Skip to main content

Advertisement

Log in

The management of amyotrophic lateral sclerosis

  • REVIEW
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The terms amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) refer to a condition characterized by motor system degeneration with relative preservation of other pathways. Although there have been advances in symptomatic treatment, ALS remains an incurable condition. Advances in ALS management prolong survival but simultaneously raise challenging ethical dilemmas for physicians, patients and their families. Here, we review current practice in the management of ALS including pharmacological treatment, nutritional management, respiratory care, and evolving strategies in the management of cognitive impairment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Chancellor AM, Warlow CP (1992) Adult onset motor neuron disease: worldwide mortality, incidence and distribution since 1950. J Neurol Neurosurg Psychiatry 55:1106–1115

    Article  PubMed  CAS  Google Scholar 

  2. Cronin S, Hardiman O, Traynor BJ (2007) Ethnic variation in the incidence of ALS: a systematic review. Neurology 68(13):1002–1007

    Article  PubMed  Google Scholar 

  3. Cleveland DW, Rothstein JD (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2:806–819

    Article  PubMed  CAS  Google Scholar 

  4. Nelson LM (1995) Epidemiology of ALS. Clin Neurosci 3:327–331

    PubMed  Google Scholar 

  5. Haley RW (2003) Excess incidence of ALS in young Gulf War veterans. Neurology 61:750

    PubMed  Google Scholar 

  6. Horner RD, Kamins KG, Feussner JR, et al. (2003) Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 61:742

    PubMed  CAS  Google Scholar 

  7. Weisskopf MG, O’Reilly EJ, Mc- Cullough ML, et al. (2005) Prospective study of military service and mortality from ALS. Neurology 64:32

    Article  PubMed  CAS  Google Scholar 

  8. Armon C (2004) Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 62:1027

    PubMed  Google Scholar 

  9. Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O (2003) Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996–2000. J Neurol Neurosurg Psychiatry 74:1258–1261

    Article  PubMed  CAS  Google Scholar 

  10. Chaudhuri KR, Crump S, al-Sarraj S, et al. (1995) The validation of El Escorial criteria for the diagnosis of amyotrophic lateral sclerosis: a clinicopathological study. J Neurol Sci 129 (Suppl):11

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Isaacs JD, Dean AF, Shaw CE, et al. (2007) Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder? J Neurol Neurosurg Psychiatry 78(7):750–753

    Article  PubMed  Google Scholar 

  13. Pugdahl K, Fuglsang-Frederiksen A, de Carvalho M, et al. (2007) Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study. J Neurol Neurosurg Psychiatry 78(7):746–749

    Article  PubMed  CAS  Google Scholar 

  14. Eisen A, Swash M (2001) Clinical neurophysiology of ALS. Clin Neurophysiol 112(12):2190–2201

    Article  PubMed  CAS  Google Scholar 

  15. Leigh PN, Ray-Chaudhuri K (1994) Motor neuron disease. J Neurol Neurosurg Psychiatry 57:886–896

    Article  PubMed  CAS  Google Scholar 

  16. Sumner AJ (1997) Consensus criteria for the diagnosis of partial conduction block and multifocal motor neuropathy. In: Kimura J Kaji R (eds) Physiology of ALS and related diseases, Elsevier, Amsterdam, pp 221–227

  17. Kaji R (1999) Diagnosis and treatment of multifocal motor neuropathy (Lewis-Sumner). Rinsho Shinkeigaku 39:107–109

    PubMed  CAS  Google Scholar 

  18. Komissarow L, Rollnik JD, Bogdanova D, et al. (2004) Triple stimulation technique (TST) in amyotrophic lateral sclerosis. Clin Neurophysiol 115(2):356–360

    Article  PubMed  Google Scholar 

  19. Kuipers-Upmeijer J, de Jager AE, Hew JM, et al. (2001) Primary lateral sclerosis: clinical, neurophysiological, and magnetic resonance findings. J Neurol Neurosurg Psychiatry 71(5):615–620

    Article  PubMed  CAS  Google Scholar 

  20. Miscio G, Pisano F, Mora G, et al. (1999) Motor neuron disease: usefulness of transcranial magnetic stimulation in improving the diagnosis. Clin Neurophysiol 110(5):975–981

