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Daniel W. Fults, Michael D. Taylor and Livia Garzia

Leptomeningeal dissemination (LMD) is the defining pattern of metastasis for medulloblastoma. Although LMD is responsible for virtually 100% of medulloblastoma deaths, it remains the least well-understood part of medulloblastoma pathogenesis. The fact that medulloblastomas rarely metastasize outside the CNS but rather spread almost exclusively to the spinal and intracranial leptomeninges has fostered the long-held belief that medulloblastoma cells spread directly through the CSF, not the bloodstream. In this paper the authors discuss selected molecules for which experimental evidence explains how the effects of each molecule on cell physiology contribute mechanistically to LMD. A model of medulloblastoma LMD is described, analogous to the invasion–metastasis cascade of hematogenous metastasis of carcinomas. The LMD cascade is based on the molecular themes that 1) transcription factors launch cell programs that mediate cell motility and invasiveness and maintain tumor cells in a stem-like state; 2) disseminating medulloblastoma cells escape multiple death threats by subverting apoptosis; and 3) inflammatory chemokine signaling promotes LMD by creating an oncogenic microenvironment. The authors also review recent experimental evidence that challenges the belief that CSF spread is the sole mechanism of LMD and reveal an alternative scheme in which medulloblastoma cells can enter the bloodstream and subsequently home to the leptomeninges.

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Michael D. Taylor and Mark Bernstein

Object. Awake craniotomy was performed as the standard surgical approach to supratentorial intraaxial tumors, regardless of the involvement of eloquent cortex, in a prospective trial of 200 patients surgically treated by the same surgeon at a single institution.

Methods. Patient presentations, comorbid conditions, tumor locations, and the histological characteristics of lesions were recorded. Brain mapping was possible in 195 (97.5%) of 200 patients. The total number of patients sustaining complications was 33 for an overall complication rate of 16.5%. There were two deaths in this series, for a mortality rate of 1%. New postoperative neurological deficits were seen in 13% of the patients, but these were permanent in only 4.5% of them. Complication rates were higher in patients who had gliomas or preoperative neurological deficits and in those who had undergone prior radiation therapy or surgery. No patient who entered the operating room neurologically intact sustained a permanent neurological deficit postoperatively. Of the most recent 50 patients treated, three (6%) required a stay in the intensive care unit, and the median total hospital stay was 1 day.

Conclusions. Use of awake craniotomy can result in a considerable reduction in resource utilization without compromising patient care by minimizing intensive care time and total hospital stay. Awake craniotomy is a practical and effective standard surgical approach to supratentorial tumors with a low complication rate, and provides an excellent alternative to craniotomy performed with the patient in the state of general anesthesia because it allows the opportunity for brain mapping and avoids general anesthesia.

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Guy L. Clifton, Halcott T. Haden, John R. Taylor and Michael Sobel

✓ Cerebral blood flow (CBF) was measured in 39 men at normocapnia and after 5% CO2 inhalation using the xenon-133 technique. Twenty-three patients had unilateral carotid artery occlusion with no angiographic evidence of contralateral carotid artery stenosis or ophthalmic collateral flow. Eleven of these patients had undergone extracranial-intracranial (EC-IC) bypass surgery. Sixteen age-matched normal men underwent CBF measurements at normocapnia and hypercapnia to provide control data. Mean hemispheric CBF was not different between hemispheres ipsilateral and contralateral to the carotid artery occlusion either in the patients who had undergone bypass surgery or in those with carotid artery occlusion alone. Considering all patients with carotid artery occlusion, mean CO2 reactivity was decreased in the hemisphere ipsilateral to the occlusion as compared to the contralateral hemisphere in both groups. Based on data from normal individuals, a hemispheric difference in CO2 reactivity of more than 0.94%/mm Hg PaCO2 or a global CO2 reactivity of less than 0.66%/mm Hg PaCO2 was considered abnormal for an individual patient. Six of 23 patients with carotid artery occlusion (three with an EC-IC bypass) had global or hemispheric abnormalities in CO2 reactivity. Patients with impaired CO2 reactivity were not distinguishable from other patients by neurological examination, presence of transient ischemic attacks, or evidence of infarction on computerized tomography scanning. This test was safe and simple to perform and may be a useful means of detecting impaired cerebrovascular collateral reserve capacity. If impaired CO2 reactivity after carotid artery occlusion proves to be associated with a high risk of subsequent stroke, the test would provide a physiological basis for selecting a subgroup of patients who could be helped by cerebral revascularization.

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Ian D. Kamaly-Asl, Navid Shams and Michael D. Taylor

Choroid plexus tumors consist of papillomas and carcinomas. A variety of germline and somatic genetic changes have been demonstrated for each of these subtypes. In this paper, the authors summarize the current knowledge of the genetic bases of these tumors.

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Anterior sacral meningocele associated with a rectal fistula

Case report and review of the literature

Michael Owen Fitzpatrick and William A. S. Taylor

✓ The authors report a case of anterior sacral meningocele associated with a rectal fistula in a patient who had presented 20 years earlier with bacterial meningitis. To their knowledge, this is the first case in which a rectal fistula developed due to an anterior sacral meningocele. The clinical presentation, diagnosis, and treatment of this uncommon lesion is discussed.

