{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:35Z","timestamp":1791920135581,"version":"4.3.4"},"reference-count":95,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neural Regen Res"],"published-print":{"date-parts":[[2022]]},"DOI":"10.4103\/1673-5374.314289","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T05:13:01Z","timestamp":1623388381000},"page":"65","source":"Crossref","is-referenced-by-count":31,"title":["Lower and upper motor neuron involvement and their impact on disease prognosis in amyotrophic lateral sclerosis"],"prefix":"10.4103","volume":"17","author":[{"given":"MariaN","family":"Zakharova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AnnaA","family":"Abramova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"key-10.4103\/1673-5374.314289-1","doi-asserted-by":"crossref","unstructured":"Agosta F, Al-Chalabi A, Filippi M, Hardiman O, Kaji R, Meininger V, Nakano I, Shaw P, Shefner J, Van Den Berg LH (2015) The El Escorial criteria: strengths and weaknesses. Amyotroph Lateral Scler Frontotemporal Degener 16:1-7.","DOI":"10.3109\/21678421.2014.964258"},{"key":"key-10.4103\/1673-5374.314289-2","doi-asserted-by":"crossref","unstructured":"Al-Chalabi A, Hardiman O, Kiernan MC, Chi\u00f2 A, Rix-Brooks B, van den Berg LH (2016) Amyotrophic lateral sclerosis: moving towards a new classification system. Lancet Neurol 15:1182-1194.","DOI":"10.1016\/S1474-4422(16)30199-5"},{"key":"key-10.4103\/1673-5374.314289-3","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez N, D\u00edez L, Avellaneda C, Serra M, Rubio M (2018) Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis. Neurologia 33:8-12.","DOI":"10.1016\/j.nrleng.2016.04.005"},{"key":"key-10.4103\/1673-5374.314289-4","doi-asserted-by":"crossref","unstructured":"Amin Lari A, Ghavanini AA, Bokaee HR (2019) A review of electrophysiological studies of lower motor neuron involvement in amyotrophic lateral sclerosis. Neurol Sci 40:1125-1136.","DOI":"10.1007\/s10072-019-03832-4"},{"key":"key-10.4103\/1673-5374.314289-5","doi-asserted-by":"crossref","unstructured":"Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, Hardiman O, Kollewe K, Morrison KE (2012) EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)\u2013revised report of an EFNS task force. Eur J Neurol 19:360-375.","DOI":"10.1111\/j.1468-1331.2011.03501.x"},{"key":"key-10.4103\/1673-5374.314289-6","doi-asserted-by":"crossref","unstructured":"Andrews JA, Bruijn LI, Shefner JM (2019) ALS drug development guidances and trial guidelines: consensus and opportunities for alignment. Neurology 93:66-71.","DOI":"10.1212\/WNL.0000000000007695"},{"key":"key-10.4103\/1673-5374.314289-7","doi-asserted-by":"crossref","unstructured":"Appel V, Stewart S, Smith G, Appel SH (1987) A rating scale for amyotrophic lateral sclerosis: description and preliminary experience. Ann Neurol 22:328-333.","DOI":"10.1002\/ana.410220308"},{"key":"key-10.4103\/1673-5374.314289-8","doi-asserted-by":"crossref","unstructured":"Appelbaum J, Roos RP, Salazar-Grueso E, Buchman A, Iannaccone S, Glantz R, Siddique T, Maselli R (1992) Intrafamilial heterogeneity in hereditary motor neuron disease. Neurology 42:1488-1492.","DOI":"10.1212\/WNL.42.8.1488"},{"key":"key-10.4103\/1673-5374.314289-9","doi-asserted-by":"crossref","unstructured":"B\u00e4umer D, Butterworth R, Menke RA, Talbot K, Hofer M, Turner MR (2014) Progressive hemiparesis (Mills syndrome) with aphasia in amyotrophic lateral sclerosis. Neurology 82:457-458.","DOI":"10.1212\/WNL.0000000000000090"},{"key":"key-10.4103\/1673-5374.314289-10","doi-asserted-by":"crossref","unstructured":"Bakkar N, Boehringer A, Bowser R (2015) Use of biomarkers in ALS drug development and clinical trials. Brain Res 1607:94-107.","DOI":"10.1016\/j.brainres.2014.10.031"},{"key":"key-10.4103\/1673-5374.314289-11","doi-asserted-by":"crossref","unstructured":"Bede