Please check out the accompanying podcast of this blog post (also known as “Annotated Bibliography”):
1. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015. doi:10.1038/nature14432.
Classic teaching is that there are no lymphatics in the central nervous system. The authors discovered functional lymphatic vessels lining the dural sinuses in mice, and point out potential lymphatics in cadaveric human dura. They found that these structures express the molecular hallmarks of lymphatic endothelial cells and are able to carry both fluid and immune cells from the cerebrospinal fluid. Further, these structures are connected to the deep cervical lymph nodes. The vessels they discovered stained with a variety of markers associated with lymphatic endothelial cells (Lyve-1, the LEC transcription factor Prox1, and podoplanin). These structures did not stain with the monocyte/macrophage marker CD68. They conclude: “The newly discovered meningeal lymphatic vessels are a novel path for cerebrospinal fluid drainage and represent a more conventional path for immune cells to egress the central nervous system. Our findings may represent the second step in the drainage of the interstitial fluid from the brain parenchyma into the periphery after it has been drained into the cerebrospinal fluid through the recently discovered glymphatic system.”
If you don’t want to wade through all the different stains and markers, just go to figure 10 of the Extended Data for the graphic summary!
2. Holliday EB, Mitra HS, Somerson JS, et al. Post-operative Proton Therapy for Chordomas and Chondrosarcomas of the Spine. Spine. 2015;40(8):1. doi:10.1097/BRS.0000000000000804.
This retrospective comparative cohort series evaluated patient treated with proton therapy for chordoma and chondrosarcoma of the spine following surgery. Nineteen patients who underwent postoperative proton therapy at a single institution from 2006 to 2012 were identified (13 with chordoma and 6 with chondrosarcoma). The median radiation dose delivered was 70 Gy. Eight patients received early adjuvant proton beam radiation (PBR) and 11 patients received salvage PBR. The median time from surgery to initiation of radiation was 9.5 months. 2-year local control was 58%, relapse free survival was 52%, and overall survival was 93.3%. Patients who received early adjuvant proton therapy had significantly better freedom from local failure than patients who received salvage radiotherapy after a local recurrence. Higher rates of recurrence were seen in patients with sacral tumors, longer surgery to radiation interval, and gross disease present at the time of radiation.
As the introduction of the paper notes, treatment with photon RT to doses <60 Gy results in recurrence rates of 50-100% and 5-year progression-free survival rates of less than 25%. While 60 Gy of conventional RT is considered inadequate for durable LC, that dose still carries the risk of significant toxicity. PBR deposits much of its energy at the end of the particle range, the Bragg peak. This may allow increased doses with sparing of adjacent tissues.
3. Liu Y, Wang J, Daams M, et al. Differential patterns of spinal cord and brain atrophy in NMO and MS. Neurology. 2015;84(14):1465–1472. doi:10.1212/WNL.0000000000001441.
The authors evaluated 35 patients with NMO, 35 patients with MS, and 35 control patients, who underwent both spinal cord and brain MRI. A variety of measurements were performed including mean upper cervical cord area (MUCCA), brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF) and spinal cord and brain lesion loads. Brain GM, WM, and CSF volumes were calculated on 3D MPRAGE images. MUCCA was measured on each available sagittal 3D T1-weighted brain dataset, on which the upper cervical cord was visible with sufficient image quality. They found that patients with NMO showed smaller ‘mean upper cervical cord area’ than the healthy controls. Patients with NMO showed lower BPF than controls, and patients with MS had lower BPF and GMF than patients with NMO. They conclude that NMO showed predominately spinal cord atrophy with mild brain atrophy, while MS demonstrated more brain atrophy, especially in the gray matter. Mean upper cervical cord area was the main MRI derived parameter for explaining clinical disability in NMO and MS. They suggest that this measurement could be included in future clinical trials.
4. Fleischman DA, Yang J, Arfanakis K, et al. Physical activity, motor function, and white matter hyperintensity burden in healthy older adults. Neurology. 2015;84(13):1294–1300. doi:10.1212/WNL.0000000000001417.
Total daily activity (exercise and nonexercise physical activity) was measured for 11 days in 167 older adults without dementia. White matter hyperintensity (WMH) volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with total WMH volume as the predictor and global motor score as the outcome. The authors conclude that higher levels of physical activity reduced the effect of WMH burden on motor function in community-dwelling older adults without dementia. Persons with the highest physical activity (90th percentile) showed no effect of WMH burden on motor function. Persons at the 50th percentile of physical activity showed an effect of WMH burden on motor function and this effect was stronger for persons at the 10th percentile. They conclude that higher levels of physical activity may provide reserve against the effects of brain pathology on motor function in older age.
Does my treadmill time count?
5. Germans MR, Coert BA, Majoie CBLM, et al. Yield of spinal imaging in nonaneurysmal, nonperimesencephalic subarachnoid hemorrhage. Neurology. 2015;84(13):1337–1340. doi:10.1212/WNL.0000000000001423.
