Decreased serum creatinine levels predict short survival in amyotrophic 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.

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Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis

Neurology ◽

10.1212/wnl.0000000000005424 ◽

2018 ◽

Vol 90 (18) ◽

pp. e1578-e1587 ◽

Cited By ~ 8

Author(s):

Toshio Shimizu ◽

Kota Bokuda ◽

Hideki Kimura ◽

Tsutomu Kamiyama ◽

Yuki Nakayama ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Multivariate Analysis ◽

Action Potential ◽

Median Nerve ◽

Rating Scale ◽

Sensory Cortex ◽

Peak Amplitude ◽

Short Survival ◽

Sporadic Als ◽

Lateral Sclerosis

ObjectiveTo investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS).MethodsA total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale–Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model.ResultsCompared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival (p = 0.002).ConclusionSensory cortex hyperexcitability predicts short survival in patients with ALS.

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

Brain Communications ◽

10.1093/braincomms/fcaa152 ◽

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.

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

10.21203/rs.3.rs-118378/v1 ◽

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.

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