Glen Stevens

Serum S100β: A noninvasive marker of blood-brain barrier function and brain lesions

S100β protein is expressed constitutively by brain astrocytes. Elevated S100β levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100β also was shown to indicate blood‐brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100β reflect BBB dysfunction, parenchymal damage, or both.

Blood-Brain Barrier Disruption and Intra-Arterial Methotrexate-Based Therapy for Newly Diagnosed Primary CNS Lymphoma: A Multi-Institutional Experience

PURPOSE Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. PATIENTS AND METHODS This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age > or = 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age < 60 years and KPS > or = 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. CONCLUSION This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.

Challenges With the Diagnosis and Treatment of Cerebral Radiation Necrosis

The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.

Response to intravenous immunoglobulin in Anti-Yo associated paraneoplastic cerebellar degeneration: case report and review of the literature

Paraneoplastic cerebellar degeneration (PCD) is a debilitating neuro-degenerative disease associated with antibodies directed against the purkinje cells of the cerebellum. Treatment using chemotherapy or other treatment of the primary tumor to various immunologically directed therapies has been attempted but outcomes have been poor. We discuss a patient with ovarian carcinoma and PCD seen in our institution who showed a marked beneficial response to intravenous immunoglobulin (IVIG) and methylprednisolone. A Medline search from 1966-2002 produced fifteen cases of PCD confirmed by antibody testing that were treated with IVIG, either alone, or with a combination of other therapies. The clinical characteristics and treatment responses of these patients are analyzed in this review. Most patients that were treated with IVIG and had what was defined as a good response were treated within one month of symptoms. Patients treated between one month and three months often had stable disease and patients treated after three months of symptoms usually had a poor outcome. Early treatment with sufficiently high doses of IVIG seems to provide a better chance of treatment success. The additional benefit of early high dose intravenous methylprednisolone is unclear. Due to the devastating nature of the disease, a trial of IVIG and steroids is warranted as early as possible in a dose of 2g/kg to any patient with a clinical picture of PCD and positive antibodies.

RESULTS OF WHOLE BRAIN RADIOTHERAPY AND RECURSIVE PARTITIONING ANALYSIS IN PATIENTS WITH BRAIN METASTASES FROM RENAL CELL CARCINOMA: A RETROSPECTIVE STUDY

PURPOSE To determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma. METHODS AND MATERIALS We identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes. RESULTS The median follow-up and survival time for all 46 patients (15 women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10 fractions. Patients who received higher radiation doses (>3000 cGy) survived longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7 months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and RPA class were confounding factors in these data. The median survival for patients by RTOG RPA class was 8.5 months for Class I (n = 2), 3 months for Class II (n = 37), and 0.6 months for Class III (n = 7, p = 0.0834). CONCLUSION Despite the relatively poor prognosis of patients who receive WBRT alone, it appears that they benefit from this palliative treatment. The RTOG RPA classification system may be a useful tool in assessing prognosis in this patient population.

Gliomatosis cerebri: treatment results with radiotherapy alone.

Gliomatosis cerebri (GC) is a rare primary brain tumor characterized by proliferation of neoplastic glial cells that typically involve multiple brain areas, with preservation of brain structures and sparing of neurons. The optimal therapeutic strategy is not well established. The impact of radiotherapy on survival in patients with GC remains undefined.

Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas

OBJECT The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS). METHODS One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6-12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method. RESULTS Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS. CONCLUSIONS Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.

The role of adjuvant radiation therapy in the treatment of spinal myxopapillary ependymomas

OBJECT the goal in this study was to determine the role of radiation therapy (RT) in the treatment of spinal myxopapillary ependymomas (MPEs). METHODS thirty-seven patients with histologically verified spinal MPEs were reviewed. Kaplan-Meier analyses and Cox proportional hazard regression were used to determine what patient and treatment factors influenced overall survival (OS) and recurrence. RESULTS at the time of initial diagnosis, the median age was 33 years and the Karnofsky Performance Scale score was 80. In 86.5% of cases, the most common presenting symptom was pain. All patients received surgery as their initial treatment. Nine patients also received RT along with surgery, with a median total dose of 50.2 Gy. The mean survival time was 12.2 years; however, only 4 of 37 patients had died at the time of this study. None of the patient or treatment parameters significantly correlated with OS. Sixteen patients (43.2%) were found to have a recurrence, with a median time to recurrence of 7.7 years. None of the patient or treatment parameters correlated with recurrence-free survival for an initial recurrence. The median time to the second recurrence (recurrence following therapy for initial recurrence) was 1.6 years. Use of RT as salvage therapy after initial recurrence significantly correlated with longer times to a second recurrence. The median recurrence-free survival time before the second recurrence was 9.6 years for those who received RT versus 1.1 years for those who did not receive RT (p = 0.0093). None of the other parameters significantly correlated with a second recurrence. CONCLUSIONS radiation therapy may have a role as salvage therapy in delaying recurrences of spinal MPEs.

Brain-Invasive Solitary Fibrous Tumor of the Meninges: Report of a Case

Solitary fibrous tumor is a mesenchymal neoplasm that most commonly arises in the pleura, but also in multiple extrapleural sites including, rarely, the meninges. Imunohistochemical findings facilitate its differentiation from other spindle cell lesions such as fibrous meningioma. Although the great majority of extrapleural solitary firous tumors behave in a benign fashion, only rare examples of brain-invasive tumors have been documented. We present a case of a brain-invasive solitary fibrous tumor arising in the meninges of a 40-year-old woman. The tumor was marked by focally prominent hypercellularity, moderate nuclear pleomorphism, and increased mitotic activity. Focal infiltration into the underlying brain parenchyma was observed. The tuor was CD34 positive and EMA negative.

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue arising in the lateral ventricle

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas are a well-described type of low-grade B-cell non-Hodgkin lymphoma. They typically arise adjacent to mucosal surfaces in the gastrointestinal tract, lung and conjunctiva, and, less frequently, in the skin, salivary gland and thyroid gland. Unusual locations, such as the genitourinary tract, thymus and meninges, have also been reported. We recently encountered a case of an intracranial MALT lymphoma in a 53-year-old man who presented with persistent headaches and a seizure. The lesion developed as a mass within the lateral ventricle, appeared to be arising from the choroid plexus, and was not associated with meninges. Histologically, there was a vaguely nodular, dense lymphoid infiltrate with occasional benign follicles colonized by marginal zone lymphoma, suggesting derivation from a focus of prior inflammation. Translocations involving the MALT1 gene were not identified but karyotypic evaluation highlighted a complex cytogenetic profile with many chromosomal abnormalities. This rare case provides insight into the pathophysiology of MALT lymphomas.