Cerebral Venous Sinus Thrombosis after Snake Envenomation

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Disease Entity

Snake envenomation is relatively common and is known to be associated with acute systemic coagulopathy complications. However, there is increasing evidence suggesting coagulopathy complications may persist after the treatment of acute snake envenomation.[1]

Epidemiology

The CDC estimates that 7,000-8,000 people in the United States are bitten by a venomous snake every year. Despite this, only 5 people on average die per year. The four most common venomous snakes in the United States are rattlesnakes, copperheads, water moccasins/cottonmouths, and coral snakes. Most snakebites happen between April and October, are more likely to be reported in the southern states, and men are more likely to be affected.[2] While most snakebites do not cause long-term complications, a recent study indicated that 13.7% of people bit by a venomous snake had at least one long-term complication such as migraines, musculoskeletal disorders, visual impairments, acute kidney injuries, and psychological distress, among others.[1] Risk factors for snake envenomation include the time of year, region of the country, occupation, and gender. Males who work outside in the south of the U.S. are at the highest risk for snakebites.[3]

Pathophysiology

Snake venom is either hemotoxic or neurotoxic. Each snake venom contains unique proteins and enzymes that can cause various pathologies including hemolysis, tissue necrosis, or anticoagulant or hypercoagulable states. Many hematologic complications, however, are due to the venom’s ability to disrupt the homeostasis of blood coagulation, leading to coagulopathy. This can manifest either as an increased risk for thrombosis or hemorrhage, often in the acute phase post-snakebite. Systemic reactions can also occur in the acute phase of snake envenomation, including a disease similar to dissemination intravascular coagulation (DIC), acute renal failure, hypovolemic shock, and even death.[1] [3] The physiologic response, possible complications, and treatment of snake envenomation are well studied in the acute phase, however, little research has been dedicated to understanding possible long-term pathologies associated with snake envenomation. The snake venom caused an immune response leading to chronic hypercoagulability has been suggested as a long-term sequelae of snake envenomation. A hypercoagulable state is a known risk factor for the development of CVST.[4]

CVST typically has two prominent clinical presentations. The first is focal manifestation due to venous infarction and is often associated with seizures and stroke-like presentation. The second is global manifestation due to venous engorgement and is often associated with increased intracranial pressure and a depressed level of consciousness.[4]

Diagnosis

Symptoms and signs

History taking focus on previous snake bites and any history of hypercoagulable state complications of either thrombosis or hemorrhage. Early signs of chronic recurrent coagulopathy following a snakebite could be variable, for example, superficial and deep venous thromboses, pulmonary embolism. Advanced signs included cerebral venous sinus thrombosis which leads to increased intracranial pressure and papilledema.

Common presenting signs of CVST include headaches, focal neurologic deficit, nausea and vomiting, seizures, pulsatile tinnitus, unilateral deafness, double vision, facial weakness, or obscuration of vision.[5]

Diagnostic procedure

Diagnostic procedures focus on brain imaging and blood tests for possible CVST but also on hepatic and hematologic work-ups which could provide insight into causes of chronic coagulopathy complications. Imaging techniques used in evaluating thrombosis, increased intracranial pressure, and papilledema (e.g., computed tomography (CT), CT venogram (CTV), magnetic resonance imaging (MRI), MR venogram (MRV), and catheter cerebral arteriography). A complete eye exam including dilated ophthalmoscopy is recommended in suspected CVST to exclude papilledema. Hematologic workup and hepatic evaluation as well as consideration for alternative etiologies should be considered (e.g., infectious, autoimmune and metabolic) in CVST from suspected snakebite.

Differential Diagnosis

The differential diagnosis for CVST includes vascular, post-surgical, traumatic, infectious, inflammatory, infiltrative, and neoplastic conditions.[5]

Management

Management in acute phase

Treatment of the acute phase of snake may include administration of antivenom in addition to supportive care (e.g., IV fluids) and any additional necessary vaccinations. Symptoms and signs of an acute snakebite envenomation should be monitored.[5]

Medical management of CVST

Medical treatment for CVST largely involves monitoring and controlling the intracranial pressure. This can be accomplished through the administration of fluids, anticoagulants, and/or surgical procedures. Surgery may be required in cases of malignant CVST.[6] Currently, CVST is treated with systemic anticoagulation or thrombolytic therapy.[5] Factors that increase the risk for complications include intracerebral hemorrhage, coma, papilledema, older age (>33), and involvement of the straight sinus.[6] Adjustments may need to be made regularly in order to treat chronic recurrent coagulopathy if present or a contributing factor to malignant CVST.

Surgical management of CVST

Surgical procedures used to treat CVST include decompressive craniotomy for cases of malignant CVST or cases with parenchymal lesions causing herniation, open thrombectomy for cases of severe neurologic deterioration, decompressive surgery for patients with lesions causing herniation, and ventriculoperitoneal (VP) shunt placement if there if fourth ventricle obliteration or in cases of benign intracranial hypertension.[6]

Complications

Complications include parenchymal edema with venous infarct and hemorrhage. This occurs in up to 50% of patients with CVST. Pulmonary embolism is another rare complication that is associated with worse outcomes. If the CVST involves the cavernous sinus, hypopituitarism can result. Some patients may experience persistent focal seizures post CVST and may require permanent anti-epileptic treatment. Trans-tentorial herniation is the most common cause of acute death related to CVST.[4]

Prognosis

The prognosis for CVST is fairly good. Certain factors may increase the risk for poor outcomes post CVST including old age, involvement of the deep veins, CNS infection, cancer, or if the patient initially presents with either coma or hemorrhage. There is little research on the prognosis of chronic CVST. The long-term impacts of snake envenomation and the prognosis associated with those complications have not been sufficiently studied.[4]

References

  1. 1.0 1.1 1.2 Jayawardana S, Arambepola C, Chang T, Gnanathasan A: Long-term health complications following snake envenoming. J Multidiscip Healthc. (11); 279-285, 2018
  2. Centers for Disease Control and Prevention. Venomous Snakes. 2021
  3. 3.0 3.1 Juckett G, Hancox JG: Venomous Snakebites in the United States: Management Review and Update. Am Fam Physician. 65(7); 1367-1375, 2002
  4. 4.0 4.1 4.2 4.3 Itrat A, Shoukat S, Kamal AK: Pathophysiology of Cerebral Venous Thrombosis - An overview. Journal of Pakistani Medical Association. (56)11; 506-508, 2006
  5. 5.0 5.1 5.2 5.3 McElveen WA, Keegan AP: Cerebral Venous Thrombosis Treatment & Management. MedScape Journal of Medicine, 2018
  6. 6.0 6.1 6.2 Enam SA: Role of Surgery in Cerebral Venous Sinus Thrombosis. Journal of the Pakistan Medical Association (56)11; 543-546, 2006
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