Authors: I. Štětkářová 1; R. Matěj 2,3; E. Ehler 4 Authors place of work: Neurologická klinika 3. LF UK a FNKV, Praha 1; Oddělení patologie a molekulární medicíny, Thomayerova nemocnice, Praha 2; Ústav patologie, 3. LF UK a FNKV, Praha 3; Neurologická klinika FZS UP a Pardubické krajské nemocnice, a. s. 4 Published in the journal: Cesk Slov Neurol N 2018; 81(5): 546-554 Category: Přehledný článek doi: https://doi.org/10.14735/amcsnn2018546
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of increased prevalence with age. The main findings are loss of peripheral and central motoneurons and their pathways with extraocular and sphincter muscle sparing. These are classical forms of ALS with loss of central and peripheral motoneurons, as well as progressive bulbar paralysis with impairment of bulbar muscles. Progressive muscle atrophy with only peripheral motoneuron lesions and primary lateral sclerosis with only central motoneuron involvement are rarely found. There are some forms of ALS associated with dementia (frontotemporal lobar dementia-motor neuron disease [FTLD-MND]) with behavioral changes, cognitive and executive dysfunction. The cause of ALS has not yet been elucidated. It is a chain of follow-up events, at the end of which is cell death in selective subpopulations of neurons. In the present paper, we describe in detail the neuropathological findings and molecular genetic analysis in familial forms of ALS. A specific drug for this disease is still unknown. Neuroprotective drugs (such as riluzole and recently edaravon) have an ambiguous effect. Symptomatic treatment is designed to manage concomitant manifestations. Different treatment options are discussed in detail.
Key words: amyotrophic lateral sclerosis – ALS – neurophysiology – motoneuron lesion – riluzole – edaravone
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
1. Mathis S, Couratier P, Julian A et al. Current view and perspectives in amyotrophic lateral sclerosis. Neural Regen Res 2017; 12(2): 181 – 184. doi: 10.4103/ 1673-5374.200794.
2. Jaiswal MK. Selective vulnerability of motoneuron and perturbed mitochondrial calcium homeostasis in amyotrophic lateral sclerosis: implications for motoneurons specific calcium dysregulation. Mol Cell Ther 2014; 2 : 26. doi: 10.1186/ 2052-8426-2-26.
3. Federico A, Cardaioli E, Da Pozzo P et al. Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 2012; 322(1 – 2): 254 – 262. doi: 10.1016/ j.jns.2012.05.030.
4. Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med 2013; 377(2): 162 – 172. doi: 10.1056/ NEJMra1603471.
5. Ambler Z, Bednařík J, Růžička E et al. Klinická neurologie – část speciální II. Praha: Triton 2010.
6. Vucic S, Kiernan MC. Utility of transcranial magnetic stimulation in delineating amyotrophic lateral sclerosis pathophysiology. Handb Clin Neurol 2013; 116 : 561 – 575. doi: 10.1016/ B978-0-444-53497-2.00045-0.
7. Iglesias C, Sangari S, E Mendili MM et al. Electrophysiological and spinal imaging evidences for sensory dysfunction in amyotrophic lateral sclerosis. BMJ Open 2015; 5(2): e007659. doi: 10.1136/ bmjopen-2015-007659.
8. Eisen A, Braak H, Del Tredici K et al. Cortical influences drive amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2017; 88(11): 917 – 924. doi: 10.1136/ jnnp-2017-315573.
9. Bräuer S, Zimyanin V, Hermann A. Prion-like properties of disease-relevant proteins in amyotrophic lateral sclerosis. J Neural Transm (Vienna) 2018; 125(4): 591 – 613. doi: 10.1007/ s00702-018-1851-y.
10. Al-Chalabi A, Hardiman O, Kiernan MC et al. Amyotrophic lateral sclerosis: moving towards a new classification system. Lancet Neurol 2016; 15(11): 1182 – 1194. doi: 10.1016/ S1474-4422(16)30199-5.
11. Vlčková E. Amyotrofická laterální skleróza. Neurol praxi 2016; 17(6): 362 – 365.
12. Hardiman O, van den Berg LH, Kiernan MC. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol 2011; 7(11): 639 – 649. doi: 10.1038/ nrneurol.2011.153.
13. Geser F, Brandmeir NJ, Kwong LK. Evidence of multisystem disorder in whole-brain map of pathological TDP-43 in amyotrophic lateral sclerosis. Arch Neurol2008; 65(5): 636 – 641. doi: 10.1001/ archneur.65.5.636.
