What is the differential diagnosis for a child presenting with epistaxis and intracerebral hemorrhage?

Differential Diagnosis for Pediatric Epistaxis with Intracerebral Hemorrhage

A child presenting with both epistaxis and intracerebral hemorrhage requires immediate evaluation for vascular malformations, inherited bleeding disorders, and hereditary hemorrhagic telangiectasia, as these represent the most life-threatening and treatable causes in this population.

Vascular Malformations (Most Common Structural Cause)

Arteriovenous malformations (AVMs) and arteriovenous fistulas account for approximately 32-48% of nontraumatic intracerebral hemorrhage in children and should be the primary structural consideration. 1

• AVMs present with hemorrhage in more than 50% of pediatric cases, with an annual bleeding risk of 2-4% and mortality from first hemorrhage between 10-30% 1, 2
• Multiple AVMs involving both cerebral and systemic circulation strongly suggest hereditary hemorrhagic telangiectasia (HHT), which classically presents with epistaxis as the earliest manifestation 2, 3
• Cavernous malformations represent 5% of vascular causes and carry substantial hemorrhagic stroke risk 1, 4
• Intracranial aneurysms are less common in children but can cause both subarachnoid and intraparenchymal hemorrhage; they occur more frequently in the posterior circulation in pediatric patients compared to adults 1

Inherited Bleeding Disorders (Critical to Exclude)

Hematologic and coagulation disorders together account for approximately 26% of pediatric intracerebral hemorrhage cases. 1

Thrombocytopenia

• Spontaneous ICH risk becomes significant when platelet counts fall below 20,000/mm³ 1
• Eight of 68 children (11.8%) in major series had thrombocytopenia as the cause of ICH 1

Coagulation Factor Deficiencies

• Factor VIII deficiency (Hemophilia A) is the most common, with severe deficiency (<1% activity) carrying the highest ICH risk 1, 5
• Factor XIII deficiency has the highest spontaneous ICH rate among all coagulation disorders 5
• Factor VII and Factor X deficiencies also predispose to ICH 5
• Congenital vitamin K deficiency can present in neonates with ICH, particularly if maternal medications (warfarin, phenytoin, barbiturates) depleted vitamin K-dependent factors 1

von Willebrand Disease

• Type 3 von Willebrand disease carries higher ICH risk than milder forms 5
• Epistaxis is a cardinal feature, with standardized bleeding questionnaires showing significantly higher epistaxis scores in affected children 6

Hereditary Hemorrhagic Telangiectasia (HHT)

HHT should be strongly considered when epistaxis and ICH coexist, especially with family history or multiple vascular malformations. 2, 3

• Epistaxis is the most common presenting symptom, typically beginning in adolescence but can occur in neonates 3, 7
• Pulmonary AVMs in HHT create risk for paradoxical emboli causing cerebral abscess or stroke 3
• Multiple cerebral AVMs are pathognomonic for HHT 2
• Neonatal presentations with ICH have been reported, though rare 7

Brain Tumors

Approximately 13.2% of pediatric intracerebral hemorrhages result from bleeding into highly malignant brain tumors. 1

• Initial presentation mimics primary hemorrhage, with tumor only identified on complete imaging 1
• Various histological types occur, but typically highly malignant 1

Cerebral Sinovenous Thrombosis

Sinovenous thrombosis causes hemorrhagic infarction in 40% of cases overall, but 72% in neonates specifically. 4

• Neonates account for 61% of pediatric cerebral venous thrombosis cases 4
• Can present with both ICH and elevated intracranial pressure 4
• Best diagnosed with MR venography or CT venography 4

Acquired Coagulopathy

• Warfarin therapy or anticoagulant exposure 1
• Hepatic failure causing multiple factor deficiencies 1
• Protein C and S deficiencies may cause hemorrhagic infarction 1

Age-Specific Considerations

Neonates and Infants

• Maternal medication exposure (warfarin, phenytoin, barbiturates) causing vitamin K deficiency 1
• Vein of Galen malformations presenting with high-output cardiac failure and hydrocephalus 1, 4
• Birth trauma must be excluded, though less likely with spontaneous epistaxis 5

Older Children and Adolescents

• Presentation more similar to adults with acute headache, vomiting, and neurological deterioration 1
• Juvenile nasopharyngeal angiofibroma in adolescent males with unilateral epistaxis and nasal obstruction 1

Critical Diagnostic Approach

Four-vessel cerebral angiography remains the gold standard and should be performed in any child with unexplained ICH, as it identifies a cause in 97% of cases when combined with complete evaluation. 1

• MRI with MRA provides noninvasive vascular assessment but may miss small malformations 1
• CT angiography is useful but lacks temporal information available from catheter angiography 1
• Complete hematologic workup including platelet count, PT/PTT, factor assays, and von Willebrand studies 1
• Family history is crucial for identifying HHT or familial bleeding disorders 2, 3

Important Clinical Pitfalls

• Do not attribute ICH to hypertension in children—unlike adults, systemic hypertension is rarely the primary cause of pediatric ICH 1
• Smaller hemorrhages in neonates may go unrecognized due to subtle presentations 1
• Failure to perform angiography may miss treatable vascular malformations in up to 89.7% of cases 1
• Epistaxis severity correlates with underlying bleeding disorder severity—frequent, prolonged, bilateral epistaxis requiring intervention suggests systemic pathology 1, 6