NMDA receptor encephalitis with cancer of unknown primary origin

Area of Science:

• Neurology
• Oncology

Background:

• N-methyl-D-aspartate receptor (NMDAR) encephalitis is often a paraneoplastic syndrome in young women, frequently linked to ovarian teratoma.
• This condition involves autoimmune attacks on NMDARs, leading to severe neurological and psychiatric symptoms.

Observation:

• Two male patients presented with NMDAR encephalitis and metastatic cancer of unknown primary origin.
• Both patients exhibited cognitive dysfunction, neurological symptoms, EEG abnormalities, and NMDAR antibodies in serum and cerebrospinal fluid.
• Treatment with pulse steroids and intravenous immunoglobulin was effective for their neurological symptoms.

Findings:

• Following neurological recovery, patients developed metastatic small cell neuroendocrine carcinoma of the parotid gland and inguinal metastatic squamous cell cancer.
• Further investigations revealed small cell lung cancer in one patient; the primary origin remained unidentified in the other.
• These cancers demonstrated slow progression rates.

Implications:

• NMDAR encephalitis can be associated with metastatic cancers in male patients, not exclusively young women.
• The findings suggest that NMDAR encephalitis may precede the clinical manifestation of certain slow-progressing metastatic cancers.
• This association warrants further investigation into the paraneoplastic potential of NMDAR encephalitis across diverse patient populations and cancer types.