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INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. METHODS: This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients' needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. PERSPECTIVE: It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. TRIAL REGISTRATION: The study is registered at ClinicalTrails.gov; NCT06418646.
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OBJECTIVE: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is an established cognitive screening instrument for patients with amyotrophic lateral sclerosis (ALS). Different from tools like the Mini-Mental State Examination (MMSE), it is adjusted for motor impairment, yet, the latter remains one of the most widely used screening instruments, also in ALS studies. Thus, it is of utmost importance to relate outcome scores of both instruments to allow for comparison in ALS patients. This study reports on the performance of ALS patients in both tests with regard to incidence and degree of cognitive impairment, and the correspondence of both, ECAS and MMSE scores. METHODS: We examined N = 84 ALS patients with the German versions of the ECAS and the MMSE. Performance in both tests regarding incidence and degree of cognitive impairment, and correspondence of frequency of cognitive impairment according to both tests was examined. The relationship between ECAS and MMSE scores was modelled with a non-linear regression model. RESULTS: All ALS patients were able to complete the ECAS, 89.3% (N = 75) were capable to complete the MMSE. Prevalence of cognitive impairment was in both tests 22.7%, however agreement was only 52.9%. Despite, regression analyses yielded a strong positive relationship (adjusted R2 = .68) between the ECAS total score and the MMSE total score. Both tests were able to identify all patients with dementia. CONCLUSION: These results suggest that the MMSE is not ideal for cognitive screening in early-stage ALS patients. However, a rough translation of MMSE scores in ECAS scores is possible to estimate the cognitive performance level of patients, with the ECAS being more discriminative in the lower range of cognitive dysfunction (ECAS score: 80-136), for which the MMSE does not define cognitive impairment (corresponding MMSE score: 27-30).
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Esclerosis Amiotrófica Lateral , Pruebas de Estado Mental y Demencia , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/psicología , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Cognición/fisiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Pruebas Neuropsicológicas , Trastornos del Conocimiento/diagnósticoRESUMEN
Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing. Methods: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded. Results: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS. Conclusion: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.
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BACKGROUND: Validation of the 2020 consensus criteria for primary lateral sclerosis (PLS) is essential for their use in clinical practice and future trials. METHODS: In a large cohort of patients diagnosed with PLS by expert opinion prior to the new criteria with detailed clinical baseline evaluation (n=107) and longitudinal follow-up (n=63), we applied the new diagnostic criteria and analysed the clinical phenotype, electromyography (EMG), diagnostic accuracy and prognosis, adding neurofilaments and MRI as potential biomarkers. RESULTS: The criteria for definite PLS were met by 28% and those for probable PLS by 19%, whereas 53% did not meet the full criteria at baseline, mainly due to the time, EMG and region criteria. Patients not meeting the criteria had less generalised upper motor neuron involvement but were otherwise similar in demographic and clinical characteristics. All patients with definite and probable PLS maintained PLS diagnosis during follow-up, while four patients not meeting the criteria developed clinical lower motor neuron involvement. Definite PLS cases showed improved survival compared with probable PLS and patients who did not meet the criteria. Despite a clinical PLS phenotype, fibrillation potentials/positive sharp waves and fasciculations in one or more muscles were a frequent EMG finding, with the extent and prognostic significance depending on disease duration. Serum neurofilament light and a multiparametric MRI fibre integrity Z-score correlated with clinical parameters and were identified as potential biomarkers. CONCLUSION: Validation of the 2020 PLS consensus criteria revealed high diagnostic certainty and prognostic significance, supporting their value for research and clinical practice.
