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Frontotemporal degeneration in amyotrophic lateral sclerosis (ALS): a longitudinal MRI one-year study

Published online by Cambridge University Press:  24 February 2020

Francesca Trojsi Open the ORCID record for Francesca Trojsi [Opens in a new window] ,
Federica Di Nardo ,
Mattia Siciliano ,
Giuseppina Caiazzo ,
Cinzia Femiano ,
Carla Passaniti ,
Dario Ricciardi ,
Antonio Russo ,
Alvino Bisecco  and
Sabrina Esposito
...Show all authors
Francesca Trojsi*
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Federica Di Nardo
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Mattia Siciliano
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Giuseppina Caiazzo
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Cinzia Femiano
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Carla Passaniti
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Dario Ricciardi
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Antonio Russo
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Alvino Bisecco
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Sabrina Esposito
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Maria Rosaria Monsurrò
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Mario Cirillo
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
Gabriella Santangelo
Affiliation:
Department of Psychology, Università degli Studi della Campania “Luigi Vanvitelli”, Caserta, Italy
Fabrizio Esposito
Affiliation:
Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Italy
Gioacchino Tedeschi
Affiliation:
Department of Advanced Medical and Surgical Sciences; MRI Research Center SUN-FISM, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
*
*Author for correspondence: Francesca Trojsi, MD, PhD, Email: [email protected]
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Abstract

Objective

Advanced neuroimaging techniques may offer the potential to monitor disease progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative, multisystem disease that still lacks therapeutic outcome measures. We aim to investigate longitudinal functional and structural magnetic resonance imaging (MRI) changes in a cohort of patients with ALS monitored for one year after diagnosis.

Methods

Resting state functional MRI, diffusion tensor imaging (DTI), and voxel-based morphometry analyses were performed in 22 patients with ALS examined by six-monthly MRI scans over one year.

Results

During the follow-up period, patients with ALS showed reduced functional connectivity only in some extramotor areas, such as the middle temporal gyrus in the left frontoparietal network after six months and in the left middle frontal gyrus in the default mode network after one year without showing longitudinal changes of cognitive functions. Moreover, after six months, we reported in the ALS group a decreased fractional anisotropy (P = .003, Bonferroni corrected) in the right uncinate fasciculus. Conversely, we did not reveal significant longitudinal changes of functional connectivity in the sensorimotor network, as well as of gray matter (GM) atrophy or of DTI metrics in motor areas, although clinical measures of motor disability showed significant decline throughout the three time points.

Conclusion

Our findings highlighted that progressive impairment of extramotor frontotemporal networks may precede the appearance of executive and language dysfunctions and GM changes in ALS. Functional connectivity changes in cognitive resting state networks might represent candidate radiological markers of disease progression.

Keywords

Amyotrophic lateral sclerosisfrontotemporal degenerationresting state functional MRIdiffusion tensor imagingvoxel-based morphometryECAS
Type
Original Research
Information
CNS Spectrums , Volume 26 , Issue 3 , June 2021 , pp. 258 - 267
Copyright
© The Author(s) 2020. Published by Cambridge University Press

