Background:  The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak.Objectives:  To provide evidence‐based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel.Methods:  All available medical reference systems were searched, and original papers, meta‐analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus.Recommendations:  Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non‐invasive positive‐pressure ventilation also improves survival and quality of life. Maintaining the patient’s ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end‐of‐life care should be discussed early with the patient and carers, respecting the patient’s social and cultural background.

Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events.

The Awaji recommendations for the use of electrodiagnostic studies in the diagnosis of amyotrophic lateral sclerosis (ALS) were proposed in 2008¹ to enable earlier diagnosis of ALS to be achieved to meet an acknowledged need to obviate diagnostic delay and to promote earlier entry into clinical trials.² For this purpose, a new algorithm was proposed on the background of the well-established revised El Escorial criteria (rEEC).³ This algorithm used the recommendations regarding topographical regions and the same number of abnormal muscles in each region as proposed in the rEEC recommendations, emphasizing the importance of a suitable clinical context. The Awaji criteria recommended that neurophysiological data should be used in the context of clinical information, not as a separate, stand-alone set of data. In addition, fasciculation potentials associated with signs of reinnervation were considered as evidence of lower motor neuron lesion, in particular in cranial-innervated or strong limb muscles. It was suggested that this new set of interpretative guidelines, which essentially followed conventional clinical practice, would increase diagnostic sensitivity without major change in specificity.¹Table 1 summarizes the similarities and differences between both sets of diagnostic criteria.

We have tested the sensitivity of a recently published approach to combining clinical and EMG data in the ‘research diagnosis’ of ALS, in 55 consecutive patients clinically diagnosed with ALS. The application of this ‘Awaji algorithm’ to the revised El Escorial diagnostic criteria for diagnosis of ALS achieved a diagnostic sensitivity of 95% for definite ALS compared with 18% using the clinical El Escorial criteria and 53% when the EMG criteria as defined in the El Escorial criteria, were applied to the same dataset. This increased sensitivity was particularly relevant for bulbar onset patients (sensitivity improved from 38% to 87%) and for patients with El Escorial clinically possible ALS (from 50% to 86%). We suggest that, in future, investigators and triallists should use the Awaji algorithm superimposed onto the El Escorial criteria, in selecting patients for research studies.

Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO‐NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease‐modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end‐of‐life management.Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.