Thyroid Function and Autoimmune Indications in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Abstract

Objective: Previous studies have shown that functional abnormalities of the thyroid are associated with the pathogenesis of several neurological diseases. However, their relationship in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis remains to be defined. Methods: Forty-three patients with anti-NMDAR encephalitis were examined for thyroid function and autoimmune indications, in comparison with 225 healthy controls (CTL). Patients were further classified into 2 subgroups based on their free tri-iodothyronine (fT3) levels. Moreover, fT3 levels were also investigated after at least three months of follow-up. The clinical characteristics of the patients and CTL were described in detail. Results: Serum levels of fT3 and thyroid-stimulating hormone (TSH) were found to be relatively lower in patients with anti-NMDAR encephalitis than in CTL (both p < 0.001). Low T3 syndrome also occurred more frequently in anti- NMDAR encephalitis (25.6 vs. 0.4%, p < 0.001). However, no statistical differences were detected between patients and CTL in terms of the positive rate of thyroid antibodies and other types of thyroid dysfunction. Patients with low T3 levels tended to have a longer hospital stay (p = 0.006), a higher rate of abnormal brain magnetic resonance imaging (MRI) findings (p = 0.033), a higher frequency of consciousness declination (p = 0.029), and a higher modified Rankin scale (mRS) score during hospitalization. Low fT3 levels were also associated with abnormal MRI findings, a decline in consciousness, and the mRS score on admission. In addition, fT3 seemed to gradually return to normal levels upon improvement of the mRS score (r = –0.649, p = 0.002). Conclusions: Low T3 syndrome often copresents in anti-NMDAR encephalitis and indicates a longer hospitalization, abnormal MRI findings, consciousness declination, and a higher clinical severity. However, fT3 levels do not seem to influence the prognosis of anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor encephalitis: a prospective study focused on thyroid hormones and functional outcome

“…Indeed, we observed that the fT3, but not fT4 or TSH, was signi cantly associated with poor functional outcome, and this effect remained signi cant after adjusting for age, gender, tumor presence and consciousness declination. Contrary to one former study (25.6%) 14 , our data didn't support the low T3 syndrome as a common nding in patients with anti-NMDAR encephalitis (6.25%), however, the relatively low fT3 value, although within the reference range, was associated with a poor functional outcome and might serve as a potential predictor of prognosis.…”

“…This constitutes the bases for evaluation of the potential association between thyroid hormones and the prognosis of anti-NMDAR encephalitis. To date, there are only a few data on this issue 13,14 , and its predictive value of functional outcome remains to be determined. Herein, we aimed to investigate the association between the thyroid hormones and functional outcome in patients with anti-NMDAR encephalitis.…”

Serum Systemic Autoantibodies in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

“…Recently, anti-thyroid antibodies abnormalities and elevated complement levels are frequent in patients with anti-NMDAR encephalitis, which are associated with the short-term prognosis (7)(8)(9). Furthermore, in our present study, only 9 in 39 of anti-NMDAR encephalitis were positive for serum systemic autoantibodies (7 ANA, 1 ANCA, and 1 centromere antibody).…”

“…Previous reports have demonstrated the intertwining relationships between systemic immune abnormalities and immune-mediated neurological disorders, such as neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (5,6). Recently, several studies have revealed anti-thyroid antibodies abnormalities and elevated complement levels are frequent in patients with anti-NMDAR encephalitis, which are associated with the outcomes (7)(8)(9). Serum systemic autoantibodies that are indicative of systemic immune diseases, such as antinuclear antibodies (ANAs), extractable nuclear antigen autoantibodies (ENAs), rheumatoid factors (RFs), and anti-neutrophil cytoplasmic antibodies (ANCAs), have also been detected in patients with AE, but the literature in this regard is limited (8,10).…”

“…Recently, several studies have revealed anti-thyroid antibodies abnormalities and elevated complement levels are frequent in patients with anti-NMDAR encephalitis, which are associated with the outcomes (7)(8)(9). Serum systemic autoantibodies that are indicative of systemic immune diseases, such as antinuclear antibodies (ANAs), extractable nuclear antigen autoantibodies (ENAs), rheumatoid factors (RFs), and anti-neutrophil cytoplasmic antibodies (ANCAs), have also been detected in patients with AE, but the literature in this regard is limited (8,10). However, the association between systemic autoantibodies and anti-NMDAR encephalitis has not been discussed.…”