Multiple Sclerosis Tremor Research Articles

Hilbert–Huang transform based instrumental assessment of intention tremor in multiple sclerosis

Objective. This paper describes a method to extract upper limb intention tremor from gyroscope data, through the Hilbert–Huang transform (HHT), a technique suitable for the study of nonlinear and non-stationary processes. The aims of the study were to: (i) evaluate the method’s ability to discriminate between healthy controls and MS subjects; (ii) validate the proposed procedure against clinical tremor scores assigned using Fahn’s tremor rating scale (FTRS); and (iii) compare the performance of the HHT-based method with that of linear band-pass filters. Approach. HHT was applied on gyroscope data collected on 20 MS subjects and 13 healthy controls (CO) during finger-to-nose tests (FNTs) instrumented with an inertial sensor placed on the hand. The results were compared to those obtained after traditional linear filtering. The tremor amplitude was quantified with instrumental indexes (TIs) and clinical FTRS ratings. Main results. The TIs computed after HHT-based filtering discriminated between CO and MS subjects with clinically-detected intention tremor (MS_T). In particular, TIs were significantly higher in the final part of the movement (TI2) with respect to the first part (TI1), and, for all components (X, Y, Z), MS_T showed a TI2 significantly higher than in CO subjects. Moreover, the HHT detected subtle alterations not visible from clinical ratings, as TI2 (Z-component) was significantly increased in MS subjects without clinically-detected tremor (MS_NT). The method’s validity was demonstrated by significant correlations between clinical FTRS scores and TI2 related to X (rs = 0.587, p = 0.006) and Y (rs = 0.682, p < 0.001) components. Contrarily, fewer differences among the groups and no correlation between instrumental and clinical indexes emerged after traditional filtering. Significance. The present results supported the use of the HHT-based procedure for a fully-automated quantitative and objective measure of intention tremor in MS, which can overcome the limitations of clinical scales and provide supplementary information about this sign.

The occurrence of dystonia in upper-limb multiple sclerosis tremor

Background: The pathophysiology of multiple sclerosis (MS) tremor is uncertain with limited phenotypical studies available. Objective: To investigate whether dystonia contributes to MS tremor and its severity. Methods: MS patients (n = 54) with and without disabling uni- or bilateral upper limb tremor were recruited (39 limbs per group). We rated tremor severity, writing and Archimedes spiral drawing; cerebellar dysfunction (SARA score); the Global Dystonia Scale (GDS) for proximal and distal upper limbs, dystonic posturing, mirror movements, geste antagoniste, and writer’s cramp. Results: Geste antagoniste, mirror dystonia, and dystonic posturing were more frequent and severe (p < 0.001) and dystonia scores were correlated with tremor severity in tremor compared to non-tremor patients. A 1-unit increase in distal dystonia predicted a 0.52-Bain unit (95% confidence interval (CI) 0.08–0.97), p = 0.022) increase in tremor severity and a 1-unit (95% CI 0.48–1.6, p = 0.001) increase in drawing scores. A 1-unit increase in proximal dystonia predicted 0.93-Bain unit increase (95% CI 0.45–1.41, p < 0.001) in tremor severity and 1.5-units (95% CI 0.62–2.41, p = 0.002) increase in the drawing score. Cerebellar function in the tremor limb and tremor severity was correlated (p < 0.001). Conclusions: Upper limb dystonia is common in MS tremor suggesting that MS tremor pathophysiology involves cerebello-pallido-thalamo-cortical network dysfunction.

