anti-NMDAR Encephalitis Presenting Research Articles

The Spectrum of Movement Disorders in Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis Both in Children and Adults: An Experience From a Single Tertiary Care Center.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a form of autoimmune encephalitis. The characteristic clinical features include seizure, psychosis-like symptoms, abnormal movements, and autonomic disturbances. Patients with anti-NMDAR encephalitis can present with various types of movement disorders. Typically, the movement disorders start following intervals of psychiatric and prodromal manifestations in young adults; however, in children, these might be an early presentation of anti-NMDAR encephalitis. The disease is under-recognized and underdiagnosed in Pakistan. Early recognition of the disease is important to commence timely treatment leading to a better prognosis. Here we present a collection of anti-NMDAR encephalitis patients, specifically focussing on the different types of movement disorders and the differences in clinical manifestations between children and adults.

A-58 Unusual Presentation of Anti-NMDAR Encephalitis in a Young Adult Male: A Case Study

Abstract Objective To illustrate an unusual presentation of anti-n-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis in a young adult male. Anti-NMDAR encephalitis is an autoimmune-mediated disorder with psychiatric and neurological features that can have lasting impact on cognition. Unique presentation, diagnosis, and assessment are presented. Method Patient is a 28-year-old, Caucasian male with a history of bipolar disorder. Initial hospital presentation was characterized by headache, tremor, and acute altered mental status. Imaging revealed chronic meningitis with diffuse leptomeningeal enhancement/multiple cranial nerve enhancement, hydrocephalus, and Chiari I malformation. He underwent external ventricular drain (EVD) placement and was discharged upon stabilization. He presented 1 month later with symptom recurrence and interval development of hydrocephalus. CSF studies were positive for NMDAR antibody. He was treated with immunotherapy. His 3-month long hospitalization was complicated by acute respiratory failure and intracerebral and intraventricular hemorrhages. He was discharged to 1 month of inpatient rehabilitation. Results Neuropsychological assessment was completed 4 months following discharge from rehabilitation. Visual deficits due to grade 1 papilledema complicated testing. Results revealed frontal deficits (focused attention, processing, and executive functions), with intact verbal learning/memory. This deviates from previous literature that specify verbal memory dysfunction as a core long-term outcome of anti-NMDAR encephalitis. Conclusions This case highlights an unusual presentation and neuropsychological assessment of anti-NMDAR encephalitis. Rare presentations of anti-NMDAR encephalitis can preclude clinical diagnosis and compromise long-term cognitive outcomes if not rapidly and effectively treated. Additionally, mood symptoms may have been early manifestation of the patient’s disease process. Despite acute complications, he demonstrated remarkable functional and cognitive recovery.

Atypical Presentation of Anti-NMDAR encephalitis in a Male Patient – an Unfortunate Mimic

Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory disorder with a predilection for females. Males present differently, with seizures rather than the better-recognized constellation of psychiatric and behavioral symptoms dominating the initial stages of the disease, providing a potential substrate for delayed recognition and treatment. Case Presentation An 18-year-old man presented with fever and “seizures. When examined, he was febrile but alert and coherent. His neurologic, respiratory, cardiovascular, and abdominal examinations were unremarkable. Diagnosed with infective meningoencephalitis, he was started on intravenous ceftriaxone and acyclovir concurrently with anti-epileptic medications. However, he deteriorated into refractory status epilepticus. Electroencephalograms showed left temporo-parietal seizures. Cerebrospinal fluid analysis revealed inflammatory features, but the virologic assays and bacterial cultures returned negative. Magnetic resonance imaging scans performed in the first and second week from symptom-onset demonstrated the interval development of widespread sulcal T2 hyperintensity, with florid and diffuse leptomeningeal enhancement. Anti-NMDAR antibodies were subsequently detected in his cerebrospinal fluid by indirect immunofluorescence. Diagnosed with anti-NMDAR encephalitis, he received plasmapheresis, methylprednisolone and immunoglobulin infusions. Conclusion Anti-NMDAR encephalitis should be considered in patients, especially males, who are treated for suspected infectious meningoencephalitis, but continue to deteriorate, even in the absence of prominent psychiatric or behavioral symptoms, considering how the initial symptoms differ between the genders. The interval development of diffuse and florid leptomeningeal enhancement on sequential magnetic resonance imaging scans of our patient has not been described in prior reports, and may be reflective of the underlying inflammatory processes.