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Consenso , Electromiografía , Imagen por Resonancia Magnética , Enfermedad de la Neurona Motora , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/diagnóstico , Estudios de Cohortes , Adulto , Anciano , Proteínas de Neurofilamentos/sangre , Biomarcadores/sangre , PronósticoRESUMEN
OBJECTIVE: This paper examines neurologists' approaches to exit strategies (ESs), such as euthanasia and physician-assisted suicide, in patients with amyotrophic lateral sclerosis (PALS) in two European countries. METHODS: In a nationwide anonymous survey, we collected responses from 237 Polish and 228 German neurologists, focusing on their practices and beliefs about ESs, as well as their viewpoints on life-sustaining measures (LSMs) (percutaneous endoscopic gastrostomy, non-invasive, and invasive ventilation). To analyze the data, we employed statistical methods, including Mann-Whitney U, Kruskal-Wallis, chi-square tests, Spearman's rank correlation, and multiple regression analysis. RESULTS: One third of the neurologists initiated the discussion about ESs with PALS. Half were ready to have this conversation upon patient's request. Age, gender, religiousness, and nationality were closely associated with this approach. One in 9 neurologists received a request to terminate an LSM, whereas 1 in 10 to implement an ES. German neurologists and palliative care trainees acquired both demands more commonly. Neurologists quoted a low quality of life, decreased mood, and being a burden to the family/closest ones as primary reasons for a wish to hasten death among PALS. Although the majority expressed a willingness to terminate an LSM at a request of the patient, most opposed the legalization of euthanasia. Younger and less religious individuals were more likely to favor accepting euthanasia. CONCLUSION: Neurologists vary significantly in their approaches to terminal care. Complex relationships exist among personal indices, shared beliefs, and current practices.
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BACKGROUND: ALS patients with hexanucleotide expansion in C9orf72 are characterized by a specific clinical phenotype, including more aggressive disease course and cognitive decline. Computerized multiparametric MRI with gray matter volumetry and diffusion tensor imaging (DTI) to analyze white matter structural connectivity is a potential in vivo biomarker. OBJECTIVE: The objective of this study was to develop a multiparametric MRI signature in a large cohort of ALS patients with C9orf72 mutations. The aim was to investigate how morphological features of C9orf72-associated ALS differ in structural MRI and DTI compared to healthy controls and ALS patients without C9orf72 mutations. METHODS: Atlas-based volumetry (ABV) and whole brain-based DTI-based analyses were performed in a cohort of n = 51 ALS patients with C9orf72 mutations and compared with both n = 51 matched healthy controls and n = 51 C9orf72 negative ALS patients, respectively. Subsequently, Spearman correlation analysis of C9orf72 ALS patients' data with clinical parameters (age of onset, sex, ALS-FRS-R, progression rate, survival) as well as ECAS and p-NfH in CSF was performed. RESULTS: The whole brain voxel-by-voxel comparison of fractional anisotropy (FA) maps between C9orf72 ALS patients and controls showed significant bilateral alterations in axonal structures of the white matter at group level, primarily along the corticospinal tracts and in fibers projecting to the frontal lobes. For the frontal lobes, these alterations were also significant between C9orf72 positive and C9orf72 negative ALS patients. In ABV, patients with C9orf72 mutations showed lower volumes of the frontal, temporal, and parietal lobe, with the lowest values in the gray matter of the superior frontal and the precentral gyrus, but also in hippocampi and amygdala. Compared to C9orf72 negative ALS, the differences were shown to be significant for cerebral gray matter (p = 0.04), especially in the frontal (p = 0.01) and parietal lobe (p = 0.01), and in the thalamus (p = 0.004). A correlation analysis between ECAS and averaged regional FA values revealed significant correlations between cognitive performance in ECAS and frontal association fibers. Lower FA values in the frontal lobes were associated with worse performance in all cognitive domains measured (language, verbal fluency, executive functions, memory and spatial perception). In addition, there were significant negative correlations between age of onset and atlas-based volumetry results for gray matter. CONCLUSIONS: This study demonstrates a distinct pattern of DTI alterations of the white matter and ubiquitous volume reductions of the gray matter early in the disease course of C9orf72-associated ALS. Alterations were closely linked to a more aggressive cognitive phenotype. These results are in line with an expected pTDP43 propagation pattern of cortical affection and thus strengthen the hypothesis that an underlying developmental disorder is present in ALS with C9orf72 expansions. Thus, multiparametric MRI could contribute to the assessment of the disease as an in vivo biomarker even in the early phase of the disease.
