| 1. |
- Kuraszkiewicz, B., et al.
(författare)
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Potential Preventive Strategies for Amyotrophic Lateral Sclerosis
- 2020
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 14
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Forskningsöversikt (refereegranskat)abstract
- It may seem useless to propose preventive measures for a disease without established pathogenesis and successful therapy, such as amyotrophic lateral sclerosis (ALS). However, we will show that ALS shares essential molecular mechanisms with aging and that established anti-aging strategies, such as healthy diet or individually adjusted exercise, may be successfully applied to ameliorate the condition of ALS patients. These strategies might be applied for prevention if persons at ALS risk could be identified early enough. Recent research advances indicate that this may happen soon.
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| 2. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 3. |
- Häggmark, Anna, et al.
(författare)
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Plasma profiling revelas three proteins associated to amyotrophic lateral sclerosis
- 2014
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 1:8, s. 544-553
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease leading to muscular paralysis and death within 3-5 years from onset. Currently, there are no reliable and sensitive markers able to substantially shorten the diagnosis delay. The objective of the study was to analyze a large number of proteins in plasma from patients with various clinical phenotypes of ALS in search for novel proteins or protein profiles that could serve as potential indicators of disease.METHODS: Affinity proteomics in the form of antibody suspension bead arrays were applied to profile plasma samples from 367 ALS patients and 101 controls. The plasma protein content was directly labeled and protein profiles obtained using 352 antibodies from the Human Protein Atlas targeting 278 proteins. A focused bead array was then built to further profile eight selected protein targets in all available samples.RESULTS: Disease-associated significant differences were observed and replicated for profiles from antibodies targeting the proteins: neurofilament medium polypeptide (NEFM), solute carrier family 25 (SLC25A20), and regulator of G-protein signaling 18 (RGS18).INTERPRETATION: Upon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology.
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| 4. |
- Andersen, Peter M., 1962-, et al.
(författare)
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Caregivers’ divergent perspectives on patients’ well-being and attitudes towards hastened death in Germany, Poland and Sweden
- 2022
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 23:3-4, s. 252-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: During the course of amyotrophic lateral sclerosis (ALS), patients and their families are faced with existential decisions concerning life-prolonging and -shortening measures. Correct anticipation of patient’s well-being and preferences is a prerequisite for patient-centered surrogate decision making.Methods: In Germany (N = 84), Poland (N = 77) and Sweden (N = 73) patient-caregiver dyads were interviewed. Standardized questionnaires on well-being (ADI-12 for depressiveness; ACSA for global quality of life) and wish for hastened death (SAHD) were used in ALS patients. Additionally, caregivers were asked to fill out the same questionnaires by anticipating patients’ perspective (surrogate perspective).Results: Caregivers significantly underestimated patients’ well-being in Germany and Poland. For Swedish caregivers, there were just as many who underestimated and overestimated well-being. The same was true for wish for hastened death in all three countries. For Swedish and Polish patients, caregivers’ estimation of well-being was not even associated with patients’ responses and the same was true for estimation of wish for hastened death in all three countries. Older caregivers and those with the most frequent encounter with the patient were the closest in their rating of well-being and wish for hastened death to the patients’ actual state, while caregivers with chronic disease him/herself were more likely to underestimate patient’s well-being.Discussion: Despite distinct cultural differences, there was a clear discrepancy between patients’ and caregivers’ perspective on patients’ well-being and preferences towards life in all three countries. This possible bias in caregivers’ judgment needs to be taken into account in surrogate decision making.
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| 5. |
- Andersen, Peter M., 1962-, et al.
