Role of perfusion CT in glioma grading and comparison with conventional MR imaging features.

BACKGROUND AND PURPOSE: Perfusion imaging using CT can provide additional information about tumor vascularity and angiogenesis for characterizing gliomas. The purpose of our study was to demonstrate the usefulness of various perfusion CT (PCT) parameters in assessing the grade of treatment-naïve gliomas and also to compare it with conventional MR imaging features. MATERIALS AND METHODS: PCT was performed in 19 patients with glioma (14 high-grade gliomas and 5 low-grade gliomas). Normalized ratios of the PCT parameters (normalized cerebral blood volume [nCBV], normalized cerebral blood flow [nCBF], normalized mean transit time [nMTT]) were used for final analysis. Conventional MR imaging features of these tumors were assessed separately and compared with PCT parameters. Low- and high-grade gliomas were compared by using the nonparametric Wilcoxon 2-sample tests. RESULTS: Mean nCBV in the high- and low-grade gliomas was 3.06 +/- 1.35 and 1.44 +/- 0.42, respectively, with a statistically significant difference between the 2 groups (P = .005). Mean nCBF for the high- and low-grade gliomas was 3.03 +/- 2.16 and 1.16 +/- 0.36, respectively, with a statistically significant difference between the 2 groups (P = .045). Cut points of >1.92 for nCBV (85.7% sensitivity and 100% specificity), >1.48 for nCBF (71.4% sensitivity and 100% specificity), and <1.94 for nMTT (92.9% sensitivity and 40% specificity) were found to identify the high-grade gliomas. nCBV was the single best parameter; however, using either nCBV of >1.92 or nCBF of >1.48 improved the sensitivity and specificity to 92.9% and 100%, respectively. The sensitivity and specificity for diagnosing a high-grade glioma with conventional MR imaging were 85.7% and 60%, respectively. CONCLUSIONS: PCT can be used for preoperative grading of gliomas and can provide valuable complementary information about tumor hemodynamics, not available with conventional imaging techniques. nCBV was the single best parameter correlating with glioma grades, though using nCBF when nCBV was <1.92 improved the sensitivity. An nCBV threshold of >1.92 was found to identify the high-grade gliomas.

Corticotropin releasing factor administered into the ventricular CSF stimulates the pituitary-adrenal axis.

Ovine corticotropin releasing factor (CRF) given intracerebroventricularly to rhesus monkeys at doses of 0.1-1 microgram/kg activates the pituitary-adrenal axis. The increases of plasma cortisol concentrations after intraventricular injection of CRF were similar to those observed after intravenous administration of this releasing factor and occurred without elevation of plasma concentrations of CRF, measured by radioimmunoassay. Thus, the cerebrospinal fluid (CSF) can serve as a conduit for delivery of CRF to the pituitary gland.

Arachnoid cysts of the posterior fossa.

Arachnoid cysts of the posterior fossa are an uncommon clinical entity. The two cases presented in this review were evaluated without vertebral angiography. We think that the development of magnetic resonance imaging may obviate the need for angiography in selected cases.

Spinal epidural abscess: evaluation of factors influencing outcome.

OBJECTIVE: The goal of this study was to critically evaluate the predictive efficacy of various clinical factors in spinal epidural abscess influencing outcome after surgical and/or medical treatment. METHODS: A retrospective analysis of 41 cases of spinal epidural abscess treated at Henry Ford Hospital between 1984 and 1992 was performed. RESULTS: Thirty patients underwent open surgery and received antibiotic therapy, and 11 patients received medical treatment alone. After a mean follow-up period of 20.9 months (range, 4-45 mo), 24 patients (58.5%) had no or minimal deficits, 9 patients (22%) had severe paresis or plegia and/or bowel/bladder dysfunction, and 8 patients (19.5%) died. Univariate analysis revealed patient age, degree of thecal sac compression, spinal location, surgical findings, and septic presentation to be significantly associated with outcome. In multiple logistic regression analysis, increasing age and degree of thecal sac compression were the only factors with significant independent association with poor outcome (P = 0.01 for both). A simple grading system (Grades 0-III) was developed, with patient age, degree of thecal sac compression, and duration of symptoms as the determining criteria. The incidence of poor outcome for patients with Grade 0 was 0%, compared to 85.7% for patients with Grade III. CONCLUSION: We conclude that long-term outcome after treatment of spinal epidural abscess can be predicted with the use of the proposed grading scheme. Surgical drainage plus parenterally administered antibiotics remains the recommended treatment, although medical treatment alone can also be used for certain patients.

Primary craniofacial chordoma: case report.

A 37-year-old man presented with right facial pain and a nonpalpable mass over the malar eminence. An incisional biopsy via the intraoral route was performed and interpreted as a vascular malformation with degenerative changes. His symptoms persisted, and a repeat biopsy was suggestive of an epithelioid nerve sheath tumor. Total resection of the tumor was planned to include the infraorbital and malar regions, the infratemporal fossa, and the pterygopalatine fossa. At surgery, the tumor was removed with tumor-free margins obtained along the course of the maxillary nerve just before its entrance into the cavernous sinus. The pathological findings and the immunohistochemistry demonstrated a typical chordoma with no chondroid or sarcomatous dedifferentiation. We think that with greater use of immunohistochemical markers and electron microscopy, patients with chordoma in this location may be diagnosed promptly and accurately.

Correlation between magnetic resonance spectroscopy imaging and image-guided biopsies: semiquantitative and qualitative histopathological analyses of patients with untreated glioma.

OBJECTIVE: Since intratumoral heterogeneity of gliomas is not adequately reflected in conventional magnetic resonance imaging (MRI), we sought to determine a correlation between different proton magnetic resonance spectroscopic imaging ((1)H MRSI) metabolic ratios and the degree of tumor infiltration in diffusely infiltrating gliomas. In this report, we describe the microscopic anatomy of gliomas on imaging. METHODS: Image-guided biopsies with semiquantitative and qualitative histopathological analyses from a series of 31 untreated patients with low- and high-grade gliomas were correlated with multivoxel (1)H MRSI referenced to the same spatial coordinates. RESULTS: This series yielded 247 tissue samples and 307 observations. Choline-containing compounds using contralateral creatine and choline for normalization or ipsilateral N-acetylaspartate appear to correlate best with the degree of tumor infiltration. Similar correlations were present within each grade after stratification. Despite the interpatient overlap of metabolic ratios between normal tissue and mild tumor infiltration, preliminary analyses revealed that (1)H MRSI appears more accurate than conventional MRI in defining the tumor boundary and quantifying the degree of tumor infiltration. CONCLUSION: This is the first study showing histopathological validation of tumor boundaries using (1)H MRSI. These results support the conclusion that (1)H MRSI accurately reflects the extent of the disease in patients with gliomas. This has important diagnostic and therapeutic implications for more accurately assessing the burden of disease as well as for planning and assessing response to therapy.

Anomalous rib presenting as cervical myelopathy: a previously unreported variant of Klippel-Feil syndrome. Case report.

A patient is reported with an anomalous rib that caused compression of the cervical spinal cord and presented with cervical myelopathy. This appears to be the first reported instance of this particular anomaly. The clinicoanatomical aspects of this case are discussed.

Prolonged external ventricular drainage with percutaneous long-tunnel ventriculostomies.

External ventricular drainage has been used extensively for management of several neurosurgical disorders. The main limitation of this procedure has been the high risk of infection, especially with prolonged drainage. In an effort to minimize the risk of infection, the authors have used a new ventriculostomy technique that involves tunneling the ventricular catheter subcutaneously to an exit site in the lower chest or upper abdomen. This report describes the results of this procedure on 100 consecutive cases. Patients requiring emergency ventriculostomies had short-tunnel ventriculostomies placed at the bedside that were converted to long-tunnel ventriculostomies in the operating room within 5 days. The average duration of drainage was 18.3 days (range 5-40 days). Cerebrospinal fluid was routinely sent for Gram staining and culture to monitor for infection. Prophylactic antibiotic medications were administered only perioperatively. No infection was observed during the first 16 days of drainage in any patient. The overall incidence of infection was 4% and blockage occurred in 6% of the cases. In this series the incidence of ventricular infection was 2.37 per 1000 ventricular drainage days, one of the lowest reported incidences of infection in the literature. This procedure provides a simple and effective method of maintaining long-term ventricular drainage with a very low risk of infection or blockage.

