Review Articles in 2006

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.

Sporadic inclusion body myositis is a slowly progressive inflammatory myopathy that is characterized histopathologically by a combination of degenerative and autoimmune inflammatory features in the muscle fibers. In this review, Marinos Dalakas describes the clinical features of sporadic inclusion body myositis, and considers potential disease mechanisms and therapeutic strategies.

Cerebral metastases are a common complication of systemic cancer, and their incidence is set to increase as cancer therapies improve and patients survive longer. In this article, Cavaliere and Schiff review the available therapeutic options for cerebral metastases, and consider the factors that are most likely to influence treatment decisions.

Idiopathic normal pressure hydrocephalus (INPH) is characterized by gait impairment, cognitive decline and urinary incontinence, and is associated with ventricular enlargement in the absence of elevated cerebrospinal fluid pressure. This review describes the diagnosis and treatment of INPH, with particular reference to the recently published INPH consensus guidelines.

Carpal tunnel syndrome results from damage to the median nerve at the wrist, and is associated with a range of symptoms, including pain and numbness in the hand. In this review, the authors describe the clinical criteria that are used by clinicians to reach a diagnosis of carpal tunnel syndrome, and discuss how the diagnosis can be supported by ancillary tests, such as nerve conduction studies and imaging.

Chronic levodopa treatment in patients with Parkinson's disease frequently results in the development of motor complications, including dyskinesias and motor fluctuations. This review presents evidence that these complications are associated with discontinuous stimulation of dopamine receptors that is induced by intermittent oral doses of levodopa, and the authors propose alternative therapeutic approaches based on the principle of continuous dopaminergic stimulation.

Over the past few years, deep brain stimulation has replaced lesioning as the neurosurgical treatment of choice for movement disorders such as Parkinson's disease, essential tremor and dystonia. In this review, Anderson and Lenz describe the original experiments that demonstrated the efficacy and safety of deep brain stimulation, and consider the technical aspects that need to be taken into account as the procedure continues to evolve.

Transcriptional dysregulation is proposed to have an important role in the pathogenesis of Huntington's disease, and recent studies have implicated abnormal modifications of histone proteins in this process. Sadri-Vakili and Jang-Ho Cha review human and animal studies that have provided evidence for such a mechanism, and discuss the therapeutic potential of histone deacetylase inhibitors in Huntington's disease.