RESUMEN
BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Masculino , Femenino , Pronóstico , Adulto , China/epidemiología , Adulto Joven , Adolescente , Estudios Prospectivos , Niño , Persona de Mediana Edad , Nomogramas , Estudios de Seguimiento , Pueblos del Este de AsiaRESUMEN
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease that has been rarely associated with AQP4-IgG and MOG-IgG demyelinating diseases, and even more rarely with multiple sclerosis. We present the case of a woman in her 40s with confirmed NMDAR encephalitis and coexistent fulminant relapse of multiple sclerosis treated with alemtuzumab 6 years prior, who had a favourable outcome following treatment with ocrelizumab. We proceed to systematic review of similar reported cases, finding a lower than anticipated prevalence of underlying malignancy compared with isolated NMDAR encephalitis, in this rare overlap syndrome.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Recurrencia , Humanos , Femenino , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Adulto , Esclerosis Múltiple/tratamiento farmacológico , Alemtuzumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
BACKGROUND: The presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE. METHODS: Charts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied. CSF and serum kappa free light chains were determined using the Freelite assay (The Binding Site Group) and the turbidimetric Optilite analyzer. RESULTS: We identified 34 patients with "definite" AE (9 anti-NMDAR AE and 25 limbic AE) and nine patients with "possible" AE. Five patients (15%) with definite AE had pleocytosis and twelve (34%) showed CSF-restricted oligoclonal bands (OCB) at isoelectric focusing. The Kappa index was >6 in 29.4% and > 3 in 50% of the definite AE patients. It was elevated (>3) in 36.4% of patients with definite AE who resulted negative to OCB testing and was the only altered parameter suggestive of an ongoing inflammatory process in the CNS in three definite AE patients with otherwise normal CSF findings (i.e. normal cell count and protein levels, no OCBs). In the possible AE group, one patient had a Kappa index >3 in the absence of OCB. CONCLUSIONS: The Kappa index could be useful, as a more sensitive marker of IS and as a supportive marker of neuroinflammation, in the diagnostic work-up of suspected AE.
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Encefalitis , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Encefalitis/diagnóstico , Encefalitis/líquido cefalorraquídeo , Encefalitis/sangre , Anciano , Estudios Retrospectivos , Adulto Joven , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/líquido cefalorraquídeo , Bandas Oligoclonales/líquido cefalorraquídeo , Bandas Oligoclonales/sangre , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/sangre , Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Cadenas kappa de Inmunoglobulina/líquido cefalorraquídeo , Cadenas kappa de Inmunoglobulina/sangre , Adolescente , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/sangre , Enfermedades Autoinmunes del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades Autoinmunes del Sistema Nervioso/inmunologíaRESUMEN
Here we described an 18-year-old woman who were initially misdiagnosed as psychiatric disorders in a psychiatric institution. She was transferred to our neurological ward because of impaired consciousness. Neuronal antibody testing confirmed the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Cerebral magnetic resonance imaging (MRI) revealed a concomitant disorder named reversible splenial lesion syndrome (RESLES). After administration of combined immunotherapy, the patient recovered completely 3 months after discharge. To our knowledge, co-occurrence of RESLES and anti-NMDAR encephalitis was only described in two patients with teratoma and we provide another case without teratoma. We highlight that anti-NMDAR antibodies can be added to the multiple causes of RESLES. It is therefore imperative for clinicians to detect anti-neuronal antibodies in patients with RESLES to avoid missed diagnosis.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Femenino , Adolescente , Imagen por Resonancia Magnética , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patologíaRESUMEN
AIMS: Anti-NMDAR encephalitis is an increasingly recognised autoimmune disorder, with evolving diagnostic criteria. This study aims to analyse the prevalence and diagnostic patterns of anti-NMDAR encephalitis in a New Zealand hospital setting. METHODS: Data from Waikato Hospital's lab database, encompassing anti-NMDAR antibody requests between August 2013 and July 2023, were examined. Cases were categorised based on age, gender and diagnostic outcomes. RESULTS: In all requests, 288/318 (91%) were processed and 10/288 (3.5%) anti-NMDAR antibodies were positive. Positive cases were equally frequent by sex, with an average age of 29.4 years. Only 6/10 were diagnosed with anti-NMDAR encephalitis, while others received alternative diagnoses. Maori ethnicity was overrepresented. This study indicates a low prevalence of anti-NMDAR encephalitis in the Waikato region, with adult predominance. Ethnic disparities were observed. The need for refining testing criteria to optimise cost-effectiveness is discussed. CONCLUSION: Anti-NMDAR encephalitis is relatively rare in Waikato Hospital, New Zealand, with diagnostic challenges related to testing criteria and ethnic diversity. Further research and consideration of testing protocols are warranted.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/epidemiología , Nueva Zelanda/epidemiología , PrevalenciaRESUMEN
RATIONALE: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease of the central nervous system that affects the meninges, brain, spinal cord, and optic nerves. GFAP astrocytopathy can coexist with a variety of antibodies, which is known as overlap syndrome. Anti-NMDAR-positive encephalitis overlap syndrome has been reported; however, encephalitis overlap syndrome with both anti-NMDAR and sulfatide-IgG positivity has not been reported. PATIENT CONCERNS: The patient was a 50-year-old male who was drowsy and had chills and weak limbs for 6 months. His symptoms worsened after admission to our hospital with persistent high fever, dysphoria, gibberish, and disturbance of consciousness. Positive cerebrospinal fluid NMDA, GFAP antibodies, and serum sulfatide antibody IgG were positive. DIAGNOSES: Autoimmune GFAP astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome. INTERVENTIONS: In addition to ventilator support and symptomatic supportive treatment, step-down therapy with methylprednisolone (1000 mg/d, halved every 3 days) and pulse therapy with human immunoglobulin (0.4 g/(kg d) for 5 days) were used. OUTCOMES: After 6 days of treatment, the patient condition did not improve, and the family signed up to give up the treatment and left the hospital. CONCLUSIONS: Patients with autoimmune GFAP astrocytopathy may be positive for anti-NMDAR and sulfatide-IgG, and immunotherapy may be effective in patients with severe conditions. LESSONS: Autoimmune GFAP astrocytopathy with nonspecific symptoms is rarely reported and is easy to be missed and misdiagnosed. GFAP astrocytopathy should be considered in patients with fever, headache, disturbance of consciousness, convulsions, and central infections that do not respond to antibacterial and viral agents. Autoimmune encephalopathy-related antibody testing should be performed as soon as possible, early diagnosis should be confirmed, and immunomodulatory therapy should be administered promptly.
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Proteína Ácida Fibrilar de la Glía , Sulfoglicoesfingolípidos , Humanos , Masculino , Persona de Mediana Edad , Proteína Ácida Fibrilar de la Glía/inmunología , Proteína Ácida Fibrilar de la Glía/sangre , Sulfoglicoesfingolípidos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Autoanticuerpos/sangre , Metilprednisolona/uso terapéutico , Encefalitis/diagnóstico , Encefalitis/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Astrocitos/inmunología , Astrocitos/patología , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/inmunologíaRESUMEN
Presented clinical observation of anti-NMDA-receptor encephalitis, which was first described in 2007, is rare and to date has not been sufficiently studied. The disease often manifests with psychopathological symptoms and catatonia, so patients are transferred into a mental healthcare institution and often require intensive care and resuscitation, due to the development of life-threatening respiratory and hemodynamic disorders. Diagnosis is based on detection of autoantibodies to the NR1- and NR2 subunits of the glutamate NMDA receptor in blood serum and cerebrospinal fluid. Pathogenesis-based therapy includes the administration of glucocorticoids and intravenous immunoglobulins, plasmapheresis, as well as the introduction of monoclonal antibodies in also used, and in severe cases, cytostatics are prescribed. The widespread comorbidity of anti-NMDA receptor encephalitis with ovarian neoplasms in women (up to 60%) requires appropriate diagnosis and early removal of ovarian neoplasms when they are detected. With timely diagnosis and adequate treatment strategies, the outcome of this rare disorder is usually positive.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Autoanticuerpos , Neoplasias Ováricas , Adulto , Femenino , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Catatonia/etiología , Catatonia/diagnóstico , Inmunoglobulinas Intravenosas/uso terapéutico , Trastornos Mentales/etiología , Trastornos Mentales/diagnóstico , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico , Plasmaféresis , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
RATIONALE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare disease and common type of autoimmune encephalitis. The prognosis of patients with comorbid disorders of consciousness is poor, and no such acupuncture treatment has been reported. We report a case of acupuncture in anti-NMDAR encephalitis with a high cerebrospinal fluid titer combined with impaired consciousness. PATIENT CONCERNS: A 13-year-old girl with anti-NMDAR encephalitis presented to our hospital with impaired consciousness. DIAGNOSES: Therefore, the patient was diagnosed with anti-NMDAR encephalitis. According to the Chinese medicine theory, the diagnosis was Shenhun(phlegm obstructs the clear orifices). INTERVENTIONS: Depending on the patient's condition, we used the Xingnao Kaiqiao acupuncture therapeutic method. OUTCOMES: After 16 weeks of acupuncture treatment, the patient awoke and resumed a normal life with no recurrence at one-year follow-up. CONCLUSION: This case demonstrated that acupuncture can be used as a complementary and alternative treatment for anti-NMDAR encephalitis.
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Terapia por Acupuntura , Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Femenino , Adolescente , Terapia por Acupuntura/métodos , Resultado del TratamientoRESUMEN
We described a challenging case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in a young girl. Despite enduring months of reduced consciousness with ongoing antibody presence, she ultimately exhibited remarkable improvement within a 5-year follow-up period. Additionally, we conducted a concise review of relevant literature on anti-NMDAR encephalitis, with a specific focus on anti-NMDAR antibodies. Our findings enhance the clinical comprehension of anti-NMDAR encephalitis and offer valuable insights to clinicians for its management.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Autoanticuerpos , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Femenino , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Receptores de N-Metil-D-Aspartato/inmunología , Niño , Trastornos de la Conciencia/etiología , Trastornos de la Conciencia/inmunologíaRESUMEN
Background: Recently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored. Case presentation: We present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids. Conclusion: Steroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Esteroides , Humanos , Masculino , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Esteroides/uso terapéutico , Resultado del Tratamiento , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis/tratamiento farmacológico , Encefalitis/inmunología , Encefalitis/diagnóstico , Receptores de N-Metil-D-Aspartato/inmunología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
In recent decades, there has been increasing biomedical and public understanding of the role of autoimmunity in neuropsychiatric illness. Popular media have highlighted patients with psychiatric illnesses who were eventually diagnosed with autoimmune neuropsychiatric illnesses such as anti- N-methyl-D-aspartate receptor encephalitis. Coverage of these cases has often drawn attention to the effects of misdiagnosis or delayed diagnosis of such diseases in psychiatric patients. Autoimmune encephalitis can have varied presentations and often involves evaluation and management from multiple medical specialties. As a result, there remains considerable uncertainty regarding how courts might gauge the legal standard of care with regard to psychiatric workup of new-onset psychiatric symptoms, and the degree to which autoimmune encephalitis must be considered. In this article we provide a brief overview of autoimmune encephalitis and autoimmune psychosis, including current diagnostic approaches to these conditions. We review case law regarding the standard of care for psychiatric disorders caused by general medical conditions. Finally, we provide a medicolegal perspective on the responsibilities of psychiatrists and other mental health professionals in the evaluation of possible autoimmune encephalitis.
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Encefalitis , Humanos , Encefalitis/diagnóstico , Nivel de Atención/legislación & jurisprudencia , Enfermedades Autoinmunes/diagnóstico , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Enfermedad de Hashimoto/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Trastornos Psicóticos/diagnósticoRESUMEN
INTRODUCTION: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types. METHODS: Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8). RESULTS: The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis. DISCUSSION: COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.
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COVID-19 , Encefalitis por Herpes Simple , Encefalitis , Enfermedad de Hashimoto , Humanos , COVID-19/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Adulto , Encefalitis/diagnóstico , Encefalitis/líquido cefalorraquídeo , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/complicaciones , Enfermedad de Hashimoto/líquido cefalorraquídeo , Enfermedad de Hashimoto/diagnóstico , Anciano , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Encefalitis Viral/diagnóstico , Encefalitis Viral/líquido cefalorraquídeo , SARS-CoV-2 , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeoRESUMEN
Psychiatrists are often the first to be consulted in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. While this disease is rare, psychiatrists need to be aware of its relevant fundamental, clinical and therapeutic aspects. We begin by reviewing the connection between anti-NMDAR encephalitis and the glutamate hypothesis of schizophrenia. Next, we focus on the profile of the patient typically afflicted with this disease. Then, we tackle the limited utility of current diagnostic criteria during the early stage of the disease. After reviewing the psychiatric features, we debate the quest for finding specific psychiatric phenotypes that could facilitate early-stage diagnosis. We conclude by discussing the treatment of psychiatric symptoms and disease outcomes. As follows, this paper presents the relevance of anti-NMDAR encephalitis for psychiatrists.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an essential differential diagnosis in Psychiatry, particularly when dealing with first-episode psychosis.Psychiatrists are often the first to be consulted in patients with NMDAR encephalitis, so they need to be aware of the relevant fundamental, clinical and therapeutic aspects of this disease.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Esquizofrenia , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/fisiopatología , PsiquiatríaRESUMEN
Objective: To analyze the clinical features of children with refractory N-methyl-D-aspartate (NMDA) receptor antibody encephalitis treated with tocilizumab. Methods: Demographic and clinical manifeatations, immunotherapy and prognosis data of 9 children with refractory NMDA receptor antibody encephalitis who received tocilizumab in the Department of Pediatrics Neurology, XiangYa Hospital of Central South University from August 2021 to September 2023 were collected retrospectively. Prognosis was evaluated using the modified Rankin scale at initial diagnosis, at the initiation of tocilizumab treatment, and at the last follow-up. Treatment related complications, neuroimaging, and electroencephalography data were analyzed. Results: Among the 9 children, 6 were male and 3 were female, with an onset age of 4.2 (2.8, 8.7) years. At the onset of the disease, 9 children had a modified Rankin scale score of 5. When tocilizumab treatment was initiated, 7 children had a score of 5, and 2 children had a score of 4. The interval between the onset and initiation of tocilizumab treatment was 12 (5, 27) months, and the treatment frequency was 8 (5, 13) times. The follow-up time was 2.8 (1.5, 3.7) years. At the last follow-up, the symptoms of 9 children, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction, were improved to varying degrees, and none of them had seizures. At the last follow-up, 4 cases with a modified Rankin scale score of 0, 1 case with a score of 1, 2 cases with a score of 3, 1 case with a score of 4 and 1 case with a score of 5. The modified Rankin scale at the last follow-up was significantly different from that at the start of tocilizumab (Z=-2.56, P=0.014). All children had no serious adverse reactions during the treatment. Conclusions: After treatment with tocilizumab, the symptoms in patients with refractory NMDA receptor antibody encephalitis, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction were improved, and none of them had seizures. The modified Rankin scale were improved, and the safety was good.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Anticuerpos Monoclonales Humanizados , Electroencefalografía , Humanos , Femenino , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Niño , Preescolar , Estudios Retrospectivos , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Pronóstico , Resultado del Tratamiento , Receptores de N-Metil-D-Aspartato/inmunología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
Autoimmune encephalitis (AIE) is a rapid, progressive neurological disorder characterized by nervous system inflammation. While the Graus criteria are the best known criteria for AIE diagnosis, other differential diagnoses meeting the Graus criteria must be considered before management. This narrative review discusses the most common etiologies that resemble AIE. We suggest routine exclusion of mimickers meeting the Graus criteria before confirming an AIE diagnosis. We reviewed 28 studies including 356 patients. The main initial diagnosis was AIE, then paraneoplastic limbic encephalitis and anti-N-methyl-D-aspartate receptor encephalitis. Only 194 patients met the possible Graus criteria. The most frequent conditions among the total population were dementia, other neurodegenerative diseases, and psychiatric and functional neurological disorders. AIE is often misdiagnosed, leading to unnecessary treatment. Despite publication of the Graus criteria, medical cases mimicking this condition are being published. Many neurological diseases entering the differential diagnosis of AIE could be excluded through a detailed history, neurological examination, laboratory analysis, and other investigations, including cerebrospinal fluid and brain magnetic resonance imaging. However, some differential diagnoses complied with the possible Graus criteria, with some having concurrent antineuronal antibodies, which were considered true mimickers. AIE diagnosis suspicion is primarily clinical, but a definitive diagnosis requires various diagnostic tools.
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Encefalitis , Humanos , Diagnóstico Diferencial , Encefalitis/diagnóstico , Encefalitis/inmunología , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/inmunología , Imagen por Resonancia Magnética , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Autoanticuerpos/sangre , Autoanticuerpos/inmunologíaRESUMEN
Introduction: Anti-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). Methods: We 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. Results: The 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. Discussion: The 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.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Inmunohistoquímica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/líquido cefalorraquídeo , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/inmunología , Biomarcadores/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/inmunología , Receptores de N-Metil-D-Aspartato/inmunología , Reproducibilidad de los ResultadosRESUMEN
Cerebellar ataxia is an uncommon and atypical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Autoanticuerpos , Tronco Encefálico , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Tronco Encefálico/patología , Autoanticuerpos/inmunología , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Femenino , Ataxia Cerebelosa/etiología , Ataxia Cerebelosa/diagnóstico , Ataxia Cerebelosa/inmunología , Cerebelo/patología , Cerebelo/diagnóstico por imagen , Receptores de N-Metil-D-Aspartato/inmunología , Adulto , Inmunoterapia , Masculino , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare. CASE PRESENTATION: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response. CONCLUSIONS: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico por imagen , Masculino , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Convulsiones/tratamiento farmacológico , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Imagen por Resonancia MagnéticaRESUMEN
Anti-NMDA receptor encephalitis is an auto-immune disorder often presenting with non-specific and heterogeneous neuropsychiatric symptoms at onset. This complicates a quick and accurate diagnosis. However, a tardy diagnosis has a negative impact on morbidity and mortality. We report about a patient with the clinical presentation of a psychotic depression, who was diagnosed with anti-NMDA receptor encephalitis only after a thorough diagnostic work-up. Neurological symptoms were wrongly attributed to the psychiatric syndrome or considered as side-effects of its treatment. We present an overview of clinical aspects of the disorder, distinctive psychiatric symptoms, diagnostic tools, treatment and prognosis.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/psicología , Diagnóstico Diferencial , Pronóstico , Femenino , Diagnóstico Tardío , MasculinoRESUMEN
BACKGROUND: Persistent somatoform pain disorder (PSPD) is often the initial diagnosis in patients seeking treatment in psychiatric departments, making it challenging to consider organic nervous system diseases. However, autoimmune encephalitis can present with atypical initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture, with antibody support, plays a crucial role in diagnosing autoimmune encephalitis. CASE PRESENTATION: This report describes a 40-year-old male adult patient who was initially diagnosed with persistent somatoform pain disorder in 2022. The patient reported a reduction in pain while resting on his back. There were no fever or relevant medical history. Despite 8 months of symptomatic treatment, the symptoms did not improve. Moreover, the patient developed confusion, gibberish speech, non-cooperation during questioning, and increased frequency and amplitude of upper limb convulsions. Lumbar puncture revealed elevated protein levels and protein-cell dissociation. The autoimmune encephalitis antibody NMDAR (+) was detected, leading to a diagnosis of autoimmune encephalitis (NMDAR). CONCLUSION: Autoimmune encephalitis (NMDAR), starting with persistent somatoform pain (PSPD), often presents with atypical symptoms and can be easily misdiagnosed. Therefore, it is important to consider the possibility of organic nervous system disease in time, and to test serum or cerebrospinal fluid antibodies to rule out organic nervous system disease after symptomatic treatment of mental disorders is ineffective. This approach facilitates the early diagnosis of autoimmune encephalitis and other underlying organic neurological disorders.