Juhani Ruutiainen

Attention related performance in two cognitively different subgroups of patients with multiple sclerosis.

To evaluate the underlying mechanisms of cognitive decline in multiple sclerosis, two clinically and demographically matched multiple sclerosis groups differing in cognitive status were assessed with attention related tasks. In addition to the attention tests recommended by the Cognitive Function Study Group of the American National Multiple Sclerosis Society, a test of sustained attention was used to evaluate the role of possible fatigue on cognitive performance. The cognitively mildly deteriorated group was slower than the cognitively preserved group and the controls on all tests of attention. The mildly deteriorated group did not, however, consistently differ from the other groups in the error scores of the attention tests. The preserved group exhibited slowness at the end of the visual vigilance test, but no deficits were found on the other attention related tests in this group. It is suggested that dissociable kinds of processing slowness are the origin of the deficits found on the attention tests in the two multiple sclerosis groups. Our preserved group exhibited signs of motor and fatigue related slowness, whereas the mildly deteriorated group also had extensive cognitive slowness. As sensitive indicators of cognitive slowness, attentional tests should be included in evaluation of the cognitive status of patients with multiple sclerosis.

Memory deficits and early cognitive deterioration in MS

Introduction– In the present study, the pattern of memory and learning deficits in two cognitively different, but clinically and demographically similar, multiple sclerosis (MS) groups was compared. Material & methods– 23 patients represented the cognitively preserved MS group and 22 patients the MS group with early cognitive decline. A control group of 35 healthy controls was also included. The cognitive status of the subjects was defined using the Mild Deterioration Battery (MDB). Furthermore, all subjects were given a set of memory and learning tests and were instructed to evaluate the frequency of their memory and learning difficulties. The Mini‐Mental State Examination (MMSE) was also administered to all subjects. Results– The cognitively deteriorated patients, even those with normal MMSE performance, showed widespread memory and learning deficits, but adequate self‐evaluation of their everyday memory and learning difficulties. The preserved group, in turn, performed similarly to the controls. Conclusion– Widespread memory and learning deficits are associated with relatively mild cognitive decline in MS. These deficits were observable in the intermediate‐length screening battery, the MDB, but not in the MMSE. The present study suggests that the accuracy of patients’own evaluations of their memory and other cognitive problems is superior to the results of very brief screening batteries, like the MMSE. Therefore, brief screening in neuropsychological assessment of MS patients is not recommendable.

Exercise capacity, disability and leisure physical activity of subjects with multiple sclerosis:

The purpo se of the present study was to examine exercise capacity and its relationship to neurological disability as measured using the Expanded Disability Status Scale (EDSS) and to leisure physical activity in subjects with multiple sclerosis (MS). Thirty-four men and 61 women (mean age 44±6.7 years, mean disease duration 5.7±6.4 years) with mild to moderate disability (EDSS range 1.0- 5.5) participated. They underwent an incremental exercise test on a leg cycling ergometer. Leisure physical activity was measured using a questionnaire. Peak oxygen uptake (VO 2peak) in men was 27.0±5.2 mL/kg/min, and in women 21.7±5.5 mL/kg/min. The disability correlated inversely with the VO 2peak both in men (r = -0.50, P =0.004) and in women (r = -0.25, P =0.05). No correlation between disease duration and VO 2peak was found. In a multivariate regression analysis, neurological disability was confirmed as a predictor of VO 2peak. No evidence of a relationship between leisure physical activity and VO 2peak was found. A main finding was that disability and exercise capacity are inter-related, even in subjects who are not severely handicapped (84% had an EDSS of B-4.0). The level of disability should be taken into account in the planning of aerobic exercise programs for fully ambulatory MS subjects.

Myelin basic protein antibodies in the serum and CSF of multiple sclerosis and subacute sclerosing panencephalitis patients.

A solid‐phase radioimmunoassay was developed for the detection of myelin basic protein antibodies of immunoglobulin G (IgG) class. Purified basic protein of myelin (MBP) was adsorbed onto polystyrene beads, followed by incubation in dilutions of serum or cerebrospinal fluid (CSF). 125I‐labelled anti‐human IgG was used to quantify antibodies bound to the solid‐phase. The assay was optimized in tests with rabbit antibodies to MBP and with 125I‐labelled anti‐rabbit IgG.

Language functions in incipient cognitive decline in multiple sclerosis

Although the mechanisms of cognitive impairment in multiple sclerosis (MS) have been extensively studied, evaluation of language functions has been given little attention. In the present study, we evaluated whether impairment of language functions is associated with cognitive decline in MS. We studied naming, reading, and writing performance of two carefully matched patient groups differing only with respect to cognitive status. In language tasks, the patients with incipient cognitive decline not only demonstrated performance slowness but also made more errors than the patients with preserved cognitive capacity and the healthy controls. The comprehensive naming error analysis revealed that the cognitively deteriorated patients produced error types not present in the other two study groups. Contrary to previous suggestions, the present study indicates that impaired language performances in MS are attributable to mild cognitive deterioration rather than to sensory or motor factors. Thus, assessment of language functions should be included in neuropsychological evaluations of MS patients.

