The clinical and electrophysiological investigation of tremor

The various forms of tremor are now classified in two axes: clinical characteristics (axis 1) and etiology (axis 2). Electrophysiology is an extension of the clinical exam. Electrophysiologic tests are diagnostic of physiologic tremor, primary orthostatic tremor, and functional tremor, but they are valuable in the clinical characterization of all forms of tremor. Electrophysiology will likely play an increasing role in axis 1 tremor classification because many features of tremor are not reliably assessed by clinical examination alone. In particular, electrophysiology may be needed to distinguish tremor from tremor mimics, assess tremor frequency, assess tremor rhythmicity or regularity, distinguish mechanical-reflex oscillation from central neurogenic oscillation, determine if tremors in different body parts, muscles, or brain regions are strongly correlated, document tremor suppression or entrainment by voluntary movements of contralateral body parts, and document the effects of voluntary movement on rest tremor. In addition, electrophysiologic brain mapping has been crucial in our understanding of tremor pathophysiology. The electrophysiologic methods of tremor analysis are reviewed in the context of physiologic tremor and pathologic tremors, with a focus on clinical characterization and pathophysiology. Electrophysiology is instrumental in elucidating tremor mechanisms, and the pathophysiology of the different forms of tremor is summarized in this review

Clinical and Neurophysiological Study of Non-Parkinsonian Tremor.

Tremor is a periodic movement about an axis, which distinguishes it from other movement disorders such as chorea, myoclonic jerks and tics which may not have a fixed period and may involve complex movements other than simple oscillation .Tremors present commonly in neurology OPD. Among these, majority of cases are Parkinsonian tremors, however non-parkinsonian tremors eg. Essential tremor, Exaggerated physiological tremor, drug induced tremor, rubral tremor, dystonic tremors etc are also seen. Essential tremors is one of the most common movement disorders. In population based studies, the prevalence of ET increases steadily with age, occurring up to in 10% of patients older than age 60 years with a median age of 15 years but there is a bimodal distribution. Tremors can be divided into two types – at rest and those seen on action. ‘Rest’ is only a relative term as some slight tonic postural maintenance is often required. Action tremors must be subdivided into those seen just with postural maintenance (postural or static tremor) and those requiring goal directed movements (intentional or kinetic tremor). A third division of action tremor is those seen only with specific types of kinetic movements such as hand writing. 1. Eighty eight patients with non-parkinsonian tremors were studied with a sex distribution of male 59.1 per cent and females 40.9 per cent. 2. Age of the studied population was ranged from 14-76 with mean age of 42.63 years. 3. Essential Tremor was the most common non-parkinsonian tremor found in our study (59.1 per cent). 4. Dystonic tremor was being the second most common non-parkinsonian tremor found in our study. 5. Enhanced physiological, rubral, task specific, cerebellar, drug induced and alcohol withdrawal were the other types of non-parkinsonian tremors seen. All types of EMG burst activity was seen in such patients. 6. The mean TRS score was 11.02 ± 5.36 SD with a range of 3.5 – 24. 7. We observed that alcohol responsiveness could not be used as a diagnostic criterion for ET in India, as many patients are teetotalers. 8. The Rest tremor ET was associated with disease that was more severe, more disseminated (extending to other body regions), and of longer duration. 9. Positive family history was found in 24 out of the 52 (46.5 per cent) ET patients, it was definite in 4, probable in 15 and possible in 6 patients. 10. Three types of burst activity in EMG analysis were seen in our study namely synchronized, mixed and alternating pattern. 11. Classical synchronized EMG burst pattern was observed in 76.9 per cent ET patients (p-0.011) with mean frequency of 9.69 ± 3.06 Hz. Such ‘fast frequency’ ET can be differentiated from enhanced physiological tremor using synchronized surface EMG burst pattern

Neurological Tremor: Sensors, Signal Processing and Emerging Applications

Neurological tremor is the most common movement disorder, affecting more than 4% of elderly people. Tremor is a non linear and non stationary phenomenon, which is increasingly recognized. The issue of selection of sensors is central in the characterization of tremor. This paper reviews the state-of-the-art instrumentation and methods of signal processing for tremor occurring in humans. We describe the advantages and disadvantages of the most commonly used sensors, as well as the emerging wearable sensors being developed to assess tremor instantaneously. We discuss the current limitations and the future applications such as the integration of tremor sensors in BCIs (brain-computer interfaces) and the need for sensor fusion approaches for wearable solutions

Design of an Assistive Device for Older Age People Suffering from Essential Tremor

Essential tremor (ET) is a nerve disorder characterized by uncontrollable shaking, or "tremors," in different parts and on different sides of the body. Areas affected often include the hands, arms, head, larynx (voice box), tongue, and chin. The lower body is rarely affected. ET is not a life-threatening disorder, unless it prevents a person from caring for him or herself. Essential tremor is characterised by rhythmic shaking that occurs during voluntary movement or while holding a position against gravity. The two types of tremor include: Action tremor – a voluntary movement such as lifting a cup to one's mouth and Postural tremor – a voluntary holding of a position against gravity such as reaching or extending one's hand or arm. Most people with essential tremor experience both postural and action tremor. Most people are able to live normal lives with this condition -- although they may find everyday activities like eating, dressing, or writing difficult. It is only when the tremors become severe that they actually cause disability. So, the aim of this project is to design an assistive device for older age people suffering from essential disorder which can be able to nullify the tremor produced in the hand with maximum percentage of efficiency and ergonomically designed for easy use. The main objective of the project is focusing on the design of an intelligent device that can recognize the tremor automatically by differentiating the frequency at normal stage and at the shaking stage in order to accomplish the neutralizing effect in the shortest possible tim

Clinical Decision Support Systems with Game-based Environments, Monitoring Symptoms of Parkinson’s Disease with Exergames

Parkinson’s Disease (PD) is a malady caused by progressive neuronal degeneration, deriving in several physical and cognitive symptoms that worsen with time. Like many other chronic diseases, it requires constant monitoring to perform medication and therapeutic adjustments. This is due to the significant variability in PD symptomatology and progress between patients. At the moment, this monitoring requires substantial participation from caregivers and numerous clinic visits. Personal diaries and questionnaires are used as data sources for medication and therapeutic adjustments. The subjectivity in these data sources leads to suboptimal clinical decisions. Therefore, more objective data sources are required to better monitor the progress of individual PD patients. A potential contribution towards more objective monitoring of PD is clinical decision support systems. These systems employ sensors and classification techniques to provide caregivers with objective information for their decision-making. This leads to more objective assessments of patient improvement or deterioration, resulting in better adjusted medication and therapeutic plans. Hereby, the need to encourage patients to actively and regularly provide data for remote monitoring remains a significant challenge. To address this challenge, the goal of this thesis is to combine clinical decision support systems with game-based environments. More specifically, serious games in the form of exergames, active video games that involve physical exercise, shall be used to deliver objective data for PD monitoring and therapy. Exergames increase engagement while combining physical and cognitive tasks. This combination, known as dual-tasking, has been proven to improve rehabilitation outcomes in PD: recent randomized clinical trials on exergame-based rehabilitation in PD show improvements in clinical outcomes that are equal or superior to those of traditional rehabilitation. In this thesis, we present an exergame-based clinical decision support system model to monitor symptoms of PD. This model provides both objective information on PD symptoms and an engaging environment for the patients. The model is elaborated, prototypically implemented and validated in the context of two of the most prominent symptoms of PD: (1) balance and gait, as well as (2) hand tremor and slowness of movement (bradykinesia). While balance and gait affections increase the risk of falling, hand tremors and bradykinesia affect hand dexterity. We employ Wii Balance Boards and Leap Motion sensors, and digitalize aspects of current clinical standards used to assess PD symptoms. In addition, we present two dual-tasking exergames: PDDanceCity for balance and gait, and PDPuzzleTable for tremor and bradykinesia. We evaluate the capability of our system for assessing the risk of falling and the severity of tremor in comparison with clinical standards. We also explore the statistical significance and effect size of the data we collect from PD patients and healthy controls. We demonstrate that the presented approach can predict an increased risk of falling and estimate tremor severity. Also, the target population shows a good acceptance of PDDanceCity and PDPuzzleTable. In summary, our results indicate a clear feasibility to implement this system for PD. Nevertheless, long-term randomized clinical trials are required to evaluate the potential of PDDanceCity and PDPuzzleTable for physical and cognitive rehabilitation effects

Characterization of \u3ci\u3eMEF2C\u3c/i\u3e-Related Disorders: Genotype, Phenotype, and Gene Pathway Dysregulation

MEF2C­-related disorders are characterized by intellectual disability, developmental delay, lack of speech, seizures, stereotypic movements, hypotonia, and brain abnormalities and are caused by pathogenic alterations involving the MEF2C gene. Despite published cases, MEF2C­-related disorders are difficult to recognize clinically. These studies sought to further characterize MEF2C­-related disorders by investigating the genotypes, phenotypes, and gene functions (or dysfunctions) associated with the disorder. Tremors have been reported in some patients with MEF2C­-related disorders, but the concept of tremors has been complicated by vague definitions and numerous categorization methods. We performed a concept analysis following the Walker and Avant method to clarify the concept and develop an operational definition of tremors. We concluded that tremors are a movement disorder characterized by shaking motions that are involuntary, oscillatory, rhythmic, non-painful, always present although vary in severity, and can be repressed by changing posture or going into a rest position. We then performed a systematic literature review to record the genotypes and comprehensive phenotype of MEF2C­-related disorders reported in the literature. Forty-three articles characterizing 117 patients met the inclusion criteria. Common features included intellectual disability, developmental delay, seizures, hypotonia, absent speech, inability to walk, stereotypic movements, and MRI abnormalities. Nonclassical findings included question mark ear, jugular pit, and a unique neuroendocrine finding. Next, we developed a survey based on validated instruments to gather developmental and clinical information from the parents of children with MEF2C-related disorders. Seventy-three parents completed the survey. Limited speech, seizures, bruxism, repetitive movements, and high pain tolerance were some of the prominent features identified from the survey data. Statistical analyses showed that patients with MEF2C variants were similarly affected as patients with deletions and females showed higher verbal abilities. This natural history study details phenotypic and developmental information of the largest single cohort reported to date. Lastly, we discussed current techniques used to investigate the mouse Mef2c gene expression and regulation in the brain. Previous unbiased RNA sequencing of whole cortex from Mef2c global heterozygous mice showed hundreds of dysregulated genes, particularly autism risk genes and microglial genes. The Cowan lab is currently performing single nuclei RNA sequencing (snRNAseq) to better understand the role of Mef2c in neurons and microglia. Techniques used include nuclei dissociation, fluorescence-activated cell sorting, library preparation and sequencing, and bioinformatic analysis of the snRNAseq data. Additional research techniques include perfusion fixation, brain extraction and slicing, and immunohistochemistry. These studies characterize the phenotype and document the severity of the disorder. The information reported will help providers diagnose and care for patients with MEF2C-related disorders. Additionally, the systematic review and survey data can be useful for further genotype-phenotype correlations, as baseline data for treatment trials, and to develop future studies

Tremor in Parkinson's Disease: Loading and Trends in Tremor Characteristics

Parkinson's disease (PD) is a neuro-degenerative chronic disorder with cardinal signs of bradykinesia, resting tremor, rigidity, and postural abnormality/instability. Tremor, which is a manifestation of both normal and abnormal activities in the nervous system, can be described as an involuntary and periodic oscillation of any limb. Such an oscillation with a small amplitude, which is barely visible to the naked eye, is present in healthy people. This is called a physiological tremor and is asymptomatic. This tremor is believed to be the result of at least two distinct oscillations. A passive mechanical oscillation that is produced by the irregularities of motor unit firing, and by blood ejection during cardiac systole. The frequency and amplitude of these oscillations are dependent on the mechanical properties of the limb including joint stiffness and limb inertia. There is another component of oscillation that does not respond to elastic or inertial loading, which is called the central component, and is believed to arise from an unknown oscillating neuronal network within the central nervous system. Unlike physiological tremor, pathological tremors are symptomatic and can impair motor performance. Parkinson's disease (PD) tremor is generally manifested at rest, but also occurs during posture or motion. Classical PD rest tremor is known to be a central tremor of 4-6 Hz and peripheral origins have only a minimal role. However, whether or not the same central mechanism remains active during action tremor (including posture and movement) should yet be answered. Contrary to PD rest tremor, reported results on action tremor in the literature are diverse; and the reason for the changes in tremor characteristics in situations other than rest, or generally during muscle activation, is not fully understood. The lack of generality in the results of studies on action tremor, makes the efforts of treatment difficult, and is a barrier for mechanical/engineering approaches of suppressing this tremor. To investigate the role of mechanisms other than classic rest tremor, and possible sub-categories of tremulous PD in yielding diverse results, this study was conducted on twenty PD patients and fourteen healthy age-matched (on average) controls. To evaluate the possible contribution of (enhanced) physiological tremor, the study considered the effect of loading on postural hand tremor in a complete range of 0-100% MVC (Maximum Voluntary Contraction). The study looked at two measures of tremor amplitude and one measure of tremor frequency, and focused on two frequency bands of classic-rest (3.5-6.5 Hz) and physiological (7.5-16.5 Hz) tremors. The study revealed that PD tremor was not uniformly distributed in the three dimensional space, and then focused on the investigation of tremor in the dominant axis, which was the same as direction of loading. It also revealed that dopaminergic medication could significantly affect tremor components only in PD band, compared to the components in the physiological band. The study was an extension to previous studies and yielded similar results for the previously reported range of loading. However, with the extended range of loading, it revealed novel results particularly after separating PD patients into sub-groups. It was hypothesized that the coexistence of physiological mechanism, and considerable difference between sub-types of tremulous PD patients, are responsible for most of the diversity in the previously reported studies. This study showed that for clearer results the sub-groups are inevitable, and that automatic classification (clustering) provided the most separable sub-groups. These sub-groups had distinct trends of load effect on tremor amplitude and frequency. No matter which categorization method was used, at least one sub-group exhibited significantly higher tremor energy compared to the healthy participants not only in the PD band, but also in the physiological band. This meant that, for some sub-groups of PD, the physiological tremor is a very important mechanism and not the same as that of healthy people. The coexistence hypothesis was also affirmed by examining tremor spectrums' peak frequency and magnitude in the two separate bands. The necessity of the separation of tremulous PD patients into sub-groups, and the coexistence of physiological and classic PD tremor mechanisms for some of them are the factor that should be considered in the design of a suppressing device and also in the proposed treatment of action tremor in this population