When Connective Tissue Becomes Neurological: A Perspective on Structural Vulnerability, Dynamic Pathology, and the Nervous System

Connective tissue supports the mechanical and physiological environment of the nervous system, but an underlying connective-tissue disorder does not by itself establish the cause of neurological symptoms. We examine the neurological relevance of meningeal, ligamentous, spinal, and neurovascular structures in Ehlers–Danlos syndromes (EDSs), distinguishing established disease mechanisms from observational associations and controversial hypotheses. We propose a clinical reasoning framework that begins with a defined neurological phenotype, identifies a plausible physiological mechanism, and then seeks concordant anatomical or physiological evidence. Two illustrative scenarios demonstrate how the approach may justify targeted investigation or, conversely, redirect attention toward more likely nonstructural diagnoses. We distinguish primary Chiari I malformation from acquired tonsillar descent associated with cerebrospinal fluid (CSF) loss; separate evidence-based investigation of spontaneous intracranial hypotension from incompletely validated provocative imaging for suspected craniocervical instability; and critically appraise the limitations of surgical series and occult tethered cord studies. The framework is a proposed aid to reasoning, not a validated diagnostic instrument, and its diagnostic accuracy, safety, resource implications, and effect on patient outcomes remain unknown. Connective-tissue vulnerability should inform hypotheses, not substitute for proof of neurological consequence.