The impact of SARS-CoV-2 immunization on COVID-19 disease course in people with myasthenia gravis.

INTRODUCTION/AIMS: There is limited knowledge regarding the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines οn coronavirus disease 2019 (COVID-19) disease course in people with myasthenia gravis. In this study, we aimed to investigate whether SARS-CoV-2 vaccination influences hospitalization and mortality due to COVID-19 in this population. METHODS: This is a retrospective analysis of administrative data extracted from the Greek nationwide database that holds the COVID-19 disease and vaccination registry, as well as all medical prescription records. The study period extended from the onset of the pandemic (February 2020) until the 10th of January 2022. RESULTS: We identified 278 people with myasthenia gravis (mean age 58.1 ± 17.2, 47.5% males) who tested positive for SARS-CoV-2. Of those, 139 (50%) were not vaccinated at the time of infection. Multivariable binary logistic regression analysis showed that the probability of hospitalization increased with age (odds ratio [OR]: 1.058; 95% confidence interval [CI], 1.036-1.080; p < .001) and immunosuppressive treatment (OR: 2.872; 95% CI 1.412-5.839; p = .004), and decreased with vaccination (OR: 0.244; 95% CI 0.132-0.453; p < .001). The probability of a fatal outcome increased with age (OR: 1.085; 95% CI 1.043-1.129; p < .001) and decreased with vaccination (OR: 0.315; 95% CI 0.125-0.791; p = .014). DISCUSSION: SARS-CoV-2 vaccination significantly reduces hospitalization and mortality due to COVID-19 in people with myasthenia gravis. This study regarding the efficacy of these vaccines, together with previous studies regarding their safety, provide evidence to support their use in people with myasthenia gravis.

Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.

BACKGROUND: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS. METHODS: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped. RESULTS: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex. CONCLUSIONS: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.

The Experience of a Tertiary Reference Hospital in the Study of Rare Neurological Diseases.

Background and Objectives: Rare diseases (RDs) are life-threatening or chronically impairing conditions that affect about 6% of the world's population. RDs are often called 'orphan' diseases, since people suffering from them attract little support from national health systems. Aim: The aim of this study is to describe the clinical characteristics of, and the available laboratory examinations for, patients who were hospitalized in a tertiary referral center and finally received a diagnosis associated with a Rare Neurological Disease (RND). Materials and Methods: Patients that were hospitalized in our clinic from 1 January 2014 to 31 March 2022 and were finally diagnosed with an RND were consecutively included. The RND classification was performed according to the ORPHAcode system. Results: A total of 342 out of 11.850 (2.9%) adult patients admitted to our department during this period received a diagnosis associated with an RND. The most common diagnosis (N = 80, 23%) involved an RND presenting with dementia, followed by a motor neuron disease spectrum disorder (N = 64, 18.7%). Family history indicative of an RND was present in only 21 patients (6.1%). Fifty-five (16%) people had previously been misdiagnosed with another neurological condition. The mean time delay between disease onset and diagnosis was 4.24 ± 0.41 years. Conclusions: Our data indicate that a broad spectrum of RNDs may reach a tertiary Neurological Center after a significant delay. Moreover, our data underline the need for a network of reference centers, both at a national and international level, expected to support research on the diagnosis and treatment of RND.

Conventional cardiovascular risk factors in Transient Global Amnesia: Systematic review and proposition of a novel hypothesis.

Transient Global Amnesia (TGA) is an enigmatic amnestic syndrome. We conducted a systematic review to investigate the relationship between the conventional cardiovascular risk factors and TGA. MEDLINE, CENTRAL, EMBASE and PsycINFO were comprehensively searched and 23 controlled observational studies were retrieved. The prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking was lower among patients with TGA compared to Transient Ischemic Attack. Regarding the comparison of TGA with healthy individuals, there was strong evidence suggesting a protective effect of diabetes mellitus on TGA and weaker evidence for a protective effect of smoking. Hypertension was associated with TGA only in more severe stages, while dyslipidemia was not related. In view of these findings, a novel pathophysiological hypothesis is proposed, in which the functional interactions of Angiotensin-II type-1 and N-methyl-D-aspartate receptors are of pivotal importance. The whole body of clinical evidence (nature of precipitating events, associations with migraine, gender-based association patterns) was integrated.

