Review Articles in 2009

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.

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.

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.

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.

Incidentally identified demyelinating pathology within the CNS has been extensively documented in neuropathological studies, and is increasingly being reported during MRI-based premortem investigations. In this article, Okuda reviews data on unanticipated demyelinating pathology from both autopsy and imaging studies, and considers the clinical implications of these findings, including the recently introduced concept of the radiologically isolated syndrome.

Early detection of a poor treatment response to disease-modifying agents could be of great benefit to patients with relapsing–remitting multiple sclerosis. Such individuals could be switched to a potentially more effective treatment before too much neurological damage has occurred. In this Review, Río and colleagues examine the use of clinical measures, MRI, and pharmacogenomics in assessing and predicting the treatment response in patients with this condition.

The incidence of Parkinson disease (PD) increases with age, so age-related conditions are expected to feature prominently among the comorbidities associated with this disease. In this article, Nanhoe-Mahabier et al. explore a possible link between PD and cerebrovascular disease, discussing the pathophysiological mechanisms that could underlie such a relationship, and considering how comorbid cerebrovascular disease might affect the clinical presentation of PD.

Chronic kidney disease is a serious global health problem, and almost all patients with severe forms of the disease develop neurological complications, which can include cognitive impairment, cerebrovascular disease and peripheral neuropathies. Krishnan and Kiernan review the clinical features and pathophysiology of the most common neurological complications of chronic kidney disease, and highlight the currently available treatment options.

Clinical overlap between the various types of neurodegenerative parkinsonism, particularly in the early stages of disease, can make differential diagnosis problematic. Biological fluid biomarker assays are being explored as adjunctive tests to aid the diagnostic work-up of patients with neurodegenerative parkinsonism, and in this article Eller and Williams cast a critical eye over the currently available cerebrospinal fluid, plasma and urine biomarkers.

Thrombolytic therapy is an effective treatment for ischemic stroke, but only when delivered within a short period after the onset of the condition. Delay in patients being admitted to hospital is one of the main reasons why the therapeutic window is often missed. This Review examines the factors that affect prehospital delay, and describes strategies designed to overcome the problem.

Sudden unexpected death in epilepsy most frequently occurs in people with chronic epilepsy, and seems to be a seizure-related event. In this article, Surges et al. review the incidence of sudden unexpected death in epilepsy and the risk factors associated with this condition, before exploring the pathological mechanisms related to chronic epilepsy that could lead to sudden death.

Bipolar disorders are recurrent mood disturbances involving periods of depression and mania. Eric Taylor discusses the management of bipolar disorders in children and adolescents, including potential differential diagnoses and the results of treatment trials in these age groups. He also outlines the distinction between classic bipolar disorders and brief emotional outbursts.

Individuals over the age of 80 years account for 30% of the total number of people with ischemic stroke. Nevertheless, elderly patients are more likely to receive suboptimal care than are younger individuals. In this Review, Derex and Nighoghossian examine the effectiveness of thrombolysis therapy, stroke-unit care, and early rehabilitation in elderly patients with stroke.

Transient loss of consciousness is a spell of unconsciousness characterized by abrupt onset, short duration, and spontaneous and complete recovery. In this article, van Dijk et al. provide an overview of the various forms of TLOC, focusing particularly on reflex syncope. They highlight key clues to the diagnosis of these conditions and emphasize the importance of a multidisciplinary approach to the management of patients with TLOC.

Glioblastoma is the most common primary malignant brain tumor in adults, causing over 10,000 deaths each year in the US alone. Given the resistance of this tumor to standard surgery, radiation and chemotherapy, attention has focused on identifying the underlying genetic lesions in the hope of developing new treatment strategies. Purow and Schiff review the current state of knowledge of the genetics of glioblastoma and discuss the implications for future therapies.

Pregnancy can have an unpredictable effect on the frequency and nature of migraines. In this article, Contag et al. examine the association of migraine with pregnancy and pregnancy-related complications, notably pre-eclampsia. The authors also review the diagnosis and management of migraine headaches that precede or develop during pregnancy, and explore the risks associated with the available treatment options.

Patients with hemianopic dyslexia experience serious reading difficulties, with word identification and the abilities to plan and guide reading eye movements being severely disturbed. In this Review, Schuett explores the clinical features and the underlying functional and anatomical bases of hemianopic dyslexia, before critically examining the available therapies for rehabilitation of this condition.