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Arun P. Amar, William T. Couldwell, Joseph C. T. Chen, and Martin H. Weiss

Object. Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of “recurrent” tumors.

Methods. Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (≤ 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome.

Conclusions. Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.

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James S. Heiden, Martin H. Weiss, Alan W. Rosenberg, Theodore Kurze, and Michael L. J. Apuzzo

✓ The authors present a series of 38 civilian patients with cervical gunshot injuries, and compare neurological recovery in patients with complete lesions and patients with incomplete lesions according to whether therapy was surgical or nonsurgical. In patients with incomplete injury, ultimate recovery was a function of the initial injury more than surgical or nonsurgical therapy; nor did patients with complete lesions show significant change in outcome with either mode of therapy. Cord pathology at laminectomy rarely provided a clue about neurological recovery, and dural decompression did not alter neurological outcome. The authors conclude that the sole indication for routine surgical intervention appears to be progressive neurological deficit.

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Gabriel Zada, Charles Y. Liu, Dawn Fishback, Peter A. Singer, and Martin H. Weiss

Object

The goal of this study was to assess the incidence of symptomatic and occult hyponatremia in patients who had undergone transsphenoidal pituitary surgery.

Methods

Patients who underwent transsphenoidal surgery at the University of Southern California University Hospital between 1997 and 2004 had serum sodium levels drawn on an outpatient basis on postoperative Day 7. Patient records were retrospectively reviewed to determine the incidence of, and risk factors for, symptomatic and asymptomatic hyponatremia.

Two hundred forty-one patients had routine serum sodium levels drawn as outpatients on postoperative Day 7. Twenty-three percent of these patients were found to be hyponatremic (Na ≤ 135 mEq/L). The overall incidence rate of symptomatic hyponatremia in the 241 patients was 5%. The majority of hyponatremic patients (80%) remained asymptomatic, whereas 20% became symptomatic. In patients with symptomatic hyponatremia, the mean sodium level at diagnosis was 120.5 mEq/L, compared with 128.4 mEq/L in asymptomatic, hyponatremic patients (p < 0.0001). Female patients were more likely to develop hyponatremia than male patients (33% compared with 22%, p < 0.03). Fifty-two percent of patients who had transient diabetes insipidus (DI) early in their postoperative course subsequently developed hyponatremia, compared with 21% of those who did not have DI (p < 0.001). Patient age, tumor type, and tumor size did not correlate with development of delayed hyponatremia. Outpatients with moderately and severely low sodium levels were 5 and 12.5 times more likely, respectively, to be symptomatic than were patients with mild hyponatremia.

Conclusions

Delayed hyponatremia occurs more frequently than was previously suspected in patients who have undergone transsphenoidal surgery, especially in female patients and those who have previously had transient DI. The majority of hyponatremic patients remain asymptomatic. Obtaining a serum sodium value on an outpatient basis 1 week after pituitary surgery is helpful in recognition, risk stratification, and subsequent intervention, and may prevent potentially serious complications.

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Christopher J. Aho, Charles Liu, Vladimir Zelman, William T. Couldwell, and Martin H. Weiss

Object. Microscopic Rathke cleft cysts are a common incidental autopsy finding, but some Rathke cleft cysts can become sufficiently large to cause visual impairment, hypothalamic—pituitary dysfunction, and headaches. In this study patients were evaluated pre- and postoperatively to ascertain the clinical significance of surgical intervention on endocrine and visual improvement. Factors correlated with cyst recurrence were also evaluated.

Methods. A retrospective analysis was conducted in 160 patients with Rathke cleft cysts who were treated between 1984 and 1995 and completed at least a 5-year follow-up period. Of these 160 patients, 118 initially exhibited symptoms of visual impairment or endocrine dysfunction, became symptomatic during the follow-up period, or were found to have cyst enlargement. These 118 patients underwent transsphenoidal surgery. Forty-two patients with incidental lesions that demonstrated no growth on magnetic resonance (MR) images were followed up without an operation.

