First Report of Interaction Among Ponticulus Posticus Anomaly and Stenosis of Carotid, Vertebral Arteries

Abstract

In humans, body asymmetry might affect vascular asymmetry. This study aimed to examine whether there is a relationship between side asymmetry and the presence of ponticulus posticus (PP) anomaly, carotid, and vertebral artery stenosis. Retrospective analysis was done on the data files of patients with carotid and vertebral arteries who were admitted to our hospital between November 2018 and December 2022 for the presence of PP anomaly. There were 31 patients (25 males and 6 females, with a median age as 69.54 years (range 51–84 years). PP anomaly was detected in 11 of 31 patients (31.48% of cases). The correlation test showed that the presence of PP was negatively correlated with carotid stenosis on the right side, but there was no such correlation on the left. This study demonstrated that there is an innovative anatomical correlation between the PP anomaly and carotid stenosis in the adult patient cohort.

Introduction

In India, stroke ranks as the third most common cause of death and the second largest contributor to disability.[1] A symptomatic carotid disease is an important issue in stroke neurology.[2] The ponticulus posticus (PP) anomaly is an osseous bridge that can be formed on the posterior arch of the atlas.[3] This foramen completely or partially encircles the vertebral artery[4] before entering the cranium. Although PP has been intensively investigated, there is currently a lack of studies about the laterally dependent relationship between carotid and vertebral artery stenosis and the PP anomaly. We believe that vertebral artery dimension changes related to the PP anomaly could be connected to carotid artery stenosis. Currently, many advancements have been observed in medical practice and radiology;[5] however, the relationship between the presence of the PP anomaly and the carotid and vertebral arteries has not been studied yet. Therefore, we conducted this study.

Materials and Methods

Recep Tayyip Erdogan University’s ethical committee gave its clearance for this work. All individuals taking part in the study gave their informed consent.

Participants

We retrospectively analyzed the data files of patients with carotid and vertebral artery conditions who admitted to our hospital between November 2018 and December 2022. Patients with poor neurological conditions and pathology affecting the atlas (e.g., dislocation, fracture, and tumor) were excluded from the study. Carotid and vertebral Computed tomographic angiography (CTAs) were performed using a 320-detector Computerized tomography (CT) scanner. Iopamidol 370, a nonionic contrast agent, was administered intravenously in a bolus. Images were captured by Toshiba Medical Systems, Japan, using the following settings: 120 kV, 100 mA, 16 × 1.5 mm collimation, 3 mm thickness, and 512 × 512 matrix. Using a workstation with three dimensional (3D) imaging software, 3D reconstructions of the pictures were performed to overlap 0.2-mm sections for better resolution. The CTA images were retrospectively reviewed. The presence of PP was graded as no PP, partial PP, semi-partial PP, and complete PP by the same neuroradiologist (HG). Figure 1a-c show the degree of PP of three different patients.

Figure 1.

(a-c) The grading of PP was displayed. (d-g) Images of a patient with asymmetric PP are depicted. It was observed that the side without PP had a hypoplastic VA. PP: pointiculus posticus, VA: vertebral artery

Doppler ultrasound examination

All patients underwent a Doppler ultrasound examination. With commercially available linear array high-frequency (5–10 MHz) transducers, the ultrasound measurements were carried out using B-mode and color Doppler ultrasonography (5–10 MHz) transducers (APLIO 500, Toshiba Medical, Japan). The radiologist (HG) performed the measurement.

Measurement

The degree of stenosis in the internal carotid artery was assessed. Spectral measurements were obtained and recorded. Vertebral artery (VA) diameter was measured at the atlas level by electronic calipers bilaterally, and their averaged value (left + right) was used in the statistical analysis.

Statistical analysis

SPSS for Windows version 23.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. The normality of the distribution was examined with the Shapiro–Wilk test. A nonparametric Wilcoxon rank test was used to compare the values of both sides. Levene’s test was used to assess the equality of variances. For the comparison of the two groups, the Mann–Whitney U test was used. The correlation coefficient was calculated between diameters measured in ultrasonography. All parameters are shown as the mean ± Standard deviation (SD) and the range. The level of statistical significance was set to P ≤ 0.01 for all tests.

Results

The data of 31 patients (25 males and 6 females) were analyzed. The median age at presentation was 69.54 years (range 51–84 years). The mean ± SD diameters of the arteries in mm and flow velocities measured by ultrasonography on the right and left sides are shown in Table 1.

Table 1.

