SURG-09. SUCCESSFUL SAFETY AND EFFICACY OF GAMMATILE INTRACRANIAL BRACHYTHERAPY IMPLANTED DURING AWAKE CRANIOTOMY

INTRODUCTION GammaTile intracranial brachytherapy utilizing cesium-131 seeds has demonstrated encouraging safety and local control results in a single-arm precommercial study, and recently received Food and Drug Administration clearance. The authors report the first case of GammaTile intraoperative brachytherapy performed during an awake craniotomy. METHODS A 50-year-old man suffered a generalized tonic-clonic seizure while a vehicle passenger. MRI revealed a 2.8 cm left lateral frontal lesion nearing his Broca’s area. Open brain biopsy revealed IDH-wildtype MGMT unmethylated GBM. Unfortunately, despite several interventions (awake craniotomy, adjuvant chemoradiation with temozolomide, Avastin, tumor treating fields) he suffered tumor progression near the left parietal resection cavity. Due to the location of this tumor, re-resection was planned with awake craniotomy and language mapping. A preoperative planning session involving Radiation Oncology and Neurosurgery identified the area of the expected postoperative bed, and consequently five GammaTiles were ordered, each containing 4 cesium-131 3.5 U seeds. RESULTS During surgery, once the tumor was mapped, bipolar stimulation was performed while the patient spoke in complete sentences until going into speech arrest on the posterior edge of the gyrus, indicative of language cortex. Following this mapping, microsurgical maximal safe resection occurred, after which areas at risk for tumor residual/recurrence were determined in consultation with Radiation Oncology. Subsequently, Neurosurgery placed all five GammaTiles (20 cesium-131 seeds total) in customized forward fashion to optimally cover the dosimetric needs of these areas. Following GammaTile placement, closure was completed and radioactive surveys of the room remained within state statue. Postoperative dosimetry yielded excellent coverage, and speech function was maintained. CONCLUSIONS The first reported case of GammaTile intraoperative brachytherapy during awake craniotomy supports the safety and feasibility of this treatment strategy. This case indicates that for patients with tumors adjacent to eloquent cortex, awake craniotomy can allow for maximum safe resection and implantation of intraoperative brachytherapy.

Altered sleep intensity upon DBS to hypothalamic sleep-wake centers in rats

Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects, and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep-wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep-wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz at 90 microA over 24 h to test the modulating effects of DBS on sleep-wake proportions, stability and spectral power in relation to baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep-wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on sleep-wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

Altered sleep intensity upon DBS to hypothalamic sleep–wake centers in rats

Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep–wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep–wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz and 90 µA over 24 h to test the modulating effects of DBS on sleep–wake proportions, stability and spectral power in relation to the baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep (SWS) as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, as evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep–wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on the sleep–wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

What have we learned from 8 years of deep brain stimulation of the anterior thalamic nucleus? Experiences and insights of a single center

OBJECTIVEIn the absence of a standard or guideline for the treatment of epilepsy patients with deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT), systematic single-center investigations are essential to establish effective approaches. Here, the authors report on the long-term results of one of the largest single-center ANT DBS cohorts.METHODSThe outcome data of 23 consecutive patients with transventricularly implanted electrodes were retrospectively analyzed with regard to adverse events, lead placement, stimulation-related side effects, and changes in seizure frequency. Depression and quality-of-life scores were collected in a subgroup of 9 patients.RESULTSAll but 2 patients initially underwent bilateral implantation, and 84.4% of all DBS leads were successfully located within the ANT. The mean follow-up time was 46.57 ± 23.20 months. A seizure reduction > 50% was documented in 73.9% of patients, and 34.6% achieved an Engel class I outcome. In 3 patients, clinical response was achieved by switching the electrode contact or changing from the monopolar to bipolar stimulation mode. Unilateral implantation seemed ineffective, whereas bilateral stimulation with successful ANT implantation only on one side led to a clinical response. Double stimulation with additional vagus nerve stimulation was safe. Changes in cycling mode or stimulation amplitude influenced therapy tolerability and, only to a lesser extent, seizure frequency. Side effects were rare and typically vanished by lowering the stimulation amplitude or changing the active electrode contact. Furthermore, depression and aspects of quality of life significantly improved with ANT DBS treatment.CONCLUSIONSThe transventricular approach as well as double stimulation proved safe. The anteroventral ANT appeared to be the most efficacious stimulation site. This systematic investigation with reluctant medication changes allowed for the development of a better idea of the association between parameter changes and outcome in ANT DBS patients, but larger samples are still needed to assess the potential of bipolar stimulation and distinct cycling frequencies. Furthermore, more multifaceted and objective assessments of treatment outcome are needed to fully assess the effects of ANT DBS treatment.

