Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector48010.17816/ACEN.2017.2.11ReviewsОбзорыUnknownStructural and functional neuroimaging in amyotrophic lateral sclerosisСтруктурная и функциональная нейровизуализация при боковом амиотрофическом склерозеhttps://orcid.org/0000-0003-0716-3737BakulinIlya S.БакулинИлья Сергеевич
Russian Federation

Cand. Sci. (Med.), researcher, Department of neurorehabilitation and physiotherapy

к.м.н., н.с. отд. нейрореабилитации и физиотерапии

bakulin@neurology.ruChervyakovAleksandr V.ЧервяковАлександр В.
Russian Federation
bakulin@neurology.ruKremnevaElena I.КремневаЕлена Игоревна
Russian Federation
bakulin@neurology.ruhttps://orcid.org/0000-0001-5539-245XKonovalovRodion N.КоноваловРодион Николаевич
Russian Federation

Cand. Sci. (Med.), senior researcher, Neuroradiology department

к.м.н., с.н.с. отд. лучевой диагностики

bakulin@neurology.ruZakharovaMaria N.ЗахароваМария Николаевна
Russian Federation
bakulin@neurology.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»06082017112768706082017Copyright ©; 2017, Bakulin I.S., Chervyakov A.V., Kremneva E.I., Konovalov R.N., Zakharova M.N.Copyright ©; 2017, Bakulin I.S., Chervyakov A.V., Kremneva E.I., Konovalov R.N., Zakharova M.N.2017Bakulin I.S., Chervyakov A.V., Kremneva E.I., Konovalov R.N., Zakharova M.N.Bakulin I.S., Chervyakov A.V., Kremneva E.I., Konovalov R.N., Zakharova M.N.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/480

Abstract. Amyotrophic lateral sclerosis (ALS) is a fatal progressive central nervous system disorder affecting the upper and lower motor neurons. It is important to study the features of the course and progression of neurodegeneration in ALS, since no effective methods for treating this disease have been developed yet. Despite the clear evidence that brain lesions in ALS are of multisystem nature, there are no objective biomarkers of lesions of the upper motor neuron and the extramotor areas of the brain. Structural and functional neuroimaging, such as MR brain morphometry, diffusion tensor imaging, MR spectroscopy, functional MRI, positron emission tomography (PET), etc., have recently been playing a significant role in studying ALS. The results of neuroimaging studies are analyzed in this review in the context of using them to diagnose, predict, and monitor the course of ALS. Diffusion tensor imaging, MR spectroscopy, PET, combination of several neuroimaging methods and their combination with transcranial magnetic stimulation are the most sensitive and specific techniques to be used to diagnose the disease. Diffusion tensor imaging and MR spectroscopy can be used to monitor and predict the disease course. The main limitations and shortcomings of the performed studies, as well as the possible outlook for using neuroimaging in ALS, are discussed.

Резюме. Боковой амиотрофический склероз (БАС) – фатальное прогрессирующее заболевание центральной нервной системы с поражением верхнего и нижнего мотонейронов. Изучение особенностей течения и распространения нейродегенеративного процесса при БАС имеют большое значение, поскольку до настоящего времени эффективные методы лечения заболевания не разработаны. В клинической практике отсутствуют объективные биомаркеры поражения верхнего мотонейрона и экстрамоторных регионов головного мозга, несмотря на очевидные доказательства мультисистемности поражения головного мозга при БАС. В последние годы большую роль в изучении БАС играют методы структурной и функциональной нейровизуализации, такие как МР-морфометрия, диффузионно-тензорная МРТ, МР-спектроскопия, фунциональная МРТ, позитронно-эмиссионная томография (ПЭТ) и другие. В обзоре анализируются результаты нейровизуализационных исследований в контексте их применения для диагностики, прогнозирования и мониторирования течения БАС. Для диагностики заболевания наиболее чувствительными и специфичными являются диффузионно-тензорная МРТ, МР-спектроскопия, ПЭТ, комбинация нескольких методов нейровизуализации и их сочетание с транскраниальной магнитной стимуляцией. Диффузионно-тензорная МРТ и МР-спектроскопия могут использоваться для мониторинга и прогнозирования течения заболевания. Обсуждаются основные ограничения и недостатки проведённых исследований, а также возможные перспективы применения нейровизуализации при БАС.