(författare)
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Therapeutic decisions in ALS patients : cross-cultural differences and clinical implications
- 2018
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Ingår i: Journal of Neurology. - : Springer Berlin/Heidelberg. - 0340-5354 .- 1432-1459. ; 265:7, s. 1600-1606
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Quantitative analysis of decision-making on therapeutic options in different sociocultural context in amyotrophic lateral sclerosis (ALS).Methods: ALS patients (n = 244) were consecutively recruited in Germany (n = 83), Poland (n = 83), and Sweden (n = 78) in a prospective cross-cultural study (www.NEEDSinALS.com). They were interviewed on preferences for therapeutic techniques including invasive (IV) and non-invasive ventilation (NIV), as well as percutaneous endoscopic gastrostomy (PEG) and on hypothetical termination of these using quantitative questions. Using standardized questionnaires, religiousness, personal values, quality of life, and depressiveness were assessed.Results: NIV was most frequently used in Germany and PEG in Sweden. Swedish patients were most liberal on initiation and termination of PEG, NIV and IV. Polish patients were mostly undecided and were least likely to consider discontinuing supportive management. Current use was partly associated with age, gender and state of physical function; also, financial support explained some variance. Future preferences on therapeutic options from the patient’s perspective were also closely associated with cultural factors. The more oriented towards traditional and conservative values, the less likely patients were to decide for invasive therapeutic devices (IV, PEG), the least likely to have ideations to discontinue any device and the more likely to have an undecided attitude.Conclusions: Current use of therapeutic options is determined by medical condition in analogy to clinical guidelines. For future considerations, other factors such as cultural background are crucial, yielding hurdles to be regarded in the implementation of advanced directives in a multicultural environment.
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| 6. |
- Berdynski, Mariusz, et al.
(författare)
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SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons. The clinical phenotype of ALS shows inter- and intrafamilial heterogeneity. The aim of the study was to analyze the relations between individual SOD1 mutations and the clinical presentation using in silico methods to assess the SOD1 mutations severity. We identified SOD1 causative variants in a group of 915 prospectively tested consecutive Polish ALS patients from a neuromuscular clinical center, performed molecular modeling of mutated SOD1 proteins and in silico analysis of mutation impact on clinical phenotype and survival analysis of associations between mutations and hazard of clinical end-points. Fifteen SOD1 mutations were identified in 21.1% familial and 2.3% sporadic ALS cases. Their effects on SOD1 protein structure and functioning inferred from molecular modeling and in silico analyses correlate well with the clinical data. Molecular modeling results support the hypothesis that folding intermediates rather than mature SOD1 protein give rise to the source of cytotoxic conformations in ALS. Significant associations between type of mutation and clinical end-points were found.
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| 7. |
- Ciećwierska, Katarzyna, et al.
(författare)
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Quality of life and depression in patients with amyotrophic lateral sclerosis – does the country of origin matter?
- 2023
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Ingår i: BMC Palliative Care. - : BioMed Central (BMC). - 1472-684X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 8. |
- De Carvalho, Mamede, et al.
(författare)
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International Survey of ALS Experts about Critical Questions for Assessing Patients with ALS
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 18:7-8, s. 505-510
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To define an applicable dataset for ALS patient registries we weighted specific clinical items as scored by worldwide ALS experts.Methods: Sixty participants were invited based on relevant clinical work, publications and personal acquaintance. They rated 160 clinical items consensually agreed by the members of our project, incorporating specialists from five European Centres. Scoring scheme was defined as: 1 - essential; 2 - important; 3 - not very important. A mixed effect model was applied to rank items and to find possible correlations with geographical region (Europe vs. outside Europe).Results: We received 40 responses, 20 from Europe and 20 from outside; 42/160 data were scored as essential by >50% of the respondents, including: date of birth, gender, date of disease onset, date of diagnosis, ethnicity, region of onset, predominant upper neuron (UMN) or lower motor neuron (LMN) impairment, proximal versus distal weakness, respiratory symptoms, dysarthria, weight loss, signs of LMN/UMN involvement, emotional incontinence, cognitive changes, respiratory signs, neck weakness, body mass index, ALSFRS-R at entry, ALSFRS-R subscores at entry, timing and pattern of spreading and staging, electromyography, spirometry, MRI, CK level, riluzole intake, genetic background, history of physical exercise and previous and current main occupation. Four components were scored as non-relevant, including place of birth, blood pressure and pain at onset. There was no significant difference between regions (European vs. non-European countries).Conclusions: Our study identified a consensual set of clinical data with 42 specific items that can be used as a minimal data set for patient registers and for clinical trials.
