Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the commonest cause of death, usually within two to five ...years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the first update of a review first published in 2009.
The primary objective of the review is to examine the efficacy of mechanical ventilation (tracheostomy and non-invasive ventilation) in improving survival in ALS. The secondary objectives are to examine the effect of mechanical ventilation on functional measures of disease progression and quality of life in people with ALS; and assess adverse events related to the intervention.
We searched The Cochrane Neuromuscular Disease Group Specialized Register (1 May 2012), CENTRAL (2012, Issue 4), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), CINAHL Plus (January 1937 to April 2012), and AMED (January 1985 to April 2012). We also searched for ongoing studies on ClinicalTrials.gov.
Randomised and quasi-randomised controlled trials involving non-invasive or tracheostomy assisted ventilation in participants with a clinical diagnosis of amyotrophic lateral sclerosis, independent of the reported outcomes. We planned to include comparisons with no intervention or the best standard care.
For the original review, four authors independently selected studies for assessment and two authors reviewed searches for this update. All authors extracted data independently from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from included studies.
For the original Cochrane review, the review authors identified and included two randomised controlled trials involving 54 participants with ALS receiving non-invasive ventilation. There were no new randomised or quasi-randomised controlled trials at this first update.Incomplete data were published for one study and we contacted the trial authors who were not able to provide the missing data. Therefore, the results of the review were based on a single study of 41 participants that compared non-invasive ventilation with standard care. It was a well conducted study with low risk of bias.The study showed that the overall median survival was significantly different between the group treated with non-invasive ventilation and the standard care group. The median survival in the non-invasive ventilation group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% CI 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, the survival and quality of life benefit was much more in the subgroup with normal to moderately impaired bulbar function (20 participants); median survival was 205 days longer (216 days in NIV group versus 11 days in the standard care group, P = 0.0059). Non-invasive ventilation did not prolong survival in participants with poor bulbar function (21 participants), although it showed significant improvement in the mean symptoms domain of the Sleep Apnoea Quality of Life Index but not in the Short Form-36 Health Survey Mental Component Summary score. Neither trial reported clinical data on intervention related adverse effects.
Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Future studies should examine the health economics of NIV and factors influencing access to NIV. We need to understand the factors, personal and socioeconomic, that determine access to NIV.
Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neurodegenerative disease. Without mechanical ventilation, death from respiratory failure usually follows within two to ...five years of the onset of symptoms.
To examine the efficacy of mechanical ventilation (tracheostomy and non-invasive ventilation) in improving survival, on disease progression and quality of life in amyotrophic lateral sclerosis.
We searched The Cochrane Neuromuscular Disease Group Trials Specialized Register (December 8 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (January 1966 to December 2008), EMBASE (January 1947 to December 2008), CINAHL Plus (January 1937 to December 2008), and AMED (January 1985 to December 2008). We also searched for ongoing studies on clinicaltrials.gov.
Randomised and quasi-randomised controlled trials involving non-invasive or tracheostomy assisted ventilation in participants with a clinical diagnosis of amyotrophic lateral sclerosis.
Four authors independently selected studies for assessment. All authors extracted data independently from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible.
Two randomised controlled trials involving 54 participants receiving non-invasive ventilation were identified and included. Incomplete data were published for one study and we contacted the trial authors who were not able to provide the missing data. Therefore the results of the review were based on a single study of 41 participants. The study showed that the overall median survival in the whole cohort after initiation of assisted ventilation was significantly different between the non-invasive ventilation and standard care groups (P = 0.0062) with a median survival for the non-invasive ventilation group patients of 48 days longer than the standard care group participants. Non-invasive ventilation significantly improved survival and quality of life in the subgroup with normal to moderately impaired bulbar function. Non-invasive ventilation did not prolong survival in patients with poor bulbar function although it showed significant improvement in the mean symptoms domain of the sleep apnoea quality-of-life index but not in the Short Form-36 quality of life mental component summary score .
Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment.
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the most common cause of death, which usually ...occurs within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the second update of a review first published in 2009.
To assess the effects of mechanical ventilation (tracheostomy-assisted ventilation and non-invasive ventilation (NIV)) on survival, functional measures of disease progression, and quality of life in ALS, and to evaluate adverse events related to the intervention.
We searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL Plus, and AMED on 30 January 2017. We also searched two clinical trials registries for ongoing studies.
Randomised controlled trials (RCTs) and quasi-RCTs involving non-invasive or tracheostomy-assisted ventilation in participants with a clinical diagnosis of ALS, independent of the reported outcomes. We included comparisons with no intervention or the best standard care.
For the original review, four review authors independently selected studies for assessment. Two review authors reviewed searches for this update. All review authors independently extracted data from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from the included studies.
