What are the potential causes of increased intracranial pressure (ICP) in a patient with a normal head computed tomography (CT) scan, history of headaches, and potential brain lesion?

Causes of Increased Intracranial Pressure with Normal Head CT

When a patient presents with increased intracranial pressure but a normal head CT, the primary diagnosis to consider is idiopathic intracranial hypertension (IIH, also called pseudotumor cerebri), followed by secondary causes including cerebral venous sinus thrombosis, medication effects, and endocrine disorders. 1

Primary Diagnosis: Idiopathic Intracranial Hypertension

IIH is defined by elevated intracranial pressure without evidence of a structural lesion or hydrocephalus on neuroimaging and normal cerebrospinal fluid composition. 1 This is the most common cause when CT appears normal but clinical signs of elevated ICP persist.

Key Clinical Features to Identify

• Headache occurs in nearly 90% of patients, typically holocephalic or unilateral throbbing, worse in the morning after supine positioning and improving with upright posture throughout the day 2
• Papilledema is the hallmark finding and a key diagnostic criterion 1, 2
• Visual disturbances including transient visual obscurations are common 2
• Pulsatile tinnitus should be specifically assessed 2
• Sixth nerve palsy causing horizontal diplopia may be present 1, 2

Patient Demographics Matter

• In postpubertal children and adults, IIH typically affects overweight females of childbearing age 1, 2
• In prepubertal children, boys and girls are equally affected 1

Secondary Causes of Elevated ICP with Normal CT

Cerebral Venous Abnormalities

Cerebral venous sinus thrombosis (CVST) can present with elevated ICP and initially normal-appearing CT. 3 This is a critical diagnosis not to miss, as it requires anticoagulation rather than standard IIH management.

• Transverse sinus stenosis is commonly associated with elevated ICP 1
• Intracranial arteriovenous fistulas can cause secondary pseudotumor cerebri 1
• CVST can even develop as a complication of IIH itself, particularly after corticosteroid use 3

Medication-Induced Causes

Several medications are well-documented causes of secondary pseudotumor cerebri 1:

• Tetracyclines (including minocycline, doxycycline)
• Vitamin A and retinoids (isotretinoin, tretinoin)
• Corticosteroids (both use and withdrawal)
• Growth hormone
• Thyroxine
• Lithium
• Trimethoprim/sulfamethoxazole 4

Endocrine Disorders

• Addison disease 1
• Hypoparathyroidism 1, 5
• Obesity itself is considered an etiologic association 5, 4
• Hypothalamic compression in IIH may induce increased appetite and result in weight gain 4

Critical Diagnostic Algorithm

Step 1: Advanced Neuroimaging is Essential

A normal head CT does NOT exclude elevated ICP—MRI with venography is required for definitive evaluation. 1, 2

• MRI of the head and orbits is the most useful imaging modality for detecting subtle signs of elevated ICP that CT misses 1, 2
• MR venography (MRV) must be included to evaluate for venous outflow obstruction or stenosis 2
• CT venography can be an alternative if MRI is contraindicated 1, 2

Step 2: Look for Specific MRI Findings

Even with "normal" brain parenchyma, these findings suggest elevated ICP 1, 2:

• Empty sella or partially empty sella (typical finding in raised ICP)
• Posterior globe flattening (56% sensitivity, 100% specificity)
• Intraocular protrusion of the optic nerve (40% sensitivity, 100% specificity)
• Horizontal tortuosity of the optic nerve (68% sensitivity, 83% specificity)
• Enlarged optic nerve sheath (mean 4.3 mm vs 3.2 mm in controls)
• Distention of the perioptic subarachnoid space
• Transverse sinus stenosis

Step 3: Lumbar Puncture for Confirmation

Elevated opening pressure >250 mm H₂O is the defining feature of IIH, with normal CSF composition (no organisms, normal white cells, normal protein and glucose). 2

• Opening pressures of 180-250 mm H₂O are concerning but may not require immediate intervention 2
• If opening pressure is ≥250 mm H₂O, remove CSF to reduce pressure to 50% of opening pressure or 200 mm H₂O, whichever is greater 2
• Removal of 20-30 mL of CSF may provide immediate symptom relief 2

Important Clinical Pitfalls

Don't Assume Normal CT Means Normal ICP

The incidence of raised ICP with strictly normal initial CT is 0-8% in severe traumatic brain injury patients, but this statistic applies to trauma—not to patients with headaches and papilledema where IIH is suspected. 1 In the non-trauma setting with clinical signs of elevated ICP, further workup is mandatory regardless of normal CT.

Don't Miss CVST

CVST can be differentiated from IIH with magnetic resonance venography, and this distinction is critical because treatment differs fundamentally (anticoagulation vs. medical ICP management). 3 Always obtain venous imaging when evaluating suspected elevated ICP.

Recognize That Venous Stenosis May Be Secondary

In patients with suspected pseudotumor cerebri, repeat MRV after CSF drainage may be helpful to determine if venous outflow obstruction is primary or secondary to increased intracranial pressure. 2 This helps distinguish primary venous pathology from secondary compression.

Visual Function Takes Priority

Where there is evidence of declining visual function, acute management to preserve vision is surgical (optic nerve sheath fenestration or CSF shunting). 2 Medical management alone may be insufficient when vision is threatened.

Management Considerations

Medical Treatment

• Weight loss has been shown to be effective in putting IIH into remission 2
• Acetazolamide is first-line medical therapy 2
• Serial lumbar punctures may be needed if pressure remains elevated 2

When to Escalate

• Neurosurgical consultation is needed if medical therapy fails 2
• Rapidly declining visual function requires urgent surgical intervention 2
• Persistent symptoms despite adequate medical management warrant consideration of CSF diversion procedures 2