Review Articles

Following the discovery that the brain is strikingly susceptible to oxidative DNA damage, considerable attention has been focused on improving our knowledge of the brain's DNA repair pathways and genomic stability. In this article, Kalluri Subba Rao reviews the current state of knowledge regarding neurological diseases that have an etiological link with DNA repair defects, discussing the relationship between the neurological phenotype and the DNA repair pathway that is compromised.

X-linked adrenoleukodystrophy is a genetic neurodegenerative disorder that is characterized biochemically by abnormal accumulation of very long chain fatty acids in all tissues of the body. In this Review, Moseret al.describe the biochemical, genetic and clinical features of this disorder, and discuss new approaches to its diagnosis and treatment, including newborn screening and the use of Lorenzo's oil.

Most human herpesviruses are neurotropic and have the capability to cause serious acute and chronic neurological diseases of the nervous system. In this article, Gilden et al. review current knowledge regarding the clinical features, pathogenesis and treatment of the various neurological complications that can result from herpesvirus infections.

Fabry's disease is an X-linked lysosomal storage disorder, the primary pathology of which is accumulation of glycosphingolipids in cells throughout the body, including the nervous system. Neurological symptoms, which include pain, abnormal sensations and stroke, are evident early in the disease course. In this Review, Møller and Jensen highlight the importance of recognizing these symptoms in order to ensure a rapid diagnosis.

Primary CNS lymphoma, an extranodal non-Hodgkin's lymphoma that invades the nervous system, accounts for around 3% of all primary brain tumors. In this Review, Hochberg et al. highlight recent advances in our understanding of the pathogenesis of primary CNS lymphoma, and they discuss current approaches to the diagnosis and therapy of this condition.

Revascularization has a pivotal role in ischemic stroke therapy, and strokes involving small blood vessels respond well to intravenously administered thrombolytic drugs. Large-vessel strokes carry higher morbidity and mortality than small-vessel strokes, and are less amenable to thrombolytic approaches. In this Review, Wade Smith assesses recent data indicating that recanalization of large vessels can be achieved using mechanical clot retrieval devices.

Intravenous immunoglobulin has an important role in the treatment of numerous neuroimmunological disorders, including Guillain–Barré syndrome and multiple sclerosis. In this article, Gold et al. review current and future indications for intravenous immunoglobulin treatment, discuss its proposed mechanisms of action, and highlight various practical issues relating to its use in the clinic.

Historically, frontotemporal lobar degeneration, corticobasal degeneration and progressive supranuclear palsy have been classified as separate disorders on the basis of distinctive clinical and pathological features. Recent studies using modern molecular and genetic approaches, however, have raised awareness of similarities between these conditions. In this Review, the authors discuss the similarities and differences between these three disorders, and present an argument for their continued separation.

In this Review, Julián Benito-León and Elan Louis discuss the epidemiology, pathophysiology, diagnosis and treatment of essential tremor, one of the most common neurological disorders in adults. This condition has traditionally been viewed as a monosymptomatic disorder characterized by a kinetic arm tremor, but the clinical spectrum is now expanding to include other motor and non-motor features.

Investigations into the mechanisms underlying neurodegenerative disease have tended to focus largely on neuronal abnormalities, but it is becoming increasingly evident that astrocytes are important players in these and other neurological disorders. In this Review, the authors describe the normal roles of astrocytes in the brain, and discuss how animal models have provided important insights into the consequences of astrocyte dysfunction.

Diabetic neuropathy is the most common complication of diabetes mellitus, and there are currently no effective treatments for this condition. In this Review, Leinninger et al. discuss the proposed role of mitochondrial degeneration in the pathogenesis of diabetic neuropathy, and highlight potential mitochondrial sites for therapeutic intervention.

Atherosclerosis, which is the underlying cause of a large proportion of strokes, has traditionally been assessed by measuring carotid intima–media thickness. As David Spence discusses in this Review, however, ultrasound measurement of carotid plaque area and volume is emerging as a powerful new tool for measuring atherosclerosis burden, and it is becoming evident that intima–media thickness and carotid plaque reflect biologically and genetically different aspects of the atherosclerotic process.

Levodopa is the mainstay of treatment for Parkinson’s disease, but it is unable to halt the progression of the disease, and it is also associated with undesirable side effects, including motor fluctuations and dyskinesia. This Review highlights new therapeutic strategies in Parkinson's disease, including neuroprotective therapies and non-dopaminergic drugs, as well as improvements to the existing dopaminergic drugs.

Most cases of human narcolepsy—a neurological disorder that is characterized by excessive daytime sleepiness and cataplexy—are attributable to a loss of neurons that produce hypocretin. This article reviews the evidence linking the loss of these cells to the genesis of narcolepsy, and considers the implications for treatment of this condition.

Cerebrovascular disease is often associated with cognitive impairment. Owing to evolving definitional criteria, however, it has proved difficult to determine the frequency of vascular cognitive disorders in the general population. In this review, Ola Selnes and Harry Vinters review the current state of knowledge in the field of vascular cognitive impairment, emphasizing the neuropathologic and neurocognitive aspects.

The development of combination antiretroviral therapy has led to dramatic reductions in HIV-related morbidity and mortality. Paradoxically, however, the rapid restoration of the immune system that ensues from this treatment can lead to a deterioration in the patient's clinical status—a condition known as immune reconstitution inflammatory syndrome (IRIS). In this Review, Riedel et al. describe the CNS manifestations of IRIS, and they propose a series of guidelines for establishing a diagnosis and managing the condition.

Wilson's disease is an inherited disorder of copper metabolism caused by a mutation in the copper-transporting gene ATP7B, and it results in excessive copper accumulation in the liver and brain. In this Review, the authors provide a comprehensive description of the disease's pathogenesis and neurological clinical presentation, and discuss the diagnosis and treatment options currently available.

Gliomas—tumors of glial cell origin—account for the majority of primary malignant brain tumors, and they are often associated with a very poor prognosis. It is hoped that by identifying genetic, behavioral, environmental and developmental contributors to glioma risk, and understanding how these various factors interact, the disease burden can ultimately be reduced.

Bacterial meningitis is associated with numerous complications, including meningoencephalitis, stroke and raised intracranial pressure. In this Review, van de Beek et al. discuss potential adjunctive therapies for managing these types of complications, citing data from both experimental and clinical studies. They also consider future adjunctive strategies that are currently being investigated in animal models.

Although adult mammalian peripheral axons are able to regenerate after injury, this does not always translate into successful functional recovery after nerve injury in humans. In this review, Ahmet Höke considers the cellular and molecular factors that limit peripheral nerve regeneration in humans, and discusses how new animal models might be developed to investigate these barriers to regeneration and to test novel therapeutic approaches.