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01-11-2018 | Original Communication

Significance of CSF NfL and tau in ALS

Authors: Stefanie Schreiber, Nicola Spotorno, Frank Schreiber, Julio Acosta-Cabronero, Jörn Kaufmann, Judith Machts, Grazyna Debska-Vielhaber, Cornelia Garz, Daniel Bittner, Nathalie Hensiek, Reinhard Dengler, Susanne Petri, Peter J. Nestor, Stefan Vielhaber

Published in: Journal of Neurology | Issue 11/2018

Abstract

Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine 181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as well. Moreover, the relationship between CSF NfL and tau measures to further axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis included 89 ALS patients [median (range) age 63 (33–83) years, 61% male, disease duration 10 (0.2–190) months] and 33 age- and sex-matched disease controls [60 (32–76), 49%]. NfL was higher and the ptau/ttau ratio was lower in ALS compared to controls [8343 (1795–35,945) pg/ml vs. 1193 (612–2616), H(1) = 70.8, p < 0.001; mean (SD) 0.17 (0.04) vs. 0.2 (0.03), F(1) = 14.3, p < 0.001], as well as in upper motor neuron dominant (UMND, n = 10) compared to classic (n = 46) or lower motor neuron dominant ALS [n = 31; for NfL: 16,076 (7447–35,945) vs. 8205 (2651–35,138) vs. 8057 (1795–34,951)], Z ≥ 2.5, p ≤ 0.01; for the ptau/ttau ratio: [0.13 (0.04) vs. 0.17 (0.04) vs. 0.18 (0.03), p ≤ 0.02]. In ALS, NfL and the ptau/ttau ratio were related to corticospinal tract (CST) fractional anisotropy (FA) and radial diffusivity (ROI-based approach and whole-brain voxelwise analysis). Factor analysis of mixed data revealed a co-variance pattern between NfL (factor load − 0.6), the ptau/ttau ratio (0.7), CST FA (0.8) and UMND ALS phenotype (− 2.8). NfL did not relate to any further neuroaxonal injury marker (brain volumes, precentral gyrus thickness, peripheral motor amplitudes, sonographic cross-sectional nerve area), but a lower ptau/ttau ratio was associated with whole-brain gray matter atrophy and widespread white matter integrity loss. Higher NfL baseline levels were associated with greater UMN disease burden, more rapid disease progression, a twofold to threefold greater hazard of death and shorter survival times. The findings that higher CSF NfL levels and a reduced ptau/ttau ratio are more associated with clinical UMN involvement and with reduced CST FA offer strong converging evidence that both are markers of central motor degeneration. Furthermore, NfL is a marker of poor prognosis, while a low ptau/ttau ratio indicates extramotor pathology in ALS.

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Meeter LH, Kaat LD, Rohrer JD, van Swieten JC (2017) Imaging and fluid biomarkers in frontotemporal dementia. Nat Rev Neurol 13(7):406–419. https://doi.org/10.1038/nrneurol.2017.75 CrossRefPubMed

Mattsson N, Insel PS, Palmqvist S, Portelius E, Zetterberg H, Weiner M, Blennow K, Hansson O (2016) Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer’s disease. EMBO Mol Med 8(10):1184–1196. https://doi.org/10.15252/emmm.201606540 CrossRefPubMedPubMedCentral

Kaiserova M, Grambalova Z, Otruba P, Stejskal D, Prikrylova Vranova H, Mares J, Mensikova K, Kanovsky P (2017) Cerebrospinal fluid levels of chromogranin A and phosphorylated neurofilament heavy chain are elevated in amyotrophic lateral sclerosis. Acta Neurol Scand. https://doi.org/10.1111/ane.12735 CrossRefPubMed

Gaiani A, Martinelli I, Bello L, Querin G, Puthenparampil M, Ruggero S, Toffanin E, Cagnin A, Briani C, Pegoraro E, Sorarù G (2017) Diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis: neurofilament light chain levels in definite subtypes of disease. JAMA Neurol 74(5):525–532. https://doi.org/10.1001/jamaneurol.2016.5398 CrossRefPubMedPubMedCentral