CADASIL in Greece: Mutational spectrum and clinical characteristics based on a systematic review and pooled analysis of published cases.

BACKGROUND: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. METHODS: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. RESULTS: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). CONCLUSIONS: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in the Russian Population.

OBJECTIVE: Cognitive dysfunction is common in multiple sclerosis (MS). The Brief International Cognitive Assessment for MS (BICAMS) battery of tests has been suggested as a measure for the evaluation of the cognitive status of MS patients. This study aims to validate the BICAMS battery in the Russian population of MS patients. METHODS: Age- and sex-matched MS patients (n = 98) and healthy individuals (n = 86) were included in the study. Symbol Digit Modalities Test (SDMT), California Verbal Learning Test, 2nd edition (CVLT-II) and the Brief Visuospatial Memory Test - Revised (BVMT-R) were administered to all participants. The battery was readministered 1 month later to 44 MS patients to investigate the test-retest reliability. RESULTS: MS patients exhibited a significantly lower performance in testing with BICAMS than the control group in all three neuropsychological tests. Test-retest reliability was good for SDMT and CVLT-II (r = .82 and r = .85, respectively) and adequate for BVMT-R (r = .70). Based on the proposed criterion for impairment as z score below 1.5 SD the mean of the control group, we found that 34/98 (35%) of MS patients were found impaired at least in one cognitive domain. Patients with Expanded Disability Status Scale score ≥3.5 performed significantly worse than controls (SDMT, p < .0001; CVLT-II, p = .03; BVMT-R, p = .0004), while those with ≤3.0 scores did not. CONCLUSION: This study demonstrates that the BICAMS battery is a valid instrument to identify cognitive impairment in MS patients and it can be recommended for routine use in the Russian Federation.

Myelin-associated oligodendrocyte basic protein rs616147 polymorphism as a risk factor for Parkinson's disease.

BACKGROUND: The rs616147 polymorphism of the myelin-associated oligodendrocyte basic protein (MOBP) gene locus has been associated with amyotrophic lateral sclerosis (ALS). ALS and Parkinson's disease (PD) are two common neurodegenerative disorders that share features regarding their etiology, pathophysiology, and genetic backgrounds. While the MOBP rs616147 polymorphism has been associated with ALS, little is known about its role in PD. OBJECTIVE: To assess the role of MOBP rs616147 on PD risk. METHODS: This case-control comparison study consists of 358 PD-affected cases and 358 controls from the Neurology Clinic of the University Hospital of Larissa, University of Thessaly, Faculty of Medicine, in Greece. The diagnosis of PD was made by a specialist neurologist according to the UK Parkinson's Disease Society Brain Bank's clinical criteria. All the participants were genotyped for the MOBP rs616147. Furthermore, in order to validate our results, we genotyped 327 patients with Alzheimer's disease (AD) for MOBP rs616147 and compared them with the control group. RESULTS: According to the univariate analysis, there was a significant association between rs616147 and PD in the dominant (OR [95% C.I.] = 0.70 [0.52-0.94], p = .018), the overdominant (OR [95% C.I.] = 0.68 [0.50-0.92], p = .011), and in the codominant (G/A VS G/G; OR [95% C.I.] = 0.66 [0.48-0.91], p = .035) modes of inheritance. In contrast, there was no association between the MOBP rs616147 polymorphism and AD. CONCLUSIONS: We provide preliminary results associating MOBP rs616147 genetic variant with PD.

Translation, cross-cultural adaptation, and validation of the Greek version of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19.

