The role of disability and depression in cognitive functioning within 2 years after multiple sclerosis diagnosis

OBJECTIVES: To investigate cognitive functioning shortly after multiple sclerosis (MS) diagnosis and to examine the relationship with disability, depression and anxiety. METHODS: Data were available for 101 recently diagnosed MS patients and 117 healthy controls. Neuropsychological and clinical assessment included Rao's Brief Repeatable Battery, Expanded Disability Status Scale (EDSS), and Hospital Anxiety and Depression scale (HADS). RESULTS: Patients had lower scores than controls on timed tasks (Paced Auditory Serial Addition Test (PASAT3, p-value adjusted for age, sex and education = 0.04; PASAT2, p = 0.001), Word List Generation Test (WLG, p = 0.04)). Scores on Symbol Digit Modalities Test (SDMT; p = 0.001), PASAT3 (p = 0.01) and PASAT2 (p < 0.001) showed significant association with EDSS. Patients with EDSS >or= 3.0 had significantly lower scores on Selective Reminding Test (SRTC, p = 0.04), SDMT (p = 0.002), PASAT3 (p = 0.002), PASAT2 (p < 0.001) and WLG (p = 0.01) than controls from the general population. Patients with clinically borderline scores of depression scored lower on SDMT (49.5 versus 57.1, p = 0.06) and PASAT3 (39.8 versus 47.1, p = 0.03). However, after adjustment for EDSS and time since disease onset, these differences were not statistically significant. CONCLUSION: Within two years after diagnosis, patients with MS had lower scores compared to healthy controls on timed tasks, suggesting cognitive slowing in patients with early MS. Cognitive impairment was associated with symptoms of depression, but this association could be explained by differences in disability.     

Effects of acute relapses on neuropsychological status in multiple sclerosis patients

Little is known about neuropsychological status changes in multiple sclerosis (MS) patients experiencing a relapse. The Symbol Digit Modalities Test (SDMT) and MS Neuropsychological Screening Questionnaire (MSNQ) are brief measures of cognitive performance and self-reported status, respectively. We retrospectively identified relapses in subjects participating in the 48-week open-label, safety-extension study of natalizumab (STRATA) to determine if changes in cognitive ability occurred during acute relapses. SDMT and MSNQ were administered prior to infusions. We analyzed SDMT and MSNQ scores pre- and post-relapse in 53 MS patients with relapses (cases) and 115 MS patients without relapses (controls) matched on age, gender, baseline SDMT and time from study initiation. ANOVA and GLM were used to compare cases versus controls overall, and stratified by EDSS cerebral functional status (cFS) scores. SDMT change pre- to post-relapse in cases was significantly lower than difference between similar time points in controls (p = 0.003). When comparing visit 2 (two visits pre-relapse) to visit 1 (first visit post-relapse), MSNQ change was significantly different between cases and controls (p = 0.012). For cFS ≤ 1, the change in SDMT was significantly different between cases and controls but not for cFS ≥ 2. These results confirm the involvement of cognitive function during some MS relapses suggesting the SDMT or MSNQ can be used to identify transitory neuropsychological status changes and cognitive relapses.     

A new assessment tool for patients with multiple sclerosis from Spanish-speaking countries: validation of the Brief International Cognitive Assessment for MS (BICAMS) in Argentina

Background: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is an international assessment tool for monitoring cognitive function in multiple sclerosis (MS) patients. BICAMS comprises the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test – Second Edition (CVLT II) and the Brief Visuospatial Memory Test – Revised (BVMT-R). Our objective was to validate and assess the reliability of BICAMS as applied in Argentina and to obtain normative data in Spanish for this population. Method: The sample composed of 50 MS patients and 100 healthy controls (HC). In order to test its reliability, BICAMS was re-administered in a subset of 25 patients. Results: The sample’s average age was 43.42 ± 10.17 years old, and average years of schooling were 14.86 ± 2.78. About 74% of the participants were women. The groups did not differ in age, years of schooling, or gender. The MS group performed significantly worse than the HC group across the three neuropsychological tests, yielding the following Cohen’s d values: SDMT: .85; CVLT I: .87; and BVMT-R: .40. The mean raw scores for Argentina normative data were as follows: SDMT: 56.71 ± 10.85; CVLT I: 60.88 ± 10.46; and BVMT-R: 23.44 ± 5.84. Finally, test–retest reliability coefficients for each test were as follows: SDMT: r = .95; CVLT I: r = .87; and BVMT-R: r = .82. Conclusion: This BICAMS version is reliable and useful as a monitoring tool for identifying MS patients with cognitive impairment.     

