Authors :
Presenting Author: Christel Benny, BS – United Neuroscience Institute
Stacey Kim, MEng, BA – Kern Medical
Aaron Fernandez, BS – United Neuroscience Institute
Alan Salim, BS – United Neuroscience Institute
Wefaq Alshami, BS – Kern Medical
Maral Bakir, PhD, ACNP – UCLA
Dawn Eliashiv, MD – David Geffen School of Medicine at UCLA
Ausuf Bari, MD, PhD – UCLA
Hari Veedu, MD, FACNS – Kern Medical, United Neuroscience Institute
Rationale:
Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple seizure types, cognitive impairment, and resistance to medical therapy. In ultra-refractory cases, those unresponsive to polytherapy and vagus nerve stimulation (VNS), treatment options are limited. Deep brain stimulation (DBS) targeting the centromedian (CM) thalamic nucleus has emerged as a potential intervention for patients with LGS. Although CM-DBS is not FDA-approved for this indication, recent findings from the ESTEL trial and other studies have demonstrated significant seizure reductions and improvements in quality of life in LGS patients undergoing CM-DBS. We present a case of a patient with LGS who failed polytherapy and VNS and experienced an approximately 80% reduction in seizure frequency within 6 months after bilateral CM-DBS implantation, highlighting its potential as a therapeutic option for patients with ultra-refractory LGS. CM-DBS implantation and DBS programming were done at UCLA Epilepsy Center and followed at Kern Medical.Methods:
A 33-year-old right-handed female with LGS and moderate intellectual disability presented with daily seizures despite polytherapy and an optimized vagus nerve stimulator (VNS). Seizures began as infantile spasms at 3 months of age and evolved into LGS. Current semiology includes generalized tonic and atonic seizures with multiple falls. The MRI was non-lesional and recent EEG showed frequent epochs of diffuse generalized paroxysmal fast activity during sleep. Failed antiseizure medications (ASMs) included divalproex sodium, felbamate, clobazam, and topiramate. At the time of DBS evaluation, she was on cannabidiol, cenobamate, and lacosamide. VNS parameters were 250 μs, 20 Hz, 2.5 mA, 60 s on/1.1 min off (51% duty cycle). Given continued seizures, she underwent bilateral CM-DBS implantation at UCLA. Intraoperative high-resolution MRI (MP2RAGE) identified the CM and targeting was performed with both direct targeting and standard stereotactic coordinates. Electrode placement was confirmed postoperatively through Suretune software. Initial stimulation was set at 1 mA, 90 μs pulse width, 145 Hz frequency, cycling 1-minute on/5-minutes off.
Results:
Prior to DBS implantation, the patient had multiple daily seizures. At 1-month post-op follow-up, there was no perceived change in seizure frequency. By 1.5 months post-op, the patient's mother reported a substantial reduction of 3-4 tonic seizures per month. At 4 month follow up, DBS output current was titrated to 1.2 mA bilaterally. At 6-month follow up, the patient continues to have 3-4 tonic seizures per month. No further titrations made to DBS.
Conclusions:
This case demonstrates a promising early response and sustained 80% reduction in seizure frequency over six months, highlighting CM-DBS as a viable salvage option for ultra-refractory LGS.
Funding: None