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Management of cervical spinal cord trauma in Southern California

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

✓ Acute cervical spinal cord injuries were reviewed in 356 patients treated by the neurosurgical community in Southern California. Neurological recovery was compared in operated and nonoperated patients with complete and incomplete cervical myelopathies. The complications of nonsurgical and surgical therapy are identified. No neurological improvement was noted in any patient with a complete lesion who underwent early surgical decompression. In those with incomplete sensorimotor paralysis, it was difficult to document any effect of surgical decompression on neurological recovery. Patients with some degree of sensory preservation had a similar incidence of motor recovery in both surgical and nonsurgical groups. With complete sensorimotor paralysis, anterior cervical fusion within the first week of injury was associated with increased pulmonary morbidity.

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Penetrating gunshot wounds of the cervical spine in civilians

Review of 38 cases

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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Prognostic variables in surgery for skull base meningiomas

Michael A. Lefkowitz, David R. Hinton, Martin H. Weiss, Steven L. Giannotta, and William T. Couldwell

The authors have retrospectively analyzed selected surgical and pathological observations made among a group of 20 patients harboring recurrent cranial base meningiomas in an attempt to reveal which factors may be important in predicting tumor recurrence. This cohort was compared with a group of 34 patients with cranial base meningiomas that underwent primary resection and in whom tumor recurrence has not been demonstrated over a median follow-up period of 33 months. Features analyzed included brain, cranial nerve, carotid artery, or muscle invasion as well as tumor cellularity, nucleolar prominence, cellular pleomorphism, and percentage of cells staining positive for the Ki-67 antigen. As expected, increased cellularity and tumor necrosis were relatively more prevalent in recurrent tumors. With regard to tumor type, atypical and anaplastic tumors were more common in the group of patients with recurrent tumor compared with the primary group (p < 0.02). As expected, increased cellularity was relatively more prominent in recurrent tumors. Invasion of muscle and bone (72%) was more frequently associated with recurrent tumors, suggesting that these characteristics may be important features of recurrent skull base meningiomas.

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Cranioplasty with the Medpor porous polyethylene Flexblock implant

Technical note

William T. Couldwell, Thomas C. Chen, Martin H. Weiss, Takanori Fukushima, and William Dougherty

✓ The authors describe the use of a porous polyethylene Flexblock implant for cosmetic cranioplasty. The implant may be used to cover any small- or medium-sized (< 8 cm) cranial defect, offering similar cosmetic results to standard alloplast cranioplasty while decreasing operation time. The porous implant design permits ingrowth of soft tissue and bone to increase implant strength and decrease the risk of infection. The Flexblock alloplast has been utilized in 25 cases with excellent cosmetic results and no implant-related complications.

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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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Petroclival meningiomas: surgical experience in 109 cases

William T. Couldwell, Takanori Fukushima, Steven L. Giannotta, and Martin H. Weiss

✓ The surgical removal of petroclival meningiomas has historically been associated with a high incidence of morbidity and mortality. The 109 consecutive patients included in the present retrospective study represent a combined series of tumors operated on by the four authors during a period from 1980 to 1992. The series is composed of 40 men and 69 women ranging in age from 25 to 75 years (mean 51 years). Surgical approaches to tumors in this series included simple retromastoid (60 cases), combined supra- and infratentorial petrosal (22), transtemporal (primary transsigmoid retrolabyrinthine, translabyrinthine, or transcochlear (12)), subtemporal (11), and frontotemporal transcavernous (eight). Gross-total removal was achieved in 75 patients (69%). Recurrence or progression of disease occurred in 14 patients (13%) over a 6.1-year mean follow-up period, and it was found within the cavernous sinus in 12 of these cases. Four recurrent cases demonstrated histological compatibility with malignant meningioma. Perioperative death occurred in four patients, and there were 56 significant complications in 35 other patients. Review of this series, with the attendant complications, has facilitated the authors' decision-making when considering the risk of gross-total removal in selected patients with asymptomatic cavernous sinus invasion or tumor adherent to the brainstem.

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Paradoxical elevation of Ki-67 labeling with protein kinase inhibition in malignant gliomas

