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Anat Cell Biol 2024; 57(4): 481-497

Published online December 31, 2024

https://doi.org/10.5115/acb.24.005

Copyright © Korean Association of ANATOMISTS.

Morphology and variations of middle cerebral artery: systematic review and meta-analysis

Urvi Sharma1 , Suman Verma2 , Subathra Adithan3 , Ashish Khobragade4

1Department of Anatomy, All India Institute of Medical Science, Rishikesh, 2Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 3Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 4Department of Community and Family Medicine, All India Institute of Medical Science, Raipur, India

Correspondence to:Suman Verma
Department of Anatomy, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
E-mail: suman2v@gmail.com

Received: January 7, 2024; Revised: April 4, 2024; Accepted: May 26, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

To review morphometry, morphology, branching patterns and anomalies of middle cerebral artery (MCA). The databases of PubMed, Google Scholar and Scopus were searched with different keywords. The review comprised of 45 studies. Meta-analysis was done for dimensions of MCA, shapes, patterns and MCA anomalies. Newcastle-Ottawa Scale was used for assessment of literature. Statistical analysis was done using R software using meta package. Thirteen research were combined to determine the proportion of MCA length and pooled proportion was 16.53 cm (15.33 to 17.72 cm); I2=98%; P-value<0.01. Nine studies were combined to determine proportion of MCA diameter and pooled proportion was 2.85 cm (2.52 to 3.17 cm); I2=100%; P-value<0.05. M1 segment mean length is more on left side as compared to right side. Mean length in males (16.57±1.40 cm) is more than females (15.9±1.32 cm). Mean diameter of M1 segment is similar on both sides. Mean diameter in males (3.20±0.09 cm) is higher than females (3.14±0.18 cm). Different branching patterns observed were single trunk, early bifurcation, bifurcation, trifurcation, quadrifurcation and multiple trunks. The most typical MCA branching pattern is bifurcation. The shapes of MCA like straight shaped, U shaped, C shaped, inverted U shaped and S-shaped of M1 segment have been described. Straight MCA is the most common shape. The MCA measurements and branching pattern will assist surgeons in limiting errors in the treatment of cerebral aneurysms and infarcts and providing the best possible result for the patients. An understanding of MCA shape will aid surgeons and physicians in effective endovascular recanalization.

Keywords: Middle cerebral artery, Cerebral angiography, Aneurysm, Embryology, Histology

Brain, most metabolically active, receives three arteries, one of which is middle cerebral artery (MCA) [1, 2]. Eighty percent of brain blood supply is via MCA [3]. Principal motor and sensory areas of arm, face, receive supply from it [4]. MCA comprises of four segments [5]. M1 is between origin of MCA and genu of insula; M2 runs from limen insula to insula’s circular sulcus; M3 from circular sulcus to sylvian fissure surface. M4 segment from sylvian fissure to branches in lateral convexity [6-9]. M1 segment, from internal carotid artery (ICA), travels towards insula [10]. Türe et al. [11] described 5 segments, where M4 and M5 were parainsular and terminal segments. M1 is most crucial as branching occurs here [6]. Demarcation line dividing M1 and M2 is identified as MCA bifurcation [11]. Atherosclerosis and cerebral aneurysms occur near bifurcations where blood flow impacts arterial wall [12, 13].

MCA supplies significant area of hemispheres and abrupt blockage can cause infarct [5]. It is second most frequent site (20%–43%) of intracranial aneurysms [14, 15]. Configuration of branching pattern is crucial in managing stenosis or aneurysms [16, 17]. Variations in arterial circulation can result in neurological impairments [8]. Thrombus can be cured with help of mechanical thrombectomy, and with interventional stroke treatment, MCA anatomy has become essential to prevent catastrophe during intravascular and neurosurgical practices [15, 18]. Branching pattern also impacts aneurysms incidence, diagnostics, surgeries, and complications [19, 20].

Anomalous MCA though accidental observations, offer supplementary blood supply in MCA block [20]. Various methods like autopsy and imaging modalities are used for analyses [21]. Because of heterogeneity of cerebral vasculature, incidence varies across populations [22]. Computed tomography angiography (CTA) is used for M1 length measurement in aneurysm clipping and for diameter to insert stent [23, 24], thus aids surgeons in managing infarcts, cerebral aneurysms, and minimising complications [25]. MCA has variety of shapes [26] and its tortuosity is related with higher risk of atherosclerosis [27]. Effective endovascular recanalization depends on shape and tortuosity [28]. Few imaging or cadaveric reports investigate MCA morphology [26, 28]. Han et al. [29] utilized magnetic resonance angiography to identify shapes of MCA in Chinese. There is limited literature on comprehensive appraisal of MCA. This systematic review focuses on MCA variations, morphometry, morphology, microstructure, and development.

