Health status and public health needs in a Togolese child health care centre modelled after the Dutch system.

BACKGROUND: The charity foundation Association Soutien Enfants Togo started a child health care (CHC) centre in Togo that was modelled after the Dutch high-quality CHC system to improve child health. AIM: To describe health care data of children who visited the centre. SUBJECTS AND METHODS: Data were routinely collected between October 2010-July 2017. Outcomes were completed vaccinations, growth, development, lifestyle, physical examination, and laboratory testing results. RESULTS: In total, 8,809 children aged 0-24 years were available. Half (47.5%) of children aged 0-4 years did not receive all eligible free vaccinations from the government. The proportions of stunted children (all) or with a developmental delay (0-4 years) were 10.1% and 9.5%, respectively. In total, 40-50% of all children did not wash their hands with soap after toilet or before eating, or did not use clean drinking water. Furthermore, 5.1-6.6% had insufficient vision, high eye pressure or hearing loss. Sickle cell disease was detected in 5.3%. CONCLUSION: A large group of children in need of prevention and early treatment were detected, informed and treated by the centre. Further research is needed to confirm if this strategy can improve children's health in Sub-Saharan Africa. Our data are available for further research.

The Distinct Traits of the UNC13A Polymorphism in Amyotrophic Lateral Sclerosis.

OBJECTIVE: The rs12608932 single nucleotide polymorphism in UNC13A is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) susceptibility, and may underlie differences in treatment response. We aimed to characterize the clinical, cognitive, behavioral, and neuroimaging phenotype of UNC13A in patients with ALS. METHODS: We included 2,216 patients with ALS without a C9orf72 mutation to identify clinical characteristics associated with the UNC13A polymorphism. A subcohort of 428 patients with ALS was used to study cognitive and behavioral profiles, and 375 patients to study neuroimaging characteristics. Associations were analyzed under an additive genetic model. RESULTS: Genotyping rs12608932 resulted in 854 A/A, 988 A/C, and 374 C/C genotypes. The C allele was associated with a higher age at symptom onset (median years A/A 63.5, A/C 65.6, and C/C 65.5; p < 0.001), more frequent bulbar onset (A/A 29.6%, A/C 31.8%, and C/C 43.1%; p < 0.001), higher incidences of ALS-FTD (A/A 4.3%, A/C 5.2%, and C/C 9.5%; p = 0.003), lower forced vital capacity at diagnosis (median percentage A/A 92.0, A/C 90.0, and C/C 86.5; p < 0.001), and a shorter survival (median in months A/A 33.3, A.C 30.7, and C/C 26.6; p < 0.001). UNC13A was associated with lower scores on ALS-specific cognition tests (means A/A 79.5, A/C 78.1, and C/C 76.6; p = 0.037), and more frequent behavioral disturbances (A/A 16.7%, A/C 24.4%, and C/C 27.7%; p = 0.045). Thinner left inferior temporal and right fusiform cortex were associated with the UNC13A single nucleotide polymorphism (SNP; p = 0.045 and p = 0.036). INTERPRETATION: Phenotypical distinctions associated with UNC13A make it an important factor to take into account in clinical trial design, studies on cognition and behavior, and prognostic counseling. ANN NEUROL 2020;88:796-806.

Reproductive risks in 35-year-old adults born very preterm and/or with very low birth weight: an observational study.

Evidence suggests that increased survival over the last decades of very preterm (VPT; gestational age < 32 weeks)- and very low birth weight (VLBW; birth weight < 1500 g)-born infants is not matched by improved outcomes. The objective of our study was to evaluate the reproductive rate, fertility, and pregnancy complications in 35-year-old VPT/VLBW subjects. All Dutch VPT/VLBW infants born alive in 1983 and surviving until age 35 (n = 955) were eligible for a POPS-35 study. A total of 370 (39%) subjects completed a survey on reproductive rate, fertility problems, pregnancy complications, and perinatal outcomes of their offspring. We tested differences in these parameters between the VPT/VLBW subjects and their peers from Dutch national registries. POPS-35 participants had less children than their peers in the CBS registry. They reported more problems in conception and pregnancy complications, including a three times increased risk of hypertension during pregnancy.Conclusion: Reproduction is more problematic in 35-year olds born VPT/VLBW than in the general population, possibly mediated by an increased risk for hypertension, but their offspring have no elevated risk for preterm birth. What is known: At age 28, the Dutch national POPS cohort, born very preterm or with a very low birth in 1983, had lower reproductive rates than the general Dutch population (female 23% versus 32% and male 7% versus 22%). What is new: At age 35, the Dutch POPS cohort still had fewer children than the general Dutch population (female 56% versus 74% and male 40% versus 56%). Females in the POPS cohort had a higher risk of fertility problems and pregnancy complications than their peers in the Dutch national registries, but their offspring had no elevated risk for preterm birth.

