Skip to main content

Advertisement

SpringerLink
Log in

Normal perfusion pressure breakthrough theory: a reappraisal after 35 years

  • Review
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

The intrinsic ability of the brain to maintain constant cerebral blood flow (CBF) is known as cerebral pressure autoregulation. This ability protects the brain against cerebral ischemia and hyperemia within a certain range of blood pressures. The normal perfusion pressure breakthrough (NPPB) theory described by Spetzler in 1978 was adopted to explain the edema and hemorrhage that sometimes occur after resection of brain arteriovenous malformations (AVMs). The underlying pathophysiology of edema and hemorrhage after AVM resection still remains controversial. Over the last three decades, advances in neuroimaging, CBF, and cerebral perfusion pressure (CPP) measurement have both favored and contradicted the NBBP theory. At the same time, other theories have been proposed, including the occlusive hyperemia theory. We believe that both theories are related and complementary and that they both explain changes in hemodynamics after AVM resection. The purpose of this work is to review the current status of the NBBP theory 35 years after its original description.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Al-Rodhan NR, Sundt TM Jr, Piepgras DG et al (1993) Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. J Neurosurg 78:167–175

    Article  CAS  PubMed  Google Scholar 

  2. Albert P (1982) Personal experience in the treatment of 178 cases of arteriovenous malformations of the brain. Acta Neurochir 61:207–226

    Article  CAS  PubMed  Google Scholar 

  3. Asgari S, Rohrborn HJ, Engelhorn T et al (2003) Intraoperative measurement of cortical oxygen saturation and blood volume adjacent to cerebral arteriovenous malformations using near-infrared spectroscopy. Neurosurgery 52:1298–1304, discussion 1304–1296

    Article  PubMed  Google Scholar 

  4. Barnett GH, Little JR, Ebrahim ZY et al (1987) Cerebral circulation during arteriovenous malformation operation. Neurosurgery 20:836–842

    Article  CAS  PubMed  Google Scholar 

  5. Batjer HH, Devous MD Sr (1992) The use of acetazolamide-enhanced regional cerebral blood flow measurement to predict risk to arteriovenous malformation patients. Neurosurgery 31:213–217, discussion 217–218

    Article  CAS  PubMed  Google Scholar 

  6. Batjer HH, Devous MD Sr, Meyer YJ et al (1988) Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough. Neurosurgery 22:503–509

    Article  CAS  PubMed  Google Scholar 

  7. Batjer HH, Devous MD Sr, Seibert GB et al (1988) Intracranial arteriovenous malformation: relationships between clinical and radiographic factors and ipsilateral steal severity. Neurosurgery 23:322–328

    Article  CAS  PubMed  Google Scholar 

  8. Chyatte D (1997) Normal pressure perfusion breakthrough after resection of arteriovenous malformation. J Stroke Cerebrovasc Dis: Off J National Stroke Assoc 6:130–136

    Article  CAS  Google Scholar 

  9. Day AL, Friedman WA, Sypert GW et al (1982) Successful treatment of the normal perfusion pressure breakthrough syndrome. Neurosurgery 11:625–630

    Article  CAS  PubMed  Google Scholar 

  10. De Salles AA, Manchola I (1994) CO2 reactivity in arteriovenous malformations of the brain: a transcranial Doppler ultrasound study. J Neurosurg 80:624–630

    Article  PubMed  Google Scholar 

  11. Fogarty-Mack P, Pile-Spellman J, Hacein-Bey L et al (1996) The effect of arteriovenous malformations on the distribution of intracerebral arterial pressures. AJNR Am J Neuroradiol 17:1443–1449

    CAS  PubMed  Google Scholar 

  12. Fry DL (1968) Acute vascular endothelial changes associated with increased blood velocity gradients. Circ Res 22:165–197

    Article  CAS  PubMed  Google Scholar 

  13. Gross PM, Heistad DD, Strait MR et al (1979) Cerebral vascular responses to physiological stimulation of sympathetic pathways in cats. Circ Res 44:288–294

    Article  CAS  PubMed  Google Scholar 

  14. Hassler W, Gilsbach J (1984) Intra- and perioperative aspects of the hemodynamics of supratentorial AV-malformations. Acta Neurochir 73:35–44

    Article  CAS  PubMed  Google Scholar 

  15. Hassler W, Steinmetz H (1987) Cerebral hemodynamics in angioma patients: an intraoperative study. J Neurosurg 67:822–831

    Article  CAS  PubMed  Google Scholar 

  16. Kader A, Young WL (1996) The effects of intracranial arteriovenous malformations on cerebral hemodynamics. Neurosurg Clin N Am 7:767–781

