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

Tremor in multiple sclerosis

Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide some relief, but published evidence of effectiveness is very limited. Most trials were of small size and of short duration. Cannabinoids appear ineffective. Tremor reduction can be obtained with stereotactic thalamotomy or thalamic stimulation. However, the studies were small and information on long-term functional outcome is scarce. Physiotherapy, tremor reducing orthoses, and limb cooling can achieve some functional improvement. Tremor in MS remains a significant challenge and unmet need, requiring further basic and clinical research

Adaptive robot training for the treatment of incoordination in Multiple Sclerosis

<p>Abstract</p> <p>Background</p> <p>Cerebellar symptoms are extremely disabling and are common in Multiple Sclerosis (MS) subjects. In this feasibility study, we developed and tested a robot therapy protocol, aimed at the rehabilitation of incoordination in MS subjects.</p> <p>Methods</p> <p>Eight subjects with clinically defined MS performed planar reaching movements while grasping the handle of a robotic manipulandum, which generated forces that either reduced (error-reducing, ER) or enhanced (error-enhancing, EE) the curvature of their movements, assessed at the beginning of each session. The protocol was designed to adapt to the individual subjects' impairments, as well as to improvements between sessions (if any). Each subject went through a total of eight training sessions. To compare the effect of the two variants of the training protocol (ER and EE), we used a cross-over design consisting of two blocks of sessions (four ER and four EE; 2 sessions/week), separated by a 2-weeks rest period. The order of application of ER and EE exercises was randomized across subjects. The primary outcome measure was the modification of the Nine Hole Peg Test (NHPT) score. Other clinical scales and movement kinematics were taken as secondary outcomes.</p> <p>Results</p> <p>Most subjects revealed a preserved ability to adapt to the robot-generated forces. No significant differences were observed in EE and ER training. However over sessions, subjects exhibited an average 24% decrease in their NHPT score. The other clinical scales showed small improvements for at least some of the subjects. After training, movements became smoother, and their curvature decreased significantly over sessions.</p> <p>Conclusions</p> <p>The results point to an improved coordination over sessions and suggest a potential benefit of a short-term, customized, and adaptive robot therapy for MS subjects.</p

Target Identification for Stereotactic Thalamotomy Using Diffusion Tractography

BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery

Stereotactic lesional surgery for the treatment of tremor in multiple sclerosis: a prospective case-controlled study.

The effect of stereotactic lesional surgery for the treatment of tremor in multiple sclerosis was examined in a prospective case-controlled study. Surgery was not undertaken in 33 patients (72% of 46 cases referred for stereotactic surgery), two of whom died within 4 months of referral. Twenty-four multiple sclerosis patients were included in the study; 13 underwent surgery and were matched against 11 controls on the basis of age, sex, expanded disability system scores (EDSS) and disease duration. Assessments were carried out at baseline/preoperatively, and then 3 and 12 months later; these included accelerometric and clinical ratings of tremor, spirography, handwriting, a finger-tapping test, nine-hole peg test, tremor-related disability, general neurological examination, Barthel Activities of Daily Living (ADL) Index of general disability, EDSS, a 0-4 ataxia scale, Mini-Mental State (MMS) examination, speech and swallowing assessments and grip strength. Postoperative MRI scans demonstrated that tremor could be attenuated by lesions centred on the thalamus in seven cases, on the zona incerta in five cases and in the subthalamic nucleus in one case. Two patients developed hemiparesis and in two cases epilepsy recurred. Two surgical patients and one control patient died between the 3 and 6 months assessments. Both groups had a significant deterioration in EDSS but not Barthel ADL Index scores at 1 year, but the difference between the groups was not significant. Similarly, no differences between the groups' rates of deterioration of speech or swallowing or MMS were found. Significant improvements in contralateral upper limb postural (P2) and kinetic tremors, spiral scores and head tremor were detected at 3 and 12 months after surgery (but not handwriting or nine-hole peg test performance). Tremor-related disability and finger-tapping speed were also significantly better 12 months after surgery, the latter having significantly worsened for the control group. A 3 Hz 'filter' for postural (P2) upper limb tremor was detected by accelerometry/spectral analysis above which tremor was always abolished and at or below which some residual tremor invariably remained. Criteria for selecting multiple sclerosis patients for this form of surgery are discussed

Tremor and Dysmetria in Multiple Sclerosis: A Neurophysiological Study.

ObjectiveThe 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.MethodsTwenty-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.ResultsCentral, 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.ConclusionDysmetria 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.SignificanceThe 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