Vertebral Artery Hypoplasia and Posterior Circulation Vulnerability: A Systematic Review of Epidemiological, Hemodynamic, and Clinical Evidence

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript addresses a clinically relevant and still controversial topic by systematically reviewing the epidemiological, haemodynamic, anatomical and neurological implications of vertebral artery hypoplasia (VAH). The authors conclude that VAH should be regarded as a vascular susceptibility phenotype rather than merely an incidental anatomical variant. However, the novelty and added value of the present review are not sufficiently and explicitly established.

Previous publications have already reviewed the possible role of VAH in posterior-circulation ischaemia, including a systematic review and meta-analysis examining its association with posterior-circulation ischaemia and a more recent systematic review and meta-analysis addressing its anatomical characteristics and prevalence. Therefore, the authors should clearly explain how the present review differs from and advances beyond these earlier syntheses.

The potentially novel contribution appears to be the integration of several previously fragmented evidence domains—epidemiology, vascular anatomy, quantitative haemodynamics, collateral circulation, vascular remodelling, computational fluid dynamics, posterior-circulation stroke and non-stroke neurological manifestations—within a single clinically oriented framework. The additional use of formal JBI risk-of-bias assessment and OCEBM evidence-level classification may also represent an important methodological contribution. Furthermore, the proposed interpretation of VAH as a context-dependent “low-flow susceptibility phenotype,” whose clinical expression depends on collateral adequacy, coexisting vascular abnormalities and acquired cerebrovascular risk factors, could constitute the principal conceptual advance of the review.

Nevertheless, these elements are currently dispersed throughout the manuscript and are not translated into a clear statement of novelty. The authors should therefore:

1. Compare the scope and methodology of the present review directly with those of previous narrative reviews and systematic reviews/meta-analyses.
2. State explicitly which evidence domains, patient phenotypes and mechanistic findings are synthesized here for the first time.
3. Clarify whether the proposed pathophysiological model is genuinely derived from the systematic synthesis or is primarily a narrative interpretation of the available evidence.
4. Explain how the findings could change the clinical interpretation of incidentally detected VAH, without overstating causality or recommending unsupported screening or treatment strategies.
5. Identify concrete implications for future research, particularly regarding standardised diagnostic thresholds, integration of vessel diameter with flow-based measurements, assessment of collateral anatomy and prospective evaluation of VAH in cerebrovascular risk-stratification models.

A dedicated paragraph entitled “Novelty and contribution to the current literature” should be added near the end of the Introduction or at the beginning of the Discussion. The Abstract should also include one concise sentence stating the specific advance provided by this review.

Comments on the Quality of English Language

The manuscript addresses a clinically relevant and still controversial topic by systematically reviewing the epidemiological, haemodynamic, anatomical and neurological implications of vertebral artery hypoplasia (VAH). The authors conclude that VAH should be regarded as a vascular susceptibility phenotype rather than merely an incidental anatomical variant. However, the novelty and added value of the present review are not sufficiently and explicitly established.

Previous publications have already reviewed the possible role of VAH in posterior-circulation ischaemia, including a systematic review and meta-analysis examining its association with posterior-circulation ischaemia and a more recent systematic review and meta-analysis addressing its anatomical characteristics and prevalence. Therefore, the authors should clearly explain how the present review differs from and advances beyond these earlier syntheses.

The potentially novel contribution appears to be the integration of several previously fragmented evidence domains—epidemiology, vascular anatomy, quantitative haemodynamics, collateral circulation, vascular remodelling, computational fluid dynamics, posterior-circulation stroke and non-stroke neurological manifestations—within a single clinically oriented framework. The additional use of formal JBI risk-of-bias assessment and OCEBM evidence-level classification may also represent an important methodological contribution. Furthermore, the proposed interpretation of VAH as a context-dependent “low-flow susceptibility phenotype,” whose clinical expression depends on collateral adequacy, coexisting vascular abnormalities and acquired cerebrovascular risk factors, could constitute the principal conceptual advance of the review.

Nevertheless, these elements are currently dispersed throughout the manuscript and are not translated into a clear statement of novelty. The authors should therefore:

1. Compare the scope and methodology of the present review directly with those of previous narrative reviews and systematic reviews/meta-analyses.
2. State explicitly which evidence domains, patient phenotypes and mechanistic findings are synthesized here for the first time.
3. Clarify whether the proposed pathophysiological model is genuinely derived from the systematic synthesis or is primarily a narrative interpretation of the available evidence.
4. Explain how the findings could change the clinical interpretation of incidentally detected VAH, without overstating causality or recommending unsupported screening or treatment strategies.
5. Identify concrete implications for future research, particularly regarding standardised diagnostic thresholds, integration of vessel diameter with flow-based measurements, assessment of collateral anatomy and prospective evaluation of VAH in cerebrovascular risk-stratification models.

A dedicated paragraph entitled “Novelty and contribution to the current literature” should be added near the end of the Introduction or at the beginning of the Discussion. The Abstract should also include one concise sentence stating the specific advance provided by this review.

Author Response

The manuscript addresses a clinically relevant and still controversial topic by systematically reviewing the epidemiological, haemodynamic, anatomical and neurological implications of vertebral artery hypoplasia (VAH). The authors conclude that VAH should be regarded as a vascular susceptibility phenotype rather than merely an incidental anatomical variant. However, the novelty and added value of the present review are not sufficiently and explicitly established.

Previous publications have already reviewed the possible role of VAH in posterior-circulation ischaemia, including a systematic review and meta-analysis examining its association with posterior-circulation ischaemia and a more recent systematic review and meta-analysis addressing its anatomical characteristics and prevalence. Therefore, the authors should clearly explain how the present review differs from and advances beyond these earlier syntheses.

The potentially novel contribution appears to be the integration of several previously fragmented evidence domains—epidemiology, vascular anatomy, quantitative haemodynamics, collateral circulation, vascular remodelling, computational fluid dynamics, posterior-circulation stroke and non-stroke neurological manifestations—within a single clinically oriented framework. The additional use of formal JBI risk-of-bias assessment and OCEBM evidence-level classification may also represent an important methodological contribution. Furthermore, the proposed interpretation of VAH as a context-dependent “low-flow susceptibility phenotype,” whose clinical expression depends on collateral adequacy, coexisting vascular abnormalities and acquired cerebrovascular risk factors, could constitute the principal conceptual advance of the review.

Answer: We sincerely thank the reviewer for this highly constructive comment. We fully agree that the novelty of our systematic review was not sufficiently emphasized in the original version despite being reflected throughout the manuscript. Following the reviewer's suggestions, we have substantially revised the Introduction, Abstract and Discussion to explicitly state the novel contribution of this systematic review and to better position it in relation to previous reviews and meta-analyses. All suggested has been accepted and it can be seen added in the track change option in the Manuscript document.

Nevertheless, these elements are currently dispersed throughout the manuscript and are not translated into a clear statement of novelty. The authors should therefore:

1. Compare the scope and methodology of the present review directly with those of previous narrative reviews and systematic reviews/meta-analyses.

Answer: Thank you; we have added this into the Introduction, Novelty and contribution to the current literature. Unlike previous reviews, which primarily focused either on the prevalence and anatomical definition of vertebral artery hypoplasia or on its association with posterior circulation ischemia, the present systematic review was designed to integrate all currently available evidence across epidemiological, anatomical, hemodynamic, imaging, computational, and neurological domains within a single clinically oriented framework. In addition to summarizing associations with posterior circulation stroke, this review synthesizes evidence regarding collateral circulation, cerebrovascular autoregulation, computational fluid dynamics, vascular remodeling, vestibular syndromes, and non-stroke neurological manifestations while also providing a structured methodological quality assessment using the Joanna Briggs Institute tools and Oxford Centre for Evidence-Based Medicine evidence classification.