Development and assessment of the inter-rater and intra-rater reproducibility of a self-administration version of the ALSFRS-R.

OBJECTIVE: The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is widely applied to assess disease severity and progression in patients with motor neuron disease (MND). The objective of the study is to assess the inter-rater and intra-rater reproducibility, i.e., the inter-rater and intra-rater reliability and agreement, of a self-administration version of the ALSFRS-R for use in apps, online platforms, clinical care and trials. METHODS: The self-administration version of the ALSFRS-R was developed based on both patient and expert feedback. To assess the inter-rater reproducibility, 59 patients with MND filled out the ALSFRS-R online and were subsequently assessed on the ALSFRS-R by three raters. To assess the intra-rater reproducibility, patients were invited on two occasions to complete the ALSFRS-R online. Reliability was assessed with intraclass correlation coefficients, agreement was assessed with Bland-Altman plots and paired samples t-tests, and internal consistency was examined with Cronbach's coefficient alpha. RESULTS: The self-administration version of the ALSFRS-R demonstrated excellent inter-rater and intra-rater reliability. The assessment of inter-rater agreement demonstrated small systematic differences between patients and raters and acceptable limits of agreement. The assessment of intra-rater agreement demonstrated no systematic changes between time points; limits of agreement were 4.3 points for the total score and ranged from 1.6 to 2.4 points for the domain scores. Coefficient alpha values were acceptable. DISCUSSION: The self-administration version of the ALSFRS-R demonstrates high reproducibility and can be used in apps and online portals for both individual comparisons, facilitating the management of clinical care and group comparisons in clinical trials.

Cognitive and behavioural changes in PLS and PMA:challenging the concept of restricted phenotypes.

OBJECTIVES: Cognitive and behavioural changes within the spectrum of frontotemporal dementia (FTD) are observed frequently in patients with amyotrophic lateral sclerosis (ALS). Whether these changes also occur in other forms of motor neuron disease (MND) is not well studied. We therefore systemically screened a large cohort of patients with primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) for cognitive and behavioural changes, and subsequently compared our findings with a cohort of patients with ALS. METHODS: Using a set of screening instruments (Edinburgh Cognitive and Behavioural ALS Screen, ALS and Frontotemporal Dementia Questionnaire, Frontal Assessment Battery, and Hospital Anxiety and Depression Scale), the presence of cognitive and behavioural changes as well as anxiety and depression in 277 patients with ALS, 75 patients with PLS and 143 patients with PMA was evaluated retrospectively. RESULTS: We found a high frequency of cognitive and behavioural abnormalities with similar profiles in all three groups. Subjects with behavioural variant FTD were identified in all groups. CONCLUSIONS: The percentage of patients with PLS and PMA with cognitive dysfunction was similar to patients with ALS, emphasising the importance for cognitive screening as part of routine clinical care in all three patient groups. With a similar cognitive profile, in line with genetic and clinical overlap between the MNDs, the view of PLS as an MND exclusively affecting upper motor neurons and PMA exclusively affecting lower motor neurons cannot be held. Therefore, our findings are in contrast to the recently revised El Escorial criteria of 2015, where PLS and PMA are described as restricted phenotypes. Our study favours a view of PLS and PMA as multidomain diseases similar to ALS.

Caregiver burden in amyotrophic lateral sclerosis: A systematic review.

BACKGROUND: Informal caregivers of patients with amyotrophic lateral sclerosis experience increased levels of caregiver burden as the disease progresses. Insight in the factors related to caregiver burden is needed in order to develop supportive interventions. AIM: To evaluate the evidence on patient and caregiver factors associated with caregiver burden in amyotrophic lateral sclerosis informal caregivers. DESIGN: A systematic review. DATA SOURCES: Four electronic databases were searched up to 2017. Studies that investigated quantitative relations between patient or caregiver factors and caregiver burden were included. The overall quality of evidence for factors was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: A total of 25 articles were included. High quality of evidence was found for the relation between caregiver burden and the factor "behavioral impairments." Moderate quality of evidence was found for the relations between caregiver burden and the factors "feelings of depression" of the caregiver and "physical functioning" of the patient. The remaining rated caregiver factors-"feelings of anxiety," "distress," "social support," "family functioning," and "age"-and patient factors-"bulbar function," "motor function," "respiratory function," "disease duration," "disinhibition," "executive functioning," "cognitive functioning," "feelings of depression," and "age"-showed low to very low quality of evidence for their association with caregiver burden. CONCLUSION: Higher caregiver burden is associated with greater behavioral and physical impairment of the patient and with more depressive feelings of the caregiver. This knowledge enables the identification of caregivers at risk for caregiver burden and guides the development of interventions to diminish caregiver burden.

