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Background: Magnetic resonance spectroscopy imaging (MRSI) non-invasively evaluates the metabolic profile of normal and abnormal brain tissue. Primary central nervous system lymphoma (PCNSL) is a highly aggressive tumor responsive to high-dose methotrexate based regimens. Patients often have complete responses but relapses are common. We characterized the MR spectra of PCNSL patients, correlated MRSI with MRI and evaluated whether early recurrence could be detected by MRSI., Methods: Patients with PCNSL had multi-voxel MRSI before, during, and after treatment. The region of interest was defined using axial FLAIR images. Metabolites assessed were N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate. Ratios of Cho/Cr, NAA/Cho, and NAA/Cr were calculated and correlated with MRI. Overall survival (OS), progression free survival (PFS), and relative risks of each of the ratios were determined., Results: MRSI was performed on 11 men and seven women; median age of 59. Sixty-seven MRSI studies were performed, 17 baseline and 48 follow-up studies. Median ratios in 16 pretreated patients were Cho/Cr-1.90, NAA/Cho-0.39, and NAA/Cr-1.27. Two patients had lipid at baseline, five had lactate and two had both. MRSI correlated with tumor response or progression on MRI; in three patients MRSI suggested disease progression prior to changes on MRI. Univariate analysis of metabolite ratios, lipid, and lactate revealed that none significantly affected PFS or OS. Kaplan-Meier analysis of the presence or absence of lipid, lactate or both revealed a trend for increased PFS., Conclusion: MRSI and MRI correlate with tumor response or progression and may allow early detection of disease recurrence. The presence or absence of lipid and/or lactate may have prognostic significance. Further research using MRSI needs to be done to validate our findings and determine the role of MRSI in PCNSL.

Leptomeningeal metastasis is a common complication of cancer. Often the diagnosis can be difficult, but early diagnosis and aggressive treatment can prevent irreversible neurologic deficits. Diagnosis is usually established by the demonstration of malignant cells in the cerebrospinal fluid (CSF) or by the presence of enhancing tumor nodules on cranial or spinal MRI. Treatment may require focal radiotherapy to symptomatic sites accompanied by chemotherapy. Intra-CSF chemotherapy requires normal CSF flow dynamics and is typically limited to the use of methotrexate, cytarabine or thiotepa. Intrathecal chemotherapy is rarely efficacious, except for hematopoietic neoplasms and, to a lesser extent, breast cancer. Increasingly, systemic chemotherapy is recognized as efficacious in the treatment of leptomeningeal metastasis in part because it has the ability to penetrate into bulky disease seen on neuroimaging. The optimum choice of therapy depends upon a thorough assessment of the neurologic extent of disease, which should include complete neuraxis imaging. Patients with extensive bulky disease may be best treated with systemic chemotherapy, whereas those with a positive CSF cytology but negative imaging may be treated with intrathecal chemotherapy and spared the systemic toxicity of intravenous drug. Despite vigorous therapy, many patients do poorly and the median survival is only about four months. Nevertheless, some patients, particularly those with leukemia, lymphoma, and breast cancer, respond and a substantial minority will be alive one to two years after diagnosis.

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm that has captured popular attention because of its rising incidence and marked chemosensitivity. It is a non-Hodgkins B-cell lymphoma (NHL) that appears confined to the central nervous system (CNS) at presentation but may be multifocal within the brain or involve the leptomeninges or eyes at diagnosis. Like systemic lymphoma, it is highly sensitive to corticosteroids, and administration of steroids should be withheld until the diagnosis has been confirmed histologically. Currently, the initial treatment of choice incorporates high-dose methotrexate (HD-MTX) either as a single agent or in combination with other systemic chemotherapies. Whole-brain radiotherapy (WBRT) can be a highly effective treatment modality when combined with MTX, but the combination causes an unacceptably high incidence of severe permanent neurotoxicity, particularly in patients over age 60. Therefore, chemotherapy alone is the initial treatment of choice in older patients. This approach is also being explored in younger patients, but it is possible that deferring radiotherapy may compromise disease control. Consequently, the role of radiotherapy remains to be clarified in newly diagnosed younger patients with PCNSL.

The authors evaluated the efficacy of a combination of rituximab and temozolomide for recurrent or refractory primary CNS lymphoma (PCNSL). Fifteen patients with a median age of 69 years had a 53% objective response rate with acceptable toxicity. Median overall survival is 14 months and median progression free survival of responding patients is 7.7 months. This combination merits further study and provides a reasonable therapeutic alternative for older patients with progressive PCNSL.

