Survival In Amyotrophic Lateral Sclerosis Patients Research Articles

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.

Riluzole: real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the commonest form of motor neuron disease and is a fatal, degenerative, multisystem disorder affecting upper and/or lower motor neurons in the motor cortex, brain stem, and spinal cord. ALS is characterized by progressive atrophy of associated bulbar, limb, thoracic, and abdominal muscles and supporting cells manifesting in a range of muscular symptoms such as weakness and wasting and eventual paralysis; the majority of patients will die from respiratory failure within 2–5 years of onset. Riluzole, a synthetic benzothiazole drug with glutamine antagonist activity, is indicated for the treatment of patients with ALS and is the only drug that has been shown to slow the course of the disease and extend survival in ALS patients. The original analyses, and subsequent meta-analyses, of data obtained from randomized controlled trials (RCTs) suggest that riluzole typically extends survival by 2–3 months and increases the chance of an additional year of survival by ~9%. However, published real-world evidence (RWE) from 10 clinical ALS databases indicates that riluzole therapy may afford much greater extension of survival, and improvements in median survival times of more than 19 months have been reported in the overall ALS patient population. This article will review the available data from RCTs and RWE on riluzole therapy.

ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.

Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high-resolution diffusion-weighted and T1-weighted images were acquired at the first visit to the outpatient clinic. Next, each of the patients was monitored carefully and survival time to death was recorded. Patients were labeled as short, medium or long survivors, based on their recorded time to death as measured from the time of disease onset. In the deep learning procedure, the total group of 135 patients was split into a training set for deep learning (n = 83 patients), a validation set (n = 20) and an independent evaluation set (n = 32) to evaluate the performance of the obtained deep learning networks. Deep learning based on clinical characteristics predicted survival category correctly in 68.8% of the cases. Deep learning based on MRI predicted 62.5% correctly using structural connectivity and 62.5% using brain morphology data. Notably, when we combined the three sources of information, deep learning prediction accuracy increased to 84.4%. Taken together, our findings show the added value of MRI with respect to predicting survival in ALS, demonstrating the advantage of deep learning in disease prognostication.

The Prognostic Role of Obstructive Sleep Apnea at the Onset of Amyotrophic Lateral Sclerosis

Background/Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of central and peripheral motor neurons. Some studies have found discordant data in the presence of sleep apnea in ALS patients. An obstructive component also occurs with upper airways hypotonia and muscle weakness that may result in an excessive reduction of airway lumen, leading to obstructive sleep apnea (OSA). The aim of this study was to assess the role of obstructive apneic events at disease onset in the ALS prognosis. Methods: A longitudinal retrospective study was conducted on 42 clinically diagnosed ALS patients. The study population was divided into 2 groups according to their obstructive apnea/hypopnea index (AHIo): group 1 consisted of 20 patients with an AHIo ≥5 and group 2 consisted of 22 patients with an AHIo <5. Both groups were compared with regard to demographic, polygraphic, and respiratory function parameters as well as ALS characteristics (bulbar onset, time between onset and first check-up, time between diagnosis and first check-up, time between first check-up and death or tracheostomy). Results: The mean survival in ALS patients with an AHIo ≥5 was significantly shorter than in ALS without OSA (p = 0.0237). The sniff nasal inspiratory pressure test was significantly correlated with AHIo, time of oxyhemoglobin saturation below 90% and the oxyhemoglobin desaturation index (p < 0.0001). Conclusions: Our study highlights the importance of an early diagnosis of OSA in ALS patients, allowing the identification of ALS patients with an OSA phenotype (AHIo ≥5), who are characterized by a worse prognosis.

Executive dysfunction and survival in patients with amyotrophic lateral sclerosis: Preliminary report from a Serbian centre for motor neuron disease

Our objective was to determine whether the presence of executive dysfunction in non-demented amyotrophic lateral sclerosis (ALS) patients might affect the longevity of survival. Forty-eight consecutive non-demented ALS patients (mean age = 52.93 ± 12.37) were followed for five years. All patients underwent clinical and neuropsychological assessments at baseline visit. Further, a yearly follow-up check for associated dementia (ALS-Dem) was completed and the time of death was recorded, when applicable. Executive deficits were shown in 49.5% of ALS patients, with the most striking differences found on the tests of verbal fluency (both phonemic and category, p < 0.01); as well as inefficient strategy on a working memory test (p < 0.05); as on the more demanding levels of the planning and problem solving task (p < 0.01). It appears that the baseline executive status might predict survival in ALS (p = 0.075), and the patients presenting executive dysfunction could have up to three times greater risk of death, after adjustment by several potential confounding factors. In conclusion, this study suggests that executive dysfunction could potentially influence survival in ALS patients. The cognitive testing might give us important clues about the prognosis of the disease. Further studies with larger sample size are necessary.

Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis.

Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs.

A single blind randomized controlled clinical trial of mexiletine in amyotrophic lateral sclerosis: Efficacy and safety of sodium channel blocker phase II trial

Fasciculations are characteristic features of amyotrophic lateral sclerosis (ALS), and suggest motor nerve hyperexcitability. Recent reports have shown that an increase in persistent nodal sodium current is associated with shorter survival in ALS patients. This objective of this trial is to study the efficacy and safety of mexiletine, a sodium channel blocker, for ALS. Sixty eligible participants were randomly allocated (1:1) to riluzole 100 mg or riluzole plus mexiletine 300 mg. The primary endpoint was change in the revised ALS functional rating scale (ALSFRS-R) scores during six months. We also monitored strength-duration time constant (SDTC, a measure of persistent sodium current) in median motor axons. Results showed that during six months of treatment, changes in the ALSFRS-R score and SDTC were –7.0 ± 7.1 and –0.04 ± 0.1, respectively, in the riluzole group and –6.9 ± 6.4 and 0.04 ± 0.1, respectively, in the mexiletine group (p = 0.96 and 0.049). Adverse events amounted 20% in the riluzole and 33% in the mexiletine groups. In conclusion, the results suggest that daily 300 mg mexiletine has no effects on axonal sodium current and ALSFRS-R deterioration in ALS. We have to attempt another trial using a higher dose of mexiletine or other agents to suppress sodium currents and ALS progression in the future.

Factors Predicting Survival in ALS Patients - Data from a Population-Based Registry in Rhineland-Palatinate, Germany

Background: The possibility to survive with amyotrophic lateral sclerosis (ALS) varies considerably and survival extends from a few months to several years. A number of demographic and clinical factors predicting survival have been described; however, existing data are conflicting. We intended to predict patient survival in a population-based prospective cohort of ALS patients from variables known up to the time of diagnosis. Methods: Incident ALS patients diagnosed within three consecutive years were enrolled and regularly followed up. Candidate demographic and disease variables were analysed for survival probability using the Kaplan-Meier method. The Cox proportional hazard regression model was used to assess the influence of selected predictor variables on survival prognosis. Results: In the cohort of 193 patients (mean age 65.8, standard deviation 10.2 years), worse prognosis was independently predicted by older age, male gender, bulbar onset, probable or definite ALS according to El Escorial criteria, shorter interval between symptom onset and diagnosis, lower Functional Rating Scale, diagnosis of frontotemporal dementia, and living without a partner. Conclusions: Taking into account these predictor variables, an approximate survival prognosis of individual ALS patients at diagnosis seems feasible.

Amyotrophic Lateral Sclerosis: Impact of Pulmonary Follow-Up and Mechanical Ventilation on Survival. A Study of 114 Cases

ObjectiveTo study the impact of ventilatory management and treatment on the survival of patients with amyotrophic lateral sclerosis (ALS). MethodRetrospective analysis of 114 consecutive patients admitted to a general hospital, evaluating demographic data, type of presentation, clinical management, treatment with mechanical ventilation and survival. Statistics: descriptive and Kaplan–Meier estimator. ResultsSixty-four patients presented initial bulbar involvement. Overall mean survival after diagnosis was 28.0 months (95%CI, 21.1–34.8). Seventy patients were referred to the pulmonary specialist (61.4%) and 43 received non-invasive ventilation (NIV) at 12.7 months (median) after diagnosis. Thirty-seven patients continued to receive NIV with no subsequent invasive ventilation. The mean survival of these patients was 23.3 months (95%CI, 16.7–28.8), higher in those without bulbar involvement, although below the range of significance. Survival in the 26 patients receiving programmed NIV was higher than in the 11 patients in whom this was indicated without prior pulmonary assessment (considered following diagnosis, P<.012, and in accordance with the start of ventilation, P<.004). A total of 7 patients were treated invasively; mean survival in this group was 72 months (95%CI, 14.36–129.6), median 49.6±17.5 (95%CI, 15.3–83.8), and despite the difficulties involved in home care, acceptance and tolerance was acceptable. ConclusionsLong-term mechanical ventilation prolongs survival in ALS. Programmed pulmonary assessment has a positive impact on survival of ALS patients and is key to the multidisciplinary management of this disease.

Dynamic principle for designing antagonistic/agonistic molecules for EphA4 receptor, the only known ALS modifier.

