***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objectives and methods : Compared to age-matched healthy controls ( n = 55 ) , patients with amyotrophic lateral sclerosis ( ALS ) ( n = 26 ) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 ( % CoQ10 ) in total plasma coenzyme Q10 , a significantly decreased level of plasma uric acid , and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids ( FFA ) . Therefore , the efficacy of edaravone , a radical scavenger , in these ALS patients was examined . Results and discussion : Among 26 ALS patients , 17 received edaravone ( 30 mg/day , one to four times a week ) for at least 3 months , and 13 continued for 6 months . Changes in revised ALS functional rating scale ( ALSFRS-R ) were significantly smaller in these patients than in edaravone-untreated ALS patients ( n = 19 ) . Edaravone administration significantly reduced excursions of more than one st and ard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids , plasma markers of tissue oxidative damage , in the satisfactory progress group ( ΔALSFRS-R ≥ 0 ) as compared to the ingravescent group ( ΔALSFRS-R < −5 ) . Edaravone treatment increased plasma uric acid , suggesting that it is an effective scavenger of peroxynitrite . However , edaravone administration did not decrease % CoQ10 . Therefore , combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients Amyotrophic lateral sclerosis ( ALS ) is a neurodegenerative disease that currently has no cure . At present , the only approved treatment for ALS is Riluzole , a glutamate release blocker that improves life expectancy by 3–6 months . ALS-Endotherapia ( GEMALS ) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment . A total of 31 patients with ALS were assessed in the current study . Deceleration of the disease was observed in 83.87 % ( P<0.0001 ) of patients and mean life expectancy was increased by 38 months . Motor functions , including breathing , walking , salivation , speech , swallowing and writing , were also improved in patients treated with GEMALS . The results of the present study demonstrate that long-term treatment with GEMALS  has a curative effect in patients with ALS . Furthermore , the overall effectiveness of GEMALS was assessed using the ALS Assessment Question naire . The score improvement was 76.2 and 100 % for men and women , respectively ( P<0.0001 ) , compared with the worldwide reference score . The present study provides a promising basis for the use of GEMALS as a therapeutic treatment for patients with ALS ; however , these results must be confirmed in a double-blinded and r and omized clinical trial The ALS Functional Rating Scale ( ALSFRS ) is a vali date d rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis ( ALS ) . One weakness of the ALSFRS as originally design ed was that it granted disproportionate weighting to limb and bulbar , as compared to respiratory , dysfunction . We have now vali date d a revised version of the ALSFRS , which incorporates additional assessment s of dyspnea , orthopnea , and the need for ventilatory support . The Revised ALSFRS ( ALSFRS-R ) retains the properties of the original scale and shows strong internal consistency and construct validity . ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile , indicating that the quality of function is a strong determinant of quality of life in ALS Amyotrophic lateral sclerosis ( ALS ) is a rare disease involving selective and progressive degeneration and disappearance of motor neurons . Oxidative stress is believed to contribute to its pathogenesis . We have investigated the efficacy and safety of edaravone , a free radical scavenger previously approved for treatment of acute cerebral infa rct ion , in ALS patients . Within an open trial design , 20 subjects with ALS received either 30 mg ( 5 subjects ) or 60 mg ( 15 subjects ) of edaravone via intravenous drip once per day . Two weeks of administration was followed by a two‐week observation period . This four‐week cycle was repeated six times . The primary endpoint was the change in the revised ALS functional rating scale ( ALSFRS‐R ) score , while the secondary endpoint was 3‐nitrotyrosine ( 3NT ) level in cerebrospinal fluid ( CSF ) . Efficacy was evaluated in the 60 mg group . During the six‐month treatment period , the decline in the ALSFRS‐R score ( 2.3±3.6 points ) was significantly less than that in the six months prior to edaravone administration ( 4.7±2.1 points ) ; the difference between the two was 2.4±3.5 points ( Wilcoxon signed rank test , p = 0.039 ) . In almost all patients , CSF 3NT , a marker for oxidative stress , was markedly reduced to almost undetectable levels at the end of the six‐month treatment period . Data from the present study suggest that edaravone is safe and may delay the progression of functional motor disturbances by reducing oxidative stress in ALS patients Edaravone is a free-radical scavenger , an agent being widely used for cerebral ischemia in Japan . To evaluate its efficacy for possible treatment of amyotrophic lateral sclerosis ( ALS ) , we performed a r and omized blind trial in ALS model mice . After identification of the clinical onset in each female G93A mutant SOD1 transgenic mouse , we intraperitoneally administered multiple doses of edaravone to the mice and observed their motor symptoms . We also counted the number of lumbar motoneurons , determined the 3-nitrotyrosine/tyrosine ratio , and evaluated the abnormal SOD1 aggregation in the spinal cord at the 10th day after the edaravone injection . Edaravone significantly slowed the motor decline of the transgenic mice . The remaining motoneurons