Definitions, etiologies and symptoms of intracranial hypertension included. Relevance of intracranial hypertension to ophthalmologist and grading of papilledema discussed. Detailed discussion of Idiopathic Intracranial Hypertension (IIH), including the diagnostic criteria, clinical and radiological diagnosis, management and monitoring of IIH discussed.

1. Intracranial
Hypertension
Dr. Obaidur Rehman
Ophthalmology resident
Government Medical College &Hospital
Chandigarh

2. Contents
Definitions
CSF circulation
Etiologies
Symptoms
Relevance to ophthalmologist
Modified Frisen’s grading
Idiopathic Intracranial
Hypertension

3. Definitions
• Intracranial pressure (ICP)
 - pressure exerted by cranium on the brain tissue, CSF, and the
brain’s blood volume
 - constantly fluctuates in response to physical activities
 - normally less than 20 mm Hg i.e. 26 cm of water
 (usually 7-15 mm Hg in supine adults)
 (J Neurosurg 1991;74:597–600)
 Intracranial volume ~ 1700 mL
 Brain 80% (1500 mL)
 CSF 10% (150 mL)
 Blood 10% (150 mL)
(Neurology 2001: 56:1746-48)

4. Intracranial hypertension
 Generally, ICP above 20 mm Hg or 25 cm water is considered
as raised
 Mild : 20-30 mm Hg
 Moderate : 31-40 mm Hg
 Severe : > 41 mm Hg
 (Neurol Clin. 2008;26(2):521-x)
 The definition of raised ICP can vary with specific pathology
- Hydrocephalus: >15 mm Hg regarded as elevated
(Journal of Neurology, Neurosurgery & Psychiatry 2004;75:813-82)

5. CSF circulation
 Production
 Choroid plexus of
 - lateral ventricles
 - third ventricle
 - fourth ventricle
 500 cc/day i.e around 20 cc/hour
 (Nature Communications 2018:9(1):2167)

6. CSF absorption
Absorption through
arachnoid villi
Dural sinuses
Jugular venous system
 Absorption of CSF also occurs though lymphatic system
Neurol Med Chir 2015

7.  Monro-Kellie doctrine
Cranium is a rigid structure, with 3 main components
Volume remains fixed
Compensatory changes occur when one component increases
(Neurol. 2001: 56:1746-48)
 Increase in the volume of contents increased pressure
within the cranial vault
 Autoregulation
Cerebral perfusion pressure = Mean arterial pressure minus
Intracranial pressure
 Clinical implication: ICP Cerebral blood flow
Brain herniation

8. Etiology
Space occupying
lesions
Hematoma
Tumor
Abscess
Increase in
intracranial contents
Cerebral edema:
infections, head
injury, encephalitis,
hypoxic injury
Disturbance in CSF
production/absorption:
Choroid plexus tumor,
obstructive
hydrocephalus
Venous sinus
obstruction:
Cerebral venous
thrombosis, depressed
fracture over a vessel
Idiopathic:
Idiopathic
Intracranial
Hypertension
Neurologic clinics 2008: 26(2): 521

9. Symptoms
 Headache: most prominent symptom
- compression of duramater
- traction on blood vessels
 Nausea
 Projectile vomiting
 Visual disturbances
 Lethargy, confusion
 Late symptoms: stupor, decreased level of consciousness
Severity of intracranial
hypertension has no correlation
with severity of symptoms

10. Relevance to the
ophthalmologist
 Variety of visual symptoms
- decreased vision
- diplopia
- visual field loss
- contrast deficits
- transient visual obscurations
 Papilledema is the hallmark of intracranial hypertension
 Chronic intracranial hypertension can lead to irreversible visual
loss

11. Development of papilledema
High intracranial pressure
High CSF pressure in subarachnoid
space
Compression of optic nerve
Axoplasmic stasis
&
Venous stasis due to central retinal vein compression
Swelling of the optic nerve head
Eye Brain. 2015;7:47-57

12. Modified Frisen’s grading
(J Neurol Neurosurg Psychiatry 1982;45 (1) 13- 18)
Grade 0: Normal optic disc
Well defined borders
No halo of obscuration of the
peripapillary nerve fiber layer
Grade 1: Minimal degree
C-shaped halo with a temporal gap
Obscures underlying details
Temporal margin normal

13.  Grade 2: Low degree

 Circumferential halo
 Elevation of nasal border
 No major vessel obscuration
 Grade 3: Moderate degree
 Obscuration of 1 or more major
 vessels leaving the disc
 Circumferential halo
 All borders elevated

14.  Grade 4: Marked degree
 Total obscuration of a segment of
 major vessel on the disc
 Elevation of all borders
 Total border obscuration
 Grade 5: Severe degree

