CGRP-pathway exposure during the pre-EBP interval in spontaneous intracranial hypotension: an exploratory...

Given hypothesized involvement of calcitonin gene-related peptide (CGRP) in trigeminovascular pain and the frequent migrainous features of spontaneous intracranial hypotension (SIH), we describe temporal associations between initiation of CGRP-pathway therapies and short-term symptom changes during the interval before image-guided epidural blood patch (pre-EBP) in seven consecutively managed SIH patients. Because this is a small retrospective uncontrolled series, we report exploratory observations only.

Work-up included selective head-up tilt testing and heavily T2-weighted MR myelography demonstrating predominantly cervicothoracic and/or multifocal spinal CSF leaks. During the pre-EBP interval patients received CGRP-pathway agents: monoclonal antibodies (fremanezumab n = 1; galcanezumab n = 3) and/or gepants (atogepant n = 4; rimegepant PRN n = 1). Five of seven patients (71%) met a pre-specified rubric of clinically meaningful improvement documented after CGRP initiation; in all seven patients with routinely charted Numeric Rating Scale (NRS, 0-10) scores the median NRS reduction was 3 points (range 1-4). Positional orthostatic features commonly persisted until after EBP. Median interval from CGRP initiation to targeted EBP was 7 days. In this small cohort we did not observe an obvious signal that pre-EBP CGRP exposure impaired subsequent clinical response to EBP; however, the sample size and short follow-up preclude conclusions about rare or delayed interactions.

These observations are hypothesis-generating only and report temporal associations between CGRP-pathway initiation and short-term symptom changes in a highly selected cohort with comorbid chronic migraine. They do not demonstrate efficacy for SIH and should not be interpreted as endorsing CGRP-pathway therapy as a treatment for SIH. Prospective, controlled trials with validated headache and orthostatic endpoints, stratification by migraine status, and peripheral/CSF biomarker assessments are required.