ADD-ONS

Pseudotumor cerebri

David Goldemund M.D.
Updated on 16/03/2024, published on 15/03/2024

Definition

pseudotumor cerebri (idiopathic intracranial hypertension – IIH) is a clinical condition characterized by an increase in intracranial pressure without evidence of intracranial space-occupying lesion, infection, hydrocephalus, or other demonstrable cause
- the term benign intracranial hypertension is not appropriate as the condition can lead to vision loss in some patients
- idiopathic intracranial hypertension – IIH is reserved for patients with NO demonstrable cause
- imaging may reveal conditions (e.g., dural sinus stenosis, VJI compression) that are either causative or aggravate the symptoms; in such patients, the term pseudotumor cerebri or secondary intracranial hypertension should be used instead of IIH
the diagnosis of IIH is based on the following criteria:
- subjective and objective signs of increased intracranial pressure
  - bilateral papilledema
  - increased CSF pressure (>250 mm H₂0 measured in the supine position)
- normal neurological findings (except for CN VI involvement)
- exclusion of space-occupying lesions or other obvious etiology on neuroimaging
pseudotumor cerebri is a diagnosis by exclusionem
in addition to headache, visual disturbances may occur – these are initially reversible with adequate therapy, but with a prolonged course, vision loss may become permanent

Epidemiology

the approximate incidence of this disease in the general population is 0.5 – 1.7/100,000 per year
- the disease is probably more common than statistics indicate, as many patients are oligosymptomatic and resolve without treatment
affects patients of all ages but most commonly occurs in young, obese women (Bezerra, 2018)
pseudotumor cerebri is rare in the pediatric population (usually in the 12-17 year age group)

Etiopathogenesis

the exact cause is unknown (as its name implies), but it is associated with some diseases or the use of certain drugs
it is necessary to distinguish secondary forms of intracranial hypertension
- the increase in intracranial pressure is a consequence of, e.g., scarring after previous meningitis or subarachnoid hemorrhage, obstruction of cranial venous drainage in venous thrombosis, etc.
proposed mechanisms:
- reduced CSF absorption (as evidenced by the findings of radioisotope cisternography and other studies)
- reduced venous outflow from the brain due to truncal obesity (due to an increase in intra-abdominal pressure and an increase in cardiac filling pressure)
- stenosis in the venous system is increasingly recognized as an important factor
  - it is not entirely clear whether it is the primary cause or whether it is a potentiating factor
  - the efficacy of venous stenting suggests a causal link
most common risk factors:
- obesity/weight gain
- female gender, pregnancy, menstrual cycle irregularities, and their hormonal treatment or use of oral contraceptives
- termination of corticosteroid therapy
- treatment of acne with tetracycline and its derivatives and/or vitamin A or its analogues

Conditions associated with higher risk of IIH

obesity
postthrombotic conditions
hematological disorders
- sideropenic anemia
- hypercoagulable states
systemic diseases
- systemic lupus erythematosus (SLE)
- chronic renal failure
- sarcoidosis
- AIDS
- Behcet’s disease
disorders of vitamin A metabolism

“empty sella” syndrome
pharmacological treatment
- tetracyclines
- indomethacin
- amiodarone
- thyroid hormones
- lithium
- growth hormone
discontinuation of corticosteroid therapy
endocrine conditions
- adrenal insufficiency
- Cushing disease
- hypothyroidism
- hypoparathyroidism
pregnancy

Clinical Presentation

headache (90%) with dizziness, occasional nausea, and vomiting
- headache lacks specific features, and commonly resembles migraine or tension type headache
- it tends to be more severe on awakening
- headache is more intense in the supine position and during Valsalva maneuver
visual disturbances
- transient, brief episodes of blurred vision
- visual field disturbances in advanced stages
pulsatile tinnitus (in ~ 60%)
eye pain
objective findings:
- papilledema
  - typically bilateral but rarely unilateral or even absent
  - initially, only a slight blurring of the disc margin is seen
  - when the congestive papilla is fully developed, the borders of the papillae are completely obliterated
  - distinguishing congestive papillae from other affections causing target edema can be difficult in some cases (pseudopapilledema)
- neurological examination is usually normal, except for visual field deficit or abducens nerve palsy (bilateral in ~ 10-20% of cases)
typically, the patient appears well despite significant papilledema

Diagnostic evaluation

Brain MRI/CT

brain CT or better MRI + CTV/MRV exclude space-occupying lesions, venous sinus thrombosis, hydrocephalus, etc.
findings supporting the diagnosis of pseudotumor cerebri include:
- papilledema (intraocular protrusion of the optic nerve disc)
- enlarged subarachnoid spaces around the optic nerves (enlarged ONSD), enhancement of the intraocular segment of the optic nerve
- (partially) empty sella turcica, enlarged Meckel cave (cavum Meckeli), enlarged subarachnoid spaces, abnormal arachnoid granulations
- narrow ventricles
- tonsillar ectopia (exclude Chiari I)
- venous outflow obstruction
  - stenosis is most commonly found in the lateral segment of the transverse sinus
  - no evidence of recent thrombosis
  - compression of the IJV, e.g., by the styloid process