Using Haptic Feedback to Improve Grasp Force Control in Multiple Sclerosis Patients

We describe a simple and low-cost system that can help multiple sclerosis (MS) patients with asymmetric impairment to exert better grasp force control in manipulation tasks. The approach consists of measuring force vectors at the fingertips of the impaired hand, computing the force imbalance among the fingers, and providing corresponding haptic signals to the fingers of the opposite hand. Tests conducted on 24 MS patients indicated that for those with mild impairment, slightly better results were obtained with an ldquoevent-cuerdquo feedback (ECF) that alerted them when the grasp forces were straying outside of a desirable range. For patients with more severe impairment, better results were obtained by providing a proportional signal, in which the frequency and duty cycle of vibration pulses were correlated directly with the magnitudes of the fingertip forces. Post-test surveys of the patients also indicated that mildly impaired subjects preferred an event-cue feedback, and more severely impaired subjects preferred the proportional feedback.

Visual object recognition in multiple sclerosis

Deficits in tasks measuring visual processing have been earlier reported in studies of MS. Yet, the nature and severity of visual-processing deficits in MS remains unclear. We used a new method in order to measure the different stages of visual processing in object recognition: shape recognition, familiarity recognition, semantic categorization, and identification with naming. Six two-choice reaction-time tasks were presented to 30 MS patients and 15 healthy controls. The patients were divided into cognitively preserved and cognitively deteriorated study groups according to their cognitive status. The purpose was to find out whether deficits at specific stages of visual processing can be found in cognitively deteriorated MS patients. Cognitively deteriorated MS patients did not perform as well as cognitively preserved MS patients or healthy controls. They were slower already at the early stage of visual processing where discrimination of whole objects from scrambled ones was required. They also had higher error rates in tasks requiring object familiarity detection and object identification with naming. Thus, cognitively deteriorated MS patients had difficulties in visual shape recognition and semantic-lexical processing. However, variation of performances was large within both of the patient groups indicating that even patients without a generalized cognitive decline may have deficits in some stages of the visual processing. We suggest that because of the heterogeneity of the patients, every single case needs to be examined separately in order to identify the possible deficits in visual processing.

Semantic memory deficit in multiple sclerosis; impaired understanding of conceptual meanings

The aim of the present study was to determine whether a cognitive decline, related to multiple sclerosis (MS), also involves deficits in semantic memory. Semantic memory function was evaluated by studying the conscious understanding of conceptual meanings. A group of MS patients with cognitive decline was presented with four tasks concerning concepts, their attributes and relationships to other concepts. The tasks were designed to measure spontaneous, cued and recognition performance separately. The patients had difficulties in understanding conceptual meanings. Easing the retrieval demands of the tasks did not help them to improve their performance which was poorer than the control groups on every task used. The results indicate a retrieval deficit combined with an underlying storage deficit in the semantic memory of MS patients with cognitive decline.

A follow-up study of chromosome 19q13 in multiple sclerosis susceptibility.

A possible role of allelic variation on chromosome 19q13 in multiple sclerosis (MS) susceptibility has been suggested. We tested association of sixteen 19q13 markers with MS in 459 families. Nominally significant associations were tested in an independent set of 323 families as well as in the pooled set of 782 families. We were not able to confirm previously suggested associations with APOE, GIPR, ZNF45, ILT6 and D19S585. In the screening dataset nominally significant associations were found with D19S867 and with APOE haplotype (p=0.007 in both), but these were not replicated in the independent dataset nor in the pooled analysis of 757 families. Thus, we were not able to detect any statistically significant allelic associations. Re-sequencing based approaches may be required for elucidating the role chromosome 19q13 with MS.

The effects of heat stress on physical functioning in persons with multiple sclerosis

Heat sensitivity is a well-recognised feature in multiple sclerosis (MS). However, little is known about how heat affects physical performance in persons with MS. The objective of the study was to evaluate the effects of short-term heat stress on physical functioning in persons with MS. Twenty-three heat-sensitive MS subjects and 19 healthy controls participated. Moderate heat exposure took place in a dry Finnish sauna. Measures of upper and lower extremity function, static and dynamic balance, and walking capacity were applied. Core body temperature was measured by a telemetric physiological monitoring system. Assessments were conducted before, immediately, 1 hour, and 1 day after the heat exposure. Subjects with MS showed a significantly (P=0.002) higher core body temperature than the controls following the heat stress. Performances in walking (P<0.001), chair rise (P=0.005) and functional reach (P=0.04) were poorer in MS subjects than in controls immediately after the heat. No prolonged heat effects were observed. An increase in ambient temperature causes a higher core body temperature rise in MS subjects than in healthy controls. This rise in temperature is associated with acute, but not prolonged detrimental effects on physical functioning.