P, Hardiman O (2018) Longitudinal structural changes in ALS: a three time-point imaging study of white and gray matter degeneration. Amyotroph Lateral Scler Frontotemporal Degener 19:232-241.","DOI":"10.1080\/21678421.2017.1407795"},{"key":"key-10.4103\/1673-5374.314289-12","doi-asserted-by":"crossref","unstructured":"Benatar M, Zhang L, Wang L, Granit V, Statland J, Barohn R, Swenson A, Ravits J, Jackson C, Burns TM, Trivedi J, Pioro EP, Caress J, Katz J, McCauley JL, Rademakers R, Malaspina A, Ostrow LW, Wuu J (2020) Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology 95:e59-69.","DOI":"10.1212\/WNL.0000000000009559"},{"key":"key-10.4103\/1673-5374.314289-13","doi-asserted-by":"crossref","unstructured":"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:e0178371.","DOI":"10.1371\/journal.pone.0178371"},{"key":"key-10.4103\/1673-5374.314289-14","first-page":"S79","volume-title":"Versailles 2nd Consensus Conference participants","author":"Brooks","year":"1 Su","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"key":"key-10.4103\/1673-5374.314289-15","doi-asserted-by":"crossref","unstructured":"Brooks BR, Miller RG, Swash M, Munsat TL (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293-299.","DOI":"10.1080\/146608200300079536"},{"key":"key-10.4103\/1673-5374.314289-16","doi-asserted-by":"crossref","unstructured":"Brown RH, Al-Chalabi A (2017) Amyotrophic lateral sclerosis. N Engl J Med 377:162-172.","DOI":"10.1056\/NEJMra1603471"},{"key":"key-10.4103\/1673-5374.314289-17","doi-asserted-by":"crossref","unstructured":"Bruyn R, Koelman J, Troost D, De Jong J (1995) Motor neuron disease (amyotrophic lateral sclerosis) arising from longstanding primary lateral sclerosis. J Neurol Neurosurg Psychiatry 58:742-744.","DOI":"10.1136\/jnnp.58.6.742"},{"key":"key-10.4103\/1673-5374.314289-18","doi-asserted-by":"crossref","unstructured":"Byrne S, Bede P, Elamin M, Kenna K, Lynch C, McLaughlin R, Hardiman O (2011) Proposed criteria for familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler 12:157-159.","DOI":"10.3109\/17482968.2010.545420"},{"key":"key-10.4103\/1673-5374.314289-19","doi-asserted-by":"crossref","unstructured":"Calvo AC, Manzano R, Mendon\u00e7a DM, Mu\u00f1oz MJ, Zaragoza P, Osta R (2014) Amyotrophic lateral sclerosis: a focus on disease progression. Biomed Res Int 2014:925101.","DOI":"10.1155\/2014\/925101"},{"key":"key-10.4103\/1673-5374.314289-20","doi-asserted-by":"crossref","unstructured":"Carvalho MD, Swash M (2009) Awaji diagnostic algorithm increases sensitivity of El Escorial criteria for ALS diagnosis. Amyotroph Lateral Scler 10:53-57.","DOI":"10.1080\/17482960802521126"},{"key":"key-10.4103\/1673-5374.314289-21","doi-asserted-by":"crossref","unstructured":"Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A, Group BAS, Group AclotBS (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. J Neurol Sci 169:13-21.","DOI":"10.1016\/S0022-510X(99)00210-5"},{"key":"key-10.4103\/1673-5374.314289-22","doi-asserted-by":"crossref","unstructured":"Chi\u00f2 A, Calvo A, Moglia C, Mazzini L, Mora G (2011) Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 82:740-746.","DOI":"10.1136\/jnnp.2010.235952"},{"key":"key-10.4103\/1673-5374.314289-23","doi-asserted-by":"crossref","unstructured":"Chi\u00f2 A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, Traynor BG (2009) Prognostic factors in ALS: a critical review. Amyotroph Lateral Scler 10:310-323.","DOI":"10.3109\/17482960802566824"},{"key":"key-10.4103\/1673-5374.314289-24","doi-asserted-by":"crossref","unstructured":"Chi\u00f2 A, Mora G, Leone M, Mazzini L, Cocito D, Giordana MT, Bottacchi E, Mutani R (2002) Early symptom progression rate is related to ALS outcome: a prospective population-based study. Neurology 