amyotrophic lateral sclerosismotor neuron diseaseneuroimagingMRIbiomarkersбоковой амиотрофический склерозболезнь мотонейронанейровизуализацияМРТбиомаркерыZavalishin I.A. (ed.). [Amyotrophic lateral sclerosis]. Moscow: Evraziуa+ , 2007, 448 p. (In Russ.).Zakharova M.N., Illarioshkin S.N., Abramycheva N.Yu. et al. [Amyotrophic lateral sclerosis]. In: Gusev E.I., Konovalov A.N., Geht A.B. (eds.) [Neurology. National guide]. Moscow: GEOTAR-Media, 2014: 420-439. (In Russ.).Turner M.R., Swash M. The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey. J Neurol Neurosurg Psychiatry 2015; 86 (6): 667-73. DOI:10.1136/jnnp-2014-308946. PMID: 25644224.Phukan J., Elamin M., Bede P. et al. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 2012; 83: 102–08. PMID: 21836033. DOI: 10.1136/jnnp-2011-300188.Blasco H., Vourc'h P., Pradat P.F. et al. Further development of biomarkers in amyotrophic lateral sclerosis. Expert Rev Mol Diagn. 2016; 16 (8): 853-68. PMID: 27275785. DOI: 10.1080/14737159.2016.1199277.Kraemer M., Buerger M., Berlit P. Diagnostic problems and delay of diagnosis in amyotrophic lateral sclerosis. Clin Neurol Neurosurg 2010; 112 (2): 103-5. PMID: 27275785. DOI:10.1080/14737159.2016.1199277.Illarioshkin S.N., Tanashyan M.M., Maksimova M.Yu. et al. [The concept of biomarkers in clinical neurology: the possibility of early diagnosis and prognosis of individual risk]. In: Piradov M.A., Illarioshkin S.N., Tanashyan M.M. (eds). [Neurology of XXI century: Diagnostic, therapeutic and research technologies. Guide for doctors] Moscow, «ATMO» , 2015; 3: 363-424. (In Russ.).Turner M.R., Verstraete E. What does imaging reveal about the pathology of amyotrophic lateral sclerosis? Curr Neurol Neurosci Rep. 2015; 15 (7): 45. PMID: 26008817. DOI 10.1007/s11910-015-0569-6.Chiò A., Pagani M., Agosta F. et al. Neuroimaging in amyotrophic lateral sclerosis: insights into structural and functional changes // Lancet Neurol. 2014; 13 (12): 1228-40. PMID: 25453462. DOI:10.1016/S1474-4422(14)70167-X.Pradat P.F., El Mendili M.M. Neuroimaging to investigate multisystem involvement and provide biomarkers in amyotrophic lateral sclerosis // Biomed Res Int. 2014; 2014: 467560. PMID: 24949452. DOI: 10.1155/2014/467560.Piradov M.A., Tanashyan M.M., Krotenkova M.V. et al. [State-of-the-art neuroimaging techniques]. Annals of Clinical and Experimentl Neurology. 2015; 9 (4): 13-20. (In Russ.).Kremneva E.I., Vorobyeva A.A., Adarcheva L.S. [Forewarned is forearmed: MRI practical aspects in Hirayama disease]. Luchevaya diagnostika i terapiya 2015; 6 (3): 35-43. (In Russ.).Bede P., Hardiman O. Lessons of ALS imaging: Pitfalls and future directions - A critical review. Neuroimage Clin 2014; 4: 436-43. PMID: 24624329. DOI: 10.1016/j.nicl.2014.02.011.Foerster B.R., Welsh R.C., Feldman E.L. 25 years of neuroimaging in amyotrophic lateral sclerosis. Nat Rev Neurol 2013; 9 (9): 513-24. PMID: 23917850. DOI: 10.1038/nrneurol.2013.153.Sabatelli M., Conte A., Zollino M. Clinical and genetic heterogeneity of amyotrophic lateral sclerosis. Clin Genet 2013; 83 (5): 408-16. PMID: 23379621. DOI: 10.1111/cge.12117.Leblond C.S., Kaneb H.M., Dion P.A., Rouleau G.A. Dissection of genetic factors