{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:39:21Z","timestamp":1791329961176,"version":"4.3.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T00:00:00Z","timestamp":1423699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Cortical hyperexcitability has been identified as an important pathogenic mechanism in motor neuron disease (<jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content>). The issue as to whether cortical hyperexcitability is a common process across the <jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content> phenotypes, including amyotrophic lateral sclerosis (<jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>) and primary lateral sclerosis (<jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>), remains unresolved. Separately, the clinical distinction between <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> and \u2018mimic disorders\u2019 such as hereditary spastic paraparesis (<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>) may be difficult, potentially delaying diagnosis. Consequently, the aim of the present study was to determine the nature and spectrum of cortical excitability changes across the <jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content> phenotypes, and to determine whether the presence of cortical dysfunction distinguishes <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cortical excitability studies were undertaken on a cohort of 14 <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content>, 82 <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> and 13 <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> patients with mutations in the <jats:italic>spastin<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cortical hyperexcitability, as heralded by reduction of short interval intracortical inhibition (<jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> 0.26%, \u22123.8% to 1.4%; <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> \u22120.15%, \u22123.6% to 7.0%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and cortical silent period duration (<jats:styled-content style=\"fixed-case\">CSP<jats:sub>PLS<\/jats:sub><\/jats:styled-content> 172.2\u00a0\u00b1\u00a05.4\u00a0ms; <jats:styled-content style=\"fixed-case\">CSP<jats:sub>ALS<\/jats:sub><\/jats:styled-content> 178.1\u00a0\u00b1\u00a05.1\u00a0ms; <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001), along with an increase in intracortical facilitation was evident in <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> phenotypes, although appeared more frequently in ALS. Inexcitability of the motor cortex was more frequent in <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> 71%, <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content> 24%, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.0001). Cortical excitability was preserved in <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cortical dysfunction appears to be an intrinsic process across the <jats:styled-content style=\"fixed-case\">MND<\/jats:styled-content> phenotypes, with cortical inexcitability predominating in <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> and cortical hyperexcitability predominating in <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>. Importantly, cortical excitability was preserved in <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>, thereby suggesting that the presence of cortical dysfunction could help differentiate <jats:styled-content style=\"fixed-case\">PLS<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content> in a clinical setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12669","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T10:29:07Z","timestamp":1423823347000},"page":"826","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Cortical excitability changes distinguish the motor neuron disease phenotypes from hereditary spastic paraplegia"],"prefix":"10.1111","volume":"22","author":[{"given":"N.","family":"Geevasinga","sequence":"first","affiliation":[{"name":"Westmead Clinical School University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Menon","sequence":"additional","affiliation":[{"name":"Westmead Clinical School University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Sue","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal North Shore Hospital Sydney NSW Australia"},{"name":"Department of Neurogenetics Kolling Institute of Medical Research University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. R.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal North Shore Hospital Sydney NSW Australia"},{"name":"Department of Neurogenetics Kolling Institute of Medical Research University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal North Shore Hospital Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Yiannikas","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal North Shore Hospital Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Kiernan","sequence":"additional","affiliation":[{"name":"Brain and Mind Research Institute and Central Clinical School University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Vucic","sequence":"additional","affiliation":[{"name":"Westmead Clinical School University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61156-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2014.05.006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14660820410021267"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20728"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.2.495"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000200962.94777.71"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880150215"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl172"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn071"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2010.12.062"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-304019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.10.1989"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.71.5.615"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20481"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2007.09.143"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12422"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00210-5"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228242.53336.90"},{"key":"e_1_2_7_20_1","first-page":"1","volume-title":"Aid to the Examination of the Peripheral Nervous System","author":"O'Brien MD","year":"2004"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.12.012"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(200003)23:3<344::AID-MUS5>3.0.CO;2-N"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.10.1951"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(86)90145-8"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2005.09.022"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00454899"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00469-5"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.12.26"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00228633"},{"key":"e_1_2_7_30_1","first-page":"361","article-title":"Motor evoked potentials (MEPs): evaluation of the different types of responses in amyotrophic lateral sclerosis and primary lateral sclerosis","volume":"36","author":"Salerno A","year":"1996","journal-title":"Electromyogr Clin Neurophysiol"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/146608202760839004"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000058900.02672.D2"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/427801a"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-004-0599-z"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000171647.09589.07"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.88.3.1279"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1993.tb00443.x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70222-3"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2004.00587.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2005.00620.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1789.2001.00388.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.37.1.8"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-15265"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2009.19"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5009-6"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.12669","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12669","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T21:02:58Z","timestamp":1695502978000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.12669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,12]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1111\/ene.12669"],"URL":"https:\/\/doi.org\/10.1111\/ene.12669","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,12]]},"assertion":[{"value":"2014-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}