14. Geser F, Martinez-Lage M, Robinson J. Clinical and pathological continuum of multisystem TDP-43 proteinopathies. Arch Neurol 2009; 66(2): 180 – 189. doi: 10.1001/ archneurol.2008.558.
15. Aulas A, Vande Velde C. Alterations in stress granule dynamics driven by TDP-43 and FUS: a link to pathological inclusions in ALS? Front Cell Neurosci 2015; 9 : 423. doi: 10.3389/ fncel.2015.00423.
16. Vucic S, Rothstein JD, Kiernan MC. Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies. Trends Neurosci 2014; 37(8): 433 – 442. doi: 10.1016/ j.tins.2014.05.006.
17. 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 – 130. doi: 10.1159/ 000351153.
18. Wu CH, Fallini C, Ticozzi N et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 2012; 488(7412): 499 – 503. doi: 10.1038/ nature11280.
19. Gorges M, Vercruysse P, Müller HP et al. Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2017; 88(12): 1033 – 1041. doi: 10.1136/ jnnp-2017-315795.
20. Katirji B, Kaminski HJ, Ruff RL (eds). Neuromuscular disorders in clinical practice. New York: Springer 2014.
21. Goutman SA. Diagnosis and clinical management of amyotrophic lateral sclerosis and other motor neuron disorders. Continuum 2017; 23(5): 1332 – 1359. doi: 10.1212/ CON.0000000000000535.
22. de Carvalho M, Swash M. Fasciculation potentials and earliest changes in motor unit physiology in ALS. J Neurol Neurosurg Psychiatry 2013; 84(9): 963 – 968. doi: 10.1136/ jnnp-2012-304545.
23. Schrooten M, Smetcoren C, Robberecht W et al. Benefit of the Awaji diagnostic algorithm for amyotrophic lateral sclerosis: a prospective study. Ann Neurol 2011; 70(1): 79 – 83. doi: 10.1002/ ana.22380.
24. Vucic S, Kiernan MC. Transcranial magnetic stimulation for the assessment of neurodegenerative disease. Neurotherapeutics 2017; 14(1): 91 – 106. doi: 10.1007/ s13311-016-0487-6.
25. Baldaranov D, Khomenko A, Kobor I et al. longitudinal diffusion tensor imaging-based assessment of tract alterations: an application to amyotrophic lateral sclerosis. Front Hum Neurosci 2017; 11 : 567. doi: 10.3389/ fnhum.2017.00567.
26. Mélé N, Berzero G, Maisonobe T et al. Motor neuron disease of paraneoplastic origin: a rare but treatable condition. J Neurol 2018; 265(7): 1590 – 1599. doi: 10.1007/ s00415-018-8881-0.
27. Ellison D, Love S, Cardao Chimelli LM et al. Neuropathology: a reference text of CNS pathology. 3rd ed. London: Mosby Elsevier 2013.
28. Dickson DW, Weller RO. Neurodegeneration. The molecular pathology of dementia and movement disorders. 2nd ed. Chichester: Wiley-Blackwell 2011.
29. Love S, Perry A, Ironside J et al. Greenfield‘s Neuropathology. 9th ed. Boca Raton: CRC Press 2015.
30. Mackenzie IR, Frick P, Neumann M. The neuropathology associated with repeat expansions in the C9ORF72 gene. Acta Neuropathol 2014; 127(3): 347 – 357. doi: 10.1007/ s00401-013-1232-4.
31. Kato S, Hayashi H, Nakashima K et al. Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis. Am J Pathol 1997; 151(2): 611 – 620.
32. Ji AL, Zhang X, Chen WW et al. Genetics insight into the amyotrophic lateral sclerosis/ frontotemporal dementia spectrum. J Med Genet 2017; 54(3): 145 – 154. doi: 10.1136/ jmedgenet-2016-104271.
33. DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72(2): 245 – 256. doi: 10.1016/ j.neuron.2011.09.011.
34. Millecamps S, Boillée S, Le Ber I et al. Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. J Med Genet 2012; 49(4): 258 – 263. doi: 10.1136/ jmedgenet-2011-100699.
35. Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/ Riluzole Study Group. N Engl J Med 1994; 330(9): 585 – 591. doi: 10.1056/ NEJM199403033300901.
36. Fang T, Al Khleifat A, Meurgey JH et al. Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study. Lancet Neurol 2018; 17(5): 416 – 422. doi: 10.1016/ S1474-4422(18)30054-1.
37. Writing Group; Edaravone (MCI-186) ALS 19 StudyGroup. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2017; 16(7): 505 – 512. doi: 10.1016/ S1474-4422(17)30115-1.
