Snakebite Induced Cerebral Venous Sinus Thrombosis: A Case Report

Abstract

Introduction:

Cerebral venous sinus thrombosis (CVST) is a rare but highly fatal neurological condition mostly caused by prothrombotic conditions like antiphospholipid syndrome, factor V Leiden, and G20210A prothrombin polymorphism. Snake bites are a rare cause of cerebral venous sinus thrombosis that must be recognized and treated promptly to improve survival.

Case presentation:

We present a case of a 25-year-old male who developed headaches and seizures following a Viper snake bite. The diagnosis was made based on a magnetic resonance venogram (MRV) showing transverse sinus thrombosis with sigmoid sinus stenosis. Initially, the patient was treated with antivenom and supportive treatment for disseminated intravascular coagulation (DIC). After the diagnosis of CVST, the patient was treated with rivaroxaban and levetiracetam. The patient improved within 1 week of treatment and was advised to follow up in 3 months.

Conclusion:

A high index of suspicion for cerebral venous sinus thrombosis is required if the patient presents with headaches, seizures, or abnormal vision following a snake bite. Early diagnosis and management can prevent further neurological damage.

Introduction

Snake bites are a dangerous incidence afflicting thousands of individuals in rural areas of tropical nation’s leading to the World Health Organization (WHO) labeling snake bites as a neglected tropical disease in 2009. ¹ Snake bites from venomous species can cause various symptoms, including superficial puncture wounds with associated pain and swelling, nausea with vomiting, dizziness, and dyspnea. ² If snake bites are to go untreated, hemorrhagic blisters, cellulitis, and necrotizing fasciitis can result, potentially even leading to life-threatening complications such as shock, and coagulopathy.^2,3 Cerebral venous sinus thrombosis (CVST) is an uncommon and deadly condition characterized by non-specific clinical symptoms such as headaches and nausea, creating difficulty in an accurate diagnosis. Autopsy studies indicate that CVST incidence is approximately 3 to 4 cases per million, with a 3:1 female-to-male ratio. ⁴ Aside from a female predominance, CVST is also known to affect children and young adults in developing countries. The dural venous sinuses, transverse, and superior sagittal sinuses are mostly involved in thrombosis.^1-6 CVST is subdivided into 3 subtypes based on the individual’s onset of symptoms: acute CVST is used to describe symptom onset for 48 hours or less; subacute CVST is for when symptoms have been present for at least 48 hours but less than 1 month; and chronic CVST for when symptoms have been present for longer than 1 month. Subacute CVST accounts for most cases of CVST, whilst chronic CVST is reported to be the least common. Imaging advancements have made it possible to detect CVST at an earlier stage, increasing its incidence. This early detection is crucial for treating CVST and has led to increasing survival rates. ⁶

Any prothrombotic condition that causes vessel wall injury and subsequent hypercoagulability due to blood stasis increase the risk of CVST. ⁴ The most frequent risk factor includes antiphospholipid syndrome, factor V Leiden, and G20210A prothrombin polymorphism. ⁴ Other conditions predisposing to cerebral venous sinus thrombosis are hereditary thrombophilia, birth control, pregnancy, head and neck infections, vasculitis, cancer, dehydration, and obesity. ⁵ The pathophysiological of CVST is poorly understood. Still, it is proposed that thrombosis leads to increased intracranial pressure, which leads to a cascade involving cytotoxic and vasogenic edema, parenchymal hemorrhage, and hemorrhagic infarction. ⁴

The common presenting symptoms of cerebral venous sinus thrombosis include signs of increased intracranial pressure, including headache, papilledema, abnormal vision, focal neurological deficits, and seizures.^4,5 Headache is a prominent symptom seen in 80% of patients with CVST. Motor weakness is a commonly observed neurological deficit. Seizures are primarily observed in patients with acute CVST presenting with focal neurological deficits. CVST can manifest in unusual ways, including recurrent falls, weakness, tingling, numbness, and cognitive impairment without any positive neurological findings. ⁶ The gold standard for diagnosis of CVST is imaging with non-contrast computed tomography (CT) of the head recommended as the initial technique. ⁴ Snake-bite-induced cerebral venous sinus thrombosis is rare and has not been well reported in the literature.^4,5 Here, we report a case of a 25-year-old male farmer who presented with CVST 1 day after a snake bite.

