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A pilot study of fat allograft transplantation in immunocompetent rabbits for potential neurosurgical applications

Laboratory investigation

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


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


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.


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.


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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Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery

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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Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test

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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The history and evolution of transsphenoidal surgery

James K. Liu, Kaushik Das, Martin H. Weiss, Edward R. Laws Jr, and William T. Couldwell

✓ Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive. Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica. He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906. His procedure underwent a number of modifications by interested surgeons, the culmination of which was A. E. Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure. From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6%. As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5%. With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate. As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches.

Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches. Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s. Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity. With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica. The evolution of the transsphenoidal approaches and their current applications and modifications are discussed.

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Experience in the surgical management of 82 symptomatic herniated thoracic discs and review of the literature

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


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%).


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.


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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The transfacet pedicle-sparing approach for thoracic disc removal: cadaveric morphometric analysis and preliminary clinical experience

Charles B. Stillerman, Thomas C. Chen, J. Diaz Day, William T. Couldwell, and Martin H. Weiss

A number of operative techniques have been described for the treatment of herniated thoracic discs. The transfacet pedicle-sparing approach allows for complete disc removal with limited spinal column disruption and soft-tissue dissection. Fifteen cadaveric spinal columns were used for evaluation of exposure, development of thoracic microdiscectomy instrumentation, and establishment of morphometric measurements. This approach was used to remove eight thoracic discs in six patients. Levels of herniation ranged from T-7 through T-11. Preoperatively, all patients had moderate to severe axial pain, and three (50%) of the six had radicular pain. Myelopathy was present in four (67%) of the six patients. Through a 4-cm opening, the ipsilateral paraspinal muscles were reflected, and a partial facetectomy was performed. The disc was then removed using specially designed microscopic instrumentation. Postoperatively, the radiculopathy resolved in all patients. Axial pain and myelopathy were completely resolved or significantly improved in all patients.

The minimal amount of bone resection and muscle dissection involved in the operation allows for: 1) decreased operative time and blood loss; 2) diminished perioperative pain; 3) shorter hospitalization time and faster return to premorbid activity; 4) avoidance of closed chest tube drainage; and 5) preservation of the integrity of the facet-pedicle complex, with potential for improvement in outcome related to axial pain. This technique appears best suited for the removal of all centrolateral discs, although it has been used successfully for treating a disc occupying nearly the entire ventral canal. The initial experience suggests that this approach may be used to safely remove appropriately selected thoracic disc herniations with good results.

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Recognition and management of delayed hyponatremia following transsphenoidal pituitary surgery

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


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


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.


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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Definition of cellular immune responses to brain antigens in human head trauma

Michael L. J. Apuzzo, Khalid M. A. Sheikh, James S. Heiden, Martin H. Weiss, and Theodore Kurze

✓ Cellular immune responses to brain antigens in patients with head injury were studied by applying the leukocyte adherence inhibition (LAI) assay. The investigation was conducted in three phases. 1) In the initial phase, evaluation of a series of 22 test and 25 control cases obtained at random during a 2- to 6-week time frame following a traumatic event indicated significant non-adherence of leukocytes (NAL) in 77% of the test group and 20% of the control group in the presence of brain antigen. 2) In a second phase, a larger test population was divided into four groups of different posttraumatic intervals. This study measured NAL in the presence of normal heart or normal brain antigen. Assays revealed an initial significant NAL in the presence of both antigens; however, after the first week following injury the majority of cases manifested significant NAL only with brain antigen. These values of NAL persisted over a 6- to 8-week period. 3) As a final phase of investigation, analysis of a sequential series of assays in 12 patients over a 90-day period indicated significant NAL in the presence of brain antigen within the first week of injury, this was followed by a drop in NAL in most of the cases. Studies at 7 to 60 days posttrauma demonstrated significant NAL with brain antigen alone, with a subsequent drop by 90 days. These observations are interpreted to represent sensitization of leukocyte subgroups to brain proteins that are immunologically recognized following the traumatic event.

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Acute fractures of the odontoid process

An analysis of 45 cases

Michael L. J. Apuzzo, James S. Heiden, Martin H. Weiss, Truman T. Ackerson, J. Paul Harvey, and Theodore Kurze

✓ Between 1969 and 1974, 45 cases of acute odontoid fracture were diagnosed and treated at this institution. The group consisted of 35 men and 10 women; 24 were between 19 and 40 years of age, and 21 were over 40 years old. Detectable myelopathy was appreciated in eight cases (18%). Diagnosis was established within 72 hours of the traumatic event. Initial evaluation disclosed displacement of the fracture in 17 cases (38%). Following reduction, the initial treatment was posterior fusion in three cases, and external immobilization in 42 cases. Excluding two deaths within the first week of treatment, 40 cases were available for follow-up analysis. Bone union failed to occur following periods of immobilization ranging from 4 to 6 months in 13 cases (33%). Fibrous union with no evidence of instability was apparent in two cases. Nonunion in displaced fractures was seen in 60%, with a rate of 88% in those displaced more than 4 mm. The rate of nonunion in undisplaced fractures was 16%. The rates of incidence of displacement (53% vs 26%) and nonunion (78% vs 33%) in those displaced were higher in individuals over 40 years of age than in those under 40 years. The incidence of nonunion in individuals aged under 40 with nondisplaced fractures was 12%; it was 25% for individuals over 40 years old. A total of 13 patients underwent posterior fusion. All eventually manifested stability at the C1–2 level. However, 69% failed to show bone union at the fracture site in a 6- to 18-month follow-up period.

This review indicates that in consideration of the fracture, external immobilization is the initial treatment of choice in all nondisplaced fractures. Displaced fractures occurring in patients over 40 years old, and those displaced more than 4 mm are candidates for internal stabilization and fusion as a primary mode of treatment.

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Effect of positive end expiratory pressure ventilation on intracranial pressure in man

Michael L. J. Apuzzo, Martin H. Weiss, Viesturs Petersons, R. Baldwin Small, Theodore Kurze, and James S. Heiden

✓ This study was designed to define the effect of positive end expiratory pressure (PEEP) ventilation on intracranial pressure (ICP). In 25 patients with severe head trauma with and without associated pulmonary injury the following parameters were simultaneously monitored under mechanical ventilation with and without PEEP: ICP, arterial blood pressure, central venous pressure, arterial blood gases, and cardiac rate. In addition, the volume-pressure response (VPR) was evaluated in each patient to assess cerebral elastance. The results indicate a significant increase in ICP with the application of PEEP only in the 12 patients who manifested increased cerebral elastance by VPR. Half of this latter group manifested impairment of cerebral perfusion pressure to levels less than 60 mm Hg. Return to baseline ICP levels was observed with termination of PEEP. No significantly consistent changes in other parameters were noted.