Drooling, also known as sialorrhea, is the uncontrolled leakage of saliva outside of the mouth due to a difficulty in swallowing. Drooling is natural in normally-developing infants from 15 to 36 months of age but generally stops by about 18 months. However, it is regarded to be abnormal if it lasts beyond the age of 4 years [1]. Pathologic drooling is related to hypersalivation or to several neurologic disorders such as Parkinson disease, cerebral palsy, amyotrophic lateral sclerosis, stroke, and traumatic brain injury. Anterior drooling—unintentional flow of saliva from the mouth—can lead to clinical and functional problems for patients or caregivers. In the case of posterior drooling, which refers to saliva that is spilled over the tongue through the isthmus of the fauces, aspirationrelated respiratory and pulmonary complications, which have significant effects on mortality and patient prognosis, can occur [2]. Thus, the management of drooling can be an important challenge for rehabilitation physicians. To date, many different treatment options have been proposed for the management of drooling. These have included postural control, radiation therapy, medications such as anticholinergics, or invasive surgical approaches such as duct ligation or gland excision [3]. However, these treatment options are often unsatisfactory, including side effects such as systemic anticholinergic effects, local damage, and increased risk of malignancy with irradiation [4].

The injection of botulinum toxin (BTX) into the submandibular and parotid glands was proposed in 1997 [5]. Since then, multiple studies have evaluated the efficacy of BTX for the treatment of drooling, especially in neurological diseases. Pharmacologically, BTX blocks the release of acetylcholine at the neurosecretory cholinergic synapses of the salivary glands, thereby decreasing salivary secretion. Generally, in the treatment of drooling with BTX injection, the parotid gland is commonly injected into one to three sites and the submandibular gland is usually injected into one site. In previous studies, BTX injection procedures were performed blind using anatomical landmarks or ultrasound (US) guidance [3]. The risks of the procedure include induced weakness of the adjacent muscles, leading to a difficulty in swallowing due to an incorrect injection of the toxin into the masseter or pharyngeal muscles [6]. Other potential risks include hematoma and injury to the carotid arteries or the facial nerve. Although recent investigations have reported the increased efficacy and safety of BTX injection under US guidance [7], there have not been any studies comparing the injection accuracy between blind and US-guided approaches. This study was designed to evaluate the injection accuracy of blind and US-guided botulinum injections into the parotid and submandibular glands of fresh cadavers.

The injection of BTX into the salivary glands for the management of drooling is widely used in patients with certain neurologic disorders. A number of previous reports have demonstrated its efficacy and safety and the procedure is now frequently used by many physicians. In the past, clinicians have usually injected BTX into both the parotid and submandibular glands using a ‘blind’ procedure [4]; however, US-guided procedures have recently become popular.

The use of US in the medical field has been increasing due to the numerous advantages of doing so. US enables dynamic, real-time monitoring during needle injection, and it is fast, less invasive, and has no associated risk of radiation exposure. However, the ‘blind’ injection method is still used by many clinicians because of its convenience. Yet, inappropriate BTX injection can damage important structures around the salivary glands, such as muscles, arteries, and nerves. Inappropriate BTX injection can also cause weakness in the adjacent muscles, resulting in swallowing or mastication difficulties. Furthermore, injury to structures such as a carotid artery or the facial nerve can be fatal to patients [10]. In addition, the accuracy of the BTX injection is an important factor that determines the efficacy of the procedure. Considering the pharmacologic mechanism of BTX, inaccurate injection into the periglandular structures will reduce the effect of the toxin at the target site [11]. Thus, increased accuracy of injections can lead to better clinical outcomes.

Considering these factors, our study compared the accuracy of blind and US-guided injection of the salivary glands. We examined the accuracy of non-US-guided versus US-guided dye injection, in two sites in the parotid glands and one site in the submandibular gland, in 12 specimens. In the parotid gland, the differences in accuracy between the two procedures was not found to be significant. Previous studies comparing non-US-guided injection and US-guided injection have reported mixed results. Some studies have reported that US-guided parotid injection improves efficacy and safety as compared to non-US-guided injection procedures [7]. However, another study reported no significant difference in parotid gland BTX injection efficacy between non-US-guided injection and US-guided injection [12]. Since the parotid gland is large, wide, and superficially located, its injection in blind procedures is thought to be relatively accurate. However, in the submandibular gland, the difference in accuracy between the two procedures was found to be statistically significant. Although the anatomical localization of the submandibular gland for BTX injection study has been reported in previous studies, a comparison of the accuracy of injection into the submandibular gland using US-guided as compared to non-guided techniques has not been reported. The submandibular gland is the major gland responsible for resting saliva secretion; while the parotid gland is predominantly active during mastication [6]. Patients with neurological disorders often suffer from drooling while in the resting state rather than during eating. Thus, control of the saliva secreted by the submandibular gland is more important than control of the saliva from the parotid gland [13]. Since the submandibular gland is smaller than the parotid gland and can present in varying positions [13], injection into the target area can be difficult. In addition, adjacent structures around the submandibular gland, such as fat tissue and complex musculature, make it difficult to palpate the gland itself; thus, making it difficult to accurately inject BTX into the gland.

In the present study, injections were incorrectly placed in various sites. In the parotid gland injections, the erroneous locations were the masseter muscles and subcutaneous fat tissue. In the submandibular gland injections, the erroneous locations were the mylohyoid muscles and subcutaneous fat tissue. The injection of toxin into the masseter muscle can cause mastication issues. More importantly, toxin injection into the mylohyoid muscle can cause severe dysphagia associated with aspiration that can be fatal to patients with neurologic disorders [9]. In addition, although we could not find evidence of penetrated neurovascular structures, dye was found just beside the facial artery in some blind injection cases. We could not reach a conclusion as to the safety of US-guided injection with regards to vasculature because there is no dynamic blood flow in cadavers. However, it is undeniable that US-guided injection in live patients decreases the risk of neurovascular puncture. Given the risk of intramuscular injection and neurovascular puncture, our position is that US guidance should be considered when managing drooling with BTX injection into the submandibular gland.

Our study has several limitations. Firstly, the sample size was small because we were limited to six fresh cadavers. Furthermore, each physician performed glandular injections in only one side of each cadaver, as repeated injections may obscure the precise location of the dyes within the glands. In the case of the parotid gland, the difference in the accuracy of injection is not as great as in the submandibular gland and was not statistically significant; however, this result might be due to the small sample size. Secondly, accuracy differed somewhat from the comparisons of efficacy that had previously been reported. Although BTX was injected into the subcutaneous tissue, its diffusion might affect the comparison of efficacy with regards to the outcome of drooling. However, comparing the rates of accuracy may be more valuable than comparing their efficacy, when considering the safety and maximal effects of BTX injection [13].

In conclusion, the present study provides evidence that US-guided BTX injection into the submandibular gland offers significantly greater accuracy over blind injection. The use of ultrasound has many advantages, including convenience and the absence of risk of radiation exposure. Therefore, when treating drooling by injecting BTX into the submandibular gland, clinicians should consider using US guidance in order to improve accuracy. Moreover, for improved safety, we think that US-guided injection into the parotid gland may also be considered.