Congenital internal carotid artery hypoplasia: A systematic review

Abstract

This review evaluates the current evidence for the clinical management of congenital internal carotid artery hypoplasia (CICAH). We summarise clinical presentations diagnostic standards, imaging recommendations, treatment and follow-up. The review was prompted by a case of CICAH in a 50-year-old female who presented to our neurosurgery clinic with an acute episode of vertigo. The patient underwent CT angiogram, which showed an unusually low right carotid bifurcation. The right internal carotid artery (ICA) was hypoplastic, and the A1 segment of the anterior cerebral artery (ACA) was absent. Skull base CT showed an ipsilateral hypoplastic carotid canal. To summarise current evidence for clinical management of CICAH we followed PRISMA guidelines to identify papers meeting our predefined inclusion criteria. We searched three databases using the terms ‘ICA’ and ‘Hypoplasia’. We reviewed 41 papers meeting our criteria. 34 were clinical reports. We performed a data extraction and quality appraisal on these reports. We found that CICAH may be less rare than previously described. Blood pressure control in CICAH is crucial due to the increased risk of stroke and aneurysm formation. Follow-up imaging is strongly recommended. Carotid doppler sonography is a powerful and underutilised diagnostic tool, and carotid canal hypoplasia is not a pathognomic sign. In conclusion, clinicians should be alert to anatomic variations such as CICAH because these produce haemodynamic changes that may have serious clinical consequences. We recommend a central registry of patients with CICAH in order to understand the longer-term natural history of the condition.

Introduction

Congenital internal carotid hypoplasia (CICAH) is an anomaly caused by incomplete development of one or both carotid arteries. This article reviews current knowledge of congenital CICAH and synthesises clinical recommendations. A case of CICAH presenting at our neurosurgery clinic prompted this investigation. Knowledge of anatomical variants is crucial for differential diagnoses, and aids proper planning for interventional radiology and surgical procedures. Ignorance of anatomical variants accounts for an estimated up to 10% of cases of malpractice. ¹ Our review includes a case report of an incidentally found left sided CICAH, associated with an extremely short common carotid artery (CCA) and aplasia of the A1 segment of the anterior cerebral artery (ACA). As the clinical management of such a case was unclear, we performed a systematic literature search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and synthesised recommendations based on our findings. This review emphasises the need for standardised clinical management protocols.

Hypoplasia can be understood as the mildest of three graded dysplasias: Agenesis, aplasia and hypoplasia. CICAH is defined as an incomplete or underdeveloped internal carotid artery (ICA), with a narrowing that typically starts 1–2 cm above the carotid bifurcation, continuing along the course of the vessel.^2,3 The condition is frequently associated with a large contralateral ICA, ⁴⁶ an observation which can be used to help differentiate CICAH from acquired disease. Imaging findings that show hypoplasia of the carotid canal is typically used to differentiate acquired ICA stenosis from a true developmental defect.

Patients can present with signs of cerebral ischemia, but many are asymptomatic as the circle of Willis maintains adequate brain perfusion. The condition reportedly has a prevalence of less than 0.01%.^4,5 CICAH is associated with an increased risk of aneurysm formation, and the associated haemodynamic changes contribute to a thrombophilic environment.

To summarise current knowledge of CICAH, we systematically reviewed papers that met our predefined inclusion criteria. We aimed to describe CICAH epidemiology, and characterise the anatomical findings and clinical presentation. Regarding clinical management, we evaluated the current evidence concerning diagnostic standards, vascular imaging and follow-up.

Methods

Search strategy and study selection

To identify relevant literature we performed a systematic search across four databases (Pubmed, Web of Science, Cochrane Library and Ovid). We formed a search string using the following MeSH (Medical subject heading) terms: ‘ICA’ AND ‘Hypoplasia’. We followed PRISMA guidelines for study design, search strategy, data extraction and analysis. The search was limited to English language articles published in the last decade (September 2011–August 2021). Two reviewers independently screened search hits against our criteria.

Inclusion criteria were: Findings of ICA hypoplasia, angiographic imaging methods and imaging of the carotid canal. Articles eligible for inclusion were case reports, case series, letters, cohort studies, reviews and epidemiological studies. Exclusion criteria were reports of ICA agenesis, ICA aplasia, acquired ICA hypoplasia, moyamoya disease and reports of hypoplastic variants of cerebral vessels other than the ICA, except when CICAH co-existed with another condition. We excluded reports without appropriate imaging because the diagnosis could not be confirmed. Ineligible articles were editorials, randomised controlled trials, and animal, in vitro or in silico experiments. Systematic search and screening was performed in duplicate on 4 separate occasions. Two researchers (HW and AZ) screened abstracts independently and reached consensus on which articles to include. We recorded all search terms, Boolean operators, number of hits in each database, and dates of searches (Supplementary data 1). We resolved differences in selection by discussion between researchers. After screening and removing repeats, a total of 41 articles were selected. This process is summarised in a PRISMA flowchart (Figure 1). We defined agenesis as: ICA non-visible, absent carotid canal; aplasia as ICA non-visible along part of its length, narrow carotid canal; and hypoplasia as ICA narrow along all or part of its length, narrow carotid canal.

