| 31. |
- Neuwirth, Christoph, et al.
(författare)
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Tracking motor neuron loss in a set of six muscles in amyotrophic lateral sclerosis using the Motor Unit Number Index (MUNIX) : a 15-month longitudinal multicentre trial
- 2015
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:11, s. 1172-1179
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Tidskriftsartikel (refereegranskat)abstract
- Background Motor Unit Number Index (MUNIX) is a novel neurophysiological measure that provides an index of the number of functional lower motor neurons in a given muscle. So far its performance across centres in patients with amyotrophic lateral sclerosis (ALS) has not been investigated. Objective To perform longitudinal MUNIX recordings in a set of muscles in a multicentre setting in order to evaluate its value as a marker of disease progression. Methods Three centres applied MUNIX in 51 ALS patients over 15 months. Six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor dig. brevis, abductor hallucis) were measured every 3 months on the less affected side. The decline between MUNIX and ALSFRS-R was compared. Results 31 participants reached month 12. For all participants, ALSFRS-R declined at a rate of 2.3%/month. Using the total score of all muscles, MUNIX declined significantly faster by 3.2%/month (p <= 0.02). MUNIX in individual muscles declined between 2.4% and 4.2%, which differed from ASLFRS-R decline starting from month 3 (p <= 0.05 to 0.002). Subgroups with bulbar, lower and upper limb onset showed different decline rates of ALSFRS-R between 1.9% and 2.8%/month, while MUNIX total scores showed similar decline rates over all subgroups. Mean intraclass correlation coefficient for MUNIX intra-rater reliability was 0.89 and for inter-rater reliability 0.80. Conclusion MUNIX is a reliable electrophysiological biomarker to track lower motor neuron loss in ALS.
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| 32. |
- Nordin, Angelica, et al.
(författare)
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Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation : a large multinational screening study
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 18:3-4, s. 256-264
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Tidskriftsartikel (refereegranskat)abstract
- A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele. In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.
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| 33. |
- 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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| 34. |
- Pinto, Susana, et al.
(författare)
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Comparison of slow and forced vital capacities on ability to predict survival in ALS
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 18:7-8, s. 528-533
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Slow (SVC) and forced (FVC) vital capacities are the most used pulmonary function tests in amyotrophic lateral sclerosis (ALS). It is unknown if they equally predict survival in ALS. The aim of the present study was to compare both measures in predicting survival in this disease.Methods: Consecutive definite/probable ALS patients (2000-2014) in whom respiratory tests were performed at baseline and four months later were included. All patients were evaluated with the revised ALS functional rating scale (ALSFRS-R), respiratory (RofALSFRS-R), bulbar (ALSFRSb), upper and lower limb subscores, SVC, FVC, maximal inspiratory (MIP) and expiratory (MEP) pressures. King's functional staging system was applied retrospectively. Survival analysis was carried out by univariate Kaplan-Meier log-rank test. Multivariate Cox proportional hazards model determined significant independent variables.Results: We included 469 patients (270 males; mean onset age 61.0 +/- 11.5 years; mean disease duration from first symptoms to first visit: 15.8 +/- 16.1months; 329 spinal and 140 bulbar onset). FVC and SVC were strongly correlated (r(2)=0.981, p<0.001). Significant survival prognostic variables (Kaplan-Meier analyses) were onset region, age, disease duration, ALSFRS-R, ALSFRSb, RofALSFRS-R, ALSFRS-R decay, SVC, FVC, MIP, MEP and King's staging (p0.01). Final Cox model including the significant variables showed similar results for FVC and SVC (p<0.001). Moreover, 1% decrease in either predicted values increased death probability by 1.02.Conclusion: FVC and SVC are inter-changeable in predicting survival in ALS.
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| 35. |
- Pinto, Susana, et al.