Brain metastases are a common complication of cancer, found in approximately 20% of patients at autopsy. The diagnosis is usually established by neuroimaging and carries a poor overall prognosis. Supportive therapies, such as corticosteroids, anticonvulsants, and anticoagulants, are necessary for most patients to address the common medical complications that often accompany brain metastases. These treatments often ameliorate symptoms and signs and improve neurologic function, but they require careful management to minimize their common toxicities. Definitive antitumor treatment may include whole-brain radiotherapy, surgery, stereotactic radiosurgery, and chemotherapy. A multimodal approach can yield prolonged survival of a year or more in some patients, particularly those with limited intracranial disease, high performance status, limited systemic cancer burden, young age, and certain tumor pathologies. However, even patients with poor prognostic factors can have some relief of neurologic symptoms and signs with the institution of therapy. Patients with recurrent brain metastases can also benefit from additional treatment, including all the modalities available at diagnosis.

Primary ocular lymphoma (POL), a lymphoma of the globe, is a restricted form of primary central nervous system lymphoma (PCNSL) that often progresses to the brain and meninges; frequently it is misdiagnosed until central nervous system (CNS) lymphoma develops. The optimal treatment has not yet been identified. We retrospectively reviewed the course and the treatment of POL in 31 patients. Seventeen patients were treated for isolated POL (group A) and 14 were treated only after CNS disease was diagnosed (group B). The treatment in both groups consisted of systemic chemotherapy, chemotherapy plus radiotherapy (RT) or RT alone. In group A, nine patients (53%) developed CNS progression and five (29%) had ocular recurrence. In group B, seven (50%) had CNS progression and three (21%) ocular relapse. To control for diagnostic lead time, median survival was calculated from initial ocular symptoms and was 60 months in group A and 35 months in group B (P < 0.05). Ocular lymphoma responds to a variety of therapies but treatment with chemotherapy and/or ocular radiotherapy (ORT) failed to prevent CNS progression. Patients whose ocular disease was identified and treated before CNS progression had a significantly improved survival.

Background: Convulsive status epilepticus may cause reversible neuroimaging abnormalities. These cortical changes have been reported rarely in association with nonconvulsive status epilepticus., Objective: To describe patients with cancer who had reversible magnetic resonance (MR) imaging abnormalities from nonconvulsive status epilepticus and whose altered mental status and MR imaging findings were initially considered to result from a structural lesion related to their underlying tumor., Design: Retrospective study., Setting: Department of Neurology at Memorial Sloan-Kettering Cancer Center, New York, NY., Patients: Eight patients with a diagnosis of nonconvulsive status epilepticus who underwent MR imaging., Results: Enhancing cortical abnormalities were observed on MR images in 4 (50%) of 8 patients with cancer who had impaired mental status and an electroencephalogram demonstrating seizure activity. Follow-up MR images showed neuroimaging improvement or resolution in all patients., Conclusions: Cortical enhancement on MR images in patients with cancer who have altered mental status may be due to nonconvulsive status epilepticus and not recurrent or metastatic tumor. If electroencephalography is not immediately available at initial evaluation, a trial of anticonvulsant therapy deserves consideration.

Background: Treatment-related leukoencephalopathy is the leading toxicity after successful treatment of primary CNS lymphoma (PCNSL). Its mechanism is poorly understood and there are no autopsy data available on such patients., Methods: From a database of immunocompetent patients with PCNSL diagnosed between 1985 and 2001, the authors identified five autopsied patients who died of leukoencephalopathy. The authors reviewed their clinical records, MRI, and autopsy findings., Results: The median age was 74 years (range 41 to 79) at PCNSL diagnosis. Symptoms of neurotoxicity developed a median of 1 month after treatment completion, and median survival was 30 months (range 22 to 68 months) after neurotoxicity onset. All had white matter hyperintensity on T2-weighted MRI, and two developed enhancing lesions 5 and 14 months following completion of treatment. At autopsy no PCNSL was identified. Myelin and axonal loss, gliosis, pallor, spongiosis, and rarefaction of the white matter were found in all; two patients had tissue necrosis that correlated with the enhancement on MRI, and one had fibrinoid necrosis of vessels. Four of the five patients had atherosclerosis of large cerebral vessels in the circle of Willis and all had small vessel disease; two had recent strokes at autopsy., Conclusions: Treatment-induced leukoencephalopathy is not a late delayed consequence of neurotoxic treatment but can be seen very early in some patients. Vascular disease may be a component of this white matter injury.

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Purpose: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL)., Patients and Methods: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue., Results: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity., Conclusion: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.