Figure 1.

PRISMA flowchart. Visual summary of study identification, selection and screening.

Data extraction and quality assessment

Data extraction and quality assessment was performed manually on all case reports. Two authors (AW and AZ) extracted the following data: first author, journal, publication year, age, gender, presenting complaint, vascular imaging modalities, lateralisation, ICA diameter, carotid canal findings, collateral circulation and associated conditions. We developed a modified version of the Joanna Briggs Institute (JBI) critical appraisal tool for quality assessment. ⁶ Inspired by the CARE checklist, ⁷ we included one additional appraisal tool item: did the patient provide informed consent? (Supplementary Data 2). Two reviewers (HW and AZ) scored papers independently, reaching consensus on 95% of the items. Disagreements were resolved via discussion with a third reviewer. From a possible total score of 16 points, papers scoring 75% or above (12–16 points) were categorised as low risk of bias, 50–75% (8–11 points) as medium risk, and 50% or less (0–7 points) as high risk of bias (Supplementary Data 3).

Results

Case report

A 50-year old female presented at our neurosurgery clinic with an acute episode of rotary vertigo with humming in the right ear. This was accompanied by an accentuated physiological tremor, dizziness, nausea without vomiting and rapid spontaneous remission. Neurological examination and blood tests were otherwise normal, there were no comorbidities, and previous medical history was insignificant. Results of magnetic resonance imaging (MRI) of the brain and cervical spine were normal with only mild areas of gliosis in the supratentorial white matter. However, MRI showed a markedly slender and coiled ICA in all captured ranges. Subsequently, the patient underwent digital subtraction angiography (DSA) and computed tomography (CT) imaging. DSA showed an anatomical variation: very short right CCA and hypoplastic right ICA (Figure 2). The right ICA was slender without stenosis and slightly coiled under the base. There was agenesis of segment A1 of the ACA, with the distal ACA filled by the anterior communicating artery (AComA) from the left. The right middle cerebral artery (MCA) was dominantly filled from the right posterior communicating artery (PComA). A skull base CT confirmed congenital ICA hypoplasia, as the right carotid canal was markedly narrow (Figure 3). These findings were explained to the patient, who was then referred back to the neurologist. The patient gave informed written consent for participation in and publication of the present study.

Figure 2.

DSA investigations. (a) DSA in the anteroposterior (AP) view of the left ICA, demonstrating normal anatomy of the left side. The ICA is normal, with no stenosis or aberrant course of the artery. (b) DSA in the AP view of the right brachiocephalic trunk. The right common carotid artery is unusually short and the right ICA shows marked hypoplasia. (c) DSA in the AP view of the right ICA. The artery is hypoplastic with increased coiling at the skull base (C1 segment). Hypoplasticity is uniform along the entire artery. A1 segment is absent. (d) DSA in the lateral view of the right vertebral artery.

Figure 3.

CT investigations. Axial CT of skull base, revealing right-sided hypoplasia of the bony carotid canal (black arrow). The right canal has a diameter of 2.69 mm, while the left canal has a diameter of 5.59 mm.

Search results

The current literature on CICAH consists mainly of clinical case reports. Our search yielded a total of 705 hits. After screening against our inclusion criteria, 41 papers were selected for review (Table 1). Thirty-four of these papers underwent data extraction (29 case reports, two letters, two case series and one meeting abstract). This represented a total of 37 cases of CICAH. The remaining articles included seven cohort studies,^9–15 one letter ¹⁶ and one review. ¹⁷ The mean age at diagnosis was 41.4 years. Genders were represented almost equally, with a slight female preponderance (F 53%, n = 18; M 47%, n = 16). Three paediatric cases did not report gender. Of our 37 cases, 9 were bilateral, 16 right-sided and 12 left-sided (Table 2). Cohort studies of CICAH place the overall prevalence of the condition above the often-stated figure of 0.01%. Below, we summarise the findings of these papers and synthesise a narrative summary of the results across four subsections: Prevalence, presenting complaints, imaging modalities and anatomical findings.

Table 1.

Summary of all records included in the systematic review.