Editors' Note: Clinical Significance of Anti-NMDAR Concurrent With Glial or Neuronal Surface Antibodies

In “Clinical Significance of Anti-NMDAR Concurrent With Glial or Neuronal Surface Antibodies,” Martinez-Hernandez et al. reported that between 4% and 7.5% of patients with anti-NMDAR encephalitis have concurrent glial or neuronal surface antibodies (glial-Ab or NS-Ab). Although they found that the presence of myelin oligodendrocyte glycoprotein (MOG) or aquaporin 4 antibodies was associated with demyelinating disorders and NS-Ab was associated with medial temporal or subcortical MRI findings, a positive glial fibrillary acidic protein (GFAP) antibody was nonspecific. McKeon et al. suggested the coexistence of GFAP antibodies and their significance may have been underreported in this study as both serum and CSF testing can be imperfect and that a phenotypic clinical-radiographic presentation associated with this antibody—a steroid-responsive meningoencephalitis with a predilection for the midbrain, cerebellar white matter, hippocampus, and cortex—may have been missed. Martinez-Hernandez et al. responded that McKeon et al. (1) misunderstood the frequency of NMDAR-Ab and GFAP-Ab co-occurrence in their cohort and (2) mischaracterized the specificity of GFAP-Ab. Lancaster reinforced Martinez-Hernandez et al.’s findings, noting that clinicians must be aware that patients with anti-NMDAR encephalitis can have multiple antibodies, which may impact presentation and prognosis. Dalmau and Martinez-Hernandez further commented that patients with NMDAR-Ab who have an atypical presentation of anti-NMDAR encephalitis should prompt consideration of the possibility that the presence of NMDAR-Ab was a false positive or that there could be concurrent antibodies but that the conclusion that any particular clinical or radiologic findings are associated with any particular antibody can only be made after careful evaluation for disease specificity. In “Clinical Significance of Anti-NMDAR Concurrent With Glial or Neuronal Surface Antibodies,” Martinez-Hernandez et al. reported that between 4% and 7.5% of patients with anti-NMDAR encephalitis have concurrent glial or neuronal surface antibodies (glial-Ab or NS-Ab). Although they found that the presence of myelin oligodendrocyte glycoprotein (MOG) or aquaporin 4 antibodies was associated with demyelinating disorders and NS-Ab was associated with medial temporal or subcortical MRI findings, a positive glial fibrillary acidic protein (GFAP) antibody was nonspecific. McKeon et al. suggested the coexistence of GFAP antibodies and their significance may have been underreported in this study as both serum and CSF testing can be imperfect and that a phenotypic clinical-radiographic presentation associated with this antibody—a steroid-responsive meningoencephalitis with a predilection for the midbrain, cerebellar white matter, hippocampus, and cortex—may have been missed. Martinez-Hernandez et al. responded that McKeon et al. (1) misunderstood the frequency of NMDAR-Ab and GFAP-Ab co-occurrence in their cohort and (2) mischaracterized the specificity of GFAP-Ab. Lancaster reinforced Martinez-Hernandez et al.’s findings, noting that clinicians must be aware that patients with anti-NMDAR encephalitis can have multiple antibodies, which may impact presentation and prognosis. Dalmau and Martinez-Hernandez further commented that patients with NMDAR-Ab who have an atypical presentation of anti-NMDAR encephalitis should prompt consideration of the possibility that the presence of NMDAR-Ab was a false positive or that there could be concurrent antibodies but that the conclusion that any particular clinical or radiologic findings are associated with any particular antibody can only be made after careful evaluation for disease specificity.

Anti-NMDAR Encephalitis Presenting as Stroke-like Episodes in Children: A Case Series from a Tertiary Care Referral Centre from Southern India.

