Report of a Case, with Some Remarks Concerning the Classification of Intracranial Epithelial Cysts
Carl F. List and John R. Williams
John Goodden, Barry Pizer, Benedetta Pettorini, Dawn Williams, Jo Blair, Mohammed Didi, Nicky Thorp, and Conor Mallucci
Optic pathway/hypothalamic gliomas (OPHGs) are generally benign tumors situated in an exquisitely sensitive brain region. The location and natural history of OPHGs has led to much debate about optimal treatment. This paper revisits the role of and optimal timing of debulking surgery in OPHG.
This paper presents a series of cases managed by the neuro-oncology team at Alder Hey Children's Hospital and a single surgeon. Data were collected retrospectively for periods prior to 2009 and prospectively thereafter. Tailored treatment strategies were used, including observation and combinations of surgery, chemotherapy, and radiotherapy. Tumor control rates and outcomes are reviewed.
Forty-two patients were treated between 1998 and 2011. Their median age at diagnosis was 5 years 7 months. Nineteen patients were positive for neurofibromatosis Type 1 (NF1) and 23 patients were negative for NF1. The median duration of follow-up was 77 months (range 21.8–142.3 months). Presenting symptoms included visual impairment (in 50% of cases), headache (in 24%), and hypothalamic/pituitary dysfunction (in 29%).
Twenty-two debulking procedures were performed in 21 patients. Four biopsies (3 open, 1 endoscopic) were also performed. The histological diagnosis was pilocytic astrocytoma in 21 patients and pilomyxoid astrocytoma in 2 patients. Ten patients (Group 1) had primary surgical debulking alone and were then observed. Four patients (Group 2) had surgical debulking, plus planned chemotherapy within 3 months. Seven patients (Group 3) required surgical debulking for progressive disease following a variety of treatments. Patient age had the greatest impact on subsequent tumor progression.
In total, 13 patients received chemotherapy, 4 on initial presentation, 4 in combination with surgery, and 5 for further tumor progression. Five patients were treated with radiotherapy, 3 prior to referral to Alder Hey.
Eleven patients required shunt insertion for hydrocephalus. Vision was stabilized for 74% of patients. The number of patients with hypothalamic/pituitary dysfunction increased from 12 at presentation to 16 by the end of treatment. The overall survival rate was 93%. Three patients died—1 from tumor progression, 1 from infective complications from tumor biopsy, and 1 from a spontaneous posterior fossa hemorrhage. NF1 was associated with improved outcome—fewer patients required active intervention and rates of visual impairment and/or or hypothalamic/pituitary dysfunction were lower.
Good long-term survival and functional outcomes can be achieved in children with OPHG. Tumor control was achieved through an individualized approach using surgery, chemotherapy, or radiotherapy in varied combinations. The authors aim to limit radiotherapy to cases involving older children in whom other therapies have failed, due to the well-described and often devastating late effects associated with midline cranial irradiation. Surgery has a clear role for diagnosis, tumor control, and relief of mass effect. In particular, primary surgical debulking of tumor (without adjuvant therapy) is safe and effective. Recent advances in intraoperative MRI may add value and need further assessment.
John R. Williams, Christopher C. Young, Nicholas A. Vitanza, Margaret McGrath, Abdullah H. Feroze, Samuel R. Browd, and Jason S. Hauptman
Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brainstem tumor affecting approximately 300 children in the US annually. Median survival is less than 1 year, and radiation therapy has been the mainstay of treatment for decades. Recent advances in the biological understanding of the disease have identified the H3K27M mutation in nearly 80% of DIPGs, leading to the 2016 WHO classification of diffuse midline glioma H3K27M-mutant, a grade IV brainstem tumor. Developments in epigenetic targeting of transcriptional tendencies have yielded potential molecular targets for clinical trials. Chimeric antigen receptor T cell therapy has also shown preclinical promise. Recent clinical studies, including prospective trials, have demonstrated the safety and feasibility of pediatric brainstem biopsy in the setting of DIPG and other brainstem tumors. Given developments in the ability to analyze DIPG tumor tissue to deepen biological understanding of this disease and develop new therapies for treatment, together with the increased safety of stereotactic brainstem biopsy, the authors present a case for offering biopsy to all children with suspected DIPG. They also present their standard operative techniques for image-guided, frameless stereotactic biopsy.