Poesen K, Schaepdryver M de, Stubendorff B, Gille B, Muckova P, Wendler S, Prell T, Ringer TM, Rhode H, Stevens O, Claeys KG, Couwelier G, D’Hondt A, Lamaire N, Tilkin P, van Reijen D, Gourmaud S, Fedtke N, Heiling B, Rumpel M, Rödiger A, Gunkel A, Witte OW, Paquet C, Vandenberghe R, Grosskreutz J, van Damme P (2017) Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease. Neurology 88(24):2302–2309. https://doi.org/10.1212/WNL.0000000000004029 CrossRefPubMed

Steinacker P, Feneberg E, Weishaupt J, Brettschneider J, Tumani H, Andersen PM, Arnim CAF von, Böhm S, Kassubek J, Kubisch C, Lulé D, Müller H-P, Muche R, Pinkhardt E, Oeckl P, Rosenbohm A, Anderl-Straub S, Volk AE, Weydt P, Ludolph AC, Otto M (2016) Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry 87(1):12–20. https://doi.org/10.1136/jnnp-2015-311387 CrossRefPubMed

Lu C-H, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84(22):2247–2257. https://doi.org/10.1212/WNL.0000000000001642 CrossRefPubMedPubMedCentral

Steinacker P, Verde F, Fang L, Feneberg E, Oeckl P, Roeber S, Anderl-Straub S, Danek A, Diehl-Schmid J, Fassbender K, Fliessbach K, Foerstl H, Giese A, Jahn H, Kassubek J, Kornhuber J, Landwehrmeyer GB, Lauer M, Pinkhardt EH, Prudlo J, Rosenbohm A, Schneider A, Schroeter ML, Tumani H, Arnim CAF von, Weishaupt J, Weydt P, Ludolph AC, Yilmazer Hanke D, Otto M (2017) Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2017-317138 CrossRefPubMed

Schaepdryver M de, Jeromin A, Gille B, Claeys KG, Herbst V, Brix B, van Damme P, Poesen K (2017) Comparison of elevated phosphorylated neurofilament heavy chains in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2017-316605 CrossRefPubMed

10.

Chen X, Chen Y, Wei Q, Ou R, Cao B, Zhao B, Shang H-F (2016) Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis. BMC Neurol 16:173. https://doi.org/10.1186/s12883-016-0689-x CrossRefPubMedPubMedCentral

11.

Gendron TF, Daughrity LM, Heckman MG, Diehl NN, Wuu J, Miller TM, Pastor P, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Benatar M, Silani V, Glass JD, Floeter MK, Jeromin A, Boylan KB, Petrucelli L (2017) Phosphorylated neurofilament heavy chain: a biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Ann Neurol. https://doi.org/10.1002/ana.24980 CrossRefPubMedPubMedCentral

12.

Brettschneider J, Petzold A, Süssmuth SD, Ludolph AC, Tumani H (2006) Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology 66(6):852–856. https://doi.org/10.1212/01.wnl.0000203120.85850.54 CrossRefPubMed

13.

Steinacker P, Huss A, Mayer B, Grehl T, Grosskreutz J, Borck G, Kuhle J, Lulé D, Meyer T, Oeckl P, Petri S, Weishaupt J, Ludolph AC, Otto M (2017) Diagnostic and prognostic significance of neurofilament light chain NF-L, but not progranulin and S100B, in the course of amyotrophic lateral sclerosis: data from the German MND-net. Amyotroph Later Scler Frontotemporal Degener 18(1–2):112–119. https://doi.org/10.1080/21678421.2016.1241279 CrossRef

14.

Feneberg E, Oeckl P, Steinacker P, Verde F, Barro C, van Damme P, Gray E, Grosskreutz J, Jardel C, Kuhle J, Koerner S, Lamari F, Amador MDM, Mayer B, Morelli C, Muckova P, Petri S, Poesen K, Raaphorst J, Salachas F, Silani V, Stubendorff B, Turner MR, Verbeek MM, Weishaupt JH, Weydt P, Ludolph AC, Otto M (2018) Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology 90(1):e22–e30. https://doi.org/10.1212/WNL.0000000000004761 CrossRefPubMed

15.

