Pseudotumor cerebri syndrome

Pseudotumor cerebri syndrome is a condition characterized by elevated intracranial pressure (ICP) and normal cerebrospinal fluid (CSF) composition, with no evidence of an intracranial mass, hydrocephalus, or other structural causes on imaging. Primary pseudotumor cerebri syndrome, also known as idiopathic intracranial hypertension, predominantly occurs in women of reproductive age with obesity. Secondary pseudotumor cerebri syndrome includes drug-induced intracranial hypertension and elevated ICP due to cerebral venous abnormalities or systemic disorders. The most common symptom is headache, but visual disturbances and pulsatile tinnitus also frequently occur. Ophthalmologic examination typically shows bilateral papilledema. MRI is performed to rule out mass effect and evaluate for structural causes of elevated ICP. Lumbar puncture shows an elevated opening pressure. Treatment includes weight loss, addressing any causes of secondary pseudotumor cerebri syndrome, and, in some cases, pharmacological treatment (e.g., with acetazolamide). Surgical intervention is indicated for patients with vision loss on presentation or vision-threatening disease refractory to conservative measures. Despite treatment, persistent symptoms and vision loss are common.

For other causes of intracranial hypertension, see "Elevated intracranial pressure and brain herniation."

• Primary pseudotumor cerebri syndrome (idiopathic intracranial hypertension) ^[1][2][3]
  • Predominantly affects women of reproductive age with obesity
  • Additional risk factors include recent weight gain and polycystic ovary syndrome.
• Secondary pseudotumor cerebri syndrome ^[2][3][4]
  • Medications (drug-induced intracranial hypertension): e.g., tetracyclines, vitamin A toxicity, retinoids, growth hormone, danazol
  • Cerebral venous disorders: e.g., cerebral venous thrombosis, decreased CSF resorption due to prior CNS infection or subarachnoid hemorrhage
  • Systemic disorders: e.g., anemia, Addison disease, hypercapnia, renal failure, systemic lupus erythematosus

A female TOAD: female sex, Tetracyclines, Obesity, excessive intake of vitamin A, and Danazol are the major risk factors for pseudotumor cerebri syndrome.

• A mismatch between production and resorption of CSF → ↑ ICP → damage to structures of the CNS and especially to the optical nerve fibers ^[1]
• Orthograde axoplasmic flow stasis at the optic nerve head leads to bilateral papilledema.

Most presentations are subacute or chronic, but a minority of patients (< 5%) present with rapidly progressive vision loss over days to weeks. ^[2][4][5]

• Headache
• Visual changes
  • Transient visual obscuration (darkening of vision)
  • Vision loss
  • Diplopia
  • Photopsia
• Retrobulbar pain
• Pulsatile tinnitus
• Cranial nerve palsies (most commonly CN VI palsy)
• Dizziness
• Neck and/or back pain ^[6]
• Cognitive disturbance

Approach ^[1][2][7]

• Perform a fundoscopic examination to evaluate for papilledema.
• Assess visual acuity and evaluate for peripheral vision loss.
• Obtain brain imaging before lumbar puncture to rule out mass effect and to evaluate for structural causes of elevated ICP.
• Perform a lumbar puncture to confirm elevated ICP and obtain a CSF sample for analysis.
• Evaluate for diagnostic criteria for pseudotumor cerebri syndrome.
• Consider laboratory studies to evaluate for causes of secondary pseudotumor cerebri syndrome.

Diagnostic criteria for pseudotumor cerebri syndrome

Revised diagnostic criteria for pseudotumor cerebri syndrome ^[3]

The following diagnostic criteria apply to both primary pseudotumor cerebri syndrome and secondary pseudotumor cerebri syndrome.

• Pseudotumor cerebri syndrome: All must be fulfilled.
  1. Papilledema
  2. Normal neurological examination, except for cranial nerve defects
  3. No hydrocephalus, mass, structural lesions, or meningeal enhancement on brain imaging
  4. Normal CSF analysis
  5. Lumbar puncture opening pressure ≥ 25 cm H₂O
• Pseudotumor cerebri syndrome without papilledema: Both must be fulfilled.
  1. Criteria 2–5 for pseudotumor cerebri syndrome are met
  2. CN VI palsy and/or imaging evidence of pseudotumor cerebri

Modified Dandy criteria for idiopathic intracranial hypertension ^[8]

• Signs and symptoms of increased ICP (e.g., headache, visual changes, pulsatile tinnitus, papilledema)
• Absence of localizing neurologic findings on neurologic examination
• Absence of deformity, displacement, or obstruction of the ventricular system with otherwise normal neurodiagnostic studies, except for:
  • Evidence of increased CSF pressure (> 20 cm H₂O)
  • Neuroimaging showing an empty sella turcica, an optic nerve sheath with filled out CSF spaces, and/or smooth-walled nonflow-related venous sinus stenosis or collapse
• Awake and alert
• No other apparent cause of intracranial hypertension

Ophthalmologic examination ^[2][7]

• Fundoscopy: bilateral papilledema
• Visual acuity testing
• Visual field testing: may show an enlarged blind spot, ; inferior nasal defects, and/or peripheral vision loss

Brain imaging ^[2][7][7]

Brain imaging is indicated for all patients before lumbar puncture to rule out mass effect and other causes of elevated ICP.

• Imaging modality
  • MRI brain with and without contrast and MR venography: preferred
  • CT head with contrast and CT venography: if MRI is contraindicated or not available
• Imaging findings in pseudotumor cerebri syndrome
  • Normal brain parenchyma; no hydrocephalus, mass, structural lesions, or meningeal enhancement
  • Empty sella turcica: shrinkage of the pituitary gland due to displacement by CSF
  • Flattening of the posterior optic globe, optic nerve changes
  • Unilateral or bilateral transverse sinus stenosis: seen in up to 90% of patients with primary pseudotumor cerebri syndrome
  • Evidence of a cerebral venous disorder (e.g., sinus vein thrombosis): may be seen in secondary pseudotumor cerebri syndrome

Lumbar puncture ^{[7] [2][5]}

• Procedure
  • Only perform after imaging has excluded space-occupying lesions with mass effect, posterior fossa masses, and obstructive hydrocephalus. ^[9][10]
  • Measure opening pressure in the lateral decubitus position with legs extended.
  • Obtain CSF samples for analysis.
• Findings
  • Normal CSF analysis
  • Elevated opening pressure (≥ 25 cm H₂O)
  • May provide temporary headache relief

Lumbar puncture is safe to perform in patients with suspected pseudotumor cerebri syndrome once conditions with a risk of brain herniation have been excluded on imaging.

Laboratory studies ^[2][4][7]

Consider laboratory studies to evaluate for suspected causes of secondary pseudotumor cerebri syndrome, e.g.:

• Complete blood count
• Renal function tests
• Hypercoagulability testing
• Morning cortisol
• Antinuclear antibodies

Approach ^[2][4][7]

• Urgently consult neurosurgery for rapid visual loss.
• Initiate conservative management of pseudotumor cerebri syndrome.
• Consider pharmacological treatment with acetazolamide.
• Routinely monitor visual acuity, peripheral vision, and papilledema. ^[5]
• Refer to neurosurgery for vision-threatening disease refractory to other measures.

Pseudotumor cerebri syndrome must be managed in consultation with neurology and ophthalmology (or neuro-ophthalmology).

Conservative management ^[11]

• Address causes of secondary pseudotumor cerebri syndrome: e.g., discontinue contributing medications.
• Manage overweight and obesity. ^[11]
• Screen for and treat comorbid obstructive sleep apnea. ^[11]
• Counsel patients on pain management and how to avoid medication overuse headaches.

Pharmacological treatment ^[2][4][5][7]

Evidence for the efficacy of pharmacological treatment is limited. Consider with specialist guidance. ^[12]

• First-line: acetazolamide (off-label) ^[1][4]
• Alternatives: topiramate, furosemide

Surgical treatment ^[1][2][7]

• Indications
  • Rapid visual loss on presentation
  • Vision-threatening disease refractory to other measures
• Procedures
  • CSF shunt (e.g., lumboperitoneal shunt, ventriculoperitoneal shunt)
  • Optic nerve sheath fenestration
  • Stenting of the dural venous sinus

• IIH typically worsens over months to years, until the condition stabilizes.
• Even with treatment, many patients will have persistent symptoms (up to 79%). ^[13]
• Severe loss of vision (or even blindness) occurs in up to 24% of patients. ^[14]