Literature search was conducted for three months, February 2023 to April 2023. Article was registered in Prospero (No. CRD42023443545). Following databases were accessed: PubMed, Google Scholar, and Scopus. Keywords were middle cerebral artery, middle cerebral artery morphometry, middle cerebral artery morphology, middle cerebral artery variations, middle cerebral artery branching patterns, middle cerebral artery anomalies, middle cerebral artery embryology. Search approach was devised for various databases (Appendix 1). Each article’s list of references was also utilised. Duplicates were excluded and 264 articles were retrieved (Fig. 1). Review comprised of 45 articles after excluding case reports, unpublished data, articles without full text and articles in languages other than English. Morphometry was noted in 19 articles, five from India and 14 studies from other countries. Morphology was described in 4, one cadaveric and three angiographic. Variations were mentioned in 20 studies, out of which 13 were cadaveric, 6 angiographic and one duplex sonography. Anomalies were noted in 20; 6 cadaveric, 13 angiographic and one autopsy. Both morphometry and morphology of MCA were noted in one, morphometry and variations in nine, morphometry and anomalies in four, variations and anomalies in five studies. Meta analysis was done on 19 studies for length and diameter.

Figure 1. Flow chart showing methodology in detail according to PRISMA guidelines.

Articles were searched by reviewers independently and those meeting inclusion criteria were selected. After selection, full-text appraisal was done. Information on total sample size, mean length, diameter, and prevalence of different anatomical shapes of MCA was extracted from each selected study. Quality assessment of studies was done using Newcastle-Ottawa Scale.

Statistical analysis was done using R software using “meta” package. Pooled analysis was shown with help of forest plots. Cochrane Q and I² statistics were calculated to determine studies’ heterogeneity. Publication bias was graphically presented by funnel plots. Asymmetry of funnel plot was statistically tested using Egger’s test. Pooled mean length and diameter were calculated for both sides of MCA and sex-wise.

Morphology

Origin of MCA is always from ICA [19, 30-33]. Morphology of MCA is straight to S-shaped [26]. Shapes like straight, C, U, inverted U and S are commonly described [26, 29, 34]. MCA extends laterally and anteriorly, is smooth, varies from concave to straight [35]. Some mention that M1 segment has concave curvature posteriorly [6, 36]. Anterior concavity is documented, but less prevalent [37].

Straight and S are most common types. C shape is cubic and spatial curve of M1. Arch shape of MCA is lateral, rostral and dorsal. Maximum incidence of straight shape was by Sharma et al. [34] (Fig. 2) and S-shaped by Kim et al. [26].

Figure 2. Incidence of shapes of middle cerebral artery in various studies.

Tortuosity of vessel increases with age. Increase in C shape incidence is noted with increasing age and then decreases slightly. However, increase in straight shape was noted with increase in age in recent study [34]. Shape of M1 segment is relevant in neurosurgical angiography, and interventional neuroradiology when maximum intensity projections are seen with three-dimensional (3D) imaging [29]. Atherosclerotic disorders arise because of artery’s anatomical characteristics [38, 39]. MCA develops cerebral atherosclerosis in 25% cases. M1 is also affected by conditions like stroke [40, 41]. Analysis of MCA shape prior to surgery may be beneficial as distribution of plaque is associated with geometry of M1 [26]. Superior plaques are more common in U or straight shaped arteries (21.7%), whereas inferior plaques (39.9%) in S- or inverted U-shaped arteries [26, 42]. Though outside wall has higher susceptibility for shear stress, disposition of plaques is less despite remodelling impact. Curved MCA has plaques scattered along inner wall [43]. Artery with reduced shear forces is more prone for plaques [44].

M1 can be transformed by angioplasty and stenting, planning of cerebrovascular surgeries follows study of vessel architecture to prevent recurring stenosis [42]. In tortuous vessel, there is decrease in stress on inner wall as centrifugal flow is directed to outer wall [45]. It makes inner wall of arteries more susceptible to atherosclerosis and intimal layer thickening [27]. In cerebral arteriosclerosis, excessive stretching as result of plaque growth may cause aneurysm [46]. Tortuosity of vasculature is related to risk of plaque, atherosclerosis and aneurysm [27]. Hazards and success rates are clinically related with vessel morphology, especially tortuosity [29, 43]. Therefore, it is necessary to understand vessel shape before endovascular operations, to assists neurosurgeons in minimising blunders.

