Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to <i>N</i>‐Methyl‐<i>D</i>‐aspartate receptor or dopamine‐2 receptor

Mohammad, Shekeeb S.; Sinclair, Kate; Pillai, Supriya; Merheb, Vera; Aumann, Tim D.; Gill, Deepak; Dale, Russell C.; Brilot, Fabienne

doi:10.1002/mds.25623

Cited by 169 publications

(151 citation statements)

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“…30,31 Interestingly, 1 patient with HSV encephalitis relapsed with chorea and had NMDAR and D2R antibodies. 32 The emerging theme of postviral autoimmunity is increasingly recognized, and it emphasizes the importance of considering immunotherapies in post-HSV relapses. [32][33][34] There were some patients with $2 etiologic associations (Supplemental Table 4), and these patients provide a challenge for diagnosis and illustrate the overlap between infectious and autoantibodyassociated syndromes.…”

Section: Discussionmentioning

confidence: 99%

“…32 The emerging theme of postviral autoimmunity is increasingly recognized, and it emphasizes the importance of considering immunotherapies in post-HSV relapses. [32][33][34] There were some patients with $2 etiologic associations (Supplemental Table 4), and these patients provide a challenge for diagnosis and illustrate the overlap between infectious and autoantibodyassociated syndromes. 32,[35][36][37][38] There were notable etiologic absences in this cohort, such as no Mycobacterium tuberculosis encephalitis.…”

Section: Discussionmentioning

confidence: 99%

“…[32][33][34] There were some patients with $2 etiologic associations (Supplemental Table 4), and these patients provide a challenge for diagnosis and illustrate the overlap between infectious and autoantibodyassociated syndromes. 32,[35][36][37][38] There were notable etiologic absences in this cohort, such as no Mycobacterium tuberculosis encephalitis. Unlike in the United Kingdom, 5 Mycobacterium tuberculosis is rare in Australian children.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Multiple case reports and, more recently, case series have demonstrated that many patients with HSVE relapse develop anti-NMDAR immunoglobulins [152,[169][170][171][172][173][174]. Antibodies targeting other known neuronal antigens and unidentified neuronal antigens have also been reported in this setting [152,153,174,175]. The precise pathogenic mechanisms remain to be elucidated, but may involve mechanisms of molecular mimicry or an autoimmune response to the release of neuronal antigens associated with host cell lysis.…”

Section: Immune-mediated Encephalitis and Apparent Hsve Relapsementioning

confidence: 99%

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be lifesaving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

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“…3 Generally, the Institute of Medicine requires the recommendations to be supported by a much higher level of evidence to be trustworthy. 4 Third, the collaborative partnership of procurement professionals with the medical team (team-huddling) starts early in the course of inpatient care before making end-of-life decisions and BDD. 5 There are no data on the influence of team-huddling on either end-of-life decision-making or BDD in potential donors.…”

Section: Practice Variability In Brain Death Determination: a Call Tomentioning

confidence: 99%

Practice variability in brain death determination: A call to action

Rady

Verheijde²,

Frank

2014

Neurology

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Herpes simplex encephalitis relapse with chorea is associated with autoantibodies to N‐Methyl‐D‐aspartate receptor or dopamine‐2 receptor

Abstract: These autoantibody findings lend support to the autoimmune hypothesis and the early use of immune suppression in post-HSE chorea.

Cited by 169 publications

References 18 publications

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

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

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

Practice variability in brain death determination: A call to action

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