Multi-polar stimulation of the left ventricle during cardio-resynchronisation therapy in patients with congestive heart failure: Randomised pilot study outcomes from parallel groups

<p><strong>Background.</strong> Cardiac resynchronisation therapy (CRT) has been used for the treatment of patients with congestive heart failure (CHF) and wide QRS complexes for more than ten years. Nevertheless, the percentage of patients unresponsive to this therapy is 30%. There is recent evidence for increased responder proportions to treatments with multipolar pacing of the left ventricle (LV) in CRT. Accordingly, the aim of this study is to evaluate the effectiveness of multi-polar pacing of LV in patients with CHF and indications for CRT.</p><p><strong>Methods.</strong> Sixty-two patients [42 men, mean age 62.5 (58–68) years] with CHF and indications for CRT (for example patients with symptomatic heart failure and QRS duration ≥130 ms with left bundle branch block and left ventricular ejection fraction ≤ 35%) were included in this prospective, pilot, randomised study. Patients were implanted with cardiac resynchronisation devices with multi-polar electrodes. After implantation, patients were randomised into two groups according to the programming of the LV stimulation vector: true bipolar stimulation (group 1, stimulation vector LVring-LVtip, n = 31) and extended-bipolar LV stimulation (group 2, standard programming LV ring to RV, n = 31). The main objective of the study was to assess the effects of true bipolar stimulation on the increase of the number of CRT responders. Responders were defined as patients with a 15% decrease in the left ventricular end systolic volume compared with the initial characteristics as detected by echocardiography. Secondary points included changes in a) left ventricular ejection fraction (LVEF), b) 6-min walk test dynamics, and c) brain natriuretic peptide. The observation period was 12 months.</p><p><strong>Results.</strong> The LV electrode was implanted in the anterior (6%), antero-lateral (8%), lateral (18%), posterior (2%), or postero-lateral (66%) branches of the coronary sinus, and the average LV stimulation threshold was 1.7 ± 1.1 V. No intra-operative complications were detected. Four patients (6.5%) underwent LV electrode re-positioning on the second day after surgery owing to diaphragmatic nerve stimulation. At the end of the observation period, the average threshold used for LV stimulation of patients in the true bi-polar stimulation group with the LVring-LVtip vector was 1.9 ± 1.5 V compared with 1.6 ± 1.3 V in the case of the extended-bipolar LV stimulation group (p = 0.88). The number of responders in the true bipolar stimulation group was 25 (80.6%) compared with 21 (67.7%) patients in the extended-bipolar LV stimulation group (p = 0.38). LVEF significantly increased in both groups compared with pre-operative values without significant differences between the groups (29.4 vs. 36.5, p &lt; 0.001 in the extended bipolar LV stimulation group; 28.0 vs. 34.9, p &lt; 0.001 in the true bi-polar stimulation group, p = 0.86 between groups). The distance covered during the 6-min walk test significantly increased in both groups compared with pre-operative values in the absence of a significant difference between the groups (p = 0.92). The decreased levels of the cerebral natriuretic peptide were 60.3 ± 42.3 pg/ml and 56.6 ± 38.5 pg/ml in the extended and true bipolar stimulation groups, respectively (p = 0.95). </p><p><strong>Conclusion.</strong> Based on the results of this pilot study, the choice of a vector for true bipolar LV stimulation demonstrated its advantage and tendency to increase the number of responders in subjects with implanted CRT devices. Subsequent multi-centre randomised trials will help determine the role of true bipolar LV stimulation and extended-bipolar stimulation from different regions of the LV to increase the response to CRT.</p><p><br />Received 24 December 2019. Revised 18 January 2020. Accepted 20 January 2020.</p><p><strong>Funding:</strong> The work is supported by a grant of the President of the Russian Federation No. МД-2893.2018.7.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p><p><strong>Author contributions</strong><br />Conception and study design: A.B. Romanov<br />Data collection and analysis: A.V. Ponomarenko, I.L. Mikheenko, E.A. Morzhanayev, A.G. Filippenko, R.E. Zhizhov, I.S. Peregudov<br />Statistical analysis: A.B. Romanov, I.L. Mikheenko<br />Drafting the article: A.V. Ponomarenko, I.L. Mikheenko, E.A. Morzhanayev<br />Critical revision of the article: A.B. Romanov, D.V. Losik, I.L. Mikheenko, A.V. Ponomarenko, V.V. Shabanov, S.N. Artemenko <br />Final approval of the version to be published: A.V. Ponomarenko, I.L. Mikheenko, E.A. Morzhanayev, A.G. Filippenko, D.V. Losik, V.V. Shabanov, I.S. Peregudov, R.E. Zhizhov, A.B. Romanov, S.N. Artemenko</p>