Survival of patients with synchronous brain metastases: an epidemiological study in southeastern Michigan.

OBJECT: It has been suggested that synchronous brain metastases (that is, those occurring within 2 months of primary cancer diagnosis) are associated with a shorter survival time compared with metachronous lesions (those occurring more than 2 months after primary cancer diagnosis). In this study the authors used data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results program to determine the incidence of synchronous brain metastases and length of survival of patients in a defined population of southeastern Michigan residents. METHODS: Data obtained in 2682 patients with synchronous brain metastases treated between 1973 and 1995 were reviewed. Study criteria included patients in whom at least one brain metastasis was diagnosed within 2 months of the diagnosis of primary cancer and those with an unknown primary source. The incidence per 100,000 population increased fivefold, from 0.69 in 1973 to 3.83 in 1995. The most frequent site for the primary cancer was the lung (75.4%). The second largest group (10.7%) consisted of patients in whom the primary site was unknown. The median length of survival was 3.2 months. There was no significant difference in the median survival of patients with primary lung/bronchus and those with an unknown primary site (3.3 months and 3.2 months, respectively). CONCLUSIONS: Patients who present with synchronous lesions have a poor prognosis, and the predominant cause of death, in more than 90% of cases, is related to systemic disease; however, despite poor median survival times, certain patients will experience prolonged survival.

Vascular endothelial growth factor expression and vascular density as prognostic markers of survival in patients with low-grade astrocytoma.

UNLABELLED: It has long been recognized that some patients with low-grade astrocytoma may survive for many years, whereas in others the disease follows a more malignant course resulting in a short survival time, usually due to malignant transformation into higher-grade tumors. OBJECT: The aim of this study was to investigate angiogenesis in the initial biopsy specimen of tumor tissue as a biological marker to identify patients with low-grade astrocytoma who are at high risk of malignant tumor transformation or death. METHODS: Tumor tissue was studied in 74 consecutively treated adult patients in whom a diagnosis of diffuse supratentorial hemispheric histologically proven fibrillary low-grade astrocytoma was made and who underwent surgery between January 1972 and January 1994. Studies were conducted using monoclonal antibodies to the antigens of the proliferation-associated Ki-67 (MIB-1), factor VIII, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). The overall 5-year survival rate for the entire patient population was 65%, with a median survival time of 7.5 years. The total mean follow-up period was 6.1 years. All tumors showed a low proliferative potential at the time of the initial operation, as demonstrated by an MIB-1 labeling index of less than 1.5%. Patients with more than seven microvessels in tumor tissue (29 cases) had a shorter survival time (mean 3.8 years) than those with seven or fewer microvessels (mean survival 11.2 years). This difference in survival times was significant by univariate (p = 0.001) and stepwise multivariate analyses (p < 0.001). Tumors with a larger number of microvessels also had a greater chance of undergoing malignant transformation (p = 0.001). Similarly, significant staining for VEGF was correlated with shorter survival times when using univariate (p = 0.003) and multivariate (p = 0.008) analyses and with a greater chance of malignant transformation (p = 0.002). Patients with tumors staining positive for VEGF (39 individuals) had a median survival time of 5.3 years, and those with tumors negative for VEGF (35 patients) had a median survival time of 11.2 years. No association was observed between bFGF, EGF, and survival or malignant transformation. The stepwise multivariate analysis included histological and clinical variables simultaneously. CONCLUSIONS: The authors have shown that microvessel density and VEGF levels are independent prognostic markers of survival in fibrillary low-grade astrocytoma. This finding leads them to propose that fibrillary diffuse low-grade astrocytoma is not a single pathological entity but is composed of a spectrum of tumors with differing propensities to undergo malignant transformation that is at least partly based on their inherent angiogenic potential.

