Visual Search in Naturalistic Scenes Reveals Impaired Cognitive Processing Speed in Multiple Sclerosis.

BACKGROUND: Standardized neuropsychological testing serves to quantify cognitive impairment in multiple sclerosis (MS) patients. However, the exact mechanism underlying the translation of cognitive dysfunction into difficulties in everyday tasks has remained unclear. To answer this question, we tested if MS patients with intact vs. impaired information processing speed measured by the Symbol Digit Modalities Test (SDMT) differ in their visual search behavior during ecologically valid tasks reflecting everyday activities. METHODS: Forty-three patients with relapsing-remitting MS enrolled in an eye-tracking experiment consisting of a visual search task with naturalistic images. Patients were grouped into "impaired" and "unimpaired" according to their SDMT performance. Reaction time, accuracy and eye-tracking parameters were measured. RESULTS: The groups did not differ regarding age, gender, and visual acuity. Patients with impaired SDMT (cut-off SDMT-z-score < -1.5) performance needed more time to find and fixate the target (q = 0.006). They spent less time fixating the target (q = 0.042). Impaired patients had slower reaction times and were less accurate (both q = 0.0495) even after controlling for patients' upper extremity function. Exploratory analysis revealed that unimpaired patients had higher accuracy than impaired patients particularly when the announced target was in unexpected location (p = 0.037). Correlational analysis suggested that SDMT performance is inversely linked to the time to first fixation of the target only if the announced target was in its expected location (r = -0.498, p = 0.003 vs. r = -0.212, p = 0.229). CONCLUSION: Dysfunctional visual search behavior may be one of the mechanisms translating cognitive deficits into difficulties in everyday tasks in MS patients. Our results suggest that cognitively impaired patients search their visual environment less efficiently and this is particularly evident when top-down processes have to be employed.

Impact of psychiatric distress and physical disability on quality of life in neuromyelitis optica spectrum disorder and chronic autoimmune demyelinating polyneuropathies.

BACKGROUND: Determinants of quality of life (QoL) in demyelinating disorders have been investigated predominantly for multiple sclerosis, especially with regard to "soft clinical signs" such as psychiatric distress. In this exploratory study, we aimed to identify common determinants of QoL for both central and peripheral demyelination in the understudied disease entities of neuromyelitis optica spectrum disorder (NMOSD) and chronic autoimmune demyelinating polyneuropathy (CADP). METHODS: 20 NMOSD and 16 CADP patients were evaluated for physical disability (EDSS and INCAT ODSS), cognitive dysfunction (neuropsychological test battery), psychiatric distress (SCL-90-R), depression (BDI), fatigue (FSMC) and quality of life (EQ-5D-3 L). A linear regression with QoL as a dependent variable and clinical parameters and demographic covariates as independent variables was computed. Additionally, a multivariate analysis of variance was computed to investigate whether NMOSD and CADP differed with regard to QoL and clinical parameters. RESULTS: Physical disability and psychiatric distress affected QoL in both NMOSD and CADP with a stronger effect for psychiatric distress in comparison to physical disability, as indicated by the higher standardized beta coefficient for psychiatric distress (b = -0.540; p = 0.002 vs. b = -0.614; p = 0.028). NMOSD reported higher subjective well-being than CADP patients (F = 6.845, p = 0.015) while having similar physical disability, cognitive dysfunction, psychiatric distress, depression and fatigue and after having accounted for the influence of age, gender, education and disease duration. CONCLUSIONS: Our findings suggest that physical disability and psychiatric distress above all clinical factors affect QoL in patients with NMOSD and CADP. Addressing adequately this aspect in demyelinating diseases would contribute to a better QoL in these patients. Furthermore, higher subjective well-being scores for NMOSD than CADP might be attributable to the distinct immunomodulatory therapy regimens and course (relapse-driven vs. chronic) of the two diseases.

Patients with chronic autoimmune demyelinating polyneuropathies exhibit cognitive deficits which might be associated with CSF evidence of blood-brain barrier disturbance.

BACKGROUND: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease. METHODS: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established. RESULTS: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates. CONCLUSIONS: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.

Cognitive Impairment in Multiple Sclerosis Is Reflected by Increased Susceptibility to the Sound-Induced Flash Illusion.

Objective: To determine whether the performance of multiple sclerosis (MS) patients in the sound-induced flash illusion (SiFi), a multisensory perceptual illusion, would reflect their cognitive impairment. Methods: We performed the SiFi task as well as an extensive neuropsychological testing in 95 subjects [39 patients with relapse-remitting MS (RRMS), 16 subjects with progressive multiple sclerosis (PMS) and 40 healthy control subjects (HC)]. Results: MS patients reported more frequently the multisensory SiFi than HC. In contrast, there were no group differences in the control conditions. Essentially, patients with progressive type of MS continued to perceive the illusion at stimulus onset asynchronies (SOA) that were more than three times longer than the SOA at which the illusion was already disrupted for healthy controls. Furthermore, MS patients' degree of cognitive impairment measured with a broad neuropsychological battery encompassing tests for memory, attention, executive functions, and fluency was predicted by their performance in the SiFi task for the longest SOA of 500 ms. Conclusions: These findings support the notion that MS patients exhibit an altered multisensory perception in the SiFi task and that their susceptibility to the perceptual illusion is negatively correlated with their neuropsychological test performance. Since MS lesions affect white matter tracts and cortical regions which seem to be involved in the transfer and processing of both crossmodal and cognitive information, this might be one possible explanation for our findings. SiFi might be considered as a brief, non-expensive, language- and education-independent screening test for cognitive deficits in MS patients.

Determinants of quality of life in relapsing-remitting and progressive multiple sclerosis.

BACKGROUND: Numerous factors can affect multiple sclerosis (MS) patients' quality of life (QoL). We investigated how physical impairment, upper extremity function, cognitive impairment, cognitive reserve, symptoms of psychological distress, depression, fatigue as well as age and disease duration contribute to patient-reported measures of QoL in relapse-remitting MS (RRMS) and progressive MS (PMS). METHODS: 39 patients with RRMS and 16 patients with PMS were evaluated for physical impairment (EDSS assessed by a neurologist), upper extremity function (9-hole peg test), cognitive deficits (broad neuropsychological test battery), cognitive reserves (highest obtained degree of education and vocabulary), symptoms of psychological distress (Symptom Checklist-90-R), depression (Beck Depression Inventory) and fatigue (Fatigue Scale for Motor and Cognitive Functions). The effects of these variables on QoL, as measured with the EQ-5D-3L, were tested with a multivariate analysis of variance. RESULTS: Degree of education, MS disease type, disease duration, BDI and SCL-90-R-scores affected significantly the EQ-5D index. Post-hoc analysis revealed that patients with university education, RRMS, shorter disease duration as well as less depression and psychological distress symptoms had significantly higher EQ-5D indices. No significant effects were observed for measures of physical disability, cognitive impairment or fatigue. CONCLUSIONS: Depression and psychological distress symptoms are among the factors with the most essential impact on subjective well-being in MS patients. Since they can be targeted by both psychopharmacological and psychotherapeutic treatment, focusing on mental comorbidity could substantially increase QoL in MS.