    CAS  PubMed  Google Scholar 

  17. Kader A, Young WL, Pile-Spellman J et al (1994) The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations. Neurosurgery 34:801–807, discussion 807–808

    Article  CAS  PubMed  Google Scholar 

  18. Massaro AR, Young WL, Kader A et al (1994) Characterization of arteriovenous malformation feeding vessels by carbon dioxide reactivity. AJNR Am J Neuroradiol 15:55–61

    CAS  PubMed  Google Scholar 

  19. Meyer B, Urbach H, Schaller C et al (2001) Is stagnating flow in former feeding arteries an indication of cerebral hypoperfusion after resection of arteriovenous malformations? J Neurosurg 95:36–43

    Article  CAS  PubMed  Google Scholar 

  20. Miyasaka Y, Yada K, Ohwada T et al (1990) Retrograde thrombosis of feeding arteries after removal of arteriovenous malformations. J Neurosurg 72:540–545

    Article  CAS  PubMed  Google Scholar 

  21. Morgan MK, Sundt TM Jr (1989) The case against staged operative resection of cerebral arteriovenous malformations. Neurosurgery 25:429–435, discussion 435–426

    Article  CAS  PubMed  Google Scholar 

  22. Muizelaar JP, Marmarou A, Ward JD et al (1991) Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 75:731–739

    Article  CAS  PubMed  Google Scholar 

  23. Muraszko K, Wang HH, Pelton G et al (1990) A study of the reactivity of feeding vessels to arteriovenous malformations: correlation with clinical outcome. Neurosurgery 26:190–199, discussion 199–200

    Article  CAS  PubMed  Google Scholar 

  24. Nornes H, Grip A (1980) Hemodynamic aspects of cerebral arteriovenous malformations. J Neurosurg 53:456–464

    Article  CAS  PubMed  Google Scholar 

  25. Osol G, Halpern W (1985) Myogenic properties of cerebral blood vessels from normotensive and hypertensive rats. Am J Physiol 249:H914–H921

    CAS  PubMed  Google Scholar 

  26. Pannier JL, Weyne J, Leusen I (1971) Effects of changes in acid–base composition in the cerebral ventricles on local and general cerebral blood flow. Eur Neurol 6:123–126

    Article  CAS  PubMed  Google Scholar 

  27. Pennings FA, Ince C, Bouma GJ (2006) Continuous real-time visualization of the human cerebral microcirculation during arteriovenous malformation surgery using orthogonal polarization spectral imaging. Neurosurgery 59:167–171, discussion 167–171

    Article  PubMed  Google Scholar 

  28. Petty GW, Massaro AR, Tatemichi TK et al (1990) Transcranial Doppler ultrasonographic changes after treatment for arteriovenous malformations. Stroke; J Cereb Circ 21:260–266

    Article  CAS  Google Scholar 

  29. Rangel-Castilla L, Gasco J, Nauta HJ et al (2008) Cerebral pressure autoregulation in traumatic brain injury. Neurosurg Focus 25:E7

    Article  PubMed  Google Scholar 

  30. Rangel-Castilla L, Lara LR, Gopinath S et al (2010) Cerebral hemodynamic effects of acute hyperoxia and hyperventilation after severe traumatic brain injury. J Neurotrauma 27:1853–1863

    Article  PubMed Central  PubMed  Google Scholar 

  31. Sekhon LH, Morgan MK, Spence I (1997) Normal perfusion pressure breakthrough: the role of capillaries. J Neurosurg 86:519–524

    Article  CAS  PubMed  Google Scholar 

  32. Spetzler RF, Hargraves RW, Mccormick PW et al (1992) Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations. J Neurosurg 76:918–923

    Article  CAS  PubMed  Google Scholar 

  33. Spetzler RF, Wilson CB, Weinstein P et al (1978) Normal perfusion pressure breakthrough theory. Clin Neurosurg 25:651–672

    CAS  PubMed  Google Scholar 

  34. Vinuela F, Nombela L, Roach MR et al (1985) Stenotic and occlusive disease of the venous drainage system of deep brain AVM’s. J Neurosurg 63:180–184

    Article  CAS  PubMed  Google Scholar 

  35. Young WL, Kader A, Ornstein E et al (1996) Cerebral hyperemia after arteriovenous malformation resection is related to “breakthrough” complications but not to feeding artery pressure. The Columbia University Arteriovenous Malformation Study Project. Neurosurgery 38:1085–1093, discussion 1093–1085

    CAS  PubMed  Google Scholar 

  36. Young WL, Kader A, Pile-Spellman J et al (1994) Arteriovenous malformation draining vein physiology and determinants of transnidal pressure gradients. The Columbia University AVM Study Project. Neurosurgery 35:389–395, discussion 395–386

