The epochal developments in the treatment of meningioma—microsurgery, skull base techniques, and radiation therapy—will be appended to include the rational application of targeted and immune therapeutics, previously ill-fitting concepts for a tumor that has traditionally been a regarded as a surgical disease. The genomic and immunological architecture of these tumors continues to be defined in ever-greater detail. Grade I meningiomas are driven by NF2 alterations or mutations in AKT1, SMO, TRAF7, PIK3CA, KLF4, POLR2A, SUFU, and SMARCB1. Higher-grade tumors, however, are driven nearly exclusively by NF2/chr22 loss and are marked by infrequent targetable mutations, although they may harbor a greater mutation burden overall. TERT mutations may be more common in tumors that progress in histological grade; SMARCE1 alteration has become a signature of the clear cell subtype; and BAP1 in rhabdoid variants may confer sensitivity to pharmacological inhibition. Compared with grade I meningiomas, the most prominent alteration in grade II and III meningiomas is a significant increase in chromosomal gains and losses, or copy number alterations, which may have behavioral implications. Furthermore, integrated genomic analyses suggest phenotypic subgrouping by methylation profile and a specific role for PRC2 complex activation. Lastly, there exists a complex phylogenetic relationship among recurrent high-grade tumors, which continues to underscore a role for the most traditional therapy in our arsenal: surgery.
Wenya Linda Bi, Vikram C. Prabhu, and Ian F. Dunn
Ignacio Jusue-Torres, Vikram C. Prabhu, and G. Alexander Jones
To better understand Walter Dandy’s intentions and the historical context of his work on hemispherectomy, the authors reviewed his original 1928 publication. Gliomas were considered incurable at that time. Presuming that the loss of motor function denoted a lack of useful tissue in that hemisphere, he pioneered radical removal of the involved cerebral hemisphere. Of the 5 patients operated on by Dandy, 1 died within 48 hours of hemorrhage because of a displaced vascular clip; 1 died of pneumonia in 2 weeks; 2 died of tumor recurrence, at 3 months and 3.5 years, respectively; and a fifth patient was lost to follow-up beyond the 2nd postoperative week.
The authors queried the Thomson Reuters Web of Science and Scopus. A total of 88 papers fulfilled inclusion criteria. Half of these papers (44/88) were published after 2012. Only 11% of papers (10/88) quoted Dandy’s paper accurately; half of them were published before 1997. Most publications (76% [67/88]) quoted Dandy incorrectly, all of them from 1997 and later. In the remaining 11 papers (13%), the accuracy of the quotes was unclear. The authors found a trend toward more accurate citation in earlier papers.
Critically reviewing Dandy’s report, with an understanding of the historical context, allows a better understanding of his intentions and the value of his contribution.
Ahmad Khaldi, Vikram C. Prabhu, Douglas E. Anderson, and Thomas C. Origitano
This study was conducted to evaluate the value of postoperative CT scans in determining the probability of return to the operating room (OR) and the optimal time to obtain such scans to determine the effects of surgery.
Between January and December 2006 (12 months), all postoperative head CT scans obtained for 3 individual surgeons were reviewed. Scans were divided into 3 groups, which were determined by the preference of each surgeon: Group A (early scans—scheduled between 0 and 7 hours); Group B (delayed scans—scheduled between 8 and 24 hours); and Group C (urgent scans—ordered because of a new neurological deficit). The initial scans were reviewed and analyzed in 2 different fashions. The first was to analyze the efficacy of the scans in predicting return to the OR. The second was to determine the optimal time for obtaining a scan. The second analysis was a review of serial postoperative scans for expected versus unexpected findings and changes in the acuity of these findings over time.
In 251 (74%) of 338 cases, the patients had postoperative head CT scans within 24 hours of surgery. Analysis 1 determined the percent of patients returning to the OR for emergency treatment based on postoperative scans: Group A (early)—133 patients, with 0% returning to the OR; Group B (delayed)—108 patients, with 0% returning to the OR; and Group C (urgent)—10 patients, with 30% returning to the OR (p < 0.05). Analysis 2 determined the optimal timing of postoperative scans and changes in scan acuity: Group A (early scan) had an 11% incidence of change in acuity on subsequent scans. Group B (delayed scan) had a 3% incidence of change in acuity on follow-up scans (p < 0.05).
Routine postoperative scans at 0–7 hours or at 8–24 hours are not predictive of return to the OR, whereas patients with a new neurological deficit in the postoperative period have a 30% chance of emergency reoperation based on CT scans. In addition, early postoperative scans (0–7 hours) fail to predict CT changes, which might evolve over time and may influence postoperative medical management.
Tara Zielke, Miri Kim, Joshua E. Simon, Ewa Borys, Vikram C. Prabhu, and Suguna Pappu
Hypertrophic cranial pachymeningitis is a rare inflammatory disorder characterized by thickening of the dura mater and multiple cranial neuropathies. Although an infectious etiology may be present, often no specific cause is discovered.
The authors described a 71-year-old man with progressive right eye vision loss, ptosis, and complete ophthalmoplegia with imaging findings suggestive of hypertrophic cranial pachymeningitis. Extensive studies, including cerebrospinal fluid studies, showed negative results. Blood serum, cell-free evaluation, and paraffin-embedded dural tissue testing had positive results for Pseudomonas aeruginosa, which allowed treatment tailored to the organism and a salutary clinical outcome.
The constellation of neurological and radiological findings may make a diagnosis difficult in an inflammatory setting. The most precise methodology for establishing a diagnosis involves sampling the dura and testing it for infectious pathology. However, if results are inconclusive, further cell-free serum sampling with next-generation sequencing is a viable option for identifying pathogens with infectious concerns. This case highlighted the importance of multimodality studies for identifying a targetable pathogen.
Edna Toubes-Klingler, Vikram C. Prabhu, Kerry Bernal, David Poage, and Susan Swindells
✓Malacoplakia is a rare chronic inflammatory disease associated with infection and immunosuppression, and very few occurrences have been reported in the cerebrum. The authors describe the case of a 41-year-old man with advanced human immunodeficiency virus (HIV) infection who presented with a very aggressive malacoplakia lesion that had extended through the scalp, temporalis muscle, skull bone, and deep through the dura mater into the superior sagittal sinus and adjacent brain. Pathological examination revealed sheets of histiocytes invading these structures, and macrophages containing numerous round bodies known as Michaelis–Guttmann bodies, pathognomic for malacoplakia. Because of the rarity of this phenomenon, appropriate treatment and management of malacoplakia are speculative. A complete resection of the lesion, antibiotic therapy, and treatment of his underlying HIV infection had a salutary effect, with the patient faring well more than 9 months postoperatively.
Vikram C. Prabhu, Mark H. Bilsky, Kedar Jambhekar, Katherine S. Panageas, Patrick J. Boland, Eric Lis, Linda Heier, and P. Kim Nelson
Object. Arterial embolization reduces blood loss in patients undergoing surgery for hypervascular spinal tumors. The objectives of this study were twofold: 1) to evaluate the role of magnetic resonance (MR) imaging in predicting tumor vascularity and 2) to assess the effectiveness of preoperative embolization in devascularizing these tumors.
Methods. Fifty-one patients with metastatic spinal neoplasms underwent angiography, preoperative embolization, and excision of the lesion between 1995 and 2000. The MR imaging studies were correlated with tumor vascularity on angiograms. Embolization was angiographically graded on a five-point scale ranging from no embolization (Grade A) to total embolization (Grade E). The embolization grade was correlated with intraoperative blood loss.
The mean age was 57 years, the male/female ratio was 1.2:1, and back pain was present in all patients. Metastatic renal cell carcinoma (30 cases) and thoracic spine involvement (33 cases) were most frequent. The positive predictive value of MR imaging in determining tumor vascularity was 77%, whereas the negative predictive value was 21%. Total embolization (Grade E) was achieved in 34 patients. A shared vascular pedicle between a radiculomedullary artery (RMA) and a tumor diminished the likelihood of complete embolization (p = 0.02). Small asymptomatic cerebellar infarctions were demonstrated in two cases. The mean intraoperative blood loss was 2586 ml. Following Grade D or E embolization, intraoperative bleeding was largely related to unembolized epidural veins.
Conclusions. Tumor histology and MR imaging findings are predictive of hypervascularity; however, hypervascular tumors may not be detected by standard MR imaging sequences. Superselective catheterization permits Grade D or E embolization in 80% of patients. Shared blood supply with an RMA is the most important factor precluding complete embolization.