Abstract Details

Title Immune Checkpoint Inhibitor-associated Diencephalic-brainstem Encephalitis and PDE10A Autoimmunity

Topic Autoimmune Neurology

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 2-005

Objective To report a case of brainstem encephalitis and Phosphodiesterase 10A (PDE10A) autoantibodies positivity secondary to immune checkpoint inhibitor neurotoxicity.

Background

PDE10A IgG comprise a rare paraneoplastic disorder of the central nervous system characterized by a T-cell mediated immune response targeting striatal neurons that express the PDE10A enzyme, which helps regulate signaling pathways involved in motor control. The clinical manifestations described with PDE10A include hyperkinetic movement disorders and parkinsonism. This syndrome has been associated with various malignancies and with use of immune checkpoint inhibitor (ICI) therapy.

Design/Methods N/A

Results A 69-year-old woman with inflammatory arthritis, interstitial lung disease, stage IV intrahepatic cholangiocarcinoma, treated previously with pembrolizumab, a PD-1 inhibitor, with progressive retroperitoneal metastases who developed fevers, headache, dizziness, binocular diplopia, and progressive somnolence two weeks following initiation of durvalumab, a PD-L1 inhibitor. On neurological examination, she was hypersomnolent and had bilateral appendicular ataxia. MRI brain revealed patchy T2/FLAIR hyperintensities within the left dorsal midbrain, superior colliculus, and right dorsal pons associated with subtle restricted diffusion. Cerebrospinal fluid (CSF) white cell count was 11 cells/µL (lymphocytic predominant). She was diagnosed with a diencephalic-rhombencephalitis secondary to ICI neurotoxicity. This was later confirmed by the presence of PDE10A antibodies in the CSF.

She was treated with a course of intravenous methylprednisolone and plasmapheresis. Cyclophosphamide and prednisone were given long-term. Patient had dramatic clinical and radiologic improvement. Subsequent MRI brain demonstrated near complete resolution of the abnormal signal.

Conclusions This case highlights a clinical phenotype of PDE10A autoimmune syndrome that differs from previously described hyperkinetic movement disorders. While this may reflect an evolving or broader disease spectrum than currently recognized given limited clinical data, it is more likely that this presentation may indicate neural autoimmunity triggered by ICI-enhanced antitumor immunity, as demonstrated by PDE10A autoantibody positivity, and potentially driven by an autoantibody that has yet to be fully characterized.

Authors/Disclosures
Hannah Kim, MD PRESENTER	Dr. Kim has nothing to disclose.
Karan S. Dixit, MD (Northwestern University)	Dr. Dixit has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Servier.
Edith Graham, MD (Northwestern University)	Dr. Graham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Graham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Graham has received research support from F. Hoffman-La Roche Ltd. The institution of Dr. Graham has received research support from Novartis.
Fred Shen, MD, PhD (Northwestern)	Dr. Shen has nothing to disclose.
Shailee S. Shah, MD	Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Shah has received publishing royalties from a publication relating to health care.

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