    Article  PubMed  CAS  Google Scholar 

  21. Chan S, Kaufmann P, Shungu DC, Mitsumoto H (2003) Amyotrophic lateral sclerosis and primary lateral sclerosis: evidence-based diagnostic evaluation of the upper motor neuron. Neuroimaging Clin N Am 13:307–326

    Article  PubMed  Google Scholar 

  22. Grosskreutz J, Peschel T, et al. (2008) Whole brain-based computerized neuroimaging in ALS and other motor neuron disorders. Amyotroph Lateral Scler 9(4):238–248

    Article  PubMed  Google Scholar 

  23. Davenport RJ, Swingler RJ, Chancellor AM, Warlow CP (1996) Avoiding false positive diagnoses of motor neuron disease: lessons from the Scottish Motor Neuron Disease Register. J Neurol Neurosurg Psychiatry 60:147–151

    Article  PubMed  CAS  Google Scholar 

  24. Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman O (2000) Amyotrophic Lateral Sclerosis Mimic Syndromes: A Population-Based Study. Arch Neurol 57:109–113

    Article  PubMed  CAS  Google Scholar 

  25. Valdmanis PN, Rouleau GA (2008) Genetics of familial amyotrophic lateral sclerosis. Neurology 70(2):144–152

    Article  PubMed  Google Scholar 

  26. Cronin S, Berger S, Ding J, Schymick JC, Washecka N, Hernandez DG, Greenway MJ, Bradley DG, Traynor BJ, Hardiman O (2008) A genome-wide association study of sporadic ALS in a homogenous Irish population. Hum Mol Genet 17(5):768–774

    Article  PubMed  CAS  Google Scholar 

  27. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM-Y (2006) Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis. Vol. 314. no. 5796, pp 130–133

  28. Arai T, Hasegawa M, Akiyama H, et al. (2006) TDP-43 is a component of ubiquitin- positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351(3):602–611

    Article  PubMed  CAS  Google Scholar 

  29. Van Deerlin VM, Leverenz JB, Bekris LM, et al. (2008) TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histological analysis. Lancet Neurology 7:416

    Google Scholar 

  30. Sreedharan J, Blair IP, Tripathi VB, et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668–1672

    Article  PubMed  CAS  Google Scholar 

  31. Kabashi E, Valdmanis PN, Dion P, et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40(5):572–574

    Article  PubMed  CAS  Google Scholar 

  32. Gitcho MA, Baloh RH, Chakraverty S, et al. (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63:535–538

    Article  PubMed  CAS  Google Scholar 

  33. Strong MJ (2008) The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 9(6):323–338

    Article  PubMed  CAS  Google Scholar 

  34. Andersen PM, Borasio GD, Dengler R, Hardiman O, Kollewe K, Leigh PN, Pradat PF, Silani V, Tomik B, EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis (2005) EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol 12(12):921–938

    Article  PubMed  CAS  Google Scholar 

  35. Miller RG, Rosenberg JA, Gelinas DF, et al. (1999) Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology 52:1311

    PubMed  CAS  Google Scholar 

  36. Chio A, Bottacchi E, Buffa C, Mutani R, Mora G, and the PARALS (2006) Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome and use of hospital facilities. J Neurol Neurosurg Psychiatry 77(8):948–950

    Article  PubMed  CAS  Google Scholar 

  37. Miller RG, Mitchell JD, Lyon M, Moore DH (2002) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev; CD001447

  38. Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M, Manca ML (2008) Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 105:2052–2057

    Article  PubMed  CAS  Google Scholar 

  39. Meininger V, Shefner J, Cudkowicz M (2008) Lithium therapy in ALS. Amyotroph Lateral Scler 9(2):122

    Article  PubMed  Google Scholar 

  40. Gordon PH, et al. (2007) Efficacy of minocycline in patients with amyotrophic lateral sclerosis: A phase III randomised trial. Lancet Neurol 6:1045

    Article  PubMed  CAS  Google Scholar 

  41. Lanka V, Cudkowicz M (2008) Therapy development for ALS: lessons learned and path forward. Amyotroph Lateral Scler 9(3):131–140

    Article  PubMed  CAS  Google Scholar 

  42. Borasio GD, Voltz R, Miller RG (2001) Palliative care in amyotrophic lateral sclerosis. Neurol Clin 19:829

    Article  PubMed  CAS  Google Scholar 

  43. Schiffer RB, Herndon RM, Rudick RA (1985) Treatment of pathologic laughing and weeping with amitriptyline. N Engl J Med 312:1480