Purpose: Anaplastic oligodendroglioma is a chemosensitive glial neoplasm. To improve disease control and postpone cranial radiotherapy, we designed a phase II study of intensive procarbazine, lomunstine and vincristine followed by high-dose thiotepa with autologous stem cell rescue for patients with newly diagnosed anaplastic or aggressive oligodendroglioma., Patients and Methods: Sixty-nine patients with a median age of 42 (range: 18-67) and a median Karnofsky Performance Score of 90 (range: 70-100) were enrolled. Sixteen patients had a prior diagnosis of low-grade oligodendroglioma and 16 had mixed oligoastrocytoma pathology. Only patients with demonstrably chemosensitive enhancing tumors or those free of enhancing tumor after surgery and induction therapy were eligible to receive high-dose thiotepa., Results: Thirty-nine patients (57%) completed the transplant regimen; their estimated median progression-free survival is 69 months and median overall survival has not been reached. Twelve transplanted patients (31%) relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with relapse; however, persistent non-enhancing tumor at transplant conferred an increased risk of relapse (p = 0.028). The transplant regimen was well-tolerated; median hospital stay was 20 days (range: 7-43) with a median time to ANC and platelet engraftment of 10 days. Thirty patients (43%) did not receive high-dose thiotepa because of stable or progressive disease (n = 21), excessive toxicity (n = 4), refusal of further therapy (n = 2), failure to obtain insurance coverage (n = 2), or other (n = 1). No treatment-related or long-term neurotoxicity was seen in the transplanted patients., Conclusions: High-dose chemotherapy with stem cell rescue as initial treatment for anaplastic oligodendroglioma is feasible and associated with prolonged tumor control in some patients.

Primary ocular lymphoma involves the globe in the absence of any systemic or central nervous system lymphoma. Diagnosis is frequently delayed and often made only after the tumor has progressed to the brain and meninges. Clinical features, cues in ancillary tests, and immunologic and molecular advances that support the diagnosis are reviewed. The current treatment options are discussed. Although advances have been made, the optimal treatment for primary ocular lymphoma remains to be identified

Objective: We conducted a clinical trial to determine if prophylactic anticonvulsants in brain tumour patients (without prior seizures) reduced seizure frequency. We stopped accrual at 100 patients on the basis of the interim analysis., Methods: One hundred newly diagnosed brain tumour patients received anticonvulsants (AC Group) or not (No AC Group) in this prospective randomized unblinded study. Sixty patients had metastatic, and 40 had primary brain tumours. Forty-six (46%) patients were randomized to the AC Group and 54 (54%) to the No AC Group. Median follow-up was 5.44 months (range 0.13-30.1 months)., Results: Seizures occurred in 26 (26%) patients, eleven in the AC Group and 15 in the No AC Group. Seizure-free survivals were not different; at three months 87% of the AC Group and 90% of the No AC Group were seizure-free (log rank test, p = 0.98). Seventy patients died (unrelated to seizures) and survival rates were equivalent in both groups (median survival = 6.8 months versus 5.6 months, respectively; log rank test, p = 0.50). We then terminated accrual at 100 patients because seizure and survival rates were much lower than expected; we would need > or = 900 patients to have a suitably powered study., Conclusions: These data should be used by individuals contemplating a clinical trial to determine if prophylactic anticonvulsants are effective in subsets of brain tumour patients (e.g. only anaplastic astrocytomas). When taken together with the results of a similar randomized trial, prophylactic anticonvulsants are unlikely to be effective or useful in brain tumour patients who have not had a seizure.

Brain metastases are one of the most feared complications of cancer because even small tumors may cause incapacitating neurologic symptoms. This article reviews the epidemiology, clinical features, treatment, and prognosis of brain metastases from system malignancies.

Purpose: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL., Patients and Methods: We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m(2), vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT., Results: Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P <.001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died., Conclusion: This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.

Purpose of Review: As treatment of the leukemias improves, patients are surviving longer. Recognizing and rapidly treating metastatic complications or avoiding neurotoxic therapies improves outcome, reduces morbidity and mortality, and limits long-term sequelae., Recent Findings: Neurologic dysfunction may result from leukemic infiltration of the nervous system or as a consequence of chemotherapy or prophylactic craniospinal irradiation. The present review summarizes common problems in the neurologic complications of leukemia and discusses recent advancements in their diagnosis and treatment., Summary: Topics covered in detail include central nervous system prophylaxis, leptomeningeal metastasis, and common hematologic complications affecting the brain. The findings aid in the clinical management of patients with leukemia., (Copyright 2002 Lippincott Williams & Wilkins)