associated with amyotrophic lateral sclerosis. Exp Neurol 2014; 262: 91-101. PMID: 24780888. DOI: 10.1016/j.expneurol.2014.04.013.Swinnen B., Robberecht W. The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol. 2014; 10: 661–70. PMID: 25311585. DOI: 10.1038/nrneurol.2014.184.Jawdat O., Statland J.M., Barohn R.J. Amyotrophic Lateral Sclerosis Regional Variants (Brachial Amyotrophic Diplegia, Leg Amyotrophic Diplegia, and Isolated Bulbar Amyotrophic Lateral Sclerosis). Neurol Clin 2015; 33(4): 775-85. PMID: 26515621. DOI: 10.1016/j.ncl.2015.07.003.Beghi E., Chio` A., Couratier P. et al.; Eurals Consortium. The epidemiology and treatment of ALS: focus on the heterogeneity of the disease and critical appraisal of therapeutic trials. Amyotroph Lateral Scler Other Motor Neuron Disord 2011; 12: 1–10. PMID: 20698807. DOI: 10.3109/17482968.2010.502940.Traynor B.J., Codd M.B., Corr B. et al. Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study. Arch Neurol 2000. 57(8); 1171-1176. PMID: 10927797.Swash M. Why are upper motor neuron signs difficult to elicit in amyotrophic lateral sclerosis? J Neurol Neurosurg Psychiatry 2012; 83 (6): 659-62. PMID: 22496581. DOI:m10.1136/jnnp-2012-302315.Bakulin I.S., Chervyakov A.V., Zakharova M.N. [Navigated transcranial magnetic stimulation possibilities in difficult diagnostic cases upper motor neuron lesions – case report]. Nervno-myshechnye bolezni 2015; 2; 32-37. (In Russ.).Huynh W., Simon N.G., Grosskreutz J. et al. Assessment of the upper motor neuron in amyotrophic lateral sclerosis. Clin Neurophysiol. 2016; 127 (7): 2643-60. PMID: 27291884. DOI: 10.1016/j.clinph.2016.04.025.Verstraete E., Foerster B.R. Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis. Neurotherapeutics. 2015; 12 (2): 403-16. PMID: 25791072. DOI: 10.1007/s13311-015-0347-9.Stuchevskaya T.R., Tyutin L.A., Pozdnyakov A.V. et al. [Brain magnetic resonance imaging in patients with classical amyotrophic lateral sclerosis and its atypical variants]. Nevrol zhurn 2015; 20 (4): 29-35. (In Russ.).Huynh W., Lam A., Vucic S. et al. Corticospinal tract dysfunction and development of amyotrophic lateral sclerosis following electrical injury. Muscle Nerve 2010; 42: 288–92. PMID: 20589889. DOI: 10.1002/mus.21681.Rocha A.J., Maia Júnior A.C. Is magnetic resonance imaging a plausible biomarker for upper motor neuron degeneration in amyotrophic lateral sclerosis/primary lateral sclerosis or merely a useful paraclinical tool to exclude mimic syndromes? A critical review of imaging applicability in clinical routine. Arquivos de neuro-psiquiatria 2012; 70: 532–9. PMID: 22836461.Hecht M.J., Fellner F., Fellner C. Hyperintense and hypointense MRI signals of the precentral gyrus and corticospinal tract in ALS: a follow-up examination including FLAIR images. J Neurol Sci. 2002; 199 (1-2): 59-65. PMID: 12084444.Jin J., Hu F., Zhang Q. et al. Hyperintensity of the corticospinal tract on FLAIR: A simple and sensitive objective upper motor neuron degeneration marker in clinically verified amyotrophic lateral sclerosis // J Neurol Sci. 2016; 367: 177-83. PMID: 27423585. DOI: 10.1016/j.jns.2016.06.005.Pronin I.N., Fadeeva L.M., Zakharova N.E. et al. [Diffusion tensor imaging and diffusion tensor tractography]. Annals of Clinical and Experimental Neurology. 