== First-line immunotherapy consists of corticosteroids, IVIg and plasma exchange given alone or in combination (detailed below). white women. Patients treated with tumour resection and immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) respond faster to treatment and less frequently need second-line immunotherapy (cyclophosphamide or rituximab, or both) than do patients without a tumour who receive comparable initial immunotherapy. More than 75% of all p150 patients have substantial recovery that occurs in inverse order of symptom development and is associated with a decline of antibody titres. Patients antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation. On the basis of models of pharmacological or genetic disruption of NMDAR, these antibody effects reveal a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis. == Introduction == In 2005, a syndrome of memory deficits, psychiatric symptoms, decreased consciousness, and hypoventilation was reported in four young women with ovarian teratomas.1Specific autoantibodies to Ethylparaben the N-methyl D-aspartate receptor (NMDAR) were soon detected in these and eight other patients with comparable neurological symptoms, seven of whom also had ovarian teratomas.2During the following 3 years we recognized 419 other patients with this syndrome, many of them children and young adults with or without an associated tumour. The discovery of this disorder, termed anti-NMDAR encephalitis, has changed the diagnostic approach to clinical problems as diverse as catatonia, subacute memory disturbance, seizures, abnormal movements, Ethylparaben and limbic encephalitis.3It has also led to the discovery of other autoimmune synaptic encephalitides mediated by antibodies against the AMPA receptor (AMPAR);4the -amino-butyric acid-B receptor (GABAB-R);5and leucine-rich, glioma-inactivated 1 (LGI1), which is the main autoantigen of limbic encephalitis previously attributed to voltage-gated potassium channels.6In addition to their clinical significance, these immune responses provide insights into the function of the neurotransmitter receptor targeted by the antibodies.7 In this Review we present our clinical experience in the diagnosis and management of hundreds of patients with anti-NMDAR encephalitis and also discuss reports from other investigators. We address the clinical presentation, differential diagnosis, frequency of tumour association, the cellular and synaptic mechanisms of the disease, and the process of recovery. We also discuss several confounding factors that often delay the acknowledgement of this disorder, and propose an algorithmic strategy to guideline treatment. == Frequency == The exact incidence of anti-NMDAR encephalitis is usually unknown, but on the basis of the quick accrual of patients and increasing quantity of case reports, it seems to be more frequent than any other known paraneoplastic encephalitis. Evidence from intensive care,911paediatric,12,13and neurology departments8lend support to this idea. In one retrospective analysis of encephalitis of unknown origin,10NMDAR antibodies were recognized in 1% of patients (aged between 18 and 35 years) admitted to an intensive care unit. A multicentre, population-based prospective study of causes of encephalitis in the UK14showed that 4% of patients experienced anti-NMDAR encephalitis; the disorder was the second most common immune-mediated cause, after acute disseminated encephalomyelitis and before all antibody-associated encephalitis, including encephalitis attributed to voltage-gated potassium channels. In another study,15a series of 200 patients with anti-Hu-antibody-associated encephalomyelitis was accrued over 13 years, and 500 cases of autoimmunity to proteins that interact with voltage-gated potassium channels were recognized over a 6-12 months period.16Thus, by comparison, our experience of 400 patients with anti-NMDAR encephalitis in just 3 years suggests a relatively frequent disorder. == The syndrome == Antibodies against the NR1 subunit of the NMDAR (NMDAR antibodies) are associated with a characteristic syndrome that evolves in Ethylparaben several stages of illness and recovery, as reported by Iizuka and colleagues17and Sansing and co-workers first.18About 70% of patients have prodomal symptoms comprising headache, fever, nausea, vomiting, diarrhoea, or upper respiratory-tract symptoms. In a few days, much less than 14 days Ethylparaben generally, individuals develop psychiatric symptoms and several have emerged by psychiatrists initially. Anxiety, insomnia, dread, grandiose delusions, hyper-religiosity, mania, and paranoia are regular manifestations; cultural withdrawal and stereotypical behavior have emerged sometimes. Short-term memory reduction can be common but underestimated because psychiatric symptoms and conversation problems often hinder the evaluation of memory space.8A rapid disintegration of language, from reduced amount of verbal output and echolalia (usually with echopraxia) to frank mutism, can be frequent and become related to cortical aphasia cannot. In small children, the behavioural modification could be challenging to detect because they present with temper tantrums frequently, hyperactivity, or irritability instead of frank psychosis. In kids, the 1st sign to become recognized can be non-psychiatriceg frequently, seizures, position epilepticus, dystonia, verbal decrease, or mutism. Some behaviours are hypersexual and violent (for example, kicking and biting caregivers and parents). Due to sleeping disorders and anxiousness, some small children need to have extreme sedation.12 This preliminary phase of the condition.