New developments and future opportunities in biomarkers for amyotrophic lateral sclerosis

1.

Mitchell JD, Callagher P, Gardham J, Mitchell C, Dixon M, Addison-Jones R, et al. Timelines in the diagnostic evaluation of people with suspected amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)--a 20-year review: can we do better? Amyotroph Lateral Scler. 2010;11(6):537–41. doi:10.3109/17482968.2010.495158.PubMedCrossRef

2.

Chadwick R, Nadig V, Oscroft NS, Shneerson JM, Smith IE. Weaning from prolonged invasive ventilation in motor neuron disease: analysis of outcomes and survival. J Neurol Neurosurg Psychiatry. 2011;82(6):643–5. doi:10.1136/jnnp.2009.193631.PubMedCrossRef

3.

Turner MR, Parton MJ, Shaw CE, Leigh PN, Al-Chalabi A. Prolonged survival in motor neuron disease: a descriptive study of the King’s database 1990–2002. J Neurol Neurosurg Psychiatry. 2003;74(7):995–7.PubMedCentralPubMedCrossRef

4.

Kim WK, Liu X, Sandner J, Pasmantier M, Andrews J, Rowland LP, et al. Study of 962 patients indicates progressive muscular atrophy is a form of ALS. Neurology. 2009;73(20):1686–92. doi:10.1212/WNL.0b013e3181c1dea3.PubMedCentralPubMedCrossRef

5.

Gordon PH, Cheng B, Katz IB, Pinto M, Hays AP, Mitsumoto H, et al. The natural history of primary lateral sclerosis. Neurology. 2006;66(5):647–53. doi:10.1212/01.wnl.0000200962.94777.71.PubMedCrossRef

6.

Chio A, Calvo A, Moglia C, Mazzini L, Mora G. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2011;82(7):740–6. doi:10.1136/jnnp.2010.235952.PubMedCrossRef

7.

Niebroj-Dobosz I, Janik P, Sokolowska B, Kwiecinski H. Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Eur J Neurol. 2010;17(2):226–31. doi:10.1111/j.1468-1331.2009.02775.x.PubMedCrossRef

8.

Fang L, Huber-Abel F, Teuchert M, Hendrich C, Dorst J, Schattauer D, et al. Linking neuron and skin: matrix metalloproteinases in amyotrophic lateral sclerosis (ALS). J Neurol Sci. 2009;285(1–2):62–6. doi:10.1016/j.jns.2009.05.025.PubMedCrossRef

9.

Tortelli R, Ruggieri M, Cortese R, D’Errico E, Capozzo R, Leo A, et al. Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression. Eur J Neurol. 2012;19(12):1561–7. doi:10.1111/j.1468-1331.2012.03777.x.PubMedCrossRef

10.

Tortelli R, Copetti M, Ruggieri M, Cortese R, Capozzo R, Leo A, et al. Cerebrospinal fluid neurofilament light chain levels: marker of progression to generalized amyotrophic lateral sclerosis. Eur J Neurol. 2015;22(1):215–8. doi:10.1111/ene.12421.PubMedCrossRef

11.

Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, et al. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015;84(22):2247–57. doi:10.1212/WNL.0000000000001642.PubMedCentralPubMedCrossRef

12.

Ganesalingam J, An J, Shaw CE, Shaw G, Lacomis D, Bowser R. Combination of neurofilament heavy chain and complement C3 as CSF biomarkers for ALS. J Neurochem. 2011;117(3):528–37. doi:10.1111/j.1471-4159.2011.07224.x.PubMedCentralPubMedCrossRef

13.

Grossman M, Elman L, McCluskey L, McMillan CT, Boller A, Powers J, et al. Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis. JAMA Neurol. 2014;71(4):442–8. doi:10.1001/jamaneurol.2013.6064.PubMedCentralPubMedCrossRef

14.

Wilke C, Deuschle C, Rattay TW, Maetzler W, Synofzik M. Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis. Neurobiol Aging. 2015;36(2):1072–4. doi:10.1016/j.neurobiolaging.2014.10.019.PubMedCrossRef

15.

Aronica E, van Vliet EA, Hendriksen E, Troost D, Lopes da Silva FH, Gorter JA, et al. A cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy. Eur J Neurosci. 2001;14(9):1485–91.PubMedCrossRef

16.

