Can biofeedback-based training alleviate fatigue and vigilance performance in fatigued MS patients?

MS related fatigue might be related to autonomous nervous system (ANS) dysfunctions or to inflammation related vagal (hyper-) activation. Consequently, influencing ANS status may lead to relieve of fatigue. We used two opposite biofeedback interventions to either increase sympathetic ("self-alert training", SAT) or parasympathetic activation ("progressive muscle relaxation", PMR). We recorded fatigue status of patients before and after a challenging vigilance task, their behavioural performance on this task, their skin conductance response (SCR), and parameters indicating parasympathetic activity concerning heart rate variability (HRV). We repeated these recordings after the biofeedback training sessions. Patients of the SAT group were able to learn to increase their SCR voluntarily. Patients of the PMR group showed increasing parameters indicating parasympathetic modulation of the HRV. The vigilance task increased their feeling of fatigue. However, there was no effect of biofeedback training on either fatigue status or performance on the vigilance task. Our results show that MS patients can learn to change voluntarily their ANS activity using biofeedback instructions based on SCR and this can be used in future studies to test the postulated link between ANS and fatigue. However, in this experimental intervention we were unable to document a relation between ANS activity and fatigue.Trial registration: ClinicalTrials.gov identifier: NCT03268187.

Relation between cognitive fatigue and circadian or stress related cortisol levels in MS patients.

Background Cortisol levels are increased in MS patients. However, the relation between cortisol, cognitive fatigue and load is still unknown and is investigated in this study. METHOD: In 40 MS patients and 20 healthy controls, cortisol levels were assessed (in saliva) in the morning and afternoon, before and after 5 runs of a cognitively demanding divided attention task (lasting in total 25-minutes). MS patients were divided in those suffering from cognitive fatigue (MS-F) or not (MS-NF). RESULTS: MS-NF patients showed elevated cortisol levels in the morning and in the afternoon before the reaction time task compared to healthy controls. Differences in cortisol levels among the four measurements were also larger compared to healthy controls and MS-F patients. These differences could not be explained by medication, EDSS score, MS course, age or gender. MS-NF patients also produced more omissions on the attention task compared to healthy controls and MS-F patients. MS-F patients experienced more fatigue after the attention task, but they did not show a task related performance decline. CONCLUSION: MS-NF patients, and not MS-F patients, deviate in cortisol release and task performance from healthy controls and from MS-F patients. We suggest that MS-NF patients suffer from a dysregulation of their circadian cortisol level.

Fatigue in Multiple Sclerosis is related to relapses, autonomic dysfunctions and introversion: A quasi-experimental study.

BACKGROUND: Fatigue in Multiple Sclerosis (MS) might be partially due to inflammatory processes. If so, relapses should increase the fatigue level. METHODS: Two groups of MS patients participated in this study. One suffered from a relapse and was treated by Methylprednisolone. The other group experienced a deterioration of their neurological condition but no relapse and received neurological rehabilitation. We assessed fatigue before admission, at admission and after discharge (t1, t2, t3). Furthermore, autonomic dysfunctions, depressive mood, apathy and extraversion were assessed at admission. Changes in fatigue were analysed with ANCOVAs and fatigue levels were analysed with regression analyses using clinical data and scores for depressive mood, apathy, extraversion and autonomic dysfunctions. RESULTS: Only patients suffering from a relapse showed a significant increment in fatigue from t1 to t2. Regression analyses revealed that autonomic dysfunctions and introversion best explained the fatigue level. CONCLUSIONS: This study shows that a relapse is accompanied by an increase in MS-related fatigue. Moreover, autonomic dysfunctions and introversion, more than depression and apathy, play a major role in the explanation of MS-related fatigue. This finding represents additional evidence for the relationship between inflammation, vagal afferent signaling, autonomic dysfunctions, introversion and the feeling of MS-related fatigue.

Capturing fatigue parameters: The impact of vagal processing in multiple sclerosis related cognitive fatigue.

BACKGROUND: Causes of fatigue in Multiple Sclerosis remain elusive. Recently, we developed a model linking cognitive fatigue to inflammatory processes based on a neuroinflammatory reflex-arc instantiated by the vagus nerve. The relation between experienced autonomic dysfunctions, based on vagal processing, and cognitive fatigue is well-known, but an examination of the association of objectively measured vagal activity and cognitive fatigue is missing. An attempt was made to collect behavioral and physiological evidence that can be associated with experienced autonomic dysfunctions and fatigue in Multiple Sclerosis patients. METHODS: Behavioral performance (response bias) and autonomic functioning (Heart rate variability and Skin conductance level) during an acoustic vigilance task were investigated in 53 Multiple Sclerosis patients. We assessed trait fatigue (independent from task), and time-on-task related increase of fatigue. Regression analysis was used to predict the fatigue status with physiological and behavioral scores. RESULTS: Response bias, indicating a reduced responsiveness, and high and very low frequency components of Heart rate variability, indicating an increased parasympathetic activity, contribute to the regression of trait fatigue. Reduced Heart rate variability (SDNN) and increased parasympathetic activity (pNN50) remained in the regression model predicting time-on-task fatigue. CONCLUSION: Cognitive fatigue in MS is related to parasympathetic activity and reduced responsiveness, supporting our model representing fatigue as inflammatory processes in the brain. Standardized subjective and objective autonomous dysfunction measures might be considered as additional assessments in MS.

Salivary IL-1ß as an Objective Measure for Fatigue in Multiple Sclerosis?