First author, publication year	Journal	Title	Publication type	Included in data extraction and quality appraisal
Aburto-Murrieta, Y. 2011	Vascular and endovascular surgery	Asymptomatic carotid rete mirabile and contralateral carotid agenesis: a case report	Case report	Yes
Agarwal, H. 2019	Neurology India	Bilateral carotid hypoplasia with multiple posterior circulation aneurysms	Case report	Yes
Aktaş, H. 2020	Surgical and radiologic anatomy	Rare congenital anomalies of the internal carotid artery: anatomic and radiologic aspects of three cases and review of the literature	Case series	Yes
Anagiotos, A. 2019	BMJ case reports	Aberrant internal carotid artery in the middle ear: the duplication variant	Case report	Yes
Bhat, D. 2011	Indian journal of radiology and imaging	Bilateral hypoplasia of the internal carotid artery	Case report	Yes
Bohm, L. 2017	American journal of medical genetics	Neuroradiographic findings in 22q11.2 deletion syndrome	Retrospective cohort	No
Chen, P. 2015	Journal of ultrasound in medicine	Internal carotid artery hypoplasia: role of colour-coded carotid duplex sonography	Retrospective cohort	No
Dawson, A. 2012	Journal of vascular surgery	Hypoplastic internal carotid artery stenosis with a low-lying carotid bifurcation causing cerebral ischemia	Case report	Yes
Deprez, F. 2015	Journal of clinical neurology	Congenital horner syndrome with heterochromia iridis associated with ipsilateral internal carotid artery hypoplasia	Case report	Yes
Diestro, J. 2021	Canadian journal of neurological science	Congenital Horner’s syndrome and internal carotid artery hypoplasia	Case report	Yes
Dinca, E. 2017	Asian journal of neurosurgery	Challenges in a case of ophthalmic artery aneurysm associated with abnormal internal carotid arteries	Case report	Yes
Franken, K. 2020	Eurorad	Hypoplasia of the internal carotid artery	Meeting abstract	Yes
Garcia-Medina, J. 2017	Canadian journal of ophthalmology	Optic nerve hypoplasia and internal carotid artery hypoplasia: a new association	Letter	Yes
Guillen-Climent, S. 2021	International journal of dermatology	Pseudoxanthoma elasticum-like syndrome with coagulation deficiency associated with carotid artery, hypoplasia and a novel gamma-glutamyl carboxylase gene mutation	Letter	Yes
Gupta, B. 2016	Brain Circulation	A rare case report of bilateral internal carotid artery hypoplasia in postpartum female: Clinical spectrum and role of various modalities in diagnosis	Case report	Yes
Gupta, R. 2019	Journal pediatric neuroscience	Arterial ischemic stroke in a Child with internal Carotid Artery Hypoplasia and Protein S Deficiency	Case report	Yes
Hou, D. 2019	Medicine (Baltimore)	Congenital internal carotid artery hypoplasia: Case report	Case report	Yes
Jianu, D. 2018	Romanian journal of morphology and embryology	Multiple congenital anomalies of carotid and vertebral arteries in a patient with an ischemic stroke in the vertebrobasilar territory. Case report and review of the literature	Case report	Yes
Lyu, D-P. 2019	Journal of stroke and cerebrovascular diseases	Acute cerebral infarction in a patient with persistent trigeminal artery and homolateral hypoplasia of internal carotid artery distal anastomosis: a case report and a mini review of the literature	Case report	Yes
Mackel, C. E. 2019	World neurosurgery	Neural crest cell failure as embryogenesis for fusiform aneurysm of the anterior communicating artery: case report and review of the literature	Case report	Yes
Melit, L. 2019	Medicine (Baltimore)	Acute ischemic stroke in a 7-month-old infant, risk factors, and diagnosis peculiarities: A case report	Case report	Yes
Mohan, D. 2015	Chirurgia (Bucur)	Surgical difficulties in a case of left ophthalmic artery ruptured aneurysm associated with right ICA hypoplasia––case report	Case report	Yes
Mujagić, S. 2016	Acta Medica Academica	Symmetry, asymmetry and hypoplasia of the intracranial internal carotid artery on magnetic resonance angiography	Prospective cohort	No
Omarjee, L. 2019	Journal of stroke	Internal carotid artery hypoplasia: a new clinical feature in pseudoxanthoma elasticum	Retrospective cohort	No
Paşaoğlu, L. 2015	Int journal of medical and pharmaceutical case reports	Unilateral hypoplasia of the internal carotid artery	Case report	Yes
Pogrebniak, A. 2021	Journal of neuro-ophthalmology	Magnetic resonance angiogram findings of internal carotid artery narrowing and anterior cerebral artery hypoplasia associated with optic atrophy after neonatal extracorporeal membrane oxygenation	Case series	Yes
Rebella, G. 2019	Acta neurologica Taiwan	Duplication of intracavernous internal carotid artery	Case report	Yes
Romeo, A. 2016	Open medicine	A rare case of persistent hypoglossal artery associated with contralateral proximal subclavian stenosis	Case report	Yes
Siddiqui, A. 2012	Journal of medical case reports	Bilateral hypoplasia of the internal carotid artery, presenting as a subarachnoid hemorrhage secondary to intracranial aneurysmal formation: a case report	Case report	Yes
Suri, S. 2020	Brain disorders and therapy	Congenital hypoplasia of the internal carotid artery (HICA): A short review	Review	No
Tugrul, S. 2013	American journal of otolaryngology	Intratympanic aberrant and hypoplastic carotid artery	Case report	Yes
Turk, Y. 2021	BMJ Case reports	Hypoplastic internal carotid artery ending as an ophthalmic artery with multiple cerebral aneurysms, fenestrated Acom and triple A2	Case report	Yes
Uchino, A. 2019	Surgical and radiologic anatomy	Hypoplasia of the internal carotid artery with associated fenestration and extremely long P1 segment of the ipsilateral posterior cerebral artery diagnosed by MR angiography	Case report	Yes
Valentino, L. 2015	Journal of pediatric and neonatal individualised medicine	Unilateral congenital hypoplasia of the internal carotid artery in a newborn: a rare case report	Case report	Yes
Vassileva, E. 2014	Comptes rendus de l’Acad’emie bulgare des sciences	Stroke due to hypoplasia of internal carotid artery: clinical and ultrasound findings	Retrospective cohort	No
Virvilis, D. 2013	Journal of vascular surgery	Bilateral retroesophageal course of the carotid arteries	Case report	Yes
Wali, A. 2016	Cureus	Hypoplastic internal carotid artery co-presenting with neurofibromatosis and intracranial masses	Case report	Yes
Yaguchi, M. 2019	Pictures in neurology	Bilateral hypoplasia of the internal carotid artery	Case report	Yes
Zhang, Z-Y. 2015	Chinese medical journal	Congenital hypoplasia of bilateral internal carotid artery with migraine-like headache with aura	Case report	Yes
Zhang, Z. 2015	Journal of stroke and Cerebrovascular Disease	Imaging Classification of internal Carotid Artery Hypoplasia Based on Distal Ophthalmic segment Occlusion	Retrospective cohort	No
Zhu, L. 2021	European journal of medical research	Monocular central retinal artery occlusion caused by bilateral internal carotid artery hypoplasia complicated with patent foramen ovale: a case report and review of literature	Case report	Yes

