Search Results

You are looking at 1 - 10 of 55 items for

  • Author or Editor: Henry Brem x
  • Refine by Access: all x
Clear All Modify Search
Full access

Hemorrhagic vestibular schwannoma: an unusual clinical entity

Case report

Dean Chou, Prakash Sampath, and Henry Brem

Hemorrhagic vestibular schwannomas are rare entities, with only a few case reports in the literature during the last 25 years. The authors review the literature on vestibular schwannoma hemorrhage and the presenting symptoms of this entity, which include headache, nausea, vomiting, sudden cranial nerve dysfunction, and ataxia. A very unusual case is presented of a 36-year-old man, who unlike most of the patients reported in the literature, had clinically silent vestibular schwannoma hemorrhage. The authors also discuss the management issues involved in more than 1000 vestibular schwannomas treated at their institution during a 25-year period.

Restricted access

The role of minocycline in the treatment of intracranial 9L glioma

Jon D. Weingart, Eric P. Sipos, and Henry Brem

✓ This study was designed to explore the question of whether minocycline, a semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis, could control the growth of the rat intracranial 9L gliosarcoma. Minocycline was tested alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started at the time of intracranial implantation of 9L gliosarcoma into male Fischer 344 rats, 5 days later, or after tumor resection.

Minocycline was delivered locally with a controlled-release polymer or systemically by intraperitoneal injection. Systemic minocycline did not extend survival time. Local treatment with minocycline by a controlled-release polymer implanted at the time of tumor implantation extended median survival time by 530% (p < 0.001) compared to treatment with empty polymer. When treatment was begun 5 days after tumor implantation, minocycline delivered locally or systemically had no effect on survival. However, after tumor resection, treatment with locally delivered minocycline resulted in a 43% increase in median survival time (p < 0.002) compared to treatment with empty polymer. Treatment with a combination of minocycline delivered locally in a controlled-release polymer and systemic BCNU 5 days after tumor implantation resulted in a 93% extension of median survival time compared to BCNU alone (p < 0.002). In contrast, treatment with a combination of systemic minocycline and BCNU did not increase survival time compared to systemic BCNU alone. These results demonstrate that minocycline affects tumor growth when delivered locally and suggest that minocycline may be a clinically effective modulator of intracranial tumor growth when used in combination with a chemotherapeutic agent and surgical resection.

Restricted access

Heterotransplantation of malignant human gliomas in neonatal rats

Rafael J. Tamargo, Jonathan I. Epstein, and Henry Brem

✓ Three human glioma cell lines (TE-671 medulloblastoma, U-87 MG glioblastoma, and U-373 MG glioblastoma) were transplanted to the quadrigeminal cistern of the brain in 37 newborn Sprague-Dawley rats and to the subcutaneous space in 30 of their siblings. Two of the three gliomas (the TE-671 medulloblastoma and the U-87 MG glioblastoma) grew both intracranially and subcutaneously. The U-373 MG glioblastoma did not grow in either site. The resulting tumors expressed unique morphological features characteristic of their tissue of origin. The newborn rat represents a model for the heterologous transplantation of human gliomas, providing a biological window for the study of these lesions.

Free access

The 5-factor modified frailty index: an effective predictor of mortality in brain tumor patients

Adham M. Khalafallah, Sakibul Huq, Adrian E. Jimenez, Henry Brem, and Debraj Mukherjee

OBJECTIVE

Health measures such as the Charlson Comorbidity Index (CCI) and the 11-factor modified frailty index (mFI-11) have been employed to predict general medical and surgical mortality, but their clinical utility is limited by the requirement for a large number of data points, some of which overlap or require data that may be unavailable in large datasets. A more streamlined 5-factor modified frailty index (mFI-5) was recently developed to overcome these barriers, but it has not been widely tested in neuro-oncology patient populations. The authors compared the utility of the mFI-5 to that of the CCI and the mFI-11 in predicting postoperative mortality in brain tumor patients.

METHODS

The authors retrospectively reviewed a cohort of adult patients from a single institution who underwent brain tumor surgery during the period from January 2017 to December 2018. Logistic regression models were used to quantify the associations between health measure scores and postoperative mortality after adjusting for patient age, race, ethnicity, sex, marital status, and diagnosis. Results were considered statistically significant at p values ≤ 0.05. Receiver operating characteristic (ROC) curves were used to examine the relationships between CCI, mFI-11, and mFI-5 and mortality, and DeLong’s test was used to test for significant differences between c-statistics. Spearman’s rho was used to quantify correlations between indices.

RESULTS

The study cohort included 1692 patients (mean age 55.5 years; mean CCI, mFI-11, and mFI-5 scores 2.49, 1.05, and 0.80, respectively). Each 1-point increase in mFI-11 (OR 4.19, p = 0.0043) and mFI-5 (OR 2.56, p = 0.018) scores independently predicted greater odds of 90-day postoperative mortality. Adjusted CCI, mFI-11, and mFI-5 ROC curves demonstrated c-statistics of 0.86 (CI 0.82–0.90), 0.87 (CI 0.83–0.91), and 0.87 (CI 0.83–0.91), respectively, and there was no significant difference between the c-statistics of the adjusted CCI and the adjusted mFI-5 models (p = 0.089) or between the adjusted mFI-11 and the adjusted mFI-5 models (p = 0.82). The 3 indices were well correlated (p < 0.01).

CONCLUSIONS

The adjusted mFI-5 model predicts 90-day postoperative mortality among brain tumor patients as well as our adjusted CCI and adjusted mFI-11 models. The simplified mFI-5 may be easily integrated into clinical workflows to predict brain tumor surgery outcomes in real time.

Restricted access

Improvement in the standard treatment for experimental glioma by fusing antibody Fc domain to endostatin

Laboratory investigation

Rachel Grossman, Betty Tyler, Lee Hwang, Patti Zadnik, Bachchu Lal, Kashi Javaherian, and Henry Brem

Object

Brain tumors pose many unique challenges to treatment. The authors hypothesized that Fc-endostatin may be beneficial. It is a newly synthesized recombinant human endostatin conjugated to the Fc domain of IgG with a long half-life (weeks) and unknown toxicity. The authors examined the efficacy of Fc-endostatin using various delivery methods.

Methods

Efficacy was assessed using the intracranial 9L gliosarcoma rat model treated with Fc-endostatin for use in rodents (mFc-endostatin), which was administered either systemically or locally via different delivery methods. Oral temozolomide (TMZ) was administered in combination with mFc-endostatin to determine if there was a beneficial synergistic effect.

Results

Intracranial delivery of mFc-endostatin via a polymer or convection-enhanced delivery 5 days after tumor implantation increased median survival, compared with the control group (p = 0.0048 and 0.003, respectively). Animals treated weekly with subcutaneous mFc-endostatin (started 5 days post–tumor implantation) also had statistically improved survival as compared with controls (p = 0.0008). However, there was no statistical difference in survival between the local and systemic delivery groups. Control animals had a median survival of 13 days. Animals treated either with subcutaneous mFc-endostatin weekly or with polymer had a median survival of 18 and 15 days, respectively, and those treated with oral TMZ for 5 days (Days 5–9) had a median survival of 21 days. Survival was further increased with a combination of oral TMZ and mFc-endostatin polymer, with a median survival of 28 days (p = 0.029, compared with TMZ alone). Subcutaneous mFc-endostatin administered every week starting 18 days before tumor implantation significantly increased median survival when compared with controls (p = 0.0007), with 12.5% of the animals ultimately becoming long-term survivors (that is, survival longer than 120 days). The addition of TMZ to either weekly or daily subcutaneous mFc-endostatin and its administration 18 days before tumor implantation significantly increased survival (p = 0.017 and 0.0001, respectively, compared with TMZ alone). Note that 12.5% of the animals treated with weekly subcutaneous mFc-endostatin and TMZ were long-term survivors.

Conclusions

Systemically or directly (local) delivered mFc-endostatin prolonged the survival of rats implanted with intracranial 9L gliosarcoma. This benefit was further enhanced when mFc-endostatin was combined with the oral chemotherapeutic agent TMZ.