Jason K. Chu, Abdullah H. Feroze, Kelly Collins, Lynn B. McGrath Jr., Christopher C. Young, John R. Williams, and Samuel R. Browd
Placement of an external ventricular drain (EVD) is a common and potentially life-saving neurosurgical procedure, but the economic aspect of EVD management and the relationship to medical expenditure remain poorly studied. Similarly, interinstitutional practice patterns vary significantly. Whereas some institutions require that patients with EVDs be monitored strictly within the intensive care unit (ICU), other institutions opt primarily for management of EVDs on the surgical floor. Therefore, an ICU burden for patients with EVDs may increase a patient’s costs of hospitalization. The objective of the current study was to examine the expense differences between the ICU and the general neurosurgical floor for EVD care.
The authors performed a retrospective analysis of data from 2 hospitals within a single, large academic institution—the University of Washington Medical Center (UWMC) and Seattle Children’s Hospital (SCH). Hospital charges were evaluated according to patients’ location at the time of EVD management: SCH ICU, SCH floor, or UWMC ICU. Daily hospital charges from day of EVD insertion to day of removal were included and screened for days that would best represent baseline expenses for EVD care. Independent-samples Kruskal-Wallis analysis was performed to compare daily charges for the 3 settings.
Data from a total of 261 hospital days for 23 patients were included in the analysis. Ten patients were cared for in the UWMC ICU and 13 in the SCH ICU and/or on the SCH neurosurgical floor. The median values for total daily hospital charges were $19,824.68 (interquartile range [IQR] $12,889.73–$38,494.81) for SCH ICU care, $8,620.88 (IQR $6,416.76–$11,851.36) for SCH floor care, and $10,002.13 (IQR $8,465.16–$12,123.03) for UWMC ICU care. At SCH, it was significantly more expensive to provide EVD care in the ICU than on the floor (p < 0.001), and the daily hospital charges for the UWMC ICU were significantly greater than for the SCH floor (p = 0.023). No adverse clinical event related to the presence of an EVD was identified in any of the settings.
ICU admission solely for EVD care is costly. If safe EVD care can be provided outside of the ICU, it would represent a potential area for significant cost savings. Identifying appropriate patients for EVD care on the floor is multifactorial and requires vigilance in balancing the expenses associated with ICU utilization and optimal patient care.
Joseph A. Carnevale, David J. Segar, Andrew Y. Powers, Meghal Shah, Cody Doberstein, Benjamin Drapcho, John F. Morrison, John R. Williams, Scott Collins, Kristina Monteiro, and Wael F. Asaad
Traumatic brain injury (TBI) remains a significant cause of neurological morbidity and mortality. Each year, more than 1.7 million patients present to the emergency department with TBI. The goal of this study was to evaluate the prognosis of traumatic cerebral intraparenchymal hemorrhage (tIPH), to develop subclassifications of these injuries that relate to prognosis, and to provide a more comprehensive assessment of hemorrhagic progression contusion (HPC) by analyzing the rate at which tIPH “blossom” (i.e., expansion), depending on a variety of intrinsic and modifiable factors.
In this retrospective study, 726 patients (age range 0–100 years) were admitted to a level 1 trauma center with tIPH during an 8-year period (2005–2013). Of these patients, 491 underwent both admission and follow-up head CT (HCT) within 72 hours. The change in tIPH volume over time, the expansion rate, was recorded for all 491 patients. Effects of prehospital and in-hospital variables were examined using ordinal response logistic regression analyses. These variables were further examined using multivariate linear regression analysis to accurately predict the extent to which a hemorrhage will progress.
Of the 491 (67.6%) patients who underwent both admission and follow-up HCT, 368 (74.9%) patients experienced HPC. These hemorrhages expanded on average by 61.6% (4.76 ml) with an average expansion rate of 0.71 ml per hour. On univariate analysis, certain patient characteristics were significantly (p < 0.05) related to HPC, including age (> 60 years), admission Glasgow Coma Scale score, blood alcohol level, international normalized ratio, absolute platelet count, transfusion of platelets, concomitant anticoagulation and antiplatelet medication, the initial tIPH volume on admission HCT, and ventriculostomy. Increased expansion rate was significantly associated with patient disposition to hospice or death (p < 0.001). To determine which factors most accurately predict overall patient disposition, an ordinal-response logistic regression identified systolic blood pressure, Injury Severity Score, admission Glasgow Coma Scale score, follow-up scan volume, transfusion of platelets, and ventriculostomy as predictors of patient discharge disposition following tIPH. A multivariate logistic regression identified several prehospital and in-hospital variables (age, Injury Severity Score, blood alcohol level, initial scan volume, concomitant epidural hematoma, presence of subarachnoid hemorrhage, transfusion of platelets, and ventriculostomy) that predicted the volumetric expansion of tIPH. Among these variables, the admission tIPH volume by HCT proved to be the factor most predictive of HPC.
Several factors contribute to the rate at which traumatic cerebral contusions blossom in the acute posttraumatic period. Identifying the intrinsic and modifiable aspects of cerebral contusions can help predict the rate of expansion and highlight potential therapeutic interventions to improve TBI-associated morbidity and mortality.
James P. McAllister II, Michael A. Williams, Marion L. Walker, John R. W. Kestle, Norman R. Relkin, Amy M. Anderson, Paul H. Gross, and Samuel R. Browd
Building on previous National Institutes of Health-sponsored symposia on hydrocephalus research, “Opportunities for Hydrocephalus Research: Pathways to Better Outcomes” was held in Seattle, Washington, July 9–11, 2012. Plenary sessions were organized into four major themes, each with two subtopics: Causes of Hydrocephalus (Genetics and Pathophysiological Modifications); Diagnosis of Hydrocephalus (Biomarkers and Neuroimaging); Treatment of Hydrocephalus (Bioengineering Advances and Surgical Treatments); and Outcome in Hydrocephalus (Neuropsychological and Neurological). International experts gave plenary talks, and extensive group discussions were held for each of the major themes.
The conference emphasized patient-centered care and translational research, with the main objective to arrive at a consensus on priorities in hydrocephalus that have the potential to impact patient care in the next 5 years. The current state of hydrocephalus research and treatment was presented, and the following priorities for research were recommended for each theme. 1) Causes of Hydrocephalus—CSF absorption, production, and related drug therapies; pathogenesis of human hydrocephalus; improved animal and in vitro models of hydrocephalus; developmental and macromolecular transport mechanisms; biomechanical changes in hydrocephalus; and age-dependent mechanisms in the development of hydrocephalus. 2) Diagnosis of Hydrocephalus—implementation of a standardized set of protocols and a shared repository of technical information; prospective studies of multimodal techniques including MRI and CSF biomarkers to test potential pharmacological treatments; and quantitative and cost-effective CSF assessment techniques. 3) Treatment of Hydrocephalus—improved bioengineering efforts to reduce proximal catheter and overall shunt failure; external or implantable diagnostics and support for the biological infrastructure research that informs these efforts; and evidence-based surgical standardization with longitudinal metrics to validate or refute implemented practices, procedures, or tests. 4) Outcome in Hydrocephalus—development of specific, reliable batteries with metrics focused on the hydrocephalic patient; measurements of neurocognitive outcome and quality-of-life measures that are adaptable, trackable across the growth spectrum, and applicable cross-culturally; development of comparison metrics against normal aging and sensitive screening tools to diagnose idiopathic normal pressure hydrocephalus against appropriate normative age-based data; better understanding of the incidence and prevalence of hydrocephalus within both pediatric and adult populations; and comparisons of aging patterns in adults with hydrocephalus against normal aging patterns.
Part 7: Active immunization of patients with anaplastic human glioma cells: a pilot study
M. Stephen Mahaley Jr., Darell D. Bigner, Lynn F. Dudka, Peggy Rae Wilds, Darlene H. Williams, Thomas W. Bouldin, John N. Whitaker, and Jane M. Bynum
✓ Twenty patients with malignant gliomas were selected for active immunization within 4 weeks following surgery. Each patient had a Karnofsky Functional Rating equal to or greater than 70, a peripheral blood lymphocyte count equal to or greater than 1000 cells/cu mm, skin test responses to one or more of four recall antigens, peripheral blood T-cells equal to or greater than half that of control, and was not receiving steroid therapy at the time of entry into the study. Each patient received subcutaneous inoculations with one of two human glioma tissue culture cell lines (D-54MG or U-251MG) monthly, with 500 µg of bacillus Calmette-Guérin cell wall (BCG-CW) being included with the first inoculation. Each patient also received levamisole, 2.5 mg/kg 3 days per week every other week. Radiotherapy and chemotherapy with BCNU were begun after the first month of immunization. Follow-up evaluations included computerized tomography brain scans, neurological examinations, Karnofsky Functional Ratings, and studies of general immune competence. No evidence of allergic encephalomyelitis was noted clinically, nor was any gross or microscopic evidence of such pathology obtained upon autopsy of three of these patients. Serial studies of general immune competence showed no alterations from those previously described with non-immunized patients. Patients who were inoculated with the U-251MG cell line have had a longer survival time compared to those inoculated with the D-54MG cell line (p < 0.0590) or compared to 58 historical cases of glioma patients treated with levamisole, radiation therapy, and chemotherapy alone (p < 0.02).
Isaac Josh Abecassis, Christopher C. Young, David J. Caldwell, Abdullah H. Feroze, John R. Williams, R. Michael Meyer, Ryan T. Kellogg, Robert H. Bonow, and Randall M. Chesnut
Decompressive craniectomy (DC) is an effective, lifesaving option for reducing intracranial pressure (ICP) in traumatic brain injury (TBI), stroke, and other pathologies with elevated ICP. Most DCs are performed via a standard trauma flap shaped like a reverse question mark (RQM), which requires sacrificing the occipital and posterior auricular arteries and can be complicated by wound dehiscence and infections. The Ludwig Kempe hemispherectomy incision (Kempe) entails a T-shaped incision, one limb from the midline behind the hairline to the inion and the other limb from the root of the zygoma to the coronal suture. The authors’ objective in this study was to define their implementation of the Kempe incision for DC and craniotomy, report clinical outcomes, and quantify the volume of bone removed compared with the RQM incision.
A retrospective review of a single-surgeon experience with DC in TBI and stroke was performed. Patient demographics, imaging, and outcomes were collected for all DCs from 2015 to 2020, and the incisions were categorized as either Kempe or RQM. Preoperative and postoperative CT scans were obtained and processed using a combination of automatic segmentation (in Python and SimpleITK) with manual cleanup and further subselection in ITK-SNAP. The volume of bone removed was quantified, and the primary outcome was percentage of hemicranium removed. Postoperative surgical wound infections, estimated blood loss (EBL), and length of surgery were compared between the two groups as secondary outcomes. Cranioplasty data were collected.
One hundred thirty-six patients were included in the analysis; there were 57 patients in the craniotomy group (44 patients with RQM incisions and 13 with Kempe incisions) and 79 in the craniectomy group (41 patients with RQM incisions and 38 Kempe incisions). The mean follow-up for the entire cohort was 251 ± 368 days. There was a difference in the amount of decompression between approaches in multivariate modeling (39% ± 11% of the hemicranium was removed via the Kempe incision vs 34% ± 10% via the RQM incision, p = 0.047), although this did not achieve significance in multivariate modeling. Wound infection rates, EBL, and length of surgery were comparable between the two incision types. No wound infections in either cohort were due to wound dehiscence. Cranioplasty outcomes were comparable between the two incision types.
The Kempe incision for craniectomy or craniotomy is a safe, feasible, and effective alternative to the RQM. The authors advocate the Kempe incision in cases in which contralateral operative pathology or subsequent craniofacial/skull base repair is anticipated.
John R. W. Kestle
Colin J. Przybylowski, Robert F. Dallapiazza, Brian J. Williams, I. Jonathan Pomeraniec, Zhiyuan Xu, Spencer C. Payne, Edward R. Laws, and John A. Jane Jr.
The object of this study was to compare the outcomes of primary and revision transsphenoidal resection (TSR) of nonfunctioning pituitary macroadenomas (NFPMAs) using endoscopic methods.
The authors retrospectively reviewed the records of 287 consecutive patients who had undergone endoscopic endonasal TSR for NFPMAs at their institution in the period from 2005 to 2011. Fifty patients who had undergone revision TSR were retrospectively matched for age, sex, and duration of follow-up to 46 patients who had undergone primary TSR. Medical and surgical complications were documented, and Kaplan-Meier analysis was performed to assess rates of radiological progression-free survival (PFS).
The median follow-up periods were 45 and 46 months for the primary and revision TSR groups, respectively. There were no significant differences between the primary and revision groups in rates of new neurological deficit (0 in each), vascular injury (2% vs 0), postoperative CSF leak (6% vs 2%), transient diabetes insipidus (DI; 15% vs 12%), chronic DI (2% vs 2%), chronic sinusitis (4% vs 6%), meningitis (2% vs 2%), epistaxis (7% vs 0), or suprasellar hematoma formation (0 vs 2%). However, patients who underwent primary TSR had significantly higher rates of syndrome of inappropriate antidiuretic hormone (SIADH; 17% vs 4%, p = 0.04). Patients who underwent primary operations also had significantly higher rates of gross-total resection (GTR; 63% vs 28%, p < 0.01) and significantly lower rates of adjuvant radiotherapy (13% vs 42%, p < 0.01). Radiological PFS rates were similar at 2 years (98% vs 96%) and 5 years (87% vs 80%, p = 0.668, log-rank test).
Patients who underwent primary TSR of NFPMAs experienced higher rates of SIADH than those who underwent revision TSR. Patients who underwent revision TSR were less likely to have GTR of their tumor, although they still had a PFS rate similar to that in patients who underwent primary TSR. This finding may be attributable to an increased rate of adjuvant radiation treatment to subtotally resected tumors in the revision TSR group.