Additional to involvement in diverse physiological and pathological processes such as axon regeneration, synaptic plasticity, and cancers, EphA4 receptor has been recently identified as the only amyotrophic lateral sclerosis (ALS) modifier. Previously, we found that two small molecules bind the same EphA4 channel at almost equivalent affinities but mysteriously trigger opposite signaling outputs: one activated but another inhibited. Here, we determined the solution structure of the 181-residue EphA4 LBD, which represents the first for 16 Eph receptors. Further NMR dynamic studies deciphered that the agonistic and antagonistic effects of two small molecules are dynamically driven, which are achieved by oppositely modulating EphA4 dynamics. Consequently, in design of drugs to target EphA4, the dynamic requirement also needs to be satisfied in addition to the classic criteria. For example, to increase the survival of ALS patients by inhibiting EphA4, the drugs must enhance, or at least not suppress, the EphA4 dynamics.

Frontal lobe function and behavioral changes in amyotrophic lateral sclerosis: a study from Southwest China.

Despite growing interest, the frequency and characteristics of frontal lobe functional and behavioral deficits in Chinese people with amyotrophic lateral sclerosis (ALS), as well as their impact on the survival of ALS patients, remain unknown. The Chinese version of the frontal assessment battery (FAB) and frontal behavioral inventory (FBI) were used to evaluate 126 sporadic ALS patients and 50 healthy controls. The prevalence of frontal lobe dysfunction was 32.5%. The most notable impairment domain of the FAB was lexical fluency (30.7%). The binary logistic regression model revealed that an onset age older than 45 years (OR 5.976, P = 0.002) and a lower educational level (OR 0.858, P = 0.002) were potential determinants of an abnormal FAB. Based on the FBI score, 46.0% of patients showed varied degrees of frontal behavioral changes. The most common impaired neurobehavioral domains were irritability (25.4%), logopenia (20.6%) and apathy (19.0%). The binary logistic regression model revealed that the ALS Functional Rating Scale-Revised scale score (OR 0.127, P = 0.001) was a potential determinant of an abnormal FBI. Frontal functional impairment and the severity of frontal behavioral changes were not associated with the survival status or the progression of ALS by the cox proportional hazard model and multivariate regression analyses, respectively. Frontal lobe dysfunction and frontal behavioral changes are common in Chinese ALS patients. Frontal lobe dysfunction may be related to the onset age and educational level. The severity of frontal behavioral changes may be associated with the ALSFRS-R. However, the frontal functional impairment and the frontal behavioral changes do not worsen the progression or survival of ALS.

Esclerosis lateral amiotrófica: impacto del seguimiento neumológico y ventilación mecánica en la supervivencia. Experiencia en 114 casos

ObjectiveTo study the impact of ventilatory management and treatment on the survival of patients with amyotrophic lateral sclerosis (ALS). MethodRetrospective analysis of 114 consecutive patients admitted to a general hospital, evaluating demographic data, type of presentation, clinical management, treatment with mechanical ventilation and survival. Statistics: descriptive and Kaplan-Meier estimator. ResultsSixty four patients presented initial bulbar involvement. Overall mean survival after diagnosis was 28.0 months (95%CI, 21.1-34.8). Seventy patients were referred to the pulmonary specialist (61.4%) and 43 received non-invasive ventilation (NIV) at 12.7 months (median) after diagnosis. Thirty seven patients continued to receive NIV with no subsequent invasive ventilation. The mean survival of these patients was 23.3 months (95%CI, 16.7-28.8), higher in those without bulbar involvement, although below the range of significance. Survival in the 26 patients receiving programmed NIV was higher than in the 11 patients in whom this was indicated without prior pulmonary assessment (considered following diagnosis, P<.012, and in accordance with the start of ventilation, P<.004). A total of 7 patients were treated invasively; mean survival in this group was 72 months (95%CI, 14.36-129.6), median 49.6±17.5 (95%CI, 15.3-83.8), and despite the difficulties involved in home care, acceptance and tolerance was acceptable. ConclusionsLong-term mechanical ventilation prolongs survival in ALS. Programmed pulmonary assessment has a positive impact on survival of ALS patients and is key to the multidisciplinary management of this disease.

Blood Volatile Organic Compounds as Potential Biomarkers for Amyotrophic Lateral Sclerosis: an Animal Study in the SOD1 G93A Mouse

