BACKGROUND: Motor neuron disease (MND), which is also known as amyotrophic 
lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base 
for the effectiveness of the symptomatic treatment therapies is limited.
OBJECTIVES: To summarise the evidence from Cochrane Systematic Reviews of all 
symptomatic treatments for MND.
METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 
November 2016 for systematic reviews of symptomatic treatments for MND. We 
assessed the methodological quality of the included reviews using the Assessment 
of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed 
standard Cochrane study (review) selection and data extraction procedures. We 
reported findings narratively and in tables.
MAIN RESULTS: We included nine Cochrane Systematic Reviews of interventions to 
treat symptoms in people with MND. Three were empty reviews with no included 
randomised controlled trials (RCTs); however, all three reported on non-RCT 
evidence and the remaining six included mostly one or two studies. We deemed all 
of the included reviews of high methodological quality. Drug therapy for 
painThere is no RCT evidence in a Cochrane Systematic Review exploring the 
efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence 
(13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to 
placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective 
(moderate-quality evidence);- vitamin E may have little or no effect 
(low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, 
riluzole, and baclofen are uncertain as the evidence is either very low quality 
or the trial specified the outcome but did not report numerical data.The review 
reported adverse effects of riluzole, but it is not clear whether other 
interventions had adverse effects. Treatment for spasticityIt is uncertain 
whether an endurance-based exercise programme improved spasticity or quality of 
life, measured at three months after the programme, as the quality of evidence 
is very low (1 RCT, comparison "usual activities", N = 25). The review did not 
evaluate other approaches, such as use of baclofen as no RCTs were available. 
Mechanical ventilation for supporting respiratory functionNon-invasive 
ventilation (NIV) probably improves median survival and quality of life in 
people with respiratory insufficiency and normal to moderately impaired bulbar 
function compared to standard care, and improves quality of life but not 
survival for people with poor bulbar function (1 RCT, N = 41, moderate-quality 
evidence; a second RCT did not provide data). The review did not evaluate other 
approaches such as tracheostomy-assisted ('invasive') ventilation, or assess 
timing of NIV initiation. Treatment for sialorrhoeaA single session of botulinum 
toxin type B injections to parotid and submandibular glands probably improves 
sialorrhoea and quality of life at up to 4 weeks compared to placebo injections, 
but not at 8 or 12 weeks after the injections (moderate-quality evidence from 1 
placebo-controlled RCT, N = 20). The review authors found no trials of other 
approaches. Enteral tube feeding for supporting nutritionThere is no RCT 
evidence in a Cochrane Systematic Review to support benefit or harms of enteral 
tube feeding in supporting nutrition in MND. Repetitive transcranial magnetic 
stimulationIt is uncertain whether repetitive transcranial magnetic stimulation 
(rTMS) improves disability or limitation in activity in MND in comparison with 
sham rTMS (3 RCTs, very low quality evidence, N = 50). Therapeutic exerciseThere 
is evidence that exercise may improve disability in MND at three months after 
the exercise programme, but not quality of life, in comparison with "usual 
activities" or "usual care" including stretching (2 RCTs, low-quality evidence, 
N = 43). Multidisciplinary careThere is no RCT evidence in a Cochrane Systematic 
Review to demonstrate any benefit or harm for multidisciplinary care in MND.None 
of the reviews, other than the review of treatment for cramps, reported that 
adverse events occurred. However, the trials were too small for reliable adverse 
event reporting.
AUTHORS' CONCLUSIONS: This overview has highlighted the lack of robust evidence 
in Cochrane Systematic Reviews on interventions to manage symptoms resulting 
from MND. It is important to recognise that clinical trials may fail to 
demonstrate efficacy of an intervention for reasons other than a true lack of 
efficacy, for example because of insufficient statistical power, the wrong 
choice of dose, insensitive outcome measures or inappropriate participant 
eligibility. The trials were mostly too small to reliably assess adverse effects 
of the treatments. The nature of MND makes it difficult to research clinically 
accepted or recommended practice, regardless of the level of evidence supporting 
the practice. It would not be ethical, for example, to design a 
placebo-controlled trial for treatment of pain in MND or to withhold 
multidisciplinary care where such care is available. It is therefore highly 
unlikely that there will ever be classically designed placebo-controlled RCTs in 
these areas.We need more research with appropriate study designs, robust 
methodology, and of sufficient duration to address the changing needs-of people 
with MND and their caregivers-associated with MND disease progression and 
mortality. There is a significant gap in studies assessing the effectiveness of 
interventions for symptoms relating to MND, such as pseudobulbar emotional 
lability and cognitive and behavioural difficulties. Future studies should use 
appropriate outcome measures that are reliable, have internal and external 
validity, and are sensitive to change in what is being measured (such as quality 
of life).