NMDA Receptor Antibodies Research Articles

N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. The FES group showed higher serum NMDAR Ab levels [(9.23 ± 4.15) ng/mL vs. (7.08 ± 2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

Clinical symptoms and psychosocial functioning in patients with schizophrenia spectrum disorders testing seropositive for anti-NMDAR antibodies: a case–control comparison with patients testing negative

Antibodies against the N-methyl-D-aspartate receptor (NMDAR) have been described in the serum of people with schizophrenia spectrum disorders (schizophrenia). However, the prevalence and clinical relevance of these antibodies in schizophrenia is unclear. This knowledge gap includes the possibility of such antibodies being associated with a distinct clinical profile, which in turn might warrant a distinct treatment approach. We aimed to assess the seroprevalence of anti-NMDAR antibodies in schizophrenia, and compare symptoms and psychosocial functioning between patients with schizophrenia who were seropositive and seronegative for these antibodies. In this case-control comparison, by combining new and existing studies, we included patients diagnosed with schizophrenia from four independent cohorts for whom anti-NMDAR serostatus had been assessed (or could be assessed by us) with live cell-based assays. Included cohorts were from the EULAST study (a trial conducted across 15 European countries and Israel), the OPTiMiSE study (an interventional study in Europe), and the PPiP1 and PPiP2 studies (conducted in the UK). Patients from these cohorts were analysed if they had complete Positive and Negative Syndrome Scale (PANSS) data. No participant had been diagnosed with autoimmune encephalitis or received treatment for this condition. After calculating the prevalence of serum anti-NMDAR antibodies, we examined possible differences in PANSS scores (negative, positive, and general symptom subscales, and total score) between anti-NMDAR-seropositive and anti-NMDAR-seronegative patients. Psychosocial functioning as measured by Personal Social Performance (PSP) score was also compared. All analyses were exploratory and no adjustment was done for multiple testing. People with lived experience were not involved in the conduct of this study. We collected individual patient data from 1114 patients with schizophrenia across the four cohorts. The study population had a mean age of 28·6 years (SD 7·6) and comprised 382 (34·3%) women and 732 (65·7%) men, including patients of White (929 [83·4%]), Asian (54 [4·8%]), Black (68 [6·1%]), and other (62 [5·6%]) ethnicities. Overall, 41 (3·7%) participants (range 3·1-4·0% across cohorts) tested positive for serum anti-NMDAR antibodies. Lower symptom severity on the negative symptoms PANSS subscale was observed for anti-NMDAR-seropositive patients (mean score 15·8 [SD 6·4]) than for anti-NMDAR-seronegative patients (18·2 [6·8]; Cohen's d=0·36; p=0·026), as well as on the general symptoms PANSS subscale (32·9 [8·9] vs 36·1 [10·1]; d=0·33; p=0·029) and total PANSS score (65·5 [18·5] vs 72·6 [19·3]; d=0·37; p=0·013). Mean PSP score was better in anti-NMDAR-positive patients (62·0 [17·0]) than in anti-NMDAR-negative patients (53·5 [16·3]; d=0·52; p=0·014). Serum NMDAR antibodies are present in 3-4% of patients with schizophrenia and are associated with relatively low severity of negative symptoms and relatively good psychosocial functioning. Thus, although the findings await replication in cohorts from other geographical regions, serum anti-NMDAR antibodies might be associated with a different form of psychotic illness. These findings could inform future prognostic and interventional studies examining whether anti-NMDAR antibodies are associated with a specific course of illness or with treatment response. None.

Cognitive impairments in autoimmune encephalitis: the role of autoimmune antibodies and oligoclonal bands.

The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a pivotal diagnostic marker for multiple sclerosis (MS). These bands play a crucial role in the diagnosis and understanding of a wide array of immune diseases. In this study, we explore the relationship between the cognitive profile of autoimmune encephalitis (AIE) and the presence of OCBs in CSF, with a particular emphasis on NMDA receptor antibodies. We studied a cohort of 21 patients across five tertiary centers, segregated into two distinct categories. One group comprised individuals who tested positive only for autoimmune encephalitis antibodies indicative of encephalitis, while the other group included patients whose CSF was positive for both autoimmune encephalitis antibodies and OCBs. Our investigation focused primarily on cognitive functions and behavioral alterations, supplemented by auxiliary diagnostic assessments such as CSF cell count, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results, evaluated for the two patient groups. To validate our findings, we employed statistical analyses such as Fisher's exact test with Benjamini-Hochberg correction. Our study included 21 patients, comprising 14 who were presented with only autoimmune encephalitis antibodies, and 7 who were dual-positive. Among these patients, we focused on those with NMDA receptor antibodies. Of these, five were dual positive, and nine were positive only for NMDA receptor antibodies. The dual-positive NMDA group, with an average age of 27 ± 16.47 years, exhibited significantly higher CSF cell counts (p=0.0487) and more pronounced language and attention deficits (p= 0.0264). MRI and EEG results did not differ significantly between the groups. Our results point to OCBs as an additional marker of disease severity in AIE, especially in NMDA receptor-antibody positive patients, possibly indicating a broader inflammatory process, as reflected in elevated CSF lymphocytes. Regular testing for OCBs in cases of suspected AIE may aid in disease prognosis and identification of patients more prone to language and attention disorders, improving diagnosis and targeting treatment for these cognitive aspects.

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

Molecularly targeted immunotherapy used to treat a novel overlap syndrome of pediatric N‐methyl‐d‐aspartate receptor encephalitis (NMDARE) and possible neurosarcoidosis

AbstractObjectiveOverlap syndromes have been described between N‐methyl‐ d‐aspartate receptor encephalitis (NMDARE) and other neuroinflammatory conditions, although rarely involving neurosarcoidosis. Molecularly targeted immunotherapy may be helpful in the empiric treatment of these conditions.MethodsWe describe a 9‐year‐old boy with new‐onset seizures and worsening encephalopathy.ResultsInitial evaluation was concerning for neurosarcoidosis, including elevated cerebrospinal fluid (CSF) and serum angiotensin‐converting enzyme and leptomeningeal with multiple cranial nerve enhancement on magnetic resonance imaging. CSF and serum cytokine profiles were used to choose targeted empiric immunotherapy, and the boy's seizure burden and encephalopathy improved after treatment with tocilizumab. The NMDA receptor antibody titer was later found to be elevated, raising suspicion for a novel overlap syndrome.InterpretationOur patient met the criteria for definite NMDARE and possible neurosarcoidosis. Given the mixed radiographic and serologic markers in this child, cytokine levels were used to direct the choice of empiric treatment, resulting in excellent clinical response. This case suggests that targeted immunotherapy informed by cytokine testing may be helpful in cases of high‐acuity pediatric neuroinflammatory disease with limited diagnostic clarity.

Clinical analysis of 9 children with refractory N-methyl-D-aspartate receptor antibody encephalitis children treated with tocilizumab

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 patievts 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.

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls

Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.

An Unfortunate Immunological Overlap: A Case Report of Neuromyelitis Optica Compounded with NMDA Receptor Antibody Encephalitis (P11-14.014)

An Unfortunate Immunological Overlap: A Case Report of Neuromyelitis Optica Compounded with NMDA Receptor Antibody Encephalitis (P11-14.014)

New-onset seizures misdiagnosed as psychogenic non-epileptic seizures: a case of paraneoplastic limbic encephalitis with primary testicular cancer

BackgroundBehavioral psychiatric symptoms can be the only warning signs of more serious conditions such as paraneoplastic limbic encephalitis. Differentiating between primary psychiatric disorders and paraneoplastic neurological syndromes is crucial as they require distinct treatment approaches. In this case report, we provide an overview of paraneoplastic encephalitis and introduce a unique case that showcases a misdiagnosis of psychogenic non-epileptic seizures (PNES) in a male as the primary symptom of paraneoplastic encephalitis due to pure seminoma. This case highlights the underlying pathophysiology of antibody-mediated paraneoplastic encephalitis and its significance.Case presentationA 31-year-old male with no known past medical history presented due to recurrent seizures. There was no prior history of epilepsy or exposure to seizure-triggering agents. Imaging and electroencephalogram findings during his initial hospitalizations pointed to a potential diagnosis of PNES. The patient continued to experience seizures following discharge, leading to repeat hospitalizations. During the fourth hospitalization, the patient received mood-stabilizing anti-seizure medications and benzodiazepines, but he deteriorated and required intubation. It was during this time that the patient was transferred to our facility. Magnetic resonance imaging of the brain revealed multifocal areas of hyperintensity and restricted diffusion with avid enhancement. Immunotherapy was initiated with improvement of non-epileptic spells and encephalopathy. Outpatient workup uncovered malignant pure seminoma with metastases to the retroperitoneum. The authors theorize that paraneoplastic neurological disorders stemming from testicular cancer led to the neurological symptoms seen in this case.ConclusionThis report highlights a rare occurrence of paraneoplastic limbic encephalitis associated with pure testicular seminoma, clinically manifested as PNES. The diagnostic challenge posed by variability of presenting symptoms in paraneoplastic encephalitis emphasizes the importance of accurate differentiation from conditions such as autoimmune encephalitis. Current diagnostic approaches for paraneoplastic and autoimmune etiologies involve detection of known antibodies, as well as brain imaging. Notable antibodies associated with psychogenic non-epileptic seizures symptoms include anti-GAD-65, anti-Ma2, KLH11-antibodies, anti-Hu, and NMDA receptor antibodies. Recognizing paraneoplastic limbic encephalitis symptoms is challenging and often leads to misdiagnosis or overlooking of malignancies highlighting the need for awareness, comprehensive evaluation and timely treatment. Through this comprehensive case analysis, we enhance the understanding of underlying mechanisms, associated symptoms, and treatment options.

A 22-Year-Old Woman with NMDA Receptor Antibody Encephalitis Possibly Triggered by SARS-CoV-2 Infection

A 22-year-old woman presented to the emergency department (ED) on two occasions with seizures, altered mental status, psychoses, and behavioral changes. Analysis of both serum and cerebrospinal fluid revealed positive anti-NMDA receptor (NMDAR) antibodies, confirming the diagnosis of NMDAR antibody encephalitis. Interestingly, 5-6 weeks before her ED visits, she had experienced a SARS-CoV-2 infection, potentially serving as a triggering factor for her autoimmune encephalitis. This case adds to the limited instances documented in the literature, highlighting the potential link between SARS-CoV-2 infection and the onset of autoimmune encephalitis

Impaired functional connectivity of the hippocampus in translational murine models of NMDA-receptor antibody associated neuropsychiatric pathology

Decreased hippocampal connectivity and disruption of functional networks are established resting-state functional MRI (rs-fMRI) features that are associated with neuropsychiatric symptom severity in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the underlying pathophysiology of NMDAR encephalitis remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 (GluN1) subunit of the NMDAR now allows for the translational investigation of functional connectivity in experimental murine NMDAR antibody disease models with neurodevelopmental disorders. Using rs-fMRI, we studied functional connectivity alterations in (1) adult C57BL/6 J mice that were intrathecally injected with a recombinant human NR1 antibody over 14 days (n = 10) and in (2) a newly established mouse model with in utero exposure to a human recombinant NR1 antibody (NR1-offspring) at the age of (2a) 8 weeks (n = 15) and (2b) 10 months (n = 14). Adult NR1-antibody injected mice showed impaired functional connectivity within the left hippocampus compared to controls, resembling impaired connectivity patterns observed in human NMDAR encephalitis patients. Similarly, NR1-offspring showed significantly reduced functional connectivity in the hippocampus after 8 weeks, and impaired connectivity in the hippocampus was likewise observed in NR1-offspring at the age of 10 months. We successfully reproduced functional connectivity changes within the hippocampus in different experimental murine systems that were previously observed in human NMDAR encephalitis patients. Translational application of this method within a combined imaging and histopathological framework will allow future experimental studies to identify the underlying biological mechanisms and may eventually facilitate non-invasive monitoring of disease activity and treatment responses in autoimmune encephalitis.

Seasonal variation and temporal relationship to the COVID-19 pandemic of NMDA receptor antibody results.

Seasonal variation and temporal relationship to the COVID-19 pandemic of NMDA receptor antibody results.

NMDA, AMPA and GABA Receptor Antibodies: Relation to Clinical and Electrophysiological Findings in Drug-Resistant Epilepsy

Abstract Background Epilepsy is a neurological disorder characterized by sudden recurrent episodes of convulsions, sensory disturbance, or loss of consciousness, resulting from abnormal electrical brain activity. It can have both genetic and acquired causes, with interaction of these factors in many cases. Auto-antibodies against synaptic receptors have been detected in a number of neurological conditions such as anti-NMDA receptor encephalitis and limbic encephalitis. Recently, three types of synaptic receptors have been the subject of research as regarding their role in the normal physiology of the nervous system, and their involvement in various neurological conditions. These receptors include AMPA receptors, NMDA receptors and GABAB receptors. Antibodies directed against these receptors may be the underlying cause of many cases of drug resistant epilepsy. Objectives To determine the prescence of autoantibodies against AMPA, NMDA and GABAB receptors in drug-resistant epilepsy and their correlation with clinical and electrophysiological findings. Methods The study was conducted on 17 epilepsy patients (12 males and 5 females) who were sampled for both CSF and blood. All CSF and serum samples were examined by the Indirect Immunofluorescence cell based technique for the detection of AntiAMPAR, Anti-NMDAR and Anti-GABAB antibodies. Results Only one case tested positive for Anti-NMDAR antibodies in CSF, while all other serum and CSF samples were negative for other antibodies. These results are still in process since our data will be used in a further study related to auto-immune drug-resistant epilepsy patients involving other auto-antibodies such as Ant-LGI1, Anti-CASPR2 and Anti-DPPX antibodies. Conclusion Testing Anti-NMDAR antibodies can be promising in detecteing drug resistant epilepsy patients even after receiving immunomodulatory treatment protocols.

Rapid deterioration of a case of anti–N-methyl-D-aspartate receptor encephalitis with an ovarian teratoma, mimicking viral encephalitis

Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis has recently emerged as an autoimmune encephalitis syndrome. Younger females are more likely to develop this condition which usually presents as a multistage illness with predominant neuropsychiatric manifestations. It is associated with the neuroglial surface antibodies developing against NMDAR. The association of ovarian teratoma has been well recognised in this condition and tumour resection will intensify the recovery of the illness along with immunotherapy. We present a case of 19-year-old female who presented with acute onset of fever, encephalopathy and facial myorhythmia mimicking acute viral encephalitis. Her clinical status deteriorated within a short period. Later, her CSF became positive for NMDAR antibody and a right ovarian teratoma was detected. Her clinical status markedly improved with immunotherapy and excision of the teratoma following a diagnosis of Anti-NMDAR encephalitis. As a potentially treatable neurological condition, clinicians should be aware of this autoimmune encephalitis syndrome causing encephalitis.

Anti- N-MethyL-D-Aspartate Receptor Encephalitis in Children Infected with Herpes Simplex

Herpes Simplex Virus (HSV) is a common cause of infectious encephalitis in children, which can lead to severe neurological sequels. There is a new perspective suggesting that herpes simplex encephalitis plays an important role in triggering the synthesis of NMDA receptor antibodies. There have been no data on the incidence of anti-NMDA receptor encephalitis in Indonesia. Herpes simplex encephalitis was found in these patients as a risk factor for anti-NMDA receptor encephalitis. A 9-year-old male patient complained of seizures such as jerking of the right hand and smacking of the lips along with fever for 4 days before being admitted to the hospital. Complaints began with slurred speech and t inability of fingers to hold objects for the previous 8 days. From the physical examination, it was reported that the patient looked seriously ill, blood pressure was 110/80 mmHg, pulse was 117 beats per minute, the temperature was 38.5 C, and respiratory rate was 24 times per minute. Another physical examination was within normal limits. The results of a complete blood count at the time of initial treatment of patients showed mild leukocytosis due to a mild increase in monocytes, whereas blood gas and electrolyte analysis showed hypoventilation at the beginning of hospitalization in which mixed acid-base disturbance, respiratory acidosis, and metabolic alkalosis occurred. Analysis of cerebrospinal fluid in these patients showed mononuclear pleocytosis and the results of immunoserological test in serum indicated HSV1 and HSV2 infection and detected anti-NMDA receptor. Both clinical and laboratory findings in this study supported encephalitis. Herpes simplex virus infection can be a risk factor for patients suffering from anti-NMDA receptor encephalitis.

Takotsubo cardiomyopathy associated with Herpes simplex encephalitis: A case report and literature review

Takotsubo cardiomyopathy (TCM) is a stress-induced cardiomyopathy characterized by transient left ventricular dysfunction. It can be triggered by various central nervous system pathologies including status epilepticus (SE) and N-methyl-d-aspartate receptor (NMDAr) encephalitis. Herpex simplex encephalitis (HSE) is a life-threatening, sporadic, encephalitis associated with focal or global cerebral dysfunction caused by herpes simplex viruses type 1(HSV-1), or less commonly, type 2(HSV-2). While approximately 20% of patients with HSE develop NMDAr antibodies, not all manifest with encephalitis clinically. We present here a 77-year-old woman admitted with HSV-1 encephalitis who presented with acute encephalopathy and seizure-like activity. Continuous EEG monitoring (cEEG) showed periodic lateralized epileptiform discharges (PLEDs) involving the left parietotemporal region but no evidence of electrographic seizures. Her early hospital course was complicated by TCM which subsequently resolved on repeat TTE. She demonstrated initial neurological improvement. However, five weeks later her mental status declined. Again, no seizures were appreciated on cEEG. Unfortunately, repeat studies including lumbar puncture and magnetic resonance imaging (MRI) of the brain were consistent with NMDAr encephalitis. She was treated with immunosuppression and immunomodulation therapies. To our knowledge we report the first case of TCM secondary to HSE without comorbid status epilepticus. However, further studies are needed to better understand the correlation between, and underlying pathophysiology of HSE and TCM, as well as any potential association with this presentation and subsequent development of NMDAr encephalitis.

Anti N-Methyl-D-Aspartate receptor antibody associated Acute Demyelinating Encephalomyelitis in a patient with COVID-19: a case report

BackgroundAnti N-Methyl-D-Aspartate (NMDA) receptor antibody associated ADEM is a diagnosis that was first described relatively recently in 2007 by Dalmau et al. The recent COVID-19 pandemic has resulted in multiple neurological complications being reported. However, there is limited data on Anti-NMDA receptor antibody associated ADEM in COVID-19 patients. Furthermore, the MRI findings in these patients have not been fully elucidated. This case report adds to the growing body of knowledge of neurological complications in COVID-19 patients.Case presentationA 50 year old Caucasian female with no previous medical co-morbidities presented with symptoms of COVID-19 and subsequently developed neurological symptoms which included confusion, limb weakness and seizures. The patient developed marked behavioural abnormalities which required attention. She was found to have anti NMDA receptor antibodies present in a significant titres, an elevated total protein on lumbar puncture and cytotoxic magnetic resonance imaging (MRI) changes in the brain and spinal cord and was subsequently diagnosed with an anti-NMDA Receptor Antibody associated ADEM. The bilateral symmetric involvement of the corticospinal tract on MRI was considered unusual in our case. She was treated with a combination of corticosteroids and plasmapheresis which halted disease progression. Thereafter she was commenced on intravenous immunoglobulin as maintenance therapy and she has shown continuous improvement with ongoing physiotherapy.ConclusionThe recognition of COVID 19 neurological complications may be difficult in the initial disease as early symptoms of lethargy, weakness and confusion may be very nondescript. However, it is imperative that these complications are sought for as they are imminently treatable. Early institution of therapy is imperative in decreasing long term neurological consequences.

Candida dubliniensis Meningitis in Immunocompetent Adults - case report and review of literature (P10-10.001)

<h3>Objective:</h3> NA <h3>Background:</h3> NA <h3>Design/Methods:</h3> We report a case and review the cases of <i>Candida dubliniensis</i> meningitis in immunocompetent adults. <h3>Results:</h3> 32 years old man with history of intravenous drug use (IVDU) presented with seizures, nuchal rigidity, and papilledema. Head CT showed communicating hydrocephalus and brain and spine MR showed diffuse leptomeningeal enhancement extending to the cauda equina. HIV, syphilis, and quantiferon-gold tests were negative but his CD4 count was 203 (430 – 1185/mm3). Lumbar puncture showed opening pressure of 45 mm H2O, CSF protein &gt; 392 mg/dl (15–45), glucose 5 mg/dL (40–70), nucleated cells 246 (0–5), 83% lymphocytes, red blood cells 1 (0–1). CSF meningitis panel was negative, but encephalitis panel showed NMDA receptor antibody. 1,3-Beta-D-glucan was 79 (&lt;60 pg/mL) in the serum and 295 in the CSF and CSF cultures grew <i>Candida dublinens</i>is. <h3>Conclusions:</h3> Chronic base of the skull meningitis has many causes including inflammatory conditions, malignancies, and infections. Invasive <i>C. dublinensis</i> infection is very rare and usually associated with immunodeficiency (HIV or post-transplant). This is the fourth case of <i>C. dublinensis</i> in an immunocompetent host described in the literature. Like our case, in two of those three reports the infection was associated with IVDU, and this information is not available for the third case. This corroborates the hypothesis that IVDU could be a risk factor for this infection. Regarding his CSF NMDA receptor antibody, he did not have limbic encephalitis, dysautonomia, seizures or psychiatric symptoms. There is a known association of this antibody and ovarian teratomas and herpes simplex encephalitis but no association with <i>Candida sp.</i> is known. Despite his low CD4 count he did not have other opportunistic infections. No etiology was identified for this finding. <b>Disclosure:</b> Dr. Horta has nothing to disclose. Dr. White has nothing to disclose. Dr. Greige has nothing to disclose. Dr. Askari has nothing to disclose. Dr. Cervantes-Arslanian has nothing to disclose.

MRI Features and their Association with Outcomes in Children with Anti-NMDA Receptor Encephalitis (S22.003)

<h3>Objective:</h3> To correlate MRI brain lesions with clinical outcomes in pediatric anti-NMDA receptor encephalitis (pNMDARE). <h3>Background:</h3> Up to 50% of MRIs in NMDARE are reportedly abnormal. However, data is limited on range and types of abnormalities, and also how abnormal MRIs associate with outcomes in pNMDARE. <h3>Design/Methods:</h3> This was a multi-center retrospective cohort study with ten institutions. NMDARE was defined as positive CSF NMDA-receptor antibody and at least one neuropsychiatric symptom. Patients with prior HSV encephalitis were excluded. Outcomes were assessed by the modified Rankin Score (mRS) at 1 year with good (mRS ≤ 2) and poor (mRS ≥ 3) outcomes and also for full recovery (mRS=0) versus incomplete recovery (mRS&gt;0). Statistical analyses were performed using SAS 16.0 (Cary, NC). <h3>Results:</h3> A total of 169 patients with pNMDARE were included, with one-year mRS available in 134/169 (79%). Abnormal MRIs were found in 59/169 (35%), and were associated with an increased likelihood of intubation and ICU admission (chi-square, p = 0.038 and p=0.045, respectively). The most common T2 FLAIR lesion locations were frontal (29/59, 49%), temporal (28/59, 47%), parietal (19/59, 32%), and hippocampal lesions (11/59, 19%). MRI enhancement was seen in 34/165 (21%) and MRI brain atrophy was seen in 4% (6/168). MRI features that predicted incomplete recovery at one year (mRS &gt; 0) was the presence of T2 frontal lobe lesions (chi-square, p = 0.0427). G-tube placement and intubation also predicted incomplete recovery. On multivariable logistic regression analysis using backward selection, one-year mRS was associated with: intubation (OR 0.232, 95%CI 0.103–0.526) and T2 frontal lesions on MRI (OR 0.373, 95% 0.148–0.938). <h3>Conclusions:</h3> Abnormal frontal lesions on MRI along with intubation may associate with one-year mRS in pNMDARE. MRIs may be a helpful tool for prognostication, which will be examined in future studies. <b>Disclosure:</b> The institution of Dr. Gombolay has received research support from CDC. The institution of Dr. Gombolay has received research support from NIH. Dr. Brenton has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cycle Pharmaceuticals. The institution of Dr. Brenton has received research support from NIH/NINDS. Dr. Brenton has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with Department of Defense. Dr. Brenton has received personal compensation in the range of $500-$4,999 for serving as a Expert Interview with MDEdge. Dr. Brenton has received personal compensation in the range of $0-$499 for serving as a Grant Reviewer with NIH. Dr. Yang has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurology Live. Dr. Yang has received research support from United Mitochondrial Disease Foundation. The institution of Dr. Stredny has received research support from Pediatric Epilepsy Research Foundation. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ogborn-Mihm Trial Lawyers. The institution of Dr. Kammeyer has received research support from Rocky Mountain Multiple Sclerosis Center. The institution of Dr. Otten has received research support from CDC. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos Health. Dr. Santoro has received personal compensation for serving as an employee of UCB. Dr. Santoro has received personal compensation for serving as an employee of Cycle Pharma. Dr. ROBLES LOPEZ has nothing to disclose. Dr. Christiana has nothing to disclose. The institution of Dr. Steriade has received research support from NIH. The institution of Dr. Steriade has received research support from Dorris Duke Fund to Retain Clinician Scientists. Miss Morris has received personal compensation in the range of $10,000-$49,999 for serving as a Research Assistant/Specialist with Emory University, School of Medicine, Department of Pediatrics, Division of Neurology. The institution of Dr. Gorman has received research support from Pfizer. The institution of Dr. Gorman has received research support from Roche / Genetech . Dr. Moodley has nothing to disclose. Dr. Hardy has nothing to disclose. Dr. Kornbluh has nothing to disclose. Ilana Kahn has nothing to disclose. Dr. Sepeta has received personal compensation in the range of $500,000-$999,999 for serving as a Grant PI with Nih. Dr. Sepeta has a non-compensated relationship as a Special volunteer with Nih that is relevant to AAN interests or activities. Dr. Yeshokumar has nothing to disclose.

Teaching NeuroImages: Prosopagnosia heralding anti-NMDA receptor encephalitis

A 23-year-old right-hand-dominant woman presented with 3 weeks of progressive difficulty recognizing faces, including her own, subsequently developing psychosis. Noncontrast CT head and MRI brain with contrast revealed a nonenhancing lesion of the right posterior temporal lobe and fusiform gyrus, with corresponding hypermetabolism on FDG-PET/CT brain (figure). EEG demonstrated right posterior temporal slowing. CSF and serum anti–NMDA receptor (NMDAR) antibodies were positive, with CT abdomen/pelvis revealing ovarian teratoma. Teratoma removal, plasmapheresis, and 1 cycle of rituximab yielded symptom resolution over 1 month. Anti-NMDAR encephalitis rarely presents with prosopagnosia,1 and in this case, is likely secondary to right fusiform gyrus dysfunction.2