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Albert N. Martins, Ludwig G. Kempe, David T. Pitkethly and Darwin J. Ferry

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Jane C. S. Perrin, Martin H. Weiss and David Yashon

✓ A family with craniofacial dysostosis affecting a father and his monozygotic twin sons is described. The father had no surgery until linear craniectomy when 3 years old; he is of normal intelligence but legally blind. Prophylactic coronal craniectomy and orbital decompression were done on the twins. One had an uncomplicated course and is developing normally. The other developed neonatal meningitis and ventriculitis with secondary hydrocephalus, plus poor vision and retarded development.

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Martin H. Weiss, Benjamin Kaufman and David E. Richards

✓ A case of cerebrospinal fluid rhinorrhea developing in a progressively enlarging empty sella is described in which the fistula was successfully obliterated via a transsphenoidal approach. A modification of the standard closure for transsphenoidal hypophysectomy enabled reconstruction of the dural floor of the sella.

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Raymond A. Martin, Frank M. Howard Jr., Charles R. Salamone and David F. Reese

✓ Two patients had the initial complaint of fluctuating paraparesis, which was most evident at menstruation. One patient had a semimonthly fluctuating deficit. Spinal cord compression and ischemia, secondary to the vascular mass, were considered the most likely mechanisms. Blood levels of estrogen and progesterone during the menstrual cycle may have had a contributory effect. Fluctuating spinal cord deficits associated with a consistent portion of the menstrual cycle should alert the physician to the possibility of an arteriovenous malformation of the spinal cord.

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David C. McCullough and Lynn A. Balzer-Martin

✓ Chiefly because of advances in prenatal diagnostic ultrasonography, prognostic data on congenital hydrocephalus have increased in pertinence. Neurosurgeons may be confronted with requests for prognostic information after discovery of gestational hydrocephalus. Because previous reports reflect technical problems, complications, and less favorable results of an evolutionary period in hydrocephalus therapy, the authors have attempted to update the prognostic picture with a review of their results in hydrocephalus that is overt at birth. The status of 37 children treated with cerebrospinal fluid shunts after delivery at term with overt hydrocephalus was evaluated after an average 6-year follow-up period. They represented 8% of all children being followed for hydrocephalus. Outcome was also reviewed in 11 patients with severe hydrocephalus who were not treated. Of treated patients, 86% survived 1 to 16 years, while all of the untreated infants died at an average of 2.5 months. Approximately two-thirds of treated patients have normal or borderline intellectual capabilities (mean IQ 96, standard deviation 22). Dandy-Walker malformation was associated with a high mortality and a very low IQ in survivors. Congenital aqueductal atresia was also associated with intellectual impairment, but children with communicating hydrocephalus and myelomeningocele were not intellectually impaired. Among the survivors with low IQ, the poor outcome was generally predictable on the basis of cortical mantle thickness and “brain mass” calculations before therapy. The findings from this partially selected series indicate that the majority of babies born with overt hydrocephalus have a good prognosis with appropriate therapy.

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Fernando Viñuela, Jacques E. Dion, Gary Duckwiler, Neil A. Martin, Pedro Lylyk, Allan Fox, David Pelz, Charles G. Drake, John J. Girvin and Gerard Debrun

✓ The authors describe their experience with 101 cerebral arteriovenous malformations (AVM's) treated by endovascular embolization followed by surgical removal. Fifty-three patients presented with intracranial hemorrhage and 35 had seizures. Based on the classification of Spetzler and Martin, two AVM's were Grade I, 13 were Grade II, 26 were Grade III, 43 were Grade IV, and 17 were Grade V, Fifty-six AVM's were in the right hemisphere, 28 were in the left hemisphere, 12 were in the corpus callosum, and five involved the cerebellum. In 50 cases, presurgical obliteration of 50% to 75% of the AVM nidus was achieved by embolization, and in 31 cases this percentage increased to between 75% and 90%. In 97 (96%) patients, complete surgical removal of the AVM was obtained.

Morbidity resulting from preoperative endovascular embolization was classified as mild in 3.9% of the cases, moderate in 6.9%, and severe in 1.98%. The death rate related to embolization was 0.9%. The immediate postsurgical morbidity was classified as mild in 5.9% of the cases, moderate in 10.8%, and severe in 5.9%. The overall long-term morbidity was mild in 5.9% of the cases, moderate in 6.9%, and severe in 1.98%. Two patients (1.98%) died due to intractable intraoperative hemorrhage and two (1.98%) as a result of postsurgical pulmonary complications.

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John R. Adler, Richard S. Cox, Irving Kaplan and David P. Martin

✓ In a series of 33 patients with reasonably controlled primary cancers, stereotactic radiosurgery was used to treat 52 brain metastases. After a mean radiological follow-up time of 5.5 months, six lesions (12%) had stabilized in size, 26 (50%) were significantly reduced, and 15 (29%) had disappeared. One large melanoma metastasis progressed relentlessly despite treatment. Five lesions (9%) had decreased in size slightly before enlarging. In two of these lesions, biopsy revealed only necrosis. In almost all cases, treatment was associated with decreased peritumoral edema. However, a group of patients with large metastases and extensive prior brain irradiation has been identified in whom prolonged symptomatic cerebral edema poses a problem. It is concluded that radiosurgery is a viable alternative to surgical resection for some cases of brain metastasis.

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John C. Chaloupka, David Goller, Robert A. Goldberg, Gary R. Duckwiler, Neil A. Martin and Fernando Viñuela

✓ An unusual case of complete anatomical compartmentalization of the cavernous sinus in a patient with bilateral Type D cavernous dural arteriovenous fistulae is described. This anatomical anomaly isolated the anterior cavernous sinus and orbital venous system, which was primarily responsible for the patient's clinical presentation. The compartmentalization of the cavernous sinus also limited options for definitive endovascular therapy to a transvenous approach via the superior ophthalmic vein.

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David G. Porter, Andrew J. Martin, Conor L. Mallucci, Catherine N. Makunura and H. Ian Sabin

✓ The authors present the case of spinal cord compression in a 16-year-old boy due to the rare vascular lesion, Masson's vegetant hemangioendothelioma.

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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.