 Obscuration of all vessels on disc
 and leaving disc

15.  Papilledema is almost always bilateral
- unilateral in Foster Kennedy syndrome
- rarely in idiopathic intracranial hypertension
J Neurosci Rural Pract. 2017;8:106-10
 Absence of papilledema does not rule out intracranial
hypertension

16. Idiopathic Intracranial Hypertension
(IIH)
 Rare disorder; ‘Idiopathic’ - No etiology is known
Diagnosis of exclusion
Historical perspective
 ‘Meningitis serosa’ by Quincke in 1897
After introduction of lumbar puncture in medicine
 In 1937, Dandy demonstrated high CSF pressure in patients with
suggestive symptoms
 ‘Pseudotumor cerebri’ : papilledema in absence of brain tumor
 ‘Benign Intracranial Hypertension’ : coined in 1950s
Not used now; disease is not benign, as thought earlier

17.  ‘Idiopathic Intracranial Hypertension’ preferred term
- introduced by Corbett and Thompson
 Certain disorders and drugs have shown association with IIH
Argument to use umbrella term ‘Pseudotumor cerebri syndrome
(PTCS)’
- only primary cases to be called IIH
- others to be called ‘secondary intracranial hypertension’
- not yet universally accepted
Neurology 2013;81;1159-1165
 Despite being known for around 125 years, still no general
consensus on this disease

18. Sociodemographics
 Worldwide incidence: 1.8 per 100,000 population
Not known in India
 Mainly affects young, obese females
Incidence in females 15-44 years: 11.1 per 100,000
 Prevalence in men found to be 10%
 Incidence in children: 0.5 - 0.9 per 100,000
Ophthalmology 2017; 124:697-700

19. Pathophysiology
 Exact mechanism inconclusive
Several theories have been put forward
1. Imbalance in CSF circulation
- most accepted theory
- decreased absorption from arachnoid villi or lymphatics
(Am J Physiol 1998; 275:889–96)
2. Role of hormones
- possible role of hormonal activity of Adipose tissue
- Insulin modulation and leptin generation could hold a
key in understanding pathogenesis
- could explain the higher incidence in females
(Br J Neurosurg. 2008; 22:187–94.)

20. 3. Role of Vitamin A
- few studies have noted high Retinol levels in CSF of
IIH patients
- toxic accumulation of Vit. A metabolites suggested as the
cause
- exact role not known
(J Neuroophthalmol. 2007; 27:258–62)
4. Transerve Sinus Stenosis
- found in several IIH patients
- still not established whether it is causative or is a result of
IIH itself
(Eur Neurol 2011; 66:334–38)

21. Associations of IIH
(secondary IIH)
 (Am J Clin Dermatol 2020; 21:163–72.)
 Called ‘secondary IIH’
 Can also be addressed as ‘Drug induced IIH’
Strong Association
Tetracyclines
Vitamin A analogues
Lithium
Steroid withdrawal
Weak association
Oral Contraceptive Pills(OCPs)
Cyclosporine
Nalidixic acid
Fluoroquinolones

22. Symptomatology
Symptom Frequency
Headache 84%
Transient Visual obscurations 68%
Backache 53%
Pulsatile tinnitus 52%
Dizziness 50%
Vision loss 32%
Double vision 18%
JAMA Neurol 2014; 71:693-701

23.  Headache
- most common symptom
- no characteristic phenotype: can be diffuse/frontal/occipetal/
ocular
- associated with photophobia/phonophobia/nausea
- severity of headache related to quality of life
 Pulsatile tinnitus
- patients report hearing ‘intracranial noises’
- due to turbulent flow in stenosed sinuses
 Radicular pain
- dural sheaths of spine getting filled up by CSF under high
pressure

24. Ocular signs and symptoms
 Visual acuity
- remains unaffected in most patients
- chronic papilledema may reach central 10 degrees of field
and affect vision
- visual acuity not a sufficient indicator of visual function loss
 Transient visual obscurations (TVOs)
- episodic blurring of vision/black out
- transient ischemia of optic nerve head
- lasts for few seconds

25.  Visual field defects
- seen in around 92% patients
- half are unaware of field deficits at presentation
- enlarged blind spot: most common
followed by nasal defects
(Brain 1991; 114:155-80)
 Contrast sensitivity (CS) deficits
- can pick up subtle visual function deficits even in presence of
intact visual acuity
- CS deficits have been seen in 75% patients
- sensitive indicator of visual function loss
(Ophthalmology 1986; 93:4-7)

26.  Development of field defect
 - papilledema: forward protrusion of the optic nerve head and
peripapillary retina
 - hyperopic peripapillary retina and a reduction in visual sensitivity
 blind spot enlargement
 - other defects: related to dysfunction or damage to nerve fiber
bundles
 (Invest Ophthalmol Vis Sci. 2016;57:805–812)
 CS deficit development
- retinogeniculate pathways between retina and visual cortex:
Magnocellular pathway: contrast detection over a range of luminances
Parvocellular : acuity and colour processing
- Engorgement of these pathways due to papilledema may hold a key
to CS loss
. The Visual Neuroscience. Cambridge, MA: MIT Press 2004:481–93.

