Background: Differentiating essential tremor (ET) and functional tremor (FT) remains challenging due to their overlapping clinical presentations. Objective: In this study, we aimed to elucidate the demographic and psychometric differences between the aforementioned tremor types to enhance the diagnostic accuracy and therapeutic strategies. Methods: In this prospective study, we included 96 patients diagnosed with ET or FT and analysed their related demographic data, clinical symptoms, and psychometric evaluation scores. Our statistical analysis involved Pearson’s chi-square tests, Fisher’s exact tests, and logistic regression to assess how the different variables impact tremor diagnosis. Results: Our study demonstrated a higher ET prevalence in males (p = 0.015). Furthermore, we demonstrated that patients with ET displayed a significantly lower body mass index and a lower age of onset compared to those with FT (p = 0.050 and p = 0.023, respectively). Our psychometric assessments revealed higher cognitive and body image scores in patients with ET, whereas those with FT scored higher on depression and anxiety scales. The misdiagnosis rate was 14.5%, emphasising the need for improved diagnostic criteria. Conclusions: We established specific demographic and psychometric distinctions between ET and FT, which could potentially benefit clinicians in making accurate diagnoses and tailoring treatment approaches. These findings support the inclusion of comprehensive psychometric evaluations into standard diagnostic procedures to better differentiate tremor types.

Tremor is a prevalent symptom associated with multiple conditions, including Essential Tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (Vim, Raprl, caudal Zi, Vo and STN) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

Dystonia and tremor are distinct movement disorders, but they overlap in certain circumstances. First, dystonia and tremor may co-exist in the same individual, in the same or different regions of the body. Second, dystonic movements are sometimes rapid and repetitive, and they may mimic tremor. The term dystonic tremor first appeared in the literature to describe a rapid and repetitive dystonic movement that mimicked tremor but could be discriminated from essential tremor. With the first consensus statement on tremor, the term dystonic tremor was instead used to describe any combination of dystonia with tremor in the same body region, a definition retained in the latest consensus statement. Both definitions continue to be used in the modern literature. To address this problem, a group of specialists in dystonia and tremor met to review the problem and develop recommendations for more consistent approach. The group agreed that a terminology that could be applied in the clinic was essential, even though laboratory-based measures may sometimes be required. The group also agreed that the term tremor should exclusively refer to rhythmic movements, and the establishment of boundaries for rhythmicity is needed. The group also agreed that repetitive movements that are grossly arrhythmic in the context of dystonia, should be called jerky dystonia, rather than terms that imply tremor. Moreover, when both tremor and dystonia coexist, they should be described according to affected body regions rather than given distinct labels.

Dystonias, characterized by excessive muscle contractions resulting in involuntary postures and movements, impact 3 million people globally, making them the third most common movement disorder. Often accompanied by tremors, dystonias have epidemiological links and non-motor features shared with isolated tremor, such as essential tremor. Both dystonia and tremor present with balance dysfunction and abnormal involuntary movements, potentially linked to abnormal cerebellar function. This study explores the perception of one’s own linear movement, heading, particularly discrimination of heading direction, in isolated cervical dystonia, isolated tremor, and their combination. The focus is on the perception of heading direction during isolated visual star-cloud movement (visual heading perception) and en bloc body movement (vestibular heading perception). Nineteen participants underwent a two-alternative forced-choice task in the vestibular and visual domains. Results reveal elevated vestibular heading perception thresholds in cervical dystonia with or without tremor, and isolated tremor compared to healthy controls. Vestibular heading perception threshold was comparable in cervical dystonia with tremor and isolated tremor, but it was even worse in isolated cervical dystonia. Visual heading perception, however, remained less affected all three conditions – isolated cervical dystonia, isolated tremor, and their combination. These findings indicate shared deficits and distinctions in the perception of linear translational heading across movement disorders, such as isolated cervical dystonia, tremor, or their combination, offering insights into their pathophysiology, particularly the involvement of cerebellum regions responsible for vestibular processing.

The increase in life expectancy, according to the World Health Organization, is a fact, and with it rises the incidence of age-related neurodegenerative diseases. The most recurrent symptoms are those associated with tremors resulting from Parkinson's Disease (PD) or Essential Tremors (ET). The main alternatives for the treatment of these patients are medication and surgical intervention, which sometimes have restrictions and side effects. Through computer simulations in Matlab software, this work investigates the performance of adaptive algorithms based on least mean squares (LMS) to suppress tremors in upper limbs, especially in the hands. The signals resulting from pathological hand tremors, related to PD, present components at frequencies that vary between 3~Hz and 6~Hz, with the more significant energy present in the fundamental and second harmonics, while physiological hand tremors, referred to as ET, vary between 4~Hz and 12~Hz. We simulated and used these signals as reference signals in adaptive algorithms, Filtered-x Least Mean Square (Fx-LMS), Filtered-x Normalized Least Mean Square (Fx-NLMS), and a hybrid Fx-LMS\&NLMS purpose. Our results showed that the vibration control provided by the Fx-LMS\&LMS algorithm is the most suitable for physiological tremors. For pathological tremors, we have used a proposed algorithm with a filtered sinusoidal input signal, Fsinx-LMS, which presented the best results in this specific case.