Boylan KB, Glass JD, Crook JE, Yang C, Thomas CS, Desaro P, Johnston A, Overstreet K, Kelly C, Polak M, Shaw G (2013) Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 84(4):467–472CrossRef

16.

Menke RA, Gray E, Lu CH, Kuhle J, Talbot K, Malaspina A, Turner MR (2015) CSF neurofilament light chain reflects corticospinal tract degeneration in ALS. Ann Clin Transl Neurol 2(7):748–755CrossRef

17.

Turner MR, Gray E (2016) Are neurofilaments heading for the ALS clinic? J Neurol Neurosurg Psychiatry 87(1):3–4. https://doi.org/10.1136/jnnp-2015-311934 CrossRefPubMed

18.

Jiménez-Jiménez FJ, Hernánz A, Medina-Acebrón S, Bustos F de, Zurdo JM, Alonso H, Puertas I, Barcenilla B, Sayed Y, Cabrera-Valdivia F (2005) Tau protein concentrations in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neurol Scand 111(2):114–117. https://doi.org/10.1111/j.1600-0404.2005.00370.x CrossRefPubMed

19.

Paladino P, Valentino F, Piccoli T, Piccoli F, La Bella V (2009) Cerebrospinal fluid tau protein is not a biological marker in amyotrophic lateral sclerosis. Eur J Neurol 16(2):257–261. https://doi.org/10.1111/j.1468-1331.2008.02405.x CrossRefPubMed

20.

Ganesalingam J, An J, Shaw CE, Shaw G, Lacomis D, Bowser R (2011) Combination of neurofilament heavy chain and complement C3 as CSF biomarkers for ALS. J Neurochem 117(3):528–537. https://doi.org/10.1111/j.1471-4159.2011.07224.x CrossRefPubMedPubMedCentral

21.

Süssmuth SD, Sperfeld AD, Hinz A, Brettschneider J, Endruhn S, Ludolph AC, Tumani H (2010) CSF glial markers correlate with survival in amyotrophic lateral sclerosis. Neurology 74(12):982–987. https://doi.org/10.1212/WNL.0b013e3181d5dc3b CrossRefPubMed

22.

Sussmuth SD, Tumani H, Ecker D, Ludolph AC (2003) Amyotrophic lateral sclerosis: disease stage related changes of tau protein and S100 beta in cerebrospinal fluid and creatine kinase in serum. Neurosci Lett 353(1):57–60CrossRef

23.

Grossman M, Elman L, McCluskey L, McMillan CT, Boller A, Powers J, Rascovsky K, Hu W, Shaw L, Irwin DJ, Lee VM-Y, Trojanowski JQ (2014) Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis. JAMA Neurol 71(4):442–448. https://doi.org/10.1001/jamaneurol.2013.6064 CrossRefPubMedPubMedCentral

24.

Wilke C, Deuschle C, Rattay TW, Maetzler W, Synofzik M (2015) Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis. Neurobiol Aging 36(2):1072–1074. https://doi.org/10.1016/j.neurobiolaging.2014.10.019 CrossRefPubMed

25.

Bourbouli M, Rentzos M, Bougea A, Zouvelou V, Constantinides VC, Zaganas I, Evdokimidis I, Kapaki E, Paraskevas GP (2017) Cerebrospinal fluid TAR DNA-binding protein 43 combined with tau proteins as a candidate biomarker for amyotrophic lateral sclerosis and frontotemporal dementia spectrum disorders. Dement Geriatr Cogn Disord 44(3–4):144–152. https://doi.org/10.1159/000478979 CrossRefPubMed

26.

Abdelhak A, Junker A, Brettschneider J, Kassubek J, Ludolph AC, Otto M, Tumani H (2015) Brain-specific cytoskeletal damage markers in cerebrospinal fluid: is there a common pattern between amyotrophic lateral sclerosis and primary progressive multiple sclerosis? Int J Mol Sci 16(8):17565–17588. https://doi.org/10.3390/ijms160817565 CrossRefPubMedPubMedCentral

27.

Brooks BR, Miller RG, Swash M, Munsat TL (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Later Scler Other Motor Neuron Disord 1(5):293–299CrossRef

28.

Woo JH, Wang S, Melhem ER, Gee JC, Cucchiara A, McCluskey L, Elman L (2014) Linear associations between clinically assessed upper motor neuron disease and diffusion tensor imaging metrics in amyotrophic lateral sclerosis. PLoS One 9(8):e105753. https://doi.org/10.1371/journal.pone.0105753 CrossRefPubMedPubMedCentral

29.

Schreiber S, Abdulla S, Debska-Vielhaber G, Machts J, Dannhardt-Stieger V, Feistner H, Oldag A, Goertler M, Petri S, Kollewe K, Kropf S, Schreiber F, Heinze HJ, Dengler R, Nestor PJ, Vielhaber S (2015) Peripheral nerve ultrasound in amyotrophic lateral sclerosis phenotypes. Muscle Nerve 51(5):669–675CrossRef

30.

Chio A, Calvo A, Moglia C, Mazzini L, Mora G (2011) Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 82(7):740–746CrossRef

31.

Shibuya K, Simon NG, Geevasinga N, Menon P, Howells J, Park SB, Huynh W, Noto Y-I, Vucic S, Kiernan MC (2017) The evolution of motor cortical dysfunction in amyotrophic lateral sclerosis. Clin Neurophysiol 128(6):1075–1082. https://doi.org/10.1016/j.clinph.2017.03.004 CrossRefPubMed

32.

Jin X, Jiang J-Y, Lu F-Z, Xia X-L, Wang L-X, Zheng C-J (2014) Electrophysiological differences between Hirayama disease, amyotrophic lateral sclerosis and cervical spondylotic amyotrophy. BMC Musculoskelet Disord 15:349. https://doi.org/10.1186/1471-2474-15-349 CrossRefPubMedPubMedCentral

33.

Nodera H, Takamatsu N, Shimatani Y, Mori A, Sato K, Oda M, Terasawa Y, Izumi Y, Kaji R (2014) Thinning of cervical nerve roots and peripheral nerves in ALS as measured by sonography. Clin Neurophysiol 125(9):1906–1911CrossRef

34.

Menke RA, Korner S, Filippini N, Douaud G, Knight S, Talbot K, Turner MR (2014) Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis. Brain 137(Pt 9):2546–2555CrossRef

35.

Machts J, Loewe K, Kaufmann J, Jakubiczka S, Abdulla S, Petri S, Dengler R, Heinze HJ, Vielhaber S, Schoenfeld MA, Bede P (2015) Basal ganglia pathology in ALS is associated with neuropsychological deficits. Neurology 85(15):1301–1309CrossRef

36.

Albuquerque M de, Branco LMT, Rezende TJR, Andrade HMT de, Nucci A, França MC (2017) Longitudinal evaluation of cerebral and spinal cord damage in Amyotrophic Lateral Sclerosis. Neuroimage Clin 14:269–276. https://doi.org/10.1016/j.nicl.2017.01.024 CrossRefPubMedPubMedCentral

37.

Walhout R, Westeneng H-J, Verstraete E, Hendrikse J, Veldink JH, van den Heuvel MP, van den Berg LH (2015) Cortical thickness in ALS: towards a marker for upper motor neuron involvement. J Neurol Neurosurg Psychiatry 86(3):288–294. https://doi.org/10.1136/jnnp-2013-306839 CrossRefPubMed

38.

Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TEJ (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31(4):1487–1505. https://doi.org/10.1016/j.neuroimage.2006.02.024 CrossRefPubMed

39.

Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA (1987) MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR 149(2):351–356CrossRef

40.

