The presence and burden of cognitive issues: discordance between the perception of neurologists and people living with multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a common symptom of multiple sclerosis (MS) and occurs in more than 40% of people living with MS (plwMS). No real-world study has assessed the perception of neurologists and plwMS on cognitive issues. METHODS: Using data from the 2011-2019 Adelphi MS Disease Specific Programme database, this real-world, retrospective, cross-sectional multi-cohort study included people aged ≥18 years with relapsing-remitting MS and secondary progressive MS from the United States, UK and the EU. Neurologists provided data on the patient record form for plwMS, with the same plwMS invited to voluntarily complete a patient self-completion form: a questionnaire about their experiences with MS. RESULTS: Of 25,374 plwMS, 4817 who provided information on cognitive and mood symptoms were included in the analysis. Of the plwMS, 68% and 59% reported feeling 'mentally fatigued' and having 'difficulty concentrating', respectively. Neurologists reported only 27% of plwMS as having 'difficulty concentrating' and 15% of plwMS as having 'short-/long-term memory problems'. Neurologists reported cognitive or mood symptoms as 'not experienced' by a higher percentage of participants with relapsing-remitting MS than secondary progressive MS. Of the plwMS who experienced 'difficulty concentrating', most had a concomitant feeling of being 'mentally fatigued' (52%), followed by 'feeling anxious or tense' (49%) and 'feeling depressed' (44%). In plwMS, caregivers reported 'difficulty concentrating' (16%) as the most common cognitive issue. CONCLUSION: A clear discordance was observed between neurologists and plwMS regarding the perception of the cognitive and neuropsychiatric issues. These results underline the under-perception of cognitive and emotional affective symptoms in plwMS during neurological consultations.

Brain age as a surrogate marker for cognitive performance in multiple sclerosis.

BACKGROUND AND PURPOSE: Data from neuro-imaging techniques allow us to estimate a brain's age. Brain age is easily interpretable as 'how old the brain looks' and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility by investigating the relationship between brain age and cognitive performance in multiple sclerosis (MS). METHODS: A linear regression model was trained to predict age from brain magnetic resonance imaging volumetric features and sex in a healthy control dataset (HC_train, n = 1673). This model was used to predict brain age in two test sets: HC_test (n = 50) and MS_test (n = 201). Brain-predicted age difference (BPAD) was calculated as BPAD = brain age minus chronological age. Cognitive performance was assessed by the Symbol Digit Modalities Test (SDMT). RESULTS: Brain age was significantly related to SDMT scores in the MS_test dataset (r = -0.46, p < 0.001) and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r = -0.24, p < 0.001) and a significant weight (-0.25, p = 0.002) in a multivariate regression equation with age. CONCLUSIONS: Brain age is a candidate biomarker for cognitive dysfunction in MS and an easy to grasp metric for brain health.

Baseline characteristics and effects of fingolimod on cognitive performance in patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Studies reporting the baseline determinants of cognitive performance and treatment effect on cognition in patients with multiple sclerosis (MS) are limited. We investigated the baseline correlates of cognition and the long-term treatment effects of fingolimod 0.5 mg once daily on cognitive processing speed and attention in patients with relapsing-remitting MS. METHODS: This post hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N = 1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline 3-second Paced Auditory Serial Addition Test (PASAT-3) scores (Spearman's rank test) and the changes from baseline in PASAT-3 (mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo-fingolimod switched (from Month 24 up to 120 months) groups. Additionally, the predictive value of PASAT-3 score for future disease outcomes was assessed (Cox or logistic regression models). RESULTS: Among the variables assessed, lower PASAT-3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p < 0.0001 for all). Fingolimod significantly improved PASAT-3 scores from baseline versus placebo at 6 (1.3; p = 0.0007), 12 (1.1; p = 0.0044) and 24 months (1.1; p = 0.0028), with a sustained effect (overall treatment effect p = 0.0012) up to 120 months. Improvements were seen regardless of baseline cognitive status (PASAT quartile). Baseline PASAT-3 score was predictive of both clinical and magnetic resonance imaging measures of disease activity at Month 24 (p < 0.001 for all). CONCLUSION: Early fingolimod treatment may offer long-term cognitive benefit in patients with relapsing-remitting MS.

