✓ The current management of malignant gliomas is unsatisfactory compared to that of other solid tumors; the expected median survival period is less than 1 year with the patient undergoing conventional surgery, radiotherapy, and chemotherapy treatment. Immunological reagents could be a useful adjunct. Human monoclonal antibodies derived from patients with astrocytic tumors might recognize subtle antigenic specificities that would differ from those recognized by xenogeneic (murine) systems. Five hybridomas, designated as BT27/1A2, BT27/2A3, BT32/A6, BT34/A5, and BT54/B8, were produced from the fusion of peripheral blood lymphocytes of four patients with astrocytic tumors to the human myeloma-like cell line TM-H2-SP2. This cell line has a 46, XX karotype and is negative for hypoxanthine guanine phosphoribosyltransferase. All five human monoclonal antibodies produced 2.4 to 44 µg/ml of immunoglobulin M, had a similar but not identical pattern of reactivity against a panel of human tumor cell lines, and failed to react with normal human astrocytes. Labeling of four neuroectodermal tumor explant cultures by BT27/2A3 was demonstrated by flow cytometry. Karyotyping of three of the five hybridomas demonstrated that two were pseudodiploid (2–3n) and one hypodiploid (< 2n). The monoclonality of the hybridomas was evaluated by Southern blot analysis of JH gene rearrangements, revealing two types of rearrangements for each hybridoma, both consistent with monoclonality. Preliminary antigen characterization indicated that at least four of the five human monoclonal antibodies were directed to cell-surface glycolipids.
Michael D. Dan, Christopher M. Schlachta, John Guy, Richard G. McKenzie, Delbert R. Dorscheid, Victor A. Sandor, Jean-Guy Villemure and Gerald B. Price
Robert G. Whitmore, Christopher Urban, Ephraim Church, Michael Ruckenstein, Sherman C. Stein and John Y. K. Lee
Widespread use of MR imaging has contributed to the more frequent diagnosis of vestibular schwannomas (VSs). These tumors represent 10% of primary adult intracranial neoplasms, and if they are symptomatic, they usually present with hearing loss and tinnitus. Currently, there are 3 treatment options for quality of life (QOL): wait and scan, microsurgery, and radiosurgery. In this paper, the authors' purpose is to determine which treatment modality yields the highest QOL at 5- and 10-year follow-up, considering the likelihood of recurrence and various complications.
The MEDLINE, Embase, and Cochrane online databases were searched for English-language articles published between 1990 and June 2008, containing key words relating to VS. Data were pooled to calculate the prevalence of treatment complications, tumor recurrence, and QOL with various complications. For parameters in which incidence varied with time of follow-up, the authors used meta-regression to determine the mean prevalence rates at a specified length of follow-up. A decision-analytical model was constructed to compare 5- and 10-year outcomes for a patient with a unilateral tumor and partially intact hearing. The 3 treatment options, wait and scan, microsurgery, and radiosurgery, were compared.
After screening more than 2500 abstracts, the authors ultimately included 113 articles in this analysis. Recurrence, complication rates, and onset of complication varied with the treatment chosen. The relative QOL at the 5-year follow-up was 0.898 of normal for wait and scan, 0.953 for microsurgery, and 0.97 for radiosurgery. These differences are significant (p < 0.0052). Data were too scarce at the 10-year follow-up to calculate significant differences between the microsurgery and radiosurgery strategies.
At 5 years, patients treated with radiosurgery have an overall better QOL than those treated with either microsurgery or those investigated further with serial imaging. The authors found that the complications associated with wait-and-scan and microsurgery treatment strategies negatively impacted patient lives more than the complications from radiosurgery. One limitation of this study is that the 10-year follow-up data were too limited to analyze, and more studies are needed to determine if the authors' results are still consistent at 10 years.
Amir R. Dehdashti, Leodante B. Da Costa, Karel G. terBrugge, Robert A. Willinsky, Michael Tymianski and M. Christopher Wallace
Dural arteriovenous fistulas are the most common vascular malformations of the spinal cord. These benign vascular lesions are considered straightforward targets of surgical treatment and possibly endovascular embolization, but the outcome in these cases depends mainly on the extent of clinical dysfunction at the time of the diagnosis. A timely diagnosis is an equally important factor, with early treatment regardless of the type more likely to yield significant improvements in neurological functioning. The outcomes after surgical and endovascular treatment are similar if complete obliteration of the fistulous site is obtained. In the present study, the authors evaluated the current role of each modality in the management of these interesting lesions.
Elias Dagnew, Jeffrey Kanski, Michael W. McDermott, Penny K. Sneed, Christopher McPherson, John C. Breneman and Ronald E. Warnick
Whole-brain radiotherapy (WBRT) after resection of a single brain metastasis can cause long-term radiation toxicity. The authors evaluated the efficacy of resection and placement of 125I seeds (without concomitant WBRT) for newly diagnosed single brain metastases.
