Search Results (68)

Essential tremor (ET) is a common movement disorder increasingly recognized as a complex syndrome with neurodegenerative features. While mitochondrial dysfunction and cellular aging are implicated in several neurodegenerative diseases, their role in ET remains unexplored. To investigate mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) in patients with ET and evaluate their potential as biomarkers of mitochondrial dysfunction and biological aging. In this cross-sectional case–control study, 68 ET patients (median age 66 years; 64.7% male) and 62 healthy controls (median age 70 years; 54.8% male) were enrolled. Relative mtDNA-CN and TL were quantified by quantitative PCR, measuring mitochondrial ND1 gene levels and telomere-to-single-copy gene (T/S) ratio, respectively, both normalized to β-actin. Associations with disease status were assessed using age- and sex-adjusted multivariable linear regression on log₂-transformed data, with statistical significance defined as p < 0.05 after false discovery rate (FDR)-corrected Wald tests. Receiver operating characteristic (ROC) and effect size (Cohen’s d) analyses were performed. ET patients showed significantly reduced mtDNA-CN (β = −2.785, 95% CI −3.700 to −1.869; p_FDR = 2.53 × 10⁻⁹) and TL (β = −2.073, 95% CI −2.758 to −1.388; p_FDR = 3.00 × 10⁻⁹), corresponding to ~6.9-fold and ~4.2-fold reductions, respectively. Age- and sex-stratified analyses confirmed consistent reductions, more pronounced in older individuals. Both biomarkers showed good discriminatory performance (mtDNA-CN: AUC = 0.83, 95% CI: 0.75–0.90; TL: AUC = 0.76, 95% CI: 0.68–0.85) and large effect sizes (Cohen’s d = |1.192| and |1.058|), respectively. Reduced mtDNA-CN and TL support the involvement of mitochondrial impairment and accelerated cellular aging in ET and may represent accessible peripheral biomarkers and provide a basis for future longitudinal and mechanistic investigations. Full article

Essential tremor (ET) is among the most prevalent movement disorders, causing significant impairment in manual dexterity and daily functioning. Although ET affects individuals across the lifespan, exercise intervention research has focused almost exclusively on older adults, leaving young adults, for whom early intervention may prevent long-term neuromuscular deterioration, critically underrepresented. Furthermore, the effects of strength–endurance oriented exercise combined with task-specific motor activities remain insufficiently explored in any ET population. This quasi-experimental pre-test–post-test study investigated the effects of a 6-week progressive strength–endurance and task-specific exercise program on tremor severity, manual dexterity, and upper extremity functional performance in young adult males with ET (n = 18; mean age: 22.6 ± 4.1 years). The 24-session intervention (four sessions/week) combined proximal upper extremity strength–endurance exercises with seven ADL-specific fine motor tasks. Tremor severity was assessed using the Fahn–Tolosa–Marin Tremor Rating Scale (FTMTRS), manual dexterity using the Nine-Hole Peg Test (NHPT), and upper extremity stability using the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST). The Wilcoxon signed-rank test was used for within-group comparisons, with rank biserial correlation (r) and Cohen’s d reported as effect size indices. Significant pre-to-post improvements were observed across nearly all outcome measures, with medium-to-large effect sizes. Spiral drawing performance improved significantly in five of six conditions (r = 0.47–0.62), with the exception of the Spiral left–B task (p = 0.083). Postural tremor, NHPT (both hands), and CKCUEST also showed significant improvements (r = 0.47–0.73). A composite tremor score, integrating all tremor sub-scores, demonstrated a 14.1% overall reduction (p = 0.001, r = 0.83), providing strong evidence of program-wide effectiveness. Session adherence was 95.8%. To our knowledge, this is one of the first studies to show that a structured strength–endurance and task-specific exercise program was associated with reductions in tremor severity and improvements in upper extremity function, specifically in young adults with ET. These findings support the clinical utility of exercise as a non-pharmacological intervention in this underserved population and highlight the importance of early, targeted intervention during young adulthood. Full article

