NMDAR Encephalitis Research Articles

A catastrophic case of anti NMDA receptor encephalitis with Japanese encephalitis, borrelia burgdorferi, bartonella henselae and herpes simplex virus co-infections

A catastrophic case of anti NMDA receptor encephalitis with Japanese encephalitis, borrelia burgdorferi, bartonella henselae and herpes simplex virus co-infections

45.4 Altered Mental Status

Anti-N-methyl-D-aspartate receptor (anti–NMDAR) encephalitis is an autoimmune disease that presents with a variety of neurological and psychiatric symptoms. In general, patients present with a nonspecific clinical exam that may create a delay in diagnosis and treatment. Patients may be admitted to psychiatric hospitals when preliminary neurologic workups are inconclusive. Psychiatrists working in an inpatient medical setting are often asked to manage aggressive symptoms that occur while patients undergo treatment. The goal of this presentation is to present a review of the literature on anti–NMDAR encephalitis diagnosis, treatment, and management of aggression in pediatric patients with a case presentation.

Successful combined targeting of B- and plasma cells in treatment refractory anti-NMDAR encephalitis

We describe an extremely severe case of therapy refractory NMDA receptor encephalitis (NMDAe) in a 26-year-old woman. After rituximab, bilateral oophorectomy, repeated cycles of high dose methylprednisolone and plasma exchange, she received repeated cyclophosphamide, tocilizumab (interleukin-6 inhibitor) and finally bortezomib (plasma cell depleting drug) leading to remission after 204days in intensive care. Two years after disease onset her cognitive functions are still affected, but slowly improving and the cerebral atrophy has been partly reversed. The cerebrospinal fluid biomarker profile suggests an early synaptic/dendritic process, with subsequent neuroaxonal degeneration motivating aggressive treatment early on.

Neuropsychiatric Manifestations of Pediatric NMDA Receptor Autoimmune Encephalitis: A Case Series From a Tertiary Care Center in India.

Although psychiatric manifestations are one of the most common presentations of pediatric N-methyl-D-aspartate receptor (NMDAR) encephalitis, there is a lack of studies that characterize psychiatric aspects of this disorder. This study was designed to address this gap. Initial clinical presentations including psychiatric symptoms, treatment details, and outcome with respect to psychiatric symptoms were collected from medical case records of children aged less than 18 years with seropositive NMDAR encephalitis from a single tertiary care center (May 2010-November 2016). The Brief Psychiatric Rating Scale for Children (BPRS-C) was administered at the time of presentation and at follow-up. Clinical records from 16 girls and 5 boys of whom 12 were prepubertal (< 12 years) and 9 were postpubertal (≥ 12 years) were analyzed. All 21 children presented with psychiatric symptoms at initial presentation. In 10 children (47.6%), psychiatric symptom was the first symptom. Major psychiatric symptoms included inappropriate crying (most common, 66.7%, n = 14), social withdrawal (57.1%, n = 12), unprovoked anger outburst (47.6%, n = 10), unprovoked screaming behavior (38.1%, n = 8), and talking to self irrelevantly (42.9%, n = 9). In addition to psychiatric symptoms, at least 1 of the following was also seen in all children: speech disturbance (85.7%, n = 18), seizure (85.7%, n = 18), or movement disorder (76.2%, n = 16). Mood symptoms (85.7%, n = 18) were the most common psychopathology. A comorbid psychiatric diagnosis (ICD-10 criteria) was made in 11 children (52.4%); the most common was organic mood disorder (n = 6). The mean BPRS-C score at presentation in prepubertal children was higher than that of postpubertal children (21 vs 17). After immune modulation, clinical improvement was noted after a mean ± SD of 7.4 ± 4.8 months in all 20 children followed up. Three of the 4 children with residual psychiatric symptoms and persistent academic difficulties were prepubertal. Psychiatric manifestations that are usually mood related are quite common in pediatric NMDAR encephalitis. Prepubertal presentation of this disorder appears to be more severe and may lead to persistent psychiatric and cognitive symptoms.