Frequency of euthanasia, factors associated with end-of-life practices, and quality of end-of-life care in patients with amyotrophic lateral sclerosis in the Netherlands: a population-based cohort study.

BACKGROUND: Amyotrophic lateral sclerosis is a progressive and lethal neurodegenerative disease that is at the forefront of debates on regulation of assisted dying. Since 2002, when euthanasia was legally regulated in the Netherlands, the frequency of this end-of-life practice has increased substantially from 1·7% of all deaths in 1990 and 2005 to 4·5% in 2015. We aimed to investigate whether the frequency of euthanasia in patients with amyotrophic lateral sclerosis had similarly increased since 2002, and to assess the factors associated with end-of-life practices and the quality of end-of-life care in patients with this disease. METHODS: Using data from the Netherlands ALS registry, we did a population-based cohort study of clinicians and informal caregivers of patients with amyotrophic lateral sclerosis to assess factors associated with end-of-life decision making and the quality of end-of-life care. We included individuals who were diagnosed with amyotrophic lateral sclerosis according to the revised El-Escorial criteria, and who died between Jan 1, 2014, and Dec 31, 2016. We calculated the frequency of euthanasia in patients with amyotrophic lateral sclerosis from reports made to euthanasia review committees (ERCs) between 2012 and 2020. Results were compared with clinic-based survey studies conducted in 1994-2005. End-of-life practices were end-of-life decisions by a clinician when hastening of death was considered as the potential, probable, or definite effect comprising euthanasia, physician-assisted suicide, ending of life without explicit request, forgoing life-prolonging treatment, and intensified alleviation of symptoms. FINDINGS: Between Jan 1, 2012, and Dec 31, 2020, 4130 reports of death from amyotrophic lateral sclerosis were made to ERCs, of which 1014 were from euthanasia or physician-assisted suicide (mean frequency 25% [SD 3] per year). Sex and gender data were unavailable from the ERC registry. Of 884 patients with amyotrophic lateral sclerosis who died between Jan 1, 2014, and Dec 31, 2016, their treating clinician was identified for 731 and a caregiver was identified for 741, of whom 356 (49%) and 450 (61%), respectively, agreed to participate in the population-based survey study. According to clinicians, end-of-life practices were chosen by 280 (79%) of 356 patients with amyotrophic lateral sclerosis who died. The frequency of euthanasia in patients with amyotrophic lateral sclerosis in 2014-16 (141 [40%] of 356 deaths in patients with amyotrophic lateral sclerosis) was higher than in 1994-98 (35 [17%] of 203) and 2000-05 (33 [16%] of 209). Median survival of patients with amyotrophic lateral sclerosis from diagnosis was 15·9 months (95% CI 12·6-17·6) for those who chose euthanasia and 16·1 months (13·4-19·1) for those who did not choose euthanasia (hazard ratio 1·07, 95% CI 0·85-1·34; p=0·58). According to caregivers, compared with other end-of-life practices, patients with amyotrophic lateral sclerosis choosing euthanasia commonly reported reasons to hasten death as no chance of improvement (53 [56%] of 94 patients who chose euthanasia vs 28 [39%] of 72 patients who chose other end-of-life practices), loss of dignity (47 [50%] vs 15 [21%]), dependency (34 [36%] vs five [7%]), and fatigue or extreme weakness (41 [44%] vs 14 [20%]). According to caregivers, people with amyotrophic lateral sclerosis-whether they chose euthanasia or did not-were satisfied with the general quality (83 [93%] of 89 patients who chose euthanasia vs 73 [86%] of 85 patients who did not) and availability (85 [97%] of 88 vs 81 [91%] of 90) of end-of-life care. INTERPRETATION: The proportion of patients with amyotrophic lateral sclerosis who chose euthanasia in the Netherlands has increased since 2002. The choice of euthanasia was not associated with disease or patient characteristics, depression or hopelessness, or the availability or quality of end-of-life care. The choice of euthanasia had no effect on overall survival. Future studies could focus on the effect of discussing end-of-life options on quality of life as part of multidisciplinary care throughout the course of the disease, to reduce feelings of loss of autonomy and dignity in patients living with amyotrophic lateral sclerosis. FUNDING: Netherlands ALS Foundation.