38. Ikeda K, Iwasaki Y, Kaji R. Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis. J Neurol Sci 2015; 354(1 – 2): 70 – 74. doi: 10.1016/ j.jns.2015.04.052.
39. Akamatsu M, Yamashita T, Hirose N et al. The AMPA receptor antagonist perampanel robustly rescues amyotrophic lateral sclerosis (ALS) pathology in sporadic ALS model mice. Sci Rep 2016; 6 : 28649. doi: 10.1038/ srep28649.
40. Trias E, Ibarburu S, Barreto-Núñez R et al. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J Neuroinflammation 2016; 13(1): 177. doi: 10.1186/ s12974-016-0620-9.
41. Imamura K, Izumi Y, Watanabe A et al. The Src/ c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis. Sci Transl Med 2017; 9(391): pii: eaaf3962. doi: 10.1126/ scitranslmed.aaf3962.
42. Bozik ME, Mitsumoto H, Brooks BR et al. A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical trial (EMPOWER) of dexpramipexole in ALS. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15(5 – 6): 406 – 413. doi: 10.3109/ 21678421.2014.943672.
43. Vieira FG, LaDow E, Moreno A et al. Dexpramipexole is ineffective in two models of ALS related neurodegeneration. PLoS One 2014; 9(12): e91608. doi: 10.1371/ journal.pone.0091608.
44. Shefner JM, Wolff AA, Meng L et al. A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2016; 17(5 – 6): 426 – 435. doi: 10.3109/ 21678421.2016.1148169.
45. Morrison KE, Dhariwal S, Hornabrook R et al. Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2013; 12(4): 339 – 345. doi: 10.1016/ S1474-4422(13)70037-1.
46. Gotaas HT, Skeie GO, Gilhus NE. Myasthenia gravis and amyotrophic lateral sclerosis: A pathogenic overlap. Neuromuscul Disord 2016; 26(6): 337 – 341. doi: 10.1016/ j.nmd.2016.03.003.
47. Watanabe H, Atsuta N, Hirakawa A et al. A rapid functional decline type of amyotrophic lateral sclerosis is linked to low expression of TTN. J Neurol Neurosurg Psychiatry 2016; 87(8): 851 – 858. doi: 10.1136/ jnnp-2015-311541.
48. Thomsen GM, Gowing G, Svendsen S, Svendsen CN. The past, present and future of stem cell clinical trials for ALS. Exp Neurol 2014; 262 : 127 – 137. doi: 10.1016/ j.expneurol.2014.02.021.
49. Staff NP, Madigan NN, Morris J et al. Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS. Neurology 2016; 87(21): 2230 – 2234. doi: 10.1212/ WNL.0000000000003359.
50. Petrou P, Gothelf Y, Argov Z et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/ 2 and 2a clinical trials. JAMA Neurol 2016; 73(3): 337 – 344. doi: 10.1001/ jamaneurol.2015.4321.
51. Baumgartner D, Marusič P, Mazanec R. Kmenové buňky v léčbě amyotrofické laterální sklerózy – přehled současných klinických zkušeností. Cesk Slov Neurol N 2017; 80/ 113(1): 27 – 33. doi: 10.14735/ amcsnn201727.
52. Hosp C, Naumann MK, Hamm H. Botulinum ToxinTreatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea. Semin Neurol 2016; 36(1): 20 – 28. doi: 10.1055/ s-0035-1571214.
53. Guidubaldi A, Fasano A, Ialongo T et al. Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson‘s disease. Mov Disord 2011; 26(2): 313 – 319. doi: 10.1002/ mds.23473.
54. Vázquez-Costa JF, Máñez I, Alabajos A et al. Safety and efficacy of botulinum toxin A for the treatment of spasticity in amyotrophic lateral sclerosis: results of a pilot study. J Neurol 2016; 263(10): 1954 – 1960. doi: 10.1007/ s00415-016-8223-z.
55. McClelland S 3rd, Bethoux FA, Boulis NM et al. Intrathecal baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle Nerve 2008; 37(3): 396 – 398. doi: 10.1002/ mus.20900
56. Ng L, Khan, Young CA et al. Symptomatic treatments for amyotrophic lateral sclerosis/ motor neuron disease. Cochrane Database Syst Rev 2017; 1: CD011776. doi: 10.1002/ 14651858.CD011776.pub2.
57. Vázquez-Costa JF, Arlandis S, Hervas D et al. Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder. J Neurol Sci 2017; 378 : 130 – 136. doi: 10.1016/ j.jns.2017.04.053.
Zvyšte si kvalifikaci online z pohodlí domova
Nemáte účet? Registrujte se
Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.
