[PMC free article] [PubMed] [Google Scholar] 19. 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 Rabbit polyclonal to HPN clinical improvement (= 0.04). Conclusions: 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 BMS-747158-02 patients with NSA-ab than in those without antibodies. GLOSSARY GAD = glutamic acid decarboxylase; LE = limbic encephalitis; NMDAR = N-methyl-D-aspartate receptor; NSA = neuronal surface antigens; nNSA = novel NSA; SCLC = small-cell lung cancer; VGKC = voltage-gated potassium channels; WBC = white blood cells. Limbic encephalitis (LE) was initially identified as a paraneoplastic neurologic syndrome characterized by subacute onset of short-term memory loss, seizures, psychiatric changes, and neuroradiological or pathologic evidence of involvement of the amygdala and medial aspect of temporal lobes.1 Paraneoplastic LE usually associates with onconeural antibodies that help to confirm the diagnosis and guide in the search of the tumor.2 However, a significant proportion of patients with paraneoplastic LE do not present onconeural antibodies.1 BMS-747158-02 Recent studies using new techniques to detect neuronal antibodies against neuronal surface antigens (NSA) identified serum antibodies against voltage-gated potassium channels (VGKC) in a group of LE patients who usually do not develop cancer3 and anti-NMDA receptor antibodies (NMDAR-ab) in young women with ovarian teratoma and an encephalitis that involves neural structures beyond the limbic system.4 In the present study, we analyzed the presence of NSA antibodies BMS-747158-02 (NSA-ab) using neuronal cultures in a series of 45 patients with paraneoplastic or idiopathic LE with the aim to identify new clinical-immunologic associations. METHODS Patients. We review all patients with final diagnosis of LE whose serum was sent to our laboratory (Barcelona, Spain) between 2000 and 2007 for analysis of antineuronal antibodies. LE was BMS-747158-02 defined by the subacute onset of short-term memory loss, behavior change, seizures, and involvement of the temporal lobes by EEG, imaging studies, or postmortem examination.2 LE was considered definite paraneoplastic if a tumor was diagnosed or the serum presented well characterized onconeural antibodies.2 The diagnosis of definite idiopathic LE required the absence of cancer and well characterized onconeural antibodies, and a follow-up of at least 3 years. LE patients with a shorter follow-up were classified as possible idiopathic LE. The information was from forms filled out from the referring neurologists, telephone interviews, and review of the medical records. Nineteen (42%) individuals were personally seen by at least one of the authors. Immunologic studies. BMS-747158-02 Onconeural antibodies (Hu, Yo, Ri, CV2, Ma2, amphiphysin, Tr, ZIC4, ANNA3, PCA2) were screened by immunohistochemistry performed on freezing sections of paraformaldehyde-perfuse rat cerebellum using an avidin-biotin immunoperoxidase technique and confirmed by immunoblot when indicated.5 NSA-ab were identified by immunocytochemistry of rat hippocampal neuronal cultures as previously described.4 Briefly, live neurons grown on coverslips were incubated with the individuals serum (dilution 1:400) or CSF (1:10) for 1 hour at 37C, washed, fixed with 4% paraformaldehyde, and immunoreacted with anti-human IgG Alexa Fluor secondary antibody (Molecular Probes, Eugene, OR). Results were photographed under a fluorescence microscope using Zeiss Axiovision software (Zeiss, Thornwood, NY). To confirm the specificity of the neuronal reactivity, all positive samples were preabsorbed.