Long term efficacy and safety of botulinum toxin A injection for crocodile tears syndrome

Gustatory lacrimation, also called crocodile tears syndrome (CTS), is an autonomic synkinesia in which patients tear excessively in response to salivary stimuli. It occurs most commonly in the setting of idiopathic or traumatic facial palsy and is thought to result from aberrant reinnervation of the lacrimal gland by salivary efferent fibres from either the seventh or ninth cranial nerve. Many patients tolerate CTS and require no intervention. For patients who cannot tolerate CTS, past treatments have included anticholinergic drugs, subtotal resection of the palpebral lobe of the lacrimal gland, and resection of the tympanic nerve proximal to the lesser superficial petrosal nerve. None of these approaches is optimal because of limited efficacy, morbidity, or both.

Injection of botulinum toxin A has been shown to be effective for a host of disorders characterised by involuntary muscle spasms, including blepharospasm, hemifacial spasm, and torticollis. Botulinum toxin A also has been used to treat a number of localised autonomic disorders, including axillary hyperhidrosis, palmar hyperhidrosis, and Frey syndrome.¹ In 1998, Boroojerdi et al reported the successful treatment of CTS by injection of botulinum toxin A directly into the lacrimal gland.² Since then, there have been five reports of similar treatments, all of which were successful.^3–7 All of these studies report complete or near complete resolution of the syndrome within a week with only infrequent, minor, and reversible complications. We now report a patient with CTS who has been successfully managed for 3 years with injections of botulinum toxin A.

Case report

A 38 year old man presented in July of 2000 with a 6 month history of right sided tearing and hyperhidrosis of the auriculotemporal region when eating or when hungry. Fourteen months previously, he had undergone a total right parotidectomy for a mixed tumour of the parotid gland. Immediately after surgery, he had a complete right sided facial palsy and numbness of the right lower face. The facial palsy resolved completely a month later, but the facial numbness persisted. Eight months later, the patient began to experience increased tearing on the right after eating, most notable after eating mints. On examination, the patient had normal facial movement but decreased sensation to light touch in the region of the second division of the trigeminal nerve and spasm of the right lower lid on palpation. In addition, he perspired from the right side of the face and had tearing from the right eye upon eating. His ocular and neurologic examinations were otherwise unremarkable.

In light of the bothersome nature of CTS to this patient, we felt a trial of botulinum toxin A was warranted. Accordingly, after obtaining consent, we injected botulinum toxin A (Botox 2.5 U) transconjunctivally into the palpebral lobe of the right lacrimal gland under direct visualisation at the slit lamp biomicroscope without complication. The patient’s excess epiphora completely resolved within 5 days, and he remained asymptomatic for 11 months. He has subsequently required injections of botulinum toxin A every 7–11 months, experiencing relief of symptoms with each injection. There have been no complications from any of the injections.

Comment

Several different groups have now reported a total of 12 cases of CTS treated with botulinum toxin A.^2–7 All of the patients reported have had complete or near complete short term resolution of symptoms with doses of botulinum toxin A (Botox) ranging from 2.5–60 U. The higher doses seem to have no additional benefit in terms of efficacy or duration.

Injection of botulinum toxin A for CTS appears to be safe, although minor complications occasionally occur. Two of the patients injected transcutaneously developed ptosis, one accompanied by a superior rectus palsy,^5,7 whereas two others developed dryness of the injected eye.⁷ These complications resolved over several months. No cases of ptosis or extraocular muscle weakness have been reported after transconjunctival injection, and our patient has had no complications with any of his injections over the last 3 years.

As with all new treatments, there are concerns about long term efficacy and safety. Botox has been found both safe and effective at the neuromuscular junction, but its long term effects on the peripheral autonomic system are unknown and one might postulate that the repeated minor trauma of the injection could eventually impair lacrimal gland function. In light of these concerns, it is encouraging to be able to report that repeated injections of botulinum toxin A continue to be effective in controlling this patient’s CTS for 3 years without complication.