Abstract Background Lennox-gastaut syndrome (LGS) is an epileptic encephalopathy often associated with behavioral and psychiatric disorders. Vagus nerve stimulation (VNS) has been approved effective for LGS treatment. Surgical resection is also an option for LGS patients with focal pathology, offering a high probability of seizure control. However, it is challenging to accurately localize the seizure focus. Case presentation The case presented here is a 19-year-old male with a 16-year history of epilepsy with comorbid severe cognitive and psychiatric disorders. He was diagnosed with LGS due to generalized slow spike-wave discharges and multiple seizure types. He was treated with VNS in 2017 at the age of 15. After that, the frequency of the short tonic seizures decreased from 4–5 times per day to 2–5 times per year, and the generalized tonic–clonic seizure pattern did not recur, which had a frequency of 2–4 times per month before the surgery. In 2019, the generalized abnormal interictal epileptiform discharges changed to be localized in the right frontal–temporal lobe at the age of 17 years (2019). Conclusions This case report suggested that the generalized epileptiform discharges evolve into localized discharges after VNS treatment, which may help reveal the primary seizure focus for resection surgery in patients with LGS.
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