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

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. Letters to the Editor classified as PTC. We would point out that this delineation, while seemingly logical, has certain drawbacks. Namely, the number of possible risk factors for IIH are numerous and it would be exceedingly difficult to ensure that all possibilities (including those that are anecdotally reported in case studies or case series) are eliminated, given the number of reported possible risk factors for increased intracranial pressure without identifiable intracranial mass effect and normal cerebrospinal fluid composition (among other modified Dandy criteria). In addition, the application of the term PTC as an older term for IIH has been used not just in our article, but in multiple instances in the literature (2–4). However, we do appreciate the merits of this comment and would appreciate readers making a note of these delineations of definitions. We appreciate and acknowledge the second point regarding the drawback that 47% of patient-visits with diagnosis of IIH were excluded from our study because of lack of appropriate comparison complete blood count (CBC) on file. These are, of course, the limitations inherent in any retrospective design. In addition, regarding the point that only 25 of 50 patients reported in our IIH group were overweight or obese (as summarized in Table 1 of our manuscript), we would like to note that 20 of 50 patients did not have any recent body mass index (BMI) available for comparison and were not therefore included in the numbers above. Of the matched controls, 16 of 50 did not have a recent BMI for comparison. This information was not included in the original manuscript and we thank the authors for allowing us an opportunity to clarify this. We regret that we are unable to define the potential interaction between BMI and hemoglobin levels although we greatly appreciate this suggestion and perhaps it could be a subject for future study. We appreciate the discussion of additional studies analyzing the relationship between IIH and anemia, and the thoughtful consideration of cases of anemia and papilledema including the therapeutic nature of a lumbar puncture, and we agree with these thoughts. We would like to clarify that our statement that “Our work suggests that routine CBC may not be necessary in typical patients with IIH” is not by any means a strong suggestion to avoid obtaining CBCs in all IIH patients. Certainly, we agree that if there are any symptoms of anemia (especially ones that do not overlap with IIH symptoms, such as palpitations, pallor, chest pain, or tachycardia, which would be likely to be present if there is severe anemia presumably causing IIH) then a CBC should be obtained. However, it has not been our current practice to obtain a routine complete blood count in young, female patients with typical IIH and we believe that this decision is a practice option. We thank the authors for their interest in our work and we share their enthusiasm for continued research efforts in this important and perplexing condition. Weijie V. Lin, MD Departments of Medicine, Surgery, and Pediatrics, e274 Santa Clara Valley Medical Center, San Jose, California Department of Medicine, Stanford University, Palo Alto, California Shauna E. Berry, DO Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas Mohammad O. Nakawah, MD Houston Methodist Neurological Institute, Houston, Texas Ama Sadaka, MD Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas Andrew G. Lee, MD Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medical College, New York, New York Department of Ophthalmology, UT Medical Branch, Galveston, Texas Department of Ophthalmology, UT MD Anderson Cancer Center, Houston, Texas Department of Ophthalmology, Baylor College of Medicine, Houston, Texas Department of Ophthalmology, Center for Space Medicine, Houston, Texas Department of Ophthalmology, Texas A&M College of Medicine, College Station, Texas Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa The authors report no conflicts of interest. REFERENCES 1. Markey KA, Mollan SP, Jensen RH, Sinclair AJ. Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. Lancet Neurol. 2016;15:78–91. 2. Wall M. Update on idiopathic intracranial hypertension. Neurol Clin. 2017;35:45–57. 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 3. Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep. 2008;8:87–93. 4. Cleves-Bayon C. Idiopathic intracranial hypertension in children and adolescents: an update. Headache. 2018;58:485–493. Neuro-Ophthalmic Features of Autoimmune Encephalitides: Letter to the Editor is weaning off the IVIg and clinically is much improved. I write this correspondence to illustrate 4 points (A–D) I have learned from this case. (A) Many of these patients present with only psychiatric symptoms early in the course of the disease (2) and eventually come to the attention of the neurologist or neuro-ophthalmologist only after the disease has progressed to a more advanced stage (3). (B) When detected and treated early, permanent disability and death may be avoided (4). (C) The NMDAR antibody test can be negative in the disorder or initially positive and then negative, as in my patient. (D) Neuroimaging for an ovarian mass may initially be normal but one must continue to survey for a tumor with serial pelvic ultrasounds (5). I enjoyed reading the recent article regarding the neuroophthalmic features of autoimmune encephalitides (1). In 2018, I evaluated a 20-year-old woman referred for pseudotumor cerebri (PTC). The patient did not have signs nor symptoms of PTC, save for a headache, and she had a completely normal neuro-ophthalmologic examination without papilledema. Brain MRI showed no signs of elevated intracranial pressure, and the lumbar puncture revealed an opening pressure of 10 cm of water with a normal formula. The patient did, however, endorse progressive neurologic symptoms over the past year consisting of memory deficits, the aforementioned headaches, “seizure-like episodes,” and infrequent dystonic posturing. She had been treated with intravenous corticosteroids early in her disease course without benefit. Given the clinical picture and lack of a psychiatric or drug abuse history, I worked the patient up for encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibodies, thyroid functions, vitamin deficiency screening, and blood glucose were obtained. The NMDAR antibodies returned “weakly positive,” and the rest of the studies returned normal. Further workup was undertaken including electroencephalography showing no seizure activity, a negative drug screen, and a computed tomography (CT) of the chest abdomen and pelvis, which was normal. NMDAR antibodies in the CSF were not detected. A repeat serum NMDAR antibody and paraneoplastic antibody panel were normal. Despite the negative workup, the high clinical suspicion for autoimmune encephalitis prompted me to treat the patient with periodic intravenous immunoglobulin (IVIg) treatments every 4–12 weeks, with relief of her symptoms; however, there was no complete resolution. During this time, several pelvic ultrasounds were undertaken, all of which were negative. Finally, after 2 years of symptoms, one of the pelvic ultrasounds detected a right ovarian mass, and its subsequent removal revealed an ovarian teratoma. The patient currently Letters to the Editor: J Neuro-Ophthalmol 2021; 41: e271-275 Michael S. Vaphiades, DO Departments of Ophthalmology, Neurology and Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama Supported in part by an unrestricted grant from the Research to Prevent Blindness, Inc, New York, New York. The author reports no conflicts of interest. REFERENCES 1. Bohm PE, Chen JJ, Bhatti TM, Eggenberger ER. Neuroophthalmic features of autoimmune encephalitides. J Neuroophthalmol 2020;40:385–397. 2. Kayser MS, Dalmau J. Anti-NMDA receptor encephalitis in psychiatry. Curr Psychiatry Rev. 2011;7:189–193. 3. Kaneko A, Kaneko J, Tominaga N, Kanazawa N, Hattori K, Ugawa Y, Moriya A, Kuzume D, Ishima D, Kitamura E, Nishiyama K, Iizuka T. Pitfalls in clinical diagnosis of anti-NMDA receptor encephalitis. J Neurol. 2018;265:586–596. 4. Mammele S, Thompson KS, Abe KK. A rapidly fatal case of antiNMDA receptor encephalitis due to acute brain edema and herniation. Neurology 2019;92:1014–1016. 5. Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol. 2016;12:1–13. e275 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.