Strokes following snakebite envenomations: A systematic review and individual patient data meta-analysis

Snakebite envenomings (SBE) are an important and neglected health issue due to their frequency and potential for severe clinical outcomes. Envenomations can cause local and systemic complications, depending on the snake species, amount of venom injected, comorbidities, timing and use of antivenom, and access to health care. Systemic effects may be fatal or lead to permanent sequelae, including strokes resulting from venom-induced vascular and tissue damage. The objective of this study is to investigate the main clinical and epidemiological characteristics of individuals who developed stroke following SBE and to identify predictors of death.

We conducted a systematic review and individual patient data meta-analysis using a predefined search strategy across MEDLINE/PubMed, LILACS, and SciELO databases, following PRISMA guidelines. A total of 100 studies were included, predominantly case reports and case series, comprising 130 individuals with stroke following SBE. Most patients were male (62.3%) and aged between 40 and 59 years (37.7%). Viperids caused 96.4% of the snakebites, particularly Daboia russelii and Bothrops spp. Most patients (90%) received antivenom therapy. Reported cases of snakebite-related stroke originated from 22 countries, mostly from India (36.9%), Brazil (13.9%) and Sri Lanka (10.8%). Ischemic strokes were more common than hemorrhagic strokes (61.5% vs. 38.5%), and multifocal brain involvement was predominant in both stroke types. Overall case-fatality was 23.4%. Sepsis [OR=6.21 (1.35-33.47); P = 0.001] and thrombocytopenia [OR=3.97 (1.66-10.03); P = 0.02] were predictors of deaths. Hemorrhagic stroke [OR=2.67 (1.15-6.31); P = 0.02], multiple brain lesions in a single hemisphere [OR=7.57 (2.33-33.39); P < 0.001], and subarachnoid hemorrhage [OR=7.00 (1.87-29.4)); P = 0.001] significantly increased the risk of death. Motor sequelae remained the most common long-term outcome (22.4%), occurring significantly more often in ischemic stroke survivors (28.8% vs. 9.4%, P = 0.05). Autopsy findings revealed intense brain alterations generally in parallel with damage in other organs such as the kidneys, lung, and heart.

Strokes from SBE represent a potential medical emergency in low- and middle-income countries where snakebites predominate, and lead to high rates of mortality and long-term disability. Recognizing stroke as a disabling and underreported consequence of snakebite is essential for improving clinical outcomes and guiding public health responses. Integrating the knowledge on predictors of death from SBE-relate strokes into health policies will be vital for reducing long-term morbidity and advancing disability-inclusive strategies.