Survival In Amyotrophic Lateral Sclerosis Patients Research Articles

Association of Single Nucleotide Polymorphism at rs2275294 in the ZNF512B Gene with Prognosis in Amyotrophic Lateral Sclerosis.

The aim of this study is to explore whether the single nucleotide polymorphism rs2275294 in the ZNF512B gene is related to the length of survival of patients with amyotrophic lateral sclerosis (ALS). This prospective study examined 212 patients with ALS, who were genotyped at the rs2275294 locus in ZNF512B using the ligase method. Genotype was compared with clinical data and survival. Kaplan-Meier survival analysis and Cox hazard regression were used to identify risk factors of shorter survival. Our results were meta-analyzed together with previous work in order to examine the potential association between the rs2275294-C allele and survival. Of the 212 patients, 166 carried the CC + CT genotype at the rs2275294 locus, while 46 carried the TT genotype. Patients with the C allele showed significantly shorter survival than those without it (34.13 ± 1.9 vs. 45.32 ± 5.7months, p = 0.036). Cox analysis identified the C allele and time from symptom onset to diagnosis as risk factors for shorter survival. Meta-analysis of 447 patients in China and Japan confirmed the rs2275294-C allele to be an independent risk factor of shorter survival in ALS patients. The C allele at the rs2275294 locus in ZNF512B is a risk factor for shorter survival in patients with ALS.

The ‘way of flowers’ and the care of patients with amyotrophic lateral sclerosis in Japan

Tracheostomy with invasive ventilation (TIV) may be required for the survival of patients at advanced stages of amyotrophic lateral sclerosis (ALS). In Japan it has been shown that a proactive approach toward TIV may prolong the survival of ALS patients by over 10 years by preventing the lethal respiratory failure that generally occurs within 3-5 years of the onset of the disease. Measures to prolong life expectancy without foregoing quality of life have produced better results in Japan than in other developed countries. This ‘Japanese bias’ has been attributed to socio-cultural and religious factors as well as to the availability of material resources in Japan. In this article, we use the concepts of onozukara in kadō (Japanese traditional flower art, also called ikebana) and amae (passive love) to illuminate features of patient care that may contribute to this ‘Japanese bias’.

Survival according to resting energy expenditure (REE) variation using two ree formulas and without indirect calorimetry in patients with amyotrophic lateral sclerosis (ALS)

Rationale: The increase of resting energy expenditure (REE) variation in ALS is a prognostic factor for the survival mainly in patients with a REE variation over +20%. Measurement of REE by indirect calorimetry (IC) compared to REE predicted with formula (Harris and Benedict [HB] 1919, HB 1984 or Mifflin) is necessary to obtain the REE variation. However, IC is not available in many centres. Jésus et al. formula is a validate formula to predict REE in ALS and can be used in the absence of an IC. The aim of this work was to study the survival of ALS patients according to REE variation with IC or Jésus formula.

Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis.

Clinical signs of upper motor neuron (UMN) involvement are important in the diagnosis of amyotrophic lateral sclerosis (ALS) though are often difficult to analyze. Many studies using both qualitative and quantitative evaluations have reported abnormal Magnetic Resonance Imaging (MRI) findings at the level of the pyramidal pathway in patients with ALS. Although the most interesting results were obtained by quantitative studies using advanced MR techniques, the qualitative evaluation of MRI images remains the most-used in clinical practice. We evaluated the diagnostic and prognostic contribution of conventional 3T-MRI in the clinical work-up of ALS patients. Two neuroradiologists retrospectively assessed 3T-MRI data of 93 ALS patients and 89 controls. The features of interest were corticospinal tract (CST) T2/FLAIR hyperintensity, motor cortex (MC) T2*/SWI hypointensity, and selective MC atrophy. All MRI features were significantly more prevalent in ALS patients than in controls. The simultaneous presence of CST FLAIR hyperintensity and MC SWI hypointensity was associated with the highest diagnostic accuracy (sensitivity: 70%; specificity: 81%; positive predictive value, PPV: 90%; negative predictive value, NPV: 51%; accuracy: 73%) and a shorter survival (HR: 6.56, p = 0.002). Conventional 3T-MRI can be a feasible tool to detect specific qualitative changes based on UMN involvement and to support clinical diagnosis of ALS. Importantly, CST FLAIR hyperintensity and MC SWI hypointensity are predictors of shorter survival in ALS patients.

