Asymmetric Mechanical Vulnerability of the Internal Carotid and Vertebral Arteries: The Investing Layer of the Deep Cervical Fascia–Carotid Sheath Coupling Hypothesis

Background: Activation of the trigeminovascular system, calcitonin gene-related peptide (CGRP) release, and central sensitization of the trigeminocervical complex are the mainstream framework for migraine and related syndromes. This framework explains the event cascade after attack initiation. It does not adequately explain why the attack threshold is systematically lowered in some individuals, such that routine head and neck movement or minor mechanical loading triggers symptoms.Objective: To propose the investing fascia–carotid sheath coupling hypothesis. In this hypothesis, the same upstream fascial mechanical abnormality produces downstream vascular events with different thresholds and phenotypes in the anterior and posterior circulations.Methods: This is a hypothesis paper, not an empirical study. Published evidence was synthesized into a testable causal chain. No new primary data are presented. The hypothesis is positioned as a peripheral mechanical upstream complement to, not a replacement for, the trigeminovascular system and central sensitization theories.Results: The proposed causal chain begins with investing fascial fibrosis and mechanical conduction through the deep cervical fascial network to the carotid sheath. Within the sheath, PIEZO mechanotransduction and CGRP signaling amplify the signal. The resulting effects are superimposed and mutually amplifying across five pathways: arterial, venous, lymphatic/glymphatic, sympathetic, and vagal. The five-pathway superposition is threshold-dependent rather than simultaneous, with the threshold defined by the sympathetic hemodynamic threshold. The term "conditional" is used once here in its standard sense, namely dependent on a stated condition; thereafter the term "threshold-dependent" is used throughout to denote the same property. Below that threshold, the superposition mainly involves the arterial, venous, lymphatic/glymphatic, and vagal pathways. The sympathetic pathway joins only after its threshold is crossed. The anterior circulation has greater autoregulatory reserve, with the compensation threshold as its characteristic node. In vivo evidence shows that dynamic cerebral autoregulation in the posterior circulation is more pressure-passive. Posterior circulation arterial walls also tend toward passive stiffening during head rotation, whereas anterior circulation arteries exhibit compensatory softening. Vertebral artery hypoplasia (VAH) provides independent systematic-review evidence for the association between posterior circulation low reserve and clinical vulnerability. However, VAH is used only as a structural reference for validation design, not as causal evidence. Two core gaps remain: Gap 1, the investing fascia-to-sheath wall transmission coefficient; and Gap 2, the reliability of mechanical measurement of the sheath wall itself. Because Gap 2 is logically prior to Gap 1 in measurement terms, a transitional measurement framework for the Gap 1–Gap 2 pair is specified so that Gap 1 study design can proceed before Gap 2 is formally closed. The framework has three components: cadaveric cervical-block indentation with deep ultrasound displacement mapping, Bayesian indirect estimation anchored on published effect sizes, and phantom–specimen two-tier calibration of device, depth, and stiffness biases. This framework yields a posterior interval and a feasibility bound for the transmission coefficient; it does not substitute for direct measurement of Gap 1 or for reliability validation of Gap 2.Conclusions: The hypothesis is at the stage of literature derivation, quantitative prediction, and tiered validation. It provides refutation criteria and a five-tier validation-method minimal testable hypothesis set comprising histology, mechanics, computation, cohort, and intervention, with tier-specific minimal test sets. These five validation-method tiers are distinct from the evidence tiers of Section 5. The anterior circulation is treated as a representative-artery construct rather than a homogeneous unit; a minimal internal stratification into cervical ICA, MCA, and ACA nodes is specified so that the anterior–posterior contrast is not confounded by unequal stratification resolution. The hypothesis should be judged not by whether it explains all functional syndromes, but by whether it can give a more precise and more falsifiable answer than the generalized statement that the neck is related to the cerebral circulation. This answer must specify the differentiated dose–response of the anterior and posterior circulations.