(författare)
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Health Status Perspectives in Amyotrophic Lateral Sclerosis
- 2017
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Ingår i: Neurodegenerative Diseases. - : S. Karger. - 1660-2854 .- 1660-2862. ; 17:6, s. 323-329
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The global perception of the health status (HS) of amyotrophic lateral sclerosis (ALS) patients before the initial diagnosis has not been addressed previously. Methods: We recorded the following at the first visit, before diagnostic information: (1) visual analog scale (VAS) of the EQ-5D; (2) the revised ALS functional rating scale (ALSFRSR), bulbar (ALSFRSb), upper limb (ALSFRSul), lower limb (ALSFRSll), and respiratory (RofALSFRS-R) subscores; and (3) forced and slow vital capacities. Correlations were tested by the Pearson correlation test. Variables were compared between groups defined by the VAS median value. p < 0.05 was considered significant. Results: Of the 156 patients included in the study (91 spinal-onset, 49 bulbar-onset, 16 axial/respiratory- onset; 95 men; mean onset age 63.9 +/- 13 years; mean disease duration 18.4 +/- 26.5 months), HS VAS was significantly lower in spinal-onset patients (p = 0.047), and particularly in spinal-onset women (p = 0.027). Disease duration had no influence. HS VAS was moderately correlated with ALS-FRS, ALSFRSul and ALSFRSll (0.4 < r < 0.5, p < 0.01), weakly correlated with RofALSFRS-R in the whole population (r = 0.171, p < 0.05), and not correlated with ALSFRSb or the respiratory tests. ALSFRSb was similar between groups defined by the HS VAS median value, but the other scores were significantly lower for poorer HS values. Conclusion: HS before diagnosis is mostly dependent on the perception of upper and lower limb function. A tool tailored to evaluate HS in bulbar-onset patients should be developed.
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| 36. |
- Pinto, Susana, et al.
(författare)
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Respiratory onset in amyotrophic lateral sclerosis : clinical features and spreading pattern
- 2023
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 24:1-2, s. 40-44
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe the clinical features and progression of patients with respiratory onset amyotrophic lateral sclerosis (ALS).Methods: We analyzed the clinical features, including respiratory tests, functional score, noninvasive ventilation (NIV) time and survival of ALS patients with respiratory-onset in our database consisting of 1688 patients. In a subset of 625 ALS patients we analyzed the spreading pattern to other bodily regions.Results: We included 1579 patients with ALS. Sixty-three patients (4%) presented respiratory-onset (79.4% men, mean onset-age 67.7 +/- 8.9yrs). All had predominant LMN involvement, and significant weight loss (>10%) was identified in 38.9%. The respiratory tests were abnormal in these respiratory-onset patients (p < 0.001). ALSFRS-R respiratory subscore was lower in this population (p < 0.001). NIV was adapted in 84.1%, sooner than in the larger group of ALS patients (p < 0.001), and survival from disease onset was shorter (p < 0.001). Respiratory-onset was a predictor of time to NIV (X-2=42.0, p < 0.001) and of survival (X-2=7.1, p = 0.008). The spreading pattern was studied in 18 patients with isolated respiratory-onset. The progression interval to the 2nd region was 4.7 +/- 5.7mo and to a 3rd region 6.1 +/- 8.7mo. Different patterns of spread had no impact on survival.Conclusions: This phenotype is typically seen in emaciated older men with predominant lower motor neuron involvement, and is associated with diaphragm paresis and central respiratory involvement. NIV adaptation is rapid but total survival is shorter than in the other patients. Spreading pattern did not affect time to NIV adaptation or total survival, as NIV support is a modifying treatment in the course of ALS.
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| 37. |
- Pinto, Susana, et al.
(författare)
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Respiratory phenotypes in amyotrophic lateral sclerosis as determined by respiratory questions on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised and their relation to respiratory tests
- 2023
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Ingår i: European Journal of Neurology. - : John Wiley & Sons. - 1351-5101 .- 1468-1331. ; 30:6, s. 1594-1599
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Forskningsöversikt (refereegranskat)abstract
- Background and purpose Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Methods Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO(2)mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. Results We included 276 patients (153 men, onset age = 62.6 +/- 11.0 years, disease duration = 13.0 +/- 9.6 months, spinal onset in 182) with mean survival of 40.1 +/- 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO(2)mean. Independent predictors for G2 were MIP and SpO(2)mean; for G3, the only independent predictor was PhrenAmpl. Conclusions These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.
