Increased Cerebrospinal Fluid Adenosine 5'-triphosphate in Patients with Amyotrophic Lateral Sclerosis

2020 ◽  
Author(s):  
Takamasa Nukui ◽  
Atsushi Matsui ◽  
Hideki Niimi ◽  
Tomohiro Hayashi ◽  
Nobuhiro Dougu ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Serum Creatinine ◽  
Disease Severity ◽  
Normal Pressure ◽  
Assay System ◽  
Atp Levels ◽  
Sum Score ◽  
Highly Sensitive ◽  
Severe Group ◽  
Lateral Sclerosis

Abstract Background: Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined CSF ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods: Forty-eight CSF samples from 45 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results: ALSFRS-R (37.9 ± 5.7 vs. 42.4 ± 2.8, p<0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis (r = -0.3862, p < 0.01). Conclusions: Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

scholarly journals Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takamasa Nukui ◽  
Atsushi Matsui ◽  
Hideki Niimi ◽  
Tomoyuki Sugimoto ◽  
Tomohiro Hayashi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Serum Creatinine ◽  
Disease Severity ◽  
Assay System ◽  
Atp Levels ◽  
Sum Score ◽  
Highly Sensitive ◽  
Severe Group ◽  
Lateral Sclerosis

Abstract Background Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08). Conclusions Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

scholarly journals Clinical Determinants of Disease Progression in Amyotrophic Lateral Sclerosis—A Retrospective Cohort Study

2021 ◽  
Vol 10 (8) ◽  
pp. 1623
Author(s):  
Maria Viktoria Requardt ◽  
Dennis Görlich ◽  
Torsten Grehl ◽  
Matthias Boentert
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Disease Progression ◽  
Rating Scale ◽  
Rapid Decline ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Hazard Ratios ◽  
Sum Score ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is ultimately fatal but characterized by substantial phenotypic heterogeneity, which is known to impact long-term course and survival. This study investigated clinical determinants of disease progression and outcome in a large cohort of patients with ALS. Methods: Retrospective analysis included comprehensive data from 625 patients who attended a tertiary ALS centre at least twice. Patients were stratified according to five distinct clinical phenotypes: classical ALS; bulbar ALS; ALS with frontotemporal dementia (ALS-FTD); upper motor neuron predominant (UMNP); and lower motor neuron predominant (LMNP). Results: This study confirmed higher age at symptom onset, shorter latency to diagnosis and more rapid decline in the revised ALS Functional Rating Scale sum score as predictors of poor prognosis. Hazard ratios for shorter survival were higher in patients with ALS-FTD versus classical ALS, and in patients with versus without chronic obstructive pulmonary disease (COPD). Mean survival was longest in the UMNP phenotype group. Conclusions: This study confirmed established predictors of shorter survival in ALS and showed that concomitant COPD in particular relates to poor outcome.

scholarly journals Informal Caregiving in Amyotrophic Lateral Sclerosis (ALS): A High Caregiver Burden and Drastic Consequences on Caregivers’ Lives

2021 ◽  
Vol 11 (6) ◽  
pp. 748
Author(s):  
Pavel Schischlevskij ◽  
Isabell Cordts ◽  
René Günther ◽  
Benjamin Stolte ◽  
Daniel Zeller ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Functional Status ◽  
Disease Severity ◽  
Caregiver Burden ◽  
Rating Scale ◽  
Depression Scale ◽  
Anxiety And Depression ◽  
Daily Routine ◽  
Work Lives ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.

scholarly journals Creatinine and C-reactive protein in amyotrophic lateral sclerosis, multiple sclerosis and Parkinson’s disease

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Can Cui ◽  
Jiangwei Sun ◽  
Yudi Pawitan ◽  
Fredrik Piehl ◽  
Honglei Chen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Serum Creatinine ◽  
Linear Mixed Model ◽  
Temporal Patterns ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Lateral Sclerosis