Amyotrophic lateral sclerosis (ALS) is a rapid progressive motor neuron disease. Currently, there are no specific or reliable biomarkers for the diagnosis of this disease, and there are no effective medical treatments. The early diagnosis and treatment of this disease has the potential to prolong the survival of ALS patients, but typically, approximately 1 year passes between the onset of symptoms and the diagnosis of this disease. Therefore, there is an urgent need to find specific biomarkers to enable early diagnosis and therapeutic intervention in this disease. Analyzing the volatile organic compounds (VOCs) present in the blood and exhaled breath is a useful and convenient approach for investigating potential biomarkers. In this study, we examined the VOCs present in blood samples from copper zinc superoxide dismutase 1 (SOD1) glycine to alanine mutation at position 93 (G93A) mice to determine whether a specific biomarker pattern exists in these transgenic mice. Blood samples from ALS mice and their age-matched littermates were analyzed using gas chromatography-mass spectrometry. A total of 12 independent compounds associated with oxidative stress were identified at the early stage of disease. The data show that there is a specific pattern of blood VOCs in ALS mice that could potentially be used as biomarkers that could improve the diagnosis of this disease. Furthermore, these compounds could also potentially be used to monitor the response to neuroprotective agents and to help us better understand the underlying mechanisms of ALS.

Non-invasive ventilation effectiveness and the effect of ventilatory mode on survival in ALS patients

Non-invasive ventilation (NIV) prolongs survival in amyotrophic lateral sclerosis (ALS), but there are no data with which to compare the effectiveness of the different ventilator modes – volume (Vol-NIV) or pressure-cycled (Pres-NIV) ventilation – in ALS. We aimed to determine whether the ventilatory mode has an effect on ventilation effectiveness and survival of ALS patients using NIV. We used a retrospective study that included all ALS patients for whom NIV was indicated in two referral units: one using Vol-NIV and the other using Pres-NIV. Demographic, functional and nocturnal gas exchange parameters at NIV initiation were recorded. Eighty-two ALS patients ventilated using Pres-NIV and 62 using Vol-NIV were included. No differences were found in survival from NIV initiation between Vol-NIV (median 15.00 (7.48–22.41) months) and Pres-NIV (median 15.00 (10.25–19.75) months, p = 0.533) patients. Effective NIV was achieved in 72.41% Vol-NIV patients and in 48.78% Pres-NIV patients (p < 0.001). Ventilator mode (OR 12.066 (4.251–32.270), p < 0.001) and severity of bulbar dysfunction (OR 1.07 (1.011–1.133), p = 0.02) were the variables correlated with effective NIV. In conclusion, although Vol-NIV provides more effective ventilation, Vol-NIV and Pres-NIV present similar survival in ALS. Effectiveness of NIV is related to the severity of bulbar dysfunction.

S16-2. Complex fasciculation potentials and survival prognosis in amyotrophic lateral sclerosis

Awaji diagnostic criteria for amyotrophic lateral sclerosis (ALS) revalued fasciculation potential (FP), preferentially of a complex form, as equivalent to fibrillation potentials or positive sharp waves. The aim of the study was to investigate the relationship of FPs between clinical features and survival in ALS patients. Eighty-five sporadic ALS patients were recruited. Concentric needle EMG was performed at the time of diagnosis for five to seven muscles in each patient. FPs were visually analyzed, and FP > 4 phases was defined as complex FP. The patients were followed until endpoints (death or tracheostomy or ventilator-use). We analyzed the relationship between FPs and other spontaneous EMG discharges, and the correlation of FPs with survival length. The complex FPs were observed in 47 patients in at least one muscle, more frequently in the upper limb muscles irrespective of onset region, and in the muscles with normal strength or mild wasting. The amount of complex FPs was significantly associated with shorter survival. The median survival was 3.1 and 1.5 years for patients without and with complex FPs, respectively ( p + 0.0017). Complex FPs might be an independent prognostic predictor for short survival in ALS.

Adipose Tissue Distribution Predicts Survival in Amyotrophic Lateral Sclerosis

Backgroundamyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to death within a few years after diagnosis. Malnutrition and weight loss are frequent and are indexes of poor prognosis. Total body fat and fat distribution have not been studied in ALS patients.ObjectivesOur aim was to describe adipose tissue content and distribution in ALS patients.DesignWe performed a cross-sectional study in a group of ALS patients (n = 62, mean disease duration 22 months) along with age and gender matched healthy controls (n = 62) using a MRI-based method to study quantitatively the fat distribution.ResultsTotal body fat of ALS patients was not changed as compared with controls. However, ALS patients displayed increased visceral fat and an increased ratio of visceral to subcutaneous fat. Visceral fat was not correlated with clinical severity as judged using the ALS functional rating scale (ALS-FRS-R), while subcutaneous fat in ALS patients correlated positively with ALS-FRS-R and disease progression. Multiple regression analysis showed that gender and ALS-FRS-R, but not site of onset, were significant predictors of total and subcutaneous fat. Increased subcutaneous fat predicted survival in male patients but not in female patients (p<0.05).ConclusionsFat distribution is altered in ALS patients, with increased visceral fat as compared with healthy controls. Subcutaneous fat content is a predictor of survival of ALS patients.