Profiles of objective and subjective cognitive function in Post-COVID Syndrome, COVID-19 recovered, and COVID-19 naïve individuals.

Post-COVID Syndrome has emerged as a significant public health concern worldwide with increasing evidence to suggest that individuals who have had an acute COVID-19 infection report lingering memory and attention difficulties, even in individuals who have fully recovered and no longer experiencing symptoms of COVID-19. The present study sought to investigate the profile of objective and subjective cognitive difficulties in people who have Post-COVID Syndrome, people who have fully recovered from an acute COVID infection and people who have never had COVID-19. We further sought to explore the extent to which self-reported fatigue and stress are related to subjective and objective cognitive difficulties. 162 participants including 50 people living with Post-COVID Syndrome, 59 people who have had COVID-19 but have fully recovered and 53 people who have never experienced symptoms of COVID-19 and had never tested positive for COVID-19 were recruited from Academic Prolific to complete a series of online questionnaires and neurocognitive tasks. Subjective cognitive function was measured using the Cognitive Failures Questionnaire and objective cognitive function was measured using the Cognitron cognitive test battery. We found that objective and subjective measures of cognitive function were not significantly related, suggesting that self-reports of "brain fog" are not reflecting objectively measured cognitive dysfunction. A MANOVA revealed that subjective cognitive deficits were driven by heightened perceived stress and fatigue and not significantly related to COVID-19 status. Objective cognitive function, however, was significantly related to perceived stress and COVID status whereby we observed significant objective cognitive deficits in people who have been exposed to an acute COVID-19 infection regardless of whether they had Post-COVID Syndrome or had fully recovered, as compared to people who had never had COVID-19. This suggests that an acute infection can have long term effects on cognitive function, even without persistent COVID-19 symptoms. Encouragingly, objective cognitive function was significantly associated with time since initial infection showing that cognitive deficits improved over time for people who had recovered from COVID-19. However, we did not observe the same improvement in individuals with Post-COVID Syndrome and observed that cognitive dysfunction was significantly related to the number of neurological symptoms presently experienced. These results add to the accumulating literature that COVID-19 is associated with significant cognitive difficulties following a COVID-19 infection, which appear to improve over time for those who have recovered from COVID-19 yet persist in people living with Post-COVID Syndrome.

Hypogammaglobulinemia: A contributing factor to multiple sclerosis fatigue?

OBJECTIVE: Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia. METHODS: PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi2 test and multivariable linear regression models were run. RESULTS: 97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 - -0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness. CONCLUSIONS: We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively.

[Neuropsychological and MRI diagnostics in secondary progressive multiple sclerosis]. / Neuropsychologische und Magnetresonanztomographie(MRT)-Diagnostik bei sekundär progredienter Multipler Sklerose.

BACKGROUND: Multiple sclerosis is a disease continuum with an initial relapsing remitting course (RRMS) and secondary progression (SPMS) at later stages. Most of the hitherto approved treatments do not adequately control for the phase of secondary progression. Thus, early detection of SPMS conversion is a key issue to initiate SPMS-tailored treatment. In this context, assessment of cognitive functions and magnetic resonance imaging (MRI) both play an important role in the longitudinal follow-up of MS patients. OBJECTIVE: To elucidate the importance of cognitive testing and MRI for prediction and detection of SPMS conversion as well as to discuss strategies for disease monitoring and for optimizing treatment in standard clinical care, particularly in outpatient settings. MATERIAL AND METHODS: Review article based on a nonsystematic literature review. RESULTS: Standardized cognitive testing can support early diagnosis of SPMS and facilitate disease monitoring. Annual application of sensitive screening tests, such as the Symbol Digit Modalities Test (SDMT) and Brief Visual Memory Test-Revised (BVMT­R) or the entire Brief International Cognitive Assessment for MS (BICAMS) test battery are recommended in this context. The MRI evidence of persistent inflammatory activity within 3 years of diagnosis as well as evidence of cortical lesions are predictive for SPMS conversion. Standardized MRI monitoring for markers of progression can substantiate clinical and neurocognitive signs of SPMS conversion. CONCLUSION: Multidisciplinary patient care involving careful clinical examination, neuropsychological testing and MRI monitoring is of great significance for the prediction of SPMS conversion and diagnostics. This enables early treatment adaptation, since pharmacological interventions in SPMS differ from those in RRMS. Continuous clinical, neuropsychological and MRI vigilance enable stringent monitoring of treatment outcomes with respect to neuroinflammatory and neurodegenerative activity as well as treatment-related complications.