Mussap M, Plebani M. Biochemistry and clinical role of human cystatin C. Crit Rev Clin Lab Sci. 2004;41(5–6):467–550. doi:10.1080/10408360490504934.PubMedCrossRef

17.

Nagai A, Ryu JK, Terashima M, Tanigawa Y, Wakabayashi K, McLarnon JG, et al. Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with cathepsin B. Brain Res. 2005;1066(1–2):120–8. doi:10.1016/j.brainres.2005.10.063.PubMedCrossRef

18.

Pasinetti GM, Ungar LH, Lange DJ, Yemul S, Deng H, Yuan X, et al. Identification of potential CSF biomarkers in ALS. Neurology. 2006;66(8):1218–22. doi:10.1212/01.wnl.0000203129.82104.07.PubMedCrossRef

19.

Ranganathan S, Williams E, Ganchev P, Gopalakrishnan V, Lacomis D, Urbinelli L, et al. Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. J Neurochem. 2005;95(5):1461–71. doi:10.1111/j.1471-4159.2005.03478.x.PubMedCentralPubMedCrossRef

20.

Tsuji-Akimoto S, Yabe I, Niino M, Kikuchi S, Sasaki H. Cystatin C in cerebrospinal fluid as a biomarker of ALS. Neurosci Lett. 2009;452(1):52–5.PubMedCrossRef

21.

Lehnert S, Costa J, de Carvalho M, Kirby J, Kuzma-Kozakiewicz M, Morelli C, et al. Multicentre quality control evaluation of different biomarker candidates for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5–6):344–50. doi:10.3109/21678421.2014.884592.PubMedCrossRef

22.

Carrette O, Burkhard PR, Hughes S, Hochstrasser DF, Sanchez JC. Truncated cystatin C in cerebrospiral fluid: Technical [corrected] artefact or biological process? Proteomics. 2005;5(12):3060–5. doi:10.1002/pmic.200402039.PubMedCrossRef

23.

Kasai T, Tokuda T, Ishigami N, Sasayama H, Foulds P, Mitchell DJ, et al. Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neuropathol. 2009;117(1):55–62. doi:10.1007/s00401-008-0456-1.PubMedCrossRef

24.

Noto Y, Shibuya K, Sato Y, Kanai K, Misawa S, Sawai S, et al. Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: specificity, sensitivity, and a possible prognostic value. Amyotroph Lateral Scler. 2011;12(2):140–3. doi:10.3109/17482968.2010.541263.PubMedCrossRef

25.

Feneberg E, Steinacker P, Lehnert S, Schneider A, Walther P, Thal DR, et al. Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(5–6):351–6. doi:10.3109/21678421.2014.905606.PubMedCrossRef

26.

Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312(5778):1389–92. doi:10.1126/science.1123511.PubMedCrossRef

27.

Henkel JS, Engelhardt JI, Siklos L, Simpson EP, Kim SH, Pan T, et al. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol. 2004;55(2):221–35. doi:10.1002/ana.10805.PubMedCrossRef

28.

Tarasiuk J, Kulakowska A, Drozdowski W, Kornhuber J, Lewczuk P. CSF markers in amyotrophic lateral sclerosis. J Neural Transm. 2012;119(7):747–57. doi:10.1007/s00702-012-0806-y.PubMedCrossRef

29.

Sussmuth SD, Sperfeld AD, Hinz A, Brettschneider J, Endruhn S, Ludolph AC, et al. CSF glial markers correlate with survival in amyotrophic lateral sclerosis. Neurology. 2010;74(12):982–7. doi:10.1212/WNL.0b013e3181d5dc3b.PubMedCrossRef

30.

Cudkowicz ME, Swash M. CSF markers in amyotrophic lateral sclerosis: has the time come? Neurology. 2010;74(12):949–50. doi:10.1212/WNL.0b013e3181d72c31.PubMedCrossRef

31.

Barone R, Sotgiu S, Musumeci S. Plasma chitotriosidase in health and pathology. Clin Lab. 2007;53(5–6):321–33.PubMed

32.

Varghese AM, Sharma A, Mishra P, Vijayalakshmi K, Harsha HC, Sathyaprabha TN, et al. Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis. Clin Proteomics. 2013;10(1):19. doi:10.1186/1559-0275-10-19.PubMedCentralPubMedCrossRef

33.

Pagliardini V, Pagliardini S, Corrado L, Lucenti A, Panigati L, Bersano E, et al. Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: a survey clinic-based study. J Neurol Sci. 2015;348(1–2):245–50. doi:10.1016/j.jns.2014.12.016.PubMedCrossRef

34.

Di Rosa M, Malaguarnera G, De Gregorio C, D’Amico F, Mazzarino MC, Malaguarnera L. Modulation of chitotriosidase during macrophage differentiation. Cell Biochem Biophys. 2013;66(2):239–47. doi:10.1007/s12013-012-9471-x.PubMedCrossRef

35.

Neusch C, Bahr M, Schneider-Gold C. Glia cells in amyotrophic lateral sclerosis: new clues to understanding an old disease? Muscle Nerve. 2007;35(6):712–24. doi:10.1002/mus.20768.PubMedCrossRef

36.

Brettschneider J, Widl K, Ehrenreich H, Riepe M, Tumani H. Erythropoietin in the cerebrospinal fluid in neurodegenerative diseases. Neurosci Lett. 2006;404(3):347–51. doi:10.1016/j.neulet.2006.06.011.PubMedCrossRef

37.

Janik P, Kwiecinski H, Sokolowska B, Niebroj-Dobosz I. Erythropoietin concentration in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. J Neural Transm. 2010;117(3):343–7. doi:10.1007/s00702-009-0354-2.PubMedCrossRef

38.

Steiner J, Bogerts B, Schroeter ML, Bernstein HG. S100B protein in neurodegenerative disorders. Clin Chem Lab Med. 2011;49(3):409–24. doi:10.1515/CCLM.2011.083.PubMedCrossRef

39.

Chio A, Calvo A, Bovio G, Canosa A, Bertuzzo D, Galmozzi F, et al. Amyotrophic lateral sclerosis outcome measures and the role of albumin and creatinine: a population-based study. JAMA Neurol. 2014;71(9):1134–42. doi:10.1001/jamaneurol.2014.1129.PubMedCrossRef

40.

Kuffner R, Zach N, Norel R, Hawe J, Schoenfeld D, Wang L, et al. Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression. Nat Biotechnol. 2015;33(1):51–7. doi:10.1038/nbt.3051.PubMedCrossRef

41.

Bozik ME, Mitsumoto H, Brooks BR, Rudnicki SA, Moore DH, Zhang B, 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):406–13. doi:10.3109/21678421.2014.943672.PubMedCrossRef

42.

Patin F, Corcia P, Madji Hounoum B, Veyrat-Durebex C, Respaud E, Piver E, et al. Biological follow-up in amyotrophic lateral sclerosis: decrease in creatinine levels and increase in ferritin levels predict poor prognosis. Eur J Neurol. 2015. doi:10.1111/ene.12754.PubMed

43.

Jokic N, Gonzalez de Aguilar JL, Pradat PF, Dupuis L, Echaniz-Laguna A, Muller A. Nogo expression in muscle correlates with amyotrophic lateral sclerosis severity. Ann Neurol. 2005;57(4):553–6. doi:10.1002/ana.20420.PubMedCrossRef

44.

Pradat PF, Bruneteau G, Gonzalez de Aguilar JL, Dupuis L, Jokic N, Salachas F, et al. Muscle Nogo-A expression is a prognostic marker in lower motor neuron syndromes. Ann Neurol. 2007;62(1):15–20. doi:10.1002/ana.21122.PubMedCrossRef

45.

Askanas V, Wojcik S, Engel WK. Expression of Nogo-A in human muscle fibers is not specific for amyotrophic lateral sclerosis. Ann Neurol. 2007;62(6):676–7. doi:10.1002/ana.21245. author reply 7.PubMedCrossRef

46.

Wojcik S, Engel WK, Askanas V. Increased expression of Noga-A in ALS muscle biopsies is not unique for this disease. Acta Myol. 2006;25(3):116–8.PubMed

47.

Si Y, Cui X, Kim S, Wians R, Sorge R, Oh SJ, et al. Smads as muscle biomarkers in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2014;1(10):778–87. doi:10.1002/acn3.117.PubMedCentralPubMedCrossRef

48.

Felice KJ. A longitudinal study comparing thenar motor unit number estimates to other quantitative tests in patients with amyotrophic lateral sclerosis. Muscle Nerve. 1997;20(2):179–85. doi:10.1002/(SICI)1097-4598(199702)20.PubMedCrossRef

49.

Shefner JM, Gooch CL. Motor unit number estimation. Phys Med Rehabil Clin N Am. 2003;14(2):243–60.PubMedCrossRef

50.

