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.

Thalamic versus midbrain tremor; two distinct types of Holmes' Tremor: a review of 17 cases.

INTRODUCTION: Holmes Tremor (HT) is a unique and debilitating movement disorder. It usually results from lesions of the midbrain and its connection but can also result from posterior thalamic injury. Clinical examination can help lesion localization between these two areas. We studied the clinical features and their radiological correlations to distinguish midbrain HT (HT-m) from thalamic HT (HT-t). METHODS: Retrospective review of 17 patients with a HT-type presentation was conducted. Tremor characteristics, associated clinical signs and radiological findings were studied. RESULTS: Eleven patients had a myorythmic rest tremor, large amplitude proximal tremor with goal-directed worsening, with or without mild distal dystonic posturing, representing HT-m. Six patients had slow, large amplitude proximal tremors and distal choreathetoid movements, significant proximal/distal dystonic posturing, associated with proprioceptive sensory loss, representing HT-t. Haemorrhagic lesions were the predominant cause of HT-m; whereas, ischaemia was more commonly associated with HT-t. CONCLUSION: When assessing patients with HT, attentiveness to the presence of associated signs in the affected limb, such as a proprioceptive sensory deficits and additional movement disorders, can aid lesion localisation, which can have implications for management.

Deep brain stimulation in dystonia: State of art and future directions.

When considering Deep Brain Stimulation (DBS) surgical treatment of dystonia syndromes, it is important to consider multiple aspects of the disease and its presentation. It is crucial to know if the dystonia is idiopathic, inherited or acquired as well as focal, segmental or generalised. Careful phenotyping of idiopathic as well as inherited dystonias and accurate diagnosis of acquired dystonias informs the decision-making process for patients and clinicians by providing them with useful predictors of outcomes of the proposed surgery. Here, we provided a review of the current literature, highlighted the areas where evidence is scarce and suggested future directions for research.

Rapid cognitive decline: not always Creutzfeldt-Jakob disease.

A patient with rapidly progressive cognitive decline over an approximately four month period was suspected to have sporadic Creutzfeldt-Jakob disease. Features thought to support this diagnosis included psychiatric symptoms (anxiety and depression), visual hallucinations and a visual field defect. However, the finding of papilloedema broadened the differential diagnosis. Although standard brain imaging and electroencephalography had shown only non-specific abnormalities, subsequent cerebral angiography disclosed an intracranial dural arteriovenous fistula. Following embolisation, the patient made a good functional recovery. Intracranial dural arteriovenous fistula merits consideration in any patient with subacute cognitive decline, and should be included in the differential diagnosis of sporadic Creutzfeldt-Jakob disease.

Perry syndrome: a disorder to consider in the differential diagnosis of Parkinsonism.

A patient with a mood disorder and a Parkinsonian syndrome with frontal cognitive impairment thought to resemble progressive supranuclear palsy defied precise diagnosis until the development of respiratory compromise, prompting consideration of the diagnosis of Perry syndrome. A mutation in the dynactin 1 gene confirmed the diagnosis. Few examples of this disorder, characterised by depression, Parkinsonism, and respiratory insufficiency, have been reported but it may be more commonly recognised with the availability of genetic testing. Perry syndrome needs to be considered in the differential diagnosis of Parkinsonism, particularly in autosomal dominant pedigrees. Diagnosis early in the disease course may facilitate monitoring and prompt intervention to avoid potentially fatal respiratory failure.

Target board test for the quantification of ataxia in tremulous patients.

OBJECTIVE: The objective was to develop and assess the validity and reliability of a target board test (TBT) for quantifying ataxia and measuring dysmetria in the presence of tremor. DESIGN: Each subject was instructed to reach out and mark a target placed at arm's length with a pen (10 times with each hand). Ten patients performed the test twice. SETTING: A hospital-based multiple sclerosis (MS) unit. SUBJECTS: Fifty-three patients with MS and upper limb tremor/ataxia and 20 healthy control subjects. The MS patients were classified into four subgroups: MS control group (n = 13), MS tremor group (n = 9), MS dysmetria group (n = 6), MS mixed (tremor and dysmetria) group (n = 25). MAIN OUTCOME MEASURES: The main outcome measures were the average radial distance away from the target (mean R) and the mean directional error (mean V) of the 10 contact points from the target. From these a dysmetria tremor index (DTI) was calculated by dividing mean V by mean R. Also used were a dysmetria scale, a dysdiadochokinesia scale and a finger-tapping test. RESULTS: Mean R correlated significantly with dysmetria, dysdiadochokinesia, kinetic tremor and (inversely) with the finger-tapping test (all p < 0.005). The median difference between two measurements of mean R for all 10 contact points was 11.3% and 19.0% and for mean V48.3% and 63.4% and DTI 57.2% and 50.5% for the right- and left-hand sides respectively, indicating the considerable directional variability within ataxia. CONCLUSION: The TBT provides simple quantitative objective measurements of upper limb ataxia.

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.

A study of tremor in multiple sclerosis.

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, 32% had distal postural tremor, 36% had distal postural and kinetic tremor, 16% had proximal postural and kinetic tremor; 4% had proximal and distal postural and kinetic tremor and 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.

Evaluation of three different ways of assessing tremor in multiple sclerosis.

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.

Frequency analysis of involuntary movements during wrist tracking: a way to identify ms patients with tremor who benefit from thalamotomy.

To identify those multiple sclerosis (MS) patients with disabling tremor who will benefit most from thalamotomy, measurements of frequency spectra of involuntary movements during visually guided wrist tracking were carried out in 11 consecutive patients with MS before and after ventrolateral thalamotomy. Thalamotomy was significantly more effective if patients had disruptive action tremor which appeared as a single peak in the frequency spectra. Such patients showed an average reduction of nearly 80% in tremor magnitude after thalamotomy. In comparison, surgery produced an average reduction of only 30% in 3 other patients who had action tremor but showed multiple peaks in the frequency spectra. Frequency analysis of involuntary movements identifies those MS patients with disabling tremor who benefited most from thalamotomy.