Table 2.

Data extraction table for all case reports reviewed.

Author publication year	Age, gender	Presenting complaint	Investigations	Leteralisation	ICA diameter (mm)	Ipsilateral carotid canal findings	Collateral circulation
Aburto-Murrieta, Y. 2011	26, F	Epilepsy evaluation	CTA, DSA	Unilateral right	—	Hypoplastic	Ipsilateral PComA
Agarwal, H. 2019	76, M	Chronic headache	CTA, DSA	Bilateral	—	Hypoplastic	Both PComAs and enlarged VA
Aktaş, H. 2020	27, H	Suspected vasculitis	CTA	Bilateral	R 2.0, L 2.0	Hypoplastic	Both PComAs
Anagiotos, A. 2019	39, F	Pulsatile tinnitus	MRA, CCDS	Unilateral right	—	Hypoplastic	Inferior tympanic artery
Bhat, D. 2011	36, M	Fall from 8 ft	DSA	Bilateral	—	Hypoplastic	Both PComAs
Dawson, A. 2012	47, M	Stroke	CTA, 3D CTA	Unilateral right	—	Hypoplastic	Persistent proatlantal artery
Deprez, F. 2015	67, M	Horner syndrome	MRA	Unilateral left	—	Hypoplastic	Ipsilateral PComA
Diestro, J. 2021	21, M	Horner syndrome	MRA	Unilateral left	R 6.5, L 2.6	Hypoplastic	Collateral cluster vessels
Dinca, E. 2017	62, F	LOC and seizure	3D-CTA,DSA	Unilateral right	—	—	—
Franken, K. 2020	50, F	Vision loss	CT, CTA, MR	Unilateral right	—	Hypoplastic	—
Garcia-Medina, J. 2017	57, F	Right pupillary defect	MRA, CCDS	Unilateral right	—	Hypoplastic	—
Guillen-Climent, S. 2021	40, M	Worsening skin laxity	CTA	Unilateral left	—	Hypoplastic	Data not available
Gupta, B. 2016	30, F	Post-partum seizure	3D CTA, CCDS, MRA	Bilateral	R 2.0, L 2.6	Hypoplastic	Collateral cluster vessels
Gupta, R. 2019	7, M	Hemiplegia	MRA, CTA, CCDS	Unilateral left	—	Hypoplastic	Ipsilateral PComA
Hou, D. 2019	58, M	Barylalia, Hemiplegia	DSA	Unilateral left	—	Hypoplastic	Contralateral ICA via ACA
Jianu, D. 2018	68, M	Vertigo gait disturbance	CTA, CCDS	Unilateral left	—	Hypoplastic	Contralateral VA hypoplasia
Lyu, D-P. 2019	48, F	Repeated TIAs	MRA, CCDS	Unilateral right	—	—	Primitive trigeminal artery
Mackel, C.E. 2019	46, M	Incidental aneurysm finding	CTA, DSA	Unilateral right	—	Hypoplastic	Supraclinoid collaterals
Melit, L. 2019	7 Months	Right Hemiparesis	CTA	Unilateral left	—	—	—
Mohan, D. 2015	49, F	LOC and seizure	DSA, CTA	Unilateral right	—	—	—
Paşaoğlu, L. 2015	56, F	Headache	CTA	Unilateral right	R 0.7	Hypoplastic	Ipsilateral PComA
Paşaoğlu, L. 2015	45, F	Headache	MRA, CTA	Unilateral right	R 1.2	Hypoplastic	—
Paşaoğlu, L. 2015	49, M	Amarosis fugax	CCDS, CTA	Unilateral right	R 1.7	Hypoplastic	—
Pogrebniak, A.2021	7 Months, -	History of ECMO	MRA	Unilateral right	—	—	—
Pogrebniak, A.2021	5 Months, -	History of ECMO	MRA	Unilateral right	—	—	Collateral cluster vessels
Rebella, G. 2019	67, F	Headache, difficulty speaking	CTA, DSA	Unilateral left	—	—	Ipsilateral PComA
Romeo, A. 2016	50, M	Dizziness, syncope, dysarthria	CCDS, 3D CTA	Unilateral right	—	—	Persistent hypoglossal artery
Siddiqui, A. 2012	48, F	Sudden onset headache	DSA	Bilateral	—	—	Both PComA
Tugrul, S. 2013	28, M	Hearing loss, aural fullness	MRA	Unilateral left	—	Hypoplastic	—
Turk, Y. 2021	40, F	Persistent headaches, LOC	MRA, DSA	Unilateral left	—	Hypoplastic	—
Uchino, A. 2019	37, F	Multiple TIAs	MRA, MIP	Unilateral left	R 3.5, L 1.0	Hypoplastic	Ipsilateral PComA
Valentino, L. 2015	Neonate, M	Seizures	CTA, 3D CTA, MIP	Unilateral right	R 2.0	Normal	—
