Kerezoudis, Panagiotis

Abstract BACKGROUND The Food and Drug Administration approved the deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) as an adjunctive therapy for drug-resistant epilepsy (DRE) in the United States in 2018. The DBS Therapy for Epilepsy Post-Approval Study is further evaluating the safety and effectiveness of ANT-DBS among different patients’ groups. For this study, devices for vagus nerve stimulation (VNS) must be removed prior to enrolment. OBJECTIVE To investigate the outcomes of concomitant ANT-DBS and VNS treatment for DRE. METHODS A retrospective analysis was performed for 33 patients who underwent ANT-DBS using previous VNS to define distinct subgroups: standard ANT-DBS (9 subjects), ANT-DBS with functional VNS (12 subjects), and ANT-DBS with the VNS implantable pulse generator explanted or turned off at the time of the DBS (12 subjects). Effectiveness and safety data were analyzed across the whole population and among subgroups. RESULTS A mean decrease in seizure frequency of 55% was observed after a mean follow-up of 25.5 mo. Approximately 67% of patients experienced ≥50% reduction in seizure frequency. Seizure reduction percentage was not significantly different among groups. Approximately 50% of subjects with no appreciable improvement and 75% of those who showed benefit after VNS (including improvement in seizure frequency, seizure severity, and seizure duration or quality of life) achieved a seizure reduction ≥50% after ANT-DBS surgery. There were no complications related to concomitant VNS and ANT-DBS. CONCLUSION ANT-DBS for DRE provides excellent results despite previous and ongoing VNS therapy. Removal of VNS does not appear to be necessary before ANT-DBS.

BACKGROUND Open surgical treatment of insular epilepsy holds particular risk of injury to middle cerebral artery branches, the operculum (through retraction), and adjacent language-related white matter tracts in the language-dominant hemisphere. Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (LITT) is a surgical alternative that allows precise lesioning with potentially less operative risk. The authors presented the case of a 13-year-old girl with intractable, MRI-negative, left (dominant hemisphere) insular epilepsy that was treated with LITT. Diffusion tensor imaging (DTI) tractography was used to aid full posterior insular lesioning in the region of stereo electroencephalography–determined seizure onset while avoiding thermal injury to the language-related superior longitudinal fasciculus (SLF)/arcuate fasciculus (AF) and inferior fronto-occipital fasciculus (IFOF). OBSERVATIONS DTI tractography was used successfully in planning insular LITT and facilitated a robust insular ablation with sharp margins at the interfaces with the SLF/AF and IFOF. These tracts were spared, and no neurological deficits were induced through LITT. LESSONS Although it is technically demanding and has important limitations that must be understood, clinically available DTI tractography adds precision and confidence to insular laser ablation when used to protect important language-related white matter tracts.

Posterior fossa (PF) diffuse gliomas in pediatric patients frequently harbor the H3 K27M mutation. Among adults, PF diffuse gliomas are rare, with limited data regarding molecular features and clinical outcomes. We identified 28 adult PF diffuse glioma patients (17 males; median: 50 y, range: 19 to 78 y), with surgery performed at our institution (13 brainstem; 15 cerebellum). Histologic subtypes included anaplastic astrocytoma (n=21), glioblastoma (n=6), and diffuse astrocytoma (n=1). Immunohistochemistry was performed for H3 K27M (n=26), IDH1-R132H (n=28), and ATRX (n=28). A 150-gene neuro-oncology-targeted next-generation sequencing panel was attempted in 24/28, with sufficient informative material in 15 (51.7%). Tumors comprised 4 distinct groups: driver mutations in H3F3A (brainstem=4; cerebellum=2), IDH1 (brainstem=4; cerebellum=4), TERT promotor mutation (brainstem=0; cerebellum=3), and none of these (n=5), with the latter harboring mutations of TP53 , PDGFRA , ATRX , NF1 , and RB1 . All TERT promoter–mutant cases were IDH-wild-type and arose within the cerebellum. To date, 20 patients have died of disease, with a median survival of 16.3 months, 1-year survival of 67.5%. Median survival within the subgroups included: H3F3A =16.4 months, IDH mutant=113.4 months, and TERT promoter mutant=12.9 months. These findings suggest that PF diffuse gliomas affecting adults show molecular heterogeneity, which may be associated with patient outcomes and possible response to therapy, and supports the utility of molecular testing in these tumors.

