Abstract
In our previous service evaluation, we reported improvement in patients’ pain scores for masseteric pain and spasm, following injection of 50 units of botulinum toxin A (BtA), measured using visual analogue scales (VAS). We have recently introduced a lower dose BtA protocol, for appropriately selected patients, aimed to evaluate whether this is also effective at relieving symptoms of masseteric pain and spasm. The rationale was to reduce side-effects and costs.
VAS scores were measured before and after treatment for 48 patients who received treatment with the original BtA protocol (“Protocol A” – the historical cohort who received 50 units) and for 46 patients who receieved a modified BtA protocol (“Protocol B” – the current cohort who received 25 units).
Patients in both treatment groups reported severe symptoms prior to treatment. Patients who received protocol B reported, on average, a 5 unit improvement in VAS following treatment (95 % confidence interval 4.3 to 5.7 improvement in VAS). There was no evidence that protocol B was less effective, despite the lower dose.
We recommend a reduced dose of BtA, of 25 units, for injection for appropriately selected patients with masseteric pain and spasm. A lower dose of BtA reduces wastage, particularly for single muscles injection and may reduce the incidence of unwanted side-effects. Reducing the standard dose of BtA will reduce costs for healthcare providers and may therefore facilitate funding for provision of intramuscular injection of BtA, where justified.
1
Introduction
Masticatory myofascial pain is a chronic facial pain, which can present as a part of the spectrum of temporomandibular joint disorder (TMD). The masticatory muscles facilitate temporomandibular joint (TMJ) movement, enabling functions including eating and speech. Disorders of the TMJ are common, often presenting with symptoms of moygenous origin, joint noises, locking or trismus. Myofascial masticatory pain characteristically presents with chronic, focal muscular pain and can present alongside trismus, headaches and cervical pain, depending on the extent of muscular involvement [ ].
The masseter muscle is one of the primary muscles of mastication. Masseteric hypertrophy can present as unilateral or bilateral swelling located at the angle of the mandible [ ]. It is associated with focal pain and can occasionally be confused with parotid swelling. The increased masseteric muscle mass aetiology may be unclear but can arise from excessive development of the muscle, often as a result of hyperfunction or parafunction. This is often accompanied by pain resulting in functional impairment, with well-established impacts on patients’ quality of life (QoL) and ability to complete daily activities such as talking and eating. While it is a benign condition, it can be prominent enough to be cosmetically disfiguring and associated with aesthetic complaints relating to an increased facial width [ , ].
Diagnosis is most commonly achieved through history taking and confirmed during clinical examination, where palpation of the trigger points elicits spot muscular tenderness, familair pain, muscle spasm, disproportionate flinching or referred pain, as the sensitised nociceptors in the trigger point are stimulated [ ]. The use of investigations such as plain film imaging, computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance elastography, to quantify asymmetries in muscle tone, and ultrasonography have all been described [ , , ] but are rarely indicated.
Varying degrees of success have been reported for some of the treatment options for masseteric hypertrophy, and its resultant pain, which range from conservative, self-supported measures for TMD, to more invasive surgical options [ , ]. Although most patients respond to self-supported management including advice to rest, physiotherapy/self-supported massage therapy, relaxation techniques, sleep hygeine advice and controversial use of occlusal splint therapy, a small number of patients do not respond to these measures [ , ]. Medical treatment with low dose tricyclic medication can be considered but for those who are reluctant to agree to this or cannot tolerate the side-effects, the next most common and efficient alternative is botulinum toxin A (BtA) injection.
BtA is a powerful neurotoxin produced by Clostridium botulinum, an anaerobic organism. When injected into a muscle it irreversibly binds to presynaptic cholinergic nerves terminals, resulting in exocytosis of acetylcholine at the neuromuscular junction and inhibition of muscular contraction. The selective paralysis results in subsequent atrophy of the muscle. Muscular recovery occurs when its motor nerve supply generates new axons, forming new synaptic contacts to re-establish the junction; BtA typically has an effect lasting between three and five months [ , ].
In 2020, we reported our results of a pilot and main study, during which patients diagnosed with masseteric hypertrophy, identified clinically and confirmed with ultrasonography, were treated with intramuscular injection of 50 units of BtA. Patients were asked to record the pain associated with their masseter muscles on a visual analogue scale (VAS) ( Fig. 1 ) of 1–10 (10 being the worst pain imaginable) prior to administration of BtA and again six weeks later at review. The results were that all patients showed an improvement in reported pain after BtA injection [ ].
While we have had success with this protocol in our department it was worthwhile to determine if a reduced dose of BtA could elicit comparable results, as this could reduce the risk of unwanted side-effects which can include weakness of a different facial muscle, difficulty talking or a transient inability to smile [ ]. The cost of BtA remains not insignificant, and with the growing importance of patient-reported outcome measures (PROMs) in the provision of healthcare in the current financial climate, it is important to ascertain treatment efficacy. Furthermore, a Cochrane review in 2013 recognised concerns about the long‐term effects of BtA and unclear therapeutic benefit regarding the treatment of masseteric hypertrophy [ ].