Multidisciplinary neurotechnology holds the promise of understanding and non-invasively treating neurodegenerative diseases. In this preclinical trial on Parkinson's disease (PD), we combined neuroscience together with the nascent field of medical virtual reality and generated several important observations. First, we established the Oculus Rift virtual reality system as a potent measurement device for parkinsonian involuntary hand tremors (IHT). Interestingly, we determined changes in rotation were the most sensitive marker of PD IHT. Secondly, we determined parkinsonian tremors can be abolished in VR with algorithms that remove tremors from patients' digital hands. We also found that PD patients were interested in and were readily able to use VR hardware and software. Together these data suggest PD patients can enter VR and be asymptotic of PD IHT. Importantly, VR is an open-medium where patients can perform actions, activities, and functions that positively impact their real lives - for instance, one can sign tax return documents in VR and have them printed on real paper or directly e-sign via internet to government tax agencies. Lastly, we generated a technical framework wherein movements in the real world can be measured side-by-side with those in virtual reality. With this framework, we observed anecdotal evidence of parkinsonian tremors being reduced in real life when our algorithms abolished digital hand tremors in VR.

Tremor is a prevalent neurological disorder characterized by involuntary shaking or trembling of body parts. This condition impairs fine motor skills and hand coordination to varying degrees and can even affect overall body mobility. As a result, tremors severely disrupt the daily lives and work of those affected, significantly limiting their physical activity space. This study developed an innovative Spatial Augmented Reality (SAR) system aimed at assisting individuals with tremor disorders to overcome their physical limitations and expand their range of activities. The system integrates eye-tracking and Internet of Things (IoT) technologies, enabling users to smoothly control objects in the real world through eye movements. It employs a virtual stabilization algorithm for stable interaction with objects in the real environment. The study comprehensively evaluated the system's performance through three experiments: 1) assessing the effectiveness of the virtual stabilization algorithm in enhancing the system's ability to assist individuals with tremors in stable and efficient interaction with remote objects; 2) evaluating the system's fluidity and stability in performing complex interactive tasks; 3) investigating the precision and efficiency of the system in remote interactions within complex physical environments. The results demonstrate that the system significantly improves the stability and efficiency of interactions between individuals with tremor and remote objects, reduces operational errors, and enhances the accuracy and communication efficiency of interactions.

A method for studying properties of the earth's surface tremor, measured by means of GPS, is proposed. Four characteristics of tremor are considered: the entropy of the distribution of wavelet coefficients, the Donoho-Johnston wavelet index, and two estimates of the spectral slope. The anomalous areas of tremor are determined by estimating the probability densities of extreme values of the studied properties. The criteria for abnormal tremor behavior are based on the proximity to, or the difference between, tremor properties and white noise. The greatest deviation from the properties of white noise is characterized by entropy minima and spectral slope and DJ index maxima. This behavior of the tremor is called "active". The "passive" tremor behavior is characterized by the maximum proximity to the properties of white noise. The principal components approach provides weighted averaged density maps of these 2 variants of extreme distributions of parameters in a sliding time window of 3 years are considered. Singular points are the points of maximum average densities. The method is applied to the analysis of daily time series from a GPS network in the West USA in 2009-2022. It turned out that singular points of tremor form well-defined clusters.

A method for studying properties of the earth's surface tremor, measured by means of GPS, is proposed. Four characteristics of tremor are considered: the entropy of the distribution of wavelet coefficients, the Donoho-Johnston wavelet index, and two estimates of the spectral slope. The anomalous areas of tremor are determined by estimating the probability densities of extreme values of the studied properties. The criteria for abnormal tremor behavior are based on the proximity to, or the difference between, tremor properties and white noise. The greatest deviation from the properties of white noise is characterized by entropy minima and spectral slope and DJ index maxima. This behavior of the tremor is called "active". The "passive" tremor behavior is characterized by the maximum proximity to the properties of white noise. The principal components approach provides weighted averaged density maps of these 2 variants of extreme distributions of parameters in a sliding time window of 3 years are considered. Singular points are the points of maximum average densities. The method is applied to the analysis of daily time series from a GPS network in the West USA in 2009-2022. It turned out that singular points of tremor form well-defined clusters.

