The Clinical Features and Prognosis of Anti-NMDAR Encephalitis Depends on Blood Brain Barrier Integrity

Abstract

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune nervous system disease that has become increasingly recognized. This retrospective study is aimed to analyze the relations between clinical manifestations and blood brain barrier (BBB) integrity in anti-NMDAR encephalitis patients. Methods: Anti-NMDAR encephalitis patients were admitted to the First Affiliated Hospital of Guangxi Medical University from April 2014 to April 2020. Patients were grouped by the normal BBB and damaged BBB groups according to the cerebrospinal fluid (CSF) albumin/serum albumin (QAlb). Neutrophil-to-lymphocyte ratio (NLR) in peripheral blood was used for estimating the inflammatory status. The modified Rankin Scale (mRS) was used to assess prognosis. Results: Seventy-three anti-NMDAR encephalitis patients were diagnosed based on the autoimmune encephalitis diagnosis criteria of 2016. Fifty-three (72.6%) patients were in the normal BBB group and twenty (27.4%) were in the BBB damaged group. There were no significant differences in gender, age, psychiatric disturbances, epilepsy, speech disorder, motor dysfunction, memory dysfunction, and autonomic dysfunction between the two groups (p>0.05). Nevertheless, the proportions of decreased consciousness, ICU admission, NLR, CSF protein and intrathecal IgG synthesis (IgGIF, IgGLoc) in the damaged BBB group were higher than that in the normal BBB group (p<0.05). Patients (79.2%) with normal BBB had good prognosis compared to patients with damaged BBB (50%) after 2 months follow-up. The median mRS before and after immunotherapy in the damaged BBB group were significantly higher than that in the normal BBB group (p<0.01, p<0.05, respectively). Additionally, QAlb increased was positively correlated with the quantitative intrathecal IgG synthesis (IgGLoc: r=0.66; IgGIF: r=0.433, all p<0.001). Conclusion: The dysfunction of BBB can be helpful in evaluating its prognosis since QAlb showed associations with ICU admission, NLR, a higher CSF protein, intrathecal IgG synthesis (IgGLoc, IgGIF) and mRS score after 2 months follow-up.

The Association of Ovarian Teratoma and Anti-N-Methyl-D-Aspartate Receptor Encephalitis: An Updated Integrative Review

“…Immunological and pathological shreds of evidence have proven that NMDAR autoantibodies were synthesized systemically and within the central nervous system (CNS) by antibody-producing cells that can cross the blood-brain barrier (BBB) [27,[61][62][63][64][65]. The central memory cells, plasma cells, and autoantibodies (specific IgG antibodies) circulated through the blood and lymphatic systems, then reached the CNS and eventually crossed the BBB.…”

“…Nevertheless, the mechanism by which the autoantibodies cross the BBB is not yet fully understood [56]. One potential explanation was that the immune and inflammatory response in patients with ovarian teratoma and anti-NMDAR encephalitis might damage the integrity of capillaries and lead to the dysfunction of BBB [65]. Notably, Jiang et al showed increasing levels of TNF-α, IL-10, and GM-CSF in patients with teratoma-related anti-NMDAR encephalitis compared to the control group, indicating the involvement of the inflammation process in the pathogenesis [52].…”

Anti-NMDAR encephalitis for psychiatrists: the essentials

“…25 Moreover, rates of seropositivity in healthy individuals are not significantly different from those in affected individuals; blood brain barrier permeability and activation of intrathecal antibody production are thought to be the major determining factors in whether disease develops. [25][26][27][28] Therefore, in practice, a positive serum resulteven in a patient with psychosisdoes not automatically equate to a diagnosis of anti-NMDAR encephalitis. 29 However, it does mean further investigation is warrantedat a minimum with CSF analysis, EEG and MRI of the headand expert neurology evaluation should be sought.…”

Characteristics and Outcomes of Autonomic Dysfunction in Anti-NMDAR Encephalitis

“…PSH was diagnosed according to the PSH-Assessment Measure (PSH-AM) proposed by Baguley et al based on the Clinical Feature Scale (CFS) and Diagnosis Likelihood Tool (DLT). The clinical features were classi ed as mild (1-6), moderate (7)(8)(9)(10)(11)(12), severe (>12) group according to CFS. Both scores were added to determine the likelihood of PSH as unlikely (< 8), possible (8-16) and probable (≥17) [15].…”

“…Approximately 10-50% of the anti-NMDAR encephalitis patients have autonomic dysfunction [2,9], including tachycardia/bradycardia, hypertension/hypotension, gastrointestinal dysfunction, urinary dysfunction, abnormal pupil movement etc., which increase patient morbidity and mortality, complicate intensive care and can lead to hemodynamic shock [10]. However, little is known regarding the correlation between autonomic instability and the prognosis of autoimmune encephalitis, and the conclusions are ambiguous [4,11].…”