Dimensions

M1 segment, due to its orientation and diameter, seems to grow laterally from ICA. It ends at intersection of sphenoidal area of Sylvian fissure and operculoinsular area where trunk of MCA makes 90-degree rotation backward and upward. MCA origin to bifurcation is pre bifurcation segment; MCA bifurcation to genu is post bifurcation segment [6]. M1 segment length can be determined from termination of ICA to MCA genu [24, 28, 47]. Several authors have measured distance from ICA termination to M1 division point [31, 35]. Thus, M1 segment ends at one of two points i.e. either genu or bifurcation, and is controversial. Fischer described that M1 segment ends at genu [48]. However, in some cases bifurcation may coincide with genu. Stroke experts have recommended that M1 ends at bifurcation [49]. Different studies still variably define M1–M2 distinction. Measurements of M2 length are important because resection of insular opercular gliomas requires intraoperative motor evoked potential monitoring through long insular arteries [50]. Post-operative healing delays and motor deficit is documented if M2 length is inadequate [51].

To obtain accurate assessment of M1 length using CTA, cursor is placed inside artery, moved incrementally while it traces its curves [35]. M1 is also measured using interactive virtual reality 3D GAIDA software [10]. It is used for preoperative visualization and semiautomatic detection of origin and final points of M1. Since outside and inner borders of vessel are not always easily distinguished, diameter is measured at center of M1 from outermost layer perpendicular to vessel wall [25]. It is also determined by calculating average at start, middle, and end of M1 [52].

Most research on MCA morphometry includes cadavers, sample size in these studies is lesser than angiographies. Blood vessels are not clearly identified in angiographic studies due to overlapping so data varies from that in cadavers [20]. Idowu et al. [24] injected Congo red dye into MCA and measured lengths of M1 and M2 segments using thread, Digital Vernier calliper (sensitivity 0.1 mm; Pierre Vernier) and artery forceps. However, Meneses et al. [53] injected ICA with 70 ml red latex (Dupont, Neoprene) to visualize MCA. Measurements were taken with digital micro calipers [54].

Pooled length and diameter of MCA (Table 1). Forest and funnel plots of meta-analysis for length and diameter (Figs. 3, 4).

Figure 3. Forest plot showing the metaanalysis of length (A) and diameter (B) of middle cerebral artery (MCA). CI, confidence interval. MRAW, mean raw.

Figure 4. Funnel plot of the studies included in the calculation of the pooled length and diameter of the middle cerebral artery (MCA).

Table 1 . Pooled length and diameter of middle cerebral artery (subgroup analysis)

SubgroupNo. of studiesSample sizePooled estimate (95% CI)I2 (%)P-value
Length
Right551814.78 (14.29–15.27)84<0.01
Left551815.45 (14.79–16.11)92<0.01
Male455216.53 (14.09–18.97)97<0.01
Female445615.86 (14.08–17.65)97<0.01
Diameter
Right91,5262.92 (2.65–3.20)99<0.01
Left91,5262.92 (2.65–3.18)99<0.01
Male68233.21 (2.85–3.57)99<0.01
Female66783.14 (2.74–3.54)100<0.01

CI, confidence interval.



Mean length in cadavers is more compared to angiographic studies [10, 17, 21, 24, 25, 28, 30, 47, 50, 55]. In both, mean length on left side is more (Table 2) [10, 17, 24, 50]. Length of M1 segment by Vuillier et al. [35], Gunnal et al. [32] and Hassan et al. [52] was more than average in other studies. Mean length in males is higher than females [10, 24, 25, 56].

Table 2 . Length of middle cerebral artery in various studies, sides and sex

ReferenceMethodNo. of casesLength of M1 segment (mm)
Umansky et al. 1988, Michigan [17]Cadaveric10415±1.1
R=15±1.10; L=15.7±1.30
Idowu et al. 2002, Nigeria [24]Cadaveric10015.43±4.29
R=14.97±4.33; L=16.18±4.20
Zurada et al. 2011, Poland [10]CTA23015.62±4.47
R=15.50±4.42; L=15.73±4.53
Rogge et al. 2015, Germany [56]Sonography10019±3.8
Shatri et al. 2017, Kosova [21]MRA26615.75±1.15
Brzegowy et al. 2018, Poland [47]CTA50015.80±5.70
Jeyakumar and Veerapandian 2018, India [22]Cadaveric3016.37±2.97
Kadam et al. 2018, India [50]Cadaveric5814.63±2.16
R=14.63±2.16; L=15.73±2.54
Fauzi et al. 2019, Indonesia [55]CTA55415.56±7.75
Reci and Bexheti 2019, North Macedonia [28]Cadaveric5021.2±3.54
Oo et al. 2021, Myanmar [30]Cadaveric10020.6±6.2
Urvi et al. 2023, India [25]CTA57814.32±1.27
R=14.19±1.39; L=14.44±1.12
Length in mm
MaleFemale
Idowu et al. 2002, Nigeria [24]Cadaveric10015.04±3.7516.12±4.78
Zurada et al. 2011, Poland [10]CTA23017.05±5.0614.86±3.93
Rogge et al. 2015, Germany [56]Sonography10019.90±4.3018.30±3.10
Urvi et al. 2023, India [25]CTA57814.31±1.3014.32±1.21