Use of the train-of-five bipolar technique to provide reliable, spatially accurate motor cortex identification in asleep patients

OBJECTIVEIntraoperative cortical and subcortical mapping techniques have become integral for achieving a maximal safe resection of tumors that are in or near regions of eloquent brain. The recent literature has demonstrated successful motor/language mapping with lower rates of stimulation-induced seizures when using monopolar high-frequency stimulation compared to traditional low-frequency bipolar stimulation mapping. However, monopolar stimulation carries with it disadvantages that include more radiant spread of electrical stimulation and a theoretically higher potential for tissue damage. The authors report on the successful use of bipolar stimulation with a high-frequency train-of-five (TOF) pulse physiology for motor mapping.METHODSBetween 2018 and 2019, 13 patients underwent motor mapping with phase-reversal and both low-frequency and high-frequency bipolar stimulation. A retrospective chart review was conducted to determine the success rate of motor mapping and to acquire intraoperative details.RESULTSThirteen patients underwent both high- and low-frequency bipolar motor mapping to aid in tumor resection. Of the lesions treated, 69% were gliomas, and the remainder were metastases. The motor cortex was identified at a significantly greater rate when using high-frequency TOF bipolar stimulation (n = 13) compared to the low-frequency bipolar stimulation (n = 4) (100% vs 31%, respectively; p = 0.0005). Intraoperative seizures and afterdischarges occurred only in the group of patients who underwent low-frequency bipolar stimulation, and none occurred in the TOF group (31% vs 0%, respectively; p = 0.09).CONCLUSIONSUsing a bipolar wand with high-frequency TOF stimulation, the authors achieved a significantly higher rate of successful motor mapping and a low rate of intraoperative seizure compared to traditional low-frequency bipolar stimulation. This preliminary study suggests that high-frequency TOF stimulation provides a reliable additional tool for motor cortex identification in asleep patients.

Awake Craniotomy for Resection of Left Temporal Cavernoma: 3-Dimensional Operative Video

Cavernomas presenting with seizures refractory to medical treatment may require surgical excision for seizure control. If superficial, they can be surgically accessible but can pose additional risks when located in or near eloquent cortex. In this 3D operative video we illustrate the technique for the resection of a left temporal cavernoma located near eloquent cortex for speech with awake surgery and cortical mapping to avoid a speech deficit postoperatively. Informed consent was obtained for this procedure. Navigation is used to localize the cavernoma following which a large craniotomy is performed exposing the temporal lobe, frontal lobe, and sylvian vein. Bipolar stimulation is used to localize speech with the patient awake until speech arrest occurs. The cavernoma is situated immediately inferior to the sulcus over which speech arrest occurs. The sulcus immediately above the cavernoma is opened and adjacent arteries are carefully preserved. The glial plane around the cavernoma is used to dissect the cavernoma from the surrounding cortex. Care is taken to remove the haemosiderin as this can act as a precipitant for ongoing seizures. In this case the patient had no neurological deficits following surgery and was seizure free.