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Esclerosis Amiotrófica Lateral , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Imagen de Difusión Tensora , Proteína C9orf72/genética , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/genética , NeuroimagenRESUMEN
OBJECTIVE: Cognitive and behavioral impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a 5-domain screening tool customized for quick cognitive screening in patients with ALS. Although the ECAS is available in Swedish at the Karolinska University Hospital (SK-ECAS), it has not yet been validated in Sweden stressing the need to assess validity and reliability of the SK-ECAS Version A. METHODS: The study included 176 patients with ALS or other motor neuron disease diagnosed between September 2017 and October 2021 at the Karolinska ALS Clinical Research Center in Stockholm, Sweden, and 35 age-matched healthy control subjects. SK-ECAS was validated against the Montreal Cognitive Assessment (MoCA) and optimal cutoffs, receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated. RESULTS: We identified an optimal cutoff of 108 for the SK-ECAS total score and 82 for the SK-ECAS ALS-specific score to detect cognitive impairment. The SK-ECAS showed good performance in indicating abnormal cognition with an AUC of 0.73 for SK-ECAS ALS-specific score and 0.77 for SK-ECAS total score. There was good internal consistency with a Cronbach's alpha of 0.79. CONCLUSIONS: This study demonstrates good validity and reliability indices for SK-ECAS Version A for the detection of cognitive impairment in newly diagnosed ALS patients.
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Background: For recurrent high-grade glioma, especially glioblastoma, no standard of care treatment exists. Due to the prolongation of progression-free survival and a cortiocosteroid-sparing effect, bevacizumab is often used in this condition. Despite initial clinical responses, there is growing evidence that bevacizumab may potentiate microstructural alterations which may cause cognitive decline, mostly affecting learning and memory. Methods: To investigate bevacizumab-associated microstructural damage of defined regions of interest (ROIs) in the white matter, diffusion tensor imaging (DTI) was performed in 10 patients with a case history or third-party report for neurological dysfunction concerning cognitive performance. Serial DTI data before and under bevacizumab were collected and longitudinal changes of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were assessed in mesiotemporal (hippocampal), frontal, and occipital regions. Results: The longitudinal DTI data under bevacizumab compared to DTI prior to bevacizumab demonstrated a significant decrease in FA and increase in AD and RD both in mesiotemporal (hippocampal) regions and in frontal regions, whereas occipital regions showed no significant alterations in DTI metrics. Conclusion: The regionally impaired microstructure in mesiotemporal (hippocampal) regions and in frontal regions is in line with the fact that neurocognitive impairment in learning and memory is mostly related to hippocampal integrity and attentional control in frontal regions. Further studies could investigate the potential of DTI to assess bevacizumab-associated microstructural damages in vulnerable brain regions.
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BACKGROUND: Given the inevitable relentless progressing nature of amyotrophic lateral sclerosis (ALS), it is essential to identify factors influencing patients' wellbeing. The study aimed to prospectively assess factors influencing the quality of life (QoL) and depression in ALS patients compared to healthy controls (HCs) from Poland, Germany and Sweden and their relationship to socio-demographic and clinical factors. METHODS: 314 ALS patients (120 from Poland, 140 from Germany, 54 from Sweden) and 311 age-, sex- and education-level-matched HCs underwent standardized interviews for quality of life, depression, functional status and pain. RESULTS: Patients from all three countries showed similar levels of functional impairment (ALSFRS-R). Overall, ALS patients assessed their quality of life as lower compared to HCs (p < 0.001 for the anamnestic comparative self-assessment (ACSA), p = 0.002 for the Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting (SEIQoL-DW). Also, the German and Swedish patients, but not the Polish, reported higher depression levels than the corresponding HCs (p < 0.001). Analysis of ALS groups revealed that functional impairment was related to a lower quality of life (ACSA) and higher depression levels among German ALS patients. Longer time since diagnosis predicted lower depression and (in male subjects) higher quality of life. CONCLUSIONS: ALS patients assess their quality of life and mood lower than healthy individuals within the studied countries. The relationships between clinical and demographic factors are moderated by country of provenance, which bears implications for the design and interpretation of scientific and clinical studies, which should reflect the complexity and heterogeneity of mechanisms determining QoL.
