Unsteady gaze fixation enhances the severity of MS intention tremor.

BACKGROUND: Patients with arm intention tremor due to multiple sclerosis (MS) often manifest eye movement deficits, illustrating the role of infratentorial brain in both ocular and manual movement control. Our previous study showed that both the amplitude of intention tremor and eye fixational movements were greatly enhanced after coordinated eye-hand action toward stationary targets vs during hand movements with continuous target fixation. OBJECTIVE: The present study tested, during coordinated step-tracking movements, the hypothesis that the amplitude of hand intention tremor was influenced by (unsteady) gaze fixation onto the target. METHODS: Simultaneously recorded eye and hand tracking movements were compared between 13 MS patients with intention tremor and 14 healthy controls over conditions in which the magnitude of the primary eye and hand tracking movements, as well as their ratio, were altered. RESULTS: Patients always made larger fixational eye movements around the visual targets than the controls. In the patient group, the size of fixational eye movements decreased following a reduction in the magnitude of the preceding saccadic movement, and most interestingly, was accompanied with a decrease in tremor amplitude. An alteration in the magnitude of the primary hand movement did not affect the tremor severity. CONCLUSIONS: In patients with multiple sclerosis with intention tremor, the unsteady gaze fixation on the visual targets is proportional to the magnitude of the preceding saccades, and influences the severity of intention tremor during eye-hand coordinated visuomotor tasks.

Effects of peripheral cooling on intention tremor in multiple sclerosis.

OBJECTIVE: To investigate the effect of peripheral sustained cooling on intention tremor in patients with multiple sclerosis (MS). MS induced upper limb intention tremor affects many functional activities and is extremely difficult to treat.Materials/ METHODS: Deep (18 degrees C) and moderate (25 degrees C) cooling interventions were applied for 15 minutes to 23 and 11 tremor arms of patients with MS, respectively. Deep and moderate cooling reduced skin temperature at the elbow by 13.5 degrees C and 7 degrees C, respectively. Evaluations of physiological variables, the finger tapping test, and a wrist step tracking task were performed before and up to 30 minutes after cooling. RESULTS: The heart rate and the central body temperature remained unchanged throughout. Both cooling interventions reduced overall tremor amplitude and frequency proportional to cooling intensity. Tremor reduction persisted during the 30 minute post cooling evaluation period. Nerve conduction velocity was decreased after deep cooling, but this does not fully explain the reduction in tremor amplitude or the effects of moderate cooling. Cooling did not substantially hamper voluntary movement control required for accurate performance of the step tracking task. However, changes in the mechanical properties of muscles may have contributed to the tremor amplitude reduction. CONCLUSIONS: Cooling induced tremor reduction is probably caused by a combination of decreased nerve conduction velocity, changed muscle properties, and reduced muscle spindle activity. Tremor reduction is thought to relate to decreased long loop stretch reflexes, because muscle spindle discharge is temperature dependent. These findings are clinically important because applying peripheral cooling might enable patients to perform functional activities more efficiently.

Effect of visual information on step-tracking movements in patients with intention tremor due to multiple sclerosis.

The effect of visual information on step-tracking movements was studied in 18 patients with intention tremor due to multiple sclerosis (MS) and 15 healthy controls. Parricipants performed a slow wrist step-tracking task with stationary targets under five visual feedback conditions. The display of the target and movement cues was selectively withdrawn to examine the effects of visual information on intention tremor and movement accuracy. Results showed that intention tremor was most pronounced when visual display of both target and movement cues was available. Withdrawing visual information of the limb movement reduced tremor more than withdrawing the visual display of the target cues. Both the patient and control group was less accurate when the display of limb movement was occluded. Patients, however, were more dependent on visual information of the limb movement for accurate motor performance than healthy controls. When the visual display of the limb movement was partially occluded between or near to the targets, tremor decreased without deterioration of movement accuracy.

Intention tremor during manual aiming: a study of eye and hand movements.

Accurate goal-directed movements toward a visual target require a precise coordination of both the oculomotor and limb motor systems. Intention tremor and eye movement deficits are frequently observed in multiple sclerosis (MS). The goal of this study was to examine the characteristics of intention tremor and simultaneously produced eye movements during rapid goal-directed movements. Eye and hand movements were synchronously measured in 16 MS patients with intention tremor and 16 control subjects. Manual performances of the patient group were characterized by a delayed onset, slower execution and aiming inaccuracies. In line with the clinically defined picture of intention tremor differences between patients and control subjects were most pronounced toward the end of the movement. Dependent variables were obviously greater in MS patients compared with control subjects, and correlated well with clinical outcome measures. The application of an inertial load to the limb did not show any effect on intention tremor. In addition to impaired limb coordination, evidence has been found that eye movements, too, were abnormal in patients compared with control subjects. Moreover, eye and hand movement deficits seemed to be closely related, suggesting a common underlying command structure. Inaccurate eye movements were likely to hamper an accurate motor performance of the hand.