Virvilis, D. 2013	72, F	Slurred speech, hypoglycemia	MRA, CTA, CCDS	Unilateral right	—	—	—
Wali, A. 2016	18, F	Known NF 1	MRA, DSA	Unilateral left	—	Hypoplastic	Contralateral ICA via enlarged ACA
Yaguchi, M. 2019	87, M	Right hemiplegia	CCDS, MRA	Bilateral	—	Hypoplastic	Both PComAs, enlarged BA and VA
Zhang, Z-Y. 2015	36, M	Chronic miagraine	CTA, CCDS	Bilateral	R 1.6, L 1.5	Hypoplastic	Both PComAs
Zhu, L. 2021	46, F	Amarosis fugax	MRA, CTA	Bilateral	—	Hypoplastic	Enlarged BA and VA

Prevalence

CICAH may be more common than previously thought. Reports often state the prevalence is 0.01%,^4,5,11,17,18 but recent studies suggest that the true prevalence is higher.^9,19,20,21 The underestimate may have prevailed due to the asymptomatic nature of the condition. The oldest patient in our review was 87, suggesting that the condition can be silent lifelong. ²² Aktas et al. retrospectively investigated 1,847 angiography records, discovering one case of ICA hypoplasia (0.054%). ⁹ Similar findings by Mujagić et al. revealed one case of ICA hypoplasia in 1,000 subjects (0.1%). ¹¹ A 2016 epidemiological study of 253 patients by Cappabiana et al. found variations in the level of carotid bifurcation, but no cases of hypoplasia. ²⁴ Johansson et al. screened 4042 CTA exams for anatomical variants of the circle of Willis and ICA variants, finding five cases of CICAH (1% of a cohort of 3,989 after excluding cases of extracranial occlusion). However, these authors do not define their diagnostic criteria for CICAH. ¹⁹ Tasar et al. retrospectively analysed 5,100 records in a 2004 cohort study. They found CICAH in 0.079% of records (n = 4). ²¹ Similar findings by Ito et al. showed prevalence of CICAH in 0.15% of 1,274 records. ²⁰ The largest cohort study reviewed was a retrospective analysis of 25,000 CCDS (colour-coded carotid duplex sonography) records, finding CICAH in nine patients (0.036%). ²³

Presenting complaints

Stroke-related symptoms were the most frequent reasons for an encounter with a physician (14 of 36 reports). Presentations included vision loss,^38,29,39 hemiplegia,^{8,28,40,41,42} dysarthria^8,35,43,44 and TIA.^33,36 Vision loss, specifically amaurosis fugax due to ophthalmic artery insufficiency was found in two cases.^29,39 In all cases that presented with signs of ischemic stroke, the lateralisation of the hypoplasia corresponded with the side of ischemia. In general, older patients were more likely to present with stroke symptoms, and younger patients were more likely to present with an incidental complaint unrelated to CICAH. ¹⁵ A higher incidence of atherosclerotic disease in older age groups suggests a cumulative effect, with ICA hypoplasia an exacerbating factor.^42,55 The youngest patients presenting with stroke symptoms were 7 month old ⁴¹ and neonate (onset of symptoms 27 h after birth). ³⁰ A 2014 study by Vassileva et al. investigated the association between CICAH and stroke in five cases. These patients were relatively young (30 years +/− 5.7), and four had no other risk factors for stroke. ¹⁴ The authors suggest CICAH is an independent risk factor for stroke in young people, challenging the generally accepted view that CICAH is asymptomatic and requires no treatment.