P2X7 Receptor Antagonism as a Potential Therapy in Amyotrophic Lateral Sclerosis.

This review focuses on the purinergic ionotropic receptor P2X7 (P2X7R) as a potential target for developing drugs that delay the onset and/or disease progression in patients with amyotrophic lateral sclerosis (ALS). Description of clinical and genetic ALS features is followed by an analysis of advantages and drawbacks of transgenic mouse models of disease based on mutations in a bunch of proteins, particularly Cu/Zn superoxide dismutase (SOD1), TAR-DNA binding protein-43 (TDP-43), Fused in Sarcoma/Translocated in Sarcoma (FUS), and Chromosome 9 open reading frame 72 (C9orf72). Though of limited value, these models are however critical to study the proof of concept of new compounds, before reaching clinical trials. The authors also provide a description of ALS pathogenesis including protein aggregation, calcium-dependent excitotoxicity, dysfunction of calcium-binding proteins, ultrastructural mitochondrial alterations, disruption of mitochondrial calcium handling, and overproduction of reactive oxygen species (ROS). Understanding disease pathogenic pathways may ease the identification of new drug targets. Subsequently, neuroinflammation linked with P2X7Rs in ALS pathogenesis is described in order to understand the rationale of placing the use of P2X7R antagonists as a new therapeutic pharmacological approach to ALS. This is the basis for the hypothesis that a P2X7R blocker could mitigate the neuroinflammatory state, indirectly leading to neuroprotection and higher motoneuron survival in ALS patients.

Statins, diabetes mellitus and prognosis of amyotrophic lateral sclerosis: data from 501 patients of a population‐based registry in southwest Germany

A wide variety of metabolic changes, including an increased incidence of diabetes mellitus (DM) and dyslipidaemia, has been described in amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate the associations of statin use and history of DM with onset of disease and survival in patients with ALS. In all, 501 patients (mean age 65.2±10.9years; 58.5% male) from the ALS Registry Swabia recruited between October 2010 and April 2016 were included in this prospective cohort study. Data were collected using a standardized questionnaire. Statin use (n=65) was not associated with overall survival (P=0.62). Age of ALS onset in patients with DM was 4.2years later (95% confidence interval 1.3-7.2years) than in patients without DM (P<0.01). The overall survival of patients with high body mass index at study entry (>27.0kg/m2 , upper quartile, n=127) was prolonged by more than 5 months compared to patients with low body mass index (<22.0kg/m2 , lower quartile, n=123; P=0.04). This study supports the view that statin use is not associated with overall survival of ALS patients, suggesting that statins are not harmful and should not be discontinued in ALS. Furthermore, the delayed onset of ALS in patients with DM may mirror the potentially protective metabolic profile associated with type 2 DM. Consistently, this study provides further evidence that high body mass index is a positive prognostic factor in ALS.

Predictive factors for gastrostomy at time of diagnosis and impact on survival in patients with amyotrophic lateral sclerosis.

