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Martin H. Weiss

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Edward H. Oldfield, John A. Jane Jr., Michael O. Thorner, Carrie L. Pledger, Jason P. Sheehan, and Mary Lee Vance

OBJECTIVE

The relationship between growth hormone (GH) and insulin-like growth factor–1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly.

METHODS

This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly.

RESULTS

Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels.

CONCLUSIONS

In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

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Vivien H. Lee, Heidi M. Connolly, Jimmy R. Fulgham, Edward M. Manno, Robert D. Brown Jr., and Eelco F. M. Wijdicks

Object

Neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage (SAH) is associated with a wide spectrum of reversible left ventricular wall motion abnormalities and includes a subset of patients with a pattern of apical akinesia and concomitant sparing of basal segments called “tako-tsubo cardiomyopathy.”

Methods

After obtaining institutional review board approval, the authors retrospectively identified among all patients admitted to the Mayo Clinic’s Neurological Intensive Care Unit between January 1990 and January 2005 those with aneurysmal SAH who had met the echocardiographic criteria for tako-tsubo cardiomyopathy. Among 24 patients with SAH-induced reversible cardiac dysfunction, the authors identified eight with SAH-induced tako-tsubo cardiomyopathy. All eight patients were women with a mean age of 55.5 years (range 38.6–71.1). Seven patients presented with a poor-grade SAH, reflected by a Hunt and Hess grade of III or IV. Four patients underwent aneurysm clip application, and four underwent endovascular coil occlusion. The initial mean ejection fraction (EF) was 38% (range 25–55%), and the mean EF at recovery was 55% (range 40–68%). Cerebral vasospasm developed in six patients, but cerebral infarction developed in only three patients.

Conclusions

The authors describe the largest cohort with aneurysmal SAH–induced tako-tsubo cardiomyopathy. In the SAH population, tako-tsubo cardiomyopathy predominates in postmenopausal women and is often associated with pulmonary edema, prolonged intubation, and cerebral vasospasm. Additional studies are warranted to understand the complex mechanism involved in tako-tsubo cardiomyopathy and its intriguing relationship to neurogenic stunned myocardium.

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Robert J. Weil, Zhengping Zhuang, Svetlana Pack, Shimareet Kumar, Lee Helman, Brian G. Fuller, Crystall L. Mackall, and Edward H. Oldfield

✓ Molecular biological techniques have begun to transform modern medicine. These techniques have shown promise in the pathological diagnosis of difficult or uncommon tumors. Accurate molecular diagnosis of the small round-cell tumors, for example, is especially important because divergent therapies may be required to eradicate such disparate lesions as neuroblastoma, lymphoma, rhabdomyosarcoma, central primitive neuroectodermal tumors/medulloblastoma, or Ewing sarcoma (ES). The authors present an unusual case of a primary, extraosseous ES arising from the intramedullary spinal cord, in which molecular studies were required for specific diagnosis and therapeutic guidance.

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James L. Frazier, G. Steven Bova, Kathryn Jockovic, Elizabeth A. Hunt, Benjamin Lee, and Edward S. Ahn

Disseminated intravascular coagulation (DIC) as a complication of surgery for ventriculoperitoneal (VP) shunts is extremely rare, and only one case has been documented in the literature. The authors present the case of a 9-year-old girl with shunted hydrocephalus who presented with a 3-day history of headaches and vomiting. A head CT showed enlarged ventricles compared with baseline. An emergent VP shunt revision was performed, during which an obstructed proximal catheter was found. Immediately after extubation, the patient became apneic and progressed to cardiopulmonary arrest. A breathing tube was reinserted followed by resuscitation attempts that led to extracorporeal membrane oxygenation. Soon after reintubation, bloody drainage was noted in the endotracheal tube, and subsequent laboratory studies were consistent with DIC. The patient died on postoperative Day 1, and autopsy findings confirmed DIC. Note that DIC is a recognized complication of trauma, particularly with brain injury, but it is rare with neurosurgical procedures. Disseminated intravascular coagulation should be considered if excessive bleeding occurs after any brain insult.

