Abstract Details

Title Rapidly Progressive Dementia from treatment with a novel IGF-1R inhibitor

Topic Autoimmune Neurology

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 9-005

Objective To present the first case of rapidly progressive dementia, related to treatment with a novel monoclonal antibody in the setting of underlying neurologic disease.

Background A 76 year old man with Graves disease was admitted after six weeks of cognitive decline, characterized by disinhibition, apraxia, memory loss, and executive dysfunction. Symptoms began two months after initiating therapy for thyroid eye disease with teprotumumab, an insulin-like growth factor type 1 receptor (IGF-1R) inhibitor. His MRI brain demonstrated findings consistent with cerebral amyloid angiopathy (CAA) with subacute bleeds. CSF studies were not suggestive of autoimmune or infectious encephalitis, and a serum paraneoplastic panel was negative. He was treated initially with steroids and IVIG, with transient improvement. He was subsequently treated with plasmapheresis and empiric rituximab, with improvement to 95% of his baseline.

Design/Methods N/A

Results N/A

Conclusions This patient presented with a rapid cognitive decline in the setting of recent treatment with an IGF-1R inhibitor. Although CAA was first diagnosed during this work up, the rapid progression of his symptoms, as well as fluctuation and response to immune-modulatory treatments, is not consistent with this as a sole cause of his symptoms. IGF-1 has been shown to play a role in the central nervous system as a promotor of neuronal survival, and has been demonstrated to be beneficial in limiting the extent of damage in animal models of hypoxic-ischemic stroke. This would suggest that ischemic brain injury may be more severe in the setting of IGF-1 signaling blockade, and underlying cerebrovascular disease may be a contraindication to treatment with IGF-1R inhibitors. Given the temporal relationship of this patient’s symptoms, lack of other causative factors after extensive workup, and improvement with immune-therapy, we suspect that this patient’s previously undiagnosed CAA was unmasked and exacerbated after treatment with teprotumumab, resulting in his presentation of rapidly progressive dementia.

Authors/Disclosures
Zoe O. Marinides, MD (Naval Medical Center Camp Lejeune) PRESENTER	Dr. Marinides has nothing to disclose.
Casey C. Gower, MD (Johns Hopkins Medical Center, Psychiatry Department)	Dr. Gower has nothing to disclose.
Charles J. Kidd, MD (Eisenhower ARMY medical center)	Dr. Kidd has nothing to disclose.
J. Kent Werner, Jr., MD, PhD (Uniformed Services University)	Dr. Werner has received personal compensation for serving as an employee of Cogentis Therapeutics. Dr. Werner has stock in Cogentis Therapeutics. Dr. Werner has received intellectual property interests from a discovery or technology relating to health care. Dr. Werner has received intellectual property interests from a discovery or technology relating to health care. Dr. Werner has received personal compensation in the range of $100,000-$499,999 for serving as a Neurologist with United States Navy. Dr. Werner has received personal compensation in the range of $50,000-$99,999 for serving as a CEO / CoFounder with Cogentis Therapeutics.

��ɫ��

��ɫ��