[Clinical practicability of the cognitive screening battery BICAMS in patients with multiple sclerosis: results of the feasibility study in Germany]. / Klinische Umsetzbarkeit der kognitiven Screeningbatterie BICAMS bei Patienten mit Multipler Sklerose: Ergebnisse der Machbarkeitsstudie in Deutschland.

BACKGROUND: Patients with multiple sclerosis (MS) suffer from cognitive impairment in 40-70% of the cases. There is evidence that the cognitive status is predictive for working ability and early retirement. Regular assessment of cognitive functionality is therefore urgently needed. PURPOSE: The German validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was evaluated in a multicentric way with respect to its feasibility in private neurological centers across Germany. METHODS: Physician assistants were trained with respect to application and scoring of BICAMS. All scored test materials were evaluated by independent neuropsychological experts. RESULTS: A total of 1606 BICAMS datasets were collected from 65 neurological centers. Of these 1573 datasets were analyzed of which 49.7% were correctly applied and scored while mistakes in application, scoring and transformation were found in 50.3%. Interrater reliability for each subtest was found to be ICC [Formula: see text] 0.953 when datasets containing mistakes were excluded. DISCUSSION: In general, BICAMS is highly recommended to be applied in standard clinical care; however, it should be emphasized that although the interrater reliability in the final sample was high, serious mistakes were found in 50.3% of cases. From these findings we conclude that nonpsychological staff have to be even more intensively trained and supervised by experts in the application and scoring of BICAMS.

On the validity of single tests, two-test combinations and the full Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in detecting patients with cognitive impairment.

BACKGROUND: The international standard to screen for cognitive impairment in multiple sclerosis (MS) is BICAMS (Brief International Cognitive Assessment for MS). However, with an application time of approximately 20 minutes, the battery might be too time consuming from a pragmatic perspective of a routine examination. OBJECTIVES: To examine the relative sensitivity and specificity of a BICAMS short version and its validity compared to the total battery. METHODS: The German BICAMS version was applied comprising the Symbol Digit Modalities Test (SDMT), the Brief Visuospatial Memory Test-Revised (BVMT-R) and the Rey Auditory Verbal Learning Test (RAVLT; German VLMT). Single tests and two-test combinations were compared regarding conformity with the total battery. RESULTS: Examining 1320 MS patients, the two-test combination of SDMT-BVMT-R was the most sensitive (92.7%) to impairment and showed the strongest agreement with the total battery (κ = 0.95). Performing binary logistic regression analyses, this combination was also validated by its association with employment status. CONCLUSION: Application of the total BICAMS battery should be the goal to strive for. However, in time-restricted clinical settings, the combined application of SDMT and BVMT-R is a recommendable alternative with an application time of 10 minutes, while single tests alone are not sufficiently sensitive.

Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis.

OBJECTIVE: Fatigue is a major disabling symptom in many chronic diseases including multiple sclerosis (MS), but treatment options are limited.Here, we tested the effectiveness of a self-guided , interactive, online fatigue management programme (ELEVIDA) based on principles of cognitive behavioural therapy (CBT) and related psychotherapeutic approaches (eg, mindfulness) for reducing fatigue in MS. METHODS: Patients with MS and self-reported fatigue were recruited via the website of the German MS Society and assigned via an automated randomisation generator (1:1, no blocking or stratification) to a 12-week online intervention (ELEVIDA, n=139, 82% female, mean age 40.8, median patient determined disease steps (PDDS) 3.0) or a waitlist control group (n=136, 79% female, mean age 41.9, median PDDS 3.0). The primary outcome was the Chalder Fatigue Scale. Outcomes were assessed at baseline, at week 12 (postintervention) and at follow-up (week 24). RESULTS: Compared with the control group, significantly greater reductions in Chalder Fatigue Scale scores were seen in the ELEVIDA group at week 12 (primary endpoint, intention-to-treat analysis: between-group mean difference 2.74 points; 95% CI 1.16 to 4.32; p=0.0007; effect size d=0.53), with effects sustained at week 24 (intention-to-treat analysis: between-group mean difference 2.19 points; 95% CI 0.57 to 3.82; p=0.0080). CONCLUSIONS: Our trial provides evidence for the effectiveness of a self-guided , internet-based intervention to reduce fatigue in MS. Interventions such as ELEVIDA may be a suitable low barrier, cost-effective treatment option for MS fatigue. TRIAL REGISTRATION NUMBER: ISRCTN registry (number ISRCTN25692173).

