{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:13:42Z","timestamp":1790723622452,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Isaacs' syndrome is a rare disease resulting from hyperexcitability of peripheral nerves causing continuous muscle fiber activity characterized by muscle twitching and stiffness at rest and delayed muscle relaxation after voluntary contraction. Our objective was to discuss the relationship of Isaacs' syndrome to paraneoplastic syndromes as reported in the available literature and in 3 patients evaluated at our academic medical center.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We review the literature on Isaacs' syndrome and describe 3 patients in whom Isaacs' syndrome heralded underlying malignancy or benign neoplasm, including their presenting symptoms, electrophysiologic findings, and laboratory and pathology results.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>In all 3 cases, clinical and electrodiagnostic testing was suggestive of Isaacs' syndrome. Two patients tested positive, and one was negative for voltage-gated potassium channel antibodies. Two of the patients developed malignant tumors, that is, one was diagnosed with metastatic thymoma and one with lymphoplasmacytic lymphoma, ranging from 6 months to 1 year after the diagnosis of Isaacs' syndrome. One patient was diagnosed with a spinal cord hemangioblastoma 5 years after he was diagnosed with Isaacs' syndrome.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our case series highlights the association of Isaacs' syndrome with a variety of neoplasms both malignant and benign. Our report also underscores the fact that Isaacs' syndrome may be diagnosed several years before a neoplasm is discovered. In our cases, Isaacs' syndrome overlapped with other neuromuscular disorders, that is, myasthenia gravis in a patient with thymoma and chronic inflammatory demyelinating polyneuropathy in a patient with lymphoplasmacytic lymphoma with paraproteinemia. To our knowledge, this is the first report of an association between Isaacs' syndrome with lymphoplasmacytic lymphoma and a spinal cord hemangioblastoma.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/cnd.0b013e318246197d","type":"journal-article","created":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T07:50:46Z","timestamp":1337759446000},"page":"228-233","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":47,"title":["Paraneoplastic Isaacs' Syndrome"],"prefix":"10.1097","volume":"13","author":[{"given":"Sandeep S.","family":"Rana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramnath Santosh","family":"Ramanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Small","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Adamovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-7-20240808","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1136\/jnnp.24.4.319","article-title":"A syndrome of continuous muscle-fiber activity.","volume":"24","author":"Isaacs","year":"1961","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"R2-7-20240808","first-page":"421","article-title":"Progressive fluctuating muscular rigidity and spasm (stiff man syndrome): report of a case and some observations in 13 other cases.","volume":"31","author":"Moers","year":"1956","journal-title":"Mayo Clin Proc"},{"key":"R3-7-20240808","first-page":"27","article-title":"Isaacs syndrome.","volume":"65","author":"Brown","year":"1984","journal-title":"Arch Phys Med Rehabil"},{"key":"R4-7-20240808","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1212\/WNL.17.3.263","article-title":". Myotonia, myokymia, hyperhiderosis and wasting of muscle.","volume":"17","author":"Greenhouse","year":"1967","journal-title":"Neurology"},{"key":"R5-7-20240808","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-0404.1977.tb05647.x","article-title":"The syndrome of continuous muscle fiber activity: evidence to suggest proximal neurogenic causation.","volume":"55","author":"Irani","year":"1977","journal-title":"Acta Neurol Scand"},{"key":"R6-7-20240808","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1001\/archneur.1972.00490170045007","article-title":". Muscle rigidity in a newborn due to continuous peripheral nerve hyperactivity.","volume":"27","author":"Black","year":"1972","journal-title":"Arch Neurol"},{"key":"R7-7-20240808","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/BF00313668","article-title":"Muscle hypertrophy and a syndrome of continuous motor unit activity in prednisone responsive Guillain-Barre polyneuropathy.","volume":"231","author":"Vasilescu","year":"1984","journal-title":"J Neurol"},{"key":"R8-7-20240808","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1212\/WNL.29.12.1612","article-title":"Isaacs syndrome with laryngeal involvement: an unusual presentation of myokymia.","volume":"29","author":"Jackson","year":"1979","journal-title":"Neurology"},{"key":"R9-7-20240808","first-page":"1601","article-title":"Syndrome of continuous muscle muscle-fiber activity: histochemical, nerve terminal and end-plate study of two cases.","volume":"48","author":"Isaacs","year":"1974","journal-title":"S Afr Med J"},{"key":"R10-7-20240808","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1212\/WNL.54.3.771","article-title":"Morvans syndrome associated with voltage-gated K channel antibodies.","volume":"54","author":"Barber","year":"2000","journal-title":"Neurology"},{"key":"R11-7-20240808","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ng1094-136","article-title":". Episodic ataxiamyokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.","volume":"8","author":"Browne","year":"1994","journal-title":"Nat Genet"},{"key":"R12-7-20240808","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0140-6736(91)90073-X","article-title":". Autoimmune aetiology for acquired neuromyotonia (Isaacs syndrome).","volume":"338","author":"Sinha","year":"1991","journal-title":"Lancet"},{"key":"R14-7-20240808","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1093\/brain\/116.2.453","article-title":"Immunological associations of acquired neuromyotonia (Isaacs syndrome). Report of five cases and literature review.","volume":"116","author":"Newsom-Davis","year":"1993","journal-title":"Brain"},{"key":"R15-7-20240808","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/(SICI)1097-4598(199604)19:4<505::AID-MUS10>3.0.CO;2-O","article-title":". Neuromyotonia, peripheral