were significantly preserved in the higher-dose edaravone-administered group , and the 3-nitrotyrosine/tyrosine ratios were reduced dose-dependently . Intriguingly , the area of abnormal SOD1 deposition in the spinal cord was significantly decreased in the higher-dose edaravone-administered group . Our results indicate that edaravone was effective to slow symptom progression and motor neuron degeneration in the ALS model mice . These favorable actions might be attributable to the yet unidentified mechanism responsible for reducing the deposition of mutant SOD1 OBJECTIVES To test the utility of a new , easy to administer instrument for assessing activities of daily living in patients with amyotrophic lateral sclerosis ( ALS ) , to vali date its accuracy , and to assess its ability to record disease progression in patients with ALS against other functional scales , quantitative isometric muscle testing , and global assessment scales . DESIGN Serial assessment s of patients who presented to four ALS treatment centers in two multicenter studies . PATIENTS Study 1 ( cross-sectional ) evaluated 75 consecutive patients who presented to four ALS treatment centers during a 2-month period . Study 2 ( longitudinal ) evaluated the progression of 53 patients who were enrolled in a multicenter , phase I-II clinical trial of recombinant human ciliary neurotrophic factor for treatment of ALS . OUTCOME MEASURES The ALS Functional Rating Scale ( ALSFRS ) was compared with quantitative myometry and with other measures of daily function in patients with ALS both cross-sectionally and longitudinally . RESULTS The first study of 75 patients evaluated the internal consistency , the test-retest reliability , and the construct validity of the ALSFRS . Internal consistency and test-retest reliability were high . Patient self-rating of upper- and lower-extremity-dependent tasks were highly correlated with measures of upper- and lower-extremity strength , respectively . Thus , the ALSFRS has good construct validity . In the second study , ALSFRS scores declined in t and em with deterioration in motor and pulmonary function , indicating its sensitivity to change . CONCLUSIONS The ALSFRS is a useful instrument for evaluation of functional status and functional change in patients with ALS . Its results are in close agreement with objective measures of muscle strength and pulmonary function . The ALSFRS may be used as a screening measure for entry into clinical trials , as a surrogate measure of function in situations in which muscle strength can not be measured directly , or as an adjunct to myometry Objective : To replicate the beneficial effect of brain-derived neurotrophic factor ( BDNF ) in 1,135 ALS patients in a multicenter trial . Background : In a phase I through II study , BDNF appeared to increase survival and retard loss of pulmonary function in ALS patients . Methods : Patients were r and omized to placebo , or 25 or 100 μg/kg BDNF for 9 months . Results : The study failed to show benefit of BDNF treatment for the primary end points . Survival in patients treated with 25 μg/kg BDNF was identical to placebo , but there was a trend toward increased survival in the 100-μg/kg group . As a whole , survival was better than anticipated when planning the study . The 9-month probability of survival was approximately 85 % across all groups . This diminished the power of the study . Among the 60 % of patients with baseline forced vital capacity of ≤91 % , survival was significantly greater for 100 μg/kg BDNF versus placebo . For the 20 % of patients treated with 100 μg/kg BDNF reporting altered bowel function as an adverse effect of BDNF in the first 2 weeks of dosing , defined as BDNF “ responders , ” 9-month survival was significantly better than for placebo ( 97.5 % versus 85 % ) . Conclusions : Although the primary end point analysis failed to demonstrate a statistically significant survival effect of BDNF in ALS , post hoc analyses showed that those ALS patients with early respiratory impairment and those developing altered bowel function showed statistically significant benefit . Further clinical trials of BDNF using either intrathecal delivery or high-dose subcutaneous administration are in progress Abstract Our objective was to explore the efficacy and safety of edaravone in amyotrophic lateral sclerosis ( ALS ) patients with a Japan ALS severity classification of Grade 3 . In a 24-week , double-blind , r and omized study , 25 patients who met all of the following criteria were enrolled : Japan ALS severity classification Grade 3 ; definite , probable , or probable-laboratory supported ALS ( El Escorial/revised Airlie House ) ; forced vital capacity ( % FVC ) ≥60 % ; duration of disease ≤3 years at consent ; and change in the revised ALS functional rating scale ( ALSFRS-R ) score of –1 to –4 points during the 12-week pre-observation period . Patients received edaravone ( n = 13 ) or placebo ( n = 12 ) for six cycles . The efficacy outcome was change in the ALSFRS-R score . The least-squares mean change in the ALSFRS-R score ± st and ard error during the 24-week treatment was –6.52 ± 1.78 in the edaravone group and –6.00 ± 1.83 in the placebo group ; the difference of –0.52 ± 2.46 was not statistically significant ( p = 0.835 ) . Incidence of adverse events was 92.3 % ( 12/13 ) in the edaravone group and 100.0 % ( 12/12 ) in the placebo group . There was no intergroup difference in the changes in the ALSFRS-R score . The incidences of adverse events were similar in the two groups 
    Output:
    
Conclusion Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients , with no severe adverse effects .