    Article  CAS  PubMed  Google Scholar 

  37. Young WL, Kader A, Prohovnik I et al (1993) Pressure autoregulation is intact after arteriovenous malformation resection. Neurosurgery 32:491–496, discussion 496–497

    Article  CAS  PubMed  Google Scholar 

  38. Young WL, Pile-Spellman J, Prohovnik I et al (1994) Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Columbia University AVM Study Project. Neurosurgery 34:601–610, discussion 610–611

    Article  CAS  PubMed  Google Scholar 

  39. Young WL, Prohovnik I, Ornstein E et al (1990) The effect of arteriovenous malformation resection on cerebrovascular reactivity to carbon dioxide. Neurosurgery 27:257–266, discussion 266–257

    Article  CAS  PubMed  Google Scholar 

  40. Young WL, Solomon RA, Prohovnik I et al (1988) 133Xe blood flow monitoring during arteriovenous malformation resection: a case of intraoperative hyperperfusion with subsequent brain swelling. Neurosurgery 22:765–769

    Article  CAS  PubMed  Google Scholar 

  41. Zacharia BE, Bruce S, Appelboom G et al (2012) Occlusive hyperemia versus normal perfusion pressure breakthrough after treatment of cranial arteriovenous malformations. Neurosurg Clin N Am 23:147–151

    Article  PubMed  Google Scholar 

  42. Zaidi HA, Abla AA, Nakaji P et al (2014) Indocyanine green angiography in the surgical management of cerebral arteriovenous malformations: lessons learned in 130 consecutive cases. Neurosurgery

Download references

Author information

Authors and Affiliations

  1. Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    Leonardo Rangel-Castilla, Robert F. Spetzler & Peter Nakaji

  2. Neuroscience Publications, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Road, Phoenix, AZ, 85013, USA

    Robert F. Spetzler

Authors
  1. Leonardo Rangel-Castilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert F. Spetzler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Nakaji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert F. Spetzler.

Additional information

Comments

Gustavo Pradilla, Daniel L. Barrow, Atlanta, USA

In this review, Rangel-Castilla and colleagues provide an overview of the basic principles supporting normal perfusion pressure breakthrough (NPPB) and occlusive hyperemia (OH) proposed to explain postoperative edema and hemorrhage following resection of arteriovenous malformations (AVMs). Supportive and disputing studies for both theories are discussed and an updated perspective that consolidates the complementary roles of both theories is presented.

Since the NPPB hypothesis was first introduced by Spetzler in 1978, multiple studies have been conducted to validate or dispute its principles (3). While studies supportive of NPPB involved preoperative and postoperative assessments of autoregulation using physiologic or pharmacologic challenges such as hyperventilation and acetazolamide, contradicting studies showed restored reactivity to hyperventilation after AVM resection and preserved autoregulation.

Similarly, Al-Rhodan and colleagues first postulated the OH theory in 1993, and since then, the concept of arterial stagnation has been supported by several studies (1). Venous outflow obstruction, the second principle of OH, has also been extensively documented by others and has provided further tools for potential identification of patients at risk. Larger observational series, however, still fail to explain the absence of OH in patients presenting with both arterial stagnation and venous outflow obstruction.

Clearly, these theories are not mutually exclusive, and the contributing influences of abnormal autoregulation, arterial stagnation, and altered venous outflow can be incorporated in patients exhibiting postoperative complications. The extent to which each factor contributes to increase the risk of postoperative complications remains uncertain, and additional physiological and biological studies that correlate radiographic findings, anatomical variations, adaptive responses, and postoperative outcomes are clearly needed.

Using a combined approach, preoperative identification of these patients can be pursued, and individualized postoperative plans can be tailored to prevent NPPB/OH. Staged preoperative embolization of large lesions and strict postoperative targeted normotension have emerged as accepted strategies to prevent NPPB/OH onset, although its efficacy remains to be demonstrated in a systematic fashion (2). The value of postoperative hyperventilation, hyperoxia, nitric oxide donors, and other experimental therapies after NPPB/OH onset is anecdotal at best.

Ongoing controversies on the benefits of treatment of unruptured AVMs will likely impact our ability to treat these patients in a proactive fashion. Differences in incidence of NPPB/OH for patients with unruptured versus ruptured AVMs are unknown, but the hemodynamic stress resulting in ruptures is likely to contribute to more severe forms of NPPB/OH, which develop in patients with less theoretical reserve to tolerate these events.

We commend the authors on an updated and inclusive perspective on this challenging topic and hope that their review stimulates new research in this fascinating phenomenon.

References

1. al-Rodhan NR, Sundt TM, Jr., Piepgras DG, Nichols DA, Rufenacht D, Stevens LN: Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. Journal of neurosurgery 78:167–175, 1993.

2. Saatci I, Geyik S, Yavuz K, Cekirge HS: Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. Journal of neurosurgery 115:78–88, 2011.

3. Spetzler RF, Wilson CB, Weinstein P, Mehdorn M, Townsend J, Telles D: Normal perfusion pressure breakthrough theory. Clinical neurosurgery 25:651–672, 1978.

Ashish Sonig, Elad I. Levy, New York, USA

The theory of normal perfusion pressure breakthrough (NPPB) was originally proposed by Spetzler et al. [1] in 1978 to describe the phenomenon of the malignant edema or hemorrhage that sometimes occurs in the ipsilateral hemisphere of a high-flow arteriovenous malformation (AVM) following resection. In the original description of NPPB, those authors suggested that patients who might suffer this complication after AVM surgery could be recognized by the presence of preoperative ischemic symptoms and/or radiographic evidence of a large AVM with poor filling of the normal hemisphere branches. To tackle the complications, they proposed two management strategies: (1) a gradual increase in perfusion to the ischemic hemisphere by staged ligation or (2) embolization of the feeding arteries and lowering of the blood pressure after surgical AVM resection.

The current understanding of AVM pathophysiology has changed, and an occlusive hyperemia theory was proposed by al-Rodhan et al. [2] in 1993. This theory was based on venous occlusion and stasis of flow in the arteries associated with a previously resected AVM. Together, these characteristics were found to be responsible for ischemia and hemorrhage following AVM treatment.

With modern technology, endovascular embolization of AVM is safer and controlled, compared with the early embolization experience. The authors of this NPPB theory reappraisal article have rightly recommended staged embolization for high-grade AVMs. This approach allows a gradual increase in perfusion to normal brain. In fact, they no longer recommend hypotension perioperatively or postoperatively. This marks a paradigm shift in AVM management, as strict blood pressure control was the standard. Management strategies continue to evolve with time, based on better understanding of disease processes and evidence arising from trials.

It is interesting to address the issue of “disruptive innovations” in neurosurgery. Endovascular coiling of aneurysms is gradually replacing the standard of aneurysm clipping. Contemporary literature is suggestive of complete cure of low-grade AVMs (Spetzler-Martin [SM] grade [3] of III or less) with embolization alone [4]. What is important is to know if there is a role for partial embolization of brain AVMs in decreasing the risk of hemorrhage or whether this approach increases the chances of hemorrhage. This question has become more important because most SM grade >III AVMs are treated with staged therapy with embolization and microneurosurgery [5, 6]. More trials and studies are needed to understand the phenomenon of postoperative ischemia and hemorrhage following AVM treatment and for the development of an appropriate management protocol.

References

1. Spetzler RF, Wilson CB, Weinstein P, Mehdorn M, Townsend J, Telles D: Normal perfusion pressure breakthrough theory. Clin Neurosurg 1978; 25:651–72.

2. al-Rodhan NR, Sundt TM, Jr., Piepgras DG, Nichols DA, Rufenacht D, Stevens LN: Occlusive hyperemia: a theory for the hemodynamic complications following resection of intracerebral arteriovenous malformations. J Neurosurg 1993; 78:167–75.

3. Spetzler RF, Martin NA: A proposed grading system for arteriovenous malformations. J Neurosurg 1986; 65:476–83.

4. Yu SC, Chan MS, Lam JM, Tam PH, Poon WS: Complete obliteration of intracranial arteriovenous malformation with endovascular cyanoacrylate embolization: initial success and rate of permanent cure. AJNR Am J Neuroradiol 2004; 25:1139–43.

5. Hartmann A, Mast H, Mohr JP, Pile-Spellman J, Connolly ES, Sciacca RR, Khaw A, Stapf C: Determinants of staged endovascular and surgical treatment outcome of brain arteriovenous malformations. Stroke 2005; 36:2431–5.

6. Natarajan SK, Ghodke B, Britz GW, Born DE, Sekhar LN: Multimodality treatment of brain arteriovenous malformations with microsurgery after embolization with onyx: single-center experience and technical nuances. Neurosurgery 2008; 62:1213–25; discussion 1225–6.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rangel-Castilla, L., Spetzler, R.F. & Nakaji, P. Normal perfusion pressure breakthrough theory: a reappraisal after 35 years. Neurosurg Rev 38, 399–405 (2015). https://doi.org/10.1007/s10143-014-0600-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-014-0600-4

Keywords

Search

Navigation