Help the AANPA Inform Medicare About Remaining NPI Problems

Background/Objective: We reported that 43% of patients with Lambert-Eaton myasthenic syndrome (LEMS) and small cell lung cancer (SCLC) had an antibody called anti-glial nuclear antibody (AGNA), defined by the immunoreaction with the nuclei of the Bergmann glia of the cerebellum. This study was undertaken to identify the antigen recognized by AGNA and to confirm the association with paraneoplastic LEMS in a larger series.Methods: We probed a fetal brain cDNA library with AGNA-positive sera. The presence of antibodies against the isolated antigen was detected by immunoblot of phage plaques from two positive clones. We studied 105 patients with LEMS (55 with SCLC), 50 with paraneoplastic neurologic syndromes, SCLC, and Hu antibodies, and 50 with only SCLC.Results: Probing of the fetal brain expression library with AGNA sera resulted in the isolation of SOX1, a highly immunogenic tumor antigen in SCLC. IgG eluted from SOX1 clones produced the same cerebellar immunoreactivity as of AGNA sera. SOX1 antibodies were present in 64% of patients with LEMS and SCLC but in none of the 50 with idiopathic LEMS (p < 0.0001). Compared with paraneoplastic LEMS, the frequency of SOX1 antibodies was significantly lower in patients with Hu antibodies (32%, p = 0.002) and in those with only SCLC (22%).Conclusions: SOX1 is the antigen recognized by anti-glial nuclear antibody-positive sera. The detection of SOX1 antibodies in patients with Lambert-Eaton myasthenic syndrome (LEMS) predicts the presence of small cell lung cancer and may be used to follow more closely those LEMS patients with no evidence of cancer at the initial workup.(C)2008AAN Enterprises, Inc.

The identification of many disease-causing and condition-predisposing gene variants has opened the door to genetic testing in the neurology clinic. Clinical genetic testing is complex, as each patient and family, disease, and test has unique complicating features. In this chapter, the clinical scenarios in which gene tests might be used are described in detail, along with a general description of the potential risks and benefits of their use in each situation. Online genetic testing resources are provided, as printed materials are often outdated in this rapidly changing field.(C) 2008 American Academy of Neurology

This review summarizes the clinical and genetic features of some of the mendelian and mitochondrial disorders associated with ischemic and hemorrhagic stroke and cerebrovascular malformations. For some conditions, such as sickle cell anemia and Fabry disease, specific diagnosis is important because there are proven disease-specific treatments. For other conditions that have as yet no proven disease-specific treatments, such as cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL) and mitochondrial encephalopathy with lactic acidosis and strokelike symptoms (MELAS), a diagnosis has prognostic value and avoids exposing patients to unnecessary, potentially harmful therapeutic agents and diagnostic tests. The genetics of common stroke is also briefly reviewed.(C) 2008 American Academy of Neurology