Journal Scan – This Month in Other Journals, February 2017

Domino JS, Baek J, Meurer WJ, et al. Emerging temporal trends in tissue plasminogen activator use. Neurology. 2016;87(21):2184-2191. doi:10.1212/WNL.0000000000003349.

Mexican Americans (MA) have an increased stroke burden when compared to their non-Hispanic white (NHW) counterparts, including increased stroke incidence and poorer neurologic, functional, and cognitive outcomes.

The authors explored the temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center. Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study from 2000-2012. There were 5,277 AIS cases identified from 4,589 individuals. tPA use was steady at 2% and began increasing in 2006, reaching 11% in subsequent years. Although ethnicity did not modify the temporal trend, Mexican Americans were less likely to receive tPA than non- Hispanic whites due to emerging ethnic differences in later years. The results suggest that increases in tPA use were greater in higher severity patients compared to lower severity patients, and a gap between MAs and NHWs in tPA administration may be emerging.  The authors conclude that as physician experience with tPA and its use in community settings increases, follow-up studies should continue to explore temporal trends in tPA as well as identify possible strategies to improve tPA use in MAs.

2 Figures (graphs), 2 Tables

Goldstein LB. IV tPA for acute ischemic stroke. Neurology. 2016;87(21):2178-2179. doi:10.1212/WNL.0000000000003366.

In this editorial on the Domino et al. paper, Dr. Goldstein notes that there were considerable barriers that slowed IV tPA adoption after it was approved by the FDA in 1996.  Eight years after FDA approval, IV tPA was being given to only 1%–2% of stroke patients. Transformation of the structure and organization of stroke care delivery were needed, and in part led to recommendations for the development of primary stroke centers and stroke care systems, each having benefits beyond the administration of IV tPA. Although there was no difference in the rate of use of IV tPA in the United States between 2001 and 2004, the rate doubled from 2005 to 2009, with a conservative estimate indicating that 3.4%–5.2% of patients with ischemic stroke were treated at the end of the decade. He concludes that the overall improvement in treatment rates is encouraging and indicates that there can be considerable gains in stroke-related care even in the absence of a locally available academic medical center.

Ivan ME, Mohammadi AM, De Deugd N, et al. Laser Ablation of Newly Diagnosed Malignant Gliomas. Neurosurgery. 2016;79(6): S17-S23. doi:10.1227/NEU.0000000000001446.

For WHO Grade III-IV the first-line treatment is cytoreduction via maximal safe surgical excision followed by temozolomide chemotherapy and radiation therapy. However, the mean survival time is low (12-14 months) or up to 21.7 months if the patients have methylguanine methyltransferase (MGMT) promoter methylation and are treated with both temozolomide and radiation therapy.

When traditional craniotomy is deemed unsafe for the patient, the need for an alternative to open surgery is required, and one option is laser interstitial thermal therapy (LITT), which ablates tissue by heat generated through light absorption. The systems available for performing the LITT procedure are Visualase Thermal Therapy System (Visualase; Medtronic, Minneapolis, Minnesota) and the NeuroBlate System (Monteris Medical, Kalamazoo, Michigan).

MR-LITT several potential advantages, in that it can reach tumors that are located deep in the brain with minimal manipulation of the overlying tissue. This allows tumors in locations such as the basal ganglia to be treated with MR-LITT when otherwise they would only be biopsied. The procedure is minimally invasive requiring a small 3-mm skin incision and insertion of a small laser probe. Therefore, there is minimal tissue disruption, which decreases the decadron needed postoperatively and shortens the hospital stay to only 1 to 2 days.

The authors performed a meta-analysis of the current literature using PubMed, OVID, and Google-scholar database systems to provide a comprehensive search of the English literature. Eighty-five articles were identified plus one that is pending publication. Four articles were accounted for in this review, including 25 patients with newly diagnosed high-grade gliomas who underwent MR-LITT treatment. On average, 82.9% of the pretreatment lesion volume was ablated. The average tumor volume treated was 16.5 cm3. The mean follow-up time was 7.6 months. Median overall survival was found to be 14.2 months. The median progression-free survival was 5.1 months. There was 1 (3.4%) major perioperative complication which was an infection. They conclude that MR-LITT is a promising technology for the treatment of small, yet difficult-to-treat newly diagnosed high-grade gliomas.

The study has many obvious limitations, the primary deficiencies being that any of the patients have a short follow-up period and this series contains a very small sample size. Also, molecular profiling, Karnofsky Performance Scale, and treatment type specifics were not available for these patients. Estimated overall survival and progression-free survival should be viewed as very preliminary data.

3 Figures (graphs), 3 Tables

Wicks RT, Jermakowicz WJ, Jagid JR, et al. Laser Interstitial Thermal Therapy for Mesial Temporal Lobe Epilepsy. Neurosurgery. 2016;79(6): S83-S91. doi:10.1227/NEU.0000000000001439.

Approximately one-third of patients with epilepsy do not achieve adequate seizure control through medical management alone. Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of medically refractory epilepsy referred for surgical management. Clinical series and two randomized controlled trials have established anterior temporal lobectomy with amygdalohippocampectomy (ATLAH) and selective amygdalohippocampectomy (SAH) to be a cost-effective procedure in cases of medically refractory MTLE.

Stereotactic laser amygdalohippocampotomy using MR–guided laser interstitial thermal therapy (MRg-LITT) is an important emerging treatment for MTLE. Summing up the limited publications (3) using stereotactic laser amygdalohippocampectomy (SLAH) for MTLE in patients with MTS with 1-year outcomes (the gold standard), including Willie et al (4 of 7, excluding their first 2 patients, who did not have radiological criteria for MTS), Wasseem et al (4 of 5), and Kang et al. (4 of 10) yields a mean seizure-free rate of 55% (12 of 22).

Most treatment failures, in the authors opinion, are attributed to technical aspects of the surgery are caused by (1) a trajectory that spares medial structures of the hippocampus, such as the subiculum or uncal apex; (2) not passing the catheter deep enough to reach the amygdala; (3) not ablating hippocampal body far enough posteriorly, to at least the level of the lateral mesencephalic sulcus; and (4) small ablation volume due to too few ablations or low power. Most treatment failures not related to technical aspects of the surgery are attributed to patient-related factors (e.g., bilateral or extratemporal seizure onsets) or patient noncompliance with antiepileptic medications.

The authors conclude that at epilepsy centers with sufficient MRg-LITT experience, SLAH is replacing or is presented as an up-front alternative to amygdalohippocampectomy or selective amygdalohippocampectomy in the surgical treatment of MTLE.

In an accompanying commentary by Diaz and Komotar, it is noted that the rate of seizure freedom (no seizures impairing consciousness) summarized here is less than that reported by Wiebe et al. for anterior temporal lobectomy (64%, N = 36) at one year after surgery. Given the sparse clinical data currently available regarding the longevity of seizure control, surgical risk, and seizure outcome, it is not clear whether clinical equipoise exists to hold SLAH as an equal alternative option to anterior temporal lobectomy in routine clinical treatment of mesial temporal lobe epilepsy.

3 Figures, 1 Table

Onishi E, Yasuda T, Yamamoto H, Iwaki K, Ota S. Outcomes of Surgical Treatment for Thoracic Myelopathy. Spine (Phila Pa 1976). 2016;41(22):E1356-E1363. doi:10.1097/BRS.0000000000001622.

The authors evaluated the clinical outcomes in patients with thoracic myelopathy in a single institution and identified prognostic factors for poor outcomes. The retrospective series consisted of 71 patients who underwent surgical treatment for thoracic myelopathy between 2000 and 2011 in a single institution. Fifty-eight patients underwent laminectomy, eight patients underwent laminectomy and posterior fusion, four patients underwent OPLL extirpation and posterior fusion, and three patients underwent OPLL extirpation.

They found a considerable degree of neurological recovery was observed after surgical treatment in patients with thoracic myelopathy. The JOA score improved significantly with an average postoperative recovery rate of 30%. Prognostic factors for poor outcomes were longer preoperative duration of symptoms, worse preoperative symptoms, OPLL and/or OLF, and large volume of intraoperative bleeding. However, patients condition deteriorated postoperatively for nine patients (12%), all of whom had OPLL and/or OLF. Also, one or more complications were experienced by 15 patients (21%), including intraoperative dural tear in nine patients, epidural hematoma needing reoperation in two patients, postoperative paralysis in three patients, and deep infection in two patients.

5 Tables, 3 Figures

Chou D, Bilsky MH, Luzzati A, et al. Malignant peripheral nerve sheath tumors of the spine: results of surgical management from a multicenter study. J Neurosurg Spine. November 2016:1-8. doi:10.3171/2016.8.SPINE151548.

First, some background:
Enneking (Enneking WF, Spainer SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcomas. Clin Orthop 1980;153:106–20) defined the surgical management of tumors, which was originally described for long bones. These principles are not entirely applicable in describing spinal tumors and must be adapted to avoid confusion. Lesion surgical margins are defined as follows: The term intralesional is appropriate for a dissection passing within the tumor mass; marginal for a dissection through the pseudocapsule or reactive tissue about the tumor; and wide where the tumor is removed with a surrounding cuff of normal tissue. The epidural space and the cord make a ‘‘radical’’ resection impossible with-out evident neurologic injury.

