What is the differential diagnosis for a 30-year-old female with a 7-month history of progressively worsening right frontal headaches, occasional right visual changes, and worsening symptoms with laying down or bending over, despite a normal ophthalmology exam, normal Head Computed Tomography (CT) scan, and normal laboratory results?

Differential Diagnosis for Progressive Right Frontal Headache with Positional Worsening

This clinical presentation—7 months of progressively worsening unilateral headache that worsens with lying down or bending over, lasting 4 days continuously, and resistant to medications—strongly suggests increased intracranial pressure from a space-occupying lesion or idiopathic intracranial hypertension, despite the normal head CT. 1

Critical Red Flags Present

This patient exhibits multiple concerning features that mandate urgent neuroimaging with MRI:

• Progressive worsening headache over 7 months indicates an evolving pathologic process rather than a primary headache disorder 1, 2
• Positional worsening with lying down or bending over suggests increased intracranial pressure, as these maneuvers increase venous pressure and intracranial volume 1, 2
• Current episode lasting 4 days exceeds the 4-72 hour duration required for migraine without aura 1, 3
• Medication resistance in a previously untreated patient is atypical for primary headache disorders 1
• Unilateral location with visual changes raises concern for structural lesions affecting the optic pathway 4

Primary Differential Considerations

1. Space-Occupying Lesion (Brain Tumor)

This is the most critical diagnosis to exclude given the progressive nature and positional worsening. 4, 1

• Progressive headache that awakens from sleep or worsens with Valsalva maneuvers (bending, coughing) is characteristic of increased intracranial pressure from mass lesions 4, 1, 2
• Visual changes with right frontal headache could indicate involvement of the optic pathway or visual cortex 4
• Head CT has limited sensitivity for isodense tumors, posterior fossa lesions, and meningeal processes 2
• MRI brain with and without contrast is mandatory as it provides superior soft-tissue resolution and can detect lesions missed on CT 4, 1, 2

2. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

This diagnosis should be strongly considered in a 30-year-old female, particularly if overweight:

• Presents with severe headaches and visual impairments, typically in females of childbearing age 4
• Positional worsening is characteristic, though classically improves with lying flat in spontaneous intracranial hypotension 1
• Normal ophthalmology exam does NOT exclude this diagnosis—papilledema may be subtle or absent early 4
• MRI findings include empty sella, dilated optic nerve sheaths, flattening of posterior globes, and tortuous optic nerves 4
• Requires MRI brain with contrast and MR venography to exclude venous sinus thrombosis as a secondary cause 4

3. Cerebral Venous Sinus Thrombosis

A critical vascular emergency that can present similarly:

• Progressive headache with positional worsening due to impaired venous drainage 1
• Visual changes from increased intracranial pressure 4
• May have normal initial CT scan 2
• Requires MR venography or CT venography for diagnosis 4
• Risk factors include oral contraceptives, pregnancy, hypercoagulable states 1

4. Chronic Migraine (Less Likely)

While migraine is common in 30-year-old females, several features argue against this diagnosis:

• Migraine attacks last 4-72 hours, not 4+ days continuously 1, 3
• Positional worsening with lying down is atypical—migraine patients prefer to lie still in dark, quiet rooms 5
• Progressive worsening over 7 months without response to any medications is unusual for new-onset migraine 1
• Chronic migraine requires ≥15 headache days/month for >3 months with ≥8 days meeting migraine criteria—this patient has continuous headache 1
• Visual changes in migraine are typically aura (gradual spread over ≥5 minutes, lasting <60 minutes), not "occasional" changes 1

5. Spontaneous Intracranial Hypotension (Unlikely)

• Classically presents with orthostatic headache that is absent or mild on waking and improves within 2 hours of lying flat 1
• This patient's headache worsens with lying down, making this diagnosis incompatible 1

Diagnoses Effectively Ruled Out

Tension-Type Headache

• Bilateral, mild-to-moderate pressing/tightening quality, not aggravated by routine activity 1
• This patient has unilateral, progressive, positionally-aggravated headache 1

Cluster Headache

• Strictly unilateral severe pain lasting 15-180 minutes with prominent autonomic symptoms (tearing, nasal congestion, ptosis) 1, 5
• No autonomic symptoms reported; duration of 4 days excludes this 5

Primary Stabbing Headache

• Ultra-brief duration of literally 1-3 seconds, not 4 days 6

Medication-Overuse Headache

• Requires ≥15 days/month of non-opioid analgesics or ≥10 days/month of other acute medications for >3 months 1
• Patient has no medication overuse history 1

Immediate Management Algorithm

Step 1: Urgent MRI Brain with and without Contrast 4, 1, 2

• Superior to CT for detecting tumors, meningeal processes, venous thrombosis, and signs of increased intracranial pressure 4, 2
• Include MR venography to evaluate for cerebral venous sinus thrombosis 4
• Include orbital sequences with fat-saturated T2 to evaluate optic nerve sheaths 4

Step 2: If MRI shows mass lesion or hydrocephalus

• Urgent neurosurgical consultation 1
• Consider dexamethasone for vasogenic edema if appropriate 4

Step 3: If MRI shows signs of increased intracranial pressure without mass

• Lumbar puncture with opening pressure measurement (contraindicated if mass effect present) 4, 7
• Opening pressure >250 mmH2O supports idiopathic intracranial hypertension 7
• Send CSF for cell count, protein, glucose, cultures to exclude infectious/inflammatory causes 2

Step 4: If MRI and LP are normal

• Reconsider primary headache disorders with atypical features 1
• Consider repeat imaging in 4-6 weeks if symptoms persist or worsen 2

Critical Pitfalls to Avoid

• Do not rely on normal head CT to exclude serious pathology—CT misses many tumors, meningeal processes, and venous thrombosis 2
• Do not assume normal ophthalmology exam excludes increased intracranial pressure—papilledema may be absent or subtle early in the disease course 4
• Do not perform lumbar puncture before neuroimaging if mass lesion is suspected—risk of herniation 2
• Do not diagnose migraine in a patient with progressive headache over months and continuous 4-day episode—this violates ICHD-3 criteria 1
• Do not delay MRI based on "normal labs"—laboratory tests are typically normal in brain tumors and idiopathic intracranial hypertension 4, 1