What are the clinical features of NMDA (N-methyl-D-aspartate) receptor encephalitis?

Clinical Features of NMDA Receptor Encephalitis

NMDA receptor encephalitis presents with a characteristic constellation of psychiatric symptoms, memory deficits, seizures, dyskinetic movements, decreased consciousness, and autonomic instability, predominantly affecting young women with a median age of 23 years. 1

Core Clinical Presentation

Psychiatric and Cognitive Symptoms

• Psychiatric symptoms or memory problems occur in 100% of patients and are often the initial presenting features 1
• Behavioral changes, personality alterations, psychosis, mania, aggression, and speech abnormalities are common psychiatric manifestations 2, 3
• Disorientation, confusion, and cognitive dysfunction with memory deficits occur frequently 2, 4
• These psychiatric symptoms can be mistaken for primary psychiatric illness, occasionally with tragic consequences if the diagnosis is delayed 2

Neurological Features

• Seizures occur in 76% of patients, with intractable seizures and refractory status epilepticus being particularly characteristic 1, 4
• Dyskinetic movements are present in 86% of patients, including choreoathetosis, orofacial dyskinesias, and other movement disorders 1, 2
• Decreased consciousness or unresponsiveness develops in 88% of patients as the disease progresses 1, 4
• Focal neurological signs may be present, though the presentation can be variable 2

Autonomic and Respiratory Dysfunction

• Autonomic instability occurs in 69% of patients, representing a severe manifestation of the disease 1
• Hypoventilation requiring mechanical ventilation develops in 66% of patients 1

Demographic and Epidemiological Features

• The median age at presentation is 25 years with a male-to-female ratio of 1:2 5
• The disease predominantly affects young women, with 91 of 100 patients in one major series being female 1
• NMDA receptor encephalitis is the single most common cause of encephalitis in patients under 30 years of age, exceeding HSV, West Nile virus, and varicella zoster virus combined 6, 4

Clinical Progression Pattern

• The presentation is typically subacute, evolving over weeks to months 2
• Fever may be present but is not universal; some patients present with low-grade pyrexia rather than high fever 2
• The disease follows a characteristic progression: psychiatric symptoms → seizures → movement disorders → decreased consciousness → autonomic instability 1

Associated Tumor Features

• 58-59% of patients have associated tumors, most commonly ovarian teratoma in women 1
• In female patients over age 18, up to 50% harbor ovarian teratomas 2, 6
• Tumors are rare in children but become increasingly common after age 18 2

Distinguishing Clinical Clues

• Faciobrachial dystonic seizures are a particularly distinctive feature that should raise suspicion 2
• Hyponatremia may be present and suggests antibody-mediated encephalitis 2
• The combination of psychiatric presentation with dyskinetic movements in a young woman is highly characteristic 2

Pediatric Considerations

• In children, epilepsy and abnormal movements are more frequent at onset compared to adults 2
• The overall clinical syndrome is similar but may present more acutely in pediatric populations 2

Important Clinical Pitfalls

• Initial presentations can be subtle, with isolated psychiatric symptoms that may be misdiagnosed as primary psychiatric disorders 2, 3
• Some patients may have a normal Glasgow Coma Score at presentation, as it is a crude tool for detecting subtle behavioral changes 2
• The disease can develop following viral infections (HSV, VZV, EBV, influenza A), so consider testing in patients with viral encephalitis who exhibit slow response or recrudescent symptoms 4
• Initial antibody testing can be falsely negative, requiring repeat testing if clinical suspicion remains high 7