59:99-103.","DOI":"10.1212\/WNL.59.1.99"},{"key":"key-10.4103\/1673-5374.314289-25","doi-asserted-by":"crossref","unstructured":"Chi\u00f2 A, Moglia C, Canosa A, Manera U, Vasta R, Brunetti M, Barberis M, Corrado L, D\u2019Alfonso S, Bersano E, Sarnelli MF, Solara V, Zucchetti JP, Peotta L, Iazzolino B, Mazzini L, Mora G, Calvo A (2019) Cognitive impairment across ALS clinical stages in a population-based cohort. Neurology 93:e984-994.","DOI":"10.1212\/WNL.0000000000008063"},{"key":"key-10.4103\/1673-5374.314289-26","doi-asserted-by":"crossref","unstructured":"Couratier P, Corcia P, Lautrette G, Nicol M, Preux PM, Marin B (2016) Epidemiology of amyotrophic lateral sclerosis: a review of literature. Rev Neurol (Paris) 172:37-45.","DOI":"10.1016\/j.neurol.2015.11.002"},{"key":"key-10.4103\/1673-5374.314289-27","doi-asserted-by":"crossref","unstructured":"de Carvalho M, Chio A, Dengler R, Hecht M, Weber M, Swash M (2005b) Neurophysiological measures in amyotrophic lateral sclerosis: markers of progression in clinical trials. Amyotroph Lateral Scler Other Motor Neuron Disord 6:17-28.","DOI":"10.1080\/14660820410020600"},{"key":"key-10.4103\/1673-5374.314289-28","doi-asserted-by":"crossref","unstructured":"de Carvalho M, Costa J, Swash M (2005a) Clinical trials in ALS: a review of the role of clinical and neurophysiological measurements. Amyotroph Lateral Scler Other Motor Neuron Disord 6:202-212.","DOI":"10.1080\/14660820510011997"},{"key":"key-10.4103\/1673-5374.314289-29","doi-asserted-by":"crossref","unstructured":"de Carvalho M, Pinto S, Swash M (2011) Does the motor cortex influence denervation in ALS? EMG studies of muscles with both contralateral and bilateral corticospinal innervation. Clin Neurophysiol 122:629-635.","DOI":"10.1016\/j.clinph.2010.07.019"},{"key":"key-10.4103\/1673-5374.314289-30","doi-asserted-by":"crossref","unstructured":"de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto H, Nodera H, Shefner J (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119:497-503.","DOI":"10.1016\/j.clinph.2007.09.143"},{"key":"key-10.4103\/1673-5374.314289-31","doi-asserted-by":"crossref","unstructured":"Dengler R (2011) Amyotrophic lateral sclerosis: Who has the lead, the upper or the lower motor neuron? Clin Neurophysiol 122:433.","DOI":"10.1016\/j.clinph.2010.07.020"},{"key":"key-10.4103\/1673-5374.314289-32","doi-asserted-by":"crossref","unstructured":"Douglass CP, Kandler RH, Shaw PJ, McDermott CJ (2010) An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease. J Neurol Neurosurg Psychiatry 81:646-649.","DOI":"10.1136\/jnnp.2009.197434"},{"key":"key-10.4103\/1673-5374.314289-33","doi-asserted-by":"crossref","unstructured":"Eisen A (2009) Amyotrophic lateral sclerosis\u2014evolutionary and other perspectives. Muscle Nerve 40:297-304.","DOI":"10.1002\/mus.21404"},{"key":"key-10.4103\/1673-5374.314289-34","doi-asserted-by":"crossref","unstructured":"Fathi D, Mohammadi B, Dengler R, B\u00f6selt S, Petri S, Kollewe K (2016) Lower motor neuron involvement in ALS assessed by motor unit number index (MUNIX): Long-term changes and reproducibility. Clin Neurophysiol 127:1984-1988.","DOI":"10.1016\/j.clinph.2015.12.023"},{"key":"key-10.4103\/1673-5374.314289-35","doi-asserted-by":"crossref","unstructured":"Floyd AG, Yu QP, Piboolnurak P, Tang MX, Fang Y, Smith WA, Yim J, Rowland LP, Mitsumoto H, Pullman SL (2009) Transcranial magnetic stimulation in ALS: utility of central motor conduction tests. Neurology 72:498-504.","DOI":"10.1212\/01.wnl.0000341933.97883.a4"},{"key":"key-10.4103\/1673-5374.314289-36","doi-asserted-by":"crossref","unstructured":"Furtula J, Johnsen B, Frandsen J, Rodell A, Christensen PB, Pugdahl K, Fuglsang-Frederiksen A (2013) Upper motor neuron involvement in amyotrophic lateral sclerosis evaluated by triple stimulation technique and diffusion tensor MRI. J Neurol 