    PubMed  CAS  Google Scholar 

  44. Brooks BR, Thisted RA, Appel SH, et al. (2004) Treatment of pseudobulbar affect in ALS with dextromethorphan/ quinidine: a randomized trial. Neurology 63:1364

    PubMed  CAS  Google Scholar 

  45. Bourke SC, Shaw PJ, Gibson GJ (2001) Respiratory function vs sleep-disordered breathing as predictors of QoL in ALS. Neurology 57:2040–2044

    PubMed  CAS  Google Scholar 

  46. Lyall RA, Donaldson N, Polkey MI, et al. (2001) Respiratory muscle strength and ventilatory failure in ALS. Brain 124:2000–2013

    Article  PubMed  CAS  Google Scholar 

  47. Stefanutti D, Benoist MR, Scheinmann P, et al. (2000) Usefulness of sniff nasal pressure in patients with neuromuscular or skeletal disorders. Am J Respir Crit Care Med 162:1507

    PubMed  CAS  Google Scholar 

  48. Morgan RK, McNally S, Alexander M, et al. (2005) Use of Sniff nasal-inspiratory force to predict survival in amyotrophic lateral sclerosis. Am J Respir Crit Care Med 171:269–274

    Article  PubMed  Google Scholar 

  49. Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ (2006) Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 5(2):140–147

    Article  PubMed  Google Scholar 

  50. Mustfa N, Walsh E, Bryant V, et al. (2006) The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology 66:1211

    Article  PubMed  CAS  Google Scholar 

  51. Newson-Davis IC, Lyall RA, Leigh PN, et al. (2001) The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in ALS: a prospective study. J Neurol Neurosurg Psychiatry 71:482–487

    Article  Google Scholar 

  52. Aboussouan LS, Khan SU, Meeker DP, et al. (1997) Effect of noninvasive positive- pressure ventilation on survival in amyotrophic lateral sclerosis. Ann Intern Med 127:450–453

    PubMed  CAS  Google Scholar 

  53. Gelinas D (2000) ALS and invasive ventilation. In: Oliver D, Borasio GD, Walsh D (eds) Palliative care in amyotrophic lateral sclerosis. Oxford: Oxford University Press, pp 56–62

  54. Borasio GD, Gelinas DF, Yanagisawa N (1998) Mechanical ventilation in ALS: a cross-cultural perspective. J Neurol 245:S7–S12

    Article  PubMed  Google Scholar 

  55. Leigh PN, Abrahams S, Al-Chalabi A, Ampong MA, Goldstein LH, Johnson J, Lyall R, Moxham J, Mustfa N, Rio A, Shaw C, Willey E; King’s MND Care and Research Team (2003) The management of motor neurone disease. J Neurol Neurosurg Psychiatry 74 (Suppl 4):iv32–iv47

    PubMed  Google Scholar 

  56. Bradley MD, Orrell RW, Clarke J, et al. (2002) Outcome of ventilatory support for acute respiratory failure in motor neurone disease. J Neurol Neurosurg Psychiatry 72:752–756

    Article  PubMed  CAS  Google Scholar 

  57. Polkey MI, Lyall RA, Green M, et al. (1999) Expiratory muscle function in ALA. Am J Resp Crit Care Med 158:734–741

    Google Scholar 

  58. Mustfa NM, Moxham J (2001) Respiratory muscle assessment in motor neurone disease. QJM 94:497–502

    Article  PubMed  CAS  Google Scholar 

  59. Stambler N, Charatan M, Cedarbaum JM (1998) Prognostic indicators of survival in ALS. ALS CNTF study group. Neurology 50:66–72

    PubMed  CAS  Google Scholar 

  60. Mazzini L, Corra T, Zaccala M, et al. (1995) Percutaneous endoscopic gastrostomy and enteral nutrition in ALS. J Neurol 242:695–698

    Article  PubMed  CAS  Google Scholar 

  61. Forbes R, Colville S, Swingler R (2004) Frequency, timing and outcome of gastrostomy tubes for amyotrophic lateral sclerosis/motor neurone disease. J Neurol 251:813–817

    Article  PubMed  Google Scholar 

  62. Kasaskis EJ, Scarlata D, Hill R, et al. (1999) A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials. J Neurol Sci 169:118–125