Electrophysiological and clinical correlates of corpus callosum atrophy in patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating disorder of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Corpus callosum (CC) is commonly involved during the disease process leading to atrophy (93%). Currently, there are no established markers of disease progression and the interplay of processes leading to brain atrophy in MS remains unknown. The primary aim of this study was to assess the frequency of CC atrophy in MS patients. Furthermore, the relationship between expanded disability status scale (EDSS) and transcranial magnetic stimulation (TMS) evoked motor potentials (MEP) were assessed to capture disease effects by independent parameters. Seventy-nine MS patients and 50 controls were included and their CC volumes were assessed. Out of 79 patients, 31 patients (39·2%) had CC atrophy. The distribution of EDSS scores among the group with CC atrophy [13 (32%) patients with EDSS 0–2; 11 (58%) patients with EDSS 2–4; 19 (24%) patients with EDSS ≥4] was not statistically significant (p>0·05). MEP latency was abnormal in 34 (43%) patients, 67 (85%) patients had abnormal MEP amplitude and CMCT was abnormal in 32 (41%) patients. The relation between EDSS and MEP was statistically significant among the patient population including the subgroup of patients with CC atrophy (p<0.05). Our results lacked to provide an association between disability and CC atrophy, but there was a correlation between CC atrophy and TMS evoked motor potentials. Early evolution of axonal degeneration and brain atrophy should be considered in terms of follow-up measures to provide long-term efficiency impacting disability, progression and brain atrophy.     

Brief International Cognitive Assessment for Multiple Sclerosis scores are associated with the cortical thickness of specific cortical areas in relapsing-remitting patients

BackgroundCognitive impairment is frequent and disabling in multiple sclerosis (MS). The Brief International Cognitive Assessment in MS (BICAMS) is a recent short battery usable in clinical practice for cognitive evaluation of MS patients.ObjectiveTo find cortical areas or brain volumes on magnetic resonance imaging (MRI) structural sequences associated with BICAMS scores in MS.MethodsIn this cross-sectional single-center study (NCT 03656055, September 4, 2018), 96 relapsing remitting-MS patients under natalizumab and without recent clinical or radiological inflammation were included. Patients underwent brain MRI and the three BICAMS tests, evaluating information processing speed (SDMT), visuo-spatial memory (BVMT-R), and verbal memory (FVLT).ResultsCortical thickness in the left frontal superior and the right precentral gyri was associated with BVMT-R scores whereas cortical thickness in the left Broca's area and the right superior temporal gyrus was associated with FVLT scores. We observed associations between white matter inflammatory lesions connected to these cortical regions and BICAMS subscores.ConclusionsBICAMS scores are associated with specific cortical areas, the cognitive domain matching the known functions of the cortical area. Specific cognitive impairments in MS may be associated with specific cortical regions, themselves influenced by white matter inflammatory lesions and demographical parameters (age, sex, education level).     

The association between retinal nerve fibre layer thickness and corpus callosum index in different clinical subtypes of multiple sclerosis

The objective of this paper is to evaluate the association between physical disability in multiple sclerosis (MS) patients, the thickness of the retinal nerve fibre layer (RNFL) and corpus callosum volumes, as expressed by the corpus callosum index (CCI). This study was based on a cohort of 212 MS patients and 52 healthy control subjects, who were age and gender matched. The MS patients included 144 women and 177 relapsing-remitting MS (RRMS) patients. Peripapillary and volumetric optical coherence tomography (OCT) scans of the macula were performed using spectral-domain OCT technology. All magnetic resonance imaging (MRI) scans were performed using 1.5-T systems. CCI and RNFL were lower in MS than healthy control subjects (0.341 versus 0.386, p < 0.01 and 92.1 versus 105.0, p < 0.01). In addition, CCI correlated with RNFL (r = 0.464, p < 0.01). This was also true for the subgroup of patients with no history of optic neuritis (ON). There is a correlation between the thickness of the RNFL and CCI values in MS patients with no history of ON, which suggests that OCT might be a suitable marker for neurodegeneration in MS clinical trials.     

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study

BackgroundRetinal abnormalities measured by optical coherence tomography (OCT) have been detected in both Parkinson's disease (PD) and Alzheimer's disease (AD). Cognitive impairment is not only found in AD, but 75–90% of PD patients will also develop dementia in the late stage of disease. We assessed whether baseline retinal nerve fiber layer (RNFL) thickness predicted worsening of cognitive status over time and the correlation between RNFL thickness and the detailed impaired cognitive domains in PD.MethodsRNFL thickness was measured using high-definition OCT in 78 non-dementia PD patients. Clinical and cognitive assessments were performed at baseline and at 3.61 ± 0.65 years follow-up. Linear mixed-effects models were used to examine associations between RNFL thickness and the changes in cognitive test scores, after adjusting for age, sex, disease duration and education.ResultsAnalysis of outcomes according to baseline RNFL tertiles showed worse performance in global cognitive tests, delayed memory, and executive functions in patients with a thin RNFL. During follow-up, greater cognitive deterioration was found in thin RNFL tertile patients. Lower baseline average RNFL thickness was associated with greater annualized decline in Mini-Mental State Examination and Montreal Cognitive Assessment.ConclusionThe correlation between RNFL thickness and cognitive dysfunction suggests that OCT may be useful for predicting cognitive dysfunction in PD patients.     

Neuropsychological deficits but not coping strategies are related to physical disability in multiple sclerosis

Detailed neuropsychological assessment was performed in 86 women (48 patients with stable relapsing-remitting multiple sclerosis (MS) and 38 matched healthy controls (HC)). Patients were categorized into patients without (EDSS < or =1, n = 26) and with physical disability (EDSS > or =2, n = 22). Patients with EDSS > or =2 scored significantly (P < 0.05) higher in Beck's depression inventory (BDI) and depression scores (DS) compared to HC and patients with EDSS < or =1. No significant differences were found with respect to the use of specific coping strategies between the patient groups, who preferred active (EDSS < or =1) or distracting (EDSS > or =2) strategies. Cognitive deficits were significantly increased in MS with EDSS > or =2 with regard to visuo-construction and visual memory, in particular with respect to geometric figures, compared to MS with EDSS < or =1. Significant positive correlations of depression variables (BDI, DS and BL) and depressive as well as denying coping strategies were found. Our results showed increased depression scores and increased cognitive deficits in advanced physically disabled patients, without selection of specific coping strategies. This supports an individual MS-specific neuropsychological therapeutic approach in order to improve disease related deficits together with social functioning.     

Memory decline evolves independently of disease activity in MS

BACKGROUND: The natural history of cognitive impairment in multiple sclerosis (MS) and its relationship with disease activity is not well known. In this study, we evaluate a prospective cohort of 44 MS patients who were followed every 3 months for 2 years. Cognitive evaluation was done at baseline and by the end of the study using the Brief Repeatable Battery-Neuropsychology. Clinical evaluation included assessment of new relapses and changes in disability (Extended Disability Status Scale (EDSS)) confirmed at 6 months. RESULTS: We found that verbal memory performance deteriorates after 2 years in patients with MS. These changes were observed in stable and active patients both in terms of relapses and disability progression, even at the beginning of the disease, and in patients with or without cognitive impairment at study entry. Attention and executive functions measured with the symbol digit modality test (SDMT) declined after 2 years in patients with confirmed disability progression. Furthermore, SDMT performance correlated with the EDSS change. CONCLUSIONS: Our findings indicate that verbal memory steadily declines in patients with MS from the beginning of the disease and independently of other parameters of disease activity.     

Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis

BACKGROUND: Studying axonal loss in the retina is a promising biomarker for multiple sclerosis (MS). Our aim was to compare optical coherence tomography (OCT) and Heidelberg retinal tomography (HRT) techniques to measure the thickness of the retinal nerve fiber layer (RNFL) in patients with MS, and to explore the relationship between changes in the RNFL thickness with physical and cognitive disability. We studied 52 patients with MS and 18 proportionally matched controls by performing neurological examination, neuropsychological evaluation using the Brief Repetitive Battery-Neuropsychology and RNFL thickness measurement using OCT and HRT. RESULTS: We found that both OCT and HRT could define a reduction in the thickness of the RNFL in patients with MS compared with controls, although both measurements were weakly correlated, suggesting that they might measure different aspects of the tissue changes in MS. The degree of RNFL atrophy was correlated with cognitive disability, mainly with the symbol digit modality test (r=0.754, P<0.001). Moreover, temporal quadrant RNFL atrophy measured with OCT was associated with physical disability. CONCLUSION: In summary, both OCT and HRT are able to detect thinning of the RNFL, but OCT seems to be the most sensitive technique to identify changes associated with MS evolution.     

Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline

Cognitive dysfunction is common in multiple sclerosis (MS), yet the magnitude of change on objective neuropsychological (NP) tests that is clinically meaningful is unclear. We endeavored to determine NP markers of the transition from employment to work disability in MS, as indicated by degree of decline on individual tests. Participants were 97 employed MS patients followed over 41.3 ± 17.6 months with a NP battery covering six domains of cognitive function. Deterioration at follow-up was designated as documented and paid disability benefits (conservative definition) or a reduction in hours/work responsibilities (liberal definition). Using the conservative definition, 28.9% reported deteriorated employment status and for the liberal definition, 45.4%. The Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test, Total Learning (CVLT2-TL) measures distinguished employed and disabled patients at follow-up. Controlling for demographic and MS characteristics, the odds ratio of a deterioration based on a change of 2.0 on the CVLT2-TL was 3.7 (95% CI 1.2–11.4 and SDMT by 4.0 was 4.2 (95% CI 1.2–14.8), accounting for 86.7% of the area under the ROC curve. We conclude that decline on NP testing over time is predictive of deterioration in vocational status, establishing a magnitude of decline on NP tests that is clinically meaningful.      

Neuropsychological deficits but not coping strategies are related to physical disability in multiple sclerosis

Detailed neuropsychological assessment was performed in 86 women (48 patients with stable relapsing-remitting multiple sclerosis (MS) and 38 matched healthy controls (HC)). Patients were categorized into patients without (EDSS ≤1, n = 26) and with physical disability (EDSS ≥2, n = 22). Patients with EDSS ≥2 scored significantly (P < 0.05) higher in Beck’s depression inventory (BDI) and depression scores (DS) compared to HC and patients with EDSS ≤1. No significant differences were found with respect to the use of specific coping strategies between the patient groups, who preferred active (EDSS ≤1) or distracting (EDSS ≥2) strategies. Cognitive deficits were significantly increased in MS with EDSS ≥2 with regard to visuo-construction and visual memory, in particular with respect to geometric figures, compared to MS with EDSS ≤1. Significant positive correlations of depression variables (BDI, DS and BL) and depressive as well as denying coping strategies were found. Our results showed increased depression scores and increased cognitive deficits in advanced physically disabled patients, without selection of specific coping strategies. This supports an individual MS-specific neuropsychological therapeutic approach in order to improve disease related deficits together with social functioning.     

Randomized controlled trial of physical activity,cognition, and walking in multiple sclerosis

The present study adopted a randomized controlled trial design and examined the effect of a physical activity behavioral intervention on cognitive and walking performance among persons with MS who have mild or moderate disability status. A total of 82 MS patients were randomly allocated into intervention or wait-list control conditions. The intervention condition received a theory-based program for increasing physical activity behavior that was delivered via the Internet, and one-on-one video chat sessions with a behavior-change coach. Participants completed self-report measures of physical activity and disability status, and underwent the oral Symbol Digit Modalities Test (SDMT) and 6-minute walk (6MW) test before and after the 6-month period. Analysis using mixed-model ANOVA indicated a significant time × condition × disability group interaction on SDMT scores (p = 0.02, partial-η ² = 0.08), such that persons with mild disability in the intervention condition demonstrated a clinically meaningful improvement in SDMT scores (~6 point change). There was a further significant time × condition interaction on 6MW distance (p = 0.02, partial-η ² = 0.07), such that those in the intervention condition demonstrated an increase in 6MW distance relative to those in the control group. The current study supports physical activity as a promising tool for managing cognitive impairment and impaired walking performance in persons with MS, and suggests that physical activity might have specific effects on cognition and non-specific effects on walking performance in this population.     

