Multiple Sclerosis Tremor Research Articles

Experimenting Transcortical Magnetic Stimulation In An Attempt To Ameliorate Tremor In Multiple Sclerosis

Experimenting Transcortical Magnetic Stimulation In An Attempt To Ameliorate Tremor In Multiple Sclerosis

The Use of IncobotulinumtoxinA in the Correction of Tremor in Multiple Sclerosis

The Use of IncobotulinumtoxinA in the Correction of Tremor in Multiple Sclerosis

Automatic Segmentation of Retinal Layers in Multiple Neurodegenerative Disorder Scenarios.

Retinal Optical Coherence Tomography (OCT) allows the non-invasive direct observation of the central nervous system, enabling the measurement and extraction of biomarkers from neural tissue that can be helpful in the assessment of ocular, systemic and Neurological Disorders (ND). Deep learning models can be trained to segment the retinal layers for biomarker extraction. However, the onset of ND can have an impact on the neural tissue, which can lead to the degraded performance of models not exposed to images displaying signs of disease during training. We present a fully automatic approach for the retinal layer segmentation in multiple neurodegenerative disorder scenarios, using an annotated dataset of patients of the most prevalent NDs: Alzheimer's disease, Parkinson's disease, multiple sclerosis and essential tremor, along with healthy control patients. Furthermore, we present a two-part, comprehensive study on the effects of ND on the performance of these models. The results show that images of healthy patients may not be sufficient for the robust training of automated segmentation models intended for the analysis of ND patients, and that using images representative of different NDs can increase the model performance. These results indicate that the presence or absence of patients of ND in datasets should be taken into account when training deep learning models for retinal layer segmentation, and that the proposed approach can provide a valuable tool for the robust and reliable diagnosis in multiple scenarios of ND.

Deep brain stimulation in multiple sclerosis-associated tremor. A large, retrospective, longitudinal open label study, with long-term follow-up

BackgroundTremor affects up to 25%-58% in multiple sclerosis (MS) population. Deep-brain stimulation (DBS) of the ventral-intermediate nucleus (VIM) of the thalamus is considered as a potential option following medical treatments. Long term DBS efficacy is not well known in these patients with a poor outcome mostly related to disease progression. ObjectiveTo report a large and retrospective study of thalamic DBS in MS tremor. MethodsWe conducted a large and retrospective study of patients with MS disabling and pharmacologically resistant upper limb tremor, who underwent thalamic DBS procedure from January 1992 to January 2015 in University Hospital of Henri Mondor, France. Demographic data, clinical assessment and activity daily living were collected. A three-month and twelve-month post-operative assessment with clinical and functional rating scales have been achieved, as well as long term follow-up for most patients. ResultsOne hundred and four patients underwent DBS procedure. There were 71 female (68%) and 33 male (32%). At three-month post-operative assessment, 64% patients were improved clinically and functionally. Among these, 93% of patients kept a good efficacy at one-year post-operative assessment. Mean duration of follow-up for these patients was 6 years. ConclusionWe described a long-term sustained clinical and functional improvement in this large and retrospective report of thalamic DBS. This neuromodulation approach could be a therapeutic option for all severe upper extremity refractory tremor in MS patients.

Novel Pathways Correlating with MS-Related Tremor, A Case-Control Study (P10-3.001)

