The development of the circulatory system, as cited by Menshawi et al , begins with the formation of the six pairs of the primitive aortic arches within the 1.3 mm embryonic stage. These primitive arches stem from the aortic sac and course through the branchial arches, and then terminate in the ipsilateral dorsal aorta. The second and third aortic arches and a cranial continuation of the dorsal aorta are noticed in a 3.7 mm embryo . The cervical part of the internal carotid artery (ICA) is derived primarily from the third aortic arch, whereas the other ICA segments represent cranial extensions of the dorsal aorta. In the embryos of 4–5.7 mm (28–30 days), the paired ICAs give the primitive maxillary artery and bifurcate into the cranial and caudal divisions. The cranial division is the precursor of the ACA, the anterior choroidal (AChA) and the middle cerebral (MCA) arteries, whereas the caudal division is the base of the posterior communicating (PCoA) and the posterior cerebral (PCA) arteries.
There are also other hypotheses about the ACA development. As cited by Niederberger et al , the ACA development initially refers to the three vessels and the presence of the anterior communicating plexus between them. The third A2 or the median artery of the corpus callosum and the anterior communicating plexus usually regress. As presented by Moffat , in the human embryo of 4–5.7 mm, the cranial division of the primitive ICA constitutes the primitive olfactory artery (POℓA) that terminates in the nasal fossa, while the secondary artery constitutes the medial olfactory artery; this latter artery will become the ACA, while the terminal portion of the POℓA usually regresses. The aplasia of one or both ACAs is probably a consequence of the incorporation of the cranial branch of the primitive ICA into the POℓA, the MCA and the AChA; however, the POℓA regresses and does not become the ACA from an unknown reason; the possible consequences are either that the normal ACA becomes bihemispheric in the case of unilateral ACA aplasia, or that MCA collaterals develop and supply the ACA territory in the case of bilateral ACA aplasia.
We found one case (1/388) of unilateral aplasia, and one case (1/388) of bilateral aplasia of the ACA in the presence of the ICA in the specimens of Serbian population. We did not include any case of ACA absence caused by the aplasia of the ICA. The frequency of less than one per cent was recorded also both in patients without vascular pathology of Turkish population , and in cadavers of Indian population . In addition to that, Dimmick and Faulder  noted that A1 aplasia could be seen in 1–2% of cases, which is supported in report by Siddiqi et al . However, Kane et al  found 9.6% of A1 aplasia in the angiograms of the patients investigated because of different pathological disorders excluding arteriovenous malformation or intracranial hemorrhage, whereas Alawad et al  found it in 4.2% of the patients with different pathology excluding cerebrovascular accidents.
Ağayev et al  noted that the genetic features of certain populations may affect the incidence of A1 aplasia; however, the studies in some countries did not confirm this finding. In Serbia, Ješić et al  discovered A1 aplasia in 2.9% of the angiograms of 1000 patients with different pathology; however we found 0.51% of (unilateral and bilateral) ACA aplasia in cadavers autopsied due to different reasons and pathology as well. In Japan, Wanibuchi et al  discovered 11.1% of A1 aplasia among nine patients with the ACA aneurysms, whereas Uchino et al  recorded 50/891 (5.6%) the patients with A1 aplasia suspected to suffer from cerebrovascular disease, while Nagahama et al  recorded 3.6% of A1 aplasia among the 55 patients hospitalized because of the instrumentation of the posterior cervical spine. In addition, Uchino et al  found a higher frequency of aplasia of the right ACA (31) vs. the left ACA (19) aplasia in Japanese population.
We found one case of a bilateral ACA aplasia among 388 cases, while Fisher  found two cases among 414 cadavers. Cho  described it as a case report.
We think that previously cited frequencies of unilateral ACA aplasia should not be taken as fixed values, especially because some authors do not distinguish ACA hypoplasia from aplasia [6, 8, 17, 31, 43, 54], or aplasia from agenesis [8, 16, 17, 23, 42]. Wanibuchi et al  described A1 hypoplasia in the text, while they marked the same case as “aplasia” in the table. Han et al  marked aplasia in the legend of the Fig. 2, although (hypoplastic) A1 is visible on the right side in the first image and on the left side in their second image. Furthermore, Chuang et al  and Saikia et al  recognized hypoplastic A1 if its diameter is either < 1 mm or absent (invisible). Some clinicians pointed out that an acquired occlusion of the A1 segment in elderly patients may be diagnosed as A1 aplasia in the MRA , as well as that the presence of the Doppler signal could not exclude the possibility of A1 aplasia in the MRA . According to the fact that there is a difficulty in distinguishing aplasia from hypoplasia of the A1 using the MRA or the DSA [8, 17, 36, 43, 54], we strongly believe that the anatomical, forensic or surgical dissections are the only relevant methods to use for their proper distinction and differentiation. In addition, from the anatomical point of view, the hypoplastic ACA is a morphologically formed vessel having its origin, course, distribution of side branches and termination, in contrast to the aplastic vessel. Further, the vascular source, i.e. the ICA should exist in the case of ACA aplasia, while it should be missing in the case of “ACA agenesis”. Another example of a contradictory description could be seen in detecting the presence of “the ACoA” in the cases of ACA aplasia [1, 3, 12, 47]. We think that in the case of unilateral (or bilateral) ACA aplasia, the ACoA cannot exist, because it develops from the plexiforme anastomosis of both ACAs [32, 33, 51]. According to the cistern of the lamina terminalis, the ACA course was divided into the pre- and postlaminar part of the ACA. A unique feature of the ACA is that it can be bihemispheric as in the cases of its hyperplasia, hypoplasia, or aplasia of the opposite ACA; however, we think that the ACoA is formed only in the first and second, but not in the third case.
As for the descriptions of the origin of the left and right ACAs from one ICA, as described by Burbank and Morris , and Kawaji et al , a persistent POℓA probably assumed the role of the “second” ACA [32, 33, 52]. Similar descriptions were also found in the articles of Pokhrel and Bhatnagar , and Saikia et al , but their schema and/or images do not correspond to the text, i.e. these images presented bihemispheric ACAs.
Hendrikse et al  proved that the flow volume in the contralateral ICA was significantly increased in the subjects with A1 aplasia comparing to the subjects with both A1 parts and comparing to the volume flow in the ipsilateral ICA. Raghothaman and Pandit  suggested that the high flow in one ACA, as a consequence of the aplasia of the opposite ACA, could have led to the formation of a large aneurysm. Although we have not found it, we are also of the opinion that unilateral A1 aplasia predisposes an aneurysm formation, as Ağayev et al  and Lazzaro et al  reported. From the Tables 2 and 3 it can be seen that the aneurysm of the ACA could be expected in “each fourth case” of aplasia of the opposite ACA. Although Chuang et al  claimed that in the absence of the ICA occlusion, A1 hypoplasia/agenesis could be an independent contributor to the risk of ischemic stroke, we found that only 4/42 of all the analyzed literature cases of A1 aplasia were accompanied with cerebral infarctions [4, 5, 12, 25], contrary to the finding of 1/50 A1 aplasia in the study by Uchino et al . The data of the analyzed single cases from 16 countries in the Table 2 indicate that aneurysms of the right ACA were more frequent among the cases of the left ACA aplasia (6/20), than vice versa (3/18).
The two recent cases belong to a female and male cadaver, as Gunal et al  reported. In some retrospective studies the authors did not keep the evidence about the gender of patients with unilateral A1 aplasia , except for in those of Kwon's and Lee's , Uchino et al , and Ješić et al , which showed that it is more frequent among males.
We noticed vascular variations associated with ACA aplasia in the Table 2 as certain authors described. However, some of them were of unique kind, such as the unilateral PCoA aplasia [30, 35, 48], or the VA aplasia , or the persistence of primitive carotid-basilar anastomoses ― the trigeminal artery , or the hypoglossal artery , or the proatlantal intersegmental artery , or an unusual course of the ACA in the A1 part [23, 36, 42]. Another rather interesting fact is that associated vascular variations were not evidenced in the 16/38 literature cases of unilateral ACA aplasia.
Fisher  presented the two cases of bilateral partial aplasia of the ACA by schema, while Cho  discovered the total bilateral aplasia of the ACA and consequently developed a leptomeningeal collateral flow from the MCA in a 64-year-old man. We did not only find bilateral ACA aplasia associated with BA ectasia and the left PCoA hypoplasia, but also MCA collaterals developed in a 68-year-old male.
Although the two recent cases of unilateral and bilateral A1 aplasia were without cerebral aneurysm or infarction, we cannot conclude that A1 aplasia is a single entity. The reason is a relatively great frequency of cerebral aneurysms calculated according to the number of every one of the recent and literature cases of A1 aplasia, or the incidences of A1 aplasia in the specimens with ACA aneurysms presented in the previous tables. This is another reason why we should investigate and compare the relations of hypoplastic ACAs and the associated abnormalities with the presented findings in this article and available literature.