WL Lau, CH Ko, WW Cheng, SK Yau, CY Lee

Abstract

Idiopathic intracranial hypertension (IIH) is a rare diseaseand local epidemiological data on childhood IIH is limited. Presenting symptomsare often nonspecific and may mimic migraine. We report an adolescent with IIHwho did not have classical predisposing risk factors. Annual incidence in HongKong is estimated to be 0.78 per 100,000 paediatric admissions to public hospitals.Enhanced awareness and prompt treatment is important as delayed diagnosis isassociated with high risk of permanent visual damage. Urgent surgical interventionis necessary for those who do not response to medical treatment.

Introduction

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri,is a rare condition characterised by raised intracranial pressure (ICP) withnormal cerebrospinal fluid (CSF) composition and absence of hydrocephalus orspace occupying lesions. It predominantly affects adult population, particularlyoverweight women of child-bearing age. The condition is rare in children.¹ As symptoms are non-specific and parents often reject invasive lumbar puncture(LP), diagnosis may be delayed resulting in permanent visual damage. We reportan adolescent who did not have classical predisposing risk factors, and reviewthe recent literature in the clinical management of IIH. Annual incidence isestimated from local epidemiological data.

Case Report

A 14-year-old Chinese girl presented with bilateral peripheral visual lossand frontal headache for one year. Her headache was throbbing in nature andwas aggravated by exercise. It was progressive with increasing frequency upto several times per day. Her headache was associated with transient visualobscurations, described as bilateral peripheral visual field loss that occurredfor five to eight seconds each time. There were no other associated symptoms.No preceding head injury, viral illness or use of medication was found. Herbirth history and past health were otherwise unremarkable.

Physical examination revealed a normal build girl with body weight at 25thpercentile, and height at 50 to 75th percentile. Body massindex was 18 kg per m² (10 to 25th percentile), bloodpressure 118/80 mmHg. There were no focal neurological deficits; systemic examinationwas unremarkable. Ophthalmologic examination revealed bilateral grade 4 papilloedema(Figure 1a). Extraocular movement was normal. Goldman visual field test showednormal visual field on both eyes but mildly enlarged blind spot on right eye.Optical coherence tomography demonstrated thickening of nerve fibre layer onright eye. Visual evoked potential was normal.

Magnetic resonance imaging (MRI) of brain showed no ventricular dilatation(Figure 1b). Magnetic resonance venography showed no abnormalities in all majordraining sinuses. Blood gas, serum cortisol, thyroid function, antinuclear antibodies,rheumatoid factor, protein C, protein S and lupus anticoagulant were all normal.Urine metabolic screening was unremarkable. LP revealed clear CSF with raisedopening pressure of 33.5 cmH₂O. CSF cell count and biochemistry werenormal; microbial smear and culture were negative.

Figure 1 (a) Grade 4 papilloedema showing total obscuration on the discof a segment of a major blood vessel on the disc.(b) Magnetic resonance imageof brain showed normal size of ventricles.

Diagnosis of IIH was established according to the Modified Criteria of Dandy,which include symptoms and signs of raised intracranial pressure, absence oflocalising neurological signs, raised cerebrospinal fluid pressure with normalCSF composition, and normal sized ventricles.³ She was started onacetazolamide 500 mg twice daily (25 mg/kg/day) and gradually stepped up to1 gram twice daily. Two weeks later there was significant improvement in headacheand visual obscurations, with partial resolution of papilloedema to grade 2.Follow up blood tests showed normal acid-base and electrolyte levels. However,further dose escalation was precluded by side effects including tingling sensationin the toes, anorexia and abdominal cramps. She was subsequently put on combinationtreatment with furosemide, with resolution of symptoms and papilloedema afterfour months.

Estimated Incidence in Hong Kong Children

We estimated the local disease incidence among children aged 0 to 18 yearsold by retrieving Hospital Authority (HA) clinical disease analysis and registrationsystem (CDARS) data from 1st May 2007 to 1st May 2012. Of a total of 434,655paediatric hospital admissions to all HA hospitals during the five year period,a total of 17 patients (9 males, 8 females) were diagnosed with IIH, yieldingan annual incidence of 0.78 per 100,000 admissions.

Discussion

IIH is a rare condition in childhood. A recent study in United Kingdom hasreported an estimated annual incidence of 0.8 per 100,000 child population aged1 to 16 years,¹ which is concordant with our current estimated localincidence of 0.78 per 100,000 admissions. However, the true incidence may beunderestimated as patients from private sectors and outpatient clinics wereexcluded in our calculation. Other factors such as coding errors in CDARS, presenceof non-specific symptoms and refusal of LP might also contribute to underestimationof local incidence.

Heightened physician awareness is important to prevent visual sequelae inchildhood IIH. Unfortunately, the presenting symptoms are often non-specificand may mimic migraine. Headache is typically generalised throbbing on presentation,aggravated by Valsalva manoeuvre. These may be associated with nausea, vomiting,stiff neck, retro-orbital pain, photophobia, pulsatile tinnitus and dizziness.Neurological examination is typically normal, with the exception of unilateralor bilateral sixth nerve palsies, which can occur in up to 50% of paediatricpatients.² Previous studies had shown that around 60% of paediatricpatients with IIH were older than 10 years old.³ Unlike in adultsand postpubertal subjects, female gender and obesity were not found to be riskfactors among prepubertal children.⁴ In the absence of common predisposingfactors (Table 1), diagnosis may be delayed till the onset of visual complications.The latter may range from transient visual obscurations (2-53%), visual fielddefects (up to 90%), to irreversible deterioration in visual acuity (20%).^2,3 The overall risk of visual impairment is up to 40%, with blindness in 4% ofpatients.^3,4 High grade papilloedema, marked visual field loss, subretinalhaemorrhage, hypertension and recent weight gain are risk factors for rapidprogression and poor visual outcome.^2,3

In children suspected of IIH, cranial imaging should be performed prior toLP to exclude space occupying lesion in the brain. MRI is superior to computertomography for detecting pathologies such as posterior fossa lesions, isodensetumours, meningeal infiltration and cerebral venous sinus thrombosis. Subtleradiological findings indicative of increased ICP include flattening of posteriorsclera, empty sella or distension of perioptic subarachnoid space.⁵

Data on normal range of CSF opening pressure is limited in children. A recentreview defines CSF opening pressure of 25 cmH₂O as diagnostic inchildren of 8 years old or older, whereas pressure of 20 cmH₂O isused in those younger than 8 years of age.³ The degree of raisedCSF pressure at presentation is not an important prognostic factor.⁶ RepeatedLP is not recommended, unless there is relapse of disease or rapid visual deterioration.

Treatment of IIH is indicated in patients with loss of visual field or acuity,persistent headache and moderate to severe papilloedema.² Acetazolamide,a carbonic anhydrase inhibitor, is the first line medication in IIH. Variableeffectiveness of 47-67% was reported in childhood cases.⁴ Recommendedstarting dose is 25 mg/kg/day given in three to four divided doses, with maximumdose of 100 mg/kg/day or 2 grams /day.⁴ As in the present case, doseescalation is often limited by side effects such as loss of appetite, fatigue,altered taste, paraesthesia of fingers and toes and abdominal cramps. Laboratorymonitor is required to look for metabolic acidosis, acute tubular necrosis,potassium and magnesium depletion. Furosemide helps to reduce reabsorption ofsodium and decrease total extracellular fluid. Combination therapy with acetazolamidehas been shown to be effective in reducing CSF pressure with good clinical response.⁴ Topiramate, with its carbonic anhydrase inhibitor activity and anorexiceffect, has also been utilised in treatment for IIH. However, its efficacy inchildren has not been established.⁴ Therapeutic LP is used as anacute relief of symptomatic IIH. However, ICP may quickly return to pre- treatmentlevel after one to two hours.⁴ LP is also poorly tolerated and difficultto perform in agitated children.

Majority of patients with IIH respond well to medical treatment. Most childrenhave resolution of symptoms and papilloedema after one week to six months oftreatment. While the optimal treatment duration has not been established, ingeneral medication may be tapered after 2 months with symptom resolution.⁴ Medication failure ranges from 18% to 22%, and a third of patients mayhave persistent papilloedema after 10 months.^2,4 Recurrence of IIH,usually peaks during first 18 months of diagnosis, is reported in 5-22% of cases.^3,4,6

Urgent referral to neuro-ophthalmologist and neurosurgeon is indicated ifthere is severe or rapid visual loss at onset, severe papilloedema with macularoedema and exudates, and intractable headache.^2,3 Children who donot respond to medication with worsening of symptoms and signs are also potentialcandidates for surgery. Surgical interventions include CSF diversion proceduressuch as lumboperitoneal or ventriculoperitoneal shunt, and optic nerve sheathfenestration.^2-4 To date, no data are available to compare efficacyof different surgical options. Choice of surgery mainly depends on availabilityof expertise and patient's preference.

Conclusion

IIH is rare in children, with an estimated annual incidence of 0.78 per 100,000paediatric admissions in Hong Kong. Heightened physician awareness is importantfor early detection and prompt treatment to prevent irreversible visual loss.

Declaration of Interest

We declare that we have no conflict of interests.

References

1. Matthews YY, Deans F, Matyka K, et al. UK surveillance of Childhood IdiopathicIntracranial Hypertension (IIH). Arch Dis Child 2012;97(Suppl 1):A1-A186.

2. Spennato P, Ruggiero C, Parlato RS, et.al. Pseudotumor cerebri. Childs NervSyst 2011;27:215-35.

3. Standridge SM. Idiopathic intracranial hypertension in children: a reviewand algorithm. Pediatr Neurol 2010;43:377-90.

4. Matthews YY. Drugs used in childhood idiopathic or benign intracranial hypertension.Arch Dis Child Educ Pract Ed 2008;3:19-25.

5. Shin RK, Balcer LJ. New developments in idiopathic intracranial hypertension.Curr Neurol Neurosci Rep 2001;1:463-70.

6. Soiberman U, Stolovitch C, Balcer LJ, Regenbogen M, Constantini S, KeslerA. Idiopathic intracranial hypertension in children: visual outcome and riskof recurrence. Childs Nerv Syst 2011;27:1913-8.