ABSTRACTBackground:Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the common causes of treatable encephalitis in children characterized by severe memory deficit, speech disturbances, seizures, autonomic dysfunction, and movement disorders. Hemiparesis/stroke-like episode is not a usual presenting complaint of NMDAR encephalitis. The objective of this study was to report confirmed cases of seropositive anti-NMDAR encephalitis in children who presented with hemiparesis/stroke-like episodes.Materials and Methods:Retrospective review of charts of patients with a diagnosis of NMDAR encephalitis was performed at the pediatric neurology department attached to a tertiary care hospital for 6 years from March 2014 to February 2020. Only those case records with NMDAR seropositivity in the cerebrospinal fluid were collected and those who presented with stroke-like episode/hemiparesis were retrieved separately and the data were extracted in a predesigned proforma and analyzed.Results:Six children of 24 seropositive anti-NMDAR encephalitis presented with hemiparesis/stroke-like episode. All the six patients presented with hemiparesis, behavioral changes, and regression of speech. Three children had seizures and one child had Epilepsia partialis continua. Two children had dystonia and choreoathetosis. Methylprednisolone followed by oral steroids were administered in all patients. Cases 1, 2, and 4 made a full recovery within 7 days, but cases 3, 5, and 6 showed improvement after 20 days following additional IVIG. Four children have cognitive decline and behavioral problems. Case 6 had relapse and recovered with rituximab.Conclusion:Anti-NMDA receptor encephalitis which is a potentially treatable disease should be considered in the differential diagnosis when a child presents with hemiparesis/stroke-like episode.

Anti-NMDAR encephalitis presenting with early and prominent orolingual dyskinesia and its association with ovarian serous cystadenoma- case report

Autoimmune encephalitis is relatively a new entity. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most common and well studied autoimmune encephalitis. We report a case of anti-NMDAR encephalitis presenting initially with orolingual dyskinesia and its association with large ovarian serous cystadenoma. She was given complete course of intravenous immunoglobulin (2GM/KG) as well as removal of the tumor. Histopathology of the cystic lesion revealed serous cystadenoma of the ovary. The patient is now on regular follow up and is doing well. To best of our knowledge, this is the first case in literature showing association of anti-NMDAR encephalitis with serous cystadenoma of ovary and orolingual dyskinesia as initial clinical presentation. Keywords: AntiNMDAR encephalitis, Intravenous immunoglobulin (IVIG), Serous cystadenoma of ovary.

Bilateral thalamic changes in anti-NMDAR encephalitis presenting with hemichorea and dystonia and acute transient psychotic disorder

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is one of the most common causes of autoimmune encephalitis. Both movement disorders and neuropsychiatric manifestations are considered core features of anti-NMDAR encephalitis. Strong clinical suspicion, along with NMDAR antibody positivity in paired sample of serum and cerebrospinal fluid, with supportive MRI changes clinch diagnosis in majority. We herein report a case of a middle-aged woman with subacute behavioral abnormalities, which were so severe that forced her to attempt suicide. Hemichorea and dystonia, which appeared later in course, are not previously reported movement disorders in combination in anti-NMDAR encephalitis. Further, magnetic resonance imaging showed bilateral thalamic hyperintensities with diffusion restriction, which are in turn not described in this entity. After amalgamation of history, especially the presence of neuropsychiatric symptoms, clinical features, physical examination, and investigations, the diagnosis of anti-NMDAR encephalitis could be established. Our case not only highlights that the combination of hemichorea and dystonia can be features of anti-NMDAR encephalitis, but adds novelty by bilateral symmetric thalamic changes.

New Onset Focal Seizure Clusters in Children: Expanding the Spectrum of Anti NMDAR Encephalitis.

Anti-N-methyl-d-aspartate receptor (Anti-NMDAR) Encephalitis classically presents with polysymptomatic presentation of behavioral or cognitive changes, seizures, and focal deficits. Large series in adults and children have described the above features. Monosymptomatic presentation of Anti NMDAR encephalitis is rare and in literature single case reports in adults and children are available. Here we report a series of 6 children presenting with seizure alone and thus expanding the clinical spectrum of Anti NMDAR encephalitis. This is a a retrospective case series of 6 cases of anti NMDAR encephalitis treated in our institute, which is a tertiary referral center between 2010 and 2014. All the patients with NMDA encephalitis were initially included. The baseline demographics, clinical presentations, investigations (CSF, MRI and EEG), course in the hospital, details of treatment, short and long term outcomes were documented from the available medical records. Children presenting with monosymptomatic seizure clusters were only included in the final analysis. Twenty eight children were diagnosed with ant NMDA R encephalitis during the study period. 22 children had classical polysymptomatic presentations and were not included in this analysis. The remaining 6 children (5 girls and one boy), who presented with only acute seizure clusters were included in the study. All children presented with acute cluster of focal seizures. Four out of six had focal status epilepticus while 2 out of six had recurrent focal seizures. Commonest semiology was clonic seizure in 4/6 and one child had dystonic seizure and one had tonic seizure. All patients were started on steroids and antiepileptic drugs. No other immunomodulators or immunosuppressants were used. On discharge all patients where seizure free and with no focal deficits. This is the first series of Anti NMDAR encephalitis presenting as new onset seizure clusters in children. Unlike the existing literature, these children did not develop any other symptoms. We propose that focal encephalitis could be the reason for this monosymptomatic presentation.

Anti-NMDAR encephalitis with simultaneous hypertrophic pachymeningitis in a 68-year-old male: a rare case report

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most frequent types of autoimmune encephalitis. However, the instigating mechanisms are as yet not fully ascertained. Cardinal clinical manifestations of anti-NMDAR encephalitis include acute behavioural change, psychosis, and catatonia. As the level of diagnosis increases, encephalitis becomes more common, but there are never been published in patients with anti-NMDAR encephalitis and simultaneous hypertrophic pachymeningitis.Case presentationA sixty-eight-year-old man who presented with mental, behavioral abnormalities, unstable walking, headaches, and erratic hand movements. The neuropsychiatric symptoms and cerebrospinal fluid examination was consistent with the diagnosis criteria of anti-NMDAR encephalitis. Magnetic resonance imaging of the brain showed a thickening of dura mater localized at the left tentorium cerebelli, left cerebral hemisphere, and cerebral falx; the thickening dura mater was characterized by an intense contrast enhancement after the administration of gadolinium. High doses of intravenous methylprednisolone were administrated during his hospitalization. After 5 days, the patient’s condition improved.ConclusionsWe herein describe a rare case of a 68-year-old man with anti-NMDAR encephalitis presenting with concomitant hypertrophic pachymeningitis. We systematically expounded anti-NMDAR encephalitis and hypertrophic pachymeningitis, and made bold conjectures on the etiology and pathogenesis of these two diseases, hoping to stimulate new ideas from clinicians and basic medical researchers.

Brain astrocytoma misdiagnosed as anti-NMDAR encephalitis: a case report

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, which is the most common type of autoimmune encephalitis, is caused by the production of autoantibodies against NMDA receptor. Anti-NMDAR encephalitis patients present with various non-specific symptoms, such as abnormal psychiatric or behaviour, speech dysfunction, cognitive dysfunction, seizures, movement disorders, decreased level of consciousness, and central hypoventilation or autonomic dysfunction.Case presentationA 67-year-old man presented with new-onset focal seizures. The brain magnetic resonance imaging (MRI) plain scan and enhanced scan showed abnormal signal on the proximal midline frontoparietal junction region. Anti-NMDAR antibody was detected in cerebrospinal fluid (CSF) and serum using a commercial kit (Euroimmune, Germany) by indirect immunofluorescence testing (IIFT) according to the manufacturer’s instructions for twice. Both of the test results were positive in CSF and serum. The patient was diagnosed as anti-NMDAR encephalitis and then was treated repeatedly with large dose of intravenous corticosteroids and gamma globulin. Accordingly, the refractory nature of seizures in this case may be attributed to NMDAR autoantibodies. When the patient presented at the hospital for the third time, the brain MRI revealed an increase in the size of the frontal parietal lesion and one new lesion in the left basal ganglia. The patient underwent a surgical biopsy and astrocytoma was confirmed by histopathology.ConclusionsAlthough the sensitivity and specificity of anti-NMDAR-IgG antibodies in CSF to diagnose anti-NMDAR encephalitis are close to 100%, it is not absolute. Anti-NMDAR antibodies were positive, which might make the diagnosis more complex. The diagnosis of atypical presentation of anti-NMDAR encephalitis requires reasonable exclusion of other disorders.