Background: Autopsy studies reveal that most primary CNS lymphomas (PCNSL) extensively infiltrate the brain. To date, there has been no correlation of autopsy findings with a modern neuroimaging assessment of tumor burden., Objective: To correlate autopsy findings in PCNSL to MRI findings., Method: From the authors' database of immunocompetent patients with PCNSL diagnosed between 1985 and 2001, 10 patients who died and had PCNSL at autopsy were identified. Their pathology was compared to MR scans obtained shortly before death., Results: The median patient age was 60 years (range 44 to 80 years). There were six men and four women. Scans were performed within 4 weeks of death in seven patients, within 3 months in two patients, and within 4 months in one. Seven had enhancing lesions consistent with recurrence, and two of the three had focal T2 abnormalities. All had periventricular white matter abnormalities on T2 MR images. At autopsy, all 10 patients had widespread lymphoma throughout the CNS, but no tumor was found systemically. All had tumor infiltration in CNS regions that were normal radiographically, including T2 sequences., Conclusions: MRI underestimates the tumor burden of PCNSL. Bulky disease is seen as a contrast-enhancing lesion because of disruption of the blood-brain barrier, but microscopic tumor infiltration may lead to T2 hyperintensity or be completely normal radiographically.

Background: The current study was conducted to characterize the impact of a prior malignancy on the diagnosis, treatment, and outcome of high-grade glioma., Methods: A retrospective study of 21 patients with a histologic diagnosis of glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO) after a prior diagnosis of solid tumor or hematologic malignancy was conducted. Glioma histology (GBM vs. AA/AO), patient age ( 60 years), and extent of resection (biopsy vs. subtotal vs. complete) were evaluated for their prognostic influence., Results: Of the 21 patients studied, 17 had GBM, 3 had AA, and 1 patient had high-grade AO. There were 25 systemic carcinomas diagnosed in 21 patients (18 solid tumors including breast carcinoma, prostate carcinoma, and melanoma and 7 hematologic malignancies). The glioma occurred within a previous radiation field in only three patients, two of whom had solid tumors and one of whom had a childhood hematologic malignancy. Surgical resection was the initial treatment for the brain tumor in 17 patients, and the majority of patients received radiation therapy and adjuvant chemotherapy. Four patients who initially were misdiagnosed as having brain metastases received whole brain radiation therapy as their initial treatment, thereby compromising optimal care. The overall median survival for all the patients in the current study was 14 months (range, 1-44 months) from the time of brain tumor diagnosis. The extent of resection was found to be the only prognostic variable that was associated with survival (P = 0.03)., Conclusions: Secondary glioma may occur in patients as a consequence of therapy for a prior malignancy, but most often represents a sporadic event. The outcome and recommended treatment are identical to those for patients with primary gliomas. Accurate diagnosis is essential; neuroimaging often is suggestive of a primary brain tumor and should initiate surgical intervention so that histopathology can be obtained early and appropriate treatment instituted., (Copyright 2002 American Cancer Society.)

Systemic high-dose methotrexate (HD-MTX) is the most effective chemotherapeutic agent in the treatment of primary central nervous system lymphoma (PCNSL). Leptomeningeal involvement is common and intrathecal methotrexate (IT-MTX) is frequently used in combination with HD-MTX, but its benefits are not established. Using a case-controlled retrospective study, matching patients treated with HD-MTX with or without IT-MTX, we found no difference in survival, disease control, or neurotoxicity.

Most primary CNS lymphomas (PCNSL) are B-cell neoplasms; T-cell lymphomas are quite rare. The authors report two young patients with T-cell PCNSL who had a complete response to chemo- and radiotherapy but developed recurrent disease and died 11 and 13 months from diagnosis. The prognosis of T-cell PCNSL may be worse than that of comparable B-cell tumors.

Primary central nervous system lymphoma (PCNSL) is widely regarded as one of the primary brain tumors most amenable to treatment. Although whole brain radiotherapy was the cornerstone of therapy for decades, recent work clearly indicates that chemotherapy has become the primary focus of treatment for this disease. The initial treatment of PCNSL for all patients, including the elderly, should be chemotherapy using a high-dose methotrexate-based regimen. Although cranial irradiation has often been combined with methotrexate, the unacceptably high incidence of late neurotoxicity, particularly in older patients, has caused many to eliminate radiotherapy, especially in those older than age 60 years. Emerging data support the validity of this approach, and the development of more efficacious chemotherapeutic regimens has been the focus of recent research.

