Neuroinflammation

Inflammatory processes contribute to neurological disorders, and many therapeutic breakthroughs in neurological disease have been immune-targeted. The choice of neuroinflammation as the theme for the 5th European Academy of Neurology Congress in 2019 and of this Focus issue highlights its importance to neurologists across the discipline.

In this Review, Lloyd and Miron consider how regulation of microglial activation influences the ability of microglia to promote remyelination in the CNS. They also discuss the potential to exploit the pre-remyelination properties of microglia to treat multiple sclerosis and other demyelinating diseases.

In this Review, Vezzani and colleagues discuss inflammatory pathways that are activated in pharmacoresistant epilepsy and can be modulated to therapeutic effect in animal models. They consider how targeting these pathways could overcome limitations of existing anti-epileptic treatments.

Ischaemic stroke causes a neuroinflammatory response, but the functional consequences of this response have been unclear. In this Review, Stoll and Nieswandt consider the roles of T cells, platelets and their interactions in this neuroinflammatory response and how these roles could be exploited therapeutically.

Migraine is one of the world’s most prevalent diseases, and approximately 2% of the general population experiences chronic migraine. Edvinsson and colleagues argue that inflammation could have an important role in migraine chronification, through a mechanism termed neurogenic neuroinflammation.

The FDA approvals of siponimod and cladribine for secondary progressive multiple sclerosis raise questions about the diagnostic criteria for multiple sclerosis phenotypes and their applicability to clinical trials. A simpler classification for the disease could be the answer.

An altered microglial landscape and ageing-related inflammatory changes contribute to the neurodegeneration associated with frontotemporal dementia (FTD). Here, Bright and colleagues discuss the evidence for a pathogenetic role of neuroinflammatory mechanisms in FTD, including links with autoimmunity and gene mutations associated with neuroinflammation.

In this Review, the authors discuss findings that are transforming our understanding of neuropsychiatric diseases and the role of inflammation in these disorders. They suggest new diagnostic and therapeutic criteria for the emerging field of neuroimmunopsychiatry.

Biologics are emerging as important therapeutic tools in myasthenia gravis. In this Review, Marinos Dalakas considers the promise of these drugs and how they could overcome the limitations of current standard treatments.

In this Review, Reindl and Waters provide an overview of what we currently know about anti-myelin oligodendrocyte glycoprotein antibodies and their association with demyelinating diseases, including the value of detection assays and evidence for antibody pathogenicity and its mechanism.

In this Review, Handel and colleagues examine the contribution of thymic T cell selection to CNS autoimmune conditions and consider how a better understanding of this contribution could lead to novel therapeutic strategies for these conditions.

In this Review, the authors describe the current data detailing the role of triggering receptor expressed on myeloid cells (TREM2) in microglial biology and Alzheimer disease (AD), and discuss the possibility of targeting TREM2 as a treatment for AD.

In this Review, the authors discuss all aspects of immune-mediated disorders of the CNS in children, from the clinical features and treatment to pathological mechanisms and biomarkers, and outline priorities for collaborative research to develop precision medicine for these disorders.

New research is increasingly challenging old notions of an immunologically isolated CNS. In this Perspectives article, Jun Chen and colleagues highlight discoveries on the beneficial roles of regulatory immune cells in brain repair and regeneration, and discuss their promise as therapies for neurological disorders.

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer immunotherapy, but these agents carry a high risk of immune-related adverse events. Here, the authors introduce the mechanisms of action of ICIs and review their adverse effects on the CNS, which result in conditions such as paraneoplastic neurological syndromes and multiple sclerosis.

Although the most common neuropathy associated with diabetes mellitus is distal symmetric polyneuropathy, inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) can also occur, and might be amenable to treatment. In this Review, Rajabally et al. consider the features of CIDP in diabetes, how this condition can be differentiated from other neuropathies, and management options for CIDP and other inflammatory neuropathies in diabetes.

The discovery that IgG4 autoantibodies against node of Ranvier proteins are linked to distinct subsets of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represents a key advance in our understanding of the chronic inflammatory neuropathies (CINs). Here, Querol and colleagues discuss the clinical implications of these autoantibodies in patients with CIDP and other immune-mediated neuropathies.

Effective drug treatments for intracerebral haemorrhage (ICH) are still lacking. However, therapies that target microglial phenotype switching might soon become available for affected patients. Here, Wang and colleagues summarize key advances in understanding of microglial function after ICH, including modulators of microglial function and interactions with other cells.

Neuroinflammation can cause acute secondary injury after traumatic brain injury (TBI), and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, the authors propose a new framework for targeted immunomodulation after TBI.