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Harvey G. Thomas, Clarisse L. Dolman, and Kenneth Berry

✓ The records of 15 patients with a diagnosis of malignant meningioma were reviewed. In one of these patients, in whom invasion of the brain and pituitary gland was the only unusual feature, the tumor was reclassified as benign. Seven tumors, four hemangiopericytomas and two transitional and one syncytial meningioma, were considered to be only borderline-malignant despite necrosis and invasion of the brain, because of few mitoses and regular architecture. Of this group of patients, four men and three women, two are alive and well, three died after incomplete resections, and two succumbed to recurrent tumor that had become inoperable. The other seven patients, six men and one woman, had lesions classified as histologically frankly malignant, on the basis of marked anaplasia and numerous mitoses. These comprised three hemangiopericytomas and three syncytial and one fibrous meningioma. One of these patients is alive and well and the others are dead, three as a result of metastases. The initial clinical course of malignant meningiomas tends to be short but is otherwise indistinguishable from that of benign meningiomas. The chances of recurrence and eventual death are high, and extracranial metastases are not rare. The tumors are most often hemangiopericytomas, but not exclusively so, and men are particularly at risk.

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Alexandra Stratton, Karla Gustafson, Kenneth Thomas, and Matthew T. James

OBJECTIVE

Spinal epidural abscess (SEA) is a life-threatening infection. It is uncertain whether medical versus surgical treatment is the ideal initial approach for neurologically intact patients with SEA. Recent evidence demonstrates that initial medical management is increasingly common; however, patients who ultimately require surgery after failed medical management may have a worse prognosis than those whose treatment was initially surgical. The primary objective of this study was to establish the current incidence of failed medical management for SEA. The secondary aim was to identify risk factors associated with the failure of medical management.

METHODS

The authors conducted a systematic review and meta-analysis by searching electronic databases (MEDLINE, Embase, CINAHL, and PubMed), recent conference proceedings, and reference lists of relevant articles. Studies that reported original data on consecutive adult patients with SEA treated medically were eligible for inclusion.

RESULTS

Twelve studies met the inclusion criteria, which included a total of 489 medically treated patients with SEA. Agreement on articles for study inclusion was very high between the reviewers (kappa 0.86). In a meta-analysis, the overall pooled risk of failed medical management was 29.3% (95% CI 21.4%–37.2%) and when medical to surgical crossover was used to define failure the rate was 26.3% (95% CI 13.0%–39.7%). Only 6 studies provided data for analysis by intended treatment, with a pooled estimate of 35.1% (95% CI 15.7%–54.4%) of failed medical management. Two studies reported predictors of the failure of medical management.

CONCLUSIONS

Although the incidence of failed medical management of SEA was relatively common in published reports, estimates were highly heterogeneous between studies, thus introducing uncertainty about the frequency of this risk. A consensus definition of failure is required to facilitate comparison of failure rates across studies.

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Leslie J. Dorfman, Inder Perkash, Thomas M. Bosley, and Kenneth L. Cummins

✓ Cerebral somatosensory evoked potentials (SEP's) were elicited by electrical stimulation of the median nerve in the arm (SEPA) and of the posterior tibial nerve in the leg (SEPL) in 23 patients with incomplete localized lesions (including traumatic injuries, neoplasms, vascular malformations and infarcts) of the low cervical, thoracic, or lumbar spinal cord. In eight of 46 attempts (left and right sides), SEPL could not be recorded. Of the remaining 38 sides, spinal somatosensory conduction velocity (SSCV, indirectly estimated) was abnormally slow (< 35 m/sec) in 20, and the amplitude of SEPL relative to SEPA (L:A ratio) was abnormally low (< 0.5) in 20 (p < 0.001 in each case, compared to normal controls). All three criteria yielded a combined 72% incidence of abnormality, correlating best with impairment of joint position sense. Serial postoperative studies in four cases documented an increase in the SSCV and L:A ratio following spinal decompression. These results demonstrate that the latency and amplitude characteristics of the cerebral SEP's from arm and leg permit quantitative evaluation of the functional status of the spinal somatosensory system.

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Vein of Galen ligation in the primate

Angiographic, gross, and light microscopic evaluation

Mary K. Hammock, Thomas H. Milhorat, Kenneth Earle, and Giovanni Di Chiro

✓ The vein of Galen was ligated in 16 Rhesus monkeys and six mongrel dogs, and the animals followed for periods up to six months. Ventricular size was determined preoperatively by pneumoencephalography. Angiography was performed prior to surgery and at intervals from the immediate postoperative period to 6 months following vein ligation. After sacrifice, all brains were serially sectioned and examined by light microscopy. In no case was hydrocephalus found to follow vein of Galen ligation. Consequences were limited to angiographic dilatation of major draining sinuses and cortical veins and microscopic dilatation of diencephalic and choroidal vessels. These changes were evident in the immediate postoperative period and persisted for as long as the animals were followed.

