Please check out the accompanying podcast of this blog post (also known as “Annotated Bibliography”):

1. Dietrich TJ, Sutter R, Froehlich JM, Pfirrmann CWA. Particulate versus non-particulate steroids for lumbar transforaminal or interlaminar epidural steroid injections: an update. Skeletal Radiol. 2015;44(2):149–155. doi:10.1007/s00256-014-2048-6.

The authors present an update on the current literature regarding the use of corticosteroids for transforaminal epidural and interlaminar epidural injections. Topics covered include a summary of recent FDA announcements, anatomy of the vascular supply to the spinal cord, the various steroid preparations, associations between complications and particulate steroids, and efficacy of the various steroid preparations. Considering all the pros and cons, the authors have decided to administer 4 mg of dexamethasone as a rapidly soluble steroid for lumbar transforaminal epidural and interlaminar epidural steroid pain injection, placing the needle tip location in the inferior zone of the neural foramen. Generally, particulate steroids are no longer employed at their institution for either transforaminal epidural or interlaminar epidural steroid injections.

Given the improved safety profile of a soluble steroid, and the poorly defined clinical benefit of a particulate steroid, this seems like a straightforward and prudent course to use the soluble agent.

2. Albers GW, von Kummer R, Truelsen T, et al. Safety and efficacy of desmoteplase given 3–9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Neurol. 2015;14(6):575–584. doi:10.1016/S1474-4422(15)00047-2.

This study is a prospective, double blind, multicenter, parallel-group, randomized trial which enrolled patients from 77 hospitals in 17 countries who had ischemic stroke and occlusion or high-grade stenosis in major cerebral arteries.  Treatment was either with desmoteplase given 3–9 h after symptom onset or placebo. Patients, investigators, staff, and the funder were masked to treatment assignment. The primary outcome was a favorable modified Rankin Scale score (0–2) at day 90. 1159 patients were screened, and 492 patients were enrolled. 247 were randomly assigned to desmoteplase and 245 to placebo. Median time from stroke onset to treatment was 6.9 h for placebo and 7.0 h for desmoteplase. Modified Rankin Scale score (0–2) at day 90 occurred in 121 (51%) patients given desmoteplase and 118 (50%) patients given placebo. The authors conclude that treatment with desmoteplase did not improve functional outcome when given to patients who had ischemic stroke and major cerebral artery occlusion beyond 3 h of symptom onset.

Bottom line: Desmoteplase is not beneficial when given 3–9 h after symptom onset to patients with major cerebral artery occlusion.

3. Hill MD, Menon BK. Desmoteplase for late treatment of stroke: still in the dark. Lancet Neurol. 2015;14(6):560–561. doi:10.1016/S1474-4422(15)00061-7.

This is the editorial that accompanies the DIAS-3 (phase 3) paper on desmoteplase versus placebo.  Desmoteplase was discovered from the saliva of the common vampire bat Desmodus rotundus and has pharmacological properties that are favorable for treatment of ischemic stroke (very high fibrin specificity, long half-life, single-bolus deliverability, and a good safety profile). They note that for this trial, the DIAS-3 investigators abandoned the quest to identify penumbra with mismatch imaging, in favor of a simpler imaging selection paradigm: small core (less than a third of the middle cerebral artery or less than a half of the anterior cerebral artery or posterior cerebral artery territories), plus evidence of a target intracranial arterial occlusion. Patients had imaging with either CT or MR. All patients had the disease of interest, ischemic stroke caused by an occluded intracranial artery. A limitation of the current paper is that details about imaging data were not presented, and it will be of interest to learn what kinds of patients were included in the study on the basis of imaging. They wonder whether a substantial proportion of patients had proximal intracranial occlusions with clinically significant clot burden; these patients are less likely to respond to thrombolysis. The authors conclude with the exhortation that we must learn how imaging as a biomarker for stroke in a reliable way across multiple vendors, multiple processing algorithms, and multiple centers.

4. Compter A, van der Worp HB, Schonewille WJ, et al. Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial. Lancet Neurol. 2015;14(6):606–614. doi:10.1016/S1474-4422(15)00017-4.

Between Jan 22, 2008, and April 8, 2013, patients with a recent transient ischemic attack or minor stroke associated with an intracranial or extracranial vertebral artery stenosis of at least 50% were enrolled from seven hospitals in the Netherlands (VAST trial). The patients were randomly assigned in a 1:1 ratio to stenting plus best medical treatment (57 patients) or best medical treatment alone (58 patients). The primary outcome was the composite of vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment. Three patients in the stenting group had vascular death, myocardial infarction, or stroke within 30 days after the start of treatment (5%) versus one patient in the medical treatment group (2%). During median follow-up of 3 years, 7 patients in the stenting group and four (7%) in the medical treatment group had a stroke in the territory of the symptomatic vertebral artery.  The authors conclude that stenting of symptomatic vertebral artery stenosis is associated with a major peri-procedural vascular complication in about 1 in 20 patients.  The risk of recurrent vertebrobasilar stroke under best medical treatment alone was low.