The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): results from the German validation study.

BACKGROUND: Recent research has convincingly shown that the ability to work mainly depends on the cognitive status in multiple sclerosis (MS). An international committee of experts recommended a brief neuropsychological battery to evaluate cognitive performance in MS. BICAMS comprises three tests, the Symbol Digit Modalities Test (SDMT), the learning trials of the California Verbal Learning Test II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). OBJECTIVE: To validate BICAMS on a sample of German MS patients and healthy controls (HCs). METHODS: According to the international guidelines for validation, examiner's instructions were standardized and translated into German. Due to the availability of better normative data for future applications in routine clinical care and classification of individual performance degree, the Rey Auditory Verbal Learning Test (RAVLT) (German version: Verbaler Lern- und Merkfähigkeits-Test, VLMT) was chosen instead of CVLT-II. 172 MS patients and 100 HCs entered the study. BICAMS was administered at baseline and retest (after 3-4 weeks). RESULTS: The groups did not differ in age, gender or education. Mean age of MS patients was 43.33 years (SD 11.64); 68% were female and 86.9% had relapsing-remitting MS. Patients performed significantly worse than HCs on the SDMT (p < 0.01) and on BVMT-R (p < 0.05) but not on VLMT. In addition, BICAMS was shown to be reliable over time: r = 0.71 for BVMT-R, r = 0.72 for VLMT and r = 0.85 for SDMT. SDMT z-score proved to be a good predictor for the ability to work in a full-time (p < 0.001) as well as in a part-time job (p < 0.001). VLMT z-score turned out to be a significant predictor only for the ability to work in a part-time job, while BVMT-R z-score showed no significant predictive value. CONCLUSION: In this German validation study with the VLMT, the modified BICAMS (BICAMS-M) turned out to reliably detect cognitive problems in MS patients and to monitor cognitive performance over time. SDMT revealed the best predictive value for working ability. Moreover, only the SDMT was able to predict the ability to work in a part-time or full-time job. Following these results, application of the SDMT is recommended for medical statements on working ability of MS patients.

Characterization of social cognition impairment in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has been associated with deficits in social cognition. However, little is known about which domains of social cognition are predominantly affected and what other factors are associated with it. The aim was (i) to characterize social cognition deficit in a group of MS outpatients and (ii) to relate impairment in social cognition to overall cognitive status, depression and fatigue. METHODS: Thirty-five MS patients (mean disease duration 12.9 years, median Expanded Disability Status Scale (EDSS) 3 and 34 healthy controls (HCs) were examined using the German version of the Geneva Social Cognition Scale to measure different domains of social cognition. Standard neuropsychological testing was applied to all patients and to 20 HCs. Patient-reported outcomes included questionnaires for fatigue, depression, anxiety and executive-behavioural disturbances. RESULTS: The mean social cognition raw score was lower in the MS patients compared to the HCs (86.5 ± 8.7 vs. 91.2 ± 5.9, P = 0.005; d = 0.6) and did not correlate with EDSS or disease duration. The difference was driven by facial affect recognition and the understanding of complex social situations (14% and 23% of patients respectively under the cut-off). The impairment in these two tasks did not correlate with general cognitive performance or depression but with fatigue. CONCLUSIONS: The impairment in our group was restricted to high order and affective social cognition tasks and independent of general cognitive performance, EDSS, disease duration and depression. Fatigue correlated with social cognition performance, which might be due to common underlying neuronal networks.

