Reviews & Analysis

The autoimmune myopathies, the best known of which are polymyositis and dermatomyositis, share a number of clinical features, including progressive proximal muscle weakness, and evidence of inflammation on muscle biopsy. Here, Mammen reviews the typical clinical presentations of the autoimmune myopathies, and discusses the relationships between distinct clinical phenotypes and myositis-specific autoantibodies.

Human leukocyte antigen (HLA) screening could identify patients at risk of adverse reactions to carbamazepine, one of the most commonly used anticonvulsants. A European genome-wide association study revealed strong correlations between HLA-A^*3101 and carbamazepine hypersensitivity. In Taiwan, HLA-B^*1502 screening led to significant reductions in the incidence of carbamazepine-induced adverse events.

Lack of the tumor suppressor protein merlin results in the development of benign nervous system tumors—most commonly schwannomas, which characterize neurofibromatosis type 2, but also meningiomas and ependymomas. Such tumors engender considerable morbidity owing to the high tumor burden and the lack of effectiveness of current treatment options. Here, Ammoun and Hanemann discuss emerging preclinical and clinical data in support of targeting four key families of receptor tyrosine kinases, as well as their downstream signaling pathways, for the treatment of schwannomas and related tumors.

Ischemic stroke is a major public health concern, and research to determine the underlying genetics of this disease is ongoing. Meschia and colleagues describe the single-gene disorders associated with stroke and progress in understanding the complex genetics of this condition, as well as discussing the relevance of pharmacogenomics and endophenotypes to stroke risk and treatment.

The considerable need for research on Alzheimer disease (AD) is complicated by the impaired capacity of patients with AD to provide informed consent to participate in research and the lack of well-defined policy guidelines on this issue. Scott Kim highlights the importance of distinguishing between capacity and authenticity when assessing the ability of a patient with AD to provide informed consent, and discusses how the role of surrogate decision-makers could be enhanced in this context.

Advances in the clinical and genetic understanding of Rett syndrome have meant that existing diagnostic guidelines for this neurodevelopmental disorder need to be revisited. New clinical criteria for the diagnosis of Rett syndrome by Neul and colleagues are welcome, but should more prominence be given to molecular diagnosis?

Charcot–Marie–Tooth disease (CMT) is a hereditary neuropathy attributed to mutations in more than 30 different genes. A recent study identified the causative mutation in 67% of 787 screened patients with CMT, and the findings raise important issues concerning genetic testing for CMT.

A new survey of British neurologists shows that no commonly accepted model exists for the diagnosis of conversion disorder. Instead, the results indicate that the neurologist's diagnosis is influenced largely by their communication with the patients.

Biomarker development is important to the therapeutic imperative for neurodegenerative diseases, as biomarkers hold transformative promise for the design and conduct of clinical trials and, ultimately, for medical management of these diseases. Some of this promise is now being realized in Alzheimer disease, and progress in Parkinson disease is accelerating.

Neuralgic amyotrophy is a distinct, painful focal neuropathy with a broad spectrum of clinical phenotypes and a complex pathophysiology. The extent of disability experienced varies from patient to patient, but many individuals are left with residual disabilities affecting their everyday lives. In this Review, Nens van Alfen provides an overview of the current clinical and pathophysiological concepts and research topics in neuralgic amyotrophy.

Cognitive impairment is commonly observed in patients with multiple sclerosis (MS), often with a heterogeneous neuropsychological presentation among patients. Benedict and Zivadinov describe the clinical features and neuropsychological tests for cognitive dysfunction in MS with a particular focus on the risk factors for this disorder. Protective factors and potential therapy for cognitive impairment in MS are also discussed.

The American Academy of Neurology has updated its 1996 assessment of the value of plasma exchange in neurology. The report confirms the efficacy of plasma exchange in inflammatory neuropathy and possibly acute CNS demyelinating disease, but not in pediatric autoimmune neuropsychiatric disorders. Its conclusions, however, are limited by inadequate evidence.

Given the aging population, understanding the link between depression and dementia could be crucial to the potential treatment and prevention of dementia in the elderly. In this Review, Byers and Yaffe describe the evidence supporting a role for both earlier-life and late-life depression in dementia. A particular focus is given to the putative biological mechanisms that underlie this association and the implications of depression treatment and prevention for the development of dementia.

New research shows that a substantial proportion of patients with acute disseminated encephalomyelitis have serum antibodies against myelin oligodendrocyte glycoprotein. The relationship between these antibodies and other demyelinating disorders such as multiple sclerosis, however, remains unclear.

A recent study has combined clinical, laboratory and imaging parameters, all acquired within 48 h of clinical onset of middle cerebral artery territory stroke, in the same logistic regression model to predict 1-month functional outcome. A composite set of five independent items was found to be associated with good outcome.

Recent revisions to the diagnostic criteria for multiple sclerosis have simplified MRI definitions for dissemination of CNS lesions in space and time, and may enable an earlier and easier diagnosis of the disease. The validity of this approach needs to be assessed in real-world clinical practice.

Various clinical scores are available to assess the outcome of chronic inflammatory demyelinating polyneuropathy (CIDP), but these existing scales have some major limitations. A novel, simple scoring system—the CIDP disease activity status—incorporates the concept of disease activity as a feature that informs the long-term outcome in CIDP patients.

Corticobasal degeneration is a rare, progressive neurodegenerative disorder with highly variable clinical presentation, and is difficult to identify in living patients. The classic clinical presentation of this disease—corticobasal syndrome—often occurs in conjunction with other neurological diseases. Kouri et al. discuss the use of imaging and biomarkers to improve diagnosis, and examine the genomic data that should provide insights into novel pathways involved in the pathogenesis of tauopathy.

Numerous neurological consequences of alcoholism have been identified, including hepatic encephalopathy, Wernicke encephalopathy, Korsakoff syndrome, Marchaifava–Bignami disease and central pontine myelinosis. Here, Zahr et al. focus on Wernicke encephalopathy and Korsakoff syndrome, exploring their position within a proposed spectrum of neurological disruption that begins with alcohol-related brain damage.

Evidence collected over the past decade has challenged the idea that essential tremor is a monosymptomatic tremorogenic disorder. In this Review, Bermejo-Pareja describes the nonmotor symptoms that are most commonly associated with essential tremor, focusing particularly on cognitive deficits.