INTRODUCTION: Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) explores optimally impact of MS on sexual activity/satisfaction/intimacy. AIM: The present study aims to provide the only validation of the Greek Version of MSISQ-19, and compare results to validation studies in other languages. METHODS: The original/English version of the MSISQ-19 was translated into Greek according to standardized guidelines, while validity/reliability, correlations with other scales and sexual dysfunction prevalence were tested. Subjects were requested to complete all questionnaires and MSISQ-19, being re-tested three weeks later. Construct-validity of the Greek version of the MSISQ-19 was confirmed with principal-component-analysis. Bartlett's test assessed correlation-adequacy between items. Pearson's correlation explored internal-construct-validity between subscales and overall score, and external-construct-validity with disease-status variables, cognitive testing and patient-reported outcomes regarding fatigue, depression/anxiety, MS impact, and quality of life. RESULTS: 201 PwMS (130 female). Mean age was 39.3 ± 11.8 years with median disease-duration 11.7 ± 7.9 years. 79.1% RRMS, PPMS (10.4%) and SPMS (10.4%). Cronbach's alpha coefficient was 0.949. MSISQ-19 correlations between items were large. Significant associations of sexual dysfunction were identified with age (rho = 0.392, p < 0.01), years of education (rho=-0.199, p = 0.006), the Expanded Disability Status Scale (rho = 0.518, p < 0.01) and MS duration (rho = 0.354, p < 0.01). Correlations were disclosed with the Brief International Cognitive Assessment for MS (rho=-0.247, p < 0.05), Modified Fatigue Impact Scale (rho = 0.374, p < 0.05), Depression Anxiety Stress Scale (rho = 0.375, p < 0.05), Multiple Sclerosis Impact Scale (rho = 0.442, p < 0.05), and EuroQoL-five-dimensional instrument (rho = 0.375, p < 0.05). Internal consistency of the Greek version of the MSISQ-19 was confirmed with Cronbach's alpha. Test-retest reliability (31 PwMS) was excellent with intraclass-correlation-coefficients > 0.90. CONCLUSION: Besides Greek MSISQ-19 satisfactory validity/reliability/reproducibility and being first to include cognitive-testing, authors estimated sexual-dysfunction prevalence affecting half PwMS.HIGHLIGHTSThis study provides the only validation of the Greek Version of the MSISQ-19.The latter was found with satisfactory validity, reliability and reproducibility.50% of the Greek PwMS sample was found to be afflicted with sexual dysfunction.This is also the first validation study to examine associations with cognitive testing.Sexual function is still an underestimated functionality parameter upon examination.

Neuropsychological correlates of cerebellar volumes in multiple sclerosis: an MRI volumetric analysis study.

The hallmark of Multiple Sclerosis (MS) pathophysiology is the damage to the myelin sheath around axons. The cerebellum is a predilection site for demyelination with a well-recognized role in motor and a rather understudied contribution to cognitive functions. The aim of this study is to investigate patterns of cerebellar grey and white matter pathology, expressed as reduced volume, as well as cortical thickness and their potential contribution to cognitive performance and disability status of patients with MS. 24 patients with MS underwent extensive neuropsychological assessment using paper and pencil tests and the Brain Health Assessment (BHA) tablet-based battery. Cerebellar lobular volumes and thickness were calculated using a volumetric analysis with automated segmentation of the cerebellum and its lobules. The main findings are a reduction of cerebellar grey matter (CGMV) and white matter volumes (CWMV) in lobule X and a widespread cerebellar cortical thinning in patients. Overall disease severity and neurological disability, assessed with the Expanded Disability Status Severity Scale, was correlated with fatigue and information processing speed tasks, but not with CGMV and CWMV. CWMV and CGMV of lobule I-II was negatively correlated with information processing speed, as well as visuospatial memory tests and, finally, inverse cortical thinning associations were noted between the whole cerebellum, lobule I-II, lobule III, lobule VI, Crus I, lobule VIIIA and information processing speed and verbal fluency tasks. The inverse associations observed may represent a compensatory mechanism activated in MS engaging additional high-level cortical areas functionally interconnected with the damaged cerebellum, in order to cope with the cognitive demands of a task.

What scans see when patients see defects: neuroimaging findings in body dysmorphic disorder.

Body dysmorphic disorder (BDD) is characterized by an individual's preoccupation with a perceived defect in their appearance which to others may be barely noticeable or even completely unnoticed. It confers significant disturbances of everyday functioning in affected persons. The present review study provides an overview of neuroimaging findings on BDD. Literature on three platforms, PubMed, Google Scholar and PsycArticles of APA PsycNet, was searched for studies on patients with BBD compared with healthy controls (HCs), with a focus on neuroimaging findings. Out of an initial yield of 414 articles, 23 fulfilled inclusion criteria and were reviewed. Among the most remarkable findings were functional abnormalities in visual processing, frontostriatal and limbic systems, reduced global efficiency of White Matter (WM) connectivity, reduced cortical thickness in temporal and parietal lobes, and correlations between these neuroimaging findings and clinical variables such as symptom severity and degree of insight. Structural, volumetric and functional neuroimaging findings in BDD affected persons may help shed light on the pathophysiology and neurobiological underpinnings of this condition. Future studies should further investigate the use of imaging findings as potential prognostic biomarkers of treatment efficacy and disease outcome.