Shen D, Cui L, Fang J, Cui B, Li D, Tai H (2016) Voxel-wise meta-analysis of gray matter changes in amyotrophic lateral sclerosis. Front Aging Neurosci 8:64PubMedPubMedCentral

41.

Husson F, Le S, Pages J (2011) Exploratory multivariate analysis by example using R. CRC, Boca Raton

42.

Cardenas-Blanco A, Machts J, Acosta-Cabronero J, Kaufmann J, Abdulla S, Kollewe K, Petri S, Schreiber S, Heinze HJ, Dengler R, Vielhaber S, Nestor PJ (2016) Structural and diffusion imaging versus clinical assessment to monitor amyotrophic lateral sclerosis. Neuroimage Clin 11:408–414CrossRef

43.

Al Chalabi A, Hardiman O (2013) The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol 9(11):617–628CrossRef

44.

Oberstadt M, Claßen J, Arendt T, Holzer M (2017) TDP-43 and cytoskeletal proteins in ALS. Mol Neurobiol. https://doi.org/10.1007/s12035-017-0543-1 CrossRefPubMed

45.

Petzold A (2005) Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci 233(1–2):183–198. https://doi.org/10.1016/j.jns.2005.03.015 CrossRefPubMed

46.

Eisen A, Weber M (2001) The motor cortex and amyotrophic lateral sclerosis. Muscle Nerve 24(4):564–573CrossRef

47.

Yuan A, Sershen H, Basavarajappa BS, Kumar A, Hashim A, Berg M, Lee J-H, Sato Y, Rao MV, Mohan PS, Dyakin V, Julien J-P, Lee VM-Y, Nixon RA (2015) Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in vivo. Mol Psychiatry 20(8):986–994. https://doi.org/10.1038/mp.2015.45 CrossRefPubMedPubMedCentral

48.

Zetterberg H, Skillbäck T, Mattsson N, Trojanowski JQ, Portelius E, Shaw LM, Weiner MW, Blennow K (2016) Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol 73(1):60–67. https://doi.org/10.1001/jamaneurol.2015.3037 CrossRefPubMedPubMedCentral

49.

Jonsson M, Zetterberg H, van Straaten E, Lind K, Syversen S, Edman A, Blennow K, Rosengren L, Pantoni L, Inzitari D, Wallin A (2010) Cerebrospinal fluid biomarkers of white matter lesions—cross-sectional results from the LADIS study. Eur J Neurol 17(3):377–382. https://doi.org/10.1111/j.1468-1331.2009.02808.x CrossRefPubMed

50.

Sjögren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K, Rosengren L, Blennow K, Wallin A (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66(3):510–516. https://doi.org/10.1002/jnr.1242 CrossRefPubMed

51.

Brureau A, Blanchard-Bregeon V, Pech C, Hamon S, Chaillou P, Guillemot J-C, Barneoud P, Bertrand P, Pradier L, Rooney T, Schussler N (2017) NF-L in cerebrospinal fluid and serum is a biomarker of neuronal damage in an inducible mouse model of neurodegeneration. Neurobiol Dis 104:73–84. https://doi.org/10.1016/j.nbd.2017.04.007 CrossRefPubMed

52.

Ballatore C, Lee VM-Y, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8(9):663–672. https://doi.org/10.1038/nrn2194 CrossRefPubMed

53.

Trojanowski JQ, Schuck T, Schmidt ML, Lee VM (1989) Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem 37(2):209–215. https://doi.org/10.1177/37.2.2492045 CrossRefPubMed

54.

Blennow K, Zetterberg H, Fagan AM (2012) Fluid biomarkers in Alzheimer disease. Cold Spring Harb Perspect Med 2(9):a006221. https://doi.org/10.1101/cshperspect.a006221 CrossRefPubMedPubMedCentral

55.

Zetterberg H (2017) Review: tau in biofluids—relation to pathology, imaging and clinical features. Neuropathol Appl Neurobiol 43(3):194–199. https://doi.org/10.1111/nan.12378 CrossRefPubMed

56.