In other words, the typical peripheral tumor definition of “en bloc resection” includes the tumor and the whole compartment of tumor origin. The epidural space compartment extends from the skull to the coccyx; therefore, the compartment is not removed even if the spinal cord is sectioned above and below the tumor. For more information on spine tumor staging, see: Donthineni R. Diagnosis and staging of spine tumors. Orthop Clin North Am. 2009;40(1):1-7, v. doi:10.1016/j.ocl.2008.10.001.

Enneking appropriate (EA) surgery for a high-grade MPNST would therefore be traditionally categorized in the extremity as an en bloc resection to achieve wide margins (i.e., removing the tumor as a single specimen with a cuff of normal tissue). Often, spinal MPNSTs involve several compartments, including nerve, soft tissue, and bone. An EA resection would include en bloc resection with wide margins of each compartment. If the margin had been transgressed either intentionally or inadvertently, the surgery would have been deemed an EI even if the surgical plan had been EA resection.

Resection of MPNSTs followed by radiation therapy is the standard treatment for extraspinal MPNSTs. The surgical technique of en bloc resection achieving wide margins is an important prognostic factor in achieving local tumor control. The objective of this study was to describe whether the type of Enneking resection in the management of spinal MPNSTs had an effect on local recurrence and survival.

In this study, patient data was extracted from the AOSpine Multicenter Primary Spinal Tumor Database, which includes approximately 1500 patients treated between 1981 and 2012 at 13 spine centers across North America, Europe, and Australia. Twenty-nine primary spine MPNSTs were identified in 12 (41%) females and 17 (59%) males with a mean age at diagnosis of 40 years (range 5–74 years). The mean tumor dimensions were 7.2cm. Survival in patients undergoing EA and EI resections in this series (56% and 50%, respectively) has improved over that previously reported (20%). Kaplan-Meier analysis conducted over a 2-year period following resection demonstrated no difference between the EA and EI cohorts for time to first local recurrence, or any difference in survival. The authors recommend that where technically feasible, en bloc surgery should be considered; however, due to the poor outcomes from both EA and EI surgery, they do not recommend surgery associated with high morbidity in cases in which doubt remains over the pathology or when wide resection is not feasible based on anatomical constraints. High-dose radiation therapy is strongly recommended, regardless of the nature of the resection.

2 Tables, 4 Figures (2 of which are Kaplan-Meier plots)

Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. November 2016. doi:10.1038/nrneurol.2016.166.

The MRI-detectable central vein inside white matter lesions has recently been proposed as a biomarker of inflammatory demyelination and, thus, may aid the diagnosis of MS. This Consensus Statement aims to provide recommendations for the definition, standardization and clinical evaluation of the central vein sign (CVS) in the diagnosis of MS. The statements are based on a review of the literature and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative.

They propose the following CVS definitions and exclusions on T2W images (usually high res 3D FLAIR):

  • Appears as a thin hypointense line or small hypointense dot
  • Can be visualized in at least two perpendicular MRI planes, and appears as a thin line in at least one plane
  • Has a small apparent diameter (<2 mm)
  • Runs partially or entirely through the lesion
  • Is positioned centrally in the lesion regardless of the lesion’s shape

Exclusion criteria for lesions:

  • Lesion is <3 mm in diameter in any plane
  • Lesion merges with another lesion (confluent lesions)
  • Lesion has multiple distinct veins
  • Lesion is poorly visible (owing to motion or other MRI-related artifacts)

They conclude that the currently available evidence from a small prospective study supports the high predictive value of the CVS in the diagnosis of MS in patients with typical CIS or atypical neurological presentations.

Exactly how to use the sign to diagnosis demyelination has not been firmly established (number, location). One proposed definition is the ‘40% rule’, first introduced by Evangelou and colleagues (Neurology 76, 534–539 (2011)) which assesses the percentage of lesions with a central vein and uses a cut-off value of 40% to radiologically distinguish MS from non-MS disease states. This rule has an obvious limitation since counting the number of lesions would be time-consuming in patients with high lesion load.

A simpler set of diagnostic rules for CVS has been introduced, consisting of the following three criteria (Mult Scler 22, 1289–1296 (2016)): if there are six or more morphologically characteristic lesions, the diagnosis is inflammatory demyelination; if there are fewer than six morphologically characteristic lesions, but morphologically characteristic lesions outnumber non-perivenous lesions, the diagnosis is inflammatory demyelination; if neither of these conditions are met, inflammatory demyelination should not be diagnosed. The morphologically characteristic lesions considered here had a ‘coffee bean’ or ‘Dawson’s finger’ appearance when the MRI slice was along the vein’s axis, and a ‘ring’ or ‘doughnut’ appearance when the MRI slice was approximately perpendicular to the vein.