260:1535-1544.","DOI":"10.1007\/s00415-012-6824-8"},{"key":"key-10.4103\/1673-5374.314289-37","doi-asserted-by":"crossref","unstructured":"Gaiani A, Martinelli I, Bello L, Querin G, Puthenparampil M, Ruggero S, Toffanin E, Cagnin A, Briani C, Pegoraro E, Sorar\u00f9 G (2017) Diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis: neurofilament light chain levels in definite subtypes of disease. JAMA Neurol 74:525-532.","DOI":"10.1001\/jamaneurol.2016.5398"},{"key":"key-10.4103\/1673-5374.314289-38","doi-asserted-by":"crossref","unstructured":"Gitler AD, Shorter J (2011) RNA-binding proteins with prion-like domains in ALS and FTLD-U. Prion 5:179-187.","DOI":"10.4161\/pri.5.3.17230"},{"key":"key-10.4103\/1673-5374.314289-39","doi-asserted-by":"crossref","unstructured":"Gladman M, Cudkowicz M, Zinman L (2012) Enhancing clinical trials in neurodegenerative disorders: lessons from amyotrophic lateral sclerosis. Curr Opin Neurol 25:735-742.","DOI":"10.1097\/WCO.0b013e32835a309d"},{"key":"key-10.4103\/1673-5374.314289-40","doi-asserted-by":"crossref","unstructured":"Gordon P, Cheng B, Katz I, Mitsumoto H, Rowland L (2009) Clinical features that distinguish PLS, upper motor neuron\u2013dominant ALS, and typical ALS. Neurology 72:1948-1952.","DOI":"10.1212\/WNL.0b013e3181a8269b"},{"key":"key-10.4103\/1673-5374.314289-41","doi-asserted-by":"crossref","unstructured":"Goyal NA, Berry JD, Windebank A, Staff NP, Maragakis NJ, van den Berg LH, Genge A, Miller R, Baloh RH, Kern R, Gothelf Y, Lebovits C, Cudkowicz M (2020) Addressing heterogeneity in amyotrophic lateral sclerosis CLINICAL TRIALS. Muscle Nerve 62:156-166.","DOI":"10.1002\/mus.26801"},{"key":"key-10.4103\/1673-5374.314289-42","doi-asserted-by":"crossref","unstructured":"Grace GM, Orange J, Rowe A, Findlater K, Freedman M, Strong MJ (2011) Neuropsychological functioning in PLS: a comparison with ALS. Can J Neurol Sci 38:88-97.","DOI":"10.1017\/S0317167100120803"},{"key":"key-10.4103\/1673-5374.314289-43","doi-asserted-by":"crossref","unstructured":"Grad LI, Rouleau GA, Ravits J, Cashman NR (2017) Clinical spectrum of amyotrophic lateral sclerosis (ALS). Cold Spring Harb Perspect Med 7:a024117.","DOI":"10.1101\/cshperspect.a024117"},{"key":"key-10.4103\/1673-5374.314289-44","doi-asserted-by":"crossref","unstructured":"Green JR, Yunusova Y, Kuruvilla MS, Wang J, Pattee GL, Synhorst L, Zinman L, Berry JD (2013) Bulbar and speech motor assessment in ALS: challenges and future directions. Amyotroph Lateral Scler Frontotemporal Degener 14:494-500.","DOI":"10.3109\/21678421.2013.817585"},{"key":"key-10.4103\/1673-5374.314289-45","doi-asserted-by":"crossref","unstructured":"Grieve SM, Menon P, Korgaonkar MS, Gomes L, Foster S, Kiernan MC, Vucic S (2016) Potential structural and functional biomarkers of upper motor neuron dysfunction in ALS. Amyotroph Lateral Scler Frontotemporal Degener 17:85-92.","DOI":"10.3109\/21678421.2015.1074707"},{"key":"key-10.4103\/1673-5374.314289-46","doi-asserted-by":"crossref","unstructured":"Hamidou B, Marin B, Lautrette G, Nicol M, Camu W, Corcia P, Arnes-Bes MC, Tranchant C, Clavelou P, Hannequin D, Maurice G, Beauvais K, Antoine JC, Danel-Brunaud V, Viader F, Preux PM, Couratier P (2017) Exploring the diagnosis delay and ALS functional impairment at diagnosis as relevant criteria for clinical trial enrolment. Amyotroph Lateral Scler Frontotemporal Degener 18:519-527.","DOI":"10.1080\/21678421.2017.1353098"},{"key":"key-10.4103\/1673-5374.314289-47","doi-asserted-by":"crossref","unstructured":"Huynh W, Simon NG, Grosskreutz J, Turner MR, Vucic S, Kiernan MC (2016) Assessment of the upper motor neuron in amyotrophic lateral sclerosis. Clin Neurophysiol 127:2643-2660.","DOI":"10.1016\/j.clinph.2016.04.025"},{"key":"key-10.4103\/1673-5374.314289-48","doi-asserted-by":"crossref","unstructured":"Huynh W, Ahmed R, Mahoney CJ, Nguyen