Amyotrophic lateral sclerosis - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Amyotrophic lateral sclerosis (ALS) is a progressive disease characterized by degeneration of motor neurons with cortical, brainstem, and ventral cord locations.
ALS usually presents as a combination of upper motor neuron and lower motor neuron symptoms and signs, involving initially one segment of the neuroaxis (i.e., cranial, cervical, thoracic, or lumbosacral), and then progressively spreading, typically to contiguous areas.
Typical presentations include limb-onset and bulbar-onset ALS or, less frequently, respiratory-onset ALS. Generalization of the symptoms follows in time, without intervals of remission, exacerbation, or stabilization, resulting in progressive disability and death.
There is no cure for ALS. The focus of medical care is to provide supportive and palliative interventions, aiming to optimize the patient's quality of life. Riluzole prolongs survival and should be offered to patients at the time of diagnosis.
Continued discussions with the patient and their family regarding advance directives, as well as methods of respiratory and nutritional support, are critical. Palliative care options should be presented and discussed before they are needed.

Quick Reference

History & Exam
- Key Factors
- Other Factors
More information...
Diagnostics Tests
More information...
Treatment Options
More information...

Definition

Epidemiology

Etiology

Pathophysiology

Citations

Key Articles

Shoesmith C, Abrahao A, Benstead T, et al. Canadian best practice recommendations for the management of amyotrophic lateral sclerosis. CMAJ. 2020 Nov 16;192(46):E1453-68.[Abstract][Full Text]
Andersen PM, Abrahams S, Borasio GD, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) - revised report of an EFNS task force. Eur J Neurol. 2012 Mar;19(3):360-75.[Abstract][Full Text]
Brooks BR, Miller RG, Swash M, et al; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9.[Abstract]
de Carvalho M, Dengler R, Eisen A, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol. 2008 Mar;119(3):497-503.[Abstract]
Shefner JM, Al-Chalabi A, Baker MR, et al. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol. 2020 Aug;131(8):1975-8.[Abstract][Full Text]
Miller RG, Jackson CE, Kasarskis EJ, et al; 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). Neurology. 2009 Oct 13;73(15):1227-33.[Abstract][Full Text]
Miller RG, Jackson CE, Kasarskis EJ, et al; 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). Neurology. 2009 Oct 13;73(15):1218-26. [Errata in: Neurology. 2009 Dec 15;73(24):2134; Neurology. 2010 Mar 2;74(9):781.][Abstract][Full Text]

