Idiopathic Intracranial Hypertension and Anemia: A Matched Case-Control Study.

W e have read with interest the article by Lin et al (1) giving the results of a retrospective, single center, matched case–control study finding no evidence to support an increased incidence of anemia in a small cohort of cases suffering from idiopathic intracranial hypertension (IIH). We would first point out that the article is not concordant with current views on the use of the terms “idiopathic intracranial hypertension” and “pseudotumor cerebri” (PTC): the authors (1) suggest that the 2 diagnostic categories are interchangeable. However, it has been maintained for some time that PTC is a valuable diagnostic category where the causative factor may not be weight gain and an alternative pathogenesis is either identified or considered possible (2). The expectation therefore is that the term IIH is reserved for cases with an elevated body mass index (BMI) with no other cause found. We accept that this scheme is not without problems: there may well be situations where there is a synergy between weight gain and other factors, such as obstructive sleep apnea. Furthermore, in a sense, it is cases of PTC with no cause found (including high BMI) that form the truly “idiopathic” group. However, given the now universal use of the term IIH in the context of an elevated BMI, our patients are better served if cases of raised intracranial pressure with neither hydrocephalus nor a directly causative mass lesion should be referred to as suffering from the PTC syndrome until all possible causes are excluded. The aim is to avoid missing treatable conditions by assuming that IIH is a uniform disorder. We agree with the Journal's editorial comment (3) regarding a potential pitfall in the study, namely that a high percentage (47%) of “IIH/PTC” patients were excluded from the study because of the lack of a complete blood count result. We also note that 50% of the IIH patients in this cohort were classified as neither overweight nor obese: these cases were therefore atypical for IIH and therefore may not be a fully representative cohort. Furthermore, in addition to anemia as a potential independent risk factor for PTC, there may be an interaction between BMI and hemoglobin (HGB) level: no analysis to identify such an interaction was reported by Lin et al. (1). A recent population-based study has investigated IIH and potential risk factors in the Swedish National Patient Registry between 2000 and 2016 (4). The author reports that the odds ratio for the presence of iron deficiency anemia in the IIH cohort vs a matched general population control group was 8.45, and in IIH vs obese controls was 4.56. This study does indicate a relationship between iron deficiency anemia and PTC, although this was not confirmed in a subanalysis on treatments used for iron deficiency anemia which were significantly increased compared with the general population controls but not compared with the obese controls. A fundamental question, of importance to clinical practice, is whether those cases with PTC and low HGB respond solely to treatment of anemia. Determining this may help to discern whether anemia is a mere association or causative of PTC. The previous literature cited by Lin et al (1) suggests that reversal of anemia may bring about remission of PTC. This may be challenged in most instances as the work-up of papilledema involves a lumbar puncture, which may have a lasting benefit in some cases (5). We have treated a series of patients with iron-deficiency anemia whose papilledema resolved following correction of anemia by intravenous iron infusion and resultant improvement of HGB. These cases underwent no other potentially confounding treatments including no lumbar puncture. Of greatest concern is that we have also treated patients with iron deficiency in association with PTC where the anemia was either undiagnosed or identified but left untreated because it was considered unrelated. We are frankly alarmed that the authors conclude that a complete blood count is not required in cases being investigated for PTC, and we believe this statement is not justified based on the evidence presented in their own findings, in the literature they cite and also now the findings presented in the Swedish nested case–control cohort (4). We therefore strongly recommend all those who investigate papilledema should certainly test for anemia, along with other potentially relevant comorbidities. If anemia is present it should be treated.