Predicting caregiving status and caregivers’ burden in multiple sclerosis. A short report

Objectives: Predicting caregiving status (CS) in multiple sclerosis (MS) is of both clinical and health policy-making value. The aim of this cross-sectional study was to assess the clinical predictors of CS, along with factors related to caregivers’ stress.

Methods: A sample of 342 clinically definite MS patients (67.5% females, 67.8% relapsing MS, mean age 43.1 ± 11.4 year-old, mean disease duration 147 ± 105.4 months, median Expanded Disability Status Scale -EDSS-3.0) was screened for CS. The Multiple Sclerosis Quality of Life-54 and Zarit Burden Interview were used to measure quality of patients’ life and the their caregivers’ burden, respectively.

Results: In total, 57.9% of patients reported at least one caregiver, 97% of which were relatives or friends. Higher EDSS was associated with higher chance of reporting a caregiver. Two EDSS cut-offs were recognized; 2.0 and 4.5, the former with increased sensitivity (78.8%) and the latter with increased specificity (82.3%) to predict CS. Patients in the mild disability group (EDSS: 0–1.5) needing a caregiver had higher subjective cognitive function, implying presumably a beneficial role of care in cognition. Age and education were showed to affect CS in the moderate disability group (EDSS: 2.0–4.5). Physical and mental disability was more pronounced in patients reporting at least one caregiver in the high disability group (EDSS above 4.5). Caregivers’ stress was significantly positively correlated with age, EDSS, and duration of the disease and negatively with cognitive, physical, and mental health.

Discussion: In conclusion, the clinical predictors of CS are known to serve well both the researchers and the clinicians.     

Depression, disability and cognitive impairment in multiple sclerosis: a cross sectional Italian study

The disability, cognitive impairment, fatigue and depression are interacting features in multiple sclerosis (MS), whose relation is still unclear. The objective of this study was to evaluate in a sample of MS patients, the frequency of depressive symptoms, its predicting factors and relation with cognitive impairment, fatigue and disability. 255 consecutive MS patients and 166 healthy subjects were assessed for the presence of depressive symptoms with the Beck Depression Inventory-Fast Screen (BDI-FS). Patients with BDI-FS ≥4 were further investigated for the presence of neuropsychological impairment. Depressive symptoms were significantly more frequent and severe in patients than in controls. EDSS score was the only predicting factor of depression (3.5 = threshold EDSS score for depressive symptoms) in patients, whereas neuropsychological impairment was not correlated with BDI-FS and fatigue was found to be significantly correlated with attention, executive function and memory test scores, as well as with BDI-FS score in patients.     

Disability Progression in Multiple Sclerosis Is Affected by the Emergence of Comorbid Arterial Hypertension

MethodsThis was a retrospective study of 2,813 patients who were followed for 20 years. We modeled the associations of several risk factors with the pattern of disability progression. The primary end point was the rate of disability progression.ResultsIn total, 2,396 patients were available for analysis, of which 1,074 (44.8%) scored 4 (EDSS4) on the Expanded Disability Status Scale (EDSS), 717 (29.9%) scored 6 (EDSS6), and 261 (10.9%) scored 8 (EDSS8). The mean times to reach scores of 4, 6, and 8 were 123.5, 163.1, and 218.9 months, respectively. Hypertension was present in 207 (8.6%) patients during follow-up. Hypertension was associated with a higher probability of reaching each EDSS score compared to non-hypertensive patients: 62% vs. 43% for EDSS4 (p<0.01), 51% vs. 28% for EDSS6 (p<0.01), and 17% vs. 10% for EDSS8 (p<0.01). Nevertheless, hypertensive MS patients experienced longer intervals to reach each EDSS score: longer by 51.6, 38.9, and 62.7 months to EDSS4, EDSS6, and EDSS8, respectively (p<0.01) when compared to non-hypertensive MS patients reaching the same EDSS scores.ConclusionsDisability progression is more prevalent amongst hypertensive MS patients. However, they experience longer time intervals between the stages of disability progression.     