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References

Hardiman, O, Al-Chalabi, A, Chiò, A, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071CrossRefGoogle ScholarPubMed
Burrell, JR, Halliday, GM, Kril, JJ, et al. The frontotemporal dementia-motor neuron disease continuum. Lancet. 2016;388(10047):919–931.CrossRefGoogle ScholarPubMed
Ahmad, K, Baig, MH, Mushtaq, G, Kamal, MA, Greig, NH, Choi, I. Commonalities in biological pathways, genetics, and cellular mechanism between Alzheimer Disease and other neurodegenerative diseases: an in silico-updated overview. Curr Alzheimer Res. 2017;14(11):1190–1197.CrossRefGoogle Scholar
Boeynaems, S, Bogaert, E, Van Damme, P, Van Den Bosch, L. Inside out: the role of nucleocytoplasmic transport in ALS and FTLD. Acta Neuropathol. 2016;132(2):159–173.CrossRefGoogle ScholarPubMed
Grad, L, Fernando, SM, Cashman, NR. From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis. Neurobiol Dis. 2015;77:257–265.CrossRefGoogle ScholarPubMed
Lulé, D, Böhm, S, Müller, HP, et al. Cognitive phenotypes of sequential staging in amyotrophic lateral sclerosis. Cortex. 2018;101:163–171.CrossRefGoogle ScholarPubMed
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;18(3–4):153–174.CrossRefGoogle ScholarPubMed
De Jesus-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.CrossRefGoogle Scholar
Renton, AE, Majounie, E, Waite, A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72(2):257–268.CrossRefGoogle ScholarPubMed
Turner, MR. Motor neuron disease: biomarker development for an expanding cerebral syndrome. Clin Medicine (Lond). 2016;6(Suppl 6):s60–s65.CrossRefGoogle Scholar
Cedarbaum, JM, Stambler, N, Malta, E, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999;169(1–2):13–21.CrossRefGoogle Scholar
van den Berg LH, , Sorenson, E, Gronseth, G, et al. Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials. Neurology. 2019;92(14):e1610–e1623.CrossRefGoogle ScholarPubMed
Menke, RA, Agosta, F, Grosskreutz, J, Filippi, M, Turner, MR. Neuroimaging endpoints in Amyotrophic Lateral Sclerosis. Neurotherapeutics. 2017;14(1):11–23.CrossRefGoogle ScholarPubMed
Menke, RAL, Körner, S, Filippini, N, et al. Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis. Brain. 2014;137(Pt 9):2546–2555.CrossRefGoogle ScholarPubMed
Menke, RAL, Proudfoot, M, Talbot, K, Turner, MR. The two-year progression of structural and functional cerebral MRI in amyotrophic lateral sclerosis. Neuroimage Clin. 2017;17:953–961.CrossRefGoogle ScholarPubMed
Cardenas-Blanco, A, Machts, J, Acosta-Cabronero, J, et al. Structural and diffusion imaging versus clinical assessment to monitor amyotrophic lateral sclerosis. Neuroimage Clin. 2016;11:408–414.CrossRefGoogle ScholarPubMed
Bede, P, Hardiman, O. Longitudinal structural changes in ALS: a three time-point imaging study of white and gray matter degeneration. Amyotroph Lateral Scler Frontotemporal Degener. 2018;19(3–4):232–241.CrossRefGoogle ScholarPubMed
Schulthess, I, Gorges, M, Müller, H-P, et al. Functional connectivity changes resemble patterns of pTDP-43 pathology in amyotrophic lateral sclerosis. Sci Rep. 2016;6:38391CrossRefGoogle ScholarPubMed
de Albuquerque, M, Branco, LM, Rezende, TJ, de Andrade, HM, Nucci, A, França, MC Jr. Longitudinal evaluation of cerebral and spinal cord damage in amyotrophic lateral sclerosis. Neuroimage Clin. 2017;14:269–276.CrossRefGoogle ScholarPubMed
Bede, P, Hardiman, O. Lessons of ALS imaging: pitfalls and future directions—a critical review. Neuroimage Clin. 2014;4:436–443.CrossRefGoogle Scholar
Schuster, C, Elamin, M, Hardiman, O, Bede, P. Presymptomatic and longitudinal neuroimaging in neurodegeneration—from snapshots to motion picture: a systematic review. J Neurol Neurosurg Psychiatry. 2015;86(10):1089–1096.CrossRefGoogle ScholarPubMed
Brooks, BR, Miller, RG, Swash, M, Munsat, TL. 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;1(5):293–299.CrossRefGoogle Scholar
Chiò, A, Calvo, A, Moglia, C, Mazzini, L, Mora, G, PARALS Study Group. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2011;82(7):740–746.CrossRefGoogle ScholarPubMed
