Journal Scan – This Month in Other Journals, December 2016

Austein F, Riedel C, Kerby T, et al. Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy. Stroke. 2016 doi:10.1161/STROKEAHA.116.013147.

The purpose of the study was to determine the accuracy of different commercial perfusion CT software packages to predict the final infarct volume (FIV) after mechanical thrombectomy. Packages evaluated included 1) Philips Brain CT Perfusion Package, Philips Healthcare, The Netherlands, 2) Siemens (Syngo Volume Perfusion CT Neuro, Siemens Healthcare, Erlangen, Germany, and 3) RAPID (iSchemaView Inc, Menlo Park, CA). CTP data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and final infarct volume were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. Final infarct volume was measured at follow-up imaging between days 1 and 8 after stroke. Significant differences were found between the packages about over- and underestimation of the ischemic core, with RAPID best-predicting hypoperfusion volume in nonsuccessfully recanalized patients. They conclude that this software package overestimated the final infarct volume to a significantly lower degree and estimated a malignant mismatch profile less often than other software.

Tan BYQ, Wan-Yee K, Paliwal P, et al. Good Intracranial Collaterals Trump Poor Alberta Stroke Program Early CT Score for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke. Stroke. 2016 doi:10.1161/STROKEAHA.116.013879.

As a nice background and reference to describe the various collateral scoring systems, see: Yeo et al, Assessment of Intracranial Collaterals on CT Angiography in Anterior Circulation Acute Ischemic Stroke, AJNR 2015.

The authors evaluated the prognostic effect of the collateral circulation in patients with thrombolysed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS score. They stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤ 7 points) and small volume infarcts (ASPECTS 8–10). They also evaluated a third group with very large volume infarcts (ASPECTS≤ 5 points). The authors then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. The Tan system targets collateral vessels in the MCA territory; the Maas system compares the vessels from side to side; and the ASPECTS collaterals system subdivides the leptomeningeal collaterals into several more objective measurable areas. Good collaterals were defined as the following: Maas system, leptomeningeal vessels equal to or greater than the contralateral side and Tan system, >50% of the MCA territory. For the ASPECTS-collaterals system, good collaterals were defined as equal or more prominent when compared with a matching region in the opposite hemisphere and poor collaterals as arteries not seen or less prominent compared with the contralateral side to form a cumulative 20-point scale. On multivariate analysis, younger age and good collaterals by ASPECTS-collaterals system were associated with good outcomes.

Barajas RF, Butowski NA, Phillips JJ, et al. The Development of Reduced Diffusion Following Bevacizumab Therapy Identifies Regions of Recurrent Disease in Patients with High-grade Glioma. Acad Radiol. 2016;23(9):1073-1082. doi:10.1016/j.acra.2016.04.004.

26 patients treated with bevacizumab for high-grade glioma underwent lesion-wide apparent diffusion coefficient analysis before therapy and at the time of clinical/radiological progression, allowing for stratification by the presence or absence of reduced diffusion. Lesions with reduced diffusion were classified into “block” or “salt & pepper” phenotypes. Eight of the 26 patients underwent image-guided tissue sampling at the time of suspected disease recurrence allowing for direct biological correlation. 62% of the cohort had developed reduced diffusion at clinical progression following bevacizumab. They conclude that following bevacizumab therapy, recurrent glioblastoma can manifest as nonenhancing regions characterized by reduced diffusion. Histologically, these MR imaging characteristics correlate with aggressive biological features of disease recurrence. Current RANO criteria recommended that enlarging areas of mass like T2 hyperintensity should be considered as evidence of tumor progression. However, current RANO criteria do not account for the development of reduced diffusion following antiangiogenic therapy. This study provides direct histologic evidence that the development of nonenhancing infiltrative T2 FLAIR prolongation associated with reduced diffusion represents recurrent disease following antiangiogenic therapy.

4 figures and 4 tables

Clark W, Bird P, Gonski P, et al. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet (London, England). 2016;0(0):1726-1733. doi:10.1016/S0140-6736(16)31341-1.

Until now, there has been no evidence that vertebroplasty was more effective than placebo in the treatment of acute, painful, osteoporotic vertebral fractures, most notably for those in the thoracolumbar region. No masked studies have exclusively examined acute fractures of less than 6 weeks’ duration.

VAPOUR was a multicenter, randomized, double-blind, placebo-controlled trial of vertebroplasty in four hospitals in Sydney, Australia. They recruited patients with one or two osteoporotic vertebral fractures of less than 6 weeks’ duration. Vertebroplasty was done with the adequate vertebral fill technique and the placebo procedure with simulated vertebroplasty. The placebo procedure was designed to simulate vertebroplasty and included subcutaneous lidocaine but not periosteal numbing. A short needle was passed into the skin incision but not as far as the periosteum. Manual skin pressure and regular tapping on the needle was done, mimicking vertebroplasty needle advance. Conversation about PMMA mixing and injection suggested that vertebroplasty was being done. 61 patients were randomly assigned to vertebroplasty and 59 to placebo. 24 (44%) patients in the vertebroplasty group and 12 (21%) in the control group had an NRS pain score below 4 out of 10 at 14 days. They conclude that vertebroplasty is superior to placebo intervention for pain reduction in patients with acute osteoporotic spinal fractures of less than 6 weeks in duration.