Development of a Rasch-Built Amyotrophic Lateral Sclerosis Impairment Multidomain Scale to Measure Disease Progression in ALS.

BACKGROUND AND OBJECTIVES: Current scales used in amyotrophic lateral sclerosis (ALS) attempt to summarize different functional domains or "dimensions" into 1 overall score, which may not accurately characterize the individual patient's disease severity or prognosis. The use of composite score risks declaring treatments ineffective if not all dimensions of ALS disease progression are affected equally. We aimed to develop the ALS Impairment Multidomain Scale (AIMS) to comprehensively characterize disease progression and increase the likelihood of identifying effective treatments. METHODS: The Revised ALS Functional Rating Scale (ALSFRS-R) and a preliminary questionnaire, based on literature review and patient input, were completed online by patients from the Netherlands ALS registry at bimonthly intervals over a period of 12 months. A 2-week test-retest, factor analysis, Rasch analysis, and a signal-to-noise optimization strategy were performed to create a multidomain scale. Reliability, longitudinal decline, and associations with survival were evaluated. The sample size required to detect a 35% reduction in progression rate over 6 or 12 months was assessed for a clinical trial that defines the ALSFRS-R or AIMS subscales as a primary endpoint family. RESULTS: The preliminary questionnaire, consisting of 110 questions, was completed by 367 patients. Three unidimensional subscales were identified, and a multidomain scale was constructed with 7 bulbar, 11 motor, and 5 respiratory questions. Subscales fulfilled Rasch model requirements, with excellent test-retest reliability of 0.91-0.94 and a strong relationship with survival (p < 0.001). Compared with the ALSFRS-R, signal-to-noise ratios were higher as patients declined more uniformly per subscale. Consequently, the estimated sample size reductions achieved with the AIMS compared with those achieved with the ALSFRS-R were 16.3% and 25.9% for 6-month and 12-month clinical trials, respectively. DISCUSSION: We developed the AIMS, consisting of unidimensional bulbar, motor, and respiratory subscales, which may characterize disease severity better than a total score. AIMS subscales have high test-retest reliability, are optimized to measure disease progression, and are strongly related to survival time. The AIMS can be easily administered and may increase the likelihood of identifying effective treatments in ALS clinical trials.

Adaptation and norming of the Edinburgh Cognitive and behavioural amyotrophic lateral sclerosis screen (ECAS) for three language groups in South Africa.

Objectives: To adapt and translate the Edinburgh Cognitive and behavioural amyotrophic lateral sclerosis screen (ECAS); to generate preliminary normative data for three language groups in South Africa (SA); to assess the convergent validity of the ECAS in SA samples. Methods: The ECAS was linguistically and culturally adapted for Afrikaans-, isiXhosa-, and English-speaking SA adults (n = 108, 100, and 53, respectively). Each language group was stratified by age and educational level. Cutoff scores for cognitive impairment were set at the group mean minus two standard deviations (SDs). A pilot sample of ALS patients and controls (n = 21 each) were administered the ECAS and an extensive neuropsychological evaluation (NPE) and the Montreal Cognitive Assessment (MoCA) to assess convergent validity. Results: Across the three language groups, the total ECAS cutoff scores ranged from 68 to 97. The ECAS score correlated significantly positively with educational level (p < 0.001) and negatively with age (p < 0.005). The restricted letter fluency task demonstrated a floor effect, particularly in Afrikaans-speakers. The mean total ECAS score (±SD) was similar in ALS patients (103.52 ± 11.90) and controls (100.67 ± 20.49; p = 0.58). Three (14.3%) ALS patients scored below the cutoff for cognitive impairment. Correlations between individual ECAS subtests and analogous NPE tests ranged from weak to moderate. The MoCA score was significantly positively correlated with the ECAS total score (r = 0.59; p = < 0.001). Conclusions: The adapted ECAS and associated normative data will aid cognitive screening of African ALS patients. Larger participant numbers are needed to assess the validity of the adapted instrument.

Improving behavioural compliance with the COVID-19 precautionary measures by means of innovative communication strategies: Social experimental studies.

