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Editor,—Idiopathic intracranial hypertension has an association with prothrombotic conditions. The recently described thrombophilic defect of activated protein C (APC) resistance, caused by the factor V Leiden mutation, has been postulated to be a factor in some cases.1 To the best of our knowledge, we describe the first two cases reported of the factor V Leiden mutation identified in association with idiopathic intracranial hypertension. Both patients had been previously well and there was no past history to suggest a clotting disorder.
A 20 year old obese white female presented to the ophthalmic department with transient obscurations of vision. She had not been taking the oral contraceptive pill. Snellen visual acuity was right eye 6/12, left eye 6/12 and gross papilloedema with macular stars was noted. Computerised tomography and magnetic resonance angiography were normal and a lumbar puncture showed an opening pressure of 75 cm of water. CSF protein, glucose, and cell count were normal as were U&Es, LFTs, TFTs, glucose, full blood count, and plasma viscosity. She was started on 250 mg of Diamox four times daily and advised to lose weight. Over the next few days acuity reduced to right eye 6/24, left eye 3/60 with extensive field restriction. Urgent optic nerve fenestration of the left eye was undertaken followed by the right 12 days later as acuity began to worsen in this eye also. Partial recovery occurred with Snellen visual acuities of right eye 6/60, left eye 6/36 but, unfortunately, the extensive field restriction remained. On thrombophilia screening, the APC resistance ratio was reduced at 1.9 (normal 2.2–4.2) on two occasions and a heterozygous factor V Leiden mutation was identified. She was referred to the haematology department to consider anticoagulation which, on discussion, was not undertaken as she was thinking of planning a family.
A 31 year old obese white female was referred by her general practitioner complaining of transient visual loss in her left eye for the previous 5 months and non-specific headaches for 2 years. She had stopped the oral contraceptive pill 5 years previously. Snellen visual acuity was right eye 6/5, left eye 6/5 and field analysis showed an enlarged blind spot in the left eye. Funduscopy revealed established papilloedema in the left eye and early papilloedema in the right. Urgent computerised tomography was normal and a lumbar puncture had an opening pressure of 37 cm of water. CSF and blood investigations were unremarkable. Visual acuity and fields remained stable on Diamox SR 250 mg twice daily and she has been able to lose weight from 15 stones. A thrombophilia screen showed a reduced APC resistance ratio of 1.9 on two occasions and a heterozygous factor V Leiden mutation was found. She was also referred to the haematology department for consideration of anticoagulation and, after discussion, was begun on warfarin.
Prothrombotic abnormalities have recently been implicated in the pathogenesis of “benign intracranial hypertension” (BIH).1 It has been suggested that reduced CSF reabsorption due to damaged arachnoid villi, secondary to microthrombus formation, could be the cause of raised intracranial pressure. Arachnoid villi dysfunction causing BIH has also been postulated in SLE and may be the result of venulitis, aseptic meningitis, or immune complex deposition and, in the antiphospholipid syndrome, possibly due to micro- occlusion.2 Such mechanisms affecting the optic nerves in addition could cause the poor outcome in case 1.
APC resistance is gaining greater recognition in the pathogenesis of ophthalmic disorders and has been implicated as a cause of central retinal vein occlusion in patients younger than 50 years.3The factor V Leiden mutation may be heterozygous or homozygous and carries a lifelong increased thrombotic risk of 5–10 fold and 50–100 fold respectively.4 As 5% of the population has the factor V Leiden mutation,5 it is felt that most individuals carrying the defect will never experience a thrombotic event unless they carry another genetic defect, such as a deficiency of protein C or S,6 7 or are exposed to a precipitating factor such as oral contraceptives, pregnancy, or surgery.8 9 Currently the criteria for anticoagulation in idiopathic intracranial hypertension are unknown owing to the absence of controlled clinical trials. It is reasonable for haematologists to offer warfarin as a short course or continuously in symptomatic patients, especially if the event is severe, and in those exposed to other risk factors who have a familial thrombotic tendency.
Without further studies addressing the association of idiopathic intracranial hypertension and thrombophilia, routine testing for the factor V Leiden mutation and other thrombophilic factors cannot be recommended in patients with idiopathic intracranial hypertension outside a clinical trial basis. However, if the mutation is found, referral should be made to a haematologist for advice concerning anticoagulation, bearing in mind the increased bleeding risk and teratogenicity of warfarin. First degree blood relatives of the patient should be warned to avoid smoking and to seek medical advice before taking oral contraceptives or accepting elective surgery: the factor V Leiden mutation is of dominant inheritance.10