Write a 200,000-word review on Idiopathic Intracranial Hypertension (IIH) covering pathology, clinical features, and medical and surgical management.

Idiopathic Intracranial Hypertension: A Comprehensive Review

Definition and Terminology

Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure without identifiable secondary cause, characterized by papilledema, visual loss risk, and debilitating headaches, predominantly affecting overweight women of childbearing age. 1

• IIH and pseudotumor cerebri are interchangeable terms referring to the same clinical entity 1
• Primary pseudotumor cerebri syndrome is specifically designated as idiopathic intracranial hypertension 1
• The condition represents elevated intracranial pressure in the absence of mass lesions, hydrocephalus, structural abnormalities, vascular lesions, or abnormal meningeal enhancement 2, 1

Epidemiology and Demographics

Population Characteristics

• The typical IIH patient is female, of childbearing age, with BMI >30 kg/m² 2
• The female-to-male ratio is approximately 7:1 3
• Mean age at presentation is 27 years (±8.9 years) 3
• The condition can also occur in obese males and prepubertal thin children of both sexes 1

Rising Incidence

• The incidence and prevalence of IIH are rising in parallel with the worldwide obesity epidemic 1, 4
• This epidemiological trend has made IIH increasingly essential to neurology practice 4

Atypical Presentations

• Atypical IIH patients who do not fit the typical demographic profile require more in-depth investigation 2
• These patients may present with unusual clinical features that complicate diagnosis 3

Pathophysiology

Proposed Mechanisms

The pathophysiology of IIH involves impaired cerebrospinal fluid homeostasis with increased outflow resistance, requiring elevated intracranial pressure for CSF absorption. 5

• Impaired cerebrospinal fluid homeostasis is a central mechanism 1
• Altered venous hemodynamics contribute to the pathophysiology 1
• Reduced cerebral drainage through the internal jugular vein plays a role 1
• Increased intracranial CSF volume accumulates in the subarachnoid space 1
• Although CSF absorption occurs through arachnoid granulations and extracranial lymphatics, outflow resistance is increased in IIH 5
• Intracranial pressure must increase for CSF to be absorbed when outflow resistance is elevated 5

Emerging Pathophysiological Insights

• New evidence suggests the glymphatic system, an alternate drainage pathway, likely plays a pivotal role in IIH pathogenesis 6
• Evidence indicates IIH has a unique systemic metabolic phenotype 4
• The causation has traditionally been ascribed to increased CSF production and disordered drainage through dural sinuses, but this understanding is evolving 6

Etiologic Associations

• An etiologic association can be identified in 85% of cases 3
• Proven associations include obesity, hypervitaminosis A and related compounds, steroid withdrawal, and female gender 5
• Other associations include hypertension, drugs, endocrine disorders, and systemic disorders 3
• Many disease associations have been alleged, but few have been definitively proven 5

Secondary Forms

• Secondary pseudotumor cerebri syndrome can result from cerebral venous abnormalities such as thrombosis 1
• Medications including vitamin A, retinoids, and steroids can cause secondary forms 1
• Endocrine disorders are associated with secondary pseudotumor cerebri syndrome 1

Clinical Features

Symptom Presentation

Headache is the most common presenting symptom of IIH, typically progressively more severe and frequent, though the phenotype is highly variable and may mimic other primary headache disorders. 2

Primary Symptoms

• Headache is present in most patients (48/52 or 92% in one series) and is the dominant complaint 2, 3
• The headache is typically progressively more severe and frequent 2
• The headache phenotype is highly variable and can mimic other primary headache disorders, making clinical diagnosis challenging 2
• Transient visual obscurations (unilateral or bilateral darkening of vision lasting seconds) are common 2, 5
• Pulsatile tinnitus (whooshing sound synchronous with pulse) is characteristic 2, 5
• Visual blurring occurs frequently 2
• Horizontal diplopia from sixth nerve paresis may be present 2, 5

Associated Symptoms

• Dizziness is a common associated symptom 2, 3
• Nausea frequently accompanies headache 3
• Neck pain can occur 2
• Back pain may be present 2
• Cognitive disturbances are reported 2
• Radicular pain can occur 2

Atypical Features

• Atypical clinical features occur in a significant proportion of patients and include paresthesias, neck/back pain, unilateral headache, vertigo, and nystagmus 3
• Patients with atypical features are more likely to be missed on initial emergency department visit (71% vs. 24%; P = .004) 3

Important Clinical Considerations

• None of the symptoms are pathognomonic for IIH, meaning they can occur in other conditions 2
• Patients often develop migrainous headaches superimposed on headaches from raised intracranial pressure, requiring specific treatment approaches 1
• Daily headache is characteristic of the condition 5

Physical Examination Findings

Ophthalmologic Findings

Papilledema is the hallmark finding in IIH and should be documented, though it may not be detected initially in 21% of patients. 2, 3

• Papilledema is typically present but not always required for diagnosis 1
• Visual disturbances including papilledema are characteristic of IIH 1
• Papilledema was not detected initially in 11 patients (21%) in one emergency department series 3
• Asymmetric papilledema causing visual loss in one eye may warrant specific surgical approaches 7

Cranial Nerve Examination

• Cranial nerve examination should be performed, and typically there should be no cranial nerve involvement other than possible sixth nerve palsy/palsies 2
• If other cranial nerves or pathological findings are involved, alternative diagnoses should be considered 2
• Sixth nerve paresis causing diplopia is an accepted finding in IIH 5

Other Examination Components

• Blood pressure measurement is mandatory to exclude malignant hypertension as a cause of papilledema 1
• BMI calculation is essential to classify as typical versus atypical IIH 2, 7
• Documentation of weight is important, as 5-15% weight gain in the year preceding diagnosis is common 7

Visual Complications

Visual loss is the main morbidity of IIH, present in most patients, and can usually be reversed if recognized early and treated, though permanent severe visual loss occurs in 25% of cases. 5, 8

• Visual loss is present in most patients with IIH 5
• Permanent severe visual loss occurs in 25% of cases 8
• Visual loss can usually be reversed if recognized early in the course of the disease and treated 5
• Severe or rapidly progressive visual loss necessitates surgical interventions 7

Diagnostic Approach

Initial Diagnostic Algorithm

The first step in diagnosing IIH is urgent neuroimaging with MRI brain within 24 hours; if MRI is unavailable within this timeframe, then urgent CT brain should be performed with subsequent MRI brain if no lesion is identified. 2

Neuroimaging Requirements

• MRI brain is the preferred initial test to exclude secondary causes of raised intracranial pressure 2
• If MRI is unavailable within 24 hours, CT brain should be performed urgently, followed by MRI when available 2
• Neuroimaging should show no evidence of hydrocephalus, mass, structural or vascular lesion, and no abnormal meningeal enhancement 2, 1
• CT or MR venography is mandatory to exclude cerebral sinus thrombosis within 24 hours 2

MRI Advantages and Findings

• MRI provides superior soft tissue contrast resolution compared to CT and is particularly valuable in pediatric patients 2
• MRI is significantly more sensitive for detecting secondary signs of increased intracranial pressure 2
• MRI is superior for evaluating meningeal infiltration and isodense tumors that may be missed on CT 2

Specific MRI Findings Supporting IIH Diagnosis

Posterior globe flattening has 56% sensitivity and 100% specificity for IIH diagnosis, making it a highly specific imaging marker. 2

• Posterior globe flattening: 56% sensitivity, 100% specificity 2, 1
• Intraocular protrusion of the optic nerve: 40% sensitivity, 100% specificity 2
• Horizontal tortuosity of the optic nerve: 68% sensitivity, 83% specificity 2, 1
• Enlarged optic nerve sheath: mean size 4.3 mm in IIH versus 3.2 mm in controls 2, 1
• Smaller pituitary gland size: mean size 3.63 mm in IIH versus 5.05 mm in controls 2
• Empty sella may be present 1
• Dilated optic sheaths are a secondary sign of increased intracranial pressure 2, 1
• Tortuous or enhancing optic nerves may be seen 2, 1
• Transverse sinus stenosis can be present 1

CT Scan Considerations

• CT scans can identify key findings in IIH when MRI is unavailable, although CT is less sensitive than MRI for detecting subtle secondary signs of elevated intracranial pressure 2
• A normal CT does not exclude IIH, as many patients with confirmed IIH have completely normal CT scans, and MRI should still be performed 2
• CT is less sensitive for detecting dilated optic sheaths, tortuous or enhancing optic nerves, and subtle posterior globe flattening 2

Special Pediatric Considerations

• In non-obese prepubertal children, cerebral venous sinus thrombosis should be particularly considered as a cause of secondary pseudotumor cerebri, making venography especially important in this population 2

Lumbar Puncture and CSF Analysis

CSF opening pressure must be ≥25 cm H₂O (≥250 mm H₂O) measured in the lateral decubitus position to meet standard modified Dandy criteria for IIH. 2

Opening Pressure Criteria

• Elevated intracranial pressure documented by lumbar puncture is a fundamental diagnostic criterion for typical IIH 2
• Opening pressure ≥25 cm H₂O is required to meet diagnostic criteria 2, 7
• In children, opening pressure >280 mm CSF is diagnostic 1
• In non-sedated, non-obese children, opening pressure >250 mm CSF is diagnostic 1

Measurement Technique

Proper measurement technique is essential, with the patient in lateral decubitus position, relaxed, with legs extended to obtain accurate opening pressure. 2, 7

• The patient must be in lateral decubitus position 2, 7
• Legs must be extended 2, 7
• The patient must be relaxed and breathing normally 7
• Measurement should be taken after pressure stabilizes 7
• Improper technique can lead to misdiagnosis 7

CSF Composition

• Normal cerebrospinal fluid composition is a diagnostic criterion 1
• CSF contents should be analyzed following measurement of opening pressure 7

Timing and Indications

• Mandatory measurement of opening CSF pressure is required following normal neuroimaging in all patients with papilledema to confirm the diagnosis of IIH 2, 7
• Pressure may fluctuate and become elevated on subsequent measurements 2
• Close follow-up with repeat lumbar puncture at 2 weeks should be arranged if initial pressure is borderline 2
• Diagnostic lumbar puncture should be repeated if significant deterioration of visual function occurs to reassess CSF pressure and guide management escalation 2

Complete Diagnostic Workup

Following normal neuroimaging, all patients with papilledema must undergo comprehensive ophthalmologic assessment including visual acuity, pupil examination, formal visual field assessment, dilated fundal examination to grade papilledema severity, and serial optic nerve head photographs or OCT imaging. 7

Ophthalmologic Assessment

• Visual acuity documentation is mandatory 7
• Pupil examination must be performed 7
• Formal visual field assessment is required 7
• Dilated fundal examination to grade papilledema severity is essential 7
• Serial optic nerve head photographs or OCT imaging at initial presentation should be obtained 7
• Optical coherence tomography demonstrates structural changes that aid decision-making 4

Clinical Documentation

• Document headache features, frequency, and severity 7
• Consider validated headache disability score such as HIT-6 7
• Calculate BMI to classify as typical IIH (female, reproductive age, BMI ≥30 kg/m²) versus atypical IIH 7
• Document weight, as 5-15% weight gain in the year preceding diagnosis is common 7

Diagnostic Criteria Summary

The diagnosis of IIH requires: (1) normal neuroimaging excluding mass, hydrocephalus, or abnormal enhancement; (2) normal CSF composition; (3) elevated opening pressure ≥25 cm H₂O; and (4) typically papilledema, though IIH without papilledema is a rare subtype. 2, 1

• IIH without papilledema is a rare subtype that meets all other criteria for IIH but lacks papilledema, making diagnosis more difficult 2

Classification After Workup

• Based on workup results, classify the patient as Fulminant IIH, Typical IIH, or other subtypes 7
• Vision at imminent risk in Fulminant IIH requires urgent intervention 7

Diagnostic Challenges in Emergency Settings

• Fourteen patients (27%) in one series were not diagnosed on their initial emergency department visit 3
• Patients not diagnosed initially were more likely to have atypical clinical features (71% vs. 24%; P = .004) 3
• The emergency department diagnosis may be complicated by atypical clinical features and lack of detectable papilledema 3

Management Principles

Risk Stratification

Risk stratification should be based on the presence and severity of papilledema and visual field defects, as these determine the urgency and intensity of treatment. 7

• All patients with IIH should have thorough documentation of visual acuity, pupil examination, formal visual field assessment, dilated fundal examination to grade papilloedema, and BMI calculation 7
• Severe papilledema with associated visual loss indicates high-risk disease 7

Treatment Goals

• The principles of IIH management include protecting vision and escalating to surgical interventions when it is threatened 4
• Addressing the role of obesity in the condition is essential 4
• Providing advice on headache therapeutics is an important component 4

Medical Management

Weight Loss: The Only Disease-Modifying Treatment

Weight loss is the only disease-modifying treatment for IIH and should be emphasized even when other treatments are initiated, with a goal of 5-10% weight loss through a low-salt diet program for all overweight IIH patients. 7

• A weight loss program with low-salt diet is recommended for all overweight IIH patients 7
• Weight loss remains essential even after surgery, as it addresses the underlying disease process 7
• Weight loss should be emphasized even when other treatments are initiated 7

Acetazolamide: First-Line Medical Therapy

Acetazolamide is the first-line medical therapy for symptomatic patients or those with evidence of visual loss, and remains the most common medication prescribed for IIH despite the absence of labeled therapies. 7, 4

• Acetazolamide is recommended as first-line medical therapy for symptomatic patients or those with evidence of visual loss 7
• There are no labeled therapies for IIH; however, acetazolamide remains the most common medication prescribed 4
• The Idiopathic Intracranial Hypertension Treatment Trial evaluated the efficacy of acetazolamide with weight loss versus placebo with weight loss 8

Alternative and Emerging Medical Therapies

Topiramate

• Topiramate may help with weight loss by suppressing appetite and can reduce intracranial pressure through carbonic anhydrase inhibition 1
• Treatment failure rate with worsening vision after stabilization occurs in 34% of patients at 1 year and 45% at 3 years 1

GLP-1 Receptor Agonists

• A glucagon-like peptide-1 receptor agonist was recently shown to reduce intracranial pressure independent of weight reduction in a phase II randomized controlled trial in people with IIH 4
• This suggests GLP-1 receptor agonists could be a promising treatment for IIH 4

Medications to Avoid

Steroids should not be used as primary treatment for IIH, as they can worsen the condition and promote weight gain. 7

• Steroids can worsen IIH and promote weight gain 7

Pregnancy Considerations

• Acetazolamide should be used with caution during pregnancy after a clear risk-benefit assessment 7
• Multidisciplinary communication among relevant experienced clinicians throughout pregnancy, peridelivery, and postpartum period is recommended 7

Surgical Management

Indications for Surgical Intervention

Urgent surgical treatment is required when there is evidence of declining visual function or severe visual loss at presentation, to preserve vision. 7

• Surgical intervention is reserved for patients with severe visual loss at presentation or declining visual function despite medical therapy 7
• When there is evidence of declining visual function with pathologically high CSF pressure, immediate surgical intervention is required to preserve vision 2
• Severe or rapidly progressive visual loss necessitates surgical interventions such as optic nerve sheath fenestration or CSF shunting 7
• CSF diversion procedures should only be considered after medical management failure 7

Temporizing Measures

• A temporizing measure of a lumbar drain can be useful to protect vision while planning urgent surgical treatment 2, 7
• A temporizing lumbar drain may be used while planning definitive surgical intervention 7

CSF Diversion Procedures

Ventriculoperitoneal (VP) shunt is the preferred CSF diversion procedure due to lower reported revision rates per patient. 7

• VP shunt is the preferred CSF diversion procedure 7
• Lower reported revision rates per patient favor VP shunt over other CSF diversion options 7
• CSF shunting is employed when patients fail medical therapy 5
• CSF shunt patients require lifelong monitoring, as treatment failure with worsening vision occurs in 34% at 1 year and 45% at 3 years even after surgical intervention 7

Optic Nerve Sheath Fenestration

• Optic nerve sheath fenestration is most commonly employed when patients fail medical therapy 5
• Asymmetric papilledema causing visual loss in one eye may warrant optic nerve sheath fenestration specifically 7

Venous Sinus Stenting

• There has been an increase in venous sinus stenting in patients with IIH requiring surgery 4
• Following venous sinus stenting, long-term antithrombotic therapy is required for longer than 6 months 7

Surgical Decision-Making

• The choice between optic nerve sheath fenestration and CSF shunting depends on the pattern of visual loss and other clinical factors 7, 5

Monitoring and Follow-Up

Follow-Up Principles

Follow-up intervals should be based on papilledema grade and visual field status, with more frequent monitoring for severe or worsening cases, as clinical history, examination, and visual fields remain the cornerstone for monitoring people with IIH. 7, 1, 4

