Cilostazol alleviates white matter degeneration caused by chronic cerebral hypoperfusion in mice: Implication of its mechanism from gene expression analysis.

Cilostazol is known to alleviate white matter demyelination due to chronic cerebral hypoperfusion in rodent models, although their pharmacological mechanisms remain unclear. In this study, we investigated the protective effect of cilostazol in relation to gene expression profile. Bilateral common carotid artery stenosis (BCAS) mice were treated with oral administration of cilostazol or placebo starting from a week after the surgery. Demyelination of the cingulum was compared between the 2 groups 2, 6, and 10 weeks after initial drug administration. Also, to examine temporal gene expression change during demyelination, DNA microarray analysis was conducted using samples from the corpus callosum of 2nd and 6th week BCAS mice. For genes that showed more than 2-fold up-regulation, their increase was validated by qPCR. Finally, to determine the effect of cilostazol towards those genes, their expression in the corpus callosum of 6-week placebo-treated and cilostazol-treated BCAS mice was compared by qPCR. Amelioration of myelin loss was observed in cilostazol-treated group, showing significant difference with those observed in placebo group after 10-week treatment. Gene ontology analysis of the 17 up-regulated (FDR<0.01) genes showed that majority of the genes were related to cell development processes. Among the validated genes, expression of Btg2 was significantly promoted in the corpus callosum of BCAS mice by administration of cilostazol. Results of this study suggest that activation of Btg2 may be one of the key pharmacological effects of cilostazol towards the white matter during chronic ischemia.

Lambert-Eaton myasthenic syndrome with anti-acetylcholine receptor antibody and anterior mediastinal tumor.

This report describes the case of a 65-year-old male who complained of muscular weakness of the legs with easy fatigability. Blood and imaging examinations showed positive anti-acetylcholine receptor antibody and an anterior mediastinal tumor (probably a thymic cyst), suggesting the diagnosis of myasthenia gravis (MG). However, neurological and electrophysiological examinations suggested the diagnosis of Lambert-Eaton myasthenic syndrome (LEMS). We searched repeatedly for malignant tumors. Small cell lung cancer (SCLC) was found. Chemotherapy reduced the SCLC and improved the patient's clinical symptoms. On the basis of an accurate diagnosis of LEMS, we were able to detect SCLC and administer chemotherapy at an early stage. Anti-P/Q-type voltage-gated calcium channel antibody was negative. In our case, MG and LEMS overlap syndrome in addition to MG should be differentiated. For the differentiation, the strict electrophysiological criteria of LEMS were useful.