Please check out the accompanying podcast of this blog post (also known as “Annotated Bibliography”):
1. CADISS Trial Investigators. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol. 2015;14(4):361–367. doi:10.1016/S1474-4422(15)70018-9.
Patients with extracranial carotid and vertebral dissection with onset of symptoms within 7 days were randomly assigned to receive antiplatelet drugs or anticoagulant drugs for 3 months. The primary endpoint was ipsilateral stroke or death in the intention-to-treat population. 126 participants were assigned to antiplatelet treatment versus 124 to anticoagulant treatment. They found no difference in efficacy of antiplatelet and anticoagulant drugs at preventing stroke and death. Stroke was rare in both groups, on the order of 1-2%. On the imaging side, the diagnosis of dissection was not confirmed after central review in 52 patients.
The Discussion section gives a succinct review of the difficulties in diagnosing dissection, particularly of the vertebral arteries. In this study, the authors note two general causes of nonconfirmed diagnoses (1/5th of the cases), due either to poor quality studies or misdiagnoses (such as atherosclerotic narrowing or hypoplastic arteries). Vertebral dissections are much more difficult to diagnose due to the tortuous anatomy, and normal variation in vessel size, as well as surrounding venous plexus signal intensity.
2. Chen L, Elias G, Yostos MP, Stimec B, Fasel J, Murphy K. Pathways of cerebrospinal fluid outflow: a deeper understanding of resorption. Neuroradiology. 2014;57(2):139–147. doi:10.1007/s00234-014-1461-9.
Interesting review evaluating the relatively sparse literature on spinal arachnoid granulations and lymphatic drainage of CSF, which involves different animal models, but little in-vitro human correlation. The authors make the case that CSF is absorbed and drained in bulk not just through cerebral arachnoid granulations but also through spinal arachnoid granulations and a lymphatic pathway involving the olfactory nerve and spinal nerve sheaths. They point out that given the advanced imaging techniques available to us, neuroradiology should be at the forefront of trying to advance knowledge in this area.
I have done a lot of myelography in my day, and I don’t remember ever seeing anything looking like a spinal arachnoid granulation. Anyone else seen any outpouchings in the spinal dural that might represent this anatomic structure?
3. Gass A, Rocca M a, Agosta F, et al. MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis. Lancet Neurol. 2015;14(4):443–454. doi:10.1016/S1474-4422(14)70294-7.
This is a comprehensive review article that deals with the pathologic changes in the spinal cord with MS, and the associated imaging features. Imaging techniques covered include standard imaging (PD, STIR, T2FSE), as well as several potential or novel techniques that might find clinical acceptance. These latter include magnetization transfer, DTI, and fMRI of the spinal cord. Proton spectroscopy of the cord is also covered, and includes a table listing the five current papers on this narrow topic. Five figures included.
4. Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol. 2015;14(4):406–419. doi:10.1016/S1474-4422(14)70305-9.
Excellent review of the complexities of the immune system and relationship to both active and progressive forms of MS. This is not easy reading, but there is a helpful glossary, and there are separate sidebar explanations of the adaptive and innate immune systems. I also found it helpful to see explanations of the differing theories of the role of the immune system in the development of lesions (CNS antigen-specific immune activation occurs first in the periphery and is then transferred to the previously unaffected CNS, OR an initiating event within the CNS causes the subsequent activation of resident microglia and an amplification of the immune reaction), and the differing theories regarding the immune system in progressive disease (primary neuro-degeneration drives disease progression OR compartmentalized inflammation drives disease progression).
Fun facts from the innate immune system sidebar in the article: “Monocytes mainly enter the CNS as part of an acute inflammatory response, whereas microglial cells arise from primitive myeloid progenitors in the yolk sac and migrate to the CNS during early embryonic development. The population of microglial cells is maintained by self-renewal with little, if any, contribution from the blood.”
5. Kim HJ, Paul F, Lana-Peixoto MA, et al. MRI characteristics of neuromyelitis optica spectrum disorder: An international update. Neurology. 2015:1165–1173. doi:10.1212/WNL.0000000000001367.
