Nothing Special   »   [go: up one dir, main page]
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Supportive and symptomatic management of amyotrophic lateral sclerosis

Nature Reviews Neurology volume 12, pages 526–538 (2016)Cite this article

Subjects

Key Points

  • The aim of the management of ALS is to maximize quality of life and minimize morbidity

  • Guidelines for symptomatic care are becoming more evidenced-based

  • Management by a specialist, clinic-based multidisciplinary team is associated with improved survival

  • In patients with respiratory failure, noninvasive ventilation prolongs survival and improves quality of life

  • Nutritional status is an independent predictor of survival and, if patients opt for enteral feeding, early gastrostomy insertion is recommended before significant weight loss takes place

  • Cognitive impairment is common in ALS and is associated with a worse prognosis; the optimal management of this problem is unclear

Abstract

The main aims in the care of individuals with amyotrophic lateral sclerosis (ALS) are to minimize morbidity and maximize quality of life. Although no cure exists for ALS, supportive and symptomatic care provided by a specialist multidisciplinary team can improve survival. The basis for supportive management is shifting from expert consensus guidelines towards an evidence-based approach, which encourages the use of effective treatments and could reduce the risk of harm caused by ineffective or unsafe interventions. For example, respiratory support using noninvasive ventilation has been demonstrated to improve survival and quality of life, whereas evidence supporting other respiratory interventions is insufficient. Increasing evidence implicates a causal role for metabolic dysfunction in ALS, suggesting that optimizing nutrition could improve quality of life and survival. The high incidence of cognitive dysfunction and its impact on prognosis is increasingly recognized, although evidence for effective treatments is lacking. A variety of strategies are used to manage the other physical and psychological symptoms, the majority of which have yet to be thoroughly evaluated. The need for specialist palliative care throughout the disease is increasingly recognized. This Review describes the current approaches to symptomatic and supportive care in ALS and outlines the current guidance and evidence for these strategies.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Recommended components of a multidisciplinary team for management of amyotrophic lateral sclerosis.
Figure 2: The Sheffield Support Snood.
Figure 3: MyNIV: An online guide for people with amyotrophic lateral sclerosis who use noninvasive ventilation.
Figure 4: A noninvasive ventilation mask.
Figure 5: A lung recruitment device.

Similar content being viewed by others

References

  1. Alonso, A., Logroscino, G., Jick, S. S. & Hernán, M. A. Incidence and lifetime risk of motor neuron disease in the United Kingdom: a population-based study. Eur. J. Neurol. 16, 745–751 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Roche, J. C. et al. A proposed staging system for amyotrophic lateral sclerosis. Brain 135, 847–852 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Balendra, R. et al. Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials. J. Neurol. Neurosurg. Psychiatry 86, 45–49 (2015).

    Article  PubMed  Google Scholar 

  4. Del Aguila, M. A., Longstreth, W. T., McGuire, V., Koepsell, T. D. & van Belle, G. Prognosis in amyotrophic lateral sclerosis. A population-based study. Neurology 60, 813–819 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Bensimon, G., Lacomblez, L. & Meininger, V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N. Engl. J. Med. 330, 585–591 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Miller, R. G., Mitchell, J. D. & Moore, D. H. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst. Rev. Issue 3 Art No.: CD001447 (2013).

  7. Miller, R. G. et al. Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review). Neurology 73, 1218–2134 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Miller, R. G. et al. Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review). Neurology 73, 1227–1233 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Centre for Clinical Practice at NICE (UK). Motor neurone disease: the use of non-invasive ventilation. [online] https://www.nice.org.uk/guidance/cg105 (2010).

  10. The EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis: et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis (MALS) - revised report of an EFNS task force. Eur. J. Neurol. 3, 360–375 (2011).

  11. The Association for Palliative Medicine of Great Britain and Ireland. APM position on Withdrawal of Ventilatory Support for Respiratory Failure at the Request of an Adult Patient. [online] http://apmonline.org/wp-content/uploads/2015/05/Withdrawal-of-Ventilatory-Suport-for-Respiratory-Failure-1307.pdf (2013).