Validation of the fatigue scale for motor and cognitive functions in a danish multiple sclerosis cohort.

BACKGROUND: Our objective was to validate the Danish translation of the Fatigue Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS) patients. MATERIALS AND METHODS: A Danish MS cohort (n = 84) was matched and compared to the original German validation cohort (n = 309) and a healthy control cohort (n = 147). The Modified Fatigue Impact Scale (MFIS) was used as reference scale and Becks Depression Inventory-Fast Screen (BDI-FS) and Expanded Disability Status Scale (EDSS) for confounding factors. We assessed internal consistencies; convergent, divergent, and predictive validity; partial correlations correcting for depression; significant differences between the mean scores of the cohorts; and sensitivity and specificity with receiver operating characteristic (ROC) curves. RESULTS: Excellent internal consistencies for the total scale and subscales were found (α = 0.91-0.95). Strong positive correlations between the two fatigue scales implied high convergent validity (total scores: r = 0.851, p < 0.01). The two cohorts corresponded well when divided into subgroups (EDSS score; age; gender). Correcting for depression did not result in any significant adjustments of the correlations. The area under the curve (AUC) for the ROC curves represented excellent accuracy (Danish MS cohort, AUC = 0.9190; German MS cohort, AUC = 0.9034). CONCLUSION: The Danish translation of the FSMC has a high convergent validity with another measure of fatigue as well as excellent internal consistency and accuracy. It is found to be an applicable and recommendable measure of fatigue in Danish MS patients.

Retrieval of the particle size distribution function from the data of lidar sensing under the assumption of known refractive index.

This paper presents a method to retrieve the particle size distribution function from the data of vertical lidar sensing. We have used 462 data models obtained at the Zvenigorod AERONET site obtained in 2011-2012. For each laser shot, we considered both fine (with particle sizes in a range from 0.05 to 0.6 µm) and coarse aerosol fractions (from 0.6 to 10 µm), with emphasize on the coarse fraction. Our suggested method is a modification of the Tikhonov method. The Tikhonov method is not optimal for coarse particles because its stabilizer does not and cannot account for the presence of the coarse mode, i.e., existence of more than one maximum of the size distribution function. The components of the matrix Wu-1 located in quadrants II and IV are sensitive to the change of these parameters. Neglecting this fact will lead again to arbitrary estimates of the contribution of the coarse particles even for exact values on the main diagonal and the two diagonals adjacent to it. Our method allows the coarse fraction up to 2.5 µm to be determined unambiguously. For larger particles (>2.5 µm) we recommend using the available sets of the coefficients, but with the level of values to be determined.

Evaluation of cognition and fatigue in multiple sclerosis: daily practice and future directions.

The so-called hidden symptoms or soft signs of multiple sclerosis comprise cognitive dysfunction, fatigue, depression and anxiety. From a patient's perspective, these symptoms are rated as exerting much more negative impact on quality of life and daily functioning than their physical symptoms. Despite this knowledge, the symptoms remain disregarded by many neurologists in clinical practice. This missing awareness can be attributed to several reasons. First, the underlying pathophysiological mechanisms determining occurrence and severity of the different symptoms are still unclear. Second, there is uncertainty in how to reliably assess them. It is undeniable that assessment can be difficult as the hidden symptoms seldom appear isolated but more often highly interact. Third, if standardized, fast and cost-effective assessment to quantify and monitor the evolution of the hidden symptoms would be feasible, the question still remains how to treat these aspects. The present article will give an overview on symptom background and assessment strategies for clinical practice.

The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis.

BACKGROUND AND PURPOSE: Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS. METHODS: In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0-7.5), 103 relapsing-remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI. RESULTS: Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 µl; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = -0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing-remitting MS. CONCLUSION: Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.

Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review.

BACKGROUND: So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population. OBJECTIVE: The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year's duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared. RESULTS: Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately. CONCLUSION: Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression.