Anti NMDA-R encephalitis induced by mycoplasma pneumoniae infection in a child

Objective: Immune-mediated encephalitis with autoantibodies has become an important component of the differential diagnosis of patients with encephalitis. Mycoplasma pneumoniae is a common respiratory pathogen mostly affecting children and adolescents can also lead to extrapulmonary diseases such as neurological manifestations including encephalitis, transverse myelitis, acute cerebellar ataxia, opsoclonus-myoclonus syndrome and movement disorders in some of which autoimmunity or formation of immune complexes are responsible. Here we report an anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis who presented with acute-onset confusion and intractable movement disorders such as myoclonus, hemiballismus, orafasial dystonia and diskinesias. Methods: A previously healthy 4-year-old boy presented with deteriorating mental status, aggresive behaviour pattern, stimulus sensitive myoclonic jerks, oromandibular dystonia and orolingual-facial dyskinesias after a febrile period with headache and vomiting. We considered immunoteraphy with high-dose intravenous corticosteroids and exchange plasmapheres thinking diagnosis of autoimmune encephalitis associated with mycoplasma infection after seroconversion. Diagnosis relied on Anti-NMDA-R positivity. Results: The majority of autoimmune encephalitis may be associated with infections. Mycoplasma pneumoniae are the main presumed infectious pathogens. It is suggested that early-onset encephalitis is a direct-type extrapulmonary manifestation involving cytokines and late-onset encephalitis is of the indirect type involving autoimmunity. Conclusion: Various clinical neurological manifestations of mycoplasma pneumoniae may be a result of the underlying patomechanisms. Further studies in this area can help to lighten the etiology of autoimmune disorders.

GRIN1 polymorphisms do not affect susceptibility or phenotype in NMDA receptor encephalitis (P6.190)

GRIN1 polymorphisms do not affect susceptibility or phenotype in NMDA receptor encephalitis (P6.190)

The evolution of EEG in the disease course of NMDA-receptor encephalitis: 2 illustrative case studies and a review of the literature (P2.236)

The evolution of EEG in the disease course of NMDA-receptor encephalitis: 2 illustrative case studies and a review of the literature (P2.236)

Lesions of the posterior limb of the internal capsule in neuromyelitis optica spectrum disorder

Posterior limb of the internal capsule lesions (PLICL) are one of the MRI features of neuromyelitis optica spectrum disorder (NMOSD). However, there is no evidence that such lesions are pathogenically related to NMOSD. We retrospectively analyzed features of PLICL in NMOSD, and other central nervous system inflammatory disorders, in 561 patients. We also examined the pathological samples of six patients. Of the 561 patients investigated, PLICL were found in 65 patients (11.6%). Lesions were bilateral in 26 cases (40%) and unilateral in 39 cases (60%). Unilateral lesions were mainly located on the left side (74.3%, 29/39). Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis. Of the six patients whose pathological samples were evaluated, all had PLICL and were negative for AQP4-IgG, and none had pathological NMOSD lesion features. These cases included three patients with multiple sclerosis, one with anti-N-methyl-D-aspartate receptor encephalitis, and two with autoimmune meningoencephalitis. In conclusion, PLICL are found not only in patients with NMOSD, but also in MS and other disorders.

Anti-N-methyl-D-aspartate receptor encephalitis associated with hepatic neuroendocrine carcinoma: A case report

Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis can present with and without tumor. Tumor associations are less common in older patients. We report a 65-year-old gentleman who presented with one week history of cough, chills, rigor and altered behavior, followed by florid visual and auditory hallucinations. Mini mental status examination score was 16/30. Both cerebrospinal fluid and plasma anti-NMDA receptor antibodies were detected. A course of intravenous methylprednisolone was given with partial symptom improvement. A hepatic neuroendocrine carcinoma was detected and confirmed on biopsy. Unfortunately, he developed several medical complications: non-ST elevation myocardial infarction, infected foot gangrene and peripheral vascular disease, which made him unsuitable for both surgery and chemotherapy. He passed away 6months later due to the progression of the malignancy. This case illustrated that NMDAR encephalitis may be associated with an uncommon hepatic neuroendocrine carcinoma in an older person, which is responsive to early treatment.

