CLINICAL ARTICLE J Neurosurg 128:277–286, 2018 Efficacy and safety of corpus callosotomy after vagal nerve stimulation in patients with drug-resistant epilepsy Jennifer Hong, MD,1 Atman Desai, MD,2 Vijay M. Thadani, MD,3 and David W. Roberts, MD1,3 1Section of Neurosurgery, Department of Surgery, 3Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; and 2Department of Neurosurgery, Stanford University School of Medicine, Palo Alto, California OBJECTIVE Vagal nerve stimulation (VNS) and corpus callosotomy (CC) have both been shown to be of benefit in the treatment of medically refractory epilepsy. Recent case series have reviewed the efficacy of VNS in patients who have undergone CC, with encouraging results. There are few data, however, on the use of CC following VNS therapy. METHODS The records of all patients at the authors’ center who underwent CC following VNS between 1998 and 2015 were reviewed. Patient baseline characteristics, operative details, and postoperative outcomes were analyzed. RESULTS Ten patients met inclusion criteria. The median follow-up was 72 months, with a minimum follow-up of 12 months (range 12–109 months). The mean time between VNS and CC was 53.7 months. The most common reason for CC was progression of seizures after VNS. Seven patients had anterior CC, and 3 patients returned to the operat- ing room for a completion of the procedure. All patients had a decrease in the rate of falls and drop seizures; 7 patients experienced elimination of drop seizures. Nine patients had an Engel Class III outcome, and 1 patient had a Class IV outcome. There were 3 immediate postoperative complications and 1 delayed complication. One patient developed pneumonia, 1 developed transient mutism, and 1 had persistent weakness in the nondominant foot. One patient pre- sented with a wound infection. CONCLUSIONS The authors demonstrate that CC can help reduce seizures in patients with medically refractory epi- lepsy following VNS, particularly with respect to drop attacks. https://thejns.org/doi/abs/10.3171/2016.10.JNS161841 KEY WORDS atonic seizure; corpus callosotomy; drug-resistant epilepsy; vagal nerve stimulation AGAL nerve stimulation (VNS) and corpus calloso- be patients with secondarily generalized seizures or mul- tomy (CC) are palliative surgical procedures that tiple seizure types.28,34 In the absence of Level I evidence can reduce seizure frequency, attenuate seizure comparing VNS to CC, the experience and preferences of Vseverity, and improve quality of life for patients with non- individual neurologists and surgeons heavily influence the localizing or unresectable drug-resistant epilepsy (DRE). recommendation for either VNS or CC in patients with This is in contrast to focal resection, where the goal is DRE who present for palliative surgery. complete control of seizures. Patient selection criteria Corpus callosotomy, which was first described by Van for VNS and for CC are not strictly defined. In general, Wagenen and Herren in the 1940s, predates by many de- VNS is recommended for patients with nonlocalizable cades the FDA approval of VNS for epilepsy in 1997.41 As or unresectable seizure disorders or those who either are a result, much of the literature describing the efficacy of unable to tolerate or choose not to undergo craniotomy, CC for DRE comes from patients who did not have the op- and is FDA approved for children older than 12 years and tion of VNS. The mechanisms of action of each treatment adults with multifocal epilepsy and multiple seizure types. are very different. Callosotomy is a disconnection proce- Patients who predominantly have drop attacks are typi- dure wherein fibers that allow seizures to propagate and cally thought to be very good candidates for CC, as may secondarily generalize are severed.13,51 In contrast, VNS is ABBREVIATIONS CC = corpus callosotomy; CPS = complex partial seizures; DRE = drug-resistant epilepsy; EEG = electroencephalography; GTC = generalized tonic- clonic; LGS = Lennox-Gastaut syndrome; LITT = laser interstitial thermal therapy; SPS = simple partial seizures; SRS = stereotactic radiosurgery; VNS = vagal nerve stimu- lation. SUBMITTED July 14, 2016. ACCEPTED October 4, 2016. INCLUDE WHEN CITING Published online March 3, 2017; DOI: 10.3171/2016.10.JNS161841. ©AANS 2018, except where prohibited by US copyright law J Neurosurg Volume 128 • January 2018 277 Unauthenticated | Downloaded 09/30/21 06:21 PM UTC J. Hong et al. a form of neuromodulation, in which continuous, intermit- in the direction of rapid cycling, until stimulation occurred tent, low-intensity electrical stimulation of the vagal nerve every 1.1 minute for 14 seconds. Patients underwent a full results in afferent spread of action potentials to subcortical year of VNS therapy before they were considered to have nuclei and the cortex; this is thought to attenuate the dura- had an adequate trial. tion and frequency of seizures.49 It is plausible that the 2 approaches are complementary Operative Technique and can work synergistically in particularly refractory pa- All CCs were performed after induction of general tients. Based on data from the VNS registry, 57% of pa- anesthesia. Patients were usually positioned supine with tients with DRE who underwent VNS after CC reported a 20 the head neutral and held in 3-point fixation by using a > 50% reduction in seizure frequency. The potential ben- Mayfield clamp. The scalp was partially shaved, and a efit of CC in patients who have already undergone VNS is transverse incision was made anterior to the coronal su- not well described. Here we review our institutional expe- ture, with two-thirds of the incision placed right of mid- rience with patients who elected to undergo CC after VNS line. A pneumatic-powered perforator and craniotome to test the hypothesis that in patients with seizures who (or, earlier in the series, a 5-cm trephine) were used to have undergone VNS without satisfactory response, CC elevate a 5-cm-long × 4-cm-wide bone flap, of which two- may produce meaningful further benefit. thirds were to the right of midline. The dura mater was opened in a curvilinear fashion based usually on the right Methods side of the superior sagittal sinus. Using a microsurgical Participants and Study Design technique, dissection was continued down the interhemi- Following approval by the Dartmouth Institutional Re- spheric fissure, with exposure of the corpus callosum at view Board, hospital records and a prospectively main- its base. A Greenberg self-retaining retractor was placed. tained epilepsy database were queried for all patients who The CC was performed extraventricularly by using a underwent CC after implantation of a VNS between 1999 microdissector, commonly with the assistance of micro- and 2015. The Current Procedural Terminology codes for suction, beginning in the midline at the junction of the both VNS (64568, 64573) and CC (61541) and the ICD-9 posterior genu and the anterior body. The dissection was code for epilepsy (345.XX) were used to identify eligible continued down to the midline cleft formed by the leaves patients. Patients were included in the study only if the of the septum pellucidum, and the existing or potential VNS surgery predated the CC surgery. cavum septum pellucidum was entered. Dissection was then continued anteriorly around the genu and posteriorly Clinical Variables and Outcomes Assessment to the narrowed isthmus of the posterior body. A ligat- ing clip was placed at the most posterior extent of the Clinical data were retrieved through retrospective CC. Hemostasis was obtained and the dura was closed chart review. Data available included age, sex, presenting with 4-0 Vicryl suture. The bone flap was replaced with symptoms, duration of seizures, seizure subtypes, medi- titanium hardware. The galea and skin were then reap- cations, VNS parameters, clinical examination, opera- proximated. Blood loss was generally < 100 ml, and the tive notes, postoperative hospital course, and outpatient time of surgery was between 2.5 and 4 hours. Barring follow-up. complications, discharge was most often on postoperative All patients were evaluated in a multidisciplinary sur- Day 3 or 4. gical epilepsy conference prior to the CC. Routine pre- Completion CCs were undertaken in a similar manner, surgical workup included history and physical examina- usually with a second, more posterior craniotomy. If the tion, long-term noninvasive video electroencephalography patient had undergone prior intracranial EEG or resection, (EEG), and imaging including MRI as well as ictal and every effort was made to anticipate a potential CC at the interictal SPECT in some patients. The recommendation first operation, or, if the initial surgery was performed at for CC was made based on persistence of drop attacks or another institution, to incorporate the previous incision secondarily generalized seizures as well as failure of VNS and bone flap into the CC surgery. This surgery is facili- therapy, defined as a < 50% reduction in seizure frequency tated by the deeper extending posterior falx and smaller with maximal titration of stimulation. residual callosum. Patients were seen in clinic for routine follow-up ap- Protocol for VNS Titration proximately 4 weeks after discharge from the hospital. All patients who underwent VNS implantation at our institution were evaluated at a multidisciplinary epilepsy Results conference. Postoperatively, adjustments were made to VNS stimulation parameters every 6 weeks as tolerated, Patient Demographic Data and then every 3 months when response to therapy began We identified 10 patients in our epilepsy registry who to plateau, or sooner if side effects became pronounced and had undergone CC following VNS. Eight patients under- intolerable. The frequency of 30 cycles per second (range went VNS placement at our institution. The median age 20–30), and pulse width 250 or 500 μsec, was usually held at the time of consideration for CC was 37 years (range constant. The current was titrated up from 0.25 mA by 8–60 years). Full-scale IQ ranged from low average to ex- 0.25 mA at each visit.