Tremor In Multiple Sclerosis

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 Status Scale (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 centerd 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.

One hundred patients with definite Multiple Sclerosis, who were randomly selected from a Multiple Sclerosis unit in London, were examined.

In order to study the prevalence, subtypes, clinical features and associated disability of Tremor in this population.

There were 35 males and 65 females with an average age of 47 years and an average disease duration of 18.8 years.

The mean Tremor duration was 13 years, with a median latency of 11 years from disease onset to appearance of Tremor.

Tremor was reported in 37 patients but was detected in 58. Tremor affected the arms (56%), legs (10%), head (9%) and trunk (7%). There were no examples of face, tongue or jaw Tremor.

All the patients had Action Tremor, either Postural or Kinetic (including Intention). Rest, Holmes' ('Rubral') and Primary Orthostatic Tremors were not encountered.

Tremor severity ranged from minimal in 27%, to mild in 16% and moderate or severe in 15% of cases.

Tremor severity correlated with the degree of Dysarthria, Dysmetria and Dysdiadochokinesia but not with grip strength.

In order to determine the clinical characteristics of these Tremors, the Action Tremors of the upper limbs were subclassified according to the predominant site and state of Tremulous activity.

Of the 50 patients with Tremor in the right arm:
1. 32% had Distal Postural Tremor, 36% had Distal Postural and Kinetic Tremor
2. 16% had proximal Postural and Kinetic Tremor
3. 4% had proximal and Distal Postural and Kinetic Tremor
4. 12% isolated Intention Tremor

Twenty-seven percent of the overall study population had Tremor-related Disability and 10% had incapacitating Tremor.

Patients with abnormal Tremor (severity grade >1/10) were more likely than those without Tremor to be wheelchair dependent and have a worse Expanded Disability Systems Score.

But Barthel activities of daily living indices and Cognitive scores were comparable in the two groups.

Objectives
To examine the comparative reliability and validity of three simple ways of rating upper limb Tremor in patients with Multiple Sclerosis.

Methods
Three examiners independently rated severity of upper limb Tremor in patients with Multiple Sclerosis on a 0-10 scale by studying videotape recordings of patients' examinations, spiral drawings, and handwriting samples.

The correlations of the Tremor severity scores with scores from arm dexterity tests and a Tremor related Disability Scale were also assessed.

Results
Rating Tremor on posture had a good intrarater and interrater reliability.

However, these reliabilities decreased when kinetic Tremor was assessed, in part because Dysmetria was a confounding factor.

The intrarater reliabilities of rating Tremor from spirals and handwriting were also good but the interrater reliabilities were only fair to moderate.

Tremor severity scored by all three methods correlated highly with scores obtained from the Nine Hole Peg Test, Finger Tapping Test, and a Tremor related Activities Of Daily Living (ADL) questionnaire.

Indicating that all three methods were valid ways of assessing Tremor in Multiple Sclerosis.

Conclusion
Multiple Sclerosis Tremors in posture can be scored using a clinical rating scale in a valid and reliable way, and from spirals and handwriting samples if the ratings are carried out by the same examiner.

However, scoring kinetic Tremor was less reliable. In addition, the Nine Hole Peg and Finger Tapping Tests provide useful objective assessments of Upper Limb function in Tremulous patients with Multiple Sclerosis.

In just 12 years since its introduction, Deep Brain Stimulation (DBS) has become well established as a safe and effective therapy in the treatment of medically refractory Movement Disorders.

Ventralis InterMedius (Vim) DBS has virtually replaced Thalamotomy in the routine clinical treatment of Essential Tremor.

Affording relief to thousands of patients who previously would not have undergone surgery, and there is increasing usage of Vim DBS in other Tremors of Intention (e.g., Multiple Sclerosis).

SubThalamic Nucleus (STN) and Globus Pallidus internus (GPi) [Basal Ganglia] DBS have revolutionized the treatment of advanced stage Parkinson's Disease.

Improving all cardinal disease features and increasing 'on' time without Dyskinesias.

Finally, DBS of various Sub-Cortical structures is being developed and tested in other less prevalent Movement Disorders such as Dystonia.

Future developments in this rapidly advancing area will no doubt include widening indications for this relatively safe surgical procedure, elucidation of the mechanisms of action of electrical stimulation.

And technological advancements improving effectiveness and convenience.

Using a PiezoElectric Transducer, the frequency and pattern of Ocular MicroTremor (OMT) between 50 normal subjects and 50 patients with Multiple Sclerosis were compared. Controls were age matched.

All records were analyzed blindly. The frequency of OMT in the normal group was 86 (SD 6) Hz, which was significantly different from that of the Multiple Sclerosis group (71 (SD) 10 Hz, p<0.001).

