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What makes a good clinical guideline? Janis Miyasaki explores this question with reference to the Parkinson's disease practice parameters published by the American Academy of Neurology in April 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.
The use of opioids for the treatment of nonmalignant chronic pain remains controversial. The authors of this Viewpoint discuss the complexities of opioid therapy and present a balanced approach to prescribing these drugs.
The prescription of cholinesterase inhibitors and memantine for the treatment of Alzheimer's disease is a matter for debate. In this Viewpoint, the authors argue that the use of these drugs is justified, provided that patients or their decision makers are given accurate information on their modest benefits.
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.
Levodopa remains the gold standard for treating Parkinson’s disease, but there has long been controversy about this drug’s potential to exert toxic effects on nigral cells, thereby accelerating disease progression. William Weiner evaluates the evidence and explores the implications of this debate for interpreting research data.
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.
As our understanding of the molecular basis of neurodegenerative diseases continues to improve, the prospect of using gene therapy to treat these conditions becomes increasingly realistic. This Viewpoint article discusses initial trials of an RNA interference gene-silencing strategy to modify the expression of mutant proteins in animal models of amyotrophic lateral sclerosis, and considers the hurdles that will need to be overcome to translate this approach into the clinic.
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.
As our understanding of the pathophysiology of spinal cord injury deepens, novel neuroprotective agents are being developed, some of which have already entered clinical trials. In this Viewpoint, Sipski and Pearse examine the status of translational research in this field, focusing specifically on issues surrounding the concurrent use of methylprednisolone. The authors also discuss other potential confounders of clinical trials for spinal cord injury and suggest possible solutions.