The authors performed a prospective, multicenter study evaluating T1 and T2-weighted spinal MR in consecutive patients with spontaneous nonperimesencephalic SAH without intracranial vascular pathology on intracranial vascular imaging. The spinal origin of the hemorrhage was found in 3 of 75 patients (4%). The lesions were 1 lumbar ependymoma and 2 cervical cavernous malformations. The yield and clinical relevance of MRI of the spinal axis in patients who present with nonperimesencephalic SAH is low. They do not recommend routine MRI of the spinal axis in this patient population. Screening might be justified in young patients (<50) with CT-negative SAH.
All patients received a nonenhanced CT, and CT angiogram. At least one DSA was performed in 78 patients (87%). My institution continues to image the spine in this patient population looking for sources of hemorrhage, despite the known low rate of success.
6. Spiotta AM, Vargas J, Zuckerman S, et al. Acute Stroke After Carotid Endarterectomy. Neurosurgery. 2015;76(4):403–410. doi:10.1227/NEU.0000000000000642.
By way of historical background, of the 1453 patients enrolled in the surgical arm of NASCET, there were 55 postoperative strokes and stroke-related deaths (3.8%), 35 of which (2.4%) occurred within 24 hours of surgery. Conventional treatment of immediate postoperative ipsilateral strokes following endarterectomy is surgical exploration. In this study, the authors performed a retrospective review of all patients undergoing acute stenting of the carotid artery after carotid endarterectomy from November 2009 to June 2013 at 4 centers (Medical University of South Carolina, the Vanderbilt University Medical Center, University of Wisconsin Hospital and Clinics, and the University of Buffalo). Eleven cases of carotid thrombosis within 72 hours of carotid endarterectomy were found. Generally, the patients emerged from anesthesia and were taken to the recovery room with a nonfocal neurological exam. These patients subsequently developed a postoperative ipsilateral middle cerebral artery stroke syndrome. The mean time from CEA to symptom onset was 22.9 hours. Diagnostic cerebral angiography demonstrated a clear dissection in 1 patient; 8 other patients demonstrated 90% occlusion of the carotid artery from thrombus at the surgical site. Six of these 8 patients had complete occlusion. Patients received stent reconstruction within 11 hours of symptom onset. In all cases, carotid recanalization was successfully completed between 32 and 160 minutes from groin puncture. There were no procedural complications. They conclude that emergent endovascular evaluation in the setting of acute post–carotid endarterectomy thrombosis is a safe and timely treatment option. This data suggests that it may be prudent to challenge the convention of treating ipsilateral strokes after CEA with immediate surgical exploration.
7. Monserrate AE, Ryman DC, Ma S, et al. Factors Associated With the Onset and Persistence of Post–Lumbar Puncture Headache. JAMA Neurol. 2015;72(3):325. doi:10.1001/jamaneurol.2014.3974.
The authors performed univariate and multivariable analyses of 338 lumbar punctures and evaluated associations of 3 post–lumbar puncture outcomes (immediate postprocedural headache, post–dural puncture headache (PDPH) at 24-hour follow-up, and PDPH receiving a therapeutic blood patch) with participant age and sex, positioning, collection method, needle size, needle insertion site, and CSF volume collected. The protocol specified a 22G Sprotte needle with gravity collection, or a 24G Sprotte needle with aspiration could be used. There were 73 immediate postprocedural headaches (21.6%), 59 PDPHs at 24-hour follow-up (17.5%), and 15 PDPHs receiving a therapeutic blood patch (4.4%). Factors that acutely lower CSF pressure (eg, seated positioning or extracting very high volumes of CSF) were associated with transient immediate postprocedural headache, without increasing the risk of PDPH at 24-hour follow-up. Collection of 17-30mL of CSF was safe and well tolerated.
While I have no qualms about taking off 30cc of CSF in patients, I do prefer to have a pre-LP brain imaging study of some type to make sure there is free flow of CSF from the brain to the spine, and no type of obstructive lesion at the craniovertebral junction.
8. Bicket MC, Horowitz JM, Benzon HT, Cohen SP. Epidural injections in prevention of surgery for spinal pain: systematic review and meta-analysis of randomized controlled trials. Spine J. 2015;15(2):348–362. doi:10.1016/j.spinee.2014.10.011.
The authors conclude that the findings in this systematic review and meta-analysis of 26 papers provide mixed results regarding the ability of ESI to reduce the need for surgery. One study examined the impact of ESI on surgery as a primary outcome and it demonstrated moderate evidence for a surgery-sparing effect for ESI in the short term. Studies including surgery as a secondary outcome provided moderate evidence of no surgery-sparing effect: only a trend for short-term but not long-term benefit was found. The authors state that the main finding in this study is that there may be a weak surgery-sparing effect for ESI in the short term but not the long term.
I find it very difficult to come to any conclusion based on this data. As the authors note, the overall methodological and technical qualities of the studies were poor. Most of the studies had limited information on the effectiveness of blinding, and many of the studies used different indications (ie, herniated disc vs. spinal stenosis), doses of steroid, volumes of injectate, and number of allotted injections. In a word, a mess.