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Esclerosis Amiotrófica Lateral , Calidad de Vida , Humanos , Masculino , Esclerosis Amiotrófica Lateral/complicaciones , Depresión/etiología , Estado de Salud , AlemaniaRESUMEN
BACKGROUND: The characterisation of presymptomatic disease-burden patterns in asymptomatic mutation carriers has a dual academic and clinical relevance. The understanding of disease propagation mechanisms is of considerable conceptual interests, and defining the optimal time of pharmacological intervention is essential for improved clinical trial outcomes. METHODS: In a prospective, multimodal neuroimaging study, 22 asymptomatic C9orf72 GGGGCC hexanucleotide repeat carriers, 13 asymptomatic subjects with SOD1, and 54 "gene-negative" ALS kindreds were enrolled. Cortical and subcortical grey matter alterations were systematically appraised using volumetric, morphometric, vertex, and cortical thickness analyses. Using a Bayesian approach, the thalamus and amygdala were further parcellated into specific nuclei and the hippocampus was segmented into anatomically defined subfields. RESULTS: Asymptomatic GGGGCC hexanucleotide repeat carriers in C9orf72 exhibited early subcortical changes with the preferential involvement of the pulvinar and mediodorsal regions of the thalamus, as well as the lateral aspect of the hippocampus. Volumetric approaches, morphometric methods, and vertex analyses were anatomically consistent in capturing focal subcortical changes in asymptomatic C9orf72 hexanucleotide repeat expansion carriers. SOD1 mutation carriers did not exhibit significant subcortical grey matter alterations. In our study, none of the two asymptomatic cohorts exhibited cortical grey matter alterations on either cortical thickness or morphometric analyses. DISCUSSION: The presymptomatic radiological signature of C9orf72 is associated with selective thalamic and focal hippocampal degeneration which may be readily detectable before cortical grey matter changes ensue. Our findings confirm selective subcortical grey matter involvement early in the course of C9orf72-associated neurodegeneration.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/genética , Teorema de Bayes , Proteína C9orf72/genética , Demencia Frontotemporal/genética , Sustancia Gris/diagnóstico por imagen , Imagen por Resonancia Magnética , Mutación , Neuroimagen , Estudios Prospectivos , Superóxido Dismutasa-1/genéticaRESUMEN
An expansion of the GGGGCC hexanucleotide in the non-coding region of C9orf72 represents the most common cause of familial amyotrophic lateral sclerosis. The objective was to describe and analyse the clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations in a large population. Between November 2011 and December 2020, clinical and genetic characteristics of n = 248 patients with amyotrophic lateral sclerosis carrying C9orf72 mutations were collected from the clinical and scientific network of German motoneuron disease centres. Clinical parameters included age of onset, diagnostic delay, family history, neuropsychological examination, progression rate, phosphorylated neurofilament heavy chain levels in CSF and survival. The number of repeats was correlated with the clinical phenotype. The clinical phenotype was compared to n = 84 patients with SOD1 mutations and n = 2178 sporadic patients without any known disease-related mutations. Patients with C9orf72 featured an almost balanced sex ratio with 48.4% (n = 120) women and 51.6% (n = 128) men. The rate of 33.9% patients (n = 63) with bulbar onset was significantly higher compared to sporadic (23.4%, P = 0.002) and SOD1 patients (3.1%, P < 0.001). Of note, 56.3% (n = 138) of C9orf72, but only 16.1% of SOD1 patients reported a negative family history (P < 0.001). The GGGGCC hexanucleotide repeat length did not influence the clinical phenotypes. Age of onset (58.0, interquartile range 52.0-63.8) was later compared to SOD1 (50.0, interquartile range 41.0-58.0; P < 0.001), but earlier compared to sporadic patients (61.0, interquartile range 52.0-69.0; P = 0.01). Median survival was shorter (38.0 months) compared to SOD1 (198.0 months, hazard ratio 1.97, 95% confidence interval 1.34-2.88; P < 0.001) and sporadic patients (76.0 months, hazard ratio 2.34, 95% confidence interval 1.64-3.34; P < 0.001). Phosphorylated neurofilament heavy chain levels in CSF (2880, interquartile range 1632-4638â pg/ml) were higher compared to sporadic patients (1382, interquartile range 458-2839â pg/ml; P < 0.001). In neuropsychological screening, C9orf72 patients displayed abnormal results in memory, verbal fluency and executive functions, showing generally worse performances compared to SOD1 and sporadic patients and a higher share with suspected frontotemporal dementia. In summary, clinical features of patients with C9orf72 mutations differ significantly from SOD1 and sporadic patients. Specifically, they feature a more frequent bulbar onset, a higher share of female patients and shorter survival. Interestingly, we found a high proportion of patients with negative family history and no evidence of a relationship between repeat lengths and disease severity.