15. Neuronal Autoantibodies and Blood-Brain Barrier Disruption in Subjects at Ultra-High Risk for Psychosis

Abstract Background: Neuronal surface autoantibodies (NSAbs) have been identified in patients with psychotic disorders, with meta-analytical evidence indicating a higher prevalence in first-episode psychosis (FEP), probably dependent on the assay used. The causal significance of these NSAbs is unclear, with a suggestion that that blood–brain barrier disruption (BBBD) may be an important additional factor. We aimed to establish whether, prior to illness onset, NSAbs and BBBD are present in subjects at ultra-high risk (UHR) for psychosis. Methods: Sera from 260 UHR subjects in the EUGEI study and 110 healthy controls were tested with a fixed cell-based assay (CBA) using HEK293 cells that had been transfected to express one of 30+ NSAbs; IgG, IgA and IgM binding was assessed using indirect immunofluorescence. Levels of S100B, a putative marker of BBBD, were assessed using a chemoluminescence assay in this cohort and an FEP cohort (n = 226). Results: NSAbs were present in 8.8% of UHR subjects and 7.3% HCs (ns) with NMDAR the most frequent antigen. Serostatus did not predict transition to psychosis, and 2 of 3 seropositive patients who transitioned to psychosis had antibodies of diverse Ig isotype. Patients with brief limited intermittent psychotic symptoms (BLIPS) were twice as likely to be seropositive at baseline compared to patients who transitioned to psychosis. Interestingly, subjects who were positive on fixed CBA for any NSAb or for only NMDAR antibodies showed trends towards higher negative syndrome scores across multiple scales. These subjects had impaired verbal memory scores as measured by the Rey auditory verbal learning test (RAVLT) (P = .0019), a finding that mirrors patients with NMDAR encephalitis and may be reflective of hippocampal dysfunction.Samples were also tested for NMDAR IgG antibodies using a live CBA; this detected a higher prevalence of NMDAR IgG antibodies in the total cohort than did fixed CBA (19 subjects (5.1%) vs 2 (0.5%); P = .0025).Mean S100B levels were higher in FEP subjects than in UHR subjects (P < .001) and controls (P < .0001). UHR subjects with high S100B levels surprisingly showed lower total psychopathology scores (BPRS; P = .032), less negative symptoms (SANS; P = .039), and disability (GAF; P = .009), whereas in FEP S100B levels were associated with worse positive psychotic symptoms. Conclusion: A minority of subjects at risk of psychosis have NSAbs detectable in serum: These individuals may have worse negative symptoms and demonstrate impaired neurocognition. Further work is required to clarify the immunological and neuroanatomical substrates of these changes. BBBD may be progressive with the development of psychosis. The paradoxical finding of improved symptoms and function in subjects with evidence of greater BBBD differentiates UHR subjects from later stage psychosis and represents an exciting avenue for further investigation.This work was supported by a grant from The Wellcome Trust.

A CASE SERIES ON ANTI NMDAR ENCEPHALITIS

N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune neurological disorder arising from the generation of antibodies which binds to the synaptic proteins. Here we present a case series of 3 cases where the different aspects of treating NMDAR encephalitis are dealt with. The association of ovarian teratoma and the importance of its removal before treating the encephalitis have been discussed in the second case. Apart from the first line and second line agents used in the therapy of NMDAR encephalitis, the importance of managing infections especially urinary tract infection and lower respiratory tract infection with antibiotics have also been discussed. The article also aims to throw light into the treatment of extrapyramidal side effects induced by antipsychotics. At the end, the significance of putting the patient on a ketogenic diet to manage refractory seizures associated with anti-NMDA receptor encephalitis has also been discussed based on reviewing literature.

Delta Brush Pattern Is Not Unique to NMDAR Encephalitis: Evaluation of Two Independent Long-Term EEG Cohorts.

Although its specificity has not previously been investigated in other cohorts, delta brush pattern (DBP) is increasingly reported in the EEGs of patients with anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis. We aimed to investigate the DBP in the EEGs of 2 cohorts; patients with change in consciousness for various causes monitored in the intensive care unit (ICU) (n = 106) and patients with mesial temporal lobe epilepsy (MTLE) with or without antineuronal antibodies (n = 76). These patients were investigated for the presence of DBP, defined as an EEG pattern characterized by delta activity at 1 to 3 Hz with superimposed bursts of rhythmic 12- to 30-Hz activity. Two investigators blindfolded for the clinical and immunological data independently analyzed the EEGs for recognition of this pattern. An EEG picture compatible with DBP was observed in 4 patients; only 1 of them (1.3%) belonged to the MTLE group. She did not bear any of the investigated autoantibodies and was seizure-free after epilepsy surgery. In the ICU group, there were 3 additional patients showing DBP with various diagnoses such as hypoxic encephalopathy, brain tumor, stroke, and metabolic derangements. All of them had died in 1-month period. Our results underlined that DBP is not unique to NMDAR encephalitis; it may very rarely occur in MTLE with good prognosis after surgery and second, in ICU patients who have high mortality rate. Therefore, the presence of this pattern should alert the clinician for NMDAR encephalitis but other possible etiologies should not be ignored.

