Chronic Migraine: A Narrative Review on the Use of Botulinum Toxin with Clinical Indications and Future Directions

Abstract

Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. The pathophysiology of CM is characterized by an abnormal activation of the trigemino-vascular system in the meninges causing a neurogenic inflammation, which explains the use of anti-inflammatory during attacks. It seems that the objective of the preventive therapy with the botulin toxin OnaBoNT-A consists in interrupting the release of CGRP and other neuropeptides as well as the activation of C-fiber nociceptor and of the nearby A-delta fibers. The protocol for migraine treatment with OnaBoNT-A injections consists of 31-39 pericranial injection sites involving seven muscle groups bilaterally in specific areas of the head and neck, with a total dose of between 155 and 195 units, every three months. The severe adverse events reported with high doses of botulin toxin for spasticity, have not been reported for CM treated with OnabotA at the labeled dose. The established improvement with onabotulinumtoxinA treatment in CM patients had a positive impact not only in reduction monthly headache days but also in improving quality of life, with reduction in both healthcare resource utilisation (HRU) and work impairment. Aim of this review was to give an overview on the use of BoNT-A in patients with CM, giving practical advices on the clinical indications.

A Single-Group Study on the Effect of OnabotulinumtoxinA in Patients with Chronic Migraine Associated with Medication Overuse Headache: Pain Catastrophizing Plays a Role

“…When OnabotulinumtoxinA is injected, it enters in the cell cytoplasm cleaving the C-terminus of Synaptosomal-Associated Protein, 25 kDa (SNAP-25), which is the target of botulinum neurotoxin type A both in motor nerve and in sensory nerve terminals. This may result in the inhibition in the release of neuropeptides, inflammatory peptides, substance P, glutamate and calcitonin gene-related peptide (CGRP) within the central nervous system, thus playing a therapeutic role in migraine prevention [ 18 , 19 ]. Its efficacy in headaches other than migraine as well as the factors associated to therapeutic success, however, are not completely clear [ 20 , 21 ].…”

Continuous Unilateral Cephalalgia Due to Systemic Lupus Erythematosus: A Case Report

“…Another presentation is neurologic lupus, which is related to psychosis and has been described in cephalalgia crisis. This inflammatory and vasculitis component may explain the intense unilateral headache described in this case since SLE is a condition strongly related to inflammation, and so is cefalalgia (6)(7)(8). The mechanism of SLE cephalalgia is not fully understood.…”

Real-World Evaluation of the Tolerability to Onabotulinum Toxin A: The RETO Study

“…A series of demographical and clinical data were collected by the time of patients' enrolment through an in-person interview, conducted by a neurologist focused on headache disorders. The evaluated variables included age, sex, age of migraine onset, duration of chronic migraine in months, number of headache days per month, number of intense headache days per month (defined as days with intensity of headache over 7/10, in a numeric rating scale (NRS), number of acute medication days per month, number of triptan use days per month, presence of concomitant medication-overuse headache (according to the International Classification of Headache Disorders (ICHD) criteria [22,23]) and type and number of prior prophylactic drugs. From the prior prophylactic drugs, we analyzed also whether there was a lack of efficacy, when used for a sufficient time and at an adequate dose, or a lack of tolerability.…”

“…Probably, the most remarkable differences between them are the way of administration and the tolerability profile. OnabotA could decrease peripheral and, indirectly, central sensitization [22,23]. Its administration is based on Phase III REsearch Evaluating Migraine Prophylaxis Therapy 1 (PREEMPT) Paradigm [12], which includes 31 injections in the cranial and cervical region.…”