Amyotrophic Lateral Sclerosis

  • Orla Hardiman
  • Matthew C. Kiernan
  • Leonard H. van den Berg
Chapter

Abstract

Amyotrophic Lateral Sclerosis (is a progressive motor system degeneration. Extra motor involvement also occurs, primarily in the form of cognitive and behavioural impairment. Up to 13 % of incident patients with ALS have a frontotemporal dementia. The pathophysiology of ALS is not well understood. 10–15 % of cases have a family history of ALS/frontotemporal dementia, and over 20 mendelian inherited “at risk” genes have been identified to date. Diagnosis is clinical, and investigations are aimed at excluding other treatable conditions. With the exception of Riluzole which has a modest effect on survival, no successful disease modifying agents have been developed to date. Optimal management of ALS requires a multidisciplinary team including early access to specialist palliative care services. Most ALS patients develop respiratory failure, and early intervention with non-invasive ventilation and aggressive secretion management can improve survival and enhance quality of life. ALS is associated with high levels of carer burden, particularly in the context of cognitive and behavioural impairment. Patients with ALS should be encouraged to consider an advanced directive regarding their preferred options at the end of their life.

Keywords

ALS MND Pathogenesis Diagnosis Multidisciplinary Management End of Life 

Suggested Reading

  1. Abrahams S, Newton J, Niven E, Foley J, Bak TH. Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(1–2):9–14. doi:10.3109/21678421.2013.805784. Epub 2013 Jun 19. PubMed.CrossRefPubMedGoogle Scholar
  2. Agosta F, Al-Chalabi A, Filippi M, Hardiman O, Kaji R, Meininger V, Nakano I, Shaw P, Shefner J, van den Berg LH, Ludolph A, The WFN Research Group on ALS/MND. The El escorial criteria: strengths and weaknesses. Amyotroph Lateral Scler Frontotemporal Degener. 2014;16:1–7.CrossRefPubMedGoogle Scholar
  3. Al-Chalabi A, Calvo A, Chio A, Colville S, Ellis CM, Hardiman O, Heverin M, Howard RS, Huisman MH, Keren N, Leigh PN, Mazzini L, Mora G, Orrell RW, Rooney J, Scott KM, Scotton WJ, Seelen M, Shaw CE, Sidle KS, Swingler R, Tsuda M, Veldink JH, Visser AE, van den Berg LH, Pearce N. Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study. Lancet Neurol. 2014;13(11):1108–13. PMC4197338.PubMedCentralCrossRefPubMedGoogle Scholar
  4. Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013;9(11):617–28. doi:10.1038/nrneurol.2013.203. Epub 2013 Oct 15. Review. PubMed.CrossRefPubMedGoogle Scholar
  5. Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, Hardiman O, Kollewe K, Morrison KE, Petri S, Pradat PF, Silani V, Tomik B, Wasner M, Weber M. EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis EFNS guidelines on the clinical management of amyotrophic lateral sclerosis(MALS)--revised report of an EFNS task force. Eur J Neurol. 2012;19(3):360–75.CrossRefPubMedGoogle Scholar
  6. Beghi E, Balzarini C, Bogliun G, Logroscino G, Manfredi L, Mazzini L, Micheli A, Millul A, Poloni M, Riva R, Salmoiraghi F, Tonini C, Vitelli E, Italian ALS Study Group. Reliability of the El Escorial diagnostic criteria for amyotrophic lateral sclerosis. Neuroepidemiology. 2002;21(6):265–70.CrossRefPubMedGoogle Scholar
  7. Beghi E, Millul A, Logroscino G, Vitelli E, Micheli A, SLALOM GROUP. Outcome measures and prognostic indicators in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2008;9(3):163–7.CrossRefPubMedGoogle Scholar
  8. Brooks BR, World Federation of Neurology Sub-Committee on Motor Neuron Diseases. El Escorial WFN criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci. 1994;124 Suppl 1:96–107.CrossRefPubMedGoogle Scholar
  9. Brooks BR, Miller RG, Swash M, Munsat TL, The World Federation of Neurology Research Committee on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2000;1:293–300.Google Scholar
  10. Byrne S, Heverin M, Elamin M, Bede P, Lynch C, Kenna K, MacLaughlin R, Walsh C, Al Chalabi A, Hardiman O. Aggregation of neurologic and neuropsychiatric disease in amyotrophic lateral sclerosis kindreds: a population-based case–control cohort study of familial and sporadic amyotrophic lateral sclerosis. Ann Neurol. 2013;74(5):699–708. doi:10.1002/ana.23969. Epub 2013 Sep 10.CrossRefPubMedGoogle Scholar