Validity of the TEMPA for the measurement of upper limb function in multiple sclerosis.

OBJECTIVE: To investigate concurrent and construct validity of the TEMPA (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Agées) in patients with upper limb dysfunction due to multiple sclerosis. SUBJECTS: Forty-three patients with upper limb dysfunction due to multiple sclerosis. DESIGN: Patients performed upper limb tests and were assessed on measures of functional independence. SETTING: National Multiple Sclerosis Centre, Melsbroek, Belgium. MAIN OUTCOME MEASURES: TEMPA, Jebsen Handfunction Test, Nine Hole Peg Test, Functional Independence Measure (FIM) and activities of daily living (ADL) self-questionnaire. RESULTS: The correlation between TEMPA and Jebsen Handfunction and the Nine Hole Peg test respectively is good (0.56-0.87) and high (0.79-0.9). The correlation between TEMPA and the FIM and ADL self-questionnaire was moderate (0.44-0.61) although mostly higher than the correlation between the Jebsen Handfunction and the Nine Hole Peg test respectively and the measures of functionality (0.22-0.55/0.1-0.47). CONCLUSIONS: This study provides data supporting the concurrent validity of the TEMPA with the Jebsen Handfunction and the Nine Hole Peg Test in patients with multiple sclerosis. The results suggest construct validity of the TEMPA for the measurement of functionality during activities of daily life in patients with upper limb dysfunction due to multiple sclerosis.

Torque variations during repeated passive isokinetic knee movements in persons with multiple sclerosis.

The purposes of this study were to investigate the effect of movement repetitions on resistive torque during passive isokinetic dynamometry of the knee and to determine the role of electromyographic activity in the stretched muscles on the torque measurements. Ten persons with multiple sclerosis and hypertonia of the knee muscles were compared with 10 healthy age- and gender-matched control subjects. During series of 10 flexion and extension movements of the knee at 60, 180 and 300 degrees/s, torque and electromyographic activity in the stretched muscles were registered. The persons with hypertonia presented a significantly larger torque reduction (p < 0.05) than the control subjects in all test conditions except for repeated knee flexion at 300 degrees/s. Electromyographic activity in the stretched muscles was not identified as the only explanatory mechanism for the reduction in hypertonia during the movement repetitions, suggesting that other factors were also involved.

Assistive technology to improve PC interaction for people with intention tremor.

Many patients with upper limb intention tremor encounter difficulties in mouse-driven interaction with the personal computer (PC). An assistive technology system ("the Tremor Control System"), consisting of a motion-filtering software program that supports multiple interfaces, was developed and validated with 36 persons with Multiple Sclerosis in a multi-center trial. PC-tests, requiring basic functions such as cursor placement and click and drag function, were able to differentiate between patients and control subjects (ANOVA: p<0.05). A significant time improvement on the PC-tests was found when using an optimal alternative interface instead of the standard PC-mouse (paired t-tests: p<0.01 for Point & Click test, p<0.05 for Drag & Drop test and p<0.1 for Double Click test). A significant time improvement was found for the Double Click test (paired t-tests: p<0.05) when the motion-filtering program was implemented. The number of patients able to perform fully the PC-tests increased with the Tremor Control System. Patients with marked intention tremor seemed to profit especially from this assistive technology. These users reported that working with the Tremor Control System was less fatiguing and more comfortable compared to the use of the standard PC-mouse.

Visuoperceptual impairment in MS patients: nature and possible neural origins.

Failures on visuoperceptual neuropsychological tasks (on neuropsychological tests of visuo-spatial perception or on tests concerning semantic properties of visual objects), may indicate focal deficits of visuoperceptual function, or could be the result of (an)other (peripheral) visual deficit(s), or be the effect of a more general cognitive decline. In multiple sclerosis (MS) patients exhibiting sufficient visual acuity and not showing severe cognitive deterioration, impairment on a comprehensive set of 31 visuoperceptual neuropsychological tasks was compared with spatial resolution deficits (SRD), temporal resolution deficits (TRD) for visual stimuli, abnormal pattern shift visual evoked potential (PSVEP) responses, and failing scores on neuropsychological tasks other than visuoperceptual tasks. Impairment on the visuoperceptual neuropsychological tasks was highly independent from the other abnormal visual and cognitive neurological impairments examined, suggesting that it mostly represented focal deficits. Only TRD in both eyes related to this impairment and this relationship was rather weak. Thus in some MS patients a slowed visual information processing may be one of the combined deficits underlying visuoperceptual neuropsychological task impairment. Given that SRD and TRD were not related to another stage of MS and reflect disturbances of a P (parvocellular channel and ventral stream projections) and M (magnocellular channel and dorsal stream projections) visual-system function respectively, demyelination of a certain M pathway may become a co-determinant of visuoperceptual neuropsychological task impairment more rapidly than damage to a certain P pathway.

Visuoperceptual impairment in multiple sclerosis patients diagnosed with neuropsychological tasks.

A comprehensive set of 31 binocular neuropsychological tasks assessing a series of spatial and non-spatial visuoperceptual abilities was used to study visuoperceptual impairment in a representative group of 49 MS-clinic patients exhibiting neither diagnosed ophthalmological afflictions nor major psychiatric diagnoses. Among these patients, true frequency rate of visuoperceptual impairment, i.e. of subjects failing four or more tasks, was estimated at 26%. The pattern of visuoperceptual impairment was non-uniform, non-selective, restricted and idiosyncratic. Only four tasks yielded significant rates of impairment. They concerned colour discrimination, the perception of the Müller-Lyer illusion and object recognition in two separate conditions. Each of the four factors identified by factor analysis had an important representative (with factor loading >0.35) among these four tasks. Failures on these tasks correlated poorly. Together, the four tasks satisfactorily predicted visuoperceptual impairment as defined by the comprehensive set of tasks (sensitivity 86.7%; specificity 81.3%), but with regard to an uncontaminated criterion, their aggregate sensitivity and specificity was only 75 and 56% respectively. Visuoperceptual neuropsychological task performance related significantly but weakly to cognitive status, physical disability and to pyramidal, cerebellar and brain stem neurological signs, and did not correlate with other clinical neurological signs, disease duration, type of MS, a history of optic neuritis, depression or medication status Multiple Sclerosis (2000) 6 241 - 254

Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients.

OBJECTIVE: To evaluate the contribution of respiratory muscle weakness (part 1) and respiratory muscle training (part 2) to pulmonary function, cough efficacy, and functional status in patients with advanced multiple sclerosis (MS). DESIGN: Survey (part 1) and randomized controlled trial (part 2). SETTING: Rehabilitation center for MS. PATIENTS: Twenty-eight bedridden or wheelchair-bound MS patients (part 1); 18 patients were randomly assigned to a training group (n = 9) or a control group (n = 9) (part 2). INTERVENTION: The training group (part 2) performed three series of 15 contractions against an expiratory resistance (60% maximum expiratory pressure [PEmax]) two times a day, whereas the control group performed breathing exercises to enhance maximal inspirations. MAIN OUTCOME MEASURES: Forced vital capacity (FVC), inspiratory, and expiratory muscle strength (PImax and PEmax), neck flexion force (NFF), cough efficacy by means of the Pulmonary Index (PI), and functional status by means of the Extended Disability Status Scale (EDSS). RESULTS: Part 1 revealed a significantly reduced FVC (43% +/- 26% predicted), PEmax (18% +/- 8% predicted), and PImax (27% +/- 11% predicted), whereas NFF was only mildly reduced (93% +/- 26% predicted). The PI (median score, 10) and EDSS (median score, 8.5) were severely reduced. PEmax was significantly correlated to FVC, EDSS, and PI (r = .77, -.79, and -.47, respectively). In stepwise multiple regression analysis. PEmax was the only factor contributing to the explained variance in FVC (R2 = .60), whereas body weight (R2 = .41) was the only factor for the PI. In part 2, changes in PImax and PEmax tended to be higher in the training group (p = .06 and p = .07, respectively). The PI was significantly improved after 3 months of training compared with the control group (p < .05). After 6 months, the PI remained significantly better in the training group. CONCLUSIONS: Expiratory muscle strength was significantly reduced and related to FVC, cough efficacy, and functional status. Expiratory muscle training tended to enhance inspiratory and expiratory muscle strength. In addition, subjectively and objectively rated cough efficacy improved significantly and lasted for 3 months after training cessation.