Abstract Serum creatinine and C-reactive protein have been proposed as potential biomarkers for neurodegenerative diseases, including amyotrophic lateral sclerosis, multiple sclerosis and Parkinson’s disease. However, longitudinal studies investigating temporal patterns of these biomarkers, including the phase before diagnosis, are rare. We performed a case–control study including all newly diagnosed patients with amyotrophic lateral sclerosis (N = 525), multiple sclerosis (N = 1815) or Parkinson’s disease (N = 3797) during 2006–2013 in Stockholm, Sweden, who participated in the Stockholm CREAtinine Measurements (SCREAM) project. For each case, we randomly selected up to five controls from SCREAM that were individually matched to the case by age, sex and county of residence (N = 2625 for amyotrophic lateral sclerosis, N = 9063 for multiple sclerosis and 18 960 for Parkinson’s disease). We collected for both the cases and the controls testing results of serum creatinine and C-reactive protein performed by healthcare providers in Stockholm during the study period. Median levels of creatinine and C-reactive protein were visualized using locally weighted smoothing curves among cases and controls. A linear mixed model was also applied to explore temporal changes within an individual. Compared to controls, patients with amyotrophic lateral sclerosis had lower levels of creatinine from 2 years before diagnosis onwards. In contrast, patients with amyotrophic lateral sclerosis had lower levels of C-reactive protein before diagnosis but higher levels after diagnosis, compared to controls. Focusing the 2 years before to 2 years after diagnosis, patients with amyotrophic lateral sclerosis displayed statistically significantly decreasing level of creatinine from 1 year before diagnosis until 2 years after diagnosis, whereas increasing level of C-reactive protein from diagnosis until 2 years after diagnosis. There were no similar patterns noted among patients with multiple sclerosis or Parkinson’s disease, or the controls of the three patient groups. Patients with amyotrophic lateral sclerosis display distinct temporal patterns of creatinine and C-reactive protein before and after diagnosis, compared to amyotrophic lateral sclerosis-free controls or patients with multiple sclerosis and Parkinson’s disease.

Spinal cord atrophy correlates with disease severity in amyotrophic lateral sclerosis

2013 ◽  
Vol 333 ◽  
pp. e447-e448
Author(s):  
H.M.T. Andrade ◽  
L.M.T. Branco ◽  
M. Albuquerque ◽  
F.P.G. Bergo ◽  
A. Nucci ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Disease Severity ◽  
Spinal Cord Atrophy ◽  
Lateral Sclerosis

scholarly journals Errata: Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

2011 ◽  
Vol 1 (2) ◽  
Author(s):  
Melinda F. Davis ◽  
Katalin H. Scherer ◽  
Timothy M. Miller ◽  
F. John Meaney
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Muscular Dystrophy ◽  
Disease Severity ◽  
Muscle Weakness ◽  
Respiratory Function ◽  
Rating Scale ◽  
Becker Muscular Dystrophy ◽  
Progressive Muscle Weakness ◽  
Lateral Sclerosis ◽  
Disease Specific

Reports an error in Davis et al. (2010).  The functional motor scale used in Davis et al. (2010) was the EK (Egen Klassifikation) Scale, rather than the Amyotrophic Lateral Sclerosis Functional Rating Scale (Steffensen et al., 2002; Cedarbaum & Stambler, 1997).  Both scales are 10-item, disease-specific measures that assess mobility and respiratory function in individuals with progressive muscle weakness.  This error does not change the conclusions. DOI:10.2458/azu_jmmss_v1i2_davis

Patterns of Misidentified Vowels in Individuals With Dysarthria Secondary to Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (8) ◽  
pp. 2649-2666
Author(s):  
Jimin Lee ◽  
Heejin Kim ◽  
Yong Jung
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Similar Rate ◽  
Directional Pattern ◽  
Vowel Duration ◽  
Spectral Change ◽  
Vowel Identification ◽  
Height Control ◽  
Severe Group ◽  
Second Formant ◽  
Lateral Sclerosis

Purpose The current study examines the pattern of misidentified vowels produced by individuals with dysarthria secondary to amyotrophic lateral sclerosis (ALS). Method Twenty-three individuals with ALS and 22 typical individuals produced 10 monophthongs in an /h/-vowel-/d/ context. One hundred thirty-five listeners completed a forced-choice vowel identification test. Misidentified vowels were examined in terms of the target vowel categories (front–back; low–mid–high) and the direction of misidentification (the directional pattern when the target vowel was misidentified, e.g., misidentification “to a lower vowel”). In addition, acoustic predictors of vowel misidentifications were tested based on log first formant (F1), log second formant, log F1 vowel inherent spectral change, log second formant vowel inherent spectral change, and vowel duration. Results First, high and mid vowels were more frequently misidentified than low vowels for all speaker groups. Second, front and back vowels were misidentified at a similar rate for both the Mild and Severe groups, whereas back vowels were more frequently misidentified than front vowels in typical individuals. Regarding the direction of vowel misidentification, vowel errors were mostly made within the same backness (front–back) category for all groups. In addition, more errors were found toward a lower vowel category than toward a higher vowel category in the Severe group, but not in the Mild group. Overall, log F1 difference was identified as a consistent acoustic predictor of the main vowel misidentification pattern. Conclusion Frequent misidentifications in the vowel height dimension and the acoustic predictor, F1, suggest that limited tongue height control is the major articulatory dysfunction in individuals with ALS. Clinical implications regarding this finding are discussed.

Sign in / Sign up

Export Citation Format

Share Document