2008; 2 (1): 32-41. (In Russ.).Foerster B.R., Dwamena B.A., Petrou M. et al. Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: a systematic review and individual patient data meta-analysis. Acad Radiol. 2013; 20 (9):1099-106. PMID: 23931423. DOI: 10.1016/j.acra.2013.03.017.Ben Bashat D., Artzi M., Tarrasch R. et al. A potential tool for the diagnosis of ALS based on diffusion tensor imaging. Amyotroph Lateral Scler. 2011; 12 (6): 398-405. DOI: 10.3109/17482968.2011.582646.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): 1361-71. DOI: 10.1111/ene.13038.Filippini N., Douaud G., Mackay C.E. et al. Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis. Neurology. 2010; 75(18): 1645-52. PMID: 21041787. DOI: 10.1212/WNL.0b013e3181fb84d1.Kaufmann P., Pullman S.L., Shungu D.C. et al. Objective tests for upper motor neuron involvement in amyotrophic lateral sclerosis (ALS). Neurology 2004; 62: 1753–57. PMID: 15159473.Kalra S., Hanstock C.C., Martin W.R. et al. Detection of cerebral degeneration in amyotrophic lateral sclerosis using high-field magnetic resonance spectroscopy. Arch Neurol 2006; 63: 1144–48. PMID: 16908742. DOI: 10.1001/archneur.63.8.1144.Zhu H., Edden R.A., Ouwerkerk R. et al. High resolution spectroscopic imaging of GABA at 3 Tesla. Magn Reson Med. 2011; 65 (3): 603-609. PMID: 21337399. DOI: 10.1002/mrm.22671.Foerster B.R., Callaghan B.C., Petrou M. et al. Decreased motor cortex gamma-aminobutyric acid in amyotrophic lateral sclerosis. Neurology. 2012; 78 (20): 1596- 1600. PMID: 22517106. DOI: 10.1212/WNL.0b013e3182563b57.Verstraete E., Veldink J.H., Hendrikse J. et al. Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2012; 83: 383-388. PMID: 21965521. DOI: 10.1136/jnnp-2011-300909.Walhout R., Westeneng H.J., Verstraete E. et al. Cortical thickness in ALS: towards a marker for upper motor neuron involvement. J Neurol Neurosurg Psychiatry 2015; 86: 288-294. PMID: 25121571. DOI: 10.1136/jnnp-2013-306839.Agosta F., Valsasina P., Riva N. et al. The cortical signature of amyotrophic lateral sclerosis. PLoS One. 2012; 7 (8): 42816. PMID: 22880116. DOI: 10.1371/journal.pone.0042816.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: 549–554. PMID: 20929296. DOI: 10.3109/17482968.2010.516265.Dalakas M.C., Hatazawa J., Brooks R.A., Di Chiro G. Lowered cerebral glucose utilization in amyotrophic lateral sclerosis. Ann Neurol 1987; 22: 580–86. PMID: 3501273. DOI:10.1002/ana.410220504.Hoffman J.M., Mazziotta J.C., Hawk T.C., Sumida R. Cerebral glucose utilization in motor neuron disease. Arch Neurol. 1992; 49: 849–54. PMID: 1524517.Pagani M., Chiò A., Valentini M.C. et al. FDG-PET in amyotrophic lateral sclerosis—functional pattern and diagnostic accuracy. Neurology 2014; 83: 1067–74. PMID: 26940764. DOI: 10.2967/jnumed.115.166272.Van Laere K., Vanhee A., Verschueren J. et al. Value of 18fluorodeoxyglucose-positron-emission tomography in amyotrophic lateral sclerosis: a prospective study. JAMA Neurol 2014; 71: 553–61. PMID: 24615479. DOI: 10.1001/jamaneurol.2014.62.Foerster B.R., Carlos R.C., Dwamena B.A. et al. Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2014; 1: 107–14. PMID: 25356389. DOI: 10.1002/acn3.30.Cervo A., Cocozza S., Sacca F. et al. The combined use of conventional MRI and MR spectroscopic imaging increases the diagnostic accuracy in amyotrophic lateral sclerosis. Eur J Radiol. 2015; 84: 151–7. PMID: 25466774. DOI: 10.1016/j.ejrad.2014.10.019.Pohl C., Block W., Traber F. et al. Proton magnetic resonance spectroscopy and transcranial magnetic stimulation for the detection of upper motor neuron degeneration in ALS patients. J Neurol Sci. 2001; 190: 21–27. PMID: 11574102.Furtula J., Johnsen B., Frandsen J. et al. Upper motor neuron involvement in amyotrophic lateral sclerosis evaluated by triple stimulation technique and diffusion tensor MRI. J Neurol. 2013; 260 (6): 1535-44. PMID: 23299622. DOI: 10.1007/s00415-012-6824-8.Bae J.S., Ferguson M., Tan R. et al. Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia. J Clin Neurol. 2016; 12 (2): 209-17. PMID: 26932257. DOI: 10.3988/jcn.2016.12.2.209.Qureshi M., Schoenfeld D.A., Paliwal Y. et al. The natural history of ALS is changing: improved survival. Amyotroph Lateral Scler Other Motor Neuron Disord. 2009; 10: 324–31. PMID: 19922119. DOI: 10.3109/17482960903009054.Rutkove S.B. Clinical Measures of Disease Progression in Amyotrophic Lateral Sclerosis. Neurotherapeutics. 2015; 12 (2): 384-93. PMID: 25582382. DOI: 10.1007/s13311-014-0331-9.Mitsumoto H., Brooks B.R., Silani V. Clinical trials in amyotrophic lateral sclerosis: why so many negative trials and how can trials be improved? Lancet Neurol. 2014; 13 (11): 1127-1138. PMID: 25316019. DOI: 10.1016/S1474-4422(14)70129-2.Keil C., Prell T., Peschel T. et al. Longitudinal diffusion tensor imaging in amyotrophic lateral sclerosis. BMC Neurosci. 2012; 13: 141. PMID: 23134591. DOI: 10.1186/1471-2202-13-141.Menke R.A., Abraham I., Thiel C.S. et al. Fractional anisotropy in the posterior limb of the internal capsule and prognosis in amyotrophic lateral sclerosis. Arch Neurol. 2012; 69: 1493–99. PMID: 22910997. DOI: 10.1001/archneurol.2012.1122.van der Graaff M.M., Sage C.A., Caan M.W. et al. Upper and extramotoneuron involvement in early motoneuron disease: a diffusion tensor imaging study. Brain. 2011; 134: 1211–28. PMID: 21362631. DOI: 10.1093/brain/awr016.Sage C.A., Peeters R.R., Gorner A. et al. Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis. Neuroimage. 2007; 34: 486–99. PMID: 17097892. DOI:10.1016/j.neuroimage.2006.09.025.Kwan J.Y., Meoded A., Danielian L.E. et al. Structural imaging differences and longitudinal changes in primary lateral sclerosis and amyotrophic lateral sclerosis. Neuroimage Clin. 2013; 2: 151–60. PMID: 24179768. DOI: 10.1016/j.nicl.2012.12.003.Agosta F., Rocca M.A., 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. PMID: 18931009. DOI: 10.1136/jnnp.2008.154252.Blain C.R., Williams V.C., Johnston C. et al. A longitudinal study of diffusion tensor MRI in ALS. Amyotroph Lateral Scler. 2007; 8 (6): 348–55. PMID: 17924235. DOI: 10.1080/17482960701548139.Mitsumoto H., Ulug A.M., Pullman S.L. et al. Quantitative objective markers for upper and lower motor neuron dysfunction in ALS. Neurology. 