MicroRNAs (miRNAs) are now recognized as the primary RNAs involved in the purposeful silencing of the cell's own message. In addition to the established role of miRNAs as developmental regulators of normal cellular function, they have recently been shown to be important players in pathological states such as cancer. The authors review the literature on the role of miRNAs in the formation and propagation of gliomas and medulloblastomas, highlighting the potential of these molecules and their inhibitors as therapeutics.
Jay D. Turner, Richard Williamson, Kaith K. Almefty, Peter Nakaji, Randall Porter, Victor Tse and M. Yashar S. Kalani
Richard W. Williamson, David A. Wilson, Adib A. Abla, Cameron G. McDougall, Peter Nakaji, Felipe C. Albuquerque and Robert F. Spetzler
Subarachnoid hemorrhage (SAH) from ruptured posterior inferior cerebellar artery (PICA) aneurysms is uncommon, and long-term outcome data for patients who have suffered such hemorrhages is lacking. This study investigated in-hospital and long-term clinical data from a prospective cohort of patients with SAH from ruptured PICA aneurysms enrolled in a randomized trial; their outcomes were compared with those of SAH patients who were treated for other types of ruptured intracranial aneurysms. The authors hypothesize that PICA patients fare worse than those with aneurysms in other locations and this difference is related to the high rate of lower cranial nerve dysfunction in PICA patients.
The authors analyzed data for 472 patients enrolled in the Barrow Ruptured Aneurysm Trial (BRAT) and retrospectively reviewed vasospasm data not collected prospectively. In the initial cohort, 57 patients were considered angiographically negative for aneurysmal SAH source and did not receive treatment for aneurysms, leaving 415 patients with aneurysmal SAH.
Of 415 patients with aneurysmal SAH, 22 (5.3%) harbored a ruptured PICA aneurysm. Eight of them had dissecting/fusiform-type aneurysms while 14 had saccular-type aneurysms. Nineteen PICA patients were treated with clipping (1 crossover from coiling), 2 were treated with coiling, and 1 died before treatment. When comparing PICA patients to all other aneurysm patients in the study cohort, there were no statistically significant differences in age (mean 57.6 ± 11.8 vs 53.9 ± 11.8 years, p = 0.17), Hunt and Hess grade median III [IQR II–IV] vs III [IQR II–III], p = 0.15), Fisher grade median 3 [IQR 3–3] vs 3 [IQR 3–3], p = 0.53), aneurysm size (mean 6.2 ± 3.0 vs 6.7 ± 4.0 mm, p = 0.55), radiographic vasospasm (53% vs 50%, p = 0.88), or clinical vasospasm (12% vs 23%, p = 0.38). PICA patients were more likely to have a fusiform aneurysm (36% vs 12%, p = 0.004) and had a higher incidence of lower cranial nerve dysfunction and higher rate of tracheostomy/percutaneous endoscopic gastrostomy placement compared with non-PICA patients (50% vs 16%, p < 0.001). PICA patients had a significantly higher incidence of poor outcome at discharge (91% vs 67%, p = 0.017), 1-year follow-up (63% vs 29%, p = 0.002), and 3-year follow-up (63% vs 32%, p = 0.006).
Patients with ruptured PICA aneurysms had a similar rate of radiographic vasospasm, equivalent admission Fisher grade and Hunt and Hess scores, but poorer clinical outcomes at discharge and at 1- and 3-year follow-up when compared with the rest of the BRAT SAH patients with ruptured aneurysms. The PICA's location at the medulla and the resultant high rate of lower cranial nerve dysfunction may play a role in the poor outcome for these patients. Furthermore, PICA aneurysms were more likely to be fusiform than saccular, compared with non-PICA aneurysms; the complex nature of these aneurysms may also contribute to their poorer outcome.
Mark P. Garrett, Richard W. Williamson, Michael A. Bohl, C. Roger Bird and Nicholas Theodore
For a diagnosis of brain death (BD), ancillary testing is performed if patient factors prohibit a complete clinical examination and apnea test. The American Academy of Neurology (AAN) guidelines identify cerebral angiography (CA), cerebral scintigraphy, electroencephalography, and transcranial Doppler ultrasonography as accepted ancillary tests. CA is widely considered the gold standard of these, as it provides the most reliable assessment of intracranial blood flow. CT angiography (CTA) is a noninvasive and widely available study that is also capable of identifying absent or severely diminished intracranial blood flow, but it is not included among the AAN's accepted ancillary tests because of insufficient evidence demonstrating its reliability. The objective of this study was to assess the statistical performance of CTA in diagnosing BD, using clinical criteria alone or clinical criteria plus CA as the gold-standard comparisons.