2. State explicitly which evidence domains, patient phenotypes and mechanistic findings are synthesized here for the first time.

Answer: Thank you, we have added following paragraph into the 2.12. subheading of the Methodology. “Specifically, this review integrates evidence regarding: epidemiology and prevalence; diagnostic criteria and imaging definitions; cerebral hemodynamics and flow measurements; collateral circulation and Circle of Willis anatomy; computational fluid dynamics; vascular remodeling; posterior circulation ischemic stroke; non-stroke neurological syndromes; anatomical variants associated with VAH”.

3. Clarify whether the proposed pathophysiological model is genuinely derived from the systematic synthesis or is primarily a narrative interpretation of the available evidence.

Answer: We have changed the description of the Figure to: Conceptual model based on the systematic synthesis of currently available evidence. Besides that, the proposed model should not be interpreted as direct causal evidence but rather as a conceptual framework integrating the findings identified across heterogeneous observational, anatomical, imaging, and hemodynamic studies included in the present systematic review. This has been added after the Figure description.

4. Explain how the findings could change the clinical interpretation of incidentally detected VAH, without overstating causality or recommending unsupported screening or treatment strategies.

Answer: We have added dedicated paragraph to the Discussion “From a clinical perspective, the present synthesis suggests that incidentally detected VAH should not automatically be dismissed as a completely benign anatomical variant. Rather, its potential clinical significance appears to depend on the coexistence of impaired collateral circulation, additional vascular abnormalities, and conventional cerebrovascular risk factors. Accordingly, isolated VAH should not be considered an indication for additional treatment or screening in otherwise asymptomatic individuals. Instead, its identification may provide complementary anatomical information that could improve individualized interpretation of posterior circulation symptoms and cerebrovascular vulnerability within the broader clinical context”.

5. Identify concrete implications for future research, particularly regarding standardised diagnostic thresholds, integration of vessel diameter with flow-based measurements, assessment of collateral anatomy and prospective evaluation of VAH in cerebrovascular risk-stratification models.

Answer: We have added this paragraph in the Conclusion: “Future research should prioritize international consensus regarding standardized diagnostic thresholds that combine vessel diameter and quantitative flow parameters rather than relying exclusively on fixed diameter criteria. Prospective longitudinal studies integrating CTA/MRA, Doppler ultrasonography, 4D-flow MRI, collateral circulation assessment, and computational hemodynamic analyses are needed to determine whether VAH independently improves cerebrovascular risk prediction beyond established vascular risk factors. Such studies should also evaluate whether incorporation of VAH into future posterior circulation risk-stratification models provides incremental prognostic value”.

6. A dedicated paragraph entitled “Novelty and contribution to the current literature” should be added near the end of the Introduction or at the beginning of the Discussion. The Abstract should also include one concise sentence stating the specific advance provided by this review.

Answer: It has been changed as proposed, in the Introduction and the Abstract. Additional paragraph has been added: Novelty and contribution to the current literature “Previous systematic reviews and meta-analyses have primarily focused either on the prevalence and anatomical characteristics of vertebral artery hypoplasia or on its association with posterior circulation ischemia. In contrast, the present review provides a broader and clinically oriented synthesis by integrating epidemiological, anatomical, hemodynamic, imaging, computational, and neurological evidence within a single systematic framework. In addition to evaluating posterior circulation stroke, this review also synthesizes evidence regarding collateral circulation, vascular remodeling, cerebrovascular autoregulation, computational fluid dynamics, vestibular and other non-stroke neurological manifestations, while incorporating a formal methodological quality assessment using the Joanna Briggs Institute critical appraisal tools and Oxford Centre for Evidence-Based Medicine levels of evidence. Based on this comprehensive synthesis, we propose an evidence-informed conceptual framework that interprets vertebral artery hypoplasia as a context-dependent low-flow vascular susceptibility phenotype whose clinical relevance depends on the interaction between congenital anatomies, collateral circulation, and acquired cerebrovascular risk factors”.