Meeter LHH, Vijverberg EG, Del Campo M, Rozemuller AJM, Donker Kaat L, Jong FJ de, van der Flier WM, Teunissen CE, van Swieten JC, Pijnenburg YAL (2018) Clinical value of neurofilament and phospho-tau/tau ratio in the frontotemporal dementia spectrum. Neurology 90(14):e1231–e1239. https://doi.org/10.1212/WNL.0000000000005261 CrossRefPubMedPubMedCentral

57.

Pijnenburg YAL, Verwey NA, van der Flier WM, Scheltens P, Teunissen CE (2015) Discriminative and prognostic potential of cerebrospinal fluid phosphoTau/tau ratio and neurofilaments for frontotemporal dementia subtypes. Alzheimers Dement (Amst) 1(4):505–512. https://doi.org/10.1016/j.dadm.2015.11.001 CrossRef

58.

Menke RAL, Abraham I, Thiel CS, Filippini N, Knight S, Talbot K, Turner MR (2012) Fractional anisotropy in the posterior limb of the internal capsule and prognosis in amyotrophic lateral sclerosis. Arch Neurol 69(11):1493–1499. https://doi.org/10.1001/archneurol.2012.1122 CrossRefPubMed

59.

Borsodi F, Culea V, Langkammer C, Khalil M, Pirpamer L, Quasthoff S, Enzinger C, Schmidt R, Fazekas F, Ropele S (2017) Multimodal assessment of white matter tracts in amyotrophic lateral sclerosis. PLoS One 12(6):e0178371. https://doi.org/10.1371/journal.pone.0178371 CrossRefPubMedPubMedCentral

60.

Rosenbohm A, Müller H-P, Hübers A, Ludolph AC, Kassubek J (2016) Corticoefferent pathways in pure lower motor neuron disease: a diffusion tensor imaging study. J Neurol 263(12):2430–2437. https://doi.org/10.1007/s00415-016-8281-2 CrossRefPubMed

61.

Acosta-Cabronero J, Nestor PJ (2014) Diffusion tensor imaging in Alzheimer’s disease: insights into the limbic-diencephalic network and methodological considerations. Front Aging Neurosci 6:266. https://doi.org/10.3389/fnagi.2014.00266 CrossRefPubMedPubMedCentral

62.

Winklewski PJ, Sabisz A, Naumczyk P, Jodzio K, Szurowska E, Szarmach A (2018) Understanding the physiopathology behind axial and radial diffusivity changes—what do we know? Front Neurol 9:92. https://doi.org/10.3389/fneur.2018.00092 CrossRefPubMedPubMedCentral

63.

Wheeler-Kingshott CAM, Cercignani M (2009) About “axial” and “radial” diffusivities. Magn Reson Med 61(5):1255–1260. https://doi.org/10.1002/mrm.21965 CrossRefPubMed

64.

Toft MH, Gredal O, Pakkenberg B (2005) The size distribution of neurons in the motor cortex in amyotrophic lateral sclerosis. J Anat 207(4):399–407. https://doi.org/10.1111/j.1469-7580.2005.00465.x CrossRefPubMedPubMedCentral

65.

Weydt P, Oeckl P, Huss A, Müller K, Volk AE, Kuhle J, Knehr A, Andersen PM, Prudlo J, Steinacker P, Weishaupt JH, Ludolph AC, Otto M (2016) Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol 79(1):152–158. https://doi.org/10.1002/ana.24552 CrossRefPubMed

Title: Significance of CSF NfL and tau in ALS
Authors: Stefanie Schreiber
Nicola Spotorno
Frank Schreiber
Julio Acosta-Cabronero
Jörn Kaufmann
Judith Machts
Grazyna Debska-Vielhaber
Cornelia Garz
Daniel Bittner
Nathalie Hensiek
Reinhard Dengler
Susanne Petri
Peter J. Nestor
Stefan Vielhaber
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 11/2018
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-018-9043-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Significance of CSF NfL and tau in ALS

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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