Study Design Retrospective. Objective The aim of this study was to explore the utilization trends of recombinant human bone morphogenetic protein (rh-BMP) in the United States using the largest inpatient administrative database. Summary of Background Data Since 2002, the rh-BMP has been widely used by the surgical spine community in fusion surgery. In light of the rising evidence regarding the safety and efficacy of this novel and expensive bone biological technology, a comprehensive examination of its utilization in the American population is warranted. Methods We queried the 2002-Q3 2015 National Inpatient Sample for patients that underwent spinal fusion with rh-BMP. We calculated population-level estimates of rh-BMP utilization trends per 100,000 spinal fusions. Trends were estimated for the overall use as well as broken down by primary versus revision fusion, fusion type, number of levels, age category, US region, and hospital type. Results A total of 5,563,282 fusions were performed, of which 19.9% (n = 1,108,984) utilized rh-BMP. We detected an increase in rh-BMP use in spinal fusion surgery from 0.7% in 2002 to a peak of 29.5% in 2010, followed by a gradual decline till Q3 2015, where it represented 14.7% of all fusion surgeries. These trends paralleled all fusion types. It was most commonly used in fusions spanning two to three levels. The South remained the most common region, whereas West has recently surpassed the Midwest. Its use is becoming more pervasive among older patients, particularly in the 65- to 74 years’ age group. Conclusion Further studies are needed to provide insights into the correlation of these trends with the technology's safety and efficacy profile in contemporary series. Level of Evidence: 3

Study Design. Retrospective analysis of a prospective registry. Objective. We utilized the Quality Outcomes Database (QOD) registry to investigate the “July Effect” at QOD spondylolisthesis module sites with residency trainees. Summary of Background Data. There is a paucity of investigation on the long-term outcomes following surgeries involving new trainees utilizing high-quality, prospectively collected data. Methods. This was an analysis of 608 patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis at 12 high-enrolling sites. Surgeries were classified as occurring in July or not in July (non-July). Outcomes collected included estimated blood loss, length of stay, operative time, discharge disposition, complications, reoperation and readmission rates, and patient-reported outcomes (Oswestry Disability Index [ODI], Numeric Rating Scale [NRS] Back Pain, NRS Leg Pain, EuroQol-5D [EQ-5D] and the North American Spine Society [NASS] Satisfaction Questionnaire). Propensity score-matched analyses were utilized to compare postoperative outcomes and complication rates between the July and non-July groups. Results. Three hundred seventy-one surgeries occurred at centers with a residency training program with 21 (5.7%) taking place in July. In propensity score-matched analyses, July surgeries were associated with longer operative times ( average treatment effect = 22.4 minutes longer, 95% confidence interval 0.9–449.0, P = 0.041). Otherwise, July surgeries were not associated with significantly different outcomes for the remaining perioperative parameters (estimated blood loss, length of stay, discharge disposition, postoperative complications), overall reoperation rates, 3-month readmission rates, and 24-month ODI, NRS back pain, NRS leg pain, EQ-5D, and NASS satisfaction score (P > 0.05, all comparisons). Conclusion. Although July surgeries were associated with longer operative times, there were no associations with other clinical outcomes compared to non-July surgeries following lumbar spondylolisthesis surgery. These findings may be due to the increased attending supervision and intraoperative education during the beginning of the academic year. There is no evidence that the influx of new trainees in July significantly affects long-term patient-centered outcomes. Level of Evidence: 3