2007; 68 (17): 1402–10. PMID: 17452585. DOI: 10.1212/01.wnl.0000260065.57832.87.Senda J., Kato S., Kaga 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. PMID: 21271792. DOI: 10.3109/17482968.2010.517850.Zhang Y., Schuff N., Woolley S.C. et al. Progression of white matter degeneration in amyotrophic lateral sclerosis: a diffusion tensor imaging study. Amyotroph Lateral Scler. 2011; 12 (6): 421–29. PMID: 21745124. DOI: 10.3109/17482968.2011.593036.Agosta F., Gorno-Tempini M.L., Pagani E. 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. PMID: 19058055. DOI: 10.1080/17482960802603841.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: 408-14. PMID: 27104135. DOI: 10.1016/j.nicl.2016.03.011.Block W., Karitzky J., Traber F. et al. Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements. Arch Neurol. 1998; 55 (7): 931–36. PMID: 9678310.Pohl C., Block W., Karitzky J., et al. Proton magnetic resonance spectroscopy of the motor cortex in 70 patients with amyotrophic lateral sclerosis. Arch Neurol. 2001; 58 (5): 729–35. PMID: 11346367.Block W., Traber F., Flacke S. et al. In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration. Amino Acids. 2002; 23 (1-3): 317–23. PMID: 12373553. DOI: 10.1007/s00726-001-0144-0.Suhy J., Miller R.G., Rule R. et al. Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI. Neurology. 2002; 58 (5): 773–79. PMID: 11889242.Rule R.R., Suhy J., Schuff N. et al. 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): 141–49. PMID: 15512902. DOI: 10.1080/14660820410017109.Unrath A., Ludolph A.C., Kassubek J. Brain metabolites in definite amyotrophic lateral sclerosis. A longitudinal proton magnetic resonance spectroscopy study. J Neurol. 2007; 254 (8): 1099–106. PMID: 17431700. DOI: 10.1007/s00415-006-0495-2.Kalra S., Tai P., Genge A, Arnold D.L. Rapid improvement in cortical neuronal integrity in amyotrophic lateral sclerosis detected by proton magnetic resonance spectroscopic imaging. J Neurol. 2006; 253 (8): 1060–63. PMID: 16609809. DOI: 10.1007/s00415-006-0162-7.Lee S., Kim H.J. Prion-like Mechanism in Amyotrophic Lateral Sclerosis: are Protein Aggregates the Key? Exp Neurobiol. 2015; 24 (1): 1-7. PMID: 25792864. DOI: 10.5607/en.2015.24.1.1.Grad L.I., Fernando S.M., Cashman N.R. From molecule to molecule and cell to cell: prion-like mechanisms in amyotrophic lateral sclerosis. Neurobiol Dis. 2015; 77: 257-65. PMID: 25701498. DOI: 10.1016/j.nbd.2015.02.009.Schmidt R., Verstraete E., de Reus M.A. et al. Correlation between structural and functional connectivity impairment in amyotrophic lateral sclerosis // Hum Brain Mapp. 2014; 35 (9): 4386-95. PMID: 24604691. DOI: 10.1002/hbm.22481.Lysogorskaia E.V., Abramycheva N.Y., Illarioshkin S.N., Zakharova M.N. [The role of RNA metabolism in the pathogenesis of amyotrophic lateral sclerosis]. Neurochemical journal 2012; 3: 247-252. (In Russ.).Brettschneider J., Del Tredici K., Toledo J.B. et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013; 74(1): 20-38. PMID: 23686809. DOI: 10.1002/ana.23937.Kassubek J., Muller H.P., 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. PMID: 24736303. DOI: 10.1093/brain/awu090.Pupillo E., Messina P., Logroscino G. et al. Long-term survival in amyotrophic lateral sclerosis: a population-based study. Ann Neurol. 