Background: Essential tremor (ET) is increasingly recognized as a heterogeneous disorder that may present with additional Parkinsonian or cerebellar features, complicating its differential diagnosis from Parkinson’s disease (PD) and degenerative ataxias (DA). Oculomotor assessment has been proposed as a potential tool for identifying disease-specific patterns. Methods: We evaluated eye movement parameters in 50 patients with ET (including subgroups with Parkinsonian and/or cerebellar signs), 50 patients with PD, 42 patients with DA, and 42 healthy controls. Reflexive, pace-induced, and cued saccades were recorded using saccadometry, while smooth pursuit and fixation were assessed with electrooculography. Group comparisons focused on saccadic metrics and the frequency of abnormalities. Results: Hypometria of pace-induced saccades was observed in patients with PD (32.0%) and DA (57.1%) but was not detected in any ET subgroup, including those with Parkinsonian or cerebellar features. Reflexive saccade hypometria was less frequent in ET patients with Parkinsonian features compared to PD (50.0% vs. 66.0%, p = 0.016). Other oculomotor parameters showed substantial overlap between groups. Conclusions: ET patients, including those with additional Parkinsonian or cerebellar signs, showed partially distinct oculomotor features compared with PD and DA, particularly in pace-induced saccades. These findings require confirmation in larger, well-characterized cohorts. Full article

Background: Essential tremor (ET) is a clinically heterogeneous disorder involving motor and non-motor features. Voluntary movement abnormalities, including movement slowness (bradykinesia), have been frequently described in ET. Among non-motor symptoms, insomnia is also frequently reported, raising the possibility of shared underlying mechanisms with bradykinesia (e.g., brainstem noradrenergic dysfunction involving the locus coeruleus due to Lewy body pathology). We investigated the relationship between movement abnormalities, as objectively quantified using finger-tapping kinematic analysis, and sleep disturbances in ET. Methods: A subsample of 29 ET patients included in a previous study underwent kinematic analysis of finger-tapping. Insomnia was evaluated using the Insomnia Severity Index (ISI). Patients were stratified according to the presence of bradykinesia (e.g, movement slowness during finger-tapping) and insomnia (ISI ≥ 8). Group comparisons and correlational analyses were performed to assess the association between kinematic measures of bradykinesia, insomnia severity and other clinical features. Results: Fourteen subjects (48.3%) exhibited bradykinesia on kinematic analysis, and eleven patients (37.9%) met the criteria for insomnia. The prevalence of insomnia was similar between patients with and without bradykinesia. Likewise, no significant differences in finger-tapping kinematics were observed between ET patients with and without insomnia. Kinematic measures of bradykinesia did not correlate with ISI scores (all p > 0.05), whereas ISI scores were significantly positively correlated with clinical tremor severity. Conclusions: The current kinematic analysis suggests no relationship between movement abnormalities and sleep disturbances in ET. While bradykinesia in ET possibly relies on the dysfunction of cerebellar–basal ganglia circuits, insomnia in ET may reflect prominent brainstem dysfunction. Larger studies integrating kinematic assessments, neuroimaging, and longitudinal designs are needed to clarify the relationship between movement and sleep disturbances in ET Full article