Bimodal presentation of Anti-NMDAR encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome, which is related to tumors, such as teratomas of the ovaries. To our knowledge, this is the first reported case of anti-NMDAR encephalitis concomitantly occurring in a pediatric patient with newly identified urothelial bladder neoplasms.A 5-year-old boy presented with a flu-like illness, disturbance of consciousness, hemiplegia, generalized tonic-clonic seizures last for 40 min, and central hypoventilation. The Computed tomography (CT) of his chest, abdomen and pelvis showed that there was a polypoid lesion on the right anterior wall of the urinary bladder. Then, a transurethral resection of the bladder tumor (TURBT) was performed, and the histopathology revealed a papillary urothelial neoplasm. He recovered gradually and had complete resolution of symptoms after the surgery and immunotherapy.Anti-NMDAR encephalitis can be caused by urothelial bladder neoplasms. Early tumor resection is beneficial to the rapid and complete recovery of patients with anti-NMDAR encephalitis.

N-Methyl-d-aspartate Receptor Antibody Encephalitis: A Concise Review of the Disorder, Diagnosis, and Management.

Anti-NMDA ( N-methyl-d-aspartate) receptor (anti-NMDAR) encephalitis is one of the most common paraneoplastic encephalitides. It occurs in both sexes, across all age ranges, and may occur in the presence or absence of an associated tumor. Its pathogenesis and clinical presentation relate to the presence of IgG1 or IgG3 antibodies targeting the NR1 subunit of the NMDA receptor, leading to a disinhibition of neuronal excitatory pathways. Initial clinical manifestations may be nonspecific, resembling a viral-like illness; however, with disease progression, symptoms can become quite severe, including prominent psychiatric features, cognitive problems, motor dysfunction, and autonomic instability. Anti-NMDAR encephalitis may even result in death in severe untreated cases. Diagnosis can be challenging, given that initial laboratory and radiographic results are typically nonspecific. The majority of patients respond to first or second-line treatments, although therapeutic options remain limited, usually consisting of tumor removal (if there is confirmation of an underlying malignancy) in conjunction with prompt initiation of immunosuppressive medications along with intravenous immunoglobulins and/or plasma exchange. Although the clinical presentation of anti-NMDAR encephalitis overlaps with several other more common neurological and psychiatric disorders, early diagnosis and treatment is essential for a positive prognosis. Here, we concisely review the pathogenesis, diagnosis, and clinical management of this disease.

F186. Common Non-Behavioral Clinical Features of Anti-NMDAR Encephalitis Presenting as a Psychiatric Disorder

Diagnosing anti-NMDA receptor encephalitis (anti-NMDArE) can be challenging because it often presents in the form of a primary psychiatric disorder, and approximately three-fourths of patients are first evaluated by a psychiatrist. Prompt and effective treatment can avert serious long-term disability or death, but timely intervention requires early recognition. Descriptions of a prototypical episode have been published, but there is enormous variability between patients with respect to how the illness course evolves. Greater awareness of its salient clinical features could promote earlier accurate diagnosis.

Early identification of anti-NMDA receptor encephalitis presenting cerebral lesions in unconventional locations on magnetic resonance imaging

To facilitate the diagnosis of anti-NMDAR encephalitis presenting with brain lesions in unconventional locations (BLUL) on MRI, we retrospectively analyzed forty-five Chinese patients. Eighteen (40.0%) of their MRI initially exhibited one or more BLUL. These locations predominantly included cerebral gray matter (cortex, basal ganglia and thalamus), as well as white matter and brainstem. Due to these BLUL, thirteen (72.2%) patients were originally misdiagnosed with other diseases and developed poor clinical and imaging outcomes. Therefore, anti-NMDAR encephalitis has unpredictable MRI findings that easily obscure its diagnosis and cause serious sequelae. Anti-NMDAR antibody tests are highly recommended in patients with BLUL.

