Receptor Antibody Encephalitis Research Articles

Chapter 26 - Autoimmune neurologic disorders in children

Autoimmune neurologic diseases are of major clinical importance in children. Antibody-mediated diseases of the central nervous system are now increasingly recognized in childhood, where the antibodies bind to cell surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The antibodies are directed towards ion channels, receptors, and membrane proteins; and the diseases include limbic encephalitis and N-methyl-d-aspartate receptor-antibody encephalitis, among many others. Additionally there are conditions where the wider immune system is implicated. Neurologic features like seizures, movement disorders, autonomic dysfunction, and sleep disorders, with neuroimaging and electrophysiologic features, may indicate a specific antibody-mediated or immune disorder. Often, phenotypic overlap is observed between these conditions, and phenotypic variation seen in children with the same condition. Nevertheless, many patients benefit from immunotherapy with substantial improvement, although huge efforts are still required to optimize the outcome for many patients. In many patients no antibodies have yet been identified, even though they respond to immunotherapies. Here we describe the known antibodies and associated diseases, discuss conditions that are thought to be immune-mediated but have no known immunologic biomarker, and provide guidelines for the investigation and classification of these disorders.

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).

N-methyl-D-aspartate receptor antibody encephalitis: how do we evaluate symptomatic treatment?

This commentary is on the original article by Mohammad et al. on pages 376–384 of this issue.

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.

Anti-NMDA Receptor Antibody Encephalitis Presenting with Unilateral Non-convulsive Status Epilepticus in a Male Patient

Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is an autoimmune antibody encephalitis with psychiatric symptoms, memory disturbances, seizures and abnormal movements. It is more common in young women. We report a young man diagnosed as anti-NMDA receptor antibody encephalitis and presenting with confusion due to non-convulsive status epilepticus involving unilateral hemisphere.

Posterior cortical and white matter changes on MRI in anti-AMPA receptor antibody encephalitis.

A 73-year-old woman presented with a 4-day history of progressive confusion. Her family reported that she was behaving erratically and had developed paranoia and hallucinations.

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.

Focal seizures in children with anti-NMDA receptor antibody encephalitis

We investigated the electroclinical features of seizures occurring in children with anti-NMDA receptor antibody encephalitis. Clinical features and video EEG recordings were analyzed from pediatric patients with anti-NMDA receptor antibody encephalitis at our center over a six year period. We identified eight pediatric patients with anti-NMDA receptor antibody encephalitis. Video EEG captured multiple focal seizures in four patients. Ictal onset in all four patients consisted of a focal rhythmic sharpened 6-12Hz activity that subsequently spread to one or both hemispheres. When there was a clinical correlate, seizure semiology was limb posturing with or without dyscognitive features. While background abnormalities were noted at presentation in three cases, the initial EEG background was normal in five, including three patients presenting with seizures. The EEG background deteriorated with clinical progression. Focal seizures are common in pediatric patients with anti-NMDA receptor antibody encephalitis and have a characteristic ictal onset pattern. Anti-NMDA receptor antibody encephalitis should be considered in the differential diagnosis of a child presenting with new onset focal seizures, irrespective of the EEG background, especially if accompanied by dyskinesia, psychiatric symptoms or impaired cognition.

GABAA receptor and LGI1 antibody encephalitis in a patient with thymoma.

Autoimmune encephalitis related to antibodies against neuronal cell surface and synaptic proteins is a new category of disorders in which the targets are well-known proteins and receptors involved in synaptic transmission and neuronal excitability. GABAA receptor is one of the latest identified antigens within this category.1 High-titer serum and CSF GABAA receptor antibodies were recently reported in 6 patients with autoimmune encephalitis associated with seizures or status epilepticus, 4 of them requiring pharmacologic-induced coma. Patients' brain MRIs showed characteristic multiple cortical and subcortical abnormalities with fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity. Antibodies to LGI1 are associated with limbic encephalitis previously attributed to voltage-gated potassium channels (VGKC).2 Coexistence of these antibodies is rare and intriguing.

Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-D-aspartate receptor antibody encephalitis: A retrospective review.

Anti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis is an increasingly recognized form of autoimmune encephalitis. Conventional treatments include therapies such as corticosteroids, intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE). Although TPE is regularly used for treatment of anti-NMDA receptor antibody encephalitis, the American Society for Apheresis has given it a category III recommendation only. Earlier administered immunotherapies in tumor-negative patients may facilitate faster recoveries, but it remains unclear whether or not TPE is superior to steroids and/or IVIG. We retrospectively evaluated 10 of 14 patients that received steroids and TPE with modified Rankin scores and subjectively assessed the point of largest sustained improvement in all 14 patients. In the patients that received both steroids and TPE at our institution during the same hospitalization (only 10 of 14 patients), 7/10 patients after TPE had improved with the modified Rankin score versus 3/10 patients after steroids. The average modified Rankin score improvement after steroids in this group was -0.1 as compared with 0.4 after TPE. Based on subjective chart review analysis during which all 14 patients were assessed, the largest sustained improvement occurred immediately following the third-fifth exchange in 9/14 patients, whereas only 2/14 patients appeared to have had significant benefit immediately following steroids. This is compelling preliminary data that suggests that corticosteroids may not be as effective compared to steroids followed by TPE. Given the importance of time-sensitive treatment, more formal studies may illuminate the ideal first-line treatment for anti-NMDA receptor antibody encephalitis.

N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children

ObjectiveN-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological...

Anti-NMDA-receptor antibody encephalitis in infants.

PurposeAnti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis is an autoimmune disorder manifesting subacutely with prominent aberrant movements and psychiatric symptoms. The clinical course is one of progressive clinical deterioration that can be halted and often reversed by early diagnosis and treatment. Patterns of presentation and etiology of anti-NMDA-receptor antibody encephalitis are dependent on age and can be challenging to recognize in very young children.ReportsSequential clinical case observations of anti-NMDA-receptor antibody encephalitis presenting in very young children were examined over a year at a single tertiary pediatric institution. Cerebrospinal fluid confirmed anti-NMDA-receptor antibodies in two cases (a 21-month-old boy and a 29-month-old girl) that demonstrated either bizarre behavioral patterns or status epilepticus both associated with progressive deterioration. Once recognized, the clinical course was arrested and reversed by aggressive treatment with plasma exchange, immunoglobulin, and high dose IV steroids.ConclusionInfants with anti-NMDA-receptor antibody encephalitis can present with frank seizures or seizure mimics. Regardless, prompt recognition and aggressive treatment of anti-NMDA-receptor antibody encephalitis, while challenging, can quickly arrest deterioration and hasten recovery, thereby, limiting neurological morbidity.

Poster 360 Prolonged Inpatient Rehabilitation in a Patient with Severe N-Methyl-D-Aspartate Receptor Antibody Encephalitis. A Case Report

PM&RVolume 6, Issue 9S p. S311-S311 Saturday Poster Presentations - Poster Hall Poster 360 Prolonged Inpatient Rehabilitation in a Patient with Severe N-Methyl-D-Aspartate Receptor Antibody Encephalitis. A Case Report Jeffrey Algra MD MS, Jeffrey Algra MD MS Montefiore Medical Center, New York, NY, United StatesSearch for more papers by this authorQian Xu MD, Qian Xu MD Montefiore Medical Center, New York, NY, United StatesSearch for more papers by this authorHeidi N. Fusco MD, Heidi N. Fusco MD Montefiore Medical Center, New York, NY, United StatesSearch for more papers by this author Jeffrey Algra MD MS, Jeffrey Algra MD MS Montefiore Medical Center, New York, NY, United StatesSearch for more papers by this authorQian Xu MD, Qian Xu MD Montefiore Medical Center, New York, NY, United StatesSearch for more papers by this authorHeidi N. Fusco MD, Heidi N. Fusco MD Montefiore Medical Center, New York, NY, United StatesSearch for more papers by this author First published: 29 September 2014 https://doi.org/10.1016/j.pmrj.2014.08.739Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume6, Issue9SSeptember 2014Pages S311-S311 RelatedInformation

N-methyl-D-aspartate receptor antibody encephalitis: how much treatment is enough?