Values are presented as mean±SD. CTA, computed tomography angiography; MRA, magnetic resonance angiography; R, right; L, left.



Mean diameter in cadavers is more compared to angiographic studies [6, 17, 24, 28, 31, 54, 57]. At center of M1, average diameter is smaller [23]. Vuillier et al. [35] noted average diameter of 3 mm at center of M1 segment [24, 35]. Mean diameter of M1 segment is similar on both sides. In cadaveric studies from India, mean diameter is 3 to 3.35 mm [31, 54]. In other studies mean diameter is 2.60 to 3.9 mm [6, 17, 24, 28, 57]. Mean right MCA diameter in CT angiographic studies is 2.23±0.39 mm to 3.31±0.56 mm, while left side mean diameter is 2.23±0.37 mm to 3.33±0.56 mm [10, 18, 29, 52, 58]..Mean diameter in males is higher than females [25, 58, 59]. Comparison of MCA diameter with other studies (Table 3) [10, 18, 24, 25, 29, 32, 52, 58, 60]. Minor differences in methods of M1 length and diameter measurement may be reason for morphometry variations. It is critical to know diameter of MCA before performing percutaneous angioplasty [33].

Table 3 . Diameter of middle cerebral artery in different studies, sides and sex

ReferenceMethodNo. of casesDiameter of middle cerebral artery (mm)
Umansky et al. 1988, Michigan [17]Cadaveric1043±0.1
Idowu et al. 2002, Nigeria [24]Cadaveric1003.49±0.51
Tarasów et al. 2007, Poland [18]MRA1142.23±0.41
Zurada et al. 2011, Poland [10]CTA2302.23±0.38
Shatri et al. 2017, Kosova [21]MRA2663.35±0.31
Reci and Bexheti 2019, North Macedonia [28]Cadaveric502.6±0.47
Fauzi et al. 2019, Indonesia [55]CTA5542.39±0.49
Srinivasa et al. 2021, India [54]Cadaveric303±0.1
Urvi et al. 2023, India [25]CTA5783.33±0.62
Diameter in mm
Right M1 segmentLeft M1 segment
Gillard et al. 1986, London [60]TPDU582.8±0.32.7±0.3
Müller et al. 1991, Switzerland [58]CTA2003.19±0.393.18±0.41
Idowu et al. 2002, Nigeria [24]Cadaveric1003.51±0.553.51±0.54
Tarasów et al. 2007, Poland [18]MRA1142.37±0.802.45±0.83
Zurada et al. 2011, Poland [10]CTA2302.23±0.392.23±0.37
Han et al. 2014, China [29]MRA8382.86±0.232.85±0.26
Gunnal et al. 2019, India [32]Cadaveric3403±0.743±0.80
Hassan et al. 2020, Egypt [52]DSA1003.31±0.563.33±0.56
Urvi et al. 2023, India [25]CTA5783.32±0.623.33±0.62
Diameter in mm
MaleFemale
Müller et al. 1991, Switzerland [58]CTA2003.33±0.423.04±0.37
Idowu et al. 2002, Nigeria [24]Cadaveric1003.44±0.483.59±0.77
Ozdogmus et al. 2008, Turkey [59]Autopsy663.47±0.473.35±0.67
Zurada et al. 2011, Poland [10]CTA2302.29±0.452.20±0.33
Shatri et al. 2017, Kosovo [21]MRA1443.40±0.323.31±0.29
Urvi et al. 2023, India [25]CTA5783.30±0.633.37±0.61

Values are presented as mean±SD. MRA, magnetic resonance angiography; CTA, computed tomography angiography; TPDU, transcranial pulsed Doppler ultrasound; DSA, digital subtraction angiography.