  11. Byrne S, Elamin M, Bede P, Shatunov A, Walsh C, Corr B, Heverin M, Jordan N, Kenna K, Lynch C, McLaughlin RL, Iyer PM, O'Brien C, Phukan J, Wynne B, Bokde AL, Bradley DG, Pender N, Al-Chalabi A, Hardiman O. Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72repeat expansion: a population-based cohort study. Lancet Neurol. 2012;11(3):232–40. doi:10.1016/S1474-4422(12)70014-5.PubMedCentralCrossRefPubMedGoogle Scholar
  12. Chiò A, Hammond ER, Mora G, Bonito V, Filippini G. Development and evaluation of a clinical staging system for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2015;86(1):38–44. doi:10.1136/jnnp-2013-306589. Epub 2013 Dec 13. PubMed.CrossRefPubMedGoogle Scholar
  13. Cronin S, Hardiman O, Traynor BJ. Ethnic variation in the incidence of ALS: a systematic review. Neurology. 2007;68(13):1002–7.CrossRefPubMedGoogle Scholar
  14. De Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, et al. Electrodiagnostic criteria for the diagnosis of ALS. Clin Neurophys. 2008;119:497–503.CrossRefGoogle Scholar
  15. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R. Expanded GGGGCC hexanucleotide repeat innoncoding region of C9ORF72causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72(2):245–56.PubMedCentralCrossRefPubMedGoogle Scholar
  16. Elamin M, Bede P, Byrne S, Jordan N, Gallagher L, Wynne B, O'Brien C, Phukan J, Lynch C, Pender N, Hardiman O. Cognitive changes predict functional decline inALS: a population-based longitudinal study. Neurology. 2013;80(17):1590–7. doi:10.1212/WNL.0b013e31828f18ac. Epub 2013 Apr 3. PubMed.CrossRefPubMedGoogle Scholar
  17. Hardiman O, van den Berg LH, Kiernan MC. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol. 2011;7(11):639–49. doi:10.1038/nrneurol.2011.153.CrossRefPubMedGoogle Scholar
  18. Logroscino G, Traynor BJ, Hardiman O, Chio A, Couratier P, Mitchell JD, Swingler RJ, Beghi E, EURALS. Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry. 2008;79(1):6–11.CrossRefPubMedGoogle Scholar
  19. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC, Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009a;73(15):1227–33.PubMedCentralCrossRefPubMedGoogle Scholar
  20. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC, Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009b;73(15):1218–26. Review. Erratum in: neurology. 2009;73(24):2134.PubMedCentralCrossRefPubMedGoogle Scholar
  21. Shatunov A, Mok K, Newhouse S, Weale ME, Smith B, Vance C, Johnson L, Veldink JH, van Es MA, van den Berg LH, Robberecht W, Van Damme P, Hardiman O, Farmer AE, Lewis CM, Butler AW, Abel O, Andersen PM, Fogh I, Silani V, Chiò A, Traynor BJ, Melki J, Meininger V, Landers JE, McGuffin P, Glass JD, Pall H, Leigh PN, Hardy J, Brown Jr RH, Powell JF, Orrell RW, Morrison KE, Shaw PJ, Shaw CE, Al-Chalabi A. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol. 2010;9(10):986–94. doi:10.1016/S1474-4422(10)70197-6.PubMedCentralCrossRefPubMedGoogle Scholar
  22. Turner MR, Hardiman O, Benatar M, Brooks BR, Chio A, de Carvalho M, Ince PG, Lin C, Miller RG, Mitsumoto H, Nicholson G, Ravits J, Shaw PJ, Swash M, Talbot K, Traynor BJ, Van den Berg LH, Veldink JH, Vucic S, Kiernan MC. Controversies andpriorities in amyotrophic lateral sclerosis. Lancet Neurol. 2013;12(3):310–22. doi:10.1016/S1474-4422(13)70036-X.PubMedCentralCrossRefPubMedGoogle Scholar
  23. Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman OM. Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: a population-based study. Arch Neurol. 2000a;57(8):1171–6.CrossRefPubMedGoogle Scholar
  24. Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman O. Amyotrophic lateral sclerosis mimic syndromes: a population-based study. Arch Neurol. 2000b;57(1):109–13.CrossRefPubMedGoogle Scholar
  25. Turner MR, Kiernan MC, Leigh PN, Talbot K. Biomarkers in amyotrophic lateral sclerosis. Lancet Neurol. 2009;8(1):94–109.CrossRefPubMedGoogle Scholar
  26. Valendra R, Jones A, Jivraj N, Steen IN, Young CA, Shaw PJ, Turner MR, Leigh PN, Al-Chalabi A, UK-MND LiCALS Study Group, Mito Target alS Study Group. Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials. J Neurol Neurosurg Psychiatry. 2015;86(1):45–9. doi:10.1136/jnnp-2013-306865. Epub 2014 Jan 24. PubMed PMID: 24463480.

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Orla Hardiman
    • 1
  • Matthew C. Kiernan
    • 2
  • Leonard H. van den Berg
    • 3
  1. 1.Academic Unit of NeurologyTrinity Biomedical Sciences InstituteDublinIreland
  2. 2.Brain and Mind Centre, Sydney Medical SchoolUniversity of Sydnes, Royal Prince Alfred HospitalCamperdownAustralia
  3. 3.Department of NeurologyUniversity Medical Center UtrechtUtrechtThe Netherlands

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