Intracranial aneurysms associated with middle cerebral artery anomalies: the clinical characteristics and treatment considerations: a systematic review

Background: As a result of its low occurrence, most of the studies on intracranial aneurysms associated with MCA anomalies were presented as case reports or small case series. In this study, a systematic review on this specific entity was conducted. Methods: A PubMed search of the published studies was performed on April 6th, 2019 for patients who had intracranial aneurysms associated with MCA anomalies. The languages included in this study were English, Chinese, and Japanese. Results: Finally, 58 articles reporting of 67 patients including 1 case in our center were included. The identified patients (37 females, 55.2%) aged from 4 to 81 (49.85 ± 15.22) years old. Fifty (50/67, 74.6%) patients presented with hemorrhagic stroke either because of rupture of the aneurysms associated with MCA anomalies or other sources. Sixty-three aneurysms (63/67, 94.0%) were saccular, 3 (4.5%) were dissecting or fusiform, and 1 (1.5%) was pseudoaneurysm. Thirty-two (32/65, 49.2%) patients had other concurrent cerebrovascular anomalies. Fifty-six (83.6%) patients underwent open surgeries, 8 (11.9%) patients underwent endovascular treatment, and 3 (4.5%) patients were conservatively managed. Fifty-six (56/61, 91.8%) patients achieved a good recovery. Conclusions: The pathophysiological genesis of MCA anomalies associated aneurysms is still obscure to us. The inflicted patients tend to have concurrent other cerebrovascular anomalies, which denotes that congenital defect in cerebrovascular development might play a role in this process. Open surgery is, hitherto, the mainstay of treatment for this specific entity. Most of the affected patients could experience a good recovery.

incidence of vascular anomalies [1]. Generally speaking, MCA anomalies includes accessory MCA (ac-MCA), duplicate MCA (d-MCA), d-MCA origin, MCA fenestration, and twig-like MCA. In rare circumstances, the MCA anomalies can be associated with intracranial aneurysms [2][3][4]. As a result of its low occurrence, most of the studies on intracranial aneurysms associated with MCA anomalies were presented as case reports or small case series. Hence, large-scale investigation on this rare entity in a single center is unrealistic. In this study, we would like to perform a systematic review on this specific entity to further elucidate its demographic, clinical, therapeutic, and prognostic characteristics. articles of which the full text or enough information could be obtained were included in this study. Reference lists of the identified articles were also manually searched for additional studies. Glasgow Outcome Scale was used for the outcome assessment. A Glasgow Outcome Scale score ≥ 4 was defined as good recovery. An aneurysm < 10 mm was defined as small aneurysm.

Methods
Definition of intracranial aneurysm associated with MCA anomalies Intracranial aneurysms located at the beginning or on the trunk of the abnormal MCAs were considered as in association with MCA anomalies. Aneurysms having no direct anatomical neighborhood with the MCA anomalies were excluded in the final analysis.

Location of ac-MCA and the associated aneurysm
Based on their sites of origin along the anterior cerebral artery (ACA), the ac-MCA were divided into 3 types: 1) originating from A1 segment of ACA, 2) originating from the anterior communicating artery (AComA) or A1-A2 junction, 3) originating from A2 segment.
The locations of aneurysms were at the beginning or on the trunk of ac-MCA.

Location of d-MCA associated aneurysm
The locations of aneurysms were at the beginning or on the trunk of d-MCA.

Location of MCA fenestration associated aneurysm
The locations of aneurysms were proximal to fenestration, in fenestration, or distal to fenestration.

D-MCA origin aneurysm
The locations of aneurysms were at the beginning of any branch of duplicate origins or on the common trunk.

General information
The PubMed search identified 113 records. Fifty-nine records were excluded based on titles and abstracts screening. After assessing the full text of the remaining 54 articles, 5 were further excluded. A manual searching of the reference lists of the remaining 49 articles was performed, which yielded 9 additional articles. Finally, 58 articles reporting of 67 patients including 1 case in our center were included for the analysis (Fig. 1

General information
The PubMed search identified 113 records. Fifty-nine records were excluded based on titles and abstracts screening. After assessing the full text of the remaining 54 articles, 5 were further excluded. A manual searching of the reference lists of the remaining 49 articles was performed, which yielded 9 additional articles. Finally, 58 articles reporting of 67 patients including 1 case in our center were included for the analysis (Figure 1).

Accessory MCA aneurysm
Nineteen studies reporting of 20 patients including 1 case in our center were identified (Table 1)  Eighteen (18/20, 90%) patients experienced good recovery.

Duplicate MCA aneurysm
Twenty-seven studies reporting of 34 patients were finally included (Table 2)

Duplicate MCA origin aneurysm
d-MCA origin aneurysm was only identified in a 49-year man incidentally, who was admitted for vertigo [59]. No other cerebrovascular anomaly was reported. The saccular unruptured d-MCA origin aneurysm was microsurgically clipped. The postoperative course was uneventful and no neurological deficit was reported.

Illustrative case
A 59-year old man was admitted for sudden onset of headache 2 days ago. He was a smoker and denied history of any chronic diseases. He was alert on admission. Physical
The plexiform arterial twigs would evolve into the MCA and lateral striate arteries through subsequent fusion and regression. Hypothetically, failure of this process can lead to diverse variations of the MCA (e.g. ac-MCA, d-MCA, MCA fenestration, d-MCA origin, and twig-like MCA) [1]. Generally speaking, the incidence of any MCA anomalies is very low [1,[61][62][63]. However, in even rarer circumstances, the MCA anomalies could be associated with intracranial aneurysms [2][3][4]. As a result of the low incidence of MCA anomalies, the reported cases of MCA anomalies associated intracranial aneurysms were all presented as case reports. Hence, the true incidence of MCA anomalies associated aneurysms in patients with MCA anomalies is still unknown. According to this study, 49.

Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.