✓ Mononuclear cell infiltrates are found to varying degrees in 30% to 60% of primary human central nervous system (CNS) gliomas. To explore the immunological importance of this, six operative glial tumors, eight non-glial tumors, and three normal brain specimens were studied. Utilizing an immunoperoxidase method, the authors examined frozen sections for lymphoid infiltrates expressing suppressor/cytotoxic and helper phenotypes, as identified with the Leu-1,2,3 monoclonal antibodies. Four of six gliomas demonstrated lymphoid infiltrates: three tumors exhibited a predominant suppressor/cytotoxic cell phenotype and the fourth showed mixed staining of suppressor/cytotoxic and helper cell phenotypes. Varying degrees of lymphoid infiltration characterized four out of eight non-glial primary CNS tumors. Two cases exhibited a prevalence of suppressor/cytotoxic phenotype cells, while two cases demonstrated a more heterogeneous pattern of phenotype expression. Normal brain sections revealed little or no evidence of mononuclear infiltrates. The immunobiological significance of these findings is discussed in the context of tumor-host interaction within the CNS.
Characterization of cell subsets with monoclonal antibodies
Roger I. von Hanwehr, Florence M. Hofman, Clive R. Taylor and Michael L. J. Apuzzo
Davis G. Taylor, Ching-Jen Chen, Thomas J. Buell, Min S. Park, J. Javier Provencio and M. Yashar S. Kalani
Randy S. Bell and Chris J. Neal
Thomas J. Buell, Davis G. Taylor, Ching-Jen Chen, Christopher I. Shaffrey, Justin S. Smith and Shay Bess
Michael J. Ellis, Samuel Cheshier, Sunjay Sharma, Derek Armstrong, Cynthia Hawkins, Eric Bouffet, James T. Rutka and Michael D. Taylor
Among the neoplastic conditions that affect patients with neurofibromatosis Type 1 (NF1) are malignant peripheral nerve sheath tumors (MPNSTs), which typically arise from peripheral nerves of the limbs, trunk, and lumbar and brachial plexuses. Ionizing radiation is an established risk factor for MPNST development, especially in susceptible patients such as those with NF1. Patients with NF1 are also at risk for intracranial aneurysms, which are increasingly being successfully managed with endovascular therapies. The authors describe the case of a 9-year-old, previously healthy girl who presented in extremis with a right frontal intracerebral hemorrhage resulting from a ruptured right middle cerebral artery (MCA) trifurcation aneurysm. Following urgent decompressive craniectomy, the patient underwent endovascular coil embolization of the MCA aneurysm without complication. Given her mother's history of NF1, the child underwent genetic testing, which disclosed signs positive for NF1. The patient recovered well, but follow-up MR imaging and MR angiography performed at 14 months demonstrated a large frontotemporal mass encasing the right MCA trifurcation. The patient underwent frontotemporal craniotomy and subtotal resection of the mass, which was histologically found to be an intracranial MPNST. The patient received chemotherapy and focal radiation therapy and remains alive at 6 months postresection. To the authors' knowledge, this represents the only known case of intracranial neoplasm arising in the region of an intracranial aneurysm repaired by endovascular coil embolization. While patients with NF1 represent a population with genetic susceptibility to radiation-induced tumors, the pathogenesis of intracerebral MPNSTs remains poorly understood.
Michael D. Taylor, James Perry, Magdalena C. Ƶlatescu, Anat O. Stemmer-Rachamimov, L. C. Ang, Yasushi Ino, Michael Schwartz, Laurence E. Becker, David N. Louis and J. Gregory Cairncross
✓ Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome 1p. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is not commonly involved in sporadic oligodendrogliomas or glioblastomas.
Nickalus R. Khan, Clinton J. Thompson, Douglas R. Taylor, Garrett T. Venable, R. Matthew Wham, L. Madison Michael II and Paul Klimo Jr.
Bibliometrics is defined as the study of statistical and mathematical methods used to quantitatively analyze scientific literature. The application of bibliometrics in neurosurgery is in its infancy. The authors calculate a number of publication productivity measures for almost all academic neurosurgeons and departments within the US.
The h-index, g-index, m-quotient, and contemporary h-index (hc-index) were calculated for 1225 academic neurosurgeons in 99 (of 101) programs listed by the Accreditation Council for Graduate Medical Education in January 2013. Three currently available citation databases were used: Google Scholar, Scopus, and Web of Science. Bibliometric profiles were created for each surgeon. Comparisons based on academic rank (that is, chairperson, professor, associate, assistant, and instructor), sex, and subspecialties were performed. Departments were ranked based on the summation of individual faculty h-indices. Calculations were carried out from January to February 2013.
The median h-index, g-index, hc-index, and m-quotient were 11, 20, 8, and 0.62, respectively. All indices demonstrated a positive relationship with increasing academic rank (p < 0.001). The median h-index was 11 for males (n = 1144) and 8 for females (n = 81). The h-index, g-index and hc-index significantly varied by sex (p < 0.001). However, when corrected for academic rank, this difference was no longer significant. There was no difference in the m-quotient by sex. Neurosurgeons with subspecialties in functional/epilepsy, peripheral nerve, radiosurgery, neuro-oncology/skull base, and vascular have the highest median h-indices; general, pediatric, and spine neurosurgeons have the lowest median h-indices. By summing the manually calculated Scopus h-indices of all individuals within a department, the top 5 programs for publication productivity are University of California, San Francisco; Barrow Neurological Institute; Johns Hopkins University; University of Pittsburgh; and University of California, Los Angeles.
This study represents the most detailed publication analysis of academic neurosurgeons and their programs to date. The results for the metrics presented should be viewed as benchmarks for comparison purposes. It is our hope that organized neurosurgery will adopt and continue to refine bibliometric profiling of individuals and departments.
Travis R. Ladner, Manus J. Donahue, Daniel F. Arteaga, Carlos C. Faraco, Brent A. Roach, L. Taylor Davis, Lori C. Jordan, Michael T. Froehler and Megan K. Strother
Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya. The authors performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD).
Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow–weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0–5 points; Grade 2, 6–9 points; and Grade 3, 10 points.
In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI 1.1–22.6, p = 0.002). The area under the curve for individual PIRAMD factors was 0.67–0.72, and for the PIRAMD grade it was 0.845. There were 0/8 (0%), 10/18 (55.6%), and 18/20 (90%) symptomatic PIRAMD Grade 1, 2, and 3 hemispheres, respectively.
A scoring system for total impairment is proposed that uses noninvasive MRI parameters. This scoring system correlates with symptomatology and may provide a measure of hemodynamic severity in moyamoya, which could be used for guiding management decisions and evaluating intervention response.
Alan M. Chen, Kunal B. Karani, J. Michael Taylor, Bin Zhang, Andrew Furthmiller, Gabriel De Vela, James L. Leach, Sudhakar Vadivelu and Todd A. Abruzzo
Although intracranial arterial aneurysms (IAAs) of childhood are usually idiopathic, it is possible that underlying arteriopathy escapes detection when using conventional diagnostic tools. Quantitative arterial tortuosity (QAT) has been studied as a biomarker of arteriopathy. The authors analyzed cervicocerebral QAT in children with idiopathic IAAs to assess the possibility of arteriopathy.
Cases were identified by text-string searches of imaging reports spanning the period January 1993 through June 2017. QAT of cervicocerebral arterial segments was measured from cross-sectional studies using image-processing software. Other imaging and clinical data were confirmed by retrospective electronic record review. Children with idiopathic IAAs and positive case controls, with congenital arteriopathy differentiated according to aneurysm status (with and without an aneurysm), were compared to each other and to healthy controls without vascular risk factors.
Cervicocerebral QAT was measured in 314 children: 24 with idiopathic IAAs, 163 with congenital arteriopathy (including 14 arteriopathic IAAs), and 127 healthy controls. QAT of all vertebrobasilar segments was larger in children with IAAs (idiopathic and arteriopathic forms) (p < 0.05). In children with congenital arteriopathy without an aneurysm, QAT was decreased for the distal cervical vertebral arteries and increased for the supraspinal vertebral artery relative to healthy children. QAT of specific cervicocerebral segments correlated with IAA size and rupture status.
Cervicocerebral QAT is a biomarker of arteriopathy in children with IAA, even in the absence of other disease markers. Additional findings suggest a correlation of cervicocerebral QAT with IAA size and rupture status and with the presence of IAA in children with congenital arteriopathy.
Iska Moxon-Emre, Eric Bouffet, Michael D. Taylor, Normand Laperriere, Michael B. Sharpe, Suzanne Laughlin, Ute Bartels, Nadia Scantlebury, Nicole Law, David Malkin, Jovanka Skocic, Logan Richard and Donald J. Mabbott
Craniospinal irradiation damages the white matter in children treated for medulloblastoma, but the treatment-intensity effects are unclear. In a cross-sectional retrospective study, the effects of treatment with the least intensive radiation protocol versus protocols that delivered more radiation to the brain, in addition to the effects of continuous radiation dose, on white matter architecture were evaluated.
Diffusion tensor imaging was used to assess fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. First, regional white matter analyses and tract-based spatial statistics were conducted in 34 medulloblastoma patients and 38 healthy controls. Patients were stratified according to those treated with 1) the least intensive radiation protocol, specifically reduced-dose craniospinal irradiation plus a boost to the tumor bed only (n = 17), or 2) any other dose and boost combination that delivered more radiation to the brain, which was also termed the “all-other-treatments” group (n = 17), and comprised patients treated with standard-dose craniospinal irradiation plus a posterior fossa boost, standard-dose craniospinal irradiation plus a tumor bed boost, or reduced-dose craniospinal irradiation plus a posterior fossa boost. Second, voxel-wise dose-distribution analyses were conducted on a separate cohort of medulloblastoma patients (n = 15).
The all-other-treatments group, but not the reduced-dose craniospinal irradiation plus tumor bed group, had lower fractional anisotropy and higher radial diffusivity than controls in all brain regions (all p < 0.05). The reduced-dose craniospinal irradiation plus tumor bed boost group had higher fractional anisotropy (p = 0.05) and lower radial diffusivity (p = 0.04) in the temporal region, and higher fractional anisotropy in the frontal region (p = 0.04), than the all-other-treatments group. Linear mixed-effects modeling revealed that the dose and age at diagnosis together 1) better predicted fractional anisotropy in the temporal region than models with either alone (p < 0.005), but 2) did not better predict fractional anisotropy in comparison with dose alone in the occipital region (p > 0.05).
Together, the results show that white matter damage has a clear association with increasing radiation dose, and that treatment with reduced-dose craniospinal irradiation plus tumor bed boost appears to preserve white matter in some brain regions.