NMDA Receptor Antibody Encephalitis Research Articles

N-methyl-D-aspartate receptor- antibody encephalitis impairs maintenance of attention to items in working memory.

NMDA receptors (NMDAR) may be crucial to working memory (WM). Computational models predict that they sustain neural firing and produce associative memory, which may underpin maintaining and binding information respectively. We test this in patients with antibodies to NMDAR (n=10, female) and compare them with healthy control participants (n=55, 20 male, 35 female). Patients were tested after recovery with a task that separates two aspects of WM: sustaining attention and feature binding. Participants had to remember two colored arrows. Then attention was directed to one of them. After a variable delay, they reported the direction of either the same arrow (congruent cue), or of the other arrow (incongruent cue). We asked how congruency affected recall precision and measured types of error. Patients had difficulty in both sustaining attention to an item over time and feature binding. Controls were less precise after longer delays and incongruent cues. In contrast, patients did not benefit from congruent cues at longer delays (Group x Congruency [long condition], p=0.041), indicating they could not sustain attention. Additionally, patients reported the wrong item (misbinding errors) more than controls after congruent cues (Group x Delay [congruent condition], main effect of group, p=<0.001). Our results suggest NMDARs are critical for both maintaining attention and feature binding.Significance Statement Computational theories suggest NMDA receptors (NMDARs) are critical for actively maintaining information, while other theories propose they allow us to associate or "bind" objects features together. This is the first causal test in humans of the role of NMDARs in actively maintaining attention in working memory and feature binding. We find patients have difficulty with both these processes in support of computational models. Notably, we demonstrate that patients with NMDA receptor-antibody encephalitis are an ideal model condition to study roles of receptors in human cognition. Secondly, few studies follow these patients long after treatment. Our findings demonstrate a specific long-term neuropsychological deficit, previously unreported to our knowledge, that highlights the need for greater focus on neurocognitive rehabilitation with these patients.

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)

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

Experience with anti NMDA receptor antibody encephalitis in a tertiary care hospital in Pakistan

Background and objective: &#x0D; Anti NMDA receptor (Anti-NMDAR) antibody encephalitis is an increasingly recognized form of auto immune encephalitis. The objective of this study was to determine the demographic, clinical and laboratory factors associated with this syndrome. &#x0D; Methods:&#x0D; All cases presenting to neurology, Pakistan institute of medical sciences, Islamabad, from June 2017 till January 2020 were reviewed retrospectively. Patients fulfilling the diagnostic criteria for Anti NMDA receptor (Anti-NMDAR) antibody encephalitis were included. All patients were evaluated with cerebrospinal fluid (CSF)routine examination, MRI brain, autoimmune encephalitis profile and for presence of oligoclonal bands (OCB) in CSF. Statistical analysis was done using SPSS version 23.0.&#x0D; Results:&#x0D; A total of 7 patients were diagnosed as having Anti-NMDARantibody encephalitis. Five patients were female and two were male. Four patients had some type of psychiatric disturbances upon presentation of these behavioral abnormalities and irritability were found in all four. Orofacial abnormal movements were found in four patients while one patient had myoclonic seizures.&#x0D; Conclusion:&#x0D; Anti-NMDARreceptor encephalitis is a common cause of encephalitis associated with neurological and psychiatric symptoms. Delay in diagnosis can occur due to non-specific symptoms and signs present in early stages of illness,this can lead to long term neurological disability.