neuropathy and myasthenia gravis.","volume":"19","author":"Martinelli","year":"1996","journal-title":"Muscle Nerve"},{"key":"R16-7-20240808","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1136\/jnnp.43.9.818","article-title":". Hyperkalaemic paralysis, neuropathy and persistent motor neuron discharges at rest in Addisons disease.","volume":"43","author":"Vilchez","year":"1980","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"R17-7-20240808","first-page":"1003","article-title":". Pseudo-myotonia.","volume":"115","author":"Sigwald","year":"1966","journal-title":"Rev Neurol"},{"key":"R18-7-20240808","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/00002826-198706000-00003","article-title":"Valproic acid in Isaac-Mertens syndrome.","volume":"10","author":"Vasilescu","year":"1987","journal-title":"Clin Neuropharmacol"},{"key":"R19-7-20240808","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1136\/jnnp.63.6.770","article-title":". Neuromuscular disorder as a presenting feature of celiac disease.","volume":"63","author":"Hadjivassiliou","year":"1997","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"R20-7-20240808","first-page":"178","article-title":". Systemic juvenile rheumatoid arthritis and associated Isaacs syndrome.","volume":"24","author":"Le-Gars","year":"1997","journal-title":"J Rheumatol"},{"key":"R21-7-20240808","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1136\/bmj.1.6176.1464","article-title":". Penicillamine-induced neuromyotonia.","volume":"1","author":"Reeback","year":"1979","journal-title":"Br Med J"},{"key":"R22-7-20240808","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1136\/jnnp.39.11.1086","article-title":"Neuromyotonia: an unusual presentation of intrathorasic malignancy.","volume":"39","author":"Walsh","year":"1976","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"R23-7-20240808","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1600-0404.1980.tb01486.x","article-title":". Electromyographic and nerve conduction findings in a patient with neuromyotonia, normocalcemic tetany and small-cell lung cancer.","volume":"61","author":"Partanen","year":"1980","journal-title":"Acta Neurol Scand"},{"key":"R24-7-20240808","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/ana.410290218","article-title":". Continuous muscle fiber activity, peripheral neuropathy and thymoma.","volume":"29","author":"Garcia-Merino","year":"1991","journal-title":"Ann Neurol"},{"key":"R25-7-20240808","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/BF02339242","article-title":". Association of neuromyotonia with peripheral neuropathy, myasthenia gravis and thymoma. A case report.","volume":"15","author":"Perini","year":"1994","journal-title":"Ital J Neurol Sci"},{"key":"R26-7-20240808","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1212\/WNL.49.1.258","article-title":". A case of Hodgkins lymphoma producing neuromyotonia.","volume":"49","author":"Caress","year":"1997","journal-title":"Neurology"},{"key":"R27-7-20240808","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1212\/WNL.44.3_Part_1.560","article-title":". Syndrome of continuous muscle fiber activity and plasmacytoma with IgM paraproteinemia.","volume":"44","author":"Zifko","year":"1994","journal-title":"Neurology"},{"key":"R28-7-20240808","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jns.2009.01.022","article-title":". Neuromyotonia as paraneoplastic manifestation of bladder carcinoma.","volume":"280","author":"Forte","year":"2009","journal-title":"J Neurol Sci"},{"key":"R29-7-20240808","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1212\/WNL.0b013e318203e91a","article-title":"Acquired neuromyotonia as a paraneoplastic manifestation of ovarian cancer.","volume":"76","author":"Issa","year":"2011","journal-title":"Neurology"},{"key":"R30-7-20240808","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0303-8467(99)00037-2","article-title":". Neuromyotonia, myocloni, sensory neuropathy and cerebellar symptoms in a patient with antibodies to neuronal nucleoproteins (anti-Hu-antibodies).","volume":"101","author":"Toepfer","year":"1999","journal-title":"Clin Neurol Neurosurg"},{"key":"R31-7-20240808","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-510X(00)00407-X","article-title":". Neuromyotonia: autoimmune pathogenesis and response to immune modulating therapy.","volume":"181","author":"Hayat","year":"2000","journal-title":"J Neurol Sci"},{"key":"R32-7-20240808","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1016\/j.clinph.2006.03.008","article-title":"Neuromyotonia.","volume":"117","author":"Maddison","year":"2006","journal-title":"Clin Neurophysiol"},{"key":"R33-7-20240808","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/1097-4598(200102)24:2<151::AID-MUS10>3.0.CO;2-7","article-title":"When is myokymia neuromyotonia.","volume":"24","author":"Guttmann","year":"2001","journal-title":"Muscle Nerve"},{"key":"R34-7-20240808","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/ana.410380505","article-title":". Acquired neuromyotonia: evidence for autoantibodies directed against K channels of peripheral nerves.","volume":"38","author":"Shillito","year":"1995","journal-title":"Ann Neurol"},{"key":"R35-7-20240808","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/ana.410410215","article-title":". Autoantibodies detected to expressed K channels are implicated in neuromyotonia.","volume":"41","author":"Hart","year":"1997","journal-title":"Ann Neurol"},{"key":"R36-7-20240808","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1093\/brain\/awf178","article-title":". Phenotypic variants of autoimmune peripheral nerve hyperexcitability.","volume":"125","author":"Hart","year":"2002","journal-title":"Brain"}],"container-title":["Journal of Clinical Neuromuscular Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00131402-201206000-00007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T19:22:43Z","timestamp":1723144963000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00131402-201206000-00007"}},"subtitle":["A Case Series and Review of the Literature"],"short-title":[],"issued":{"date-parts":[[2012,6]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.1097\/cnd.0b013e318246197d","relation":{},"ISSN":["1522-0443"],"issn-type":[{"value":"1522-0443","type":"print"}],"subject":[],"published":{"date-parts":[[2012,6]]}}}