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Thomas L. Slamovits, Kenneth V. Cahill, Patrick A. Sibony, Andrew Dekker, and Bruce L. Johnson

✓ The authors report their experience with five patients presenting with cavernous sinus syndrome who, on computerized tomography (CT) studies, were shown to have a lesion simultaneously involving the cavernous sinus and a portion of the orbit. All patients underwent an orbital fine-needle aspiration biopsy (FNAB). A specific cytological diagnosis was made in three of the five patients. To obtain pathological diagnosis in the case of cavernous sinus tumors, invasive diagnostic procedures are sometimes necessary. Extension of lesions from the cavernous sinus into adjacent areas should be carefully looked for on CT scans. In the specific subset of patients with cavernous sinus tumors and simultaneous orbital involvement, orbital FNAB may provide a simple alternative to more invasive procedures. The limitations of the procedure are discussed.

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Zvi Ram, Stuart Walbridge, Thomas Shawker, Kenneth W. Culver, R. Michael Blaese, and Edward H. Oldfield

✓ Eradication of malignant brain tumors by in situ intratumoral, retrovirally mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, which sensitizes the tumor cells to ganciclovir, has recently been demonstrated in animal models. The observation that tumors studied in vitro and in animals can be completely eliminated despite only partial transduction of the tumor suggests a bystander mechanism that affects nontransduced tumor cells. Such a bystander effect is not completely understood and may represent a combination of several factors that lead to tumor eradication. Endothelial cells of the tumor blood vessels were shown to occasionally integrate the retroviral vector and thus become sensitized to ganciclovir. In the presence of vector-producer cells, which continuously release infectious viral particles, diffuse multifocal hemorrhages occurred during ganciclovir administration. When the tumor was composed of cells that had been transduced with the thymidine kinase gene before inoculation, no infectious viral particles were present within the tumor, no transduction of endothelial cells occurred, and no hemorrhages were observed during ganciclovir therapy. These observations suggest that tumor regression may be due, in part, to destruction of in vivo HSVtk-transduced endothelial cells after exposure to ganciclovir, resulting in tumor ischemia as one possible bystander mechanism.

The authors investigated this hypothesis using the subcutaneous 9L gliosarcoma tumor model in Fischer rats. The tumors were evaluated with Doppler color-flow and ultrasound imaging during the various phases of the study. Twenty rats received intratumoral injections of HSVtk retroviral vector-producer cells (6 × 107 cells/ml) 21 days after bilateral flank tumor inoculation. Ten rats were subsequently treated with intraperitoneal ganciclovir (15 mg/kg/ml twice a day) for 14 days starting on Day 7 after producer cell injection; 10 control rats received intraperitoneal saline injections (1 ml twice a day) instead of ganciclovir. Ultrasound and flow images were obtained before cell injection, before and during ganciclovir or saline administration, and after cessation of treatment. The number, location, and ultrasonographic appearance of tumor vessels and the tumor volumes were recorded.

The number of blood vessels in the tumors increased over time in both groups before treatment. Intratumoral cell injection without ganciclovir administration did not influence tumor growth or intratumoral vasculature. However, tumor vasculature decreased after initiation of ganciclovir therapy in the HSVtk-transduced tumors (p < 0.05). Early patchy or diffuse necrotic changes associated with ultrasonographic evidence of scattered intratumoral hemorrhage occurred in tumors treated with ganciclovir. Reduction of the tumor blood supply may be an important feature of HSVtk transduction-mediated tumor regression and may, at least partially, account for the degree of tumor destruction that occurs despite the lack of transduction of all tumor cells.

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Thomas J. Buell, Daniel M. S. Raper, I. Jonathan Pomeraniec, Dale Ding, Ching-Jen Chen, Davis G. Taylor, and Kenneth C. Liu

Stenosis of the transverse sinus (TS) and sigmoid sinus (SS), with a trans-stenosis pressure gradient, has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH). MRI has shown improvement in TS and SS stenosis after high-volume lumbar puncture (HVLP) in a subset of patients with IIH. The authors present the first report of an IIH patient with immediate post-HVLP TS and SS trans-stenosis pressure gradient reduction and an attendant increase in TS and SS cross-sectional area confirmed using intravascular ultrasonography (IVUS). Recurrence of the patient’s TS-SS stenosis coincided with elevated HVLP opening pressure, and venous sinus stent placement resulted in clinical improvement. This report suggests that TS and SS stenosis may be a downstream effect of elevated intracranial pressure in IIH, rather than its principal etiological mechanism. However, the authors hypothesize that endovascular stenting may obliterate a positive feedback loop involving trans-stenosis pressure gradients, and still benefit appropriately selected patients.

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Shabbar F. Danish and Paul J. Marcotte

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Praveen V. Mummaneni, J. Kenneth Burkus, Regis W. Haid, Vincent C. Traynelis, and Thomas A. Zdeblick

Object

The authors report the results of a prospective randomized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion (ACDF) in patients treated for symptomatic single-level cervical degenerative disc disease (DDD).

Methods

Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and randomly assigned to one of two treatment groups: 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System (Medtronic Sofamor Danek); 265 patients in the control group underwent decompressive ACDF. Eighty percent of the arthroplasty-treated patients (223 of 276) and 75% of the control patients (198 of 265) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery.

Analysis of all currently available postoperative 12- and 24-month data indicated a two-point greater improvement in the neck disability index score in the investigational group than the control group. The arthroplasty group also had a statistically significant higher rate of neurological success (p = 0.005) as well as a lower rate of secondary revision surgeries (p = 0.0277) and supplemental fixation (p = 0.0031). The mean improvement in the 36-Item Short Form Health Survey Physical Component Summary scores was greater in the investigational group at 12 and 24 months, as was relief of neck pain. The patients in the investigational group returned to work 16 days sooner than those in the control group, and the rate of adjacent-segment reoperation was significantly lower in the investigational group as well (p = 0.0492, log-rank test). The cervical disc implant maintained segmental sagittal angular motion averaging more than 7°. In the investigational group, there were no cases of implant failure or migration.

Conclusions

The PRESTIGE ST Cervical Disc System maintained physiological segmental motion at 24 months after implantation and was associated with improved neurological success, improved clinical outcomes, and a reduced rate of secondary surgeries compared with ACDF.

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Matthew J. McGirt, Ketan R. Bulsara, Thomas J. Cummings, Kent C. New, Kenneth M. Little, Henry S. Friedman, and Allan H. Friedman

Object. The prognostic value of differentiating between recurrent malignant glioma and a lesion due to radiation effect by performing stereotactic biopsy has not been assessed. Thus, this study was undertaken to determine such value.

Methods. Between 1995 and 2001, 114 patients underwent magnetic resonance (MR) imaging—guided stereotactic biopsy to differentiate lesions caused by a recurrence of malignant astrocytoma and by radiation effect. All patients had previously undergone tumor resection (World Health Organization Grade III or IV) followed by radiotherapy. Disease diagnosis based on biopsy and patient characteristics were assessed as predictors of survival according to results of a multivariate Cox regression analysis. The diagnosis determined with the aid of biopsy was compared with that established during a subsequent resection in 26 patients.

Survival following stereotactic biopsy was markedly increased in patients suffering from radiation effect compared with those harboring recurrent malignant glioma (p < 0.0001). In patients with radiation effect on biopsy, an increasing patient age (p < 0.05), having had two compared with one prior resection (p < 0.05), and a decreasing time from radiotherapy to biopsy (p < 0.001) were factors associated with decreased survival. Nevertheless, in patients with biopsy-defined radiation effect at second progression or with an age younger than 50 years the survival rate remained higher than that in patients with recurrent tumor on biopsy (p < 0.01). A biopsy-based diagnosis of radiation effect obtained less than 5 months after radiotherapy was not associated with an increased rate of patient survival compared with a diagnosis of recurrent malignant glioma on biopsy (p = 0.286). Eighty-six percent of lesions initially determined to be due to radiation effect on biopsy fewer than 5 months after radiotherapy were characterized as recurrent glioma by a mean of 11 months later. In contrast, only 25% of lesions initially diagnosed as attributable to radiation effect on biopsy more than 5 months after radiotherapy were classified as recurrent glioma a mean of 12 months later (p < 0.05).

Conclusions. With the aid of stereotactic biopsy the authors demonstrated prognostic significance in differentiating recurrent malignant astrocytoma from a lesion due to radiation effect in patients presenting more than 5 months after having undergone radiotherapy. In patients who presented earlier than 5 months after radiotherapy, radiation effect on biopsy was not associated with an improved rate of survival compared with that in patients harboring recurrent malignant astrocytoma.