In a retrospective review from two institutions (1997–2003), 15 women and 11 men (mean age 55 years) with single brain metastasis underwent gross-total resection and placement of permanent low-activity 125I seeds. Primary systemic cancer sites varied. Patients were monitored clinically and radiographically. With neuroimaging evidence of local recurrence or new distant metastasis, further treatment was administered at the physician's discretion. By the median follow-up evaluation (12 months), the local tumor control rate was 96%. Distant metastases occurred in three patients within 3 months, suggesting synchronous metastasis, and in six patients more than 3 months after treatment, indicating metachronous metastasis. Treatment in these cases included radio-surgery in seven patients, WBRT in two, and resection together with 125I seed placement in one. Two patients who suffered radiation necrosis required operative intervention (lesion diameter > 3 cm, total activity > 40 mCi). All 26 patients who had been treated using resection and placement of 125I seeds had a stable or an improved Karnofsky Performance Scale score. At the last review, nine of 16 living patients showed no evidence of treatment failure. The median actuarial survival rate was 17.8 months (Kaplan–Meier method).
Permanent 125I brachytherapy applied at the initial operation without WBRT provided excellent local tumor control. Local control and patient survival rates were at least as good as those reported for resection combined with WBRT. Although the authors noted a higher incidence of distant metastases compared with that reported in other studies of initial WBRT, these metastases were generally well controlled with a combination of surgery, stereotactic radiosurgery, and, less often, WBRT. Twenty-four patients (92%) never required WBRT, thus avoiding potential long-term radiation-induced neurotoxicity.
Gregory C. Wiggins, Michael J. Rauzzino, Christopher I. Shaffrey, Russ P. Nockels, Richard Whitehill, Mark E. Shaffrey, James Wagner and Tord D. Alden
This study was conducted to determine the safety, efficacy, and complication rate associated with the anterior approach in the use of a new titanium mesh interbody fusion cage for the treatment of unstable thoracolumbar burst fractures. The experience with this technique is compared with the senior authors' (C.S., R.W., and M.S.) previously published results in the management of patients with unstable thoracolumbar burst fractures.
Between 1996 and 1999, 21 patients with unstable thoracolumbar (T12-L3) burst fractures underwent an anterolateral decompressive procedure in which a titanium cage and Kaneda device were used. Eleven of the 21 patients had sustained a neurological deficit, and all patients improved at least one Frankel grade (average 1.2 grades). There was improvement in outcome in terms of blood loss, correction of kyphosis, and pain, as measured on the Denis Pain and Work Scale, in our current group of patients treated via an anterior approach when compared with the results in those who underwent a posterior approach.
In our current study the anterior approach was demonstrated to be a safe and effective technique for the management of unstable thoracolumbar burst fractures. It offers superior results compared with the posterior approach. The addition of the new titanium mesh interbody cage to our previous anterior technique allows the patient's own bone to be harvested from the corpectomy site and used as a substrate for fusion, thereby obviating the need for iliac crest harvest. The use of the cage in association with the Kaneda device allows for improved correction of kyphosis and restoration of normal sagittal alignment in addition to improved functional outcomes.
Avital Perry, Christopher S. Graffeo, Waleed Brinjikji, William R. Copeland III, Alejandro A. Rabinstein and Michael J. Link
Spontaneous intracranial hypotension (SIH) is an uncommon headache etiology, typically attributable to an unprovoked occult spinal CSF leak. Although frequently benign, serious complications may occur, including cerebral venous thrombosis (CVT). The objective of this study was to examine a highly complicated case of CVT attributable to SIH as a lens for understanding the heterogeneous literature on this rare complication, and to provide useful, evidence-based, preliminary clinical recommendations. A 43-year-old man presented with 1 week of headache, dizziness, and nausea, which precipitously evolved to hemiplegia. CT venography confirmed CVT, and therapeutic heparin was initiated. He suffered a generalized seizure due to left parietal hemorrhage, which subsequently expanded. He developed signs of mass effect and herniation, heparin was discontinued, and he was taken to the operating room for clot evacuation and external ventricular drain placement. Intraoperatively, the dura was deflated, suggesting underlying SIH. Ventral T-1 CSF leak was identified, which failed multiple epidural blood patches and required primary repair. The patient ultimately made a complete recovery. Systematic review identified 29 publications describing 36 cases of SIH-associated CVT. Among 31 patients for whom long-term neurological outcome was reported, 25 (81%) recovered completely. Underlying coagulopathy/risk factors were identified in 11 patients (31%). CVT is a rare and potentially lethal sequela occurring in 2% of SIH cases. Awareness of the condition is poor, risking morbid complications. Evaluation and treatment should be directed toward identification and treatment of occult CSF leaks. Encouragingly, good neurological outcomes can be achieved through vigilant multidisciplinary neurosurgical and neurocritical care.
Christopher Uff, Daniel Frith, Catriona Harrison, Michael Powell and Neil Kitchen
Although he was not the first man to operate on the brain, Sir Victor Horsley was the world's first surgeon appointed to a hospital post to perform brain surgery, which happened in 1886 at the National Hospital for Neurology and Neurosurgery, Queen Square, London. The authors examined the patient records between 1886 and 1899 and found 151 operations performed by Sir Victor Horsley at the National Hospital, including craniotomies, laminectomies, and nerve divisions. The authors present the outcome data and case illustrations of cerebral tumor resections and laminectomies from the nineteenth century. Outcomes and notable pioneering achievements are highlighted.
Michael M. McDowell, Jason E. Blatt, Christopher P. Deibert, Nathan T. Zwagerman, Zachary J. Tempel and Stephanie Greene
Chiari malformation type II (CM-II) in myelomeningocele is associated with a significant rate of mortality and poor outcome. Death is frequently heralded by the onset or progression of neurological symptoms. The authors sought to identify predictors of poor outcome and mortality within the myelomeningocele population at Children’s Hospital of Pittsburgh.
A retrospective chart and radiology review was performed on all infants who underwent primary closure of a myelomeningocele defect at Children’s Hospital of Pittsburgh between the years of 1995 and 2015. Preoperative symptoms and signs leading to CM-II decompression, as well as operative details and postoperative changes in these symptoms and signs, were investigated in detail and correlated to outcome. Poor outcome was defined as death, stridor, or ventilator dependence. Deceased patients were separately assessed within this subgroup.
Thirty-two (21%) of 153 patients were found to have symptomatic CM-II. Of the 32 patients meeting inclusion criteria, 12 (38%) had poor outcomes. Eight patients (25%) died since initial presentation; 5 of these patients (16% of the overall cohort) died within the 1st year of life and 3 (9%) died during adolescence. Seven (88%) of the 8 patients who died had central apnea on presentation (p = 0.001) and 7 (44%) of the 16 patients who developed symptoms in the first 3 months of life died, compared with 1 (6.3%) of 16 who developed symptoms later in childhood (p = 0.04). The median Apgar score at 1 minute was 4.5 for patients who died and 8 for surviving patients (p = 0.006). The median diameter of the myelomeningocele defect was 5.75 cm for patients who died and 5 for those who survived (p = 0.01). The anatomical level of defect trended toward higher levels in patients who died, with 4 patients in that group having an anatomical level at L-2 or higher compared with 5 of the surviving patients (p = 0.001). The median initial head circumference for the 5 patients dying in the 1st year of life was 41.5 cm, versus 34 cm for all other patients (p = 0.01).
CM-II in spina bifida is associated with a significant mortality rate even when surgical intervention is performed. Death is more frequent in symptomatic patients presenting prior to 1 year of age. Late deaths are associated with symptom progression despite aggressive surgical and medical intervention. In this patient cohort, death was more likely in patients with symptomatic presentation during the first 3 months of life, low Apgar scores, large myelomeningocele defects, early central apnea, and large head circumference at birth.
Michael M. Safaee, Vedat Deviren, Cecilia Dalle Ore, Justin K. Scheer, Darryl Lau, Joseph A. Osorio, Fred Nicholls and Christopher P. Ames
Proximal junctional kyphosis (PJK) is a well-recognized, yet incompletely defined, complication of adult spinal deformity surgery. There is no standardized definition for PJK, but most studies describe PJK as an increase in the proximal junctional angle (PJA) of greater than 10°–20°. Ligament augmentation is a novel strategy for PJK reduction that provides strength to the upper instrumented vertebra (UIV) and adjacent segments while also reducing junctional stress at those levels.
In this study, ligament augmentation was used in a consecutive series of adult spinal deformity patients at a single institution. Patient demographics, including age; sex; indication for surgery; revision surgery; surgical approach; and use of 3-column osteotomies, vertebroplasty, or hook fixation at the UIV, were collected. The PJA was measured preoperatively and at last follow-up using 36-inch radiographs. Data on change in PJA and need for revision surgery were collected. Univariate and multivariate analyses were performed to identify factors associated with change in PJA and proximal junctional failure (PJF), defined as PJK requiring surgical correction.
A total of 200 consecutive patients were included: 100 patients before implementation of ligament augmentation and 100 patients after implementation of this technique. The mean age of the ligament augmentation cohort was 66 years, and 67% of patients were women. Over half of these cases (51%) were revision surgeries, with 38% involving a combined anterior or lateral and posterior approach. The mean change in PJA was 6° in the ligament augmentation group compared with 14° in the control group (p < 0.001). Eighty-four patients had a change in PJA of less than 10°. In a multivariate linear regression model, age (p = 0.016), use of hook fixation at the UIV (p = 0.045), and use of ligament augmentation (p < 0.001) were associated with a change in PJA. In a separate model, only ligament augmentation (OR 0.193, p = 0.012) showed a significant association with PJF.
Ligament augmentation represents a novel technique for the prevention of PJK and PJF. Compared with a well-matched historical cohort, ligament augmentation is associated with a significant decrease in PJK and PJF. These data support the implementation of ligament augmentation in surgery for adult spinal deformity, particularly in patients with a high risk of developing PJK and PJF.