  12. National Institute for Clinical Excellence, U. K. Motor neurone disease: assessment and management. NG521–47 [online] https://www.nice.org.uk/guidance/NG42 (2016).

  13. Chio, A., Buffa, C., Mutani, R., Bora, G. & PARALS. Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome and use of hospital facilities. J. Neurol. Neurosurg. Psychiatry 77, 948–950 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Aridegbe, T. et al. The natural history of motor neuron disease: assessing the impact of specialist care. Amyotroph. Lateral Scler. Frontotemporal Degener. 14, 13–19 (2013).

    Article  PubMed  Google Scholar 

  15. Rooney, J. et al. A multidisciplinary clinic approach improves survival in ALS: a comparative study of ALS in Ireland and Northern Ireland. J. Neurol. Neurosurg. Psychiatry 86, 496–501 (2015).

    Article  PubMed  Google Scholar 

  16. Van den Berg, J. P. et al. Multidisciplinary ALS care improves quality of life in patients with ALS. Neurology 65, 1264–1267 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. O'Brien, M., Jack, B. & Douglas Mitchell, J. Multidisciplinary team working in motor neurone disease: patient and family carer views. Br. J. Neurosci. Nurs. 7, 580–585 (2011).

    Article  Google Scholar 

  18. Hogden, A., Greenfield, D., Nugus, P. & Kiernan, M. C. What influences patient decision-making in amyotrophic lateral sclerosis multidisciplinary care? A study of patient perspectives. Patient Prefer. Adherence 6, 829–838 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hobson, E. V. et al. Using technology to improve access to specialist care in amyotrophic lateral sclerosis: A systematic review. Amyotroph. Lateral Scler. Frontotemporal Degener. 17, 313–324 (2016).

    Article  PubMed  Google Scholar 

  20. Baldinger, R., Katzberg, H. D. & Weber, M. Treatment cramps amyotroph. lateral sclerosis/motor neuron disease. Cochrane Database Syst. Rev. Issue 4 Art No.: CD004157 (2012).

    Google Scholar 

  21. Federal Register Online Drug Products Containing Quinine; Enforcement Action Dates. [online] http://www.fda.gov/OHRMS/DOCKETS/98fr/06-9713.htm (2006).

  22. El-Tawil, S. et al. Quinine Muscle Cramps. Cochrane Database Syst. Rev. 4, CD005044 (2015).

    Google Scholar 

  23. Bedlack, R. S., Pastula, D. M., Hawes, J. & Heydt, D. Open-label pilot trial of levetiracetam for cramps and spasticity in patients with motor neuron disease. Amyotroph. Lateral Scler. 10, 210–215 (2009).

    Article  PubMed  Google Scholar 

  24. Weiss, M. D. et al. A randomized trial of mexiletine in ALS. Neurology 86, 1474–1481 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ashworth, N. L., Satkunam, L. E. & Deforge, D. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst. Rev. 2, CD004156 (2012).

    Google Scholar 

  26. Kheder, A. & Nair, K. P. S. Spasticity: pathophysiology, evaluation and management. Pract. Neurol. 12, 289–298 (2012).

    Article  PubMed  Google Scholar 

  27. Drory, V. E., Goltsman, E., Reznik, J. G., Mosek, A. & Korczyn, A. D. The value of muscle exercise in patients with amyotrophic lateral sclerosis. J. Neurol. Sci. 191, 133–137 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Marquardt, G. & Lorenz, R. Intrathecal baclofen for intractable spasticity in amyotrophic lateral sclerosis. J. Neurol. 246, 619–620 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Marquardt, G. & Seifert, V. Use of intrathecal baclofen for treatment of spasticity in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 72, 275–276 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. McClelland, S. et al. Intrathecal baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle Nerve 37, 396–398 (2008).

    Article  CAS  PubMed  Google Scholar 

  31. Chio, A. et al. Pain in amyotrophic lateral sclerosis: a population-based controlled study. Eur. J. Neurol. 19, 551–555 (2011).

    Article  PubMed  Google Scholar 

  32. Brettschneider, J., Kurent, J. & Ludolph, A. Drug therapy for pain in amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst. Rev. 6, CD005226 (2013).