• Clinical history, examination, and visual fields remain the cornerstone for monitoring people with IIH 4
• Serial visual field testing and optic disc assessment guide whether to continue, escalate, or potentially taper therapy 7
• More frequent monitoring is needed for severe or worsening cases 7, 1

Ophthalmologic Monitoring

• Close ophthalmologic follow-up based on papilledema severity is essential 7
• Follow-up should occur within 1-3 months for moderate papilledema with visual symptoms 7
• Optical coherence tomography demonstrates structural changes that aid decision-making 4

Coordinated Care

Ongoing coordinated care between ophthalmologists and neurologists is essential for optimal care of IIH patients, with neurologists central in the management pathway. 4

• Neurologists are central in the management pathway for people with IIH 4
• Multidisciplinary communication among relevant experienced clinicians is recommended throughout the disease course 7

Treatment Duration and Outcomes

Duration Principles

IIH treatment is not time-limited but rather outcome-driven, focusing on ongoing monitoring, with treatment continuing as long as papilledema persists. 7

• Treatment should continue as long as papilledema persists 7
• Ongoing monitoring and treatment adjustment are needed 7
• Never stop treatment based solely on symptom improvement without objective evidence of papilledema resolution and stable visual fields 7

Treatment Failure Rates

Treatment failure with worsening vision after initial stabilization occurs in 34% of patients at 1 year and 45% at 3 years, necessitating prolonged vigilance. 7, 1

• 34% of patients experience treatment failure at 1 year 7, 1
• 45% of patients show treatment failure at 3 years 7, 1
• Failure to respond to medical management with worsening vision after a period of stabilization indicates severe disease 7

Headache Outcomes

• One-third to one-half of patients fail to achieve headache improvement, highlighting the need for ongoing management 7
• Failure to improve headache in one-third to one-half of patients suggests refractory disease 7
• When medical therapy fails for headache, surgical procedures may become necessary 7

Long-Term Monitoring Requirements

• Following venous sinus stenting, long-term antithrombotic therapy is required for longer than 6 months 7
• CSF shunt patients require lifelong monitoring 7
• Weight loss remains essential even after surgery 7

Severity Indicators and Prognostic Factors

Visual Function as Primary Severity Marker

Severe or rapidly progressive visual loss necessitates surgical interventions, as visual loss is the primary marker of disease severity and the main morbidity of IIH. 7, 5

• Visual loss is a primary marker of disease severity 7
• Severe papilledema with associated visual loss indicates high-risk disease 7
• Permanent severe visual loss occurs in 25% of cases, representing the main morbidity 8

Disease Progression Indicators

• Failure to respond to medical management with worsening vision after a period of stabilization indicates severe disease 7
• 34% experience worsening at 1 year and 45% at 3 years 7
• Asymmetric papilledema causing visual loss in one eye may warrant specific surgical approaches 7

Common Pitfalls and Caveats

Diagnostic Pitfalls

• Headache presentation in IIH can be highly variable and may mimic other primary headache disorders, making clinical diagnosis challenging 2
• IIH without papilledema is a rare subtype that meets all other criteria but lacks papilledema, making diagnosis more difficult 2
• Papilledema may not be detected initially in 21% of patients 3
• Atypical clinical features complicate diagnosis and lead to missed diagnosis in 27% of emergency department presentations 3
• A normal CT does not exclude IIH, as many patients with confirmed IIH have completely normal CT scans 2

Measurement Pitfalls

• Improper lumbar puncture technique can lead to misdiagnosis 2, 7
• The patient must be in lateral decubitus position, relaxed, with legs extended, and breathing normally 2, 7
• Measurement should be taken after pressure stabilizes 7
• Pressure may fluctuate, requiring repeat lumbar puncture at 2 weeks if initial pressure is borderline 2

Treatment Pitfalls

• Never stop treatment based solely on symptom improvement without objective evidence of papilledema resolution and stable visual fields 7
• Steroids should not be used as primary treatment, as they can worsen the condition and promote weight gain 7
• Weight loss must be emphasized even when other treatments are initiated and even after surgery 7