Background: Essential tremor (ET) is a common movement disorder that predominantly affects older adults, with rising global prevalence due to population aging. Pharmacological treatments, including propranolol and primidone, are often limited by inadequate efficacy or poor tolerability, and surgical options carry inherent risks. Acupuncture has shown promise as an alternative or adjunctive therapy for ET, but evidence comparing the effectiveness of different acupuncture modalities remains limited. Objective: To systematically evaluate the comparative efficacy and safety of various acupuncture-related interventions for essential tremor (ET) through a network meta-analysis, and to provide evidence-based recommendations for clinical practice. Methods: We systematically searched eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM) from inception to 20 October 2025. Randomized controlled trials (RCTs) evaluating any form of acupuncture therapy for ET were included. Conventional pairwise meta-analysis and network meta-analysis were performed to compare the efficacy (response rate, Tremor Six Score) and safety (adverse events) of different interventions. Surface under the cumulative ranking curve (SUCRA) values were used to rank treatment modalities. Results: Twenty randomized controlled trials involving 1067 participants were included. Traditional meta-analysis indicated that acupuncture-related interventions significantly outperformed controls in improving response rate [RR 4.36, 95% CI (3.14, 6.03), p < 0.00001], reducing Tremor Six Score [MD −1.99, 95% CI (−2.25, −1.73), p < 0.00001], and lowering the incidence of adverse events [RR 0.13, 95% CI (0.07, 0.25), p < 0.00001]. Network meta-analysis based on SUCRA values revealed that: for symptom relief, scalp acupuncture (S) demonstrated the highest effectiveness (SUCRA = 81.5%); for reducing Tremor Six Score, manual acupuncture (A) showed the most significant effect (SUCRA = 76.6%); and for safety outcomes, Acupuncture + Scalp Acupuncture + Propranolol (A+S+P) achieved the highest SUCRA score (SUCRA = 73.1%). Conclusions: This network meta-analysis demonstrates that acupuncture-related interventions are effective and safe for treating essential tremor. However, caution is warranted in interpreting these findings due to methodological limitations in the included randomized controlled trials (small sample sizes, lack of blinding, inadequate allocation concealment), sparse data for some interventions, and the concentration of studies within China, which limits their generalizability. Despite these limitations, acupuncture offers a valuable non-pharmacological treatment option for patients with poor medication tolerance. Future large-scale, multicenter trials with rigorous designs are needed to validate these findings. Full article

Background/Objectives: This study aimed to describe temporal trends in deep brain stimulation (DBS) use for Parkinson’s disease (PD), essential tremor (ET), and dystonia; characterize patient age and sex distribution and comorbidity; assess postoperative complications and in-hospital mortality (IHM) after implantation and explantation; and explore sex-specific differences in utilization and outcomes. Methods: We conducted a retrospective nationwide population-based study using the Spanish National Hospital Discharge Database (RAE-CMBD) from 2002 to 2019. All hospital admissions with DBS implantation or explantation/revision and a diagnosis of PD, ET, or dystonia were identified. Sociodemographic variables, the Charlson Comorbidity Index (CCI), length of hospital stay (LOHS), postoperative complications, and IHM were analyzed across three calendar periods and stratified by diagnosis and sex. Results: A total of 4883 admissions for DBS electrode implantations and 497 admissions for DBS explantation/revision were recorded. PD accounted for 82.6% of implantations, followed by ET (11.2%) and dystonia (6.3%). DBS activity increased significantly over time, while median LOHS declined from 12 to 6 days for implantations and from 13 to 5 days for explantations. Overall IHM after implantation was 0.27%, decreasing to 0.05% in 2014–2019; IHM after explantation was 0.6%. Most hospitalizations had low comorbidity (CCI = 0 in 87.8%), although comorbidity increased over time. Men represented approximately 60% of procedures in PD and ET. Women with PD underwent DBS at older ages, despite similar LOHS and IHM. Postoperative complications were recorded in 14.6% of implantations, mainly hardware-related issues (5–6%) and infections (1–2%), whereas infections (33%) and mechanical problems (27%) predominated among explantations. Conclusions: DBS use in Spain has expanded substantially, with shorter hospital stays and very low in-hospital mortality. Sex-related differences in utilization are increasing, and hardware complications and infections remain the most frequent conditions associated with explantation. As complications were identified only during the same hospitalization as the DBS procedure, late post-discharge events are not captured and could be underestimated; patient-level risks cannot be derived. Full article

