Significant improvement in paraneoplastic neurological syndromes without identifiable anti-neural antibodies in patients with breast cancer after breast surgery.

Paraneoplastic neurological syndromes (PNS) are neurological disorders that occur in close association with tumors without direct metastasis or invasion of the tumors and in which anti-neural antibodies may be present. Cerebellar ataxia is a common form of PNS in patients with breast cancer. However, reports of symptom improvement with breast cancer treatment are more common in patients with positive anti-neural antibodies and are rarely seen in those with negative anti-neural antibodies. In addition, there have been few quantitative evaluations of symptom improvement. We report a case in which neurological symptoms significantly improved after surgical treatment for breast cancer. The patient was a 78-years-old woman with subacute progressive cerebellar ataxia. A subsequent diagnosis of breast cancer led to the diagnosis of "PNS probable". A comprehensive search for anti-neural antibodies was negative in all cases. The quantitative index of the Scale for the Assessment and Rating of Ataxia (SARA) score, a standard evaluation method for ataxia in spinocerebellar degeneration, improved after breast cancer surgery. This case may provide a rationale for treating breast cancer patients negative for anti-neural antibodies, with the possibility of improving neurological symptoms.

Lambert-Eaton Myasthenic Syndrome Complicated by anti-GABAB Receptor Encephalitis.

A 74-year-old man experienced diplopia, generalized muscle weakness, and acute respiratory failure. He was diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) and treated with immunotherapy, but no improvement was observed, and additional symptoms, including central apnea and hallucinations, appeared. Subsequent serum and cerebrospinal fluid (CSF) analyses confirmed the presence of GABAB receptor antibodies, indicating the coexistence of autoimmune encephalitis. Although there were no findings of malignancy, it is highly likely that occult small-cell lung carcinoma was present. When atypical symptoms occur in patients with LEMS, it is important to consider the possibility of concomitant autoimmune encephalitis.

Primary amines protect against retinal degeneration in mouse models of retinopathies.

Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore 11-cis-retinal and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomerized product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing Food and Drug Administration (FDA)-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by MS. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that shows features of Stargardt's disease and age-related retinal degeneration.