Central Slab versus Whole Brain to Measure Brain Atrophy in Multiple Sclerosis.

BACKGROUND: Structural Image Evaluation using Normalization of Atrophy (SIENA) is used to measure brain atrophy in multiple sclerosis (MS). However, brain extraction is prone to artefacts in the upper and lower parts of the brain. To overcome these shortcomings, some pivotal MS trials used a central slab instead of the whole brain as input for SIENA. The aim of this study was to compare the internal consistency and statistical dispersion of atrophy measures, associations with clinical outcomes and required sample sizes in clinical trials between these two approaches. METHODS: Brain volume change was assessed using SIENA in 119 MS patients with 5-years follow-up on 3D T1-weighted Magnetization Prepared Rapid Gradient Echo datasets using the whole brain or a central slab ranging from -10 to +60 mm Montreal Neurological Institute atlas coordinates. The statistical analysis included the quartile coefficient of dispersion, partial correlations with clinical outcomes and sample size calculations. Clinical outcome measures comprised the Expanded Disability Status Scale, MS Functional Composite and Symbol Digit Modalities Test. RESULTS: Annualized brain atrophy rates were higher using central slab than whole brain as input for SIENA (-0.51 ± 0.49 vs. -0.37 ± 0.39% per year, p < 0.001). Central and whole brain volume change showed comparable statistical dispersion and similarly correlated with clinical outcomes at 5-years follow-up. Sample size calculations estimated 14% fewer patients required to detect a given treatment effect when using the central slab instead of the whole brain option in SIENA. CONCLUSION: Central slab and whole brain SIENA produced comparable statistical dispersion with similar associations to clinical outcomes.

The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients.

OBJECTIVE: The objective of this paper is to investigate the relationship between total and regional corpus callosum (CC) atrophy, neuropsychological test performance and fatigue in multiple sclerosis (MS) patients. METHODS: We conducted a cross-sectional study in 113 MS patients: mean age 48 ± 11 years, 75/113 women, 84/113 relapsing-remitting MS, mean disease duration 21 ± 9 years, mean Expanded Disability Status Scale (EDSS) score 3.2 ± 1.7. All patients underwent brain magnetic resonance imaging, standardised neurological assessment and comprehensive cognitive testing including assessments for fatigue and depression. Total and regional CC atrophy was assessed using the corpus callosum index (CCI). RESULTS: CCI correlated more strongly with T2- and T1-lesion volume and whole brain volume than with disease duration or EDSS score. CCI correlated strongly with the verbal fluency test (VFT), Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT). Multivariate regression analysis revealed that atrophy of the posterior CC segment was significantly associated with poor outcome in the PASAT, VFT and SDMT. In contrast, atrophy of the anterior CC segment was significantly associated with fatigue severity and poor outcome in the long-term memory test. CONCLUSIONS: Atrophy of the CC is associated with cognitive impairment and fatigue. Regional CCI results indicate that these associations are partially spatially segregated.

Progression in disability and regional grey matter atrophy in relapsing-remitting multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS) regional grey matter (GM) atrophy has been associated with disability progression. OBJECTIVE: The aim of this study was to compare regional GM volume changes in relapsing-remitting MS (RRMS) patients with progressive and stable disability, using voxel-based morphometry (VBM). METHODS: We acquired baseline and 1-year follow-up 3-dimensional (3D) T1-weighted magnetic resonance imaging (MRI) data of RRMS patients, using two 1.5-Tesla scanners. Patients were matched pair-wise with respect to age, gender, disease duration, medication, scanner and baseline Expanded Disability Status Scale (EDSS) into 13 pairs, with either progressive EDSS (≥ 1 point change y(-1)) or stable EDSS, as well as into 29 pairs with either progressive Multiple Sclerosis Functional Composite (MSFC) at ≥ 0.25% decrease in y(-1) in any component, or stable MSFC. We analysed longitudinal regional differences in GM volumes in the progressive and stable EDSS and MSFC groups, respectively, using VBM. RESULTS: Significant GM volume reductions occurred in the right precuneus, in the progressive EDSS group. Differential between-group effects occurred in the right precuneus and in the postcentral gyrus. Further longitudinal GM volume reductions occurred in the right orbicular gyrus, in the progressive MSFC group, but no between-group differences were observed (non-stationary cluster-wise inference, all P(corrected) < 0.05). CONCLUSION: These results suggested a direct association of disability progression and regional GM atrophy in RRMS.

Default mode network alterations during language task performance in children with benign epilepsy with centrotemporal spikes (BECTS).

Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic epileptic disorder in children. Besides reported cognitive deficits, functional alterations mostly in the reorganization of language areas have also been described. In several publications, it has been reported that activation of the default mode network (DMN) can be reduced or altered in different neuropsychiatric and neurological disorders in adults. Whether this also holds true for children with epilepsy has so far not been clarified. To determine the functional activation of the DMN in children with BECTS, 20 patients and 16 healthy controls were examined using functional magnetic resonance imaging (fMRI), while a sentence generation task and a reading task were applied in a block design manner. To study the default mode network and the functional alterations between groups, an independent component analysis (ICA) was computed and further analyzed using SPM5. Compared with controls, children with BECTS showed not only significantly less activation of the DMN during the rest condition but also less deactivation during cognitive effort. This was most apparent in the precuneus, a key region of the DMN, while subjects were generating sentences. From these findings, we hypothesize that children with BECTS show a functional deficit that is reflected by alterations in the DMN.

Predictive value of synaptic plasticity for functional decline in patients with multiple sclerosis.

Background: Previous research suggested that quadripulse (QPS)-induced synaptic plasticity is associated with both cognitive and motor function in patients with multiple sclerosis (MS) and does not appear to be reduced compared to healthy controls (HCs). Objective: This study aimed to explore the relationship between the degree of QPS-induced plasticity and clinically significant decline in motor and cognitive functions over time. We hypothesized that MS patients experiencing functional decline would exhibit lower levels of baseline plasticity compared to those without decline. Methods: QPS-induced plasticity was evaluated in 80 MS patients (56 with relapsing-remitting MS and 24 with progressive MS), and 69 age-, sex-, and education-matched HCs. Cognitive and motor functions, as well as overall disability status were evaluated annually over a median follow-up period of 2 years. Clinically meaningful change thresholds were predefined for each outcome measure. Linear mixed-effects models, Cox proportional hazard models, logistic regression, and receiver-operating characteristic analysis were applied to analyse the relationship between baseline plasticity and clinical progression in the symbol digit modalities test, brief visuospatial memory test revised (BVMT-R), nine-hole peg test (NHPT), timed 25-foot walk test, and expanded disability status scale. Results: Overall, the patient cohort showed no clinically relevant change in any functional outcome over time. Variability in performance was observed across time points in both patients and HCs. MS patients who experienced clinically relevant decline in manual dexterity and/or visuospatial learning and memory had significantly lower levels of synaptic plasticity at baseline compared to those without such decline (NHPT: ß = -0.25, p = 0.02; BVMT-R: ß = -0.50, p = 0.005). Receiver-operating characteristic analysis underscored the predictive utility of baseline synaptic plasticity in discerning between patients experiencing functional decline and those maintaining stability only for visuospatial learning and memory (area under the curve = 0.85). Conclusion: Our study suggests that QPS-induced plasticity could be linked to clinically relevant functional decline in patients with MS. However, to solidify these findings, longer follow-up periods are warranted, especially in cohorts with higher prevalences of functional decline. Additionally, the variability in cognitive performance in both patients with MS and HCs underscores the importance of conducting further research on reliable change based on neuropsychological tests.

The role of fatigue in patients with complex regional pain syndrome.

BACKGROUND AND PURPOSE: Fatigue affects patients across a variety of neurological diseases, including chronic pain syndromes such as complex regional pain syndrome (CRPS). In CRPS, fatigue is often underestimated, as the focus lies in the assessment and managing of pain and sensorimotor deficits. This study aimed to investigate the prevalence, characteristics, and influence of fatigue on CRPS severity and quality of life in these patients. Such insights could enhance the clinical management of this challenging condition. METHODS: In this prospective study, 181 CRPS patients and 141 age and gender-matched individuals with injury but without chronic pain were interviewed using the Fatigue Scale for Motor and Cognitive Function to assess fatigue. Depressive symptoms and quality of life (QoL) were also evaluated as additional outcome measures. Statistical analysis was performed to examine differences in fatigue prevalence between the groups, as well as associations with CRPS severity, pain levels, and clinical phenotype. In addition, best subsets regression was used to identify the primary factors influencing QoL. Fatigue was tested in a mediation analysis as a mediator between pain and depression. RESULTS: CRPS patients showed significantly higher fatigue levels compared to controls (CRPS: 75 [IQR: 57-85] vs. controls: 39 [IQR: 25-57]). Based on the FSMC, 44.2% in the control group experienced fatigue, while 85% of patients with CRPS experienced fatigue (p < 0.001), of which 6% were mild, 15% moderate, and 67% severe. In CRPS severe fatigue was associated with higher pain intensities compared to no fatigue (pain at rest: p = 0.003; pain during movement: p = 0.007) or moderate fatigue (pain during movement: p = 0.03). QoL in our cohort was mainly influenced by pain (pain during movement: adj.R2 = 0.38; p < 0.001, pain at rest: Δadj.R2 = 0.02, p = 0.007) and depressive symptoms (Δadj.R2 = 0.12, p < 0.001). Subsequent analyses indicated that pain and depressive symptoms primarily impact QoL in CPRS whereas fatigue may exert an indirect influence by mediating the connection between pain and depression (p < 0.001). CONCLUSIONS: This pioneering study investigates the prevalence of fatigue in CRPS patients and its relation to disease characteristics. Our results indicate a high prevalence of severe fatigue, strongly correlated with pain intensity, and its importance in the interaction between pain and depression in CRPS. These findings underscore the significant role of fatigue as a disease factor in CRPS. Therefore, the evaluation of CRPS-related disability should include a standardized assessment of fatigue for comprehensive clinical management.

Peering further into the mind's eye: combining visual evoked potential and optical coherence tomography measures enhances insight into the variance in cognitive functioning in multiple sclerosis.

BACKGROUND: Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone. OBJECTIVE: We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS. OCT measures included Retinal Nerve Fiber Layer Volume (RNFLV), Papillo-Macular Bundle Volume (PBMV), and Macular Volume (MV). VEP measures included latency of the P100, and inter-ocular latency. Cognitive performance was evaluated across seven separate domains of performance, and for overall cognition, using the NeuroTrax computerized testing battery. RESULTS: Both OCT and VEP measures were significantly correlated with cognitive performance across several domains. Linear regression models that controlled for the influence of visual acuity revealed (1) that reduced MV was significantly predictive of poorer visual-spatial functioning, and (2) that delayed VEP latency was significantly predictive of performance in global cognitive functioning and visual-spatial functioning, after controlling for multiple comparisons. Among PwMS with normal visual acuity, PwMS with a combination of both relatively low MV and delayed VEP latency tended to have poorer performance in the domains of global, executive, and visual-spatial functioning compared to PwMS with both high MV and normal VEP latency. CONCLUSION: Approaches that combine the use of OCT and VEP measures can enhance insight into underlying factors that contribute to variance in cognitive functioning in PwMS.

Exploring the relationship between manual dexterity and cognition in people with multiple sclerosis: 9-hole peg and multiple cognitive functions.

AIM AND RATIONALE: Problems with manual dexterity and cognition impact the everyday performance of people with multiple sclerosis (PwMS). Accumulated findings point to the relationship between deficits in manual dexterity and auditory domains of cognition with a lack of evidence on visuospatial and verbal aspects of cognitive functioning. Therefore, this study explores the relationship between manual dexterity and cognition in a cohort of PwMS. METHOD: This cross-sectional study collected data from 63 PwMS aged 22 to 55 through a convenient sampling method. Participants were diagnosed with relapsing-remitting multiple sclerosis (RRMS). Cognition was measured using a multi-domain computerized cognitive testing, NeuroTrax, and manual dexterity was measured using a 9-hole peg assessment. Spearman correlation was used to identify the correlation among cognition subtests as well as with manual dexterity. Linear regression analysis was also conducted to identify whether manual dexterity predicts cognitive functioning. RESULTS: A significant negative correlation was found between 9-hole peg scores and global cognitive scores (GCS), r = -0.34, p = 006. The manual dexterity scores were also shown to predict GCS, R2= 0.165, p = 0.001. CONCLUSION: Manual dexterity was found to not only predict cognitive dysfunction but was also associated with multiple cognitive domains. Understanding the relationship between manual dexterity and cognition and the inferred progression of deficits can assist clinicians to provide interventions at earlier stages of disease progression to potentially increase daily functioning and quality of life (QoL).