Case Report

A 25-year-old male presented to the emergency room reporting having been bitten by a Viper snake on his left leg 1 day ago. He was unable to identify the species of the snake when prompted but noted severe left leg pain associated with swelling of the leg shortly afterward. He received his initial management of wound cleaning in the form of washing the wound with tape water and injection ketorolac for pain local basic health unit and the patient was advised against the movement while shifting to the tertiary care hospital for further management. On arrival, the patient was in shock with the vital signs, blood pressure of 90/60 mm of Hg, pulse rate of 118 beats per minute, respiratory rate of 25 breaths per minute, and oxygen saturation of 93%. The patient also had 3 episodes of hematemesis and a complaint of diplopia. Initial laboratory investigations were sent, and the patient was resuscitated in the emergency department, and he received three 10-mL polyvalent anti-snake venom, an injection of ceftriaxone 2 g, and tetanus toxoid. On examination, the left leg was found to have superficial puncture wounds consistent with fang marks just above the ankle, swelling (2 cm greater than the right leg), and bruises at the site of the cannula. The rest of the neurological examination was normal. Initial lab results displayed elevated international normalized ratios (INR), bilirubin, D-dimers, leukocytes, and thrombocytopenia (Table 1). The patient was admitted to the medical unit and treated as a case of disseminated intravascular coagulation. On the first day of his admission to the hospital, his left leg swelling increased and extended to the mid-thigh. Shortly afterward, he developed a severe headache and had 2 episodes of a generalized tonic-clonic seizure. From a clinical standpoint, he improved significantly, as shown by the improvement from initial labs (Table 1). A doppler ultrasound of the left lower limb excluded venous thrombosis. His magnetic resonance imaging (MRI) did not reveal any abnormalities while his magnetic resonance venogram (MRV) showed transverse sinus thrombosis with sigmoid sinus stenosis (Figure 1) and (Figure 2). Further workup for thrombophilia and secondary causes of hypercoagulability revealed no abnormalities (Table 2). He was started on tablet rivaroxaban (initially 15 mg twice daily for 3 weeks then 20 mg once daily) and tablet levetiracetam (500 mg twice daily). The patient’s was advised to follow up with MRV after 3 months. The patient has one seizure episode after 2 months of treatment due to noncompliance with the antiepileptics and was advised to take the same treatment same treatment for the next 3 months. The patient failed to follow up after 2 months, and a follow up MRV was not done which was planned at 12 weeks.

Table 1.

Initial laboratory investigations.

Investigations	Results before treatment	Results after treatment	Units	Reference range
Hemoglobin	18.1	12.4	g/dL	14-18
Total leukocyte count	34 000	8000	cells/µL	4000-11 000
Platelets	19 000	206 000	cells/µL	150 000-450 000
Blood Urea nitrogen	26.5	21.2	mg/dL	10-50
Serum creatinine	1.4	1.2	mg/dL	0.42-1.06
Total bilirubin	1.1	-	mg/dL	0.1-1.2
Direct bilirubin	0.5	-	mg/dL	<0.3
Serum Albumin	3.9	-	g/dL	3.5-5.5
Bleeding time	12	7	minutes	1-9
PT	16	13	seconds	12
aPTT	32	31	seconds	30
INR	1.28	1.1	-	0.8-1.1
D- dimers	10 978	760	ng/mL	<500

Abbreviations: PT, prothrombin time; aPTT, activated partial thromboplastin time; INR, international normalized ratio; mg/dL, milligram per deciliter; g/dL, gram per deciliter; ng/mL, nanogram per milliliter; µL, microliter.

Figure 1.

Magnetic Resonance Imaging (MRI) of the brain showing normal brain with no evidence of stenosis or thrombosis.

Figure 2.

Magnetic resonance venogram (MRV) showing transverse sinus thrombosis (Red arrow) and sigmoid sinus stenosis (Green arrow).

Table 2.

Thrombophilia screen.

Investigations	Results (%)	Reference range
Protein C	91.1	69.1-140
Free Protein S	117.6	67-140
Anti-thrombin	115.7	75.1-125
Serum Homocysteine	15.18	5.46-16.2

Discussion

It is critical for early recognition of thrombosis of the venous sinuses of the brain despite its rarity, as intervention can have a significant impact on mortality. ⁷ A wide range of cerebral venous sinuses can be affected, but the most affected sinuses are the transverse sinuses and superior sigmoid sinuses. ⁴ Cerebral venous sinus thrombosis can present as headache, seizures, focal neurological deficit, cranial nerve syndromes, visual abnormalities, or pseudotumor cerebri-like syndrome. ⁴ A long list exists of causes and risk factors associated with cerebral venous sinus thrombosis, including, but not limited to, inherited and acquired thrombotic state, infections, inflammatory diseases, hematological conditions, and certain pharmacological drugs. Inherited thrombotic conditions are the most common causes in developed countries ⁴ whereas snake bites are a rare cause of cerebral venous sinus thrombosis.^4,5 The summary of similar cases with same conclusion has been evident from literature search as shown in Table 3

Table 3.