Preventive management of cerebrospinal fluid leakage in translabyrinthine surgery.

A simple technique can be used to prevent cerebrospinal fluid (CSF) leakage through the nose and the wound in translabyrinthine surgery. This method, evolved from Glasscock's technique of packing the eustachian tube, adds only 5 to 10 minutes to the procedure. The procedure was modeled in the temporal bones of 20 human cadavers, and the findings are described. With this technique, no nasal CSF leaks occurred in a consecutive series of 25 patients who underwent acoustic tumor surgery. Factors thought to be necessary for the success of the technique are discussed.

Obstructive sleep apnea syndrome and acromegaly.

Obstructive sleep apnea syndrome is a complex disorder that has been associated with a variety of abnormalities of the upper airway, including tonsil and adenoid hypertrophy, nasal obstruction, retrognathia, and macroglossia. The cause of the airway obstruction in acromegaly is believed to be related to osseous and soft-tissue changes surrounding the upper airway, which lead to narrowing and subsequent collapse during sleep. We describe the results of treatment in seven patients with both sleep apnea and acromegaly. Four patients were treated by transsphenoidal hypophysectomy alone with a resolution of sleep apnea syndrome. One underwent hypophysectomy followed by postoperative radiation therapy, which reduced his apnea. Three patients underwent unsuccessful uvulopalatopharyngoplasty. Successful treatment of the primary disorder, in this case acromegaly, resulted in improved breathing during sleep in five patients. This series would suggest that acromegalic patients with sleep apnea should be treated for their pituitary tumor to reduce growth hormone before consideration of surgery to enlarge or bypass the upper airway.

The transcondylar approach to the jugular foramen: a comparative anatomic study.

The standard neurosurgical approach to the jugular foramen involves suboccipital craniectomy with access along the petrous bone. However, even after wide removal of the foramen magnum, only limited access into the infratemporal fossa can be obtained. The neurootologic exposures provide excellent infratemporal access but limited exposure to the posterior fossa, resulting in hearing loss and facial paresis or paralysis. Using cadaver specimens, we exposed the jugular foramen region by the transcondylar approach. A retromastoid incision is extended into the neck. The transverse foramen of the atlas is opened and the vertebral artery transposed medially, thereby providing exposure into the infratemporal fossa. A suboccipital craniectomy extending anterior to the sigmoid sinus is performed, and the posterolateral occipital condyle is resected. After resection of the sigmoid sinus, cranial nerves 9 through 12 are easily identified extracranially in the infratemporal fossa and can be followed proximally through their foramina to the brain stem. We compared the transcondylar approach to three standard approaches, morphometrically and anatomically, and found that the transcondylar approach not only compares favorably but also offers advantages in that it preserves auditory and facial nerve function and is useful for one-stage tumor resection.

Cytogenetic findings in pituitary adenoma: results of a pilot study.

Pituitary adenomas are the most common tumors of the sellar region and are, with rare exception, benign neoplasms. The natural history of these lesions is only poorly understood and, although histologic, immunocytologic, and ultrastructural characteristics have been well established, predicting the natural history of individual tumors is, at best, unreliable. In an effort to better characterize pituitary adenomas, we have analyzed the karyotypes of 18 surgical specimens and attempted to correlate with the morphologic appearance and the clinical data, for example, endocrinologic subtypes, histology, and tumor invasiveness. Most hormonal subtypes were studied including seven growth hormone-prolactin (GH-PRL), two Prolactin (PRL), two Adrenocorticotrophin (ACTH), seven nonsecretory (NULL). No correlations with morphology or invasiveness could be made. Of 7 null cell adenomas, five (71%) had normal karyotypes, whereas of 11 hormone-secreting adenomas three (28%) were normal. Of seven tumors with mixed GH-PRL activity, six had abnormal karyotypes. At least three chromosomes harbored abnormalities shared by more than two tumors. The results demonstrate that chromosome abnormalities are also found in benign tumors. These findings, however, suggest that hormone-secreting adenomas may be more likely to be associated with karyotypic abnormalities especially those of the GH-PRL variety. Genetic abnormalities associated with chromosomes 1, 4, 7, and 19 were common and warrant further investigation.

Practice parameters for the management of single brain metastasis.

OBJECT: In January 1998 the Guidelines and Outcomes Committee of the American Association of Neurological Surgeons (AANS) issued a charge for the development of evidence-based practice parameters focusing on the treatment of patients with single metastasis to the brain. The charge was imposed in response to the significant controversy surrounding questions relating to the optimal management strategies for patients with single brain metastasis. METHODS: A team consisting of physicians from the AANS, the American Academy of Neurology, and the American Association of Therapeutic Radiation Oncology convened and the literature was reviewed. Methodically drawing from the best of Class I, II, and III levels of available evidence, authors sought to determine how the literature addressed and disposed of the question of the optimal management for an adult with a known history of cancer and a single metastatic brain lesion. Framing the question in this specific manner allowed researchers to focus directly on treatment issues, without having to consider diagnostic issues. CONCLUSIONS: The results of the evidence-based analysis demonstrated that there was insufficient information to establish standards of care. Data from the literature does, however, support a guideline stating that surgical resection accompanied by whole brain radiation therapy is associated with the best survival rate. Additional lower-quality evidence supports an option for management with radiosurgery.

Permeability estimates in histopathology-proved treatment-induced necrosis using perfusion CT: can these add to other perfusion parameters in differentiating from recurrent/progressive tumors?

BACKGROUND AND PURPOSE: Differentiating treatment effects from RPT is a common yet challenging task in a busy neuro-oncologic practice. PS probably represents a different aspect of angiogenesis and vasculature and can provide additional physiologic information about recurrent/progressive enhancing lesions. The purpose of the study was to use PS measured by using PCT to differentiate TIN from RPT in patients with previously irradiated brain tumor who presented with a recurrent/progressive enhancing lesion. MATERIALS AND METHODS: Seventy-two patients underwent PCT for assessment of a recurrent/progressive enhancing lesion from January 2006 to November 2009. Thirty-eight patients who underwent surgery and histopathologic diagnosis were included in this analysis. Perfusion parameters such as PS, CBV, CBF, and MTT were obtained from the enhancing lesion as well as from the NAWM. RESULTS: Of 38 patients, 11 were diagnosed with pure TIN and 27 had RPT. Patients with TIN showed significantly lower mean PS values than those with RPT (1.8 ± 0.8 versus 3.6 ± 1.6 mL/100 g/min; P value=.001). The TIN group also showed lower rCBV (1.2 ± 0.3 versus 2.1 ± 0.7; P value<.001), lower rCBF (1.2 ± 0.5 versus 2.6 ± 1.7; P value=.004), and higher rMTT (1.4 ± 0.4 versus 1.0 ± 0.4; P value=.018) compared with the RPT group. CONCLUSIONS: PCT and particularly PS can be used in patients with previously treated brain tumors to differentiate TIN from RPT. PS estimates can help increase the accuracy of PCT in differentiating these 2 entities.

In vivo correlation of tumor blood volume and permeability with histologic and molecular angiogenic markers in gliomas.