Utility of neuropsychological testing for guiding treatment decisions in paediatric multiple sclerosis.

In the past years, there has been growing awareness about childhood onset multiple sclerosis (MS) and the relevance of psychosocial aspects such as cognitive disturbances, fatigue and depression in this population. We describe a case of a 16-year-old patient with relapsing-remitting multiple sclerosis (RRMS) who presented at our clinic with severe fatigue symptoms and who underwent repeated neuropsychological examinations. A sudden significant slowing indicated a new relapse while neurological examination did not. This case highlights the high sensitivity and clinical relevance of neuropsychological testing in patients with juvenile MS even in the context of treatment decisions.

Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis.

BACKGROUND: Cortical lesions (CLs) have been reported to be a better predictor for cognitive impairment than white matter (WM) lesions in relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: The objectives of this article are to investigate the contribution of CLs and WM lesions to cognitive impairment in 91 patients with MS and clinically isolated syndrome, and to test potential associations of CLs and WM lesions with fatigue and depression. METHODS: Lesions were scored and segmented on 3D double inversion recovery sequences, according to their location (cortical, WM). Normalised grey matter volume was also determined. Cognitive performance was assessed with the SDMT and PASAT-3, fatigue with the FSMC and depression with the German version of the CES-D. RESULTS: CL volume did not correlate with fatigue or depression, but correlated significantly with both neuropsychological outcome measures: PASAT-3 (r = -0.275, p = 0.009) and SDMT (r = -0.377, p < 0.001). Multiple regression analyses with age, WM lesions, CLs and GM volume as independent variables, however, did not reveal CL volume as a significant predictor of neuropsychological outcomes, whereas WM lesion volume significantly predicted SDMT and by trend PASAT performance. CONCLUSIONS: These findings suggest a role of WM lesions in the development of cognitive deficits, especially information-processing speed, which may be higher than previously assumed. ABBREVIATIONS CES-D: Center for Epidemiologic Studies Depression scale (ADS-L: Allgemeine Depressions Skala-L, German version of CES-D), CIS: clinically isolated syndrome, CL: cortical lesion, DIR: double inversion recovery, EDSS: Expanded Disability Status Scale, FSMC: fatigue scale for motor and cognitive functions, GM: grey matter, MRI: magnetic resonance imaging, MS: multiple sclerosis, PASAT-3: paced auditory serial addition test 3s, PPMS: primary progressive multiple sclerosis, RRMS: relapsing-remitting multiple sclerosis, SDMT: symbol digit modalities test, SPM: statistical parametric mapping, SPMS: secondary progressive multiple sclerosis, WM: white matter.

Cognitive impairment and cortical reorganization in children with benign epilepsy with centrotemporal spikes.

PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. This study aimed to clarify whether children with BECTS with left- or right-hemispheric, or bilateral focus have specific neuropsychological language deficits when compared to healthy controls, whether these deficits correlate functionally with language network organization (typical vs. atypical), and whether cofactors such as duration, handedness, and medication have a relevant impact on language reorganization processes. METHODS: Twenty-seven patients and 19 healthy controls were examined with several neuropsychological tests (German version of the Wechsler Intelligence Scale for Children [WISC-IV], Regensburger verbal fluency test [RWT], Corsiblock forward and backward and Hand-Dominanz-Test [HDT]) and with two language paradigms on functional magnetic resonance imaging (fMRI): silent reading of word-pairs and silent generation of simple sentences. KEY FINDINGS: Although neuropsychological test results only differed by trend between BECTS patients and controls, language laterality indices (LIs) in fMRI were significantly lower in patients than in controls. In particular, the anterior language network with Broca's area and the supplementary motor area (SMA) revealed the lowest LIs and showed the most bilateral or right hemispheric activations in the sentence generation task. Medication and duration of epilepsy did not have any significant effect on language reorganization and patients' performances. SIGNIFICANCE: Language reorganization in BECTS patients takes place in bilateral or right hemispheric language networks, with a strong focus in anterior language regions. These functional changes can be interpreted as important compensatory strategies of the central nervous system (CNS) to stabilize cognitive, especially language performance.