<h3>Objective:</h3> Identifying the white matter fiber pathways responsible for tremor in Multiple Sclerosis (MS). <h3>Background:</h3> MS-related tremor is characteristically resistant to treatment, affecting 25% and 58% of the patients with MS. <h3>Design/Methods:</h3> Patients with MS-related tremor (n=36) had 3.0 T MRI scans with T1-weighted, FLAIR, and diffusion-weighted (DWI) sequences. Subjects were gender and age-matched with a control MS group (n = 36) without tremor. Using regional brain diffusivity measures obtained from MRICloud and diffusion connectometry findings from DSI Studio, we identified 53 tracts-of-interest associated with MS-related tremor. Tractography of the identified tracts was performed in DSI Studio. The diffusion data were reconstructed using generalized q-sampling. A supervised atlas-based tractography method was used to segment the pathways using tract-specific parameters set based on neuroanatomical topology and standardized across subjects. We obtained the partial spearman correlation coefficients (r_s) for tremor severity with mean tract diffusivity measures adjusting for possible confounders. <h3>Results:</h3> Of the 53 tracts, 5 showed negative correlation between mean tract fractional anisotropy (FA) and tremor severity: the left medial lemniscus (r_{s =} −0.55, p = &lt; .001), the forceps minor of the corpus callusom (r_{s =} −0.45, p = 0.009), the right anterior corticostriatal tract (r_{s =} −0.413, p = 0.017), the forceps major of the corpus callusom (r_s = −0.376, p = 0.031), and the fornix (r_s = −0.367, p = 0.035). Of these tracts 3 had radial diffusivity (RD) values significantly correlating with tremor severity, namely the left medial lemniscus (r_s = 0.429, p = 0.013), the right anterior corticostriatal tract (r_s = 0.379, p = 0.029), and the forceps minor of corpus callosum (r_s = 0.369, p = 0.034). <h3>Conclusions:</h3> Using two independent techniques, we identified pathways associated with MS-related tremor. For the first time, we show that commissural, medial lemniscus, and striatal tracts correlate with tremor severity. <b>Disclosure:</b> Mr. Bayoumi has nothing to disclose. Khader Hasan has nothing to disclose. The institution of Dr. Lincoln has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Lincoln has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Lincoln has received research support from Deaprtment of Defense. The institution of Dr. Lincoln has received research support from National Institutes of Health. The institution of Dr. Lincoln has received research support from EMD-Serono. Dr. Lincoln has received intellectual property interests from a discovery or technology relating to health care.

Machine learning aided classification of tremor in multiple sclerosis.

SummaryBackgroundTremors are frequent and disabling in people with multiple sclerosis (MS). Characteristic tremor frequencies in MS have a broad distribution range (1–10 Hz), which confounds the diagnostic from other forms of tremors. In this study, we propose a classification method for distinguishing MS tremors from other forms of cerebellar tremors.MethodsElectromyogram (EMG), accelerometer and clinical data were obtained from a total of 120 [40 MS, 41 essential tremor (ET) and 39 Parkinson's disease (PD)] subjects. The proposed method - Soft Decision Wavelet Decomposition (SDWD) - was used to compute power spectral densities and receiver operating characteristic (ROC) analysis was performed for the automatic classification of the tremors. Association between the spectral features and clinical features (FTM - Fahn-Tolosa-Marin scale, UPDRS - Unified Parkinson's Disease Rating Scale), was assessed using a support vector regression (SVR) model.FindingsOur developed analytical framework achieved an accuracy of up to 91.67% using accelerometer data and up to 91.60% using EMG signals for the differentiation of MS tremors and the tremors from ET and PD. In addition, SVR further revealed strong significant correlations between the selected discriminators and the clinical scores.InterpretationThe proposed method, with high classification accuracy and strong correlations of these features to clinical outcomes, has clearly demonstrated the potential to complement the existing tremor-diagnostic approach in MS patients.FundingThis work was supported by the German Research Foundation (DFG): SFB-TR-128 (to SG, MM), MU 4354/1-1(to MM) and the Boehringer Ingelheim Fonds BIF-03 (to SG, MM).

Connectomic analysis of unilateral dual-lead thalamic deep brain stimulation for treatment of multiple sclerosis tremor.

Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead (ventralis intermedius + ventralis oralis posterior) thalamic deep brain stimulation. Preoperative T1-weighted MRI and postoperative head CTs were used, along with applied programming settings, to estimate the volume of tissue activated for each patient. The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression (r = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression (r = −0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor.

