Neurology: Neuroimmunology & Neuroinflammation



Online-Only SupplementsTable e-1 . Clinical features of previous reported cases of thymoma-associated paraneoplastic encephalitis.PatientsAuthorSex, age in yearsPresentation and main symptomsHistory of autoimmunityMRICSFEEGAnti-Neuronal AbsTreatmentOutcomes1Mcardle (1988) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"5s6j3v8va","properties":{"formattedCitation":"(1)","plainCitation":"(1)"},"citationItems":[{"id":131,"uris":[""],"uri":[""],"itemData":{"id":131,"type":"article-journal","title":"Limbic encephalitis associated with malignant thymoma","container-title":"Pathology","page":"292-295","volume":"20","issue":"3","source":"NCBI PubMed","abstract":"A case of limbic encephalitis associated with recurrent malignant thymoma in a 41-year-old male is described. The patient presented with confusion, loss of memory, hallucinations, abnormal behaviour, tachycardia and profuse sweating. Investigations were unrewarding and the patient's clinical state deteriorated until his death 1 month after presentation. The diagnosis was made at autopsy when bilateral extensive neuronal loss with reactive gliosis, confined to the medial temporal cortex and Ammon's horn, was revealed.","ISSN":"0031-3025","note":"PMID: 3205599","journalAbbreviation":"Pathology","language":"eng","author":[{"family":"McArdle","given":"J P"},{"family":"Millingen","given":"K S"}],"issued":{"date-parts":[["1988",7]]},"PMID":"3205599"}}],"schema":""} (1) M, 41Confusion, memory deficitsANA (serum)Not availableoligoclonal IgG bands Not AvailableNoPartial, thymectomy, radiation, corticosteroidsDeath (1 month)2Ingenito (1990) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1q1v5b75ll","properties":{"formattedCitation":"(2)","plainCitation":"(2)"},"citationItems":[{"id":51,"uris":[""],"uri":[""],"itemData":{"id":51,"type":"article-journal","title":"Limbic encephalitis associated with thymoma","container-title":"Neurology","page":"382","volume":"40","issue":"2","source":"NCBI PubMed","ISSN":"0028-3878","note":"PMID: 2300266","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Ingenito","given":"G G"},{"family":"Berger","given":"J R"},{"family":"David","given":"N J"},{"family":"Norenberg","given":"M D"}],"issued":{"date-parts":[["1990",2]]},"PMID":"2300266"}}],"schema":""} (2) M, 59Confusion, memory deficit, hyper somnolence, axial cerebellar ataxiaNoNot reported13 WBCSlow activity with frontal intermittent rhythmic delta activityNoCorticosteroidsDeath (51 days after admission, symptoms onset were 7 months before admission3Cunningham (1994) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"5aSmEfPA","properties":{"formattedCitation":"(3)","plainCitation":"(3)"},"citationItems":[{"id":122,"uris":[""],"uri":[""],"itemData":{"id":122,"type":"article-journal","title":"Limbic encephalitis secondary to malignant thymoma","container-title":"The Annals of thoracic surgery","page":"250-251","volume":"58","issue":"1","source":"NCBI PubMed","abstract":"A 56-year-old woman presented with memory loss and an enlarging mediastinal mass on chest roentgenogram. Physical findings were normal except for an altered mental status examination consistent with dementia. Further radiologic assessment was nondiagnostic. Surgical resection of a malignant thymoma resulted in clinical improvement. Treatment for limbic encephalitis should be directed at the underlying disease, and symptoms may improve if the tumor is eradicated.","ISSN":"0003-4975","note":"PMID: 8037541","journalAbbreviation":"Ann. Thorac. Surg.","language":"eng","author":[{"family":"Cunningham","given":"J D"},{"family":"Burt","given":"M E"}],"issued":{"date-parts":[["1994",7]]},"PMID":"8037541"}}],"schema":""} (3)F, 56Confusion, memory deficit, emotional labilityNoLeft temporallobe corticaland subcorti-cal lesionsnoted onT2 (no figures available)Elevated protein levelNot reportedNo(Negative anti-Hu)Thymectomy, radiation, chemotherapy (three cycles of cisplatinandetoposide)Significant improvement4Antoine (1995) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2q2epqq99k","properties":{"formattedCitation":"(4)","plainCitation":"(4)4"},"citationItems":[{"id":181,"uris":[""],"uri":[""],"itemData":{"id":181,"type":"article-journal","title":"Limbic encephalitis and immunological perturbations in two patients with thymoma","container-title":"Journal of neurology, neurosurgery, and psychiatry","page":"706-710","volume":"58","issue":"6","source":"NCBI PubMed","abstract":"Two patients with clinical and radiological evidence of limbic encephalitis associated with an invasive lymphoepithelial thymoma who improved after thymectomy and radiotherapy are reported. The serum of both patients and the CSF of one of them contained different types of antibodies that immunoreacted with human and rat brain and newborn rat thymus. After treatment of the tumour, the antibody titres decreased. Similar antibodies were not found in various controls. Two out of 16 patients with thymoma, myasthenia gravis, and no CNS involvement had low titres of antibodies reacting with the brain. It is suggested that in some patients with thymoma, an autoimmune reaction involving antigens common to the brain and thymus is possibly misdirected against the CNS.","ISSN":"0022-3050","note":"PMID: 7608671","journalAbbreviation":"J. Neurol. Neurosurg. Psychiatr.","language":"eng","author":[{"family":"Antoine","given":"J C"},{"family":"Honnorat","given":"J"},{"family":"Anterion","given":"C T"},{"family":"Aguera","given":"M"},{"family":"Absi","given":"L"},{"family":"Fournel","given":"P"},{"family":"Michel","given":"D"}],"issued":{"date-parts":[["1995",6]]},"PMID":"7608671"}}],"schema":""} (4)F, 58Confusion, visual and auditory hallucinations, short term memory lossNoBefore treatment: increased signals on T2 weighted sequences in right hippocampusAfter treatment –normal (No figures available)36 lymphocytes/m3Protein 0,3 g/lEpileptic discharges in the right temporal lobeAnti-neuronal Cytoplasmatic (serum 1/1500 and CSF 1/100)Thymectomy and radiationNo residual symptoms5Antoine (1995) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"csRLC9RN","properties":{"formattedCitation":"(4)","plainCitation":"(4)4"},"citationItems":[{"id":181,"uris":[""],"uri":[""],"itemData":{"id":181,"type":"article-journal","title":"Limbic encephalitis and immunological perturbations in two patients with thymoma","container-title":"Journal of neurology, neurosurgery, and psychiatry","page":"706-710","volume":"58","issue":"6","source":"NCBI PubMed","abstract":"Two patients with clinical and radiological evidence of limbic encephalitis associated with an invasive lymphoepithelial thymoma who improved after thymectomy and radiotherapy are reported. The serum of both patients and the CSF of one of them contained different types of antibodies that immunoreacted with human and rat brain and newborn rat thymus. After treatment of the tumour, the antibody titres decreased. Similar antibodies were not found in various controls. Two out of 16 patients with thymoma, myasthenia gravis, and no CNS involvement had low titres of antibodies reacting with the brain. It is suggested that in some patients with thymoma, an autoimmune reaction involving antigens common to the brain and thymus is possibly misdirected against the CNS.","ISSN":"0022-3050","note":"PMID: 7608671","journalAbbreviation":"J. Neurol. Neurosurg. Psychiatr.","language":"eng","author":[{"family":"Antoine","given":"J C"},{"family":"Honnorat","given":"J"},{"family":"Anterion","given":"C T"},{"family":"Aguera","given":"M"},{"family":"Absi","given":"L"},{"family":"Fournel","given":"P"},{"family":"Michel","given":"D"}],"issued":{"date-parts":[["1995",6]]},"PMID":"7608671"}}],"schema":""} (4)F, 67Confusion, agitation, hallucination, short memory lossAnti-striated muscle antibody (1/10)Before treatment: mild increased signals in the right hippocampus on T2 weighted sequencesNormal after treatment (no figures available)NormalEpileptic discharges in the left temporal lobeAnti-neuronal Nuclear (serum and CSF)ThymectomyRadiotherapyMild memory deficits (necessity of noting her shopping requirements)6Evoli (1999) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"VmaO3YLO","properties":{"formattedCitation":"(5,6)","plainCitation":"(5,6)"},"citationItems":[{"id":43,"uris":[""],"uri":[""],"itemData":{"id":43,"type":"article-journal","title":"Multiple