To conclude, the currently available evidence from a small prospective study supports the high predictive value of the CVS in the diagnosis of MS in patients with typical CIS or atypical neurological presentations.

2 very helpful figures regarding appearance of CVS

Eduardo Corrales C, Mudry A, Jackler RK. Perpetuation of errors in illustrations of cranial nerve anatomy. J Neurosurg. October 2016:1-7. doi:10.3171/2015.12.JNS151203.

In 1778, a 23-year-old medical student named Samuel Thomas von Soemmerring (1755–1830), of Goettingen, Germany, numbered the CNs from I to XII. Soemmerring, who rose to become one of the most eminent anatomists by the turn of the 19th century, ranked the CNs according to their rostrocaudal exit points from the brainstem. Of the 28 anatomy texts evaluated, the great majority use illustrations rather than photographs to depict the brainstem entry and exit points of the CNs. These contemporary atlases showed that nearly all works emulate the 1778 anatomical arrangement of Soemmerring in which the rostrocaudal sequence is abducens (VI)-facial (VII)-vestibulocochlear (VIII) nerves.

The authors evaluated 100 MRs for the anatomic position of the nerves. Among the 100 MR images studied, the exit location of CN VI was caudal to the CN VII/VIII complex in 93%, equal to this complex in 3%, and rostral to this complex in 4%. Furthermore, the exit position of CN VII was caudal to CN VIII on multiple MR images. Contrary to classic teaching and numerous illustrations, at microsurgery, CNs VII and VIII do not exit from a sulcus, but rather from the smooth surface of the lower lateral pons. CN VI, which exits from the anterior pontine surface, DOES arise from the pontomedullary sulcus. The authors conclude that the “two-century tradition of inaccurate anatomical drawings illustrates that even scientists may be susceptible to the comforting allure of traditional thought, with its potential to suppress critical thinking. Perhaps it could be said that the most dogmatic rule in science and medicine is that dogma is alive and well in both fields.

So…. 1,2,3,4,5,8,7,6,9,10,11,12.

5 Figures, 1 Table

Song F, Hou Y, Sun G, et al. In vivo visualization of the facial nerve in patients with acoustic neuroma using diffusion tensor imaging-based fiber tracking. J Neurosurg. 2016;125(October):1-8. doi:10.3171/2015.7.JNS142922.

In this single-center, retrospective review of 16 patients, the authors evaluated the repeatability of applying DTI-FT to reconstructing the FN under existing clinical conditions in patients with acoustic neuroma. They also compared the visualization results of the preoperative FN and the observed FN conditions to validate the accuracy of the technology. MRI data in the DICOM format were uploaded in the 3D Slicer software (; Harvard University). The data format conversion, anatomical images of the tumor, fiber tracking, and 3D visualization of the FN were determined by the software. Each FN was visualized by two separate operators at the same time, both of whom were blind to the patients’ clinical findings. The neural fasciculus courses that simultaneously passed through the 2 ROIs consisting of the IAC and root entry zone (REZ) regions of FN were successfully tracked and reconstructed in 14 patients. The fasciculus of 1 patient was short and passed only 1 ROI of the REZ region of FN, and failed to be tracked and reconstructed. In 14 patients evaluated with DTI-FT comparison validations were carried out for the visualization results, intraoperative actual course, and its positional relationship with the tumor by microscopic observation and direct FN electrophysiological stimulation. FN visualization was consistent with the actual situation of the operation in 13 of 14 patients (92.9%), with one patient having inconsistent results. They conclude that the success rate of visualizing the FN by DTI-FT was 93.3% and the accuracy rate of the visualization results of the FN was 92.9%. DTI-FT, in combination with FN electrophysiology monitoring during operation, provides better protection of FN functions.

4 Figures

Journal Scan – This Month in Other Journals, February 2017
Jeffrey Ross • Mayo Clinic, Phoenix

Dr. Jeffrey S. Ross is a Professor of Radiology at the Mayo Clinic College of Medicine, and practices neuroradiology at the Mayo Clinic in Phoenix, Arizona. His publications include over 100 peer-reviewed articles, nearly 60 non-refereed articles, 33 book chapters, and 10 books. He was an AJNR Senior Editor from 2006-2015, is a member of the editorial board for 3 other journals, and a manuscript reviewer for 10 journals. He became Editor-in-Chief of the AJNR in July 2015. He received the Gold Medal Award from the ASSR in 2013.

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