    Google Scholar 

  33. World Health Organization. Cancer pain relief: with a guide to opioid availability. [online] http://apps.who.int/iris/bitstream/10665/37896/1/9241544821.pdf (WHO 1996).

  34. Oliver, D. J. et al. Medication in the last days of life for motor neuron disease/amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 11, 562–564 (2010).

    Article  PubMed  Google Scholar 

  35. Connolly, S., Galvin, M. & Hardiman, O. End-of-life management in patients with amyotrophic lateral sclerosis. Lancet Neurol. 14, 435–442 (2015).

    Article  PubMed  Google Scholar 

  36. Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257–268 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. DeJesus-Hernandez, M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245–256 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cooper-Knock, J. et al. Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72. Brain 135, 751–764 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Majounie, E. et al. Frequency of the C9orfF72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 11, 323–330 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gordon, P. H. et al. A prospective cohort study of neuropsychological test performance in ALS. Amyotroph. Lateral Scler. 11, 312–320 (2010).

    Article  PubMed  Google Scholar 

  41. Elamin, M. et al. Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology 76, 1263–1269 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Woolley, S. C. & Strong, M. J. Frontotemporal dysfunction and dementia in amyotrophic lateral sclerosis. Neurol. Clin. 33 1–20 (2016).

    Google Scholar 

  43. Abrahams, S., Newton, J., Niven, E., Foley, J. & Bak, T. H. Screening for cognition and behaviour changes in ALS. Amyotroph. Lateral Scler. Frontotemporal Degener. 15, 9–14 (2014).

    Article  PubMed  Google Scholar 

  44. McCluskey, L. et al. ALS-Plus syndrome: non-pyramidal features in a large ALS cohort. J. Neurol. Sci. 345, 118–124 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gallagher, J. P. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol. Scand. 80, 114–117 (1989).

    Article  CAS  PubMed  Google Scholar 

  46. Brooks, B. R. et al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine. Neurology 63, 1364–1370 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Pioro, E. P. et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann. Neurol. 68, 693–702 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Iannaccone, S. & Ferini-Strambi, L. Pharmacologic treatment of emotional lability. Clin. Neuropharmacol. 19, 532–535 (1996).

    Article  CAS  PubMed  Google Scholar 

  49. Szczudlik, A., Słowik, A. & Tomik, B. [The effect of amitriptyline on the pathological crying and other pseudobulbar signs]. Neurol. Neurochir. Pol. 29, 663–674 (1995).

    CAS  PubMed  Google Scholar 

  50. Kurt, A., Nijboer, F., Matuz, T. & Kübler, A. Depression and anxiety in individuals with amyotrophic lateral sclerosis: epidemiology and management. CNS Drugs 21, 279–291 (2007).

    Article  PubMed  Google Scholar 

  51. Pizzimenti, A., Aragona, M., Onesti, E. & Inghilleri, M. Depression, pain and quality of life in patients with amyotrophic lateral sclerosis: a cross-sectional study. Funct. Neurol. 28, 115 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Gauthier, A. et al. A longitudinal study on quality of life and depression in ALS patient-caregiver couples. Neurology 68, 923–926 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Rabkin, J. G. et al. Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study. Muscle Nerve 39, 297–303 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Mackenzie, L. et al. Communications Technology and Motor Neuron Disease: An Australian Survey of People With Motor Neuron Disease. JMIR Rehabil. Assist Technol. 3, e2 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Reed, H. et al. Head-Up; An interdisciplinary, participatory and co-design process informing the development of a novel head and neck support for people living with progressive neck muscle weakness. J. Med. Eng. Technol. 39, 404–410 (2014).

    Article  PubMed  Google Scholar 

  56. Baxter, S. et al. Evaluating a novel cervical orthosis, the Sheffield Support Snood, in patients with amyotrophic lateral sclerosis/motor neuron disease with neck weakness. Amyotroph. Lateral Scler. Frontotemporal Degener. 17, 436–442 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. Fried-Oken, M. et al. Purposes of AAC device use for persons with ALS as reported by caregivers. Augment. Altern. Commun. 22, 209–221 (2006).

