Search

Objective: Pain currently plays a subordinate role in the clinical care of patients with ALS. We aim to examine epidemiological and clinical characteristics of pain as well as its impact throughout the disease course., Methods: During a longitudinal follow-up at three time points, 151 ALS patients from three German outpatient clinics completed the Brief Pain Inventory, ALS-Functional Rating Scale-Extension and ALS Depression Inventory. Analysis of variance and covariance with repeated measures were performed., Results: Pain was prevalent in 56% of the 151 patients at baseline and in 70% of the remaining 40 patients at the third survey. Of the 28 patients with pain who participated in all three surveys, about two thirds suffered from an average pain intensity corresponding to at least moderate pain on the numerical rating scale (NRS ≥ 4). Patients reported different pain qualities and localized the pain most frequently in the extremities, back and neck. Pain moderately impaired the functions of daily living. Pain intensity, pain quality and pain-related impairment did not significantly change over time. One third of the patients suffered from clinically relevant depressive symptoms. However, there was no conclusive evidence of a link between pain intensity and depressive symptoms., Conclusion: Pain is frequent and constitutes an additional strain on ALS patients who have to endure a rapidly progressive and severely debilitating disease. This study contributes to better understanding of the characteristics of pain and its impact on ALS patients throughout the disease course and may thus help to more effectively address this symptom. more...

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive, neurodegenerative disorder affecting upper and lower motor neurons. Approximately 10% of patients suffer from familial ALS (FALS) with mutations in different ubiquitously expressed genes including SOD1, C9ORF72, TARDBP, and FUS. There is compelling evidence for mitochondrial involvement in the pathogenic mechanisms of FALS and sporadic ALS (SALS), which is believed to be relevant for disease. Owing to the ubiquitous expression of relevant disease-associated genes, mitochondrial dysfunction is also detectable in peripheral patient tissue. We here report results of a detailed investigation of the functional impairment of mitochondrial oxidative phosphorylation (OXPHOS) in cultured skin fibroblasts from 23 SALS and 17 FALS patients, harboring pathogenic mutations in SOD1, C9ORF72, TARDBP and FUS. A considerable functional and structural mitochondrial impairment was detectable in fibroblasts from patients with SALS. Similarly, fibroblasts from patients with FALS, harboring pathogenic mutations in TARDBP, FUS and SOD1, showed mitochondrial defects, while fibroblasts from C9ORF72 associated FALS showed a very mild impairment detectable in mitochondrial ATP production rates only. While we could not detect alterations in the mtDNA copy number in the SALS or FALS fibroblast cultures, the impairment of OXPHOS in SALS fibroblasts and SOD1 or TARDBP FALS could be rescued by in vitro treatments with CoQ 10 (5 μM for 3 weeks) or Trolox (300 μM for 5 days). This underlines the role of elevated oxidative stress as a potential cause for the observed functional effects on mitochondria, which might be relevant disease modifying factors., (Copyright © 2021 Elsevier Inc. All rights reserved.) more...

Context: There is no evidence-based treatment for fatigue in amyotrophic lateral sclerosis (ALS), and identification of treatable causes determines management strategies. Although dyspnea is a key symptom of ALS and effectively treatable, it has not been sufficiently investigated whether dyspnea may be a fatigue-promoting factor., Objectives: To determine the level of fatigue in dyspneic ALS patients and whether fatigue is promoted by dyspnea. We further evaluated the correlation of fatigue with respiratory function tests., Methods: About 101 dyspneic patients and 20 matched controls completed the ALS Functional Rating Scale-Extension and the Fatigue Severity Scale. Dyspneic patients additionally completed the Dyspnea-ALS Scale and the ALS Assessment Questionnaire and underwent respiratory function tests (forced vital capacity, sniff nasal inspiratory pressure, mean inspiratory and expiratory pressure with respective relaxation rates, and blood gases). Multiple regression and correlation analyses were conducted., Results: Dyspneic patients had significantly higher fatigue scores than nondyspneic patients, and their fatigue significantly affected quality of life. Dyspnea alone explained up to 24% of the variance in fatigue. No associations were observed between fatigue and respiratory function tests. Patients with noninvasive ventilation reported significantly more dyspnea and fatigue., Conclusion: Fatigue is a frequent and bothersome symptom in dyspneic ALS patients. Dyspnea-related distress is, in contrast to objective indicators of respiratory impairment, a determining factor of experienced fatigue. There is an urgent need for further symptom relief beyond noninvasive ventilation. Adequate treatment of dyspnea has the potential for synergies in symptom management arising from the association between fatigue and dyspnea., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.) more...

