A considerable portion of autoimmune encephalitis (AE) does not respond to conventional immunotherapies and subsequently has poor outcomes. We aimed to determine the efficacy of tocilizumab, an anti-interleukin-6 antibody, in rituximab-refractory AE compared with other treatment options. From an institutional cohort of AE, 91 patients with inadequate clinical response to first-line immunotherapy and following rituximab were retrospectively reviewed. Patients were grouped according to their further immunotherapy strategies. Thirty (33.0 %) patients were included in the tocilizumab group, 31 (34.0 %) in the additional rituximab group, and 30 (33.0 %) in the observation group. Outcomes were defined as the favorable modified Rankin Scale scores (≤2) at 1 and 2 months from the initiation of each treatment strategy and at the last follow-up. Favorable clinical response (improvement of the modified Rankin Scale scores by ≥ 2 points or achievement of the mRS scores ≤ 2) at the last follow-up was also analyzed. The tocilizumab group showed more frequent favorable mRS scores at 2 months from treatment initiation and at the last follow-up compared with those at the relevant time points of the remaining groups. The majority (89.5 %) of the patients with clinical improvement at 1 month from tocilizumab treatment maintained a long-term favorable clinical response. No serious adverse effects of rituximab or tocilizumab were reported. Therefore, we suggest that tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab. The tocilizumab-mediated clinical improvement manifests as early at 1 month after treatment initiation.

This study provides Class IV evidence that rituximab improves mRS scores for patients with autoimmune limbic encephalitis who fail first-line therapy.

In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, we analysed the efficacy of a combined immunotherapy protocol consisting of teratoma removal, steroid, intravenous immunoglobulin (IVIG), rituximab and tocilizumab (T-SIRT). This cohort study included seventy-eight consecutive patients treated for anti-NMDAR encephalitis between Jan 2014 and Oct 2019 in a national referral hospital. Detailed 2-year disease time course was analysed using Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at every 2 weeks for 12 weeks from baseline, every month for the next 3 months and then every 3 months. Treatment regimens at each time point were categorized as SI, SIR, or SIRT with/without teratoma removal (T). Adverse events were classified according to the Common Terminology Criteria for Adverse-Events (CTCAE v5.0), where a severe adverse event was defined as an adverse event with CATAE grade 4. In a linear mixed model analysis, using the SIRT regimen was more effective than SIR or SI regimens in lowering CASE scores (P < 0.001 and P = 0.001, respectively). The presence of teratoma (P = 0.001), refractory status epilepticus (P < 0.001) and a higher CASE score at baseline (P < 0.001) predicted a higher CASE score at each time point. Completion of the (T)-SIRT regimen within 1 month of onset resulted in better 1-year improvements in CASE score (P < 0.001) and modified Rankin scale scores (P = 0.001), compared to those of using other regimens within 1 month or delaying teratoma removal for more than 1 month. Pneumonia was a frequent adverse event (52/78, 66.7%) in the whole study population and neutropenia was frequent during SIRT (11/52, 21.2%), but the regimen was well tolerated in most patients. We concluded that the early application of combined immunotherapy consisting of T-SIRT had better efficacy than was found for delayed or partial application of this combination in anti-NMDAR encephalitis.

The hippocampus and other medial temporal lobe structures have been linked to both memory and spatial cognition, but it has been unclear how these ideas are connected. We carried out parallel studies of path integration in patients with medial temporal lobe lesions and rats with hippocampal lesions. Subjects entered a circular arena without vision, searched for a target, and then attempted to return to the start location. Patients performed accurately, and as well as controls, so long as the outward path was relatively direct and the target was found within 20 s. In sharp contrast, rats with hippocampal lesions were impaired, even when the outward path was shorter than 1 m, involved no turns, and the target was found within 3 s. We suggest that patients succeeded because performance could be supported by working memory and that patients and rats differ after hippocampal lesions in their ability to construct a coherent working memory of spatial environments.amnesia | navigation T wo ideas have been central to recent discussions about the function of the hippocampus and other medial temporal lobe (MTL) structures. One idea emphasizes the role of these structures in memory (1-3) and the other emphasizes their role in spatial cognition, including spatial navigation and path integration (4-6). Path integration refers to the ability to use selfmotion cues as one moves through space to keep track of a reference location (7,8). These two ideas are compatible with each other to a large extent, because path integration requires memory, but there is potential mismatch as well, and it has been unclear how the two ideas relate to each other.Discussion of the MTL and memory typically draws a fundamental distinction between working memory and long-term memory. Working memory (the limited amount of information that can be held in mind by active maintenance) is thought to be independent of the MTL and spared after MTL damage (9-12), whereas long-term memory is impaired (13). One might therefore expect that path integration should be intact after MTL damage whenever performance can be managed within working memory. In one study (14), memory-impaired patients with bilateral damage to the hippocampus or adjacent MTL structures were able to path integrate as well as controls in conditions when working memory likely supported performance (i.e., for paths involving only one or two turns and trial durations shorter than 35 s). In this study, however, the procedure was quite different from the standard methods traditionally used to test path integration in experimental animals.Discussions about path integration in rodents emphasize the possible role of hippocampal place cells and entorhinal grid cells in computing information about spatial location (5, 6). If MTL structures are needed to carry out the computations needed for path integration, then MTL damage should impair path integration even in the case of short paths and short trial durations. That is, in the case of path integration, the distinction between working memory and long-t...

