Improvement of NMDA encephalitis by active lymph node removal.
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ABSTRACT:
SUBMITTER: Iwamoto T
PROVIDER: S-EPMC4126996 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To report the definitive diagnosis of anti-NMDA receptor (NMDAR) encephalitis in four Japanese women previously diagnosed with "juvenile acute nonherpetic encephalitis" of unclear etiology, and to describe their long-term follow-up in the absence of tumor resection.We extensively reviewed the case histories with current clinical and laboratory evaluations that include testing for antibodies to NR1/NR2 heteromers of the NMDAR in serum/CSF available from the time of symptom onset (4 to 7 years ago) and the present.All patients sequentially developed prodromal symptoms, psychosis, hypoventilation, severe orofacial dyskinesias, and bizarre immunotherapy-resistant involuntary movements that lasted 1 to 12 months. Two patients required mechanical ventilation for 6 and 9 months. Initial tests were normal or unrevealing, including the presence of nonspecific CSF pleocytosis, and normal or mild changes in brain MRI. Eventually, all patients had dramatic recovery of cognitive functions, although one had bilateral leg amputation due to systemic complications. Antibodies to NR1/NR2 heteromers were found in archived serum or CSF but not in long-term follow-up samples. An ovarian teratoma was subsequently demonstrated in three patients (all confirmed pathologically).1) These findings indicate that "juvenile acute nonherpetic encephalitis" or a subset of this disorder is mediated by an antibody-associated immune response against NR1/NR2 heteromers of the NMDA receptor (NMDAR). 2) Our patients' clinical features emphasize that anti-NMDAR encephalitis is severe but potentially reversible and may precede by years the detection of an ovarian teratoma. 3) Although recovery may occur without tumor removal, the severity and extended duration of symptoms support tumor removal.
| S-EPMC2586938 | biostudies-literature
Project description:In the current S2 guidelines, the standard surgical therapy for patients with vulvar cancer also includes inguino-femoral lymphadenectomy. However, in view of the severe side-effects associated with this approach such as problems with wound healing, lymphoceles and lymphoedema, the search is on for alternative treatments that could decrease treatment-associated morbidity and improve patients' quality of life, particularly for node-negative patients. The sentinel lymph node technique is currently the gold standard in the treatment of unifocal breast cancer (clinically negative axilla), and studies on the use of this technique in the treatment of vulvar cancer are promising. To date, the diagnostic accuracy of this method in vulvar cancer has only been evaluated in a single, one-arm, non-randomised, multicentre study. In preparation for a multicentre study, in 2010 we surveyed 41 German hospitals to investigate how often they used the sentinel lymph node technique compared to inguino-femoral lymphadenectomy. The hospitals were grouped according to hospital size and number of patients treated for vulvar cancer. The decision criteria to determine the type of procedure performed were also investigated. Finally, the hospitals were asked whether they would be willing to participate in a prospective clinical study to evaluate the sentinel lymph node technique in patients with vulvar cancer. The majority of surgeons questioned (73?%) already had some experience with this technique in patients with vulvar cancer. In our survey, 27?% of hospitals carried out inguino-femoral lymphadenectomy, 10?% used the sentinel lymph node technique, and 63?% used both methods. In 24?% of hospitals, the standard procedure consisted of the sentinel lymph node technique supplemented by inguino-femoral lymphadenectomy. Only 20?% of the institutions surveyed in our study carried out sentinel lymph node biopsy alone in accordance with the criteria of the consensus recommendations. The majority of the investigated institutions were willing to participate in a randomised prospective clinical study to evaluate the effectiveness of sentinel lymph node sampling in patients with vulvar cancer.
| S-EPMC3859150 | biostudies-literature
Project description:Lymph nodes are important peripheral immune organs in which numerous important immune responses occur. During the process of lymphatic metastasis, lymph nodes are also sites through which tumor cells must pass. Therefore, it is essential to develop a drug delivery system that can specifically transfer immunostimulatory medicine into lymph nodes to block lymphatic metastasis. Here, we developed a nucleic acid drug delivery system containing cationic agarose (C-agarose) and CpG oligodeoxynucleotides. C-agarose has a high affinity for Siglec-1 on the surface of lymph node sinus macrophages, which have a high specificity for targeting lymph nodes. Subcutaneous implantation of C-agarose+CpG gel caused the accumulation of CpG in the lymph node sinus macrophages and generated antitumor immune responses in the lymph node. C-agarose+CpG gel treatment decreased the metastasis size in the tumor-draining lymph node (TDLN) and lung metastatic nodules and suppressed tumor growth in both a mouse 4T1 breast cancer model and a B16F10 melanoma model. On this basis, this study proposes a nonsurgical invasive lymph node targeting immunotherapy concept that may provide a new approach for antitumor metastasis.
| S-EPMC6529739 | biostudies-literature
Project description:Chronic imaging windows in mice have been developed to allow intravital microscopy of many different organs and have proven to be of paramount importance in advancing our knowledge of normal and disease processes. A model system that allows long-term intravital imaging of lymph nodes would facilitate the study of cell behavior in lymph nodes during the generation of immune responses in a variety of disease settings and during the formation of metastatic lesions in cancer-bearing mice. We describe a chronic lymph node window (CLNW) surgical preparation that allows intravital imaging of the inguinal lymph node in mice. The CLNW is custom-made from titanium and incorporates a standard coverslip. It allows stable longitudinal imaging without the need for serial surgeries while preserving lymph node blood and lymph flow. We also describe how to build and use an imaging stage specifically designed for the CLNW to prevent (large) rotational changes as well as respiratory movement during imaging. The entire procedure takes approximately half an hour per mouse, and subsequently allows for longitudinal intravital imaging of the murine lymph node and surrounding structures for up to 14 d. Small-animal surgery experience is required to successfully carry out the protocol.
