Reviews & Analysis

The DNA repair enzymeO⁶-methylguanine-DNA methyltransferase (MGMT) antagonizes the effects of alkylating agents, and its expression is associated with resistance to cancer therapy based on these compounds. Weller et al. consider the prognostic and predictive value of MGMT gene silencing in gliomas and describe the assays that are commonly used to evaluate MGMT status, focusing particularly on MGMT promoter methylation, which is the key mechanism of MGMTgene silencing.

Despite growing interest in both the clinical and scientific aspects of sudden unexpected death in epilepsy (SUDEP), knowledge about the disease mechanisms remains limited. The epileptic baboon—the first natural nonhuman primate model of SUDEP—offers a potential model to evaluate the genetic factors and pathophysiology underlying this mysterious condition.

Prospective research participants, patients and consumers are faced with a cacophony of information about the risks and benefits of brain scans. In light of new data on incidental findings, the professional community has a duty to explicitly and systematically encourage questions that promote rational decision-making and informed choice.

Radiotherapy is administered to most patients with low-grade glioma. A well-designed, retrospective study assessed neurocognitive function in patients who had received radiotherapy for low-grade gliomas versus those who had not. Cognitive function did not differ markedly between groups after 6 years, but by 12 years this feature was worse in the group that received radiotherapy.

The International Classification of Headache Disorders II has undergone several revisions in attempts to meet the challenges of accurately diagnosing medication overuse headache and chronic migraine. Newly proposed revisions to the classification are likely to make diagnoses of all secondary headaches more straightforward than before.

Neurons that seem to be specifically involved in relaying pruritogenic sensory information to the brain have been identified in lamina I of the spinal cord. Are these neurons part of the long sought-after neural pathway for itch? The answer to this question could be important for the development of antipruritogenic drugs.

Collateral circulation is a potent predictor of revascularization and clinical outcomes after acute ischemic stroke, and various features of collateral flow may be seen with a variety of neuroimaging techniques. Maas et al. investigated assessment of collaterals on CT angiography source images as a predictive tool in ischemic stroke.

In multiple sclerosis, the ability of clinicians to provide a prognosis for a patient and the design and interpretation of clinical trials both rely heavily on prognostic factors identified from systematic natural history studies. Degenhardt and colleagues outline their criteria for well-designed natural history studies in multiple sclerosis and review the prognostic factors identified from such investigations for the various forms of the disease.

Cavernous malformations (CMs) are vascular malformations that mainly occur in the brain. Many patients with such lesions are asymptomatic; however, individuals with CMs can present with seizures, focal neurological deficits or intracranial hemorrhage. In this Review, Batra and colleagues examine the pathology, natural history and imaging of CMs. Furthermore, the authors discuss the use of pharmacology, surgical resection and stereotactic radiosurgery in the management of such lesions.

Susac syndrome is characterized by a classic triad of symptoms-encephalopathy, branch retinal artery occlusions and hearing loss. Dörr and colleagues present a case of Susac syndrome that highlights how this condition can be easily missed when the triad of symptoms develops successively. Their findings suggest that optical coherence tomography, which detected axonal damage and a reduction of macular volume, could be a valuable complementary tool for the follow-up of patients.

The view of cognitive impairment in elderly individuals has evolved over the centuries, from a normal inevitable part of aging, through demonic possession and hardening of blood vessels, to Alzheimer disease. As Fotuhi et al. discuss in this article, individuals over 80 years of age rarely have 'pure Alzheimer disease' or 'pure vascular dementia'. The authors present a new framework, known as the dynamic polygon hypothesis, which reflects the complex interplay of factors that contribute to cognitive impairment in the oldest old.

Continuous EEG monitoring in intensive care units seems to affect physicians' decisions regarding prescription of anticonvulsant drugs. We are just beginning to understand what the EEG patterns mean and to learn whether and when these prescribing changes matter.

Biomarkers are generally used as diagnostic and prognostic tools in clinical practice, but are not yet available for neuropathies. Studies now suggest that neural protein levels in serum and cerebrospinal fluid reflect axonal damage and predict poor outcome in patients with immune-mediated neuropathy, although validation studies are needed to define their clinical relevance.

A new device, comprising a catheter and wire combination that aspirates clot from an occluded vessel, has received FDA approval for the treatment of stroke. Although the device accomplishes the removal of clot at a higher rate than usual, improvement in patient outcomes remains elusive.

The incidence of cerebral microbleeds, which are acknowledged to be markers of hypertensive vasculopathy and cerebral amyloid angiopathy, increases with age. Cerebral microbleeds are particularly prevalent in patients with intracerebral hemorrhage, and a population-based, cross-sectional study indicates that they are also positively associated with antiplatelet drug use.

Generic drug substitution can markedly decrease the cost of health care. For conditions where agents have a relatively narrow therapeutic index, notably epilepsy, financial savings through generic substitution might be offset by increases in patient complications and related costs. Results from a study with topiramate support this view, particularly when a patient receives a drug from multiple manufacturers.

Data from a large multicenter study demonstrate that donepezil can delay the rate of progression from mild cognitive impairment to Alzheimer disease in patients with depressive symptoms, but not in individuals without notable depression. How important are these findings for clinical practice in neurology and psychiatry?

High-grade gliomas are highly vascularized tumors that represent attractive targets for antiangiogenic therapies. In this article, Norden et al. discuss the rationale for targeting angiogenesis in high-grade gliomas and review the published clinical trial evidence, focusing primarily on therapies that target vascular endothelial growth factor and its receptors.

Primary dystonia is characterized by involuntary twisting and turning movements that occur in the absence of overt brain lesions or evidence of neurodegeneration. As Tanabe et al. discuss in this article, advances in structural and functional imaging have facilitated the identification of motor circuit abnormalities in patients with primary dystonia. In addition, the discovery of dystonia-related genes is providing important insights into the cell biological mechanisms that underlie circuit dysfunction.

Despite its relative rarity, pediatric multiple sclerosis (MS) is an important entity, as it provides unique insights into disease processes related to MS. Clinical, MRI and laboratory data suggest differences in the immune response and CNS environment between adults and children with MS. Yeh et al. provide a comprehensive overview of the pediatric MS field, including epidemiology, disease mechanisms, diagnosis and treatment.