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PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive motor impairment leading to early death. Religiousness is one of the factors potentially alleviating the psychological burden of patients. However, its role might vary according to cultural context. Our study aimed to analyze religiosity, and its clinical, psychological and socio-demographic correlates in ALS patients and controls, comparing two European countries with different cultural backgrounds. METHODS: 268 Polish and German ALS patients, including 18 with locked-in syndrome (LIS) and 198 healthy controls (HC) were interviewed about religiousness, quality of life (Qol), depression, functional status and pain. A follow-up was conducted on 71 patients. RESULTS: Polish subjects had a significantly higher level of public, private and general religiosity than the German sample. Importantly, we found no difference in total and public religiousness between ALS patients and HC within either population. Only the private religiousness was significantly higher in German patients compared to controls. In the same sample, private religiousness correlated with functional impairment due to disease progression. In ALS groups and LIS patients, religiousness did not correlate with any disease-associated factors: disease duration, pain, Qol or depression. Follow-up comparisons in the ALS group revealed worsening functional status, increased depression and no significant change in religiosity. CONCLUSIONS: Religiosity was linked to the cultural background rather than ALS. Generally, it did not correlate with clinical, psychological and socio-demographic parameters and was stable throughout disease progression. The only exception was the relationship between the functional decline and private religiosity among German patients.
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Esclerosis Amiotrófica Lateral , Calidad de Vida , Humanos , Calidad de Vida/psicología , Esclerosis Amiotrófica Lateral/psicología , Religión , Dolor , Progresión de la EnfermedadRESUMEN
Objective: Age and years of education are strong predictors of cognitive performance in several versions of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and cutoffs for the Swedish and Polish versions are not established yet. Here we evaluated the performance of healthy subjects on the national versions of the Swedish and Polish ECAS and compared cognitive performance on three European translations of the ECAS. Methods: The ECAS performances of healthy subjects from Sweden (n = 111), Poland (n = 124) and Germany (n = 86) were compared. Based on the test results on the national versions of ECAS, age- and education-adjusted cutoffs were compared for the German, Swedish and Polish versions, respectively. Results: Age and years of education correlated with performance in the ECAS. Swedish subjects under the age of 60 years and Swedish subjects with low education level scored significantly higher in memory than the respective German and Polish subgroups. German and Polish subjects over 60 years of age performed significantly better in language than the respective Swedish subgroup. The Polish cohort in total had lower executive scores compared to the Swedish cohort, and lower than the German subjects in the higher education subgroup. Conclusions: The results highlight the importance of establishing age- and education-adjusted ECAS cutoffs not only in general, but also for seemingly similar populations of different origins. The results should be taken into account when comparing cognition data across patient populations including in drug trials where an ECAS test result is being used as an inclusion criterium or outcome measure.
