Overview
Definition:
Cerebral venous sinus thrombosis (CVST) is a thromboembolic obstruction of the dural venous sinuses and/or cerebral veins
It is a potentially devastating condition characterized by headache, seizures, and focal neurological deficits, often mimicking other neurological emergencies
Prompt diagnosis and appropriate management, including anticoagulation, are crucial for improving outcomes.
Epidemiology:
CVST is rare in children, with an incidence estimated at 0.67-1.5 per 100,000 children per year
Neonates and infants have a higher incidence than older children
Risk factors include dehydration, infection (especially otitis media and mastoiditis), prothrombotic states (inherited thrombophilia, malignancy), trauma, hyperviscosity syndromes, and certain medications
Neonates are particularly susceptible due to immature coagulation systems and dehydration.
Clinical Significance:
CVST in children can lead to significant morbidity and mortality
Complications include venous infarction, cerebral hemorrhage, venous hypertension, hydrocephalus, and permanent neurological deficits
Understanding the nuances of anticoagulation in this population is vital for preventing clot propagation, reducing stroke risk, and facilitating venous recanalization, thereby improving long-term neurodevelopmental outcomes for affected children
This topic is frequently tested in DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Headache, often severe and progressive
Seizures, which can be focal or generalized
Vomiting
Lethargy or decreased level of consciousness
Focal neurological deficits (e.g., weakness, visual disturbances, cranial nerve palsies)
Irritability in infants
Fever in cases of associated infection.
Signs:
Papilledema, indicating increased intracranial pressure
Focal neurological deficits consistent with the affected venous territory
Seizures may be observed
Signs of underlying etiology (e.g., otitis media, dehydration)..
Diagnostic Criteria:
Diagnosis is primarily based on neuroimaging
Definitive diagnosis is established by visualizing thrombus in the cerebral venous sinuses or veins
Imaging modalities include MRI with venography (MRV) or CT with venography (CTV), which are the gold standards
Magnetic Resonance Angiography (MRA) can also be useful
Absence of flow on venography confirms thrombosis.
Diagnostic Approach
History Taking:
Detailed history focusing on onset and character of headache, presence and type of seizures, recent infections (especially otitis media, sinusitis), dehydration, trauma, use of estrogen-containing medications (in adolescents), known thrombophilia, family history of thrombosis, and any recent surgery or immobilization
Red flags include sudden severe headache, focal neurological deficits, and unexplained seizures.
Physical Examination:
Complete neurological examination to assess mental status, cranial nerves, motor and sensory function, reflexes, and coordination
Fundoscopy for papilledema
Examination for signs of infection (e.g., otitis media, mastoiditis)
Assessment of hydration status.
Investigations:
Blood tests: Complete blood count (CBC) with differential, coagulation profile (PT, aPTT, INR), D-dimer (may be elevated but non-specific, particularly in neonates), liver function tests (LFTs), renal function tests (RFTs)
Thrombophilia screen (antithrombin III, protein C, protein S, Factor V Leiden mutation, prothrombin gene mutation, antiphospholipid antibodies) should be performed after initial anticoagulation is established and the acute phase has passed
Imaging: MRI brain with MRV is the investigation of choice for diagnosis
CT brain with CTV is an alternative
Echocardiography may be considered to rule out paradoxical embolism in cases of right-to-left shunt.
Differential Diagnosis:
Migraine, meningitis, encephalitis, brain tumor, intracranial hemorrhage, metabolic encephalopathy, other causes of increased intracranial pressure, venous infarction without thrombosis.
Management
Initial Management:
Stabilization of the patient
Management of seizures with antiepileptic drugs (AEDs) such as levetiracetam or phenobarbital
Control of intracranial pressure (ICP) if elevated using head elevation, osmotic therapy (mannitol or hypertonic saline), and hyperventilation if necessary
Management of fever and electrolyte imbalances
Prompt initiation of anticoagulation is the mainstay of treatment unless contraindicated.