    Article  PubMed  Google Scholar 

  58. Hwang, C.-S., Weng, H.-H., Wang, L.-F., Tsai, C.-H. & Chang, H.-T. An eye-tracking assistive device improves the quality of life for ALS patients and reduces the caregivers' burden. J. Mot. Behav. 46, 233–238 (2014).

    Article  PubMed  Google Scholar 

  59. Mills, T., Bunnell, H. T. & Patel, R. Towards personalized speech synthesis for augmentative and alternative communication. Augment. Altern. Commun. 30, 226–236 (2014).

    Article  PubMed  Google Scholar 

  60. Marchetti, M. & Priftis, K. Brain-computer interfaces in amyotrophic lateral sclerosis: A metanalysis. Clin. Neurophysiol. 126, 1255–1263 (2015).

    Article  PubMed  Google Scholar 

  61. Desport, J. C. et al. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am. J. Clin. Nutr. 74, 328–334 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Jawaid, A. et al. A decrease in body mass index is associated with faster progression of motor symptoms and shorter survival in ALS. Amyotroph. Lateral Scler. 11, 542–548 (2010).

    Article  PubMed  Google Scholar 

  63. Marin, B. et al. Alteration of nutritional status at diagnosis is a prognostic factor for survival of amyotrophic lateral sclerosis patients. J. Neurol. Neurosurg. Psychiatry 82, 628–634 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Paganoni, S., Deng, J., Jaffa, M., Cudkowicz, M. E. & Wills, A.-M. Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis. Muscle Nerve 44, 20–24 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Genton, L., Viatte, V., Janssens, J. P., Héritier, A. C. & Pichard, C. Nutritional state, energy intakes and energy expenditure of amyotrophic lateral sclerosis (ALS) patients. Clin. Nutr. 30, 553–559 (2011).

    Article  CAS  PubMed  Google Scholar 

  66. Bouteloup, C. et al. Hypermetabolism in ALS patients: an early and persistent phenomenon. J. Neurol. 256, 1236–1242 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Funalot, B., Desport, J.-C., Sturtz, F., Camu, W. & Couratier, P. High metabolic level in patients with familial amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 10, 113–117 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Wills, A.-M. et al. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet 383, 2065–2072 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Plowman, E. K. Is There a Role for Exercise in the Management of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis? J. Speech Lang. Hear. Res. 58, 1151–1166 (2015).

    Article  PubMed  Google Scholar 

  70. Plowman, E. K. et al. Impact of expiratory strength training in amyotrophic lateral sclerosis. Muscle Nerve 54, 48–53 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Plowman, E. K. et al. Autologous myoblasts attenuate atrophy and improve tongue force in a denervated tongue model: a pilot study. Laryngoscope 124, E20–E26 (2014).

    Article  PubMed  Google Scholar 

  72. Restivo, D. A. et al. ALS dysphagia pathophysiology: differential botulinum toxin response. Neurology 80, 616–620 (2013).

    Article  CAS  PubMed  Google Scholar 

  73. Stavroulakis, T., Walsh, T., Shaw, P. J. & McDermott, C. J., Progas Study. Gastrostomy use in motor neurone disease (MND): A review, meta-analysis and survey of current practice. Amyotroph. Lateral Scler. Frontotemporal Degener. 14, 96–104 (2013).

    Article  PubMed  Google Scholar 

  74. Stavroulakis, T. et al. The impact of gastrostomy in motor neurone disease: challenges and benefits from a patient and carer perspective. BMJ Support. Palliat. Care 6, 52–59 (2016).

    Article  PubMed  Google Scholar 

  75. Group, P. S. Gastrostomy in patients with amyotrophic lateral sclerosis (ProGas): a prospective cohort study. Lancet Neurol. 14, 702–700 (2015).

    Article  Google Scholar 

  76. Stavroulakis, T. et al. Factors influencing decision-making in relation to timing of gastrostomy insertion in patients with motor neurone disease. BMJ Support. Palliat. Care 4, 57–63 (2013).