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Esclerosis Amiotrófica Lateral , Trastornos del Conocimiento , Humanos , Persona de Mediana Edad , Anciano , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Polonia/epidemiología , Suecia/epidemiología , Esclerosis Amiotrófica Lateral/psicología , Pruebas Neuropsicológicas , Escolaridad , Cognición , LenguajeRESUMEN
OBJECTIVES: Up to 50% of patients with amyotrophic lateral sclerosis (ALS) present with cognitive problems and behavioral dysfunctions including recognition of human faces presenting different emotions. We investigated whether impaired processing of emotional faces is associated with abnormal scan paths during visual exploration. METHODS: Cognitively unimpaired patients with ALS (n = 45) and matched healthy controls (n = 37) underwent neuropsychological assessment and video-based eye tracking. Eye movements were recorded while participants visually explored faces expressing different emotions (neutral, disgusted, happy, fearful, and sad) and houses mimicking faces. RESULTS: Compared with controls, patients with ALS fixated significantly longer to regions which are not relevant for emotional information when faces expressed fear (p = 0.007) and disgust (p = 0.006), whereas the eyes received less attention in faces expressing disgust (p = 0.041). Fixation duration in any area of interest was not significantly associated with the cognitive state or clinical symptoms of disease severity. DISCUSSION: In cognitively unimpaired patients with ALS, altered gaze patterns while visually exploring faces expressing different emotions might derive from impaired top-down attentional control with possible involvement of subliminal frontotemporal areas. This may account for indistinctness in emotion recognition reported in previous studies because nonsalient features retrieve more attention compared with salient areas. Current findings may indicate distinct emotion processing dysfunction of ALS pathology, which may be different from, for example, executive dysfunction.
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Esclerosis Amiotrófica Lateral , Humanos , Emociones , Reconocimiento en Psicología , Ojo , Movimientos Oculares , Expresión FacialRESUMEN
Spinal muscular atrophy (SMA) is a disabling disease that affects not only the patient's health-related quality of life (HRQoL), but also causes a high caregiver burden (CGB). The aim of this study was to evaluate HRQoL, CGB, and their predictors in SMA. In two prospective, cross-sectional, and multi-center studies, SMA patients (n = 39) and SMA patient/caregiver couples (n = 49) filled in the EuroQoL Five Dimension Five Level Scale (EQ-5D-5L) and the Short Form Health Survey 36 (SF-36). Caregivers (CGs) additionally answered the Zarit Burden Interview (ZBI) and the Hospital Anxiety and Depression Scale (HADS). Patients were clustered into two groups with either low or high HRQoL (EQ-5D-5L index value <0.259 or >0.679). The latter group was mostly composed of ambulatory type III patients with higher motor/functional scores. More severely affected patients reported low physical functioning but good mental health and vitality. The CGB (mean ZBI = 22/88) correlated negatively with patients' motor/functional scores and age. Higher CGB was associated with a lower HRQoL, higher depression and anxiety, and more health impairments of the CGs. We conclude that patient and CG well-being levels interact closely, which highlights the need to consider the health of both parties while evaluating novel treatments.
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Objective: To analyze the quality of life (QoL) and frequency of depression in primary caregivers of patients with amyotrophic lateral sclerosis (ALS) in two neighboring European countries. Methods: a cross-sectional study performed in 164 dyads of ALS patients and caregivers followed at clinical ALS centers in Poland and Germany between 2015 and 2018. The quality of life (Anamnestic Comparative Self-Assessment - ACSA, Quality of Life in Life-Threatening Illness - Family Carer Version - QOLLTI-F) and depression (ALS-Depression-Inventory 12-Items - ADI-12) of the caregivers was assessed and correlated with caregivers- and patient-related factors. Patient's clinical status was assessed by ALS Functional Rating Scale - revised and the Behavioral Score of the Edinburgh Cognitive and Behavioral ALS Screen. Results: the caregivers reported a positive QoL associated with functional and behavioral status of the patient, disease duration and caregivers's depression The most impaired domains of the QoL differed depending on the country of provenance, cultural background and/or social support of the caregivers. Depression was present in 1/3 of the caregivers and was significantly more frequent in the Polish group. It positively correlated with female gender, disease duration, sleep disturbances and functional decline. Both QoL and mood were significantly lower in the caregivers more burdened with the functional care of the patients. Conclusions: the wellbeing of caregivers of ALS patients is affected by patient-related and culture-specific conditions. Understanding the needs and background of psychological adaptation of the caregivers from various countries may translate into better QoL and local patient care.