paraneoplastic diseases associated with thymoma","container-title":"Neuromuscular disorders: NMD","page":"601-603","volume":"9","issue":"8","source":"NCBI PubMed","abstract":"Here we report a patient with a lymphoepithelial thymoma who developed in chronological sequence limbic encephalitis, neuromyotonia and myasthenia gravis. The patient presented with limbic encephalitis associated with an invasive thymoma and improved after surgery and cytotoxic therapy. Two months after thymectomy, neuromyotonia associated with hyperhidrosis and mild motor neuropathy occurred and the patient was given plasma-exchange and prednisone therapy. Five months later he developed mild generalised myasthenia gravis. Anti-acetylcholine receptor antibodies, previously repeatedly negative, were found positive at the onset of clinical signs of myasthenia gravis.","ISSN":"0960-8966","note":"PMID: 10619720","journalAbbreviation":"Neuromuscul. Disord.","language":"eng","author":[{"family":"Evoli","given":"A"},{"family":"Lo Monaco","given":"M"},{"family":"Marra","given":"R"},{"family":"Lino","given":"M M"},{"family":"Batocchi","given":"A P"},{"family":"Tonali","given":"P A"}],"issued":{"date-parts":[["1999",12]]},"PMID":"10619720"},"label":"page"},{"id":1359,"uris":[""],"uri":[""],"itemData":{"id":1359,"type":"article-journal","title":"Paraneoplastic diseases associated with thymoma","container-title":"Journal of Neurology","page":"756-762","volume":"254","issue":"6","source":"link.","abstract":"Background Thymoma is frequently associated with paraneoplastic diseases (PDs), most commonly with myasthenia gravis (MG). This association is thought to depend on thymoma’s capacity to produce and export T lymphocytes. Objective (1) To determine the frequency and characteristics of thymoma-associated PDs other than MG; (2) to evaluate T cell maturation in thymomas with and without PDs. Methods We studied 260 patients with thymoma (associated with MG in 228). The occurrence of PDs was monitored together with the tumor outcome. Phenotypic characterization of thymocyte subsets in 14 thymoma samples (7 with and 7 without MG) was performed by FACS. Results A total of 47 PDs was diagnosed in 41/260 patients (15.8 %). Neurological PDs included neuromyotonia, limbic encephalitis, polymyositis, subacute hearing loss, psychosis and sleep disorders. A broad spectrum of nonneurological PDs were observed, among these, hematological and cutaneous diseases prevailed. Like MG, these disorders occurred either in the presence of the thymoma or at different times after thymomectomy; their onset often heralded a tumor recurrence. In thymomas from MG subjects, we found an increased proportion of fully mature CD4 single positive (SP) thymocytes and a reduced frequency of CD4SPCD25+ cells; the latter finding may reflect a deficient generation of T regulatory cells, a reduced intratumorous activation of T cells, or both. Conclusions We confirm the strong association of thymoma with PDs. These disorders often occurred in MG patients and their course in relation to thymoma was similar to that of MG. In accordance with previous observations, we found some alterations in the intratumorous production of mature CD4+ T cells that could be involved in the pathogenesis of paraneoplastic autoimmunity.","DOI":"10.1007/s00415-006-0429-z","ISSN":"0340-5354, 1432-1459","journalAbbreviation":"J Neurol","language":"en","author":[{"family":"Evoli","given":"Amelia"},{"family":"Minicuci","given":"Giacomo Maria"},{"family":"Vitaliani","given":"Roberta"},{"family":"Battaglia","given":"Alessandra"},{"family":"Marca","given":"Giacomo Della"},{"family":"Lauriola","given":"Libero"},{"family":"Fattorossi","given":"Andrea"}],"issued":{"date-parts":[["2007",6,1]]},"accessed":{"date-parts":[["2014",6,19]]}},"label":"page"}],"schema":""} (5,6)M,32New onset generalized tonic-clonic seizures and confusion, memory deficitsMyasthenia GravisNeuromyotoniaBefore treatment: increased signal and swelling of both hippocampi on T2-weighted images 25 cells/mm3Normal protein and glucoseTheta background activity with sharp waves on both temporal lobesNo(negative anti-Hu)Thymectomy, radiation, chemotherapy (cyclophosphamide, doxorubicin, vincristine and metilprednisolone), corticosteroids, PLEXMild memory deficits, (“good condition and has returned to work”)Dependent on corticosteroids7Rickman (2000) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"GAzIMxGy","properties":{"formattedCitation":"(7)","plainCitation":"(7)"},"citationItems":[{"id":18,"uris":[""],"uri":[""],"itemData":{"id":18,"type":"article-journal","title":"Fulminant autoimmune cortical encephalitis associated with thymoma treated with plasma exchange","container-title":"Mayo Clinic proceedings","page":"1321-1326","volume":"75","issue":"12","source":"NCBI PubMed","abstract":"A 55-year-old man presented with fever, malaise, dysarthria, and intermittent twitching of his right hand. He progressed rapidly to aphasia, intractable myoclonic seizures, and unresponsiveness. Magnetic resonance imaging (MRI) of the head demonstrated multiple nonenhancing areas of signal abnormality involving the cortex of both cerebral hemispheres. Extensive evaluation revealed no infectious cause for his symptoms. Muscle acetylcholine receptor binding and modulating antibodies, striational antibodies, and a neuronal autoantibody specific for collapsin response-mediator protein were detected. An invasive thymoma was discovered and resected. Brain biopsy revealed microglial activation, gliosis, and scant perivascular lymphocytic inflammation. His condition worsened despite treatment with anticonvulsants, intravenous corticosteroids, and antimicrobials. Plasma exchange was performed. The myoclonus stopped; he regained consciousness and gradually improved to the point that he could talk and ambulate with assistance. An MRI revealed regression of the lesions with residual cortical atrophy. This case demonstrates that paraneoplastic encephalitis may occur with thymoma and may extend to cortical regions outside the limbic system.","DOI":"10.4065/75.12.1321","ISSN":"0025-6196","note":"PMID: 11126843","journalAbbreviation":"Mayo Clin. Proc.","language":"eng","author":[{"family":"Rickman","given":"O B"},{"family":"Parisi","given":"J E"},{"family":"Yu","given":"Z"},{"family":"Lennon","given":"V A"},{"family":"Vernino","given":"S"}],"issued":{"date-parts":[["2000",12]]},"PMID":"11126843"}}],"schema":""} (7)M,55Malaise, fever, cough, dysarthria, intermittent twitching of right hand. One week after short-term memory, word finding difficulty. Nystagmus, vertical gaze impairment, jerking movements of face, neck and arms, and left lower extremity. Intractable seizuresAchR andStriational antibodiesMRI1: Patchy T2 hyperintensity in the gray matter of both cerebral hemisphere with no gadolinium enhancementMRI 2 (D35): multiples areas of cortical signal abnormalities most prominent in the temporal lobes and spare subcortical and posterior fossa structuresMRI 3 (D105): cortical atrophy and reduced number of lesions, temporal lobe are still prominentCSF 1: protein 69 mg/dLCSF 2: protein 63 mg/dlMultifocal, independent, periodic, lateralizing epileptiform discharges (PLEDs)Fig 2)Anti-CRMP-5Partial thymectomy, pulse therapy (methylpredinisolone), PLEXInitial responseRecurrence of symptoms Died (9 months)8D’Avino (2001) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"odM0imS9","properties":{"formattedCitation":"(8)","plainCitation":"(8)"},"citationItems":[{"id":33,"uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Limbic encephalitis associated with thymic cancer: a case report","container-title":"Journal of neurology","page":"1000-1002","volume":"248","issue":"11","source":"NCBI PubMed","ISSN":"0340-5354","note":"PMID: 11757949","shortTitle":"Limbic encephalitis associated with thymic cancer","journalAbbreviation":"J. Neurol.","language":"eng","author":[{"family":"D'Avino","given":"C"},{"family":"Lucchi","given":"M"},{"family":"Ceravolo","given":"R"},{"family":"Mussi","given":"A"},{"family":"Malandrini","given":"A"},{"family":"Annunziata","given":"P"},{"family":"Siciliano","given":"G"}],"issued":{"date-parts":[["2001",11]]},"PMID":"11757949"}}],"schema":""} (8)M, 61Short term memory loss, confusion, irritability, hallucinations, feeding disorders, loss of weight, generalized tonic clonic seizures (not described if it was refractoryMMSE: 23/30 NoNormal (No available figures)Positive OBTheta backaground activity with sharp waves in both fronto-temporal lobesAntibody reactivity to Purkinje cells (serum and CSF)Thymectomy, radiationMild memory deficitsMMSE: 29 9Fujii (2001) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8onHr7FB","properties":{"formattedCitation":"(9)","plainCitation":"(9)"},"citationItems":[{"id":79,"uris":[""],"uri":[""],"itemData":{"id":79,"type":"article-journal","title":"Limbic encephalitis associated with recurrent thymoma: a postmortem study","container-title":"Neurology","page":"344-347","volume":"57","issue":"2","source":"NCBI PubMed","abstract":"The authors report an autopsied patient with limbic encephalitis and recurrent thymoma. The immunohistochemical study showed selective depositions of immunoglobulin G on the neurons in the limbic system and the tumor cells of the recurrent thymoma. The immunoblotting study detected two types of antibodies that react with the human brain, rat brain, and rat thymus.","ISSN":"0028-3878","note":"PMID: 11468328","shortTitle":"Limbic encephalitis associated with recurrent thymoma","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Fujii","given":"N"},{"family":"Furuta","given":"A"},{"family":"Yamaguchi","given":"H"},{"family":"Nakanishi","given":"K"},{"family":"Iwaki","given":"T"}],"issued":{"date-parts":[["2001",7,24]]},"PMID":"11468328"}}],"schema":""} (9) M,55Confusion, memory deficit, irritability, mania, 3 generalized tonic clonic seizuresMyastenia Gravis 15-years previoulsyAChR antibodiesBilateral highIntensity (no available figures)NormalNo epileptic dischargesHippocampus showing human IgG at autopsyThymectomyDeath (4months)10Vernino (2002) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Ldq2KuE7","properties":{"formattedCitation":"(10)","plainCitation":"(10)"},"citationItems":[{"id":76,"uris":[""],"uri":[""],"itemData":{"id":76,"type":"article-journal","title":"Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma","container-title":"Neurology","page":"929-932","volume":"59","issue":"6","source":"NCBI PubMed","abstract":"Neurologic autoimmunity frequently occurs with thymoma, particularly myasthenia gravis and skeletal muscle-specific autoantibodies. Type 1 antineuronal nuclear antibody (ANNA-1/\"anti-Hu\"), which is recognized as an immunoglobulin G marker of small-cell lung carcinoma, has not been reported with thymoma. The authors identified four patients (three under age 40) with ANNA-1 and a paraneoplastic neurologic complication of thymoma. Retrospective testing of stored serum from 172 patients with thymoma revealed ANNA-1 in 3%. This report extends the oncologic implications of ANNA-1 seropositivity.","ISSN":"0028-3878","note":"PMID: 12297583","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Vernino","given":"Steven"},{"family":"Eggenberger","given":"Eric R"},{"family":"Rogers","given":"Lisa R"},{"family":"Lennon","given":"Vanda A"}],"issued":{"date-parts":[["2002",9,24]]},"PMID":"12297583"}}],"schema":""} (10) F, 66Hoarseness, unilateral loss of hearing, vertigo, arreflexiaNoNot reportedNot reportedNot reportedANNA-1 (anti-Hu), VGCC (serum)Partial thymectomy, chemotherapy (two cycles of cisplatinandetoposide Death (7 months)11Vernino (2002) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ge79fPTQ","properties":{"formattedCitation":"(10)","plainCitation":"(10)"},"citationItems":[{"id":76,"uris":[""],"uri":[""],"itemData":{"id":76,"type":"article-journal","title":"Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma","container-title":"Neurology","page":"929-932","volume":"59","issue":"6","source":"NCBI PubMed","abstract":"Neurologic autoimmunity frequently occurs with thymoma, particularly myasthenia gravis and skeletal muscle-specific autoantibodies. Type 1 antineuronal nuclear antibody (ANNA-1/\"anti-Hu\"), which is recognized as an immunoglobulin G marker of small-cell lung carcinoma, has not been reported with thymoma. The authors identified four patients (three under age 40) with ANNA-1 and a paraneoplastic neurologic complication of thymoma. Retrospective testing of stored serum from 172 patients with thymoma revealed ANNA-1 in 3%. This report extends the oncologic implications of ANNA-1 seropositivity.","ISSN":"0028-3878","note":"PMID: 12297583","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Vernino","given":"Steven"},{"family":"Eggenberger","given":"Eric R"},{"family":"Rogers","given":"Lisa R"},{"family":"Lennon","given":"Vanda A"}],"issued":{"date-parts":[["2002",9,24]]},"PMID":"12297583"}}],"schema":""} (10) M, 34Presented with dysphagia and dysarthria being diagnosed as myasthenia gravis. After 1 month presented with confusion, auditory hallucination, and tonic clonic seizuresMyastenia Gravis AChR antibodiesNormal (no available figures)10 WBC with normal protein concentrationDiffuse slowing over the left temporal lobeANNA-1 (anti-Hu),PLEX, thymectomy, corticosteroids“Three months later, he was noted to be intermittently withdrawn and confused; no seizures were observed”12Vernino (2002) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"PFPJEd32","properties":{"formattedCitation":"(10)","plainCitation":"(10)"},"citationItems":[{"id":76,"uris":[""],"uri":[""],"itemData":{"id":76,"type":"article-journal","title":"Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma","container-title":"Neurology","page":"929-932","volume":"59","issue":"6","source":"NCBI PubMed","abstract":"Neurologic autoimmunity frequently occurs with thymoma, particularly myasthenia gravis and skeletal muscle-specific autoantibodies. Type 1 antineuronal nuclear antibody (ANNA-1/\"anti-Hu\"), which is recognized as an immunoglobulin G marker of small-cell lung carcinoma, has not been reported with thymoma. The authors identified four patients (three under age 40) with ANNA-1 and a paraneoplastic neurologic complication of thymoma. Retrospective testing of stored serum from 172 patients with thymoma revealed ANNA-1 in 3%. This report extends the oncologic implications of ANNA-1 seropositivity.","ISSN":"0028-3878","note":"PMID: 12297583","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Vernino","given":"Steven"},{"family":"Eggenberger","given":"Eric R"},{"family":"Rogers","given":"Lisa R"},{"family":"Lennon","given":"Vanda A"}],"issued":{"date-parts":[["2002",9,24]]},"PMID":"12297583"}}],"schema":""} (10) F, 34Recurrent vertigo, tinnitus, and vomitingClonic activity of the tongue and jaw (seizures?)DysautonomiaMRI 1: normalMRI 2:Non-enhancing left temporal lesionMRI 3 (11 days after):Four new enhancing cortical lesions (figure 1)Elevated protein 78 mg/dLNot reportedANNA-1, VGKCThymectomyResidual symptoms, constipation, fixed right pupil13Vernino (2002) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"12lekie8t0","properties":{"formattedCitation":"(10)","plainCitation":"(10)"},"citationItems":[{"id":76,"uris":[""],"uri":[""],"itemData":{"id":76,"type":"article-journal","title":"Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma","container-title":"Neurology","page":"929-932","volume":"59","issue":"6","source":"NCBI PubMed","abstract":"Neurologic autoimmunity frequently occurs with thymoma, particularly myasthenia gravis and skeletal muscle-specific autoantibodies. Type 1 antineuronal nuclear antibody (ANNA-1/\"anti-Hu\"), which is recognized as an immunoglobulin G marker of small-cell lung carcinoma, has not been reported with thymoma. The authors identified four patients (three under age 40) with ANNA-1 and a paraneoplastic neurologic complication of thymoma. Retrospective testing of stored serum from 172 patients with thymoma revealed ANNA-1 in 3%. This report extends the oncologic implications of ANNA-1 seropositivity.","ISSN":"0028-3878","note":"PMID: 12297583","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Vernino","given":"Steven"},{"family":"Eggenberger","given":"Eric R"},{"family":"Rogers","given":"Lisa R"},{"family":"Lennon","given":"Vanda A"}],"issued":{"date-parts":[["2002",9,24]]},"PMID":"12297583"}}],"schema":""} (10)F, 39 Dysphagia, generalized weakness (attributed to Myasthenia Gravis)Personality changesMyasthenia GravisAChR andStriational antibodiesNormal (no available figures)Not reportedNot reportedANNA-1, CRMP-5,Partial Thymectomy, radiation, chemotherapy (etoposide, cysplatin), corticosteroid, PLEXNot