Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache

Abstract

Background: Onabotulinumtoxin A (BOTOX) is an FDA-approved treatment for chronic migraine headaches (MHs) that involves on-label, high-dose administration across 31 anatomic sites. Anatomically specific peripheral nerve trigger sites have been identified that contribute to MH pathogenesis and are amenable to both BOTOX injection and surgical decompression. These sites do not always correlate with the on-label FDA-approved injection pattern, but represent a more targeted approach. The efficacy of peripheral nerve-directed BOTOX injection as an independent long-term therapeutic option has not been investigated.

Methods: The technique for peripheral nerve-directed therapeutic long-term BOTOX injection is described. A retrospective review was subsequently completed for 223 patients with MH. Sixty-six patients elected to proceed with diagnostic BOTOX injections. Of these, 24 continued long-term therapeutic BOTOX injections, whereas 42 matriculated to surgery. Outcomes were tracked.

Results: Initial outcomes included significant improvement in migraine headache index (MHI) (53.5 ± 83.0, P < 0.006), headache days/mo (9.2 ± 12.7, P < 0.0009), and migraine severity (2.6 ± 2.5, P < 0.00008) versus baseline. MHI improved from the initiation of diagnostic injections to the establishment of steady-state injections (P < 0.002), and further improved over time (P < 0.05, mean follow-up 615 days) with no desensitization observed. Decompressive surgery resulted in significant improvement in MHI (100.8 ± 109.7, P < 0.0000005), headache days/mo (10.8 ± 12.7, P < 0.000002), migraine severity (3.0 ± 3.8, P < 0.00001), and migraine duration in hours (16.8 ± 21.6, P < 0.0007). MHI improvement with surgery was better than long-term BOTOX injections (P < 0.05).

Conclusions: Though inferior to surgical decompression, preliminary data demonstrate that targeted peripheral nerve-directed BOTOX injection is an effective primary therapy for MH representing a possible alternative to nondirected BOTOX injection with decreased dosage requirements and potentially decreased cost.

Fig. 1.

Current FDA-approved injection pattern versus targeted peripheral nerve–directed injection pattern. The current FDA-approved injection pattern includes chemodenervation of 7 head and neck muscle groups (A–C). The total units of BOTOX injected for each site bilaterally include: corrugators 10U, procerus 5U, frontalis 20U (A), temporalis 40U (B), occipitalis 30U, cervical paraspinal 20U, and trapezius 30U (C). By comparison, peripheral nerve–directed BOTOX injection targets fewer sites with a smaller total quantity of BOTOX (D–F). The total units of BOTOX injected for each site bilaterally include: supraorbital nerve/supratrochlear nerve 25U (D), zygomaticotemporal nerve 37.5U (E), and greater occipital nerve 50U (F).

Video Graphic 1.

Targeted BOTOX injection technique for the greater occipital nerve (GON) trigger site.

Video Graphic 2.

Targeted BOTOX injection technique for the supraorbital and supratrochlear nerve (SON/STN) trigger site.

Video Graphic 3.

Targeted BOTOX injection technique for the zygomaticotemporal nerve (ZTN) trigger site.

Fig. 2.

Peripheral nerve–directed BOTOX improves migraine symptoms over time. Compared with baseline, significant improvement was noted in MHI, headache days per month and migraine severity after patients had reached a steady-state, long-term injection regimen. Interval, further improvement was noted in MHI and headache days per month at the last follow-up visit. MHI: frequency × severity × duration. Frequency: number of migraine days within past month. Severity: migraine severity on 1–10 scale, with 1 = best and 10 = worst. Duration: fraction of 24 hours. A mixed effects regression model was utilized to evaluate these data, presented as ±SEM with P-values.

Fig. 3.

Long-term peripheral nerve–directed BOTOX (green) versus surgical decompression (blue) (A, B). Data were derived as the difference between baseline and the last follow-up visit. Differences in MHI were evaluated using Student’s t test and are presented as ±1 standard deviation. *P ≤ 0.05.