Gastrostomy is recommended in patients with Amyotrophic Lateral Sclerosis (ALS) in the presence of weight loss over 10% as compared to usual weight, repeated aspirations or meal time duration longer than 45min. Currently, the impact of gastrostomy on survival of ALS patients is not clear. i) to describe diagnosis factors associated with the indication for gastrostomy ii) to evaluate survival of ALS patients with gastrostomy indication according to their acceptance of feeding tube placement. Patients with ALS were included and followed in the ALS referral centre of Limoges's teaching hospital between 2006 and 2017. Neurological, nutritional and respiratory status was assessed prospectively from diagnosis to death. Statistical analysis was performed using Mann-Whitney test, Chi2 tests, Cox model and multivariate logistic regression. Two hundred and eighty-five patients were included. Among the 182 for whom gastrostomy was indicated, 63.7% accepted the placement. The median time was 7.3 months [IQR: 3.2-15.0] and 2.7 months [IQR: 0.9-5.8] respectively from diagnosis to indication and from indication to placement. Weight loss >5% significantly increased the risk of death by 17% (p<0.0001). At time of diagnosis, bulbar onset, a loss of one point in the body mass index or on the bulbar functional scale were all positively associated with indication for gastrostomy (aOR=10.0 [95%CI: 1.96-25.0]; p=0.002, aOR=1.17 [95%CI: 1.02-1.36]; p=0.025 and aOR=1.19 [95%CI: 1.06-1.32]; p=0.002, respectively). However, gastrostomy placement did not have any impact on survival (aHR=1.25 [95%CI: 0.88-1.79]; p=0.22). Both neurological and nutritional criteria were associated with an indication for gastrostomy at diagnosis. Gastrostomy placement had no impact on survival. The study of earlier gastrostomy placement might be of interest in further prospective studies.

Life Course Adiposity and Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study.

Observational studies have indicated that life course adiposity is associated with amyotrophic lateral sclerosis (ALS). However, whether such an association reflects causality remains unclear. We aimed to determine whether life course adiposity such as birth weight (BW), childhood body mass index (BMI), adult BMI, body fat percentage (BF%), and waist-to-hip ratio (WHR) have causal effects on ALS. Single nucleotide polymorphisms (SNPs) significantly associated with life course adiposity were used as instrumental variables to estimate the causal effects on ALS. We used summary-level data from a cohort of 20,806 cases and 59,804 controls in a Mendelian randomization (MR) framework. Genetically predicted one standard deviation (1-SD) increase in BF% was associated with lower risk of ALS (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.54-0.83, p = 3.25E-04) after Bonferroni correction (p < 0.05/5). Genetically predicted 1-SD higher childhood BMI was suggestively associated with lower risk of ALS (OR = 0.88, 95% CI = 0.78-0.99, p = 0.031). The weighted median method indicated a suggestive association between BMI and ALS (OR = 0.86, 95% CI = 0.69-0.96, p = 0.016). Neither a genetically predicted 1-SD increase in BW (inverse variance weighted [IVW]: OR = 1.01, 95% CI = 0.87-1.17, p = 0.939) nor WHR adjusted for BMI (IVW: OR = 0.90, 95% CI = 0.76-1.05, p = 0.178) was associated with ALS. Our findings provide novel evidence supporting a causal role of higher adiposity, taken as a whole, on lower risk of ALS. A deeper understanding of the energy metabolism of ALS is more likely to identify feasible nutritional interventions and even novel therapeutic targets that might improve the survival of ALS patients. Ann Neurol 2020;87:434-441.