Those in the Multiple Sclerosis group with clinical evidence of BrainStem or Cerebellar Disease (n=36) had an average OMT frequency of 67 (SD 9) Hz (p<0.001) compared with normal (n=86).

Whereas those with no evidence of BrainStem or Cerebellar involvement (n=14) had a frequency of 81.2 (SD 6) Hz (p<0.05, n=64).

The differences between the two Multiple Sclerosis groups were also significant (p<0.001, n=50). At least one abnormality (frequency and pattern) of OMT activity was seen in 78% of patients with Multiple Sclerosis.

In the presence of BrainStem or Cerebellar Disease 89% had abnormal records whereas in the absence of such disease 50% had abnormal records.

This is the first report of the application of this technique to patients with Multiple Sclerosis. The results suggest that OMT activity may be of value in the assessment of Multiple Sclerosis.

Objective
To assess Tremor control and side effects in patients with Multiple Sclerosis (MS) treated with chronic Thalamic stimulation for relief of Upper Extremity Tremor.

Methods
Five patients were studied before and after Thalamic placement of a Deep Brain stimulation (DBS) System.

Preoperative and postoperative evaluation included Magnetic Resonance Imaging, Extended Disability Status Scale (EDSS), the Bain-Finchley Visual Analog Scale for Tremor, video recording and NeuroPsychological testing.

Stereotactic targeting of the Vim Nucleus was done using Computed Tomography; intraoperative testing was done under local anesthesia before permanent implantation.

Results
Functionally useful Tremor suppression was obtained in 3/5 patients.

NeuroPsychological deficits of higher Cortical function, Memory and VisuoSpatial coordination were observed in all patients before surgery.

In 1 patient with improved postoperative VisuoSpatial coordination, worsened Memory was found.

New BrainStem Plaque formation was seen several weeks after surgery in 1 patient who had an acute worsening of MS which improved after high-dose IntraVenous Steroids.

Conclusions
Chronic Thalamic stimulation may help selected patients with MS-induced Tremor.

Given the complexity of their underlying illness, patients must be selected carefully, and long-term follow-up is vital to evaluate the true utility of DBS.

Copyright 2000 S. Karger AG, Basel

A Japanese woman, aged 42, was admitted because of Paroxysmal attacks consisting of Paresthesias of the left face, Tremor in the right hand, Epigastric Pain and Urinary Incontinence.

A year prior to the admission, she noticed some difficulty in writing, Dysarthria and unsteadiness of walking. These symptoms had been persistent since then.

At the end of March, 1991, these symptoms rapidly worsened, and she fell down frequently. She also experienced pain behind both Eyes, numbness in her left fingers and toe, Urinary Frequency and the above-mentioned attacks.

Neurological Examination disclosed Bilateral Internuclear Ophthalmoplegia and upbeating Nystagmus on upward gaze.

Titubation in the head, Scanning Speech, Dysmetria in all limbs, exaggerated reflexes in jaw and both legs, bilateral Extensor Plantar reflexes and Ankle Clonus.

SEP showed delayed Cortical response with stimulation of the Median Nerves bilaterally and of the right Posterior Tibial Nerve. P40 was absent with the left Posterior Tibial Nerve stimulation.

VEP was normal. T₂-weighted image of MRI showed multiple high intensity areas located around the Third Ventricle, Crus Cerebri and the right upper part of the Pons.

The diagnosis of Multiple Sclerosis was made. Each Paroxysmal attack started with numbness in the left face and burning sensation in the neck. Almost simultaneously Tremor in the right hand began.

The surface EMG showed the rhythmic contractions in the dorsal hand muscles and wrist extensors at a frequency of 6-7 Hz, and sometimes it revealed synchronized contractions of finger flexors and the dorsal hand muscles.

A few seconds later she felt painful sensation in the Epigastric region, and the Tremor gradually increased in its intensity.

A 23-year-old female was admitted to our hospital complaining of Tremor in the upper extremities and Gait disturbance.

Beginning at age 18, this patient experienced tingling of the right fingers, Gait disturbance, Dysesthesia of both hands, and Tremor in the upper extremities.

These symptoms disappeared several weeks after each onset. At age 21, Gait disturbance and coarse Tremor in the upper extremities developed. They were exaggerated and occurred repeatedly.

On Neurological Examination, the right Optic Disc was slightly pale. She had Nystagmus in all directions with Ocular movements. Deep tendon reflexes were hypoactive throughout.

There was no Tremor in the upper extremities at rest, but during the voluntary movements especially in maintaining certain posture coarse Tremor developed.

When performing goal-directed motion, such as finger-nose test, the Tremor became worse near the terminal position.

