A Case of Idiopathic Intracranial Hypertension/Pseudotumor Cerebri Syndrome Cured by Myomectomy

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD A Case of Idiopathic Intracranial Hypertension/ Pseudotumor Cerebri Syndrome Cured by Myomectomy Wendy Phillips, BSc, PhD, FRCP, John Somner, FRCOphth I diopathic intracranial hypertension (IIH) is a condition characterized by raised intracranial pressure (opening pressure .25 cm H2O), papilledema, normal imaging, and spinal fluid. The typical patient is an overweight female of reproductive age. In atypical patients, a secondary cause should be considered. IIH is also known as pseudotumor cerebri syndrome (PTCS), especially when there is a secondary cause (i.e., is not “idiopathic”). There are many secondary causes including drugs, endocrine disorders, obstruction to venous drainage, and syndromic causes. As the name suggests, the pathophysiology of IIH is unknown. There are several theories including leptin resistance, inflammation, increased central venous pressure from abdominal fat, disordered sex hormones, and dysfunctional adipose 11-beta-steroid dehydrogenase (1). We report the case of an atypical IIH/PTCS patient with massive fibroids, whose IIH/PTCS resolved postmyomectomy. Our patient, a nonobese woman of African origin, with a body mass index (BMI) of around 20, first presented at the age of 25 years. She received ulipristal acetate, a progesterone receptor modifier for the treatment of fibroids, in early 2018, for a total of 9–10 months. She was seen in September 2018 with chronic migraine, but in March 2019, she presented with postural headache and visual disturbance and was found to have papilledema (Fig. 1). Her visual acuity was normal. Opening pressure was 35 cm H2O, and cerebrospinal fluid (CSF) constituents, routine bloods (including full blood count and thyroid function tests), and magnetic resonance (MR) venogram were all normal. Over the next few months, her fields and disc swelling remained relatively stable but did not improve despite (intermittent) treatment with acetazolamide. In September 2019, her fibroids (which reached to the sternum) (Fig. 2) were removed. From that time, her headaches resolved, and her discs returned to normal (Fig. 1). Fibroids (leiomyomas) are benign monoclonal tumors from uterine myocytes that secrete extracellular matrix in a Department of Neurology, Princess Alexandra Hospital NHS Trust, Harlow, United Kingdom. The authors report no conflicts of interest. Address correspondence to Wendy Phillips, BSc, PhD, FRCP, Department of Neurology, Princess Alexandra Hospital NHS Trust, Hamstel Road, Harlow CM20 1QX, United Kingdom; E-mail: w. [e-mail] e156 steroid-dependent fashion. They are very common, particularly in obese and African women. There may be a genetic predisposition to developing fibroids. Aromatase, an enzyme that converts androgens to estrogen, is found at a higher level in fibroids, compared with surrounding myometrium. Estrogen and growth factors are secreted by fibroids in an autocrine fashion. Chronic inflammation is believed to contribute to pathophysiology. Estrogen and progesterone are believed to be important in the growth of fibroids by several mechanisms including modulation of miRNAs and upregulation of growth factors through the Wnt/beta-catenin pathway (2). It seems unlikely that the fibroid and IIH were not related, particularly given our patient has an atypical phenotype for IIH. It does not seem likely either that a common predisposing factor was responsible for IIH, given it resolved with myomectomy, suggesting the fibroid itself was driving the IIH. Ulipristal does not seem a likely cause, given her IIH continued despite cessation of the drug. There are several possible mechanisms for the link between fibroid in our patient and IIH. First, given the fibroid was very large, it is possible it elevated intracranial pressure (ICP) through a mechanical effect (3). Raised intraabdominal pressure (IAP) can increase ICP through intrathoracic pressure (ITP). This causes a back pressure in jugular veins and so decreases drainage of CSF and blood, leading to raised ICP. Furthermore, the valveless venous system (VVS) transmits IAP to the spinal canal and brain. Venous blood and CSF drain from the brain through the jugular veins (on to the vena cava) and the VVS that runs alongside the spinal column. There are large numbers of anastomoses and interconnectivity between these two systems. Given the lack of valves in the VVS, bidirectional flow can occur; it can act as a large reservoir of blood, and pressure can shift from one blood compartment to another. The VVS can shift pressure to the venous system in the brain and can thus increase ICP in the enclosed rigid cavity of this compartment. Second, while it is known fibroids secrete in an autocrine fashion, systemic effects have been described, for example, erythrocytosis from erythropoietin secreted by fibroids. This, however, was not the mechanism of IIH/PTCS in our patient, given her normal hemoglobin. There are other possible candidates including high testosterone, which has Phillips and Somner: J Neuro-Ophthalmol 2023; 43: e156-e158 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Fundal appearance and optical coherence tomography (OCT) preoperatively showing papilledema (OCT preoperative right eye [RE] and OCT preoperative left eye [LE]) and postoperatively showing resolution of papilledema (OCT postoperative RE and OCT postoperative LE). Phillips and Somner: J Neuro-Ophthalmol 2023; 43: e156-e158 e157 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence nately, we did not have access to the pathological tissue to investigate its transcriptome. There is little evidence in the literature to support this possibility, and we conclude that a mechanical effect is the most likely mechanism of reversible IIH/PTCS. There is no published association between fibroids and IIH/PTCS. This may be because our patient had a fibroid that was so unusually large it produced a mechanical increase in venous pressure, or fibroids are indeed important in the pathogenesis of IIH/PTCS, but their effect is masked because of concomitant obesity (which is a risk factor for both fibroids and obesity). Finally, it may be that the tumor in our patient was unusual in producing a systemic effect from a secreted hormone or growth factor, for example, although this seems to be the least likely possibility. In conclusion, our case demonstrates a possible causal link between large fibroid and IIH/PTCS, which may be relevant to the mechanism of IIH in obese subjects. STATEMENT OF AUTHORSHIP Conception and design: W. Phillips, J. Somner. Acquisition of data: Not applicable. Analysis and interpretation of data: Not applicable. Drafting the manuscript: W. Phillips. Revising the manuscript for intellectual content: W. Phillips, J. Somner. Final approval of the completed manuscript: W. Phillips, J. Somner. FIG. 2. Intraoperative photograph of fibroid removal (September 2019). REFERENCES been associated with increased incidence of fibroids, although this may be a predisposing factor, as opposed to pathological secretion by the fibroids. It is possible that fibroids secrete hormones or other substances that predispose to IIH/PTCS. Disordered metabolism has been proposed to cause or contribute to IIH (1), including leptin resistance, inflammation, disordered sex hormones, and dysfunctional adipose 11-beta-steroid dehydrogenase. Unfortu- e158 1. Hornby C, Mollan SP, Botfield H, OʼReilly MW, Sinclair AJ. Metabolic concepts in idiopathic intracranial hypertension and their potential for therapeutic intervention. J Neuroophthalmol. 2018;38:522–530. 2. Stewart EA, Laughlin-Tommaso SK, Catherino WH, Lalitkumar S, Gupta D, Vollenhoven B. Uterine fibroids. Nat Rev Dis Primers. 2016;2:16043. 3. Depauw PRAM, Groen RJM, Van Loon J, Peul WC, Malbrain MLNG, De Walle JJ. The significance of intraabdominal pressure in neurosurgery and neurological disease: a narrative review and a conceptual proposal. Acta Neurochir. 2018;161:855–864. Phillips and Somner: J Neuro-Ophthalmol 2023; 43: e156-e158 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.