5. Turan TN, Chimowitz MI. Yet again no benefit of stenting over medical therapy. Lancet Neurol. 2015;14(6):565–566. doi:10.1016/S1474-4422(15)00049-6

This is the accompanying editorial for the VAST trial paper.  The VAST study is the largest clinical trial for the comparison of outcomes in patients with symptomatic extracranial or intracranial vertebral artery stenosis randomly assigned to stenting versus medical treatment.  Potential reasons for the failure of stenting are multifactorial. The mechanism of stroke in unilateral vertebral artery atherosclerosis is typically artery-to-artery embolism and not hypoperfusion, so a strategy for prevention of artery-to-artery embolism (such as plaque stabilization with statins and prevention of thrombus formation with antiplatelet agents), is likely to be more effective than revascularization which increase flow. Also, inclusion of patients with intracranial vertebral artery stenosis in the VAST trial, who have been shown to be at high risk of peri-procedural stroke after stenting in SAMMPRIS and VISSIT trials would require that stenting is particularly effective in patients with extracranial vertebral stenosis for stenting to be superior to medical therapy overall.  They authors conclude that the results of studies have shown that medical therapy obviates the need for endovascular revascularization in stable coronary artery stenosis (COURAGE trial), renal artery stenosis (CORAL trial), symptomatic intracranial arterial stenosis (SAMMPRIS  and VISSIT trials), and vertebral artery stenosis (VAST). Continuing the search from costly endovascular procedures for patients with these diseases does not seem warranted when effective medical therapies are available.

6. Bond AE, Jane JA, Liu KC, Oldfield EH. Changes in cerebrospinal fluid flow assessed using intraoperative MRI during posterior fossa decompression for Chiari malformation. J Neurosurg. 2015;122(5):1068–1075. doi:10.3171/2015.1.JNS132712.

The authors studied intraoperative MRI (iMRI) in patients undergoing posterior fossa decompression for Chiari I malformation to examine the utility of iMRI to determine if the decompression was adequate.  All patients had preoperative supine imaging.  15 Chiari I patients underwent prone pre-incision iMRI cine studies with the neck flexed in position for surgery. The patient then underwent a bone decompression of the foramen magnum and arch of C-1, and the MRI was repeated. 14/15 (93%) patients demonstrated significant improvement of CSF flow dorsal to the tonsils with positioning only. In most patients the improvement after positioning alone was so prominent that further improvement after bone decompression was difficult to see.  They conclude that the impact of positioning on the results of iMRI is so profound that any intraoperative assessment tool currently in use is severely limited by this phenomenon.

The confusion continues with the authors noting that surgery in 6 patients failed, and 4 patients underwent revision surgery even though the iMRI demonstrated adequate space and flow during surgery after bone decompression.

7. Chen R, Shi B, Zheng X, et al. Anatomic Study and Clinical Significance of the Dorsal Meningovertebral Ligaments of the Thoracic Dura Mater. Spine. 2015;40(10):692–698. doi:10.1097/BRS.0000000000000860.

The authors performed a dissection-based study of 18 embalmed thoracic specimens investigating the dorsal meningovertebral ligaments of the thoracic dura.  The dorsal meningovertebral ligaments anchored the dura mater to the lamina or ligamentum flavum and displayed a relatively even distribution along the upper thoracic region (T1–T7) and a gradual increase in frequency in the lower thoracic region from T7 to T12. Meningovertebral ligaments can immobilize the dura mater by restricting its range of motion and also have supportive and protective functions in the structure.  The authors speculate that unrecognized thoracic dorsal meningovertebral ligaments might be one potential cause for dural laceration and epidural hemorrhage during surgery.

The nomenclature of these dural ligaments which attach to the adjacent ligaments and bone is confusing. The most familiar of these is probably the anterior dural ligament (Hofman’s ligament) that connects the ventral dura to the posterior longitudinal ligament.  “Meningovertebral ligament” might be generic enough to use for these structures seen both dorsal and ventral to the thecal sac.

8. Cutsforth-Gregory JK, Lanzino G, Link MJ, Brown RD, Flemming KD. Characterization of radiation-induced cavernous malformations and comparison with a nonradiation cavernous malformation cohort. J Neurosurg. 2015;122(5):1214–1222. doi:10.3171/2015.1.JNS141452.

This retrospective case series identified 32 patients with radiation-induced cavernous malformations (56.2% men), with a median age of 31.1 years at diagnosis. The median latency from radiation treatment to radiation-induced cavernous malformation diagnosis was 12.0 years.  The lesions were always within the previous radiation port.  These lesions are less likely to be symptomatic compared to non-radiation cavernous malformations, and more likely to be multiple.  The risk of hemorrhage appears greater than non-radiation CM (4% vs. 2%).