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| 38. |
- Pinto, Susana, et al.
(författare)
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Sniff nasal inspiratory pressure (SNIP) in amyotrophic lateral sclerosis : Relevance of the methodology for respiratory function evaluation
- 2018
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Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print). - : Elsevier. - 0303-8467 .- 1872-6968. ; 171, s. 42-45
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We investigated two different methodological approaches for determining nasal inspiratory pressure during a sniff (SNIP) in patients with Amyotrophic Lateral Sclerosis (ALS). Patients and Methods: We included 37 ALS patients and 11 controls. SNIP was measured in the sitting position, performed in each nostril with (SNIPocclud) and without (SNIPopen) closing the contralateral nostril. The best of 3 consistent results was considered for analyses. Patients were also assessed with MIP and the revised functional ALS rating scale (ALSFRS-R). Mann-Whitney U test, Wilcoxon test and Spearman's rank correlation coefficient with Bonferroni correction were applied. Coefficient of variation (CV) was calculated. Results: SNIP was significantly lower in patients than controls, either for SNIPopen (p = 0.011) or SNIPocclud (p = 0.002). SNIPopen values were significantly lower both in ALS patients and controls than SNIPocclud (p < 0.001 and p = 0.007, respectively). SNIPopen CV was 8.14% and 8.51%, while SNIPocclud CV was 4.98% and 6.37%, respectively for controls and patients. SNIPopen and SNIPocclud were strongly correlated in both groups (r = 0.761 for controls; r = 0.768 for patients). In ALS, both methods were moderately correlated with MIP (respectively r = 0.525, p = 0.006 and r = 0.685, p < 0.001) and the respiratory subscore of ALSFRS-R (respectively r = 0.525, p = 0.001 and r = 0.64, p < 0.001). Although bulbar and spinal onset patients presented no differences for SNIPopen (p = 0.157), significant differences were found for SNIPocclud (p = 0.018). Conclusion: SNIPocclud should be considered when evaluating ALS patients as its values present lower variability and favor longer follow-up.
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| 39. |
- Pinto, Susana, et al.
(författare)
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SVC Is a Marker of Respiratory Decline Function, Similar to FVC , in Patients With ALS
- 2019
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Respiratory function is a critical predictor of survival in amyotrophic lateral sclerosis (ALS). We aimed to determine if slow vital capacity (SVC) is a predictor of functional loss in ALS as compared to forced vital capacity (FVC). Methods: Consecutive ALS patients in whom respiratory tests were performed at baseline and 6 months later were included. All patients were evaluated with revised ALS functional rating scale (ALSFRS-R) and the respiratory tests, SVC, and FVC. Significant independent variables of functional decay were assessed by univariate Kaplan-Meier log-rank test and multivariate Cox proportional hazards model. A monthly decay not exceeding 0.92 in ALSFRS was considered as the time event. Results: We included 232 patients (134 men; mean onset-age 59.1 +/- 11.23 years; mean disease duration from first symptoms to first visit: 14.5 +/- 12.9 months; 166 spinal and 66 bulbar onset). All variables studied declined significantly between the two evaluations (p < 0.001). FVC and SVC were strongly correlated at study entry (r2 = 0.98, p < 0.001) and FVC and SVC decays between first evaluation and 6 months after were the only significant prognostic variables of functional decay (p < 0.001). Conclusion: FVC and SVC decay are inter-changeable in predicting functional decay in ALS. Pharmacological interventions reducing the decline rate of FVC and SVC can have a positive impact on the global functional impairment, with relevant implications for clinical trials' design and interpretation.
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| 40. |
- Ruggeri, Kai, et al.
(författare)
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The globalizability of temporal discounting
- 2022
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
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Tidskriftsartikel (refereegranskat)abstract
- Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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