The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project

Gable, Mary; Sheriff, Heather; Dalmau, Josep; Tilley, Drake H.; Glaser, Carol

doi:10.1093/cid/cir1038

Cited by 637 publications

(501 citation statements)

References 16 publications

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“…Encephalitides with NMDAR antibodies are the most common CNS antibody-mediated diseases with an incidence exceeding that of any single viral etiology in young patients [59]. The characteristic clinical syndrome of a polysymptomatic encephalopathy affects both adults and children with approximately 40 % of the patients presenting under the age of 18 years and many below the age of 50 years [60].…”

Section: Antibodies To Identified Cns Proteinsmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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Section: Antibodies To Identified Cns Proteinsmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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“…Risk factors for an abnormal outcome are also defined. 4 and a prospective study of adults (n = 134) and children (n = 69) with encephalitis found that infectious encephalitis and immunemediated forms were identified in 42% and 21% of the cohort, respectively. 5 However, most of the previous larger studies of encephalitis in children were undertaken before the advent of neuronal autoantibody testing.…”

Section: What This Study Addsmentioning

confidence: 99%

“…Autoantibody detection is important as immune suppression may improve outcomes, particularly when given early in the disease. 2,3 A recent study suggested that Nmethyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis, the bestknown autoimmune form, is more common than herpes simplex virus (HSV) encephalitis in children and young adults, 4 and a prospective study of adults (n = 134) and children (n = 69) with encephalitis found that infectious encephalitis and immunemediated forms were identified in 42% and 21% of the cohort, respectively. 5 However, most of the previous larger studies of encephalitis in children were undertaken before the advent of neuronal autoantibody testing.…”

Section: What This Study Addsmentioning

confidence: 99%

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

et al. 2015

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BACKGROUND AND OBJECTIVES: Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immunemediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome.METHODS: By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis).RESULTS: An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. CONCLUSIONS:We have defined clinical and radiologic phenotypes of infectious and immunemediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/ autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority. WHAT'S KNOWN ON THIS SUBJECT:Encephalitis is a serious and disabling condition. There are infectious and immune-mediated causes of encephalitis, but many cases remain undiagnosed. WHAT THIS STUDY ADDS:This large single-center study on childhood encephalitis provides insight into the relative frequency and clinicoradiologic phenotypes of infectious, autoantibody-associated, and unknown encephalitis. Risk factors for an abnormal outcome are also defined. 4 and a prospective study of adults (n = 134) and children (n = 69) with encephalitis found that infectious encephalitis and immunemediated forms were identified in 42% and 21% of the cohort, respectively. 5 However, most of the previous larger studies of encephalitis in children were undertaken before the advent of neuronal autoantibody testing. [6][7][8] We studied clinical and radiologic features, serum autoantibodies in acute archived samples, and longterm outcomes in a large ret...

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“…The results of the California Encephalitis Project shed light on the importance of anti-NMDA receptor encephalitis as one more prevalent than infectious causes in younger cohort (<18 years) [1]. Since its first description in 2007, anti N-methyl Daspartate (NMDA) receptor encephalitis is an increasingly identified cause for autoimmune/paraneoplastic encephalitis [2].…”

Section: Editorialmentioning

confidence: 99%

Use of Zolpidem in Disorders of Consciousness Secondary to Autoimmune Encephalitis

Appu¹

2017

J Neuropsychiatry

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EditorialAutoimmune encephalitis is an increasingly identified area for practitioners in Neurology, Child Neurology and Psychiatry. The results of the California Encephalitis Project shed light on the importance of anti-NMDA receptor encephalitis as one more prevalent than infectious causes in younger cohort (<18 years) [1]. Since its first description in 2007, anti N-methyl Daspartate (NMDA) receptor encephalitis is an increasingly identified cause for autoimmune/paraneoplastic encephalitis [2]. Clinical features consist of a prodromal phase of infection (usually viral) associated with headaches, followed by an early phase characterized by psychosis, confusion, amnesia and dysphasia. We have reported hyper religious behavior in our patient [3]. Later stage consists of movement disorders (orolingual dyskinesia), autonomic instability (resulting in mechanical ventilation and coma) and catatonia. Brain MRI is often normal. EEG changes in the form of extreme delta brushes have been described in comatose patients, suggestive of prolonged clinical course [4]. Relation to ovarian teratoma in females demand a thorough evaluation for occult tumors. NMDA receptor encephalitis is responsive to immunotherapy (IVIG, Steroids, Plasma exchange and anti-CD20 antibody, Rituximab), if initiated early in its clinical course, and surgery as indicated for teratomas. We had previously reported a patient in minimally conscious state secondary to NMDA receptor, who after immunotherapy and tumor removal, had responded temporally to Zolpidem and would act appropriately as long as the medication lasts [3]. Based on the clinical experience, we had suggested use of Zolpidem as an adjunct to immunotherapy in patients with anti NMDA receptor encephalitis. This leads us to question the effect of Zolpidem in patients with disorders of consciousness.Zolpidem is an non benzodiazepine imidazopyridine compound that selectively binds to alpha-1 subunit of GABA-A receptor resulting in release of inhibitory neurotransmitter gamma amino butyric acid (GABA). Numerous case reports, case series, cohort studies, randomized placebo controlled studies have reported a wide range of response (no response to significant response) [4][5][6][7][8][9]. Beware of small sample size for these studies. A recent meta-analysis of 67 studies on use of Zolpidem in neurological non-insomnia cases showed that only 11 studies had 10 or more patients. The study concludes a wide range of transient efficacy for Zolpidem in a wide range of neurological disorders especially movement disorders and disorders of consciousness. However, the data is limited by small sample size of individual studies [10].Verdict-A case by case review is still required for the use of Zolpidem in patients with disorders of consciousness in general. In patients with NMDA encephalitis, Zolpidem may be a reasonable adjunct therapy after initial immunotherapy.

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The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project

Abstract: Anti-NMDAR encephalitis rivals viral etiologies as a cause of encephalitis within the CEP cohort. This entity deserves a prominent place on the encephalitic differential diagnosis to avoid unnecessary diagnostic and treatment costs, and to permit a more timely treatment.

Cited by 637 publications

References 16 publications

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

Use of Zolpidem in Disorders of Consciousness Secondary to Autoimmune Encephalitis

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