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| 9. |
- Decarvalho, Mamede, et al.
(författare)
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Peripheral neuropathy in ALS : Phenotype association
- 2021
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 92:10, s. 1133-1134
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a rare and progressive neurodegenerative disease mainly affecting upper and lower motor neurons but also causing multisystem involvement, in particular, associated with cognitive changes. Minor sensory fibre dysfunction has been described in the past1 and confirmed in recent studies.2 In a multicentre study investigating a population of 88 patients with ALS, the ESTEEM group (a European Telematic Project for quality assurance within Clinical Neurophysiology) reported sensory polyneuropathy (PNP) in 12.5% of the patients, not influenced by age, disease duration and onset region.In this study, we aimed to readdress prevalence of and risk factors for PNP in a larger population of patients with ALS. A large number of variables, including gene mutations, were assessed.
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| 10. |
- Diekmann, Kristin, et al.
(författare)
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Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group
- 2020
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Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 267:7, s. 2130-2141
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with loss of muscle function. The pathogenesis is still unclear and the heterogeneity of ALS phenotypes is huge. We investigated a large population of ALS patients and controls concerning comorbidities and medications to detect specific risk or protective factors regarding onset and progression of ALS.Methods: We investigated a cohort of 200 ALS patients pro- and retrospectively compared to a control group. For comparison of frequencies of comorbidities and medication intake, uni- and multivariate binary logistic regressions were performed. To analyze the influence of comorbidities and medication on the progression of ALS, we used linear regression analysis.Results: ALS patients showed a relevantly higher prevalence of strokes and depression compared to controls. Moreover, ALS patients reported relevantly more often regular physical activity and their BMI was lower. The coexistence of coronary heart disease was associated with a relevantly faster disease progression. Intake of contraceptives was relevantly higher in controls compared with ALS patients.Conclusions: Our results suggest stroke, lower BMI, and regular physical activity as risk factors for ALS. Strokes could be a possible trigger of the pathogenetic pathway of ALS and the lower BMI with consecutively lower rate of hyperlipidemia supports the hypothesis of premorbid hypermetabolism in ALS patients. Coexistence of coronary heart disease possibly has a negative influence on respiratory involvement. Contraceptives could be beneficial due to a protective effect of estrogen. Information on influencing factors can help to elucidate the pathogenesis of ALS or provide approaches for possible therapeutic options.
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| 11. |
- Finsel, Julia, et al.
(författare)
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Determining impairment in the Swedish, Polish and German ECAS : the importance of adjusting for age and education
- 2023
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 24:5-6, s. 475-484
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 12. |
- Gromicho, Marta, et al.
(författare)
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Motor neuron disease beginning with frontotemporal dementia : clinical features and progression
- 2021
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 22:7-8, s. 508-516
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study disease characteristics, progression and outcome in a group of motor neuron disease (MND) patients beginning with frontotemporal dementia (FTD) by comparing them with patients with the typical motor-onset.Methods: 849 patients recruited from tertiary centers were studied according to FTD-onset and motor-onset. We studied clinical data, functional decline and survival.Results: Twenty six patients (3.1%) had FTD-onset of whom seven (26.9%) had coincident motor dysfunction. In those with isolated FTD-onset, motor symptoms developed after a median of 12 months (IQR: 4-18). FTD-onset patients were older at presentation; the bulbar-region was more frequently first affected than in the motor-onset group; there was a predominant upper motor neuron (UMN) phenotype; fasciculations were less common than in motor onset disease but facial and upper limb apraxia was more frequent; as well as ALS and FTD familial history. No differences were observed for gender, frequency of C9orf72 hexanucleotide repeat expansion, family history of Alzheimer's and Parkinson's diseases, median delay from motor symptoms to diagnosis, median ALSFRS-R rate of change, handedness, emotional lability, depression, weight loss, resting tremor, bradykinesia, sensory changes or neuropathy. Clinical and demographic features were similar between FTD-onset patients developing bulbar MND and bulbar-onset ALS patients. Once bulbar symptoms manifested functional progression and survival were similar to those of bulbar-onset ALS patients.Conclusions: MND patients with FTD-onset have a distinctive phenotype characterized by predominant UMN presentation and rapid progression to bulbar involvement. The main factor impacting functional decline and survival is the onset of bulbar dysfunction.
