Early Clinical Approach Prevents Severe Neurotoxicity Following Cobra Envenoming: An Integrated Experimental and...

Background: Cobras (Naja sp.) are medically important snakes in Thailand. Envenoming by the monocled cobra (N. kaouthia) often causes neurotoxicity, most notably ptosis, ophthalmoplegia, local tissue necrosis and progressive paralysis leading to respiratory failure. Early antivenom administration and respiratory support are medically significant for effective treatment. Methods: In this study, we determined the association between the time course of cobra envenoming and related neurotoxic outcomes using the clinical profiles of cobra envenomed patients. We also demonstrated histopathological changes in the neuromuscular junction of the diaphragm in experimentally envenomed rats. Results: A retrospective study of 69 cases of cobra envenoming in Central and Southern Thailand shows that delayed arrival beyond one hour at hospital was common among younger adults (47.0% aged 10-29) and associated with more severe neurotoxicity, including higher rates of ptosis (41.2%, p = 0.032) and referrals (41.2% vs. 15.4%, p = 0.040). Antivenoms (22 Monovalent and 1 Polyvalent) were administered to 23 (33.3%) envenomed victims and caused adverse reactions in 9 cases (39.1%). Neurotoxicity following cobra envenoming in the clinical section correlated with histopathological examination of envenomed rat diaphragms. Transmission electron microscopy (TEM) revealed degeneration of the neuromuscular junction and diaphragm within 1 h following experimental cobra envenomation, which worsened by 4 h. Intravenous administration of antivenom at recommended doses reduced diaphragmatic damage but failed to prevent presynaptic degeneration after 90 min of envenoming. Conclusions: Clinically, extraocular muscle paralysis was the earliest manifestation. Early monitoring and prompt administration of antivenom are essential to reduce neurotoxicity and relevant complications.