    Article  PubMed  Google Scholar 

  77. Johnson, J. et al. Eating-derived pleasure in amyotrophic lateral sclerosis as a predictor of non-oral feeding. Amyotroph. Lateral Scler. 13, 555–559 (2012).

    Article  PubMed  Google Scholar 

  78. National Institute for Clinical Excellence, UK. Dementia: supporting people with dementia and their carers in health and social care [online] https://www.nice.org.uk/guidance/cg42 (NICE 2014).

  79. Bourke, S. C. et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol. 5, 140–147 (2006).

    Article  PubMed  Google Scholar 

  80. Shefner, J. M., Watson, M. L., Meng, L. & Wolff, A. A. The Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener Amyotroph. Lateral. Scler. Frontotemporal Degener. 14, 574–581 (2013).

    Article  CAS  Google Scholar 

  81. Orion Corporation, Orion Pharma. Effects of ODM-109 on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS). Clinicaltrials.gov [online] https://clinicaltrials.gov/ct2/show/NCT02487407.

  82. Carratù, P. et al. Early treatment with noninvasive positive pressure ventilation prolongs survival in Amyotrophic Lateral Sclerosis patients with nocturnal respiratory insufficiency. Orphanet J. Rare Dis. 4, 10 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Terzano, C. & Romani, S. Early use of non invasive ventilation in patients with amyotrophic lateral sclerosis: what benefits? Eur. Rev. Med. Pharmacol. Sci. 19, 4304–4313 (2015).

    CAS  PubMed  Google Scholar 

  84. O'Neill, C. L. et al. Non-invasive ventilation in motor neuron disease: an update of current UK practice. J. Neurol. Neurosurg. Psychiatry 83, 371–376 (2012).

    Article  PubMed  Google Scholar 

  85. Pinto, A., de Carvalho, M., Evangelista, T., Lopes, A. & Sales- Luís, L. Nocturnal pulse oximetry: a new approach to establish the appropriate time for non-invasive ventilation in ALS patients. Amyotroph. Lateral Scler. Other Motor Neuron. Disord. 4, 31–35 (2003).

    Article  PubMed  Google Scholar 

  86. Rafiq, M. K. et al. Using transcutaneous carbon dioxide monitor (TOSCA 500) to detect respiratory failure in patients with amyotrophic lateral sclerosis: A validation study. Amyotroph. Lateral Scler. 13, 528–532 (2012).

    Article  CAS  PubMed  Google Scholar 

  87. Baxter, S. K. et al. The initiation of non-invasive ventilation for patients with motor neuron disease: patient and carer perceptions of obstacles and outcomes. Amyotroph. Lateral Scler. Frontotemporal Degener. 14, 105–110 (2013).

    Article  PubMed  Google Scholar 

  88. Baxter, S. K. et al. The impact on the family carer of motor neurone disease and intervention with noninvasive ventilation. J. Palliat. Med. 16, 1602–1609 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Gonzalez-Bermejo, J. et al. Prognostic value of efficiently correcting nocturnal desaturations after one month of non-invasive ventilation in amyotrophic lateral sclerosis: a retrospective monocentre observational cohort study. Amyotroph. Lateral Scler. Frontotemporal Degener. 14, 373–379 (2013).

    Article  PubMed  Google Scholar 

  90. Berlowitz, D. J. et al. Identifying who will benefit from non-invasive ventilation in amyotrophic lateral sclerosis/motor neurone disease in a clinical cohort. J. Neurol. Neurosurg. Psychiatry 87, 280–286 (2016).

    Article  PubMed  Google Scholar 

  91. Hobson, E. V. et al. Management of sialorrhoea in motor neuron disease: a survey of current UK practice. Amyotroph. Lateral Scler. Frontotemporal Degener. 14, 521–527 (2013).

    Article  CAS  PubMed  Google Scholar 

  92. Jackson, C. E. et al. Randomized double-blind study of botulinum toxin type B for sialorrhea in als patients. Muscle Nerve 39, 137–143 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Barbero, P. et al. Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia. J. Neurol. 262, 2662–2667 (2015).