Length of MCA increases but diameter decreases with advance in age. MCA diameter increases from 25 to 44 years of age, then dropped from 45 to 64 years, with second rise beyond 65 years [59]. According to Tarasów et al. [18], length and diameter of MCA increased with age. However, length of M1 segment showed increase with age but there was slight increase in diameter with age by Zurada et al. [10]. Around 18.2%–38.9% have MCA aneurysms, of which 80% occur near bifurcation and 20% proximally. Most aneurysms are seen at M1 division, thus it’s length is critical before clipping aneurysm [23, 47]. Sylvian fissure is opened surgically in two ways: from proximal to distal in short M1 segment and distal to proximal in long segment. Greater average length of M1 segment will therefore make it easier for surgeon to access and expose aneurysm’s neck [10].

Variations in branching pattern

Though variations in MCA are less common [24, 32], increase shear stress due to them cause damage to arterial wall resulting in vascular deformity and aneurysm [14]. MCA is most common site of stroke and aneurysm [61], main location of aneurysms is bifurcation as it generates turbulence and higher shear stress [33, 62]. MCA branching affects surgical approach to aneurysms [19], important in diagnosis and management of subarachnoid haemorrhage, stroke, aneurysm repair [63].

Because of cerebral arteries variability, populations have different prevalence of MCA branching [22]. Branching patterns observed in MCA: single trunk, early bifurcation, bifurcation, trifurcation, quadrifurcation and multiple trunks (Fig. 5, Table 4). Bifurcation (Fig. 5C) is most prevalent, incidence is 48% and 96.5%, in cadaveric studies [28, 50]. In imaging studies, it’s 73% to 98% [35, 64]. Variations are likely due to geographical and methodological differences [33]. M1 splits into two trunks. Superior trunk serves anterior lobule while inferior sustains posterior lobule of insular cortex [2]. Blockage of superior trunk raises incidence of contralateral hemiparesis [65], due to inclination of these arteries towards parietal region [65]. Revascularization can be done by superficial temporal artery and external or internal carotids to MCA anastomosis using saphenous vein graft [66]. Superior branch is most suitable for anastomosis, supplies precentral and postcentral gyri. However, anastomosis of inferior branch have low risk of neurological deficit [53]. Minimum of 1 mm exterior diameter of MCA branch is necessary for maintaining long-term patency of anastomosis [67]. Vascular anatomy is thus significant predictive factor in M1 occlusion [56].

Figure 5. Branching patterns and anomalies of middle cerebral artery (MCA). (A) Single trunk MCA (0.2% to 20.6%): main trunk (blue arrow) continues without dividing into trunks. (B) Early bifurcation of MCA (0.5% to 24%): main trunk bifurcates (blue arrow) at a distance of ≤5 mm from origin. (C) Bifurcation (blue arrow) of MCA into upper and lower trunks (48% to 98%). (D) Trifurcation (blue arrow) of MCA into upper, middle and lower trunks (1% to 29%). (E) Quadrifurcation (blue arrow) of MCA into four branches (0.7% to 3.8%). (F) Duplication of MCA (0.5% to 2.9%)-duplicated vessel (blue arrow) originates from internal carotid artery (ICA) and runs parallel to the main trunk of MCA. (G) Accessory MCA (0.1% to 2.7%)-it originates from anterior cerebral artery (ACA) and runs parallel to main trunk of MCA (blue arrow). (H) Fenestration of MCA (0.1% to 3%)-division of artery into 2 lumens (blue arrow) that unite distally.

Table 4 . Incidence of branching patterns of middle cerebral artery in various studies

ReferenceType of studyNo. of casesBranching pattern %
Pattern 1Pattern 2Pattern 3Pattern 4Quadrifurcation
Gibo et al. 1981, Florida [6]Cadaveric50--7812-
Umansky et al. 1984, Michigan [7]Cadaveric70--64291
Umansky et al. 1988, USA [17]Cadaveric1043.8-66.3263.8
Meneses et al. 1997, Brazil [53]Cadaveric14--85.67.2-
Tanriover et al. 2003; Florida [19]Cadaveric50--8812-
Vuillier et al. 2008, France [35]MRA10017-739-
Ogeng’o et al. 2011, Kenya [33]Cadaveric2886.25.282.310.80.7
Sadatomo et al. 2013, Japan [76]MRA124--92.77.3-
Rogge et al. 2015, Germany [56]Duplex sonography100--6332-
Brzegowy et al. 2018, Poland [47]CTA500--86.213.8-
Jeyakumar and Veerapandian 2018, India [22]Cadaveric30--73.326.6-
Kadam et al. 2018, India [50]Cadaveric58--96.51.7Multiple trunks-1.7
Reci and Bexheti 2019, North Macedonia [28]Cadaveric50-244826-
Fauzi et al. 2019, Indonesia [55]Cerebral angiography554---9.40.7
Gunnal et al. 2019, India [32]Cadaveric34020.6-64.712.42.4
Żyłkowski et al. 2021, Poland [77]CTA198--85.18.9-
Pai et al. 2005, India [31]Cadaveric10--8020-
Srinivasa et al. 2021, Myanmar [54]Cadaveric3010-7310-
Oo et al. 2021, Myanmar [30]Cadaveric1001237216-
Sharma et al. 2023, India [64]CTA5780.20.5981-