Other Online Resources

MDA (Muscular Dystrophy Association): ALS division

Referenced Articles

1. Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. 2013 Nov;9(11):617-28.[Abstract]
2. Gordon PH, Cheng B, Katz IB, et al. The natural history of primary lateral sclerosis. Neurology. 2006 Mar 14;66(5):647-53.[Abstract]
3. Tartaglia MC, Rowe A, Findlater K, et al. Differentiation between primary lateral sclerosis and amyotrophic lateral sclerosis: examination of symptoms and signs at disease onset and during follow-up. Arch Neurol. 2007 Feb;64(2):232-6.[Abstract][Full Text]
4. Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998 Dec;51(6):1546-54.[Abstract]
5. Strong MJ, Abrahams S, Goldstein LH, et al. Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):153-74.[Abstract][Full Text]
6. Beck M, Giess R, Magnus T, et al. Progressive sudomotor dysfunction in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2002 Jul;73(1):68-70.[Abstract][Full Text]
7. Shimizu T, Kawata A, Kato S, et al. Autonomic failure in ALS with a novel SOD1 gene mutation. Neurology. 2000 Apr 11;54(7):1534-7.[Abstract]
8. GBD 2016 Motor Neuron Disease Collaborators. Global, regional, and national burden of motor neuron diseases 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Dec;17(12):1083-97.[Abstract][Full Text]
9. GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):459-80.[Abstract][Full Text]
10. Chiò A, Logroscino G, Traynor BJ, et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology. 2013;41(2):118-30.[Abstract][Full Text]
11. Shoesmith C, Abrahao A, Benstead T, et al. Canadian best practice recommendations for the management of amyotrophic lateral sclerosis. CMAJ. 2020 Nov 16;192(46):E1453-68.[Abstract][Full Text]
12. Logroscino G, Traynor BJ, Hardiman O, et al; EURALS. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2010 Apr;81(4):385-90.[Abstract][Full Text]
13. Worms PM. The epidemiology of motor neuron diseases: a review of recent studies. J Neurol Sci. 2001 Oct 15;191(1-2):3-9.[Abstract]
14. Cronin S, Hardiman O, Traynor BJ. Ethnic variation in the incidence of ALS: a systematic review. Neurology. 2007 Mar 27;68(13):1002-7.[Abstract]
15. Lin CL, Bristol LA, Jin L, et al. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron. 1998 Mar;20(3):589-602.[Abstract][Full Text]
16. Kawahara Y, Ito K, Sun H, et al. Glutamate receptors: RNA editing and death of motor neurons. Nature. 2004 Feb 26;427(6977):801.[Abstract][Full Text]
17. Feldman EL, Goutman SA, Petri S, et al. Amyotrophic lateral sclerosis. Lancet. 2022 Oct 15;400(10360):1363-80.[Abstract]
18. Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59-62.[Abstract]
19. Beal MF. Mitochondria take center stage in aging and neurodegeneration. Ann Neurol. 2005 Oct;58(4):495-505.[Abstract]
20. Lin H, Schlaepfer WW. Role of neurofilament aggregation in motor neuron disease. Ann Neurol. 2006 Oct;60(4):399-406.[Abstract]
21. van Es MA, Hardiman O, Chio A, et al. Amyotrophic lateral sclerosis. Lancet. 2017 Nov 4;390(10107):2084-98.[Abstract]
22. Kirola L, Mukherjee A, Mutsuddi M. Recent updates on the genetics of amyotrophic lateral sclerosis and frontotemporal dementia. Mol Neurobiol. 2022 Sep;59(9):5673-94.[Abstract]
23. Rutherford NJ, Heckman MG, Dejesus-Hernandez M, et al. Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. Neurobiol Aging. 2012 Dec;33(12):2950.e5-7.[Abstract][Full Text]
24. Roggenbuck J, Eubank BHF, Wright J, et al. Evidence-based consensus guidelines for ALS genetic testing and counseling. Ann Clin Transl Neurol. 2023 Nov;10(11):2074-91.[Abstract][Full Text]
25. McKay KA, Smith KA, Smertinaite L, et al. Military service and related risk factors for amyotrophic lateral sclerosis. Acta Neurol Scand. 2021 Jan;143(1):39-50.[Abstract][Full Text]
26. Re DB, Yan B, Calderón-Garcidueñas L, et al. A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk. J Neurol. 2022 May;269(5):2359-77.[Abstract][Full Text]
27. Weisskopf MG, O'Reilly EJ, McCullough ML, et al. Prospective study of military service and mortality from ALS. Neurology. 2005 Jan 11;64(1):32-7.[Abstract]
28. Lacorte E, Ferrigno L, Leoncini E, et al. Physical activity, and physical activity related to sports, leisure and occupational activity as risk factors for ALS: a systematic review. Neurosci Biobehav Rev. 2016 Jul;66:61-79.[Abstract]