Right and left side carotid vertebral changes

Descriptives
		N	Mean±SD	Std. Error	95% Confidence Interval
Carotid stenosis	Right	25	70.40±14.64	2.92	64.35-76.44
	Left	25	72.20±16.46	3.29	65.40-78.99
Carotid PSV	Right	31	153.16±70.43	12.65	127.32-178.99
	Left	31	157.87±67.28	12.08	133.19-182.55
Carotid diamater	Right	30	11.26±1.66	0.30	0.03-1.18
	Left	30	10.97±1.51	0.27	0.02-1.04
Vertebra PSV	Right	31	76.70±47.24	8.48	59.37-94.04
	Left	31	78.93±59.18	10.63	57.22-100.64
Vertebral Diamater	Right	31	3.19±0.66	0.11	2.95-3.44
	Left	31	3.38±0.48	0.08	3.20-3.56

PSV: peak systolic velocities, SD: standard deviation

The mean ± SD diameters of the carotid arteries in mm measured by ultrasonography were 11.2 ± 0.6 on the right and 10.9 ± 0.4 on the left side. However, the vertebral artery diameter was 3.19 ± 0.6 mm on the right side and 3.38 ± 0.7 on the left side [Table 1]. The difference in diameter of carotid and vertebral arteries between the left and right sides was not statistically significant. The mean peak systolic velocities (PSV) of the carotid arteries in cm/s were 153.16 ± 17.3 on the right side and 157.87 ± 19.2 on the left side. The PSV values of the vertebral artery were 76.70 ± 8 on the right side and 78.93 ± 13.3 on the left side [Table 1]. While analyzing flow parameter ratios separately, it was noted that both values were greater on the left side than on the right side. However, the difference was not statistically significant (P > 0.05). PP anomaly was detected in 11 of 31 patients, accounting for 31.48% of cases. The regression analysis and Mann–Whitney U test were performed for age, lumen diameter, and flow velocities of the vertebral and carotid arteries. Only the age of patients and right-side carotid stenosis were statistically significant. Sex differences in diameters and flow, and the presence of PP, were not observed. In Kendall’s tau_b correlation test, significantly negative correlations were identified between carotid stenosis and age for the presence of PP on the right side. (P < 0.05). On the left side, only the age of patients was correlated with the presence of PP. Table 2 shows a negative correlation between the presence of PP and right-side carotid stenosis. Figure 1a-c displays the grading of PP. Figure 1d-g show a patient with asymmetric PP. Hypoplastic VA was noted on the side without PP.

Table 2.

Negative correlation between presence of PP and right side carotis stenosis

Correlations
Sides of PPs	Correlation test	Right side carotid stenosis	PSV of right carotid	Left side carotid stenosis	PSV of right carotid left carotid
The presence of PP on the right side	Correlation Coefficient	-0.38*	-0.22	0.07	0.17
	Sig. (2-tailed)	0.02	0.12	0.65	0.24
	N	25	31	25	31
The presence of PP on the left side	Correlation Coefficient	-0.13	-0.01	0.10	0.06
	Sig. (2-tailed)	0.44	0.93	0.55	0.67
	N	25	31	25	31

*Correlation is significant at the 0.05 level (2-tailed). PP: ponticulus posticus, PSV: peak systolic velocities

Discussion

In this investigation, the PP anomaly and carotid artery stenosis on the right side were found to be negatively correlated, but not on the left side. Human laterality with the PP anomaly may lead to functional changes in the carotid-vertebral arteries and carotid stenosis.

The rationale of this study

This study investigates the hypothesis of whether there is an association between side asymmetry of the PP anomaly and carotid artery stenosis in adult patients. A negative correlation was found between right carotid artery stenosis and PP development (P < 0.05). The rationale of this hypothesis relies on the fact that age-dependent changes occur in the human body. Humans’ biological diversity may contribute to the asymmetries that each person experiences.[6] As we age, a wide range of gross-level neuroanatomical changes occur.[7] As people age normally, extracranial arteries are prone to show morphological variations. In this study, the ages of the patients were analyzed. Age-dependent vertebral and carotid artery diameter changes might occur. Only the age of patients was different between the dominant and nondominant sides (P < 0.05). The human body is asymmetrical both morphologically and physiologically, even though it superficially seems to be symmetrical along the midline.[8] The hemispheric asymmetry of humans can be correlated with vascular anatomy. The cerebral arteries themselves and the patterns of aortic branching both exhibit the asymmetry of the human vasculature. Cerebral blood flow is affected by vascular wall elasticity. Atherosclerosis is an important systemic disease. A more advanced stage of atherosclerotic disease, large vessel intracranial atherosclerotic stenosis, is characterized by narrowing of the vessel lumen.[9] There may be some interaction between carotid artery anatomy, geometry, and aberrant growth of blood-moving forces. Compared to bilateral carotid artery stenosis, unilateral carotid artery stenosis is more prevalent. The data of the present study indicate that there is an asymmetry between the side of the PP anomaly and side of the carotid stenosis. The vertebral arteries typically have unequal diameters on each side. In the case of asymmetrical vertebral arteries, the velocity is proportional to the diameter. In this study, involvement was more commonly located on the left than on the right side [see Table 1]. There is a connection between the carotid artery and vertebral arteries. Therefore, we hypothesized that local factors such as the PP anomaly may cause side-related differences in the development of asymmetric carotid artery stenosis. This study indicates that the presence of an asymmetrical PP anomaly leads to asymmetrical vertebral arteries and, indirectly, asymmetrical carotid artery stenosis.

