What is the clinical review of cerebral venous thrombosis (CVT), including its pathophysiology, risk factors, and clinical presentation, in a patient with anorexia nervosa presenting with headache and left lower extremity weakness?

Cerebral Venous Thrombosis: Clinical Review

Pathophysiology

Cerebral venous thrombosis results from thrombus formation in the cerebral veins and dural sinuses, causing obstruction of venous outflow that leads to increased intracranial pressure, venous congestion, and potential parenchymal injury. 1

The pathophysiologic cascade unfolds as follows:

• Venous outflow obstruction increases capillary hydrostatic pressure, leading to vasogenic edema 1
• Progressive venous hypertension can cause blood-brain barrier breakdown and hemorrhagic venous infarction 2
• Impaired CSF resorption through arachnoid granulations elevates intracranial pressure, present in over 80% of patients 3
• Deep venous system involvement particularly affects consciousness due to involvement of thalamic and basal ganglia structures 4

Risk Factors

Prothrombotic conditions are the predominant risk factors for CVT, with particular attention needed for women under age 50. 3, 1

Major Risk Factors:

• Oral contraceptive use - the most common medication-related risk factor 3, 1
• Pregnancy and postpartum period 1
• Inherited thrombophilias (Factor V Leiden, prothrombin gene mutation, protein C/S deficiency) 1
• Prior venous thromboembolic events 1
• Malignancy 1
• Recent infection or underlying inflammatory disease 3, 1
• Recent neurosurgery 1
• Dehydration - particularly relevant in anorexia nervosa patients 4

Special Consideration:

In the context of anorexia nervosa, dehydration represents a critical and often underrecognized risk factor that should prompt immediate consideration of CVT when neurological symptoms develop 4

Clinical Presentation

Headache is the cardinal symptom of CVT, occurring in nearly 90% of patients, and can be the sole manifestation in up to 25% of cases. 4, 5, 3

Headache Characteristics:

• Typically diffuse and progressively worsening over days to weeks 4, 5
• Can present acutely or with severe intensity, which correlates significantly with CVT diagnosis 6
• May be localized rather than diffuse in many cases 6
• Can mimic migraine patterns but characteristically progresses in severity rather than following typical migraine patterns 5
• Unlike migraine, often accompanied by signs of increased intracranial pressure 5

Focal Neurological Deficits:

• Hemiparesis and aphasia are the most common focal deficits 4, 3
• Deficits may fluctuate or progress, distinguishing them from typical arterial stroke 5
• Left lower extremity weakness, as in your patient, suggests involvement of the superior sagittal sinus with parasagittal cortical venous infarction 4

Seizures:

• Occur in approximately 40% of patients, both focal and generalized 4, 5
• This frequency is substantially higher than in arterial stroke and should raise suspicion for CVT 5

Signs of Increased Intracranial Pressure:

• Papilledema and diplopia (sixth nerve palsy) are common manifestations 4, 3
• These findings should prompt immediate consideration of CVT in any patient with progressive headache 3

Altered Mental Status:

• Particularly associated with deep venous system involvement 4
• Ranges from confusion to coma depending on extent of thrombosis 4

Diagnostic Approach

Initial Laboratory Studies:

• Complete blood count, chemistry panel, PT, and aPTT should be obtained immediately 4, 3
• D-dimer may be elevated but a normal level does not exclude CVT, especially with limited clot burden 4, 5
• Screen for prothrombotic conditions including oral contraceptive use, inflammatory diseases, and infectious processes 3

Imaging:

• Non-contrast CT is normal in up to 70% of CVT cases 5, 2
• When abnormal, CT may show hyperdensity of cortical vein/dural sinus ("dense vein sign") or "empty delta" sign on contrast-enhanced imaging 4, 2
• MRI with MR venography is the most sensitive diagnostic tool and should be obtained when CVT is suspected 4, 5, 3
• CT venography is an acceptable alternative when MRI is unavailable or contraindicated 5, 2

Lumbar Puncture:

• Elevated opening pressure is present in over 80% of patients 3
• No specific CSF abnormalities exist for CVT 3
• Unless meningitis is suspected, lumbar puncture is typically not useful when radiographic confirmation is available 3

Clinical Pitfalls

The most dangerous pitfall is dismissing CVT as migraine or tension headache, particularly in young women on oral contraceptives. 5, 1

Key warning signs that distinguish CVT from benign headache:

• Progressive worsening rather than episodic pattern 5
• Presence of papilledema or sixth nerve palsy 4, 3
• Any focal neurological deficit, even if fluctuating 5
• Seizure occurrence 5
• Altered mental status 4

In patients with anorexia nervosa presenting with headache and focal deficits, dehydration-induced CVT must be considered immediately, as this population has a specific and modifiable risk factor. 4