Hemorrhagic events associated with unfused or twig-like configuration of the Middle cerebral artery: A rare vascular anomaly with clinical relevance

Abstract

Introduction

Twig-like middle cerebral artery configuration (Tw-MCA) is a rare and commonly misdiagnosed vascular anomaly characterized by a plexiform arterial network that replaces the normal M1 segment. The prevalence and clinical relevance of this anomaly is not fully established.

Material and methods

We sought to explore the prevalence of Tw-MCA in patients clinically referred to digital angiography in a single academic comprehensive endovascular center and evaluated the radiological and clinical findings among patients with hemorrhagic events.

Results

From 2011 to 2020, a total of 10,234 patients underwent a cerebral angiography at our institution. During this period, 9 (0.088%) Tw-MCAs were identified. Out of these, 5 patients (62.5%) were admitted due to an intracranial hemorrhage. Two patients had a ruptured intracranial aneurysm on the anterior communicating artery, one with multiple brain aneurysms; two patients presented an intraparenchymal hematoma (IPH) due to the presence of a periventricular anastomosis and one patient an intraventricular hemorrhage with unclear origin.

Conclusion

Tw-MCA is a very rare vascular anomaly associated with hemorrhagic events. Adequate identification of this anomaly is essential in order to avoid misdiagnosis as steno-occlusive disorders.

Introduction

The middle cerebral artery (MCA) is considered to be the most complex of the cerebral arteries and is the earliest phylogenetic vascular structure in the evolving neocortex. Anatomical variations of the MCA are less frequently observed in comparison to other major intracranial arteries, although duplications, fenestrations and accessory MCAs have been previously reported.^1,2 Recently, a new type of vascular anomaly has been reported, comprising an absence of the proximal MCA trunk replaced by a plexiform collateral network, which merges distally to reconstruct the MCA trunk (Figure 1). This anomaly has been defined as twig-like (Tw-MCA) or unfused MCA and has an estimated prevalence of 0.1–4%, with a still unknown pathogenesis and clinical relevance.³ A recent report relates Tw-MCAs with vascular hemorrhagic events due to other morphological anomalies, such as anterior cerebral artery (ACA) and anterior communicating artery (ACOMA) aneurysms or lenticulostriate arteries (LSA) anastomosing to medullary arteries in the periventricular area, all considered to be prone to rupture.⁴ Therefore, we attempted to explore the prevalence of Tw-MCAs in a large population of patients undergoing digital angiography at a single institution and to describe their clinical and angiographic characteristics in patients presenting with hemorrhagic intracranial events.

Figure 1.

Different stages in MCA development. Cerebral arteries in a 11 mm human embryo (a). At this stage, a plexiform arterial network arises from the distal internal carotid artery, at the lateral aspect of the telencencephalic vesicles (1), proximal to the primitive olfactory artery. At a later stage, the plexiform network progressively turns into multiple arterial twigs eventually fusing into a single arterial channel, becoming the M1 segment. A hypothetical evolutionary arrest during this process may result in the twig-like MCA phenotype in adults (b). Normal adult configuration MCA (c).

Material and methods

We retrospectively evaluated electronic hospital records of all consecutive patients undergoing a neurovascular diagnostic or interventional angiography between 2011 and 2020 at our single academic comprehensive endovascular center and specifically studied the prevalence and characteristics of Tw-MCAs. Furthermore, we recorded the presence of vascular events and explored the characteristics of those patients with intracranial hemorrhagic events, including IPH, intraventricular hemorrhage (IVH) or subarachnoid hemorrhage (SAH) who were identified with non-contrast brain computed tomography (CT) or magnetic resonance imaging (MRI).

Complementary magnetic resonance angiography (MRA) or CT angiography (CTA) were routinely performed in all patients with intracranial vascular events. Using DSA, a Tw-MCA was defined as the presence of the following features 1) plexiform arterial network with a steno-occlusive lesion on the MCA; 2) presence of LSA arising from the plexiform network; and 3) anterograde flow and normal configuration of the MCA branches distal to the network (Figure 2).

Figure 2.