Background and Objectives: Essential tremor (ET) is the most prevalent movement disorder, yet its neurophysiological basis remains incompletely understood. Emerging evidence indicates that ET may involve non-motor manifestations, including auditory dysfunction. Given the anatomical convergence of tremor-related and auditory pathways at the brainstem level, electrophysiological assessment of the auditory system may provide insights into ET pathophysiology. This study aimed to evaluate auditory pathway function in patients with essential tremor using conventional audiometry, brainstem auditory evoked potentials (BAEP), and medium-latency auditory evoked potentials (MLAEP), and to examine their associations with tremor characteristics. Materials and Methods: Thirty patients with ET (mean age 56.6 ± 19.2 years; 15 women) and 30 healthy controls with similar age and sex distribution underwent pure-tone audiometry, BAEP, and MLAEP recordings. Tremor severity and distribution were assessed using a standardized evaluation based on the Fahn–Tolosa–Marin Tremor Rating Scale. Results: Conventional audiometry demonstrated normal hearing thresholds in 63.3% of ET patients and 83% of controls, while sensorineural hearing loss was observed in 36.6% and 16.6%, respectively (p > 0.05). High-frequency hearing loss (HFHL) was significantly more prevalent in the ET group (p = 0.003). BAEP analysis revealed significant prolongation of peak latencies in right-sided waves II and III and left-sided waves I and II in ET patients compared with controls (p < 0.05), whereas interpeak latencies (I–III, III–V, I–V) did not differ between groups. MLAEP latencies (Na, Pa, Nb) showed no significant differences between ET patients and controls (all p > 0.05) and were not associated with tremor severity, disease duration, or hearing asymmetry. Conclusions: High-frequency hearing loss is more prevalent in essential tremor, and selective BAEP latency changes observed in the context of preserved interpeak intervals suggest predominantly delayed peripheral auditory input rather than a primary brainstem conduction abnormality. Preserved MLAEP responses indicate relative sparing of thalamocortical auditory processing, supporting the concept of essential tremor as a multisystem network disorder in which altered auditory input may interact with broader network-level mechanisms. Full article

Essential tremor (ET) negatively affects neuromuscular control and hand function in older adults. Resistance exercise may enhance musculoskeletal and functional capacity, yet its modality-specific effects in ET remain unclear. This study compared the effects of home-based and aquatic resistance training on tremor severity, manual dexterity, and handgrip strength in older adults with ET. Twenty-seven participants were randomly assigned using block randomization to a home-based resistance exercise group (HBREG; n = 9), an aquatic resistance exercise group (AREG; n = 9), or a control group (CG; n = 9). Both intervention groups completed an 18-session resistance exercise program, with initial sessions supervised and subsequent sessions performed independently under regular monitoring. Tremor severity (FTMTRS), manual dexterity (Nine-Hole Peg Test), and handgrip strength were assessed pre- and post-intervention. Within-group changes were analyzed using the Wilcoxon signed-rank test and between-group differences using the Kruskal–Wallis test with Bonferroni-adjusted Mann–Whitney U tests (p < 0.05). Both HBREG and AREG demonstrated significant improvements in drawing and pouring tremor tasks, manual dexterity, and handgrip strength compared with the control group, with large effect sizes across outcomes. No significant differences were observed between the two exercise modalities, and no improvement occurred in the highest-difficulty spiral-B task. These findings indicate that both home-based and aquatic resistance training are safe and effective non-pharmacological strategies for reducing tremor severity and enhancing upper-extremity function in older adults with ET. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

Background: Essential tremor (ET) is among the most common neurological disorders, requiring precise diagnosis and severity assessment for personalized and effective management. Methods: This study explores an innovative approach to evaluate ET severity using the gold-standard Archimedes spiral test. The family-based dataset covers the entire range of tremor severity, from very mild (level 1) to advanced stages, offering a valuable resource for studying early diagnosis and tracking disease progression. The proposed method introduces a machine learning pipeline that combines Principal Component Analysis (PCA), linear discriminant analysis (LDA), and support vector machines (SVMs) to classify ET severity based on Archimedean spiral radius data. Results: By incorporating the Fahn–Tolosa–Marin Tremor Rating Scale (FMT-TRS), the pipeline effectively distinguishes between tremor presence and severity. Its robustness was demonstrated through rigorous cross-validation and tests involving Gaussian noise perturbations. Conclusions: These results underscore the machine learning-based pipeline’s potential as a non-invasive and trustworthy diagnostic tool for clinical use and telemedicine applications. Moreover, the combination of geometric features, FMT-TRS scores, clinically oriented evaluation metrics, and classical statistical and machine learning models offers a robust, interpretable, explainable, and clinically meaningful analytical framework. Full article