Jagtap SA, Kuruvilla A, Govind P, Nair MD, Sarada C, Varma RP. Multipoint incremental motor unit number estimation versus amyotrophic lateral sclerosis functional rating scale and the medical research council sum score as an outcome measure in amyotrophic lateral sclerosis. Ann Indian Acad Neurol. 2014;17(3):336–9. doi:10.4103/0972-2327.138522.PubMedCentralPubMedCrossRef

51.

Shefner JM, Watson ML, Simionescu L, Caress JB, Burns TM, Maragakis NJ, et al. Multipoint incremental motor unit number estimation as an outcome measure in ALS. Neurology. 2011;77(3):235–41. doi:10.1212/WNL.0b013e318225aabf.PubMedCentralPubMedCrossRef

52.

Neuwirth C, Barkhaus PE, Burkhardt C, Castro J, Czell D, de Carvalho M, et al. Tracking motor neuron loss in a set of six muscles in amyotrophic lateral sclerosis using the Motor Unit Number Index (MUNIX): a 15-month longitudinal multicentre trial. J Neurol Neurosurg Psychiatry. 2015. doi:10.1136/jnnp-2015-310509.PubMed

53.

Baumann F, Henderson RD, Ridall PG, Pettitt AN, McCombe PA. Use of Bayesian MUNE to show differing rate of loss of motor units in subgroups of ALS. Clin Neurophysiol. 2012;123(12):2446–53. doi:10.1016/j.clinph.2012.04.022.PubMedCrossRef

54.

Vucic S, Kiernan MC. Axonal excitability properties in amyotrophic lateral sclerosis. Clin Neurophysiol. 2006;117(7):1458–66. doi:10.1016/j.clinph.2006.04.016.PubMedCrossRef

55.

Kanai K, Kuwabara S, Misawa S, Tamura N, Ogawara K, Nakata M, et al. Altered axonal excitability properties in amyotrophic lateral sclerosis: impaired potassium channel function related to disease stage. Brain. 2006;129(Pt 4):953–62. doi:10.1093/brain/awl024.PubMedCrossRef

56.

Cheah BC, Lin CS, Park SB, Vucic S, Krishnan AV, Kiernan MC. Progressive axonal dysfunction and clinical impairment in amyotrophic lateral sclerosis. Clin Neurophysiol. 2012;123(12):2460–7. doi:10.1016/j.clinph.2012.06.020.PubMedCrossRef

57.

Kanai K, Shibuya K, Sato Y, Misawa S, Nasu S, Sekiguchi Y, et al. Motor axonal excitability properties are strong predictors for survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(7):734–8. doi:10.1136/jnnp-2011-301782.PubMedCrossRef

58.

Rutkove SB. Electrical impedance myography: Background, current state, and future directions. Muscle Nerve. 2009;40(6):936–46. doi:10.1002/mus.21362.PubMedCentralPubMedCrossRef

59.

Rutkove SB, Caress JB, Cartwright MS, Burns TM, Warder J, David WS, et al. Electrical impedance myography as a biomarker to assess ALS progression. Amyotroph Lateral Scler. 2012;13(5):439–45. doi:10.3109/17482968.2012.688837.PubMedCentralPubMedCrossRef

60.

Rutkove SB, Caress JB, Cartwright MS, Burns TM, Warder J, David WS, et al. Electrical impedance myography correlates with standard measures of ALS severity. Muscle Nerve. 2014;49(3):441–3. doi:10.1002/mus.24128.PubMedCrossRef

61.

Shellikeri S, Yunusova Y, Green JR, Pattee GL, Berry JD, Rutkove SB, et al. Electrical impedance myography in the evaluation of the tongue musculature in amyotrophic lateral sclerosis. Muscle Nerve. 2015. doi:10.1002/mus.24565.PubMed

62.

Dengler R. Electromyography and muscle ultrasound in ALS diagnosis, complementary or competitive? Clin Neurophysiol. 2012;123(8):1485–6. doi:10.1016/j.clinph.2011.12.007.PubMedCrossRef

63.

Arts IM, Overeem S, Pillen S, Kleine BU, Boekestein WA, Zwarts MJ, et al. Muscle ultrasonography: a diagnostic tool for amyotrophic lateral sclerosis. Clin Neurophysiol. 2012;123(8):1662–7. doi:10.1016/j.clinph.2011.11.262.PubMedCrossRef

64.

