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Darryl Lau, Cecilia L. Dalle Ore, Patrick Reid, Michael M. Safaee, Vedat Deviren, Justin S. Smith, Christopher I. Shaffrey and Christopher P. Ames

OBJECTIVE

The benefits and utility of routine neuromonitoring with motor and somatosensory evoked potentials during lumbar spine surgery remain unclear. This study assesses measures of performance and utility of transcranial motor evoked potentials (MEPs) during lumbar pedicle subtraction osteotomy (PSO).

METHODS

This is a retrospective study of a single-surgeon cohort of consecutive adult spinal deformity (ASD) patients who underwent lumbar PSO from 2006 to 2016. A blinded neurophysiologist reviewed individual cases for MEP changes. Multivariate analysis was performed to determine whether changes correlated with neurological deficits. Measures of performance were calculated.

RESULTS

A total of 242 lumbar PSO cases were included. MEP changes occurred in 38 (15.7%) cases; the changes were transient in 21 cases (55.3%) and permanent in 17 (44.7%). Of the patients with permanent changes, 9 (52.9%) had no recovery and 8 (47.1%) had partial recovery of MEP signals. Changes occurred at a mean time of 8.8 minutes following PSO closure (range: during closure to 55 minutes after closure). The mean percentage of MEP signal loss was 72.9%. The overall complication rate was 25.2%, and the incidence of new neurological deficits was 4.1%. On multivariate analysis, MEP signal loss of at least 50% was not associated with complication (p = 0.495) or able to predict postoperative neurological deficits (p = 0.429). Of the 38 cases in which MEP changes were observed, the observation represented a true-positive finding in only 3 cases. Postoperative neurological deficits without MEP changes occurred in 7 cases. Calculated measures of performance were as follows: sensitivity 30.0%, specificity 84.9%, positive predictive value 7.9%, and negative predictive value 96.6%. Regarding the specific characteristics of the MEP changes, only a signal loss of 80% or greater was significantly associated with a higher rate of neurological deficit (23.0% vs 0.0% for loss of less than 80%, p = 0.021); changes of less than 80% were not associated with postoperative deficits.

CONCLUSIONS

Neuromonitoring has a low positive predictive value and low sensitivity for detecting new neurological deficits. Even when neuromonitoring is unchanged, patients can still have new neurological deficits. The utility of transcranial MEP monitoring for lumbar PSO remains unclear but there may be advantages to its use.

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Min Ho Lee, Kyung Hwan Kim, Kyung Rae Cho, Jung Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife surgery (FGKS) has recently been used to treat large brain metastases. However, little is known about specific volume changes of lesions during the course of treatment. The authors investigated short-term volume changes of metastatic lesions during FGKS.

METHODS

The authors analyzed 33 patients with 40 lesions who underwent FGKS for intracranial metastases of non–small-cell lung cancer (NSCLC; 25 patients with 32 lesions) and breast cancer (8 patients with 8 lesions). FGKS was performed in 3–5 fractions. Baseline MRI was performed before the first fraction. MRI was repeated after 1 or 2 fractions. Adaptive planning was executed based on new images. The median prescription dose was 8 Gy (range 6–10 Gy) with a 50% isodose line.

RESULTS

On follow-up MRI, 18 of 40 lesions (45.0%) showed decreased tumor volumes (TVs). A significant difference was observed between baseline (median 15.8 cm3) and follow-up (median 14.2 cm3) volumes (p < 0.001). A conformity index was significantly decreased when it was assumed that adaptive planning was not implemented, from baseline (mean 0.96) to follow-up (mean 0.90, p < 0.001). The average reduction rate was 1.5% per day. The median follow-up duration was 29.5 weeks (range 9–94 weeks). During the follow-up period, local recurrence occurred in 5 lesions.

CONCLUSIONS

The TV showed changes with a high dose of radiation during the course of FGKS. Volumetric change caused a significant difference in the clinical parameters. It is expected that adaptive planning would be helpful in the case of radiosensitive tumors such as NSCLCs or breast cancer to ensure an adequate dose to the target area and reduce unnecessary exposure of normal tissue to radiation.