MRA, magnetic resonance angiography; CTA, computed tomography angiography.



Emboli get stuck at bifurcation, preventing them from heading further [65]. In 18% to 80%, infarct with neurological impairments occurs following acute thrombus in MCA [68]. Understanding variations is critical for preventing redundant endovascular procedures and developing safe interventional practices [69].

Curved MCA stem and spread of thrombus into branches reduce technical effectiveness of thrombectomy in M1 occlusions [70]. Understanding branching is necessary for preservation of long insular artery and prevention of postoperative motor impairments [71].

Single trunk is continuation of main trunk without splitting till posterior end of lateral fissure (Fig. 5A) [32]. MCA occlusion here will have greater region of ischemia [72]. Its significance is closer to trifurcation since few occurrences mirror it [33].

Early bifurcation is MCA branching at 0.5 cm or less from origin. (Fig. 5B) [20]. Jain [73] reported branching at 1.6 cm. According to Dimmick and Faulder [63], it occurred at 1 cm. M1 can be short (3–12 mm), medium (13–22 mm), long (23–40 mm) [74]. Early bifurcation is associated with perforating branches from post-bifurcation portion of MCA. To prevent damage of perforating branches, care must be taken during aneurysm surgery [30]. Early bifurcation has less clinical importance since it’s not associated with higher risk of aneurysm [63].

Trifurcation or quadrifurcation is presence of three or four terminal MCA trunks (Fig. 5D, E) [28]. Trifurcations are favourable lodging sites for emboli, resulting in ischaemia [75]. Incidence of trifurcation in cadavers is 1.7% to 29% while in angiographic studies it’s 1% to 13.8% [7, 49, 50, 64, 76, 77]. Amount of ischemia resulting from blockage of one trunk is reduced with multiple secondary trunks, thus blockage in trifurcation causes less severe neurological damage [17].

Anomalies

In duplication, two arteries have distinct origins and no caudal junction (Fig. 5F) (Table 5). [78]. Duplicated MCA arise from early MCA branching and classified as direct bifurcation due to origin from ICA [79]. Basal ganglia and frontal lobe receive collateral supply from duplicated MCA, and its blockage presents with aphasia, hemiparesis [80].

Table 5 . Incidence of middle cerebral artery anomalies in different studies

ReferenceMethodNo. of casesVariation (%)
Umansky et al. 1984, Michigan [7]Autopsy140A-3
Tran-Dinh 1986, Australia [89]Cadaveric150A-2
Yamamoto et al. 1992, Japan [85]Cerebral angiography910A-1.5
D-0.8
Komiyama et al. 1998, Japan [79]Cerebral angiography1,000D-0.4
A-0.4
Uchino et al. 2000, Japan [80]MRA850D-2.1
A-1.17
F-0.5
Gailloud et al. 2002, Switzerland [82]CTA2,340F-0.4
Idowu et al. 2002, Nigeria [24]Cadaveric100A-1
Tanriover et al. 2003, Florida [19]Cadaveric100D-1
A-2
Uchino et al. 2006, Japan [90]MRA4,000F-0.15
Vuillier et al. 2008, France [35]MRA100F-3
Kim et al. 2009, Korea [91]Cerebral angiography2,500A-1.2
Dimmick and Faulder 2009, Australia [63]CTA300D-0.2-2.9
A-2.7
F-0.17
Chang et al. 2011, Korea [92]CTA1,182D-0.6
Uchino et al. 2012, Japan [93]MRA6,982D-0.1
F-0.2
Bozek et al. 2012, Poland [94]CTA2,280F-2.5
Kovac et al. 2014, Serbia [95]CTA910F-0.2
Gunnal et al. 2019, India [32]Cadaveric340D-0.9
A-2.1
Reci and Bexheti 2019, North Macedonia [28]Cadaveric50D-2
A-2
Oo et al. 2021, Myanmar [30]Cadaveric100D-1
Sharma et al. 2023, India [64]CTA578D-0.3
F-0.2

MRA, magnetic resonance angiography; CTA, computed tomography angiography; A, accessory; D, duplication; F, fenestration.