The upper cervical spinal cord is measured in a large longitudinal amyotrophic lateral sclerosis (ALS) cohort to evaluate its role as a biomarker. Specifically, the cervical spinal cord´s cross-sectional area (CSA) in plane of the segments C1-C3 was measured semi-automatically with T1-weighted 3T MRI sequences in 158 ALS patients and 86 controls. Six-month longitudinal follow-up MRI scans were analyzed in 103 patients. Compared to controls, in ALS there was a significant mean spinal cord atrophy (63.8 mm² vs. 60.8 mm², p = 0.001) which showed a trend towards worsening over time (mean spinal cord CSA decrease from 61.4 mm² to 60.6 mm² after 6 months, p = 0.06). Findings were most pronounced in the caudal segments of the upper cervical spinal cord and in limb-onset ALS. Baseline CSA was related to the revised ALS functional rating scale, disease duration, precentral gyrus thickness and total brain gray matter volume. In conclusion, spinal cord atrophy as assessed in brain MRIs in ALS patients mirrors the extent of overall neurodegeneration and parallels disease severity. more...

A few systematic imaging studies employing ultrasound (HRUS) and magnetic resonance imaging (MRI) have suggested tongue measures to aid in diagnosis of amyotrophic lateral sclerosis (ALS). The relationship between structural tongue alterations and the ALS patients' bulbar and overall motor function has not yet been elucidated. We here thus aimed to understand how in-vivo tongue alterations relate to motor function and motor function evolution over time in ALS. Our study included 206 ALS patients and 104 age- and sex-matched controls that underwent HRUS and 3T MRI of the tongue at baseline. Sonographic measures comprised coronal tongue echointensity, area, height, width and height/width ratio, while MRI measures comprised sagittal T1 intensity, tongue area, position and shape. Imaging-derived markers were related to baseline and longitudinal bulbar and overall motor function. Baseline T1 intensity was lower in ALS patients with more severe bulbar involvement at baseline. Smaller baseline coronal (HRUS) and sagittal (MRI) tongue area, smaller coronal height (HRUS) and width (HRUS) as well as more rounded sagittal tongue shape predicated more rapid functional impairment - not only of bulbar, but also of overall motor function - in ALS. Our results suggest that in-vivo sonography und MRI tongue measures could aid as biomarkers to reflect bulbar and motor function impairment., Competing Interests: Declaration of Competing Interests None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.) more...

Background: Dyspnea is frequent in amyotrophic lateral sclerosis (ALS) and one of the most bothersome symptoms. The recently developed Dyspnea-ALS-Scale (DALS-15) is a disease-specific patient-reported outcome to detect and quantify dyspnea., Objectives: To analyze in a case-based approach the diagnostic and clinical implications and the benefit of the DALS-15 for individual patients in daily clinical routine., Methods: Dyspnea was assessed by the 15-item comprising DALS-15 in two patients with ALS. Spirometry was performed and blood gases were analyzed. Results were evaluated in the clinical context of the respective patients., Results: In one patient the presence of dyspnea detected by the DALS-15 indicated noninvasive ventilation (NIV) although forced vital capacity (FVC) and blood gas analysis were well preserved. After NIV implementation, the DALS-15 was helpful to determine the patient's need for medication, the timing of NIV titration and the adaptation of NIV sessions. In another patient, who was anarthric and no longer able to perform spirometry due to severe bulbar impairment, the DALS-15 allowed a standardized assessment of dyspnea-related distress independently of bulbar dysfunction., Conclusion: The DALS-15 provides a deeper insight into the respiratory status of individual patients. It helps to diagnose respiratory impairment in patients in whom NIV should be considered although FVC and blood gas results do not reveal indication for NIV. It is also valuable for the guidance of patients in later stages of respiratory impairment when NIV is already implemented, and in patients with severe bulbar dysfunction. The DALS-15 can improve specific symptom management and coordination of care and therefore has the potential to optimize individual treatment in ALS patients with dyspnea. more...