The authors prospectively enrolled 22 adult patients undergoing workup for BD. All patients had cranial imaging and clinical examination results consistent with BD. In patients who met the AAN clinical criteria for BD, the authors performed CA and CTA so that both tests could be compared with the gold-standard clinical criteria. In cases that required ancillary testing, CA was performed as a confirmatory study, and CTA was then performed to compare against clinical criteria plus CA. Radiographic data were evaluated by an independent neuroradiologist. Test characteristics for CTA were calculated.
Four patients could not complete the standard BD workup and were excluded from analysis. Of the remaining 18 patients, 16 met AAN criteria for BD, 9 of whom required ancillary testing with CA. Of the 16 patients, 2 who also required CA ancillary testing were found to have persistent intracranial flow and were not declared brain dead at that time. These patients also underwent CTA; the results were concordant with the CA results. Six patients who were diagnosed with BD on the basis of clinical criteria alone also underwent CA, with 100% sensitivity. For all 18 patients included in the study, CTA had a sensitivity of 75%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 33%.
Clinical examination with or without CA remains the gold standard in BD testing. Studies assessing the statistical performance of CTA in BD testing should compare CTA to these gold standards. The statistical performance of CTA in BD testing is comparable to several of the nationally accepted ancillary tests. These data add to the growing medical literature supporting the use of CTA as a reliable ancillary test in BD testing.
Adib A. Abla, David A. Wilson, Richard W. Williamson, Peter Nakaji, Cameron G. McDougall, Joseph M. Zabramski, Felipe C. Albuquerque and Robert F. Spetzler
Cerebral vasospasm following subarachnoid hemorrhage (SAH) causes significant morbidity in a delayed fashion. The authors recently published a new scale that grades the maximum thickness of SAH on axial CT and is predictive of vasospasm incidence. In this study, the authors further investigate whether different aneurysm locations result in different SAH clot burdens and whether any concurrent differences in ruptured aneurysm location and maximum SAH clot burden affect vasospasm incidence.
Two hundred fifty patients who were part of a prospective randomized controlled trial were reviewed. Most outcome and demographic variables were included as part of the prospective randomized controlled trial. Additional variables were also collected at a later time, including vasospasm data and maximum clot thickness.
Aneurysms were categorized into 1 of 6 groups: intradural internal carotid artery aneurysms, vertebral artery (VA) aneurysms (including the posterior inferior cerebellar artery), basilar trunk or basilar apex aneurysms, middle cerebral artery aneurysms, pericallosal aneurysms, and anterior communicating artery aneurysms. Twenty-nine patients with nonaneurysmal SAH were excluded. Patients with pericallosal aneurysms had the least average maximum clot burden (5.3 mm), compared with 6.4 mm for the group overall, but had the highest rate of symptomatic vasospasm (56% vs 22% overall, OR 4.9, RR 2.7, p = 0.026). Symptomatic vasospasm occurrence was tallied in patients with clinical deterioration attributable to delayed cerebral ischemia. There were no significant differences in maximum clot thickness between aneurysm sites. Middle cerebral artery aneurysms resulted in the thickest mean maximum clot (7.1 mm) but rates of symptomatic and radiographic vasospasm in this group were statistically no different compared with the overall group. Vertebral artery aneurysms had the worst 1-year modified Rankin scale (mRS) scores (3.0 vs 1.9 overall, respectively; p = 0.0249). A 1-year mRS score of 0–2 (good outcome) was found in 72% of patients overall, but in only 50% of those with pericallosal and VA aneurysms, and in 56% of those with basilar artery aneurysms (p = 0.0044). Patients with stroke from vasospasm had higher mean clot thickness (9.71 vs 6.15 mm, p = 0.004).
The location of a ruptured aneurysm minimally affects the maximum thickness of the SAH clot but is predictive of symptomatic vasospasm or clinical deterioration from delayed cerebral ischemia in pericallosal aneurysms. The worst 1-year mRS outcomes in this cohort of patients were noted in those with posterior circulation aneurysms or pericallosal artery aneurysms. Patients experiencing stroke had higher mean clot burden.