Objective: In our search for a new augmentation therapy for stroke patients, we administered cilostazol, an antiplatelet agent. Subjects: The patients suffered from mild hemiparesis or cognitive disorder showing reduced cerebral perfusion in the prefrontal cortex. Methods: We evaluated the functional cerebral blood flow (CBF) before and after the administration of cilostazol using near-infrared resonance spectroscopy (NIRS) during a verbal fluency task (VFT). Results: For the patient with cognitive disorder, statistically significant improvements were observed in the number of generated words in the VFT before and after administration of 50 mg cilostazol (p<0.05, Mann-Whitney U test). Another patient without cognitive disorder, however, showed no significant VFT improvement after administration of cilostazol. Effect size data revealed large or very large effects of cilostazol on brain activation (oxy-Hb levels) at the affected side prefrontal cortex for both patients. The patient with cognitive disorder showed significant improvement in VFT performance as well as an increase in bilateral prefrontal CBF after cilostazol administration. Discussion: These findings suggest that, for patients with cerebrovascular lesions suffering from cognitive disorder, cilostazol may be promising as a drug to improve cognitive function in addition to preventing recurrent cerebral infarction.
Cite this paper
Y. Hara and S. Obayashi, "Increased Cerebral Cortex Perfusion in Stroke Patients with Cognitive Disorder Following Cilostazol Administration, Two Cases Report," Neuroscience and Medicine, Vol. 3 No. 4, 2012, pp. 357-361. doi: 10.4236/nm.2012.34043.
 Y. Shinohara, Y. Katayama, S. Uchiyama, T. Yamaguchi, S. Handa, K. Matsuoka, Y. Ohashi, N. Tanahashi, H. Yamamoto, C. Genka, Y. Kitagawa, H. Kusuoka, K. Nishimaru, M. Tsushima, Y. Koretsune, T. Sawada and C. Hamada, “Cilostazol for Prevention of Secondary Stroke (CSPS 2): An Aspirin-Controlled, Double-Blind, Randomised Non-Inferiority Trial,” Lancet Neurology, Vol. 9, No. 10, 2010, pp. 959-968.
 T. Tanaka, T. Ishikawa, M. Hagiwara, K. Onoda, H. Itoh and H. Hidaka, “Effects of Cilostazol, a Selective CAMP Phosphodiesterase Inhibitor on the Contraction of Vascular Smooth Muscle,” Pharmacology, Vol. 36, No. 5, 1988, pp. 313-320. doi.org/10.1159/000138400
 T. Watanabe, N. Zhang, M. Liu, R. Tanaka, Y. Mizuno and T. Urabe, “Cilostazol Protects Against Brain White Matter Damage and Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion,” Stroke, Vol. 37, No. 6, 2006, pp. 1539-1545.
 S. Kobayashi, S.Yamaguchi, T. Katsube, M. Kitani, K. Okada and T. Tsunematsu, “Long-Term Effect of Cilostazol on Cerebral Blood Flow in Chronic Cerebral Infarction,” Arzneimittelforshung, Vol. 35, No. 7A, 1985, pp. 1193-1197.
 V. Toronov, A. Webb, J. H. Choi, M. Wolf, A. Michalos, E. Gratton and D. Hueber, “Investigation of Human Brain Hemodynamics by Simultaneous Near-Infrared Spectroscopy and Functional Magnetic Resonance Imaging,” Medical Physics, Vol. 28, No. 4, 2001, pp. 521-527.
 H. Akiyama, S. Kudo and T. Shimizu, “The Absorption, Distribution and Excretion of a New Antithrombotic and Vasodilating Agent, Cilostazol, in Rat, Rabbit, Dog and Man,” Arzneimittelforschung, Vol. 35, No. 7A, 1985, pp. 1124-1132.
 M. Okamoto, H. Dan, K. Sakamoto, K. Takeo, K. Shimizu, S. Kohno, I. Oda, S. Isobe, T. Suzuki, K. Kohyama and I. Dan, “Three-Dimensional Probabilistic Anatomical Cranio-Cerebral Correlation via the International 10-20 System Oriented for Transcranial Functional Brain Mapping,” Neuroimage, Vol. 21, No. 1, 2004, pp. 99-111.
 M. L. Schroeter, S. Zysset, F. Kruggel and D. Y. von Cramon, “Age Dependency of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy,” Neuroimage, Vol. 19, No. 3, 2003, pp. 555-564. doi:10.1016/S1053-8119(03)00155-1
 J. E. Harrison, P. Buxton, M. Husain and R. Wise, “Short Test of Semantic and Phonological Fluency: Normal Performance, Validity and Test-Retest Reliability,” British Journal of Clinical Psychiatry, Vol. 39, No. 2, 2000, pp. 181-191. doi:10.1348/014466500163202
 T. Kono, K. Matsuo, K. Tsunashima, K. Kasai, R. Takizawa, M. A. Rogers, H. Yamasue, T. Yano, Y. Taketani and N. Kato, “Multiple-Time Replicability of Near-Infrared Spectroscopy Recording during Prefrontal Activation Task in Healthy Men,” Neuroscience Research, Vol. 57, No. 4, 2007, pp. 504-512.
 Y. Mochizuki, M. Oishi and T. Mizutani, “Effects of Cilostazol on Cerebral Blood Flow, P300, and Serum Lipid Levels in the Chronic Stage of Cerebral Infarction,” Journal of Stroke and Cerebrovascular Disease, Vol. 10, No. 2, 2001, pp. 63-69. doi:10.1053/jscd.2001.24657
 T. Nakamura, H. Houchi, A. Minami, S. Sakamoto, K. Tsuchiya, Y. Niwa, K. Minakuchi and Y. Nakaya, “Endotheliumdependent Relaxation by Cilostazol, a Phosphodiesterase III Inhibitor, on Rat Thoracic Aorta,” Life Science, Vol. 69, No. 15, 2001, pp. 1709-1715.