This commentary is on the case report by Tatencloux et al. on pages 95–99 of this issue.

Sudden and isolated Broca's aphasia: A new clinical phenotype of anti NMDA receptor antibodies encephalitis in children

BackgroundAnti NMDA receptor (anti NMDAR) encephalitis is a well-characterized entity in children associating movement disorders, psychiatric features and speech difficulties. Novel phenotypes have been described in adults. Methods and ResultsA 4-year-old girl presented partial seizures which evolved towards sudden and isolated Broca's aphasia. Anti NMDAR antibodies were positive in CSF and serum confirming anti NMDAR encephalitis. Clinical recovery was observed after a specific treatment. ConclusionThis case widens the clinical spectrum of anti-NMDAR encephalitis in children and awareness of this newly identified symptom is important as early treatment is a predictor of good outcome

A case of inflammatory peripheral nerve destruction antedating anti-NMDA receptor encephalitis

NMDA receptor (NMDAR) antibody encephalitis is the second most common autoimmune encephalitis after acute disseminated encephalomyelitis, presenting with a multistage clinical progression with prodromal signs, psychiatric abnormalities, reduced levels of consciousness, epileptic seizures, dyskinesias, and autonomic dysfunction.1 Pathogenic NMDAR autoantibodies downregulate NMDARs in cultured hippocampal neurons2 and after injection into the rat brain.3 Teratomas are common in adult women and are believed to trigger the antibody response against NMDARs by ectopically expressing neuronal antigens.1 Causal factors in tumor-negative patients are largely unknown. Recent studies showed that infectious encephalitides with herpes simplex virus (HSE) are associated with the generation of NMDAR antibodies4 and that antibodies cause immunotherapy-responsive relapsing symptoms post-HSE.5 It is unknown, however, whether further types of neuronal damage can trigger a secondary immune response leading to NMDAR encephalitis.

Herpes Simplex and NMDA Encephalitides

Investigators at University of Texas Southwestern Medical Center, Dallas, TX, report 2 male patients, an infant and adult, with confirmed herpes simplex encephalitis (HSE) and anti-NMDA receptor antibody encephalitis.

Herpes Simplex Encephalitis as a Potential Cause of Anti–N-Methyl-d-Aspartate Receptor Antibody Encephalitis

Encephalitis mediated by anti-N-methyl-D-aspartate (NMDA) receptor antibodies and herpes simplex (HS) encephalitis are seemingly separate causes of encephalopathy in adults and children. Herpes simplex encephalitis is infectious, and anti-NMDA receptor antibody encephalitis is autoimmune in origin. Both can cause seizures and encephalopathy, although the latter can also cause psychiatric symptoms and movement disorders. Owing to the rarity of these 2 diseases, patients with co-occurrence are important because they alert clinicians to possible links between 2 seemingly separate processes. In a case series of 2 patients observed at our center, we describe an infant and an adult who had confirmed HS encephalitis and then developed confirmed anti-NMDA receptor antibody encephalitis. Polymerase chain reaction testing for HS virus was performed. Testing for NMDA receptor antibodies was performed by Associated Regional and University Pathologists Laboratory in Salt Lake City, Utah. We conclude that atypical cases of HS or other viral encephalitides should be investigated for concomitance of an autoimmune encephalitis. We suspect that the pathophysiologic mechanisms by which HS virus infects neurons produce a higher likelihood of contracting anti-NMDA receptor antibody encephalitis.