Review Articles in 2016

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease predominantly affecting upper and lower motor neurons. Here, the authors outline previous and current efforts to characterize genes that are associated with ALS, and describe what is currently known about the genetic architecture of ALS.

The majority of patients who receive radiotherapy for brain tumours go on to develop disability, but the pathophysiological mechanisms of radiation-associated cognitive decline remains poorly understood. Here, Makale and colleagues review animal model and patient data on the mechanisms of radiotherapy-associated CNS damage and posit that early damage — occurring before 6 months after irradiation — contributes to long-term cognitive disability.

Rett syndrome (RTT) is a rare, progressive neurodevelopmental disorder that almost exclusively affects girls, and is caused by a mutation in theMECP2gene. The authors highlight major milestones in RTT over the past 50 years, and acknowledge the international collaborations that are driving this research programme.

Lifestyle and environmental factors, some which are potentially modifiable, have important roles in the risk of multiple sclerosis (MS), and some of these risk factors, such as Epstein–Barr virus infection, smoking and obesity in adolescence, interact with genetic risk factors. Here, Olsson and colleagues summarize recent data on modifiable environmental and lifestyle factors in MS, with a focus on gene–environment interactions.

Cryptococcal meningitis is a major cause of morbidity and mortality in immunocompromized individuals, and, even in apparently immunocompetent individuals, carries a high risk of mortality. Treatment in immunocompromized patients is challenging because these patients are at risk of immune reconstitution inflammatory syndrome (IRIS). This Review summarizes the diagnosis and treatment of cryptococcal disease in various disease.

Neuroinflammation is central in many neurological conditions, and 'big data' have the potential to elucidate the complexity of inflammatory processes. This Review considers how the drive to collect and analyse big data is increasing our understanding of neuroinflammation in disease, and how these data can be used to improve clinical management.

Unruptured intracranial aneurysms (UIAs) have a prevalence of 3% in the adult population. Currently, there is a large variability in how patients with UIAs are managed. Here, the authors review the latest human data on the formation, progression and rupture of intracranial aneurysms, as well the risks associated with preventive treatment.

The primary headache disorders are among the most common diseases worldwide. Nathaniel Schuster and Alan Rapoport discuss new and emerging preventive and acute treatments that have the potential to address unmet needs of patients with headache disorders, and to help treat and reduce headache-associated disability.

Opportunistic infections of the CNS, such as cryptococcal meningitis, cerebral toxoplasmosis, and tuberculous meningitis, are a major cause of morbidity and mortality in HIV-positive individuals. This Review provides an update on diagnosis and treatment of opportunistic infections, as well as management of immune reconstitution inflammatory syndrome in the setting of HIV-associated CNS infections.

The earliest stages of Parkinson disease (PD) offer the best opportunity to intervene, but detecting early disease is difficult. In this Review, Postuma and Berg provide an overview of established and potential markers of prodromal PD, and consider how these markers can be combined to identify patients who have prodromal PD and could benefit from treatment.

Evidence is accumulating that cortical dysfunction — in particular, cortical hyperexcitability — is an early feature of amyotrophic lateral sclerosis (ALS), thereby lending support to the 'dying-forward' hypothesis of ALS pathogenesis. The authors present an overview of recent insights into ALS pathophysiology, focusing on the importance of cortical hyperexcitability as a pathogenic and diagnostic biomarker.

Owing to a lack of objective diagnostic tools, the diagnosis of mild traumatic brain injury (TBI) and related conditions, such as postconcussive syndrome and chronic traumatic encephalopathy must be made on clinical grounds. Here, Zetterberg and Blennow review the most recent developments in search for biomarkers for mild TBI and related conditions.

Proinflammatory conditions have been associated with an increased risk of stroke. In this Review, Esenwa and Elkind look at the association between infection, inflammation and ischaemic stroke, and discuss recommended approaches to reducing the risk of stroke associated with inflammation.

Angelman syndrome is a severe neurodevelopmental disorder, the characteristics of which include severe learning disability, epilepsy, ataxia, and a happy, sociable disposition. The authors review past and recent developments in Angelman syndrome research, highlighting the role of multicentre and international collaboration in addressing this rare condition.

Medication-overuse headache (MOH) is a common disorder, but it remains under-recognized, and although several risk factors have been identified, the pathophysiology of the disorder is not completely understood. Here, Hans-Christoph Diener and colleagues review the epidemiology and pathophysiology of MOH, and suggest strategies for prevention and treatment.

Brain–computer interfaces (BCIs) enable severely disabled patients to interact with the environment. In this Review, Chaudhary et al. provide an overview on current use of BCIs for communication, movement and rehabilitation in patients who are paralyzed as a result of amyotrophic lateral sclerosis, stroke or spinal cord injury.

In this Review, Mishra and Yong consider how myeloid cells — monocytes, macrophages, microglia and dendritic cells — contribute to the pathology of multiple sclerosis (MS). The authors also consider how current multiple sclerosis treatments might directly and indirectly affect these cells.

Although no cure exists for amyotrophic lateral sclerosis (ALS), supportive and symptomatic care can prolong survival and improve quality of life. This Review discusses best strategies to manage symptoms in patients with ALS, including respiratory and nutritional support. Such interventions should involve a specialist multidisciplinary team, and patient should be given an active role in planning of the care.

Cognitive and behavioural comorbidities are common in children with epilepsy, and correlate with worse quality of life, increased behavioural and language problems and worse social skills, all of which adversely affect long-term psychosocial functioning. This review outlines the most common cognitive comorbidities in different types of epilepsy, and outlines the current understanding of the pathophysiology of epilepsy-associated cognitive and neurodevelopmental problems in children with epilepsy. Moreover, the authors provide suggestions for screening for cognitive comorbidity in this patient group.

Drawing on data from the Global Burden of Disease 2013 Study, Feigin and colleagues highlight the increasing global stroke burden, which indicates deficiencies in current primary prevention strategies. The authors present a four-point plan to improve primary stroke prevention, which includes a shift in emphasis from a high-risk approach to a more comprehensive approach that targets people at all levels of cardiovascular disease risk.