Progress in autoimmune epileptic encephalitis

Purpose of review Autoimmune epileptic encephalopathy is a potentially treatable neurological syndrome characterized by the coexistence of a neuronal antibody in serum and, often, cerebrospinal fluid. Patients present with combinations of seizures, neuropsychiatric features, movement disorder, and cognitive decline, but some patients have isolated seizures either at first presentation or during their illness. This review summarizes our current understanding of the roles of specific neuronal antibodies in epilepsy-related syndromes and aims to aid the clinician in diagnosis and treatment. Recent findings Antigen discovery methods in three neuroimmunology centres independently identified antibodies to different subunits of the γ amino butyric acid-A receptor; high levels of these antibodies were found mainly in patients with severe refractory seizures. These and other antibodies were also found in a proportion (<10%) of children and adults with epilepsy. A clinical study comparing immunotherapy in patients with autoantibodies or without an identified target antigen found neuroinflammatory features were predictive of a therapeutic response. New in-vitro and in-vivo studies, and spontaneous animal models, have confirmed the pathogenicity and epileptogenicity of neuronal antibodies and their relevance to other mammals. Summary Neuronal antibodies are an important cause of autoimmune epileptic encephalopathy, early recognition is important as there may be an underlying tumour, and early treatment is associated with a better outcome. In the absence of an antibody, the clinician should adopt a pragmatic approach and consider a trial of immunotherapy when other causes have been excluded

Total gastrectomy with simultaneous pancreaticosplenectomy or splenectomy in patients with advanced gastric carcinoma

A splenectomy or distal pancreaticosplenectomy is often performed simultaneously with total gastrectomy in the treatment of gastric carcinoma to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. However, the negative impact of splenectomy and pancreaticosplenectomy has also been reported. A retrospective analysis was performed to evaluate the outcomes of distal pancreaticosplenectomy and total gastrectomy, splenectomy and total gastrectomy, and gastrectomy alone in the patients with advanced gastric carcinoma without distant metastasis. Prognostic factors were examined. No significant differences existed in 5-year survival in the patients who underwent gastrectomy with splenectomy, gastrectomy with distal pancreaticosplenectomy, or gastrectomy alone. Neither splenectomy, nor distal pancreaticosplenectomy were prognostic factors. However, distal pancreaticosplenectomy was an independent predictor of pancreatic fistula. In conclusion, the addition of distal pancreaticosplenectomy or splenectomy to total gastrectomy for gastric cancer increases the risk of severe complications, but does not improve survival. © 1999 Cancer Research Campaig

Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity

Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. Here, we show that in preclinical autoimmunity and established systemic lupus erythematosus, plasmacytoid dendritic cells are not effector cells, have lost capacity for Toll-like-receptor-mediated cytokine production and do not induce T cell activation, independent of disease activity and the blood interferon signature. In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity