A systematic review and meta-analysis published in PLoS Neglected Tropical Diseases reported a significant association between stroke and snakebite envenoming (SE), highlighting a severe but underrecognized neurologic complication. For clinicians working in or referring patients from SE-prone areas, these findings highlight the need for heightened vigilance, access to neuroimaging, and structured referral pathways.

The study was conducted by researchers at the Universidade do Estado do Amazonas (UEA) and the Fundação de Medicina Tropical Dr Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil, in collaboration with other national and international institutions.

Researchers have found that stroke may represent a systemic consequence of SE and have described it as a potentially severe complication that may be more common than previously assumed.

The analysis evaluated the principal clinical and epidemiologic characteristics of 130 individuals who developed stroke after SE. In addition, the researchers identified predictors of death through a meta-analysis of 100 studies. Patient data were compiled from the MEDLINE/PubMed, LILACS, and SciELO databases, following the PRISMA guidelines.

A total of 100 studies were included, predominantly case reports and case series, comprising 130 individuals with stroke after SBE. The reported cases of snakebite-related stroke originated from 22 countries, mostly India (36.9%), Brazil (13.9%), and Sri Lanka (10.8%). Reports from 19 other countries were also included.

Fatal Predictors

The most affected individuals were male (62.3%) aged between 40 and 59 years (37.7%). Most patients (90%) received antivenom treatment.

Species from the Viperidae family accounted for 96.4% of bites, particularly Daboia russelii and Bothrops species.

The overall mortality rate was 23.4%. Sepsis and thrombocytopenia were the predictors of death. Hemorrhagic stroke (HS), multiple brain lesions in a single hemisphere, and subarachnoid hemorrhage significantly increase the risk for mortality.

Venom Mechanism

In an interview with Medscape’s Portuguese edition, Wuelton Marcelo Monteiro, PharmD, MSc, PhD, full researcher at the FMT-HVD and associate professor of epidemiology at the UEA, explained that snake venoms, especially those from the Viperidae family, are known for their ability to interfere with hemostasis.

“The action of venom proteases, including metalloproteases and serine proteases, triggers clot formation through activation of different coagulation factors, inducing a procoagulant event, followed by consumption of clotting factors and leading to a state of reduced blood coagulability,” he explained.

Monteiro noted that venom toxins can impair platelet function, causing transient or persistent thrombocytopenia. In most cases, this occurs despite antivenom administration.

Sepsis, identified as a predictor of death, is associated with systemic inflammation, endotheliopathy with blood-brain barrier disruption, coagulopathy with microthrombi formation, impaired cerebral perfusion, and autoregulation. According to Monteiro, these pathologic processes may amplify venom-induced changes, increasing the vulnerability to stroke-related injuries.

Carlos Roberto de Medeiros, MD, PhD, physician and researcher at the Laboratório de Ecologia e Evolução, Instituto Butantan, and the Vector-Borne and Zoonotic Diseases Unit within Coordenadoria de Vigilância em Saúde, São Paulo, Brazil, explained that when a snakebite occurs, it is not possible to determine how much venom was injected. The amount of venom delivered, along with factors such as snake species, timely antivenom administration, age, and comorbidities, determines the severity of SE.

He emphasized that venom composition varies not only between species but also among individuals of the same species. “For example, the venom of a juvenile jararaca snake differs from that of an adult of the same species because of dietary differences. SE by juveniles may cause greater coagulopathy than that caused by adults.”

Despite this, over decades of medical practice, Medeiros witnessed only one case of stroke related to snakebite. “These cases are extremely rare in Brazil and are seen primarily in Bothrops snakebite accidents,” he said.

Infrastructure Gaps

Although the researchers did not identify a significant association between delayed antivenom administration and stroke occurrence, limited healthcare infrastructure had other adverse consequences.

These findings suggest that secondary complications related to SE, leading to death after stroke, could be mitigated with broader access to structured healthcare services.

More than 70% of the affected individuals experienced long-term sequelae, most commonly motor deficits (22.4%).

Monteiro noted that in many remote or resource-limited settings, the lack of neuroimaging and intensive care support is a major barrier to the timely recognition and treatment of neurologic deterioration. Clinicians should remain alert to warning signs, such as decreased level of consciousness, nausea, vomiting, and focal deficits. Rapid referral to centers equipped with CT and intensive care resources is essential for managing these patients.

He added that establishing regional referral networks and strengthening training for healthcare professionals at the community level may reduce delays in diagnosing such cases. Incorporating telemedicine support and standardized stroke alert protocols could further improve early detection and care coordination. “Considering the high mortality associated with HS, especially where imaging is unavailable, maintaining a high index of suspicion and ensuring early stabilization remain crucial to prevent avoidable deaths,” said Monteiro.

Neglected Morbidity

According to Iago Navas Perissinotti, MD, member of the Academia Brasileira de Neurologia, Brazil’s Ministry of Health SVS SINAN system recorded 28,208 snakebites in 2025, with 129 reported deaths, primarily in the northern and northeastern regions.

Speaking with Medscape’s Portuguese edition, he said “Although snakebite is a notifiable condition, these figures are likely underestimated, particularly in remote areas.”

He emphasized that although stroke related to SE is uncommon, several factors make it a neglected cause of increased morbidity and neurologic disability in Brazil. These include delayed initial care because most snakebites occur in rural or hard-to-reach areas, limited access to acute stroke therapies and neurosurgical or neurointensive care, and barriers to rehabilitation and specialized follow-up.

Brazil has established programs for the management of venomous animal injuries and acute stroke care, including epidemiologic surveillance systems, mandatory reporting, public production and distribution of antivenom, and basic care guidelines. However, access to these resources remains uneven, particularly in regions distant from major urban centers and in rural areas.

Perissinotti noted that the low incidence of stroke related to snakebites may not, on its own, justify specific public policies. Nonetheless, the issue underscores the importance of maintaining, integrating, and strengthening national and state programs that address both venomous animal injuries and stroke.

Protocol Approach

Speaking with Medscape’s Portuguese edition, Esteban Ortiz-Prado, MD, PhD, physician and researcher at the OneHealth Global Research Group, Faculty of Health Sciences, Universidad de Las Américas, Quito, Ecuador, discussed the findings of his systematic review published in Heliyon in early 2025 on cerebrovascular events induced by snake envenomation.

He identified delayed presentation and limited diagnostic capacity in low-resource settings as key barriers to the recognition and management of stroke triggered by SE. Symptom onset varies. Neurologic manifestations such as hemiparesis, aphasia, ptosis, and altered level of consciousness may develop minutes to days after the bite, and in some cases, as late as 6 days, he said.

He added that the accurate identification of snake species and the specific venom involved remains a major challenge. Without precise identification, the selected antivenom may be inappropriate, and stroke may be misattributed to the systemic effects of SE.

Investment in telemedicine and rapid identification kits could help mitigate these barriers and reduce the global burden, he said.

Ortiz-Prado emphasized the need for a multidisciplinary protocol for managing stroke related to SE, based on World Health Organization guidance and current scientific evidence.

Key components include:

• Initial assessment and stabilization within 1 hour after the bite
• Antivenom administration and systemic support
• Specific neurologic diagnosis
• Management of complications and follow-up
• Prevention and awareness

For neurologic diagnosis, if symptoms are present, urgent CT or MRI is recommended to differentiate ischemic stroke from HS. Hemiparesis and aphasia occur in more than 15% and 16% of cases, respectively. Coagulopathy should also be assessed. Platelet transfusion is indicated when the platelet count is < 50,000 cells/mm³.

Therapeutic guidelines recommend antiplatelet agents, such as acetylsalicylic acid or clopidogrel, for ischemic stroke without thrombolysis because of the risk for bleeding.

According to Ortiz-Prado, adopting such protocols may standardize care in low- and middle-income countries, reduce disability resulting from snakebites, and optimize resource use.

This story was translated from Medscape’s Portuguese edition.