{"paper_id":"e0d10381-d88b-472e-9d1c-033695971099","body_text":"Review began\n 10/05/2021 \nReview ended\n 11/14/2021 \nPublished\n 11/16/2021\n© Copyright \n2021\nFrankel et al. This is an open access article\ndistributed under the terms of the Creative\nCommons Attribution License CC-BY 4.0.,\nwhich permits unrestricted use, distribution,\nand reproduction in any medium, provided\nthe original author and source are credited.\nDOI:\n 10.7759/cureus.19621\nStatus Migrainosus and Endometriosis: A Case\nReport and Review of the Literature\nLexi R. Frankel \n, \nRichard \nMedina \n, \nMichael Ashley \n, \nJose L. Batista \n, \nLivasky Concepion \n1.\n College of Allopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine,\nDavie, USA \n2.\n Internal Medicine, Aventura Hospital and Medical Center, Aventura, USA \n3.\n Medicine, Aventura Hospital\nand Medical Center, Aventura, USA \n4.\n Graduate Medical Education (GME), Aventura Hospital and Medical Center,\nAventura, USA\nCorresponding author: \nLexi R. Frankel, \nlf970@mynsu.nova.edu\nAbstract\nStatus migrainosus is a migraine complication describing an attack lasting longer than 72 hours. In this\npaper, we present a case of a 34-year-old female with a history of severe endometriosis and hypercoagulable\nfactor type II disease who presented to the emergency department (ED) with a three-week history of new-\nonset intractable migraine with aura. Imaging findings revealed a frontal T2/FLAIR hyperintensity, venous\nanomaly, and bilateral optic nerve thickening. The patient was admitted for three days of inpatient\ntreatment with improvement of her symptoms.\nCategories:\n Neurology, Obstetrics/Gynecology, Internal Medicine\nKeywords:\n endometriosis, factor ii mutation, migraine, migraine with aura, status migrainosus\nIntroduction\nMigraine is a highly debilitating disorder, affecting up to 12% of the population annually. Status\nmigrainosus, or intractable migraine, is a complication of migraine describing an attack lasting longer than\n72 hours \n[1]\n. There is a strong genetic component to migraine, and its incidence is further increased among\nwomen and patients with endometriosis and hypercoagulable disorders \n[2,3]\n. The diagnosis of migraine has\nbeen linked to increased risk of stroke, multiple sclerosis, cardiovascular disorders, and psychiatric disorders\n[4-6]\n.\nMigraine with aura is described as migraine headache with reversible transient focal neurological symptoms\ndeveloping from the cortex or brainstem. While the vast majority of auras are visual, symptoms may also\ninclude sensory, motor, retinal, brainstem, or speech disturbances. Migraine with aura is associated with a\ntwofold increase in ischemic stroke risk when compared with migraine without aura \n[7]\n. As the presentation\nof migraine with aura is often nonspecific and mimics other disorders, its diagnosis and workup are\ncomplicated. In the presence of other comorbidities, the diagnosis of complex migraine becomes challenging\nand often requires imaging to rule out cerebral-vascular accidents and other pathologies associated with\nsignificant morbidity and mortality.\nCase Presentation\nIn this case, we present a 34-year-old female with a past medical history of endometriosis, factor II\nhypercoagulable disorder, and menstrual migraine without aura who presented with three weeks of\nintractable migraine with neurological features. She described a bilateral squeezing frontal headache that\nremained at a “7/10” pain severity for three weeks prior to arrival. One week before she presented, she began\nexperiencing visual disturbances consistent with a scintillating scotoma that lasted for about two to three\nhours every day. A few days later, she began experiencing tongue numbness and left face paresthesia that\nmigrated to various locations of her face followed by her left flank (Figure \n1\n). The next day, she was\nevaluated by a neurologist via a telehealth visit and was subsequently diagnosed with intractable complex\nmigraine with aura and prescribed methylprednisolone and ubrogepant (calcitonin gene-related peptide\nreceptor antagonist) 100 mg as a rescue treatment. However, the following morning, she woke up with\nanomic dysphasia and another episode of tongue numbness, after which she presented to the emergency\ndepartment (ED) for evaluation. She did not take her prescribed medications from her telehealth visit,\nincluding ubrogepant and methylprednisolone, prior to arrival. In the ED, she endorsed a headache,\nnausea, dizziness on standing, photophobia, and resolution of her paresthesias. Physical examination was\ngrossly intact with preservation of motor strength, sensation, and cranial nerves. On analysis of complete\nblood count (CBC) and comprehensive metabolic panel (CMP), a decreased hemoglobin of 10.6 g/dL with a\nmean corpuscular volume of 73.6 fl consistent with microcytic anemia was the only abnormal finding. This\nfinding was consistent with this patient’s history of iron deficiency anemia secondary to heavy menstrual\nbleeding. Head computed tomography angiography (CTA) revealed mild thickening of the bilateral optic\nnerves (Figure \n2\n). Brain magnetic resonance imaging (MRI) demonstrated a nonspecific 1 cm right frontal\nsubcortical bright T2/FLAIR hyperintensity (Figure \n3\n) and a small adjacent developmental venous anomaly\nwithout evidence of thrombosis (Figure \n4\n). Although unlikely, early thrombosis could not be ruled out.