Objective: To identify the causes of an altered mental status in a cancer population., Methods: We studied 140 confused patients with cancer (100 prospectively and 40 retrospectively) between January 1, 1991, and June 30, 1992, to determine clinical findings, causes, and outcome., Results: All patients had non-central nervous system cancers. The most common primary cancer types were lung (20%), gastrointestinal tract (18%), leukemia and lymphoma (17%), and breast (11%). Median patient age was 73 years, and 49% were men. Disseminated systemic metastases were present in 50% of patients; 34% were confused at hospital admission and 66% developed confusion during hospitalization. Symptoms included lethargy or coma in 61% of patients, agitation in 44%, disorientation in 83%, lateralizing signs in 41%, delusions or hallucinations in 28%, and seizures in 9%. A single cause of the altered mental status was found in 33% of patients, whereas 67% had multiple causes. Drugs, especially opioids, were associated with altered mental status in 64% of patients, metabolic abnormalities in 53%, infection in 46%, and recent surgery in 32%. A structural brain lesion was the sole cause of encephalopathy in 15% of patients. Although delirium improved in 67% of patients, it was a poor prognostic factor for overall outcome. Thirty-day mortality was 25%, and 44% of patients died within 6 months, usually from progression of the underlying cancer. Prolonged delirium suggested infection or coagulopathy. Younger patients and those with hypoxemia or kidney or liver dysfunction were more likely to die (P<.05)., Conclusion: Patients with cancer usually have multiple causes of delirium, many of which are treatable, with rapid improvement in their cognitive status.

Purpose: The use of preradiotherapy (RT) methotrexate (MTX) has improved disease control and survival in patients with primary CNS lymphoma (PCNSL). The reported protocol was designed to optimize and enhance the chemotherapeutic component of treatment., Patients and Methods: Fifty-two patients were treated with five cycles of high-dose MTX 3.5 g/m(2), procarbazine 100 mg/m(2)/d, and vincristine 1.4 mg/m(2). Thirty patients received whole-brain RT (45 Gy). Twenty-two older patients deferred RT to diminish the risk of delayed neurotoxicity; these patients are compared with 12 older patients who completed the entire treatment regimen. Most patients (n = 35) received high-dose cytarabine after RT., Results: Objective response rate to the induction chemotherapy regimen was 90%; overall median survival is 60 months. Grade 3 or 4 myelosuppression was seen in 30 patients, primarily in association with cytarabine; grade 3 nephrotoxicity due to MTX was seen in two patients. Older patients had similar median survival with or without the addition of RT: 32 versus 33 months, respectively. However, late neurotoxicity was significantly more common in those older patients who received RT (P: =.00004). Patients younger than 60 years who received the complete treatment regimen have not reached median disease-free or overall survival., Conclusion: Increasing the dose of MTX and adding procarbazine and vincristine improved disease control and overall survival in patients with newly diagnosed PCNSL. Younger patients in particular fared extremely well with this treatment regimen. In older patients, deferring whole-brain RT did not compromise overall survival but did reduce treatment-related toxicity.

Objective: To evaluate an integrated battery of preoperative functional magnetic resonance imaging (fMRI) tasks developed to identify cortical areas associated with tactile, motor, language, and visual functions., Methods: Sensitivity of each task was determined by the probability that a targeted region was activated for both healthy volunteers (n = 63) and surgical patients with lesions in these critical areas (n = 125). Accuracy of each task was determined by the correspondence between the fMRI maps and intraoperative electrophysiological measurements, including somatosensory evoked potentials (n = 16), direct cortical stimulation (n = 9), and language mapping (n = 5), and by preoperative Wada tests (n = 13) and visual field examinations (n = 6)., Results: For healthy volunteers, the overall sensitivity was 100% for identification of the central sulcus, visual cortex, and putative Wernicke's area, and 93% for the putative Broca's area (dominant hemisphere). For patients with tumors affecting these regions of interest, task sensitivity was 97% for identification of the central sulcus, 100% for the visual cortex, 91% for the putative Wernicke's area, and 77% for the putative Broca's area. These sensitivities were enhanced by the use of multiple tasks to target related functions. Concordance of the fMRI maps and intraoperative electrophysiological measurements was observed whenever both techniques yielded maps and Wada and visual field examinations were consistent with fMRI results., Conclusion: This integrated fMRI task battery offers standardized and noninvasive preoperative maps of multiple critical functions to facilitate assessment of surgical risk, planning of surgical routes, and direction of conventional, intraoperative electrophysiological procedures. Thus, a greater range of structural and functional relationships is brought to bear in the service of optimal outcomes for neurosurgery.

Neurologic complications of cancer and its therapy are varied and common, but there are few true neurologic emergencies. However, when a neurologic emergency does occur, rapid diagnosis and treatment can preserve neurologic function and, in some circumstances, save a life. Epidural spinal cord compression, raised intracranial pressure (ICP), status epilepticus, and intracerebral hemorrhage (ICH) are the most common neurologic emergencies in the cancer patient. This chapter details the clinical features, possible etiologies, diagnostic tests, and treatment options for each of these complications.

