Abstract

Postural instability is one of the most debilitating symptoms of Parkinson’s disease and the best clinical prognostic indicator of progressive disease. Significant differences in neuropathology, neurochemistry, response to L-dopa therapy and stereotactic surgery as well as prognosis have been identified in subtypes when patients with predominant postural instability and gait difficulty (PIGD)/Type B were differentiated from those with predominant symptoms of tremor and rigidity/Type A. Postural instability is resistant to the therapeutic effects of L-dopa, despite its continued efficacy on other Parkinson’s symptomatology, implicating the nondopaminergic mechanism of postural instability in Parkinson’s disease. Patients with significant postural instability and gait disorders were found to have a decreased level of serotonin in the ventricular CSF, combined with an elevated level of 5-hydroxytryptophan, implicating the decreased activity of the AADC enzyme and serotonin deficits in the type B/PIGD vs the type A/tremor of Parkinson’s disease.

Quantitative analysis of postural instability confirmed the absent therapeutic effect of L-dopa on postural instability and the therapeutic effect of PVP in the ON and OFF state for postural instability. The exacerbation of postural stability in the ON state postoperatively may be explained by the deficit in serotonin secondary to the competitive inhibition of L-dopa for the common enzyme AADC. ON vs OFF state specific improvement in postural stability postoperatively supported the nonstructural neurochemical nature of PD and confirmed evidence that the effect of the PVP is neuromodulatory and nondopaminergic in nature. Finally, the differential responses in the right vs the left limb postoperatively encourages reevaluation of the corticofugal fibers and the role of the thalamocortical as well as reticulotegmental-cortical motor loop in postural instability.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

George Maeda

Second Advisor

Raymond Hall

Third Advisor

Robert P. Iacono

Fourth Advisor

John Leonora

Fifth Advisor

Grenith Zimmerman

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1998

Date (Title Page)

6-1998

Language

English

Library of Congress/MESH Subject Headings

Parkinson Disease -- drug therapy; Serotonin -- analysis

Type

Dissertation

Page Count

xi; 139

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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