Vitamin D and tension-type headache: causal association or epiphenomenon?

Background-Purpose: Low serum vitamin D (VD) has been already associated with a series of highly prevalent pain-related conditions, including fibromyalgia, migraine and chronic widespread pain. Considering the potential interplay between VD and pain signalling pathways, the association of VD with tension-type headache (TTH) was reviewed.Methods: A multifaceted narrative approach assessing the relationship of serum VD with TTH and TTH parameters, as well as the efficacy of VD supplementation for the prevention of TTH, was fostered. MEDLINE, CENTRAL and EMBASE were comprehensively searched for this purpose, while Google Scholar was also explored according to a structured approach. ClinicalTrials.gov and European Union Clinical Trials Register were explored for ongoing prevention trials.Results: Although available evidence was suggestive of an association between VD and TTH, mainly of the chronic type, the causal nature of the association remains to be determined. Considering the lack of longitudinal evidence, this relationship could arguably reflect behavioural patterns of headache sufferers. On the other hand, evidence principally originated from tertiary clinical settings (severe comorbidity burden) and researchers tend to report a concomitant association of both entities with generalized musculoskeletal compromise. In this context, the association between TTH and VD may represent nothing more than a secondary by-product of the simultaneous relationship of other comorbid diseases-conditions with both TTH and low serum VD. Regarding its efficacious properties, only one ongoing trial specifically designed to explore the efficacy of VD in chronic TTH in adults was retrieved.Conclusions: There is no evidenced based indication for VD supplementation in TTH.

Blood Metabolomics May Discriminate a Sub-Group of Patients with First Demyelinating Episode in the Context of RRMS with Increased Disability and MRI Characteristics Indicative of Poor Prognosis.

Biomarker research across the health-to-disease continuum is being increasingly applied. We applied blood-based metabolomics in order to identify patient clusters with a first demyelinating episode, and explored the prognostic potential of the method by thoroughly characterizing each cluster in terms of clinical, laboratory and MRI markers of established prognostic potential for Multiple Sclerosis (MS). Recruitment consisted of 11 patients with Clinically Isolated Syndrome (CIS), 37 patients with a first demyelinating episode in the context of Relapsing-Remitting MS (RRMS) and 11 control participants. Blood-based metabolomics and hierarchical clustering analysis (HCL) were applied. Constructed OPLS-DA models illustrated a discrimination between patients with CIS and the controls (p = 0.0014), as well as between patients with RRMS and the controls (p = 1 × 10−5). Hierarchical clustering analysis (HCL) for patients with RRMS identified three clusters. RRMS-patients-cluster-3 exhibited higher mean cell numbers in the Cerebro-spinal Fluid (CSF) compared to patients with CIS (18.17 ± 6.3 vs. 1.09 ± 0.41, p = 0.004). Mean glucose CSF/serum ratio and infratentorial lesion burden significantly differed across CIS- and HCL-derived RRMS-patient clusters (F = 14.95, p < 0.001 and F = 6.087, p = 0.002, respectively), mainly due to increased mean values for patients with RRMS-cluster-3. HCL discriminated a cluster of patients with a first demyelinating episode in the context of RRMS with increased disability, laboratory findings linked with increased pathology burden and MRI markers of poor prognosis.

Deciphering the Role of the rs2651899, rs10166942, and rs11172113 Polymorphisms in Migraine: A Meta-Analysis.

