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One characteristic of migraine is recurrent headache attacks, which are known to be induced by changes in climatic variables such as atmospheric pressure, humidity, and outside temperature. However, the relationship between temperature changes and migraine remains unclear. Therefore, we investigated the relationship between body temperature changes and cortical spreading depression (CSD) using KCl-induced rat models of CSD. We initially induced CSD under controlled conditions at a room temperature of 28°C on an operating table maintained at 37°C. Subsequently, we controlled the operating table temperature to induce a second round of CSD under conditions of either a 10 ± 1% increase or decrease in body temperature. We ensured 1 h rest period between the first and second inductions of CSD. The results indicated that the number of CSDs significantly increased after body temperature elevation (before, 8.8 ± 1.2 times vs. after, 13.4 ± 1.3 times; p = 0.0003). The mean percentage change in cerebral blood flow decreased after body temperature increased (before, 33.1 ± 2.4% vs. after, 18.2 ± 1.4%; p = 0.006). There were no significant changes in CSD after body temperature decreased. The susceptibility of the cortex to CSD may increase under conditions of elevated body temperature.

IntroductionAnti-NMDA receptor encephalitis is an autoimmune disorder caused by autoantibodies (abs) against the conformational epitope on GluN1 subunits. GluN1-abs have been determined with cell-based assay (CBA) co-expressing GluN1/GluN2 subunits. However, commercial fixed CBA expressing only GluN1 subunit has increasingly been used in clinical practice. The ab titers can be determined with serial dilutions, but its clinical significance remains unclear. We aimed to develop an H-intensity scale (HIS) score to estimate GluN1-ab titers in cerebrospinal fluid (CSF) with one-time immunostaining using both commercial CBA and immunohistochemistry and report its usefulness. “H” is the initial of a patient with high CSF GluN1-ab titers (1:2,048).MethodsWe first determined the reliability of CBA in 370 patients with suspected autoimmune encephalitis by comparing the results between commercial CBA and established assay in Dalmau’s Lab. Then, we made positive control panels using the patient H’s CSF diluted in a fourfold serial dilution method (1:2, 1:8, 1:32, 1:128, 1:512, and 1:2,048). Based on the panels, we scored the intensity of ab reactivity of 79 GluN1-ab-positive patients’ CSF (diluted at 1:2) on a scale from 0 to 6 (with ≥1 considered positive). To assess inter-assay reliability, we performed immunostaining twice in 21 patients’ CSF. We investigated an association between the score of CSF obtained at diagnosis and the clinical/paraclinical features.ResultsThe sensitivity and specificity of CBA were 93.7% (95% CI: 86.0–97.3) and 98.6% (95% CI: 96.5–99.5), respectively. Linear regression analysis showed a good agreement between the scores of the first and second assays. Patients with a typical spectrum, need for mechanical ventilation support, autonomic symptoms/central hypoventilation, dyskinesias, speech dysfunction, decreased level of consciousness, preceding headache, ovarian teratoma, and CSF leukocyte count >20 cells/µL had a higher median HIS score than those without, but HIS score was not associated with sex, age at onset, or seizure. HIS score at diagnosis had a significant effect on 1-year functional status.DiscussionThe severity of disease and four of the six core symptoms were associated with higher GluN1-ab titers in CSF at diagnosis, which may play a role in poor 1-year functional status. An incomplete phenotype can be attributed to low CSF GluN1-ab titers.