Theme 12 Respiratory and nutritional management

Background: Previous studies explored the associations between body weight index (BMI) at diagnosis, weight change after diagnosis and survival in amyotrophic lateral sclerosis (ALS). But significance of weight stability before diagnosis remains to be established.Objective: The aim of this study is to clarify the weight loss from baseline (6 months before diagnosis) to diagnostic and the effect on disease prognosis.Methods: Total of 911 patients were enrolled from 2014 to 2018 in West China Hospital of Sichuan University. BMI is divided into four subgroups: lean, normal, overweight, and obese. The formula for calculating the rate of weight change = (weight at baseline - weight at diagnosis)/weight at baseline * 100%. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazard models.Results: The mean age of onset was 55.4 ± 11.1 years. The percentage of overweight and obesity in ALS at baseline were significantly lower than healthy controls. The median of weight loss was 2.9%. 36.9% patients had weight loss more than 5%, and 16.5% of them lose weight more than 10%. Patients with bulbar onset, bulbar impairment, lower ALS functional rating scale-revised score had more serious weight loss. The Kaplan-Meier curve showed that, compared to other patients, patients with weight loss more than 10% had a shorter survival time (30.5 months vs. 48.8 months, log-rank p < 0.001). Cox analysis showed that the weight loss was found to be an independent predictor of survival after adjusting for other survival factors (HR= 1.165, p trend <0.001). Each additional increased class of weight loss was associated with a 16.5% (95% CI: 7.3%-26.5%) increased risk of mortality and worse survival.Discussion and conclusion: Our study suggested that the weight variation is associated with survival in ALS patients. This has strong implications for management of nutritional issues in ALS, that the patient education and therapy recommendation should be earlier and standardize to promote the nutritional support and prognosis.

Neurophysiologic studies and survival in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Neurophysiology techniques support the diagnosis. Evaluate the relationship between nerve conduction studies (NCS)/EMG and survival of ALS patients. 15 consecutive cases of ALS fulfilling El Escorial-Awaji Shima criteria in the Instituto Nacional de Nutrición Salvador Zubirán at Mexico City, from 2016 to 2019. Other etiologies were excluded with laboratorial and imaging studies. We collected informed consent, clinico-epidemiological data and performed a standard NCS/EMG to each patient, the relationship between NCS/EMG parameters and survival was evaluated by Spearman and Pearson correlation in SPSS® version 25 software. 10 male, mean age was 57.7 ± 13.1 years. The gap between symptoms onset and diagnosis was 12.8±16 months; cervical was the most common first presentation, 4 patients (26.7%) were diabetics; normal findings on MRI was found in 80%. NCS showed that the most affected nerves were: median (distal latency (DL) averages: 3.85 m/s, Compound muscle action potential (CMAP) amplitudes: 2.97 μV, conduction velocities (CV): 43.3 m/s. Ulnar nerves: DL: 3.32 m/s, CMAP amplitudes: 3.98 μV, CV: 50.37 m/s) (Table 1). F waves latencies were found abnormal in 4/15 patients in median, cubital and peroneal nerves; sensory affection was found in 4/15 patients in peroneal and sural nerves. EMG revealed denervation changes, poor recruitment in all the studied muscles including paraspinals; the muscle unit action potentials (MUAP) parameters showed reinnervation changes (Table 2). We found a bilateral good correlation between tongue MUAP duration (p = 0.047) and months of life. NCS showed predominantly an axonal damage in the studied nerves. Tongue MUAP's duration was correlated with a shorter survival time (Graph 1).

Survival benefit of multidisciplinary care in amyotrophic lateral sclerosis in Spain: association with noninvasive mechanical ventilation.

PurposeMultidisciplinary care has become the preferred model of care for patients with amyotrophic lateral sclerosis (ALS). It is assumed that the sum of interventions associated with this approach has a positive effect on survival. The objective of the study was to evaluate the impact of a multidisciplinary care approach on the survival of patients with ALS.Patients and methodsWe performed a retrospective review of prospectively collected data in a tertiary referral center in Spain. Participants were patients with definite or probable ALS managed in a multidisciplinary care program. We compared demographic and survival data of patients with definite or probable ALS treated in a referral center without and with implementation of a multidisciplinary care program. We performed time-dependent multivariate survival analysis of the use of noninvasive mechanical ventilation (NIMV) and gastrostomy.ResultsWe evaluated 398 consecutive patients, of whom 54 were treated by a general neurologist and 344 were treated in the multidisciplinary care clinic. Patients receiving multidisciplinary care were older (62 vs 58 years), tended to have bulbar onset disease (30% vs 17.7%), and were more likely to receive riluzole (88.7% vs 29.6%, p<0.01), NIMV (48.8% vs 29.6%, p>0.001), and nutrition via gastrostomy (32.3% vs 3.7%, p<0.01). Kaplan–Meier analysis showed a 6-month increase in survival (log-rank, 16.03, p<0.001). Application of the Andersen-Gill model showed that the variables associated with reduced mortality were reduced time to NIMV and gastrostomy and the duration of both, thus reflecting compliance.ConclusionsMultidisciplinary care increased the survival of ALS patients in our study population. Timely use of respiratory support and gastrostomy are fundamental aspects of this benefit.