\n1\n2\n3\n2\n4\n \nOpen Access Case Report\nHow to cite this article\nFrankel L R, Medina R, Ashley M, et al. (November 16, 2021) Status Migrainosus and Endometriosis: A Case Report and Review of the Literature.\nCureus 13(11): e19621. \nDOI 10.7759/cureus.19621\n\nSubsequent chest X-ray, neck CTA, head MRA, neck MRA, and orbit MRI were obtained, all of which were\nunremarkable.\nFIGURE\n 1: Visual depiction of the patient’s migrating sensory aura\n(black stars) from the tongue (1) to the left side of the face (2) to the left\nflank (3).\n \n2021 Frankel et al. Cureus 13(11): e19621. DOI 10.7759/cureus.19621\n2\n of \n7\n\nFIGURE\n 2: Brain CT revealing mild thickening of the bilateral optic\nnerves (black arrows).\n \n2021 Frankel et al. Cureus 13(11): e19621. DOI 10.7759/cureus.19621\n3\n of \n7\n\nFIGURE\n 3: Brain MRI demonstrating a 1 cm right frontal subcortical\nbright T2/FLAIR hyperintensity without evidence of abnormal\nenhancement (black arrow).\n \n2021 Frankel et al. Cureus 13(11): e19621. DOI 10.7759/cureus.19621\n4\n of \n7\n\nFIGURE\n 4: Brain MRI demonstrating a small adjacent developmental\nvenous anomaly (black arrow) adjacent to the right frontal subcortical\nbright T2/FLAIR hyperintensity.\nAfter several hours, her headache did not improve, and she was admitted to the floor for further\nmanagement. The patient was treated with butalbital/acetaminophen/caffeine 50 mg/325 mg/40 mg once,\nketorolac 15 mg IV once, dexamethasone 6 mg PO once, and metoclopramide 10 mg IV once. Neurology was\nconsulted. The following morning, the patient refused the prescribed medications for fear of triggering\nincreased pain or another neurological disturbance. She was counseled on the importance of compliance and\ntook her prescribed medications as directed. Neurology began a three-day course of methylprednisolone 1 g\ndaily, topiramate 25 mg three times a day, and naproxen 500 mg twice a day. The condition of the patient\nimproved, and she was discharged with significant improvement of her symptoms. She was instructed to\ncontinue taking topiramate 25 mg three times daily, naproxen 500 mg two times daily as needed, and\nubrogepant 100 mg as needed for migraine rescue treatment.\nDiscussion\nTo our knowledge, this is the first case report of a patient with worsening endometriosis presenting with\nnew-onset migraine with aura. The patient presented in this report had a 10-year history of stage IV\nendometriosis, requiring five endometriotic implant ablation surgeries and two endometrioma resections.\nThis patient had a pelvic MRI in 2019 that showed growth of uterine and ovarian lesions compared with a\nprevious MRI. A gynecological examination by her OB/GYN in 2019 also demonstrated growth of ovarian and\nvaginal implants. At this time, two years prior to admission, the patient’s OB/GYN recommended surgery for\nher growing lesions, which she deferred for fear of being in the hospital during the COVID-19 pandemic.\nAdditionally, this patient’s history of type II hypercoagulable disease prevented her from taking oral\ncontraceptive pills (OCPs) to control endometriosis symptoms and growth. The incidence of migraine has\nbeen previously associated with endometriosis \n[8,9]\n. The use of estrogen-containing OCPs in patients\nsuffering from migraine with aura is contraindicated due to the risk of increased vasodilation, migraine\nfrequency, and stroke \n[10]\n. As a result, this patient was unable to take OCPs for endometriosis. While GnRHa\nare an option for patients with severe endometriosis, this patient had already been treated three years prior\nwith a GnRHa for six months. She deferred further GnRHa therapy as a result of side effects. This patient’s\nworsening endometriosis over the past two years combined with her deferral of surgery and GnRHa therapy\nand inability to take OCPs likely contributed to her late-onset development of complex migraine. New-onset\ncomplex migraine in a woman of childbearing age may warrant further investigation into whether the\npatient has undiagnosed or worsening endometriosis.