Complete resection, as observed on MR images 3 months postoperatively, was obtained in 114 (97%) of 118 patients. Vision improved postoperatively in 57 (98%) of 58 patients. Hypogonadism improved in 11 (18%) of 62 patients, growth hormone deficiency resolved in 14 (18%) of 78 patients, and hypocortisolemia resolved in one (14%) of seven patients. Twenty-two patients (19%) began to exhibit symptoms of diabetes insipidus, which had not been present preoperatively. The total 5-year recurrence rate was 18% (21 of 118 patients), with 12 patients requiring a repeated operation. Surgical and pathological factors that were found to be statistically associated with recurrence were the use of a fat and/or fascial graft for closure (p < 0.01) and the presence of squamous metaplasia in the cyst wall (p < 0.01). The extent of resection of the cyst wall was not associated with an increased rate of recurrence. In 42 (69%) of 61 patients the incidental cysts did not progress on imaging studies or clinically.

Conclusions. This is the largest series of patients with symptomatic Rathke cleft cysts who received operative intervention and participated in the longest postoperative follow up reported in the literature. The high recurrence rate (18%) supports the theory that a relationship exists between a symptomatic Rathke cleft cyst and craniopharyngioma. Improvements in visual and endocrine dysfunction can be expected after surgical decompression of the optic apparatus and the hypothalamic—pituitary axis.

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Matthew S. Agam, Michelle A. Wedemeyer, Bozena Wrobel, Martin H. Weiss, John D. Carmichael, and Gabriel Zada

OBJECTIVE

Pituitary adenomas (PAs) are benign neoplasms that are frequently encountered during workup for endocrinopathy, headache, or visual loss. Transsphenoidal surgery remains the first-line approach for PA resection. The authors retrospectively assessed complication rates associated with transsphenoidal PA resection from an institutional database.

METHODS

A retrospective analysis of 1153 consecutive transsphenoidal pituitary adenoma resections performed at the Keck Hospital of USC between November 1992 and March 2017 was conducted. Microscopic transsphenoidal resection was performed in 85.3% of cases, and endoscopic transsphenoidal resection was performed in 14.7%. Analysis of perioperative complications and patient and tumor risk factors was conducted.

RESULTS

The overall median hospital stay was 3 days. There was 1 perioperative death (0.1%). Surgical complications included postoperative cerebrospinal fluid leak (2.6%), epistaxis (1.1%), postoperative hematoma (1.1%), meningitis (1.0%), cranial nerve paresis (0.8%), hydrocephalus (0.8%), vision loss (0.6%), stroke (0.3%), abdominal hematoma or infection (0.2%), carotid artery injury (0.1%), and vegetative state (0.2%). Perioperative medical complications included bacteremia/sepsis (0.5%), pneumonia (0.3%), myocardial infarction (0.3%), and deep venous thrombosis/pulmonary embolism (0.1%). Endocrine complications were the most frequent, including transient diabetes insipidus (4.3%), symptomatic hyponatremia (4.2%), new hypopituitarism (any axis) (3.6%), permanent diabetes insipidus (0.3%), and adrenal insufficiency (0.2%). There were no significant differences between microscopic and endoscopic approaches with regard to surgical complications (6.4% vs 8.8%, p = 0.247) or endocrine complications (11.4 vs 11.8%, p = 0.888). Risk factors for surgical complications included prior transsphenoidal surgery (11.4% vs 6.8%, p = 0.025), preoperative vision loss (10.3% vs 6.8%, p = 0.002), and presence of PA invasion on MRI (8.5% vs 4.4%, p = 0.007).

CONCLUSIONS

In this single tertiary center study assessing complications associated with transsphenoidal PA resection, the rate of death or major disability was 0.26%. Risk factors for complications included prior surgical treatment and PA invasion. No differences in complication rates between endoscopic and microscopic surgery were observed. When performed at experienced pituitary centers, transsphenoidal surgery for PAs may be performed with a high degree of safety.

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Charles B. Stillerman, Thomas C. Chen, William T. Couldwell, Wei Zhang, and Martin H. Weiss

Object

The authors aimed to develop management strategies for the treatment of herniated thoracic discs and to define indications for selection of surgical approaches. Symptomatic thoracic discs requiring surgery are rare. Between 1971 and 1995, 71 patients with 82 herniated thoracic discs were surgically treated by the authors. The treated group included 34 men and 37 women whose ages ranged from 19 to 75 years, with a mean age of 48 years. The most common sites of disc herniation requiring surgery were from T-8 to T-11. Evidence of antecedent trauma was present in 37% of the patients. Preoperative symptoms included pain (localized, axial, or radicular) in 54 (76%) of the 71 patients, evidence of myelopathy that is, motor impairment in 43 (61%), hyperreflexia and spasticity in 41 (58%), sensory impairment 43 (61%), and bladder dysfunction in 17 (24%).

Methods

Radiological diagnosis for the patients in this series was accomplished by means of myelography, computerized tomography myelography, or magnetic resonance imaging. Classification of the disc location into two groups reveals that 94% were centrolateral and 6% were lateral. Evidence of calcification was present in 65% of patients, and in 7% intradural extension was noted at surgery. Ten patients (14%) were found to have multiple herniations. Four surgical approaches were used for the removal of these 82 disc herniations: transthoracic in 49 (60%), transfacet pedicle-sparing in 23 (28%), lateral extracavitary in eight (10%), and transpedicular in two (2%). Postoperative evaluation revealed improvement or resolution of pain in 47 (87%) of 54, hyperreflexia and spasticity in 39 (95%) of 41, sensory changes in 36 (84%) of 43, bowel/bladder dysfunction in 13 (76%) of 17, and motor impairment in 25 (58%) of 43. Complications occurred in a total of 12 (14.6%) of 82 discs treated surgically. Major complications were seen in three patients and included perioperative death from cardiopulmonary compromise, instability requiring further surgery, and an increase in the severity of a preoperative paraparesis.

Conclusions

Review of this series, with the attendant complications, together with evaluation of several contemporary thoracic disc series, has facilitated the authors' decision-making process when considering the comprehensive management of these patients, including the selection of a surgical approach.

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Joseph C. T. Chen, Arun P. Amar, SooHo Choi, Peter Singer, William T. Couldwell, and Martin H. Weiss

Object. Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission.

Methods. The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery.

The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 µg/dl (83 nmol/L) on postoperative Day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission.

Conclusions. Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone—producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD.

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John S. Kuo, Cynthia Hawkins, James T. Rutka, and Martin H. Weiss

Object

The authors investigated the feasibility of using fat allografts (chemically treated to reduce the host immune response) for neurosurgical applications.

Methods

Subcutaneous fat specimens collected from New Zealand White rabbits were treated with DNAse I and sodium deoxycholate to reduce immunogenicity before subcutaneous, midscapular implantation in immunocompetent recipient rabbits. Allograft incorporation and the host-allograft response were examined at 1, 6, and 11 weeks by histopathological analysis. Control specimens of autograft and untreated fat allograft implants were examined for comparison.

Results

The host immune response was markedly reduced in the region around the chemically treated fat allografts when compared with untreated allografts, and was similar to the tolerant host response to autografts.

Conclusions

Based on their results, the authors suggest that fat allografts processed for reduced immunogenicity may be a convenient, viable alternative for neurosurgical applications.

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Mamoru Kittaka, Steven L. Giannotta, Vladimir Zelman, Jorge D. Correale, Christopher M. DeGiorgio, Martin H. Weiss, and Berislav V. Zlokovic

A reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca++ channel (VSCC) antagonist, exerts neuroprotective effects when administered 10 minutes following an ischemic insult, and if it does, whether this is due to its vasodilatory action and effect on cerebral blood flow (CBF) or to direct blockade of Ca++ entry into ischemic brain cells. An increase in the intracellular calcium, [Ca++]i, plays a major role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, inconsistent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats at 10 minutes after the onset of ischemia, and 8, 16, and 24 hours after occlusion. Cortical CBF was determined by laser-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific marker for the incidence of neuronal injury, was measured in plasma. The CBF in the ischemic core and periphery, as well as brain temperature and physiological parameters, were not affected by nicardipine during occlusion or reperfusion. However, nicardipine treatment significantly improved motor neurological outcome by 32%, and the infarction and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 28%, 37%, and 53%, respectively. Nicardipine also significantly reduced the neuron-specific enolase plasma levels by 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respectively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous effects that do not depend on CBF.

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Steven M. Grunberg, Martin H. Weiss, Irving M. Spitz, Jamshid Ahmadi, Alfredo Sadun, Christy A. Russell, Lois Lucci, and Lani L. Stevenson

✓ The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors.

The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (≥ 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective improvement (improved extraocular muscle function or relief from headache). The side effects of long-term mifepristone therapy have been mild. Fatigue was noted in 11 of the 14 patients. Other side effects included hot flashes in five patients, gynecomastia in three, partial alopecia in two, and cessation of menses in two. Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma.