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BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).
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Background and Objectives: The purpose of this study is to enhance the quality of life in elderly patients with lung cancer by understanding relations of uncertainty, appraisal of uncertainty, self-efficacy, and quality of life targeting elderly patients with lung cancer receiving anticancer therapy, and also analyzing the factors affecting the quality of life based on Mishel's theory. Materials and Methods: The subjects were a total of 112 lung cancer patients aged 65 or older receiving anticancer therapy. The data was collected by using self-report questionnaires targeting patients in hemato-oncology at Chungbuk National University Hospital. The data were analyzed using descriptive statistics, a t-test, an analysis of variance, Pearson's correlational coefficients, and hierarchical regression analysis. Results: In stage 1, anticancer therapy (chemotherapy) (ß = -0.34, p < 0.001), economic condition (low) (ß = -0.30, p < 0.001), the number of anticancer therapies (three times or more) (ß = -0.29, p < 0.001), and education (graduation from high school or higher) (ß = 0.18, p = 0.033) were influencing factors (F = 0.52, p < 0.001). In stage 2, self-efficacy (ß = 0.41, p < 0.001), appraisal of uncertainty: danger (ß = -0.29, p < 0.001), appraisal of uncertainty: opportunity (ß = 0.18, p = 0.018), the number of anticancer therapies (three times or more) (ß = -0.17, p = 0.006), and anticancer therapy (chemotherapy) (ß = -0.14, p = 0.031) were influencing factors, which showed 74.2% explanatory power (F = 26.17, p < 0.001). Conclusions: In order to improve the quality of life of subjects, it would be necessary to develop interventions for raising their self-efficacy by considering their degree of education, economic condition, the types and numbers of anticancer therapies, and understanding of the appraisal of uncertainty about the disease is assessed as an opportunity factor or a danger factor.
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Neoplasias Pulmonares , Qualidade de Vida , Idoso , Humanos , Incerteza , Autoeficácia , Escolaridade , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL-1 receptor antagonist that blocks biologic activity of IL-1ß) are recommended.
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Epilepsia Resistente a Medicamentos , Encefalite/complicações , Síndromes Epilépticas , Convulsões Febris , Adolescente , Canabidiol/uso terapêutico , Criança , Pré-Escolar , Dieta Cetogênica , Epilepsia Resistente a Medicamentos/classificação , Epilepsia Resistente a Medicamentos/diagnóstico , Síndromes Epilépticas/complicações , Síndromes Epilépticas/fisiopatologia , Humanos , Doenças do Sistema Imunitário/complicações , Lactente , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Convulsões Febris/classificação , Convulsões Febris/diagnóstico , Estado Epiléptico/classificação , Estado Epiléptico/diagnósticoRESUMO
BACKGROUND: This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC). METHODS: One-hundred-and-sixty-four patients were randomised (1:1) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint. RESULTS: In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI: 0.48-0.99), particularly in patients aged <65 years, with more advanced disease (i.e., extensive-stage disease, time to relapse: 3-6 months), or Eastern Cooperative Oncology Group performance status 1 or 2. More belotecan recipients completed all treatment cycles (53% vs. 35%; p = 0.022). CONCLUSIONS: The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged <65 years, with more advanced disease, or poor performance.
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Camptotecina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/uso terapêutico , Idoso , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores da Topoisomerase I/efeitos adversos , Inibidores da Topoisomerase I/uso terapêutico , Topotecan/efeitos adversosRESUMO
OBJECTIVE: The goal of this study was to assess the success rate and complications of stereo-electroencephalogra-phy (sEEG) and laser interstitial thermal therapy (LITT) in the treatment of nonlesional refractory epilepsy in cingulate and insular cortex. METHODS: The authors retrospectively analyzed the treatment response in 9 successive patients who underwent insular or cingulate LITT for nonlesional refractory epilepsy at their center between 2011 and 2019. Localization of seizures was based on inpatient video-EEG monitoring, neuropsychological testing, 3-T MRI, PET scan, magnetoencephalography scan, and/or ictal SPECT scan. Eight patients underwent sEEG, and 1 patient had implantation of both sEEG electrodes and subdural grids for localization of epileptogenic zones. LITT was performed in 5 insular cases (4 left and 1 right) and 3 cingulate cases (all left-sided). One patient also underwent both insular and cingulate LITT on the left side. All of the patients who underwent insular LITT as well as 2 of the 3 who underwent cingulate LITT were right-hand dominant. The patient who underwent insular plus cingulate LITT was also right-hand dominant. RESULTS: Following LITT, 67% of the patients were seizure free (Engel class I) at follow-up (mean 1.35 years, range 0.6-2.8 years). All patients responded favorably to treatment (Engel class I-III). Two patients developed small intracranial hemorrhages during the sEEG implantation that did not require surgical management. One patient developed a large intracranial hemorrhage during an insular LITT procedure that did require surgical management. That patient experienced aphasia, incoordination, and hemiparesis, which resolved with inpatient rehabilitation. No permanent neurological deficits were noted in any of the patients at last follow-up. Neuropsychological status was stable in this cohort before and after LITT. CONCLUSIONS: sEEG can be safely used to localize seizures originating from insular and cingulate cortex. LITT can successfully treat seizures arising from these deep-seated structures. The insula and cingulum should be evaluated more frequently for seizure onset zones.
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N-methyl-D-aspartate receptor (NMDA-R) antibody encephalitis is an immune-mediated disorder characterized by the presence of anti-NMDA antibody in serum and cerebrospinal fluid, with a characteristic combination of psychological and neurological signs and symptoms. The scientific knowledge pertaining to the management of anti-NMDA-R encephalitis is growing. It is important that neuroscience nurses be aware of treatments as well as the newest novel treatment options available. Early aggressive intervention is imperative to recovery. The first line of treatment often includes high-dose steroids, intravenous immunoglobulin, and therapeutic plasma exchange. Second-line therapy for refractory NMDA-R encephalitis includes intravenous rituximab and cyclophosphamide. Even with these treatments, up to 25% of patients may be left with severe deficits or have a fatal outcome. It is well known that penetration of monoclonal anti-CD20 antibody therapy (rituximab) into the cerebrospinal fluid is 0.1% of that in the serum. Therefore, efficacy of rituximab in the treatment of NMDA encephalitis may be improved by intrathecal administration in selected cases with a poor response to intravenous rituximab. We present a case of anti-NMDA-R encephalitis that was refractory to first- and second-line therapies, who responded to intrathecal rituximab, to highlight a novel treatment that may be able to prevent long-term disability and improve clinical outcomes.
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Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Injeções Espinhais , Rituximab/uso terapêutico , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Ciclofosfamida/uso terapêutico , Eletroencefalografia , Feminino , Humanos , Imunossupressores/uso terapêutico , Enfermagem em Neurociência , Convulsões , Adulto JovemRESUMO
Standard treatment for locally advanced (stage III-IV) head and neck squamous cell cancer (LA-HNSCC) is concurrent chemoradiation therapy (CCRT) with cisplatin 100âmg/m every 3 weeks. For medically unfit patients susceptible to treatment-related adverse events, low-dose weekly cisplatin (30-40âmg/m) can be used as an alternative. In this study, we retrospectively compared the therapeutic outcomes of low-dose weekly cisplatin regimen and standard regimen in CCRT for LA-HNSCC.The medical records of histologically confirmed LA-HNSCC patients were retrospectively reviewed from January 1, 2007 to December 31, 2012. Patients who were treated with CCRT as initial treatment were included.Among 220 patients eligible, 65 (29.5%) were treated with cisplatin dosing schedule of 100âmg/m every 3 weeks and 155 (70.5%) with 30 to 40âmg/m weekly. The overall response rate in 3-weekly group was 92.3% and did not differ from that in weekly group (91.0%). The median progression-free survival of the weekly group was not attained but was not significantly different from that of 3-weekly group (50.7 months, 95% confidence interval [CI] 42.2-59.1 months) (Pâ=â.81). Also, the median overcall survival did not differ significantly between 2 groups (Pâ=â.34).In the present study, low-dose weekly cisplatin showed therapeutic outcomes comparable to standard-dose cisplatin in CCRT for LA-HNSCC. Prospective comparison of standard-dose three-weekly and low-dose weekly cisplatin is warranted.
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Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/métodos , Terapia Combinada , Esquema de Medicação , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: In T4a laryngeal cancer with thyroid cartilage invasion, no optimal frontline treatment has yet been defined in controlled trials. METHODS: We reviewed data from 89 patients with T4a laryngeal cancer featuring thyroid cartilage invasion who were treated initially with either total laryngectomy (n = 53) or a larynx-preservation strategy (n = 36). RESULTS: The median progression-free survival (PFS) of the total laryngectomy group had not been attained at the time of analysis and was thus significantly longer than that of the larynx-preservation group (8.7 months). The median overall survival (OS) of patients who underwent total laryngectomy was 87.2 months, significantly longer than that of the larynx-preservation group (31.3 months). The survival benefit of primary surgery compared to a larynx-preservation strategy was more striking in patients of lower N classifications. CONCLUSION: Total laryngectomy may be a better therapeutic option to treat T4a laryngeal cancer featuring thyroid cartilage invasion, especially in patients exhibiting limited nodal involvement (N0/N1). © 2016 Wiley Periodicals, Inc. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1271-1277, 2016.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Tratamentos com Preservação do Órgão/métodos , Cartilagem Tireóidea/patologia , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/patologia , Laringectomia/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Apocrine carcinoma is a rare malignant adnexal neoplasm. The differential diagnosis between apocrine carcinoma and cutaneous metastasis is often difficult. Here, we report a case of locally recurrent penile apocrine carcinoma initially diagnosed as metastatic adenocarcinoma of the colon. A 75-year-old man with a history of surgical resection due to sigmoid colon cancer and penile metastasis two years prior to this study presented with a nodule at the left penile base. He underwent a wide local resection of the penile mass under a suggested preoperative diagnosis of extra-mammary Paget's disease (EMPD) associated with previous sigmoid colon cancer. However, the previously and currently resected penile masses were identified as primary apocrine carcinoma upon hematoxylin and eosin (H&E) staining and immunohistochemical staining. Although the incidence is extremely rare, both clinicians and pathologists should be alert to the possibility of synchronous double primary apocrine carcinoma in cancer patients with malignant cutaneous lesions.
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Synchronous bilateral breast cancer is extremely rare in men and has not, up to date, been reported in Korea. A 54-year-old man presented with a palpable mass in the right breast. The right nipple was retracted and bilateral axillary accessory breasts and nipples were present. On physical examination, a 2 cm-sized mass was palpated directly under the right nipple, and, with squeezing, bloody discharge developed in a single duct of the left nipple. There was no palpable mass in the left breast, and axillary lymph nodes were not palpable. Physical examination of external genitalia revealed a unilateral undescended testis on the left side. Synchronous bilateral breast cancer was diagnosed using mammography, ultrasonography, and core-needle biopsy. Histopathological examination revealed invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast. Bilateral total mastectomy, sentinel lymph node biopsy, and excision of accessory breasts in the axilla were performed.
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Medically refractory status epilepticus (RSE) causes high morbidity and mortality in children. There are no evidence-based guidelines for treatment. Epilepsy surgery is a treatment option for RSE. We describe a 9-year-old boy treated successfully for RSE with complete corpus callosotomy (CC). Epilepsy surgery should be considered for prolonged RSE. In the absence of evidence of focal epileptogenesis, complete corpus callosotomy may be effective in select cases.
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Corpo Caloso/cirurgia , Psicocirurgia/métodos , Estado Epiléptico/cirurgia , Criança , Eletroencefalografia , Humanos , Masculino , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography (CT) scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.
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BACKGROUND: Functional hemispherectomy is effective in carefully selected patients, resulting in a reduction of seizure burden up to complete resolution, improvement of intellectual development, and developmental benefit despite possible additional neurological deficit. Despite apparent hemispheric pathology on brain magnetic resonance imaging (MRI) or other imaging tests, scalp electroencephalography (EEG) could be suggestive of bilateral ictal onset or even ictal onset contralateral to the dominant imaging abnormality. We aimed to investigate the role of scalp EEG lateralization pre-operatively in predicting outcome. METHODS: We retrospectively reviewed 54 patients who underwent hemispherectomy between 1991 and 2009 at Medical College of Georgia (1991-2006) and Cincinnati Children's Hospital Medical Center (2006-2009) and had at least one year post-operative follow-up. All preoperative EEGs were reviewed, and classified as either lateralizing or nonlateralizing, for both ictal and interictal EEG recordings. RESULTS: Of 54 patients, 42 (78%) became seizure free. Twenty-four (44%) of 54 had a nonlateralizing ictal or interictal EEG. Further analysis was based on etiology of epilepsy, including malformation of cortical development (MCD), Rasmussen syndrome (RS), and stroke (CVA). EEG nonlateralization did not predict poor outcome in any of the etiology groups evaluated. CONCLUSION: Scalp EEG abnormalities in contralateral or bilateral hemispheres do not, in isolation, predict a poor outcome from hemispherectomy. Results of other non-invasive and invasive evaluations should be used to determine candidacy.
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Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Lateralidade Funcional/fisiologia , Hemisferectomia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Couro Cabeludo/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The leukocyte common antigen (CD45) is a transmembrane-type protein tyrosine phosphatase that has five isoforms. METHODS: We generated seven murine mAbs against human CD45 by injecting cells from different origins, such as human thymocytes, PBMCs, and leukemic cell lines. By using various immunological methods including flow cytometry, immunohistochemistry, and immunoprecipitation, we evaluated the reactivity of those mAbs to CD45 of thymus as well as tonsil lysates. Furthermore, we transiently transfected COS-7 cells with each of gene constructs that express five human CD45 isoforms respectively, and examined the specificities of the mAbs against the transfected isoforms. RESULTS: In case of thymocytes, lymphocytes, and monocytes, all the seven mAbs demonstrated positive reactivities whereas none was reactive to erythrocytes and platelets. The majority of immune cells in formalin-fixed paraffin-embedded thymus and tonsil tissues displayed strong membranous immunoreactivity, and the main antigen was detected near 220 kDa in all cases. Among the mAbs, four mAbs (AP4, DN11, SHL-1, and P6) recognized a region commonly present in all the five isoforms. One mAb, YG27, recognized four isoforms (ABC, AB, BC, and O). Two mAbs, P1 and P14, recognized the isoforms that contain exon A encoded regions (ABC and AB). CONCLUSION: In this study, we confirmed that AP4, DN11, SHL-1, YG27 and P6, are mAbs reactive with the CD45 antigen whereas P1 and P14 are reactive with the CD45RA antigen.
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BACKGROUND: Antibody mediated anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a recently reported diagnosis of clinical importance. Recognition of the syndrome, especially in pediatric populations, is difficult and often undiagnosed and/or confused with neurological disorders with similar clinical features. RESULTS: We report a case of an 11 year old female with explosive-onset epilepsy and predominantly unilateral frontal lobe abnormalities on magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) neuroimaging. A diagnosis of Rasmussen syndrome (RS) was considered. Cerebrospinal fluid analysis revealed strong positivity for NMDA receptor antibodies. Screening for occult ovarian teratoma with computed tomography (CT) and MRI initially did not demonstrate associated tumor. Treatment with steroids and plasma exchange improved her clinical course and subsequent MRI showed resolution. CONCLUSION: NMDA receptor encephalitis has variable neuroimaging manifestations, and can mimic other entities. We emphasize the clinical syndrome of NMDA receptor encephalitis and consideration of the diagnosis in evaluating a child with explosive-onset epilepsy, unilateral imaging abnormalities, and neurocognitive decline.