reported14 aAnces (2005) – patient 5 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"GsaGmAZi","properties":{"formattedCitation":"(11)","plainCitation":"(11)"},"citationItems":[{"id":146,"uris":[""],"uri":[""],"itemData":{"id":146,"type":"article-journal","title":"Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates","container-title":"Brain: a journal of neurology","page":"1764-1777","volume":"128","issue":"Pt 8","source":"NCBI PubMed","abstract":"We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.","DOI":"10.1093/brain/awh526","ISSN":"1460-2156","note":"PMID: 15888538","shortTitle":"Treatment-responsive limbic encephalitis identified by neuropil antibodies","journalAbbreviation":"Brain","language":"eng","author":[{"family":"Ances","given":"Beau M"},{"family":"Vitaliani","given":"Roberta"},{"family":"Taylor","given":"Robert A"},{"family":"Liebeskind","given":"David S"},{"family":"Voloschin","given":"Alfredo"},{"family":"Houghton","given":"David J"},{"family":"Galetta","given":"Steven L"},{"family":"Dichter","given":"Marc"},{"family":"Alavi","given":"Abass"},{"family":"Rosenfeld","given":"Myrna R"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2005",8]]},"PMID":"15888538"}}],"schema":""} (11) corresponds to Lai (2009) patient 2 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"79hpl1vub","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":19,"uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location","container-title":"Annals of neurology","page":"424-434","volume":"65","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.\nMETHODS: We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.\nRESULTS: Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.\nINTERPRETATION: Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.","DOI":"10.1002/ana.21589","ISSN":"1531-8249","note":"PMID: 19338055","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Lai","given":"Meizan"},{"family":"Hughes","given":"Ethan G"},{"family":"Peng","given":"Xiaoyu"},{"family":"Zhou","given":"Lei"},{"family":"Gleichman","given":"Amy J"},{"family":"Shu","given":"Huidy"},{"family":"Matà","given":"Sabrina"},{"family":"Kremens","given":"Daniel"},{"family":"Vitaliani","given":"Roberta"},{"family":"Geschwind","given":"Michael D"},{"family":"Bataller","given":"Luis"},{"family":"Kalb","given":"Robert G"},{"family":"Davis","given":"Rebecca"},{"family":"Graus","given":"Francesc"},{"family":"Lynch","given":"David R"},{"family":"Balice-Gordon","given":"Rita"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19338055"}}],"schema":""} (12)F, 44Hippocampal syndrome; pure short-term memory loss. Evolved to extensive LE, focal motor seizuresNot reportedMRI(1) : normal MRI (2, after 5 days): mild temporal lobe FLAIR abnormalities (right>left), no contraste enhancement0 WBC, protein 63 mg/dL, glucose 64 mg/dLNot reportedNeuropil antibodies Later prove to be AMPAR Abs ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2og8p4hqf1","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":19,"uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location","container-title":"Annals of neurology","page":"424-434","volume":"65","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.\nMETHODS: We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.\nRESULTS: Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.\nINTERPRETATION: Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.","DOI":"10.1002/ana.21589","ISSN":"1531-8249","note":"PMID: 19338055","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Lai","given":"Meizan"},{"family":"Hughes","given":"Ethan G"},{"family":"Peng","given":"Xiaoyu"},{"family":"Zhou","given":"Lei"},{"family":"Gleichman","given":"Amy J"},{"family":"Shu","given":"Huidy"},{"family":"Matà","given":"Sabrina"},{"family":"Kremens","given":"Daniel"},{"family":"Vitaliani","given":"Roberta"},{"family":"Geschwind","given":"Michael D"},{"family":"Bataller","given":"Luis"},{"family":"Kalb","given":"Robert G"},{"family":"Davis","given":"Rebecca"},{"family":"Graus","given":"Francesc"},{"family":"Lynch","given":"David R"},{"family":"Balice-Gordon","given":"Rita"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19338055"}}],"schema":""} (12)Thymectomy, corticosteroids, IVIgReturned to baseline15Ances (2005) – patient 6 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"6g65ljh4j","properties":{"formattedCitation":"(11)","plainCitation":"(11)"},"citationItems":[{"id":146,"uris":[""],"uri":[""],"itemData":{"id":146,"type":"article-journal","title":"Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates","container-title":"Brain: a journal of neurology","page":"1764-1777","volume":"128","issue":"Pt 8","source":"NCBI PubMed","abstract":"We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.","DOI":"10.1093/brain/awh526","ISSN":"1460-2156","note":"PMID: 15888538","shortTitle":"Treatment-responsive limbic encephalitis identified by neuropil antibodies","journalAbbreviation":"Brain","language":"eng","author":[{"family":"Ances","given":"Beau M"},{"family":"Vitaliani","given":"Roberta"},{"family":"Taylor","given":"Robert A"},{"family":"Liebeskind","given":"David S"},{"family":"Voloschin","given":"Alfredo"},{"family":"Houghton","given":"David J"},{"family":"Galetta","given":"Steven L"},{"family":"Dichter","given":"Marc"},{"family":"Alavi","given":"Abass"},{"family":"Rosenfeld","given":"Myrna R"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2005",8]]},"PMID":"15888538"}}],"schema":""} (11) corresponds to Lai (2009) - patient 3 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NBzAWuTf","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":19,"uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location","container-title":"Annals of neurology","page":"424-434","volume":"65","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.\nMETHODS: We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.\nRESULTS: Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.\nINTERPRETATION: Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.","DOI":"10.1002/ana.21589","ISSN":"1531-8249","note":"PMID: 19338055","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Lai","given":"Meizan"},{"family":"Hughes","given":"Ethan G"},{"family":"Peng","given":"Xiaoyu"},{"family":"Zhou","given":"Lei"},{"family":"Gleichman","given":"Amy J"},{"family":"Shu","given":"Huidy"},{"family":"Matà","given":"Sabrina"},{"family":"Kremens","given":"Daniel"},{"family":"Vitaliani","given":"Roberta"},{"family":"Geschwind","given":"Michael D"},{"family":"Bataller","given":"Luis"},{"family":"Kalb","given":"Robert G"},{"family":"Davis","given":"Rebecca"},{"family":"Graus","given":"Francesc"},{"family":"Lynch","given":"David R"},{"family":"Balice-Gordon","given":"Rita"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19338055"}}],"schema":""} (12) M,38Confusion, agitation, short-term memory loss, generalized tonic-clonic seizures (prior episode of Limbic Encephalitis 5 years earlier). Evolved to hippocampal and multifocal encephalitis, and stiff person syndromeStiff personFLAIR abnormalities in right medial and lateral temporal lobe, right frontal, left insular and left occipital regions. No contrast enhancement.7 WBC, protein 50 mg/dL, glucose 92 mg/dL, positive OB. Positive ISAb, IgG index not examinedNot reportedNeuropil antibodies Later prove to be AMPAR Abs ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"phSw019b","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":19,"uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location","container-title":"Annals of neurology","page":"424-434","volume":"65","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.\nMETHODS: We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.\nRESULTS: Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.