For the original Cochrane Review, the review authors identified two RCTs involving 54 participants with ALS receiving NIV. There were no new RCTs or quasi-RCTs at the first update. One new RCT was identified in the second update but was excluded for the reasons outlined below.Incomplete data were available for one published study comparing early and late initiation of NIV (13 participants). We contacted the trial authors, who were not able to provide the missing data. The conclusions of the review were therefore based on a single study of 41 participants comparing NIV with standard care. Lack of (or uncertain) blinding represented a risk of bias for participant- and clinician-assessed outcomes such as quality of life, but it was otherwise a well-conducted study with a low risk of bias.The study provided moderate-quality evidence that overall median survival was significantly different between the group treated with NIV and the standard care group. The median survival in the NIV group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% confidence interval 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, in the subgroup with normal to moderately impaired bulbar function (20 participants), median survival was 205 days longer (216 days in the NIV group versus 11 days in the standard care group, P = 0.0059), and quality of life measures were better than with standard care (low-quality evidence). In the participants with poor bulbar function (21 participants), NIV did not prolong survival or improve quality of life, although there was significant improvement in the mean symptoms domain of the Sleep Apnea Quality of Life Index by some measures. Neither trial reported clinical data on intervention-related adverse effects.
Moderate-quality evidence from a single RCT of NIV in 41 participants suggests that it significantly prolongs survival, and low-quality evidence indicates that it improves or maintains quality of life in people with ALS. Survival and quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Adverse effects related to NIV should be systematically reported, as at present there is little information on this subject. More RCT evidence to support the use of NIV in ALS will be difficult to generate, as not offering NIV to the control group is no longer ethically justifiable. Future studies should examine the benefits of early intervention with NIV and establish the most appropriate timing for initiating NIV in order to obtain its maximum benefit. The effect of adding cough augmentation techniques to NIV also needs to be investigated in an RCT. Future studies should examine the health economics of NIV. Access to NIV remains restricted in many parts of the world, including Europe and North America. We need to understand the factors, personal and socioeconomic, that determine access to NIV.
Maximal expiratory mouth pressure is a well established test that is used to assess expiratory muscle strength. However, low values are difficult to interpret, as they may result from technical ...difficulties in performing the test, particularly in patients with facial muscle weakness or bulbar dysfunction. We hypothesized that measuring the gastric pressure during a cough, a natural maneuver recruiting the expiratory muscles, might prove to be a useful additional test in the assessment of expiratory muscle function. Mouth expiratory and cough gastric pressures were measured in 99 healthy volunteers to obtain normal values and in 293 patients referred for respiratory muscle assessment to compare the two measurements. Between-occasion within-subject coefficient of variation, assessed in 24 healthy volunteers, was 10.3% for mouth pressure and 6.9% for cough. Mean +/- SD cough gastric pressure for normal males was 214.4 +/- 42.2 and 165.1 +/- 34.8 cm H2O for females. In 171 patients deemed weak by a low mouth expiratory pressure, 42% had a normal cough gastric pressure. In 105 patients deemed weak by a low cough gastric pressure, 5.7% had a normal expiratory mouth pressure. Low maximal expiratory mouth pressures do not always indicate expiratory muscle weakness. Cough gastric pressure provides a useful complementary test for the assessment of expiratory muscle strength.
Motor neurone disease (MND) is a devastating illness which leads to muscle weakness and death, usually within 2-3 years of symptom onset. Respiratory insufficiency is a common cause of morbidity, ...particularly in later stages of MND and respiratory complications are the leading cause of mortality in MND patients. Non Invasive Ventilation (NIV) is the current standard therapy to manage respiratory insufficiency. Some MND patients however do not tolerate NIV due to a number of issues including mask interface problems and claustrophobia. In those that do tolerate NIV, eventually respiratory muscle weakness will progress to a point at which intermittent/overnight NIV is ineffective. The NeuRx RA/4 Diaphragm Pacing System was originally developed for patients with respiratory insufficiency and diaphragm paralysis secondary to stable high spinal cord injuries. The DiPALS study will assess the effect of diaphragm pacing (DP) when used to treat patients with MND and respiratory insufficiency.
108 patients will be recruited to the study at 5 sites in the UK. Patients will be randomised to either receive NIV (current standard care) or receive DP in addition to NIV. Study participants will be required to complete outcome measures at 5 follow up time points (2, 3, 6, 9 and 12 months) plus an additional surgery and 1 week post operative visit for those in the DP group. 12 patients (and their carers) from the DP group will also be asked to complete 2 qualitative interviews.
The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND with respiratory muscle weakness. The project is funded by the National Institute for Health Research, Health Technology Assessment (HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association and the Henry Smith Charity.
Current controlled trials ISRCTN53817913. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.
A woman in her 20s presented with progressive weakness of her left arm and leg, slurred speech and swallowing difficulties. The clinical presentation and neurophysiological tests were consistent with ...motor neuron disease. She was referred to the regional ventilation unit for respiratory muscle function testing. This confirmed restrictive spirometry and borderline sniff nasal inspiratory pressure and cough peak expiratory flow. Three years later, she presented with an unplanned pregnancy and expressed the wish to continue the pregnancy to term. She was monitored throughout pregnancy with interval respiratory muscle testing and was reviewed in the high-risk pregnancy anaesthetic clinic. She was also closely monitored by the obstetrics and gynaecology team. A multidisciplinary team meeting between all stakeholders agreed on caesarean section delivery at 34 weeks. The pregnancy and the delivery were without complications; the baby was healthy and both mother and baby remain well to date.
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