Other frequent presenting complaints were headache (six reports),^{3,15,29,44,59,62} and seizure (four reports).^28,30,63,64 SAH (subarachnoid haemorrhage) due to a ruptured aneurysm was the cause of these symptoms in four reports.^3,28,63,64

Imaging modalities

While DSA is considered gold standard for diagnosing vascular pathologies, among our reports, CTA was the most frequently utilised modality (21 records). The second most frequently utilised was MRA (17 records). DSA was used in 10 records. DSA has the problem of superimposition, which may complicate the characterisation of vascular malformations. Our study revealed that CCDS is a useful tool in assessing CICAH. Twelve of the records utilised CCDS as part of the diagnostic workup. CCDS has the advantage of assessing vessel wall thickness, and can identify plaques as a hyperechoic mass. This is crucial for differentiating atherosclerotic disease from congenital hypoplasia. Ide et al. suggest that CCDS alone is sufficient for CICAH diagnosis, ⁴⁵ but their study of only two cases does not consider the broad morphology the condition can encompass. A 2015 cohort study tested the use of CCDS by reviewing 25,000 sonograms and diagnosing CICAH in nine records, establishing the importance of CCDS in the diagnosis of CICAH. The authors recommend confirming the diagnosis with skull base CT to visualise the carotid canal.

Anatomical findings

The normal diameter of the ICA lumen is between 4 and 5 mm.^27,28 ICA diameter is not commonly investigated; only eight of the reviewed records reported it (Table 2). Excluding the neonate, seven records of CICAH that report a lumen diameter represent in total 10 hypoplastic arteries. The mean diameter was 1.73 mm (95% CI: 0.46). This is in accordance with the results of Zhang et al. who retrospectively assessed 20 patients diagnosed with CICAH, finding the mean diameter of a hypoplastic artery to be 1.6 mm (range 1.4–1.9 mm). ¹⁵

It is well established in the literature that a standard diagnostic investigation for CICAH is CT of the skull base to visualise the carotid canal. Of the 36 reviewed cases, 26 reported an associated hypoplastic carotid canal. One record reported the canal diameter as 2.5 mm on the right and 2.8 mm on the left. ²⁸ A normal carotid canal diameter is 5.27 mm (SD +/−0.62) according to a recent study. ³⁴ Ten cases did not state whether the carotid canal was investigated, and one reported a carotid canal with a normal diameter. In this case the diagnosis was based on the exclusion of other causes of ICA lumen narrowing. ³⁰

The most frequent collateral circulation pattern was the PComA (12 of 36 reports). Half of these cases were bilateral, with both PComAs enlarged.^{3,9,22,33,60,62} In the unilateral cases, the enlarged PComA was ipsilateral to the hypoplastic ICA.^{28,29,32,44,61,65} Other patterns of collateral circulation were via an enlarged vertebrobasilar system (3 reports), or via the contralateral ICA and enlarged ACA (3 reports). Three reports identified persistent primitive vessels. These were the proatlantic, ⁸ hypoglossal ³⁵ and trigeminal ³⁶ arteries.

Syndromic associations

CICAH has been associated with a number of genetic syndromes, and there is some evidence that the etiogenesis of CICAH has a genetic component. A hypoplastic ICA appears as part of syndromes such as pseudoxanthoma elasticum (PXE), Klippel-Feil syndrome, PHACE syndrome, neurofibromatosis 1 and 2, and neurocristopathies Goldenhar syndrome and DiGeorge syndrome.^{10,16,51,67,69} One study found a strong association between PXE and CICAH, recommending that all patients with PXE should be screened for CICAH. ¹⁶ One report in our review was a case of PXE-like syndrome with CICAH. Combined, these findings suggest a role for elastin degradation in the pathogenesis of CICAH. A 2017 cohort study of patients with DiGeorge syndrome revealed a high number of CICAH in this population. ¹⁰ CICAH was associated with neurocristopathy again in a 2019 report by Mackel et al. In this report the authors describe neural crest cell failure as the cause of ICA hypoplasia. The authors suggest referral for genetic evaluations when a finding of CICAH coincides with other congenital malformations. ⁵²