Frontal DSA projection of the left ICA in early and late arterial phase (a,b). Lateral DSA projection of the left external carotid demonstrating the lack of transdural anastomosis (c). Tridimensional DSA reconstruction shows the diagnostic criteria, the white arrow shows no evidence of stenosis in the ACA or the ICA. The vascular plexus of the MCA is presented with the LSA arising from the plexus (white Asterix) and the normal configuration of the M2 and M3 segments (white head arrow) (d).

The presence of leptomeningeal collaterals was not considered an exclusion criterion to define a Tw-MCA, although the presence of transdural collaterals or homolateral internal carotid artery stenosis excluded its diagnosis. The clinical history and demographic data of each patient were retrospectively collected from the institutional clinical records, and the angiograms of patients with suspected Tw-MCA patterns were reviewed independently at a Xclera PACS (Philips Healthcare, Cleveland, US) workstation by two experienced neuroradiologists. The angiographic variables analyzed included laterality, the presence and characteristics of intracranial aneurysms, periventricular and leptomeningeal anastomosis.

All procedures performed were in accordance with the ethical standards of the Institutional Review Board (IRB) and the 1964 Helsinki Declaration and its updated amendments. A separate committee approval was obtained for habeas data waive.

Results

From 2011 to 2020, a total of 10,234 patients underwent a neurovascular diagnostic or interventional angiography at our institution. During that period, 9 (0.088%) Tw-MCA configurations were identified. Five patients (62.5%) were admitted due to an intracranial bleeding, whereas 3 patients were admitted due to clinical indications not related to any hemorrhage, that is to say,: one patient with a stroke involving the non-Tw-MCA, one patient with an incidental homolateral non-ruptured temporal arteriovenous malformation presenting with a headache, one patient presenting an incidental Tw-MCA and one patient diagnosed with seizures in which a right Tw-MCA was identified on MRA and DSA, with no other vascular findings.

The mean age of the patients with hemorrhagic events was 52.2 ± 9 years. The right side was involved in three cases (60%). Among the hemorrhagic events, two patients presented a SAH (both grade IV in the modified Fisher scale [mFs]), both with ruptured AcomA aneurysms, and one with an associated unruptured posterior communicating aneurysm (Table 1).

Two women presented an intraparenchymal hematoma (a frontal and frontoparietal hematoma, respectively), ipsilateral to the Tw-MCA. Both patients showed angiographic evidence of periventricular anastomosis between the lenticulostriate and medullary arteries (Figure 3). A 64-year-old woman presented an intraventricular hemorrhage with no clear bleeding cause on DSA or MRA with a right Tw-MCA configuration.

Figure 3.

Forty-eight-year-old female with a right frontal paraventricular IPH shown in non-contrast brain CT (a), frontal DSA projection of the right ICA with a Tw MCA configuration (b), oblique DSA projection with the presence of ipsilateral periventricular anastomoses (black circle) between an LSA (black arrow) and a medullary artery in the periventricular zone (c).

Among patients with SAH; a 59-year-old man had a ruptured left axis AcomA aneurysm causing a mFS-4 SAH. The patient also had an unruptured PcomA aneurysm, a right Tw MCA configuration, and the vascular ACA dominance was contralateral to the Tw-MCA. Both aneurysms were treated with coils. The second patient was a 48-year-old female, admitted with a ruptured right axis AcomA aneurysm causing a mFS-4 SAH, and a homolateral Tw-MCA aneurysm. Both aneurysms were treated with coils. Angiographic follow-up at 3 years showed no changes in the Tw-MCA configuration in these patients (Figure 4).

Figure 4.

Forty-eight-year-old female who suffered a SAH due to a right axis ruptured AcomA aneurysm with an associated bleb formation and left Tw-MCA configuration (a,b,c). The aneurysm was treated with coils, at the three-year follow-up DSA, no modifications were identified in the Tw-MCA pattern, with occlusion of the previously treated aneurysm (d).

Discussion

Among the several anatomical variations of intracranial arteries, most without clinical relevance, the Tw-MCA has been associated with hemorrhagic events.^5,6 The development of the cerebrovascular system is a complex and continuous process deeply entangled with the progressive differentiation of the brain parenchyma, covering membranes and head and neck tissue, beginning with the formation of the internal carotid artery (ICA), derived from the third branchial arch arteries and the distal part of the dorsal aorta, at the 3 mm embryonic stage.⁷ After 28–30 days of fetal development, the ICA divides into its cranial and caudal portions. The cranial division supplies the olfactory and optic regions eventually developing the anterior choroidal artery (AChoA), ACA and MCA. The caudal branch will originate the PComA, from which eventually both the posterior cerebral artery (PCA) and the posterior choroidal arteries (PChA) will emerge.⁸ After 34–36 days of embryonic development (11–12 mm), multiple plexiform arterial twigs start to emerge between the AChoA proximally and the developing ACA distally, giving rise to the lateral striate arteries and, the precursors of the MCA.³ At this stage, the MCA has a plexiform configuration, however, it is the major blood source of the cerebral hemispheres. At the 16–18 mm stage, the MCA fuses into a single channel and further sprouts into the growing cerebral hemispheres, with the appearance of the cerebral sulci and convolutions transforming the initial rectilinear course to a more tortuous shape, finally reaching an approximate adult configuration at the 40 mm embryo stage.⁹ To date, the mechanisms behind the formation of the Tw-MCA are not well understood, although it might represent a type of evolutionary arrest of the developing MCA in its fetal form by an unknown underlying mechanism or fetal vascular insult.^5,6

It has been postulated that a normal adult MCA can withstand the pressure transmitted from the ICA, however, fetal arterial twigs are usually thinner, and the muscular layer is less developed. When such abnormal vessels are exposed to the hemodynamic stress from an average- lumen ICA, MCA aneurysms might develop and become prone to rupture.¹⁰ The plexiform shape of the proximal MCA segment may also induce an abnormal hemodynamic stress distally, therefore explaining the higher incidence of unruptured and ruptured ACA and AComA aneurysms.⁵

It is important to recognize Tw-MCA angiographic features for diagnosis and surveillance. The two main angiographic differential diagnoses for this anomaly are Moyamoya disease and chronic MCA dissection. Moyamoya disease is a non-atherosclerotic progressive steno-occlusive idiopathic arteriopathy that most frequently affects the intracranial ICAs and proximal segments of the MCAs and ACAs, and rarely the posterior circulation.¹¹ Usually, Moyamoya disease is bilateral, although unilateral cases have been reported.¹² Cerebral angiography in these patients shows bilateral and symmetrical stenosis or occlusion at the ICA terminus and adjacent proximal MCA and ACA, with a rich collateral network of abnormal vessels (Moya-Moya vessels) in the vicinity of the stenotic segments, usually in the basal ganglionic region. Transdural collateral anastomoses arising from the external carotid artery (ECA) are evident in most of these cases, as opposed to Tw-MCA configuration¹³ in which the affected vasculature is an unilateral plexiform M1 segment of the MCA instead of the main MCA trunk with normal distal vasculature and anterograde flow, perforators arising from the plexiform arterial network, no stenosis of the supraclinoid segments of the ICA or the ACA, no progressive steno-occlusive behavior as there are no associated ischemic events and no presence of transdural collaterals through the ECA.⁸

The information available related to this anomaly is, to date, very scarce. To the best of our knowledge, a total of only 35 patients has been published since 2005, when in a seminal publication Liu et al. reported two cases also presenting a SAH related to the rupture of aneurysmal dilations found between the twig-like vessels of the proximal MCA segment, and the term “twig-like MCA” was coined.⁵ That same year, Cekirge reported a 32-year old male who presented with a SAH secondary to a ruptured AComA aneurysm concomitant with the abovementioned anomaly, at that time named by the authors as an “unfused embryonic MCA”.³ In the largest series of cases, Seo et al. reported 15 patients of a so-called “probable Tw-MCA”.¹⁴ An interesting fact observed in almost every report in the current literature is the presence of related aneurysms, mostly located on the ACA or AComA.^3,6,15

In our cohort including 10,234 patients, the prevalence of Tw-MCAs was 0.088%, a figure slightly lower than the previously reported which ranged between 0.1% and 4%.^4,5,14 However, those reports analyzed smaller patient populations, Liu et al reported 2 cases of Tw-MCAs among 1,814 patients, with a local incidence of 0.11%,⁵ Kim et al. reported 1 case of Tw-MCA in 488 patients, estimating an incidence of 0.22%¹⁵ In the literature, of the 35 cases reported, 21 are females (60%) with a mean age of 49.7 ± 16.6 years. In our study, the mean age was 49.2 ± 7 years, and 80% were female. In previous reports of Tw-MCAs, hemorrhagic events were reported in 54% of the patients, 19 cases with intracranial bleeding (54%) and 15 (79%) with ruptured intracranial aneurysms from a total of 17 aneurysms, 6 in the MCA, 7 in the ICA, 3 in the ACA and one in the posterior lateral choroidal artery. 73% of all the aneurysms were homolateral to the Tw-MCA⁴ and only four were incidental (25%). In our series, 5 patients (66%) presented a hemorrhagic event, two of which suffered a SAH, both caused by a ruptured ACA aneurysm, and one also had multiple brain aneurysms associated.

The presence of an ipsilateral intraparenchymal hematoma may be related to rupture of either abnormal collateral vessels,⁴ deeply located aneurysms or the immature arterial twigs.^4–6 Periventricular anastomoses, defined as a connection between a perforating or choroidal artery and a medullary artery, located in the periventricular zone, have been reported as a hemorrhagic risk factors in patients with Moya-Moya disease.¹⁶ These types of anastomoses probably serve as a collateral pathway to the cortex and compensate for the decrease in cerebral blood flow bypassing the aplastic M1 segment, however, several mechanisms are proposed in order to explain the rupture of these anastomoses. First the dilatation of the LSA with histological changes, formation of microaneurysms and marked attenuation of the wall thickness with diminution of the elastic lamina that predispose to rupture, this was proposed by Yamashita et al.¹⁷ The last mechanism is the fragility of the anastomosis in the abnormal connection between vessels reported by Funaki et al.¹⁶

Two patients presented with IPH in our series, and both presented this type of anastomosis on the same side of the bleeding. In our report, one patient presented a connection of the lenticulostriate artery with a medullary artery at the frontal horn of the lateral ventricle (Figure 2) and the second patient presented a connection of an anterior choroidal artery connecting with a medullary artery under the lateral wall of the lateral ventricle (Figure 5). Identification of the periventricular anastomosis can be troublesome due to the small size of the arteries involved. However, it has been postulated that the sole identification of the proximal part of the medullary artery is considered a positive indicator for the presence of periventricular anastomosis.¹⁸

Figure 5.

Diagnostic DSA with tridimensional reconstruction showing a periventricular anastomosis, the anterior choroidal artery (black arrow) ending in a medullary periventricular artery in the lateral ventricle (black circle), (d) in a female patient with a left temporal IPH with a homolateral Tw-MCA.

Table 1.

Anatomical and radiographic findings.

Patient number	Age	Gender	Twig side	Bleeding type	Bleeding cause	Other vascular findings
1	59	M	R	mFs IV SAH	L-axis AcomA aneurysm	R-PcomA Aneurysm
2	48	F	R	mFs IV SAH	R-Axis AcomA aneurysm	No
3	48	F	R	R-IPH	Rupture of abnormal collateral vessels, deeply located aneurysms or the immature arterial twigs	No
4	42	F	L	L-IPH	Rupture of abnormal collateral vessels, deeply located aneurysms or the immature arterial twigs	No
5	64	F	R	Intraventricular hemorrhage	Not determined	No

Limitations

Our study has the same limitations inherent to all retrospective studies. Furthermore, we were unable to perform computed hemodynamic analysis of flow in the intracranial vasculature.

Conclusion

In conclusion, Tw-MCAs are a very rare vascular anomaly only recently described, with underlying mechanisms which are still unknown probably related to an arrested embryological development, that eventually contributes to an abnormally weak angioarchitecture that might evolve to develop anterior circulation aneurysms and hemorrhagic events. Radiologists and neurosurgeons must be aware of its consequences, and diagnostic efforts must be made to differentiate this condition from the Moya-Moya syndrome and other degenerative steno-occlusive diseases of the MCA.

ORCID iDs

Rene Viso https://orcid.org/0000-0002-4209-6640

Ivan Lylyk https://orcid.org/0000-0002-6048-4225

Pablo Albiña https://orcid.org/0000-0002-0434-5466

Esteban Scrivano https://orcid.org/0000-0001-8824-9545