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Normal perfusion pressure breakthrough phenomenon: experimental models

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Abstract

One of the most life-threatening complications after the obliteration of intracranial arteriovenous malformations is the development of oedema and/or multifocal haemorrhage. Two main theories have been postulated so far in order to explain this situation. On one hand, “normal perfusion pressure breakthrough phenomenon” is based on the loss of cerebral vessel autoregulation due to the chronic vasodilation of perinidal microcirculation. On the other hand, the “occlusive hyperaemia” deals with thrombotic and venous obstruction phenomena that may also generate such manifestations. The aim of this study is to resume the main concepts of the “normal perfusion pressure breakthrough phenomenon” theory as well as the related animal models described up to date, their advantages and disadvantages, and the main conclusions obtained as a result of the experimental research.

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Acknowledgments

The authors thank Cristina Ruiz Quevedo for assistance in the translation of the manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, Fundación Jiménez Díaz (IIS-FJD), Avda Reyes Católicos 2, 28040, Madrid, Spain

    Raquel Gutiérrez-González

  2. Department of Neurosurgery, La Paz University Hospital, P Castellana 261, 28046, Madrid, Spain

    Alvaro Pérez-Zamarron

  3. Department of Neurosurgery, Clínico San Carlos University Hospital, Prof. Martin Lagos, 28040, Madrid, Spain

    Gregorio Rodríguez-Boto

  4. Department of Surgery, Faculty of Medicine, Complutense University of Madrid, 28040, Madrid, Spain

    Gregorio Rodríguez-Boto

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  1. Raquel Gutiérrez-González
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Correspondence to Raquel Gutiérrez-González.

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Comments

K.-P. Sein and I. Erol Sandalcioglu, Hannover, Germany

The treatment of cerebral arteriovenous malformations (AVM) remains challenging, not only in terms of determining the right treatment indication and treatment strategy. Once obliteration of the nidus is achieved, the knowledge and understanding of hemodynamic changes is of utmost importance to guide the patient after treatment through this period in order to prevent haemorrhage. Since the normal perfusion pressure breakthrough theory was introduced in 1978, numerous experimental and animal models have been suggested. Gutierrez-Gonzalez and coworkers nicely summarized the pathophysiological concepts and different animal models and their major results. As the authors also point out the limitations of the listed studies, the need of valuable models for future investigations becomes evident.

Peter Nakaji, Phoenix, USA

The original paper proposing the theory of normal perfusion pressure breakthrough (NPPB) with arteriovenous malformations is now four decades old. Since that time, much debate has been had on the subject, though for many it has become an accepted, if uncommon, phenomenon. More frequently, postoperative haemorrhage has been attributed to incomplete closure of fragile AVM feeding vessels, and edema and brain swelling have been felt to be due to loss of normal venous drainage in the course of AVM resection. In this review by Dr. Raquel Gutierrez-Gonzalez et al., the authors describe and examine the experimental models for studying NPPB.

The questions that a cerebrovascular neurosurgeon has about NPPB revolve around predicting who might have a state of chronic steal-induced vasodilation and thus be at risk, and what to do about it, preferably before haemorrhage and swelling occur. For example, one strategy I routinely employ in my practice at the Barrow Neurological Institute is to induce relative mild hypotension on an empiric basis on my post-resection AVM patients (e.g. target SBP first 24 h 100 mmHg, then 120 mmHg for 24 h, then 140 mmHg for 24 h, followed by ‘normal’ blood pressure for that patient). However, this practice is not actually tailored to the individual patient, about whose regional haemodynamics we know little.

So how can the experimental models clarify things further? Animal models often have anatomy very different from a human and are largely based on fistula creation, which, while similar, is not the same as an AVM. The fistulas made are often at a distance to the brain (e.g. in the neck) and may not have the same combination of hypotension on the brain and hypertension in the venous drainage bed as a real AVM has. Furthermore, all AVMs have been in place a very long time, whereas any changes occurring in response to a fistula are relatively short term. The authors voice similar concerns. Their review of this field leads to the conclusion that despite admirable efforts of researchers to date, better models are needed.

Perhaps the best model is the real patient. In the modern era, an increase in observations obtained from humans with AVMs may be the most productive direction for such investigation. Pre- and postoperative flow imaging using perfusion MRI coupled with intraoperative pre- and post-resection direct brain visualization using laser speckle imaging, for example, might be more illuminating. Even the placement of a flow probe into the brain near the operative bed for postoperative monitoring would be both ethical and reasonable, given the risks patients must tolerate in the periresection period. In short, the authors remind us that there are still many opportunities for meaningful investigation in the NPPB field.

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Gutiérrez-González, R., Pérez-Zamarron, A. & Rodríguez-Boto, G. Normal perfusion pressure breakthrough phenomenon: experimental models. Neurosurg Rev 37, 559–568 (2014). https://doi.org/10.1007/s10143-014-0549-3

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