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William P. Nobis, Karina A. González Otárula, Jessica W. Templer, Elizabeth E. Gerard, Stephen VanHaerents, Gregory Lane, Guangyu Zhou, Joshua M. Rosenow, Christina Zelano and Stephan Schuele

OBJECTIVE

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death for patients with refractory epilepsy, and there is increasing evidence for a centrally mediated respiratory depression as a pathophysiological mechanism. The brain regions responsible for a seizure’s inducing respiratory depression are unclear—the respiratory nuclei in the brainstem are thought to be involved, but involvement of forebrain structures is not yet understood. The aim of this study was to analyze intracranial EEGs in combination with the results of respiratory monitoring to investigate the relationship between seizure spread to specific mesial temporal brain regions and the onset of respiratory dysfunction and apnea.

METHODS

The authors reviewed all invasive electroencephalographic studies performed at Northwestern Memorial Hospital (Chicago) since 2010 to identify those cases in which 1) multiple mesial temporal electrodes (amygdala and hippocampal) were placed, 2) seizures were captured, and 3) patients’ respiration was monitored. They identified 8 investigations meeting these criteria in patients with temporal lobe epilepsy, and these investigations yielded data on a total of 22 seizures for analysis.

RESULTS

The onset of ictal apnea associated with each seizure was highly correlated with seizure spread to the amygdala. Onset of apnea occurred 2.7 ± 0.4 (mean ± SEM) seconds after the spread of the seizure to the amygdala, which was significantly earlier than after spread to the hippocampus (10.2 ± 0.7 seconds; p < 0.01).

CONCLUSIONS

The findings suggest that activation of amygdalar networks is correlated with central apnea during seizures. This study builds on the authors’ prior work that demonstrates a role for the amygdala in voluntary respiratory control and suggests a further role in dysfunctional breathing states seen during seizures, with implications for SUDEP pathophysiology.

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Matthew D. Hall, Yazmin Odia, Joshua E. Allen, Rohinton Tarapore, Ziad Khatib, Toba N. Niazi, Doured Daghistani, Lee Schalop, Andrew S. Chi, Wolfgang Oster and Minesh P. Mehta

Diffuse intrinsic pontine gliomas (DIPGs) frequently harbor the histone H3 K27M mutation. Gliomas with this mutation commonly overexpress dopamine receptor (DR) D2 and suppress DRD5, leading to enhanced sensitivity to DRD2 antagonism. This study reports the first clinical experience with the DRD2/3 antagonist ONC201 as a potential targeted therapy for H3 K27M–mutant DIPG. One pediatric patient (a 10-year-old girl) with H3 K27M–mutant DIPG was enrolled in an investigator-initiated, IRB-approved compassionate-use study and began single-agent ONC201 treatment 1 month after completing radiotherapy. The study endpoints were clinical and radiographic response (primary) and toxicities (secondary).

The patient presented with House-Brackmann grade IV facial palsy and unilateral hearing loss. MRI demonstrated a 2.3 × 2.1 × 2.8–cm pontomedullary tumor. Stereotactic biopsy confirmed H3 K27M–mutated DIPG. The tumor was treated with radiotherapy, but 1 month after completion of that treatment, the tumor and neurological symptoms showed only minimal change, and ONC201 treatment was initiated as described above. The tumor volume sequentially decreased by 26%, 40%, and 44% over the next 6 months, and remained stable at 18 months. Ipsilateral hearing normalized and the facial palsy improved to House-Brackmann grade I by 4 months. After 1 year of ONC201 treatment, 2 new lesions were identified outside of the prior high-dose radiotherapy volume. The patient was treated with dexamethasone, bevacizumab, and additional focal radiotherapy to these new tumors. These tumors remained stable in size over the subsequent 6 months on MRI. To date, no adverse events have been observed or reported due to ONC201. The patient remains clinically improved as of the latest follow-up visit, 19 months after starting ONC201 and 22 months from diagnosis. This case supports further investigation of this novel agent targeting H3 K27M–mutated DIPG.

