Statistics from Altmetric.com
We have read with interest the article by Giesset al,1 which showed that botulinum toxin A (BoNT/A) might be a new treatment option for sialorrhoea in patients with bulbar palsy. We have recently conducted a similar study which was interrupted due to serious side effects.
In September 1998 we injected 25 MU Botox into the parotid glands of a 59 year old women who had ALS with pronounced bulbar palsy. We noticed a reduction of the sialorrhoea but facial weakness on the left side worsened significantly.
After this experience we developed a protocol for the treatment of sialorrhoea in patients with ALS with bulbar palsy by retrograde injection of BoNT/A through the salivary duct into the salivary glands. We chose the retrograde way of administration of BoNT/A for this pilot study because we thought that this technique would avoid facial weakness.
After informed consent the patients received 12.5 mouse units (MU) BoNT/A (BotoxR) retrogradly into each parotid and sublingual gland from a small catheter inserted into the salivary duct. Neurological examination and quantification of saliva production were performed before the BoNT/A injection and on days 1, 3, 7, 14, and 28, as well as after 2 and 3 months. Technetium 99m scintigraphy was performed before and 7 days after the injection. Quantification of saliva production was performed with a simple method: the patients were asked to expectorate as much saliva as possible into a paper handkerchief for 10 minutes. This procedure was repeated twice. The mean of the difference in weight of the handkerchief before and after these procedures was taken as the maximum expectorated saliva production (MESP). Quality of life and the clinical effect of the treatment were evaluated by a questionnaire.
We treated a 60 year old woman (patient 1) and a 69 year old women (patient 2) with this new technique. Both had certain ALS according to the El Escorial criteria, with severe bulbar palsy with durations of 23 and 28 months respectively. Both patients had a significant reduction of MESP seven daysafter the injection (76% and 58%; from 5420 mg to 1301 mg, and 4365 to 1829 mg) which lasted for 4 to 8 weeks. Technecium 99m scintigraphy showed a significant reduction of radiotracer uptake into the injected salivary glands in both patients (figure). Both patients estimated the injection procedure as painful. Patient 1 developed a severe swelling of the right sublingual salivary gland and base of the tongue 3 days after the injection which was treated with antibiotics and corticosteroids. Patient 2, who was able to swallow with difficulty before the injection, mentioned impairment of swallowing between days 4 and 21. Both patients had a “moderate” improvement of sialorrhoea but did not want the injections to be repeated. After these experiences we decided to stop the pilot study.
The injection of BoNT/A through the salivary duct reduces the activity of the salivary glands significantly for several weeks but has serious side effects. Local and systemic effects of BoNT/A are probably pronounced in ALS.2 Subclinical EMG abnormalities distant to the injection sites have been described in therapeutic doses, but also systemic weakness has been found.3 As there are some reports that BoNT/A injections, even in low doses, may exaggerate pre-existing neuromuscular diseases,2 4 careful monitoring of neurological symptoms, which is difficult in a progressive disease, is needed to exclude side effects of BoNT/A. The drug is effective in reducing drooling5 but we need more data about the safety of BoNT/A before it can be used safely for the treatment of sialorrhoea in ALS. The transductal approach in particular seems to have unacceptable side effects.
The authors reply:
We appreciate the comments by Winterholleret al on our article1-1 on botulinum toxin (BTX/A) treatment of sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). Although we did not find any serious side effects after transcutaneousinjections of BTX/A into the parotid and submandibular glands Winterholler et al report on sublingual salivary gland infection in one patient and deterioration of dysphagia in another patient after a transductalapproach. These complications support our notion that the individually tolerated dose of BTX/A in patients with ALS may be low and also indicate that the transcutaneous approach as performed in several studies1-1-1-3 may be safer than the retrograde transductal injection. This is not unexpected as the transductal approach has possibly a higher risk of infection because of the reduced salivary gland secretion rate found in patients with ALS.1-1 In addition, the total dose of 25 MU Botox for the sublingual glands may be rather high in view of the close anatomical relation of these glands to the pharyngeal muscles. We therefore underscore our previous suggestion to start with injections of the parotid glands alone and to cautiously escalate the dose and number of injected glands.1-1 In view of the potential risk of BTX/A in deteriorating ALS symptoms injections should be restricted to otherwise intractable and extremely disabled patients with ALS who have sialorrhoea.