29. Visser AE, Rooney JPK, D'Ovidio F, et al. Multicentre, cross-cultural, population-based, case-control study of physical activity as risk factor for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2018 Aug;89(8):797-803.[Abstract]
30. Julian TH, Glascow N, Barry ADF, et al. Physical exercise is a risk factor for amyotrophic lateral sclerosis: convergent evidence from Mendelian randomisation, transcriptomics and risk genotypes. EBioMedicine. 2021 Jun;68:103397.[Abstract][Full Text]
31. Alonso A, Logroscino G, Hernán MA. Smoking and the risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2010 Nov;81(11):1249-52.[Abstract][Full Text]
32. Armon C. Smoking may be considered an established risk factor for sporadic ALS. Neurology. 2009 Nov 17;73(20):1693-8.[Abstract][Full Text]
33. Sutedja NA, Veldink JH, Fischer K, et al. Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: a systematic review. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):302-9.[Abstract]
34. Kamel F, Umbach DM, Munsat TL, et al. Lead exposure and amyotrophic lateral sclerosis. Epidemiology. 2002 May;13(3):311-9.[Abstract][Full Text]
35. Andersen PM, Abrahams S, Borasio GD, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) - revised report of an EFNS task force. Eur J Neurol. 2012 Mar;19(3):360-75.[Abstract][Full Text]
36. National Institute for Health and Care Excellence. Motor neurone disease: assessment and management. Jul 2019 [internet publication].[Full Text]
37. Mahoney CJ, Sleeman R, Errington W. Assessment of suspected motor neuron disease. BMJ. 2022 Nov 23;379:e073857.[Abstract]
38. Shoesmith CL, Findlater K, Rowe A, et al. Prognosis of amyotrophic lateral sclerosis with respiratory onset. J Neurol Neurosurg Psychiatry. 2007 Jun;78(6):629-31.[Abstract]
39. Shipe C, Zivkovic SA. Electrodiagnostic evaluation of motor neuron disorders. Am J Electroneurodiagnostic Technol. 2004 Mar;44(1):30-6.[Abstract]
40. de Carvalho M, Swash M. Nerve conduction studies in amyotrophic lateral sclerosis. Muscle Nerve. 2000 Mar;23(3):344-52.[Abstract]
41. Daube JR. Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor neuron disorders. Muscle Nerve. 2000 Oct;23(10):1488-502.[Abstract]
42. Raaphorst J, de Visser M, Linssen WH, et al. The cognitive profile of amyotrophic lateral sclerosis: a meta-analysis. Amyotroph Lateral Scler. 2010 Feb 26;11(1-2):27-37.[Abstract]
43. Lomen-Hoerth C. Characterization of amyotrophic lateral sclerosis and frontotemporal dementia. Dement Geriatr Cogn Disord. 2004;17(4):337-41.[Abstract]
44. Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology. 2002 Oct 8;59(7):1077-9.[Abstract]
45. Kornberg, AJ, Pestronk A. The clinical and diagnostic role of anti-GM1 antibody testing. Muscle Nerve. 1994 Jan;17(1):100-4.[Abstract]
46. Pestronk A, Cornblath DR, Ilyas AA, et al. A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside. Ann Neurol. 1988 Jul;24(1):73-8.[Abstract]
47. Gourie-Devi M, Nalini A. Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta Neurol Scand. 2003 Mar;107(3):215-20.[Abstract]
48. Blexrud MD, Windebank AJ, Daube JR. Long-term follow-up of 121 patients with benign fasciculations. Ann Neurol. 1993 Oct;34(4):622-5.[Abstract]
49. Chasens ER, Umlauf MG. Post-polio syndrome. Am J Nurs. 2000 Dec;100(12):60-3, 65, 67.[Abstract]
50. Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Mov Disord. 2017 Jun;32(6):853-64.[Abstract]
51. von Kügelgen I, Starke K. Noradrenaline and adenosine triphosphate as co-transmitters of neurogenic vasoconstriction in rabbit mesenteric artery. J Physiol. 1985 Oct;367:435-55.[Abstract][Full Text]
52. Brooks BR; Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic lateral sclerosis" workshop contributors. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci. 1994 Jul;124 Suppl:96-107.[Abstract]
53. Brooks BR, Miller RG, Swash M, et al; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9.[Abstract]
54. de Carvalho M, Dengler R, Eisen A, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol. 2008 Mar;119(3):497-503.[Abstract]
55. Shefner JM, Al-Chalabi A, Baker MR, et al. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol. 2020 Aug;131(8):1975-8.[Abstract][Full Text]
56. Paganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis. N Engl J Med. 2020 Sep 3;383(10):919-30.[Abstract][Full Text]