Reliability of torque measurements during passive isokinetic knee movements in healthy subjects.

In the literature, few data are available about the reliability of torque measured during passive isokinetic knee movements. This study investigated the consistency of torque measurements during passive knee movements at 60, 180 and 300 degrees/second in 30 healthy subjects. Intraclass correlation values ranged between 0.78 and 0.92 when the results of two consecutive tests were compared. When retests were performed after repositioning the subjects, intraclass correlation values ranged between 0.43 and 0.87. These findings indicate the necessity for meticulous standardization of the test situation. Series of 10 consecutive movements, specifically repetitions of knee flexion at 180 and 300 degrees/second, indicated that torque measurements during the first two movements were less stable than those following. A concurrent change in electromyographic activity in the rectus femoris muscle suggested that these torque variations resulted from habituation of the stretch reflex.

A questionnaire assessment of unmet needs for rehabilitation services and resources for people with multiple sclerosis: results of a pilot survey in five European countries. Needs Task group of MARCH (Multiple Sclerosis and Rehabilitation, Care and Health Services Research in Europe).

OBJECTIVE: To develop an international services and needs assessment instrument (SUN) for people with multiple sclerosis and their carers and to pilot this in different countries of the European Community. DESIGN: Interview study of people with multiple sclerosis, their carers and nominated key professionals examining the unmet needs of patients and carers. SETTING: Belgium, Estonia, Greece, Italy and the United Kingdom. MAIN OUTCOME MEASURES: Needs assessment questionnaire. RESULTS: The study comprised 137 people with multiple sclerosis, 125 carers and 111 professionals. Patients reported on average 2.9 unmet needs for themselves; their carers and professionals reported on average 2.4. Needs were categorized into seven broad categories. Due to difficulties experienced by the local researchers in distinguishing between needs and objectives a large proportion of needs had to be assigned to the 'other' category. CONCLUSIONS: The SUN is a valuable and practicable tool for the identification of unmet needs for people with multiple sclerosis and their carers. Formal validation and reliability testing of the different language versions is recommended.

Using the Short Form-36 with multiple sclerosis patients in five countries: a cross-cultural comparison.

Questionnaires measuring health-related quality of life are increasingly used in international studies of medical effectiveness. It is important to know if data from these instruments are comparable across countries. We initiated a collaboration among five research groups--from the USA, The Netherlands, Belgium, France, and the UK--in the field of health-related quality of life in multiple sclerosis. All groups used the 36-item Short Form Health Survey. The goal of our study was to make a cross-cultural comparison. In the five countries under study the sample size varied from 50 to 134 patients with multiple sclerosis. The survey was completed by a total of 457 patients, who were heterogeneous in relation to age, duration of illness, severity and type of multiple sclerosis. There appeared to be major differences among the samples in scores on each of the eight scales. These findings may be influenced by differences in method of recruitment, demographic and disease-related characteristics, administration, and cultural factors. After having performed a number of analyses, it appeared that the differences were mainly attributable to sampling effects; however, cultural influences could not be excluded.

Temporal resolution deficits in the visual fields of MS patients.

We assessed the relationship between temporal resolution and MS-induced neuropathy. A diagnostic strategy comprising assessments of temporal resolution at 16 points in the extra-foveal visual field up to 12 degrees from the fovea was first compared with foveal temporal resolution and with a standard VEP procedure in the same MS patients. At the group level, foveal temporal resolution was less sensitive to demyelination than the 16-point diagnostic strategy, the detection rate of which was comparable to that of the VEP procedure. Cross-sensitivity of the VEP and the 16-point diagnostic procedure was low. Subsequently, the average severity of MS-induced temporal resolution deficits was studied at three retinal loci of the same size but different eccentricities. Foveal deficits were not significantly greater than more peripheral deficits within the central 12 degrees.

Pelvic floor rehabilitation in multiple sclerosis.