A method is proposed for analyzing the tremor of the earth's surface, measured by GPS, in order to highlight prognostic effects. The method is applied to analysis of daily time series of vertical displacements in Japan. The network of 1047 stations is divided into 15 clusters. The Huang Empirical Mode Decomposition (EMD) is applied to the time series of principal components from clusters with subsequent calculation of instantaneous amplitudes using the Hilbert transform. To ensure the stability of estimates of the waveforms of the EMD decomposition, 1000 independent additive realizations of white noise of limited amplitude were averaged before the Hilbert transform. Using a parametric model of the intensities of point processes, we analyze the connections between the instants of sequences of times of the largest local maxima of instantaneous amplitudes averaged over the number of clusters and the times of earthquakes in the vicinity of the Japan with minimum magnitude thresholds of 5.5 for the time interval 2012-2023. It is shown that part of the intensity of the sequence of times of seismic events, due to the influence of the times of the most expressive local extrema of instantaneous amplitudes, significantly exceeds the reverse influence.

The X-linked FMR1 gene contains a non-coding trinucleotide repeat in its 5’ region that in normal, healthy individuals contains 20-44 copies. Large expansions of this region (>200 copies) cause fragile X syndrome (FXS), but expansions of 55-199 copies (referred to as premutation alleles) predispose carriers to a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). The cytopathological mechanisms underlying FXTAS are poorly understood, but abnormalities in mitochondrial function are believed to play a role. We previously reported that lymphoblastoid cell lines (LCLs, or lymphoblasts) of premutation carriers have elevated mitochondrial respiratory activities. In the carriers, especially those not clinically affected with FXTAS, AMPK activity was shown to be elevated. In the FXTAS patients, however, it was negatively correlated with brain white matter lesions, suggesting a protective role in the molecular mechanisms. Here we report an enlarged and extended study of mitochondrial function and associated cellular stress-signalling pathways in lymphoblasts isolated from male and female premutation carriers, regardless of their clinical status, and healthy controls. The results confirmed the elevation of AMPK and mitochondrial respiratory activities and reduction of reactive O2 species (ROS) levels in premutation cells and revealed for the first time that TORC1 activities are reduced. Extensive correlation, multiple regression and Principal Components analysis revealed the best fitting statistical explanations of these changes in terms of the other variables measured. These suggested which variables might be the most “proximal” regulators of the others in the extensive network of known causal interactions amongst the measured parameters of mitochondrial function and cellular stress signalling. In the resulting model, the premutation alleles activate AMPK and inhibit both TORC1 and ROS production, the reduced TORC1 activity contributes to activation of AMPK activation and of nonmitochondrial metabolism, and the higher AMPK activity results in elevated catabolic metabolism, mitochondrial respiration and ATP steady state levels. In addition the results suggest a separate CGG repeat number-dependent elevation of TORC1 activity that is insufficient to overcome the inhibition of TORC1 in premutation cells, but may presage the previously reported activation of TORC1 in FXS cells.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

Essential Tremor (ET) is among the most common neurological movement disorders, with incidence rates increasing with age. The disorder is characterized by a bilateral action tremor of the upper limbs, enduring for a minimum of three years in duration, and shows early signs of onset with progression over time. Recent terminology has categorized a subcategory of ET, known as Essential-Tremor Plus (ET-Plus), which consists of a combination of symptoms that include tremors at rest and additional neurological signs. This includes memory impairment, gait disturbances, or various other neurological symptoms that do not have full clinical significance for diagnosis and suggest a more complex underlying neurological condition. Abnormalities located primarily in the cerebellum, including the loss and damage to Purkinje Cells (PC), were core pathological features of cerebellar damage in postmortem ET. Given the complexity and uncertainty of the pathophysiological aspects of tremor generation, treatment options are still limited, and current therapeutic measures lack the capacity to fully alleviate symptoms. In consideration, there are current pharmaceutical, stimulation, and genetic studies being conducted to characterize the etiology and pathophysiology of ET and aid in the reduction of progression and symptoms. In this review, we will discuss various aspects of ET including neurophysiology, pathophysiology, genetic factors and etiology, treatment options and future directions of advancements for ET management.

Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli, thus exerting crucial neuroprotection for cerebellar ataxias and corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. Earliest changes were detected at 3 months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, impacting communication and excitability of cerebellar neurons. Discovery of such risk versus progression markers improves the assessment of pre-symptomatic treatments in SCA2 and related disorders.