Turner, MR, Cagnin, A, Turkheimer, FE, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [(11)C](R)-PK11195 positron emission tomography study. Neurobiol Dis. 2004;15(3):601–609.CrossRefGoogle Scholar
Poletti, B, Solca, F, Carelli, L, et al. The validation of the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Amyotroph Lateral Scler Frontotemporal Degener. 2016;17(7–8):489–498.CrossRefGoogle Scholar
Siciliano, M, Trojano, L, Trojsi, F, et al. Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-Italian version: regression based norms and equivalent scores. Neurol Sci. 2017;38(6):1059–1068.CrossRefGoogle ScholarPubMed
Abrahams, S, Newton, J, Niven, E, Foley, J, Bak, TH. Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15(1–2):9–14.CrossRefGoogle ScholarPubMed
Hays, RD, Anderson, R, Revicki, D. Psychometric considerations in evaluating health-related quality of life measures. Qual Life Res. 1993;2(6):441–449.CrossRefGoogle ScholarPubMed
Hyvärinen, A, Karhunen, J, Oja, E. Independent Component Analysis. New York, NY: John Wiley and Sons; 2001.CrossRefGoogle ScholarPubMed
Esposito, F, Scarabino, T, Hyvärinen, A, et al. Independent component analysis of fMRI group studies by self-organizing clustering. Neuroimage. 2005;25(1):193–205.CrossRefGoogle ScholarPubMed
Greicius, MD, Flores, BH, Menon, V, et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 2007;62(5):429–437.CrossRefGoogle ScholarPubMed
Mantini, D, Perrucci, MG, Del Gratta, C, Romani, GL, Corbetta, M. Electrophysiological signatures of resting state networks in the human brain. Proc Natl Acad Sci USA. 2007;104(32):13170–13175.CrossRefGoogle ScholarPubMed
Smith, SM, Fox, PT, Miller, KL, et al. Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci USA. 2009;106(31):13040–13045.CrossRefGoogle Scholar
Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC. Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med. 1995;33(5):636–647.CrossRefGoogle ScholarPubMed
Smith, SM, Jenkinson, M, Johansen-Berg, H, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 2006;31(4):1487–1505.CrossRefGoogle ScholarPubMed
Wakana, S, Caprihan, A, Panzenboeck, MM, et al. Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage. 2007;36(3):630–644.CrossRefGoogle ScholarPubMed
Hua, K, Zhang, J, Wakana, S, et al. Tract probability maps in stereotaxic spaces: analysis of white matter anatomy and tract-specific quantification. Neuroimage. 2008;39(1):336–347.CrossRefGoogle ScholarPubMed
Ashburner, J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38(1):95–113.CrossRefGoogle ScholarPubMed
Farb, NAS, Grady, CL, Strother, S, et al. Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation. Cortex. 2013;49(7):1856–1873.CrossRefGoogle ScholarPubMed
Damoiseaux, JS, Rombouts, SA, Barkhof, F, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA. 2006;103(37):13848–13853.CrossRefGoogle ScholarPubMed
Greicius, MD, Krasnow, B, Reiss, AL, Menon, V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA. 2003;100(1):253–258.CrossRefGoogle ScholarPubMed
Agosta, F, Canu, E, Valsasina, P, et al. Divergent brain network connectivity in amyotrophic lateral sclerosis. Neurobiol Aging. 2013;34(2):419–427.CrossRefGoogle ScholarPubMed
Filippi, M, Agosta, F, Scola, E, et al. Functional network connectivity in the behavioral variant of frontotemporal dementia. Cortex. 2013;49(9):2389–2401.CrossRefGoogle ScholarPubMed
Beeldman, E, Raaphorst, J, Klein Twennaar, M, et al. The cognitive profile of behavioural variant FTD and its similarities with ALS: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2018;89(9):995–1002.CrossRefGoogle ScholarPubMed
Crespi, C, Dodich, A, Cappa, SF, et al. Multimodal MRI quantification of the common neurostructural bases within the FTD-ALS continuum. Neurobiol Aging. 2018;62:95–104.CrossRefGoogle ScholarPubMed
Eisen, A, Braak, H, Del Tredici, K, Lemon, R, Ludolph, AC, Kiernan, MC. Cortical influences drive amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(11):917–924.CrossRefGoogle ScholarPubMed
Braak, H, Brettschneider, J, Ludolph, AC, Lee, VM, Trojanowski, JQ, Del Tredici, K. Amyotrophic lateral sclerosis—a model of corticofugal axonal spread. Nat Rev Neurol. 2013;9(12):708–714.CrossRefGoogle ScholarPubMed