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Charles H. Tator, Michael Fehlings, Kevin Thorpe and Wayne Taylor

A multicenter retrospective study was performed in 36 participating North American centers to examine the use and timing of surgery in the treatment of acute spinal cord injury (SCI). The study was conducted to obtain information required for the planning of a randomized controlled trial of early compared with late decompressive surgery.

The records of all patients aged 16 to 75 years with acute SCI who were admitted to the 36 centers within 24 hours of injury over a 9-month period (August 1994 to April 1995) were examined to obtain data on admission variables, methods of diagnosis, use of traction, and surgical variables including type and timing of surgery.

A total of 585 patients with acute SCI or cauda equina injury were admitted to these centers, although approximately half were ultimately excluded because they did not meet inclusion criteria. Common causes for exclusion were late admission, age, gunshot wound, and an absence of spinal cord compression demonstrated on imaging studies. Thus, only approximately 50% of acute SCI patients would be eligible for inclusion in a study of acute decompressive procedures. Although 100% of patient underwent computerized tomography (CT) scaning, only 54% underwent magnetic resonance imaging, and CT myelography was performed in only 6%. Complete neurological injuries (American Spinal Injury Association Grade A) were present in 57.8%. Traction was applied in only 47% of patients with cervical injuries, of which only 42% demonstrated successful decompression by traction. Neurological deterioration occurred in 8.1% of patients after traction. Surgery was performed in 65.4% of patients. The timing of surgery varied widely: less than 24 hours in 23.5% of patients; 25 to 48 hours in 15.8%; 48 to 96 hours in 19.0%; and 5 days or longer in 41.7% of patients.

These data indicate that whereas surgery is commonly performed in patients with acute SCI, one-third of the cases are managed nonoperatively, and there is very little agreement on the optimum timing of surgical treatment. The results of this study confirm the need for a randomized controlled trial to determine the optimum timing of surgical decompressive procedures in patients with SCI.

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Paul A. Northcott, James T. Rutka and Michael D. Taylor

Advances in the field of genomics have recently enabled the unprecedented characterization of the cancer genome, providing novel insight into the molecular mechanisms underlying malignancies in humans. The application of high-resolution microarray platforms to the study of medulloblastoma has revealed new oncogenes and tumor suppressors and has implicated changes in DNA copy number, gene expression, and methylation state in its etiology. Additionally, the integration of medulloblastoma genomics with patient clinical data has confirmed molecular markers of prognostic significance and highlighted the potential utility of molecular disease stratification. The advent of next-generation sequencing technologies promises to greatly transform our understanding of medulloblastoma pathogenesis in the next few years, permitting comprehensive analyses of all aspects of the genome and increasing the likelihood that genomic medicine will become part of the routine diagnosis and treatment of medulloblastoma.

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Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumors

Characterization of cell subsets with monoclonal antibodies

Roger I. von Hanwehr, Florence M. Hofman, Clive R. Taylor and Michael L. J. Apuzzo

✓ Mononuclear cell infiltrates are found to varying degrees in 30% to 60% of primary human central nervous system (CNS) gliomas. To explore the immunological importance of this, six operative glial tumors, eight non-glial tumors, and three normal brain specimens were studied. Utilizing an immunoperoxidase method, the authors examined frozen sections for lymphoid infiltrates expressing suppressor/cytotoxic and helper phenotypes, as identified with the Leu-1,2,3 monoclonal antibodies. Four of six gliomas demonstrated lymphoid infiltrates: three tumors exhibited a predominant suppressor/cytotoxic cell phenotype and the fourth showed mixed staining of suppressor/cytotoxic and helper cell phenotypes. Varying degrees of lymphoid infiltration characterized four out of eight non-glial primary CNS tumors. Two cases exhibited a prevalence of suppressor/cytotoxic phenotype cells, while two cases demonstrated a more heterogeneous pattern of phenotype expression. Normal brain sections revealed little or no evidence of mononuclear infiltrates. The immunobiological significance of these findings is discussed in the context of tumor-host interaction within the CNS.

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Mustafa Nadi, Navid Khezri, Tahani Ahmad, Michael Ellis, Eric Bouffet, James T. Rutka and Michael D. Taylor

Medulloblastoma is a highly malignant brain tumor of childhood. Although craniospinal dissemination within the subarachnoid space is common, invasion of the dural sinuses is rare. Here, the authors report on a 15-year-old girl who presented with a right cerebellar mass, obstructive hydrocephalus, and radiographic evidence of tumor invasion into the right transverse–sigmoid sinus junction. The patient underwent posterior fossa craniotomy, gross-total resection of the intraparenchymal component of the right cerebellar tumor, and coagulation of the tumor invading the transverse sinus. After pathological confirmation of anaplastic medulloblastoma, the patient underwent craniospinal radiation therapy and high-dose chemotherapy. At 2 years posttreatment, the child was neurologically intact with no radiographic evidence of residual disease or recurrence. The implications for disease prognosis and management are discussed.