Background: Low-grade oligodendrogliomas and mixed gliomas can be indolent and remain unchanged for years. Optimal timing and effectiveness of initial treatment is uncertain and therapy can be associated with toxicity., Methods: Retrospective review of patients diagnosed between 1979 and 1997 with low-grade oligodendroglioma or mixed glioma. Time to progression, survival, prognostic factors, and treatment toxicities were evaluated., Results: A total of 106 patients (77 oligodendroglioma, 29 mixed glioma) were identified; median age was 36.7 years. Initial presenting symptoms were seizures in 76 (72%) and headache in 11 (10%); tumor was diagnosed as an incidental finding in five patients. Tumor progression was diagnosed in 72 patients (68%). Overall median time to progression (MTTP) was 5.0 years (range 0.5 to 14.2). Median overall survival (OS) was 16.7 years. No prognostic factors reached statistical significance. MTTP and OS were not significantly affected by treatment. Of 62 patients who received radiation therapy, 9 (15%) developed radiation necrosis and 13 developed radiation therapy-related cognitive changes, requiring ventriculoperitoneal shunting in six. Significant myelosuppression was seen in 35 of 76 (46%) patients treated with chemotherapy., Conclusions: Low-grade oligodendroglioma and mixed glioma have a long median overall survival. There were no apparent differences in either immediate versus deferred treatment or choice of initial therapy on disease-free or overall survival. Chemotherapy was associated with significant acute toxicity in almost one half of patients; radiation therapy produced late neurotoxicity in one third, justifying deferred treatment until clinically necessary.

Objective: To report the characteristics of cerebral sinus thrombosis (CST) in cancer patients diagnosed by MRI and MR venography (MRV)., Background: CST is a complication of cancer with multiple etiologies and variable symptoms at presentation. Most reports in cancer patients were before the use of MRI and MRV, which has simplified the diagnosis of CST., Methods: The neurology database at Memorial Sloan-Kettering Cancer Center was used to identify cancer patients with a diagnosis of CST between January 1994 and April 1998., Results: Twenty patients were identified. Nine had hematologic malignancies (HMs) and 11 had solid tumors (STs). The median interval from cancer diagnosis to presentation was 4 months for HMs and 20 months for STs. The most common symptom was headache. MRI and MRV correlated in all but three patients, and MRV was more sensitive in four patients. The most frequently involved cerebral sinus was the superior sagittal sinus. Multiple sinuses were affected in 8 of 19 patients. Five patients had a cerebral or subarachnoid hemorrhage and three had infarction. Disorders of coagulation were the most frequent etiology in patients with HM; compression or invasion of the cerebral sinus from dural/calvarial metastasis was the main cause in those with ST. Treatment was directed at the underlying cause. Ten of 20 patients improved clinically and 3 of 6 patients improved radiologically., Conclusion: MRI and MRV can diagnose CST accurately in cancer patients. Causes of CST depend on cancer type, and treatment varies with etiology. Most patients have a good outcome.

Primary central nervous system (CNS) lymphoma is a non-Hodgkin's lymphoma restricted to the nervous system. The incidence of this lymphoma is rising in the immunocompetent population but may be decreasing in patients with the acquired immune deficiency syndrome (AIDS) due to the introduction of highly active antiretroviral therapy. A periventricular, diffusely enhancing lesion on magnetic resonance imaging (MRI) is suggestive of primary CNS lymphoma, but a stereotactic biopsy is needed to make a definitive diagnosis. Concurrent leptomeningeal and ocular involvement is common in this brain tumor. Because primary CNS lymphoma is exquisitely sensitive to steroids, these drugs should be withheld until tissue is obtained for diagnosis. Age and performance status are important prognostic factors, regardless of specific treatment. Methotrexate in high doses is the single most effective chemotherapeutic agent for primary CNS lymphoma. It substantially improves survival when combined with radiation therapy and is better than radiotherapy alone as a single agent. Multimodality treatment results in delayed cognitive neurotoxicity, particularly in older patients. New treatment protocols have focused on the use of chemotherapy alone.

Nervous system metastases occur in about 25% of patients with systemic cancer (Table 1) and usually involve the brain parenchyma, leptomeninges, and spinal epidural space. Although they are ominous, they can be effectively treated in many patients, reducing disability and prolonging life. Treatment may include surgery, and radiation therapy and chemotherapy are often necessary. The choice of agents is often made on the basis of the primary tumor. Even when sustained remission cannot be achieved, effective palliation can be accomplished in most patients.