Autistic Regression Sequelae or Relapse for NMDA Receptor Antibody Encephalitis

Objective To highlight a pediatric presentation of autistic regression secondary to relapsing NMDA receptor antibody encephalitis (NMDARAE) post-HSV infection. Background It is reported that 30% of patients develop NMDA receptor antibodies (NMDARA) after HSV Encephalitis. Previous studies have demonstrated a significant association between prior HSV-1 infection and NMDARAE, a diagnosis often overlooked due to diverse neurological manifestations. Design/Methods NA. Results This case highlights a 5-year-old female presenting with fever and refractory status epilepticus, was diagnosed with HSV Encephalitis requiring prolonged hospitalization. At discharge she had insomnia, mutism, dyskinetic movements, atonic seizures, and developmental regression. At 3 months post-discharge EEG exhibited multiple generalized myoclonic, myoclonic tonic, and atonic seizures, MRI brain demonstrated right temporal lobe encephalomalacia with immunologic workup demonstrating positive serum and CSF NMDARA. She underwent treatment with intravenous steroids followed by plasmapheresis and then rituximab with an improved clinical response and seizure control at 6 months. At 9 months, she displayed behavioral changes with diagnosis of ADHD with autistic regression. Workup was positive for NMDARA in the CSF (18 months post-presentation) and EEG showed diffuse epileptiform discharges activated during sleep. She was treated with steroids followed by rituximab. At follow-up, she showed improved social interaction, sleep, and seizure control with persistence of some autistic and ADHD features. Conclusions About 90% of patients with NMDARE present with prominent behavioral manifestations, with challenges in differentiating from psychiatric diseases. Relapse is reported in 12-24% of cases and is associated with delayed treatment and the female gender. NMDARAE relapse post-HSV Encephalitis is underreported, especially cases demonstrating autistic regression, as in our case. In conclusion, given overlapping and subtle symptoms, it is crucial to recognize the varying presentations and early diagnosis of NMDARAE relapse for effective treatment and better outcome.

Cervical lymph nodes and ovarian teratomas as germinal centres in NMDA receptor-antibody encephalitis.

Autoantibodies against the extracellular domain of the N-methyl-d-aspartate receptor (NMDAR) NR1 subunit cause a severe and common form of encephalitis. To better understand their generation, we aimed to characterize and identify human germinal centres actively participating in NMDAR-specific autoimmunization by sampling patient blood, CSF, ovarian teratoma tissue and, directly from the putative site of human CNS lymphatic drainage, cervical lymph nodes. From serum, both NR1-IgA and NR1-IgM were detected more frequently in NMDAR-antibody encephalitis patients versus controls (both P < 0.0001). Within patients, ovarian teratoma status was associated with a higher frequency of NR1-IgA positivity in serum (OR = 3.1; P < 0.0001) and CSF (OR = 3.8, P = 0.047), particularly early in disease and before ovarian teratoma resection. Consistent with this immunoglobulin class bias, ovarian teratoma samples showed intratumoral production of both NR1-IgG and NR1-IgA and, by single cell RNA sequencing, contained expanded highly-mutated IgA clones with an ovarian teratoma-restricted B cell population. Multiplex histology suggested tertiary lymphoid architectures in ovarian teratomas with dense B cell foci expressing the germinal centre marker BCL6, CD21+ follicular dendritic cells, and the NR1 subunit, alongside lymphatic vessels and high endothelial vasculature. Cultured teratoma explants and dissociated intratumoral B cells secreted NR1-IgGs in culture. Hence, ovarian teratomas showed structural and functional evidence of NR1-specific germinal centres. On exploring classical secondary lymphoid organs, B cells cultured from cervical lymph nodes of patients with NMDAR-antibody encephalitis produced NR1-IgG in 3/7 cultures, from patients with the highest serum NR1-IgG levels (P < 0.05). By contrast, NR1-IgG secretion was observed neither from cervical lymph nodes in disease controls nor in patients with adequately resected ovarian teratomas. Our multimodal evaluations provide convergent anatomical and functional evidence of NMDAR-autoantibody production from active germinal centres within both intratumoral tertiary lymphoid structures and traditional secondary lymphoid organs, the cervical lymph nodes. Furthermore, we develop a cervical lymph node sampling protocol that can be used to directly explore immune activity in health and disease at this emerging neuroimmune interface.

Movement disorders in emergencies

Movement disorder emergencies refer to clinical scenarios, evolving acutely or subacutely in which the clinical presentation is dominated by a primary movement disorder, and failures to accurately diagnose and manage the patient may result in significant morbidity or even mortality. Whilst this entity may seem to be relatively uncommon compared to other medical emergencies, the last two decades have seen increasing recognition of various movement disorder emergencies as recognised in the literature to include such diverse entities from acute forms of parkinsonism, chorea, dystonia, myoclonus, and tics to acute abnormal movements manifestations in those with underlying disorders like Wilson's disease, NMDA-receptor antibody encephalitis, and several acquired disorders. In this session, important not-to-miss emergencies will be divided into hypokinetic, hyperkinetic, and movement disorder conditions with neuropsychiatric emergencies. The presentation of each example will be supported by video illustrations with the objectives to highlight clinical features, precipitating factors, prodromal symptoms or signs that are associated with specific forms of movement disorder emergencies as well as management strategies. During this pandemic era, examples of movement disorder emergencies related to COVID-19 infection will also be presented and discussed.

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

ObjectiveTo create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE).MethodsAfter selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement).ResultsCorticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3–12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided.ConclusionThese international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients.

Radiomic Phenotypes Distinguish Atypical Teratoid/Rhabdoid Tumors from Medulloblastoma.

Atypical teratoid/rhabdoid tumors and medulloblastomas have similar imaging and histologic features but distinctly different outcomes. We hypothesized that they could be distinguished by MR imaging-based radiomic phenotypes. We retrospectively assembled T2-weighted and gadolinium-enhanced T1-weighted images of 48 posterior fossa atypical teratoid/rhabdoid tumors and 96 match-paired medulloblastomas from 7 institutions. Using a holdout test set, we measured the performance of 6 candidate classifier models using 6 imaging features derived by sparse regression of 900 T2WI and 900 T1WI Imaging Biomarker Standardization Initiative-based radiomics features. From the originally extracted 1800 total Imaging Biomarker Standardization Initiative-based features, sparse regression consistently reduced the feature set to 1 from T1WI and 5 from T2WI. Among classifier models, logistic regression performed with the highest AUC of 0.86, with sensitivity, specificity, accuracy, and F1 scores of 0.80, 0.82, 0.81, and 0.85, respectively. The top 3 important Imaging Biomarker Standardization Initiative features, by decreasing order of relative contribution, included voxel intensity at the 90th percentile, inverse difference moment normalized, and kurtosis-all from T2WI. Six quantitative signatures of image intensity, texture, and morphology distinguish atypical teratoid/rhabdoid tumors from medulloblastomas with high prediction performance across different machine learning strategies. Use of this technique for preoperative diagnosis of atypical teratoid/rhabdoid tumors could significantly inform therapeutic strategies and patient care discussions.

A Metabolic Brain Pattern Associated With Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis causes substantial neurological disability. Autoantibodies causing encephalitis directed against the neuronal cell surface or synapse are of diagnostic importance giving the possibility of successful immunotherapy. In this study, we aim to provide supporting evidence that brain 18F-FDG-PET may be helpful in identifying likely patterns of regional brain glucose metabolism. Thirty-three patients (18 men and 15 women; age range of 17-55 y) with positive NMDA receptor antibody encephalitis that underwent an 18F-FDG-PET imaging examination were prospectively selected and compared with a reference group of 14 brain 18F-FDG-PET scans from healthy volunteers using voxel-based statistical analysis. Clusters of hyper- and hypo-metabolism were reported for the whole sample of patients (FWE-correctedP< 0.05), and uncorrected atP< 0.005 for a group of relapsedpatients. Mixed metabolic patterns (focal/bilateral hypermetabolism in the temporal lobe, insula, and cerebellum; associated with severe bilateral hypometabolism in the occipital and parietal lobes) were found. Our findings suggest that 18F-FDG-PET should be included as an imaging tool when assessing affected patients in the clinical workup to rule out anti-NMDA encephalitis and help determine the most effective treatment.

NMDA receptor antibody encephalitis presenting as Transient Epileptic Amnesia

Transient Epileptic Amnesia (TEA) is a subtype of temporal lobe epilepsy, typically presenting in a person's early 60s, and of unknown aetiology. Encephalitis caused by antibodies to NMDA receptors (NMDARE) has not previously been documented in TEA. We describe a 47-year-old male who satisfied criteria for TEA, but given his atypical symptoms, was also screened for autoimmune epilepsy. High levels of serum NMDAR antibodies were found, suggesting NMDARE. Immunosuppressive treatment gradually eliminated the NMDA receptor antibodies. Our case extends the clinical spectrum associated with neuronal cell-surface autoantibodies to include atypical cases of TEA.

Malignant tumors in autoimmune encephalitis with anti-NMDA receptor antibodies.

The aim of this study was to describe specificities of patients with NMDA receptor antibody (NMDAR-Ab) encephalitis associated with a malignant tumor. Retrospective observational study of 252 patients with NMDAR-Ab encephalitis of the French Paraneoplastic Neurological Syndrome Reference Center. Patients were classified in three groups: (1) non-malignant ovarian teratomas, (2) malignant ovarian teratomas (immature), and (3) other malignant tumors. Sixty patients (23.8%) had an associated tumor and 15 (6%) were malignant. No particular neurological symptom was observed in these patients. Ovarian teratomas were the most frequent (51 cases) with 6 of them immature (11.8% of teratomas). Nine patients (3.6%) developed other malignant tumors (3 small cell lung carcinomas, 1 uterine adenocarcinoma, 1 prostate adenocarcinoma, 1 Hodgkin lymphoma, 1 pineal dysgerminoma, 1 neuroblastoma and 1 pancreatic neuroendocrine tumor). Among patients with a cancer other than teratoma, 6/9 were elderly patients (median age 65 years, representing 30% of elderly patients with such encephalitis) compared to a median age of 26years in adult patients included herein. The clinical course was similar in the three groups, other than a higher death rate among patients with malignant tumors (86 versus 2%; p < 0.001) mainly due to tumor progression (5/7 deaths). Immature ovarian teratomas represent 11.8% of all teratomas in patients with NDMAR-Ab encephalitis. The other malignant tumors are mainly observed in elderly patients. The presence of a malignant tumor does not impact the neurological presentation but is directly associated with a higher risk of death.

S62. Computational diagnosis of ion channel dysfunction in NMDA receptor antibody encephalitis

Introduction NMDA receptor (NMDAR) antibody encephalitis is an autoimmune disorder causing acute psychosis, confusion and seizures. Electroencephalography (EEG) findings are usually non-specific, with diagnosis confirmed by demonstration of serum/CSF autoantibodies. Improved clinical outcomes depend on early institution of immunotherapies. A non-invasive measure of NMDAR function could facilitate early treatment, and enable tracking of disease activity. Recent biophysical modeling advances allow inference of ion channel dynamics from macroscopic measures of brain activity. Here, we show that clinically relevant diagnoses of NMDAR ion channel dysfunction can be obtained using a microcircuit model fitted to individual human EEG data. Methods We compared resting state EEG cross-spectra from patients with NMDAR encephalitis, encephalopathy unrelated to NMDAR dysfunction, and non-encephalopathic controls. We fit biophysical models (dynamic causal models – DCMs) of connected neuronal ensembles, simulating post-synaptic membrane potentials and EEG spectra through lead field projection. We used canonical variate analysis (CVA) and an empirical Bayesian approach searching candidate models across the groups to reveal specific synaptic deficits. Results Clinical severity was matched between encephalopathic groups. However, there were clear differences in EEG cross-spectra at low (2–4 Hz) and high (28–40 Hz) frequencies, with increased beta-gamma power present in NMDAR antibody encephalitis patients. Subject-specific DCMs mapped model parameters representing dynamics at NMDA, AMPA and GABA receptors to spectral data features. Four inter-connected sources described delta-theta and beta-gamma cross-spectra observed at scalp sensors. Each source comprised a neural mass model with four neuronal subpopulations, with dynamics determined by intrinsic connections mediated via ionotropic receptors. Dynamics along intrinsic and extrinsic connections could reproduce scalp-based EEG recordings. Parameter estimate CVA showed significant differences between patients with and without NMDAR encephalitis in NMDAR parameters. A parametric empirical Bayes (PEB) analysis demonstrated that the group effects of NMDAR encephalitis were specific to NMDA model parameters, in contrast to other encephalopathies where differences were seen across receptor subtypes. Conclusion Neurological and psychiatric practice lack diagnostic probes to assess disease mechanisms at the neuronal level non-invasively in humans. We show that biophysical models of EEG applied to clinical EEG data identify abnormal NMDAR signaling in patients with NMDAR encephalitis but not in patients with other encephalopathies or neurological controls. By comparing model parameter estimates from these patient groups, we selectively identify NMDAR dysfunction in a multi ion-channel model. Given that EEG is ubiquitously available, our findings suggest the feasibility of EEG neuromodeling as a unique assay of brain dysfunction at the molecular-level.

Generalized and Lateralized Rhythmic Patterns

The relationship between generalized and lateralized rhythmic delta activity (RDA) and seizures is more ambiguous than the relationship between periodic discharges and seizures. Although frontally predominant generalized RDA is not associated with seizures, occipitally predominant RDA may be associated with the absence of seizures. Lateralized RDA seems to be more strongly associated with the presence of seizure activity. Appropriate recognition of generalized RDA and lateralized rhythmic delta activity may be confounded by benign etiologies of RDA, such as phi rhythm, slow alpha variant, subclinical rhythmic electrographic discharges of adults, or hyperventilation-induced high-amplitude rhythmic slowing. Angelman syndrome and NMDA-receptor antibody encephalitis can also produce morphologically distinct patterns of RDA.

Anti- NMDA Receptor Antibody Encephalitis: - A Review of Nine Patients with Clinical Presentation, Investigations, Treatment and Outcome in Singapore

Objective: To report on epidemiology, clinical and laboratory features of patients diagnosed with anti-N-methyl-Daspartate receptor (NMDAR) encephalitis admitted to Singapore general hospital over the period of four years. This is the first study for the local population. Introduction: Anti –NMDA receptor encephalitis is a severe form of encephalitis that associates with antibodies against NMDA receptors resulting in a neuropsychiatric syndrome. It has been considered as a Paraneoplastic syndrome. Methods: Nine patients (6 female and 3 male) admitted to neurology unit from March 2010 to Oct 2013 were studied retrospectively. Diagnosis of anti-NMDA receptor antibody encephalitis was based on encephalitis plus positive CSF serology. Result: Younger age group affected more (range 16 to 65 years). Clinical presentation usually involves the triad of psychotic (100%); seizures (66%) and movement disorder (45%). Autonomic instability observed in two third (66%) of patients. Serum serology is positive only in 55% patients. CSF analysis was variable. MRI brain was largely unremarkable (77%). Tumour occurrence was seen in 66%; 83% in females, 33% in males. The outcome was favourable in two third patients with the best prognosis in female patients when the tumour was found and resected and worst in male patients with tumour unresected. Conclusion: Results are consistent with the current literature in terms of epidemiology, investigations and outcome. However, it requires the larger number of patients with longer follow-up to prove its association with a tumour in patients who has no evidence of malignancy at diagnosis.

Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome.

The natural history of NMDA receptor (NMDAR) antibody encephalitis in adults and children is altered by treatment with immunosuppressive therapy or tumor removal.1 In adult cohorts, early initiation of immunotherapy appears to be beneficial.1,2 In the largest series to date, Titulaer et al.1 demonstrated that earlier treatment was associated with a modified Rankin Scale (mRS) score of 2 or less in a cohort of 501 adults and children (univariate analysis p = 0.009, multivariable analysis p < 0.0001). Multivariable analysis on 177 children within the cohort showed that earlier treatment was associated with an mRS score of 2 or less, although this did not reach statistical significance ( p = 0.067).1 An mRS score of 2 indicates slight disability and that the patient is unable to carry out all previous activities. Acknowledgment: The authors thank Drs. Roberta Biancheri, Blaithnaid McCoy, Sarbani Raha, David Cohen, Sebastian Lebon, Ming-Chi Lai, Darcy Krueger, Johan Penzien, and Mered Parnes for providing additional patient data.

Does a Standardized Multidisciplinary Approach Improve Outcomes for Children with NMDA Receptor Antibody Encephalitis? A Preliminary Assessment of a Single Center Experience (S35.008)

Does a Standardized Multidisciplinary Approach Improve Outcomes for Children with NMDA Receptor Antibody Encephalitis? A Preliminary Assessment of a Single Center Experience (S35.008)

Does a Standardized Multidisciplinary Approach Improve Outcomes for Children with NMDA Receptor Antibody Encephalitis? A Preliminary Assessment of a Single Center Experience (I6-5E)

Does a Standardized Multidisciplinary Approach Improve Outcomes for Children with NMDA Receptor Antibody Encephalitis? A Preliminary Assessment of a Single Center Experience (I6-5E)

G64(P) Focal seizure, hemiparasis, hemiplagia and nmda receptor antibody encephalitis – atypical presentation

Aim We present an atypical case of NMDAR Ab Encephalitis (N-methyl-D-Aspartate Receptor Antibody Encephalitis) with recurrent right sided focal seizures, right hemiparesis and hemiplegia. The youngest case in UK to be described without significant psychiatric component. Methods 4 years 10 month old girl born in UK to Zimbabwean Parents. She had been well with not relevant family history. She presented with right sided focal seizure and reduced movement. She had 2 episodes of generalised tonic convulsions involving the right side associated with loss of consciousness which lasted for 2 min and then 10 min; 5 min apart. The seizures was managed with diazepam. No preceding trauma, fever, neck pain, headache or vomiting. Her right sided weakness which improved within 2 h. She was then re admitted 4 days later with right focal seizure with persisting right sided weakness, dysarthria and right sided facial palsy. She had amnesia without any new psychotic features Baseline blood and CSF Investigation were normal. Lyme serology, ASOT, Lupus screen, all viral PCR and throat swab were negative. ECG, Echo and EEG was normal. CSF amino acid, ammonia, Lyme titre, oligoclonal bands, mitochondrial DNA, acylcarnitine profile was normal. MRI showed possible left MCA infarct with a picture of encephalitis with oedema. She was treated with antibiotics, lorazepam, Aspirin and Omeprazole. Repeat MRI ruled out a stroke so Aspirin was stopped and started on IV methylprednisolone. Repeated MRI brain suggested an inflammatory process with evidence of maturing damage suggestive of neurometabolic or neuroinflammatory disorder. Importantly the CSF and blood NMDAR antibody returned positive with rising titres of blood NMDAR ab. Results NMDA Receptor Antibody Encephalitis was diagnosed and treated with Prednisolone 30 mg OD for 8/52, advised avoiding live vaccines and IVIG 1 g/kg for 2/7. MMF 200 mg BD planned for 18–24 months- dose to be adjusted based on response. Monthly NMDAR ab blood and CSF have been positive for 10 months after diagnosis. She is on Annual surveillance for tumours with MRI or USS. She continues to have physiotherapy and Neuropsychology input. Conclusion Atypical focal seizures may need further evaluation and NMDAR ab considered with atypical presentations resulting in better outcome.

NMDA receptor antibodies associated with distinct white matter syndromes.

Objective:To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders.Method:Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody–positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated.Results:Three distinct clinicoradiologic phenotypes were recognized: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers.Conclusion:Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease.