Associated
conditions which can cause raised ICP.
Also called Pseudotumour cerebri or Benign
Intracranial Hypertension
Clincal signs of raised ICP without a structural cause
Incidence 1-2/100,000 overall
o Varies greatly with obesity of population
o 13-14/100,000 in obese people
Women (92%) > men
Childbearing age 15-44 (mean 31).
Rarely seen in children and elderly.
Obesity is major RF up to 95% obese
o In particular recent weight gain
Adrenal insufficiency
Cushings syndrome
Hypo/hyperthyroidism
Hypoparathyroidism
Haematological
Severe anaemia
Polycythemia vera
Obstructive sleep apnoea
COPD
SLE
Uraemia/renal failure
Behcets
Psittacosis
Growth hormone
Tetracyclines
Vitamin A derivatives (inc ATRA, isotretinoin)
Fluroquinolones**
Steroid withdrawal
Bactrim
Tamoxifen
Ciclosporin
Lithium
Indomethacin
Cimetidine
Nalidixic acid
Levothyroxine
Danazol
Implanon
Many others with less defined association
**
Many theories
Abnormal CSF production/absorption
o Production rate is normal in IIH patients therefore unlikely the cause
o Some experiments have indicated abnormal absorption however the mechanism is unclear.
Intracranial venous hypertension
o Subtle structural abnormalities of venous system have been noted but it is unclear if these are primary of secondary
o Transverse sinus (TS) stenosis is most commonly associated abnormality. Unilateral TS stenosis occurs in 30% of normal people. Bilateral TS is rare.
o Bilateral TS flow defects found in ~65% of IIH patients and none in control group in one study.
o Proposed that stenosis may occur due to the raised ICP instead of as cause however some (small) studies show persisting TS after reduction in ICP via LP.
Increased central venous pressure
o Due to increased intra-abdominal pressure in obese patients transmitted to intracranial pressure
Inflammation theory
o Increased pro-inflammatory cytokines in some patients. Inflammation associated with obesity.
Thrombosis theory
o High levels of anti-phospholipid antibodies in many patients. Abnormal levels of fibrinogen in others.
o ?Microthrombi causing obstruction of CSF drainage.
Headache (92%)
Transient visual obscurations (72%)
Intracranial noises (pulsatile tinnitus) (60%)
Photopsia (sparkles) (54%)
Retrobulbar pain (44%)
Diplopia (38%)
Sustained visual loss (26%)
Dizziness, nausea and vomiting
Headache
o Highly variable in character often generalised
o May have some postural change, worse in morning.
o NSAIDS may relieve
o Pain with eye movement or globe compression can occur
Visual changes
o Transient visual loss/obscurations lasting seconds, unilateral or bilateral. Shadows, dark patches or dark spots.
o Variable frequency does not correlate with severity.
o Diplopia usually horizontal
o Visual field defects (see below)
Papilloedema (approaching 100% of patients)
o Can be unilateral (10% in one study)
Visual field loss (~30% on presentation, up to 90% on perimetry during course of disease)
o Enlargement of blind spot common
o General field constrictions
o Arcuate scotoma
o Nasal field loss
Sixth nerve palsy (unilateral or bilateral)
Most other cranial nerves can be affected in rare cases Particularly
1. Symptoms and signs, if present, are only those of raised ICP or papilloedema
2. Elevated ICP on LP
3. Normal CSF composition
4. Normal neuroimaging specifically no space occupying lesion or venous sinus thrombosis
5. No other cause of raised ICP apparent
MRV to exclude venous sinus thrombosis
There are some MRI findings suggestive of IIH
1. Flattening of the posterior sclera
2. Distension of the perioptic subarachnoid space
3. Enhancement of the prelaminar optic nerve
4. Empty sella
5. Intra-ocular protrusion of the prelaminar optic nerve
6. Vertical tortuosity of the orbital optic nerve
Opening pressure - <20cm normal, >25 abnormal, 20-25 equivocal (see Neurology 2006, 67: 1690)
Serial LPs to measure progress may not correlate well with symptoms and should be used with caution.
Visual field testing
Papilloedema
Secondary causes of raised ICH
o Venous sinus thrombosis
o Jugular or other venous abnormality
o Mass lesion
o Obstructive hydrocephalus
o Decreased CSF absorption arachnoid granulation adhesions after SAH or meningitis
o Increased CSF production choroid plexus papilloma
o Raised ICP secondary to medications or systemic disease
Malignant HTN can give papilloedema and headache
Cease any medications that may worsen (e.g.
tetracyclines)
Weight loss
o Many reports suggesting significant improvement in papilloedema with weight loss.
o A ~6% or >2.5kg weight loss has been associated with improvement
o Surgically induced weight loss also effective (lap banding, gastric bypass etc.)
Acetazolamide
o Reduces CSF production (probably by reduction of sodium ion channel transport across the coroid plexus epithelium).
o Causes weight loss ?contribution to effect
o NORDIC IIHHT trial demonstrated benefit for visual field and papilloedema (See Clinical trials below)
o Start 250mg- 500mg BD increase as needed/tolerated (up to 2-4g/day) (tablets are 250mg)
o SE: Digital and oral paraesthesia, anorexia, malaise, metallic taste, fatigue, N+V, electrolyte abnormalities, metabolic acidosis, kidney stones.
Topiramate
o Has some weak activity of carbonic anhydrase and may reduce CSF production
o Causes weight loss
o One study of 40 pts vs acetazolamide - both equally effective, significantly more weight loss with TPX.
May be useful in addition to acetazolamide
No good evidence
May be useful in short term, but can worsen problem in the long term and are generally no longer used except in cases of rapid deterioration.
Serial lumbar punctures
o Probably effective (in small trials)
o Generally used as temporary measure
Reserved for progressive disease especially deteriorating vision
VP or LP shunting
o VP shunting can be difficult given normal sized ventricles
o Significant proportion of patients will need revision of shunt with time
o LP shunts are easier to perform but fail at twice the rate and often have more SE.
Optic nerve sheath fenestration
o Effective at reducing papilloedema
o Does not significantly reduce ICP or headache
o 40% of patients have transient complications ocular motility disturbance, pupillary dysfunction, retinal vascular complications.
Venous sinus stenting experimental
o ?Total of 22 patients treated of which 14 improved.
o 49/52 patients with unilateral stents had resolution of symptoms
- 2 patients with severe somplications
- Ahmed RM, ANJR 2011
- Need to
- 10% of patients had eventual restonis
o J neurointerventional surgery meta-analysis
Visual testing probably the most important aspect of monitoring
Serial LPs for pressure do not correlate well with symptoms and papilloedema
Natural history is generally slow worsening
A subset of patients have a more fulminant course
Treatment tends to result in stabilisation of the condition.
Visual loss or severe visual impairment is concern (occurring in up to 15%)
After stabilisation 8-38% will have a recurrence of symptoms.
IIH poor prognostic factors:
Rapid onset
Drug induced
Severe obesity
Black race
Gender
Anaemia
OSA
HTN
VA/Colour vision or VF deficits
JAMA 2014
165 patients (86 Acetazolamide, 79 Placebo)
18-60yrs
IIH by Dandy Criteria
Visual loss perimetric mean deviation of -2dB to -7dB
Bilateral papilloedema
Elevated CSF pressure
Naοve to treatment
No visual loss or very severe visual loss
Use of topiramate
Mean age ~29
Female ~80%
Mean Weight 107kg, BMI 40
Papilloedema grade: Mainly spread across 2,3 and 4.
CSF pressure mean ~34cm
Both arms received diet programme and including low sodium
Randomized to placebo or acetazolamide 500mg bd initially, followed by increases of 250mg/week to a maximum dosage of 4g/day (40% of patients ended up on 4g/day).
Dose escalation stopped if: papilloedema became <1 in both eyes, PMD improved to -1dB or better in each eye, unless other symptoms suggested dose escalation should continue.
Patients could down titrate treatment if side effects to a minimum of 125mg daily.
Treatment failure defined as
o Patinet with baseline PMD up to -3.5dB got worse by >2db
o Patient with baseline PMD -3.5 to -7dB got worse by >3dB
|
|
Acetazolamide |
Placebo |
P value |
|
Discontinued drug |
9 |
1 |
|
|
Mean PMD change |
1.43dB |
0.71dB |
0.05 |
|
Papilloedema change |
-1.31 |
-0.61 |
<0.001 |
|
Headache score (HIT-6) |
-9.56 |
-9.11 |
NS (0.77) |
|
VA |
2.65 |
2.64 |
NS (0.99) |
|
Weight Loss |
-7.5kg |
-3.45kg |
|
|
Visual QOL scores (VFQ-25) |
8.33 |
1.98 |
0.003 |
|
SF-36 (general QOL) |
5.84 |
2.82 |
0.03 |
|
Treatment failures |
1 |
6 |
|
85 patients elected to have a repeat LP at 6 months (not a random sample)
o Change in opening pressure:
- Acetazolamide group - 112.3mm
- Placebo group 52.4mm
- Treatment effect -60mm
|
Side effects occurring more frequently with treatment (%) |
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Pareasthesia |
47.7 |
6.3 |
<0.05 |
|
Nausea |
30.2 |
12.7 |
<0.05 |
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Fatigue |
16.3 |
1.3 |
<0.05 |
|
Dysgeusia |
15.1 |
0 |
<0.05 |
|
Diarrhoea |
14 |
3.8 |
<0.05 |
|
Vomiting |
14 |
3.8 |
<0.05 |
|
Tinnitus |
12.8 |
3.8 |
<0.05 |
|
Side effects occurring in both groups at similar rate |
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Elevated ALT |
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Dizziness |
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Dyspepsia |
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Headache |
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Infection |
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Serious Adverse events in Acetazolamide group (1 of each): Renal impairment, pancreatitis, diverticulitis, allergic reaction, hypokalaemia
N.B. Only a mild decrease in potassium was seen, no patients required supplementation (except perhaps the patient who developed hypokalaemia??)
9 acetazolamide patients discontinued drug, 1 placebo
Acetazolamide
o Improves visual field deficits (not VA)
o Reduces papilloedema
o Reduces pressure by 60mm
o Improves QOL measures (despite side effects)
o Does not improve headache