57. Benatar M, Kurent J, Moore DH. Treatment for familial amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006153.[Abstract][Full Text]
58. Lee CN. Reviewing evidences on the management of patients with motor neuron disease. Hong Kong Med J. 2012 Feb;18(1):48-55.[Abstract][Full Text]
59. Miller RG, Jackson CE, Kasarskis EJ, et al; 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). Neurology. 2009 Oct 13;73(15):1227-33.[Abstract][Full Text]
60. Van den Berg JP, Kalmijn S, Lindeman E, et al. Multidisciplinary ALS care improves quality of life in patients with ALS. Neurology. 2005 Oct 25;65(8):1264-7.[Abstract]
61. Lazovic M, Nikolic D, Boyer FC, et al. Evidence-based position paper on Physical and Rehabilitation Medicine practice for people with amyotrophic lateral sclerosis. Eur J Phys Rehabil Med. 2022 Apr;58(2):271-9.[Abstract][Full Text]
62. Taylor LP, Besbris JM, Graf WD, et al. Clinical guidance in neuropalliative care: an AAN position statement. Neurology. 2022 Mar 8;98(10):409-16.[Abstract][Full Text]
63. van Eenennaam RM, Kruithof WJ, van Es MA, et al. Discussing personalized prognosis in amyotrophic lateral sclerosis: development of a communication guide. BMC Neurol. 2020 Dec 14;20(1):446.[Abstract][Full Text]
64. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012 Mar 14;(3):CD001447.[Abstract][Full Text]
65. Miller RG, Jackson CE, Kasarskis EJ, et al; 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). Neurology. 2009 Oct 13;73(15):1218-26. [Errata in: Neurology. 2009 Dec 15;73(24):2134; Neurology. 2010 Mar 2;74(9):781.][Abstract][Full Text]
66. Bensimon G, Lacomblez L, Meininger V; ALS/Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med. 1994 Mar 3;330(9):585-91.[Abstract][Full Text]
67. Weber G, Bitterman H. Riluzole-induced neutropenia. Neurology. 2004 May 11;62(9):1648.[Abstract]
68. Abe K, Itoyama Y, Sobue G, et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):610-7.[Abstract][Full Text]
69. Abe K, Aoki M, Tsuji S, et al; Writing Group; Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017 Jul;16(7):505-12.[Abstract]
70. Brooks BR, Berry JD, Ciepielewska M, et al. Intravenous edaravone treatment in ALS and survival: an exploratory, retrospective, administrative claims analysis. EClinicalMedicine. 2022 Oct;52:101590.[Abstract][Full Text]
71. Witzel S, Maier A, Steinbach R, et al; German Motor Neuron Disease Network (MND-NET). Safety and effectiveness of long-term intravenous administration of edaravone for treatment of patients with amyotrophic lateral sclerosis. JAMA Neurol. 2022 Feb 1;79(2):121-30.[Abstract][Full Text]
72. Khan A, Frazer-Green L, Amin R, et al. Respiratory management of patients with neuromuscular weakness: an American College of Chest Physicians clinical practice guideline and expert panel report. Chest. 2023 Mar 13 [Epub ahead of print].[Abstract][Full Text]
73. Morgan RK, McNally S, Alexander M, et al. Use of Sniff nasal-inspiratory force to predict survival in amyotrophic lateral sclerosis. Am J Respir Crit Care Med. 2005 Feb 1;171(3):269-74.[Abstract][Full Text]
74. Gonzalez Calzada N, Prats Soro E, Mateu Gomez L, et al. Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation. Amyotroph Lateral Scler Frontotemporal Degener. 2016 Jul-Aug;17(5-6):337-42.[Abstract]
75. Radunovic A, Annane D, Rafiq MK, et al. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2017 Oct 6;(10):CD004427.[Abstract][Full Text]
76. McDermott CJ, Bradburn MJ, Maguire C, et al; DiPALS Writing Committee; 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. 2015 Sep;14(9):883-92.[Abstract][Full Text]
77. Gonzalez-Bermejo J, Morélot-Panzini C, Tanguy ML, et al. Early diaphragm pacing in patients with amyotrophic lateral sclerosis (RespiStimALS): a randomised controlled triple-blind trial. Lancet Neurol. 2016 Nov;15(12):1217-27.[Abstract]
78. McKim DA, Road J, Avendano M, et al; Canadian Thoracic Society Home Mechanical Ventilation Committee. Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011 Jul-Aug;18(4):197-215.[Abstract][Full Text]
79. Moss AH, Casey P, Stocking CB, et al. Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes. Neurology. 1993 Feb;43(2):438-43.[Abstract]
80. Borasio GD, Voltz R, Miller RG. Palliative care in amyotrophic lateral sclerosis. Neurol Clin. 2001 Nov;19(4):829-47.[Abstract]
