Discussion
In this paper, we shared a case of acute pulmonary complication that resulted in the need for intensive care and intubation on the third day after treatment of focal spasticity with BoNTA in a patient with CPM. When we examined the literature in terms of BoNTA-related pulmonary complications, we found that Oliver et al. published clinical correspondence in 2018, in which they described a gradual decrease in pulmonary function over time, which returned to normal after BoNTA discontinuation during long-term treatment of migraine (11). We did not see any case in which pulmonary involvement developed in an acute dramatic manner as in our case. In addition, a multicenter study conducted in 2006 investigating the pulmonary effect of BoNTA reported that this treatment was safe without pulmonary complications (12).
It is known that after BoNTA applications, respiratory failure may develop due to paralysis of the respiratory muscles, which may result in death. In our case, we initially considered the paralysis of the respiratory muscles since the patient worsened approximately 72 hours after the BoNTA injection. Pulmonary involvement was not expected at first, and it was thought that the respiratory muscles were likely to be affected by toxins and that a tracheostomy would probably be required. However, the presence of bilateral consolidation in the lungs and areas of infiltration of ground-glass opacity on the thoracic CT taken during the intensive care period further complicated the case by revealing that the situation was not actually expected based on our knowledge that systemic complications associated with BoNTA therapy were uncommon and such an acute pulmonary complication had never been encountered before. However, the radiological findings on thoracic CT being interpreted in favor of ARDS, clinical indications, and absence of any other condition that could explain the etiology supported the possibility of a BoNTA-related pulmonary complication.
In a study in which the intranasal administration of BoNTA-related pulmonary involvement was evaluated in mice, some histopathological changes were detected in the lungs despite the protection of the animals against neurotoxic effects. Although this situation was not considered to be direct toxin poisoning, it was suggested to have occurred with alveolar hemorrhage due to pulmonary capillary endothelial injury caused by a secondary cytokine-mediated inflammatory reaction triggered by the toxin, which led to the development of interstitial edema (13). Similarly, in two studies, Ermert et al. observed widespread endothelial weakening in the electron microscopic examination of the lungs of rabbits poisoned with botulinum toxin c2 and found edema formation due to increased permeability in pulmonary capillaries (14,15).
In the retrospective evaluation of our patient, the ground glass opacities observed in the thoracic CT scan, rapid improvement in her clinical state according to the laboratory findings, and increased pulmonary capillary permeability and endothelial damage due to BoNTA and other toxin types reported in animal experiments in the literature primarily suggested that our patient developed an acute pulmonary complication in which pulmonary edema was seen due to increased capillary permeability associated with BoNTA.