[Fatigue in patients with multiple sclerosis--pathogenesis, clinical picture, diagnosis and treatment]. / Fatigue bei Patienten mit Multipler Sklerose--Pathogenese, Klinik, Diagnostik und Therapie.

Fatigue is a frequent and restricting symptom of multiple sclerosis (MS). Starting from its pathogenetic mechanisms, the article develops an approach to the differential diagnosis of fatigue in MS patients. Over the past years, the use of functional imaging techniques has given important information on the mechanisms of this highly variable clinical picture. Considering our improved understanding of the interdependency of immune pathology and the clinical presentation of neuropsychological disorders, the relationship between immunomodulatory treatments and fatigue is receiving increased attention. Therefore, this article not only reports on the most recent data on pharmacological, physical and psychological interventions in the symptomatic treatment of fatigue, but also puts a special accent on data concerning the interactions between the rapidly growing number of immunomodulatory treatments in MS.

Reduced magnetisation transfer ratio in cognitively impaired patients at the very early stage of multiple sclerosis: a prospective, multicenter, cross-sectional study.

OBJECTIVES: Cognitive impairment belongs to the core symptoms in multiple sclerosis (MS) and can already be present at the very early stages of the disease. The present study evaluated cognitive functioning after the first clinical presentation suggestive of MS and brain tissue damage in a non-lesion focused MRI approach by using magnetisation transfer imaging (MTI). SETTING AND PARTICIPANTS: 47 patients (15 men and 32 women; mean age: 31.17 years) after the first clinical event suggestive of MS were recruited in six different MS centres in Germany and underwent a neuropsychological test battery including tests for attention, memory and executive function as well as depression and fatigue. MTI and conventional MRI measures (T1/T2 lesion load) were assessed. In addition, Magnetisation Transfer Ratio (MTR) maps were calculated. Primary outcome measure was the investigation of cognitive dysfunction in very early MS in correlation to MRI data. RESULTS: 55.3% of patients with MS failed at least one test parameter. Specifically, 6% were reduced in working memory, 14.9% in focused attention, 25.5% in figural learning and up to 14.9% in executive function. When the sample was subdivided into cognitively impaired and preserved, MTR scores within the cognitively impaired subgroup were significantly lower compared with the preserved group (t(43)=2.346, p=0.02*). No significant differences between the two groups were found in T2-weighted and T1-weighted lesion volume. CONCLUSIONS: After the first MS-related clinical event, 55.3% of patients showed distinct cognitive deficits. Cognitively impaired patients had significantly lower whole brain MTR, but no differences in focal brain lesion volumes supporting the idea that early cognitive deficits may be related to diffuse loss of brain tissue integrity.

BECTS evolving to Landau-Kleffner Syndrome and back by subsequent recovery: a longitudinal language reorganization case study using fMRI, source EEG, and neuropsychological testing.

By means of a longitudinal case study, we demonstrated the course of cerebral reorganization of language representation due to epilepsy in a child with benign epilepsy with centro-temporal spikes (BECTS) evolving to Landau-Kleffner Syndrome (LKS) and returning to BECTS. The child underwent the following procedures at the ages of 8.2, 8.6, and 9.3 years: 3D source EEG imaging, language fMRI (sentence generation and reading), and neuropsychological testing. He had a follow-up testing at the age of 10.8 years. Further, 24-h EEGs were regularly performed. At the age of around 8 years, the child was diagnosed initially with left-hemispheric BECTS, which evolved to LKS with continuous bilateral discharges. In addition, 3D source imaging data revealed a left anterior temporal focus with a spreading to the right parietal and left centro-parietal areas. The patient had verbal agnosia with poor verbal yet good performance indices. Functional magnetic resonance imaging (fMRI) showed a left-hemispheric reading network but sentence generation was impossible to perform. After initiation of adequate treatment, continuous discharges disappeared, and only very rare left-hemispheric centro-temporal spikes remained. Verbal IQ and performance IQ increased at the age of 8.6 years. Functional magnetic resonance imaging showed, at this time, a right-hemispheric language activation pattern for sentence generation and reading. At the ages of 9.3 and 10.8 years, language tasks remained right-hemispheric and verbal IQ remained stable, but right-hemispheric non-verbal functions decreased due to possible crowding-out mechanisms.

Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).

BACKGROUND: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. OBJECTIVE: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use. METHODS: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients. RESULTS: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test - Second Edition and the Brief Visuospatial Memory Test - Revised learning trials if a further 10 minutes could be allocated for testing. CONCLUSIONS: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.

MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial.

OBJECTIVE: Health-related quality of life (HRQOL) is often much reduced among individuals with multiple sclerosis (MS), and incidences of depression, fatigue, and anxiety are high. We examined effects of a mindfulness-based intervention (MBI) compared to usual care (UC) upon HRQOL, depression, and fatigue among adults with relapsing-remitting or secondary progressive MS. METHODS: A total of 150 patients were randomly assigned to the intervention (n = 76) or to UC (n = 74). MBI consisted of a structured 8-week program of mindfulness training. Assessments were made at baseline, postintervention, and 6 months follow-up. Primary outcomes included disease-specific and disease-aspecific HRQOL, depression, and fatigue. Anxiety, personal goal attainment, and adherence to homework were secondary outcomes. RESULTS: Attrition was low in the intervention group (5%) and attendance rate high (92%). Employing intention-to-treat analysis, MBI, compared with UC, improved nonphysical dimensions of primary outcomes at postintervention and follow-up (p < 0.002); effect sizes, 0.4-0.9 posttreatment and 0.3-0.5 at follow-up. When analyses were repeated among subgroups with clinically relevant levels of preintervention depression, fatigue, or anxiety, postintervention and follow-up effects remained significant and effect sizes were larger than for the total sample. CONCLUSIONS: In addition to evidence of improved HRQOL and well-being, these findings demonstrate broad feasibility and acceptance of, as well as satisfaction and adherence with, a program of mindfulness training for patients with MS. The results may also have treatment implications for other chronic disorders that diminish HRQOL. CLASSIFICATION OF EVIDENCE: This trial provides Class III evidence that MBI compared with UC improved HRQOL, fatigue, and depression up to 6 months postintervention.

The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue.

Fatigue symptoms are reported by a majority of patients with multiple sclerosis (MS). Reliable assessment, however, is a demanding issue as the symptoms are experienced subjectively and as objective assessment strategies are missing. The objective of this study was to develop and validate a new tool, the Fatigue Scale for Motor and Cognitive Functions (FSMC), for the assessment of MS-related cognitive and motor fatigue. A total of 309 MS patients and 147 healthy controls were included into the validation study. The FSMC was tested against several external criteria (e.g. cognition, motivation, personality and other fatigue scales). The item-analysis and validation procedure showed that the FSMC is highly sensitive and specific in detecting fatigued MS patients, that both subscales significantly differentiated between patients and controls (p < 0.01), and that internal consistency (Cronbach's alpha alpha > 0.91) as well as test-retest reliability (r > 0.80) were high. Cut-off values were determined to classify patients as mildly, moderately or severely fatigued. In conclusion, the FSMC is a new scale that has undergone validation based on a large sample of patients and that provides differential quantification and graduation of cognitive and motor fatigue.

Partial atrioventricular septal defect in the fetus: diagnostic features and associations in a multicenter series of 30 cases.