Although primarily used for treatment of stress incontinence, pelvic floor rehabilitation has been reported to have some value in the treatment of detrusor instability and urgency. In neurogenic bladder dysfunction due to Multiple Sclerosis, many authors have suggested the possible use of pelvic floor rehabilitation as a treatment modality. Therefore, we designed an open prospective trial to look at the possible role of pelvic floor rehabilitation in voiding dysfunction due to MS, concentrating upon the clinical and neurological parameters in relation to the outcome. A new scoring system for pelvic floor dysfunction is introduced. Thirty female patients were evaluated. In 25, the strength of the pelvic floor was significantly improved after one month (p < 0.001). In all patients but one the endurance score improved significantly (p < 0.001) as did the exhaustibility score (p = 0.01). The relaxation score on the other hand did not show any significant evolution despite intensive training. Cystometric findings after one month did not significantly differ from the initial cystometric findings. There was a significant increase in the mean functional bladder capacity as read from the voiding charts from 173.8 cc +/- 53.9 cc to 208.5 cc +/- 57.6 cc (p = 0.005). Also the mean urinary frequency decreased significantly from 12.7 +/- 3.6 to 9.1 +/- 2.6 (p < 0.01) as did the mean number of daily incontinent episodes from 2.8 +/- 1.3 to 1.5 +/- 1.5 (p < 0.01). Pelvic floor rehabiltation has a place in the treatment of MS patients with a low Kurtzke score and without pelvic floor spasticity.

Temporal and spatial resolution in foveal vision of multiple sclerosis patients.

Deficits of spatial and temporal resolution were compared in a group of 49 definite multiple sclerosis(MS) patients showing no major evidence of previous optic neuritis attack but representative of the population of the Belgian National MS Centre as to age and the most important disease variables. Resolution in the two domains was measured foveally with forced-choice staircase psychophysical procedures using Landoldt C and double flash stimuli, respectively. The two measurements were equally sensitive to MS-induced deficits and did not exhibit cross-sensitivity. Since discrete deficits of either kind were equally prevalent and outnumbered combined deficits, this suggests a nonselective but nonuniform destruction of M and P visual pathway function in these patients.

Clinical assessment of pelvic floor dysfunction in multiple sclerosis: urodynamic and neurological correlates.

We present a study on the clinical assessment of pelvic floor dysfunction in 30 female patients with proven multiple sclerosis (MS). A scoring system for pelvic floor muscle testing by digital vaginal palpation is proposed. The concept of pelvic floor spasticity in MS is introduced. The relationship of our findings with the neurological findings and urodynamic data is presented. Pelvic floor spasticity correlates well with the presence of detrusor-external sphincter dyssynergia and with more severe spinal cord disease.

Toxicity in a double-blind, placebo-controlled pilot trial with D-penicillamine and metacycline in secondary progressive multiple sclerosis.

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficacious protease inhibitors than those used in the combination therapy described here.

Psychological functioning in primary progressive versus secondary progressive multiple sclerosis.

Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2) and mean age of onset of MS of 30.7 years (SD 11.1). Patients completed questionnaires measuring among others the following aspects of psychological functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL-90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards handicap (GHAS). Patients with a PP-MS scored significantly better on 5 out of 14 subscales than patients with SP-MS (p < .05). On the basis of our operationalizations of psychological functioning, the findings support the conclusion that on average 18 years after diagnosis of MS, amongst patients attending an MS unit, primary progressive patients were found to have better psychological functioning.

Quality of life in multiple sclerosis: the disability and impact profile (DIP).

Seventy-three Dutch and Flemish patients with definite multiple sclerosis (MS) were assessed by means of the Disability and Impact Profile (DIP), which is a 2 x 39 item, self-administered questionnaire with parallel questions about disabilities and their importance for or impact on the patient, resulting in a profile of weighted scores. It was designed as a tool for clinical assessment of quality of life (QoL) domains in MS patients. Group data showed more than 50% loss on weighted scores for "walk", "clean home", "work" and "worry about deterioration". In individual patients a median of 7 (range 0-23) major disruptions of quality of life (MD-QoL: loss on weighted score more than 50%) was found. Prevalence of MD-QoL in more than 10% of the patients was found for as many as 31 disabilities and > 50% for 3 ("clean home", "work" and "worry about deterioration"). Results in the MS group were compared with available data from 25 patients with rheumatoid arthritis (RA) and 25 patients with a spinal cord lesion (SCl). Weighted scores of "read", "memory" and "concentration" were significantly lower in the MS group than in the RA and SCl groups. Significantly lower weighted scores in both the MS and RA groups were found for "worry about deterioration", "physical endurance", "clean home", "work", "see" and "write". In conclusion, major disruptions in many domains of QoL were found in MS patients. Weighted score profiles for MS were in accordance with clinical manifestations. Unlike Kurtzke's Extended Disability Status Scale, DIP assesses a wide range of potentially MS-affected human activities, and also takes into account the subjective perception of disabilities.