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Lily H. Kim, Edward H. Lee, Michelle Galvez, Murat Aksoy, Stefan Skare, Rafael O’Halloran, Michael S. B. Edwards, Samantha J. Holdsworth, and Kristen W. Yeom

OBJECTIVE

Spine MRI is a diagnostic modality for evaluating pediatric CNS tumors. Applying diffusion-weighted MRI (DWI) or diffusion tensor imaging (DTI) to the spine poses challenges due to intrinsic spinal anatomy that exacerbates various image-related artifacts, such as signal dropouts or pileups, geometrical distortions, and incomplete fat suppression. The zonal oblique multislice (ZOOM)–echo-planar imaging (EPI) technique reduces geometric distortion and image blurring by reducing the field of view (FOV) without signal aliasing into the FOV. The authors hypothesized that the ZOOM-EPI method for spine DTI in concert with conventional spinal MRI is an efficient method for augmenting the evaluation of pediatric spinal tumors.

METHODS

Thirty-eight consecutive patients (mean age 8 years) who underwent ZOOM-EPI spine DTI for CNS tumor workup were retrospectively identified. Patients underwent conventional spine MRI and ZOOM-EPI DTI spine MRI. Two blinded radiologists independently reviewed two sets of randomized images: conventional spine MRI without ZOOM-EPI DTI, and conventional spine MRI with ZOOM-EPI DTI. For both image sets, the reviewers scored the findings based on lesion conspicuity and diagnostic confidence using a 5-point Likert scale. The reviewers also recorded presence of tumors. Quantitative apparent diffusion coefficient (ADC) measurements of various spinal tumors were extracted. Tractography was performed in a subset of patients undergoing presurgical evaluation.

RESULTS

Sixteen patients demonstrated spinal tumor lesions. The readers were in moderate agreement (kappa = 0.61, 95% CI 0.30–0.91). The mean scores for conventional MRI and combined conventional MRI and DTI were as follows, respectively: 3.0 and 4.0 for lesion conspicuity (p = 0.0039), and 2.8 and 3.9 for diagnostic confidence (p < 0.001). ZOOM-EPI DTI identified new lesions in 3 patients. In 3 patients, tractography used for neurosurgical planning showed characteristic fiber tract projections. The mean weighted ADCs of low- and high-grade tumors were 1201 × 10−6 and 865 × 10−6 mm2/sec (p = 0.002), respectively; the mean minimum weighted ADCs were 823 × 10−6 and 474 × 10−6 mm2/sec (p = 0.0003), respectively.

CONCLUSIONS

Diffusion MRI with ZOOM-EPI can improve the detection of spinal lesions while providing quantitative diffusion information that helps distinguish low- from high-grade tumors. By adding a 2-minute DTI scan, quantitative diffusion information and tract profiles can reliably be obtained and serve as a useful adjunct to presurgical planning for pediatric spinal tumors.

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Timothy W. A. Vogel, Alexander O. Vortmeyer, Irina A. Lubensky, Youn-Soo Lee, Makoto Furuta, Barbara Ikejiri, H. Jeffrey Kim, Russell R. Lonser, Edward H. Oldfield, and Zhengping Zhuang

Object. Von Hippel—Lindau (VHL) disease is characterized by multiple tumors in specific organs. The cell of origin and the reason for the particular organ distribution of the tumors remains unknown. Endolymphatic sac tumor (ELST) is one of the lesions associated with VHL disease. Data from previous studies of VHL disease—associated hemangioblastomas (HBs) and renal cell carcinomas (RCCs) have indicated that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth.

Methods. The authors studied ELSTs from five patients with VHL germline mutations. Analysis of the five ELST samples revealed loss of the wild-type allele, consistent with Knudson's two-hit hypothesis for tumorigenesis. All five ELST specimens were characterized microscopically and by immunohistochemical analysis. Coexpression of Epo and Epo-R was found in all five tumors on immunohistochemical studies and confirmed through reverse transcription—polymerase chain reaction and Western blot analysis.

Conclusions. Expression of Epo appears to be a result of VHL gene deficiency, whereas the simultaneous coexpression of Epo-R may reflect a developmental mechanism of tumorigenesis. Coexpression of Epo and Epo-R in ELSTs together with the morphological and genetic similarities of these lesions with other VHL disease—associated tumors indicates that VHL disease—associated tumors in different organs share common pathogenetic pathways.

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Jennifer L. Quon, Michelle Han, Lily H. Kim, Mary Ellen Koran, Leo C. Chen, Edward H. Lee, Jason Wright, Vijay Ramaswamy, Robert M. Lober, Michael D. Taylor, Gerald A. Grant, Samuel H. Cheshier, John R. W. Kestle, Michael S. B. Edwards, and Kristen W. Yeom

OBJECTIVE

Imaging evaluation of the cerebral ventricles is important for clinical decision-making in pediatric hydrocephalus. Although quantitative measurements of ventricular size, over time, can facilitate objective comparison, automated tools for calculating ventricular volume are not structured for clinical use. The authors aimed to develop a fully automated deep learning (DL) model for pediatric cerebral ventricle segmentation and volume calculation for widespread clinical implementation across multiple hospitals.

METHODS

The study cohort consisted of 200 children with obstructive hydrocephalus from four pediatric hospitals, along with 199 controls. Manual ventricle segmentation and volume calculation values served as “ground truth” data. An encoder-decoder convolutional neural network architecture, in which T2-weighted MR images were used as input, automatically delineated the ventricles and output volumetric measurements. On a held-out test set, segmentation accuracy was assessed using the Dice similarity coefficient (0 to 1) and volume calculation was assessed using linear regression. Model generalizability was evaluated on an external MRI data set from a fifth hospital. The DL model performance was compared against FreeSurfer research segmentation software.

RESULTS

Model segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls). The model generalized to external MR images from a fifth pediatric hospital with a Dice score of 0.926. The model was more accurate than FreeSurfer, with faster operating times (1.48 seconds per scan).

CONCLUSIONS

The authors present a DL model for automatic ventricle segmentation and volume calculation that is more accurate and rapid than currently available methods. With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow.

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The effect of C2–3 disc angle on postoperative adverse events in cervical spondylotic myelopathy

Presented at the 2018 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Bryan S. Lee, Kevin M. Walsh, Daniel Lubelski, Konrad D. Knusel, Michael P. Steinmetz, Thomas E. Mroz, Richard P. Schlenk, Iain H. Kalfas, and Edward C. Benzel

OBJECTIVE

Complete radiographic and clinical evaluations are essential in the surgical treatment of cervical spondylotic myelopathy (CSM). Prior studies have correlated cervical sagittal imbalance and kyphosis with disability and worse health-related quality of life. However, little is known about C2–3 disc angle and its correlation with postoperative outcomes. The present study is the first to consider C2–3 disc angle as an additional radiographic predictor of postoperative adverse events.

METHODS

A retrospective chart review was performed to identify patients with CSM who underwent surgeries from 2010 to 2014. Data collected included demographics, baseline presenting factors, and postoperative outcomes. Cervical sagittal alignment variables were measured using the preoperative and postoperative radiographs. Univariable logistic regression analyses were used to explore the association between dependent and independent variables, and a multivariable logistic regression model was created using stepwise variable selection.

RESULTS

The authors identified 171 patients who had complete preoperative and postoperative radiographic and outcomes data. The overall rate of postoperative adverse events was 33% (57/171), and postoperative C2–3 disc angle, C2–7 sagittal vertical axis, and C2–7 Cobb angle were found to be significantly associated with adverse events. Inclusion of postoperative C2–3 disc angle in the analysis led to the best prediction of adverse events. The mean postoperative C2–3 disc angle for patients with any postoperative adverse event was 32.3° ± 17.2°, and the mean for those without any adverse event was 22.4° ± 11.1° (p < 0.0001).

CONCLUSIONS

In the present retrospective analysis of postoperative adverse events in patients with CSM, the authors found a significant association between C2–3 disc angle and postoperative adverse events. They propose that C2–3 disc angle be used as an additional parameter of cervical spinal sagittal alignment and predictor for operative outcomes.

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Martin H. Weiss and William T. Couldwell