Background and PurposeAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune synaptic encephalitis and it often responds to treatment. We analyzed the clinical characteristics of anti-NMDAR encephalitis in Korea.MethodsSerum and/or cerebrospinal fluid (CSF) of adult patients (aged ≥18 years) with encephalitis of undetermined cause were screened for anti-NMDAR antibodies using a cell-based indirect immunofluorescence assay. The patients came from 41 university hospitals.ResultsOf the 721 patients screened, 40 were identified with anti-NMDAR antibodies and clinical details of 32 patients were obtained (median age, 41.5 years; 15 females). Twenty-two patients (68.8%) presented with psychiatric symptoms, 16 (50%) with seizures, 13 (40.6%) with movement disorders, 15 (46.9%) with dysautonomia, 11 (34.4%) with memory disturbance, and 11 (34.4%) with speech disturbance. Magnetic resonance imaging, electroencephalography, and CSF examinations yielded nonspecific findings. Tumor information was only available for 22 patients: 5 patients had tumors, and 2 of these patients had ovarian teratomas. Twenty-two patients received immunotherapy and/or surgery, and therapeutic responses were analyzed in 21 patients, of which 14 (66.7%) achieved favorable functional outcomes (score on the modified Rankin Scale of 0-2).ConclusionsThis study investigated the clinical characteristics of adult anti-NMDAR encephalitis in Korea. Currently, elderly patients who do not have tumors are commonly diagnosed with this condition. Understanding the detailed clinical characteristics of this disease will improve the early detection of anti-NMDAR encephalitis in patients both young and old.

No abstract

We evaluated two different perspectives about the function of the human hippocampus-one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.T wo traditions of work have influenced discussion about the function of the hippocampus (1). One tradition is based on work with memory-impaired patients and the idea that the hippocampus is important for a particular kind of memory (2, 3). The other tradition is based on work with rodents and the idea that the hippocampus is critical for spatial mapping (4). Its possible role in spatial processing has been recently explored in humans as well (5), and it has been proposed that the human hippocampus is essential for the ability to construct spatially coherent scenes (6, 7).This view of hippocampal function has depended on evidence from two kinds of tasks: boundary extension and scene construction (6,8). Boundary extension refers to the tendency to reconstruct a scene such that it has a larger background than was actually presented (9). In the Mullally et al. (8) study, memoryimpaired patients exhibited boundary extension less strongly than controls. Scene construction refers to the ability to imagine and describe spatially coherent scenes. In two studies, memoryimpaired patients made few references to space when visualizing and describing imagined scenes (6,8).It is unclear how to reconcile such findings with the view that the hippocampus chiefly supports memory functions. In particular, the idea that the construction and visualization of scenes involves the hippocampus seems at odds with the historic distinction between short-term (working) memory and long-term memory and the related idea that short-term memory is independent of the hippocampus (10-12). According to this perspective, hippocampal damage should not impair performance on spatial tasks, so long as testing puts no burden on long-term memory. In an attempt to clarify these issues, we gave tests of boundary extension, scene construction, and memory to patients with well-characterized lesions limited to the hippocampus or large lesions of the medial temporal lobe.Results Experiment 1. Both controls and hippocampal patients exhibited boundary extension. That is, both groups drew the central objects such that they occupied less area than in the original photographs ( Fig. 1 controls = 61.9% of the original area, hippocampal patients = 62.5% of the original area, P < 0.01). The extent of reduction was simil...

This study developed a composite measure of green consumption behaviors, incorporating multiple dimensions of green consumption behaviors. As a result of an extensive literature review, four value orientations were proposed: health-related egoistic value orientation, resourcerelated egoistic value orientation, altruistic value orientation, and biospheric value orientation. And a composite measure of green consumption which measured green consumption behavior manifesting the suggested value orientations were proposed and empirically tested using a Korean sample. After empirical testing and validating the proposed composite measure according to the measurement validation procedure proposed by Nunnally (New York: McGraw-Hill Book Company, 1978), the composite measure of green consumption behaviors was revised to three dimensions of green consumption behaviors: health-conscious green consumption behavior, resource-conscious green consumption behavior, and socially conscious green consumption behavior that combined originally suggested altruistic and biospheric value orientations. A multivariate regression analysis was employed to test the usability of the composite measure of green consumption behaviors and to identify the determinants of green consumption behaviors. As hypothesized, the results of regression analysis showed that perceived consumer effectiveness, reference persons, and perceived market situation are significant determinants of green consumption behaviors, and the effects of environmental concern and socioeconomics are limited. Based on these findings, public policy and marketing implications that promote green consumption are also proposed.