Context: Dyspnea is a cardinal but often underestimated symptom in amyotrophic lateral sclerosis (ALS). The lack of a satisfying assessment tool leads to diagnostic uncertainty and bears the risk that established life-prolonging and symptom-relieving therapeutic options will not be adequately applied., Objectives: The objective of this study was to develop and validate a German language disease-specific patient-reported outcome measure to assess dyspnea in ALS by combination of a qualitative and quantitative approach using Rasch analysis., Methods: Based on input from clinical experts and patients, a preliminary 35-item questionnaire was developed and completed by 94 patients with ALS having dyspnea. Data were subjected to Rasch analysis and tested for required measurement issues such as appropriate response categories, the absence of differential item functioning, local independence, and unidimensionality., Results: After iterative Rasch analyses, the final 15-item Dyspnea-ALS-Scale (DALS-15) was obtained. The scale satisfies the axioms of the Rasch model with good fit statistics, the absence of local dependency, and differential item functioning as well as acceptable unidimensionality. The DALS-15 is optimally targeted and suitable for group and individual use. It shows excellent test-retest reliability and convergent validity., Conclusion: The DALS-15 satisfies strictest modern measurement criteria and has interval scale properties. It fills an important gap in assessment and could be most helpful to optimize symptom management in patients with ALS., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.) more...

Background: Pain is a common symptom in patients with amyotrophic lateral sclerosis (ALS). Coping plays a central role in adjustment to pain. Objective: This study evaluates the use of different pain coping strategies in patients with ALS and investigates the interplay of maladaptive coping, and the patient's affective state and pain. Methods: One hundred and fifty ALS patients from three German outpatient clinics completed the Brief Pain Inventory (BPI), the ALS-Functional Rating Scale-Extension (ALSFRS-EX), the ALS Depression Inventory (ADI-12), the subscale "emotional functioning" of the ALS Assessment Questionnaire (ALSAQ-40) and the Coping Strategies Questionnaire (CSQ). Based upon the results of correlational analyses, multiple regression analyses were performed to identify predictors of pain severity and to explore factors contributing to maladaptive coping. Results: Pain was prevalent in 56% (n = 84) of the patients. Patients applied different adaptive coping strategies as well as the maladaptive strategy "catastrophizing". Regression analysis indicated that the CSQ-subscale "catastrophizing" significantly predicted pain intensity, explaining 34.0% of the variance (p < 0.001). Pain-related catastrophizing was associated with higher pain-related functional impairments and worse emotional functioning. The ADI-12 sum score as an indicator for depressive symptoms contributed significantly to the maladaptive coping strategy "catastrophizing" (p < 0.001) and explained 40.8% of the variance. Conclusion: Patients with ALS apply different strategies to cope with pain. Catastrophizing is an important determinant of higher pain intensity ratings and is associated with higher pain interferences and decreased emotional well-being. Pain-related catastrophizing is promoted by depressive symptoms. Catastrophizing and depressive symptoms thus represent important targets of individualized pain-management strategies. [ABSTRACT FROM AUTHOR] more...

Background: Although pain is common in amyotrophic lateral sclerosis (ALS) and an effectively treatable symptom, it is widely under-recognized and undertreated. This study investigates epidemiological and clinical characteristics of pain, its impact and pharmacological treatment in ALS patients. In addition, opportunities for further optimization of pain therapy need to be identified. Methods: Patients from three German ALS outpatient clinics were asked to complete the Brief Pain Inventory and the ALS Functional Rating Scale—Extension and to participate in semi-structured telephone interviews. Results: Of the 150 study participants, 84 patients reported pain. Pain occurred across all disease stages, predominantly in the neck, back and lower extremities. It was described with a broad spectrum of pain descriptors and mostly interfered with activity-related functions. Of the 84 pain patients, 53.8% reported an average pain intensity ≥4 on the numerical rating scale (NRS), indicating pain of at least moderate intensity, and 64.3% used pain medication. Irrespective of the medication type, 20.4% of them had no sufficient pain relief. Thirteen out of 30 patients without pain medication reported an average NRS value ≥4. Eleven of them—mainly in the context of high pain interference with daily functions—were supposed to benefit from adequate pain therapy. However, many patients had relevant concerns and misconceptions about pain therapy. Conclusion: Given the frequency, extent and multi-faceted impact of pain, it is necessary to systematically assess pain throughout the disease course. Potentials to optimize pain therapy were seen in the subset of patients with insufficient pain relief despite medication and in those patients without pain medication but high pain interference. However, there is a need to respond to patients' barriers to pain therapy. [ABSTRACT FROM AUTHOR] more...