27.  Diplopia
- seen in 10-20% patients
- due to 6th nerve palsy (false localising sign)
- owing to the long course 6th nerve traverses intracranially
(Eye 1998; 12:111-18)
 Fundus findings
- papilledema is the ophthalmic hallmark of IIH
- absence does not rule out IIH if suggestive signs and
symptoms present
- optic nerve dysfunction and vascular compromise may lead
to optic atrophy in chronic cases
permanent visual loss

28.  Investigations
 OCT scan
 - non-invasive, sensitive and objective
- provides quantitative, continuous data that correlates with the
modified Frisen’s grade
- ability to pick up subtle changes that may no be apparent on
fundoscopy
Parameters
 RNFL thickness: significantly increased in more than 90% eyes
- sensitive indicator in monitoring IIH
- higher thickness noted even in eyes of IIH patients without
papilledema
- only parameter seen to vary significantly before and after CSF
removal
Eur J Neurol 2019; 26:808-e57

29.  Neuro-retinal rim thickness and area
- significant increase seen in IIH patients
 ONH cup volume
- reduction seen in IIH
- zero cup volume seen in several patients
fluid collection in ONH and expansion of
neuro-retinal rim compress the cup
 Macular GCL plus inner plexiform layer (IPL) (GCL–IPL)
- remains mostly unchanged
- not affected by ONH swelling, even in severe papilledema
Clinical Neurology and Neurosurgery 2015;130: 122–27

31.  Enhanced depth imaging (EDI)-OCT
- imaging deep ocular structures and to improve the image
quality of deeper structures
- visualize structures 500–800 μm deeper than with conventional
OCT
 - anterior displacement of lamina cribrosa in IIH (due to reduced
trans-LC pressure difference i.e. IOP – CSF pressure)
Eur J Ophthalmol 2017; 27 (1): 55-61

32.  Configuration of Bruch’s membrane on EDI-OCT
- upward defection of Bruch’s membrane toward the vitreous
- due to raised ICP
- differentiating papilledema from pseudopapilledema
Ann Eye Sci 2018;3:35

33.  Magnetic Resonance Imaging
 Rule out other causes of raised ICP
- space occupying mass lesions, hydrocephalus
 Venography – to look for thrombosed cerebral venous sinuses
 Most common finding in IIH : distended perioptic subarachnoid
space (95% patients)
- transmission of high ICP into
subarachnoid space within
optic nerve sheath
- sensitivity: 80%
- specificity: 96%
- normal: 4.8-6.2 mm2
(Current Problems in Diagnostic Radiology 2019; 49:205-14)

34.  Partially empty sella (85% patients)
- due to flattening of Pituitary gland
- result of chronically elevated ICP
- concavity of superior part of Pituitary
- sensitivity: 88%; specificity: 92%
- sella turcica houses the pituitary gland
- CSF filling turcica compresses the pituitary
Current Problems in Diagnostic Radiology 2019; 49:205-14

36.  Tortuous optic nerve (62% patients)
- optic nerve fixed proximally at orbital apex, distally at the
globe
- middle portion is
free and mobile
- High ICP leads to
kinking of the
mid portion
- sensitivity: 40%
specificity: 91%
 Flattening of posterior part of globe
(43-71% patients)
- due to high ICP
 - sensitivity: 43%
 - specificity: 100%
Current Problems in Diagnostic Radiology 2019; 49:205-14

37.  Other MRI findings
- meningocoeles (incidence: 11%)
- prominent Meckel’s cave (incidence 9-11%)
- enlarged foramen ovale (incidence not known)
Lumbar puncture (LP)
 Guarded LP should be performed when high ICP suspected
 Diagnostic as well as therapeutic
 Shows elevated CSF opening pressure in IIH
( >25 cm of water)
 CSF sample collected sent for analysis to rule out other
pathologies

39. Diagnosis of IIH
 Modified Dandy's Criteria
 1. Symptoms of raised intracranial pressure – headache,
nausea, vomitting, transient visual obscurations or
papilledema
 2. No localizing signs with the exception of Abducens nerve
palsy
 3. Patient is awake and alert
 4. Normal CT/MRI findings without evidence of thrombosis
 5. Lumbar puncture (LP) opening pressure of >25 cm of
water and, normal biochemical and cytological composition of
CSF
 6. No other explanation for raised intracranial pressure
 J Clin Neuro-ophthalmol 1985; 5:55–6.