And this was added in the Abstract: “Unlike previous reviews focusing primarily on prevalence or stroke associations, this review integrates epidemiological, anatomical, hemodynamic, computational, and neurological evidence within a unified clinically oriented framework and proposes an evidence-informed conceptual model of VAH as a context-dependent low-flow vascular susceptibility phenotype”.

Kind regards

Reviewer 2 Report

Comments and Suggestions for Authors

Thanks for the authors’ submission.

This systematic review addresses the clinical significance of vertebral artery hypoplasia (VAH) and holds substantial potential for clinical translation. The authors synthesize multidimensional evidence encompassing epidemiology, hemodynamics, anatomical variations, and clinical outcomes, proposing the central thesis of reclassifying VAH from a "benign anatomical variant" to a "posterior circulation vulnerability phenotype." The article is well-structured, the methodology is reasonably rigorous (following PRISMA 2020, PROSPERO registration, JBI quality appraisal, and OCEBM grading), the number of included studies (n=48) is considerable, and the discussion introduces an integrated pathophysiological model, adding academic value.

Major Comments

The literature search was conducted solely in PubMed/MEDLINE. Although supplemented by manual searches and Google Scholar, core databases such as Embase, Web of Science, and the Cochrane Library were not included. For a manuscript claiming to be a "systematic review," relying on a single database introduces significant selection bias, potentially omitting key clinical studies from Europe and Asia. Please supplement the search in at least Embase and Web of Science. If resource constraints prevent re-searching, this must be explicitly acknowledged in the Limitations section as a major limitation, along with a discussion regarding its impact on the robustness of the conclusions.

Table 1 is visibly truncated in the PDF (right margin cut off), leaving the "Key findings" and "Level of evidence" columns incomplete. For instance, the key findings for Chen et al. cut off at "...strong correlation between VA diameter and flow volume; reduced net vertebral flow in VAH," and Siva et al. ends with "...High VAH prevalence; V4," rendering the context unclear. Please reformat Table 1 to ensure all column content is visible. Consider splitting the table or using a landscape format. Provide the complete table content in the Supplementary Materials.

The authors abandoned quantitative meta-analysis citing "methodological and clinical heterogeneity" but failed to provide quantitative metrics of heterogeneity (e.g., I² statistic) or display forest plots/attempts at subgroup analysis. This prevents readers from assessing the actual degree of heterogeneity or whether a meaningful pooling was truly impossible. Please report at least the I² values and Cochran’s Q test p-values to quantify heterogeneity for primary outcomes (e.g., OR for VAH and PCS). If pooling remains unfeasible, explicitly state in the Results section that "heterogeneity was excessively high (I² > 80%), precluding meta-analysis," rather than vaguely attributing it to "methodological heterogeneity." Consider performing exploratory meta-analyses on specific subgroups (e.g., studies using CTA and identical diameter thresholds).

While discussing and comparing findings with the meta-analyses by Katsanos et al. (Refs. 82, 83), the authors only offer a general statement of "consistent overall agreement" lacking specific data comparisons. For example: What was the pooled OR reported by Katsanos et al.? How does it compare to newer studies included here (e.g., Li et al. 2026, OR=1.48)? In which subgroups do the conclusions diverge? Add a paragraph systematically comparing this review with previous meta-analyses regarding effect sizes, inclusion criteria, and sources of heterogeneity. Explicitly delineate how this review advances prior understanding (e.g., incorporating more hemodynamic/CFD evidence and refined anatomical stratification).