William T. Couldwell, Martin H. Weiss, Ronald E. Law, and David R. Hinton

✓ The monoclonal antibody Ki-67 recognizes a nuclear antigen expressed in the G1, S, G2, and M phase of the cell cycle and has been used extensively as an indicator of cellular proliferation in malignant gliomas, both in the laboratory and clinically. Recently, protein kinase C (PKC) inhibitors have been demonstrated to inhibit malignant glioma growth both in in vitro and in vivo. This study was undertaken to determine whether Ki-67 could function as an indicator of cellular proliferation rate after PKC inhibition in gliomas and to explore cell cycle specificity of such inhibition. Both established and low-passage malignant glioma cell lines have previously been shown to be sensitive to growth inhibition by the PKC inhibitors staurosporine and tamoxifen in vitro (IC50 in the nanomolar and micromolar ranges, respectively), as measured by cell numbers, [3H]thymidine uptake, and flow-cytometric DNA analysis. However, in the same cells that are inhibited by staurosporine and tamoxifen on these assays, and on the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay in the present study, the Ki-67 labeling index paradoxically increased in a dose-related manner with the same treatments, as measured by immunohistochemistry and confirmed by flow cytometry. For example, in established line U-87, a 20.5% decrease in thymidine uptake and a 28.5% decrease in absorbance on the MTT assay produced by tamoxifen at 1 µM was associated with an increase in Ki-67 labeling from 42% to 62%; staurosporine, which produces a 78.8% decrease in thymidine uptake in cell line A-172 at 10 nM, produced an increase in Ki-67 labeling from 19% to 32%. In this regard, Ki-67 labeling of glioblastoma tissue from a patient treated with high-dose tamoxifen yielded results within the range of 10% to 15% (consistent with values seen in untreated glioblastoma), despite tumor regression with treatment. The authors' interpretation of these results is that these PKC inhibitors are halting the cell cycle in the G1 phase or the G1—S transition (beyond G0 but before S-phase), resulting in a paradoxical increase in labeling while arresting growth. Two important implications from these observations are that Ki-67 is not a reliable indicator of cellular proliferation after treatment with PKC inhibitors and that these inhibitors used at the doses given above halt cell growth in a phase-specific manner.

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Surgical outcomes in 118 patients with Rathke cleft cysts

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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Significance of postoperative fluid diuresis in patients undergoing transsphenoidal surgery for growth hormone–secreting pituitary adenomas

Clinical article

Gabriel Zada, Walavan Sivakumar, Dawn Fishback, Peter A. Singer, and Martin H. Weiss


Following successful transsphenoidal surgery in patients with growth hormone (GH)–secreting pituitary adenomas, a characteristic fluid diuresis has been described. In this paper the authors aimed to further analyze the degree of fluid diuresis as it relates to postoperative GH levels.


Between 2000 and 2008, 85 patients underwent transsphenoidal surgery for a GH-secreting adenoma at the USC University Hospital. A retrospective chart review was conducted. Postoperative fluid intake, output, and balance within 48 hours following surgery, as well as endocrinological data were recorded and analyzed. Patients with postoperative diabetes insipidus and those with insufficient data were excluded from analysis.


Seventy-one patients were included in the analysis. The mean age was 46 years (range 16–74 years). There were 36 males (51%) and 35 females (49%). Patients with negative fluid balances at 48 hours after surgery were more than twice as likely to have a GH level of < 1.5 ng/ml (55 vs 25%, p = 0.023). At 48 hours after surgery, patients with a negative overall fluid balance had a significantly lower median GH level than those with a positive overall fluid balance (1.3 vs 2.4 ng/ml, p = 0.039). This difference was even more pronounced in patients with microadenomas and a negative overall fluid balance. By 48 hours following surgery, patients with postoperative Day 1 GH levels < 1.5 ng/ml had, on average, experienced diuresis of fluid > 1.1 L (median 1.5 L) more than patients with GH levels > 1.5 ng/ml.


Successful resection of GH-secreting adenomas is associated with a more pronounced fluid diuresis and negative overall fluid balance within 48 hours following transsphenoidal surgery. Patients with a negative fluid balance by postoperative Day 2 have a higher likelihood of having significantly reduced postoperative GH levels that may correlate with long-term surgical remission.

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Correlation of meningioma hormone receptor status with hormone sensitivity in a tumor stem-cell assay

Steven M. Grunberg, Anna Marie Daniels, Helmut Muensch, John R. Daniels, Leslie Bernstein, Virginia Kortes, and Martin H. Weiss

✓ Several investigators have detected progesterone receptors in a high percentage of meningioma specimens and have noted progesterone receptors to be more common than estrogen receptors in these specimens. However, a functional significance of such hormone receptor positivity in control of meningioma growth has not been described. This paper describes a paired test of the estrogen and progesterone receptor assay as the biochemical assay and of the human tumor stem-cell clonogenic assay (HTSCCA) as the functional assay in 17 meningioma specimens. Only one (6%) of the 17 specimens was estrogen receptor-positive, while 11 (69%) of 16 specimens were progesterone receptor-positive. The HTSCCA revealed that only two (15%) of 13 specimens were sensitive to estradiol while five (31%) of 16 specimens were sensitive to progesterone. Comparison of progesterone results for the 15 specimens on which both hormone receptor assay and HTSCCA were performed revealed correlation in a majority of cases; four specimens were positive for both assays and five specimens were negative for both assays. No specimen that was negative for progesterone receptors was sensitive to progesterone by HTSCCA. These results suggest that the hormone receptor and sensitivity pattern of meningiomas may differ from that of breast cancer, and that progesterone addition or ablation may be a reasonable therapeutic approach for meningiomas.