Long-term neuromuscular alterations during botulinum toxin treatment for chronic migraine

Abstract

Objective

To evaluate early and long-term neuromuscular and clinical effects of botulinum toxin type A (BoNTA) in women with chronic migraine undergoing sustained treatment.

Methods

Forty female patients were stratified by cumulative BoNTA exposure (treatment-naïve, ∼1 year, 2–5 years, >5 years). Clinical outcomes included migraine frequency, pain burden, and quality of life. Neurophysiological assessments during one treatment cycle comprised motor nerve conduction studies, quantitative EMG, jitter analysis, and blink reflex. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were also measured.

Results

BoNTA significantly reduced migraine days (p = 0.0008) with sustained benefit across treatment groups. Neuromuscular side effects were reported in 75% of patients treated for ≥1 year, including ptosis, diplopia, and shoulder weakness. In treatment-naive patients, frontalis CMAP amplitudes declined significantly from baseline to week 12 (p = 0.0006), whereas cumulative reductions were most pronounced in the trapezius muscle in patients treated for 2–5 years (p < 0.0001). EMG showed spontaneous activity consistent with denervation in up to 60% of patients and myopathic patterns in 30–40% of long-term-treated individuals. Abnormal jitter in the orbicularis oculi was present in 47% at week 12. NfL levels were higher in long-term treated groups at week 4 (p = 0.0095), while GFAP remained unchanged. Subtle blink reflex abnormalities suggested possible central modulation.

Conclusions

BoNTA is associated with persistent neuromuscular alterations, with early effects in facial muscles and cumulative changes in the trapezius.

Significance

These findings support the occurrence of treatment-dependent neuromuscular side effects and highlight the need for monitoring during long-term therapy.