40.  IIH diagnosis in absence of papilledema
- suggestive signs and symptoms of raised ICP
- CSF opening pressure on Lumbar puncture > 25 cm of water
- characteristic MRI findings present

41. Adult IIH Pediatric IIH
Incidence 1.8 per 100,000 0.9 per 100,000
Sex ratio F >> M F = M
Relation with
obesity
High preponderance in
obese individuals
No such preponderance.
Predilection for overweight
patients begins only after
puberty (hormonal change)
Systemic
associations
With obstructive sleep
apnoea.
Not well established
Hypoparathyroidism
Thyroid replacement
therapy
Treatment with recombinant
human growth hormone
CSF opening
pressure for
diagnosis
> 25 cm of water > 28 cm of water
(sedation leads ro
hypercapnia
Leads to artefactual CSF
pressure elevation)

42. Management
 No defined guidelines for treatment and monitoring exist
Lumbar
puncture
• helps to establish
CSF opening
pressures
• relieves headache
as excess CSF
drained out
Lifestyle
modification
• Low sodium diet
• Weight reduction
Carbonic
anhydrase
inhibitors
• Reduce aqueous
production
• Acetazolamide
• Topiramate

43.  Acetazolamide
- carbonic anhydrase inhibitor
- decreases ion and water transport across choroid plexus
- reduces CSF production
- no standardised fixed regimen of dose/duration
- previous studies have used doses of 1 gm daily to upto 4 gm
 daily (Invest Ophthalmol Vis Sci. 2016;57:805–812)
- Side effects: parasthesias, lethargy
- Monitor SERFT
Contra-indicated in liver failure/renal failure

44.  Topiramate
- weak CA inhibitor
Added advantages - weight reduction
- side-effect profile better
- used in migraine prophylaxis
 - no standardised regimen
 - has been used in doses of 25 mg to 100 mg daily
 - side effects: parasthesias, lethargy, drowsiness
 - inadequate as a lone treating agent; can be used in
combination with Acetazolamide
Curr Treat Options Neurol. 2013;15(1):1-12

45. Surgical management
 No clear recommendations exist
 Tried in patients with rapidly progressive neuropathy and when
medical treatment fails
 CSF diversion procedures - lumboperitoneal shunting (LPS)
- ventriculo-peritoneal shunting (VPS)
- failure rates high: LPS (11%) ad VPS (14%)
- revision rates even higher: LPS (60%) and VPS (30%)
 Optic nerve sheath decompression
- in patients with severe visual loss
- improves papilledema but no effect on ICP
Indian J Ophthalmol 2014;62:996-8.

46.  VPS is more effective but more challenging
 ONSD

47.  To study efficacy of Acetazolamide in conjunction with weight
reduction in IIH with mild visual loss
F:M = 30:1
 1 gm Acetazolamide in divided doses versus placebo in 165 IIH
patients
Gradually raised to 4 gm in some patients, depending on
severity
 At 6 months, patients receiving the drug had better visual field
outcomes
 Patients receiving the drug also reported significant
improvement in quality of life

48.  6% mean body weight loss was seen in patients who had
complete resolution of marked papilledema
Average 3% body weight loss in patients who had
downgrading of papilledema
(BMC Ophthalmol 2007; 7:15)
 Patients receiving Acetazolamide and Topiramate
- achieved significant improvement in visual fields
- significantly lowered CSF pressure at 6 months
than patients receiving Acetazolamide alone
(Bali Medical Journal 2018; 7: 201-4.)

49. Thesis data on IIH
 30 IIH patients
F 22
M 8
 Mean age 33.27 ± 10.68 years
 Avg BMI 26.59 ± 4.76 kg/m2 (obese category for Asians)
73%
27%
IIH patients
Females Males

50.  Baseline visual parameters recorded
 70% eyes had 6/6 Snellen visual acuity at presentation
 98.3% eyes had papilledema at presentation
 Follow up at 1 month and 3 month post treatment
 Contrast sensitivity and RNFL thickness: the only parameters
that showed significant difference even after one month of
therapy initiation
 RNFL thickness was the only parameter that correlated
significantly with grade of disc edema

51.  T. Acetazolamide 750-1000 mg/day in divided doses
T. Topiramate 25-50 mg/day if intolerant to acetazolamide or
not improving on Acetazolamide alone

55. Prognosis of IIH
 Difficult to ascertain for each individual patients
 Stable course in most while few may suffer permanent visual
loss
 Lumbar puncture is associated with relief in headache
symptoms
 Acetazolamide associated with improvement in visual outcome
and quality of life
 Weight gain is a poor prognostic factor
J Obes. 2017;2017:5348928.

56. Take home message
 All patients with chronic headache must undergo fundus
examination
 Even in absence of papilledema, diagnosis of intracranial
hypertension should be kept in mind when suggestive signs
and symptoms present
 Contrast sensitivity testing and RNFL thickness are useful for
monitoring and follow up
Thank you!