The patient's gait was broad-based, with the trunk trembling. There were no Sensory disturbances, Dysarthria, or Bowel or Bladder Dysfunction. Laboratory studies were normal except for high IgG% in the CerebroSpinal Fluid.

An ElectroMyogram using surface electrodes recorded rhythmic bursts of about 4c/s, alternating between the Extensor and the Flexor muscles of the right arm.

MRI of T₂-weighted images showed many high-intensity areas located around the bilateral Ventricles and near the area of the Decussation of Superior Cerebellar Peduncle.

A diagnosis of Multiple Sclerosis was made in this case based on the patient's history of illness and MRI findings.

The Tremor in her right upper extremity was too intense and coarse to be described as Tremor, and should better be called "Hyperkinesies Volitionnelles (HV)".

Background
Deep Brain Stimulation (DBS) offers a non-ablative alternative to Thalamotomy for the surgical treatment of medically refractory Tremor in Multiple Sclerosis.

However, relatively few outcomes have been reported.

Objective
To provide a systematic review of the published cases of DBS use in Multiple Sclerosis and to present four additional patients.

Methods
Quantitative and qualitative review of the published reports and description of a case series from one center.

Results
In the majority of reported cases (n=75), the surgical target for DBS implantation was the VentroInteroMedial Nucleus of the Thalamus.

Tremor reduction and improvement in daily functioning were achieved in most patients, with 87.7% experiencing at least some sustained improvement in Tremor control postsurgery.

Effects on daily functioning were less consistently assessed across studies; in papers reporting relevant data, 76.0% of patients experienced improvement in daily functioning.

Adverse effects were similar to those reported for DBS in other patient populations.

Conclusions
Few of the studies reviewed used highly standardized quantitative outcome measures, and follow up periods were generally one year or less.

Nonetheless, the data suggest that chronic DBS often produces improved Tremor control in Multiple Sclerosis.

Complete cessation of Tremor is not necessarily achieved, there are cases in which Tremor control decreases over time, and frequent reprogramming appears to be necessary.

Deep Brain Stimulation of the Thalamus (Thalamic DBS) is an established therapy for medically intractable Essential Tremor and Tremor caused by Multiple Sclerosis.

In both disorders, motor disability results from complex interaction between Kinetic Tremor and accompanying Ataxia with voluntary movements. In clinical studies, the efficacy of Thalamic DBS has been thoroughly assessed.

However, the optimal anatomical target structure for NeuroStimulation is still debated and has never been analyzed in conjunction with objective measurements of the different aspects of motor impairment.

In 10 Essential Tremor and 11 Multiple Sclerosis patients, we analyzed the effect of Thalamic DBS through each contact of the quadripolar electrode on the ContraLateral Tremor Rating Scale, accelerometry and kinematic measures of reach-to-grasp-movements.

These measures were correlated with the anatomical position of the stimulating electrode in stereotactic space and in relation to nuclear boundaries derived from intraoperative microrecording.

We found a significant impact of the stereotactic z-coordinate of stimulation contacts on the TRS, accelerometry total power and spatial deviation in the deceleration and target period of reach-to-grasp-movements.

Most effective contacts clustered within the SubThalamic Area (STA) covering the posterior Zona Incerta and PreLemniscal Radiation.

Stimulation within this region led to a mean reduction of the Lateralized Tremor Rating Scale by 15.8 points which was significantly superior to stimulation within the Thalamus (P < 0.05, student's t-test).

STA stimulation resulted in reduction of the accelerometry total power by 99%, whereas stimulation at the Ventral Thalamic border (68%) or within the Thalamus proper (2.5%) was significantly less effective (P < 0.01).

Concomitantly, STA stimulation led to a significantly higher increase of Tremor frequency and decrease in EMG synchronization compared to stimulation within the Thalamus proper (P < 0.001).

In reach-to-grasp movements, STA stimulation reduced the spatial variability of the movement path in the deceleration period by 28.9% and in the target period by 58.4%.

Whereas stimulation within the Thalamus was again significantly less effective (P < 0.05), with a reduction in the deceleration period between 6.5 and 21.8% and in the target period between 1.2 and 11.3%.

An analysis of the nuclear boundaries from intraoperative microrecording confirmed the anatomical impression that most effective electrodes were located within the STA.

Our data demonstrate a profound effect of Deep Brain Stimulation of the Thalamic region on Tremor and Ataxia in Essential Tremor and Tremor caused by Multiple Sclerosis.

The better efficacy of stimulation within the STA compared to Thalamus proper favors the concept of a modulation of Cerebello-Thalamic Projections underlying the improvement of these symptoms.