Discussion

Embryologic origins of ICA

In humans, at development day 24 the ICA is the first cerebral artery to form. ⁴⁶ The ICA has two embryonic origins: The distal part of the dorsal aorta, which forms anatomic segments C1–C6, and the distal part of the third aortic arch, which forms C7, the cervical segment (figure 4). At day 28 of embryogenesis, the ICA continues into anterior and posterior divisions, with the anterior forming branches to supply the developing forebrain, and the posterior forming progenitors of the diencephalic and mesencephalic arteries. The anterior division will eventually give rise to the ACA and MCA. At day 35, buds that eventually form the MCA appear on the anterior division of the embryonic ICA. The common carotid buds from the third aortic arch proximally, giving rise to the external carotid which forms via angiogenesis. As both the ICA and CCA share the third aortic arch as an embryonic origin, this may explain why CCA hypoplasia is an associated finding in CICAH.

Figure 4.

(a) 5th Embryonic week, showing the aortic arches. The third aortic arch will form the proximal part of the ICA. (b) 8th Embryonic week. ICA forms from the distal part of the dorsal aorta. (c) Fully developed vessels Illustration created by Helen Whitley on Autodesk SketchBook Pro 5.2 254 x 190 mm (72 x 72 DPI).

Theories of etiogenesis

Lasjaunaias et al. was the first to describe six segments of the ICA and theorised that aplasia or hypoplasia arises from underdevelopment of one or more of these segments. ⁴⁷ There are two major theories of etiogenesis. One claims that regression of the first and third aortic arch triggers ICA underdevelopment, and the second suggests that failure of the primitive anastomoses to regress renders a fully developed ICA unnecessary for adequate brain perfusion.^9,21,48 Some reports suggest that intercavernous collaterals develop if an embryonic insult occurs before complete development of the circle of Willis.^49,50 It is established in the literature that carotid canal development depends upon the presence of the embryonic ICA. However, not all cases of CICAH are accompanied by a hypoplastic carotid canal. ¹⁷ One such case was identified in our literature search. ³⁰ We suggest that CICAH cases in which carotid canal hypoplasia is absent represent cases in which a normally-developing ICA spontaneously regressed.

Diagnostic issues

The biggest challenge for the diagnostician is differentiating congenital hypoplasia from acquired stenosis. Differentials include atherosclerotic disease, carotid dissection, arteritis, thrombosis, fibromuscular dysplasia, SAH, cerebral infarct, moyamoya disease, ICA agenesis or other angiopathies. A range of imaging modalities are used to diagnose CICAH. Three studies used a minimum diameter threshold to define hypoplasia. Omarjee et al. used a diameter of <3 mm assessed by CCDS, with bone CT of the carotid canal to confirm diagnosis. ¹⁶ Yang et al. used a definition based on the findings of Chen et al.: CCDS findings of a lumen diameter <4 mm, with decreased flow volume and without significant atherosclerosis or wall thickening.^13,23 Diameter can be approximated from imaging modalities such as CTA and MRA, but CCDS can additionally differentiate between acquired and congenital narrowing, characterise flow changes, and identify localised areas of hemodynamic stress. In our opinion CCDS is a powerful tool in the diagnosis of CICAH and currently underutilised. However, despite its evident advantages, CCDS is unlikely to replace DSA as the gold standard due to a high level of experience and expertise required on the part of the sonographer.

Although there is agreement in the literature that CT imaging of the carotid canal is crucial in the diagnosis of CICAH, this is not completely unproblematic. Carotid canal hypoplasia is also seen in patients with moyamoya disease. ³⁴ and early onset CCA stenosis leads to carotid canal narrowing. This puts the diagnostic landmark of carotid canal narrowing into question. Additionally, carotid canals naturally exhibit a high level of natural asymmetry. ⁵³

Classification

CICAH lacks a standard classification system, as many of the reviewed reports noted. Even the terms ‘aplasia’ and ‘hypoplasia’ are used interchangeably.^4,21,57,58 Lie et al. proposed a classification system for ICA variants in 1968, with six types (A–F) according to collateral circulation. ⁵⁴ Although some cases we reviewed belonged to type E, the majority were unclassifiable. Some authors suggested a type that fitted best with their observations, and others noted that their cases had elements of more than one type.^39,40,59,60

Zhang et al. suggested a new classification based on visualisation of the ophthalmic segment. ¹⁵ They identified 20 cases of CICAH and divided them into two groups: ophthalmic segment occlusion (60%, n = 12) and non-ophthalmic segment occlusion (40%, n = 8). The ophthalmic segment occlusion group had less ischemic events, presumably due to adequate circulation from the PComA. The group without ophthalmic segment occlusion had more ischemic events, and a broader range of collateral circulation types with no dominant pattern. With circulation provided by the PComA, it is possible that ophthalmic segment occlusion occurs after the circle of Willis has already formed. A larger cohort is necessary before this system can be widely used to classify CICAH.

