Clinical Spectrum, Treatment and Outcome of Children with Autoimmune Encephalitis.

OBJECTIVE: To assess the clinical spectrum, treatment, and outcome of children with autoimmune encephalitis (AE). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Paediatrics, The Aga Khan University Hospital, Karachi, Pakistan, from January 2017 to December 2021. METHODOLOGY: Medical records of children with a diagnosis of AE were reviewed for clinical features, treatment details, and outcomes. Outcome was defined as good (0-2) or poor (3-6) based on a modified Rankin Scale (mRS) score at 3-month follow-up. Descriptive statistics were reported and logistic regression was used to assess the prognostic factors associated with outcome. RESULTS: Thirty-three patients were identified with AE. Thirteen (39.3%) were antibody positive. Anti-N-methyl-D-aspartate receptor (NMDAR) antibody was seen in 92% of positive cases. Behavioural abnormalities (87.8%), seizures (81.8%), movement disorders (66.6%), psychiatric symptoms (63.6%), and mutism (33.3%) were the prominent symptoms. Thirty (91%) patients received first-line immunotherapy. Good outcome was seen in 14 (48.2%) patients. Univariable analysis showed that the odds of having poor outcome were 2.5 (95% confidence interval [CI] 0.37-16.88, p=0.34) in patients with chorea. In addition, an elevated cerebrospinal fluid (CSF) protein had an odds ratio (OR) of 8.6 (CI 0.88-84.83, p=0.064) and positive CSF antibodies had an OR of 3.7 (CI 0.79-17.72, p=0.095) for a poor outcome. Mortality was seen in 4 (12.1%) patients. CONCLUSION: A very low threshold is needed for the diagnosis of AE in children presenting with behavioural symptoms and chorea. Although the odds for poor prognosis were higher in patients with chorea, elevated CSF protein and positive CSF antibodies, the p-value did not come out significant. KEY WORDS: Autoimmune encephalitis, Antibodies, NMDAR, Immunotherapies, mRS score, Outcome.

[Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis Associated with Anterior Mediastinal Mature Teratoma].

We report a 27 years-old previously healthy male admitted to a psychiatric hospital because of abnormal behavior. He was suspected meningoencephalitis with fever, abnormal sweating, muscle tone, confusion, and introduced to the neurology department of our hospital. After admission, increasing convulsions and apnea attack required mechanical ventilation therapy. Anti-N-methyl-D-aspartate( NMDA) - receptor encephalitis was diagnosed based on positive (20-fold) anti-NMDA antibody in cerebrospinal fluid examination. An enhanced chest computed tomography (CT) showed a 43 mm cystic mass with calcification of the anterior mediastinum. He underwent the tumor resection under median sternotomy on the 18th hospital day. The plasmapheresis and steroid therapies were treated after the operation. The consciousness level gradually improved, the patient was withdrawn from the respirator on the post operative day( POD) 35, and transferred to a rehabilitation hospital on POD 60. The pathological result was mature teratoma. However, no specific findings such as inflammatory cell infiltration into nerve components were observed. Anti-NMDA receptor encephalitis was established by Dalmau in 2007 as encephalitis associated with ovarian teratoma. It presents mainly in young adult women with psychiatric symptoms, and requires mechanical ventilation management due to disturbance of consciousness, convulsions, and central hypoventilation in a short period of time. It presents severe symptoms in the acute phase and shows a unique clinical finding with a good prognosis even though it shows a protracted course. Treatment requires prompt tumor detection and early resection, as well as methylprednisolone (mPSL) pulse, plasmapheresis, and high-dose gamma globulin therapy. It is a neurological disease that requires emergency response, and the understanding and prompt response of related departments is important.

Brain magnetic resonance imaging as predictors in pediatric anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: To investigate the associations between brain magnetic resonance imaging (MRI) changes and clinical profiles in children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: Clinical data and brain MRI results of children diagnosed with anti-NMDAR encephalitis in Guangzhou Women and Children's Medical Center from October 2014 to June 2022 were retrospectively studied. RESULTS: A total of 143 children (Male: female 54:89) were enrolled, with a mean onset age of 6.8 years (6.8 ± 3.1). 40.6 % (58/143) of patients had abnormal initial brain MRI. Lesions in temporal lobe (34.5 %, 20/58) and frontal lobe (25.9 %, 15/58) were relatively common. Children with abnormal initial brain MRI were prone to have fever (P = 0.023), dystonia (P = 0.037), positive MOG antibodies (P = 0.015), higher cerebrospinal fluid (CSF) white blood cell count (WBC) (P = 0.019) and to receive rituximab treatment (P = 0.037). There were no significant differences in modified Rankin Scale (mRS) scores before immunotherapy, after immunotherapy and at last follow-up between the normal initial brain MRI group and abnormal group. No initial brain MRI changes were found to be associated with relapses. Brain MRI was reviewed in 72 patients at last follow-up with a median follow-up time of 25.5 months and 48.6 % (35/72) of patients had abnormal brain MRI. The mRS score of the group with normal brain MRI at last follow-up was significantly lower than that of the abnormal group. CONCLUSIONS: About 40.0 % of children with anti-NMDAR encephalitis had abnormal initial brain MRI. Initial brain MRI was associated with certain clinical profiles, but not with relapse and prognosis. Around half of patients had abnormal brain MRI at last follow-up and were prone to have higher mRS score.

The Patient Perspective in Encephalitis Research.

Research on autoimmune and infectious encephalitis has made substantial progress in recent years in revealing the pathophysiology of these diseases, establishing robust diagnostic criteria, and developing promising treatment options, with a range of clinical trials currently underway. Outcome measures in studies on autoimmune and infectious encephalitis mainly relied on established and widely used tools such as the modified Rankin Scale (mRS). However, the mRS was developed to assess stroke outcome and has a strong focus on motor symptoms and the degree of dependence in daily activities. For example, approximately 80% of patients with anti-NMDA receptor encephalitis (i.e., the most common autoimmune encephalitis variant) achieve a good outcome 2 years after disease onset when evaluated using the mRS.1 In contrast to these findings, recent studies show that a majority of patients with anti-NMDA receptor encephalitis suffer from relevant and persistent cognitive impairment, despite mRS scores indicating good or very good recovery.2,3 This shows that the mRS fails to detect clinically relevant long-term symptoms in these patients. Indeed, persisting cognitive deficits with their detrimental effect on quality of life are specifically important in the frequently very young patients with encephalitis. More recently, encephalitis-specific scores have been developed, e.g., the CASE score for the clinical assessment of patients with autoimmune encephalitis.4 While this score is tailored to symptoms in autoimmune encephalitis, it has a strong focus on acute disease symptoms and is less well suited to capture long-term sequalae.

Electroconvulsive therapy for catatonia in anti-NMDA receptor encephalitis: A case series.

BACKGROUND: Anti-NMDAR encephalitis is the most common cause of immune-mediated catatonia. CASE SERIES: Three females presented with neuropsychiatric symptoms and were empirically treated with first-line immunotherapy and ovarian teratoma resection for suspected autoimmune encephalitis, preceding diagnostic confirmation via NMDAR antibody positivity. They required escalating large doses of benzodiazepines for refractory malignant catatonia resulting in ICU level care. ECT treatments were initiated, and patients were gradually noted to have clinical improvement as was measured by the Bush-Francis Catatonia Rating Scale. CONCLUSIONS: Clinicians should recognize catatonia among patients with suspected anti-NMDAR encephalitis and consider the early implementation of ECT into treatment algorithms.

Clinical characteristics and prognosis in patients with neuronal surface antibody-mediated autoimmune encephalitis: a single-center cohort study in China.

Objective: This retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy. Methods: Clinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis. Results: Overall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0-2), and 21 patients had a poor prognosis (mRS 3-6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p<0.001). Multivariate analysis indicated that elevated neutrophil-to-lymphocyte ratio (NLR) and tumour presence were independent risk factors for poor prognosis. The regression equation of the model was logit(P)=-3.480 + 0.318 NLR+2.434 with or without tumour (with assignment =1, without assignment =0). The prediction probability generated by the regression model equation was used as the independent variable for receiver operating curve (ROC) analysis. The results showed that the area under the curve (AUC) of the prediction probability was 0.847 (95% CI, 0.733-0.961; p < 0.001). Conclusions: Different AE subtypes demonstrated different clinical symptom spectra throughout the disease stage. Anti-LGI1 encephalitis and anti-CASPR2 encephalitis were more sensitive to first-line and second-line treatments. Anti-GABABR encephalitis had the worst prognosis among the abovementioned subtypes. The regression equation constructed using NLR and tumour presence effectively predicted the poor prognosis.

Anti-N-methyl-d-aspartate receptor encephalitis: mimicker of lupus and multiple sclerosis.

Anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is a B-cell-mediated autoimmune encephalitis with wide non-specific symptoms like acute-onset psychiatric or neurological ones mimicking various other conditions. A careful history and appropriate workup, including cerebrospinal fluid analysis for anti-NMDAR antibodies, imaging, and electroencephalogram, should be conducted, considering all differential diagnoses that can mimic its presentation. Combination therapy with high-dose steroids, plasma exchange, or immunoglobulin therapy has been shown to be more efficacious. In patients who fail first-line therapy, rituximab or cyclophosphamide should be considered. It is essential to rule out ovarian teratoma or other occult malignancies that can cause NMDARE, as removal of the tumor itself resolves this condition. Timely diagnosis and early intervention are necessary to avoid an untoward outcome.

Pediatric anti-NMDAR encephalitis with demyelination on brain MRI: A single center study.

OBJECTIVE: To explore the clinical characteristics, immunotherapy response, and prognosis of pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis associated with demyelination on brain magnetic resonance (MRI). METHODS: We retrospectively reviewed the medical records of children diagnosed with anti-NMDAR encephalitis in our hospital between January 2016 and December 2021. All children with evidence of demyelination on brain MRI were included. RESULTS: A total of 183 anti-NMDAR encephalitis children were included; 8.7 % (16/183) of them had demyelination on brain MRI. Nine were positive for myelin oligodendrocyte glycoprotein (MOG)-IgG, while two were positive for both MOG-IgG and glial fibrillary acidic protein (GFAP)-IgG. Four patients had a history of acquired demyelinating syndromes and encephalitis, respectively, while nine (56.3 %) had atypical symptoms of anti-NMDAR encephalitis. All children had supratentorial demyelination on brain MRI; four of them had additional infratentorial lesions. All children received first-line immunotherapy; four were administered repeated first-line immunotherapy and/or rituximab because of poor initial response. During the follow-up, 37.5 % (6/16) of the children relapsed, but all responded well to immunotherapy. There were no significant differences in mRS score before immunotherapy, response to first-line immunotherapy, and long-term prognosis between anti-NMDAR encephalitis children with and without demyelination. However, patients with demyelination were more likely to have a history of acquired demyelinating syndromes or unexplained cortical encephalitis and to relapse. CONCLUSION: Pediatric anti-NMDAR encephalitis can co-occur with demyelination and has a high rate of MOG-IgG positivity. A history of acquired demyelinating syndromes or unexplained cortical encephalitis and atypical symptoms may indicate demyelination in children with anti-NMDAR encephalitis. Pediatric anti-NMDAR encephalitis with demyelination is more likely to relapse and needs a closer follow-up. However, it remains unknown whether more intensive immunotherapy is required in these patients.

Patient with concurrent anti-NMDAR autoimmune encephalitis and immature teratoma of the ovary.

In young women with anti-N-methyl-D-aspartate receptor (anti-NMDAR) autoimmune encephalitis (AE), co-occurrence with ovarian teratoma is common. While the management of mature teratoma with AE is well documented, literature on managing immature teratoma (IT) in tandem with AE is relatively scarce. Here, we report a case of a female patient in her early adolescence who presented with abdominal pain and was diagnosed with grade 3 IT combined with anti-NMDAR AE after an ovarian tumour was discovered and resected. Postsurgery, the patient received immunotherapy, chemotherapy and antiepileptic therapy, and two follow-up evaluations showed no signs of recurrence or sequelae. This case highlights the importance of a high index of suspicion for concurrent AE in the presence of ovarian teratoma, particularly IT, and the crucial role of concurrent administration of immunotherapy and chemotherapy following tumour resection in impacting prognosis.

Analysis of the relation between cerebrospinal fluid antibody titers and clinical characteristics in pediatric patients with anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: This retrospective study aimed to investigate the relationship between cerebrospinal fluid (CSF) antibody titers of N-methyl-d-aspartate receptor (NMDAR), and clinical characteristics in pediatric patients with anti-NMDAR encephalitis. METHODS: The clinical and laboratory characteristics of hospitalized patients with anti-NMDAR encephalitis, stratified by antibody titers in CSF and disease severity, were retrospectively studied. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and prognosis of patients were recorded, and each observed indicator was statistically analyzed. RESULTS: A total of 103 pediatric anti-NMDAR encephalitis patients were enrolled in the study, including 41 males (39.8%) and 62 females (60.2%) with a mean age of 8.0 ± 4.0 years. The proportion of patients with cognitive dysfunction and the positive pathogen was higher in the high-titer group than in the low-titer group (p = 0.023, p = 0.042). Consciousness disturbance that occurred as an initial symptom or during the course in the severe group was higher than in the non-severe group (p = 0.002, p < 0.001). More patients in the high-titer group received plasma exchange (PE) than in the low-titer group (p = 0.022). The cure rate of patients was higher with PE (65.2%) than with Corticosteroids and (or) intravenous immunoglobulin (58.1%). CONCLUSIONS: Patients with symptoms of disturbance of consciousness may be severer. The severity in pediatric anti-NMDAR encephalitis patients was not correlated with anti-NMDAR antibody titers. Patients with high CSF antibody titers had a better prognosis after early PE therapy.

A small mature cystic ovarian teratoma associated with anti-NMDA receptor encephalitis and acute respiratory failure: A case report.

OBJECTIVE: To report a rare case of anti-N-Methyl-d-aspartate receptor encephalitis (anti-NMDARE) presented by mental and behavioral changes and seizures accompanied with respiratory failure. CASE REPORT: A 37-year-old multiparous woman was initially presented with abnormal mental behavior and the diagnosis of schizophrenia was made, but the disease progressed rapidly to general convulsion and acute respiratory failure. Although active treatment, including steroids, intravenous immunoglobulins (IVIGs) and plasma exchange was applied, no significant improvement was obtained. Transvaginal ultrasound and pelvic magnetic resonance image (MRI) were arranged and the results showed a suspicious cystic lesion (3 × 2.3 cm) at the right ovary. Laparoscopic unilateral salpingo-oophorectomy was performed and final pathology reported a matured cystic teratoma, suggesting that this patient had anti-NMDARE secondary to ovarian mature teratoma. After surgery, the clinical condition was dramatically improved and she recovered completely without sequelae. CONCLUSION: Although it is well-known about the relation between anti-NMDARE and ovarian mature teratoma, this small tumor may result in the missing diagnosis. Remind us to consider the possibility of any small ovarian cystic lesion-related anti-NMDARE in women with autoimmune encephalitis.

Autoantibodies Targeting Unknown Epitope Autoimmune Encephalitis and the Effect of Modified Electroconvulsive Therapy: Report of Three Cases.

Objective: Generally autoimmune encephalitis (AE) cases present with central nervous system symptoms. Many types of autoantibodies are associated with autoimmune encephalitis, with anti-N-methyl-D-aspartate receptor being the most commonly reported. However, autoimmune encephalitis cases with autoantibodies targeting unknown epitopes are increasingly recognized. This article aims to summarize the clinical experience and assess the feasibility of modified electroconvulsive therapy (MECT) as an adjunctive treatment method for autoimmune encephalitis patients with poor response to first-line immunotherapy and mainly displaying psychiatric symptoms. Methods: This work reports three cases of which two have been diagnosed as autoantibodies targeting unknown epitope autoimmune encephalitis while one has been diagnosed as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and all were effectively treated with MECT. Results: All three cases that otherwise failed to respond to standard immunotherapy for controlling psychiatric symptoms exhibited excellent clinical outcomes following MECT. The underlying mechanism of action of MECT is unclear and whether such an effect involves a neurotransmitter rebalance in the brain remains uncertain. At present, we have observed only a small number of clinical cases, warranting further research among a larger number of clinical cases and more systematic multicenter retrospective analysis. Conclusions: It should be noted that, while our experience supports the utility of MECT in the treatment of certain cases of AE, this option should be regarded as an adjuvant therapy after standard immunosuppressive therapy. Clinicians must be aware that patients should be provided with psychiatric or neurological services for timely diagnosis along with timely and appropriate treatment.

Anti-N-methyl-d-aspartate receptor encephalitis preceded by meningitis lasting up to 60 days.

Long-lasting meningitis complicated by N-methyl-d-aspartate receptor (NMDAR) encephalitis has not been discussed widely in the literature. Herein, we present two cases of anti-NMDAR encephalitis preceded by meningitis. The patients had 60- and 22-day periods of preceding meningitis, which improved with intravenous methylprednisolone and plasmapheresis. No tumors were detected in either of the patients. Although meningitis preceding anti-NMDAR encephalitis is not rare, our patients, especially those who had it for a duration of 60 days, had longer durations of meningitis. This manuscript foregrounds that anti-NMDAR encephalitis might be included in the differential diagnosis of long-lasting meningitis.

Clinical scales in autoimmune encephalitis-A retrospective monocentric cohort study.

OBJECTIVE: Assessing severity of antibody-mediated encephalitis (AE) or paraneoplastic encephalitis (PE) requires valid and reliable scores to guide treatment decisions and predict outcome both in clinical routine and studies. We aimed to validate the prognostic value of the clinical assessment scale in autoimmune encephalitis (CASE) and the anti-NMDAR-encephalitis one-year functional status (NEOS) score in patients suffering from AE and PE in a large monocentric cohort. METHODS: We retrospectively applied the CASE and NEOS score to patients with definite AE and PE treated at a tertiary hospital. Correlations were established between the CASE and NEOS score and the modified Rankin scale (mRs). Multivariable analyses were calculated to identify predictors of outcome. RESULTS: Thirty-four patients (27 AE, 7 PE) were included. Correlations between mRS and CASE score were strongest in patients with AE compared to PE at all intervals, but in the subgroups (LGI1, NMDAR, GAD, miscellaneous surface antibodies, PE) the correlation was strongest in the interval after baseline. Patients with AE seemed to display better outcomes compared to PE, which was underlined by multivariable analysis. Improvement was mostly observed within 6-12 months after disease onset, after which little or no further improvement was noted with some exception for two patients with anti-NMDARE who recovered substantially even after 12 months of treatment. The NEOS score significantly predicted the outcome at last follow-up in patients with AE with a sensitivity of 79% at a cut-off value of 2 points (AUC 0.79, 95% CI 0.58-0.99, p = 0.04). INTERPRETATION: The CASE and NEOS score are suitable supplementary tools in addition to the mRS for capturing diverse symptoms, for grading and monitoring symptom severity.

Concurrent NMDAR and GFAP Antibody Encephalitis During Pregnancy.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune antibody encephalitis, commonly affecting young women with comorbid ovarian teratoma. It typically presents with alteration of consciousness, psychosis, movement disorders eventually deteriorating with seizures, dysautonomia and central hypoventilation requiring critical level of care that may last weeks to months. Removal of teratoma and immunosuppressant therapy support can led to a dramatic recovery.To our knowledge, this is the first illustrated case in the literature of a pregnant woman presenting with concurrent autoimmune NMDAR and anti-glial gibrillary acidic protein(GFAP) antibody encephalitis in the setting of an ovarian teratoma. Despite the teratoma removal and receiving various forms of immunosuppressant therapy, a meaningful neurological improvement was observed following the delivery. After a prolonged hospitalisation and recovery period, the patient and her offspring made an excellent recovery highlighting the significance of early diagnosis and management.

Autoimmune encephalitis: Epidemiology, pathophysiology and clinical spectrum (part 2).

Autoimmune encephalitis (AE) represents a growing number of severe autoimmune-inflammatory diseases affecting both the white and grey matter of the brain. In part 1 of this series we focused on the epidemiology, pathophysiology and clinical presentation of this condition, with two illustrative cases. In this part, we will introduce the clinical criteria for AE, particularly for the diagnosis of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, which were developed to facilitate immune treatment in suspected cases before antibody results are available. We subsequently discuss the work up, differential diagnosis and treatment options for patients with this disease.

Anti-NMDAR encephalitis in Southeast Asia - A single-centre, longitudinal study.

AIMS: To describe the clinical features and outcomes of anti-NMDA receptor encephalitis (ANMDARE) in Southeast Asian (SEA) patients. METHOD: SEA patients diagnosed and treated for ANMDARE at Singapore General Hospital between January 2010 and June 2020 were included in this observational study, in which their clinical features and outcomes were retrospectively analysed. RESULTS: We studied 20 patients: 11 Chinese, 3 Tagalogs, 2 Malays, 2 Indians, 1 Eurasian and 1 Javanese. Their median age was 28 years. 15 were females, amongst whom teratomas were demonstrated in 13 (12 ovarian, 1 mediastinal). Delirium and seizures were the two commonest events leading to their presentation at our facility. 1 male had biliary neuroendocrine tumour. Comparison between genders revealed a strong male predilection for early seizures and insomnia; females were four times likelier than males to develop movement disorders or have underlying neoplasms. Patients with dysautonomia required longer ICU stay beyond 14 days, but their outcomes at 1 year did not differ. When reviewed at 1 year, none had clinical relapses, and outcomes were favourable (mRS 0-2) in nearly two-thirds. CONCLUSIONS: SEA patients with ANMDARE frequently present with delirium and seizures. Underlying neoplasms are very common in females. Differences in clinical characteristics may exist between the two genders. Recognition of these can facilitate diagnosis, and permit earlier initiation of appropriate treatment strategies, and thus improve outcomes of SEA patients.

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Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory disease of the central nervous system, and little is known about its immune mechanism at present. There is a lack of disease-related biomarkers in cerebrospinal fluid except anti-NMDAR antibody, which leads to delayed diagnosis and treatment in some patients. Therefore, there has been an increasing number of studies on related cytokines in recent years to assess whether they can be used as new biomarkers for evaluating disease conditions and assisting diagnosis and treatment. Current studies have shown that some cytokines may be associated with the progression of anti-NMDAR encephalitis, and this article reviews the research advances in such cytokines associated with anti-NMDAR encephalitis.

[Analysis of the risk factors for poor prognosis and recurrence in patients with anti-NMDAR encephalitis].

To investigate the risk factors of poor prognosis and recurrence in patients with anti-NMDAR encephalitis. A single center, observational cohort study was used to retrospectively analyze 44 patients with anti NMDAR encephalitis hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from January 2014 to October 2020. The results showed that the interval from onset to immunotherapy in the poor prognosis group was significantly longer than that in the good prognosis group (t=2.045,P=0.047), and the course of disease in the poor prognosis group was significantly longer than that in the good prognosis group (t=4.127,P=0.000 2). The number of patients with clinical manifestations of dyskinesia was significantly increased (Fisher exact test: P=0.014). The patients with abnormal brain MRI in the poor prognosis group were significantly more than those in the good prognosis group (Fisher exact test: P=0.017), and the patients with slow wave>50% in the poor prognosis group were significantly more than those with slow wave <50% (Fisher exact test: P<0.001). Patients with the first onset of immunotherapy time <3 months, long course of disease, high intracranial pressure, and high cerebrospinal fluid protein are prone to relapse. Bivariate logistic regression analysis showed that patients with dyskinesia, abnormal brain MRI, and slow wave EEG more than 50% were risk factors for poor prognosis (OR values were 4.687, 4.978, and 24.500, respectively; P values were 0.018, 0.016, and 0.000, respectively). The time of first-line immunotherapy for the first onset<3 months was the risk factor for recurrence (OR 17.231, P=0.010). In conclusion, dyskinesia, abnormal brain MRI and slow wave of EEG more than 50% may be the risk factors for poor prognosis of patients. The duration of immunotherapy less than 3 months after the first onset might be the risk factor for recurrence.

Status dystonicus in adult patients with anti-N-methyl-D-aspartate-acid receptor encephalitis.

OBJECTIVE: Status dystonicus (SD) is a severe movement disorder (MD) and has rarely been recognized in anti-N-methyl-D-aspartate-acid receptor (NMDAR) encephalitis, particularly in adult patients. We aim to explore the clinical characteristics and outcome of SD in anti-NMDAR encephalitis. METHODS: Patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital from July 2013 to December 2019 were prospectively enrolled. SD was diagnosed based on the patients' clinical manifestations and video EEG monitoring. Outcome was evaluated 6 and 12 months after enrollment using the modified Ranking Scale (mRS). RESULTS: A total of 172 patients with anti-NMDAR encephalitis, including 95 males (55.2%) and 77 females (44.8%) with a median age of 26 years (interquartile range 19 to 34) were enrolled. Eighty patients (46.5%) presented with movement disorder (MD), 14 of whom suffered from SD, which manifested as chorea (14/14, 100%), orofacial dyskinesia (12/14, 85.7%), generalized dystonia (8/14, 57.1%), tremor (8/14, 57.1%), stereotypies (5/14, 35.7%), and catatonia (1/14, 7.1%) of the trunk and limbs. All SD patients exhibited disturbed consciousness and central hypoventilation, requiring intensive care. SD patients also had high cerebrospinal fluid NMDAR antibody titers, a higher proportion of ovarian teratoma, higher mRS scores upon enrollment, longer duration to recover, and poorer outcomes at 6 (P < 0.05) but not at 12 months as compared to non-SD patients. CONCLUSION: SD is not uncommon in anti-NMDAR encephalitis patients and relates to the severity and worse short-term outcome of the anti-NMDAR encephalitis. Early recognition of SD and timely treatment is important to shorten the time needed for recuperation.