Grimm A, Prell T, Decard BF, Schumacher U, Witte OW, Axer H, et al. Muscle ultrasonography as an additional diagnostic tool for the diagnosis of amyotrophic lateral sclerosis. Clin Neurophysiol. 2015;126(4):820–7. doi:10.1016/j.clinph.2014.06.052.PubMedCrossRef

65.

Vucic S, Cheah BC, Yiannikas C, Kiernan MC. Cortical excitability distinguishes ALS from mimic disorders. Clin Neurophysiol. 2011;122(9):1860–6. doi:10.1016/j.clinph.2010.12.062.PubMedCrossRef

66.

Vucic S, Nicholson GA, Kiernan MC. Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain. 2008;131(Pt 6):1540–50. doi:10.1093/brain/awn071.PubMedCrossRef

67.

Vucic S, Kiernan MC. Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease. Brain. 2006;129(Pt 9):2436–46. doi:10.1093/brain/awl172.PubMedCrossRef

68.

Mitsumoto H, Ulug AM, Pullman SL, Gooch CL, Chan S, Tang MX, et al. Quantitative objective markers for upper and lower motor neuron dysfunction in ALS. Neurology. 2007;68(17):1402–10. doi:10.1212/01.wnl.0000260065.57832.87.PubMedCrossRef

69.

Attarian S, Vedel JP, Pouget J, Schmied A. Progression of cortical and spinal dysfunctions over time in amyotrophic lateral sclerosis. Muscle Nerve. 2008;37(3):364–75. doi:10.1002/mus.20942.PubMedCrossRef

70.

Floyd AG, Yu QP, Piboolnurak P, Tang MX, Fang Y, Smith WA, et al. Transcranial magnetic stimulation in ALS: utility of central motor conduction tests. Neurology. 2009;72(6):498–504. doi:10.1212/01.wnl.0000341933.97883.a4.PubMedCentralPubMedCrossRef

71.

Menon P, Geevasinga N, Yiannikas C, Howells J, Kiernan MC, Vucic S. Sensitivity and specificity of threshold tracking transcranial magnetic stimulation for diagnosis of amyotrophic lateral sclerosis: a prospective study. Lancet Neurol. 2015;14(5):478–84. doi:10.1016/S1474-4422(15)00014-9.PubMedCrossRef

72.

Neary D, Snowden JS, Mann DM, Northen B, Goulding PJ, Macdermott N. Frontal lobe dementia and motor neuron disease. J Neurol Neurosurg Psychiatry. 1990;53(1):23–32.PubMedCentralPubMedCrossRef

73.

Kew JJ, Leigh PN, Playford ED, Passingham RE, Goldstein LH, Frackowiak RS, et al. Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study. Brain. 1993;116(Pt 3):655–80.PubMedCrossRef

74.

Turner MR, Cagnin A, Turkheimer FE, Miller CC, Shaw CE, Brooks DJ, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis. 2004;15(3):601–9. doi:10.1016/j.nbd.2003.12.012.PubMedCrossRef

75.

Turner MR, Rabiner EA, Hammers A, Al-Chalabi A, Grasby PM, Shaw CE, et al. [11C]-WAY100635 PET demonstrates marked 5-HT1A receptor changes in sporadic ALS. Brain. 2005;128(Pt 4):896–905. doi:10.1093/brain/awh428.PubMedCrossRef

76.

Lanctot KL, Herrmann N, Ganjavi H, Black SE, Rusjan PM, Houle S, et al. Serotonin-1A receptors in frontotemporal dementia compared with controls. Psychiatry Res. 2007;156(3):247–50. doi:10.1016/j.pscychresns.2007.07.003.PubMedCrossRef

77.

Bowen DM, Procter AW, Mann DM, Snowden JS, Esiri MM, Neary D, et al. Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy. Psychopharmacology (Berl). 2008;196(4):603–10. doi:10.1007/s00213-007-0992-8.CrossRef

78.

Pereira JB, Ibarretxe-Bilbao N, Marti MJ, Compta Y, Junque C, Bargallo N, et al. Assessment of cortical degeneration in patients with Parkinson’s disease by voxel-based morphometry, cortical folding, and cortical thickness. Hum Brain Mapp. 2012;33(11):2521–34. doi:10.1002/hbm.21378.PubMedCrossRef

79.

