Identifying targets for diagnosis, prognosis, and treatment.

Abstract

This issue of Neurology® Neuroimmunology & Neuroinflammation (N2) incorporates exciting studies on the biology of immunologic and inflammatory biomarkers and the importance of knowing the benefits and complications of targeted therapies. In addition, the issue includes several clinically relevant reports on viral and autoimmune encephalitis. The concept of precision medicine, recently re-enhanced by public media, is not new in clinical and basic research. An interesting example is the case presented by Euskirchen et al.1 of a patient with life-threatening brainstem neurohistiocytosis in the context of Erdheim-Chester disease and cutaneous Langerhans cell histiocytosis. Detection of a BRAF mutation in affected tissues led to the selection of a specific BRAF inhibitor (vemurafenib), resulting in a rapid clinical response. On the other hand, Kornberg et al.2 suggest that the use of targeted therapies in an inappropriate context, such as fingolimod and natalizumab in neuromyelitis optica (NMO) instead of multiple sclerosis (MS), carries the risk of disease exacerbation. The authors postulate that a combination of drug effects, including an increase of blood-brain barrier permeability allowing CNS entry of Th17 lymphocytes, was responsible for the clinical worsening in the case they present. In another report, Hillen et al.3 postulate that natalizumab may have contributed to fulminant liver failure related to hepatitis B infection in a patient receiving the drug for relapsing-remitting MS (RRMS). Svenningsson et al.4 show that rituximab, a drug used for both MS and NMO, rapidly distributes to the peripheral compartment following intrathecal administration. Ultra-low doses of intrathecal rituximab were sufficient to cause complete and prolonged depletion of B lymphocytes in both the CNS and systemic compartments, an observation with potential implications for other disorders, such as autoimmune encephalitis.