Peripheral monocytes and soluble biomarkers in autoimmune encephalitis.

BACKGROUND AND OBJECTIVES: Autoimmune encephalitis (AE) is an inflammatory disease of the central nervous system which can result in long-term seizures and cognitive dysfunction despite treatment with immunotherapy. The role of the innate immune system in AE is not well established. To investigate the contribution of innate immunity to AE and its long-term outcomes we evaluated peripheral monocytes and serum cytokines in the periphery of patients with AE. METHODS AND RESULTS: We recruited 40 patients with previously diagnosed AE and 28 healthy volunteers to our cross-sectional observation study and evaluated their peripheral blood monocytes via flow cytometry and serum cytokines (CCL-2, CCL-17, G-CSF, GM-CSF, IFNγ, IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα) via ELISA.Compared with controls the AE cohort had expansion of the 'pro-inflammatory' CD14+CD16+ monocyte sub-population (7.13% vs 5.46%, p < 0.01) with higher levels of serum IL-6 (2.34 pg/mL vs 0.54 pg/mL, p < 0.001). These changes were most significant in anti-LGI-1 antibody mediated AE, an AE subtype with poor long-term cognitive outcomes. CONCLUSION: Expansion of the peripheral CD14+CD16+ monocyte population and increased serum IL-6 in AE is reflective of changes seen in other systemic inflammatory and neurodegenerative conditions. These changes may indicate a persistent pro-inflammatory state in AE and may contribute to poor long-term outcomes.

Electroclinical biomarkers of autoimmune encephalitis.

OBJECTIVE: To evaluate the utility of electroencephalography (EEG) changes as diagnostic and prognostic biomarkers in acute autoimmune encephalitis (AIE). METHODS: One hundred and thirty-one patients with AIE were recruited retrospectively across 7 hospitals. Clinical data were collected during admission and at 12 months. EEGs were reviewed using a standard reporting proforma. Associations between EEG biomarkers, AIE subtypes, and clinical outcomes were assessed using logistic regression modeling. RESULTS: Presence of superimposed fast activity (OR 34.33; 95% CI 3.90, 4527.27; p < 0.001), fluctuating EEG abnormality (OR 6.60; 95% CI 1.60, 37.59; p = 0.008), and hemispheric focality (OR 28.48; 95% CI 3.14, 3773.14; p < 0.001) were significantly more common in N-methyl-d-aspartate receptor (NMDAR) antibody-associated patients with AIE compared to other AIE subtypes. Abnormal background rhythm was associated with a poor mRS (modified Rankin score) at discharge (OR 0.29; 95% CI 0.10, 0.75; p = 0.01) and improvement in mRS at 12 months compared with admission mRS (3.72; 95% CI 1.14, 15.23; p = 0.04). SIGNIFICANCE: We have identified EEG biomarkers that differentiate NMDAR AIE from other subtypes. We have also demonstrated EEG biomarkers that are associated with poor functional outcomes.

Generalized and orofacial choreoathetosis: a case report of anti-CV2 paraneoplastic syndrome after cardiac arrest.

CV2/CRMP5 is the most common antibody accompaniment of paraneoplastic choreoathetosis. We present a case of paraneoplastic choreothetosis with associated cerebellar dysfunction, peripheral neuropathy, and likely dysautonomia. Our patient developed a movement disorder after a cardiopulmonary arrest, which unfortunately masked the true etiology of his symptoms. He was later found to have extensive stage small cell lung cancer, with further evaluation revealing seropositivity for anti-CV2 antibodies. Choreoathetosis is a known sequelae of hypoxic-ischemic brain injury, but clinicians should continue to keep an open mind. The utility of immunotherapy is unclear in these circumstances and many physicians adopt a symptom-based approach.

Prognosticating autoimmune encephalitis: A systematic review.

OBJECTIVE: To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis. METHODS: We performed a systematic literature search using MEDLINE, Embase, PubMed and PsychInfo databases. We selected studies that explored the correlation between early clinical and paraclinical findings, and patient outcomes. Data was extracted, analyzed and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Forty four publications detailing 2823 subjects matched our inclusion criteria. There was considerable heterogeneity in methodology, patient profile, investigation results and clinical outcome measures. Findings were often discrepant for cases of anti-NMDAR encephalitis when compared with other causes of autoimmune encephalitis. Delay in immunotherapy contributed to a variety of worse outcomes for patients with different subsets of autoimmune encephalitis. Altered consciousness, ICU admission and no use of immunotherapy were variables associated with poor prognosis in anti-NMDAR encephalitis. Older age, sex, the presence of status epilepticus, CSF abnormalities and MRI changes were unlikely to have significant prognostic value. The influence of antibody titers, autonomic dysfunction and underlying malignancy was unclear. CONCLUSIONS: A number of variables were identified to have potential predictive value for outcomes in autoimmune encephalitis. Heterogeneous study design, size and quality were major limiting factors in this review.