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| 13. |
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| 14. |
- Kliest, Tessa, et al.
(författare)
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Clinical trials in pediatric ALS: a TRICALS feasibility study
- 2022
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
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| 15. |
- Korner, Sonja, et al.
(författare)
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Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population
- 2019
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Ingår i: Aging and Disease. - Fort Worth : International Society on Aging & Disease. - 2152-5250. ; 10:2, s. 205-216
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly affecting upper and lower motor neurons in the brain and spinal cord. Pathogenesis of ALS is still unclear, and a multifactorial etiology is presumed. The remarkable clinical heterogeneity between different phenotypes of ALS patients suggests that environmental and lifestyle factors could play a role in onset and progression of ALS. We analyzed a cohort of 117 ALS patients and 93 controls. ALS patients and controls were compared regarding physical activity, dietary habits, smoking, residential environment, potentially toxic environmental factors and profession before symptom onset and throughout the disease course. Data were collected by a personal interview. For statistical analysis descriptive statistics, statistical tests and analysis of variance were used. ALS patients and controls did not differ regarding smoking, diet and extent of physical training. No higher frequency of toxic influences could be detected in the ALS group. ALS patients lived in rural environment considerably more often than the control persons, but this was not associated with a higher percentage of occupation in agriculture. There was also a higher percentage of university graduates in the ALS group. Patients with bulbar onset were considerably more often born in an urban environment as compared to spinal onset. Apart from education and environment, ALS phenotypes did not differ in any investigated environmental or life-style factor. The rate of disease progression was not influenced by any of the investigated environmental and life-style factors. The present study could not identify any dietary habit, smoking, physical activity, occupational factor as well as toxic influences as risk factor or protective factor for onset or progression of ALS. Living in rural environment and higher education might be associated with higher incidence of ALS.
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| 16. |
- Kuzma-Kozakiewicz, Magdalena, et al.
(författare)
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An observational study on quality of life and preferences to sustain life in locked-in state
- 2019
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Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 93:10, s. E938-E945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This is an observational study on well-being and end-of-life preferences in patients with amyotrophic lateral sclerosis (ALS) in the locked-in state (LIS) in a Polish sample within the EU Joint Programme-Neurodegenerative Disease Research study NEEDSinALS (NEEDSinALS.com).Methods: In this cross-sectional study, patients with ALS in LIS (n = 19) were interviewed on well-being (quality of life, depression) as a measure of psychosocial adaptation, coping mechanisms, and preferences towards life-sustaining treatments (ventilation, percutaneous endoscopic gastroscopy) and hastened death. Also, clinical data were recorded (ALS Functional Rating Scale-revised version). Standardized questionnaires (Anamnestic Comparative Self-Assessment [ACSA], Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), ALS Depression Inventory-12 items [ADI-12], schedule of attitudes toward hastened death [SAHD], Motor Neuron Disease Coping Scale) were used, which were digitally transcribed; answers were provided via eye-tracking control. In addition, caregivers were asked to judge patients' well-being.Results: The majority of patients had an ACSA score >0 and a SEIQoL score >50% (indicating positive quality of life) and ADI-12 <29 (indicating no clinically relevant depression). Physical function did not reflect subjective well-being; even more, those with no residual physical function had a positive well-being. All patients would again choose the life-sustaining techniques they currently used and their wish for hastened death was low (SAHD <10). Caregivers significantly underestimated patient's well-being.Interpretation: Some patients with ALS in LIS maintain a high sense of well-being despite severe physical restrictions. They are content with their life-sustaining treatments and have a strong will to live, which both may be underestimated by their families and public opinion.