Neurophysiological index is associated with the survival of patients with amyotrophic lateral sclerosis

ObjectiveTo investigate the association between Neurophysiological Index (NI) and the survival of patients with Amyotrophic Lateral Sclerosis (ALS). MethodsPatients diagnosed with ALS in the Department of Neurology, West China Hospital, Sichuan University from May 2015 to May 2017 were enrolled in this study, and then were followed up every 3 months until 31st May 2018. According to the mean NI values, the participants were categorized into high NI and low NI groups. Differences between groups were compared with parametric or non-parametric test, whichever was more appropriate. Kaplan-Meier method and Cox regression model were used to calculate the survival analysis. ResultsOne hundred and ninety one sporadic ALS patients including 78 female and 113 male were included in this study. Among them, 5 (2.6%) patients were lost to follow-up, 79 patients were still alive while 102 patients died at the last follow up. The median survival time from symptom onset to death was 33 months, as estimated by Kaplan-Meier analysis. ALS patients with lower NI exhibited to have shorter median survival time compared to the patients with high NI. Through multivariate Cox regression analysis, NI, the revised ALS functional rating scale (ALSFRS-R), diagnostic delay and age at disease onset were found to be associated with the survival of ALS patients. ConclusionOur findings indicate that NI provides a single number that seems to associate with the survival of ALS. SignificanceNI is readily available and reproducible, and it could be utilized as a potential biomarker for survival in further multicenter clinical trials in ALS.

Systematic review of the prognostic role of body mass index in amyotrophic lateral sclerosis

Studies have suggested that obesity is associated with better prognosis among individuals with various types of neurodegenerative diseases, and while some studies suggest that the same is true of amyotrophic lateral sclerosis (ALS), other works cast doubt on this conclusion. Therefore, we conducted a meta-analysis to systematically evaluate the role of body mass index in the prognosis of ALS. PubMed was systematically searched to identify eligible articles, and data on long-term survival were meta-analyzed in terms of hazard ratios (HR) with corresponding 95% confidence intervals (CI). Level of heterogeneity among studies and publication bias were estimated. A total of 17 studies with 9991 ALS patients were included in the review. Each increase of 1 kg/m2 in body mass index was associated with significantly better long-term overall survival (HR 0.95, 95%CI 0.93–0.97; p < 0.001). Obesity may also be a strong predictor of favorable long-term prognosis (HR 0.73; 95%CI 0.62–0.86; p < 0.001). Our results suggest that higher body mass index and obesity are associated with better long-term survival of ALS patients.

Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that still lacks reliable diagnostic biomarkers. This study aims to evaluate the diagnostic and prognostic potential of CSF total Tau (t-Tau), phospho-Tau (p-Tau) and p-Tau/t-Tau ratio in ALS patients using CSF neurofilament light (NFL) as the reference biomarker. Eighty-five incident ALS, 30 ALS-mimicking (AM) diseases and 51 other non-neurodegenerative diseases (ONND) were included in the study. ALS patients had higher levels of CSF t-Tau and lower p-Tau/t-Tau ratio than AM (p = 0.005 and p = 0.006) and ONND (p < 0.001). CSF t-Tau levels discriminated ALS from AM with a sensitivity of 69% and specificity of 60%, and from ONND with a sensitivity of 88% and specificity of 51%. These values were lower than the accuracy of CSF NFL in ALS (sensitivity 86% and specificity 87% in distinguishing ALS from AM and sensitivity 83% and specificity 75% from ONND); CSF t-Tau correlated with progression rate and SNIP. CSF p-Tau did not show relation with any ALS clinical features. CSF NFL significantly correlated with all considered clinical parameters. High levels of CSF t-Tau and NFL were related to poor survival. CSF t-Tau showed no reliable diagnostic significance but the relation between the high levels of CSF t-Tau and short survival suggests the potential prognostic role of this biomarker in ALS. However, CSF NFL was confirmed to be the most reliable and efficient tool for diagnosis and prediction of clinical progression and survival in ALS patients.