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Vincent Prinz, Simon Bayerl, Nora Renz, Andrej Trampuz, Marcus Czabanka, Johannes Woitzik, Peter Vajkoczy and Tobias Finger

OBJECTIVE

Loosening of pedicle screws is a frequent complication after spinal surgery. Implant colonization with low-virulent microorganisms forming biofilms may cause implant loosening. However, the clinical evidence of this mechanism is lacking. Here, the authors evaluated the potential role of microbial colonization using sonication in patients with clinical pedicle screw loosening but without signs of infection.

METHODS

All consecutive patients undergoing hardware removal between January 2015 and December 2017, including patients with screw loosening but without clinical signs of infection, were evaluated. The removed hardware was investigated using sonication.

RESULTS

A total of 82 patients with a mean (± SD) patient age of 65 ± 13 years were eligible for evaluation. Of the 54 patients with screw loosening, 22 patients (40.7%) had a positive sonication result. None of the 28 patients without screw loosening who served as a control cohort showed a positive sonication result (p < 0.01). In total, 24 microorganisms were detected in those 22 patients. The most common isolated microorganisms were coagulase-negative staphylococci (62.5%) and Cutibacterium acnes (formerly known as Propionibacterium acnes) (25%). When comparing only the patients with screw loosening, the duration of the previous spine surgery was significantly longer in patients with a positive microbiological result (288 ± 147 minutes) than in those with a negative result (201 ± 103 minutes) (p = 0.02).

CONCLUSIONS

The low-virulent microorganisms frequently detected on pedicle screws by using sonication may be an important cause of implant loosening and failure. Longer surgical duration increases the likelihood of implant colonization with subsequent screw loosening. Sonication is a highly sensitive approach to detect biofilm-producing bacteria, and it needs to be integrated into the clinical routine for optimized treatment strategies.

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Jack J. Haslett, Lindsey A. LaBelle, Xiangnan Zhang, J Mocco, Joshua Bederson and Christopher P. Kellner

OBJECTIVE

Carotid artery disease is a common illness that can pose a significant risk if left untreated. Treatment via carotid endarterectomy (CEA) or carotid artery stenting (CAS) can also lead to complications. Given the risk of adverse events related to treating, or failing to treat, carotid artery disease, this is a possible area for litigation. The aim of this review is to provide an overview of the medicolegal factors involved in treating patients suffering carotid artery disease and to compare litigation related to CEA and CAS.

METHODS

Three large legal databases were used to search for jury verdicts and settlements in cases related to untreated carotid artery disease, CEA, and CAS. Search terms included “endarterectomy,” “medical malpractice,” “carotid,” “stenosis,” “stenting,” “stent,” and combinations of those words. Three types of cases were considered relevant: 1) cases in which the primary allegation was negligence performing a CEA or perioperative care (CEA-related cases); 2) cases in which the primary allegation was negligence performing a CAS or perioperative care (CAS-related cases); and 3) cases in which the plaintiff alleged that a CEA or CAS should have been performed (failure-to-treat [FTT] cases).

RESULTS

One hundred fifty-four CEA-related cases, 3 CAS-related cases, and 67 FTT cases were identified. Cases resulted in 133 verdicts for the defense (59%), 64 settlements (29%), and 27 plaintiff verdicts (12%). The average payout in cases that were settled outside of court was $1,097,430 and the average payout in cases that went to trial and resulted in a plaintiff verdict was $2,438,253. Common allegations included a failure to diagnose and treat carotid artery disease in a timely manner, treating with inappropriate indications, procedural error, negligent postprocedural management, and lack of informed consent. Allegations of a failure to timely treat known carotid artery disease were likely to lead to a payout (60% of cases involved a payout). Allegations of procedural error, specifically where the resultant injury was nerve injury, were relatively less likely to lead to a payout (28% of cases involved a payout).

CONCLUSIONS

Both diagnosing and treating carotid artery disease has serious medicolegal implications and risks. In cases resulting in a plaintiff verdict, the payouts were significantly higher than cases resolved outside the courtroom. Knowledge of common allegations in diagnosing and treating carotid artery disease as well as performing CEA and CAS may benefit neurosurgeons. The lack of CAS-related litigation suggests these procedures may entail a lower risk of litigation compared to CEA, even accounting for the difference in the frequency of both procedures.

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Constantin Roder, Till-Karsten Hauser, Ulrike Ernemann, Marcos Tatagiba, Nadia Khan and Benjamin Bender

OBJECTIVE

The purpose of this study was to evaluate chronological patterns of arterial wall contrast enhancement in contrast-enhanced high-resolution MRI (CE-HR-MRI) in patients with moyamoya disease (MMD).

METHODS

The authors performed a blinded analysis of clinical and imaging data from MMD patients. Data were analyzed chronologically for each patient and the intensity of arterial wall enhancement was correlated with the clinical and imaging-based progression status of the disease.

RESULTS

A total of 31 MMD patients and 61 imaging time points were included. CE-HR-MRI results were available for 56 time points, representing 112 hemispheric analyses. No arterial wall contrast enhancement (grade 1) was seen in 54 (48%) of the analyses, mild enhancement (grade 2) in 24 (21%), moderate enhancement (grade 3) in 15 (13%), and strong (grade 4) mainly concentric arterial wall contrast enhancement in 19 (17%). Grade 4 contrast enhancement was significantly (p < 0.001) associated with clinical disease progression within 6 months (before or after the MRI) compared to grades 1–3, with positive and negative predictive values of 0.8 and 0.88, respectively. Grades 1 and 2 (no contrast enhancement and only mild contrast enhancement) were highly predictive for stable disease (negative predictive value: 0.95).

CONCLUSIONS

A specific chronological increasing and decreasing pattern of arterial wall contrast enhancement associated with “beginning” as well as progression of angiopathy occurs in MMD patients. In clinical practice, CE-HR-MRI of the arterial wall may help to identify patients at risk of new strokes caused by disease progression and hence impel early treatment for future stroke prevention. Understanding of this temporary enhancement of the arterial wall might also bring new insights into the etiology of MMD.

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Damian A. Almiron Bonnin, Matthew C. Havrda, Myung Chang Lee, Linton Evans, Cong Ran, David C. Qian, Lia X. Harrington, Pablo A. Valdes, Chao Cheng, Chris I. Amos, Brent T. Harris, Keith D. Paulsen, David W. Roberts and Mark A. Israel

OBJECTIVE

5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods.

METHODS

The authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles.

RESULTS

In this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors.

CONCLUSIONS

These results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.

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Lauren E. Rotman, James R. Hackney, Benjamin M. McGrew, Winfield S. Fisher III and Curtis J. Rozzelle

Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder that is phenotypically similar to Noonan syndrome and is associated with mutations in BRAF, MEK1, MEK2, and KRAS. The relationship between malignancy risk and CFCS is unclear with few cases published in the literature. The purpose of this paper is to describe the case of a patient with CFCS presenting in extremis as a result of a large intracerebral hemorrhage arising from a temporal bone mass with histopathology most consistent with chondroblastoma and secondary aneurysmal bone cyst. This is the first case to document an association between CFCS and chondroblastoma.

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Michael A. Williams, Sean J. Nagel, Mark G. Luciano, Norman Relkin, Thomas J. Zwimpfer, Heather Katzen, Richard Holubkov, Abhay Moghekar, Jeffrey H. Wisoff, Guy M. McKhann II, James Golomb, Richard J. Edwards and Mark G. Hamilton

OBJECTIVE

The authors describe the demographics and clinical characteristics of the first 517 patients enrolled in the Adult Hydrocephalus Clinical Research Network (AHCRN) during its first 2 years.

METHODS

Adults ≥ 18 years were nonconsecutively enrolled in a registry at 6 centers. Four categories of adult hydrocephalus were defined: transition (treated before age 18 years), unrecognized congenital (congenital pattern, not treated before age 18 years), acquired (secondary to known risk factors, treated or untreated), and suspected idiopathic normal pressure hydrocephalus (iNPH) (≥ age 65 years, not previously treated). Data include etiology, symptoms, examination findings, neuropsychology screening, comorbidities, treatment, complications, and outcomes. Standard evaluations were administered to all patients by trained examiners, including the Montreal Cognitive Assessment, the Symbol Digit Modalities Test, the Beck Depression Inventory–II, the Overactive Bladder Questionnaire Short Form symptom bother, the 10-Meter Walk Test, the Boon iNPH gait scale, the Lawton Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) questionnaire, the iNPH grading scale, and the modified Rankin Scale.

RESULTS

Overall, 517 individuals were enrolled. Age ranged from 18.1 to 90.7 years, with patients in the transition group (32.7 ± 10.0 years) being the youngest and those in the suspected iNPH group (76.5 ± 5.2 years) being the oldest. The proportion of patients in each group was as follows: 16.6% transition, 26.5% unrecognized congenital, 18.2% acquired, and 38.7% suspected iNPH. Excluding the 86 patients in the transition group, who all had received treatment, 79.4% of adults in the remaining 3 groups had not been treated at the time of enrollment. Patients in the suspected iNPH group had the poorest performance in cognitive evaluations, and those in the unrecognized congenital group had the best performance. The same pattern was seen in the Lawton ADL/IADL scores. Gait velocity was lowest in patients in the suspected iNPH group. Categories that had the most comorbidities (suspected iNPH) or etiologies of hydrocephalus that directly cause neurological injury (transition, acquired) had greater degrees of impairment compared to unrecognized congenital, which had the fewest comorbidities or etiologies associated with neurological injury.

CONCLUSIONS

The clinical spectrum of hydrocephalus in adults comprises more than iNPH or acquired hydrocephalus. Only 39% of patients had suspected iNPH, whereas 43% had childhood onset (i.e., those in the transition and unrecognized congenital groups). The severity of symptoms and impairment was worsened when the etiology of the hydrocephalus or complications of treatment caused additional neurological injury or when multiple comorbidities were present. However, more than half of patients in the transition, unrecognized congenital, and acquired hydrocephalus groups had minimal or no impairment. Excluding the transition group, nearly 80% of patients in the AHCRN registry were untreated at the time of enrollment. A future goal for the AHCRN is to determine whether patients with unrecognized congenital and acquired hydrocephalus need treatment and which patients in the suspected iNPH cohort actually have possible hydrocephalus and should undergo further diagnostic testing. Future prospective research is needed in the diagnosis, treatment, outcomes, quality of life, and macroeconomics of all categories of adult hydrocephalus.

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Jennifer Kollmer, Paul Preisser, Martin Bendszus and Henrich Kele

Diagnosis of spontaneous fascicular nerve torsions is difficult and often delayed until surgical exploration is performed. This case series raises awareness of peripheral nerve torsions and will facilitate an earlier diagnosis by using nerve ultrasound (NUS) and magnetic resonance neurography (MRN). Four patients with previously ambiguous upper-extremity mononeuropathies underwent NUS and 3T MRN. Neuroimaging detected proximal torsions of the anterior and posterior interosseous nerve fascicles within median or radial nerve trunks in all patients. In NUS, most cases presented with a thickening of affected nerve fascicles, followed by an abrupt caliber decrease, leading to the pathognomonic sausage-like configuration. MRN showed T2-weighted hyperintense signal alterations of fascicles at and distal to the torsion site, and directly visualized the distorted nerves. Three patients had favorable outcomes after being transferred to emergency surgical intervention, while 1 patient with existing chronic muscle atrophy was no longer eligible for surgery. NUS and MRN are complementary diagnostic methods, and both can detect nerve torsions on a fascicular level. Neuroimaging is indispensable for diagnosing fascicular nerve torsions, and should be applied in all unclear cases of mononeuropathy to determine the diagnosis and if necessary, to guide surgical therapies, as only timely interventions enable favorable outcomes.

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Tae-Jin Song, Seung-Hun Oh and Jinkwon Kim

OBJECTIVE

Cerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.

METHODS

This was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.

RESULTS

A total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).

CONCLUSIONS

Consistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.