Excellent review article defining the imaging characteristics that might help define NMO from MS. Diagnostic criteria for NMO require both optic neuritis and myelitis. However, the identification of anti-AQP4 antibodies beyond these NMO diagnostic criteria seem to indicate a broader clinical phenotype, the so-called “NMO spectrum disorder” (NMOSD). Brain lesions have been reported from 51% – 89% in seropositive patients with NMOSD. These lesions may have characteristic features that help distinguish them from MS, such as diencephalic lesions surrounding the third ventricles and cerebral aqueduct, and lesions in the dorsal brainstem adjacent to the fourth ventricle, including the area postrema and the nucleus tractus solitarius. Corpus callosum lesions have been seen in 12% – 40% of patients with NMOSD, and tend to be located immediately next to the lateral ventricles, following the ependymal lining.
Four figures and a table that outlines the differences in imaging appearance between MS and NMO.
6. Klekamp J. Chiari I malformation with and without basilar invagination: a comparative study. Neurosurg Focus. 2015;38(4):E12. doi:10.3171/2015.1.FOCUS14783.
This is a case series of 323 patients who underwent 350 operations between 1985 and 2013 for Chiari 1 malformations. Patients with (n = 46) or without (n = 277) basilar invagination in addition to Chiari 1 malformation were defined. Patients with invagination were separated into groups: those with (n = 31) and without (n = 15) ventral compression by the odontoid in the foramen magnum. All operations included a foramen magnum decompression with arachnoid dissection, opening of the fourth ventricle, and a duraplasty (with a variety of materials). The authors conclude that Chiari 1 malformations without invagination and those with invaginations but without ventral compression should be treated by foramen magnum decompression alone. Most patients with ventral compression can be treated by posterior decompression, realignment, and stabilization. Anterior decompression should be reserved for patients with symptomatic brainstem compression.
9 figures, including 5 MR examinations of different patients. There is a flow chart which is also helpful, with the major decision branch points of 1) invagination or 2) no invagination, and then the second branch point for the invagination group of 1) ventral compression or 2) no ventral compression. Transoral decompression is reserved for ventral compression with lower cranial nerve dysfunction.
7. Park MS, Moon S-H, Lee H-M, et al. Diagnostic value of oblique magnetic resonance images for evaluating cervical foraminal stenosis. Spine J. 2015;15(4):607–611. doi:10.1016/j.spinee.2014.10.019.
The authors preformed a retrospective study on 26 patients with evaluation of the intra- and interobserver variabilities for assessing cervical foraminal stenosis using oblique MRI imaging compared to standard orthogonal views. Two reviewers blindly identified the presence of foraminal stenosis as definite or indeterminate on the sagittal, axial, and oblique images. The oblique or axial views had significantly greater confidence rates for determining the presence of foraminal stenosis than the sagittal views (92.3%, 88.1% vs. 58.0%, respectively).
A useful technique, although not widely utilized mainly due to modern day time constraints, since it requires two separate sequences which are not primary in making a diagnosis. The authors used a FSE TR3500 / TE148, 2 mm slices, FOV 249 mm, 512 x 247, 3 NEX.
8. Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348(6230):56–61. doi:10.1126/science.aaa8172.
Detailed review on the science behind checkpoint therapy for treating cancer. The most familiar agent is the antibody against CTLA-4 (ipilimumab)(pronounced – i pi LIM ue mab”), which was FDA approved in 2011. The agent nivolumab (pronounced – NYE-vol-U-Mab), which is an antibody against PD-1 (programmed death 1 checkpoint inhibitor) was approved in 2014. Neuroradiologists are most familiar with these agents as a cause of hypophysitis (up to 10% of treated patients in some series) See Carpenter et al., AJNR 30:1751-53, 2009.
Recent important papers have been published on the utility of these agents in melanoma and lung cancer. See also: Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., … Spigel, D. R. (2015). Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer. New England Journal of Medicine, 1–13. doi:10.1056/NEJMoa1504627
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., … Wolchok, J. D. (2015). Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. New England Journal of Medicine, 1–12. doi:10.1056/NEJMoa1504030