The genetic basis of migraine is rather complex. The rs2651899 in the PR/SET domain 16 (PRDM16) gene, the rs10166942 near the transient receptor potential cation channel subfamily M member 8 (TRPM8) gene, and the rs11172113 in the LDL receptor-related protein 1 (LRP1) gene, have been associated with migraine in a genome-wide association study (GWAS). However, data from subsequent studies examining the role of these variants and their relationship with migraine remain inconclusive. The aim of the present study was to meta-analyze the published data assessing the role of these polymorphisms in migraine, migraine with aura (MA), and migraine without aura (MO). We performed a search in the PubMed, Scopus, Web of Science, and Public Health Genomics and Precision Health Knowledge Base (v7.7) databases. In total, eight, six, and six studies were included in the quantitative analysis, for the rs2651899, rs10166942, and rs11172113, respectively. Cochran's Q and I2 tests were used to calculate the heterogeneity. The random effects (RE) model was applied when high heterogeneity was observed; otherwise, the fixed effects (FE) model was applied. The odds ratios (ORs) and the respective 95% confidence intervals (CIs) were calculated to estimate the effect of each variant on migraine. Funnel plots were created to graphically assess publication bias. A significant association was revealed for the CC genotype of the rs2651899, with the overall migraine group (RE model OR: 1.32; 95% CI: 1.02−1.73; p-value = 0.04) and the MA subgroup (FE model OR: 1.40; 95% CI: 1.12−1.74; p-value = 0.003). The rs10166942 CT genotype was associated with increased migraine risk (FE model OR: 1.36; 95% CI: 1.18−1.57; p-value < 0.0001) and increased MO risk (FE model OR: 1.41; 95% CI: 1.17−1.69; p-value = 0.0003). No association was detected for the rs11172113. The rs2651899 and the rs10166942 have an effect on migraine. Larger studies are needed to dissect the role of these variants in migraine.

Prevalence, clinical characteristics and outcomes of Guillain-Barré syndrome spectrum associated with COVID-19: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach. METHODS: A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients. RESULTS: Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I2  = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27, 95% CI 1.32%-8.09%; I2  = 0%). In SARS-CoV-2-infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95% CI 3.5%-60.4%; I2  = 46%) and 42.8% (95% CI 32.8%-53%; I2  = 0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls. CONCLUSION: GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.

MOBP rs616147 Polymorphism and Risk of Amyotrophic Lateral Sclerosis in a Greek Population: A Case-Control Study.

Background and Objectives: To date, only one study has investigated the association between the rs616147 polymorphism of the Myelin-associated Oligodendrocyte Basic Protein (MOBP) locus and Amyotrophic Lateral Sclerosis (ALS). Materials and Methods: A case-control study was performed. Patients with definite sporadic ALS were prospectively and consecutively recruited from the inpatient and outpatient clinics of the Neurology Department of the General University Hospital of Larissa, Central Greece. Community based, age and sex matched healthy individuals with a free personal and family history constituted the control group. Results: A total of 155 patients with definite sporadic ALS and an equal number of healthy controls were genotyped. The power of our sample size was slightly above 80% and MOBP rs616147 was determined to be in Hardy-Weinberg Equilibrium among healthy participants (p = 1.00). According to the univariate analysis, there was no significant relationship between rs616147 and ALS [log-additive OR = 0.85 (0.61, 1.19), over-dominant OR = 0.73 (0.46, 1.15), recessive OR = 1.02 (0.50, 2.09), dominant OR = 0.74 (0.47, 1.16), co-dominant OR1 = 0.71 (0.44, 1.14) and co-dominant OR2 = 0.88 (0.42, 1.84). Additionally, the effect of rs616147 on the age of ALS onset was determined insignificant using both unadjusted and adjusted (sex, site of onset) cox-proportional models. Finally, rs616147 was not related to the site of ALS onset. Conclusions: Our study is the first to report the absence of an association between MOBP rs616147 and ALS among individuals of Greek ancestry. Additional, larger nationwide and multi-ethnic studies are warranted to shed light on the connection between rs616147 and ALS.

Cognitive Fatigability is Independent of Subjective Cognitive Fatigue and Mood in Multiple Sclerosis.