81. Simon ST, Higginson IJ, Booth S, et al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016 Oct 20;(10):CD007354.[Abstract][Full Text]
82. Dorst J, Doenz J, Kandler K, et al. Fat-rich versus carbohydrate-rich nutrition in ALS: a randomised controlled study. J Neurol Neurosurg Psychiatry. 2022 Mar;93(3):298-302.[Abstract]
83. Castanheira A, Swash M, De Carvalho M. Percutaneous gastrostomy in amyotrophic lateral sclerosis: a review. Amyotroph Lateral Scler Frontotemporal Degener. 2022 May;23(3-4):176-89.[Abstract]
84. Katzberg, HD, Benatar M. Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004030.[Abstract][Full Text]
85. Chio A, Finnochiaro E, Meineri P, et al; ALS Percutaneous Endoscopic Gastrostomy Study Group. Safety and factors related to survival after percutaneous endoscopic gastrostomy in ALS. Neurology. 1999 Sep 22;53(5):1123-5.[Abstract]
86. ProGas Study Group. Gastrostomy in patients with amyotrophic lateral sclerosis (ProGas): a prospective cohort study. Lancet Neurol. 2015 Jul;14(7):702-9.[Abstract][Full Text]
87. Pattee GL, Plowman EK, Focht Garand KL, et al. Provisional best practices guidelines for the evaluation of bulbar dysfunction in amyotrophic lateral sclerosis. Muscle Nerve. 2019 May;59(5):531-6.[Abstract]
88. Light J, McNaughton D, Beukelman D, et al. Challenges and opportunities in augmentative and alternative communication: research and technology development to enhance communication and participation for individuals with complex communication needs. Augment Altern Commun. 2019 Mar;35(1):1-12.[Abstract]
89. James E, Ellis C, Brassington R, et al. Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis. Cochrane Database Syst Rev. 2022 May 20;(5):CD006981.[Abstract][Full Text]
90. Stone CA, O'Leary N. Systematic review of the effectiveness of botulinum toxin or radiotherapy for sialorrhea in patients with amyotrophic lateral sclerosis. J Pain Symptom Manage. 2009 Feb;37(2):246-58.[Abstract][Full Text]
91. Tysnes OB. Treatment of sialorrhea in amyotrophic lateral sclerosis. Acta Neurol Scand Suppl. 2008 May;117(s188):77-81.[Abstract]
92. McGeachan AJ, Mcdermott CJ. Management of oral secretions in neurological disease. Pract Neurol. 2017 Apr;17(2):96-103.[Abstract][Full Text]
93. Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68:693-702.[Abstract]
94. Lui AJ, Byl NN. A systematic review of the effect of moderate intensity exercise on function and disease progression in amyotrophic lateral sclerosis. J Neurol Physical Therapy. 2009 Jun;33(2):68-87.[Abstract][Full Text]
95. Dal Bello-Haas V, Florence JM. Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Rev. 2013 May 31;(5):CD005229.[Abstract][Full Text]
96. Newrick PG, Langton-Hewer R. Pain in motor neuron disease. J Neurol Neurosurg Psychiatry. 1985 Aug;48(8):838-40.[Abstract][Full Text]
97. Marvulli R, Megna M, Citraro A, et al. Botulinum toxin type A and physiotherapy in spasticity of the lower limbs due to amyotrophic lateral sclerosis. Toxins (Basel). 2019 Jul 1;11(7):381.[Abstract][Full Text]
98. Meyer T, Funke A, Münch C, et al. Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol:cannabidiol (THC:CBD). BMC Neurol. 2019 Sep 7;19(1):222.[Abstract][Full Text]
99. Rabkin JG, Albert SM, Del Bene ML, et al. Prevalence of depressive disorders and change over time in late-stage ALS. Neurology. 2005 Jul 12;65(1):62-7.[Abstract][Full Text]
100. Zarotti N, Mayberry E, Ovaska-Stafford N, et al. Psychological interventions for people with motor neuron disease: a scoping review. Amyotroph Lateral Scler Frontotemporal Degener. 2021 Feb;22(1-2):1-11.[Abstract]
101. British Psychological Society. Psychological interventions for people with Huntington's disease, Parkinson's disease, motor neurone disease, and multiple sclerosis. Jan 2021 [internet publication].[Full Text]
102. Pender N, Pinto-Grau M, Hardiman O. Cognitive and behavioural impairment in amyotrophic lateral sclerosis. Curr Opin Neurol. 2020 Oct;33(5):649-54.[Abstract]
103. Cairns NJ, Bigio EH, Mackenzie IR, et al; Consortium for Frontotemporal Lobar Degeneration. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol. 2007 Jul;114(1):5-22.[Abstract][Full Text]
104. Flemming K, Turner V, Bolsher S, et al. The experiences of, and need for, palliative care for people with motor neurone disease and their informal caregivers: a qualitative systematic review. Palliat Med. 2020 Jun;34(6):708-30.[Abstract][Full Text]