In fenestration, arterial lumen divides into many channels with muscularis and endothelial layers, sharing adventitia (Fig. 5G) [81]. Continuation of arterial branches that merges into definitive MCA is known as fenestration. Cadaveric studies report greater frequency of fenestration because direct viewing of anatomic specimen allows better visualisation [82]. Fenestration has limited clinical significance, aneurysm rarely arises at its proximal end [83]. Advance imaging techniques have equipped radiologists to identify more variations. Recently, higher incidence fenestration (5.2%) was observed in 3D rotational angiography [84].

Artery from A1 segment of anterior cerebral artery (ACA) is termed as accessory MCA (Fig. 5H) [85]. Accessory MCA arises from ICA between anterior choroidal artery’s origin and ICA’s terminal bifurcation [73]. It’s difficult to distinguish duplicated MCA from accessory MCA. Both serve MCA’s region and come from distinct backgrounds. Duplicate artery originates from distal ICA, whereas accessory is little branch of ACA [86]. Anomalous MCA is frequently associated with aneurysms but might be incidental finding [87]. Rarely, cases with both duplicated and accessory MCA have been documented [87, 88]. Incidence of branching pattern and anomalies [6, 17, 19, 22, 24, 28, 30-33, 35, 47, 50, 53-56, 63, 64, 76, 77, 79, 80, 82, 85, 89-95].

Thirteen studies (n=2,700) were used for pooled length of MCA (Table 6). Pooled mean length was 16.53 cm (95% CI, 15.33–17.72) with Higgins and Thompson I2 value of 98%. Pooled mean diameter was 2.85 cm (95% CI, 2.52–3.17) I2value of 100%. Total of nine studies were used for pooled diameter (n=2,106). Heterogeneity between studies included to calculate pooled length was tested using Begg’s and Mazumdar’s rank correlation test z=1.1 P=0.272. Heterogeneity between these studies was also tested using Egger’s test t=2.61, df=11, P=0.024. Subgroup analysis was done side and sex-wise. Mean pooled length of MCA was greater on left side. Mean pooled length was greater among males. Pooled mean diameter is equal on both sides and was slightly greater among males. Subgroup analysis was done to find pooled proportion of different shapes, patterns, anomalies. Most common pattern was type 3 (0.81 [95% CI, 0.73–0.87]), I2=92%, and common shape was straight (0.39 [95% CI, 0.34–0.44]), I2=88%. Most common anomalies were accessory and duplicated MCA.

Table 6 . Pooled analysis of pattern, shapes, and anomalies of middle cerebral artery

SubgroupNo. of studiesSample sizePooled estimate (95% CI)I2 (%)P-value
Pattern
171,5400.06 (0.02–0.16)89<0.01
241,0160.04 (0.01–0.15)93<0.01
3192,7920.81 (0.73–0.87)92<0.01
4203,3460.12 (0.08–0.17)86<0.01
Quadrifurcation61,4140.01 (0.01–0.03)39<0.15
Shapes
S47730.18 (0.15–0.21)530.10
U23290.34 (0.29–0.40)85<0.01
Inverted U23290.06 (0.04–0.09)96<0.01
Straight33540.39 (0.34–0.44)88<0.01
Anomalies
Accessory116,4400.01 (0.01–0.02)320.14
Duplication1112,3920.01 (0.00–0.02)81<0.01
Fenestration918,3400.00 (0.00–0.01)94<0.01

Fixed effect model was used to find out pooled analysis due to less number of studies. CI, confidence interval.



Microstructural changes with age and aneurysm

MCA is muscular artery whose composition is similar to elastic arteries. Elastic tissue is reduced to well-defined, fenestrated internal elastic lamina, and diffuse exterior elastic lamina. Tunica media has thick smooth muscle layer, scattered collagen and elastin. Vasa vasorum is in adventitial layer, but little branches may be seen in media. Compared to other extracranial arteries, MCA has comparatively thinner tunica media and poorly developed external elastic lamina [96].

Well-developed internal elastic lamina, tunica media and adventitia were noted in MCA by Idowu et al. [96]. Media tapered near bifurcation and completely replaced by adventitia. Tunica media was thus thicker than adventitia except at bifurcation. However, tunica adventitia was broader at bifurcations (0.21 mm) [96].