    Article  Google Scholar 

  63. Boitano LJ, Jordan T, Benditt JO (2001) Noninvasive ventilation allows gastrostomy tube placement in patients with advanced ALS. Neurology 56(3):413–414

    PubMed  CAS  Google Scholar 

  64. Bello-Haas VD, Florence JM, Kloos AD, Scheirbecker J, Lopate G, Hayes SM, Pioro EP, Mitsumoto H (2007) A randomized controlled trial of resistance exercise in individuals with ALS. Neurology 68(23):2003–2007

    Article  PubMed  Google Scholar 

  65. Rabkin JG, Albert SM, Del Bene ML, O’Sullivan I, Tider T, Rowland LP, Mitsumoto H (2005) Prevalence of depressive disorders and change over time in late-stage ALS. Neurology 65:62–67

    Article  PubMed  CAS  Google Scholar 

  66. Albert SM, Rabkin JG, Del Bene ML, et al. (2005) Wish to die in end-stage ALS. Neurology 65:68

    Article  PubMed  CAS  Google Scholar 

  67. Gauthier A, Vignola A, Calvo A, Cavallo E, Moglia C, Sellitti L, Mutani R, Chio A (2007) A longitudinal study on quality of life and depression in ALS patientcaregiver couples. Neurology 68(12):923–926

    Article  PubMed  CAS  Google Scholar 

  68. McDonald ER, Wiedenfeld SA, Hillel A, et al. (1994) Survival in amyotrophic lateral sclerosis. The role of psychological factors. Arch Neurol 51:17

    PubMed  CAS  Google Scholar 

  69. Phukan J, Pender N, Hardiman O (2007) A Review of Cognitive Impairment in ALS. Lancet Neurol 6(11):994–1003

    Article  PubMed  CAS  Google Scholar 

  70. Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B (2003) Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60:1094–1097

    PubMed  CAS  Google Scholar 

  71. Barson FP, Kinsella GJ, Ong B, Mathers SE (2000) A neuropsychological investigation of dementia in motor neurone disease (MND). J Neurol Sci 180(1–2):107–113

    Article  PubMed  CAS  Google Scholar 

  72. Geser NJ, Brandmeir LK, Kwong M, Martinez-Lage L, Elman L, McCluskey SX, Xie V, Lee M-Y, Trojanowski JQ (2008) Evidence of Multisystem Disorder in Whole-Brain Map of Pathological TDP-43 in Amyotrophic Lateral Sclerosis. F. Arch Neurol 65:636–641

    Article  PubMed  Google Scholar 

  73. Olney RK, Murphy J, Forshew D, Garwood E, Miller BL, Langmore S, Kohn MA, Lomen-Hoerth C (2005) The effects of executive and behavioural dysfunction on the course of ALS. Neurology 65:1774–1777

    Google Scholar 

  74. Mathuranath PS, Nestor P, Berrios GE, et al. (2000) A brief cognitive test battery to differentiate Alzheimer’s disease and frontotemporal dementia. Neurology 55:1613–1620

    PubMed  CAS  Google Scholar 

  75. Perry RJ, Miller B (2001) Behaviour and treatment in frontotemporal dementia. Neurology 56:S46–S51

    PubMed  CAS  Google Scholar 

  76. Hecht MJ, Graesel E, Tigges S, et al. (2003) Burden of care in amyotrophic lateral sclerosis. Palliat Med 17:327–333

    Article  PubMed  Google Scholar 

  77. Chio A, Gauthier A, Calvo A, et al. (2005) Caregiver burden and patients’ perception of being a burden in ALS. Neurology 64(10):1780–1782

    Article  PubMed  CAS  Google Scholar 

  78. de Carvalho M, Dengler R, Eisen A, et al. (2007) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119(3):497–503

    Article  PubMed  Google Scholar 

  79. Baekand WS, Desai NP (2007) ALS: Pitfalls in the Diagnosis. Practical Neurology 7:74–81

    Google Scholar 

  80. Sejvar JJ, Holman RC, Bresee JS, et al. (2005) ALS mortality in the United States 1997–2001. Neuroepidemiology 25(3):144–152

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Phukan MB, MRCPI.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Phukan, J., Hardiman, O. The management of amyotrophic lateral sclerosis. J Neurol 256, 176–186 (2009). https://doi.org/10.1007/s00415-009-0142-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-009-0142-9

Key words

Navigation