Therapeutic maps for a sensor-based evaluation of deep brain stimulation programming.

Programming in deep brain stimulation (DBS) is a labour-intensive process for treating advanced motor symptoms. Specifically for patients with medication-refractory tremor in multiple sclerosis (MS). Wearable sensors are able to detect some manifestations of pathological signs, such as intention tremor in MS. However, methods are needed to visualise the response of tremor to DBS parameter changes in a clinical setting while patients perform the motor task finger-to-nose. To this end, we attended DBS programming sessions of a MS patient and intention tremor was effectively quantified by acceleration amplitude and frequency. A new method is introduced which results in the generation of therapeutic maps for a systematic review of the programming procedure in DBS. The maps visualise the combination of tremor acceleration power, clinical rating scores, total electrical energy delivered to the brain and possible side effects. Therapeutic maps have not yet been employed and could lead to a certain degree of standardisation for more objective decisions about DBS settings. The maps provide a base for future research on visualisation tools to assist physicians who frequently encounter patients for DBS therapy.

In vivo high-resolution structural MRI-based atlas of human thalamic nuclei

Thalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are few high spatial resolution (1 mm3 or higher) in vivo MRI thalamic atlases available currently. The goal of this work is the development of an in vivo MRI-based structural thalamic atlas at 0.7 × 0.7 × 0.5 mm resolution based on manual segmentation of 9 healthy subjects using the Morel atlas as a guide. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available.

Tremor and Dysmetria in Multiple Sclerosis: A Neurophysiological Study

Objective:The mechanisms contributing to the pathogenesis of tremor and/or dysmetria in multiple sclerosis (MS) are poorly understood. Abnormal oscillations within the olivo-cerebello-thalamo-cortical networks are believed to play an important part in tremor aetiology, but could also contribute to intention dysmetria due to disruptions in motor timing. Conversely, delayed central motor conduction times are a common feature of ataxias, but could also contribute to the expression of dysmetria in MS. This study examined the roles of central conduction delays in the manifestation of tremor and/or dysmetria in MS.Methods:Twenty-three individuals with MS participated: 8 with no movement disorder, 6 with tremor, 4 with pure dysmetria and 5 with both tremor and dysmetria. Median nerve somatosensory evoked potentials (SEPs), transcranial magnetic stimulation (TMS) over the motor cortex and cervical spine, stretch reflexes were used assess sensory and motor conduction times.Results:Central, but not peripheral, sensory conductions time were significantly delayed in participants with dysmetria, regardless of the presence of tremor. Similarly, the TMS evoked muscles responses and the long-latency component of stretch reflexes were significantly delayed in those with dysmetria, but not pure tremor.Conclusion:Dysmetria in MS is associated with delays in central conduction of sensory or motor pathways, or both, likely leading to disruption of muscle activation timing and terminal oscillations that contribute to dysmetria.Significance:The presence of dysmetria in MS is associated with decreased conduction velocities in central sensory and/or motor pathways likely reflects greater demyelination of these axons compared to those with no movement disorder or pure tremor.

Automated thalamic nuclei segmentation using multi-planar cascaded convolutional neural networks

