Clinico-Radiological Overlap Between Autoimmune Encephalitis and Tuberous Sclerosis Complex: A Case Report

Introduction: Autoimmune encephalitis (AIE) is an acquired immune-mediated condition, whereas tuberous sclerosis complex (TSC) is a genetic disorder with autosomal dominant inheritance. Both conditions can present with seizures, often leading to diagnostic challenges at both clinical and radiological levels. Here, we present a case that highlights such a diagnostic dilemma. Case: A 21-year-old male with a normal antenatal, birth, and developmental history presented with focal to bilateral tonic–clonic seizures preceded by an auditory aura, with onset at 15 years of age. Despite treatment with antiepileptic medications, he continued to experience seizures. There was a family history of seizures. On detailed neurological examination, findings were largely unremarkable, except for the presence of hypopigmented macules over the neck and small subcutaneous nodules. Based on the clinical presentation, differential diagnoses of temporal lobe epilepsy, AIE, and TSC were considered. Serial magnetic resonance imaging brain revealed findings suggestive of subependymal hamartomas with focal gliosis, with differential considerations including AIE and cortical tubers. Electroencephalography demonstrated left temporal spikes. Cerebrospinal fluid (CSF) analysis showed 58 mg/dL proteins and 10 white blood cells. CSF AIE panel was normal and serum paraneoplastic panel showed positive anti-Yo antibodies. Antiepileptic drugs were optimized. Patient was given steroids for possibility of AIE and he became seizure-free. Genetic testing identified an IRAK4 gene variant. The patient remains on regular follow-up with serial neuroimaging, which has demonstrated resolution of previously noted lesions. Clinically, he continues to do well and has resumed his occupational activities. Discussion/Conclusion: This case illustrates the diagnostic dilemma between AIE and TSC in a young patient presenting with refractory focal seizures and overlapping imaging features. A favorable response to immunotherapy and resolution of radiological abnormalities supported an autoimmune etiology whereas strong family history with hypopigmented macules and subcutaneous nodules could not rule out TSC despite genetic testing showing IRAK4 variant gene. Publication History Article published online: 15 July 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Private Limited A-13A, Graphix Tower 1, 6th floor, Sector 62, Noida 201309, Uttar Pradesh, India