Anxiety state affects information processing speed in patients with multiple sclerosis

The aim of this study was to investigate the impact of anxiety on the cognitive performance of a clinical sample of relapsing—remitting (RR) MS patients. One hundred ninety patients (140 females) were included in the study and assessed through the beck depression inventory, the state-trait anxiety inventory and the Rao’s brief repeatable battery which assesses cognitive domains most frequently impaired in MS. As for neuropsychological performance, a total of 76 (40 %) subjects fulfilled our criterion for cognitive impairment. Tests most frequently failed by cognitive impairment (CI) patients were those assessing complex attention and information processing speed [Simbol Digit Modalities Test (SDMT), Paced Auditory Serial Auditory Test (PASAT) 3 and 2] and verbal memory. In the univariate analysis, state anxiety was related to failure on the SDMT (p = 0.042), and marginally, to failure on the PASAT-3 (p = 0.068), and to the presence of CI (p = 0.082). Moderate/severe depression was detected in 38 (20 %) patients and fatigue in 109 (57 %). Higher depression scores were related to impairment on the ST (OR = 1.05; 95 % CI 1.01–1.10; p = 0.029).     

Choroidal Thickness in Multiple Sclerosis: An Optical Coherence Tomography Study

Background and PurposeTo identify changes in the choroidal thickness (CT) in multiple sclerosis (MS) patients with and without optic neuritis (ON) using enhanced-depth-imaging optical coherence tomography (EDI-OCT).MethodsThis cross-sectional study included 96 eyes with MS and 28 eyes of healthy controls. All participants underwent an ophthalmologic examination and EDI-OCT scanning (Spectralis, Heidelberg Engineering, Germany) to assess the CT and the retinal nerve fiber layer (RNFL) thickness. MS patients were divided into two groups: 1) with and 2) without a history of ON. The CT was evaluated in the fovea and at six horizontal and six vertical points at 500, 1,000, and 1,500 µm from the fovea. Paired t-tests were used to compare the groups, and p-value<0.05 was considered as significant.ResultsAt all 13 measurements points, the CT was thicker in MS patients than in the healthy controls and was thinner in eyes with ON than in the contralateral eyes, but these differences were not statistically significant. However, the CT was always larger in all points in eyes with a history of ON than in the control eyes. The RNFL was significantly thinner (p<0.05) in both MS and ON eyes than in the control eyes.ConclusionsThe CT did not differ between MS and control eyes, but it was significantly larger in patients with a history of ON, in whom the RNFL was thinner. Further studies are necessary to establish the possible role of the choroid in MS.     

Eyes are mirror of the brain: comparison of multiple sclerosis patients and healthy controls using OCT

Abstract

Objective: To evaluate the thickness of choroid and retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients with and without optic neuritis using enhanced depth imaging optical coherence tomography (EDI-OCT).

Methods: In this cross-sectional study, both eyes of 52?MS patients [n?=?104 eyes; 62 eyes of MS patients without optic neuritis (MS-NON) and 42 eyes of MS patients with optic neuritis (MS-ON)] and only one eye of 36 healthy control subjects (n?=?36 eyes) were evaluated. Complete ophthalmologic examination and EDI-OCT scanning were completed for all participants. Choroidal thickness measurements were executed at three different points.

Results: Choroidal thickness measurements were similar between MS patients and healthy control subjects. However, the mean subfoveal choroidal thickness was increased significantly in MS-ON group (399.13?±?82.91?μm) compared to MS-NON group (342.71?±?82.46?μm; p?=?0.004). Mean RNFL thickness was significantly reduced in MS patients (90.42?±?13.31?μm) compared to healthy controls (101.18?±?10.75?μm; p?<?0.001). Moreover, temporal RNFL thickness was significantly thinner in MS-ON group (54?±?14.50?μm) than MS-NON group (62.15?±?15.88?μm; p?=?0.01). In MS patients, temporal RNFL thickness was correlated with both Expanded Disability Status Score (r?=?0.383; p?<?0.001) and longer disease duration (r=–0.202; p?=?0.04).

Conclusion: The results of the present study suggest that RNFL thickness can be used as an important parameter while following up with MS patients. However, more studies using EDI-OCT are required with larger MS patient groups and automated method.     

The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population

Objective: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population.

Methods: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5^th, 7^th, 10^th, and 15^th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers.

Results: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5^th year of disease duration was found in carriers of DRB1*07 allele (p _cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p _cor = 0.0305).

Discussion: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.