BACKGROUND AND OBJECTIVES: Autoimmune encephalitis (AE) refers to a heterogenous group of inflammatory CNS diseases. Subgroups with specified neural autoantibodies are more homogeneous in presentation, trigger factors, outcome, and response to therapy. However, a considerable fraction of patients has AE features but does not harbor detectable autoantibodies and is referred to as antibody-negative AE. Our aim was to describe clinical features, trigger factors, treatments, and outcome of a cohort of comprehensively tested antibody-negative AE patients. METHODS: This retrospective monocentric study recruited adult patients whose serum and/or CSF was sent to our tertiary center for neural antibody testing between 2011 and 2020, who entered the diagnostic algorithm as possible antibody-negative AE and had the following: (1) probable antibody-negative AE, definite antibody-negative acute disseminated encephalomyelitis (ADEM), or definite autoimmune limbic encephalitis (LE) according to diagnostic criteria; (2) available data on MRI of the brain, CSF, and EEG; and (3) stored serum and/or CSF samples. These samples were reanalyzed using a comprehensive combination of cell-based and tissue-based assays. RESULTS: Of 2,250 patients tested, 33 (1.5%) were classified as possible antibody-negative AE. Of these, 5 were found to have antibodies by comprehensive testing, 5 fulfilled the criteria of probable AE (3F:2M, median age 67, range 42-67), 4 of definite autoimmune LE (2F:2M, median age 45.5, range 27-60 years), one of definite antibody-negative ADEM, 2 of Hashimoto encephalopathy, one had no samples available for additional testing, and 15 had no further categorization. Of 10 probable/definite AE/LE/ADEM, one had a malignancy and none of them received an alternative diagnosis until the end of follow-up (median 18 months). In total, 80% (8/10) of patients received immunotherapy including corticosteroids, and 6/10 (60%) patients received rituximab, azathioprine, cyclophosphamide, plasma exchange, or IV immunoglobulins. Five (50%) patients improved, one (10%) stabilized, one (10%) worsened, and 3 (30%) died. All deaths were considered to be related to encephalitis. We did not observe differences of immunotherapy-treated patients in likelihood of improvement with or without nonsteroidal immunotherapy (with 2/6, without 1/2). DISCUSSION: Antibody-negative AE should be diagnosed only after comprehensive testing. Diagnostic effort is important because many patients benefit from immunotherapy and some have malignancies.

• MeSH
• autoimunitní nemoci nervového systému * diagnóza   terapie   MeSH
• autoimunitní nemoci MeSH
• autoprotilátky MeSH
• dospělí MeSH
• encefalitida * diagnóza   terapie   MeSH
• Hashimotova nemoc MeSH
• lidé středního věku MeSH
• lidé MeSH
• limbická encefalitida MeSH
• nádory * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH

BACKGROUND AND PURPOSE: The aim was to report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: The clinical records of 163 patients with LE were reviewed. Immunohistochemistry on rat brain, cultured neurons and cell-based assays were used to identify neuronal autoantibodies. Patients were included if (i) there was adequate clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging information to classify the syndrome as LE, (ii) magnetic resonance images were accessible for central review and (iii) serum and CSF were available and were confirmed negative for neuronal antibodies. RESULTS: Twelve (7%) of 163 LE patients [median age 62 years; range 40-79; 9 (75%) male] without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short-term memory leading to hospital admission in a few weeks (median time 2 weeks; range 0.5-12). In four patients the short-term memory dysfunction remained as an isolated symptom during the entire course of the disease. Seizures, drowsiness and psychiatric problems were unusual. Four patients had solid tumors (one lung, one esophagus, two metastatic cervical adenopathies of unknown primary tumor) and one chronic lymphocytic leukemia. CSF showed pleocytosis in seven (58%) with a median of 13 white blood cells/mm3 (range 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins and combinations of both drugs or with rituximab. Clinical improvement occurred in six (54%) of 11 assessable patients. CONCLUSIONS: Despite the discovery of new antibodies, 7% of LE patients remain seronegative. Antibody-negative LE is more frequent in older males and usually develops with predominant or isolated short-term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy.

• Klíčová slova
• antibodies, autoimmune, limbic encephalitis, paraneoplastic,
• MeSH
• autoantigeny imunologie   MeSH
• autoprotilátky analýza   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• imunoterapie MeSH
• krátkodobá paměť MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• leukocytóza MeSH
• leukocyty imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• limbická encefalitida imunologie   psychologie   terapie   MeSH
• magnetická rezonanční tomografie MeSH
• nádory komplikace   MeSH
• neurony imunologie   MeSH
• poruchy paměti etiologie   psychologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH