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The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

From 1977 to 1988, 56 patients with a preoperative diagnosis of Cushing's disease were treated by transsphenoidal microsurgical exploration of the pituitary gland. In 42 patients, a discrete tumor was found and a selective adenomectomy was performed. Total hypophysectomy was performed in nine patients. In an attempt to preserve pituitary function, a technique of subtotal hypophysectomy was utilized in the remaining five patients. Regular and adequate follow-up results were obtained in 53 patients. A sustained remission was obtained in 45 of these 53 patients for a remission rate of 84.9%. Eight patients were classified as therapeutic failures. The causes for failure included: 1) invasive tumor; 2) hyperplasia mistaken for an adenoma; 3) a presumed ectopic source of adrenocorticotropic hormone; 4) misdiagnosis; 5) atypical tumor; and 6) recurrence of disease after remission. In cases of therapeutic failure, the original diagnosis of Cushing's disease must be reevaluated and treatment continued until sustained remission is achieved. Necessary measures to help avoid surgical failures and an approach for further diagnostic and therapeutic maneuvers in these cases are discussed.

An anatomical-angiographic classification for carotid-cavernous sinus fistulas is introduced and a series of 14 patients with spontaneous carotid-cavernous sinus fistulas is reviewed to illustrate the usefulness of such a classification for patient evaluation and treatment. Fistulas are divided into four types: Type A are direct high-flow shunts between the internal carotid artery and the cavernous sinus; Type B are dural shunts between meningeal branches of the internal carotid artery and the cavernous sinus; Type C are dural shunts between meningeal branches of the external carotid artery and the cavernous sinus; and Type D are dural shunts between meningeal branches of both the internal and external carotid arteries and the cavernous sinus. The anatomy, clinical manifestations, angiographic evaluation, indications for therapy, and therapeutic options for spontaneous carotid-cavernous sinus fistulas are discussed.

A neuroradiological technique for demonstrating the empty sella syndrome using a low dose of intrathecally injected Amipaque (metrizamide) combined with computerized tomography scanning is described. Two case reports illustrating the potential value of the technique are presented. We have performed 55 cisternograms and have demonstrated the empty sella syndrome in six patients. The procedure is easier to perform and the morbidity is less than in pneumoencephalography.

A technique involving the combined use of Amipaque (metrizamide) and computerized tomography scanning is described for the evaluation of ventriculoperitoneal and ventriculoureteral shunt function. The results of three illustrative cases from a series of nine patients are given. In five patients, the technique demonstrated obstruction that was later confirmed at surgery. In the other four patients, it showed patency in the shunt system, and no surgery was performed, thereby obviating unnecessary shunt revisions.

Hypophysectomy was performed in six patients with advanced carcinoma other than from breast and prostate gland to alleviate pain. Two patients received significant and lasting relief of pain; one achieved relief but died from progression of disease 5 weeks after surgery; one patient, initially relieved, had recurrence of pain 3 months later; one had about 50% relief; and one received no benefit. Possible mechanisms for pain relief include changes in pituitary hormones, prostaglandins, and the newly isolated brain peptides, alpha and beta endorphin. These preliminary observations will require further critical evaluation in a larger series to determine the effectiveness of hypophysectomy in relieving pain in cancer other than from the breast and prostate. The results, nevertheless, do imply that a different approach to pain, namely endocrine manipulation, may be beneficial in certain cancer patients.

The authors present the results of transsphenoidal microsurgery in 100 women with the amenorrhea-galactorrhea syndrome caused by pituitary adenomas associated with hyperprolactinemia (prolactinomas). As the surgical results were closely related to the preoperative levels of serum prolactin, the patients were divided into two groups: patients with preoperative prolactin less than 200 ng/ml (Group 1), and those with preoperative prolactin greater than 200 ng/ml (Group 2). The results in Group 1 (72 patients) were significantly better. In this group, 56 (78%) patients regained normal menstrual cycles, and 55 (76%) had return of elevated prolactin to normal following surgery. In Group 2 (28 patients), however, only 11 (39%) resumed normal menstrual periods postoperatively, and 13 (*46%) had return of elevated prolactin levels to normal. There was good correlation between tumor size and the preoperative level of prolactin. Of the 72 women in Group 1, 58 (81%) had tumors less than 1 cm (microadenomas), whereas of the 28 women in Group 2, only four (14%) had tumors of that size. All patients with visual field deficits preoperatively improved or had a normal visual examination postoperatively; none was made worse by surgery. Four patients (three in Group 2) have required additional surgery and/or irradiation. In the last six patients of the series, contrast-enhanced coronal computerized tomography slices made with the updated General Electric scanner detected five microadenomas. Considering that a relatively high percentage of sellar polytomograms are negative in patients with proven microadenomas (that is, only 40 of 72 patients in Group 1 has abnormal polytomography), it is likely that sellar polytomography will significantly decrease in importance in the diagnostic work-up of these patients. The authors provide a rationale for transsphenoidal microsurgery in these patients as opposed to other forms of management, such as bromocriptine therapy and irradiation.

Previous studies have demonstrated that cerebrospinal fluid (CSF) from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure, contains 15 to 30 nM 3',5' cyclic adenosine monophosphate (cAMP). The concentration of this cyclic nucleotide was measured by radioimmunoassay in 133 samples of CSF from the lateral ventricle of 26 patients who were comatose following acute head trauma for periods up to 40 days. Concentration of CSF cAMP in diminishing coma Grades V, IV, III, II, and I was 1.5 +/- 0.1 nM; 1.24 +/- 0.34 nM; 3.14 +/- 0.7 NM; 10.06 +/- 3.47 nM; and 13.36 +/- 1.38 nM, respectively. After the sensorium cleared (coma Grade 0), cAMP was 22.0 +/- 1.7 nM. The correlation between the grade of coma and cAMP concentration was -0.80 (p greater than 0.01). These results imply that alteration in the level of consciousness following head trauma is associated with a disturbance of cAMP metabolism within the central nervous system. Possible mechanisms explaining this observation as well as therapeutic implications are discussed.

Transsphenoidal microsurgical hypophysectomy was performed in 53 men with disseminated carcinoma (Stage IV) of the prostate gland. The mean age was 64.8 years. Forty-three of the 53 men had severe pain due to their disease. Significant pain relief was obtained following hypophysectomy, usually within 24 hours, in 39 (91%) of these 43 patients. Objective remission occurred in 16 (36%) of 45 patients in whom the follow-up review was adequate to make this decision. Although dramatic, pain relief was not permanent in every patient. Four patients died in the early postoperative period, and in one, death was directly related to the operative procedure. Significant complications included partial diabetes insipidus in 40 cases (75.5%), and cerebrospinal fluid leaks in six (11.3%). The authors conclude that hypophysectomy is an appropriate operation in patients with disseminated carcinoma of the prostate gland, particularly when pain is a significant feature of the illness. Further, the transsphenoidal microsurgical approach appears to be the operative procedure of choice for performing hypophysectomy.

The combined effect upon cerebral blood flow (CBF) of an elevation of cerebrospinal fluid pressure (CSFP) and changes in respiratory CO2 was studied in nine baboons under chloralose anesthesia. The animals were mildly hyperventilated and provided with increasing amounts of CO2 in O2-air. Arterial CO2 tensions (PaCO2) increased from 17 to 58 mm Hg. Internal carotid blood flow (ICBF) was measured at normal CSFP and at hydrostatically maintained 50 mm Hg CSFP. It was found that: 1) end-tidal CO2 may be used as a substitute for arterial PaCO2 determinations; 2) this elevation of CSFP has little effect on ICBF during hypercapnia and normocapnia; however, 3) during hypocapnia the ICBF is reduced an additional 20% when CSFP is elevated; that is, ICBF is reduced 50% from normal when end-tidal CO2 is reduced to 2% at this elevated level of CSFP. Caution should be exercised during hyperventilation therapy particularly if the elevated CSFP or intracranial pressure (ICP) is not reduced to approach normal levels; in these conditions, the combination of decreasing PaCO2 and elevated ICP may reduce CBF below critical levels and thus lead to cerebral hypoxia.

A modification of the transseptal, transsphenoidal appraoch to the sella turcica is described; it consists of a unilateral separation of the nasal mucosa from the nasal septum. Experience with the technique in 215 cases has indicated that it is a useful, practical appraoch. The advantages are that the septum is spared, reoperation is made easier, and the procedure is quicker than the bilateral septal procedure. Asymptomatic nasal septal perforations (less than 3 mm) were seen in eight of 215 cases, and represented the only complication related to the operation.

A retrospective study was made of 195 patients who had ruptured intracranial aneurysms without significant intracerebral hematomas and who recovered to at least Grade III by Hunt and Hess' classification. The first 121 patients underwent aneurysm surgery 10 days to 2 weeks after subarachnoid hemorrhage (SAH) without repeat preoperative angiography and without special attention to volume replacement or avoidance of hypotension. Vasospasm resulted in cerebral ischemia in 15% of this group, more than half of these postoperatively, and was treated successfully in half the patients with a combination of aminophylline and isoproterenol. The later 74 patients were managed with aggressive maintenance of normal circulating blood volume and preoperative angiography at 2 weeks following SAH. If significant vasospasm persisted on angiography, surgery was delayed an additional week and, if spasm was still present then, aminophylline and isoproterenol was added prophylactically to aggressive volume replacement before surgery. In this second group of patients, the incidence of clinical vasospasm was essentially unchanged; however, it was almost completely limited to the preoperative period, and was more effectively treated with aminophylline and isoproterenol. Postoperative vasospasm was almost completely eliminated from the second group of patients.

The heterotopic transfer of composite tissue, with microvascular anastomosis of an arterial supply and venous drainage to locally existing vessels, has received considerable attention in the plastic surgical literature. The use of latissimus dorsi musculocutaneous free flaps has been reported in the repair of large defects of the scalp, cranium, and dura following resection of invasive neoplasms or trauma. When the defect involves primarily subcutaneous tissue loss resulting in abnormal contour, omental free flaps provide effective coverage and restoration of contour. In addition, the inherent capability of the omentum to combat infection and form an ideal bed for the establishment of skin or bone grafts provides further indications for its use. The authors have used omental free flaps in nine cases to reconstruct gunshot wounds of the head, orbit, and face, heal chronic cavitating frontal sinus infections, form a base over exposed dura for reconstruction of the skull with rib grafts, and cover large defects after resection of invasive tumors or infected scalp. These wounds of neurosurgical interest were reconstructed with acceptable structural and aesthetic results. The indications, surgical techniques, results, alternative procedures, and potential complications of this procedure are discussed. The authors believe that omental free flaps should be considered an option in the armamentarium of reconstructive approaches for skull, dural, scalp, orbital, and facial wounds.

The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia.

Ventricular fluid pressure (VFP) and volume-pressure response were measured during nitroglycerin (NTG) infusion in nine patients anesthetized with N2O and fentanyl. The patients' ventilation was controlled, and PaCO2 was kept at 32 +/- 4 mm Hg. When an infusion of 0.01% NTG was given intravenously to decrease the mean blood pressure to 95.1%, 84.7%, and 78.2% of control, the VFP increased from control levels of 9.94 +/- 2.14 mm Hg to 12.89 +/- 2.25, 15.6 +/- 2.85, and 14.43 +/- 3.45 mm Hg, respectively. The volume-pressure response showed a significant increase when blood pressure decreased to 84.7% and 78.2% of control. These results suggest that intravenous NTG caused an increase in the intracranial pressure and a decrease in the intracranial compliance.

This overview of neurosurgical practice examines patterns of case management, using several areas such as head injury, brain tumors, and the delivery of health care to illustrate the changes that have taken place over the past 40 years and the changes that might be expected in the next 40 years. The rapid pace of progress has indicated further exciting growth of this specialty into the 21st century; however, what remains constant is the dynamic character of the neurosurgeon. This view of the past and the possibilities for future innovation enables neurosurgeons of all generations to have a sense of pride in the achievements generated by their peers.

