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

Letters to the Editor Bilateral Atypical Retrobulbar Optic Neuritis Associated With Tuberculosis in an Immunocompetent Patient: Response W e thank Dr. Patil for the comments offered in response to our report of an immunocompetent patient with bilateral atypical retrobulbar optic neuritis associated with tuberculosis (1). There is no diagnostic criterion for tuberculous retrobulbar optic neuropathy, in either immunocompetent or immunocompromised individuals, and no specific diagnostic test is available. The presumed diagnosis of tuberculous retrobulbar optic neuritis in our patient was made after the presence of consistent clinical signs, tuberculous lesions on chest imaging, identification of acid-fast bacilli by culture of sputum samples, radiographic features of retrobulbar optic neuropathy, and exclusion of other possible causes of atypical optic neuritis including systemic inflammatory diseases and vascular, toxic, neoplastic, and hereditary forms of optic neuropathy. A lumbar puncture to culture Mycobacterium tuberculosis from the cerebrospinal fluid is insensitive and was not performed in our patient. Our patient did not experience a beneficial response to systemic corticosteroids. This could be related to the delayed presentation of our patient who had already experienced visual loss 9 weeks before his hospital attendance. Dr. Patil commented on the possibility of using much higher doses of corticosteroids to maximize visual outcomes in patients with presumed tuberculous retrobulbar optic neuritis. However, there is a paucity of efficacy data to inform the optimal formulation, dose, and duration of steroid use in patients with tuberculous retrobulbar optic neuritis. Regarding rifampicin lending itself to using higher 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 e272 doses of corticosteroids, few studies have reported that rifampicin increases the metabolism of steroids because it acts as a glucocorticoid receptor ligand and can induce its transcriptional regulation capabilities (2,3). However, subsequent reports have found that rifampicin did not enhance nuclear translocation of glucocorticoid receptors or induce a glucocorticoid-dependent promoter (4,5). Bilateral retrobulbar optic neuritis associated with tuberculosis is a rare presentation and its most optimal management remains a challenging decision for ophthalmologists. Timothy H. M. Fung, FRCOphth Archana Pradeep, FRCOphth Department of Ophthalmology, The Queens Medical Centre, EENT Centre, Nottingham, United Kingdom The authors report no conflicts of interest. REFERENCES 1. Fung TH, Pradeep A. Bilateral atypical retrobulbar optic neuritis associated with tuberculosis in an immunocompetent patient. J Neuroophthalmol. 2021;41:e174–e176. 2. Blanchard JS. The ying and yang of rifampicin. Nat Med. 1998;4:14–15. 3. Calleja C, Pascussi JM, Mani JC, Maurel P, Vilarem MJ. Rifampicin: a glucocorticoid receptor ligand. Nat Med. 1998;4:1090–1091. 4. Jaffuel D, Demoly P, Gougat C, Mautino G, Bousquet J, Mathieu M. Rifampicin is not an activator of the glucocorticoid receptor in A549 human alveolar cells. Mol Pharmacol. 1999;55:841–846. 5. Herr AS, Wochnik GM, Rosenhagen MC, Holsboer F, Rein T. Rifampicin is not an activator of glucocorticoid receptor. Mol Pharmacol. 2000;57:732–737. 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 Letters to the Editor: J Neuro-Ophthalmol 2021; 41: e271-275 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor 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 irondeficiency 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 Idiopathic Intracranial Hypertension and Anemia: A Matched Case–Control Study: Response W e thank the authors for their thoughtful and informative letter to the editor in response to our article: “Idiopathic Intracranial Hypertension and Anemia: A Matched CaseControl Study.” We have read it carefully and with interest. Letters to the Editor: J Neuro-Ophthalmol 2021; 41: e271-275 with other potentially relevant comorbidities. If anemia is present it should be treated. Gordon T. Plant, MD Department of Neurology, University College London, London, United Kingdom Sui H. Wong, MBBS, MD, MA Department of Neuro-Ophthalmology, Moorfields Eye Hospital, Guys and St Thomas' NHSFT, London, United Kingdom Anna Sundholm, MD, PhD Department of Neurology, Karolinska University Hospital, Solna, Sweden Department of Clincial Neuroscience, Karolinska Institute, Solna, Sweden Susan P. Mollan, MBBS Department of Neuro-Ophthalmology, University Hospitals Birmingham, Birmingham, United Kingdom The authors report no conflicts of interest. REFERENCES 1. Lin WV, Berry S, Nakawah MO, Sadaka A, Lee AG. Idiopathic intracranial hypertension and anemia: a matched case–control study. J Neuroophthalmology. 2020;40:163–168. 2. Fraser C, Plant GT. The syndrome of pseudotumor cerebri and idiopathic intracranial hypertension. Curr Opin Neurol. 2011;24:12–17. 3. Hamedani AG, Pineles SL, Moss HE. The case-control study in neuro-ophthalmology. J Neuroophthalmol. 2020;40:144–147. 4. Sundholm A. Idiopathic Intracranial Hypertension in Sweden— Epidemiological Studies Focused on Incidence and Risk. Thesis: May 2020; Karolinska Institutet. Available at: https:// openarchive.ki.se/xmlui/bitstream/ handle/10616/47092/ Thesis_Anna_Sundholm.pdf. Accessed December 18, 2020. 5. Mollan SP, Mitchell JL, Sinclair AJ. Tip of the iceberg in idiopathic intracranial hypertension. Pract Neurol. 2019;19:178–179. In response to the first point regarding definitions of idiopathic intracranial hypertension (IIH) and pseudotumor cerebri (PTC), we appreciate the comments regarding using the term PTC over IIH when risk factors (such as anemia or medication use) can be identified (1). We appreciate this delineation of terms. In our study, all patients were diagnosed with IIH by the modified Dandy criteria. With this understanding, patients who have any identifiable risk factor (whether anemia is considered such a factor) should be e273 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.