\nINTERPRETATION: Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.","DOI":"10.1002/ana.21589","ISSN":"1531-8249","note":"PMID: 19338055","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Lai","given":"Meizan"},{"family":"Hughes","given":"Ethan G"},{"family":"Peng","given":"Xiaoyu"},{"family":"Zhou","given":"Lei"},{"family":"Gleichman","given":"Amy J"},{"family":"Shu","given":"Huidy"},{"family":"Matà","given":"Sabrina"},{"family":"Kremens","given":"Daniel"},{"family":"Vitaliani","given":"Roberta"},{"family":"Geschwind","given":"Michael D"},{"family":"Bataller","given":"Luis"},{"family":"Kalb","given":"Robert G"},{"family":"Davis","given":"Rebecca"},{"family":"Graus","given":"Francesc"},{"family":"Lynch","given":"David R"},{"family":"Balice-Gordon","given":"Rita"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19338055"}}],"schema":""} (12)Thymectomy, corticosteroids, plasmapheresis, IVIgMild residual memory deficits and steroid-dependent muscle spasms and rigidity16Ohshita (2006) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"CN0xzTT3","properties":{"formattedCitation":"(13,14)","plainCitation":"(13,14)"},"citationItems":[{"id":1309,"uris":[""],"uri":[""],"itemData":{"id":1309,"type":"article-journal","title":"Voltage-gated potassium channel antibodies associated limbic encephalitis in a patient with invasive thymoma","container-title":"Journal of the Neurological Sciences","page":"167-169","volume":"250","issue":"1–2","source":"ScienceDirect","abstract":"Recently, limbic encephalitis (LE) associated with Voltage-gated potassium channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive thymoma. There was a close temporal relationship between the clinical course and the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab-associated LE cases, our cases showed the more extensive high intensity lesions on MRI and the absence of seizure and hyponatremia.","DOI":"10.1016/j.jns.2006.08.003","ISSN":"0022-510X","journalAbbreviation":"Journal of the Neurological Sciences","author":[{"family":"Ohshita","given":"Tomohiko"},{"family":"Kawakami","given":"Hideshi"},{"family":"Maruyama","given":"Hirofumi"},{"family":"Kohriyama","given":"Tatsuo"},{"family":"Arimura","given":"Kimiyoshi"},{"family":"Matsumoto","given":"Masayasu"}],"issued":{"date-parts":[["2006",12,1]]},"accessed":{"date-parts":[["2014",6,13]]}}},{"id":1308,"uris":[""],"uri":[""],"itemData":{"id":1308,"type":"article-journal","title":"Identification and Characterization of GABAA Receptor Autoantibodies in Autoimmune Encephalitis","container-title":"Journal of Neuroscience","page":"8151-8163","volume":"34","issue":"24","source":"CrossRef","DOI":"10.1523/JNEUROSCI.4415-13.2014","ISSN":"0270-6474, 1529-2401","language":"en","author":[{"family":"Ohkawa","given":"T."},{"family":"Satake","given":"S."},{"family":"Yokoi","given":"N."},{"family":"Miyazaki","given":"Y."},{"family":"Ohshita","given":"T."},{"family":"Sobue","given":"G."},{"family":"Takashima","given":"H."},{"family":"Watanabe","given":"O."},{"family":"Fukata","given":"Y."},{"family":"Fukata","given":"M."}],"issued":{"date-parts":[["2014",6,11]]},"accessed":{"date-parts":[["2014",6,13]]}}}],"schema":""} (13,14)F, 593 years earlier years, invasive thymoma had been diagnosed and treated with thymectomy and radiotherapySubacute onset of amnesia (short-term memory impairment), disorientation, and; 10 months later, progressive memory impairment and recurrence of thymomaPositive single-stranded DNA antibodiesT2/FLAIR images demonstrated bilateral hyperintense areas in the medial part of the temporal lobe. High intensity lesions were also seen in the right insular cortex, as well as bilaterally in the frontobasal cortex and cingulate gyrusMild elevation of the protein content (60 mg/dl)NormalVGKC (LGI1) andAnti-GABAaR ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"iWmAy4Nz","properties":{"formattedCitation":"(14)","plainCitation":"(14)"},"citationItems":[{"id":1308,"uris":[""],"uri":[""],"itemData":{"id":1308,"type":"article-journal","title":"Identification and Characterization of GABAA Receptor Autoantibodies in Autoimmune Encephalitis","container-title":"Journal of Neuroscience","page":"8151-8163","volume":"34","issue":"24","source":"CrossRef","DOI":"10.1523/JNEUROSCI.4415-13.2014","ISSN":"0270-6474, 1529-2401","language":"en","author":[{"family":"Ohkawa","given":"T."},{"family":"Satake","given":"S."},{"family":"Yokoi","given":"N."},{"family":"Miyazaki","given":"Y."},{"family":"Ohshita","given":"T."},{"family":"Sobue","given":"G."},{"family":"Takashima","given":"H."},{"family":"Watanabe","given":"O."},{"family":"Fukata","given":"Y."},{"family":"Fukata","given":"M."}],"issued":{"date-parts":[["2014",6,11]]},"accessed":{"date-parts":[["2014",6,13]]}}}],"schema":""} (14)Chemotherapy (carboplatin and etoposide)Mental state partially improved17Chaudhry (2007) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"jtrfl8t5i","properties":{"formattedCitation":"(15)","plainCitation":"(15)"},"citationItems":[{"id":116,"uris":[""],"uri":[""],"itemData":{"id":116,"type":"article-journal","title":"Paraneoplastic limbic encephalitis attributable to thymoma","container-title":"Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer","page":"879-880","volume":"2","issue":"9","source":"NCBI PubMed","DOI":"10.1097/JTO.0b013e3181461b13","ISSN":"1556-1380","note":"PMID: 17805070","journalAbbreviation":"J Thorac Oncol","language":"eng","author":[{"family":"Chaudhry","given":"Mohammed S"},{"family":"Waters","given":"Marie"},{"family":"Gilligan","given":"David"}],"issued":{"date-parts":[["2007",9]]},"PMID":"17805070"}}],"schema":""} (15)F, 67Memory deficits, cognitive impairment. MMSE: 23NoBilateral increased signal on FLAIR in both hippocampi. More extensive similar changes were on the left side extending to trigone and up to the level of the corpus callosum.Protein: 67 mg/ 100 ml Positive OBNot reportedNegative for anti-Hu, anti-Ri, anti-Yo and VKGCThymectomy, chemotherapy (cyclophosphamide, doxorubicin, cisplatin), rituximabe, PLEXProgressive cognitive deficits18 Khella (2007) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"0Xr5Qfcw","properties":{"formattedCitation":"(16)","plainCitation":"(16)"},"citationItems":[{"id":168,"uris":[""],"uri":[""],"itemData":{"id":168,"type":"article-journal","title":"Thymoma, myasthenia gravis, encephalitis, and a novel anticytoplasmic neuronal antibody","container-title":"Neurology","page":"1302-1303","volume":"69","issue":"12","source":"NCBI PubMed","DOI":"10.1212/01.wnl.0000276949.33134.cb","ISSN":"1526-632X","note":"PMID: 17875920","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Khella","given":"Sami L"},{"family":"Souyah","given":"Nizar"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2007",9,18]]},"PMID":"17875920"}}],"schema":""} (16) F, 41Headache, diplopia, nausea, dizziness. After 9 weeks: recent memory loss, neck weakness on flexion and extension, horizontal and down beating.14 weeks from symptoms onset: sudden worsening of true vertigo and dysphagia, hyper somnolence and gait ataxiaMyasthenia GravisAchR antibodiesBright signal on T2 weighted and FLAIR in the right globus palidus and substantia nigra and both thalami (no available figure)43 WBC (66% of lymphocytes)Negative OBNot reportedUnknown antigen.in Serum and CSF, Probably not exposed on cell surfacePrednisone 1mg per kg for 90 days, IVIg (350 g), PLEX and cyclophosphamideInitial partial responseDeath with 31 days19Gesundheit (2008) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8xHetnsn","properties":{"formattedCitation":"(17)","plainCitation":"(17)"},"citationItems":[{"id":68,"uris":[""],"uri":[""],"itemData":{"id":68,"type":"article-journal","title":"Sudden psychotic symptoms in a 28-year-old male with thymoma","container-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology","page":"4353-4355","volume":"26","issue":"26","source":"NCBI PubMed","DOI":"10.1200/JCO.2008.16.0879","ISSN":"1527-7755","note":"PMID: 18779623","journalAbbreviation":"J. Clin. Oncol.","language":"eng","author":[{"family":"Gesundheit","given":"Benjamin"},{"family":"Lerer","given":"Bernard"},{"family":"Budowski","given":"Einat"},{"family":"Neuman","given":"Tzahi"},{"family":"Gomori","given":"John M"},{"family":"Or","given":"Reuven"}],"issued":{"date-parts":[["2008",9,10]]},"PMID":"18779623"}}],"schema":""} (17)M, 28Hallucinations, incoherent speech,“bizarre” disorganized movements of the limbsNoShowed subtle mesial temporal hyperintensity on FLAIRNot reportedUnremarkableNot reportedThymectomyIVIgNo residual symptoms20Graus (2008) - patient 4 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"jgibt5sfa","properties":{"formattedCitation":"(18)","plainCitation":"(18)"},"citationItems":[{"id":32,"uris":[""],"uri":[""],"itemData":{"id":32,"type":"article-journal","title":"Neuronal surface antigen antibodies in limbic encephalitis: clinical-immunologic associations","container-title":"Neurology","page":"930-936","volume":"71","issue":"12","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE).\nMETHODS: Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE.\nRESULTS: NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04).\nCONCLUSIONS: In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies.","DOI":"10.1212/01.wnl.0000325917.48466.55","ISSN":"1526-632X","note":"PMID: 18794496","shortTitle":"Neuronal surface antigen antibodies in limbic encephalitis","journalAbbreviation":"Neurology","language":"eng","author":[{"family":"Graus","given":"F"},{"family":"Saiz","given":"A"},{"family":"Lai","given":"M"},{"family":"Bruna","given":"J"},{"family":"López","given":"F"},{"family":"Sabater","given":"L"},{"family":"Blanco","given":"Y"},{"family":"Rey","given":"M J"},{"family":"Ribalta","given":"T"},{"family":"Dalmau","given":"J"}],"issued":{"date-parts":[["2008",9,16]]},"PMID":"18794496"}}],"schema":""} (18) correspond to Lai (2009) - patient 5 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"Ejgqsa8D","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":19,"uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location","container-title":"Annals of neurology","page":"424-434","volume":"65","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.\nMETHODS: We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.\nRESULTS: Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.\nINTERPRETATION: Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.","DOI":"10.1002/ana.21589","ISSN":"1531-8249","note":"PMID: 19338055","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Lai","given":"Meizan"},{"family":"Hughes","given":"Ethan G"},{"family":"Peng","given":"Xiaoyu"},{"family":"Zhou","given":"Lei"},{"family":"Gleichman","given":"Amy J"},{"family":"Shu","given":"Huidy"},{"family":"Matà","given":"Sabrina"},{"family":"Kremens","given":"Daniel"},{"family":"Vitaliani","given":"Roberta"},{"family":"Geschwind","given":"Michael D"},{"family":"Bataller","given":"Luis"},{"family":"Kalb","given":"Robert G"},{"family":"Davis","given":"Rebecca"},{"family":"Graus","given":"Francesc"},{"family":"Lynch","given":"David R"},{"family":"Balice-Gordon","given":"Rita"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19338055"}}],"schema":""} (12)F, 41Behavior change, confusionNot reportedNot performed (diagnosis if limbic encephalitis performed on autopsy)15 WBCNot reportedCRMP-5 (CV-2) and NSA antibodies, later proved to be AMPAR Abs ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1qdtim4meu","properties":{"formattedCitation":"(12)","plainCitation":"(12)"},"citationItems":[{"id":19,"uris":[""],"uri":[""],"itemData":{"id":19,"type":"article-journal","title":"AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location","container-title":"Annals of neurology","page":"424-434","volume":"65","issue":"4","source":"NCBI PubMed","abstract":"OBJECTIVE: To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.\nMETHODS: We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.\nRESULTS: Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.\nINTERPRETATION: Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.","DOI":"10.1002/ana.21589","ISSN":"1531-8249","note":"PMID: 19338055","journalAbbreviation":"Ann. Neurol.","language":"eng","author":[{"family":"Lai","given":"Meizan"},{"family":"Hughes","given":"Ethan G"},{"family":"Peng","given":"Xiaoyu"},{"family":"Zhou","given":"Lei"},{"family":"Gleichman","given":"Amy J"},{"family":"Shu","given":"Huidy"},{"family":"Matà","given":"Sabrina"},{"family":"Kremens","given":"Daniel"},{"family":"Vitaliani","given":"Roberta"},{"family":"Geschwind","given":"Michael D"},{"family":"Bataller","given":"Luis"},{"family":"Kalb","given":"Robert G"},{"family":"Davis","given":"Rebecca"},{"family":"Graus","given":"Francesc"},{"family":"Lynch","given":"David R"},{"family":"Balice-Gordon","given":"Rita"},{"family":"Dalmau","given":"Josep"}],"issued":{"date-parts":[["2009",4]]},"PMID":"19338055"}}],"schema":""} (12)NoDeath (2 weeks)21Monstad (2009) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qvmKD0Fs","properties":{"formattedCitation":"(19)","plainCitation":"(19)"},"citationItems":[{"id":172,"uris":[""],"uri":[""],"itemData":{"id":172,"type":"article-journal","title":"CRMP5 antibodies found in a patient with limbic encephalitis and myasthenia gravis","container-title":"Journal of neurology, neurosurgery, and psychiatry","page":"241-242","volume":"80","issue":"2","source":"NCBI PubMed","abstract":"Collapsin response mediator protein 5 (CRMP5) antibodies are often associated with thymoma or small cell lung cancer and paraneoplastic syndromes such as limbic encephalitis (LE). A patient is described with myasthenia gravis who, following thymectomy and immunosuppression, acquired a viral infection and developed LE and increased levels of serum CRMP5 antibodies. The cognitive symptoms improved and CRMP5 antibody levels decreased after plasma exchange, suggesting that CRMP5 antibodies may have contributed to the development of LE.","DOI":"10.1136/jnnp.2008.149336","ISSN":"1468-330X","note":"PMID: 19151024","journalAbbreviation":"J. Neurol. Neurosurg. Psychiatr.","language":"eng","author":[{"family":"Monstad","given":"S E"},{"family":"N?stbakken","given":"J K"},{"family":"Vedeler","given":"C A"}],"issued":{"date-parts":[["2009",2]]},"PMID":"19151024"}}],"schema":""} (19)F,49Progressive loss of memory for recent eventsMGAchR antibodiesBilateral hippocampal lesions on FLAIR(after treatment)10 WBCNegative OBEpileptic discharges in both temporal lobesCRMP5Thymectomy, PLEXShort memory deficits22Hammound (2009) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"MLDzaDdx","properties":{"formattedCitation":"(20)","plainCitation":"(20)"},"citationItems":[{"id":78,"uris":[""],"uri":[""],"itemData":{"id":78,"type":"article-journal","title":"Multifocal paraneoplastic cortical encephalitis associated with myasthenia gravis and thymoma","container-title":"Archives of neurology","page":"1407-1409","volume":"66","issue":"11","source":"NCBI PubMed","abstract":"OBJECTIVES: To report a case of multifocal cortical encephalitis associated with thymoma and to establish an association of this thymoma-related paraneoplastic syndrome with voltage-gated potassium channel antibodies.\nDESIGN: Case report.\nSETTING: University hospital.\nPATIENT: A 43-year-old woman with a history of seropositive myasthenia gravis and successfully treated invasive thymoma. Four years after thymectomy, she presented with seizure and rapidly progressive confusion and aphasia. Myasthenia gravis remained in pharmacological remission. Magnetic resonance imaging of the brain showed innumerable cortically based signal abnormalities as well as extensive left mesial temporal lobe abnormality with minimal enhancement.\nRESULTS: Chest computed tomography showed abnormal pleural thickening of the left lung, which proved to be recurrent metastatic thymoma. Results of serological evaluation were positive for acetylcholine receptor, striational, and voltage-gated potassium channel antibodies. She showed partial improvement in response to immunotherapy and chemotherapy but ultimately died 2 months later of tumor complications.\nCONCLUSIONS: Thymoma and myasthenia gravis may be associated with other autoimmune neurological disorders including paraneoplastic encephalitis. This second case of thymoma-associated multifocal cortical encephalitis demonstrates that autoimmune encephalitis can extend to cortical regions outside the limbic system. Autoimmune encephalitis should be considered in the differential diagnosis of patients with myasthenia gravis or thymoma who develop new cognitive symptoms.","DOI":"10.1001/archneurol.2009.235","ISSN":"1538-3687","note":"PMID: 19901174","journalAbbreviation":"Arch. Neurol.","language":"eng","author":[{"family":"Hammoud","given":"Khaled"},{"family":"Kandimala","given":"Geetha"},{"family":"Warnack","given":"Worthy"},{"family":"Vernino","given":"Steven"}],"issued":{"date-parts":[["2009",11]]},"PMID":"19901174"}}],"schema":""} (20) F, 43Seizures (not refractory), confusion and rapidly progressive mutismMGAchR antibodiesNumerous cortically based signal abnormalities on FLAIR as well as extensive left mesial temporal lobe abnormality with minimal enhancement70 WBCprotein: 101 mg/dL with normal glucose levelIntermittent periodic lateralized epileptiform discharges in the left temporal regionVGKCThymectomy, radiation, chemotherapy, corticosteroids, IVIgDeath (2 months)23Rizzardi (2009) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"278vb8oer","properties":{"formattedCitation":"(21)","plainCitation":"(21)"},"citationItems":[{"id":37,"uris":[""],"uri":[""],"itemData":{"id":37,"type":"article-journal","title":"Paraneoplastic extra limbic encephalitis associated with thymoma","container-title":"Interactive cardiovascular and thoracic surgery","page":"755-756","volume":"9","issue":"4","source":"NCBI PubMed","abstract":"We report the case of a 55-year-old woman with thymoma diagnosed after finding of extra limbic encephalitis. She presented neurologic symptoms as seizure and aphasia; magnetic resonance imaging (MRI) of the brain showed multiple lesions located in insular, parietal and temporal lobes (in cortical and sub-cortical area). Brain biopsies confirmed the diagnosis of encephalitis and CT-scan of the thorax showed an anterior mediastinal mass suspected for thymoma. The patient was submitted to thymectomy through a median sternotomy and we assisted to secondary reduction of cerebral lesions and total remission of symptoms.","DOI":"10.1510/icvts.2009.211276","ISSN":"1569-9285","note":"PMID: 19622540","journalAbbreviation":"Interact Cardiovasc Thorac Surg","language":"eng","author":[{"family":"Rizzardi","given":"Giovanna"},{"family":"Campione","given":"Andrea"},{"family":"Scanagatta","given":"Paolo"},{"family":"Terzi","given":"Alberto"}],"issued":{"date-parts":[["2009",10]]},"PMID":"19622540"}}],"schema":""} (21)F, 55Seizure and aphasiaNoT2/FLAIR multiple lesions located in insular, parietal andtemporal lobes (in cortical and sub-cortical area) including limbic and extra limbic systemNormalFocal epileptic discharges in temporal-parietal left regionNoThymectomy, RadiationNo residual symptoms and disease free24Werry (2009) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"vuuTSyPB","properties":{"formattedCitation":"(22)","plainCitation":"(22)"},"citationItems":[{"id":170,"uris":[""],"uri":[""],"itemData":{"id":170,"type":"article-journal","title":"Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG antineuronal antibodies in a patient with thymoma","container-title":"Journal of neurology","page":"129-131","volume":"256","issue":"1","source":"NCBI PubMed","DOI":"10.1007/s00415-009-0826-1","ISSN":"1432-1459","note":"PMID: 19267170","journalAbbreviation":"J. Neurol.","language":"eng","author":[{"family":"Werry","given":"C"},{"family":"G?tz","given":"F"},{"family":"Wurster","given":"U"},{"family":"Stangel","given":"M"},{"family":"Giess","given":"R"},{"family":"Heidenreich","given":"F"},{"family":"Windhagen","given":"A"}],"issued":{"date-parts":[["2009",1]]},"PMID":"19267170"}}],"schema":""} (22)M, 32 Vertigo, diplopia and nystagmus, clumsiness of the left hand, olfactory disturbances, progressive gait ataxia, myoclonic jerkingMG developed after encephalitisMRI1: normalMRI 2(4 weeks later): spots of cortical hyperintensity of the insula bilaterally, the medial right temporal lobe and in the left parieto-occipital region on T2-weighted images. No contrast enhancement.CSF (1): 4 WBC Protein 58 mg/dL Negative OBCSF (2): 25WBC Protein: 65 mg/dLShowed epileptic changesCRMP-5Corticosteroids, Thymectomy, PLEX, IVIgAlmost complete recovery except for complaints of headache, fatigue. After on year developed diplopia and ptosis and was diagnosed as MG25Erkmen (2010) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"LQHr5uXO","properties":{"formattedCitation":"(23)","plainCitation":"(23)"},"citationItems":[{"id":31,"uris":[""],"uri":[""],"itemData":{"id":31,"type":"article-journal","title":"Thymoma-associated paraneoplastic encephalitis (TAPE): diagnosis and treatment of a potentially fatal condition","container-title":"The Journal of thoracic and cardiovascular surgery","page":"e17-20","volume":"141","issue":"2","source":"NCBI PubMed","DOI":"10.1016/j.jtcvs.2010.10.022","ISSN":"1097-685X","note":"PMID: 21167513","shortTitle":"Thymoma-associated paraneoplastic encephalitis (TAPE)","journalAbbreviation":"J. Thorac. Cardiovasc. Surg.","language":"eng","author":[{"family":"Erkmen","given":"Cherie Parungo"},{"family":"Fadul","given":"Camilo E"},{"family":"Dalmau","given":"Josep"},{"family":"Erkmen","given":"Kadir"}],"issued":{"date-parts":[["2011",2]]},"PMID":"21167513"}}],"schema":""} (23)M, 61Seizure, memory lossNoBilateral foci of cortical and subcortical non-enhancing signal abnormalities on T2 weighted imagesLymphocytic pleocytosisNot reportedLGI1Thymectomy, radiation, methylprednisolone, IVIgNo residual symptoms and disease free26Miyasaki (2012) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"FijKn2nC","properties":{"formattedCitation":"(14,24)","plainCitation":"(14,24)"},"citationItems":[{"id":145,"uris":[""],"uri":[""],"itemData":{"id":145,"type":"article-journal","title":"Paraneoplastic encephalitis associated with myasthenia gravis and malignant thymoma","container-title":"Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia","page":"336-338","volume":"19","issue":"2","source":"NCBI PubMed","abstract":"We present a patient with type B2 thymoma (World Health Organization Thymoma Classification) with the complications of anti-muscle acetylcholine receptor antibody-positive myasthenia gravis and anti-voltage-gated potassium channel antibodies associated with paraneoplastic encephalitis. A timing difference between the onset of these neurological disorders and a dissociation of clinical symptoms was observed during the disease. This report alerts clinicians that long-term follow-up is needed where patients have a residual thymoma and attention should be paid to other concomitant autoimmune disorders.","DOI":"10.1016/j.jocn.2011.05.026","ISSN":"1532-2653","note":"PMID: 22227397","journalAbbreviation":"J Clin Neurosci","language":"eng","author":[{"family":"Miyazaki","given":"Yu"},{"family":"Hirayama","given":"Masaaki"},{"family":"Watanabe","given":"Hirohisa"},{"family":"Usami","given":"Noriyasu"},{"family":"Yokoi","given":"Kohei"},{"family":"Watanabe","given":"Osamu"},{"family":"Sobue","given":"Gen"}],"issued":{"date-parts":[["2012",2]]},"PMID":"22227397"}},{"id":1308,"uris":[""],"uri":[""],"itemData":{"id":1308,"type":"article-journal","title":"Identification and Characterization of GABAA Receptor Autoantibodies in Autoimmune Encephalitis","container-title":"Journal of Neuroscience","page":"8151-8163","volume":"34","issue":"24","source":"CrossRef","DOI":"10.1523/JNEUROSCI.4415-13.2014","ISSN":"0270-6474, 1529-2401","language":"en","author":[{"family":"Ohkawa","given":"T."},{"family":"Satake","given":"S."},{"family":"Yokoi","given":"N."},{"family":"Miyazaki","given":"Y."},{"family":"Ohshita","given":"T."},{"family":"Sobue","given":"G."},{"family":"Takashima","given":"H."},{"family":"Watanabe","given":"O."},{"family":"Fukata","given":"Y."},{"family":"Fukata","given":"M."}],"issued":{"date-parts":[["2014",6,11]]},"accessed":{"date-parts":[["2014",6,13]]}}}],"schema":""} (14,24)M, 46Subacute onset of aphasia, visual hallucination,and generalized seizures with delirium; residual thymomaMG AchR antibodiesAxial T2-weighted brain MR image showing multifocal signal abnormalityProtein: 60 mg/dLElectroencephalogram showed diffuse slow wave back- ground and theta (h) waves with epileptic discharges dominant in the left temporal lobeVGKC (LGI1)Anti-GABAaR ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"847j3tjlr","properties":{"formattedCitation":"(14)","plainCitation":"(14)"},"citationItems":[{"id":1308,"uris":[""],"uri":[""],"itemData":{"id":1308,"type":"article-journal","title":"Identification and Characterization of GABAA Receptor Autoantibodies in Autoimmune Encephalitis","container-title":"Journal of Neuroscience","page":"8151-8163","volume":"34","issue":"24","source":"CrossRef","DOI":"10.1523/JNEUROSCI.4415-13.2014","ISSN":"0270-6474, 1529-2401","language":"en","author":[{"family":"Ohkawa","given":"T."},{"family":"Satake","given":"S."},{"family":"Yokoi","given":"N."},{"family":"Miyazaki","given":"Y."},{"family":"Ohshita","given":"T."},{"family":"Sobue","given":"G."},{"family":"Takashima","given":"H."},{"family":"Watanabe","given":"O."},{"family":"Fukata","given":"Y."},{"family":"Fukata","given":"M."}],"issued":{"date-parts":[["2014",6,11]]},"accessed":{"date-parts":[["2014",6,13]]}}}],"schema":""} (14)Corticosteroids and IVIg; AEDEpileptic seizures disappeared; severe cognitive impairment and psychological symptoms remained27Shaulov (2012) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"un9viYVd","properties":{"formattedCitation":"(25)","plainCitation":"(25)"},"citationItems":[{"id":77,"uris":[""],"uri":[""],"itemData":{"id":77,"type":"article-journal","title":"Myasthenia gravis appearing 18 years after resection of benign thymoma with subsequent limbic encephalitis","container-title":"Journal of the neurological sciences","page":"146-147","volume":"317","issue":"1-2","source":"NCBI PubMed","abstract":"Thymoma is associated with multiple autoimmune disorders, most commonly myasthenia gravis (MG). However, symptomatic MG may first present following thymectomy. We report an unusual patient with paraneoplastic limbic encephalitis diagnosed a few months after total thymectomy for asymptomatic thymoma, followed 18 years later by the onset of symptomatic MG without evidence of tumor recurrence.","DOI":"10.1016/j.jns.2012.03.007","ISSN":"1878-5883","note":"PMID: 22483854","journalAbbreviation":"J. Neurol. Sci.","language":"eng","author":[{"family":"Shaulov","given":"Adir"},{"family":"Rottenstreich","given":"Misgav"},{"family":"Peleg","given":"Hagit"},{"family":"Spiegel","given":"Maya"},{"family":"Shichman","given":"Boris"},{"family":"Argov","given":"Zohar"}],"issued":{"date-parts":[["2012",6,15]]},"PMID":"22483854"}}],"schema":""} (25)F, 66Short term memory loss, grand mal seizureMG AchR antibodiesMultiple T2 weighted high signal hiperintensities in the hippocampi bilaterally, with no enhancement with gadoliniumNormalNormalNegative anti-HUThymectomy, AEDNo residual symptoms developed MG 18 years after encephalitis.28Aysal (2013) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1jOEwaS3","properties":{"formattedCitation":"(26)","plainCitation":"(26)"},"citationItems":[{"id":120,"uris":[""],"uri":[""],"itemData":{"id":120,"type":"article-journal","title":"Paraneoplastic extralimbic encephalitis associated with thymoma and myastenia gravis: three years follow up","container-title":"Clinical neurology and neurosurgery","page":"628-631","volume":"115","issue":"5","source":"NCBI PubMed","DOI":"10.1016/j.clineuro.2012.06.016","ISSN":"1872-6968","note":"PMID: 22771306","shortTitle":"Paraneoplastic extralimbic encephalitis associated with thymoma and myastenia gravis","journalAbbreviation":"Clin Neurol Neurosurg","language":"eng","author":[{"family":"Aysal","given":"F"},{"family":"Baybas","given":"S"},{"family":"Sel?uk","given":"H H"},{"family":"Sozmen","given":"V"},{"family":"Ozturk","given":"M"},{"family":"Kucukoglu","given":"H"},{"family":"Urer","given":"N H"}],"issued":{"date-parts":[["2013",5]]},"PMID":"22771306"}}],"schema":""} (26)M, 433 secondarily generalized tonic-clonic seizureRefractory complex partial seizures MGAchR antibodiesHyper intense lesions on T2/FLAIR on the left temporo-parietal, left insular, left frontal subcortical white matter, and the right hippocampus without contrast enhancementNormalBackground activity was disorganized (7-9 Hz)Negative for VGKCIVIg, thymectomy, DAENo residual symptoms29Suh (2013) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"CIEP4pvl","properties":{"formattedCitation":"(27)","plainCitation":"(27)"},"citationItems":[{"id":53,"uris":[""],"uri":[""],"itemData":{"id":53,"type":"article-journal","title":"Paraneoplastic encephalitis associated with thymoma: a case report","container-title":"The Korean journal of thoracic and cardiovascular surgery","page":"234-236","volume":"46","issue":"3","source":"NCBI PubMed","abstract":"A 42-year-old woman with short-term memory loss visited Gangnam Severance Hospital, and her chest X-ray and computed tomography revealed a right anterior mediastinal mass. On hospital day two, she suddenly presented personality changes and a drowsy mental status, so she required ventilator care in the intensive care unit. She underwent thymectomy, and was pathologically diagnosed with thymoma, type B1. Her mental status eventually recovered by postoperative day 90. Paraneoplastic encephalopathy associated with thymoma is very rare, and symptoms can be improved by thymectomy. We report a case of paraneoplastic encephalopathy associated with a thymoma.","DOI":"10.5090/kjtcs.2013.46.3.234","ISSN":"2233-601X","note":"PMID: 23772416","shortTitle":"Paraneoplastic encephalitis associated with thymoma","journalAbbreviation":"Korean J Thorac Cardiovasc Surg","language":"eng","author":[{"family":"Suh","given":"Jee Won"},{"family":"Haam","given":"Seok Jin"},{"family":"Song","given":"Suk Won"},{"family":"Shin","given":"Yu Rim"},{"family":"Paik","given":"Hyo Chae"},{"family":"Lee","given":"Doo Yun"}],"issued":{"date-parts":[["2013",6]]},"PMID":"23772416"}}],"schema":""} (27)F, 42Short-term memory loss, personality changes and severe agitationMGAchR antibodiesMultifocal high intensity signals in the cerebral cortex including the limbic area on T2 flare imagesNot reportedDiffuse delta background activity and moderate diffuse cerebral dysfunctionNegative for anti-Hu, anti-Ri and anti-YoThymectomy, radiotherapyNo residual symptoms30 Alexopoulos (2014) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"j6uodh48h","properties":{"formattedCitation":"(28)","plainCitation":"(28)"},"citationItems":[{"id":2406,"uris":[""],"uri":[""],"itemData":{"id":2406,"type":"article-journal","title":"Autoimmune encephalitis with GABAB antibodies, thymoma, and GABAB receptor thymic expression","container-title":"Neurology? Neuroimmunology & Neuroinflammation","volume":"1","issue":"4","source":"PubMed Central","URL":"","DOI":"10.1212/NXI.0000000000000039","ISSN":"2332-7812","note":"PMID: 25364773\nPMCID: PMC4215391","journalAbbreviation":"Neurol Neuroimmunol Neuroinflamm","author":[{"family":"Alexopoulos","given":"Harry"},{"family":"Dagklis","given":"Ioannis E."},{"family":"Akrivou","given":"Sofia"},{"family":"Bostantjopoulou","given":"Sevasti"},{"family":"Dalakas","given":"Marinos C."}],"issued":{"date-parts":[["2014",10,29]]},"accessed":{"date-parts":[["2014",12,4]]},"PMID":"25364773","PMCID":"PMC4215391"}}],"schema":""} (28)M, 25Recurrent episodes of vertigo, dizziness, hiccups, nausea, and vomiting, tongue myoclonusNormal10 WBC, protein 85, normal glucosePositive OBNormalHu, CV2, GABAbThymectomy, oral prednisolone, PLEX, corticosteroids, azathioprineSlight dizziness and vertigo in the supine position FootnotesAchR antibodies to acetylcholine receptors; AED, anti-epileptic drugs; ANNA-1, type-1 anti-neuronal nuclear antibody; anti-neuronal Ab, anti-neuronal antibodies; AMPAR Abs , α -amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies; ANA, antinuclear antibody; CRMP5, collapsin response mediator; CSF, cerebrospinal fluid; EEG, electroencephalogram; FLAIR, fluid attenuated inversion recovery; GAD, glutamic acid decarboxylase;ISAb, intrathecal synthesis of antibodies, IVIg, intravenous immunoglobulin G; LGI1, Leucine-rich Glioma Inactivated 1; MMSE, Mini-Mental State Examination; MRI, magnetic ressonance imaging; NSA, novel surface antigens; OB, oligoclonal bands; PLEX, plasma exchange; VGKC, Voltage-gated potassium channel antibody; WBC, white blood cell count; a This patient had thymic carcinomaeTable References: ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1. McArdle JP, Millingen KS. Limbic encephalitis associated with malignant thymoma. Pathology (Phila). 1988 Jul;20(3):292–295. 2. Ingenito GG, Berger JR, David NJ, Norenberg MD. Limbic encephalitis associated with thymoma. Neurology. 1990 Feb;40(2):382. 3. Cunningham JD, Burt ME. Limbic encephalitis secondary to malignant thymoma. Ann Thorac Surg. 1994 Jul;58(1):250–251. 4. Antoine JC, Honnorat J, Anterion CT, Aguera M, Absi L, Fournel P, et al. Limbic encephalitis and immunological perturbations in two patients with thymoma. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):706–710. 5. Evoli A, Lo Monaco M, Marra R, Lino MM, Batocchi AP, Tonali PA. Multiple paraneoplastic diseases associated with thymoma. Neuromuscul Disord NMD. 1999 Dec;9(8):601–603. 6. Evoli A, Minicuci GM, Vitaliani R, Battaglia A, Marca GD, Lauriola L, et al. Paraneoplastic diseases associated with thymoma. J Neurol. 2007 Jun 1;254(6):756–762. 7. Rickman OB, Parisi JE, Yu Z, Lennon VA, Vernino S. 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