Epidemiology and diagnostic challenges of anti-NMDAR encephalitis: a study from the Waikato region.

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.

Prevalence and Factor Associated with Anti-N-Methyl-D-Aspartate Receptor Encephalitis Among Patients with Medical Conditions: A Systematic Review and Meta-Analysis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune encephalitis due to immune production of anti-NMDAR antibodies against the NR1 subunit of the NMDA receptor which is present throughout the central nervous system. This condition had been reported to be prevalent in patients with certain medical conditions; however so far, there have been limited systematic reviews and meta-analyses on the prevalence and factors associated. OBJECTIVE: This study was to determine the prevalence and factors associated with anti-NMDAR encephalitis among affected patients. MATERIAL AND METHODS: The protocol of this study has been registered (2019: CRD42019142002) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary outcome was the incidence or prevalence of anti-NMDAR encephalitis and secondary outcomes were factors associated with anti-NMDAR encephalitis. RESULTS: There were 11 studies and a total of 873 million patients taken from high-risk populations across 11 countries that were included in the primary analysis. The overall pooled prevalence of anti-NMDAR encephalitis among patients with medical conditions was 7.0% (95% CI = 4.4, 9.6). Those with first episode of psychosis or schizophrenia were at a higher risk of developing anti-NMDAR encephalitis with an odds ratio of 5.976 (95% CI = 1.122, 31.825). CONCLUSION: We found that almost one-tenth of patients with medical conditions had anti-NMDAR encephalitis; particularly those with first episode of psychosis or schizophrenia were among the high-risk medical conditions.

Racial and Ethnic Disparities in the Incidence of Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of NMDA and encephalitis were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population. RESULTS: We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups. DISCUSSION: Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.

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.

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.

Seizure Evolution and Outcome in Pediatric Autoimmune Encephalitis.

BACKGROUND: Our study aimed to characterize seizure incidence and seizure outcome of pediatric autoimmune encephalitis (AE) focusing on subgroup analysis based on antibody (Ab). METHODS: Among 110 pediatric patients with AE, we compared seizure characteristics and outcomes in 68 patients with seizure, who satisfied the proposed criteria of pediatric AE. Accordingly, patients were classified into three groups, anti-myelin oligodendrocyte glycoprotein (anti-MOG) AE, anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) AE, and Ab-negative AE. Univariate and multivariate analyses were performed to evaluate the risk factors for postencephalitic seizures, defined as persisting seizures six months after onset. RESULTS: Seizure incidence in the anti-NMDAR (88.9%) and Ab-negative (71.1%) groups differed from anti-MOG group (37.8%). Median seizure frequency within six months was higher in the Ab-negative group (6.0, interquartile range [IQR] 3.0 to 13.0) than in the anti-NMDAR group (3.0, IQR 2.0 to 4.5) and anti-MOG group (2.0, IQR 1.0 to 5.0). Patients in the Ab-negative group tended to develop postencephalitic seizures more frequently and have a lower seizure freedom rate than those in the anti-NMDAR and anti-MOG groups. Ab-negative status, high seizure frequency within six months, and the presence of status epilepticus were associated with the development of postencephalitic seizures on univariate analysis. On multivariate analysis, Ab-negative status remained the only significant variable linked with postencephalitic seizure (odds ratio, 4.17; 95% confidence interval, 1.02 to 18.05). CONCLUSIONS: We delineated the seizure incidence, evolution, and outcome of pediatric patients with Ab-positive and Ab-negative AE. Ab-negative status is predictive of higher seizure burden, more frequent development of postencephalitic seizures, and less favorable seizure outcome than anti-NMDAR and anti-MOG Ab-positive status.

A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India.

OBJECTIVES: Autoimmune encephalitis (AIE) is a group of rare, increasingly recognized, potentially reversible, noninfectious causes of unexplained encephalitis. It affects any age-group and has a plethora of clinical presentations, the most common being the neuropsychiatric manifestation. The diagnosis of this entity at the right time and proper treatment with immunotherapy can save many lives. In this study, we describe the demographic profile, clinical spectrum, diagnosis, and treatment of 42 patients with features of AIE. MATERIALS AND METHODS: This is a prospective study where 42 cases were selected from a tertiary care center in Northwestern India. Patients with suspected AIE underwent detailed clinical assessment, routine blood tests, magnetic resonance imaging (MRI) brain, electroencephalography (EEG), cerebrospinal fluid (CSF) study, and autoimmune profile in blood and CSF. Screening for malignancy was done in all patients with computer tomography (CT) thorax and abdomen and tumor markers. RESULTS: Among 42 patients, males, and females were almost equally affected. The mean age of onset was 31 years. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) Encephalitis was the commonest of all AIE (57%) followed by anti-leucine-rich glioma inactivated-1 (anti-LGI-1) related AIE (11.9%), anti-contactin-associated protein 2 (anti-CASPR2) related AIE (4.7%), and steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) related to antithyroid peroxidase (anti-TPO) antibody (2.3%). Neuropsychiatric manifestation is the commonest. The seizure was noted in around 72% of patients, the commonest in the anti-NMDAR group. Faciobrachial dystonic seizure (FBDS) was noted in all five anti-LG1-1 encephalitis patients. CSF abnormalities were seen in 33.3% of patients in the form of pleocytosis or raised protein, or both. MRI abnormality was seen in 52% of patients. EEG was abnormal in 10% of patients, and delta brush was noted in three anti-NMDAR patients. All patients received immunotherapy in the form of intravenous immunoglobulin (IVIg) or pulse IV methylprednisolone (IVMPS), or both. Two patients nonresponsive to IVIg and IVMPS received rituximab. Almost all patients responded to immunotherapy. CONCLUSION: Autoimmune encephalitis (AIE), a potentially treatable immune-responsive entity, is a common neurological problem and may be an answer to a large number of cases having unexplained encephalitis. Good clinical acumen and knowledge are required for early diagnosis and treatment of this potentially reversible disorder. How to cite this article: Sharma B, Paul M, Bagaria AK. A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India. J Assoc Physicians India 2023;71(9):39-44.

Evaluating the incidence and predictors of anti-NMDAR encephalitis in a contemporary cohort of patients diagnosed with dermoid tumors: A national inpatient sample analysis.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a form of encephalitis previously associated with dermoid tumors. However, most studies in the literature evaluating the disease are case reports and small patient cohorts, limiting robust statistical analysis. Here, we demonstrate predictors of anti-NMDAR encephalitis in a large cohort of US patients. METHODS: We used the 2016 National Inpatient Sample (NIS) to identify a cohort of 24,270 admitted for an ovarian dermoid tumor. Of these patients, 50 (0.21%) were diagnosed with anti-NMDAR encephalitis. Patient demographics, hospital characteristics, length of stay (LOS), and complications were collected. Statistical analysis consisted of odds ratios with chi-square testing to compare categorical variables. RESULTS: The mean age of all patients with dermoid tumors was 45.5 ± 18.0 years, and the mean age of patients with diagnosed anti-NMDAR encephalitis was 27.4 ± 4.9 years. The mean LOS in the dermoid tumor cohort was 3.5 ± 4.9 days, while the mean LOS in the anti-NMDAR encephalitis cohort was 31.9 ± 25.9 days (p < 0.001). The mean cost in the dermoid tumor cohort was $44,813.18±$54,305.90, while the mean cost in the anti-NMDAR encephalitis cohort was $445,628.60±$665,423.40 (p < 0.001). Patients with age above 30 years with dermoid tumors had significantly lower odds of developing anti-NMDAR encephalitis compared to patients younger than 30 years (OR: 0.19; 95%CI: 0.045-0.67; p-value: 0.003). White patients had significantly lower odds of developing anti-NMDAR encephalitis (OR: 0.19; 95%CI: 0.026-0.77; p-value: 0.013), and Black patients had significantly higher odds of developing anti-NMDAR encephalitis (OR: 3.45; 95%CI: 1.00-12.46; p-value: 0.044). CONCLUSION: Patient predictors of developing anti-NMDAR encephalitis include age, race, ethnicity and patients who go on to develop anti-NMDAR encephalitis have a significantly increased hospital LOS and cost compared to those who do not. Future research, including multi-center clinical trials and longitudinal data, is necessary to fully cement the findings of this manuscript.

Analysing triggers for anti-NMDA-receptor encephalitis including herpes simplex virus encephalitis and ovarian teratoma: results from the Queensland Autoimmune Encephalitis cohort.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (anti-NMDA-R) encephalitis is a complex autoimmune neuropsychiatric syndrome. Although initially associated with ovarian teratoma, subsequent studies have demonstrated that anti-NMDA-R encephalitis may occur without an identifiable cause or be triggered by viral infection of the central nervous system such as herpes simplex virus encephalitis (HSVE). AIM: To present details from a Queensland cohort analysing triggering events in patients with anti-NMDA-R encephalitis in an Australian context. METHODOLOGY: The authors identified patients with anti-NMDA-R encephalitis diagnosed and managed through public hospitals in Queensland, Australia, between 2010 and the end of 2019. Data collected included demographics, clinical presentation, investigation results, management and outcome measurements. RESULTS: Thirty-one cases of anti-NMDA-R encephalitis were included in the study. Three cases of anti-NMDA-R encephalitis were triggered by prior HSVE, five cases were associated with ovarian teratoma and 23 cases had no identifiable trigger. There were an additional three cases in which anti-NMDA receptor antibodies were present in the context of other disease states but where the patient did not develop anti-NMDA-R encephalitis. Cases triggered by HSVE or associated with ovarian teratoma experienced a more severe disease course compared to cases with no identifiable trigger. All groups responded to immunosuppressive or immunomodulatory therapy. Analysis of clinical characteristics revealed a complex heterogeneous syndrome with some variability between groups. CONCLUSION: In this cohort, the number of cases of anti-NMDA-R encephalitis triggered by HSVE is comparable to those triggered by ovarian teratoma. However, the majority of cases of anti-NMDA-R encephalitis had no identifiable trigger or associated disease process.

Anti-NMDAR Encephalitis in the Netherlands, Focusing on Late-Onset Patients and Antibody Test Accuracy.

BACKGROUND AND OBJECTIVES: To describe the clinical features of anti-NMDAR encephalitis, emphasizing on late-onset patients and antibody test characteristics in serum and CSF. METHODS: Nationwide observational Dutch cohort study, in patients diagnosed with anti-NMDAR encephalitis between 2007 and 2019. RESULTS: One hundred twenty-six patients with anti-NMDAR encephalitis were included with a median age of 24 years (range 1-86 years). The mean annual incidence was 1.00/million (95% CI 0.62-1.59). Patients ≥45 years of age at onset (19%) had fewer seizures (46% vs 71%, p = 0.021), fewer symptoms during disease course (3 vs 6 symptoms, p = 0.020), and more often undetectable serum antibodies compared with younger patients (p = 0.031). In the late-onset group, outcome was worse, and all tumors were carcinomas (both p < 0.0001). CSF was more accurate than serum to detect anti-NMDAR encephalitis (sensitivity 99% vs 68%, p < 0.0001). Using cell-based assay (CBA), CSF provided an unconfirmed positive test result in 11/2,600 patients (0.4%); 6/11 had a neuroinflammatory disease (other than anti-NMDAR encephalitis). Patients with anti-NMDAR encephalitis, who tested positive in CSF only, had lower CSF antibody titers (p = 0.003), but appeared to have an equally severe disease course. DISCUSSION: Anti-NMDAR encephalitis occurs at all ages and is less rare in the elderly patients than initially anticipated. In older patients, the clinical phenotype is less outspoken, has different tumor association, and a less favorable recovery. Detection of antibodies in CSF is the gold standard, and although the CBA has very good validity, it is not perfect. The clinical phenotype should be leading, and confirmation in a research laboratory is recommended, when in doubt.