Devasagayam S, Wyatt B, Leyden J, Kleinig T. Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought. Stroke. 2016 doi:10.1161/STROKEAHA.116.013617.

The incidence of cerebral venous thrombosis has been reported as being between 2-5 cases per million per year. However, a recent report suggested a much higher incidence (13 million person-years). The purpose of this study was to accurately determine the incidence of cerebral venous thrombosis in Adelaide, South Australia by using a novel ascertainment methodology. ICD discharge codes were searched to identify all patients with a potential diagnosis of cerebral venous thrombosis. All neuroimaging performed in public hospitals is entered into a central searchable data repository. They additionally searched all 259,101 neuroimaging studies performed between 2005 and 2011. The reports of these studies were searched for text variations containing “venous thromb”. A total of 168 cases were identified by the combined ICD and neuroimaging searches. Of the 105 cases of confirmed cerebral venous thrombosis, 59 (56%) were identified with both ICD and radiology database searches, 40 (38%) by radiology alone, and 6 (6%) by ICD coding alone. Therefore, the radiology database search correctly ascertained 94% of all cases. With 105 cases confirmed, and the population of 953 390 adults, this equates to an incidence of 15.7 cases per million per year.

Interesting use of big data.

Eklund A, Nichols TE, Knutsson H. Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proc Natl Acad Sci. 2016;113(33):201602413. doi:10.1073/pnas.1602413113.

Functional MRI (fMRI) is 25 years old, yet its most common statistical methods have not been validated using real data. The authors used resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses. Using this null data with different experimental designs, they estimate the incidence of significant results. In theory, they should have found 5% false positives (for a significance threshold of 5%), but instead they found that the most common software packages for fMRI analysis (SPM, FSL, AFNI) can result in false-positive rates of up to 70%. They conclude that these results question the validity of many fMRI studies (40,000?) and may have a large impact on the interpretation of weakly significant neuroimaging results.

Points out a couple of recurring difficulties in published results in general, that of over use of “significance” as an ultimate judge of importance and validity, and of the generally poor representation of reproducibility papers in the literature.

Everson RG, Holly LT, Batzdorf U. Chiari I Malformation in the Adult. Neurosurg Q. 2016;26(3):200-213.

This is a very nice review article on Chiari I malformation, including history, nomenclature, symptoms, epidemiology and genetics, imaging and treatment. Not the greatest quality MR images, but they make their point. The authors also describe, to their mind, some specific variants of a relatively small posterior fossa which can be further broken down into: Anterior (encroachment of the posterior fossa by basilar invagination, platybasia, odontoid invagination); Roof type (which shows a low insertion of the tentorium cerebelli into the occipital bone, that is, a low-lying torcula, resulting in an almost vertical tentorium which it appears almost parallel to the clivus on sagittal imaging); Floor type (thickened occipital bone, horizontal occipital bone, upward sloping posterior edge of foramen magnum); and Mass type (space-occupying lesions, commonly arachnoid cysts or extra-axial tumors).

12 Figures

Godel T, Pham M, Heiland S, Bendszus M, Bäumer P. Human dorsal-root-ganglion perfusion measured in-vivo by MRI. Neuroimage. 2016; 141:8187. doi:10.1016/j.neuroimage.2016.07.030.

This paper is worth the read if only for the explanatory neuroanatomy of the DRG, which is much more complex than I realized.

In 46 normal subjects, a T1-weighted, dynamic-contrast-enhanced (DCE) VIBE sequence was acquired through the L5 ganglia level with the following sequence parameters: TR/TE 3.3/1.11 ms; flip angle 15°; 24 slices; resolution 1.3 x 1.3 x 3.0 mm3. The contrast agent (Dotarem, Guerbet, France) was administered intravenously at the beginning of the third frame of the sequence at the standard concentration of 0.1 mmol/kg with a flow rate of 3.5 ml/s by automated injection. A total of 24 frames were recorded with a rate of 7.46 s/frame. A 15- channel receive/transmit spine coil and an 8-channel receive body flex coil (Siemens) were used. Transfer-constant (Ktrans) and interstitial-volume-fraction (interstitial-leakage-fraction, Ve) were modeled for the DRG and spinal nerve by applying the Tofts-model. Statistical analyses included pairwise comparisons of L5/S1 DRG vs. spinal nerve. Furthermore, distinct physiological zones within the S1 DRG were compared (cell body rich area (CBRA) vs. nerve fiber rich area (NFRA)). DRG showed a significantly increased permeability compared to spinal nerve combined with an increased interstitial leakage of contrast agent into the extravascular-extracellular-space. They conclude that the non-invasive and in-vivo measurement of human DRG perfusion by MRI is a feasible technique. They speculate that the technique may become particularly useful for future research on the poorly understood human sensory neuropathies and pain syndromes.

Journal Scan – This Month in Other Journals, December 2016
Jeffrey Ross
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