The review focuses heavily on ischemic outcomes. However, is VAH also associated with posterior circulation hemorrhagic stroke (e.g., cerebellar or brainstem hemorrhage)? There are scattered reports in the literature, and from a hemodynamic perspective (low flow, high resistance), a negative correlation with hemorrhage risk seems plausible. This warrants mention in the discussion. Add a paragraph stating: "This review found no clear association between VAH and hemorrhagic stroke, possibly related to the design of the included studies; nevertheless, this gap merits attention in future research."

Abstract, Line 47:​ "non- stroke neurological syndromes" → "non-stroke neurological syndromes".

Page 6, Line 378:​ "without a significant association with accurate foramen variation" → "arcuate foramen".

Table 1:​ "contralateral compensation story flow increase" → "contralateral compensatory flow increase".

Page 22, Line 604:​ "posterior circulation substerrirories" → "subterritories".

Engage a native English speaker or professional scientific editing service for thorough language polishing throughout the manuscript.

The PROSPERO registration number provided is CRD420261442242, but this record is not retrievable via the PROSPERO database. This may be a typographical error or the registration may not yet be public. Verify the registration number and confirm in the revised manuscript that the record is publicly accessible on the PROSPERO website (registration should precede data extraction and be visible upon submission).

The authors state "no restrictions regarding publication date were applied," yet the search cutoff date is June 8, 2026. It is essential to specify the earliest year of the included studies so readers can understand the temporal span of the evidence base. Add a sentence in the Results section stating: "The publication years of the included studies ranged from [Earliest Year] to 2026."

The text references "Figure 2" illustrating the pathophysiological model, but this figure is missing from the PDF (likely omitted due to submission formatting). Ensure Figure 2 is uploaded completely in the revised manuscript, with a clear legend explaining the logical sequence of events.

Some references lack volume numbers or page ranges (e.g., Refs. 3, 18), and DOI formats are inconsistent (some include "https://", others do not). Standardize all references according to the journal's required EndNote output style.

 

If the authors can cite the following articles, it would be appreciated:

Lv X, Lv M, Li Y, Yang X, Jiang C, Wu Z. Endovascular treatment of ruptured and unruptured vertebral artery aneurysms. Neuroradiol J. 2011 Oct 31;24(5):677-86.

Author Response

Thanks for the authors’ submission.

This systematic review addresses the clinical significance of vertebral artery hypoplasia (VAH) and holds substantial potential for clinical translation. The authors synthesize multidimensional evidence encompassing epidemiology, hemodynamics, anatomical variations, and clinical outcomes, proposing the central thesis of reclassifying VAH from a "benign anatomical variant" to a "posterior circulation vulnerability phenotype." The article is well-structured, the methodology is reasonably rigorous (following PRISMA 2020, PROSPERO registration, JBI quality appraisal, and OCEBM grading), the number of included studies (n=48) is considerable, and the discussion introduces an integrated pathophysiological model, adding academic value.

Answer: We sincerely thank the reviewer for highly constructive comments. We have answered each suggestion, and changes made in the Manuscript document are marked in the Track Changes option.

Major Comments

The literature search was conducted solely in PubMed/MEDLINE. Although supplemented by manual searches and Google Scholar, core databases such as Embase, Web of Science, and the Cochrane Library were not included. For a manuscript claiming to be a "systematic review," relying on a single database introduces significant selection bias, potentially omitting key clinical studies from Europe and Asia. Please supplement the search in at least Embase and Web of Science. If resource constraints prevent re-searching, this must be explicitly acknowledged in the Limitations section as a major limitation, along with a discussion regarding its impact on the robustness of the conclusions.