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Esclerosis Amiotrófica Lateral , Calidad de Vida , Humanos , Femenino , Calidad de Vida/psicología , Esclerosis Amiotrófica Lateral/psicología , Cuidadores/psicología , Depresión/etiología , Depresión/psicología , Estudios TransversalesRESUMEN
Objective: The goal of this meta-analysis is to improve insight into the development of cognition over the course of ALS and to assess predictors of cognitive performance.Method: A literature search was conducted in Pubmed and Web of Science on 29 July 2019 and 16 March 2021. Data were screened in Endnote® Version X9 (London, UK). Meta-analyses and meta-regressions were calculated for cross-sectional data using Rstudio®. Studies were assigned to temporal and physical categories and Hedges' g was calculated for the respective categories to provide an estimate of a cognitive course based on cross-sectional data. Due to low numbers and heterogeneity in reporting, longitudinal studies were analyzed descriptively.Results: A total of N = 45 cross-sectional and N = 13 longitudinal studies were included. Impairments in all cognitive domains, except verbal IQ, were found in ALS patients (PALS). PALS showed stable cognitive performances in cross-sectional and in most longitudinal studies. PALS with symptoms for 18-24 months and PALS who had an ALSFRS-R score of 40-36 were the most frequently reported subgroup regarding neuropsychology. Age was related to visuospatial functioning, and depressiveness to attention. In longitudinal studies, impact of site of onset and cognitive status at baseline on cognitive course was found.Conclusion: Despite vast evidence for cognitive impairment at disease onset in different domains, evidence for evolution of these deficits is rather limited, suggesting that PALS present with cognitive impairment early in the course possibly in a sense of disease trait.
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Esclerosis Amiotrófica Lateral , Trastornos del Conocimiento , Disfunción Cognitiva , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Estudios Transversales , Cognición , Trastornos del Conocimiento/diagnósticoRESUMEN
INTRODUCTION: Inevitable disease progression in amyotrophic lateral sclerosis (ALS) forces patients and their caregivers (CGs) to reflect on end-of-life treatment. The CGs are often heavily burdened with their role of surrogate decision-makers. The aim of the study was to analyze attitudes of CGs and presumable attitudes of ALS patients from the CGs' perspective towards palliative care in advanced disease stages. MATERIAL AND METHODS: One hundred and sixty four CGs from Germany and Poland were interviewed regarding their own preferences and patients' ideational attitudes towards life-prolonging (invasive and non-invasive ventilation, tube feeding) and life-shortening methods (termination of measures, active measures if permitted by law). The data were correlated with patient- and CG-related factors: demographic and clinical data, care commitment, depression and quality of life (QoL). RESULTS: The CGs were mostly female spouses of ALS patients, with secondary/higher education. Nearly 70% (81% in Poland, 57% in Germany; p = 0.0001) reported positive attitudes towards life-prolonging methods, which positively correlated with religiousness and negatively with patients' age. Approximately 40% of CGs (25% and 51% respectively; p = 0.001) reported positive attitudes towards life-shortening methods. It positively correlated with time since diagnosis and negatively with the CG's QoL, religiosity and religious/spiritual faith as factors that significantly influenced end-of-life decisions. There was a strongly positive correlation between CGs' positive attitudes towards life-shortening methods and presumed positive patients' attitudes assessed by their CGs ( p < 0.000001). CONCLUSIONS: Although attitudes towards treatment differed between countries, the CGs of ALS patients were generally positive towards life-prolonging treatment. A greater acceptance of life-shortening methods in the case of longer disease duration and poorer QoL may indicate worse coping with disease progression and weaker adaptation mechanisms in CGs compared to those previously reported in ALS patients. A close resemblance of the CGs' answers to probable patients' attitudes reported by the CGs indicates that many GCs might actually express their own culturally shaped attitudes towards end-of-life methods. In light of earlier-reported discrepancies between presumed opinions of the CGs and of patients themselves, a greater focus should be placed on thorough discussions on future treatment options with ALS patients in the presence of their CGs, to stay in line with the patient's authentic will.