PurposeTo develop a fast and accurate convolutional neural network based method for segmentation of thalamic nuclei. MethodsA cascaded multi-planar scheme with a modified residual U-Net architecture was used to segment thalamic nuclei on conventional and white-matter-nulled (WMn) magnetization prepared rapid gradient echo (MPRAGE) data. A single network was optimized to work with images from healthy controls and patients with multiple sclerosis (MS) and essential tremor (ET), acquired at both 3 T and 7 T field strengths. WMn-MPRAGE images were manually delineated by a trained neuroradiologist using the Morel histological atlas as a guide to generate reference ground truth labels. Dice similarity coefficient and volume similarity index (VSI) were used to evaluate performance. Clinical utility was demonstrated by applying this method to study the effect of MS on thalamic nuclei atrophy. ResultsSegmentation of each thalamus into twelve nuclei was achieved in under a minute. For 7 T WMn-MPRAGE, the proposed method outperforms current state-of-the-art on patients with ET with statistically significant improvements in Dice for five nuclei (increase in the range of 0.05–0.18) and VSI for four nuclei (increase in the range of 0.05–0.19), while performing comparably for healthy and MS subjects. Dice and VSI achieved using 7 T WMn-MPRAGE data are comparable to those using 3 T WMn-MPRAGE data. For conventional MPRAGE, the proposed method shows a statistically significant Dice improvement in the range of 0.14–0.63 over FreeSurfer for all nuclei and disease types. Effect of noise on network performance shows robustness to images with SNR as low as half the baseline SNR. Atrophy of four thalamic nuclei and whole thalamus was observed for MS patients compared to healthy control subjects, after controlling for the effect of parallel imaging, intracranial volume, gender, and age (p < 0.004). ConclusionThe proposed segmentation method is fast, accurate, performs well across disease types and field strengths, and shows great potential for improving our understanding of thalamic nuclei involvement in neurological diseases.

Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes.

The most common causes of acquired pendular nystagmus (APN) are multiple sclerosis (MS) and oculopalatal tremor (OPT), both of which result in poor visual quality of life. The objective of our study was to evaluate the effects of memantine and gabapentin treatments on visual function. We also sought to correlate visual outcomes with ocular motor measures and to describe the side effects of our treatments. This study was single-center cross-over trial. A total of 16 patients with chronic pendular nystagmus, 10 with MS and 6 with OPT were enrolled. Visual acuity (in logarithm of the minimum angle of resolution [LogMAR]), oscillopsia amplitude and direction, eye movement recordings, and visual function questionnaires (25-Item National Eye Institute Visual Functioning Questionnaire [NEI-VFQ-25]) were performed before and during the treatments (gabapentin: 300 mg 4 times a day and memantine: 10 mg 4 times a day). A total of 29 eyes with nystagmus were evaluated. Median near monocular visual acuity improved in both treatment arms, by 0.18 LogMAR on memantine and 0.12 LogMAR on gabapentin. Distance oscillopsia improved on memantine and on gabapentin. Median near oscillopsia did not significantly change on memantine or gabapentin. Significant improvement in ocular motor parameters was observed on both treatments. Because of side effects, 18.8% of patients discontinued memantine treatment-one of them for a serious adverse event. Only 6.7% of patients discontinued gabapentin. Baseline near oscillopsia was greater among those with higher nystagmus amplitude and velocity. This study demonstrated that both memantine and gabapentin reduce APN, improving functional visual outcomes. Gabapentin showed a better tolerability, suggesting that this agent should be used as a first-line agent for APN. Data from our investigation emphasize the importance of visual functional outcome evaluations in clinical trials for APN.

Vocal wow in an adapted reflex resonance model.

Vocal wow and tremor are slow modulations of the voice presumed to result from integration of auditory and somatosensory feedback, respectively. This distinction has important implications for diagnosis and treatment of neurological disorders that may differentially impact these systems, but the underlying mechanisms remain poorly understood. An important contribution on this matter is the reflex resonance model [Titze et al. (2002). J. Acoust. Soc. Am. 111(5), 2272-2282], which demonstrates that a 4-7 Hz vibrato (or tremor) can indeed be elicited by adjusting feedback parameters in a simple model of laryngeal muscle activation, mediated by time-delayed somatosensory feedback. This paper expands on this model by incorporating an auditory feedback loop and shows that wow emerges as feedback parameters exceed critical values described by a Hopf bifurcation. The wow period increases with delay and is almost invariant with respect to gain for delays above 200 ms. Parametric formulas for recovering feedback parameters from the acoustic signal are presented. With both feedback loops in place, auditory and somatosensory parameters interact and alter vocal modulations. Model predictions are illustrated in two subjects, one with a diagnosis of multiple sclerosis and intermittent tremor. Findings suggest that phonatory instabilities provide considerable insight into normal and pathogenic changes to the sensorimotor control of voice.