First reported cases of anti-NMDA receptor encephalitis in Vietnamese adolescents and adults

IntroductionAnti-NMDA receptor encephalitis is increasingly recognised as an important differential diagnosis in patients with encephalitis of unknown aetiology. We report the first case series of patients diagnosed in Vietnam. MethodsSamples of CSF from patients with presumed encephalitis but negative microbiological investigations, who exhibited dyskinesia, autonomic instability or psychosis were tested for antibodies against the NR1 subunit of the glutamate (type-NMDA) receptor using an indirect immunofluorescence assay. ResultsOf 99 patients admitted with all-cause encephalitis over an 18month period, 9.1% (n=9 patients, 5 female, median age 28years) had confirmed NMDAR encephalitis. All patients were admitted from one mental health hospital, and the incidence may therefore be an underestimate. Common features included reduction in speech (n=9), catatonia (n=9), convulsions (n=7), dyskinesia (n=9), rigidity (n=9) and autonomic dysfunction (n=7). Aside from a modest lymphocytic pleocytosis, routine CSF analysis was usually normal. No female patient had ovarian teratoma detected by abdominal ultrasound. Most patients were treated with high dose corticosteroids, and one patient received intravenous immunoglobulin. The median duration of hospitalization was 75days and no patient died during admission. ConclusionsAnti-NMDA receptor encephalitis is an important differential diagnosis to consider for patients presenting with acute onset psychiatric symptoms, who develop ensuing seizures, movement or autonomic disorder in Vietnam. A stronger evidence base for management and access to second line immunotherapy agents may help to reduce morbidity from this disease.

A Case of Catatonia Later Diagnosed with NMDA Receptor Encephalitis

A Case of Catatonia Later Diagnosed with NMDA Receptor Encephalitis

A case of anti–NMDA receptor encephalitis developed with parkinsonism

A case of anti–NMDA receptor encephalitis developed with parkinsonism

Teratoma-associated NMDAr encephalitis: management considerations.

Teratoma-associated NMDAr encephalitis: management considerations.

NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: The 2016 Cotzias Lecture.

Investigations during the last 10 years have revealed a group of disorders mediated by antibodies against ion channels and synaptic receptors, which cause both neurologic and psychiatric symptoms. In this review, I discuss the process of discovery and immunologic triggers of these disorders, and use anti-NMDA receptor encephalitis to emphasize the importance of understanding the underlying physiopathologic mechanisms in those diseases. A better knowledge of these mechanisms reveals points of convergence with other disorders (e.g., schizophrenia), suggests treatment strategies beyond immunotherapy, and is helping us understand how memories are formed and retrieved.

Anti-N-methyl-d-aspartate receptor encephalitis associated with intracranial Angiostrongylus cantonensis infection: a case report

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently described paraneoplastic syndrome with prominent neuropsychiatric symptoms. Many of these cases are associated with neoplasma especially teratoma. In addition, a few of cases with anti-NMDAR antibodies triggered by viral infection have been reported, but never by parasitic infection. Here, we report a novel case of NMDA receptor encephalitis in a 51-year-old male related to the development of anti-NMDAR antibodies triggered by Angiostrongylus cantonensis infection.

Spontaneous recovery of memory functions in an untreated case of anti NMDAR encephalitis – a reason to maintain hope

Objective: Anti N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder that was only fully discovered recently and neuropsychological outcome data remains sparse. We present the case of BA, a 19-year-old male, which illustrates the cognitive outcome in an untreated case over a time period of over 2½ years.Method: We conducted three cognitive assessments, including tests of memory and executive functioning, over this time period and considered the evidence for reliable change in memory function using the Wechsler Advanced Clinical Solutions (ACS) serial assessment package.Results: Our findings revealed mild memory problems 6 months post-discharge with, at best, static and potentially declining memory functioning at follow-up assessment 12 months post-discharge. However, the results of testing at 30 months post-discharge revealed significant improvements in immediate and delayed memory index performances.Conclusions: Our report of a case of anti-NMDAR encephalitis provides evidence for spontaneous improvements in memory functioning occurring more than 2 years after initial assessment and also demonstrates both the utility and potential limitations of the ACS serial assessment software when used in a relatively typical clinical assessment situation.

Successful treatment of anti-NMDA receptor encephalitis with a prompt ovarian tumour removal and prolonged course of plasmapheresis: A case report.

Anti-N-methyl-d-aspartate-receptor (NMDAR) encephalitis is an uncommon autoimmune disorder with a wide spectrum of neuropsychiatric symptoms. There is a great requirement to emphasize the importance of a multidisciplinary team approach in the process of diagnosis and treatment of the potentially fatal condition, including psychiatrists, neurologists, gynaecologists and intensivists. Physicians must be aware that psychiatric and neurological disorders, which are typical features for NMDAR encephalitis in young women with ovarian tumours, may progress into status epilepticus and respiratory insufficiency. This disease can only be successfully treated with prompt surgical intervention and an early implementation of a wide array of immunosuppressive therapies. Optimal timing of initiation of therapeutic plasma exchange, as well as duration of treatment necessary to achieve desirable outcomes in patients with NMDAR remains unknown. The present case report aims to raise awareness about the importance of early implementation of this potentially life-saving therapy and continuing the treatment courses until full subsidence of symptoms.