Cerebral Venous Sinus Thrombosis (CVST) after snakebite is a condition that occurs as a complication of acute systemic coagulopathy due to snake envenomation.
According to estimates by the US CDC, 7,000 to 8,000 people are bitten by venomous snakes each year in the United States. The annual number of deaths averages only 5. The main venomous snakes inhabiting the United States are the following four species.
Snakebites tend to occur frequently from April to October, with higher incidence in southern states. They are more common in men, and men engaged in outdoor work are at the highest risk.
Acute complications have been extensively studied, but long-term sequelae should not be overlooked. Among venomous snakebite patients, 13.7% had at least one long-term complication including migraine, musculoskeletal disorders, visual impairment, acute kidney injury, or psychological distress3. Neurological symptoms of snakebites have also been summarized in recent systematic reviews, showing that neurotoxic snakebites frequently cause ptosis, limb muscle weakness, and respiratory muscle paralysis4.
It has been reported that 13.7% of venomous snakebite patients have at least one long-term complication. These include visual impairment, migraines, musculoskeletal disorders, acute kidney injury, and psychological distress. CVST is considered one of these complications.
The subjective symptoms of CVST are diverse, with the following being the main ones.
CVST presents different clinical pictures depending on two pathophysiological mechanisms.
Venous infarction type
Focal neurological deficits: Stroke-like symptoms such as hemiparesis, aphasia, and sensory disturbances.
Seizures: Caused by cortical irritation due to venous infarction.
Facial nerve palsy: Weakness of facial muscles is observed.
Venous congestion type
Increased intracranial pressure: Generalized elevation of intracranial pressure due to venous congestion.
Decreased level of consciousness: In severe cases, may progress to coma.
Papilledema: Appears bilaterally, causing visual acuity and visual field deficits.
Ophthalmologically, papilledema is an important sign of increased intracranial pressure. Bilateral papilledema is confirmed by ophthalmoscopy. It may be accompanied by bilateral abducens nerve palsy, which is often detected as esotropia in children.
As an initial sign of chronic recurrent coagulopathy after snakebite, superficial and deep vein thrombosis or pulmonary embolism may precede progression to CVST with increased intracranial pressure and papilledema25.
Papilledema, diplopia, transient visual disturbance, and abducens nerve palsy may occur. Papilledema occurs bilaterally as a result of increased intracranial pressure and, if left untreated, can lead to irreversible visual impairment. Early detection by fundus examination under mydriasis is important.
Snake venom is broadly classified into two types: hemotoxic and neurotoxic. The specific proteins and enzymes contained in snake venom cause hemolysis, tissue necrosis, anticoagulation, and hypercoagulability 25.
In the acute phase, snake venom disrupts hemostatic homeostasis, leading to coagulopathy. This increases the risk of thrombosis or bleeding.
The main systemic reactions in the acute phase are as follows:
| Reaction | Pathophysiology |
|---|---|
| DIC-like disease | Disseminated intravascular coagulation |
| Acute renal failure | Renal blood flow impairment and nephrotoxicity |
| Hypovolemic shock | Fluid loss / increased vascular permeability |
| Death | Irreversible damage in severe cases |
As a long-term complication of snakebite, snake venom is thought to trigger an immune response leading to a chronic hypercoagulable state. Hypercoagulability is a known risk factor for CVST and forms the basis of the mechanism by which CVST develops after snakebite12.
In the differential diagnosis of common risk factors for CVST, infectious, autoimmune, and metabolic etiologies should also be considered.
In the medical history, the following past medical conditions are important.
Select imaging tests to evaluate stenosis or occlusion of the cerebral venous sinuses.
| Test Method | Characteristics |
|---|---|
| CT | Useful for emergency evaluation. Detects hemorrhagic changes. |
| CT venography (CTV) | Visualizes occlusion or thrombosis of venous sinuses. |
| MRI | Detailed evaluation of parenchymal lesions and brain edema. |
| MR venography (MRV) | Standard evaluation method for venous sinus stenosis/occlusion. |
| Catheter cerebral angiography | Performed when detailed vascular evaluation is needed. |
MRV can most accurately evaluate stenosis/occlusion of the cerebral venous sinuses. Definitive diagnosis requires measurement of cerebrospinal fluid pressure, but before that, it is standard to rule out space-occupying lesions and hydrocephalus with CT/MRI.