    Article  CAS  PubMed  Google Scholar 

  94. Dogu, O., Apaydin, D., Sevim, S., Talas, D. U. & Aral, M. Ultrasound-guided versus “blind” intraparotid injections of botulinum toxin-A for the treatment of sialorrhoea in patients with Parkinson's disease. Clin. Neurol. Neurosurg. 106, 93–96 (2004).

    Article  PubMed  Google Scholar 

  95. Meijer, J.-W. G., van Kuijk, A. A., Geurts, A. C. H., Schelhaas, H. J. & Zwarts, M. J. Acute deterioration of bulbar function after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis. Am. J. Phys. Med. Rehabil. 87, 321–324 (2008).

    Article  PubMed  Google Scholar 

  96. Neppelberg, E., Haugen, D. F., Thorsen, L. & Tysnes, O.-B. Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis. Eur. J. Neurol. 14, 1373–1377 (2007).

    Article  CAS  PubMed  Google Scholar 

  97. Guy, N. et al. Comparison of radiotherapy types in the treatment of sialorrhea in amyotrophic lateral sclerosis. J. Palliat Med. 14, 391–395 (2011).

    Article  PubMed  Google Scholar 

  98. Suárez, A. A. et al. Peak flow and peak cough flow in the evaluation of expiratory muscle weakness and bulbar impairment in patients with neuromuscular disease. Am. J. Phys. Med. Rehabil. 81, 506–511 (2002).

    Article  PubMed  Google Scholar 

  99. Sancho, J., Servera, E., Díaz, J. & Marín, J. Predictors of ineffective cough during a chest infection in patients with stable amyotrophic lateral sclerosis. Am. J. Respir. Crit. Care Med. 175, 1266–1271 (2007).

    Article  PubMed  Google Scholar 

  100. Tzeng, A. C. & Bach, J. R. Prevention of pulmonary morbidity for patients with neuromuscular disease. Chest 118, 1390–1396 (2000).

    Article  CAS  PubMed  Google Scholar 

  101. Rafiq, M. K. et al. A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 16, 448–455 (2015).

    Article  CAS  PubMed  Google Scholar 

  102. Lange, D. J. et al. High-frequency chest wall oscillation in ALS: an exploratory randomized, controlled trial. Neurology 67, 991–997 (2006).

    Article  CAS  PubMed  Google Scholar 

  103. DiPALS Writing Committee, on behalf of the DiPALS Study Group Collaborators. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 14, 883–892 (2015).

  104. United States Food and Drug Administration. Safety and summary sheet of probably benefit. [online] http://www.accessdata.fda.gov/cdrh_docs/pdf10/H100006b.pdf

  105. Assistance Publique - Hôpitaux de Paris. Early stage amyotrophic lateral sclerosis phrenic stimulation (RespiStimALS) Clinicaltrials.gov [online] https://clinicaltrials.gov/ct2/show/NCT01583088.

  106. Barrow Neurological Institute. Diaphragm pacing system (DPS) in participants with amyotrophic lateral sclerosis (ALS) (DPS in ALS) Clinicaltrials.gov [online] https://clinicaltrials.gov/ct2/show/NCT01938495.

  107. Synapse Biomedical. Humanitarian device exemption post-approval study of NeuRx diaphragm pacing system for amyotrophic lateral sclerosis. Clinicaltrials.gov [online] https://clinicaltrials.gov/ct2/show/NCT01605006

  108. Whitehead, B., O'Brien, M. R., Jack, B. A. & Mitchell, D. Experiences of dying, death and bereavement in motor neurone disease: A qualitative study. Palliat. Med. 26, 368–378 (2012).

    Article  PubMed  Google Scholar 

  109. Aoun, S. M., Connors, S. L., Priddis, L., Breen, L. J. & Colyer, S. Motor Neurone Disease family carers' experiences of caring, palliative care and bereavement: an exploratory qualitative study. Palliat. Med. 26, 842–850 (2012).

    Article  PubMed  Google Scholar 

  110. Baxter, S. K. et al. The use of non-invasive ventilation at end of life in patients with motor neurone disease: A qualitative exploration of family carer and health professional experiences. Palliat. Med. 27, 516–523 (2013).