C, Tu S, Caga J, Loh P, Lin CS, Kiernan MC (2020) The impact of cognitive and behavioral impairment in amyotrophic lateral sclerosis. Expert Rev Neurother 20:281-293.","DOI":"10.1080\/14737175.2020.1727740"},{"key":"key-10.4103\/1673-5374.314289-49","doi-asserted-by":"crossref","unstructured":"Ince P, Evans J, Knopp M, Forster G, Hamdalla H, Wharton S, Shaw P (2003) Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS. Neurology 60:1252-1258.","DOI":"10.1212\/01.WNL.0000058901.75728.4E"},{"key":"key-10.4103\/1673-5374.314289-50","doi-asserted-by":"crossref","unstructured":"Jaiser SR, Mitra D, Williams TL, Baker MR (2019) Mills\u2019 syndrome revisited. J Neurol 266:667-679.","DOI":"10.1007\/s00415-019-09186-3"},{"key":"key-10.4103\/1673-5374.314289-51","doi-asserted-by":"crossref","unstructured":"Jaiswal MK (2019) Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs. Med Res Rev 39:733-748.","DOI":"10.1002\/med.21528"},{"key":"key-10.4103\/1673-5374.314289-52","doi-asserted-by":"crossref","unstructured":"Jawdat O, Statland JM, Barohn RJ, Katz JS, Dimachkie MM (2015) Amyotrophic lateral sclerosis regional variants (brachial amyotrophic diplegia, leg amyotrophic diplegia, and isolated bulbar amyotrophic lateral sclerosis). Neurol Clin 33:775-785.","DOI":"10.1016\/j.ncl.2015.07.003"},{"key":"key-10.4103\/1673-5374.314289-53","doi-asserted-by":"crossref","unstructured":"Karam C, Scelsa SN, Macgowan DJ (2010) The clinical course of progressive bulbar palsy. Amyotroph Lateral Scler 11:364-368.","DOI":"10.3109\/17482960903513159"},{"key":"key-10.4103\/1673-5374.314289-54","doi-asserted-by":"crossref","unstructured":"Kassubek J, Pagani M (2019) Imaging in amyotrophic lateral sclerosis: MRI and PET. Curr Opin Neurol 32:740-746.","DOI":"10.1097\/WCO.0000000000000728"},{"key":"key-10.4103\/1673-5374.314289-55","doi-asserted-by":"crossref","unstructured":"Kaufmann P, Mitsumoto H (2002) Amyotrophic lateral sclerosis: objective upper motor neuron markers. Curr Neurol Neurosci Rep 2:55-60.","DOI":"10.1007\/s11910-002-0054-x"},{"key":"key-10.4103\/1673-5374.314289-56","doi-asserted-by":"crossref","unstructured":"Krarup C (2011) Lower motor neuron involvement examined by quantitative electromyography in amyotrophic lateral sclerosis. Clin Neurophysiol 122:414-422.","DOI":"10.1016\/j.clinph.2010.06.027"},{"key":"key-10.4103\/1673-5374.314289-57","doi-asserted-by":"crossref","unstructured":"Le Forestier N, Maisonobe T, Piquard A, Rivaud S, Crevier-Buchman L, Salachas F, Pradat PF, Lacomblez L, Meininger V (2001) Does primary lateral sclerosis exist? A study of 20 patients and a review of the literature. Brain 124:1989-1999.","DOI":"10.1093\/brain\/124.10.1989"},{"key":"key-10.4103\/1673-5374.314289-58","doi-asserted-by":"crossref","unstructured":"Logroscino G (2016) Classifying change and heterogeneity in amyotrophic lateral sclerosis. Lancet Neurol 15:1111.","DOI":"10.1016\/S1474-4422(16)30206-X"},{"key":"key-10.4103\/1673-5374.314289-59","doi-asserted-by":"crossref","unstructured":"Ludolph A, Drory V, Hardiman O, Nakano I, Ravits J, Robberecht W, Shefner J (2015) A revision of the El Escorial criteria-2015. Amyotroph Lateral Scler Frontotemporal Degener 16:291-292.","DOI":"10.3109\/21678421.2015.1049183"},{"key":"key-10.4103\/1673-5374.314289-60","doi-asserted-by":"crossref","unstructured":"McAlary L, Plotkin SS, Yerbury JJ, Cashman NR (2019) Prion-like propagation of protein misfolding and aggregation in amyotrophic lateral sclerosis. Front Mol Neurosci 12:262.","DOI":"10.3389\/fnmol.2019.00262"},{"key":"key-10.4103\/1673-5374.314289-61","doi-asserted-by":"crossref","unstructured":"McCombe PA, Wray NR, Henderson RD (2017) Extra-motor abnormalities in amyotrophic lateral sclerosis: another layer of heterogeneity. Expert Rev Neurother 