Reviews & Analysis

Two recent studies highlight the importance of prompt, coordinated intervention after stroke. A meta-analysis confirms that intravenous thrombolysis is effective within 4.5 h of onset, irrespective of age (below or above 80 years) and stroke severity. Another study demonstrates successful reorganization of care through centralization of stroke services in England.

A pandemic influenza vaccine with a specific type of vaccine antigen has been linked to an increased incidence of narcolepsy in children from 2009–2010. However, the recent retraction of an article that reported a putative autoantigen means that the search for the mechanisms behind the vaccine–narcolepsy connection continues.

Activation of the immune system during pregnancy can have varied effects on fetal development, and converging evidence highlights maternal immune activation as a risk factor for multiple neurological conditions. In this Review, Knuesel and colleagues discuss the involvement of maternal immune activation in schizophrenia, austim spectrum disorders, epilepsy and other disorders. The authors then discuss how preclinical data indicate a possible link between prenatal exposure to infection and susceptibility to neurodegenerative disease, and they go on to identify fertile ground for further translational research.

Amyotrophic lateral sclerosis (ALS) is a genotypically and phenotypically heterogeneous disease, as reflected in the variability in age and site of onset, extent of extramotor involvement, and survival. Cognitive involvement is also common, and corroborates the connection between ALS and frontotemporal lobar degeneration. In this article, Robberecht and Swinnen review phenotypic heterogeneity in ALS and discuss some of its implications for understanding ALS pathogenesis and development of therapeutic interventions.

Functional and structural connectivity measures, assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease and other neurodegenerative disorders. In this article, Pievani et al. evaluate the evidence that connectivity biomarkers are associated downstream with clinical phenotypes and topographic brain imaging markers of neurodegeneration, and upstream with molecular determinants of neurodegeneration and susceptibility genes.

Finding a peripheral biomarker for early Alzheimer disease (AD) is a major challenge. A recent study has validated a plasma protein signature that is associated with mild cognitive impairment and AD, and could predict conversion; however, longitudinal cohort studies of presymptomatic individuals are needed to confirm the findings.

The risks of seizures and antiepileptic drug (AED) teratogenicity must be balanced when treating pregnant women with epilepsy. Two recent articles address these risks for newer AEDs. Lamotrigine and levetiracetam carried low risks of malformations, and topiramate exhibited a dose-dependent risk. Levetiracetam controlled seizures more effectively than lamotrigine and topiramate.

The fifth edition of the American Psyciatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) was published in 2013, and with it came new diagnostic criteria for mild cognitive impairment and dementia. In this Review, members of the working group tasked with writing the DSM-5 criteria for neurocognitive disorders present the new approach to categorization and diagnosis. Three key syndromes are recognized—delirium, mild neurocognitive disorder and major neurocognitive disorder—and each can have distinct aetiological subtypes.

Preventive strategies for Alzheimer disease (AD) will depend on the identification of modifiable risk factors for this disorder. A new study has quantified the relative contributions of seven major risk factors for AD, and concludes that around one-third of AD cases are likely to be preventable.

Chronic subdural haematoma (CSDH)—an 'old' collection of blood and blood breakdown products in the subdural space—is one of the most common neurological disorders, especially among elderly individuals. The current consensus is that symptomatic CSDH is best treated by surgical evacuation, usually via burr hole craniostomy. This Review provides an overview of the contemporary management of CSDH, and considers future approaches that could optimize patient care and outcomes.

Amyotrophic lateral sclerosis (ALS) shows complex inheritance. A new meta-analysis of three data sets has replicated previous estimates of the heritability attributable to common genetic variation, corroborated some previously identified disease-associated genetic loci, and suggested novel loci. Despite such efforts, our understanding of the genetic architecture of ALS remains limited.

Though effective for parkinsonian motor symptoms, deep brain stimulation (DBS) of the subthalamic nucleus has variable effects on speech. A new study focusing on patients' perceptions reported that DBS recipients complain of greater speech disturbance than do non-DBS recipients. Patients should be made more aware of this possible adverse effect of DBS.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with wide-ranging clinical manifestations that can involve the CNS and PNS. In this article, Jeltsch-David and Muller review the clinical features and pathogenesis of neuropsychiatric SLE (NPSLE), focusing on the aspects that might aid identification of biomarkers. They also discuss the classification and treatment of NPSLE, and identify avenues for future research.

Noninvasive brain stimulation (NIBS) is a promising approach for facilitating recovery of motor function after stroke, but trials assessing its efficacy have provided contradictory results. Di Pino and colleagues propose a unified 'bimodal balance–recovery model' for stroke recovery that takes into account the individual residual structural reserve and could aid tailoring of treatment for individual patients, thereby increasing the efficacy of NIBS in stroke rehabilitation.

Primary progressive aphasia (PPA) is caused by asymmetric, selective neurodegeneration of cerebral areas involved in language. Agrammatic and semantic PPAs are typically manifestations of frontotemporal lobar degeneration, whereas the logopenic PPA is more often associated with Alzheimer disease pathology. Here, Mesulam et al. review the subclassification, clinical features and neuropathology of PPA, and discuss how increased knowledge of PPA has advanced our understanding of the neural substrates of the language network.

Levodopa is the standard therapy for Parkinson disease, but prolonged use promotes the development of adverse motor effects. A new trial compared the effectiveness of levodopa administration early in the disease with therapies that used alternative dopaminergic agents before levodopa. No clinically relevant differences were found between the treatment strategies.

In complex regional pain syndromes (CRPS), pain—typically of neuropathic type—in the affected limb is accompanied by a variety of sensory, motor and autonomic signs and symptoms. Treatment for CRPS has been largely adapted from therapies for neuropathic pain states, but a better understanding of CRPS pathologenesis might provide opportunities for mechanism-based treatment. Here, the authors discuss available and emerging mechanism-based treatments in CRPS, including pharmacotherapy targeting central and peripheral sensitization and aberrant inflammatory response; sympathetic ganglion block interventions; and alleviation of symptoms by reversing body perception disturbances.

Copy number variants (CNVs; deletions or duplications of chromosomal regions) have emerged as an important cause of human disease. In a recent study, epilepsy could be attributed to a pathogenic CNV in 5% of patients, but understanding the implications of a CNV for an individual patient can be challenging.

Many patients with brain tumours possess inadequate mental capacity to provide informed consent, but this situation often goes undetected because clinicians do not routinely conduct formal cognitive assessments. This oversight should be recognized and rectified to enable optimum ethical and medical care of these vulnerable individuals.

Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerve, and can lead to paralysis and blindness. Currently, several treatment options for NMO exist, but many have been adapted from multiple sclerosis, and no controlled clinical trials specific to NMO have been conducted to date. Here, Marios Papadopoulos and colleagues review the various treatment strategies in NMO, and discuss the drugs that are in development or could be repurposed to treat this condition.