\nHypercoagulable diseases and states have also been implicated in the development of migraine \n[3]\n. The most\ncurrently accepted theory of the link between migraine and hypercoagulability is that ischemia caused by\n \n2021 Frankel et al. Cureus 13(11): e19621. DOI 10.7759/cureus.19621\n5\n of \n7\n\nmicroemboli leads to cortical spreading depression in migraineurs, often seen as a migrating aura \n[3]\n. In this\npatient, cortical spreading depression may have been responsible for the migration of her aura from her\ntongue to several areas of her face and to her flank. The patient in this report suffered from hypercoagulable\nfactor II disease, further supporting the microembolic pathophysiology of her disease progression. As the\nlink between clotting and migraines has become more clear in recent years, some studies have even\nquestioned screening all women suffering from migraine with aura for biological thrombophilia \n[11]\n.\nImaging patients undergoing migraine is another diagnostic challenge. The findings on brain MRI may\ninclude T2/FLAIR hyperintensities, representing microemboli \n[12]\n. However, as this finding is nonspecific\nand it may correlate with inflammatory processes such as infection or multiple sclerosis, further monitoring\nand clinical correlation are warranted. The nonspecific 1 cm right frontal subcortical bright T2/FLAIR\nhyperintensity on this patient’s MRI likely signified microembolic changes secondary to years of menstrual\nmigraine. Although this finding was not redemonstrated on orbit or brain MRI, this patient’s head CTA\ndemonstrated bilateral mild thickening of the optic nerves. In the setting of this patient’s baseline\nhypercoagulable state, this thickening may be the result of prolonged ischemia, swelling, or thickening of\nthe optic nerves, which has been correlated with migraine with visual aura \n[13]\n. This imaging finding may\nexplain this patient’s scintillating scotoma. This patient’s MRI also demonstrated a small venous anomaly\n(Figure \n4\n). Previous studies have noted a possible correlation between such venous anomalies and migraine;\nhowever, the majority of these studies are based on case reports and retrospective data \n[14]\n. This venous\nanomaly was also an important source of migraine to consider in this patient that further complicated the\netiology of her disease.\nThis patient’s initial refusal to take her medications as directed is not an uncommon phenomenon among\nmigraineurs. In fact, one study noted the increased prevalence of cephalalgiaphobia, the fear of headache\nattack or headache worsening, in patients suffering from migraine \n[15]\n. As a result of fear of migraine\nattacks, patients often take prophylactic medication without necessity or develop food or medication\naversion. Our case highlights the prevalence of cephalalgiaphobia in patients with migraine and recognizes\nthe necessity of early recognition of this phenomenon for early treatment of migraine attacks in the acute\nsetting. Another barrier that may have prevented proper care in this patient was the telehealth approach of\nher neurology appointment prior to presentation. This type of visit may have prevented a full physical\nexamination, which could have precluded proper treatment.\nThe limitations of this case report are important factors to consider. Importantly, this report represents the\nfindings of a single patient and therefore may not be widely applicable. While this patient presented with\nnew-onset migraine with aura in the setting of worsening endometriosis, causation cannot be assumed from\nthis one report. For this reason, we suggest that further studies be conducted on a larger scale to assess the\ncorrelation between these variables.\nConclusions\nWhile endometriosis and chronic migraine have been linked previously in the literature, this is the first case\nreport to discuss worsening endometriosis in a patient with new-onset status migrainosus. Status\nmigrainosus and migraine with aura, especially in the setting of a history of hypercoagulable disease and\nendometriosis, is a diagnostic challenge requiring extensive workup and imaging. For women with status\nmigrainosus, we suggest an investigation into gynecological history to assess for history or symptoms of\nendometriosis. Further research on the association between new-onset migraine with aura and\nendometriosis is suggested to prevent and treat this debilitating condition.\nAdditional Information\nDisclosures\nHuman subjects:\n Informed consent for treatment and open access publication was obtained or waived by all\nparticipants in this study. \nConflicts of interest:\n In compliance with the ICMJE uniform disclosure form, all\nauthors declare the following: \nPayment/services info:\n All authors have declared that no financial support\nwas received from any organization for the submitted work. \nFinancial relationships:\n All authors have\ndeclared that they have no financial relationships at present or within the previous three years with any\norganizations that might have an interest in the submitted work. \nOther relationships:\n All authors have\ndeclared that there are no other relationships or activities that could appear to have influenced the\nsubmitted work.\nReferences\n1\n. \nVécsei L, Szok D, Nyári A, Tajti J: \nTreating status migrainosus in the emergency setting: what is the best\nstrategy?\n. 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