{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:20Z","timestamp":1772168960553,"version":"3.50.1"},"reference-count":15,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T00:00:00Z","timestamp":1470096000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G (\n                    <ns4:italic>e.g<\/ns4:italic>\n                    ., a GABA receptor antagonist) and\/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone\u2014regardless of whether they present with syphilitic ALS or non-syphilitic ALS\u2014may be effective at treating this rapidly progressive, highly devastating disease.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.9318.1","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T10:20:09Z","timestamp":1470133209000},"page":"1904","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS"],"prefix":"10.12688","volume":"5","author":[{"given":"Bert","family":"Tuk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2016,8,2]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"942-55","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis.","volume":"377","author":"M Kiernan","year":"2011","journal-title":"Lancet."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"5-27","DOI":"10.4449\/aib.v149i1.1260","article-title":"The diagnosis of Amyotrophic lateral sclerosis in 2010.","volume":"149","author":"V Silani","year":"2011","journal-title":"Arch Ital Biol."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"310-22","DOI":"10.1016\/S1474-4422(13)70036-X","article-title":"Controversies and priorities in amyotrophic lateral sclerosis.","volume":"12","author":"M Turner","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref-4","first-page":"41-4","article-title":"[Amyotrophic lateral sclerosis syndrome of syphilitic origin. 5 cases.]","volume":"146","author":"M el Alaoui-Faris","year":"1990","journal-title":"Rev Neurol (Paris)."},{"key":"ref-5","doi-asserted-by":"crossref","first-page":"187-209","DOI":"10.1128\/CMR.12.2.187","article-title":"Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features.","volume":"12","author":"A Singh","year":"1999","journal-title":"Clin Microbiol Rev."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"72-82","DOI":"10.1016\/j.mcn.2014.10.001","article-title":"Block of GABAA receptor ion channel by penicillin: electrophysiological and modeling insights toward the mechanism.","volume":"63","author":"A Rossokhin","year":"2014","journal-title":"Mol Cell Neurosci."},{"key":"ref-7","article-title":"Penicillin G summary of product characteristics"},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.12688\/f1000research.8774.1","article-title":"Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis [version 1; referees: awaiting peer review].","volume":"5","author":"B Tuk","year":"2016","journal-title":"F1000Res."},{"key":"ref-9","article-title":"Hydrocortisone Summary of product characteristics"},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"101-6","DOI":"10.1016\/0304-3940(87)90178-9","article-title":"Cortisol: a potent biphasic modulator at GABAA-receptor complexes in the guinea pig isolated ileum.","volume":"82","author":"J Ong","year":"1987","journal-title":"Neurosci Lett."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"344-51","DOI":"10.1002\/(SICI)1096-9861(20000410)419:3<344::AID-CNE6>3.0.CO;2-Z","article-title":"GABAA receptor subunit expression within hypophysiotropic CRH neurons: a dual hybridization histochemical study.","volume":"419","author":"W Cullinan","year":"2000","journal-title":"J Comp Neurol."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/2051-5960-2-66","article-title":"CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic lateral sclerosis.","volume":"2","author":"M Evans","year":"2014","journal-title":"Acta Neuropathol Commun."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3109\/17482968.2012.727425","article-title":"Amyotrophic lateral sclerosis mimic syndrome due to neurosyphilis.","volume":"14","author":"M Chraa","year":"2013","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"15593-8","DOI":"10.1073\/pnas.0808259105","article-title":"Hippocampal-dependent learning requires a functional circadian system.","volume":"105","author":"N Ruby","year":"2008","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"129-138","DOI":"10.1177\/2042018810380214","article-title":"Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy.","volume":"1","author":"S Chan","year":"2010","journal-title":"Ther Adv Endocrinol Metab."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T12:36:11Z","timestamp":1544013371000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,2]]},"references-count":15,"URL":"https:\/\/doi.org\/10.12688\/f1000research.9318.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.10034.r16950","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.10034.r15388","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.10034.r15388","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.10034.r16950","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,2]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.10034.r15388, Pieter Gaillard, 2-BBB Medicines BV, Leiden, The Netherlands, 22 Aug 2016, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1#referee-response-15388","order":0,"name":"referee-response-15388","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.10034.r16950, Alan Gill, ALS Therapy Development Institute, Cambridge, MA, USA, 21 Oct 2016, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/5-1904\/v1#referee-response-16950","order":1,"name":"referee-response-16950","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}