17:561-577.","DOI":"10.1080\/14737175.2017.1273772"},{"key":"key-10.4103\/1673-5374.314289-62","doi-asserted-by":"crossref","unstructured":"Miscio G, Pisano F, Mora G, Mazzini L (1999) Motor neuron disease: usefulness of transcranial magnetic stimulation in improving the diagnosis. Clin Neurophysiol 110:975-981.","DOI":"10.1016\/S1388-2457(99)00030-9"},{"key":"key-10.4103\/1673-5374.314289-63","doi-asserted-by":"crossref","unstructured":"Mitsumoto H, Ulu\u011f A, Pullman S, Gooch C, Chan S, Tang M-X, Mao X, Hays A, Floyd A, Battista V (2007) Quantitative objective markers for upper and lower motor neuron dysfunction in ALS. Neurology 68:1402-1410.","DOI":"10.1212\/01.wnl.0000260065.57832.87"},{"key":"key-10.4103\/1673-5374.314289-64","doi-asserted-by":"crossref","unstructured":"Mulder DW, Kurland LT, Offord KP, Beard CM (1986) Familial adult motor neuron disease: amyotrophic lateral sclerosis. Neurology 36:511-517.","DOI":"10.1212\/WNL.36.4.511"},{"key":"key-10.4103\/1673-5374.314289-65","doi-asserted-by":"crossref","unstructured":"Neuwirth C, Barkhaus PE, Burkhardt C, Castro J, Czell D, de Carvalho M, Nandedkar S, St\u00e5lberg E, Weber M (2017) Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in amyotrophic lateral sclerosis. Clin Neurophysiol 128:495-500.","DOI":"10.1016\/j.clinph.2016.11.026"},{"key":"key-10.4103\/1673-5374.314289-66","doi-asserted-by":"crossref","unstructured":"Petrov D, Mansfield C, Moussy A, Hermine O (2017) ALS clinical trials review: 20 years of failure. Are we any closer to registering a new treatment? Front Aging Neurosci 9:68.","DOI":"10.3389\/fnagi.2017.00068"},{"key":"key-10.4103\/1673-5374.314289-67","doi-asserted-by":"crossref","unstructured":"Ravits J, Paul P, Jorg C (2007) Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. Neurology 68:1571-1575.","DOI":"10.1212\/01.wnl.0000260965.20021.47"},{"key":"key-10.4103\/1673-5374.314289-68","doi-asserted-by":"crossref","unstructured":"Rinaldi F, Motti D, Ferraiuolo L, Kaspar BK (2017) High content analysis in amyotrophic lateral sclerosis. Mol Cell Neurosci 80:180-191.","DOI":"10.1016\/j.mcn.2016.12.001"},{"key":"key-10.4103\/1673-5374.314289-69","doi-asserted-by":"crossref","unstructured":"Roche JC, Rojas-Garcia R, Scott KM, Scotton W, Ellis CE, Burman R, Wijesekera L, Turner MR, Leigh PN, Shaw CE (2012) A proposed staging system for amyotrophic lateral sclerosis. Brain 135:847-852.","DOI":"10.1093\/brain\/awr351"},{"key":"key-10.4103\/1673-5374.314289-70","doi-asserted-by":"crossref","unstructured":"Sach M, Winkler G, Glauche V, Liepert J, Heimbach B, Koch MA, Bu\u00c8chel C, Weiller C (2004) Diffusion tensor MRI of early upper motor neuron involvement in amyotrophic lateral sclerosis. Brain 127:340-350.","DOI":"10.1093\/brain\/awh041"},{"key":"key-10.4103\/1673-5374.314289-71","doi-asserted-by":"crossref","unstructured":"Sharma R, Hicks S, Berna CM, Kennard C, Talbot K, Turner MR (2011) Oculomotor dysfunction in amyotrophic lateral sclerosis: a comprehensive review. Arch Neurol 68:857-861.","DOI":"10.1001\/archneurol.2011.130"},{"key":"key-10.4103\/1673-5374.314289-72","doi-asserted-by":"crossref","unstructured":"Statland JM, Barohn RJ, McVey AL, Katz JS, Dimachkie MM (2015) Patterns of weakness, classification of motor neuron disease, and clinical diagnosis of sporadic amyotrophic lateral sclerosis. Neurol Clin 33:735-748.","DOI":"10.1016\/j.ncl.2015.07.006"},{"key":"key-10.4103\/1673-5374.314289-73","doi-asserted-by":"crossref","unstructured":"Stephens B, Guiloff RJ, Navarrete R, Newman P, Nikhar N, Lewis P (2006) Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study. J Neurol Sci 244:41-58.","DOI":"10.1016\/j.jns.2005.12.003"},{"key":"key-10.4103\/1673-5374.314289-74","doi-asserted-by":"crossref","unstructured":"Strong MJ, Abrahams S, Goldstein LH, Woolley S, McLaughlin P, Snowden J, Mioshi E, Roberts-South A, Benatar M, Hortob\u00e1Gyi