| S-EPMC5592697 | biostudies-literature
Project description:BackgroundTo validate the prognostic impacts of the left gastric artery lymph node (No. 7 LN) metastasis and investigate whether the No. 7 LN metastasis should be considered as the predictive LN for extra-gastric LN metastases.MethodsBetween January 2003 and December 2011, a total of 1,586 patients who underwent R0 gastrectomy were retrospected. Patients with LN metastases were divided into three groups: (I) patients with only peri-gastric LN metastases (peri-gastric group); (II) patients with peri-gastric and only No. 7 LN metastases (No. 7 group); and (III) patients with other extra-gastric LN metastases (extra-gastric group). Propensity score matching (PSM) was adopted to accurately evaluate prognoses of all patients after surgery.ResultsOf 1,586 patients, 235 (14.82%) were pathologically identified to present with the No. 7 LN metastases. Patients with the No. 7 LN metastases presented the significantly lower survival rate both before and after adjustment by pTNM stage, compared to those without the No. 7 LN metastases. Patients in the No. 7 group were identified to present the significant lower survival rate than those in the peri-gastric group, and to present the similar median overall survival (OS) to those in the extra-gastric group. In addition, patients with extra-gastric LN except No. 7 LN metastases failed to show any superiority of survival outcomes, compared with those with extra-gastric LN metastases including the No. 7 LN metastasis.ConclusionsThe No. 7 LN metastases had the crucial survival implications. Nevertheless, the No. 7 LN failed to be considered as the predictive LN for the extra-gastric LN metastases in gastric cancer (GC).
| S-EPMC7327347 | biostudies-literature
Project description:BACKGROUND:Completion lymph node dissection (CLND) is recommended for melanoma patients with positive sentinel lymph node biopsies (SLNB); however, 50% do not undergo CLND. We sought to determine CLND trends over time, and factors contributing to variability. METHODS:The NCDB was queried for patients undergoing wide local excision (WLE), with or without SLNB and CLND. Cohorts were created based on demographic/socioeconomic variables and era of treatment (Era 1: 2003-07, Era 2: 2008-12). Univariate and multivariate analyses identified factors associated with performance of or trends in CLND. RESULTS:122?849 underwent WLE with SLNB. Of 24?267 (19.8%) with +SLNB, 13?594 (56.0%) continued to CLND. In multivariate analyses, Medicaid (OR 0.78; P?=?0.04) or Medicare (OR 0.79; P?<?0.01) in Era 1 and patients without insurance in Era 2 (OR 0.78; P?=?0.01) underwent less CLND. In both eras, Blacks (OR 0.45; P?<?0.01, OR 0.59; P?<?0.01), head/neck lesions (OR 0.72; P?<?0.01, OR 0.66; P?<?0.01) and lower extremity lesions (OR 0.75; P?<?0.01, OR 0.72; P?<?0.01) underwent less CLND. However, Blacks experienced greatest increase in CLND usage (+9.2%). CONCLUSIONS:CLND usage continues to be low and racial/socioeconomic disparities persist. Until the results of MSLT-2 become available, continued focus on understanding poor adherence to, and improving rates of CLND is necessary.
| S-EPMC6208358 | biostudies-other
Project description:ObjectiveTo describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients ?45 years old.MethodObservational cohort study.ResultsIn a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients ?45 years old. Compared with younger adults (18-44 years), older patients were more often male (45% vs. 12%, p < 0.0001), had lower frequency of tumors (23% vs. 51%, p = 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p = 0.009) and treatment (7 vs. 4 weeks, p = 0.039), and had less favorable outcome (modified Rankin Scale score 0-2 at 2 years, 60% vs. 80%, p < 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05-0.39, p = 0.0001), early treatment (OR 0.60, CI 0.47-0.78, p < 0.0001), no need for intensive care (OR 0.09, CI 0.04-0.22, p < 0.0001), and longer follow-up (p < 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10-7.76, p = 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up.ConclusionsAnti-NMDAR encephalitis is less severe in patients ?45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome.
| S-EPMC3795591 | biostudies-literature
Project description:Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.
| S-EPMC5297824 | biostudies-literature
Project description:Tumor resection is recommended in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, however it is often difficult during an early stage of the disease. We report here the efficacy of early tumor removal in a patient with anti-NMDAR encephalitis. This 21-year-old woman was admitted to another hospital with rapidly progressive psychiatric symptoms, a decreased level of consciousness, and seizures. Abdominal CT showed a pelvic mass. On day 1 of admission to our center, she developed hypoventilation requiring mechanical support. She had orofacial dyskinesias with well-coordinated, pseudo-piano playing involuntary finger movements. Based on these clinical features, she was immediately scheduled for tumor resection on day 3. While awaiting surgery, she began to receive high-dose intravenous methylprednisolone. After tumor removal, she received plasma exchange, followed by intravenous immunoglobulin and additional high-dose methylprednisolone. Two weeks after tumor removal, she started following simple commands and progressive improvement, although she remained on mechanical ventilation for 10 weeks due to nocturnal central hypoventilation. Anti-NMDAR antibodies in serum/CSF were detected. Pathological examination showed immature teratoma with foci of infiltrates of B- and T-cells. Early tumor resection with immunotherapy facilitates recovery from this disease, but central hypoventilation may require long mechanical support. Non-jerky elaborate finger movements suggest antibody-mediated disinhibition of the cortico-striatal systems.
| S-EPMC3740121 | biostudies-literature
Project description:To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer.Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis.SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028).Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer.
| S-EPMC5078820 | biostudies-other