Brettschneider, J, Del Tredici, K, Toledo, JB, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013;74(1):20–38.CrossRefGoogle ScholarPubMed
Ludolph, AC, Brettschneider, J. TDP-43 in amyotrophic lateral sclerosis—is it a prion disease? Eur J Neurol. 2015;22(5):753–761.CrossRefGoogle ScholarPubMed
Müller, HP, Turner, MR, Grosskreutz, J, et al. A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2016;87(6):570–579.CrossRefGoogle ScholarPubMed
Kassubek, J, Müller, HP, Del Tredici, K, et al. Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDp-43 pathology. Brain. 2014;137(Pt 6):1733–1740.CrossRefGoogle ScholarPubMed
Kassubek, J, Müller, HP, Del Tredici, K, et al. Imaging the pathoanatomy of amyotrophic lateral sclerosis in vivo: targeting a propagation-based biological marker. J Neurol Neurosurg Psychiatry. 2018;89(4):374–381.CrossRefGoogle ScholarPubMed
Schmidt, R, de Reus, MA, Scholtens, LH, van den Berg, LH, van den Heuvel, MP. Simulating disease propagation across white matter connectome reveals anatomical substrate for neuropathology staging in amyotrophic lateral sclerosis. Neuroimage. 2016;124(Pt A):762–769.CrossRefGoogle ScholarPubMed
Do-Ha, D, Buskila, Y, Ooi, L. Impairments in motor neurons, interneurons and astrocytes contribute to hyperexcitability in ALS: underlying mechanisms and paths to therapy. Mol Neurobiol. 2018;55(2):1410–1418.CrossRefGoogle Scholar
Tedeschi, G, Trojsi, F, Tessitore, A, et al. Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33(5):886–898.CrossRefGoogle Scholar
Schuster, C, Kasper, E, Machts, J, et al. Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis. J Neurol. 2014;261(10):1871–1880.CrossRefGoogle ScholarPubMed
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):383–388.CrossRefGoogle ScholarPubMed
Buchanan, CR, Pettit, LD, Storkey, AJ, Abrahams, S, Bastin, ME. Reduced structural connectivity within a prefrontal-motor-subcortical network in amyotrophic lateral sclerosis. J Magn Reson Imag. 2015;41(5):1342–1352.CrossRefGoogle ScholarPubMed
Verstraete, E, Veldink, JH, Mandl, RC, van den Berg, LH, van den Heuvel, MP. Impaired structural motor connectome in amyotrophic lateral sclerosis. PLoS One. 2011;6(9):e24239.CrossRefGoogle ScholarPubMed
Zhou, C, Hu, X, Hu, J, et al. Altered brain network in amyotrophic lateral sclerosis: a resting graph theory-based network study at voxel-wise Level. Front Neurosci. 201;10:204.Google Scholar
Blain, CRV, Williams, VC, Johnston, C, et al. A longitudinal study of diffusion tensor MRI in ALS. Amyotroph Lateral Scler. 2007;8(6):348–355.CrossRefGoogle ScholarPubMed
Agosta, F, Rocca, MA, Valsasina, P, 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):53–55.CrossRefGoogle ScholarPubMed
Agosta, F, Pagani, E, Petrolini, M, et al. Assessment of white matter tract damage in patients with amyotrophic lateral sclerosis: a diffusion tensor MR imaging tractography study. AJNR Am J Neuroradiol. 2010;31(8):1457–1461.CrossRefGoogle ScholarPubMed
Schuster, C, Elamin, M, Hardiman, O, Bede, P. The segmental diffusivity profile of amyotrophic lateral sclerosis associated white matter degeneration. Eur J Neurol. 2016;23(8):1361–1371.CrossRefGoogle ScholarPubMed
Agosta, F, Ferraro, PM, Riva, N, et al. Structural brain correlates of cognitive and behavioral impairment in MND. Hum Brain Mapp. 2016;37(4):1614–1626.CrossRefGoogle ScholarPubMed
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):1645–1652.CrossRefGoogle ScholarPubMed
Rajagopalan, V, Pioro, EP. Differential involvement of corticospinal tract (CST) fibers in UMN-predominant ALS patients with or without CST hyperintensity: a diffusion tensor tractography study. Neuroimage Clin. 2017;14:574–579.CrossRefGoogle ScholarPubMed
Christidi, F, Zalonis, I, Kyriazi, S, et al. Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study. Brain Imaging Behav. 2014;8(4):497–505.CrossRefGoogle ScholarPubMed
Christidi, F, Karavasilis, E, Zalonis, I, et al. Memory-related white matter tract integrity in amyotrophic lateral sclerosis: an advanced neuroimaging and neuropsychological study. Neurobiol Aging. 2017;49:69–78.CrossRefGoogle ScholarPubMed
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