Summary of the literature search.

Authors	Title	Source	Patient	Findings	Outcomes
Ghosh et al 5	Cerebral venous sinus thrombosis following Russell’s viper (Daboia russelii) envenomation: A case report and review of the literature	Toxicon	female	Patient developed cerebral venous sinus thrombosis preceded by features of disseminated bleeding diathesis following Russell’s viper bite. The cerebral venous sinus thrombosis was diagnosed by magnetic resonance imaging.	The patient responded well to treatment with antivenom and subcutaneous enoxaparin and had no demonstrable neurological deficits at 3 months of follow-up.
Das et al 8	A patient of Russell’s viper envenomation presenting with cortical venous thrombosis: An extremely uncommon presentation	J Postgrad Med	female	Patient presented with edematous, red, hot, and tender left foot with two fang marks and presence of bilateral ptosis. Moreover there was persistent hematuria, raised BT, PT, and aPTT	On seventh admission day, all coagulation parameters were normalized and hematuria disappeared. Anticoagulant therapy was then started and continued for 3 months.
Pal et al 9	Cerebral infarction: an unusual manifestation of viper snake bite	Int J Res Med Sci.	Male	Patient was presented with renal failure and cerebral infarction in spite of early ASV institution. CT scan revealed large infarct involving right middle cerebral artery territory. Hematological parameters revealed features of Disseminated Intravascular Coagulation	In the absence of other possible precipitants of DIC, snake bite was considered as the culprit event and thrombotic manifestation of DIC dominated the clinical spectrum
Prasad et al 10	Multiple Cerebral and Cerebellar Infarctions following Russell’s Viper (Daboia Russelii) Envenomation - A Case Report	Clin Med Rev Case Rep	Male	Patient developed irritability, vomiting, blurred vision, ptosis, ophthalmoplegia, and, difficulty in breathing with inspiratory stridor & difficulty in swallowing followed by left-sided hemiparesis. Contrast CT of the brain revealed bilateral occipital and bilateral cerebellar infarctions.	Better outcomes have been reported with immediate AVS treatment. Despite early treatment with AVS, this patient developed cerebral infarctions involving both anterior and posterior circulation territories and passed away.
Sahoo et al 11	A Rare Case of Stroke Due to Multiple Ischemic Infarctions following Russell’s Viper Envenomation	Med J DY Patil Vidyapeeth	Male	Patient presented with snakebite over the right foot, developed local swelling of the right foot and decreased movement of right upper and lower limb. Computed tomography scan of the brain showed multiple infarctions involving left frontotemporal lobe, right basal ganglia, right thalamus, occipital lobe, and cerebellar region.	He was treated with equine polyvalent anti-snake venom (ASV) of total dose 30 vials. Mannitol injection. patient showed good recovery, At 6 months of follow-up, he was able to walk with the help of support and power was of 4/5 in the right upper and lower limb with spasticity.

Snake bites are a common yet neglected trauma prevalent in tropical countries such as India and Pakistan. Unfortunately, it can cause significant mortality and morbidity with several complications following a snake bite, including thrombosis. ¹² Arterial thrombosis following a snake bite is a widely encountered and studied complication of snake bites, while venous thrombosis is rare and less commonly encountered. The mechanism for snake bite-induced venous sinus thrombosis is direct endothelial injury, stasis, or hypercoagulability, best described by Virchow’s triad.^12-15

In this report, we observe a case of snake bite in a young male patient whose initial presentation was concerning due to disseminated intravascular coagulation. However, he developed a headache and generalized tonic-clonic seizures throughout his treatment which was concerning for an accompanying neurological condition. MRI and MRV, the gold standard of diagnosis of CVST, revealed transverse sinus thrombosis, an uncommon and rare presentation of a snake bite.^16-19 Cerebral venous sinus thrombosis usually manifests with headache, visual abnormalities, and seizures.^16,17 Non-contrast CT can visualize a thrombus as a dense clot and string or cord sign and can also visualize accompanying cerebral edema and intracranial hemorrhage. ⁴ Prompt treatment is necessary with anticoagulation and rarely with endovascular procedures; otherwise, it can result in disability and death. Acute CVST has a mortality rate of 5.6%.^4,17

Given the above case report, a snake bite can present with cerebral venous sinus thrombosis. Hence a high index of suspicion should be kept if the patient develops a headache, seizures, or abnormal vision.

Conclusion

The risk of cerebral venous sinus thrombosis following a snake bite is relatively low. If diagnosed and treated early, it has a good prognosis, but if left untreated, it can significantly impact morbidity and mortality. As such, headaches, seizures, or abnormal vision after a snake bite should raise a high index of suspicion for CVST.