Reviews & Analysis

The characteristic muscle weakness in myasthenia gravis (MG) is caused by antibodies against target molecules the neuromuscular junction. Here, Nils Gilhus and colleagues review how these antibodies and other biomarkers can be used to guide MG subgroup classification and treatment, as well as the best tests to detect these antibodies. Moreover, they discuss how the various antibodies are involved in MG pathogenesis.

A recent study of clinical and genetic characteristics in patients with hereditary spastic paraplegia highlights the difficulties of making clinicogenetic correlations in a heterogeneous group of diseases. Genetic analysis beyond the causative variants, and independent of the core clinical symptoms (pyramidal signs versus ataxia), might offer a more pertinent way to approach phenotypic variability.

The end of 2015 saw the passing of John F. Kurtzke and Richard T. Johnson, two legends in neurology, and founding fathers of neuroepidemiology, neurovirology and neuroimmunology. Here, we pay tribute to these two giants by discussing their impact on the genesis of these profoundly important disciplines.

Two new studies highlight the potential of neuroimaging to aid the differential diagnosis of neurodegenerative disease, for both clinical practice and emerging trials. Although this approach holds great promise, meaningful implementation of neuroimaging as part of a tailored precision medicine strategy may require additional imaging and non-imaging biomarkers.

In addition to the functional impairments that can arise after stroke, about one-third of stroke survivors experience neuropsychiatric disorders such as depression, anxiety or apathy. In this Review, Ferro and colleagues provide an update on the diagnosis and pathophysiology of the acute and long-term psychiatric consequences of stroke, and discuss available treatments and management strategies for these stroke-associated disorders.

Nonconvulsive status epilepticus has subtle symptoms and can be difficult to treat, meaning it is associated with considerable morbidity and mortality. In this Review, Sutter and colleagues discuss the epidemiology, clinical features and diagnosis of nonconvulsive status epilepticus, and discuss current recommendations for treatment.

The limb-girdle muscular dystrophies (LGMDs) comprise more than 30 genetically defined neuromuscular diseases that share the determining features of weakness and wasting of the pelvic and shoulder girdle muscles. Next-generation sequencing (NGS) technologies are continuing to expand the range of genes and phenotypes associated with the LGMDs. In this article, Thompson and Straub review the international collaborations that are addressing translational research issues in the LGMDs, and the lessons learned from large-scale NGS programmes.

Classification of migraine into different endophenotypes could aid diagnosis and treatment, but requires detailed characterization of different phenotypes. A new study provides insight into the clinical features of migraine with unilateral cranial autonomic symptoms, but raises questions about the value of such classifications.

A new study has shown that both in patients with multiple sclerosis (MS) and in healthy controls, dopamine inhibits production of IL-17 and IFN-γ by peripheral blood mononuclear cells. The finding adds to previous evidence for the potential benefit of dopaminergic drugs in MS.

Fingolimod is approved for the treatment of relapsing–remitting multiple sclerosis (MS), and evidence suggests that it has neuroprotective effects. The recent INFORMS phase III trial in primary progressive MS demonstrated no beneficial effects of fingolimod on disability progression or whole-brain atrophy, but provides important information for future therapeutic development.

A recent longitudinal study indicates that the incidence of new-onset epilepsy has remained stable in children and young adults but has increased in elderly individuals over the past 40 years. Rather than signalling a failure to prevent epilepsy, however, this phenomenon might be attributable to the comorbidities of epilepsy.

Despite highly effective combination antiretroviral therapies, the prevalence of HIV-associated neurocognitive disorder (HAND) has not reduced. To date, clinical trials of HAND therapies have been unsuccessful, calling for better understanding of HAND pathogenesis to develop more-effective treatment strategies. In this Review, Justin McArthur and colleagues discuss recent proceedings in understanding the immunopathogenesis of HAND, drawing from human studies and animal models.

Epilepsy develops in many patients with glioma, and the two presentations are currently treated with independent therapies. In this Review, Huberfeld and Vecht provide an overview of the evidence that epilepsy and gliomas share pathogenic mechanisms that could be targeted to simultaneously manage seizures and target tumours. They consider the benefits and risks of using antiepileptic drugs to treat gliomas, and antitumour drugs to control epilepsy.

The range of immunomodulatory therapies to treat multiple sclerosis (MS) has widened markedly in recent years, and MS treatments have become more efficient. This improvement in efficacy has been accompanied by an increased risk of treatment-associated infections. In this Review, Winkelman et al. discuss the modes of action of the currently available MS therapies and detail the specific infections associated with each treatment. They consider how this information can influence the daily clinical use of MS therapies, so as to minimize the associated infectious risk.

Rare neurological diseases require widely distributed networks of centres, investigators and patients to foster multidisciplinary investigations and recruit sufficient numbers of patients for research studies and clinical trials. In this article, Jen and colleagues highlight the role of two networks, the Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and the Clinical Research Consortium for Studies of Cerebellar Ataxias (CRC-SCA), in bringing together the various stakeholders in patient-oriented research into rare neurological channelopathies.

Access to the brain remains a challenge in surgical and drug treatment of neurological disorders, but therapeutic use of ultrasound offers a realistic alternative to overcome the challenges. In this Review, the authors provide an overview of how ultrasound can be used for neurosurgery to ablate pathological tissue, for drug delivery by opening the blood–brain barrier, and for neuromodulation.

In auditory neuropathy, sensory transduction and amplification is preserved, but abnormal neural encoding of sound stimuli impairs speech comprehension severely, beyond what would be expected on the basis of increased threshold of audibility. Here, Moser and Starr provide an overview of the mechanisms of auditory neuropathy, including auditory synaptopathy. Moreover, the authors provide a brief guide to physiological and psychophysical tests for the clinical diagnosis of the disorders, discuss the strategies for hearing rehabilitation, and provide an outlook on future therapies.

Frontotemporal dementia often presents with a variety of movement disorders, and several genetic mutations have been associated with the various presentations. In this Review, Baizabal-Carvallo and Jankovic characterize the clinical and pathological phenotypes of frontotemporal dementia, and discuss the genetic correlates of these phenotypes.

Prognostic scoring systems are widely used as objective outcome predictors in neurocritical care, for example, after haemorrhagic stroke. A new study, however, has unexpectedly shown that clinicians can predict outcome after intracerebral haemorrhage more accurately than do formal scoring scales.

Tinnitus, prevalent in up to 15% of the world population, is typically linked to noise-associated hearing loss, but the relationship between noise exposure and tinnitus is not straightforward: not all humans or model animals develop tinnitus after noise-associated cochlear damage, and the mechanisms involved in tinnitus involve central auditory system and nonauditory brain areas. This Review provides an overview of current understanding of neural mechanisms of tinnitus, which is essential for developing effective treatments for this disorder.