Background: Differentiating Parkinson’s disease (PD) from essential tremor (ET) is often challenging, especially in early or atypical cases. Dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with ¹²³I-Ioflupane supports diagnosis, and semi-quantitative tools such as DaTQUANT^® and BasGanV2™ provide objective measures. This study compared their diagnostic performance when integrated with supervised machine learning. Methods: We retrospectively analysed ¹²³I-Ioflupane SPECT scans from 169 patients (133 PD, 36 ET). Semi-quantitative analysis was performed using DaTQUANT^® v2.0 and BasGanV2™ v.2. Classification tree (ClT), k-nearest neighbour (k-NN), and support vector machine (SVM) models were trained and validated with stratified shuffle split (250 iterations). Diagnostic accuracy was compared between the two software packages. Results: All classifiers reliably distinguished PD from ET. DaTQUANT^® consistently achieved higher accuracy than BasGanV2™: 93.8%, 93.2%, and 94.5% for ClT, k-NN, and SVM, respectively, versus 90.9%, 91.7%, and 91.9% for BasGanV2™ (p < 0.001). Sensitivity and specificity were also consistently higher for DaTQUANT^® than BasGanV2. Class imbalance (PD > ET) was addressed using Synthetic Minority Over-sampling Technique (SMOTE). Conclusions: Machine learning analysis of ¹²³I-Ioflupane SPECT enhances differentiation between PD and ET. DaTQUANT^® outperformed BasGanV2™, suggesting greater suitability for AI-driven decision support. These findings support the integration of semi-quantitative and AI-based approaches into clinical workflows and highlight the need for harmonised methodologies in movement disorder imaging. Full article

Background/Objectives: Essential tremor (ET) is the most common movement disorder worldwide. It negatively affects patients’ activities of daily living (ADL) and quality of life. Unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy has been proven as a highly effective and safe treatment option for patients with refractory ET. The aims of this study are to explore the effectiveness and safety of tcMRgFUS thalamotomy in patients with ET in a real-world setting. Methods: Patients who underwent tcMRgFUS thalamotomy at the University Hospital of Palermo were prospectively enrolled. Scores obtained by Quality of Life in Essential Tremor Questionnaire (QUEST) and The Essential Tremor Rating Assessment Scale (TETRAS) were compared before and after tcMRgFUS thalamotomy. Predictors of tcMRgFUS thalamotomy effectiveness were explored by multivariable Cox regression analyses. All the adverse events (AEs) during and after the procedure were collected. Results: Fifty patients were included (80% male; median age at tcMRgFUS 67.4 years). After procedure, the QUEST score decreased by 46.2%, while TETRAS-ADL and TETRAS Performance (TETRAS-PE) decreased by 52.2% and 51.8%, respectively. Temperature peak and longitudinal lesion diameter positively correlated with the magnitude of QUEST and TETRAS-PE reduction. A higher baseline TETRAS-PE score predicted a good prognosis (HR = HR 6.6 [95% CI: 2.1–21.3]; p = 0.001). AEs were mild to moderate and transient, while permanent AE was observed only in one case. Conclusions: This real-world study confirms the higher effectiveness and the favorable safety profile of tcMRgFUS thalamotomy in patients with ET by reducing the tremor-related interference in quality of life, disability in ADL, and tremor severity. Full article

