Examples of antibodies associated with paraneoplastic limbic encephalitis include Hu (ANNA-1), Ma2, CV2/CRMP5, AMPA receptor, GABAB, GluR5, and NMDA receptor.4, 5 GABABR antibodyCassociated encephalitis was first described in 2010 2010 in a retrospective evaluation of serum and CSF from patients suspected to have limbic encephalitis.6 Since then, several case series have been published further characterizing the disorder. 7C10 While patients may test positive for additional autoantibodies, it is the GABAB receptor antibody that is believed to confer the symptoms associated with paraneoplastic limbic encephalitis (PLE). small cell cancer presenting with PLE. strong class=”kwd-title” KEY WORDS: paraneoplastic, limbic encephalitis, thymic small cell carcinoma, GABABR antibody CASE PRESENTATION A 55-year-old male with a history of coronary artery disease, tobacco abuse, and anxiety presented with an episode of bilateral upper and lower extremity tremor associated with loss of consciousness and subsequent hour-long period of confusion. He was diagnosed with a Gatifloxacin hydrochloride benzodiazepine withdrawal seizure and he was discharged on levetiracetam. Over the following days, the patients wife observed that he continued to have difficulty conversing as well as ongoing sleep disturbance, agitation, and hallucinations. He was readmitted and a lumbar puncture was performed which showed a monocytic pleocytosis. CSF culture and meningitis/encephalitis nucleic acid detection screening were unfavorable?for infectious etiology. EEG revealed epileptiform abnormalities in bilateral temporal lobes and a brief electrographic seizure in the right temporal region. Brain MRI showed a small meningioma and symmetric T2 prolongation within the hippocampi without abnormal enhancement. CT chest showed conglomerate lymphadenopathy encasing the pulmonary artery, right hilar Gatifloxacin hydrochloride lymphadenopathy, and a peripheral left lung mass that seemed to be consistent with a hamartoma. Mediastinoscopy and lymph node (LN) biopsy were performed. Post-operatively, the patient continued to be combative and agitated with hallucinations. He was intubated for airway protection and transferred to our hospital for further care. On admission, he had normal vital signs. He was awake but not oriented and unable to follow commands. Neurologic exam was notable for dysarthria and global aphasia with perseveration. Viral screening and rheumatologic Rabbit Polyclonal to OR2AT4 screening were unremarkable (Table ?(Table1).1). A serum autoimmune evaluation panel was notable for GABAB receptor Ab (GABABR) positivity (Mayo Medical Laboratories) (Table ?(Table2).2). Additionally, a CSF autoimmune evaluation panel was positive for GABABR Ab with a 1:256 titer (normal ?1:2)(Mayo Medical Laboratories). Pathology from your excisional mediastinal LN biopsy showed linens of neoplastic cells with scant cytoplasm, high nuclear to cytoplasm ratio, and round to oval nuclei Gatifloxacin hydrochloride with irregular nuclear membrane (Fig. ?(Fig.1).1). Tumor necrosis and ?60 mitotic figures/10 high-power fields were also present. IHC staining was positive for AE1/AE3, synaptophysin, CD56, and PAX-8, and unfavorable for chromogranin-A and TTF-1. Additional in-house staining showed positivity to p-40, CD5, and CK5/6. Morphology, strong diffusely positive CD56 and synaptophysin IHC staining and unfavorable IHC staining for p-40 and CK 5/6 were consistent with a diagnosis of small cell carcinoma. Positive PAX-8 staining in combination with unfavorable TTF-1 staining was consistent with thymic origin of small cell carcinoma. Table 1 Viral Screening and Rheumatologic Screening thead th rowspan=”1″ colspan=”1″ Test Name /th th rowspan=”1″ colspan=”1″ Test result /th /thead Hepatitis serology (A-C)NegativeEpstein Barr computer virus (EBV)NegativeCytomegalovirus (CMV)NegativeHerpes Simplex Computer virus (HSV)NegativeHIVNegativeDS-DNANegativeRheumatoid Factor (RF)NegativeSCL-70 antibodyNegativeAnti-Smith antibodyNegativeSS-A/Ro antibodyNegativeSS-B/La antibodyNegativeAntineutrophil antibody (ANA)NegativeAntineutrophil cytoplasmic antibodies (ANCA)Unfavorable Open in a separate window Table 2 Mayo Medical center Laboratories?Encephalopathy, Autoimmune Evaluation Panel (Serum) thead th colspan=”2″ rowspan=”1″ Test name /th /thead GAD65 Ab, SAnti-neuronal nuclear Ab, type 1NMDA-R Ab CBA, SAnti-neuronal nuclear Ab type 2Neuronal (V-G) K+ channel Ab, SAnti-neuronal nuclear Ab type 3LGI1-IgG CBA, SAnti-glial nuclear Ab, type 1CASPR2-IgG CBA, SPurkinje cell cytoplasmic Ab type 1GABA-B-R Ab CBA, SPurkinje cell cytoplasmic Ab type 2AMPA-R Ab, CBA, SPurkinje cell cystoplasmic Ab type TrAmphiphysin Ab, SN-type calcium channel AbCRMP-5-IgG, SP/Q-type calcium channel AbAChR ganglionic neuronal Ab, SAch receptor (muscle mass)-binding Ab Open in a separate window Open in a separate window Physique 1 Excisional mediastinal lymph node biopsy. a H&E, ?40, with mitotic figure (arrow) and linens of neoplastic cells with round to oval nuclei and high N/C ratio. b Strongly positive CD 56; representative of neuroendocrine differentiation. c Strongly positive synaptophysin staining; representative of neuroendocrine differentiation. d Positive PAX-8 staining favoring thymic carcinoma rather than lung carcinoma. The patient was treated with two courses of IVIG, plasma exchange, and two doses of rituximab with the goal of reducing autoantibody titers. Gatifloxacin hydrochloride Four cycles of cisplatin plus etoposide chemotherapy were administered to treat the underlying malignancy with the intention of treating the inciting etiology. He continued to have episodes of agitation and hallucinations, requiring intermittent restraints, constant.
