Review Articles

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.

Blood has not generally been regarded as a significant route of transmission for variant Creutzfeldt–Jakob disease (vCJD), but three cases of vCJD transmission through blood transfusion have recently come to light. In this review, Aguzzi and Glatzel discuss these findings in relation to experimental data on prion disease transmission, and consider the possible implications for the safety of blood products.

Stroke and peripheral neuropathy are recognized neurological complications of diabetes, and epidemiological evidence is now emerging to implicate the prediabetic state of impaired glucose tolerance as a risk factor for these conditions. Singleton and Smith assess this evidence, and also consider the possibility of a link between impaired glucose tolerance and cognitive dysfunction.

Since its first appearance in the US in 1999, the arthropod-borne flavivirus West Nile virus has emerged as the main cause of epidemic meningoencephalitis in North America. DeBiasi and Tyler review the epidemiology, clinical features, diagnosis and prognosis of West Nile virus neuroinvasive disease, and discuss current treatments and prospects for future therapies.

It is becoming clear that certain forms of many human neurological disorders, including myotonia, periodic paralysis, epilepsy and migraine, can be attributed to genetically induced ion-channel dysfunction. In this review, Michael Hanna discusses the clinical, genetic and electrophysiological features of a range of neurological channelopathies that are caused by mutations in single genes.

Rett syndrome, a neurodevelopmental disorder that predominantly affects females, is caused by mutations in theMECP2gene. The age of onset usually ranges from 6 to 18 months of age, after an initial period of apparently normal development. In this article, Uta Francke reviews the current state of knowledge about the molecular and cellular mechanisms that underlie Rett syndrome.

There is increasing evidence to indicate that the immune system has a central role in the pathogenesis of multiple sclerosis. In this review, Hemmer et al. present findings from animal and human studies that have provided important insights into the immunology of multiple sclerosis, and discuss how this knowledge is guiding the development of new therapeutic strategies.

Careful clinical management is vital for pregnant women with epilepsy, because both seizures and antiepileptic drugs can be harmful to the unborn child. In this article, Alison Pack reviews current evidence for a link between antiepileptic drug exposure and congenital malformations, and considers how epilepsy might best be managed in the context of a pregnancy.

The dystroglycanopathies are a group of muscular dystrophies that are caused by glycosylation defects in α-dystroglycan, an important membrane protein that binds to the extracellular matrix. In this review, Paul Martin summarizes the genetic and clinical features of these disorders, and discusses the possible roles of dystroglycanopathy-associated genes in α-dystroglycan glycosylation.

A number of epidemiological studies have provided evidence for a link between type 2 diabetes and Alzheimer's disease. In this review, Mary Haan weighs up this evidence, considers some potential biological mechanisms that might underlie the link, and discusses how targeting the risk factors for type 2 diabetes might also help in reducing the incidence of Alzheimer's disease.

The postgenomic era has seen important advances in the ability to perform large-scale analysis, using microarrays, of the genome at the level of gene sequence, gene copy number and messenger RNA transcript expression. In this review, Coppola and Geschwind discuss how microarray technology is being used to study of the genetics and pathogenesis of neurological disorders, and how it might be used in the future for patient diagnosis and classification into treatment groups.

Parkinson disease has traditionally been perceived as a non-hereditary condition, but in recent years, the identification of heritable forms of the disease linked to mutations in single genes has challenged this view. This review highlights recent progress in establishing the neurogenetic basis of Parkinson disease, and considers scenarios in which genetic testing for this condition might be warranted.

Neuropathic pain is caused by damage to the parts of the nervous system that normally signal pain. Attempts to classify neuropathic pain patients on the basis of disease etiology or lesion topography have met with limited success, and in this review Ralf Baron presents an alternative system based on molecular mechanisms. He discusses how this approach might lead to the development of more rational treatments for neuropathic pain.

Even in cases of well-controlled type 1 diabetes, cerebral glucose levels are frequently abnormal, and this is thought to have an impact on brain development and function. This article reviews the emerging literature that documents pathophysiological CNS changes and neurocognitive deficits in adults and children with type 1 diabetes, and discusses the implications for the clinical management of these patients.