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Esclerosis Amiotrófica Lateral , Humanos , Femenino , Masculino , Esclerosis Amiotrófica Lateral/terapia , Calidad de Vida , Cuidadores , Muerte , Progresión de la EnfermedadRESUMEN
OBJECTIVE: To investigate intercultural neurologists' perception of well-being in patients with amyotrophic lateral sclerosis (ALS) using gastrostomy (PEG), non-invasive, and/or invasive ventilation (NIV/IV) and to analyse the determinants and impact on the management of the above medical interventions (MIs). METHODS: The study was based on anonymous questionnaires addressing the clinical approach and personal attitude towards the use of PEG, NIV and IV in ALS patients completed by 465 neurologists: 228 from Germany and 237 from Poland. RESULTS: The German and Polish neurologists estimated the quality of life in ALS patients using PEG and NIV as neutral, whilst low in individuals using IV. A regression model revealed an independent influence of palliative care training (PCT) and age on that attitude in the German group. Higher values of estimated patients' depressiveness on PEG, NIV and IV were found amongst the Polish neurologists. Marital status, experience in ALS and being a parent independently influenced the perception of patients' depressiveness in the German, whilst marital status, age and PCT were factors in the Polish group. Amongst German neurologists, a higher perception of patients' depressiveness in individuals using PEG, NIV and IV was linked to the later timing of the MIs discussion. In the Polish group, it was a lower estimation of QoL in patients using PEG. CONCLUSION: Neurologists' perception of ALS patients' well-being on MIs reflects their demographic status, professional experience and potentially their cultural background. This perception plays an important role in the timing of MIs discussion, possibly influencing the decision-making process.
Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/terapia , Calidad de Vida , Encuestas y Cuestionarios , Neurólogos , GastrostomíaRESUMEN
Introduction: Diffusion tensor imaging (DTI) can be used to map disease progression in amyotrophic lateral sclerosis (ALS) and therefore is a promising candidate for a biomarker in ALS. To this end, longitudinal study protocols need to be optimized and validated regarding group sizes and time intervals between visits. The objective of this study was to assess the influences of sample size, the schedule of follow-up measurements, and measurement uncertainties on the statistical power to optimize longitudinal DTI study protocols in ALS. Patients and methods: To estimate the measurement uncertainty of a tract-of-interest-based DTI approach, longitudinal test-retest measurements were applied first to a normal data set. Then, DTI data sets of 80 patients with ALS and 50 healthy participants were analyzed in the simulation of longitudinal trajectories, that is, longitudinal fractional anisotropy (FA) values for follow-up sessions were simulated for synthetic patient and control groups with different rates of FA decrease in the corticospinal tract. Monte Carlo simulations of synthetic longitudinal study groups were used to estimate the statistical power and thus the potentially needed sample sizes for a various number of scans at one visit, different time intervals between baseline and follow-up measurements, and measurement uncertainties. Results: From the simulation for different longitudinal FA decrease rates, it was found that two scans per session increased the statistical power in the investigated settings unless sample sizes were sufficiently large and time intervals were appropriately long. The positive effect of a second scan per session on the statistical power was particularly pronounced for FA values with high measurement uncertainty, for which the third scan per session increased the statistical power even further. Conclusion: With more than one scan per session, the statistical power of longitudinal DTI studies can be increased in patients with ALS. Consequently, sufficient statistical power can be achieved even with limited sample sizes. An improved longitudinal DTI study protocol contributes to the detection of small changes in diffusion metrics and thereby supports DTI as an applicable and reliable non-invasive biomarker in ALS.