Chen Z, Ma L. Grey matter volume changes over the whole brain in amyotrophic lateral sclerosis: A voxel-wise meta-analysis of voxel based morphometry studies. Amyotroph Lateral Scler. 2010;11(6):549–54. doi:10.3109/17482968.2010.516265.PubMedCrossRef

80.

Consonni M, Iannaccone S, Cerami C, Frasson P, Lacerenza M, Lunetta C, et al. The cognitive and behavioural profile of amyotrophic lateral sclerosis: application of the consensus criteria. Behav Neurol. 2013;27(2):143–53. doi:10.3233/BEN-2012-110202.PubMedCrossRef

81.

Raaphorst J, de Visser M, Linssen WH, de Haan RJ, Schmand B. The cognitive profile of amyotrophic lateral sclerosis: A meta-analysis. Amyotroph Lateral Scler. 2010;11(1–2):27–37. doi:10.3109/17482960802645008.PubMedCrossRef

82.

Giordana MT, Ferrero P, Grifoni S, Pellerino A, Naldi A, Montuschi A. Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review. Neurol Sci. 2011;32(1):9–16. doi:10.1007/s10072-010-0439-6.PubMedCrossRef

83.

Senda J, Kato S, Kaga T, Ito M, Atsuta N, Nakamura T, et al. Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study. Amyotroph Lateral Scler. 2011;12(1):59–69. doi:10.3109/17482968.2010.517850.PubMedCrossRef

84.

Agosta F, Gorno-Tempini ML, Pagani E, Sala S, Caputo D, Perini M, et al. Longitudinal assessment of grey matter contraction in amyotrophic lateral sclerosis: A tensor based morphometry study. Amyotroph Lateral Scler. 2009;10(3):168–74. doi:10.1080/17482960802603841.PubMedCrossRef

85.

Elamin M, Phukan J, Bede P, Jordan N, Byrne S, Pender N, et al. Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology. 2011;76(14):1263–9. doi:10.1212/WNL.0b013e318214359f.PubMedCrossRef

86.

Roccatagliata L, Bonzano L, Mancardi G, Canepa C, Caponnetto C. Detection of motor cortex thinning and corticospinal tract involvement by quantitative MRI in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2009;10(1):47–52. doi:10.1080/17482960802267530.PubMedCrossRef

87.

Verstraete E, van den Heuvel MP, Veldink JH, Blanken N, Mandl RC, Hulshoff Pol HE, et al. Motor network degeneration in amyotrophic lateral sclerosis: a structural and functional connectivity study. PLoS One. 2010;5(10):e13664. doi:10.1371/journal.pone.0013664.PubMedCentralPubMedCrossRef

88.

Verstraete E, Veldink JH, Hendrikse J, Schelhaas HJ, van den Heuvel MP, van den Berg LH. Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(4):383–8. doi:10.1136/jnnp-2011-300909.PubMedCrossRef

89.

Menke RA, Korner S, Filippini N, Douaud G, Knight S, Talbot K, et al. Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis. Brain. 2014;137(Pt 9):2546–55. doi:10.1093/brain/awu162.PubMedCentralPubMedCrossRef

90.

Li J, Pan P, Song W, Huang R, Chen K, Shang H. A meta-analysis of diffusion tensor imaging studies in amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33(8):1833–8. doi:10.1016/j.neurobiolaging.2011.04.007.PubMedCrossRef

91.

Filippini N, Douaud G, Mackay CE, Knight S, Talbot K, Turner MR. Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis. Neurology. 2010;75(18):1645–52. doi:10.1212/WNL.0b013e3181fb84d1.PubMedCentralPubMedCrossRef

92.

Menke RA, Abraham I, Thiel CS, Filippini N, Knight S, Talbot K, et al. Fractional anisotropy in the posterior limb of the internal capsule and prognosis in amyotrophic lateral sclerosis. Arch Neurol. 2012;69(11):1493–9. doi:10.1001/archneurol.2012.1122.PubMedCrossRef

93.

Turner MR, Agosta F, Bede P, Govind V, Lule D, Verstraete E. Neuroimaging in amyotrophic lateral sclerosis. Biomark Med. 2012;6(3):319–37. doi:10.2217/bmm.12.26.PubMedCrossRef

94.

Liu C, Jiang R, Yi X, Zhu W, Bu B. Role of diffusion tensor imaging or magnetic resonance spectroscopy in the diagnosis and disability assessment of amyotrophic lateral sclerosis. J Neurol Sci. 2015;348(1–2):206–10. doi:10.1016/j.jns.2014.12.004.PubMedCrossRef

95.