OBJECTIVES: Behavioural measures such as social distancing are crucial to prevent the spread of COVID-19. People sometimes have difficulty to comply with these behavioural measures for various reasons. Insight is needed into evidence-based strategies that can promote compliance. In the present study, we examined whether behaviour change techniques (volitional help sheet (VHS), behavioural journalism (BJ) and empathy inductions (EI)) could promote behavioural compliance with the COVID-19 measures. METHODS: Three online experiments were carried out (N = 424-593) among Dutch adult citizens, using a randomized 2-group post-test and 1-week follow-up design. In each experiment, a control group was compared with the experimental condition (respectively VHS, BJ or EI condition). RESULTS: Two out of the three different strategies did result in favourable changes with regard to the compliance-related measures. The VHS contributed to changes in perceived susceptibility of others (t = -2,78; f**2 = 0,019), perceived severity (t = -3,65; f**2 = 0,032) and individual behavioural compliance measures. People exposed to the VHS were more likely to receive less visitors (w = 16638; p = 0.003)and avoid crowds (w = 16631; p = 0.003). EI increased the perceived vulnerability of others. Video-based role model stories, based on BJ did not result in any changes. CONCLUSIONS: Behaviour change strategies may contribute to promoting behavioural compliance and could be used in public health communication. The empathy induction can be used to enhance other protection motives, while the volitional help sheet effectively can help people to overcome compliance barriers. Behavioural science can add to fighting the COVID-19 pandemic.

Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform.

BACKGROUND: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. METHODS: We used harmonized aggregated data from 15 population-based cohorts of children born at <32 weeks of gestational age (GA) or <1500 g from 1985 to 2013 in 13 countries with information on maternal education and assessments of general development at 2-3 years and/or intelligence quotients between 4 and 15 years. Term-born controls (≥37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. RESULTS: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (<27 vs ≥27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. CONCLUSIONS: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.

Multimodal longitudinal study of structural brain involvement in amyotrophic lateral sclerosis.

OBJECTIVE: To understand the progressive nature of amyotrophic lateral sclerosis (ALS) by investigating differential brain patterns of gray and white matter involvement in clinically or genetically defined subgroups of patients using cross-sectional, longitudinal, and multimodal MRI. METHODS: We assessed cortical thickness, subcortical volumes, and white matter connectivity from T1-weighted and diffusion-weighted MRI in 292 patients with ALS (follow-up: n = 150) and 156 controls (follow-up: n = 72). Linear mixed-effects models were used to assess changes in structural brain measurements over time in patients compared to controls. RESULTS: Patients with a C9orf72 mutation (n = 24) showed widespread gray and white matter involvement at baseline, and extensive loss of white matter integrity in the connectome over time. In C9orf72-negative patients, we detected cortical thinning of motor and frontotemporal regions, and loss of white matter integrity of connections linked to the motor cortex. Patients with spinal onset displayed widespread white matter involvement at baseline and gray matter atrophy over time, whereas patients with bulbar onset started out with prominent gray matter involvement. Patients with unaffected cognition or behavior displayed predominantly motor system involvement, while widespread cerebral changes, including frontotemporal regions with progressive white matter involvement over time, were associated with impaired behavior or cognition. Progressive loss of gray and white matter integrity typically occurred in patients with shorter disease durations (<13 months), independent of progression rate. CONCLUSIONS: Heterogeneity of phenotype and C9orf72 genotype relates to distinct patterns of cerebral degeneration. We demonstrate that imaging studies have the potential to monitor disease progression and early intervention may be required to limit cerebral degeneration.

Psychological distress and coping styles of caregivers of patients with amyotrophic lateral sclerosis: a longitudinal study.

Objectives: To assess psychological distress levels over time in caregivers of patients in the early stage of amyotrophic lateral sclerosis (ALS) and to investigate the association between caregivers' coping styles and psychological distress over time. Methods: Fifty-four caregivers were followed in a RCT of patients in the early stage of ALS. Questionnaires were administered at baseline, 4, 7, and 10 months. Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS) and task-, emotion-, and avoidance-oriented coping styles were identified with the short version of the Coping Inventory for Stressful Situations (CISS-21). Analyses were performed using linear mixed models. Results: Caregivers' psychological distress increased by 0.24 points on the HADS per month (p = 0.01). An emotion-oriented coping style was positively associated with psychological distress in caregivers (b = 0.90, p < 0.01), but did not influence the development of psychological distress over time. The avoidance-oriented coping style and the task-oriented coping style were not significantly related to psychological distress. Conclusion: Feelings of distress increase in ALS caregivers during the course of the disease of the patient. Emotion-oriented coping is related to psychological distress; however, emotional coping and distress might represent overlapping constructs. Focusing on one coping style in the care for ALS caregivers may be too simplistic for the complex situations they face, as it ignores the fact that people may require different coping strategies in different situations.