Background: The causes of fatigue in multiple sclerosis (MS) and other inflammatory disorders are not well understood. One possible cause that might explain fatigue in inflammatory disorders appears to be the immunological process itself, triggering neural activity that is experienced as fatigue. Objectives: To investigate whether salivary IL-1ß concentration, associated with systemic inflammation, is related to subjective fatigue in MS. Methods: 116 MS patients (62 relapsing remitting MS, 54 secondary progressive MS) and 51 healthy controls participated in this study. Salivary concentration of IL-1ß was determined using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Fatigue was assessed using various fatigue scales. We compared IL-1ß concentration between groups and performed regression analyses to investigate which variables best predict fatigue scores. Results: We found that the IL-1ß concentration best predicts fatigue scores in relapsing remitting MS patients, even though the IL-1ß concentration did not differ significantly between relapsing remitting MS patients and healthy controls. Secondary progressive MS patients showed a somewhat elevated IL-1ß concentration compared to relapsing remitting MS patients and healthy controls. Furthermore, disease modifying treatment had a significant effect on the IL-1ß concentration, with treated patients showing a lower IL-1ß concentration than non-treated patients. Conclusions: The present study points to a significant relation between the proinflammatory cytokine IL-1ß and fatigue in relapsing remitting MS patients. It also suggests a potential effect of disease modifying treatment on the peripheral IL-1ß concentration.

Subjective Cognitive Fatigue and Autonomic Abnormalities in Multiple Sclerosis Patients.

BACKGROUND: Cognitive fatigue and autonomic abnormalities are frequent symptoms in MS. Our model of MS-related fatigue assumes a shared neural network for cognitive fatigue and autonomic failures, i.e., aberrant vagus nerve activity induced by inflammatory processes. Therefore, they should occur in common. OBJECTIVE: To explore the relationship between cognitive fatigue and autonomic symptoms in MS patients, using self-reported questionnaires. METHODS: In 95 MS patients, cognitive fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions and autonomic abnormalities with the Composite Autonomic Symptom Scale-31 (COMPASS-31). We used exploratory correlational analyses and hierarchical regression analysis, controlling for age, depressive mood, disease status, and disease duration, to analyze the relation between autonomic abnormalities and cognitive fatigue. RESULTS: The cognitive fatigue score strongly correlated with the COMPASS-31 score (r = 0.47, p < 0.001). Regression analysis revealed that a model, including the COMPASS-31 domains: pupillomotor, orthostatic intolerance, and bladder, best predict the level of cognitive fatigue (R2 = 0.47, p < 0.001) after forcing the covariates into the model. CONCLUSION: In MS patients, cognitive fatigue and autonomic dysfunction share a proportion of variance. This supports our model assuming that fatigue might be explained at least partially by inflammation-induced vagus nerve activity.

Synergy effects of combined multichannel EMG-triggered electrical stimulation and mirror therapy in subacute stroke patients with severe or very severe arm/hand paresis.

BACKGROUND: Neurorehabilitation requires the development of severity-dependent and successful therapies for arm/hand rehabilitation in stroke patients. OBJECTIVE: To evaluate the effectiveness of adding mirror therapy to bilateral EMG-triggered multi-channel electrostimulation for the treatment of severe arm/hand paresis in stroke patients. METHODS: The subjects of this randomized, controlled, multicentre study were stroke patients who had suffered their first insult between 1 and 6 months before study start and had severe or very severe arm/hand paresis, as classified by Fugl-Meyer-Assessment. Subjects were randomly allocated to an intervention group (n = 16) or control group (n = 17). Both groups were treated for 3 weeks (5x week, 30 minutes) with bilateral EMG-triggered multi-channel electrostimulation. The intervention group additionally received mirror feedback of the unaffected limb. The primary outcome measure was motor recovery of the upper extremities, as measured by the Fugl-Meyer Assessment. RESULTS: The Intervention Group with very severe paresis had significantly better motor recovery in total Fugl-Meyer Assessment (p = 0.017) at a medium effect size (Cohen) of d = 0.7, due to a significant recovery of shoulder and elbow function (p = 0.003) in the Fugl-Meyer Assessment Part A subtest. For subjects with severe paresis, additional mirror therapy did not significantly influence outcome. CONCLUSION: Additional mirror therapy in combination with EMG-triggered multi-channel electrostimulation is therapeutically beneficial for post-acute stroke patients with very severe arm/hand paresis.

The High Rate CIS Auditory Brainstem Implant for Restoration of Hearing in NF-2 Patients.

AIM: Hearing preservation is one of the major goals of acoustic neuroma surgery. In NF-2 patients, bilateral hearing loss is frequently caused by the disease or results from its treatment. Several implant devices for electrical stimulation of the cochlear nucleus have been developed to restore serviceable hearing in these patients. We report our experience and results using a high rate continuous interleaved sampling (CIS) auditory brainstem implant (ABI). METHODS: Between June 1997 and May 2004, 24 NF-2 patients were managed by our group. In 20 patients an ABI was implanted successfully. The cochlear nucleus was located using anatomical landmarks and E-ABR recordings after resection of the neuroma via a retrosigmoid approach in the semi-sitting position. The 12-channel stimulating electrode array was inserted and fixed in the lateral recess. There were no surgical complications related to implantation apart from pseudomeningo that were managed by lumbar drainage. RESULTS: In one patient the electrode array became dislocated and this necessitated revision surgery which was successful. One patient failed to gain benefit from the implant. Overall, 70% of electrodes were found to be serviceable for auditory stimulation, 5.3% of electrodes were primarily nonauditory, and in 7.8% side effects during stimulation were observed. Lip reading was improved by more than 100% as a result of the additional auditory input. For many patients, comprehension of open speech was restored to a useful level. Almost all patients were able to perceive environmental sounds and tinnitus was masked. CONCLUSIONS: Restoration of hearing using ABIs in NF-2 patients is a safe and promising procedure for those who would otherwise be totally deaf. The high rate CIS speech processing strategy has proven to be very useful and effective in direct cochlear nucleus stimulation.