The immunology underlying CNS autoantibody diseases.

The past two decades have seen a considerable paradigm shift in the way autoimmune CNS disorders are considered, diagnosed, and treated; largely due to the discovery of novel autoantibodies directed at neuroglial surface or intracellular targets. This approach has enabled multiple bona fide CNS autoantibody-associated diseases to thoroughly infiltrate the sphere of clinical neurology, facilitating advances in patient outcomes. This review focusses on the fundamental immunological concepts behind CNS autoantibody-associated diseases. First, we briefly review the broad phenotypic profiles of these conditions. Next, we explore concepts around immune checkpoints and the related B cell lineage. Thirdly, the sources of autoantibody production are discussed alongside triggers of tolerance failure, including neoplasms, infections and iatrogenic therapies. Penultimately, the role of T cells and leucocyte trafficking into the CNS are reviewed. Finally, biological insights from responses to targeted immunotherapies in different CNS autoantibody-associated diseases are summarised. The continued and rapid expansion of the CNS autoantibody-associated field holds promise for further improved diagnostic and therapeutic paradigms, ultimately leading to further improvements in patient outcomes.

Acute disseminated encephalomyelitis in an older adult following prostate resection.

Acute disseminated encephalomyelitis (ADEM) is an uncommon, autoimmune, demyelinating disorder of of the central nervous system. It is rare in adults beyond 65 years. Here, we describe a novel presentation following urological surgery. Using illustrative features from our case study, we describe some of the clinical features, aetiologies, diagnostic uncertainties and pathogenic mechanisms of the disease. A 69 year old gentleman underwent transurethral resection of the prostate. He then developed confusion, unsteadiness, behavioural disturbance and left-sided hemiparesis. On admission he was febrile with left hemiplegia and ataxia. Neuroimaging showed multifocal, posterior-predominant semi-confluent lesions. Autoimmune serology and virology were negative. Cerebrospinal fluid revealed mildly elevated protein. Brain biopsy confirmed a diagnosis of ADEM. ADEM is a predominantly a childhood disorder and rare in older adults. It is precipitated by vaccinations, viral, bacterial or parasitic infections. It is rarely described after surgical intervention. Differential diagnosis is wide and includes multiple sclerosis (MS), encephalitides and encephalopathies. Treatment is with corticosteroids, plasma exchange, intravenous immunoglobulin or cyclophosphamide. Up to a quarter will experience recurrence and 10% progress to MS. Further study is needed to determine its pathogenic and immunological characteristics.

Healthcare professionals are less confident in managing acute toxicity related to the use of new psychoactive substances (NPS) compared with classical recreational drugs.

BACKGROUND: The features of acute classical recreational drugs or new psychoactive substances (NPS) toxicity fall into three broad groups: (i) stimulant; (ii) hallucinogenic and (iii) depressant. Currently, there is no information available on healthcare professionals knowledge/confidence in managing the acute toxicity related to NPS use. AIM: We have compared knowledge and confidence of managing acute toxicity related to use of NPS with that seen with the use of to classical recreational drugs. DESIGN AND METHODS: Physicians/nurses completed a questionnaire survey to self-assess on a 5-point scale their knowledge (1-little knowledge; 5-very knowledgeable) and confidence (1-little confidence; 5-very confident) of managing acute toxicity related to the use of classical recreational drugs or NPS. Differences between knowledge and confidence for classical recreational drugs and NPS were assessed using paired Student's t-test; comparison between doctors, nurses and the frequency of managing acute classical recreational drug/NPS toxicity was assessed using unpaired Student's t-test. RESULTS: One hundred and eighty-eight (82 physicians, 106 nurses) completed the survey. Classical drug compared with NPS knowledge: nurses 2.9 ± 1.0 vs. 2.1 ± 1.0, P < 0.001; physicians 3.1 ± 0.8 vs. 2.1 ± 1.0, P < 0.001. There was no difference between nurses and physicians in classical drug (P = 0.11) or NPS (P = 0.89) knowledge. Confidence in managing classical drug toxicity compared with NPS confidence: nurses 3.0 ± 1.1 vs. 2.3 ± 1.1, P < 0.001; physicians 3.0 ± 0.9 vs. 2.1 ± 1.0, P < 0.001. There was no difference between nurses and physicians in classical drugs (P = 0.85) or NPS (P = 0.33) confidence. CONCLUSIONS: Physicians/nurses are less confident in managing acute NPS toxicity. Management of toxicity is not dependent on knowing the drug/NPS, but should be on the basis of these clinical signs/symptoms. Training/education should focus on the concept of managing the pattern of toxicity that an individual presents with rather than the actual drug(s).