A neuropsychological and behavioral study of PLS.

Background: Primary lateral sclerosis (PLS) is a rare motor neuron disease characterized by progressive degeneration of upper motor neurons, resulting in spasticity and disability. There is, however, mounting evidence that the disease is not limited to upper motor neurons alone and that cognitive and behavioral changes within the spectrum of frontotemporal dementia (FTD) are part of the clinical phenotype. Objectives: To provide an in-depth classification of the cognitive and behavioral profiles of PLS by using the golden standard, a full neuropsychological evaluation, as well as a comprehensive behavioral assessment in a cohort of 30 cases. Results: Only 7 out of 30 PLS patients scored within normal range on all of the tests within our battery. The neuropsychological profile of PLS consists of deficits in social cognition (affective theory of mind (ToM) in particular), fluency, executive functions and memory. Using the revised Strong criteria, we could classify 57% of patients within the FTD spectrum (of which 17% had behavioral variant FTD). An additional 20% of patients had deficits which were not characteristic of FTD. Conclusions: This study confirms that PLS is not a restricted phenotype (only affecting upper motor neurons) and that behavioral and cognitive changes are common. Therefore, clinicians treating PLS patients should routinely assess cognition and behavior as part of routine care as cognitive and behavioral changes impact management, decision-making and care-giver burden. This assessment should be sensitive to the neuropsychological profile of PLS (social cognition (affective ToM in particular), fluency, executive functions and memory) and behavioral changes.

Derivation of norms for the Dutch version of the Edinburgh cognitive and behavioral ALS screen.

BACKGROUND: The Edinburgh cognitive and behavioral ALS screen (ECAS) was developed specifically to detect cognitive and behavioral changes in patients with amyotrophic lateral sclerosis (ALS). Differences with regard to normative data of different (language) versions of neuropsychological tests such as the ECAS exist. OBJECTIVE: To derive norms for the Dutch version of the ECAS. METHODS: Normative data were derived from a large sample of 690 control subjects and cognitive profiles were compared between a matched sample of 428 patients with ALS and 428 control subjects. RESULTS: Age, level of education, and sex were significantly associated with performance on the ECAS in the normative sample. ECAS data were not normally distributed and therefore normative data were expressed as percentile ranks. The comparison of ECAS scores between patients and control subjects demonstrated that patients obtained significantly lower scores for language, executive function, verbal fluency, and memory, which is in line with the established cognitive profile of ALS. CONCLUSION: For an accurate interpretation of ECAS results, it is important to derive normative data in large samples with nonparametric methods. The present normative data provide healthcare professionals with an accurate estimate of how common or uncommon patients' ECAS scores are and provide a useful supplement to existing cut-off scores.

Assessment of the factorial validity and reliability of the ALSFRS-R: a revision of its measurement model.

The amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) is a widely used primary outcome measure in amyotrophic lateral sclerosis (ALS) clinical practice and clinical trials. ALSFRS-R items cannot, however, validly be summed to obtain a total score, but constitute domain scores reflecting a profile of disease severity. Currently, there are different measurement models for estimating domain scores. The objective of the present study is, therefore, to derive the measurement model that best fits the data for a valid and uniform estimation of ALSFRS-R domain scores. Data from 1556 patients with ALS were obtained from a population-based register in The Netherlands. A random split of the sample provided a calibration and validation set. Measurement models of the ALSFRS-R were investigated using both exploratory factor analyses and confirmatory factor analyses. The measurement model with a four-factor structure (i.e., bulbar, fine motor, gross motor, and respiratory function), with correlated factors and cross-loading items on dressing and hygiene and turning in bed and adjusting bed clothes on both motor function scales, provided the best fit to the data in both sets. Correlation between factors ranged from weak to modest, confirming that the ALSFRS-R constitutes a profile of four clinically relevant domain scores rather than a total score that expresses disease severity. The internal consistency of the four domain scores was satisfactory. Our revision of the measurement model may allow for a more adequate estimation of disease severity and disease progression in epidemiological studies and clinical trials.