Answer: Thank you for this important comment. We agree that searching multiple bibliographic databases is important to minimize the risk of missing potentially relevant studies. We would like to clarify that the literature search was not limited to PubMed/MEDLINE. In addition to PubMed/MEDLINE, we searched the Cochrane Library and Wiley Online Library, and Google Scholar was used as a supplementary source. Furthermore, the reference lists of included studies and relevant review articles were manually screened, and targeted searches were performed using combinations of vertebral artery hypoplasia and specific neurological and cerebrovascular outcomes. To clarify this point, we have revised the Methods section to explicitly describe all information sources and the corresponding search strategies. We acknowledge that Embase and Web of Science were not searched and have therefore explicitly recognized this as a limitation of the review. Nevertheless, the use of multiple complementary sources, supplementary Google Scholar searches, targeted searches, and manual screening of reference lists was intended to maximize the retrieval of relevant literature.

Table 1 is visibly truncated in the PDF (right margin cut off), leaving the "Key findings" and "Level of evidence" columns incomplete. For instance, the key findings for Chen et al. cut off at "...strong correlation between VA diameter and flow volume; reduced net vertebral flow in VAH," and Siva et al. ends with "...High VAH prevalence; V4," rendering the context unclear. Please reformat Table 1 to ensure all column content is visible. Consider splitting the table or using a landscape format. Provide the complete table content in the Supplementary Materials.

Answer: We thank the reviewer for identifying this formatting issue. Table 1 has been reformatted. In addition, the complete versions of Tables 1- 5 have been provided as an additional file.

The authors abandoned quantitative meta-analysis citing "methodological and clinical heterogeneity" but failed to provide quantitative metrics of heterogeneity (e.g., I² statistic) or display forest plots/attempts at subgroup analysis. This prevents readers from assessing the actual degree of heterogeneity or whether a meaningful pooling was truly impossible. Please report at least the I² values and Cochran’s Q test p-values to quantify heterogeneity for primary outcomes (e.g., OR for VAH and PCS). If pooling remains unfeasible, explicitly state in the Results section that "heterogeneity was excessively high (I² > 80%), precluding meta-analysis," rather than vaguely attributing it to "methodological heterogeneity." Consider performing exploratory meta-analyses on specific subgroups (e.g., studies using CTA and identical diameter thresholds).

Answer: Thank you for this important methodological comment. The rationale for not performing a quantitative meta-analysis was prespecified in the Methods section (Sections 2.11 and 2.12), where we described the substantial heterogeneity in study design, populations, imaging modalities, VAH definitions, comparator groups, and reported outcomes. Because the available studies did not provide sufficiently comparable data for reliable statistical pooling, pooled effect estimates and statistical measures of heterogeneity (Cochran’s Q and I²) were not calculated. We have further clarified this rationale in the Results section to make the decision not to perform quantitative synthesis explicit to the reader.

While discussing and comparing findings with the meta-analyses by Katsanos et al. (Refs. 82, 83), the authors only offer a general statement of "consistent overall agreement" lacking specific data comparisons. For example: What was the pooled OR reported by Katsanos et al.? How does it compare to newer studies included here (e.g., Li et al. 2026, OR=1.48)? In which subgroups do the conclusions diverge? Add a paragraph systematically comparing this review with previous meta-analyses regarding effect sizes, inclusion criteria, and sources of heterogeneity. Explicitly delineate how this review advances prior understanding (e.g., incorporating more hemodynamic/CFD evidence and refined anatomical stratification).

Answer: We thank the reviewer for this valuable comment. We have revised the Discussion to provide a direct quantitative comparison with previous meta-analyses and recent evidence. Specifically, we now report the pooled RR of 2.12 (95% CI 1.60–2.82) from Katsanos et al., which remained significant after exclusion of an outlier (RR 1.81, 95% CI 1.58–2.06; I² decreased from 75% to 0%), and compare these findings with the recent longitudinal study by Li et al., which reported an adjusted OR of 1.48 (95% CI 1.02–2.00). We also clarify differences in study populations, outcomes, VAH definitions, and sources of heterogeneity. Finally, we emphasize that our review extends previous evidence by integrating newer longitudinal, hemodynamic/CFD, collateral, vascular remodeling, and anatomical data.