2014; 75 (2): 287-97. PMID:24382602. DOI: 10.1002/ana.24096.Chiò A., Logroscino G., Hardiman O. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009; 10 (5-6): 310-23. PMID: 24382602. DOI: 10.1002/ana.24096.Kalra S., Vitale A., Cashman N.R. et al. Cerebral degeneration predicts survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2006; 77 (11): 1253-5. PMID: 16835288. DOI: 10.1136/jnnp.2006.090696.Pyra T., Hui B., Hanstock C. et al. Combined structural and neurochemical evaluation of the corticospinal tract in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010; 11 (1-2): 157-65. PMID: 19242831. DOI: 10.3109/17482960902756473.Agosta F., Pagani E., Petrolini M. et al. MRI predictors of long-term evolution in amyotrophic lateral sclerosis. Eur J Neurosci. 2010; 32: 1490–96. PMID: 21044177. DOI: 10.1111/j.1460-9568.2010.07445.x.Konrad C., Henningsen H., Bremer J. et al. Pattern of cortical reorganization in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. Exp Brain Res. 2002; 143 (1): 51-6. PMID: 11907690. DOI: 10.1007/s00221-001-0981-9.Lulé D., Diekmann V., Kassubek J. et al. Cortical plasticity in amyotrophic lateral sclerosis: motor imagery and function. Neurorehabil Neural Repair. 2007; 21 (6): 518-26. PMID: 17476000. DOI: 10.1177/1545968307300698.Stanton B.R., Williams V.C., Leigh P.N. et al. Altered cortical activation during a motor task in ALS. Evidence for involvement of central pathways. J Neurol. 2007; 254 (9): 1260-7. PMID: 17385077. DOI: 10.1007/s00415-006-0513-4.Poujois A., Schneider F.C., Faillenot I. et al. Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis. Hum Brain Mapp. 2013; 34 (10): 2391-401. DOI: 10.1002/hbm.22070. PMID: 22461315. DOI: 10.1002/hbm.22070.Chervyakov A.V., Bakulin I.S., Savitskaya N.G. et al. Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis. Muscle Nerve. 2015; 51(1): 125-31. PMID: 25049055. DOI: 10.1002/mus.24345.Bakulin I.S., Chervyakov A.V., Suponeva N.A. et al. Motor cortex hyperexcitability, neuroplasticity and degeneration in amyotrophic lateral sclerosis. In book: H. Foyaca-Sibat (ed.). Novel Aspects of Amyotrophic Lateral Sclerosis. InTech, 2016; 47–72.Turner M.R., Hammers A., Al-Chalabi A. et al. Distinct cerebral lesions in sporadic and "D90A" SOD1 ALS: studies with [11C]flumazenil PET. Brain. 2005; 128 (pt 6): 1323-1329. PMID: 15843422. DOI: 10.1093/brain/awh509.Bede P., Bokde A.L., Byrne S. et al. Multiparametric MRI study of ALS stratified for the C9orf72 genotype. Neurology 2013; 81: 361–69. PMID: 23771489. DOI: 10.1212/WNL.0b013e31829c5eee.Ng M.C., Ho J.T., Ho S.L. et al. Abnormal diffusion tensor in nonsymptomatic familial amyotrophic lateral sclerosis with a causative superoxide dismutase 1 mutation. J Magn Reson Imaging. 2008; 27: 8–13. PMID: 18022844. DOI: 10.1002/jmri.21217.Carew J.D., Nair G., Andersen P.M. et al. Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS. Neurology. 2011; 77 (14): 1370–5. PMID: 21940617. DOI: 10.1212/WNL.0b013e318231526a.Walhout R., Schmidt R., Westeneng H.J. et al. Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers. Neurology. 2015; 85 (20): 1780-8. PMID: 26497991. DOI: 10.1212/WNL.0000000000002135.