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

1. Crowley RW, Ducruet AF, Kalani MYS, Kim LJ, Albuquerque FC, McDougall CG. Neurological morbidity and mortality associated with the endovascular treatment of cerebral arteriovenous malformations before and during the Onyx era. J Neurosurg. 2015;122(6):1492–1497. doi:10.3171/2015.2.JNS131368.

Is the use of Onyx associated with increased complications relative to N-butyl cyanoacrylate (NBCA)? The authors retrospectively reviewed patients with cerebral AVMs undergoing embolization at the Barrow Neurological Institute from 1995-2012. Endovascular treatment of 342 cerebral AVMs was performed over 446 treatment sessions. Onyx was used in 105 AVMs, and NBCA in 229 AVMs. AVMs treated with Onyx had a higher mean number of arterial pedicles embolized than did NBCA cases. Unexpected immediate postprocedural permanent neurological deficits were present in 9.6%. Patients who experienced complications had a higher mean number of embolization sessions than those without complications. Spetzler-Martin grade was not associated with differences in outcome, and the use of Onyx was not associated with a difference in morbidity relative to NBCA.

The authors believe that they were are able to achieve a greater degree of embolization with Onyx without increasing morbidity, but NBCA still has a role, particularly with high-flow fistulas.

2. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015. doi:10.1056/NEJMoa1407279.

They defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter (encodes telomerase), mutations in IDH (distinctive tumor metabolism), and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). The groups were triple-positive, TERT & IDH mutations, IDH mutation only, triple-negative and TERT mutation only. They scored tumors as negative or positive for each of these markers in 1087 gliomas, and 11,590 controls. Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants. Patients who had gliomas with only TERT mutations had poorer overall survival than did patients who had gliomas that were triple-negative, gliomas with TERT and IDH mutations, gliomas with only IDH mutations, or triple-positive gliomas, and are primarily grade IV gliomas. Triple-positive gliomas are most strongly associated with the oligodendroglial histologic type and better survival. Among adults with gliomas, those with tumors that have only IDH mutations have the earliest mean age at onset (37 years) and an intermediate prognosis. Patients who had gliomas with only TERT mutations were significantly older (59).

The authors found consistent associations between the molecular groups and 1) age at diagnosis, 2) survival, 3) patterns of acquired alterations, and 4) germline variants across the different data sets used in the study. Individualized genomics truly has arrived.

3. McTaggart R a, Ansari S a, Goyal M, et al. Initial hospital management of patients with emergent large vessel occlusion (ELVO): report of the standards and guidelines committee of the Society of NeuroInterventional Surgery. J Neurointerv Surg. 2015. doi:10.1136/neurintsurg-2015-011984.

Worth reading in its entirety, but the highpoints include: In addition to non-contrast CT (NCCT) brain scan, CT angiography (CTA) should be performed in all patients who meet an institutional threshold for clinical stroke severity. Activation of the neurointerventional team should occur as soon as possible. CT perfusion or diffusion-perfusion mismatch may provide additional value, but cannot delay endovascular treatment. Routine use of general anesthesia should be avoided.

Check out table 1, which shoots for an idea time interval of Door to NCCT interpretation of <15 minutes, and Door to CTA interpretation of <20 minutes.

The following two articles (#4,5) are opposing perspectives on the role of amyloid in Alzheimer’s disease (AD):

4. Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18(6):794–799. doi:10.1038/nn.4017.

   5 comments on PubPeer

Many other causes could be part of this disease. AD can be viewed as a tauopathy. AD may represent a failure of autophagy and/or lysosomal function. Loss of Ca++ homeostasis, due perhaps to excitotoxic activity, may lie at the heart of AD. A failure of neuronal cell cycle control, or perhaps it is all due to neuroinflammation. Amyloid is a frequent contributor to the AD disease process, but the evidence suggests that it is neither necessary nor sufficient (my bold addition).

100 references, 1 Table and 1 Figure.

5. Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and “wingmen.” Nat Neurosci. 2015;18(6):800–806. doi:10.1038/nn.4018.

It has become clear that the idea that amyloid causes AD via a simple, linear model of toxicity is very likely incorrect. Amyloid is an initiator of a complex network of pathologic changes in the brain, many of them tau-dependent, that culminates years later in neurodegeneration. Amyloid is necessary, but not sufficient to cause AD (my bold addition).

134 references, with 1 Figure.

6. The Cancer Genome Atlas Research Network. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 2015:150610140038004. doi:10.1056/NEJMoa1402121.

They performed genome wide analyses of 293 lower-grade gliomas from adults, and correlated with outcome. Three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. WHO classifications have recognized lower-grade gliomas with mixed histologic features (oligoastrocytoma). These results indicate that lower-grade gliomas with an IDH mutation have either 1p/19q codeletion or a TP53 mutation, with few gaps or overlaps, reflecting two distinct molecular mechanisms of oncogenesis, and they do not provide evidence for a bio- logic or genetic signature specific to oligoastrocytoma. Tumors with wild-type IDH were molecularly and clinically distinct from subtypes with mutated IDH, with most showing a striking resemblance to primary glioblastoma.

Genomic analysis can predict behavior of low-grade gliomas, while histology cannot.

7. Ellingson BM, Salamon N, Woodworth DC, Holly LT. Correlation between degree of subvoxel spinal cord compression measured with super-resolution tract density imaging and neurological impairment in cervical spondylotic myelopathy. J Neurosurg Spine. 2015;22(1):631–638. doi:10.3171/2014.10.SPINE14222.

Structural MRI and DTI images were collected for 27 patients with cervical spondylosis with (n = 21) and without (n = 6) functional impairment as defined by the modified Japanese Orthopaedic Association Scale (mJOA). DTI was performed axially through the site of compression in a total of 20 directions with 10 averages. Probabilistic tractography was performed at 0.5-mm isotropic spatial resolution. There was a strong negative correlation between maximum tract density and mJOA score. A ratio of maximum fiber tract density at the site of compression to fiber tract density at C-2 greater than 1.45 had 82% sensitivity and 70% specificity for identifying patients with moderate to severe impairment. They conclude that DTI can be used as a surrogate for determining spinal cord integrity in patients with cervical spondylosis.

As the authors note, one major limitation is that the study does not provide guidance as to how patients with increased tract density respond following surgical intervention.

8. Sikkema T, Uyttenboogaart M, van Dijk JMC, et al. Clinical Features and Prognosis of Intracranial Artery Dissection. Neurosurgery. 2015;76(6):663–670. doi:10.1227/NEU.0000000000000696.

This single center cohort study of 60 patients evaluated the clinical features and prognosis of patients with intracranial arterial dissection (IAD), with special emphasis on the location (anterior vs posterior circulation) and clinical presentation. In 18 patients, the IAD was involving the anterior circulation. 35.3% of patients with intracranial arterial dissection in the anterior circulation had unfavorable functional outcome vs 39.0% in patients with intracranial arterial dissection in the posterior circulation. Low Glasgow Coma Scale score on admission and older age were independent predictors of unfavorable functional outcome. There were no significant differences between IAD in the anterior and posterior circulation.

As noted by Dr. Ogilvy in the comments section for this article, the current management of these lesions is now quite different based on the availability of flow-diverting devices. Prior to the advent of flow diversion, dissecting lesions had to be treated with parent vessel occlusion with or without extracranial-intracranial or intracranial-intracranial artery bypass. Given these advances in endovascular techniques, clinical outcomes may well improve.