Movement zyxwvutsrqponm Disorders Vol. 9, No. zyxwvutsrqpo 2, 1994, zyxwvutsrqponm pp. 201-206 zyxwvutsrqpon 0 1994 Movement Disorder Society Novel Rat Cardiac Arrest Model of Pos thypoxic My oclonus Daniel D. Truong, Rae R. MatsumoJo, Philip H. Schwartz, Matthew J. Hussong, and *?Claude G. Wasterlain Parkinson’s and Movement Disorders Research Laboratory, Department zyxw of Neurology, California College of Medicine, University of California Irvine, Irvine; *Departments of Neuroscience and Neurology, School of Medicine, University of California Los Angeles, Los Angeles; and ?Epilepsy Research Laboratories, Veterans Administration Medical Center, Sepulveda, California, U.S.A. Summary: We describe the time course of and pharmacology associated with auditory-induced muscle jerks following cardiac arrest in rats. The data indi- cate that several key features of this model mimic those of human posthypoxic myoclonus. Similar to the human form, the muscle jerks appear in the rats following an acute hypoxic episode (cardiac arrest). Initially, it is known that both spontaneous and auditory-induced myoclonus are present in these ani- mals; some cardiac-arrested rats also exhibit seizures. Over the first few days after the arrest, episodes of both the seizure activity and spontaneous myo- clonus disappear. The auditory-induced myoclonus continues to worsen, reaches a peak about 2 weeks after the arrest, then declines over time to subnormal levels. The auditory-induced muscle jerks exhibited by the cardiac arrested animals are attenuated by the typical antimyoclonic drugs 5-hydroxy- tryptophan, valproic acid, and clonazepam. In addition, the novel anticonvul- sant felbamate was found to have antimyoclonic properties. The data suggest that this rat cardiac arrest model may be a valuable tool for investigating the pathophysiologic mechanisms of posthypoxic myoclonus and for developing new therapeutic strategies for treating the disorder. Key Words: Myoclonus- Ischemia-Clonazepam-Valproic acid-Serotonin-Felbamate- Glycine. Myoclonus is defined as sudden, brief, shock- like, involuntary movements caused by active mus- cular contractions or inhibitions (1). It is manifested in a wide variety of pathologic conditions affecting the central nervous system (2). In this report, we focus on posthypoxic myoclonus, first described by Lance and Adams (3). The myoclonus associated with this syndrome arises from acute hypoxic epi- sodes, such as those resulting from cardiac arrest; these jerks are a type of action myoclonus, the most disabling form of the disorder (4). Address correspondence and reprint requests to Dr. Daniel D. Truong, University of California Irvine, College of Medicine, Department of Neurology, 154 Med Surge I, Irvine, CA 92717- 4290, U.S.A. Patients with posthypoxic myoclonus exhibit ei- ther spontaneous or stimulus-induced myoclonus (1,5,6) and the majority suffer from seizures (7,8). Although posthypoxic myoclonus may improve over time, treatment is currently inadequate (4,9). Little is known about the neuropathology associ- ated with posthypoxic myoclonus because system- atic studies are difficult in humans, and until re- cently, no satisfactory animal model was available to study the disorder. In most animal models of myoclonus, the disorder is either chemically in- duced or genetic in nature, rather than the result of an acute hypoxic episode (10-17). In addition, whether animal models of transient, cerebral isch- emia result in posthypoxic myoclonus, as is seen in humans, is not clear (18-20). zyx 201