Melanoma as a possible cause of autoimmune encephalitis

1. A woman developed anti-AMPA receptor encephalitis in the setting of metastatic melanoma.

2. Following a short delay, she responded well to vemurafenib and cobimetinib. At the end of the study at 9 months, she remained in complete remission.

Evidence Rating Level: 4 (below average)          

Study Rundown: Anti-AMPA receptor encephalitis can occur as a rare but serious paraneoplastic consequence of many different tumors, including lung, breast, and thymus cancer.  In this study, a 61-year-old woman was admitted to the hospital with classic neurological symptoms of encephalitis and supraclavicular and axillary lymphadenitis.  An antibody panel confirmed anti-AMPA antibodies, and a nodal biopsy showed epithelioid malignant cells with surface markers consistent with melanoma.  The patient responded well to vemurafenib and cobimetinib and was in complete remission at the end of the study nine months later.  Though tumor-associated anti-AMPA receptor encephalitis have been reported before, this represented the first case linked to melanoma.  It is also the first case where the patient responded to treatment, demonstrating the importance of early diagnosis.  However, the reason for the patient’s delayed response to vemurafenib and cobimetinib remains uncertain.

Click to read the study in Annals

Relevant Reading: Clinical Spectrum of Encephalitis Associated With Antibodies Against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor

In-Depth [case report]:  In this study, a 61-year old woman was admitted to the hospital with symptoms of inattention, memory problems, mild dysmetria, and supraclavicular and axillary lymphadenopathy.  A cerebrospinal fluid analysis showed lymphocytic pleocytosis, mildly elevated protein, and normal glucose, but with no signs of infection.  Magnetic resonance imaging revealed bilateral, evolving hyperintensitiies in the striatum, and an electroencephalogram showed diffuse slowing.  Finally, a positive anti-AMPA receptor assay confirmed the diagnosis of immune-mediated encephalitis.  The patient was started on high-dose steroids and intravenous immunoglobulin, but her neurological condition deteriorated rapidly over the next three weeks and she fell into a coma.  Meanwhile biopsy of her active nodes revealed epithelioid malignant cells that stained positive for S-100, negative for Melan-A, and positive for BRAF-V600E, which was strongly suggestive of melanoma.  She was started on a vemurafenib and cobimetinib with no immediate effect.  Four weeks later, she abruptly woke from her coma.  PET scans at 3- and 9 months post treatment showed no signs of cancer recurrence.

Image: PD

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