Orris

Paraneoplastic anti NMDA receptor encephalitis

Reading File
Reading File
Finding Sources
Searching PubMed

"anti-NMDA receptor encephalitis" AND paraneoplastic

Searching the Web

anti-NMDA receptor encephalitis tumor screening paraneoplastic consensus recommendations

Finding Sources
Searching PubMed

"anti-NMDA receptor encephalitis" AND teratoma

Reading Web Page

https://www.neurology.org/doi/10.1212/NXI.0000000000001052

Paraneoplastic anti-NMDA receptor encephalitis

Anti-NMDA receptor encephalitis is an autoimmune encephalitis caused by IgG antibodies against the GluN1 subunit of the NMDA receptor. It can be paraneoplastic, most characteristically associated with an ovarian teratoma, but many cases have no detectable tumour. It is therefore better considered a tumour-associated autoimmune encephalitis rather than assuming every case is paraneoplastic.

Typical presentation

Often evolves over days to weeks:
  1. Viral-like prodrome in some patients
  2. Psychiatric and cognitive symptoms: agitation, psychosis, insomnia, memory impairment, mutism
  3. Speech dysfunction: reduced speech, echolalia, aphasia
  4. Seizures
  5. Movement disorder: orofacial-limb dyskinesias, dystonia, choreoathetosis
  6. Decreased consciousness, autonomic instability, hypoventilation
It commonly affects children and young adults, especially females. The neurology text notes that anti-NMDA antibodies are relevant in both paraneoplastic and non-paraneoplastic encephalitis. Adams and Victor's Principles of Neurology, 12th Edition.

Tumour association

  • Ovarian teratoma is the main associated neoplasm, particularly in post-pubertal females.
  • Less commonly, other germ-cell tumours or carcinomas may be found.
  • In males and young children, a tumour is less frequent, but tumour screening is still required.
  • Teratomas contain neural tissue expressing NMDA receptors, which can initiate an immune response that cross-reacts with brain NMDA receptors.

Diagnosis

Diagnosis combines the clinical syndrome with antibody testing and exclusion of infectious encephalitis.
  • CSF anti-GluN1 IgG antibodies: preferred confirmatory test. CSF is more sensitive and specific than serum alone.
  • CSF often shows lymphocytic pleocytosis, oligoclonal bands, or raised protein.
  • EEG: usually abnormal, typically diffuse slowing. Extreme delta brush is suggestive but not required.
  • MRI brain: normal in many cases; otherwise nonspecific cortical, medial temporal, or white-matter T2/FLAIR abnormalities.
  • Test for mimics, particularly HSV encephalitis and other infectious, toxic-metabolic, epileptic, and psychiatric disorders.

Tumour search

Do this urgently and do not wait for antibody results if clinical suspicion is high.
  • Female patients: pelvic ultrasound and/or pelvic MRI for ovarian teratoma.
  • CT or MRI of chest, abdomen, and pelvis as clinically appropriate.
  • Consider FDG-PET/CT if initial screening is negative but suspicion remains high.
  • Repeat surveillance may be necessary when initial imaging is negative, especially in post-pubertal females or relapse. The pediatric international consensus recommends early tumour screening with abdominal-pelvic ultrasound or MRI plus chest CT/MRI, and further imaging such as PET when warranted by severe or treatment-refractory disease (consensus recommendations).

Treatment

Treat the immune process and any tumour in parallel.
  1. Prompt tumour removal if a teratoma or other causally associated tumour is found. This is a major determinant of recovery.
  2. First-line immunotherapy: high-dose corticosteroids, IVIG, plasma exchange, or a combination.
  3. Second-line therapy if there is insufficient improvement: commonly rituximab, with cyclophosphamide considered in selected severe or refractory cases.
  4. ICU and symptomatic care: seizure management, airway/ventilatory support, treatment of autonomic instability, nutrition, dyskinesia control, and management of agitation and sleep disturbance.
  5. Rehabilitation and long-term follow-up: cognitive, behavioural, psychiatric, speech, and physical recovery can take months to years.

Prognosis

Many patients substantially recover, but recovery is usually slow and incomplete neuropsychiatric deficits can persist. Earlier immunotherapy and early tumour excision are associated with better outcomes. Relapse is possible, especially when treatment is delayed, immunotherapy is incomplete, or an occult/recurrent tumour remains.

Key clinical point

A young woman with new-onset psychosis, seizures, dyskinesias, autonomic dysfunction, or unexplained reduced consciousness should be evaluated urgently for anti-NMDAR encephalitis and ovarian teratoma. Do not label the presentation as primary psychiatric illness alone.
For tumour screening context, the EFNS review specifically identifies teratoma as the relevant ovarian tumour in anti-NMDAR-associated paraneoplastic syndromes (EFNS tumour-screening guidance).
This is a shared conversation. Sign in to Orris to start your own chat.