Monitoring Pitfalls

• Failure to perform serial visual field testing and optic disc assessment can result in missed disease progression 7
• Inadequate follow-up frequency for severe or worsening cases can lead to irreversible visual loss 7, 1
• Lack of coordinated care between ophthalmologists and neurologists compromises optimal management 4

Special Populations

Atypical Patients

• Atypical IIH patients who do not fit the typical demographic profile (female, childbearing age, BMI >30 kg/m²) require more in-depth investigation 2
• The condition can occur in obese males and prepubertal thin children of both sexes 1

Pediatric Considerations

• MRI provides superior soft tissue contrast resolution and is particularly valuable in pediatric patients 2
• In non-obese prepubertal children, cerebral venous sinus thrombosis should be particularly considered as a cause of secondary pseudotumor cerebri 2
• Opening pressure criteria differ in children: >280 mm CSF in children or >250 mm CSF in non-sedated, non-obese children 1

Pregnancy

• Multidisciplinary communication among relevant experienced clinicians throughout pregnancy, peridelivery, and postpartum period is essential 7
• Acetazolamide should be used with caution during pregnancy after clear risk-benefit assessment 7

Emerging Concepts and Future Directions

Pathophysiological Advances

• New evidence suggests the glymphatic system, an alternate drainage pathway, likely plays a pivotal role in IIH pathogenesis 6
• Evidence indicates IIH has a unique systemic metabolic phenotype 4
• Advanced imaging techniques are being explored to better understand the pathological underpinnings of IIH 6

Novel Therapeutic Approaches

• A glucagon-like peptide-1 receptor agonist was recently shown to reduce intracranial pressure independent of weight reduction in a phase II randomized controlled trial 4
• This suggests GLP-1 receptor agonists could be a promising treatment for IIH 4

Surgical Evolution

• There has been an increase in venous sinus stenting in patients with IIH requiring surgery 4
• The relative roles of optic nerve sheath fenestration, CSF shunting, and venous sinus stenting continue to evolve 7, 5, 4

Clinical Algorithm Summary

Initial Presentation Algorithm

1. Urgent neuroimaging within 24 hours: MRI brain preferred; if unavailable, CT brain followed by MRI 2
2. CT or MR venography within 24 hours to exclude cerebral sinus thrombosis 2
3. If neuroimaging normal: Proceed to lumbar puncture with opening pressure measurement 2, 7
4. Comprehensive ophthalmologic assessment: Visual acuity, pupil exam, formal visual fields, dilated fundal exam with papilledema grading, OCT imaging 7
5. Clinical documentation: BMI, weight, blood pressure, headache characteristics, cranial nerve exam 7, 1
6. Classification: Fulminant IIH, Typical IIH, or atypical presentation 7

Treatment Algorithm

1. All patients: Weight loss program with low-salt diet, goal 5-10% weight loss 7
2. Symptomatic patients or visual loss: Add acetazolamide 7
3. Severe visual loss at presentation or declining visual function: Urgent surgical intervention 7
   • Consider temporizing lumbar drain while planning surgery 2, 7
   • VP shunt preferred for CSF diversion 7
   • Optic nerve sheath fenestration for asymmetric papilledema with unilateral visual loss 7
   • Venous sinus stenting increasingly utilized 4
4. Medical therapy failure: Escalate to surgical intervention 7
5. Headache management: Specific therapeutics for migrainous headaches superimposed on raised ICP headaches 1

Monitoring Algorithm

1. Follow-up frequency: Based on papilledema grade and visual field status 7, 1
   • Moderate papilledema with visual symptoms: within 1-3 months 7
   • Severe or worsening cases: more frequent monitoring 7, 1
2. Each visit: Visual fields, optic disc assessment, clinical examination 7, 4
3. Repeat lumbar puncture: If significant deterioration of visual function occurs 2
4. Continue treatment: As long as papilledema persists 7
5. Coordinated care: Ongoing communication between neurology and ophthalmology 4

Treatment Failure Algorithm

1. Recognition: Worsening vision after initial stabilization (34% at 1 year, 45% at 3 years) 7, 1
2. Reassessment: Repeat lumbar puncture, comprehensive visual assessment 2
3. Escalation: Surgical intervention if not already performed 7
4. Post-surgical failure: Consider alternative surgical approach or revision 7
5. Lifelong monitoring: Even after successful surgical intervention 7