Prolonged coma afterhead trauma is associated with depletion of 3', 5' cyclic adenosine monophosphate (cAMP) in the cerebrospinal fluid (CSF). Because cAMP has previously been implicated in neurorendocrine secretion, this study examines the pituitay-hypothalamic function in 15 adult male patients (to exclude the effects of puberty and menses) with traumatic coma lasting longer than 2 weeks. Ventricular CSF cAMP was measured at 2- to 4-day intervals for 10 to 25 days. Simultaneously, plasma hormone concentrations were also determined. In all 15 cases, CSF cAMP and plasma levels of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4, triiodothyronine (T3), luteinzing hormone (LH), follicle-stimulating hormone (FSH), and testerone became subnormal. In 11 patients whose level of consciousness fluctuated, the reduction in plasma T4 and testerone were proportional to both severity of coma ( r greater than 0.81, p less than 0.05) and depletion of CSF cAMP (r greater than 0.81, p less than 0.05). In four patients who remained deeply comatose for 17 to 25 days, the hypothyroidism and hypogonadism persisted. In six patients who regained consciousness, both endocrine defects improved partially or completely. Injection of 1) thyrotrophic-releasing hormone and 2) gonadotrophic-releasing hormone elicited normal or supernormal increases in plasma concentrations of 1) TSH, and 2) LH and FSH, reduced, respectively, suggesting a suprahypophyseal deficiency. These observations demonstrate that suprahypophyseal hypothryoidism and hypogonadism may occur regularly in patients with traumatic coma lasting longer than 2 weeks.

A transoral, transsphenoidal microsurgical technique for exposing the pituitary stalk and gland of the rhesus monkey is described and illustrated. The technique has proved to be a safe and practical method for performing a variety of pituitary operations in a total of 37 animals. The procedures have included complete hypophysectomy, posterior lobe resection, pituitary stalk section, collection of portal venous blood, collection of pituitary venous blood, and placement of lessions in the organum vasculosum of the lamina terminalis.

The authors have reviewed the results of transsphenoidal microsurgical management in 69 patients with prolactin-secreting pituitary adenomas who had preoperative serum prolactin levels over 200 ng/ml. The patients were divided into three groups based on their preoperative serum prolactin levels: over 200 to 500 ng/ml (Group A); over 500 to 1000 ng/ml (Group B); and over 1000 ng/ml (Group C). The percentage of successful treatment ("control rate") was 68%, 30%, and 14%, respectively, in these three groups of patients. Based on these results, the authors offer guidelines for the management of patients with prolactin-secreting pituitary adenomas associated with exceptionally high serum prolactin levels. The surgical control rate of 68% in Group A seems to justify surgery for these patients, while primary medical care with bromocriptine is recommended for most patients with serum prolactin levels over 500 ng/ml.

Bromocriptine inhibits prolactin secretion and causes size reduction of prolactin-secreting adenomas. The effect of the drug upon pituitary tumors other than prolactinomas is uncertain. The authors report a prospective series of 12 patients with pituitary macroadenomas in whom bromocriptine was administered for 6 weeks prior to transsphenoidal surgery. Five of the patients had computerized tomographic documentation of significant reductions in tumor size (Group A) and six had no change (Group B) during 3 and 6 weeks of bromocriptine administration. One patient who demonstrated size reduction in his tumor was not assigned to either group as he was treated with high-dose dexamethasone concurrently with the bromocriptine. Pathological examination (light and electron microscopy and immunocytochemistry) indicated that all Group A patients harbored tumors with prolactin granules whereas all Group B tumors lacked such granules. Adenoma cells in the responsive tumors were involuted with reduced cytoplasmic, nuclear, and nucleolar areas. Neither widespread cell necrosis, infarction, nor vascular injury was observed. Two of the five Group A patients discontinued bromocriptine prior to completion of the 6-week protocol and had a rapid return of their tumors to pre-treatment size. Although bromocriptine has been reported to cause shrinkage of nonfunctional tumors, there was no radiological evidence of size reduction or pathological changes in the nonfunctional tumors of this series. Interestingly, serum levels of prolactin were modestly elevated (84 and 113 ng/ml) in two of the six Group B patients, an elevation due to stalk compression rather than secretion by adenoma cells. This finding underscores the fact that failure of bromocriptine to reduce pituitary tumor size in the presence of hyperprolactinemia may occur because the tumor is other than a prolactinoma. This is the first moderate-sized group of patients in whom pathological changes in responsive prolactinomas during bromocriptine therapy have been demonstrated. As bromocriptine is not tumoricidal, and thus not curative, there is insufficient evidence to recommend this drug as primary therapy for either prolactin-secreting or nonfunctional macroadenomas, but the drug may have potential as a preoperative adjunct to effect shrinkage of prolactinomas and theoretically, at least, make excision easier and possibly more complete.