The clinical relevance of this study

We hypothesized that there is a mutual relationship between the internal carotid and vertebral arteries and the PP anomaly. This point is a hypothetical causative matter in the relationship between the PP anomaly and the carotid-vertebral arteries. The present study is a pilot study, and our results highlighted the existence of a laterality-dependent association between the carotid-vertebral arteries and the PP anomaly. Some findings point to possible differences between left and right carotid and vertebral artery changes. Figure 1d-g show a situation in a patient with asymmetric PP. In this study, hypoplastic VA was noted on the side without PP, so PP may be a protective structure against hypoplasia of the VA.

An essential statistical tool for assessing the strength of a relationship between two or more variables is correlation.[10] In this study, a negative correlation was observed on the right side between PP grade and carotid artery stenosis (P < 0.05) see Table 2. These two variables exhibit equal magnitude and opposite direction movement. The correlation coefficient r is crucial in this situation.[10] The degree and direction of a linear relationship between the aforementioned variables are measured. R’s value is always in the range of +1 and −1. The coefficient in this study was −0.323 [see Table 2]. The negative correlation between differences in right-side PP grade and carotid stenosis rate may show the protective role of PP in occlusive carotid diseases; we think that it is important to recognize this finding. Understanding the cause of this negative correlation is crucial, because in opposite directions, PP grade and carotid stenosis on the right side may be a key component in the protective role of PP grade. However, this negative correlation could also be a pure coincidence, as it was not observed on the left side. There is no study in the literature comparing the laterality of the PP anomaly to the characteristics of the carotid vertebral arteries between males and females. In this study, sex differences in diameters, flow, and the presence of PP were not observed.

There is no doubt that hemodynamically significant basilar artery and vertebral changes can be the cause of posterior circulation stroke. This paper shows that there is a relationship between the PP anomaly and carotid stenosis. Several factors could reduce the blood flow through the vertebral arteries. PP anomaly is the emergence of a complete or incomplete bony ridge at the location of the traditional vertebral artery groove (sulcus arteriae vertebralis) on the posterior arch of the atlas.[3] The PP anomaly’s function is directly tied to its anatomy,[4] This anomaly completely or partially encircles the vertebral artery, especially the V3 segment. It is a rare anomaly.[4] It is well known that the posterior fossa, including the brainstem and cerebellar area, is primarily supplied with blood through the vertebral artery. We think that ischemic posterior circulation stroke is associated with the PP abnormality and influences acute stroke intervention, but no study has been published on the relationship between PP and ischemic lesion of the posterior cerebral circulation. We are planning to investigate the effect of the PP anomaly on posterior circulation stroke and acute stroke intervention.

Limitations

The study’s sample size is still a drawback. Calculations of the group size “a priori” were not done.

Conclusion

The human body’s innate asymmetry may be the cause of structural variations and influence the pathophysiology of illnesses.[11] The anatomical features of the skull base, including the cervical structures, may differ asymmetrically on the right and left sides.[12] It is important to understand how the existence of the PP anomaly changes the anatomy of this region. In this study, a negative correlation was observed between carotid artery stenosis and PP anomalies on the right side. Comprehending the anatomic relationships between the carotid and vertebral arteries from the perspective of the PP anomaly is crucial. Research, such as our study, utilizing observational data is beneficial since it provides a foundation for future investigation.[13] Though causality cannot be established from this study alone, our results show a carotid artery or vascular correlate with PP asymmetry. This study indicates that laterality leads to a distinct form of morphological and functional changes in the carotid artery and the presence of PP on the right size. This study also indicates that primary vascular asymmetry of the carotid and vertebral arteries could cause the observed PP anomaly-related vertebral asymmetry, or vice versa. More studies are required.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.