Perform in the left lateral decubitus position and measure the opening pressure. An opening pressure of 25 cm H2O or higher is considered abnormally elevated and indicates increased intracranial pressure.
If CVST is suspected, a complete ophthalmic examination including dilated fundus examination is recommended.
In CVST suspected due to snakebite, hematological evaluation and liver function assessment are performed, along with investigation of alternative etiologies (infectious, autoimmune, metabolic). Differential diagnoses include vascular, postoperative, traumatic, infectious, inflammatory, infiltrative, and neoplastic diseases.
First, head CT/MRI is performed to rule out space-occupying lesions and hydrocephalus, and MRV is used to evaluate stenosis or occlusion of the cerebral venous sinuses. Ophthalmologically, a dilated fundus examination is performed to check for papilledema, and fluorescein fundus angiography and OCT are used as adjuncts. Lumbar puncture is performed to measure cerebrospinal fluid pressure, along with hematological evaluation and liver function assessment.
In the acute phase immediately after a snakebite, prioritize the following procedures.
Anticoagulation Therapy
Warfarin therapy: In Japan, warfarin therapy is used for cerebral venous sinus thrombosis. Early treatment preserves visual function, but delayed treatment leads to irreversible damage.
Systemic anticoagulation: Aimed at preventing thrombus extension and promoting recanalization 125.
Thrombolytic therapy: Selected for cases where medical management is difficult.
Intracranial Pressure Management
Monitoring and control of intracranial pressure: Combination of fluids, anticoagulants, and surgical procedures.
Administration of Diamox and mannitol: Used together with lumbar puncture in idiopathic intracranial hypertension (Diamox is not covered by insurance).
Regular treatment adjustments: Continuous management is necessary if there is a chronic recurrent coagulation disorder.
In severe cases that cannot be managed medically, surgical intervention is required.
The risk of complications increases when the following factors are present.
For malignant CVST or parenchymal lesions causing brain herniation, decompressive craniectomy is selected; for marked neurological deterioration, direct thrombectomy is chosen. Ventriculoperitoneal shunt is indicated for fourth ventricle obstruction or benign intracranial hypertension.
Snake venom is broadly classified into hematotoxic and neurotoxic types. The main cause of hematological complications is coagulopathy due to disruption of coagulation homeostasis by snake venom.
In the acute phase, the risk of thrombosis or bleeding increases through the following pathways:
The chronic phase mechanism (hypothesis) is thought to be as follows.
Snake venom induces an immune response, leading to a persistent state of chronic hypercoagulability. This condition is a known risk factor for CVST and is believed to explain the development of CVST after snakebite.
CVST involves two clinical presentations.
Snakebite has been reported as one of the acquired causes of visual impairment, and the progression from papilledema to visual dysfunction is important.
Research on long-term complications including CVST after snakebite is currently very limited.
Yousaf M, Khan QA, Anthony MR, et al. Snakebite Induced Cerebral Venous Sinus Thrombosis: A Case Report. Clin Med Insights Case Rep. 2023;16:11795476231165864. PMID: 37033678. https://pubmed.ncbi.nlm.nih.gov/37033678/ ↩ ↩2 ↩3
Ghosh R, León-Ruiz M, Roy D, Naga D, Sardar SS, Benito-León J. Cerebral venous sinus thrombosis following Russell’s viper (Daboia russelii) envenomation: A case report and review of the literature. Toxicon. 2022;218:8-13. PMID: 36041514. https://pubmed.ncbi.nlm.nih.gov/36041514/ ↩ ↩2 ↩3 ↩4 ↩5
Jayawardana S, Arambepola C, Chang T, Gnanathasan A. Long-term health complications following snake envenoming. J Multidiscip Healthc. 2018;11:279-285. PMID: 29983571. https://pubmed.ncbi.nlm.nih.gov/29983571/ ↩ ↩2
Pandit K, Rawal A, Maskey HMS, Nepal G. Neurological and neuro-ophthalmological manifestations of snake bite: a systematic review. Ann Med Surg (Lond). 2023;86(1):353-364. PMID: 38222724. https://pubmed.ncbi.nlm.nih.gov/38222724/ ↩
Sidow NO, Ibrahim AA, Hilowle NM, et al. Viber Snakebite Presenting with Cerebral Venous Thrombosis: A Very Rare Case Report from Somalia. Vasc Health Risk Manag. 2024;20:471-476. PMID: 39439784. https://pubmed.ncbi.nlm.nih.gov/39439784/ ↩ ↩2 ↩3