Association between macronutrient intake and amyotrophic lateral sclerosis prognosis

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and the nutritional state of ALS patients is associated with survival. The purpose of the present study was to investigate whether macronutrient intake at early stage of the disease was positively associated with survival and duration from symptom onset to death, tracheostomy, or non-invasive ventilation (NIV) in ALS.Methods: ALS patients diagnosed according to EI Escorial criteria were recruited from 2011 to 2016 and followed up until 2017, when they reached the endpoint of death, tracheostomy, or NIV use. Dietary intake was estimated based on a 24-hour recall conducted less than 2 years from symptom onset, and the survival time was defined as the duration from symptom onset to the endpoint.Results: ALS patients were categorized as short-term group (n=79) and long-term group (n=69) according to the mean survival time (33.03±14.01 months). Short-term survival was negatively associated with fat, protein, and meat intake, and positively associated with carbohydrate intake after adjustment for confounders. In addition, the survival time was positively associated with fat, protein, and meat intake but was not associated with carbohydrate intake.Discussion: The present study suggested that higher intake of fat and protein, particularly from meat at early stage of the disease, could prolong the survival of ALS patients. However, further clinical trials are necessary to confirm the beneficial effects of higher fat and protein intake on mortality in ALS patients.

Bulbar impairment score and survival of stable amyotrophic lateral sclerosis patients after noninvasive ventilation initiation.

There is general agreement that noninvasive ventilation (NIV) prolongs survival in amyotrophic lateral sclerosis (ALS) and that the main cause of NIV failure is the severity of bulbar dysfunction. However, there is no evidence that bulbar impairment is a contraindication for NIV. The aim of this study was to determine the effect of bulbar impairment on survival in ALS patients with NIV.ALS patients for whom NIV was indicated were included. Those patients who refused NIV were taken as the control group.120 patients who underwent NIV and 20 who refused NIV were included. The NIV group presented longer survival (median 18.50 months, 95% CI 12.62–24.38 months) than the no-NIV group (3.00 months, 95% CI 0.82–5.18 months) (p<0.001) and also in those patients with severe bulbar dysfunction (13.00 months (95% CI 9.49–16.50 months) versus 3.00 months (95% CI 0.85–5.15 months), p<0.001). Prognostic factors for ALS using NIV, adjusted for NIV failure, were severity of bulbar dysfunction (hazard ratio (HR) 0.5, 95% CI 0.92–0.97; p=0.001) and time spent with oxygen saturation measured by pulse oximetry <90% (%sleepSpO2<90) using NIV (HR 1.12, 95% CI 1.01–1.24; p=0.02).Severe bulbar impairment in ALS does not always prevent NIV from being used, but the severity of bulbar dysfunction at NIV initiation and %sleepSpO2<90 while using NIV appear to be the main prognostic factors of NIV failure in ALS.

Therapeutic effects of percutaneous endoscopic gastrostomy on survival in patients with amyotrophic lateral sclerosis: A meta-analysis.