Ophthalmologic examination

examination of the fundus ⇒ bilateral papilledema
detection of the visual field defects in advanced stages

Lumbar puncture, CSF analysis

opening CSF pressure > 25 cm H₂O in the supine position
- CSF pressure should be measured in the absence of treatment to lower intracranial pressure
- CSF pressure may be measured by lumbar puncture performed in the lateral decubitus position without sedative medications or by epidural or intraventricular monitoring
- in obese patients, borderline values of 15-25cm H₂O cannot be considered clear proof of intracranial hypertension
- if the opening pressure is 20-25 cm H₂O, additional findings are needed to make the diagnosis
- opening pressure may fluctuate throughout the day (repeated or prolonged lumbar or intraventricular pressure monitoring may detect these fluctuations)
CSF composition is normal (which excludes inflammation, meningeal carcinomatosis, etc.)
relief of the headache after cerebrospinal fluid (CSF) removal is supportive of the diagnosis but not on its own diagnostic: it may be seen in patients with other headache types

Neurosonology

detection of optic disc elevation
detection of enlarged optic nerve sheath diameter (ONSD)

DSA

catheter venography allows the detection of stenosis in the outflow venous system, venous manometry, and stenting of intrasinus stenosis
measurement of the pressure gradient from the superior sagittal sinus to the internal jugular vein and right atrium allows detection of the focal pressure difference across the stenosis (transstenotic gradient)

Others

an endocrinological or rheumatological examination

IHS classification ICHD-3

Headache attributed to idiopathic intracranial hypertension (IIH) → ICHD-3

new headache, or a significant worsening of a pre-existing headache, fulfilling criterion C
both of the following are present:
- idiopathic intracranial hypertension (IIH) has been diagnosed
- cerebrospinal fluid (CSF) opening pressure exceeds 25 cm CSF (or 28 cm CSF in obese children) in the absence of treatment to lower intracranial pressure
either or both of the following are present:
- headache has developed or significantly worsened in temporal relation to the IIH or led to its discovery
- headache is accompanied by either or both of the following:
  - pulsatile tinnitus
  - papilloedema
    - it is necessary to distinguish pseudopapilledema or optic disc edema (e.g. neuritis, drusen, etc.)
    - IIH should be diagnosed with caution in patients without this sign – medication-overuse headache should be excluded in such patients
no other ICHD-3 diagnosis better explains the headache

Modified Dandy criteria (Friedman, 2002)

signs and symptoms of intracranial hypertension
increased lumbar puncture opening pressure (> 25 cm H₂0)
normal cerebral spinal fluid contents
normal neurological findings except for papilledema and/or CN VI palsy, normal mental status
absence of ventricular enlargement/displacement or space-occupying or vascular lesion on CT+CTV/MRI+
other causes of increased ICP identified

Differential diagnosis

space-occupying lesion
- tumor (primary or metastatic)
- abscess
- SDH
dural sinus or jugular vein thrombosis (septic, aseptic)
Chiari malformation type I (Fukuoka, 2017)

Management

management is based on the elimination of triggering factors and symptomatic medication
if this is not effective and vision deteriorates, surgical/endovascular treatment is indicated

Causal therapy

the primary task is lifestyle modification and weight reduction in obese patients (for BMI >30 kg/m2, a weight reduction of ∼10-15% is recommended)
discontinue risky medications (see above)
compensate diseases that may be associated with increased intracranial pressure (e.g., Addison’s disease or SLE)
address rare causes or comorbidities within the outflow venous system (see interventional procedures)

Medication

acetazolamide
- first-line treatment; as a carbonic anhydrase inhibitor, it reduces the production of CSF
- initial dose is 500 mg 2-3 times daily PO., with the total amount increasing up to 2-3 g/day
- common adverse effects include paresthesia of the fingers and lips, nausea, vomiting, decreased attention, renal impairment, or metabolic acidosis; in these cases, the dosage should be adjusted individually according to tolerability
- in most patients, acetazolamide acts quickly and effectively, with resolution of the optic disc edema and stabilization of the perimeter finding in ~2-4 months
furosemide
- 20-100 mg PO daily with careful monitoring of potassium levels
- possible side effects of furosemide therapy include hyponatremia, hypocalcemia, hypocalcemia, and ototoxicity
topiramate
If the condition does not improve, mannitol infusion
administration of corticosteroids has no sustained therapeutic effect; on the contrary, their rapid discontinuation may worsen the condition
interventional and surgical treatment should be considered in refractory patients

Endovascular and surgical treatment

invasive treatment is used when visual impairment progresses despite medication
optic nerve sheath fenestration
- hard sheaths in the ampullary portion of the optic nerve are
- this alleviates drainage of the cerebrospinal fluid and reduces axonal compression
- the disadvantage is the limited duration of the effect; a relapse may be observed within ~ 3 months; in these patients, neurosurgical intervention is then indicated
lumboperitoneal or ventriculoperitoneal shunt
sinus and jugular vein stenting
- reserved for severe cases with transstenotic gradient >8 mmHg
- good results
internal jugular vein decompression (removal of the external compression – muscle, bones, etc.)
serial lumbar puncture
- post-puncture discomfort may include headache and blurred vision, which may mimic the worsening of IC hypertension