Idiopathic Intracranial Hypertension (IIH)

Definition

Epidemiology

• Mean age: ~29 years
• 97.6% female
• Mean BMI: ~39.9 kg/m²
• Incidence rises sharply with increasing obesity

Pathophysiology

• Impaired CSF absorption at arachnoid granulations (possibly due to adipokines or hormonal influences on CSF secretion/resorption)
• Venous outflow obstruction: Bilateral transverse sinus stenosis is found in nearly all IIH patients. Whether it is the cause or consequence is debated — a self-perpetuating cycle may exist where elevated ICP compresses the sinuses → venous outflow obstruction → further ICP rise
• Hormonal/metabolic factors: Obesity, sex steroids, vitamin A metabolism disorders, and glucocorticoid dysregulation have all been implicated

Clinical Features

• Headache is the most common presenting symptom; most common phenotypes are migraine (52%) and tension-type (22%)
• Transient visual obscurations result directly from papilledema and raised ICP
• Diplopia results from CN VI (lateral rectus) palsy — a false localizing sign from raised ICP
• Pulsatile/pulse-synchronous tinnitus is characteristic

Diagnostic Criteria

Pressure must be measured in the lateral decubitus position. Sitting pressures are invalid. LP opening pressure ≥250 mm CSF is required.

Workup

1. MRI brain with contrast — mandatory before LP to exclude intracranial mass, hydrocephalus
2. MR Venography (MRV) — to exclude cerebral venous sinus thrombosis (key IIH mimic) and assess for bilateral transverse sinus stenosis
3. Lumbar puncture with manometry — CSF should be clear, colorless, with normal protein/glucose/cells; high opening pressure confirms diagnosis
4. Ophthalmologic evaluation — confirm papilledema (distinguish from pseudopapilledema/drusen), assess visual fields and acuity

• Partially empty sella
• Bilateral optic nerve sheath distension
• Flattening of posterior sclera
• Bilateral transverse sinus flow gaps/stenosis on MRV

Imaging

Secondary Causes ("Pseudotumor Cerebri") — Must Exclude

Management

1. Conservative

• Weight loss: 5–10% body weight reduction can normalize ICP and resolve papilledema

2. Medical

• Acetazolamide (carbonic anhydrase inhibitor — reduces CSF production): First-line drug
  • Start: 500 mg twice daily
  • Titrate up as tolerated; doses up to 4 g/day supported by IIHTT evidence
  • The IIHTT showed acetazolamide + weight loss improves papilledema, ICP, and quality of life
• Topiramate: Alternative/adjunct (also promotes weight loss)
• Other diuretics: Furosemide used as adjunct
• Headache management: Migraine-specific therapies (triptans, etc.) based on phenotype

3. Surgical / Procedural

4. Lumbar puncture

• Serial LPs can provide temporary relief (headache + visual obscurations)
• Used as a bridge to definitive therapy, especially in pregnancy

IIH in Pregnancy

• Typically worsens with pregnancy; most commonly develops around 14th gestational week
• Visual loss in ~10–20%
• MRV is mandatory to exclude cerebral venous thrombosis
• Management:
  • Diet modification (avoid ketosis)
  • Serial LPs preferred over medications
  • Acetazolamide is controversial in pregnancy; most guidelines suggest avoiding in the first trimester; restrict its use to after 20 weeks when clinically essential
  • Corticosteroids (dexamethasone/prednisone) for 2-week courses when vision is threatened
  • ONSF or lumboperitoneal shunting if vision fails despite serial LPs
  • Vaginal delivery with epidural analgesia is generally preferred

Prognosis

• Most patients improve with weight loss ± acetazolamide
• Permanent vision loss can occur in untreated or refractory cases — visual fields (especially nasal inferior) are at greatest risk
• Risk of recurrence if weight is regained
• In pregnancy, IIH typically resolves postpartum; recurrence in subsequent pregnancies is unusual

Key References

• Bradley and Daroff's Neurology in Clinical Practice, Chapter 102
• IIHTT (IIH Treatment Trial) — Friedman et al., 2014; Smith and Friedman, 2017
• Mollan et al., J Neurol Neurosurg Psychiatry 2018 (consensus guidelines)
• Friedman et al., Neurology 2013 (revised diagnostic criteria)
• Yiangou et al., Nat Rev Neurol 2023 — recent review on disease mechanisms (PMID: 37957260)
• Friedman DI, Neurol Clin 2024 — updated clinical review of pseudotumor cerebri syndrome (PMID: 38575259)

Pseudobulbar Palsy vs Bulbar Palsy

Core Concept

Clinical Features Comparison

Pseudobulbar Affect (Emotional Lability)

• Spontaneous, unmotivated, or disproportionate laughing and crying
• Does not reflect the patient's actual emotional state
• Results from bilateral corticobulbar tract damage releasing brainstem emotional expression circuits from cortical inhibition
• Often causes significant embarrassment to the patient

"Spontaneous or unmotivated crying and laughter uniquely characterize pseudobulbar palsy." — Bradley and Daroff's Neurology in Clinical Practice

Causes

Bulbar Palsy (LMN)

• Motor neuron disease (progressive bulbar palsy — the most common cause)
• Guillain-Barré syndrome (acute onset, no atrophy)
• Poliomyelitis
• Diphtheria
• Syringobulbia
• Brainstem tumors / infarcts (if targeting motor nuclei)
• Myasthenia gravis (NMJ — mimics bulbar palsy)
• Kennedy disease (spinobulbar muscular atrophy — X-linked LMN)
• Fazio-Londe disease (childhood progressive bulbar palsy)

Pseudobulbar Palsy (UMN)

• Bilateral lacunar infarcts (most common — "lacunar state")
• ALS (mixed UMN + LMN — unique situation where both coexist)
• Multiple sclerosis
• Diffuse hypoxic-ischemic encephalopathy
• Progressive supranuclear palsy (PSP)
• Wilson disease
• Bilateral MCA territory strokes
• Cerebral vasculitis

"The most common pathologic bases are lacunar infarctions or other cerebrovascular lesions, diffuse hypoxic-ischemic encephalopathy, ALS, and multiple sclerosis." — Adams and Victor's Principles of Neurology, 12th Ed.

Special Case: ALS (Mixed Bulbar + Pseudobulbar)

Neuroanatomical Pathway Diagram

Quick Memory Summary