Primary central nervous system lymphoma (PCNSL) is a relatively uncommon primary brain tumor, but it has become the focus of many clinical trials because of its rising incidence and unique sensitivity to systemic chemotherapeutic agents. Radiotherapy can achieve high response rates and remissions in most patients, but survival is usually only 12-18 months because disease recurs. The addition of systemic chemotherapy, particularly intravenous methotrexate, had markedly improved disease control and many patients can achieve a durable remission and occasionally cure of their disease. Conventional systemic lymphoma drug combinations such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are ineffective. High-dose methotrexate is the single most active and important agent in the treatment of this disease. Whether improved disease control can be accomplished by adding other drugs to high-dose methotrexate or whether it is sufficient as a single agent has yet to be answered. High-dose methotrexate combined with cranial irradiation yields a median survival of at least 40 months and five year survival rates of 22%. However, neurotoxicity is substantial in a significant proportion of patients, particularly those over the age of 60 at the time of treatment. As many as 50% of such patients develop severe dementia. This is particularly important in a disease where approximately half of patients above the age of 60 had presentation. Efforts are now being directed towards not only improving disease control but also minimizing late neurotoxicity. Most efforts are currently directed towards using chemotherapy as the sole modality in the treatment of PCNSL, but both an optimal chemotherapy regimen, and the role of radiotherapy remain to be determined.

The authors describe specific MRI features that suggest the diagnosis of varicella zoster encephalitis. MRI initially revealed discrete, subcortical, nonenhancing lesions that coalesced and developed enhancement. Gray matter involvement was seen later. Autopsy revealed spherical lesions of demyelination and hemorrhagic cavitation confirmed as varicella zoster encephalitis. Characteristic MR features may suggest the diagnosis of varicella zoster encephalitis, enabling definitive diagnostic testing and early institution of antiviral treatment.

Background: The incidence of primary CNS lymphoma (PCNSL) is believed to be increasing in immunocompetent patients but this may not be universally true. The objective of this study was to determine in a population if the incidence of PCNSL is increasing, if the histologic subtypes are changing, and to describe the clinicopathologic and outcome characteristics of PCNSL., Patients and Methods: We identified all Alberta residents with a histologic diagnosis of PCNSL from 1 January 1975 to 31 December 1996 using the Alberta Cancer Registry. Annual age-standardized incidence rates (ASIR), clinicopathologic and outcome characteristics were determined., Results: There were 50 immunocompetent PCNSL patients; the median age was 64 and 30 were male. Their median survival was 10.15 months. Histology was available for review in 37 (74%) patients: 19 (51%) were diffuse large cell, 16 (43%) were immunoblastic and 2 (5%) were unclassifiable malignant lymphomas. The ASIR ranged from 0.178-1.631/10(6) and no change in ASIR was found (test for trend, P = 0.26) for gender or age. The ASIR of malignant gliomas did not change either but increased for all other non-Hodgkin's lymphoma (94.95-138.7610(6); test for trend, P = 0.0001) The number of brain biopsies increased from 1979-1985 (test for trend, P < 0.0001) but remained stable from 1986-1996 (test for trend, P = 0.99)., Conclusions: Unlike several other populations, PCNSL is not becoming significantly more common in Alberta. If this difference is real (i.e., not due to differences in cancer registry coding practices etc.) comparisons between Albertans and other populations in whom the incidence is rising may provide clues regarding the etiology of PCNSL.

Objective: To evaluate prognostic factors and survival of adult patients with brainstem gliomas., Background: Brainstem glioma is a disease found primarily in children, with a median survival of only 9 to 12 months. However, the prognosis and survival of adults with this disease has not been determined with precision., Methods: We conducted a retrospective analysis of patients older than 16 years at Memorial Sloan-Kettering Cancer Center with histologically proved or presumed brainstem glioma diagnosed between 1989 and 1997. We assessed the effect of gender, age at diagnosis, cranial nerve involvement, duration of symptoms, exophytic component, MRI enhancement, site of disease, treatment, and Karnofsky performance status on survival., Results: Twenty-three patients were identified, but complete information was available in only 19 (12 males and 7 females). Patients ranged in age from 17 to 70 years (median, 40 years). Twelve patients were treated with radiotherapy at diagnosis and seven were observed, three of whom received subsequent radiotherapy. Median survival is 54 months (range, 3 to 98 months) and the 5-year survival is 45%. There was a trend for patients with a higher performance status at diagnosis to have longer survival, but this did not reach statistical significance. Other factors did not affect survival., Conclusion: Adults with brainstem gliomas may survive significantly longer than children, suggesting the disease may be less aggressive in adults. Furthermore, some patients with a long duration of symptoms or tectal or cervicomedullary tumors may be managed initially with observation alone.

We combined two randomized prospective Brain Tumor Study Group data sets to analyze the effects of prognostic factors on survival by treatment group. Adjuvant chemotherapy increased long-term survival regardless of prognostic factors. Pathological review revealed that oligo dendrogliomas were overrepresented among long-term survivors independent of therapy. Prognostic factors do not predict benefit from adjuvant nitrosourea in malignant gliomas, and long-term survival with chemotherapy is not explained by oligodendroglial tumors.