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Samuel Romano-Feinholz, Víctor Alcocer-Barradas, Alejandra Benítez-Gasca, Ernesto Martínez-de la Maza, Cristopher Valencia-Ramos and Juan Luis Gómez-Amador

OBJECTIVE

The authors conducted a pilot study on hybrid fluorescein-guided surgery for pituitary adenoma resection and herein describe the feasibility and safety of this technique.

METHODS

In this pilot study, the authors included all consecutive patients presenting with pituitary adenomas, functioning and nonfunctioning. They performed a hybrid fluorescein-guided surgical technique for tumor resection. An endonasal endoscopic approach was used; after exposure of the rostrum of the sphenoid sinus, they administered a bolus of 8 mg/kg of fluorescein sodium (FNa) intravenously, and during resection, they alternated between endoscopic and microscopic techniques to guide the resection under a YELLOW 560 filter.

RESULTS

The study included 15 patients, 7 men (47%) and 8 women (53%). Of the pituitary adenomas, 7 (46%) were nonfunctioning, 6 (40%) were GH secreting, 1 (7%) was prolactin secreting, and 1 (7%) was ACTH secreting. There were no FNa-related complications (anaphylactic reactions); yellowish staining of urine, skin, and mucosa was seen in all patients and resolved in a maximum time of 24 hours. After color spectrophotometric analysis, the authors identified a statistical difference in fluorescence among tumor, gland, and scar tissue (p = 0.01).

CONCLUSIONS

This is the first study of its kind to describe the feasibility and safety of using FNa to guide the resection of pituitary adenomas. The authors found this technique to be safe and feasible. It may be used to obtain better surgical results, especially for hormone-producing and recurring tumors, as well as for reducing the learning curve in pituitary adenoma surgery.

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Valeria Guglielmi and Daniel M. Mandell

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Cecilia L. Dalle Ore, Stephen T. Magill, Adam J. Yen, Maryam N. Shahin, David S. Lee, Calixto-Hope G. Lucas, William C. Chen, Jennifer A. Viner, Manish K. Aghi, Philip V. Theodosopoulos, David R. Raleigh, Javier E. Villanueva-Meyer and Michael W. McDermott

OBJECTIVE

Extracranial meningioma metastases are uncommon, occurring in less than 1% of patients diagnosed with meningioma. Due to the rarity of meningioma metastases, patients are not routinely screened for distant disease. In this series, we report their experience with meningioma metastases and results of screening for metastases in select patients with recurrent meningiomas.

METHODS

All patients undergoing resection or stereotactic radiosurgery for primary or recurrent meningioma from 2009 to 2017 at a single center were retrospectively reviewed to identify patients who were diagnosed with or underwent imaging to evaluate for systemic metastases. Imaging to evaluate for metastases was performed with CT scanning of the chest, abdomen, and pelvis or whole-body PET/CT using either FDG or 68Ga-DOTA-octreotate (DOTATATE) tracers in 28 patients. Indications for imaging were symptomatic lesions concerning for metastasis or asymptomatic screening in patients with greater than 2 recurrences being evaluated for additional treatment.

RESULTS

Of 1193 patients treated for meningioma, 922 (77.3%) patients had confirmed or presumed WHO grade I tumors, 236 (19.8%) had grade II tumors, and 35 (2.9%) had grade III tumors. Mean follow-up was 4.3 years. A total of 207 patients experienced recurrences (17.4%), with a mean of 1.8 recurrences. Imaging for metastases was performed in 28 patients; 1 metastasis was grade I (3.6%), 16 were grade II (57.1%), and 11 were grade III (39.3%). Five patients (17.9%) underwent imaging because of symptomatic lesions. Of the 28 patients screened, 27 patients had prior recurrent meningioma (96.4%), with a median of 3 recurrences. On imaging, 10 patients had extracranial lesions suspicious for metastasis (35.7%). At biopsy, 8 were meningioma metastases, 1 was a nonmeningioma malignancy, and 1 patient was lost to follow-up prior to biopsy. Biopsy-confirmed metastases occurred in the liver (5), lung (3), mediastinum (1), and bone (1). The observed incidence of metastases was 0.67% (n = 8). Incidence increased to 2% of WHO grade II and 8.6% of grade III meningiomas. Using the proposed indications for screening, the number needed to screen to identify one patient with biopsy-confirmed malignancy was 3.83.