OBJECTIVE Acute traumatic subdural hematoma (atSDH) can be a life-threatening neurosurgical emergency that necessitates immediate evacuation. The elderly population can be particularly vulnerable to tearing bridging veins. The aim of this study was to evaluate inpatient morbidity and mortality, as well as predictors of inpatient mortality, in a national trauma database. METHODS The authors queried the 2016–2017 National Trauma Data Bank registry for patients aged 65 years and older who had undergone evacuation of atSDH. Patients were categorized into three age groups: 65–74, 75–84, and 85+ years. A multivariable logistic regression model was fitted for inpatient mortality adjusting for age group, sex, race, presenting Glasgow Coma Scale (GCS) category (3–8, 9–12, and 13–15), Injury Severity Score, presence of coagulopathy, presence of additional hemorrhages (epidural hematoma [EDH], intraparenchymal hematoma [IPH], and subarachnoid hemorrhage [SAH]), presence of midline shift > 5 mm, and pupillary reactivity (both, one, or none). RESULTS A total of 2508 patients (35% females) were analyzed. Age distribution was as follows: 990 patients at 65–74 years, 1096 at 75–84, and 422 at 85+. Midline shift > 5 mm was present in 72% of cases. With regard to additional hemorrhages, SAH was present in 21%, IPH in 10%, and EDH in 2%. Bilaterally reactive pupils were noted in 90% of patients. A major complication was observed in 14.4% of patients, and the overall mortality rate was 18.3%. In the multivariable analysis, the presenting GCS category was found to be the strongest predictor of postoperative inpatient mortality (3–8 vs 13–15: OR 3.63, 95% CI 2.68–4.92, p < 0.001; 9–12 vs 13–15: OR 2.64, 95% CI 1.79–3.90, p < 0.001; 30% of overall variation), followed by the presence of SAH (OR 2.86, 95% CI 2.21–3.70, p < 0.001; 25% of overall variation) and the presence of midline shift > 5 mm (OR 2.40, 95% CI 1.74–3.32, p < 0.001; 11% of overall variation). Model discrimination was excellent (c-index 0.81). Broken down by age decile group, mortality increased from 8.0% to 15.4% for GCS 13–15 to around 36% for GCS 9–12 to almost as high as 60% for GCS 3–8, particularly in those aged 85 years and older. CONCLUSIONS The present results from a national trauma database will, the authors hope, assist surgeons in preoperative discussions with patients and their families with regard to expected postoperative outcomes following surgical evacuation of an atSDH.

OBJECTIVEThe sitting or semisitting position in neurosurgery allows for several technical advantages, including improved visualization of the surgical field. However, it has also been associated with an increased risk of venous air embolisms and positioning-related complications that limit its commonplace adoption. The authors report a large, single-center series of cervical spine procedures performed with patients in the sitting or prone position in order to assess the perceived risk of intraoperative and postoperative complications associated with the sitting position.METHODSNoninstrumented, single-level posterior cervical spine procedures performed with patients in the sitting/semisitting or prone position from 2000 to 2016 at a single institution were reviewed. Institutional abstraction tools (DataMart and Chart Plus) were used to collect data from the medical records. The two positions were compared with regard to preoperative factors, intraoperative variables, and postoperative outcomes. Multivariable logistic regression models were fitted for 30-day readmission, 30-day return to the operating room, and complication rates.RESULTSA total of 750 patients (sitting, n = 480; prone, n = 270) were analyzed. The median age was 53 years for those who underwent surgery in the prone position and 50 years for those who underwent surgery in the sitting position (IQRs 45–62 years and 43–60 years, respectively), and 35% of the patients were female. Sitting cases were associated with significantly longer anesthetic times (221 minutes [range 199–252 minutes] vs 205 minutes [range 179–254 minutes]) and operative times (126 minutes [range 101–163 minutes] vs 149 minutes [120–181 minutes]). Cardiorespiratory events in the postanesthesia care unit (PACU) were comparable between the two groups, with the exception of episodes of apnea (2.6% vs 0.6%, p = 0.041) and hypoventilation (4.4% vs 0.8%, p < 0.003), which were more frequent in the prone-position cohort. On multivariable analysis, the effect of the sitting versus the prone position was not significant for 30-day readmission (OR 0.77, 95% CI 0.34–1.71, p = 0.52) or reoperation (OR 0.71, 95% CI 0.31–1.60, p = 0.40). The sitting position was associated with lower odds of developing any complication (OR 0.31, 95% CI 0.16–0.62, p < 0.001).CONCLUSIONSBased on the intraoperative and postoperative complications chosen in this study, the sitting position confers a similar safety profile to the prone position. This can be explained by a more anatomic positioning accounting for reduced temporary neurological deficits and reduced PACU-associated hypoventilation noted in this series. Nevertheless, the findings may also reflect institutional familiarity, experience, and mastery of this position type, and outcomes may not reflect practices in general.