Our aim was therefore to determine whether a reduced dose of BtA was effective in the management of patients’ perceptions of painful masseteric hypertrophy.
2
Methodology
The methodology followed that of our 2020 service evaluation [ ]. The selection criteria was patients who: a) had a degree of unilateral or bilateral masseteric hypertrophy/enlargement; b) had associated pain and a perceived limitation of mouth opening; c) had no other underlying pathological cause of their signs and symptoms; d) had not respond after three months of conservative management, as outlined below.
Some patients had been involved in the previous service evaluation (termed “Protocol A” – the historical cohort who received 50 units) and therefore had previously undergone the following conservative measures. Those who has not previously had BtA injection initially undertook a three-month period of self-supported management, following assessment by a specialist physiotherapist at the hospital. They were advised about daily warm compresses, massage, and taking regular analgesia/non-steroidal anti-inflammatory medication during this period. Parafunctional habits were identified and excluded. At three-month review, patients who reported little or no improvement in pain and still had evident masseteric enlargement on clinical examination were recruited into this service evaluation (termed “Protocol B” – the current cohort who received 25 units). Hypertrophy was not measured. No exclusions were made for age or gender, and all patients were classed as grade I or II by the American Society of Anaesthesiologists’ physical classification system. No patients were rejected after the service evaluation began. In our pilot study, which preceded Protocol A, ultrasound scanning was used to measure the maximum masseteric thickness before and after BtA. In Protocol A, no patient received a postoperative ultrasound scan. This was because all pilot study patients showed little to moderate improvement in ultrasound-guided measurement of masseter muscle mass and this did not relate to clinical outcomes. Therefore, ultrasound was not completed for protocol B as this measurement was not relevant to our primary aims of VAS scores and our focus was on patient-reported outcome measures. Painful masseteric hypertrophy does not require ultrasound for diagnosis. The process of the two protocols can be seen in Fig. 2 .
Suitable patients were assessed by a single consultant Oral and Maxillofacial Surgeon (OMFS) and it was confirmed it was appropriate for them to receive a lower dose for clinical reasons, as opposed to for the purposes of a trial. All patients were aware of this and consented accordingly. Patient selection was therefore based on the aforementioned selection criteria and patients who opted to proceed with BtA an adjunctive treatment modality to self-supported management. The patients who were selected for a lower dose were either those who had reported a reduction in VAS scores following treatment using protocol A but continued to experience symptoms and thus sought repeat injections, as well as new patients who had not yet received BtA treatment. Directly prior to recruitment, patients had open and closed mouth sectional dental panoramic tomographs to assess movement and formation of the mandibular condyle and to screen for hard tissue pathology only. Those with pathology were excluded from this service evaluation. Imaging to screen for disc displacement was not undertaken.
Patients recorded the pain associated with their masseter muscles on a VAS of 1–10, immediately prior to the administration of BtA and again six weeks later at clinical review. These VASs were retained in the patient’s hospital notes.
All patients were given intramuscular masseteric injection of BtA by the same consultant OMFS. The drug used for injection was Botox® (Allergan). Each 50-unit vial of Botox® was diluted with normal saline to a concentration of 25 units/ml. Each muscle received a 25-unit dose of BtA, following the same injection protocol as Protocol A i.e via multiple injection points into the muscle but this time with the Protocol B dose. At administration the muscle was palpated and BtA injected into the thickest or most hypertrophied aspect. Injection, subsequent to aspiration to avoid intravenous placement, was with a 25-gauge needle.
Data analysis was carried out using the statistical software environment R. Pre-and post-treatment scores are paired data and tests for difference following treatment were carried out with paired T-tests. Pre-treatment scores between protocols were compared using unpaired T-tests. Protocol efficacy was tested by regressing the post-treatment score on the protocol (adjusted for the pre-treatment score to account for differences at baseline).
After discussion with our local institutional research and development review board, an exception from the requirement of ethics approval was granted, and this evaluation was registered as a service evaluation project.
3
Results
46 patients (76 masseter muscles) met the eligibility criteria. VAS scores were available before and six weeks after treatment (termed “VASpre” and “VASpost”). 48 patients received treatment with the original BtA protocol of 50 units per muscle (termed “Protocol A”) and 46 patients with a modified, lower-dose protocol of 25 units per muscle (termed “Protocol B”). These results have been presented as a violin plot in Fig. 3 , to demonstrate the distribution of the numerical data and Table 1 . Patients in this group demonstrated a high burden of symptoms prior to treatment, compared with the pre-treatment scores of those in Protocol A.