    Article  PubMed  Google Scholar 

  111. Phelps, K., Regen, E., Oliver, D., McDermott, C. & Faull, C. Withdrawal of ventilation at the patient's request in MND: a retrospective exploration of the ethical and legal issues that have arisen for doctors in the UK. BMJ Support. Palliat. Care. http://dx.doi.org/10.1136/bmjspcare-2014-000826 (2015).

  112. National Clinical Guideline Centre. Care of Dying Adults in the Last Days of Life. NG31 [online] www.nice.org.uk/guidance/ng31?unlid=8981581202016219221856 (2015).

  113. Motor Neurone Disease Association. MND Just in Case kit - information for professionals [online] http://www.mndassociation.org/forprofessionals/mndmanagement/mnd-just-in-case-kit/ (2015).

  114. Sancho, J., Servera, E., Díaz, J. L., Bañuls, P. & Marín, J. Home tracheotomy mechanical ventilation in patients with amyotrophic lateral sclerosis: causes, complications and 1-year survival. Thorax 66, 948–952 (2011).

    Article  PubMed  Google Scholar 

  115. Spataro, R., Bono, V., Marchese, S. & La Bella, V. Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis. J. Neurol. Sci. 323, 66–70 (2012).

    Article  PubMed  Google Scholar 

  116. Heritier Barras, A.-C. et al. Is tracheostomy still an option in amyotrophic lateral sclerosis? Reflections of a multidisciplinary work group. Swiss Med. Wkly. 143, w13830 (2013).

    PubMed  Google Scholar 

  117. Hayashi, H. & Oppenheimer, E. A. ALS patients on TPPV: totally locked-in state, neurologic findings and ethical implications. Neurology 61, 135–137 (2003).

    Article  PubMed  Google Scholar 

  118. Motor Neurone Disease Association. Pathway for Preparing to Withdraw Non-Invasive Ventilation (NIV) in Patients with MND) [online] http://www.mndassociation.org/wp-content/uploads/2015/02/leicestershire-and-rutland-pathway-and-guidelines-for-withdrawing-niv.pdf

  119. Peters, M., Jenkinson, C., Doll, H., Playford, E. D. & Fitzpatrick, R. Carer quality of life and experiences of health services: a cross-sectional survey across three neurological conditions. Health Qual. Life Outcomes 11, 1–1 (2013).

    Article  Google Scholar 

  120. Goldstein, L. H., Atkins, L., Landau, S., Brown, R. & Leigh, P. N. Predictors of psychological distress in carers of people with amyotrophic lateral sclerosis: a longitudinal study. Psychol. Med. 36, 865–875 (2006).

    Article  CAS  PubMed  Google Scholar 

  121. O'Brien, M. R., Whitehead, B., Jack, B. A. & Mitchell, J. D. The need for support services for family carers of people with motor neurone disease (MND): views of current and former family caregivers a qualitative study. Disabil. Rehabil. 34, 247–256 (2012).

    Article  PubMed  Google Scholar 

  122. Craig, P. et al. Developing and evaluating complex interventions: the new Medical Research Council guidance. BMJ 337, a1655–a1655 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Bourke, S. C., Williams, T. L., Bullock, R. E., Gibson, G. J. & Shaw, P. J. Non-invasive ventilation in motor neuron disease: current UK practice. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 3, 145–149 (2002).

    Article  CAS  PubMed  Google Scholar 

  124. Chio, A. et al. Non-invasive ventilation in amyotrophic lateral sclerosis: a 10 year population based study. J. Neurol. Neurosurg. Psychiatry 83, 377–381 (2012).

    Article  PubMed  Google Scholar 

  125. I've got nothing to lose by trying it. Weighing up claims about cures and treatments for medical conditions. Sense about Science. [online] www.senseaboutscience.org/data/files/resources/136/Ive-got-nothing-to-lose_web.pdf (2013).

  126. Zettler, P. J. & Greely, H. T. The strange allure of state 'right-to-try' laws. JAMA Intern. Med. 174, 1885–1886 (2014).