Restricted access

Local delivery of mitoxantrone for the treatment of malignant brain tumors in rats

Francesco DiMeco, Khan W. Li, Betty M. Tyler, Ariel S. Wolf, Henry Brem, and Alessandro Olivi

Object. Mitoxantrone is a drug with potent in vitro activity against malignant brain tumor cell lines; however, its effectiveness as a systemic agent has been hampered by poor central nervous system penetration and dose-limiting myelosuppression. To avoid these problems, we incorporated mitoxantrone into biodegradable polymeric wafers to be used for intracranial implantation, a strategy that has been shown to be safe and successful in the treatment of malignant gliomas. The authors investigated the release kinetics, toxicity, distribution, and efficacy of mitoxantrone delivered from intracranially implanted biodegradable wafers in the treatment of 9L gliosarcoma in Fischer 344 rats.

Methods. Mitoxantrone released from the biodegradable wafer matrix reached therapeutic drug concentrations in the brain for at least 35 days. Only animals with implanted wafers of the highest drug loading dose (20% mitoxantrone by weight) showed signs of significant toxicity. In three separate efficacy experiments, animals treated with mitoxantrone-loaded biodegradable wafers had significantly improved survival compared with control animals. The combined median survival for each treatment group was the following: 0% mitoxantrone wafers, 19 days; 1%, 30 days, p < 0.0001; 5%, 34 days, p < 0.0001; and 10%, 50 days, p < 0.0001.

Conclusions. These findings establish that mitoxantrone delivered from intracranially implanted biodegradable wafers is effective in the treatment of malignant gliomas in rodents and should be considered for future clinical application in humans.

Restricted access

Facial nerve injury in acoustic neuroma (vestibular schwannoma) surgery: etiology and prevention

Prakash Sampath, Michael J. Holliday, Henry Brem, John K. Niparko, and Donlin M. Long

✓ Facial nerve injury associated with acoustic neuroma surgery has declined in incidence but remains a clinical concern. A retrospective analysis of 611 patients surgically treated for acoustic neuroma between 1973 and 1994 was undertaken to understand patterns of facial nerve injury more clearly and to identify factors that influence facial nerve outcome.

Anatomical preservation of the facial nerve was achieved in 596 patients (97.5%). In the immediate postoperative period, 62.1% of patients displayed normal or near-normal facial nerve function (House—Brackmann Grade 1 or 2). This number rose to 85.3% of patients at 6 months after surgery and by 1 year, 89.7% of patients who had undergone acoustic neuroma surgery demonstrated normal or near-normal facial nerve function.

The surgical approach appeared to have no effect on the incidence of facial nerve injury. Poor facial nerve outcome (House—Brackmann Grade 5 or 6) was seen in 1.58% of patients treated via the suboccipital approach and in 2.6% of patients treated via the translabyrinthine approach. When facial nerve outcome was examined with respect to tumor size, there clearly was an increased incidence of facial nerve palsy seen in the immediate postoperative period in cases of larger tumors: 60.8% of patients with tumors smaller than 2.5 cm had normal facial nerve function, whereas only 37.5% of patients with tumors larger than 4 cm had normal function. This difference was less pronounced, however, 6 months after surgery, when 92.1% of patients with tumors smaller than 2.5 cm had normal or near normal facial function, versus 75% of patients with tumors larger than 4 cm.

The etiology of facial nerve injury is discussed with emphasis on the pathophysiology of facial nerve palsy. In addition, on the basis of the authors' experience with these complex tumors, techniques of preventing facial nerve injury are discussed.

Full access

Late-onset facial nerve degeneration after vestibular schwannoma surgery: incidence, putative mechanisms, and prevention

Prakash Sampath, Laurence D. Rhines, Michael J. Holliday, Henry Brem, and Donlin M. Long

Delayed facial nerve dysfunction after vestibular schwannoma surgery is a poorly understood phenomenon that has been reported to occur in 15 to 29% of patients undergoing microsurgery. It is a condition characterized by spontaneous deterioration of facial nerve function in a patient who has otherwise normal or near-normal facial function in the immediate postoperative period. This delayed paralysis is generally reported to occur in the first few days postsurgery, with the majority of patients eventually recovering their immediate postoperative facial function. However, infrequently, it can also occur more than 1 week after surgery (so-called late-onset facial nerve palsy).

The authors reviewed facial nerve outcome in 611 patients who underwent microsurgery between 1973 and 1994. The facial nerve was anatomically preserved in 596 patients (97.5%), and 90% of patients had House-Brackmann[6] Grade 1 or 2 function 1 year after surgery. Late-onset facial dysfunction was seen in 13 patients (2.1%). All of these had significant deterioration in facial nerve function between 1 and 4 weeks postoperatively, and all showed improvement by 1 year. In this study, the focus on these patients who developed late-onset facial palsy. The incidence, treatment strategies, and outcomes will be discussed with emphasis on possible pathophysiological mechanisms that contribute to this relatively rare condition.

Full access

Facial nerve injury in acoustic neuroma (vestibular schwannoma) surgery: etiology and prevention

Prakash Sampath, Michael J. Holliday, Henry Brem, John K. Niparko, and Donlin M. Long

Facial nerve injury associated with acoustic neuroma surgery has declined in incidence but remains a clinical concern. A retrospective analysis of 611 patients surgically treated for acoustic neuroma between 1973 and 1994 was undertaken to understand patterns of facial nerve injury more clearly and to identify factors that influence facial nerve outcome.

Anatomical preservation of the facial nerve was achieved in 596 patients (97.5%). In the immediate postoperative period, 62.1% of patients displayed normal or near-normal facial nerve function (House-Brackmann Grade 1 or 2). This number rose to 85.3% of patients at 6 months after surgery and by 1 year, 89.7% of patients who had undergone acoustic neuroma surgery demonstrated normal or near-normal facial nerve function.

The surgical approach appeared to have no effect on the incidence of facial nerve injury. Poor facial nerve outcome (House-Brackmann Grade 5 or 6) was seen in 1.58% of patients treated via the suboccipital approach and in 2.6% of patients treated via the translabyrinthine approach. When facial nerve outcome was examined with respect to tumor size, there clearly was an increased incidence of facial nerve palsy seen in the immediate postoperative period in cases of larger tumors: 60.8% of patients with tumors smaller than 2.5 cm had normal facial nerve function, whereas only 37.5% of patients with tumors larger than 4 cm had normal function. This difference was less pronounced, however, 6 months after surgery, when 92.1% of patients with tumors smaller than 2.5 cm had normal or near normal facial function, versus 75% of patients with tumors larger than 4 cm.

The etiology of facial nerve injury is discussed with emphasis on the pathophysiology of facial nerve palsy. In addition, on the basis of the authors' experience with these complex tumors, techniques of preventing facial nerve injury are discussed.

Restricted access

Effectiveness of controlled release of a cyclophosphamide derivative with polymers against rat gliomas

Kevin D. Judy, Alessandro Olivi, Kwame G. Buahin, Abraham Domb, Jonathan I. Epstein, O. Michael Colvin, and Henry Brem

✓ Most malignant gliomas grow despite treatment by standard chemotherapeutic agents. The authors explored the use of an innovative drug, 4-hydroperoxycyclophosphamide (4HC), delivered via a controlled-release biodegradable polymer to determine whether local delivery would enhance efficacy. This drug is an alkylator-type chemotherapeutic agent derived from cyclophosphamide. Unlike the parent drug, which requires activation by hepatic microsomes, 4HC is active in vitro. Two rat glioma cell lines, 9L and F98, were treated in cell culture with medium containing 4HC. Both cell lines were more sensitive to 4HC than to a nitrosourea, BCNU, an agent of established value in the local therapy of gliomas.

Ninety Fischer 344 rats implanted with 9L or F98 gliomas were treated with an intracranial polymer implant containing 0% to 50% loaded 4HC in the polymer, and it was found that 20% 4HC—loaded polymers caused minimum local brain toxicity and maximum survival. These polymers were then used to compare the in vivo efficacy of 4HC to BCNU in rats implanted with 9L glioma. Animals with brain tumors treated with 4HC had a median survival span of 77 days compared to the median survival of 21 days in BCNU-treated animals and median survival of 14 days in untreated animals. Long-term survival for more than 80 days was 40% in the 4HC-treated rats versus 30% in the BCNU-treated rats.

The polymer carrier used in this study was a copolyanhydride of dimer erucic acid and sebacic acid 1:1, which was able to maintain the hydrolytically unstable 4HC in a stable state for local delivery. Thus, it is concluded that 4HC-impregnated polymers provide an effective and safe local treatment for rat glioma.