This Month in Archives of Neurology

Liu and colleagues Article use a genomewide association study approach to identify novel susceptibility genes for glioma. In their study, they genotyped 550 000 tagging single-nucleotide polymorphisms in a total of 1878 cases and 3670 controls, with validation in 3 additional independent series, totaling 2545 glioma cases and 2953 controls. They have identified 5 genomic risk loci for glioma. Genomewide association studies are a major advance in defining the genomic changes causal of glioma and provide a greater understanding of the biological basis of this disease that will lead to the development of novel therapeutic interventions.

Clarke et al Article point out in their analysis that approximately 51 000 primary brain tumors are diagnosed in the United States each year, 36% of which are gliomas. Of these, half are glioblastoma or World Health Organization grade IV astrocytoma. Glioblastoma is the most aggressive form of glioma and, despite recent advances, continues to have a grim prognosis. The current standard of care for glioblastoma begins with maximal safe surgical resection. After surgery, the combination of radiation with temozolomide followed by adjuvant temozolomide was shown to be significantly, though modestly, better than radiation therapy alone. There remains a great need to search for more effective treatments for this difficult disease. They review recent advances in the treatment of glioblastoma.

Malignant gliomas are often highly vascularized, and significant advances have been made in the last few decades in our understanding of the mechanisms of tumor angiogenesis. Recently, bevacizumab, an antibody against vascular endothelial growth factor, has demonstrated significant activity in recurrent glioblastomas resulting in US Food and Drug Administration approval and raising the prospect of other antiangiogenic drugs entering clinical trials. Iwamoto and Fine Article provide data on the latest developments in this emerging and encouraging field of antiangiogenesis immunotherapy.

Gerstner and Batchelor Article indicate that primary central nervous system lymphoma (PCNSL), an uncommon variant of extranodal non-Hodgkin lymphoma, can affect any part of the neuraxis including the eyes, brain, leptomeninges, or spinal cord. Primary central nervous system lymphoma accounts for approximately 3% of all the primary central nervous system tumors diagnosed each year in the United States. Owing to the rarity of PCNSL, the disease has been challenging to study and an effective standard of care has been difficult to establish. Unfortunately, although durable remissions may be achieved for some patients with PCNSL, the tumor relapses in most cases. In this review, they focus on PCNSL in the immunocompetent host.

Graber and Nolan Article emphasize that myelopathy is a devastating neurologic complication of cancer. Their review addresses the pathophysiology, clinical findings, diagnosis, and treatment of some of the myelopathies that affect patients with cancer. In view of new data, epidural spinal cord compression and paraneoplastic syndromes are emphasized.

Groves Article finds that the treatment of patients with leptomeningeal metastases is multifaceted and complex. Even with an aggressive approach, therapeutic outcomes are uniformly disappointing. Advances in the understanding of the homing of cancer cells to the central nervous system and of cancer metastasis in general, as well as more effective anticancer drugs that are adequately delivered to the central nervous system and cerebrospinal fluid, are needed to improve outcomes for patients with leptomeningeal metastases. These advances may lead to better treatments for this disease and, ultimately, its prevention.

Nabors et al Article report the results of a clinical trial of ABT-510 (Abbott Laboratories, Abbott Park, Illinois), a thrombospondin-1 mimetic drug with antiangiogenic properties. Their phase I dose escalation trial was designed to determine the maximum tolerated dose of ABT-510 when used concurrently with temozolomide and radiotherapy. They report that ABT-510, at subcutaneous doses of up to 200 mg/d, is tolerated well with concurrent temozolomide and radiotherapy in patients with newly diagnosed glioblastoma, and low-density arrays provided a useful method of exploring gene expression profiles.

McKeon et al Article evaluate the cancer detection rate of whole-body positron emission tomography–computed tomography (PET-CT) in a paraneoplastic neurological context. They report that PET-CT improves the detection of cancers when the results of other screening tests are negative, particularly in the setting of seropositivity for a neuronal nuclear or cytoplasmic autoantibody marker of cancer. These new findings are important in showing the diagnostic value of PET-CT in identifying early cancers in patients who have positive paraneoplastic autoantibodies.

Giometto and colleagues Article present a summary of a database that includes the classic paraneoplastic syndromes plus several other, less–well characterized syndromes in association with cancer. The patients were recruited in 20 European centers from January 2000 to December 2008. They analyze the different types of paraneoplastic syndromes, the most frequent tumor and antibody associations, clinical characteristics of individual syndromes, and possible therapeutic and prognostic strategies.

Lee and colleagues Article quantify size and localization differences between tumors presenting with seizures vs nonseizure neurological symptoms. They report that the influence of size and location of the tumors on their propensity to cause seizures varies with the grade of the tumor. In high-grade gliomas, rapidly growing tumors, particularly those situated in deeper structures, present with non–seizure-related symptoms. In low-grade gliomas, lesions in the temporal lobe or the insula grow large without other symptoms and eventually cause seizures. Quantitative image analysis allows for the mapping of regions in each group that are more or less susceptible to seizures.

Rosati et al Article evaluate the efficacy and safety of levetiracetam in the management of epilepsy in patients with glioma. The results of their study provide good evidence that levetiracetam is efficacious and safe in patients with epilepsy due to glioma.

Bertoni and colleagues Article evaluate the possible association between Parkinson disease and melanoma in North America. They report that the prevalence (5-year limited duration) of invasive malignant melanoma in the US cohort of patients with Parkinson disease (n = 1692) was 2.24-fold higher (95% confidence interval, 1.21-4.17) than expected in age- and sex-matched populations in the US Surveillance Epidemiology and End Results database. The age- or sex-adjusted risk ratio for any melanoma for a US patients was more than 7 times that expected from confirmed cases of the American Academy of Dermatology skin cancer screening programs. Despite difficulties in comparing other databases with this study population, the study supports increased melanoma screening in patients with Parkinson disease.