Integrative Analysis of 334 Patients with Blister-Like Aneurysms

L. Yang, X. Huang, X. Tan
Department of Neurology
The Second Xiangya Hospital of Central South University
Changsha, China

H. Zhou
Department of Neurology
The First Xiangya Hospital of Central South University
Changsha, China

H.X. Bai
Department of Radiology
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania

We read with great interest a recent article by Peschillo et al1 on blister-like aneurysms. The authors performed a meta-analysis of 334 patients with blister-like aneurysms who were treated with either an operation or endovascular therapy. The authors found that endovascular treatment had lower morbidity and mortality and provided a better outcome compared with surgical approaches, especially in patients with low Hunt and Hess (HH) scale and Fisher grades. Only the HH and Fisher grades were clear predictors of outcomes in multivariate analysis, but the method of treatment was not.

We commend the authors for performing a meta-analysis of this type of aneurysm because it is a rare disease with imprecise definition and no existing guidelines on optimal management.2 However, we have significant concerns about the methodologies and results. First, the authors did not specify how they handled the data in their meta-analysis. It seems that the authors performed an integrative analysis of individual patients pooled from each individual study instead of a “meta-analysis.” If this is the case, did the authors exclude a study because it did not specify clinical presentation, method of treatment, or outcome? The exact criteria used for study inclusion were not clear; this problem increases the potential for publication bias. A previous systematic review of 331 patients showed that results from multivariate analysis were influenced by the number of cases in a single study and the journal Impact Factor.3

Second, for studies that did not provide information on HH or Fisher grade, did the authors assign their own scores as they did for the modified Rankin Scale score? From our experience, assignment of these parameters on the basis of limited information reported in published articles can significantly bias the results. In addition, inclusion of both HH and Fisher grades simultaneously in the multivariate analysis may be inappropriate because they can provide similar information (ie, covariates).

Third, the authors did not specify whether all the patients included in the analysis presented with subarachnoid hemorrhage. For example, of the 8 patients with blister-like aneurysms presented by Chalouhi et al,4 1 patient presented with sentinel headache, and in 2 patients, the aneurysm was incidentally discovered. If a patient presents with SAH, the treatment considerations will be completely different from those for a patient whose blister-like aneurysm was discovered incidentally.5 Similarly, the outcomes will be significantly different as well.

Last, publications from earlier years are likely to be on microsurgical management or coils, while more recent studies will focus on new endovascular treatment methods. Consequently, a patient who would be selected for endovascular treatment today on the basis of presentation would have undergone microsurgical clipping in 1997. This trend is clearly shown in Fig 4 of Szmuda et al.3

In summary, the authors presented interesting results based on an integrative analysis of patients with blister-like aneurysms. Even though one acknowledges the inherent limitations of such analysis, the study can still benefit from better definitions of the following: 1) inclusion criteria, 2) handling of missing data (eg, HH and Fisher grades, mRS), and 3) presentation of patients (SAH versus incidental).

Footnote

Li Yang was supported by National Natural Science Foundation, 2014, grant number 81301988 and the Shenghua Yuyin Experts Project of Central South University.

References

  1. Peschillo S, Cannizzaro D, Caporlingua A, et al. A systematic review and meta-analysis of treatment and outcome of blister-like aneurysms. AJNR Am J Neuroradiol 2015 Dec 3. [Epub ahead of print]
  2. Gonzalez AM, Narata AP, Yilmaz H, et al. Blood blister-like aneurysms: single center experience and systematic literature review. Eur J Radiol 2014;83:197–205
  3. Szmuda T, Sloniewski P, Waszak PM, et al. Towards a new treatment paradigm for ruptured blood blister-like aneurysms of the internal carotid artery? A rapid systematic review. J Neurointerv Surg 2015 Mar 19. [Epub ahead of print]
  4. Chalouhi N, Zanaty M, Tjoumakaris S, et al. Treatment of blister-like aneurysms with the Pipeline embolization device. Neurosurgery 2014;74:527–32; discussion 532
  5. van Rooij WJ, de Gast A, Sluzewski M, et al. Coiling of truly incidental intracranial aneurysms. AJNR Am J Neuroradiol 2006;27:293–96

Reply

S. Peschillo
Department of Neurology and Psychiatry, Endovascular
Neurosurgery/Interventional Neuroradiology
“Sapienza,” University of Rome
Rome, Italy

D. Cannizzaro
Department of Neurology and Psychiatry, Neurosurgery
“Sapienza,” University of Rome
Rome, Italy

E. Di Stasio
Institute of Biochemistry and Clinical Biochemistry
Catholic University of Sacred Heart
Rome, Italy

A. Caporlingua, P. Missori
Department of Neurology and Psychiatry, Neurosurgery
“Sapienza,” University of Rome
Rome, Italy

We are grateful for the opportunity to answer questions from Yang et al.

