Autoimmune encephalitis (AE) manifests with diverse, non-specific symptoms, sometimes leading to underreported misdiagnosis. Though seizures occur in about 6% of Neurofibromatosis type-1 (NF1) cases, isolated refractory seizures linked to undiagnosed NF1. This case report emphasizes the potential for AE misdiagnosis which was eventually diagnosed with NF1.

This report presents a detailed case study and literature review addressing the complexities of misdiagnosing AE, particularly concerning NF1.

A 32-year-old Caucasian man was referred for refractory epilepsy and presumed AE. His symptoms began at 27 with confusion, vomiting, and amnesia thought to be in the setting of uremia. Subsequently, he represented with generalized tonic-clonic seizures. Due to MRI showing subtle hyperintensity in bilateral mesial temporal lobes, he was diagnosed as autoimmune encephalitis.  Despite, serum and CSF autoimmune/paraneoplastic antibody panels being negative multiple times, he continued to be treated, as seronegative AE with multiple immunotherapies including high-dose steroids, monthly high-dose monthly IVIG, rituximab and mycophenolate mofetil. Notably, during our assessment, café au lait spots were observed, and the patient reported learning difficulties in childhood. Whole gene exome sequencing and mitochondrial analysis ultimately revealed a heterozygous variant (c.2509 T>C p.W837R) consistent with NF1. This suggested that his symptoms and refractory epilepsy were most likely primarily due to NF1. Consequently, immunosuppressive treatment was halted, and patient was referred to specialized clinics for multidisciplinary follow-up.

This case highlights the importance of careful clinical assessment and diagnostic workup for refractory neurologic disorders.  Misdiagnosis of autoimmune encephalitis can lead to unnecessary immunosuppression, potentially complications and delay appropriate diagnosis and treatment.  A comprehensive approach is required for suspected AE patient's and sometimes genetic conditions such as NF1 should also be considered.