Reduced long-term cost and increased patient satisfaction with rechargeable implantable pulse generators for deep brain stimulation.

Deep brain stimulation (DBS) has revolutionized the treatment of neurological disease, but its therapeutic efficacy is limited by the lifetime of the implantable pulse generator (IPG) batteries. At the end of the battery life, IPG replacement surgery is required. New IPGs with rechargeable batteries (RC-IPGs) have recently been introduced and allow for decreased reoperation rates for IPG replacements. The authors aimed to examine the merits and limitations of these devices. The authors reviewed the medical records of patients who underwent DBS implantation at their institution. RC-IPGs were placed either during initial DBS implantation or during an IPG change. A cost analysis was performed that compared RC-IPGs with standard IPGs, and telephone patient surveys were conducted to assess patient satisfaction. The authors identified 206 consecutive patients from 2011 to 2016 who underwent RC-IPG placement (mean age 61 years; 67 women, 33%). Parkinson's disease was the most common indication for DBS (n = 144, 70%), followed by essential tremor (n = 41, 20%), dystonia (n = 13, 6%), depression (n = 5, 2%), multiple sclerosis tremor (n = 2, 1%), and epilepsy (n = 1, 0.5%). DBS leads were typically placed bilaterally (n = 192, 93%) and targeted the subthalamic nucleus (n = 136, 66%), ventral intermediate nucleus of the thalamus (n = 43, 21%), internal globus pallidus (n = 21, 10%), ventral striatum (n = 5, 2%), or anterior nucleus of the thalamus (n = 1, 0.5%). RC-IPGs were inserted at initial DBS implantation in 123 patients (60%), while 83 patients (40%) were converted to RC-IPGs during an IPG replacement surgery. The authors found that RC-IPG implantation resulted in $60,900 of cost savings over the course of 9 years. Furthermore, patient satisfaction was high with RC-IPG implantation. Overall, 87.3% of patients who responded to the survey were satisfied with their device, and only 6.7% found the rechargeable component difficult to use. In patients who were switched from a standard IPG to RC-IPG, the majority who responded (70.3%) preferred the rechargeable IPG. RC-IPGs can provide DBS patients with long-term therapeutic benefit while minimizing the need for battery replacement surgery. The authors have implanted rechargeable stimulators in 206 patients undergoing DBS surgery, and here they demonstrate the cost-effectiveness and high patient satisfaction associated with this procedure.

Personalised profiling to identify clinically relevant changes in tremor due to multiple sclerosis

BackgroundThere is growing interest in sensor-based assessment of upper limb tremor in multiple sclerosis and other movement disorders. However, previously such assessments have not been found to offer any improvement over conventional clinical observation in identifying clinically relevant changes in an individual’s tremor symptoms, due to poor test-retest repeatability.MethodWe hypothesised that this barrier could be overcome by constructing a tremor change metric that is customised to each individual’s tremor characteristics, such that random variability can be distinguished from clinically relevant changes in symptoms. In a cohort of 24 people with tremor due to multiple sclerosis, the newly proposed metrics were compared against conventional clinical and sensor-based metrics. Each metric was evaluated based on Spearman rank correlation with two reference metrics extracted from the Fahn-Tolosa-Marin Tremor Rating Scale: a task-based measure of functional disability (FTMTRS B) and the subject’s self-assessment of the impact of tremor on their activities of daily living (FTMTRS C).ResultsUnlike the conventional sensor-based and clinical metrics, the newly proposed ’change in scale’ metrics presented statistically significant correlations with changes in self-assessed impact of tremor (maxR2>0.5,p<0.05 after correction for false discovery rate control). They also outperformed all other metrics in terms of correlations with changes in task-based functional performance (R2=0.25 vs. R2=0.15 for conventional clinical observation, both p<0.05).ConclusionsThe proposed metrics achieve an elusive goal of sensor-based tremor assessment: improving on conventional visual observation in terms of sensitivity to change. Further refinement and evaluation of the proposed techniques is required, but our core findings imply that the main barrier to translational impact for this application can be overcome. Sensor-based tremor assessments may improve personalised treatment selection and the efficiency of clinical trials for new treatments by enabling greater standardisation and sensitivity to clinically relevant changes in symptoms.

Longitudinal follow-up of dual-lead thalamic deep brain stimulation for patients with treatment refractory multiple sclerosis tremor (P4.8-044)

Longitudinal follow-up of dual-lead thalamic deep brain stimulation for patients with treatment refractory multiple sclerosis tremor (P4.8-044)

Comment on the letter to editor: Closed loop stimulation for tremor was invented in 1980

We thank Professors Blomstedt and Hariz for drawing our attention to the pioneering work of Brice and McLellan on tremor in multiple sclerosis [1]. These authors were the first to realise and demonstrate the potential of closed-loop control in Deep Brain Stimulation. Such control adjusts stimulation parameters in real-time based on continuous feedback input signals that reflect the patient's fluctuating clinical state, and has the potential to increase the therapeutic window available to patient and clinician.

Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis

Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor (p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

Validation of a precision tremor measurement system for multiple sclerosis

BackgroundTremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. New MethodWe present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. ResultsVelocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p = 0.002) in healthy subjects. Comparison with Existing MethodsSubjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. ConclusionsTREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.

P66. Long term follow-up in bilateral deep brain stimulation of VIM in MS-related tremor

Tremor in Multiple Sclerosis is an important cause for disability. As medical treatment often does not provide a sufficient reduction of tremor amplitude, deep brain stimulation is an important option in these patients. Because in previous studies often unilateral stimulation of the VIM was performed, the aim of our retrospective analysis was to evaluate the effect of bilateral stimulation on tremor amplitude, activities of daily living, and due to an additional effect on axial tremor, improvement of global disability (EDSS) and mobility. Data from 22 Patients (12 male an 10 female) were included in our analysis. Surgery was performed at the mean age of 37,7 (range 22–54). The present evaluation included Extended Disability Status Scale (EDSS) preoperatively and 3–6 month after surgery. The clinical tremor rating (Fahn Tolosa Marin Tremor Rating Scale A–C) was scored preoperatively, 3–6 month, 1–2 years, 3–5 years and >5 years postoperatively. After surgery the clinical tremor rating showed a significant improvement of tremor amplitude in the Stim-ON condition compared to baseline parameters before surgery 3–6 month (n = 16; Fahn A p = 0.005; Fahn B p = 0.003) and 1–2 years (n = 12; Fahn A p = 0.013; Fahn B p = 0.068) but no significant improvement 3–5 and >5 years after surgery. Concerning the activities of daily living (Fahn C) no significant change could be observed during the whole period. Two patients, who were dependent on a wheelchair because of severe tremor of the lower extremities, could walk with assistance during a postoperative period of 6 respectively 24 month. Expectedly no significant change of the EDSS score could be observed (mean 6.3; range 3–8) compared to preoperative values (mean 6.1; range 3.5–8.0). 3–6 month after surgery 6.3). Global disability was not changed under treatment with bilateral stimulation of the VIM. A significant improvement of mobility was observed in only two of 22 patients, whereby impaired mobility in only 5 cases was caused by tremor and ataxia. An important problem are the tremor scales which do not appropriately reflect the changes in these most severely handicapped patients. Deep brain stimulation in Patients with Multiple Sclerosis can improve tremor amplitude, but the benefit beyond 2 years is limited. These limitations should be considered in shared decision making with the patient.