We have analyzed each one of the critiques, and these are our comments to the numbered points below raised by the authors:

1) “It seems that the authors performed an integrative analysis of individual patients pooled from each individual study instead of a ‘meta-analysis.’”

We performed a comprehensive literature search in the PubMed and Scopus data bases on blister-like aneurysms. The aim of the work, as specified at the end of the introductory paragraph, was “to perform a systematic review and meta-analysis of the various types of treatment to compare their efficacy and safety.”

We have tried to do both and as described in the article, all included studies were noncomparative.

2) “If this is the case, did the authors exclude a study because it did not specify clinical presentation, method of treatment, or outcome?”

In the “Materials and Methods” section, we specified the exclusion criteria: “43 articles were excluded either because the patients did not have blister-like aneurysms or because the patients’ presentations or angiographic outcomes were not described.” Therefore, we have included only patients with specific data regarding the clinical onset or with enough detail to obtain such information.

3) “The exact criteria used for study inclusion were not clear; this problem increases the potential for publication bias.”

In the third paragraph of “Materials and Methods,” we specified the following: 1) patient presentation described by using validated scales (Hunt and Hess [HH] and Fisher), 2) treatment technique (endovascular, surgical, combined), 3) long-term neurologic outcome (a good neurologic outcome was defined as a modified Rankin Scale score of 2). When an mRS score was not available, good neurologic outcome was determined from the description of the clinical results (eg, terms such as “no morbidity” or “good recovery”). We think that this is clear enough.

4) “A previous systematic review of 331 patients showed that results from multivariate analysis were influenced by the number of cases in a single study and the journal Impact Factor.”

We partially agree with this comment because some inadequate studies may hamper a good meta-analysis. Furthermore, another bias could be the definition of a blister-like aneurysm. Thus, in the article, we proposed a definition.

Our purpose was to offer a systematic review and meta-analysis of the various types of treatment of blister-like aneurysms on the basis of current literature. As we wrote in our article, further prospective studies are recommended to support our results.

5) “Second, for studies that did not provide information on HH or Fisher grade, did the authors assign their own scores as they did for modified Rankin Scale score? From our experience, assignment of these parameters on the basis of limited information reported in published articles can significantly bias the results.”

We have included studies that provided information on HH and Fisher grades, besides studies that described clinical and radiologic details that have allowed extraction of HH and Fisher grades. Studies that did not provide information (clinical and radiologic onset characteristics, HH or Fisher grades) have been excluded from the analysis.

We totally disagree with Yang et al that this can “significantly bias the results”; if the information is enough to extract the score (ie, a CT scan or a description of clinical status at admission), how this could alter the results?

6) “In addition, inclusion of both HH and Fisher grades simultaneously in the multivariate analysis may be inappropriate because they can provide similar information (ie, covariates).”

This is potentially true. However, multivariate analysis performed including the model, alternatively, HH or Fisher grades (with other variables) yielded similar results, thus confirming that both HH and Fisher grades are independent predictors of the clinical outcome in our study.

“In summary, the authors presented interesting results based on an integrative analysis of patients with blister-like aneurysms. Even though one acknowledges the inherent limitations of such analysis, the study can still benefit from better descriptions of the following: 1) inclusion criteria, 2) handling of missing data (eg, HH and Fisher grades, mRS), and 3) presentation of patients (SAH versus incidental).”

All these points were discussed above.

In conclusion, we hope that we have answered all the questions raised. We thank Yang et al for helping to clarify some important issues.

Probably this article has some limitations, and many times we have written that further prospective studies must be performed to confirm these results: “Larger and homogeneous cohorts of patients will help to elucidate the optimal treatment for patients with subarachnoid hemorrhage due to blister-like aneurysms” in the “Conclusions” paragraph.

Our article was reviewed by 2 independent reviewers and a Senior Editor from theAmerican Journal of Neuroradiology, who are undisputed experts on this topic. The acceptance of the manuscript and publication in such an important journal confirmed the quality of our work.

Blood blister-like aneurysms are one my team’s main fields of interest; we tried to do our best to add new elements to better understand these complex lesions.

Integrative Analysis of 334 Patients with Blister-Like Aneurysms
letters
Letters to the Editor • American Journal of Neuroradiology

Beginning with the February 2010 issue, Letters to the Editor and any applicable replies are now posted on AJNR Blog after their publication in the online journal. Comments on published letters and replies are encouraged.