Douaud G, Filippini N, Knight S, Talbot K, Turner MR. Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis. Brain. 2011;134(Pt 12):3470–9. doi:10.1093/brain/awr279.PubMedCrossRef

96.

Schmidt R, Verstraete E, de Reus MA, Veldink JH, van den Berg LH, van den Heuvel MP. Correlation between structural and functional connectivity impairment in amyotrophic lateral sclerosis. Hum Brain Mapp. 2014;35(9):4386–95. doi:10.1002/hbm.22481.PubMedCentralPubMedCrossRef

97.

Foerster BR, Callaghan BC, Petrou M, Edden RA, Chenevert TL, Feldman EL. Decreased motor cortex gamma-aminobutyric acid in amyotrophic lateral sclerosis. Neurology. 2012;78(20):1596–600. doi:10.1212/WNL.0b013e3182563b57.PubMedCentralPubMedCrossRef

98.

Pohl C, Block W, Karitzky J, Traber F, Schmidt S, Grothe C, et al. Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis. Arch Neurol. 2001;58(5):729–35.PubMedCrossRef

99.

Foerster BR, Welsh RC, Feldman EL. 25 years of neuroimaging in amyotrophic lateral sclerosis. Nat Rev Neurol. 2013;9(9):513–24. doi:10.1038/nrneurol.2013.153.PubMedCentralPubMedCrossRef

100.

Sharma KR, Saigal G, Maudsley AA, Govind V. 1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis. NMR Biomed. 2011;24(10):1270–6. doi:10.1002/nbm.1687.PubMedCentralPubMedCrossRef

101.

Sudharshan N, Hanstock C, Hui B, Pyra T, Johnston W, Kalra S. Degeneration of the mid-cingulate cortex in amyotrophic lateral sclerosis detected in vivo with MR spectroscopy. AJNR Am J Neuroradiol. 2011;32(2):403–7. doi:10.3174/ajnr.A2289.PubMedCrossRef

102.

Rule RR, Suhy J, Schuff N, Gelinas DF, Miller RG, Weiner MW. Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5(3):141–9. doi:10.1080/14660820410017109.PubMedCentralPubMedCrossRef

103.

Dadon-Nachum M, Melamed E, Offen D. The “dying-back” phenomenon of motor neurons in ALS. J Mol Neurosci. 2011;43(3):470–7. doi:10.1007/s12031-010-9467-1.PubMedCrossRef

104.

Valsasina P, Agosta F, Benedetti B, Caputo D, Perini M, Salvi F, et al. Diffusion anisotropy of the cervical cord is strictly associated with disability in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2007;78(5):480–4. doi:10.1136/jnnp.2006.100032.PubMedCentralPubMedCrossRef

105.

Cohen-Adad J, El Mendili MM, Morizot-Koutlidis R, Lehericy S, Meininger V, Blancho S, et al. Involvement of spinal sensory pathway in ALS and specificity of cord atrophy to lower motor neuron degeneration. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(1):30–8. doi:10.3109/17482968.2012.701308.PubMedCrossRef

106.

Agosta F, Rocca MA, Valsasina P, Sala S, Caputo D, Perini M, et al. A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients. J Neurol Neurosurg Psychiatry. 2009;80(1):53–5. doi:10.1136/jnnp.2008.154252.PubMedCrossRef

107.

Ikeda K, Murata K, Kawase Y, Kawabe K, Kano O, Yoshii Y, et al. Relationship between cervical cord 1H-magnetic resonance spectroscopy and clinoco-electromyographic profile in amyotrophic lateral sclerosis. Muscle Nerve. 2013;47(1):61–7. doi:10.1002/mus.23467.PubMedCrossRef

108.

Carew JD, Nair G, Pineda-Alonso N, Usher S, Hu X, Benatar M. Magnetic resonance spectroscopy of the cervical cord in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011;12(3):185–91. doi:10.3109/17482968.2010.515223.PubMedCrossRef

109.

Carew JD, Nair G, Andersen PM, Wuu J, Gronka S, Hu X, et al. Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology. 2011;77(14):1370–5. doi:10.1212/WNL.0b013e318231526a.PubMedCentralPubMedCrossRef

At a glance: The STEP trials

Springer Medicine

New developments and future opportunities in biomarkers for amyotrophic lateral sclerosis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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