PP13.10 – 2890: Chronic and relapsing paediatric anti-NMDAR encephalitis: Two cases and a literature review

Background Clinical presentation of anti-NMDAR encephalitis is usually by a combination of neurologic, psychiatric and autonomic dysfunction. Prompt recognition and early immunotherapy is associated with better outcomes. The relapse rate has been reported to be 12–24%. Pruss et al. described the presence of NMDAR antibodies in the course of 30% of individuals with herpes simplex encephalitis (HSE). In a paediatric sample with HSE, 7 out of 20 children (35%) relapsed and 3 out of those 7 patients were found to be NMDAR antibodies positive. Case 1 This 12-year-old boy presented with fever and confusion. Herpes simplex DNA PCR was positive on cerebrospinal fluid (CSF). He received intravenous acyclovir with excellent response and clearance of his CSF. He represented few days later with epilepsia partialis continua requiring intensive care unit (ICU) admission. Serum anti-NMDAR antibodies were positive. He was treated with steroids, plasmapharesis, rituximab and cyclophosmide. He made a slow recovery over a few weeks; however serum anti-NMDAR antibodies continue to be positive with persistent elevation of CSF protein over the following 8 months despite regular immunotherapy. Case 2 This 15-year-old girl presented initially with seizures and agitation. She subsequently developed orofacial dyskinesia with worsening encephalopathy and seizures necessitating ICU admission. Serum anti-NMDAR antibodies were positive. She was treated with steroids, plasmapharesis and rituximab with good recovery. She represented 30 months later with psychiatric symptoms. Anti-NMDAR antibodies were positive in the CSF but negative in the serum. She responded well to immunotherapy. Discussion and conclusion: In their large cohort, Titulaer et al defined a relapse as “new onset or worsening of symptoms occurring after at least 2 months of clinical improvement”. Clinical recovery can take up to 18 months, however no literature exists regarding length of seropositivity. These two cases illustrate the variable natural history of the condition.

Long duration between presentation of probable anti-N-methyl-D-aspartate receptor encephalitis and either clinical relapse or positive serum autoantibodies

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune encephalitis first described in 2007. This condition has a well-characterised clinical phenotype with a multistage presentation beginning with prodromal symptoms, psychosis, cognitive deficits, and seizures, which can progress to involve movement disorders, catatonia, autonomic instability, and central hypoventilation requiring ventilatory support. Our first patient demonstrates, to our knowledge, the longest duration between the presentation of anti-NMDAR encephalitis and clinical relapse that has thus far been described. Our second patient highlights a clinical scenario where positive serum autoantibodies are demonstrated six years following complete clinical recovery, in the absence of clinical features of a relapse or a malignancy on screening. These patients highlight the importance of long-term follow up and tumour surveillance, and the role of electroconvulsive therapy in the management of catatonia. These cases also support the need for future studies evaluating the role of maintenance immunosuppression in patients at high risk for relapses.

Anti-NMDA Receptor Encephalitis Presenting with Focal Non-Convulsive Status Epilepticus in a Child

A previously healthy 9-year-old girl presented to an emergency department (ED) with headache, dizziness, blurry vision, and abnormal visual perceptions. She was diagnosed with migraine, treated symptomatically, and discharged. Over the course of days, she became progressively somnolent, and returned to the ED, where she was found to have a right inferior quadrantanopsia and sixth nerve palsy. Magnetic resonance imaging (MRI) of the brain showed gyral swelling of the left parieto-occipital lobe. Continuous electroencephalogram (EEG) monitoring revealed focal non-convulsive status epilepticus (NCSE) in the left occipital region. Cerebrospinal fluid (CSF) was positive for antibodies directed against the N-methyl-d-aspartate receptor (NMDAR). This case is the first report of anti-NMDAR encephalitis presenting with focal non-convulsive status epilepticus (NCSE).