecture of a closed-loop control system in which two areas of BG are stimulated simultaneously to decrease the following three indicators: hand tremor, the level of a delivered stimulation signal in the disease condition, and the level of a delivered stimulation signal in health condition to the disease condition. One area (STN: subthalamic nucleus) is stimulated with an adaptive sliding mode controller and the other area (GPi: Globus Pallidus internal) with partial state feedback controller. The simulation results of stimulating two areas of BG showed satisfactory performance.

Botulinum Toxin for the Treatment of Hand Tremor.

The aim of this study is to review our longitudinal experience with onabotulinumtoxinA (onaBoNT-A) injections for medically refractory hand tremor. We performed a retrospective review of our database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at least 2 sessions with follow-up. The majority were injected into the forearm flexors (FF), although treatment was individualized. During the specified period, 91 patients (53 essential tremor, 31 dystonic tremor, 6 Parkinson's disease tremor, and 1 cerebellar outflow tremor) met our inclusion criteria. The mean age (SD) was 64.8 years (12.8), and mean duration of follow-up was 29.6 months (25.1) with mean of 7.7 (6.3) treatment visits. FF were injected in 89 (97.8%) patients, exclusively in 74 (81.3%), and 15 (16.5%) were injected in FF and other muscles. EMG guidance was used in 5 patients (5.5%). On a 0⁻4 "peak effect" rating scale (0 = no effect, 4 = marked improvement in severity and function), 80.2% and 85.7% of patients reported moderate or marked improvement (score 3 or 4) at their first and last follow-up visit, respectively. There was no statistically significant difference in the outcomes between first and last visit: average "peak effect" rating score (3.2 versus 3.4), "global" rating score (3.0 versus 3.2), latency of response (4.5 versus 3.8 days), and total duration of response (12.7 versus 12.8 weeks), except onaBoNT-A dose (65.0 versus 78.6 U/limb, p = 0.002). Of 1095 limb injections, there were 134 (12.2%) non-disabling and transient (mean 36 days) adverse events (132 limb weakness, 2 pain). OnaBoNT-A injections are safe and effective in the treatment of hand tremor.

Hand Tremor Questionnaire: A Useful Screening Tool for Differentiating Patients with Hand Tremor between Parkinson's Disease and Essential Tremor.

BACKGROUND AND PURPOSE: Hand tremor is one of the most frequent symptoms in movement disorders, and differential diagnoses for hand tremor include Parkinson's disease (PD) and essential tremor (ET). However, accurately differentiating between PD and ET in clinical practice remains challenging in patients presenting with hand tremor. We investigated whether a questionnaire-based survey could be useful as a screening tool in patients with hand tremor. METHODS: A questionnaire related to hand tremor consisting of 12 items was prospectively applied to patients with PD or ET in three movement-disorder clinics. Each question was analyzed, and a query-based scoring system was evaluated for differentiating hand tremors between PD and ET. RESULTS: This study enrolled 24 patients with PD and 25 patients with ET. Nine of the 12 questions differed significantly between PD and ET: 1 about resting tremor, 4 questions about action tremor, and 4 about asymmetry. A receiver operating characteristics curve analysis revealed that the 9-item questionnaire showed a good discrimination ability, with a sensitivity of 88% and a specificity of 84%. CONCLUSIONS: The developed Hand Tremor Questionnaire might be a good screening tool for hand tremors in patients with PD and ET.

Health effects of manganese exposures for welders in Qingdao City, China.

OBJECTIVES: To document if manganese from welding causes health effects including neurological symptoms associated with manganese exposure. MATERIAL AND METHODS: An anonymous questionnaire survey for a total of 505 welders at 3 welding facilities in Qingdao City, China was administered and analyzed. RESULTS: Numerous symptoms were reported by the welders including difficulty with eyes for 43% of them, sore throat for 30% of them, and tremors were reported by over 18% of them. Tremors were associated with longer periods of work as a welder and correlated with the relative cleanliness at the 3 different facilities. Tremors did not correlate with smoking. CONCLUSIONS: Manganese-exposed welders reported a variety of symptoms related to work and showed neurological disturbances that correlated with amount of exposure. Int J Occup Med Environ Health 2017;30(2):241-247.

WITHDRAWN: Creative activity aid using active tremor cancellation.

Ahead of Print article withdrawn by publisher.

Factors affecting hand tremor and postural sway in children.

OBJECTIVES: It is crucial to consider covariates relevant for outcome variables in developing dose-effect relations of environmental hazardous toxins. The aim of this study was to clarify the covariates affecting hand tremor and postural sway in children. METHODS: Hand tremor and postural sway, as well as hair mercury concentrations, were measured in 155 boys and 148 girls at age 7 years. RESULTS: Current mercury concentrations in child hair ranged from 0.35 to 6.32 µg/g (geometric mean, 1.71 µg/g for boys and 1.58 µg/g for girls), and were not significantly correlated with the neuromotor parameters. All hand tremor and postural sway parameters, except for tremor intensity at 1-6 Hz with non-dominant hand, were significantly larger in the boys than in the girls. Using multiple regression analysis, some postural sway parameters were related negatively to age in the boys and girls (p<0.05), and positively to height (p<0.05). Similarly, hand tremor parameters were positively related to age, height and heart rate either in the boys or in the girls (p<0.05). Also, there were positive relationships between tremor intensity at 1-6 Hz and transversal and sagittal sways at 1-2 Hz and 2-4 Hz (p<0.05). CONCLUSIONS: Heart rate and postural sway, together with age, sex, and height, should be considered in interpreting hand tremor in children. Hand tremor or postural sway may not be so sensitive or specific to methylmercury exposures at levels of less than 7 µg/g in hair.