CONCLUSIONS

Systemic imaging of patients with multiply recurrent meningioma or symptoms concerning for metastasis may identify extracranial metastases in a significant proportion of patients and can inform decision making for additional treatments.

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Mohammed Adeeb Sebai, Panagiotis Kerezoudis, Mohammed Ali Alvi, Jang Won Yoon, Robert J. Spinner and Mohamad Bydon

OBJECTIVE

Spinal peripheral nerve sheath tumors (PNSTs) are a group of rare tumors originating from the nerve and its supporting structures. Standard surgical management typically entails laminectomy with or without facetectomy to gain adequate tumor exposure. Arthrodesis is occasionally performed to maintain spinal stability and mitigate the risk of postoperative deformity, pain, or neurological deficit. However, the factors associated with the need for instrumentation in addition to PNST resection in the same setting remain unclear.

METHODS

An institutional tumor registry at a tertiary care center was queried for patients treated surgically for a primary diagnosis of spinal PNST between 2002 and 2016. An analysis focused on patients in whom a facetectomy was performed during the resection. The addition of arthrodesis at the index procedure comprised the primary outcome. The authors also recorded baseline demographics, tumor characteristics, and surgery-related variables. Logistic regression was used to identify factors associated with increased risk of fusion surgery.

RESULTS

A total of 163 patients were identified, of which 56 (32 had facetectomy with fusion, 24 had facetectomy alone) were analyzed. The median age was 48 years, and 50% of the cohort was female. Age, sex, and race, as well as tumor histology and size, were evenly distributed between patients who received facetectomy alone and those who had facetectomy and fusion. On univariate analysis, total versus subtotal facetectomy (OR 9.0, 95% CI 2.01–64.2; p = 0.009) and cervicothoracic versus other spinal region (OR 9.0, 95% CI 1.51–172.9; p = 0.048) were significantly associated with increased odds of performing immediate fusion. On multivariable analysis, only the effect of total facetectomy remained statistically significant (OR 6.75, 95% CI 1.47–48.8; p = 0.025).

CONCLUSIONS

The authors found that total facetectomy and cervicothoracic involvement may be highly associated with the need for concomitant arthrodesis at the time of index surgery. These findings may help surgeons to determine the best surgical planning for patients with PNST.

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Xin Wang, Zhiqi Mao, Zhiqiang Cui, Xin Xu, Longsheng Pan, Shuli Liang, Zhipei Ling and Xinguang Yu

OBJECTIVE

Primary Meige syndrome is characterized by blepharospasm and orofacial–cervical dystonia. Deep brain stimulation (DBS) is recognized as an effective therapy for patients with this condition, but previous studies have focused on clinical effects. This study explored the predictors of clinical outcome in patients with Meige syndrome who underwent DBS.

METHODS

Twenty patients who underwent DBS targeting the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) at the Chinese People’s Liberation Army General Hospital from August 2013 to February 2018 were enrolled in the study. Their clinical outcomes were evaluated using the Burke–Fahn–Marsden Dystonia Rating Scale at baseline and at the follow-up visits; patients were accordingly divided into a good-outcome group and a poor-outcome group. Putative influential factors, such as age and course of disease, were examined separately, and the factors that reached statistical significance were subjected to logistic regression analysis to identify predictors of clinical outcomes.

RESULTS

Four factors showed significant differences between the good- and poor-outcome groups: 1) the DBS target (STN vs GPi); 2) whether symptoms first appeared at multiple sites or at a single site; 3) the sub-item scores of the mouth at baseline; and 4) the follow-up period (p < 0.05). Binary logistic regression analysis revealed that initial involvement of multiple sites and the mouth score were the only significant predictors of clinical outcome.

CONCLUSIONS

The severity of the disease in the initial stage and presurgical period was the only independent predictive factor of the clinical outcomes of DBS for the treatment of patients with Meige syndrome.