The review focuses heavily on ischemic outcomes. However, is VAH also associated with posterior circulation hemorrhagic stroke (e.g., cerebellar or brainstem hemorrhage)? There are scattered reports in the literature, and from a hemodynamic perspective (low flow, high resistance), a negative correlation with hemorrhage risk seems plausible. This warrants mention in the discussion. Add a paragraph stating: "This review found no clear association between VAH and hemorrhagic stroke, possibly related to the design of the included studies; nevertheless, this gap merits attention in future research."

Answer: We have added a paragraph to the Discussion addressing hemorrhagic posterior circulation events. We now explicitly state that our review found no clear evidence of an association between VAH and cerebellar or brainstem hemorrhage, while acknowledging that this relationship remains insufficiently characterized and warrants further investigation.

Abstract, Line 47:​ "non- stroke neurological syndromes" → "non-stroke neurological syndromes".

Page 6, Line 378:​ "without a significant association with accurate foramen variation" → "arcuate foramen".

Table 1:​ "contralateral compensation story flow increase" → "contralateral compensatory flow increase".

Page 22, Line 604:​ "posterior circulation substerrirories" → "subterritories".

Answer: All of the above have been checked and corrected; thank you.

Engage a native English speaker or professional scientific editing service for thorough language polishing throughout the manuscript.

Answer: We thank the reviewer for this suggestion. The manuscript has undergone comprehensive language editing to improve grammar, clarity, terminology, and overall readability throughout the text.

The PROSPERO registration number provided is CRD420261442242, but this record is not retrievable via the PROSPERO database. This may be a typographical error or the registration may not yet be public. Verify the registration number and confirm in the revised manuscript that the record is publicly accessible on the PROSPERO website (registration should precede data extraction and be visible upon submission).

Answer: We verified the registration number, and we provide the link to the PROSPERO website where the published version can be seen, as a screenshot of the first page in the supplementary material.

The authors state "no restrictions regarding publication date were applied," yet the search cutoff date is June 8, 2026. It is essential to specify the earliest year of the included studies so readers can understand the temporal span of the evidence base. Add a sentence in the Results section stating: "The publication years of the included studies ranged from [Earliest Year] to 2026."

Answer: The publication years of the included studies ranged from 1999 to 2026.

The text references "Figure 2" illustrating the pathophysiological model, but this figure is missing from the PDF (likely omitted due to submission formatting). Ensure Figure 2 is uploaded completely in the revised manuscript, with a clear legend explaining the logical sequence of events.

Answer: We thank the reviewer for identifying this formatting issue. Figure 2 has now been included in the revised manuscript together with a complete legend explaining each component of the proposed conceptual framework. It has been submitted as Additional files together with all Tables from the results.

Some references lack volume numbers or page ranges (e.g., Refs. 3, 18), and DOI formats are inconsistent (some include "https://", others do not). Standardize all references according to the journal's required EndNote output style.

Answer: All references have been carefully reviewed and reformatted according to the journal's reference style. Missing bibliographic information has been added where available, and DOI formatting has been standardized throughout the reference list.

If the authors can cite the following articles, it would be appreciated:

Lv X, Lv M, Li Y, Yang X, Jiang C, Wu Z. Endovascular treatment of ruptured and unruptured vertebral artery aneurysms. Neuroradiol J. 2011 Oct 31;24(5):677-86.

Answer: We have accepted this proposition and added the following paragraph: Although VA hypoplasia has predominantly been investigated as a risk factor for posterior circulation ischemic events, its relationship with hemorrhagic complications remains insufficiently explored. Some reports of fusiform vertebral artery aneurysms suggest that altered flow dynamics and reduced contralateral vertebral artery capacity may influence aneurysm behavior; nevertheless, current evidence is insufficient to establish whether VA hypoplasia modifies hemorrhagic risk.

Kind regards

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The paper was well revised, can be acceptable

Reviewer 2 Report

Comments and Suggestions for Authors

Thanks for the authors' revision.