T, Rosenfeld J, Silani V, Ince PG, Turner MR (2017) Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): revised diagnostic criteria. Amyotroph Lateral Scler Frontotemporal Degener 18:153-174.","DOI":"10.1080\/21678421.2016.1267768"},{"key":"key-10.4103\/1673-5374.314289-75","doi-asserted-by":"crossref","unstructured":"Swash M (2012) Why are upper motor neuron signs difficult to elicit in amyotrophic lateral sclerosis? J Neurol Neurosurg Psychiatry 83:659-662.","DOI":"10.1136\/jnnp-2012-302315"},{"key":"key-10.4103\/1673-5374.314289-76","doi-asserted-by":"crossref","unstructured":"Swash M, de Carvalho M (2004) The neurophysiological index in ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 5:108-110.","DOI":"10.1080\/17434470410020067"},{"key":"key-10.4103\/1673-5374.314289-77","doi-asserted-by":"crossref","unstructured":"Takeda T, Kitagawa K, Arai K (2020) Phenotypic variability and its pathological basis in amyotrophic lateral sclerosis. Neuropathology 40:40-56.","DOI":"10.1111\/neup.12606"},{"key":"key-10.4103\/1673-5374.314289-78","doi-asserted-by":"crossref","unstructured":"Talman P, Duong T, Vucic S, Mathers S, Venkatesh S, Henderson R, Rowe D, Schultz D, Edis R, Needham M, Macdonnell R, McCombe P, Birks C, Kiernan M (2016) Identification and outcomes of clinical phenotypes in amyotrophic lateral sclerosis\/motor neuron disease: Australian National Motor Neuron Disease observational cohort. BMJ Open 6:e012054.","DOI":"10.1136\/bmjopen-2016-012054"},{"key":"key-10.4103\/1673-5374.314289-79","doi-asserted-by":"crossref","unstructured":"Triggs WJ, Menkes D, Onorato J, Yan RS, Young MS, Newell K, Sander HW, Soto O, Chiappa KH, Cros D (1999) Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease. Neurology 53:605-611.","DOI":"10.1212\/WNL.53.3.605"},{"key":"key-10.4103\/1673-5374.314289-80","doi-asserted-by":"crossref","unstructured":"Trojsi F, Siciliano M, Femiano C, Santangelo G, Lunetta C, Calvo A, Moglia C, Marinou K, Ticozzi N, Drago Ferrante G, Scial\u00f2 C, Sorar\u00f9 G, Conte A, Falzone YM, Tortelli R, Russo M, Sansone VA, Chi\u00f2 A, Mora G, Poletti B, et al. (2017) Comorbidity of dementia with amyotrophic lateral sclerosis (ALS): insights from a large multicenter Italian cohort. J Neurol 264:2224-2231.","DOI":"10.1007\/s00415-017-8619-4"},{"key":"key-10.4103\/1673-5374.314289-81","doi-asserted-by":"crossref","unstructured":"Turner MR, Brockington A, Scaber J, Hollinger H, Marsden R, Shaw PJ, Talbot K (2010) Pattern of spread and prognosis in lower limb-onset ALS. Amyotroph Lateral Scler 11:369-373.","DOI":"10.3109\/17482960903420140"},{"key":"key-10.4103\/1673-5374.314289-82","doi-asserted-by":"crossref","unstructured":"Turner MR, Gerhard A, Al-Chalabi A, Shaw CE, Hughes RAC, Banati RB, Brooks DJ, Leigh PN (2005) Mills\u2019 and other isolated upper motor neurone syndromes: in vivo study with 11C-(R)-PK11195 PET. J Neurol Neurosurg Psychiatry 76:871-874.","DOI":"10.1136\/jnnp.2004.047902"},{"key":"key-10.4103\/1673-5374.314289-83","doi-asserted-by":"crossref","unstructured":"Turner MR, Barohn RJ, Corcia P, Fink JK, Harms MB, Kiernan MC, Ravits J, Silani V, Simmons Z, Statland J, van den Berg LH, Mitsumoto H (2020a) Primary lateral sclerosis: consensus diagnostic criteria. J Neurol Neurosurg Psychiatry 91:373-377.","DOI":"10.1136\/jnnp-2019-322541"},{"key":"key-10.4103\/1673-5374.314289-84","doi-asserted-by":"crossref","unstructured":"Turner MR, Barohn RJ, Corcia P, Fink JK, Harms MB, Kiernan MC, Ravits J, Silani V, Simmons Z, Statland J, van den Berg LH, Mitsumoto H (2020b) Primary lateral sclerosis: consensus diagnostic criteria. J Neurol Neurosurg Psychiatry 91:373-377.","DOI":"10.1136\/jnnp-2019-322541"},{"key":"key-10.4103\/1673-5374.314289-85","doi-asserted-by":"crossref","unstructured":"van den Berg LH, Sorenson E, Gronseth G, Macklin EA, Andrews