Clinical considerations

As previously noted, there is no current clinical management protocol for CICAH. In our review, the most common clinical presentations were stroke symptoms. The relationship between CICAH and stroke is not directly causal; rather CICAH represents an often-overlooked risk factor. Many case reports focus on preventing ischemic events as the mainstay of clinical management. We suggest even asymptomatic patients should be monitored for cerebrovascular risk. This means blood pressure control, monitoring cholesterol and lipid levels, and necessary lifestyle modifications.

It is established in the literature that CICAH is associated with a greater frequency of aneurysm formation. The incidence of aneurysm formation is 2–4% among the general population, increasing to 23–45% with ICA malformations.^17,56 Frequent locations of aneurysm formation are the basilar artery and the contralateral PComA. Aneurysm formation is associated with increased haemodynamic stress in the compensatory collateral circulation.^4,15,17,24 We recommend regular follow-up and vascular imaging investigations in asymptomatic patients. The treatment of aneurysm associated with CICAH should always be on a case-by-case basis.

CICAH has important implications for surgical and endovascular procedures. Whether an intervention is feasible or desirable depends on the particular anatomy, technology available, experience of the surgeon, and the wishes of the patient. If the decision is made to operate, there are specific features of a hypoplastic artery that present technical challenges. Luminal narrowing hinders the advance of a guiding catheter, and hypoplastic arteries tend to be particularly tortuous. This may increase the risk of vessel wall damage and consequent thromboembolic complications. Collateral feeder vessels must be carefully assessed, as these may offer safer alternative pathways. ⁵⁷ Pre-operative diagnosis of CICAH is critical, especially if both hemispheres are perfused by one dominant ICA. However, in emergent procedures where pre-operative diagnosis is not possible, it is important for the clinician to have a general understanding of the variety of anatomical variants that may be present, as this can guide decision-making, reduce complications and ultimately improve clinical outcomes.

Limitations

There are various potential sources of bias in this review. Left-sided CICAH is reportedly more prevalent than right-sided.^21,25,26 However, we found a higher number of right-sided CICAH among the reports reviewed (16 right-sided and 12 left-sided). This may indicate publication bias, reflecting greater interest in a rarer anomaly. Additionally, we excluded abstracts or posters that lacked sufficient information (imaging investigations) to confirm a diagnosis. These unavoidable sources of bias are inextricable from the methodology.

Our modified JBI critical appraisal tool was designed to identify possible sources of bias in the reports reviewed, but there is an element of subjectivity involved in scoring. To address this, two authors scored reports independently, and discussed discrepancies with a third author. Since the scoring system was designed for reports in which CICAH was the primary diagnosis, reports in which CICAH was a secondary finding scored lower on our appraisal. We did not differentiate between imaging methods used in the selected studies. DSA has a risk of misinterpretation due to superimposition. MRA has a high incidence of motion artefacts, and less spatial resolution than CTA. CTA has better visualisation of the surrounding soft tissue and bone, and more sophisticated post-processing software available. This issue was partly addressed by our points-based quality appraisal, as we scored papers according to how many imaging modalities were used, and how clearly the results were described (Supplementary data 2).

Conclusion

Thirty-seven cases of CICAH have been reported in the last decade, and cohort studies suggest the condition may be less rare than previously thought. This finding emphasises the need for standardised clinical management. We identified CCDS as a powerful and underutilised tool for diagnosing CICAH. CCDS can help differentiate between congenital and acquired vascular diseases. We suggest a multimodal approach to vascular imaging, and that DSA or MRA should not be used in isolation due to the potential for unreliable results. Our results suggest that carotid canal hypoplasia is not a pathognomic sign of CICAH. However, we recommend imaging of the carotid canal as part of the diagnostic work-up, especially if it is not feasible to assess vessel wall thickness.

There is evidence that asymptomatic CICAH patients should have regular neurological follow-ups. CICAH is an independent risk factor for stroke, and an under-recognised cause of stroke in young people. Follow-up should include managing modifiable risk factors for atherosclerotic disease. CICAH patients should have regular imaging to assess aneurysm risk. Blood pressure control is crucial in these patients. Our review has identified the need for widely accepted clinical guidelines, and we consider a central register of CICAH patients necessary to develop standardised protocols and optimise outcomes.

Abbreviations

CICAH

Congenital internal carotid artery hypoplasia

ICA

Internal carotid artery

CCA

Common carotid artery

MCA

Middle cerebral artery

ACA

Anterior communicating artery

PComA

Posterior communicating artery

AComA

Anterior communicating artery

CTA

Computed tomography angiography

MRA

Magnetic resonance angiography

DSA

Digital subtraction angiography

CCDS

Colour-coded carotid duplex sonography

SAH

Subarachnoid haemorrhage

ORCID iDs

Helen Whitley https://orcid.org/0000-0002-2798-296X

Ondřej Bradáč https://orcid.org/0000-0003-4364-5522