Pathophysiology Of Neurosurgical Disorders

Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

Syringomyelia, a cyst in the spinal cord, causes progressive paralysis in affected patients, including patients in childhood and early adulthood. Understanding the mechanism causing syringomyelia may permit the identification of treatment that is more effective and less invasive. The purpose of this study is to establish the mechanism(s) of the progression of syringomyelia. A clinical study elucidating the basis of syringomyelia associated with the Chiari I malformation was completed in which the mechanism was shown, paradoxically, to be one that is outside, not inside, the spinal cord. Successful surgery, by a procedure that does not invade the nervous system, eliminated the anatomic cause of the excess pressure waves and resulted in consistent resolution of syringomyelia. The demonstration of this mechanism should result in less invasive surgery and more effective treatment for this form of progressive paralysis. In a related study (Protocol 92-N-0226), we are continuing to evaluate and treat subjects with Chiari I-type syringomyelia but who have had unsuccessful surgery elsewhere. In these subjects we have found that previous surgery failed simply because it did not relieve the obstruction of the cerebrospinal pathways at the foramen magnum. In another clinical study (Protocol 01-N-0085) we are studying primary spinal syringomyelia, a type of syringomyelia not associated with Chiari I malformation. A preliminary finding is that obstruction of the spinal subarachnoid space in primary spinal syringomyelia is associated with enlarged CSF pressure waves superior to the obstruction. Successful surgery for primary spinal syringomyelia opens CSF pathways, reduces CSF pressure waves to normal, and resolves syringomyelia, as had successful surgery in our studies of Chiari I-type syringomyelia. This association suggests that primary spinal syringomyelia and Chiari I-type syringomyelia arise from a similar mechanism. [unreadable] [unreadable] The process by which the Chiari I malformation develops is unknown. Ectopia of the cerebellar tonsils, which is the defining characteristic of the Chiari I malformation, may result because the posterior fossa does not develop normally. In a clinical study of families with multiple members affected by the Chiari I malformation (Protocol 00-N-0089), we are using MRI scans of the brain to evaluate for Chiari I malformation and to measure the size of the osseous structures and volume of the posterior fossa. After phenotyping family members as being affected or unaffected by these traits, we collect DNA specimens from them for genotyping. Genotyping has recently been completed at the Center for Inherited Disease Research and linkage analysis will be performed over the next few months. Finding a genetic locus for the Chiari I malformation would lead to a better understanding of the etiology of the Chiari I malformation.[unreadable] [unreadable] Laboratory and clinical investigation of central nervous system vascular disorders is ongoing. Delayed cerebral vasospasm is the most common cause of death or disability in patients with subarachnoid hemorrhage who survive to reach the hospital. We have investigated the mechanism of delayed vasospasm and have demonstrated the presence of nitric oxide (NO) synthase-based dysfunction of the endothelium in a primate model of vasospasm. We have observed that nitrite acts as a nitric oxide donor and in a preclinical study in primates have shown that chronic intravenous infusion of sodium nitrite prevents vasospasm after subarachnoid hemorrhage. We recently received IRB and FDA approval for a clinical protocol to study the safety of intravenous nitrite infusion in normal subjects.