Journal Scan – This Month in Other Journals, March 2017

Daou B, Chalouhi N, Starke RM, et al. Clipping of previously coiled cerebral aneurysms: efficacy, safety, and predictors in a cohort of 111 patients. J Neurosurg. 2016;125(December):1-7. doi:10.3171/2015.10.JNS151544.

This retrospective cohort study evaluated the efficacy and safety of microsurgical clipping in the treatment of recurrent, previously coiled cerebral aneurysms and to identify risk factors that can affect the outcomes of this procedure. The mean patient age was 50.5 years, the mean aneurysm size was 7 mm, and 97.3% of aneurysms were in the anterior circulation. Complete aneurysm occlusion, as assessed by intraoperative angiography, was achieved in 97.3% of aneurysms (108 of 111 patients). Among patients, 1.8% had a recurrence after clipping. Retreatment was required in 4.5% of patients after clipping. Major complications were observed in 8% of patients and mortality in 2.7%. Ninety percent of patients had a good clinical outcome. Aneurysm size and location in the posterior circulation were significantly associated with higher complications. All 3 patients who had coil extraction experienced a postoperative stroke.

They conclude that surgical clipping is an appropriate treatment strategy for the management of recurrent cerebral aneurysms after endovascular coiling. Direct clipping of the aneurysm neck is feasible in most cases of recurrent, previously coiled cerebral aneurysms. Coil extraction should not regularly be attempted because it is associated with high morbidity. In other words, when direct clipping is not possible because of coil loops extending into the aneurysm neck, or with transmural calcification and scarring, other techniques such as wrapping should be considered.

Serrone JC, Tackla RD, Gozal YM, et al. Aneurysm growth and de novo aneurysms during aneurysm surveillance. J Neurosurg. 2016;125(6):1374-1382. doi:10.3171/2015.12.JNS151552.

Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 unruptured intracranial aneurysms. The incidence of unruptured intracranial aneurysm growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for unruptured intracranial aneurysm growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed. During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth. Four de novo aneurysms were formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth ( ≥ 5 mm = 8.7%).

They conclude that aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted.

3 Tables, 3 Figures (Kaplan-Meier curves)

Goodfellow JA, Willison HJ. Guillain-Barré syndrome: a century of progress. Nat Rev Neurol. 2016;12(12):723-731. doi:10.1038/nrneurol.2016.172.

Excellent review of the history and pathophysiology of Guillain–Barré syndrome. In 1916, Guillain, Barré and Strohl (three WWI physicians) reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts —novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years later, substantial progress has been made with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has shown that primary axonal injury can be the underlying disease.

The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes.

More specifically, the typical form of GBS shows demyelination, but patients may also exhibit extensive Wallerian-like degeneration of sensory and/or motor axons. This condition is classified as a type of GBS and subdivided according to the axons affected; the terms acute motor and sensory axonal neuropathy (AMSAN) and acute motor axonal neuropathy (AMAN). The pathology found in AMSAN and AMAN is macrophage invasion of the periaxonal space at the paranodal and nodal regions, with immunoglobulin and complement deposition. This is in direct contrast to the macrophage-mediated myelin stripping and the antibody and complement deposition in Schwann cells in the demyelinating form of GBS. This demyelinating form is known as acute inflammatory demyelinating polyneuropathy (AIDP).

I have always found the various acronyms associated with GBS very confusing. Hopefully, this makes it slightly clearer.

Treurniet KM, Yoo AJ, Berkhemer OA, et al. Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke. Stroke. 2016;47(12):2972-2978. doi:10.1161/STROKEAHA.116.014565.

Thrombus location and the length of the occlusion are known to be associated with recanalization rates in patients treated with intravenous treatment (IVT). Both parameters are included in the clot burden score (CBS) in which a lower score reflects more extensive thrombus. Patients with a lower CBS have lower odds of reperfusion and larger final infarct volumes at follow-up in patients treated with IVT.

The aim of this exploratory post hoc analysis was to assess the relation of clot burden score with neurological improvement and endovascular treatment effect. For 499 of 500 patients in the MR CLEAN study, the clot burden score was determined. Two experienced observers from the core imaging committee assigned the appropriate clot burden score per the methods of Puetz et al. (Int J Stroke. 2008;3:230–236. doi: 10.1111/j.17474949.2008.00221.x). A score of 10 on the CBS indicates that no occlusion is present. Two points are deducted for lack of contrast opacification in the supraclinoid ICA and both proximal and distal M1 segments. One point is deducted for lack of opacification in an M2 branch, the A1 segment, or the infraclinoid ICA. For instance, an occlusion of the M1 and both proximal M2 branches would be scored 10 – 2(prox M1) -2 (distal M1) -1(M2 branch) -1 (M2 branch) = CBS 4.

Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale. They conclude that a higher CBS is associated with improved outcome and may be used as a prognostic marker. The found no evidence that CBS modifies the effect of intra-arterial treatment.

2 Tables, 3 Figures

Lot of clot = bad. Minimal clot = better.

Why do people make scales where the lower number is a worse score? Shouldn’t a big number be bad?

Parikh NS, Cool J, Karas MG, Boehme AK, Kamel H. Stroke Risk and Mortality in Patients With Ventricular Assist Devices. Stroke. 2016;47(11):2702-2706. doi:10.1161/STROKEAHA.116.014049.

Ventricular Assist Devices are associated with several thrombotic and hemorrhagic complications, such as pump thrombosis, systemic bleeding, thromboembolic stroke, and intracranial hemorrhage. It is customary to maintain Ventricular Assist Devices patients on therapeutic anticoagulation with warfarin and an antiplatelet agent, typically aspirin.

Using administrative claims data from acute care hospitals in California, Florida, and New York from 2005 to 2013, the authors identified patients who underwent VAD placement, defined by the ICD9 code 37.66. Ischemic and hemorrhagic strokes were identified by previously validated coding algorithms. They used survival statistics to determine the incidence rates and Cox proportional hazard analyses to examine the associations. Among 1813 patients, they identified 201 ischemic strokes and 116 hemorrhagic strokes during 3.4 years of follow-up after implantation of a VAD. The incidence of stroke was 8.7% per year. The annual incidence of ischemic stroke (5.5%) was nearly double that of hemorrhagic stroke (3.1%). Stroke was strongly associated with subsequent in-hospital mortality. Female sex was independently associated with stroke. This association was not present for ischemic stroke but was particularly pronounced for hemorrhagic stroke. In the overall sample, the cumulative hemorrhagic stroke rate in women (14%) was substantially greater than in men (8.8%). In summary, in a large, population-based sample of patients, ≈1 in every 10 patients experienced a stroke each year after VAD implantation. This is comparable to the contemporary incidence of gastrointestinal hemorrhage of ≈10% per year and of pump thrombosis of 9% at 12 months.

1 Table, 3 Figures (graphs)

Carey RM. Quantifying Scientific Merit. Circ Res. 2016;119(12):1273-1275. doi:10.1161/CIRCRESAHA.116.309883.

This is an opinion piece on that dreaded metric, the Impact Factor (IF). The IF, a citation based tool, was developed in 1955 by Eugene Garfield and has been released annually since 1975 for those journals indexed in Journal Citation Reports. IF is defined as the mean number of citations received per article published in a specific journal during the year of interest (the numerator) divided by the total number of citable articles published in the journal during the previous 2 years (the denominator). Citable articles include original research papers and reviews but also include clinical practice guidelines, scientific statements, advisories, position papers. Also, there is a gray zone that includes perspectives, commentaries, essays, highlights, and opinions.

Many criticisms of the IF have been brought forward, including:

  1. citation mingling—citations to original research articles are commingled with citations to guidelines, statements, advisories, and other nonoriginal material, often just to inflate the journal’s IF. These pieces often have nothing to do with the competence, expertise, vision, or efficiency of the editorial team or the viewpoint or philosophy of the journal but are coveted by journals only to raise their IFs.
  2. Self-citation—IF can be influenced by author citation of his or her own work to promote self-recognition in science.
  3. Restricted evaluation period—IF is based on a relatively narrow 2-year time frame, which is too short to assess long-term scientific impact.
  4. Subject dependency—a less important article on a common disease is more likely to be cited than a consequential article on a rare disease.
  5. Publication emplacement influence—articles in journals with high IFs are more likely to be cited than similar papers in journals with lower IFs.
  6. Indiscriminant parity among authors—all coauthors of a multiauthor paper are cited identically, despite widely varying contributions to the work.
  7. Disproportionate significance—use of mean, rather than median, citation counts conveys disproportionately high importance for a few highly cited articles.
  8. Skewed citation distributions—different disciplines and subdisciplines have different citation patterns.

None the less, most research scientists seek to publish their findings in journals with the highest possible IF, despite widespread condemnation of its use in predicting the long-term importance of a new discovery. IF continues to be inappropriately used in publication, employment, compensation, grant funding, and promotion and tenure decisions. Potential solutions brought forward in this article include 1) calculation of IF based on original scientific contributions only; (2) use the 5-year IF; and (3) eliminate self-citation. For journals reporting clinical trials and population research, an index of readership, such as downloads, would better reflect true influence. For journals that report both basic and clinical research, a hybrid measure would assess both research quality and influence. He concludes with the exhortation that the time has come for the scientific publishing community and its leaders to thoughtfully choose the right set of metrics or promulgate a hybrid metric or series of metrics that can most accurately reflect the scope of readership and the long-term significance of its contributions to science.