OBJECTIVE: To assess the anatomical features and the associations of partial atrioventricular septal defect (pAVSD) in the fetus. METHODS: This was a retrospective multicenter study of 30 cases of confirmed pAVSD seen since 1996 at two referral centers. The following variables were available for analysis in all cases: indications for fetal echocardiography, diagnostic features, associated cardiac, extracardiac and chromosomal anomalies and fetoneonatal outcome. At fetal echocardiography, the echocardiographic features deemed indicative of pAVSD were: 1) ostium primum atrial septal defect and 2) loss of the normal offset appearance of the atrioventricular valves. RESULTS: Eighteen of the 30 (60%) cases were diagnosed before 24 weeks of gestation and 12 were diagnosed later. Suspicion of congenital heart disease and known aneuploidy (trisomy 21) accounted for 60% of the referral indications. The two anatomical landmarks deemed indicative of pAVSD were detected in all cases at echocardiography. Twelve cases were isolated (one with increased nuchal transluceny at the 12-week scan, one with polyhydramnios, one with fetal growth restriction) including four that were detected on routine ultrasound examination by the authors. Additional cardiac anomalies were present in five (17%) cases, four of which involved aortic coarctation. There were associated chromosomal anomalies in 13 (43%); however, excluding the six cases referred because of known Down syndrome, the adjusted association rate with aneuploidy was 29.2% (7/24). Extracardiac anomalies, including non-chromosomal syndromes, were present in 10 cases (33.3%). Regarding fetoneonatal outcome, there were 13 terminations of pregnancy, one early neonatal death and 16 survivors, including four with mild to severe neurodevelopmental delay due to associated syndromic conditions. CONCLUSIONS: We describe the key echocardiographic features of pAVSD in the fetus. In addition, we have confirmed that the association with trisomy 21 holds also for pAVSD, though to a lesser extent, with a 12.5% association rate in this series. In the fetus, pAVSD seems to be associated with a high rate of chromosomal/non-chromosomal syndromic conditions, including skeletal dysplasias. Inutero, aortic coarctation represents the most frequently associated cardiac lesion (13.3%).

Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns.

BACKGROUND: Multiple sclerosis (MS) is often accompanied by cognitive dysfunction. A negative correlation between cerebral lesion load and atrophy and cognitive performance has been pointed out almost consistently. Further, the distribution of lesions might be critical for the emergence of specific patterns of cognitive deficits. OBJECTIVE: The current study evaluated the significance of total lesion area (TLA) and central atrophy for the prediction of general cognitive dysfunction and tested for a correspondence between lesion topography and specific cognitive deficit patterns. METHODS: Thirty-seven patients with MS underwent neuropsychological assessment and magnetic resonance imaging. Lesion burden and central atrophy were quantified. Patients were classified into three groups by means of individual lesion topography (punctiform lesions/periventricular lesions/confluencing lesions in both periventricular and extra-periventricular regions). RESULTS: TLA was significantly related to 7 cognitive variables, whereas third ventricle width was significantly associated with 20 cognitive parameters. The three groups differed significantly in their performances on tasks concerning alertness, mental speed, and memory function. CONCLUSION: Third ventricle width as a straight-forward measure of central atrophy proved to be of substantial predictive value for cognitive dysfunction, whereas total lesion load played only a minor role. Periventricular located lesions were significantly related to decreased psychomotor speed, whereas equally distributed cerebral lesion load did not. These findings support the idea that periventricular lesions have a determinant impact on cognition in patients with MS.

Fatigue in multiple sclerosis: relation to depression, physical impairment, personality and action control.

Although fatigue is one of the most common symptoms of multiple sclerosis, it is yet poorly understood and therefore difficult to manage. To clarify the nature of fatigue we investigated its relationship to depression, physical impairment, personality and action control and compared these variables between a sample of 41 MS patients and 41 healthy controls. Physical impairment was assessed by the EDSS and all other dimensions, using questionnaires. Stepwise linear regression analyses revealed that physical impairment was related to physical fatigue in MS patients. Depression was the main factor influencing fatigue among both, MS patients and controls. What clearly differentiated the two groups was the correlation between fatigue and action control. Decreased levels of action control imply attentional and motivational deficits and were only found in fatigued MS patients. Our study indicates that motivational disturbances might be specific for MS related fatigue.