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Johannes A. Mayer, Laura A. Hruby, Stefan Salminger, Gerd Bodner and Oskar C. Aszmann

OBJECTIVE

Spinal accessory nerve palsy is frequently caused by iatrogenic damage during neck surgery in the posterior triangle of the neck. Due to late presentation, treatment regularly necessitates nerve grafts, which often results in a poor outcome of trapezius function due to long regeneration distances. Here, the authors report a distal nerve transfer using fascicles of the upper trunk related to axillary nerve function for reinnervation of the trapezius muscle.

METHODS

Five cases are presented in which accessory nerve lesions were reconstructed using selective fascicular nerve transfers from the upper trunk of the brachial plexus. Outcomes were assessed at 20 ± 6 months (mean ± SD) after surgery, and active range of motion and pain levels using the visual analog scale were documented.

RESULTS

All 5 patients regained good to excellent trapezius function (3 patients had grade M5, 2 patients had grade M4). The mean active range of motion in shoulder abduction improved from 55° ± 18° before to 151° ± 37° after nerve reconstruction. In all patients, unrestricted shoulder arm movement was restored with loss of scapular winging when abducting the arm. Average pain levels decreased from 6.8 to 0.8 on the visual analog scale and subsided in 4 of 5 patients.

CONCLUSIONS

Restoration of spinal accessory nerve function with selective fascicle transfers related to axillary nerve function from the upper trunk of the brachial plexus is a good and intuitive option for patients who do not qualify for primary nerve repair or present with a spontaneous idiopathic palsy. This concept circumvents the problem of long regeneration distances with direct nerve repair and has the advantage of cognitive synergy to the target function of shoulder movement.

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Haariss Ilyas, Joshua L. Golubovsky, Jingxiao Chen, Robert D. Winkelman, Thomas E. Mroz and Michael P. Steinmetz

OBJECTIVE

The objective of this study was to evaluate the incidence and risk factors for 90-day readmission and reoperation after elective surgery for lumbar spinal stenosis (LSS).

METHODS

The authors performed a retrospective consecutive cohort analysis of patients undergoing posterior lumbar decompression with or without fusion for LSS with claudication from January 2014 through December 2015.

RESULTS

Data were collected on 1592 consecutive patients. The mean age at surgery was 67.4 ± 10.1 years and 45% of patients were female. The 90-day reoperation rate was 4.7%, and 69.3% of the reoperations occurred within the first 30 days. The 90-day readmission rate was 7.2%. Multivariable analysis showed that postoperative development of a surgical site infection (SSI; odds ratio [OR] 14.09, 95% confidence interval [CI] 7.86–25.18), acute kidney injury (AKI; OR 6.76, 95% CI 2.39–19.57), and urinary tract infection (UTI; OR 3.96, 95% CI 2.43–6.37), as well as a history of congestive heart failure (CHF; OR 3.03, 95% CI 1.69–5.28), were significant risk factors for readmission within 90 days. Male sex (OR 0.60, 95% CI 0.38–0.92) was associated with decreased odds for readmission. With regards to reoperation, development of SSI (OR 25.06, 95% CI 13.54–46.51), sepsis (OR 7.63, 95% CI 1.52–40.59), UTI (OR 2.54, 95% CI 1.31–4.76), and increased length of stay (LOS; OR 1.25, 95% CI 1.17–1.33) were found to be significant risk factors. A subsequent analysis found that morbid obesity (OR 6.99), history of coronary artery disease (OR 2.263), increased duration of surgery (OR 1.004), and LOS (OR 1.07) were significant risk factors for developing an SSI.

CONCLUSIONS

Overall, this study found rates of 4.7% and 7.2% for reoperation and readmission, respectively, within 90 days: 30.7% of the reoperations and 44.7% of the readmissions occurred beyond the first 30 days. A diagnosis of SSI, AKI, UTI, and history of CHF were significant factors for readmission, while male sex was associated with decreased odds for readmission. A diagnosis of SSI, sepsis, UTI, and increased LOS were found to be significant predictors for reoperation. Understanding 90-day complication rates is imperative because there has been increased discussion and healthcare policy extending the global postoperative window to 90 days. Current literature supports a readmission rate of 3%–9% after spine surgery. However, this literature either is limited to a 30-day window or does not stratify between different types of spine surgeries.