To report prolonged seizure freedom and improved quality of life after combining anterior nucleus of the thalamus deep brain stimulation (ANT-DBS) with vagus nerve stimulation (VNS) in a patient with drug resistant genetic generalized epilepsy (GGE).  

Neuromodulation remains at forefront of management in patients with drug-resistant epilepsies though efficacy has been palliative and FDA approved in focal epilepsies.  While polytherapy with anti-seizure medications (ASMs) is common, dual neuromodulation has received limited attention.

A 32-year-old female patient with drug resistant GGE who failed 10 antiseizure medications underwent video-EEG monitoring. EEG revealed 3-3.5 Hz generalized polyspike-and-wave discharges and generalized paroxysmal fast activity in brief run lasting less than 3 seconds increased during sleep. Seizures were not recorded. VNS model 106 Aspire SR was implanted at age 23 achieving parameters of 1.5 mA, 25 Hz, 250 μs, 14 sec on, 1.1 min off. Despite improvement with seizure reduction, ongoing monthly convulsions resulted in recurrent injuries. The patient subsequently underwent bilateral ANT-DBS placement with inferior most contacts on both sides well-positioned at the junction of the mammillothalamic tracts for monopolar stimulation at 5 V, 145 Hz, and 90 µs. 

Neuro- “modulation” was observed in our patient with VNS following implantation of ANT-DBS by gradual reduction diminishing seizure frequency, intensity, and duration to ultimately become seizure-free for 21 months. Stable doses of Onfi 20 mg po bid and Keppra 1500 mg po bid were continued. After combining ANT-DBS with her incomplete VNS response she married, became employed, and was able to retain driving privileges and lead an independent lifestyle. 

Identifying a subset of patients with GGE responsive to polyneuromodulation promises personalized therapy for those with life-altering effects from generalized seizures. We speculate that the thalamic network connectivity may be modulated by dual ANT-DBS and VNS, leading to targeted neurobiological therapy in some patients with GGE.