27. Detection of postural oscillatory movement without clinically manifested tremor in multiple sclerosis: A pilot study

Background Tremor is an involuntary rhythmic oscillatory movement of a body. It belongs to one of the most prevalent and disabling feature in multiple sclerosis (MS). Objectives The types of tremor in MS are still not unified. The aim of our work was to detect which types of oscillatory movements of upper extremities are present in MS without clinical manifestation of the tremor. Material and Methods Ten patients with MS (9 women, mean age 37 ± 11 years, mean EDSS 3,9 ± 0,8, mean length of the disease 10,2 ± 7,3) and 10 healthy controls participated in this study. Postural tremor was measured with open and closed eyes using an accelerometer LIS 3LV02DQ, ST Micro. The most complex resting signal was measured in upright position, when one arm was hanging freely next to the body and second arm was raised forward. Tremor sensor was placed on the index finger of arm that was raised forward. Frequency, rhythmicity and change of amplitudes were analyzed by spectral analysis. Results In healthy subjects with open eyes the spectral analysis showed 3 prevailing frequencies of oscillatory movements: (a) 2–3 Hz, (b) 7–10 Hz, and (c) 12–14 Hz. When eyes were closed, the lowest frequencies disappeared. Oscillatory movement of 7–10 Hz was the most frequent type in MS and significantly differs from healthy subjects. The amplitude of oscillatory movements in MS was profoundly higher than in healthy individuals. Conclusions Difference of frequency of oscillatory movements in MS with the most prominent manifestation at 7–10 Hz may correspond to early desinhibition of motor control probably at subcortical level. Supported by Research Projects of Charles University PRVOUK P34, 260045/SVV/2014.

The therapeutic potential of cannabinoids for movement disorders.

There is growing interest in the therapeutic potential of marijuana (cannabis) and cannabinoid-based chemicals within the medical community and, particularly, for neurological conditions. This interest is driven both by changes in the legal status of cannabis in many areas and increasing research into the roles of endocannabinoids within the central nervous system and their potential as symptomatic and/or neuroprotective therapies. We review basic science as well as preclinical and clinical studies on the therapeutic potential of cannabinoids specifically as it relates to movement disorders. The pharmacology of cannabis is complex, with over 60 neuroactive chemicals identified to date. The endocannabinoid system modulates neurotransmission involved in motor function, particularly within the basal ganglia. Preclinical research in animal models of several movement disorders have shown variable evidence for symptomatic benefits, but more consistently suggest potential neuroprotective effects in several animal models of Parkinson's (PD) and Huntington's disease (HD). Clinical observations and clinical trials of cannabinoid-based therapies suggests a possible benefit of cannabinoids for tics and probably no benefit for tremor in multiple sclerosis or dyskinesias or motor symptoms in PD. Data are insufficient to draw conclusions regarding HD, dystonia, or ataxia and nonexistent for myoclonus or RLS. Despite the widespread publicity about the medical benefits of cannabinoids, further preclinical and clinical research is needed to better characterize the pharmacological, physiological, and therapeutic effects of this class of drugs in movement disorders.

Clinical, neurophysiological and neuroimaging study of tremor in multiple sclerosis

To identify clinical types of tremor in multiple sclerosis (MS) and clarify their pathophysiological mechanisms. We examined 124 patients with MS, including 58 patients with tremor, using clinical (digital spiralography), neurophysiological (tremor electromyography, visual and sensory evoked potentials, transcranial magnetic stimulation with tremor resetting, long latency reflexes, electroencephalography) and neuroimaging (MRI, morphometry) methods. Five main variants of tremor were identified: distal postural and postural-intention (variant 1), distal intention (variant 2), proximal and distal intention and postural-intention (variant 3), Holmes (variant 4), axial (variant 5). Postural tremor (variants 1, 3) and rest tremor (variant 4) are caused by the central oscillators. Intention tremor (variants 2, 3), postural-intention tremor (variant 4), axial (variant 5) are caused by the pathology of cerebellar feedback loops. Clarification of mechanisms for the development of tremor in MS allowed to develop a scheme of differential treatment.

Novel Mathematical Model may Provide Drug-Naïve Strategy to Relieve Postural Tremor in Multiple Sclerosis

Multiple Sclerosis (MS) is a progressive neurodegenerative condition. There isn’t any effective strategy for the remission of MS signs and currently applied options have merely a relieving effect on the symptoms. Achieving new treatment strategies to overcome MS symptoms has always been among the researchers’ priorities. The present paper aims to introduce a mathematical modeling of postural tremor in subjects with MS to study the effect of electric stimulations (Trans cranial Magnetic Stimulation and Deep Brain Stimulation) on MS motor symptoms.

Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey

Objectives(1)To describe the prevalence and severity of tremor in patients with multiple sclerosis (MS) registered within a large North American MS registry; (2) to provide detailed descriptions on the characteristics...

5.: Dystonic features are common in multiple sclerosis-related tremor and contribute to its severity

Detailed phenomenological studies are needed to characterize multiple sclerosis (MS)-related tremor and investigate factors that may predict its severity. We completed a detailed, blinded study in order to define clinical features that may be unique to MS tremor patients and that may inform the underlying pathophysiology of MS tremor. The objectives of this study were to investigate clinical factors that contribute to tremor severity in patients with MS, and to determine if dystonia is more common in MS tremor patients than disease-matched, non-tremor controls. We recruited 54 MS patients with and without disabling arm tremor matched for age, sex and disability. Both limbs were assessed in bilateral tremor, resulting in 39 limbs per group. Cerebellar function was rated with the Scale for the Assessment and Rating of Ataxia. Assessments of tremor severity (Bain score for tremor severity, writing and drawing) and dystonia (Global Dystonia Scale [GDS] for proximal and distal arms) using video and handwriting recordings were completed. All samples were shuffled and rated by a blinded movement disorder expert. The presence and severity of dystonic posturing, mirror movements and geste antagonistes were scored. We found associations ( p p p p = 0.022) increase in tremor severity and a 1 unit ( p = 0.001) increase in drawing scores. One unit increase in proximal GDS predicted a 0.93 unit increase ( p p = 0.050) increase in writing scores and a 1.5 unit ( p = 0.002) increase in drawing score. The results of this study demonstrate the importance of recognizing dystonia as part of the complex movement disorder that represents MS tremor. The presence of dystonia points to injury in the cerebello-pallido-thalamo-cortical network and could explain the efficacy of onabotulinumtoxin-A therapy in the treatment of MS tremor.

Intraoperative smile in a multiple sclerosis patient with medication-refractory tremor

Deep brain stimulation has been utilized to improve disease symptoms in patients with Parkinson’s disease, dystonia, essential tremor, and other neuropsychiatric syndromes such as depression and obsessive compulsive disorder. Deep brain stimulation has also been observed to improve tremor for select patients with multiple sclerosis. During intraoperative stimulation in these multiple sclerosis patients, researchers have observed a wide spectrum of motor and sensory phenomena, but no stimulation-induced emotional responses have been reported. We detailed intraoperative smiling associated with stimulation of the ventralis oralis anterior/ventralis oralis posterior border region of the left thalamus. A single patient with medication-resistant multiple sclerosis tremor experienced smiling, laughing, and subjective euphoria during intraoperative stimulation of the left thalamus. Specifically, during intraoperative stimulation of the left thalamic ventralis oralis anterior border, the patient developed a contralateral smile which progressed to a bilateral smile and was accompanied by a feeling of subjective happiness. The smile habituated in approximately 60 seconds and it was reproducible on a repeat stimulation. The patient could subjectively feel the facial movement, and, at higher voltages, the movement was described as a pulling sensation. Stimulation of the anterior ventralis oralis anterior border of the left thalamus in an multiple sclerosis patient produced a unilateral smile that rapidly developed into a bilateral smile accompanied by euphoria. There were presumed capsular side effects at higher voltages. The exact mechanism by which stimulation of the thalamus produced a smile and mood elevation is unknown, but we speculate that the smile could be induced by stimulation of corticobulbar fibers arising from the caudal cingulate motor area connecting the contralateral facial nerve nucleus.

The treatment of tremor.

Tremor is a hyperkinetic movement disorder characterized by rhythmic oscillations of one or more body parts. It can be disabling and may impair quality of life. Various etiological subtypes of tremor are recognized, with essential tremor (ET) and Parkinsonian tremor being the most common. Here we review the current literature on tremor treatment regarding ET and head and voice tremor, as well as dystonic tremor, orthostatic tremor, tremor due to multiple sclerosis (MS) or lesions in the brainstem or thalamus, neuropathic tremor, and functional (psychogenic) tremor, and summarize main findings. Most studies are available for ET and only few studies specifically focused on other tremor forms. Controlled trials outside ET are rare and hence most of the recommendations are based on a low level of evidence. For ET, propranolol and primidone are considered drugs of first choice with a mean effect size of approximately 50 % tremor reduction. The efficacy of topiramate is also supported by a large double-blind placebo-controlled trial, while other drugs have less supporting evidence. With a mean effect size of about 90 % deep brain stimulation in the nucleus ventralis intermedius or the subthalamic nucleus may be the most potent treatment; however, there are no controlled trials and it is reserved for severely affected patients. Dystonic limb tremor may respond to anticholinergics. Botulinum toxin improves head and voice tremor. Gabapentin and clonazepam are often recommended for orthostatic tremor. MS tremor responds only poorly to drug treatment. For patients with severe MS tremor, thalamic deep brain stimulation has been recommended. Patients with functional tremor may benefit from antidepressants and are best be treated in a multidisciplinary setting. Several tremor syndromes can already be treated with success. But new drugs specifically designed for tremor treatment are needed. ET is most likely covering different entities and their delineation may also improve treatment. Modern study designs and long-term studies are needed.

Tremor in Multiple Sclerosis: The Intriguing Role of the Cerebellum (P03.213)

Tremor in Multiple Sclerosis: The Intriguing Role of the Cerebellum (P03.213)

The dynamics of finger tremor in multiple sclerosis is affected by whole body position

Multiple sclerosis (MS) is a disease that results in widespread damage to the nervous system. One consequence of this disease is the emergence of enhanced tremor. This study was designed to (1) compare the tremor responses of persons with MS to that of healthy adults and to (2) examine the impact of whole body position (i.e., seated/standing) on tremor. Bilateral postural tremor was recorded using accelerometers attached to each index finger. Results revealed some similarity of tremor between groups in regard to the principal features (e.g., presence of peaks in similar frequency ranges). However, significant differences were observed with tremor for the MS persons being of greater amplitude, more regular (lower ApEn) and more strongly coupled across limbs compared to the elderly. The effects of body position were consistent across all subjects, with tremor increasing significantly from sitting-to-standing. However, the tremor increase for the MS group was greater than the elderly. Overall, the tremor for MS group was negatively affected by both this disease process and the nature of the task being performed. This latter result indicates that tremor does not simply reflect the feed-forward output of the neuromotor system but that it is influenced by the task constraints.

Understanding Tremor in Multiple Sclerosis: Prevalence, Pathological Anatomy, and Pharmacological and Surgical Approaches to Treatment

Understanding Tremor in Multiple Sclerosis: Prevalence, Pathological Anatomy, and Pharmacological and Surgical Approaches to Treatment

Understanding tremor in multiple sclerosis: prevalence, pathological anatomy, and pharmacological and surgical approaches to treatment.

Given that tremor is one of the most prevalent and disabling features of multiple sclerosis (MS), we will review the most significant milestones in tremor in this disease in recent years, focusing on prevalence, clinical features, anatomical basis, and treatment. Data for this review were identified by searching MEDLINE with the search terms "multiple sclerosis" and "tremor". References were also identified from relevant articles published between January 1966 and May 2012. The predominant type of MS tremor is a large-amplitude, postural, and kinetic tremor, which most commonly affects the arms, although tremor can also involve head, neck, vocal cords, and trunk. Involvement of the tongue, jaw, or palate has not been reported. Although the anatomical basis underlying tremor in MS is poorly understood, the link between the cerebellum and the MS-related tremor is supported by clinical and experimental studies. Currently available medication is often unsuccessful in most cases. Surgical treatment can be a satisfactory alternative to treat severe and disabling tremor. Tremor in MS patients could be considered as an advanced consequence of the disease and its presence suggests a more aggressive course. MS tremor can be severe and very disabling for a small group of patients. Treatment of MS tremor remains a great challenge. Recent studies suggest that dissociating tremor from cerebellar dysfunction using selected clinical tests would be the key issue to successful surgical treatment. Understanding the pathophysiology and biochemistry of tremor production in MS may lead to new therapeutic approaches.

Oculopalatal tremor in multiple sclerosis with spontaneous resolution

Oculopalatal tremor (myoclonus) is a rare movement disorder that develops after brainstem or cerebellar stroke, tumor, or following radiation. We describe a patient with transient OPT from relapsing-remitting multiple sclerosis (MS) and review the imaging changes over the course of his OPT.

Neurolaryngology

The neuroanatomy of voice and speech is complex. An intricate neural network is responsible for ensuring the main functions of the larynx: airway protection, cough and Valsalva production, and providing voice. Coordination of these roles is very susceptible to disruption by neurological disorders. Neurological disorders that affect laryngeal function include Parkinson's disease, stroke, amyotrophic lateral sclerosis, multiple sclerosis, dystonia and essential tremor. A thorough neurological evaluation should be routine for any patient presenting with voice complaints suggestive of neurogenic cause. Endoscopic visualisation of the larynx using a dynamic voice assessment with a flexible laryngoscope is a crucial part of the evaluation and ancillary tests are sometimes performed. Otolaryngologic evaluation is important in the diagnosis and treatment of neurological disorders that affect laryngeal function.