J, Baloh RH, Benatar M, Berry JD, Chio A, Corcia P, Genge A, Gubitz AK, Lomen-Hoerth C, McDermott CJ, Pioro EP, Rosenfeld J, Silani V, Turner MR, Weber M, Brooks BR, et al. (2019) Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials. Neurology 92:e1610-e1623.","DOI":"10.1212\/WNL.0000000000007242"},{"key":"key-10.4103\/1673-5374.314289-86","doi-asserted-by":"crossref","unstructured":"van den Bos MAJ, Geevasinga N, Higashihara M, Menon P, Vucic S (2019) Pathophysiology and diagnosis of ALS: insights from advances in neurophysiological techniques. Int J Mol Sci 20:2818.","DOI":"10.3390\/ijms20112818"},{"key":"key-10.4103\/1673-5374.314289-87","doi-asserted-by":"crossref","unstructured":"van der Graaff MM, de Jong JM, Baas F, de Visser M (2009) Upper motor neuron and extra-motor neuron involvement in amyotrophic lateral sclerosis: a clinical and brain imaging review. Neuromuscul Disord 19:53-58.","DOI":"10.1016\/j.nmd.2008.10.002"},{"key":"key-10.4103\/1673-5374.314289-88","doi-asserted-by":"crossref","unstructured":"Van Laere K, Wilms G, Van Damme P (2016) Neurological picture. FDG-PET findings in three cases of Mills\u2019 syndrome. J Neurol Neurosurg Psychiatry 87:222-223.","DOI":"10.1136\/jnnp-2014-309952"},{"key":"key-10.4103\/1673-5374.314289-89","doi-asserted-by":"crossref","unstructured":"Verma A, Bradley WG (2001) Atypical motor neuron disease and related motor syndromes. Semin Neurol 21:177-187.","DOI":"10.1055\/s-2001-15263"},{"key":"key-10.4103\/1673-5374.314289-90","doi-asserted-by":"crossref","unstructured":"Vucic S, Rutkove SB (2018) Neurophysiological biomarkers in amyotrophic lateral sclerosis. Curr Opin Neurol 31:640-647.","DOI":"10.1097\/WCO.0000000000000593"},{"key":"key-10.4103\/1673-5374.314289-91","doi-asserted-by":"crossref","unstructured":"Vucic S, Nicholson GA, Kiernan MC (2008) Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis. Brain 131:1540-1550.","DOI":"10.1093\/brain\/awn071"},{"key":"key-10.4103\/1673-5374.314289-92","doi-asserted-by":"crossref","unstructured":"Westeneng HJ, Debray TPA, Visser AE, van Eijk RPA, Rooney JPK, Calvo A, Martin S, McDermott CJ, Thompson AG, Pinto S, Kobeleva X, Rosenbohm A, Stubendorff B, Sommer H, Middelkoop BM, Dekker AM, van Vugt J, van Rheenen W, Vajda A, Heverin M, et al. (2018) Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model. Lancet Neurol 17:423-433.","DOI":"10.1016\/S1474-4422(18)30089-9"},{"key":"key-10.4103\/1673-5374.314289-93","doi-asserted-by":"crossref","unstructured":"Zarei S, Carr K, Reiley L, Diaz K, Guerra O, Altamirano PF, Pagani W, Lodin D, Orozco G, Chinea A (2015) A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int 6:171.","DOI":"10.4103\/2152-7806.169561"},{"key":"key-10.4103\/1673-5374.314289-94","doi-asserted-by":"crossref","unstructured":"Zhang HG, Chen L, Tang L, Zhang N, Fan DS (2017) Clinical features of isolated bulbar palsy of amyotrophic lateral sclerosis in Chinese population. Chin Med J (Engl) 130:1768-1772.","DOI":"10.4103\/0366-6999.211538"},{"key":"key-10.4103\/1673-5374.314289-95","doi-asserted-by":"crossref","unstructured":"Zufiria M, Gil-Bea FJ, Fernandez-Torron R, Poza JJ, Mu\u00f1oz-Blanco JL, Rojas-Garcia R, Riancho J, de Munain AL (2016) ALS: a bucket of genes, environment, metabolism and unknown ingredients. Prog Neurobiol 142:104-129.","DOI":"10.1016\/j.pneurobio.2016.05.004"}],"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:57:55Z","timestamp":1786733875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.314289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":95,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022]]}},"alternative-id":["314289"],"URL":"https:\/\/doi.org\/10.4103\/1673-5374.314289","relation":{},"ISSN":["1673-5374"],"issn-type":[{"value":"1673-5374","type":"print"}],"subject":[],"published":{"date-parts":[[2022]]}}}