Ewa Gruszka

Stimulated peripheral production of interferon-gamma is related to fatigue and depression in multiple sclerosis

OBJECTIVES The aim of the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depression and clinical variables. METHODS Forty MS patients (30 women, 10 men, aged 22-60 years): 20 fatigued and 20 non-fatigued were involved in the study. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS), depression level - using Beck Depression Inventory (BDI). Production of IFNγ by stimulated peripheral blood CD3+CD4+ T lymphocytes, assessed using flow cytometry, was compared between MS patients with different levels of fatigue and controls. Correlations were searched out between immunological findings and BDI, age, duration and course of MS, relapse rate, disability (assessed in Expanded Disability Status Scale - EDSS) and its progression. RESULTS Stimulated production of IFNγ by CD3+CD4+ T lymphocytes was higher in severely fatigued patients in comparison with non-fatigued ones and controls, tended to correlate with FSS and MFIS, and correlated with BDI. No relationships were found between immunological findings and disease-related variables. CONCLUSION Stimulated production of IFNγ by peripheral CD3+CD4+ T lymphocytes is related to fatigue and depression in MS patients.

Sleep disturbances in patients with multiple sclerosis

Sleep disturbances constitute one of the important yet underestimated aspects of functioning of patients with multiple sclerosis (MS). The objective of this study was to evaluate sleep disturbances in patients with MS, with regard to demographic factors, disease-related variables, co-existing conditions and fatigue. In 100 MS patients, Epworth Sleepiness Scale (ESS) and a questionnaire about sleep disturbances (SlD) were implemented. ESS and SlD results were analyzed with regard to age, gender, duration of MS, type of its course, degree of disability in Expanded Disability Status Scale (EDSS), MS therapies, coexisting diseases, results of Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). ESS score indicated increased daytime sleepiness in 19 patients. In SlD, 49 subjects reported sleep disturbances and 35 more than one of their kind (most commonly terminal and middle insomnia). No relationships were found between ESS and SlD scores and age, gender, MS duration, type of its course, EDSS or coexisting diseases. In 36 patients, somatic complaints interfered with sleep. The patients with depression had significantly lower ESS result and those currently treated with immunomodulation had significantly lower SlD score. SlD score correlated positively with FSS and MFIS. Sleep disturbances in MS patients may occur independently from demographic and disease-related variables, but they are often influenced by the symptoms of MS and therapies used. Sleep disturbances may contribute to fatigue in the course of MS.

Neuropsychological testing and event-related potentials in the assessment of cognitive performance in the patients with multiple sclerosis—A pilot study

AIMS The aim of the study was to evaluate cognitive impairment in multiple sclerosis (MS) patients using neuropsychological testing (NT) and auditory event-related potentials (ERPs) with reference to clinical variables, with an attempt to re-assess NT and ERP results after a year. METHODS The study comprised 21 patients with MS. ERPs results were compared to age-matched controls. Correlations were searched among ERPs and NT results, duration of MS and disability. NT and ERPs were repeated after a year and their results were compared with the initial ones. RESULTS In NT, 90-100% of patients showed impaired memory and attention. Latencies of ERPs were prolonged in patients compared with controls. NT results correlated with clinical variables and N2 parameters. Results of NT, but not ERPs, improved after a year. CONCLUSIONS MS patients present with moderate cognitive impairment and ERP abnormalities, with dysfunction of subcortical-prefrontal circuit as their possible background. NT are more useful than ERP in monitoring cognitive performance in MS patients.

Event-related potentials and cognitive performance in multiple sclerosis patients with fatigue

The aim of this study was to evaluate event-related potentials (ERP) and cognition in multiple sclerosis (MS) patients with regard to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS/MFISmod). N200 and P300 components of auditory ERP were analyzed. Cognition was evaluated by means of Brief Repeatable Battery of Neuropsychological Tests (BRBNT). The results of ERP and BRBNT were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P300 latency was significantly longer in the whole MS group and in the fatigued patients than in the controls. A positive correlation was found between P300 latency and MFIS/MFISmod results, independent from age and MS-related variables. The fatigued patients scored less than non-fatigued ones in tests evaluating memory, visuomotor abilities and attention. Results of these tests correlated significantly with fatigue measures, independently from MS-related variables. Fatigue in MS patients showed significant relationships with impairment within the memory and attention domains. Parameters of auditory ERP, as electrophysiological biomarkers of cognitive performance, were not independently linked to fatigue.