Aging of MCA shows changes in intima, comprise of hypocellular fibrous tissue with few elastic fibres. After 60 years, intima thickening is highly noticeable [97].

At bifurcation, gaps in tunica media and thinning of media are reported in 60% and 25% cases. Width of gaps in tunica media vary from 30–1,000 µm. Scanning electron microscopy shows folds or rugae in intima of postmortem vessels and there are approximate 18 folds/mm. Loss of rugae is seen just proximal to bifurcation and intima is flattened in 50% [98].

Absence or fragmented elastin is crucial in aneurysm formation [99]. Gaps in tunica media are common but aneurysms are seen only in 2%. Aneurysm has walls of fibrous tissue 30–300 µm thick with few elastic fibres. Smooth muscle of media ceases abruptly at aneurysm necks. There may be greater strain between elastic and inelastic parts of vessel wall, altering stresses at bifurcation. It may damage elastic lamina, intima and predispose to aneurysm [98].

Developmental basis of variations

MCA development is associated with lobes of cerebrum [48, 100]. It is shaped like spider web and appears as plexiform network from ICA [100]. As brain develops, it gives rise to vessel with terminal circulation and few escape pathways. MCA is first detected at 4 weeks and 12 mm embryos [5].

At 28–30 days, ICA branches into cranial and caudal divisions. Cranial division gives primitive arteries at 7–12 mm stage, largest being anterior choroidal artery. Cranial branch continues as ACA, caudal division as posterior communicating. At 12–14 mm stage, plexiform arterial twigs arise from cranial division which by fusion and regression, form trunk of MCA and lateral striate arteries. It supplies significant portion of cerebral hemispheres, although it’s plexiform. At 16–18 mm stage, plexiform vessels fuse to form single artery. Primitive olfactory artery (POA) is last branch of cranial division of ICA. It has two branches: one supplies nasal fossa and other, medially, goes to developing olfactory nerve root. Latter is medial olfactory artery, which unites with artery from other side at mid-line area of future anterior communicating artery. POA diminishes around 43–45 days of development (20–24 mm) (Fig. 6). Derivatives of POA like recurrent artery of Heubner, medial striate artery extends in lateral direction, supplies basal ganglia and anastomose with lateral striate groups [100].

Figure 6. Showing schematic presentation of development of middle cerebral artery (MCA). (A) Internal carotid artery (1) branches to form a cranial division (2) and caudal division at 4–5 mm stage (3). (B) Primitive anterior choroidal artery (4) arises from cranial division at a stage of 7–12 mm and cranial division continues as anterior cerebral artery (5). (C) Arterial twigs (7) appear distal to anterior choroidal artery (6) at a stage of 12–14 mm. (D) Caudal division continuing as posterior communicating artery (9); cranial division continuing as primitive olfactory artery (10); development of plexiform network from arterial twigs (8). (E) Disappearing plexiform network (11); development of MCA from plexiform network (12); development of medial olfactory artery from primitive olfactory artery (13); branch of primitive olfactory artery supplying nasal fossa (14); recurrent artery of Heubner arising from primitive olfactory artery (15). (F) MCA becoming prominent after regression of plexiform network at a stage of 16–18 mm (16); and (G) at 40 mm stage MCA acquires adult configuration (17).

Segmental fusion failure can lead to early bifurcation, trifurcation, quadrifurcation, and single trunk development [100].

This review has few limitations as aneurysm cases comparison with others could not be done due to limited data for analysis, differences between cadaveric and angiographic studies were not statistically analysed. This review has excluded fetal, animal and few studies due to incomplete data.

Present study has provided meta-analysis, sub group analysis and pooled analysis of data related to morphometry, morphology, variations and anomalies of MCA. However, earlier authors have provided meta-analysis on different treatment procedures related to pathology of MCA.

M1 segment of MCA is mostly straight (39%) and S-shaped (18%) in morphology. Mean M1 segment length and diameter is 16.53 cm and 2.85 cm, respectively. Left MCA is longer but diameter is same on two sides. Males have greater mean length and mean diameter than females most prevalent branching pattern for MCA is bifurcation (81%). Awareness of MCA morphology and branching pattern will aid surgeons to minimise errors and provide best possible outcomes.

Conceptualization: US, SV, SA, AK. Data acquisition: US, SV, SA, AK. Data analysis or interpretation: US, SV, SA, AK. Drafting of the manuscript: US, SV, SA, AK. Critical revision of the manuscript: SV, SA. Approval of the final version of the manuscript: US, SV, SA, AK.

No potential conflict of interest relevant to this article was reported.

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