Medical Management:
Anticoagulation is the cornerstone of treatment
The primary goal is to prevent clot propagation and extension, and to promote recanalization
* **Low Molecular Weight Heparin (LMWH):** Enoxaparin is the preferred agent in pediatric CVST
* **Neonates:** Typically dosed at 100-150 units/kg/dose every 12 hours subcutaneously (SC)
Anticoagulant effect is monitored by anti-Xa levels (target 0.5-1.0 U/mL)
* **Infants and Children:** Typically dosed at 100-150 units/kg/day divided into two doses SC
Anti-Xa levels should be monitored, especially in preterm infants or those with significant renal impairment
* **Unfractionated Heparin (UFH):** May be used intravenously (IV) for rapid titration or when anticoagulation reversal is frequently required, especially in cases with intracranial hemorrhage
Dosing is typically a bolus of 50-100 units/kg followed by an infusion of 10-25 units/kg/hour, adjusted to maintain an aPTT of 1.5-2.5 times the control value (or an anti-Xa level of 0.3-0.7 U/mL)
* **Transition to Warfarin:** Once the patient is clinically stable and pain is controlled, typically after 5-7 days of heparin therapy, transition to oral anticoagulation with warfarin can be initiated
Warfarin is usually overlapped with heparin for 4-5 days until the INR reaches the therapeutic target (usually 2.0-3.0)
* **Direct Oral Anticoagulants (DOACs):** Data on the use of DOACs (e.g., rivaroxaban, apixaban) in pediatric CVST is still evolving, and they are generally considered second-line or for specific indications, often in older children and adolescents where appropriate dosing and monitoring protocols are established
Their use requires careful consideration and often consultation with pediatric hematology.
Surgical Management:
Surgical intervention is reserved for specific, severe cases
Indications include:
* Neurological deterioration despite optimal medical management
* Mass effect leading to herniation
* Venous infarction with significant edema or hemorrhagic transformation that is life-threatening
* Decompressive craniectomy may be considered to reduce intracranial pressure
* Thrombectomy or thrombolysis (intracranial or systemic) is generally reserved for severe, life-threatening CVST with significant neurological deficits or rapidly progressing infarction, and carries a higher risk of hemorrhage
Its use in children is still debated and typically reserved for exceptional circumstances and specialized centers.
Supportive Care:
Close neurological monitoring for any deterioration
Management of complications such as hydrocephalus, venous infarction, and hemorrhage
Adequate hydration and electrolyte balance
Nutritional support
Pain management
Prophylaxis for deep vein thrombosis (DVT) in immobile patients, although anticoagulation for CVST itself provides this
Rehabilitation services (physiotherapy, occupational therapy, speech therapy) as needed.
Complications
Early Complications:
Intracranial hemorrhage (most common and serious), cerebral infarction, cerebral edema, hydrocephalus, status epilepticus, neurological deterioration, recurrent thrombosis.
Late Complications:
Chronic headache, cognitive deficits, learning disabilities, visual field defects, epilepsy, focal neurological deficits, post-thrombotic syndrome.
Prevention Strategies:
Early recognition and management of risk factors such as dehydration and infections
Careful management of fluid balance in neonates
Judicious use of medications known to increase thrombotic risk
Prompt diagnosis and treatment of thrombophilia
Avoiding unnecessary immobility.
Prognosis
Factors Affecting Prognosis:
Age of the patient (neonates and infants have a worse prognosis), severity of neurological deficit at presentation, presence and extent of intracranial hemorrhage, underlying cause of thrombosis, promptness of diagnosis and initiation of treatment, and development of complications
The presence of venous infarction is a significant negative prognostic factor.
Outcomes:
With prompt diagnosis and appropriate management, a significant proportion of children can achieve a good recovery
However, long-term sequelae are common
Mortality rates in pediatric CVST range from 5-10%, and up to 30-40% of survivors have neurological deficits
Recurrence is rare but possible.
Follow Up:
Long-term follow-up is essential
This includes regular neurological examinations, monitoring for seizures and cognitive development, ophthalmological assessment for visual disturbances and papilledema, and assessment for academic and developmental progress
Repeat neuroimaging may be considered in certain cases
Duration of anticoagulation is typically for 3-6 months if a reversible risk factor is identified, or indefinitely if a persistent prothrombotic state (e.g., inherited thrombophilia) is present, or if the etiology remains unclear and there is evidence of residual thrombosis
This decision should be individualized and guided by expert consensus.
Key Points
Exam Focus:
Anticoagulation is the primary treatment for CVST
LMWH (enoxaparin) is the preferred agent in pediatrics, with specific dosing for neonates and older children
Anti-Xa monitoring is crucial
Transition to warfarin with INR monitoring (2.0-3.0)
Recognize risk factors and clinical presentation
MRV/CTV are diagnostic gold standards.
Clinical Pearls:
Always consider CVST in a child with unexplained headache, seizures, or focal neurological deficits, especially in the presence of risk factors
D-dimer is less reliable in neonates
Perform thrombophilia testing after the acute phase
Differentiate between hemorrhagic and non-hemorrhagic infarction when deciding on anticoagulation
Be aware of potential medication interactions with warfarin.
Common Mistakes:
Delaying diagnosis by attributing symptoms to common pediatric ailments
Inappropriate dosing or lack of monitoring of anticoagulants
Failure to investigate underlying thrombophilias
Discontinuing anticoagulation prematurely
Not managing intracranial hypertension aggressively.