Magnetic resonance spectroscopy findings as related to fatigue and cognitive performance in multiple sclerosis patients with mild disability

BACKGROUND The origin of fatigue in multiple sclerosis (MS) remains unclear. Magnetic resonance spectroscopy (MRS) provides an insight into metabolic properties of the brain. OBJECTIVES The aim of the study was to evaluate brain MRS measurements in MS patients, with regard to fatigue and cognition. METHODS The study comprised 32 MS patients and 43 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) and cognition - using the Brief Repeatable Battery of Neuropsychological Tests (parts of BRBNT). MRS voxels were placed in the parietal white matter (PWM) and the posterior cingulate gyrus (PCG); N-acetyl-aspartate (NAA), choline (Cho) and myoinositol (mI) to creatine (Cr) ratios were determined. Relationships were searched between MRS measurements and fatigue as well as BRBNT results. RESULTS MS patients in comparison with controls showed decreased NAA/Cr and increased mI/Cr ratios in PCG and PWM, respectively. No significant relationships between MRS parameters and fatigue measures, BRBNT results or MS-related variables were found. CONCLUSIONS The decrease of NAA and increase of mI within white and gray matters in MS patients do not show a significant relationship with cognitive performance or fatigue.

Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue.

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I–V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients.

Cognitive performance, fatigue and event-related potentials in patients with clinically isolated syndrome.

OBJECTIVES Cognitive impairment and fatigue are regarded as important aspects of multiple sclerosis. The aim of this study was to evaluate cognitive performance, the level of fatigue and parameters of event-related potentials (ERP) in patients diagnosed with clinically isolated syndrome (CIS). PATIENTS AND METHODS The study comprised 44 patients with CIS and 45 healthy controls. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBNT), fatigue - using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Auditory ERP were performed and the parameters of N200 and P300 components were analyzed. Neuropsychological and electrophysiological measures were referred to clinical and radiological features of the disease activity. RESULTS Forty five% of patients failed in at least one test from BRBNT, mainly within the domains of memory and attention. In 18% of patients FSS corresponded with moderate or severe fatigue. The mean latency of N200 and P300 was significantly longer and amplitude of P300 was lower in those patients with CIS than in the controls. Significant correlations were found between the results of MFIS and tests evaluating verbal memory and attention, as well as between N200 latency and results of tests for verbal memory. CONCLUSIONS Cognitive performance and fatigue deserve attention from the earliest clinical stage of MS. Abnormalities of event-related potentials in CIS suggest early impact of the disease on functional neural networks.

Cognitive impairment, event-related potentialsand immunological status in patientswith systemic lupus erythematosus

BACKGROUND Cognitive impairment (CI) is a frequent problem in lupus patients, regardless of their overt neuropsychiatric (NP) involvement. OBJECTIVES The aim of our study was to test cognitive abilities in systemic lupus erythematosus (SLE) patients by means of neuropsychological testing and event-related potentials (ERPs), and to search for their cognitive abilities correlations with a wide range of auto-antibodies. MATERIAL AND METHODS A total of 37 SLE patients were subjected to a battery of neuropsychological tests, recommended by the American College of Rheumatology (ACR), and to ERPs. They were also tested for a wide range of auto-antibodies (anti-cardiolipin (aCL), anti-β2-glycoprotein I (anti-β2-GPI), lupus anticoagulant, anti-dsDNA, anti-nucleosome, anti-ribosomal P (anti-Rib-P), anti-ganglioside, anti-Ro/SS-A, and anti-La/SS-B. RESULTS Cognitive impairment was found in 35% of patients, mostly with NP SLE (NPSLE), and was associated with higher disease activity, measured by the SLE Disease Activity Index (SLEDAI), and with a longer duration of central nervous system (CNS) involvement. There were no differences in the immunological status between CI patients and those without cognitive decline, but some antibodies were correlated with worse results in certain neuropsychological tests (anti-dsDNA and worse results of Rey Complex Figure Test - RCFTc for copying and RCFTr for recall, and of verbal fluency test (VFT); aCL IgG and worse results in Digit Span (DS) and in RCFTc). Event-related potentials showed prolonged N200 and P300 latencies in SLE patients in comparison to controls, but no differences were found between SLE and NPSLE patients. Mean P300 latency was significantly longer in patients without anti-nucleosome antibodies. CONCLUSIONS Event-related potentials can be used as a complementary tool in assessing CI in SLE patients. The immunological status of patients with CI did not differ from that of patients without cognitive problems.

Dynamics of Magnetic Resonance Image Changes in a Patient with Creutzfeldt-Jakob Disease

apraxia, extrapyramidal symptoms and motor perseveration were noted ( fig. 1 a, d), in the progression stage (third month with generalized myoclonus, severe deterioration) ( fig. 1 b, e) and in the last phase (fourth month) with akinetic mutism and autonomic dysfunction ( fig. 1 c, f). The authors indicate the possibility of employing new MRI techniques in the assessment of the changes in cerebral dynamics and their correlations with clinical symptoms in Creutzfeldt-Jakob disease patients [1, 2] . Magnetic resonance proton spectroscopy and diffusion-weighted images were conducted on a 61-year-old woman with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease, with positive 14-3-3 protein. Initially, EEG showed delta waves paroxysmal discharges, then sluggish basic activity with periodic sharp and slow wave complexes. Consecutive neuroimages were performed at the beginning of the disease (second month) when cognition and behavioral impairment, aphasia, Received: January 15, 2013 Accepted: May 8, 2013 Published online: July 25, 2013