Percutaneous endoscopic gastrostomy (PEG) is a method widely used for patients with amyotrophic lateral sclerosis (ALS); nevertheless, its effect on survival remains unclear. The purpose of this meta-analysis study was to determine the effects of PEG on survival in ALS patients. Relevant studies were retrieved from PubMed, EmBase, and the Cochrane Library databases, from inception to June 2017. Studies comparing PEG with other procedures in ALS patients were included. Odds ratios (ORs) in a random-effects model were used to assess the survival at different follow-up periods. Briefly, ten studies involving a total of 996 ALS patients were included. Summary ORs indicated that PEG administration was not associated with 30-day (OR = 1.59; 95%CI 0.93–2.71; P = 0.092), 10-month (OR = 1.25; 95%CI 0.72–2.17; P = 0.436), and 30-month (OR = 1.28; 95% CI 0.77–2.11; P = 0.338) survival rates, while they showed a beneficial effect in 20-month survival rate (OR = 1.97; 95%CI 1.21–3.21; P = 0.007). The survival rate was significantly prominent in reports published before 2005, and in studies with a retrospective design, sample size <100, mean age <60.0 years, and percentage male ≥50.0%. To sum up, these findings suggested that ALS patients administered with PEG had an increased 20-month survival rates, while there was no significant effect in 30-day, 10-month, and 30-month survival rates.

Greater axonal persistent sodium currents correlate with more rapid disease progression in patients with amyotrophic lateral sclerosis

Background: Two types of abnormalities of axonal ionic currents have been reported in amyotrophic lateral sclerosis (ALS): increased persistent sodium currents and reduced potassium currents in motor axons, both of which lead to axonal hyperexcitability and thereby generation of fasciculations. Previous study showed that greater axonal persistent sodium currents and early depolarizing sign in the recovery cycle could correlate with shorter survival in ALS patients.

Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis.

To evaluate serum creatine kinase (CK) levels of amyotrophic lateral sclerosis (ALS) patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients. We analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI), serum creatinine (Cr), and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan-Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS. Baseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20-2,574 U/L), and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169) versus 117 (111) U/L, p < 0.001] and in patients with limb onset ALS than with bulbar onset ALS (p < 0.001). CK levels were also correlated with serum Cr (p = 0.011) and the spontaneous potential score of electromyography (EMG) (p = 0.037) but not correlated with age (p = 0.883), disease duration (p = 0.116), or BMI (p = 0.481). Log CK was independently correlated with survival of ALS patients (HR = 0.457, 95% confidence interval 0.221-0.947, p = 0.035) after adjusting for age, sex, site of onset, serum Cr, and BMI. Serum CK levels of ALS patients were correlated with sex, site of onsite, serum Cr, and spontaneous activity in EMG. Serum CK could be an independent prognostic factor for survival of ALS patients.

Adipokines, C-reactive protein and Amyotrophic Lateral Sclerosis \u2013 results from a population- based ALS registry in Germany

To investigate the associations of leptin, adiponectin and high-sensitive (hs) C-reactive protein (CRP) with risk and prognosis of amyotrophic lateral sclerosis (ALS). Data from a population-based case-control study in Southern Germany (10/2010–6/2014) of 289 ALS patients (mean age of 65.7 (SD 10.5) years, 59.5% men) and 506 controls were included. During median follow-up of 14.5 months of 279 ALS patients 104 (53.9% men, 68.9 (10.3) years) died. Serum samples were measured for leptin, adiponectin and hs-CRP. Conditional logistic regression was used to estimate ALS risk. Survival models were used to appraise the prognostic value. ALS patients were characterized by lower levels of school education, BMI and smoking prevalence. Adjusted for covariates, leptin was inversely associated with ALS risk (top vs. bottom quartile: OR 0.49; 95% CI 0.29–0.80), while for adiponectin a positive association was found (OR 2.89; 95% CI 1.78–4.68). Among ALS patients increasing leptin concentrations were associated with longer survival (p for trend 0.002), while for adiponectin no association was found (p for trend 0.55). For hs-CRP no association was found. Leptin and adiponectin, two key hormones regulating energy metabolism, were strongly and independently related with ALS risk. Leptin levels were further negatively related with overall survival of ALS patients.