Background and Objectives: Essential tremor (ET) is a common neurological disorder, typically presenting as bilateral, rhythmic, and symmetric kinetic or postural tremors. In contrast, Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia, and postural instability. Although both disorders involve tremor, ET and PD differ in clinical presentation and pathophysiology: ET generally involves action tremor and has a strong familial component, while PD more commonly presents with resting tremor and a weaker family history. A subset of ET patients may develop Parkinsonian features over time, although the relationship between ET and subsequent PD remains unclear. Genetic studies have identified only a few pathogenic variants in ET, suggesting it develops as a result of multifactorial genetic and environmental influences rather than simple Mendelian inheritance. ET is also recognized as a risk factor for developing PD, although the underlying mechanisms remain poorly understood. This study aimed to clarify potential genetic overlaps and distinctions in patients diagnosed with both ET and PD. Materials and Methods: We retrospectively analyzed 40 patients with a family history of ET or PD who were initially diagnosed with ET and later developed PD. Genetic screening and clinical assessments were conducted to investigate associated variants and clinical features. Results: Among these 40 patients, 17 different mutations were detected in 16 individuals. Three pathogenic or likely pathogenic variants were identified. The clinical characteristics and treatment responses of these patients were reviewed in relation to their genetic findings. Notably, none of the identified variants had previously been reported in association with PD following ET. Conclusions: A comprehensive clinical and genetic evaluation of ET patients who develop PD may offer insights into the underlying pathophysiology and inform future therapeutic strategies. Our findings support the need for further studies to explore the genetic landscape of patients with overlapping ET and PD features. Full article

Clinical differentiation between Parkinson’s disease (PD) and essential tremor (ET) may be challenging, highlighting the need for easily assessable diagnostic biomarkers. Neuronally derived extracellular vesicles (NDEVs) have been proposed as a peripheral matrix that can well recapitulate the cellular composition of neurons. We investigated the clinical usefulness of NDEV oligomeric and p129-α-synuclein levels in discriminating between patients with PD and those with ET. NDEV oligomeric and p129-α-synuclein species were assessed using an ELISA in 43 patients with PD, 21 patients with ET, and 45 healthy controls (HCs). NDEV oligomeric α-synuclein levels were significantly higher in PD in comparison with ET and HCs, while p129-α-synuclein values were significantly lower in HCs compared to other groups. By using a receiver operator characteristic (ROC) analysis, oligomeric-α-synuclein achieved an excellent classification performance in distinguishing PD from both ET and HCs (AUC: 0.976 and 0.997, respectively), while lower performance was obtained in differentiating ET from HCs (AUC: 0.85). On the other hand, p129-α-synuclein accurately discriminated both PD and ET from HCs (AUC: 0.997 and 0.952, respectively) but had very low performance in differentiating PD from ET (AUC: 0.47). Our study suggests that NDEV oligomeric α-synuclein is an accurate blood-derived biomarker to differentiate PD from ET, while p129-α-synuclein may be useful in distinguishing ET from HCs. Full article

Background: As the number of individuals diagnosed with neurodegenerative disorders (NDs) rises, there is a growing need to enhance both the quantity and quality of approaches used to treat these debilitating conditions. The progression of NDs can cause muscle weakness in the lower or upper limbs. We particularly focus on the area of the upper limb, specifically grip rehabilitation, by developing a system (VRGrip) that can reliably record electromyography (EMG) events of the hand flexor muscles to control an adaptive and engaging game using grip exertion. The purpose of this study was to determine the feasibility of using the VRGrip system. Methods: We prototyped a three-component wearable system consisting of an e-textile forearm band (E-band), data acquisition module (DAM), and a computer game. This allows participants to play a game by squeezing their dominant hand. A feasibility study was completed with 9 individuals who self-reported an ND (including Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Charcot–Marie–Tooth disease (CMT), spinal muscular atrophy (SMA), and essential tremor (ET)) and 12 individuals who self-reported to be relatively healthy (RH). Each participant completed 15 min of gameplay (three trials of five minutes), where they would squeeze a resistive ball to trigger in-game actions. The user experience was then evaluated via a User Satisfaction Evaluation Questionnaire (USEQ; scored 0–30, with 30 being best). Results: Analysis of the grip detection reliability during the feasibility study resulted in an F1 score of 0.8343 ± 0.1208 for the healthy participant group and 0.8401 ± 0.1034 for the ND participant group. The USEQ (Avg. score: 4.65 ± 0.51) indicated that participants found the system comfortable, engaging, and enjoyable. Additionally, we potentially identified age-related changes in muscle fatigue. Conclusion: The results of this study demonstrate that our VRGrip system could be used for hand grip detection in a virtual environment. In the future, we aim to conduct longitudinal studies to determine if repeated use of the system has merit for grip rehabilitation. Full article