BACKGROUND: Sustained cognitive testing is used to detect cognitive fatigability and is often considered a substitute for subjective cognitive fatigue (CF). However, the relationship between cognitive fatigability and subjective CF in people with multiple sclerosis (PwMS) remains undetermined. OBJECTIVE: To explore potential associations between fatigability induced by sustained cognitive testing and subjective CF in PwMS. METHODS: We gave 120 PwMS and 60 demographically matched, healthy individuals the Beck Depression Inventory-FastScreen (BDI-FS) to measure mood and the Modified Fatigue Impact Scale to measure CF. In addition, we used the Quotient ADHD Test, a sustained attention test, to measure cognitive fatigability. We also explored potential correlations between the individuals' performance on the sustained attention test and thalamic volume using recent MRI scans. RESULTS: Forty-one (34.2%) of the PwMS exhibited cognitive fatigability. These 41 were found to be significantly older (P=0.006), had been diagnosed with the disease for longer (P=0.03), had higher scores (P<0.001) on the Expanded Disability Status Scale, and had reduced thalamic volume (P=0.04) compared with the 79 (65.8%) PwMS not exhibiting cognitive fatigability. The PwMS exhibiting cognitive fatigability scored similarly on the BDI-FS (P=0.21) and self-reported similar rates of CF (P=0.62) as the PwMS not exhibiting cognitive fatigability. CONCLUSION: Cognitive fatigability induced by sustained cognitive testing is not an accurate clinical alternative to subjective CF. This study provides evidence to support cognitive fatigability and CF in PwMS as two distinct concepts.

Computerized cognitive rehabilitation for treatment of cognitive impairment in multiple sclerosis: an explorative study.

In this explorative study, forty-seven patients with relapsing-remitting multiple sclerosis were randomized to a custom 6-week cognitive rehabilitation intervention (n = 23) using the BrainHQTM web-based platform and to a control group condition (n = 24). Cognitive rehabilitation intervention consisted of two 40-minute sessions per week. All patients were tested with the Brief International Cognitive Assessment for Multiple Sclerosis battery, the Stroop Color-Word Test, and the trail making test, while the Beck Depression Inventory - Fast Screen questionnaire was used as a measure of mood and the cognitive reserve index as a measure of cognitive reserve. We used the reliable change index, to calculate clinically meaningful changes of performance, and to discriminate between responders and non-responders of this intervention. Statistically significant improvement of the group receiving treatment was observed mainly on measures of verbal and non-verbal episodic memory and, to a lesser extent, on reading speed, selective attention/response inhibition, and visual attention. Verbal memory and visual attention improvements remained significant after considering the corrected for multiple comparisons level of significance. According to reliable change index scores, 12/23 (52.2%) of patients in the intervention group presented meaningful improvement in at least one measure (Greek Verbal Learning Test: 26%, Brief Visuospatial Memory Test-Revised: 17.4%, Stroop-Words test: 13%). This explorative study provides evidence that, at least in the short term, cognitive rehabilitation may improve the cognitive performance of multiple sclerosis patients.

Dysphagia Prevalence, Attitudes, and Related Quality of Life in Patients with Multiple Sclerosis.

Dysphagia in patients with multiple sclerosis (MS) is associated with significant morbidity and has profound impact on the quality of life (QoL). This study aimed to analyze the dysphagia prevalence, attitudes, and dysphagia-related QoL in patients with MS, not at relapse. A prospective study of 108 consecutively recruited patients. The patients were asked to report dysphagia and completed a general dysphagia questionnaire (the Eating Assessment Tool-10, EAT-10), a disease-specific dysphagia questionnaire (the Dysphagia in Multiple Sclerosis, DYMUS), and a dysphagia-related QoL questionnaire (the Swallowing-Quality of Life). Twenty-six percent of the patients reported dysphagia. Many more were classified as dysphagic by the questionnaires (34.3% by EAT-10 and 44.4% by DYMUS). Overall, one out of four patients reported difficulties or choking while drinking fluids and eating food, cough related to eating, food sticking in the throat, need for food and drink segmentation, and repetitive swallows. The pleasure of eating was found to be moderately affected. The patients seem to cope well with the psychological and social impact of dysphagia. Serious consideration must be given to patients' perceptions and attitudes towards dysphagia. Our patients reported very little fear associated with their swallowing difficulties and choking. Apparently, they do not perceive the severity of their symptoms as an actual danger, as they have developed coping strategies. Dysphagia is common in MS patients not at relapse, even with mild disease-related impairment. Swallowing should be systematically assessed with validated questionnaires in all patients with MS at the course of the disease.

"Radiologically Isolated" Spinal Cavernoma Associated with Familial Cerebral Cavernomatosis.

We describe a 45 year-old woman with a randomly discovered cavernous malformation of the cervical cord following investigation for neck injury. She had multiple brain cavernomas increasing in number over the following two years. She was finally diagnosed with familial cavernomatosis due to a PDCD10 mutation (CCM3).