Isolated neurosarcoidosis can present with a wide range of central nervous system manifestations. We present two cases of cauda equina sarcoidosis misdiagnosed initially as leptomeningeal malignancy, and review the literature. This unusual manifestation of neurosarcoidosis is typified by an indolent, chronic process with limited response to corticosteroid therapy.

The number of primary brain tumors in the aging population has increased over the past few decades. Although overall survival rates for many patients with primary central nervous system neoplasms have not changed drastically, patients with particular tumor types are benefitting from new treatments. Many factors must be considered when treating primary brain tumors in the elderly, including overall medical condition, tumor biology, and social issues.

Background: Brain abscesses in pediatric patients are rare events, and the causative organism and prognosis vary with the population under study. Children with cancer seem to be particularly susceptible to the development of brain abscesses because of the immunological changes induced by cancer and its treatment. We reviewed the records of children who developed a brain abscess during treatment of a malignancy to define the clinical characteristics, prognosis, and management of these patients., Procedure: We performed a retrospective review of the clinical and laboratory characteristics of all cancer patients younger than age 20 years who were admitted to our institution between 1980 and 1996 for a brain abscess., Results: Twelve children were identified. Cancer diagnoses were brain tumor in two, systemic PNET in two, and leukemia in eight. Six patients had multiple abscesses. Eleven received prior chemotherapy. Abscesses were surgically excised or aspirated in seven, and empiric antibiotics were given to the other five. At surgery, Listeria monocytogenes, Aspergillus fumigatus (3), Fusarium, and Candida lusitanea were cultured. Aspergillus was identified in other locations in four patients. Abscesses were successfully treated in seven patients, two of whom received antibiotics only; five patients (42%) died from infection., Conclusions: Mortality is high in this immunosuppressed population, in part due to the preponderance of fungal infection. The finding of very rare organisms suggests that drainage and culture should be performed whenever possible; empiric antibiotics that include an antifungal agent may, on occasion, be successful.

Meningeal metastasis occurs in 3-8% of all cancer patients, producing neurologic morbidity and a high mortality. Diagnosis is best established by the demonstration of malignant cells in the cerebrospinal fluid. However, in patients with known cancer, MR scan with gadolinium may be diagnostic when subarachnoid nodules can be demonstrated in the head or spine. Therapy usually involves radiotherapy to symptomatic sites, often followed by intrathecal chemotherapy. Intrathecal chemotherapy is best delivered by an intraventricular reservoir system but can also be delivered by repeated lumbar puncture. Methotrexate, cytarabine and thiotepa are the most common agents instilled into the subarachnoid space. Their limited efficacy can be explained by their restricted spectrum of antitumor activity. Patients with leptomeningeal metastasis from leukemia, lymphoma or breast cancer tend to respond best and this may, in part, be attributed to the relative sensitivity of these primary tumor types to the agents administered intrathecally. Systemic chemotherapy may prove a more attractive alternative to intrathecal drugs since it can penetrate into bulky disease, reach all areas of the subarachnoid space, and not be restricted by CSF bulk flow. The prognosis for patients with leptomeningeal metastasis is poor, most individuals surviving a median of only about four months. Occasional patients do have prolonged survival and improvement of their neurologic function.

Objective: To assess the clinical benefit of ventriculoperitoneal shunting in patients suffering from radiotherapy-induced leukoencephalopathy., Design: Retrospective review of a single institutional experience., Patients: Thirty-one patients with the postradiotherapy syndrome received ventriculoperitoneal shunts. All had a history of cranial irradiation, progressive ventriculomegaly visible on neuroimaging scans, and neurologic decline; other causes of hydrocephalus were excluded. All 31 patients had cognitive deficits: 30 had gait disturbance and 24 were incontinent., Results: Twenty-four (80%) of 30 assessable patients achieved symptomatic improvement an average of 1.6 months after ventriculoperitoneal shunting. Incontinence and gait problems were more likely to improve than cognition. Sixteen (53%) of 30 patients achieved a good overall functional outcome, and incontinence was the only feature significantly associated with good outcome (P=.04). Neither cerebrospinal fluid-opening pressure nor tap tests predicted improvement from ventriculoperitoneal shunting. Median duration of improvement was 6 months, and median survival after receiving the shunt was 14.5 months. Shunt-related complications occurred in 10 (33%) of 30 patients, with 1 fatal outcome., Conclusions: Our results from ventriculoperitoneal shunting in selected patients with radiation-induced hydrocephalus suggest potential benefit. Improvement is incomplete and temporary, but can improve quality of life. Reliable predictors of successful shunt outcome were not identified.