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| 17. |
- Kuzma-Kozakiewicz, Magdalena, et al.
(författare)
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Putative founder effect in the Polish, Iranian and United States populations for the L144SSOD1mutation associated with slowly uniform phenotype of amyotrophic lateral sclerosis
- 2021
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 22:1-2, s. 80-85
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Tidskriftsartikel (refereegranskat)abstract
- Mutations inSOD1cause approximately 12-25% of familial ALS and approximate to 2% of apparently sporadic ALS cases. Clinical phenotypes linked to SOD1 mutations are heterogeneous and intra-familial variability of the clinical phenotype is frequently observed. SOD1 L144S mutation, identified also in Brazil, Iran and United States, is the second most frequent mutation among ALS patients in Poland. So far, 10 FALS pedigrees with SOD1 L144S mutation have been reported worldwide. The aim of the study was to establish the origin of SOD1 L144S mutation in geographically distinct populations. The clinical presentation of the Polish patients was compared with those from the previously reported populations (26 ever-reported patients). Clinically, L144S mutation is associated with both sporadic and familial ALS of relatively slow uniform course, a prevalent onset in the lower limbs, either classic or PMA presentation and a long survival time. Like in the case of other previously described SOD1 mutations, there was an intra-familial heterogeneity and reduced penetrance for ALS was observed. We propose that the L144S SOD1 mutation in the three studied populations has a common founder most likely of Polish origin.
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| 18. |
- Oeckl, Patrick, et al.
(författare)
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Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS
- 2016
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 17:5-6, s. 404-413
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a reverse round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n=150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p<0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 +/- 19.1%. We calculated a diagnostic cut-off of >568.5pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up.
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| 19. |
- Van Damme, Philip, et al.
(författare)
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European academy of neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European reference network for neuromuscular diseases (ERN EURO-NMD)
- 2024
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management.Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.
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| 20. |
- Weber, Christian, et al.
(författare)
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Existential decision-making in a fatal progressive disease : how much do legal and medical frameworks matter?
- 2017
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Ingår i: BMC Palliative Care. - : Springer Science and Business Media LLC. - 1472-684X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when it comes to end-of-life decision-making a number of differences exist in the more specific regulations of individual countries. These differences and how they might nevertheless impact patient’s choices will be addressed in the current debate.Main text: In this article we show how the legal and medical frameworks of Germany, Poland and Sweden differ with regard to end-of-life decisions for patients with a fatal progressive disease. Taking Amyotrophic Lateral Sclerosis (ALS) as an example, we systematically compare clinical guidelines and healthcare law, pointing out the country-specific differences most relevant for existential decision-making. A fictional case report discusses the implications of these differences for a patient with ALS living in either of the three countries. Patients with ALS in Germany, Poland and Sweden are confronted with a similar spectrum of treatment options. However, the analysis of the normative frameworks shows that the conditions for making existential decisions differ considerably in Germany, Poland and Sweden. Specifically, these differences concern (1) the legal status of advance directives, (2) the conditions under which life-sustaining therapies are started or withheld, and (3) the legal regulations on assisted dying.Conclusion: According to the presented data, regulations of terminating life-sustaining treatments and the framework of “informed consent” are quite differently understood and implemented in the legal setting of the three countries. It is possible, and even likely, that these differences in the legal and medical frameworks have a considerable influence on existential decisions of patients with ALS.
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