    Article  PubMed  Google Scholar 

  127. Medical Innovation Bill [HL] 2014–2015. UK Parliament website. [online] http://services.parliament.uk/bills/2014-15/medicalinnovation.html

  128. Wicks, P. et al. Subjects no more: what happens when trial participants realize they hold the power? BMJ 348, g368–g368 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Wicks, P. et al. Sharing Health Data for Better Outcomes on PatientsLikeMe. J. Med. Internet Res. 12, e19 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Stiggelbout, A. M. et al. Shared decision making: really putting patients at the centre of healthcare. BMJ 344, e256 (2012).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

E.V.H. is funded by a National Institute for Health Research (NIHR) Doctoral Research Fellowship. C.J.M. receives funding from the NIHR, the Motor Neuron Disease Association and EU Joint Programme – Neurodegenerative Disease Research (JPND). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Author information

Authors and Affiliations

  1. Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Rd, Sheffield, S10 2HQ, UK

    Esther V. Hobson & Christopher J. McDermott

Authors
  1. Esther V. Hobson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher J. McDermott
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

E.V.H. and C.J.M. were both involved in all aspects of manuscript preparation.

Corresponding author

Correspondence to Christopher J. McDermott.

Ethics declarations

Competing interests

E.V.H. and C.J.M. are investigators in a number of clinical studies of symptomatic treatments, interventions and drugs in amyotrophic lateral sclerosis. These include remote monitoring of noninvasive ventilation (receiving equipment from Phillips), and telehealth (funded by the National Institute for Health Research (NIHR), UK, and the Motor Neuron Disease Association, UK, in collaboration with Mylan) and a clinical trial of levosimendan (funded by Orion Pharma). C.J.M. has also been an investigator on clinical trials including diaphragmatic pacing (funded by the NIHR), the Sheffield Support Snood (funded by the NIHR), cough augmentation (funded by the Motor Neuron Disease Association UK), tirasemtiv (funded by Cytokinetics) and dexpramipexole (funded by Biogen Idec).

Related links

PowerPoint slides

Glossary

Noninvasive ventilation (NIV)

The provision of bilevel inspiratory and experiatory ventilatory support through the patient's upper airway using a mask.

Advanced planning

A formal decision-making process that aims to help patients establish decisions about future care

Behavioural variant of FTD

The predominant symptoms of this disorder are executive dysfunction and behavioural changes.

Environmental controls

Electronic assistive technology that enables people with significant disabilities to independently access equipment in their environment, such as home or hospital.

Eye-gaze grids

A basic form of communication aid where a patient points to or looks at letters on an alphabet board in order to spell out words.

Eye-gaze software

Computer software that tracks eye movements allowing the patient to navigate and control a computer by tracking where they are looking.

Voice banking

A software records multiple examples of the patients voice to synthesize a voice similar to the patients' own, which can be used as a replacement when using communication software.

Type 2 respiratory failure

Inadequate ventilation that causes hypercapnoea (as opposed to type 1 respiratory failure, which causes hypoxaemia) and, if severe, hypoxia; in ALS, respiratory failure is caused by neuromuscular weakness of respiratory muscles.

Breath stacking

A technique to improve lung recruitment and cough: multiple inspiratory breaths are taken in succession and held (rather than exhaled) until full lung capacity is reached and exhalation is then allowed; the effectiveness of the process can be improved by using lung-recruitment bags.

Euthanasia

With the patient's consent, a doctor acts directly to end the patient's life, for examply by administering a lethal injection.

Refusal or withdrawal of treatment

At the patient's request, treatment can be declined or withdrawn, even if the lack of treatment has the potential to hasten the patient's death.

Physician-assisted suicide

A doctor knowingly and intentionally provides a person with the knowledge, means, or both required to commit suicide, for example by counselling about lethal doses of drugs, prescribing such lethal doses or supplying the drugs.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hobson, E., McDermott, C. Supportive and symptomatic management of amyotrophic lateral sclerosis. Nat Rev Neurol 12, 526–538 (2016). https://doi.org/10.1038/nrneurol.2016.111

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2016.111

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing