N-methyl-d-aspartate Receptor Antibody Encephalitis Research Articles

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.

Disease progression and brain atrophy in NMDAR encephalitis: Associated factor & clinical implication

ObjectiveWe investigated the longitudinal pattern, determining factors, and clinical implications of brain volume changes in N‐methyl d‐aspartate receptor‐antibody (NMDAR) encephalitis.MethodsBaseline clinical profiles, treatment profiles, and outcome measured using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) and modified Rankin scale (mRS) were obtained from a long‐term clinical database documenting an NMDAR encephalitis cohort. In serial MRI, the change in the normalized volume of different brain regions from the baseline evaluation was measured. At each MRI evaluation time point, the cumulative disease burden (CASE score × months) and the cumulative duration of status epilepticus were also evaluated.ResultsThirty‐six patients were followed‐up for 28.5 months (range 12–63 months). The volume ratio at last MRI to baseline was the lowest in the cerebellum (94.4 ± 5.7%, p < 0.001). Once developed, cerebellar volume reduction followed a progressive course until 2 years from disease onset. The degree of cerebellar volume reduction was positively correlated with mRS and total CASE scores (all, p < 0.001), and CASE scores in the domains of memory, language, and psychiatric problems, gait instability/ataxia, and weakness (all, p < 0.01). In linear mixed model analyses, the degree of cerebellar volume reduction was associated with cumulative disease burden up to 2 years (p < 0.001) and duration of status epilepticus (p < 0.001), and delayed removal of teratoma for ≥1 month (p = 0.006).InterpretationIn NMDAR encephalitis, cerebellar volume reduction was progressive once developed. Cerebellar volume reduction might reflect disease burden and extent of progression and be associated with poor outcomes in multiple functional domains.

Pediatric Autoimmune Encephalitis in Sri Lanka: A Single-Center Experience over 7 Years

AbstractPediatric autoimmune encephalitis (AE) remains a diagnostic and therapeutic challenge in resource-poor settings. Minimizing delay in diagnosis and appropriate escalation of treatment will help reduce both the short- and long-term neurodisabilities. A retrospective observational study was performed on children consecutively diagnosed with possible AE and then prospectively followed up in a single tertiary care children's hospital in Sri Lanka. Serum and cerebrospinal fluid were tested for neuroglial surface-binding autoantibodies using cell-based assays in majority of these children. Twenty-five children (mean age 7.6 years, standard deviation = 4) were recruited. In these children, presenting symptom was psychiatric in 11 children (44%), seizures in 10 (40%), language regression in 2 (8%), and combination of psychosis and convulsions in 2 (8%). Psychiatric presentations were more common in older (&gt;6 years) compared with young children (p = 0.001), while neurological presentations were more common in children aged ≤6 years (p = 0.001). N-methyl-D-aspartate receptor (NMDAR) antibodies were detected in 9 (45%) and unspecified voltage-gated potassium channel antibodies in 1 (5%) of the 20 tested. All received intravenous steroids and immunoglobulins; 19 (76%) plasma exchange; 7 (29%) rituximab. Complete/substantial improvement at 3 months occurred in 64%. Pediatric Cerebral Performance Category score at last review was 1 (normal function for age) in 43%. Higher proportion of younger children required less intense therapy and had better recovery (56%). Death (8%), incomplete recovery (71%), and relapses (8%) were more in older children. Clinical presentation and disease outcomes were different in children aged &lt;6 years compared with older age group. NMDAR antibody encephalitis was the commonest AE syndrome identified in this cohort.

Neurological and cognitive outcomes after antibody‐negative autoimmune encephalitis in children

AIMTo characterize the neurological and cognitive outcomes in children with antibody‐negative autoimmune encephalitis (Ab‐negative AE).METHODA cohort of children presenting to our institution over a 10‐year period with autoimmune encephalitis was identified by structured retrospective review of medical records. Clinical features at presentation and final follow‐up were recorded. Neuropsychological testing was performed in a subset of patients. Outcomes after Ab‐negative AE were compared with outcomes after N‐methyl‐D‐aspartate receptor antibody encephalitis (NMDARE).RESULTSForty‐four patients (26 females, 18 males, median age 9y 2mo [interquartile range 4y 5mo–11y 8mo], 23 with NMDARE) with a diagnosis of autoimmune encephalitis were included. Postencephalitic epilepsy was more frequent after Ab‐negative AE compared to NMDARE (61% vs 14%, p=0.002). Cognitive testing was performed in a subset of patients (n=21; Ab‐negative AE=11, NMDARE=10). Full‐scale IQ was lower after Ab‐negative AE than NMDARE (mean IQ 75 vs 92, p=0.02), primarily because of reduced verbal comprehension index (80 vs 98, p=0.01) and working memory index (77 vs 95, p=0.09). The cognitive function most commonly impaired was executive function (80% [8/10] vs 22% [2/9]).INTERPRETATIONAb‐negative AE was associated with poorer cognitive outcomes than NMDARE at 1‐year follow‐up. Further studies are required to evaluate if immunotherapy can be optimized to improve outcome.

BIZARRE BEHAVIORS: AUTOIMMUNE ENCEPHALITIS MASQUERADING AS A PSYCHIATRIC SYNDROME

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: N-methyl-D-aspartate (NMDA) receptor antibody encephalitis, a type of autoimmune encephalitis, first described in 2007, is predominant in females with female to male ratio of 8:2 and about 37% patients being younger than 18 years at presentation.[1,2] It is considered a part of paraneoplastic syndrome, as more than half of the cases have an underlying malignancy, ovarian teratoma being the most common.[3,4] CASE PRESENTATION: A 20 year old male with asthma was brought into the Emergency Department for seizures. He checked himself into a behavioral health facility for bizarre behavior. He received chlorpromazine, causing generalized tonic clonic seizure. He received Lorazepam and Levetiracetam. Continuous electroencephalogram showed no further seizure activity and CT head was non-diagnostic for any structural abnormalities. He was afebrile and tachycardic on examination, along with him being, initially unrousable to verbal as well as tactile stimuli. Eventually he developed more aggressive mannerism, requiring 4 point tough restraints. Not being controlled with lorazepam and haloperidol, a Dexmedotomide drip was started.Laboratory data including urine drug screen was unremarkable except elevated CK (3127 U/L). MRI Brain and lumbar puncture revealed no acute abnormality. Meningitis panel consisting of E.coli, H.influenzae, Listeria monocytogene, N. meningitidis, Strep pneumoniae and agalactiae, Cytomegalovirus, Herpes simplex 1 and 2, Varicella zoster virus, Enterovirus and C.neo was non detectable. CSF gram stain showed no organisms. Staining for acid fast bacilli and PCR for west nile virus and Lyme were negative. Autoimmune encephalitis panel came back positive for NMDA receptor antibody encephalitis for which he received IV steroids and IVIG. DISCUSSION: The characteristic picture of NMDA receptor antibody encephalitis can be divided into 3 phases: I with respiratory symptoms and mild fever, II with psychiatric manifestations and III with development of neurological symptoms.[5] Psychiatric symptoms consist of delusions, hallucinations, anxiety and mania while neurological manifestations includes movement disorder, autonomic instability, central hypoventilation and coma.[3,5] It is difficult to differentiate from primary psychiatric disorder if a patient presents with psychiatric symptoms. Early suspicion and diagnosis are key to start treatment in the form of immunotherapy or removal of the tumor.[6] CONCLUSIONS: The differential of NMDA receptor antibody encephalitis must be considered in young patients with neuropsychiatric symptoms as they are often misdiagnosed with psychiatric disorders, which impedes early treatment.The removal of the tumor and immunotherapy generally carry a good prognosis with complete recovery. REFERENCE #1: Engen K, Agartz I. Anti-NMDA-reseptorencefalitt [Anti-NMDA-receptor encephalitis]. Tidsskr Nor Laegeforen. 2016 Jun 21;136(11):1006-9. Norwegian. doi: 10.4045/tidsskr.15.0795. PMID: 27325034. REFERENCE #2: Josep Dalmau, Thais Armangué, Jesús Planagumà, Marija Radosevic, Francesco Mannara, Frank Leypoldt, Christian Geis, Eric Lancaster, Maarten J Titulaer, Myrna R Rosenfeld, Francesc Graus, An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models, The Lancet Neurology, Volume 18, Issue 11, 2019, Pages 1045-1057, ISSN 1474-4422, https://doi.org/10.1016/S1474-4422(19)30244-3. REFERENCE #3: Dalmau J, Gleichman AJ, Hughes EG et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7: 1091 - 8 DISCLOSURES: No relevant relationships by Devashish Desai, source=Web Response No relevant relationships by Pushti Khandwala, source=Web Response No relevant relationships by Goonja Patel, source=Web Response No relevant relationships by Rajagopalan Rengan, source=Web Response

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis

Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear. To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. Systematic search in PubMed from inception to January 1, 2019. Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data. Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models. The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset). Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05). Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

Comparison of N-methyl-D-aspartate receptor antibody assays using live or fixed substrates.

The diagnostic criteria for N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis require the presence of CSF antibodies against the NMDAR, whereas serum antibodies are considered specific only if accompanied by CSF antibodies. Current assays include in-house immunochemistry (IHC), or cell-based assays (CBA) which use live (L-CBA) or fixed cells (F-CBA), and commercially available fixed-cells CBA (C-CBA), but these have not been compared in parallel. We compared the L-CBA with F-CBA, C-CBA, and IHC using sera and CSFs archived from > 30,000 received for testing and previously positive by L-CBA. Referring neurologists, if identified, provided "definite" or "unlikely" diagnoses of NMDAR-Ab encephalitis for 31 paired serum-CSF samples and 53 unpaired sera. There was good concordance between paired sera and CSFs, with 13/16 "definite" pairs positive, and 7/8 "unlikely" pairs negative in all in-house assays. In unpaired "definite" sera, L-CBA was most sensitive. However, 19/24 serum samples from "unlikely" patients were positive by L-CBA, with only 5/24 and 1/24 positive by F-CBA and IHC, respectively. In available samples, C-CBA demonstrated high sensitivity for CSF, but surprisingly low sensitivity for serum. Overall, regardless of the technique, CSF results were accurate and easy to interpret, but if CSF is unavailable, negative serum C-CBA results in cases with suspected NMDAR-Ab encephalitis could be repeated by a more sensitive in-house assay. Although these assays are sensitive, particularly for CSF, referral of sera with low pre-test probability should be avoided to reduce clinically-irrelevant "false positive" results.

Catatonic features in children and adolescents with N-methyl-d-aspartate receptor antibody encephalitis.

Catatonia is a psychomotor dysregulation syndrome of diverse aetiology, increasingly recognised as a prominent feature of N-methyl-d-aspartate receptor antibody encephalitis (NMDARE) in adults. No study to date has systematically assessed the prevalence and symptomatology of catatonia in children with NMDARE. We analysed 57 paediatric patients with NMDARE from the literature using the Bush-Francis Catatonia Rating Scale. Catatonia was common (occurring in 86% of patients), manifesting as complex clusters of positive and negative features within individual patients. It was both underrecognised and undertreated. Immunotherapy was the only effective intervention, highlighting the importance of prompt recognition and treatment of the underlying cause of catatonia.

Prevalence of N-Methyl-d-Aspartate Receptor antibody (NMDAR-Ab) encephalitis in patients with first episode psychosis and treatment resistant schizophrenia on clozapine, a population based study

IntroductionN-methyl-d-aspartate receptor antibody (NMDAR-Ab) encephalitis consensus criteria has recently been defined. We aimed to examine the prevalence of NMDAR-Ab encephalitis in patients with first episode psychosis (FEP) and treatment resistant schizophrenia (TRS) on clozapine, using clinical investigations, antibody testing and to retrospectively apply diagnostic consensus criteria. MethodsAdult (18-65 years old) cases of FEP meeting inclusion criteria were recruited over three years and assessed using the Structured Clinical Interview for DSM-IV disorders (SCID). NMDAR-Ab was identified using a live cell-based assay (L-CBA). Seropositive cases were clinically investigated for features of encephalitis including neuro-imaging, EEG and CSF where possible. Serum was retested using immunohistochemistry (IHC) as part of diagnostic criteria guidelines. A cohort of patients with TRS was also recruited. Results112 FEP patients were recruited over 3 years. NMDAR-Ab seroprevalence was 4/112 (3.5%) cases. One case (<1%) was diagnosed with definite NMDAR-Ab encephalitis and treated with immunotherapy. One of the three other seropositive cases met criteria for probable encephalitis. However all three were ultimately diagnosed with mood disorders with psychotic features. None have developed neurological features at three year follow up. 1/100 (1%) of patients with TRS was 100 patients with TRS were recruited. One case (1%) seropositive for NMDAR-Ab but did not meet criteria for encephalitis. ConclusionsNMDAR-Ab encephalitis as defined by consensus guidelines occured rarely in psychiatric services in this study. Further studies are needed to establish pathogenicity of serum NMDAR-Ab antibodies. Psychiatric services should be aware of the clinical features of encephalitis.

1447 A Rare but Fatal Case of N-methyl-D-aspartate Receptor Antibody Encephalitis Associated With a Pancreatic Neuroendocrine Tumor

INTRODUCTION: N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is an autoimmune inflammatory condition of the brain thought to be paraneoplastic given its strong association with malignancy, but such related tumors are rarely detected in older males. To our knowledge, there is only a single case report of NMDAR-Ab encephalitis related to a pancreatic neuroendocrine tumor (NET). Here, we report a case of NMDAR-Ab encephalitis associated with pancreatic NET that was fatal despite early tumor resection. CASE DESCRIPTION/METHODS: A 79-year-old man with hypertension presented with acute onset of confusion, agitation, and urinary and bowel incontinence. He was living independently but had progressive short-term memory loss over the year prior. Electroencephalogram showed diffuse slowing without seizure activity. Magnetic resonance imaging of the brain noted trace sulcal FLAIR hyperintensity in perirolandic regions. Cerebrospinal fluid (CSF) analysis revealed elevated protein (96 mg/dL), low nucleated cell count, no oligoclonal bands, and negative infectious serology and cultures. CSF paraneoplastic panel was positive for anti-NR1 antibody, confirming the diagnosis of NMDAR-Ab encephalitis. Malignancy workup revealed a 1.2 cm mass in the pancreatic tail, and endoscopic ultrasound-guided fine-needle biopsy showed positive staining for synaptophysin and chromogranin A consistent with a well-differentiated NET. The patient rapidly declined from worsening encephalopathy and required percutaneous gastrostomy tube placement. He underwent laparoscopic distal pancreatectomy and splenectomy with intravenous immunoglobulin and glucocorticoids, but a repeat CT abdomen next month showed peritoneal metastases with diffuse uptake on somatostatin receptor scintigraphy and rising serum chromogranin A (603 ng/mL). He had no significant neurologic recovery and eventually died on comfort measures without further interventions. DISCUSSION: Though rare, prior cases of NMDAR-Ab encephalitis associated with NET described the importance of early surgical removal of the underlying tumor to provide the best chance of neurologic recovery. Metastatic disease portends a poor prognosis as it renders encephalitis impossible to resolve. Worldwide experience with NMDAR-Ab encephalitis is limited and further observations are needed to refine current treatment strategies.

Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis.

See Roberts and Breakspear (doi:10.1093/brain/awy136) for a scientific commentary on this article.Neurological and psychiatric practice frequently lack diagnostic probes that can assess mechanisms of neuronal communication non-invasively in humans. In N-methyl-d-aspartate (NMDA) receptor antibody encephalitis, functional molecular assays are particularly important given the presence of NMDA antibodies in healthy populations, the multifarious symptomology and the lack of radiological signs. Recent advances in biophysical modelling techniques suggest that inferring cellular-level properties of neural circuits from macroscopic measures of brain activity is possible. Here, we estimated receptor function from EEG in patients with NMDA receptor antibody encephalitis (n = 29) as well as from encephalopathic and neurological patient controls (n = 36). We show that the autoimmune patients exhibit distinct fronto-parietal network changes from which ion channel estimates can be obtained using a microcircuit model. Specifically, a dynamic causal model of EEG data applied to spontaneous brain responses identifies a selective deficit in signalling at NMDA receptors in patients with NMDA receptor antibody encephalitis but not at other ionotropic receptors. Moreover, though these changes are observed across brain regions, these effects predominate at the NMDA receptors of excitatory neurons rather than at inhibitory interneurons. Given that EEG is a ubiquitously available clinical method, our findings suggest a unique re-purposing of EEG data as an assay of brain network dysfunction at the molecular level.

NMDAR antibody encephalitis and fluctuating catatonia

N‐Methyl D‐aspartate receptor (NMDAR) antibody encephalitis has varied presentations and may often be seen in psychiatry because of a range of associated psychiatric manifestations. Here, the authors present a case of prolonged catatonia that occurred in episodes and continued for months before being successfully diagnosed as a cause of NMDAR antibody encephalitis.

Autoimmune encephalitis following haematopoietic stem cell transplant: a new clinical entity or a previously unrecognised one?

Central nervous system (CNS) autoimmunity, characterized by the presence of antibodies binding to brain receptors, ion channels, and related proteins (1) is increasingly recognized in children (2). Childhood-onset autoimmune encephalitis may be associated with tumours, particularly in post-pubertal girls with N-Methyl-D-aspartate receptor (NMDAR) antibody encephalitis (3), but the majority of these encephalitides are presumed to have a post infectious trigger (1,4). Recently, in a large single-centre study of 164 Australian children presenting with encephalitis, 10% were identified as having an autoimmune aetiology, a frequency which surpassed that of any single virus identified (5), mirroring cases reported in the California encephalitis project, where the frequency of NMDAR antibody encephalitis surpassed that of any of the identified viral encephalitides (6). This discovery, that several forms of encephalitis result from neuronal antibodies, and are immunotherapy-responsive, has led to a paradigm shift in the diagnostic approach with a focus on how to recognize, diagnose and treat these conditions early (2).

Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease

BackgroundPatients with encephalitis associated with antibodies against N-methyl-D-aspartate-receptor antibody (NMDAR-ab) encephalitis frequently show psychotic symptoms, amnesia, seizures and movement disorders. While brain MRI in NMDAR-ab encephalitis is often normal, abnormalities...

NMDA receptor autoantibodies in sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) and N-methylD-aspartate receptor antibody (NMDAR-Ab) encephalitis [1], share similar clinical features including prominent psychiatric symptoms, memory problems, and seizures (Table 1). Previously, other forms of autoimmune encephalitis have been misdiagnosed as CJD, including Hashimoto’s and voltage-gated potassium channel complex antibody-associated encephalopathies [2, 3]. Here, conversely, we describe two patients presenting with progressive cognitive impairment and NMDAR-Abs with confirmed sCJD at post mortem. A retrospective review of 100 pathologically confirmed cases of sCJD seen by the UK National CJD surveillance unit [4] over the past 2 years identified six tested for NMDAR-Abs at presentation in whom results were available: four were negative and two positive. Both NMDAR-Ab positive cases presented with subacute cognitive decline and behavioral disturbance leading to serum testing for the antibodies. Patient A progressed to an akinetic mute state over 3 months and patient B over 9 months. Both had basal ganglia high signal on MRI brain imaging, a positive 14-3-3 immunoassay and elevated S100b level. Patient A twice had positive serum NMDARAb levels at dilutions up to 1:80. He was given 3 days of intravenous methylprednisolone and continued to deteriorate, dying 9 days later. Patient B deteriorated over 9 months. Some months after discharge to palliative care, his earlier positive serum NMDAR-Ab titre of 1:80 was discovered. Both had sporadic CJD confirmed at post mortem. CSFs were negative for NMDAR-Abs in all six cases. The presentation and clinical evolution in these two cases was consistent with sCJD and the positive NMDARAb results were surprising. Detecting NMDAR-Abs involves the demonstration of autoantibodies binding to a cell line expressing the NR1 and NR2B subunits [5]. All positive sera (tested at 1:20 initially) are checked against cells expressing other antigens, and the cells alone, to exclude any false-positive results [5, 6]. Positive results in healthy individuals or other disease controls are very rare; not found in 160 neurological disease controls [5]. The existence of these antibodies in two out of six patients with confirmed CJD is therefore intriguing. The titres were low, but at a level seen in patients with NMDAR-Ab encephalitis. One possibility is that these antibodies occurred as a secondary event resulting from an immune response to NMDARs released from damaged neurons. An altered composition of NMDAR has been implicated in cell death Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6489-3) contains supplementary material, which is available to authorized users.

N-Methyl d-aspartate receptor antibody encephalitis associated with myelitis

Encephalitis associated with antibodies to the N-methyl d-aspartate receptor (NMDA-R) was first described in young women with ovarian teratoma [1]. It has subsequently been described in men, children and in those without an underlying tumour [2]. Characteristic clinical features include neuropsychiatric symptoms, seizures, movement disorders, hypoventilation and autonomic instability. Spinal cord disease in association with other typical clinical features has been described in only one patient previously [3,7].We report a patient presenting with myelitis, with typical features of NMDA-R associated encephalitis manifesting 3months later.

Paroxysmal EEG pattern in a child with N-methyl-d-aspartate receptor antibody encephalitis

A previously healthy 8-year-old male presented with cognitive regression, sleep disturbance, hallucinations, and severe attacks of agitation and oligoclonal bands in the cerebrospinal fluid. N-methyl-d-aspartate receptor (NMDAR) antibodies in serum and cerebrospinal fluid were detected 2 months after onset of symptoms. Bursts of agitation were initially considered to be epileptic leading to the administration of a high dose of benzodiazepines. Video-electroencephalography (EEG) failed to disclose any correlation between the episodes of agitation and paroxysmal rhythmic slow activity on EEG persisting throughout and after attacks of agitation. Clinical improvement and EEG normalization followed an initial plasma exchange performed 3 months after onset of disease. This particular paroxysmal EEG pattern in NMDAR antibody encephalitis suggests that it may result from the combination of reduced NMDAR function and major γ-aminobutyric acid (GABA)-ergic activation.

Disease-relevant autoantibodies in first episode schizophrenia

Disease-relevant autoantibodies in first episode schizophrenia