Rapidly progressive cognitive decline and drug-induced encephalopathy secondary to teprotumumab for thyroid eye disease: a case report and narrative literature review
- 1Department of Neurology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
Abstract
Background: Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R), is an approved targeted therapy for thyroid eye disease (TED). Teprotumumab-associated encephalopathy is an extremely rare but potentially severe central nervous system adverse event, with only three cases reported globally to date. We report the first Han-Chinese patient with Graves’ disease and associated TED complicated by teprotumumab-associated encephalopathy, together with a narrative review of all published cases, to raise clinicians’ awareness and improve early recognition and management of this rare complication.
Case presentation: A 56-year-old Chinese man with Graves’ disease and TED developed acute progressive apathy and encephalopathy characterised by multidomain cognitive and behavioral dysfunction 20 days after the third teprotumumab infusion, with an admission MMSE score of 15. Contrast-enhanced brain MRI, cerebrospinal fluid (CSF) examination, and autoimmune encephalitis antibody screening were unremarkable. Prolonged video-electroencephalography(VEEG) demonstrated intermittent diffuse bilateral slow-wave activity, and widespread interictal epileptiform discharges without electrographic or clinical seizures. Systematic workup excluded infectious, autoimmune, metabolic, and psychiatric encephalopathy. Treatment-emergent hyperglycemia was confirmed as a secondary aggravating factor rather than the primary cause. The patient achieved prominent neurological recovery after individualized treapeutic plasma exchange (TPE) and symptomatic management, with a Naranjo score of 6 indicating probable drug-related encephalopathy.
Narrative literature review: Synthesis of all three previously published teprotumumab-associated encephalopathy cases demonstrates that neurological toxicity can develop as early as the third infusion cycle. These cases present consistent neuroimaging features with variable CSF profiles, and thyroid autoantibody elevation predominantly reflects pre-existing Graves’ disease-related autoimmune background instead of directly mediating neurotoxicity. TPE generally facilitates neurological recovery but may be complicated by procedural hypersensitivity and fluctuating therapeutic responses. Notably, interictal epileptiform discharges on VEEG represent a newly identified neurophysiological manifestation of this rare adverse event. A three-hit interacting pathogenic hypothesis is proposed: impaired IGF-1R-dependent neurotrophic signalling serves as the core injury mechanism, while underlying thyroid autoimmunity and treatment-related metabolic disturbance act as susceptibility-modifying factors.
Discussion: This case expands the ethnic and clinical spectrum of teprotumumab-related encephalopathy. Diffuse interictal epileptiform discharges without ictal changes reflect reactive cortical hyperexcitability secondary to acute encephalopathy. Metabolic disturbance merely exacerbated neurological impairment. Limitations include single-case constraints, simultaneous multi-intervention therapy, and lack of direct intracranial mechanistic evidence.
Conclusion: Teprotumumab-associated encephalopathy is a rare but serious adverse event. Close neurological surveillance and are essential during medication. Accumulated cases are needed to establish unified diagnostic and therapeutic criteria.
Related
- Rapidly Progressive Buschke-Löwenstein Tumor Managed With Wide Local Excision and Healing by Secondary Intention: A Case Report and Literature Review.
- Teprotumumab-associated persistent unilateral hearing loss in dysthyroid optic neuropathy: a case report with review of the literature
- Occult Multiple Arterial Occlusions in Behçet’s Disease Manifesting as Posterior Reversible Encephalopathy Syndrome Secondary to Renovascular Hypertension
- Chronic lesion expansion persists in secondary progressive multiple sclerosis and is associated with neurodegeneration
- Longitudinal Changes in Structural and Functional Brain Imaging and Their Association with Cognitive and Neuropsychiatric Symptoms in Hashimoto Encephalopathy with Anti-NAE Antibody
BibTeX
@article{cheng2026rapidly,
title = {{Rapidly progressive cognitive decline and drug-induced encephalopathy secondary to teprotumumab for thyroid eye disease: a case report and narrative literature review}},
author = {Zhi-Juan Cheng and Shi-Xian Zhou and Zi-Ying He and Ze-Fang Deng and Chuan Zeng and Wei-Ping Chen and Jiang-Long Tu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1985279},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985279/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Rapidly progressive cognitive decline and drug-induced encephalopathy secondary to teprotumumab for thyroid eye disease: a case report and narrative literature review
AU - Zhi-Juan Cheng
AU - Shi-Xian Zhou
AU - Zi-Ying He
AU - Ze-Fang Deng
AU - Chuan Zeng
AU - Wei-Ping Chen
AU - Jiang-Long Tu
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1985279
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1985279/full
AB - Background: Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R), is an approved targeted therapy for thyroid eye disease (TED). Teprotumumab-associated encephalopathy is an extremely rare but potentially severe central nervous system adverse event, with only three cases reported globally to date. We report the first Han-Chinese patient with Graves’ disease and associated TED complicated by teprotumumab-associated encephalopathy, together with a narrative review of all published cases, to raise clinicians’ awareness and improve early recognition and management of this rare complication. Case presentation: A 56-year-old Chinese man with Graves’ disease and TED developed acute progressive apathy and encephalopathy characterised by multidomain cognitive and behavioral dysfunction 20 days after the third teprotumumab infusion, with an admission MMSE score of 15. Contrast-enhanced brain MRI, cerebrospinal fluid (CSF) examination, and autoimmune encephalitis antibody screening were unremarkable. Prolonged video-electroencephalography(VEEG) demonstrated intermittent diffuse bilateral slow-wave activity, and widespread interictal epileptiform discharges without electrographic or clinical seizures. Systematic workup excluded infectious, autoimmune, metabolic, and psychiatric encephalopathy. Treatment-emergent hyperglycemia was confirmed as a secondary aggravating factor rather than the primary cause. The patient achieved prominent neurological recovery after individualized treapeutic plasma exchange (TPE) and symptomatic management, with a Naranjo score of 6 indicating probable drug-related encephalopathy. Narrative literature review: Synthesis of all three previously published teprotumumab-associated encephalopathy cases demonstrates that neurological toxicity can develop as early as the third infusion cycle. These cases present consistent neuroimaging features with variable CSF profiles, and thyroid autoantibody elevation predominantly reflects pre-existing Graves’ disease-related autoimmune background instead of directly mediating neurotoxicity. TPE generally facilitates neurological recovery but may be complicated by procedural hypersensitivity and fluctuating therapeutic responses. Notably, interictal epileptiform discharges on VEEG represent a newly identified neurophysiological manifestation of this rare adverse event. A three-hit interacting pathogenic hypothesis is proposed: impaired IGF-1R-dependent neurotrophic signalling serves as the core injury mechanism, while underlying thyroid autoimmunity and treatment-related metabolic disturbance act as susceptibility-modifying factors. Discussion: This case expands the ethnic and clinical spectrum of teprotumumab-related encephalopathy. Diffuse interictal epileptiform discharges without ictal changes reflect reactive cortical hyperexcitability secondary to acute encephalopathy. Metabolic disturbance merely exacerbated neurological impairment. Limitations include single-case constraints, simultaneous multi-intervention therapy, and lack of direct intracranial mechanistic evidence. Conclusion: Teprotumumab-associated encephalopathy is a rare but serious adverse event. Close neurological surveillance and are essential during medication. Accumulated cases are needed to establish unified diagnostic and therapeutic criteria.
SN - 1664-3224
ER -