Evidence Based Treatment of Idiopathic Intracranial Hypertension. (IIHT)

Andras Rozsa, MD PhD, Coptic Hospital, Kenya

Statement of problem:

Idiopathic Intracranial hypertension (formerly benign intracranial hypertension or pseudotumor cerebri) is a serious disorder with therapeutic uncertainties. It may affect young obese women, with body mass index around 40, and presents with headache, visual obscurations, back pain, and pulsatile tinnitus. One to four per one hundred thousand people may be affected every year. The condition endangers vision. There is a lack of uniform agreement concerning medical management with diuretics; and there is a lack of guidelines concerning the necessity and timing of surgical interventions.

 In a 2015 Cochran Review concluded that “although…..the included RCT showed modest benefits for acetazolamide for some outcomes, there is insufficient evidence to recommend or reject the efficacy of this intervention”.

Purpose of this Study:

To find any new evidence based results published since the Cochrane Database Review of IIHT released in 2015 August.

Methodology and Theoretical Orientations:

Online research of MEDLINE, Cochrane Library and CENTRAL, MEDSCAPE, PLOS, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform.

Findings:

New results of one trial were published in multiple articles: “Idiopathic Intracranial Hypertension Treatment Trial”. This was a randomized, double-masked, placebo-controlled study.

165 patients were enrolled with mild vision loss. 86 patients were randomized to acetazolamide, 79 to placebo group.

Quality of life questionnaire results reported improvement in visual field, and neck pain, pulsatile tinnitus, and dizziness/vertigo that outweighed the side effect of acetazolamide.

All 165 patients had lumbar puncture at enrollment, 85 at 6 month. There was an association between cerebro -spinal pressure (CSFp) and Frisen papilla edema grade (FPG) at baseline.  At 6 months, acetazolamide had similar effect on CSFp in subjects with high FPG and in subjects with low FPG . Only modest association was found between CSFp and FPG.

In patients with IIH and mild visual loss the use of acetazolamide with low-sodium weight -reduction diet compared with diet alone resulted in modest improvement in visual field function. The study found profound effect of weight loss on outcome.

89 (43 acetazolamide, 46 placebo) of 165 subjects meet criteria to enroll to asses papilla edema to SD-OCT (spectral domain optical coherence tomography). Acetazolamide group had significantly greater reduction of retinal nerve fiber and total retinal thickness.

Conclusions and Significance:

In the light of new publications it is still not clear the medication or weight loss resulted in positive outcomes. Only mild cases were enrolled in the cited study. There are no data regarding drug adverse affects, neither explanations of high drop-out rate. No CSF studies results provided except changes in opening pressure. Further RCTs needed to provide conclusive evidences of interventions.

References:

1.       Piper RJ, Kalyvas AV, Young AMH et al: Interventions for idiopathic intracranial hypertension (Review) Cochrane Database of Systematic Reviews 2015, Issue 8. Art No.: CD003434

2.       Effect of Acetazolamide on Visual Function in Patients With Idiopathic Intracranial Hypertension   and Mild Visual Loss. The Idiopathic Intracaranial Hypertension Treatment Trial. The NORDIC   Idiopathiac Intracranial Hypertension Study Group Writing Committee.  JAMA. 2014; 311(16): 1641-1652

3.       Kattah JC, Pula JH, Mejico LJ et al: CSF pressure, papillaedema grade, and response to acetazolamide in the Idiopathic Intracranial Hypertension Treatment Trial. Journal of Neurology. Published online 10 July 2015

4.       Mall M, Kupersmith MJ, Kieburtz KD et al: The Idiopathc Intracranial Hypertension Trial. JAMA Neurol. 2014 June; 71(6): 693-70 

      The OCT Sub-Study Committee and the NORDIC Idiopathic Intracranial Hypertension Study Group. Papiledema Outcomes from the OCT Substudy of the Idiopathic Intracranial Hypertension Treatment Trial. Ophtalmology. 2015 September; 122(9): 1939-1945

      Bruce BB, Digre KB, McDermott MP et al: Quality of life at 6 month in the Idiopatica Intracranial Hypertension Treatment Trial. Neurology. 2016 November; 87: 1871-1877

      Wall M, Johnson CA, Cello KE et al.; for the NORDIC Idiopathic Intracranial Hypertension Study Visual field outcomes for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) Invest Ophtalmol Vis Sci. 2016; 57; 805-812.