Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas.

OBJECTIVE: This prospective clinical trial was undertaken to assess the rate of tumor recurrence in patients with endocrine-inactive pituitary macroadenomas who underwent gross total surgical resection of their tumors and did not receive adjuvant radiotherapy. METHODS: Between December 1987 and July 1994, 45 patients with endocrine-inactive pituitary macroadenomas underwent transsphenoidal surgery. In 38 (84%) of these patients, gross total surgical resection was achieved and was confirmed by postoperative magnetic resonance imaging (n = 37) or computed tomography (n = 1). After receiving counseling from the neurosurgeon concerning the risks and benefits of radiation therapy, 32 of the 38 patients elected not to receive adjuvant radiotherapy. Patients were followed through March 1998 with radiographic imaging obtained every 6 months for the first 2 years, annually for postoperative Years 3 and 4, and then every 2 to 3 years thereafter. The study end point was defined as radiographic tumor recurrence or patient death. RESULTS: The mean follow-up duration for the study group was 5.5 years. During that time, 2 of 32 (6%) patients developed recurrence, at 18 and 24 months, respectively, after initial surgery. Both were successfully treated using radiation therapy, with one requiring additional surgery. Three additional patients died as a result of unrelated causes 9, 12, and 49 months, respectively, after initial surgery. Immunocytochemical analysis revealed 66% of the tumors to be weak gonadotroph cell adenomas, 22% to be null cell adenomas, 9% to be silent prolactinomas, and 3% to be silent corticotroph cell adenomas. CONCLUSION: This study demonstrates a 6% 5-year recurrence rate in patients with endocrine-inactive pituitary macroadenomas treated using gross total surgical resection alone. Reserving radiation therapy for the infrequent patient with recurrence and sparing the majority of patients the associated risks inherent in its use seems reasonable.

Pallidotomy microelectrode targeting: neurophysiology-based target refinement.

OBJECTIVE: Microelectrode recording can refine targeting for stereotactic radiofrequency lesioning of the globus pallidus to treat Parkinson's disease. Multiple intraoperative microelectrode recording/stimulating tracks are searched and assessed for neuronal activity, presence of tremor cells, visual responses, and responses to kinesthetic input. These physiological data are then correlated with atlas-based anatomic data to approximate electrode location. On the basis of these physiological properties, one or more tracks are selected for lesioning. This study analyzes the track physiological factors that seem most significant in determining the microelectrode recording track(s) that will be chosen for pallidal lesioning. METHODS: Thirty-six patients with Parkinson's disease underwent microelectrode-guided pallidotomy. Between one and five microelectrode recording tracks were made per patient. Usually, one (n = 23) or two (n = 12) of these tracks were lesioned. Electrode positions in the x (mediolateral) and y (anteroposterior) axes were recorded and related to track neurophysiological findings and final lesion location. The stereotactic location and sequence of microelectrode tracks were recorded and plotted to illustrate individual search patterns. These patterns were then compared with those noted in other patients. Neurophysiological data obtained from recording tracks were analyzed. A retrospective analysis of track electrophysiology was performed to determine the track characteristics that seemed most important in the surgeon's choice of the track to lesion. Track physiological properties included general cell spike amplitude, tremor synchronous neuronal firing, kinesthetically responsive neuronal firing, and optic track responses (either phosphenes reported by the patient during track microstimulation or neuronal firing in response to light stimulus into the patient's eyes). Orthogonally corrected postoperative magnetic resonance images were used to confirm the anatomic lesion locations. RESULTS: In patients who had a single mapped track lesioned, specific track electrophysiological characteristics identified the track that would be lesioned most of the time (20 of 24 patients). Tracks that exhibited a combination of tremor synchronous firing, joint kinesthesia, and visual responsivity were lesioned 17 (85%) of 20 times. Analysis of intraoperative electrode movement in the x and y axes indicated a significant subset of moves but did not result in microelectrode positioning closer to the subsequently lesioned track. Accuracy of initial electrode movement in the x and y axes was most highly correlated with a measure of first-track electrophysiological activity. The number of microelectrode recording tracks did not correlate with clinical outcome. Anatomic analysis, using postoperative magnetic resonance imaging, revealed that all lesions were placed in the globus pallidus. Most patients (35 of 36) improved after surgery. CONCLUSION: The level of electrophysiological activity in the first track was the best predictive factor in determining whether the next microelectrode move would be closer to the ultimately lesioned track. The analysis of electrode track location and neurophysiological properties yields useful information regarding the effectiveness of microelectrode searching in the x and y axes. Within an institution, the application of this modeling method may increase the efficiency of the microelectrode refinement process.

Growth factors rescue embryonic dopamine neurons from programmed cell death.

Poor survival of embryonic dopamine neurons is a primary problem limiting the value of neurotransplantation for Parkinson's disease. Several neurotrophic factors have been shown to promote dopamine neuron survival when used individually in culture. We have found that two peptides, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF), have additive effects on cell survival when used in combination. These growth factors reduced the number of dopamine cells undergoing apoptotic cell death. The neurotrophic factors induced proliferation of astrocytes but not dopamine neurons. When cell proliferation was blocked by cytosine arabinoside, the beneficial effects of IGF-I and bFGF were abolished, suggesting that effects of the growth factors were mediated, at least in part, by factors associated with glia. These results indicate that growth factors in combination may prove useful for enhancing dopamine neuron survival for neurotransplantation.

Magnitude of microelectrode refinement in pallidotomy and thalamotomy.

The relative accuracy of starting point algorithms in microelectrode-guided stereotactic pallidotomy and thalamotomy was evaluated using postoperative magnetic resonance imaging (MRI) data. Multiplanar reformations were performed to align postoperative MRI in anterior-posterior, dorsal-ventral and mediolateral planes. Three-dimensional distance and direction from the pallidal and thalamic stereotactic starting points to the respective radiofrequency lesions were measured. Similar magnitude of microelectrode refinement in pallidotomy and thalamotomy suggested similar accuracy of algorithms used to set the stereotactic starting point. Fewer microelectrode-recording tracts were required to identify optimal lesioning sites in thalamotomy compared to pallidotomy. Lesions were consistently localized anterior and superior to the starting point and a refined starting point algorithm may reduce the number of microelectrode recording tracts.