BACKGROUND AND PURPOSE: Tumor angiogenesis is very heterogeneous and in vivo correlation of perfusion imaging parameters with angiogenic markers can help in better understanding the role of perfusion imaging as an imaging biomarker. The purpose of this study was to correlate PCT parameters such as CBV and PS with histologic and molecular angiogenic markers in gliomas. MATERIALS AND METHODS: Thirty-six image-guided biopsy specimens in 23 patients with treatment-naive gliomas underwent PCT examinations. We correlated MVD, MVCP, VEGFR-2 expression, tumor cellularity, and WHO grade of the image-guided biopsy specimens with the PCT parameters. Histologic sections were stained with hematoxylin-eosin, CD34, and VEGFR-2 and examined under a light microscope. These histologic and molecular angiogenic markers were correlated with perfusion parameters of the region of interest corresponding to the biopsy specimen. Pearson correlation coefficients and multiple regression analyses by using clustering methods were performed to assess these correlations. RESULTS: CBV showed a significant positive correlation with MVD (r = 0.596, P < .001), whereas PS showed a significant positive correlation with MVCP (r = 0.546, P = .001). Both CBV (r = 0.373, P = .031) and PS (r = 0.452, P = .039) also showed a significant correlation with WHO grade. VEGFR-2 positive specimens showed higher PS and CBV; however, neither was statistically significant at the .05 level. CONCLUSIONS: CBV showed a significant positive correlation with MVD, whereas PS showed a significant positive correlation with MVCP, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels; hence, in vivo evaluation of these could be important in a better understanding of tumor angiogenesis.

Quantitative estimation of permeability surface-area product in astroglial brain tumors using perfusion CT and correlation with histopathologic grade.

BACKGROUND AND PURPOSE: Glioma angiogenesis and its different hemodynamic features, which can be evaluated by using perfusion CT (PCT) imaging of the brain, have been correlated with the grade and the aggressiveness of gliomas. Our hypothesis was that quantitative estimation of permeability surface area product (PS), cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in astroglial brain tumors by using PCT will correlate with glioma grade. High-grade gliomas will show higher PS and CBV as compared with low-grade gliomas. MATERIALS AND METHODS: PCT was performed in 32 patients with previously untreated astroglial tumors (24 high-grade gliomas and 8 low-grade gliomas) by using a total acquisition time of 170 seconds. World Health Organization (WHO) glioma grades were compared with PCT parameter absolute values by using Student or nonparametric Wilcoxon 2-sample tests. Receiver operating characteristic (ROC) analyses were also done for each of the parameters. RESULTS: The differences in PS, CBV, and CBF between the low- and high-grade tumor groups were statistically significant, with the low-grade group showing lower mean values than the high-grade group. ROC analyses showed that both CBV (C-statistic 0.930) and PS (C-statistic 0.927) were very similar to each other in differentiating low- and high-grade gliomas and had higher predictability compared with CBF and MTT. Within the high-grade group, differentiation of WHO grade III and IV gliomas was also possible by using PCT parameters, and PS showed the highest C-statistic value (0.926) for the ROC analyses in this regard. CONCLUSIONS: Both PS and CBV showed strong association with glioma grading, high-grade gliomas showing higher PS and CBV as compared with low-grade gliomas. Perfusion parameters, especially PS, can also be used to differentiate WHO grade III from grade IV in the high-grade tumor group.

Rapid damage to membranes of Neisseria gonorrhoeae caused by human neutrophil granule extracts.

Neisseria gonorrhoeae were exposed to extracts of human neutrophil granules and effects on gonococcal growth and membranes were determined. Enumeration of gonococci by phase-contrast microscopy at 0 and 60 min revealed that they underwent very limited cell division after exposure to granule extract. At 60 min, treated gonococci tended to clump, and some lost their refractivity under phase-contrast optics, indicating membrane damage. Treated and untreated gonococci utilized oxygen at similar rates at time 0; treated gonococci utilized oxygen at a relatively constant rate for 60 min, even though colony-forming ability (i.e. viability) decreased by 90%, whereas untreated gonococci showed a steadily increasing rate of oxygen consumption over the same period, which essentially paralleled increase in colony-forming ability. Membrane ultrastructure of untreated and treated gonococci was compared in thin section by transmission electron microscopy. Extract treatment resulted in a time-related increase in disruption of the bacterial outer membrane, which became apparent almost immediately after treatment. This was accompanied by increasingly aberrant septum structure. Extract treatment also increased the resolution of peptidoglycan by electron microscopy, as early as 10 min after treatment. These data suggest that extract treatment of gonococci caused a rapid loss of the ability to form colonies on agar concomitant with alteration of gonococcal peptidoglycan and outer-membrane structure, but with little alteration of inner-membrane function.