Surgical therapy for multiple sclerosis tremor: a 12‐year follow‐up study

Severe multiple sclerosis (MS) tremor causes disability poorly responsive to medication. Deep brain stimulation (DBS) or thalamotomy can suppress tremor, but long-term outcomes are unclear. Nine patients with MS tremor underwent disability measures at baseline and 12 months post-surgery (six thalamotomy, three DBS) in 1997-1998 (previously reported, Matsumoto et al., Neurology 2001;57:1876-82). We report the prospective 12-year follow-up of this cohort for tremor, disability, and death. Surgery was initially successful in all. Tremor recurred in all patients within median 3 months, although two DBS patients were tremor-free for 5 years. Median tremor-free survival (tremor-free time/survival time) was 4.3%. At 12-year follow-up, four survivors (two thalamotomy, two DBS) (Expanded Disability Status Scale scores 8-8.5) were severely disabled. Five patients were dead (four thalamotomy, one DBS) median 5.8 years post-operative. Surgery benefit for severe tremor was overall short-lived (median 3 months), with long-term poor prognosis. Although two DBS patients had sustained 5-year tremor-suppression, the observed progressive disability and death in this cohort bear importance for long-term success in future MS tremor surgery trials.

The Wilson films — MS Tremor

Action tremor was for a long time considered to be a defining symptom of multiple sclerosis. The Wilson films include a short segment showing a female patient suffering from relatively severe action tremor. Tremor is the most common movement disorder in multiple sclerosis, and can be very disabling in some patients. Insights into the frequency and treatment of tremor in multiple sclerosis have changed since the Wilson films were taken, and are reviewed herein.

Pharmacological tests of hypotheses for acquired pendular nystagmus

Acquired pendular nystagmus (APN) occurs with multiple sclerosis (MS) and oculopalatal tremor (OPT); distinct features of the nystagmus have led to the development of separate models for their pathogenesis. APN in MS has been attributed to instability in the neural integrator, which normally ensures steady gaze. APN in OPT may result from electrotonic coupling between neurons in the hypertrophied inferior olivary nucleus, which induces maladaptive learning in cerebellar cortex. We tested these two hypotheses by analyzing the effects of gabapentin, memantine, and baclofen on both forms of nystagmus. No drug changed the dominant frequency of either form of APN, but the variability of frequency was affected with gabapentin and memantine in patients with OPT. The amplitude of APN in both MS and OPT was reduced with gabapentin and memantine, but not baclofen. Analyzing the effects of drug therapies on ocular oscillations provides a novel approach to test models of nystagmus.

Unilateral Thalamic Deep Brain Stimulation for Disabling Kinetic Tremor in Multiple Sclerosis

Surgical options of multiple sclerosis (MS) tremor treatment are limited and narrowed to thalamotomy or deep brain stimulation of the thalamic nucleus ventralis intermedius. Lack of qualification protocol frequently results in poor outcome. To determine prospectively the efficacy and safety of unilateral ventralis intermedius deep brain stimulation as a tool to control disabling kinetic arm tremor related to MS. Neurological and neuropsychological evaluations were performed 1 month and 1 day before surgery and 1, 3, and 6 months after surgery. The evaluation included measurement of tremor and dexterity, Extended Disability Status Scale, Mini Mental State Examination, and quality-of-life assessment. Nine consecutive patients were enrolled in the group. Mean age at the time of surgery was 38.9 ± 9 years; median Extended Disability Status Scale at baseline was 7.1. Mean MS duration was 11.7 years, and mean tremor duration was 6.11 years. Mean postural and kinetic scores and hand capacity were measured. One month after surgery, median scores off and on stimulation were 12 and 6 for postural tremor, 12 and 10.5 for kinetic tremor score, 12 and 7.5 for manual capacity, and 22 and 20 for functional handicap, respectively. Similar results were 10 and 4, respectively, at the 3-month follow-up. Six months after surgery, median scores off and on stimulation were 10.4 and 4 for postural tremor and 12 and 7.8 for kinetic tremor, respectively. This prospective study confirms the value and safety of ventralis intermedius deep brain stimulation for treatment of kinetic tremor related to MS. Accurate and precise presurgical qualification plays a key role in successful treatment.