Reon BJ, Anaya J, Zhang Y, et al. Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis. PLOS Med. 2016;13(12):e1002192. doi:10.1371/journal.pmed.1002192.

Long non-coding RNAs (lncRNA) are defined as non-protein coding transcripts longer than 200 nucleotides. This rather arbitrary limit distinguishes lncRNAs from small regulatory RNAs such as microRNAs. lncRNAs play a critical role in various biological pathways including the immune system, muscle differentiation, neural lineage commitment, lineage specification, and synaptogenesis. In addition to their role in normal physiological processes, lncRNAs are also important regulators of disease processes. In cancer, lncRNAs can act as either tumor suppressors or oncogenes, and have been shown to regulate tumor growth and metastasis in breast, prostate, and liver cancer. The role of lncRNAs in gliomas has not been well characterized.

This study was undertaken to determine to what extent lncRNAs are dysregulated in glial tumors, whether lncRNA expression can be used to assess patient prognosis, and to determine which of the thousands of newly discovered lncRNAs should be prioritized for studies. The authors analyzed over 700 publicly available glioma, glioblastoma, and normal brain RNA sequencing datasets and identified hundreds of lncRNAs with altered expression in gliomas or glioblastomas relative to normal brain tissue. Using lncRNA expression and Cox regression modeling, they developed a survival algorithm including 64 lncRNAs that could separate glioma patients into two distinct prognostic groups.

This is a complex paper, but gives a hint at the direction this whole field is going…just getting more complex, beyond the old IDH1 mutation that we are all familiar with.

6 Figures, 1 Table

Bowen LN, Smith B, Reich D, Quezado M, Nath A. HIV-associated opportunistic CNS infections: pathophysiology, diagnosis, and treatment. Nat Rev Neurol. 2016;12(11):662-674. doi:10.1038/nrneurol.2016.149.

In this review, the authors discuss several of the most common CNS opportunistic infections, with an emphasis on clinical pearls, pathology, MRI findings, and management. They review common clinical presentations of IRIS in opportunistic infections, discuss paradoxical and unmasking IRIS, summarize the use of MRI as a diagnostic tool in HIV-IRIS.

Toxoplasmosis can present as either abscess, diffuse encephalitis (rare) or chorioretinitis. Cerebral toxoplasmosis was rare until the 1980s when the incidence markedly increased in concert with the AIDS pandemic. The first cases of toxoplasmosis complicating an HIV infection were described in 1983. Today, T. gondii remains the most prevalent HIV-associated opportunistic CNS infection, with an estimated seroprevalence of 13.2% in the general populace of the US, and 75% in endemic areas.

Cerebral abscesses are the most common manifestation of toxoplasmosis in patients with HIV infection. In patients with HIV, toxoplasma tends to localize in the basal ganglia to a greater extent than in any other area besides the cortex; thus, toxoplasmosis results in movement disorders more often than does any other HIV-associated opportunistic infection. Diffuse encephalitis caused by toxoplasmosis is a very rare condition and is only seen in patients with AIDS or, rarely, in other immunosuppressed states. Pathological evaluation shows widespread microglial nodules containing bradyzoites and tachyzoites, but no necrosis that is typical of cerebral abscesses. Toxoplasmosis chorioretinitis is rare even in immunocompromised patients. T. gondii has a predilection for the eye, as demonstrated by the fact that this infection is the most common cause of infectious posterior uveitis. In patients with AIDS, toxoplasmosis chorioretinitis can manifest as retinal lesions that are predominantly unilateral and necrotic.

Also covered are PML, TB, Cryptococcus, and CMV.

With HIV infection, effective antiretroviral therapy can normalize CD4+ T cell counts and thereby lead to immune reconstitution, which can result in a dysregulated inflammatory immune response against the infecting pathogen and the host and the subsequent paradoxical worsening of symptoms (paradoxical IRIS). Immune reconstitution can also result in a sudden presentation of the previously asymptomatic and therefore unrecognized opportunistic infection (unmasking IRIS). These distinctions have real clinical impact. For instance, patients with HIV who develop PML-IRIS have a higher likelihood of surviving the PML than do HIV-positive patients who do not develop IRIS. Moreover, patients who were diagnosed with PML-IRIS at the onset of ART, referred to as having an unmasking IRIS, had longer survival, lower mortality, and lower lesion loads seen on brain MRI than did patients with paradoxical IRIS.

5 Figures

Journal Scan – This Month in Other Journals, March 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.