Available online 28 September 2022

AbstractBackground

The purpose of this review is to present the current literature and to highlight the most recent findings in brain arteriovenous malformations (bAVM)-related epilepsy research.

Methods

We searched Medline, PubMed, Biblioinserm, Cochrane Central to study the latest research reports about the different factors that could be responsible for the genesis of bAVM-related epilepsy. We analyzed if epileptogenesis has any characteristics traits and its relation with the vascular malformation. The results of different treatments on epilepsy were considered. Typical errors that may lead towards incorrect or worse management of the seizures for these patients were also examined.

Results

The development of bAVM results from multifactorial etiologies and bAVM-related epileptogenesis is likely specific for this pathology. Different types of evidence demonstrate a bidirectional relationship between bAVM and epilepsy. Currently, there is not enough published data to determine what may be the right management for these patients.

Conclusions

A better understanding of epileptogenesis in conjunction with knowledge of the complex alterations of structures and functions following bAVM-related seizures is necessary. Identification of biomarkers that can identify subgroups most likely to benefit from a specific intervention are needed to help guide clinical management. A new concept for the treatment of epilepsy related to an unruptured bAVM that cannot be treated invasively is proposed as well as new therapeutic perspectives. The next necessary step will be to propose additional algorithms to improve the development of future trials.

Introduction

Brain arteriovenous malformations (bAVMs) are anomalies of the intracranial vasculature, with an irregular tendency to rupture and as of yet incompletely deciphered pathophysiology. bAVMs are generally considered a congenital disorder, composed of abnormally developed dilated arteries and veins and are characterized microscopically by the absence of a capillary network [1]. However, an appreciable fraction of sporadic bAVM (sbAVM) may have a post-natal genesis [2]. A large variety of genetic, molecular and biological factors are involved in the process of sbAVM formation [3]. In clinical practice, is very important to understand the mechanisms and factors involved in vascular integrity or rupture [4].

We performed a search of the contemporary literature to review current information on bAVMs and how new knowledge will impact their potential future management. A comprehensive review of English-language literature was performed on PubMed, Medline, Biblioinserm, and Cochrane Central, using the key words: “brain”; “arteriovenous”; “malformations”; “epilepsy”; “seizures”; “genetics”; “molecular,” “exploration”; “treatment”; “management,” “embolization”; “radiosurgery”; “microsurgery”. Additional articles were located by cross-referencing articles encountered initially through PubMed searches. Inclusion criteria comprised literature reviews; meta-analyses; clinical trials; case reports; case series; genetics and molecular studies discussing clinical presentation; diagnostic tests; management of patients with cerebral bAVMs. It is commonly known that epileptic seizures are often associated with sbAVM and sbAVMs themselves may be the cause of epilepsy. No so much importance has been accorded to bAVM-related epilepsy; but this subject merits greater consideration.

Section snippetsEpilepsy and bAVM reciprocal duality

bAVMs are common causes of intracerebral hemorrhage (ICH). However, even bAVMs without symptomatic ICH can induce epileptic seizures. According to many authors, seizures represent the second most common manifestation of cerebral bAVMs. Considering unruptured and symptomatic bAVMs, epilepsy is the most frequent mode of presentation with an incidence of around 30% (17%–43%) [5]. Various types of seizures and epilepsy are associated with 20–45% of bAVMs [6]. Eight percent of patients with

New advances in the exploration of sporadic brain arteriovenous malformations

A subset of bAVMs has a higher propensity for causing seizures. Unfortunately, a thorough epileptological analysis is not usually performed in this bAVM-related epilepsy. Routine electroencephalography (EEG) appears to be underused and there is limited data available to assess the impact of video-EEG or electrocorticography (ECoG) on seizure-free outcomes for these patients [72]. Modern imaging techniques are applied in the work-up of DRE patients and evaluate various aspects of vascular and

Efficacy of medical and interventional therapy for epilepsy

Correctly defining the mode of presentation of bAVM is a critically important step because it carries prognostic and therapeutic implications for the patient, mainly because of the 2-to-3-fold higher mortality compared to non-epileptic patients [89], [90]. According to the International League Against Epilepsy (ILAE) criteria, any patient with a bAVM presenting a first attack must be considered epileptic [91]. Observational studies and case series suggest that patients with bAVM-related

Conclusions

In this review, we focused on recent discoveries in bAVM. Uncovering bAVM pathogenesis is essential for the development of specific therapies to minimize the need for invasive procedures. Newer studies are beginning to identify SNPs associated with bAVM formation, which are located in genes responsible for angiogenesis. Considering that bAVMs are likely multifactorial in origin, SNPs affecting genes in inflammatory or angiogenic pathways may act as a “second hit” when present in the setting of

Disclosure of interest

The author declares that she has no competing interest.

References (144)R. van Lanen et al.Ultra-high field magnetic resonance imaging in human epilepsy: a systematic review

Neuroimage

(2021)

J. Castañeda-Cabral et al.Increased protein expression of VEGF-A, VEGF-B, VEGF-C and their receptors in the temporal neocortex of pharmacoresistant temporal lobe epilepsy patients

J Neuroimmunol

(2019)

S.F. Shakur et al.Effects of nidus microarchitecture on cerebral arteriovenous malformation hemodynamics

J Clin Neurosci

(2016)

J. SchrammChapter 4. Seizures associated with cerebral arteriovenous malformationsR.A. Solomon et al.Arteriovenous malformations of the brain

N Engl J Med

(2017)

A. Dalton et al.De novo intracerebral arteriovenous malformations and a review of the theories of their formation

Br J Neurosurg

(2018)

L.B. Do Prado et al.Recent advances in basic research for brain arteriovenous malformation

Int J Mol Sci

(2019)

C. Stapf et al.Arteriovenous malformations of the brain

N Engl J Med

(2017)

B. Rohn et al.Relief of epilepsy and headache and quality of life after microsurgical treatment of unruptured brain AVM – audit of a single-center series and comprehensive review of the literature

Neurosurg Rev

(2017)

C.B. Josephson et al.Scottish audit of intracranial vascular malformations (SAIVMs) steering committee and collaborators et al. Seizure risk from cavernous or arteriovenous malformations: prospective population-based study

Neurology

(2011)

D.J. Englot et al.Seizure predictors and control after microsurgical resection of supratentorial arteriovenous malformations in 440 patients

Neurosurgery

(2012)

V. Benes et al.Brain ateriovenous malformation. Pathogenesis, epidemiology, diagnosis, treatment and outcome

(2017)

H. Mast et al.“Steal” is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations

Stroke

(1995)

P. Moftakhar et al.Cerebral arteriovenous malformations. Part 2: physiology

Neurosurg Focus

(2009)

S. RossittiPathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: the hydraulic hypothesis

Surg Neurol Int

(2013)

E.A. Winkler et al.Reductions in brain pericytes are associated with arteriovenous malformation vascular instability

J Neurosurg

(2018)

C. Stapf et al.Incident hemorrhage risk of brain arteriovenous malformations located in the arterial borderzones

Stroke

(2000)

J. Gault et al.Pathobiology of human cerebrovascular malformations: basic mechanisms and clinical relevance

Neurosurgery

(2004)

I.E. Sandalcioglu et al.Vascular endothelial growth factor plasma levels are significantly elevated in patients with cerebral arteriovenous malformations

Cerebrovasc Dis Basel Switz

(2006)

D.L. Kraemer et al.Vascular malformations and epilepsy: clinical considerations and basic mechanisms

Epilepsia

(1994)

M.P. Marks et al.Vascular characteristics of intracerebral arteriovenous malformations in patients with clinical steal

AJNR Am J Neuroradiol

(1991)

F. Turjman et al.Epilepsy associated with cerebral arteriovenous malformations: a multivariate analysis of angioarchitectural characteristics

AJNR Am J Neuroradiol

(1995)

M.T. Lawton et al.Brain arteriovenous malformations

Nat Rev Dis Primers

(2015)

J. Fierstra et al.Impaired peri-nidal cerebrovascular reserve in seizure patients with brain arteriovenous malformations

Brain

(2011)

S. Liu et al.Factors associated with seizure occurrence and long-term seizure control in pediatric brain arteriovenous malformation: a retrospective analysis of 89 patients

BMC Neurol

(2015)

C.L. Sturiale et al.Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series

Eur J Neurol

(2013)

F. Galletti et al.Brain arteriovenous malformations and seizures: an Italian study

J Neurol Neurosurg Psychiatry

(2014)

J.C. Benson et al.MR characteristics of unruptured intracranial arteriovenous malformations associated with seizure as initial clinical presentation

J Neurointerv Surg

(2020)

C.B. Josephson et al.Intracranial vascular malformations and epilepsy

Semin Neurol

(2015)

A. Ogaki et al.Vascular abnormalities in the epileptic brain

Front Pharmacol

(2020)

D. Ding et al.Radiosurgery for unruptured brain arteriovenous malformations: an international multicenter retrospective cohort study

Neurosurgery

(2017)

G.G. Leblanc et al.Biology of vascular malformations of the brain

Stroke

(2009)

R. Daneman et al.The blood-brain barrier

Cold Spring Harb Perspect Biol

(2015)

M. Bankstahl et al.Blood-brain barrier leakage during early epileptogenesis is associated with rapid remodeling of the neurovascular unit

eNeuro

(2018)

W. Löscher et al.Structural, molecular, and functional alterations of the blood-brain barrier during epileptogenesis and epilepsy: a cause, consequence, or both?

Int J Mol Sci

(2020)

T. Cam Ha et al.Seizures elevate gliovascular unit Ca2+ and cause sustained vasoconstriction

JCI Insight

(2020)

E.A. Van Vliet et al.Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy

Brain

(2007)

A. Vezzani et al.The role of inflammation in epilepsy

Nat Rev Neurol

(2011)

A. Vezzani et al.Neuroinflammatory pathways as treatment targets and biomarkers in epilepsy

Nat Rev Neurol

(2019)

B.D. Semple et al.Immune challenges and seizures: how do early life insults influence epileptogenesis?

Front Pharmacol

(2020)

View full text

© 2022 Elsevier Masson SAS. All rights reserved.