105. Lipp A, Trottenberg T, Schink T, et al. A randomized trial of botulinum toxin A for treatment of drooling. Neurology. 2003 Nov 11;61(9):1279-81.[Abstract]
106. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage. 2004;28:140-175.[Abstract]
107. Baloh RH, Johnson JP, Avalos P, et al. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. 2022 Sep;28(9):1813-22.[Abstract][Full Text]
108. Cudkowicz ME, Lindborg SR, Goyal NA, et al. A randomized placebo-controlled phase 3 study of mesenchymal stem cells induced to secrete high levels of neurotrophic factors in amyotrophic lateral sclerosis. Muscle Nerve. 2022 Mar;65(3):291-302.[Abstract][Full Text]
109. Abdul Wahid SF, Law ZK, Ismail NA, et al. Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2019 Dec 19;(12):CD011742.[Abstract][Full Text]
110. Mora JS, Genge A, Chio A, et al; AB10015 Study Group. Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2020 Feb;21(1-2):5-14.[Abstract][Full Text]
111. Chen JJ. Overview of current and emerging therapies for amytrophic lateral sclerosis. Am J Manag Care. 2020 Aug;26(9 suppl):S139-45.[Abstract][Full Text]
112. ClinicalTrials.gov. Efficacy and safety of masitinib versus placebo in the treatment of ALS patients. Mar 2022 [internet publication].[Full Text]
113. Oskarsson B, Maragakis N, Bedlack RS, et al. MN-166 (ibudilast) in amyotrophic lateral sclerosis in a phase IIb/III study: COMBAT-ALS study design. Neurodegener Dis Manag. 2021 Dec;11(6):431-43.[Abstract][Full Text]
114. Miller T, Cudkowicz M, Shaw PJ, et al. Phase 1-2 trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2020 Jul 9;383(2):109-19.[Abstract][Full Text]
115. Miller TM, Cudkowicz ME, Genge A, et al; VALOR and OLE Working Group. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2022 Sep 22;387(12):1099-110.[Abstract]
116. ClinicalTrials.gov. Long-term evaluation of BIIB067. Sep 2021 [internet publication].[Full Text]
117. ClinicalTrials.gov. A study of BIIB067 when initiated in clinically presymptomatic adults with a confirmed superoxide dismutase 1 mutation (ATLAS). Oct 2022 [internet publication].[Full Text]
118. ClinicalTrials.gov. A study to evaluate the efficacy and safety of reldesemtiv in patients with amyotrophic lateral sclerosis (ALS) (COURAGE-ALS). Jan 2023 [internet publication].[Full Text]
119. ClinicalTrials.gov. A study to evaluate, safety, tolerability, pharmacodynamic (PD) markers and pharmacokinetics (PK) of AP-101 in participants with amyotrophic lateral sclerosis (ALS). Aug 2022 [internet publication].[Full Text]
120. ClinicalTrials.gov. Phase 2 study for SAR443820 in participants with amyotrophic lateral sclerosis (ALS) (HIMALAYA). Jan 2023 [internet publication].[Full Text]
121. ClinicalTrials.gov. HEALEY ALS Platform Trial - regimen E SLS-005 - trehalose. Mar 2022 [internet publication].[Full Text]
122. Turner MR, Parton MJ, Shaw CE, et al. Prolonged survival in motor neuron disease: a descriptive study of the King's database 1990-2002. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):995-7.[Abstract][Full Text]
123. Chiò A, Logroscino G, Hardiman O, et al; Eurals Consortium. Prognostic factors in ALS: a critical review. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):310-23.[Abstract]
124. Eisen A, Schulzer M, MacNeil M, et al. Duration of amyotrophic lateral sclerosis is age dependent. Muscle Nerve. 1993 Jan;16(1):27-32.[Abstract]
125. Spencer KR, Foster ZW, Rauf NA, et al. Neuropathological profile of long-duration amyotrophic lateral sclerosis in military veterans. Brain Pathol. 2020 Nov;30(6):1028-40.[Abstract][Full Text]
126. Czaplinski A, Yen AA, Appel SH. Forced vital capacity (FVC) as an indicator of survival and disease progression in an ALS clinic population. J Neurol Neurosurg Psychiatry. 2006 Mar;77(3):390-2.[Abstract]
127. Goutman SA, Boss J, Iyer G, et al. Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles. Muscle Nerve. 2022 Nov 2 [Epub ahead of print].[Abstract][Full Text]
128. Sanofi-Aventis. Rilutek® (riluzole) tablets: prescribing information. Nov 2012 [internet publication].[Full Text]
129. Farrag K, Shastri YM, Beilenhoff U, et al. Percutaneous endoscopic gastrostomy (PEG): a practical approach for long term management. BMJ. 2019 Jan 22;364:k5311.[Abstract]