Utilization of unilateral and bilateral stereotactically placed adrenomedullary-striatal autografts in parkinsonian humans

Abstract

A limited clinical pilot study involving an amalgam of specialized disciplines including neurology, neuropharmacology, neuropsychology, neurosurgery, neuroanesthesia, neuroradiology, surgical pathology, neuropathology, and urological surgery was organized to clarify issues related to patient selection, optimization of grafting materials, design of a safe, effective, standardized, and reproducible surgical technique, and possible modification of clinical patterns. After initial assessment of 82 Parkinsonian patients for periods of 6 to 20 months, 10 (age, 39-68 years) were selected for unilateral or bilateral adrenomedullary autografts to the caudate nucleus with ependymal and cerebrospinal fluid contact, employing image-directed stereotactic methods. Selection was made only after clear definition of clinical pattern and optimization of medication responses. Adrenal glands were harvested by a retroperitoneal approach (mean estimated blood loss less than 75 ml). Care was taken to maximize the graft content of medullary tissue. Stereotactic methods afforded standardized, reproducible, precise targeting and transit trajectory with unilateral or bilateral placement of materials within the striatum (tissue volume, 80 mm3) with access to the ventricular fluid of the frontal horn. Considerable variability in satisfactory donor medullary tissue was encountered. One patient did not undergo grafting because of unsatisfactory medullary tissue. No significant surgical complications were noted and all patients were ready for discharge 7 days after surgery. One patient who manifested no apparent clinical change died 6 weeks after bilateral grafting of unrelated causes during a lithotripsy procedure. Postmortem examination disclosed precise graft placement with a paucity of structurally preserved medullary cells. Postoperative observations, including parameters of clinical observation, medication schedules and records, patient and family commentaries, and imaging studies (computed tomograms and single photon emission computed tomograms), have been made for periods from 16 to 20 months. Sustained improvement in preexisting clinical patterns and reduction in drug requirements were observed in 4 of 8 patients. No increased benefit could be ascribed to bilateral graft placement. These observations would indicate a safe, and reproducible surgical method. In addition, the clinical observations indicate favorable alterations in the established pattern of the disorder, which would justify further cautious exploration of alternate donor sources or refinements of biological graft site manipulations.