Idiopathic Intracranial Hypertension (IIH) in Pregnancy
Idiopathic intracranial hypertension (IIH) in pregnancy
Heinrich Quincke in 1893 described the first case of elevated intracranial pressure (ICP) and called it “meningitis serosa.” In 1904 Nonne termed this “pseudo-tumor cerebri.” The term “benign intracranial hypertension” was then coined by Foley in 1955 but subsequently the more descriptive name “idiopathic intracranial hypertension” (IIH) has gained acceptance because of the often non-benign and sometimes significant vision loss that can occur.
IIH is a disease characterized by elevated ICP and its associated signs and symptoms in an otherwise alert and awake patient, with no apparent cause. It is seen predominantly in overweight women of childbearing age. It is a diagnosis of exclusion and defined by diagnostic clinical, lumbar puncture, and radiographic criteria. Patients with IIH in pregnancy typically have the same evaluation, course, and treatment as non-pregnant patients with IIH but with some exceptions described below. Patients with IIH in pregnancy have the same spontaneous abortion rate as the general population and it is not generally considered to be a high risk pregnancy. Additionally, visual outcomes for IIH in pregnancy are believed to be the same as for non-pregnant IIH patients.
Incidence and prevalence
The majority of IIH patients are child bearing aged females, with a female to male ratio of 8:1. Thus, it is not surprising that IIH often occurs in pregnancy. The incidence of IIH in women of childbearing age is 0.9/ 100,000. The incidence in obese women increases to 19.3/100,000. 61% of cases of IIH occur in the first trimester, although it can occur in any trimester.
There have been several case reports and review articles suggesting pregnancy as a risk factor for IIH. However, IIH in pregnancy occurs at the same rate as the general population, therefore, pregnancy is not considered an etiologic factor and might be better explained by the weight gain that occurs normally in pregnancy and that IIH occurs predominantly in women of childbearing age. 
The pathophysiology of IIH with or without pregnancy is still not fully known. Some theories include increased cerebrospinal (CSF) production, decreased CSF drainage, and increased cerebral venous sinus pressure as the leading cause. Hormones may potentially play a role in the pathophysiology of IIH, however this has not been adequately studied. 
It is important to calculate body mass index (BMI) as obesity is a risk factor for IIH. It is also important to measure blood pressure to help rule out hypertensive emergency or eclampsia/pre-eclampsia. A full eye exam including dilated fundus exam is recommended to detect papilledema. Formal visual field testing is also recommended to assess baseline and follow patients for the development of vision loss which is the most feared complication of IIH.
Signs and symptoms
The clinical manifestations of IIH in pregnancy are similar to the signs and symptoms in the non-pregnant population. Headache is the most common presenting symptom usually described as a daily, throbbing, positional headache with nausea and with or without vomiting. Other symptoms such as pulsatile tinnitus, dizziness, neck pain, back pain, and radicular pain may also be present. Visual symptoms include transient visual obscurations, diplopia, and visual loss. Visual loss is the most serious and feared outcome of IIH in both the general population and pregnancy.
Headache in pregnancy is a particularly important symptom to pay attention to as it may be a sign of a serious and life- threatening diseases such as eclampsia, meningitis, or cerebral venous thrombosis. These diseases may present similarly to IIH with headache, nausea and vomiting, neck stiffness, or visual disturbances and therefore need a proper workup.
The diagnosis of IIH in pregnancy (as well as in non-pregnant patients) is made by using the modified Dandy Criteria: (1) increased ICP and associated symptoms, (2) without localizing neurological findings, (3) patient is alert and oriented, (4) normal neurodiagnostic studies except for increased CSF pressure and (5) no other cause of increased ICP .
IIH is a diagnosis of exclusion, therefore when doing a proper workup for suspected IIH, an ophthalmologist should make efforts to exclude other more serious causes of increased ICP. Questions concerning past history of headache, associated symptoms, history of drug use during or before pregnancy, past psychiatric history, and a thorough review of symptoms are necessary.
Magnetic resonance imaging (MRI) and MR venography (MRV) of the brain with and without contrast are the neuroimaging procedure of choice in IIH but gadolinium is not recommended in pregnancy. There is no data to demonstrate any adverse effects of MRI in pregnancy, but there are also few studies to prove it is safe. This risk needs to be communicated with the patient.  The current recommendation is to defer contrast agents in pregnancy as it has been shown experimentally to cause developmental delay without congenital anomalies when given in 2.5 times the human dose to rats and 7.5 times the human dose to rabbits.
A diagnostic lumbar puncture measuring the opening CSF pressures has no contraindications in pregnancy and may be done safely to aid in the diagnosis of IIH.
Computed tomography (CT) could have deleterious effects on the fetus due to ionizing radiation and therefore is not the first choice when evaluating a possible IIH. In addition, CT is not as sensitive or specific as MRI and MRV in diagnosing intracranial tumors, meningeal disease, and cerebral venous and dural sinus thromboses. 
There are no laboratory tests used in the diagnosis of IIH in pregnancy. It may be important, however, for obstetrics to check the blood pressure as well as routine monitoring of urine protein, complete blood counts (CBC), serum creatinine, and liver function testing (LFT).
- Cerebral venous and dural sinus thrombosis
- Pre-eclampsia with or without severe features
- Intracranial space occupying lesion
- Hypertensive emergency
Diet and weight control. A low fat diet and pregnancy appropriate weight gain are recommended for pregnant patients. Weight gain is physiologically normal in pregnancy, but too much weight gain can be detrimental. There is little literature that defines a “healthy” amount of weight gain in pregnant patients with IIH. Friedman recommended controlling weight gain during pregnancy to no more than 20 pounds.
Analgesics: The use of simple nonsteroidal anti-inflammatory drugs (NSAIDs) are generally safe during pregnancy with the exception of the third trimester due to the risk of premature closure of the fetal ductus arteriosus and oligohydramnios. Opioids are not typically used to treat the headaches in IIH due to risk of fetal dependence and withdrawal symptoms.
Diuretics: Acetazolamide is the most common diuretic used to treat IIH. It is a carbonic anhydrase inhibitor that reportedly decreases CSF production. It is a Food and Drug Administration (FDA) category C drug. The FDA categorizes class C fetal risk factor as: “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.” There are no well controlled studies detailing the effects of acetazolamide in pregnant women or fetuses. Animal studies in rodents has shown a possible relation to limb abnormalities but these have not been reproducible in primates or observed in humans. There has been a single report by Worsham and colleagues in 1978, of sacrococcygeal teratoma, in an infant born to a mother treated with acetazolamide throughout her pregnancy. Because of this, the use of acetazolamide in pregnancy is often limited to after 20 weeks of gestation after consultation with obstetrics.
Steroids: Corticosteroids are considered a category B in terms of fetal risk factor. The FDA describes a class B as: “Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.” Because of the adverse effects of corticosteroids, they are generally reserved for acute settings of IIH in pregnancy.
Serial Lumbar Punctures
Serial lumbar punctures performed 10 days to 2 weeks apart, can help improve headaches. The limiting factor in many is the technical difficulty of performing a lumbar puncture in a pregnant woman, especially if obese. Additionally, serial lumbar punctures are not well received by many patients. Serial lumbar punctures may however be an option in the pregnant patient who fails or refuses medical therapy and wishes to delay or avoid surgery. 
Optic nerve sheath fenestration (ONSF) is a procedure that involves making a small window in the optic nerve sheath to release CSF. It is considered safer than other surgical options in IIH but has yet to be extensively studied in pregnancy. ONSF is typically reserved for patients with moderate to severe or progressive visual loss in a patient who has failed or is unable to receive medical therapy. It is considered by most experts to be safe in pregnancy. 
CSF diversion procedures (e.g. lumboperitoneal shunt (LPS) and ventriculoperitoneal shunt (VP)), create a connection from the CSF to the peritoneal abdominal cavity to relieve elevated ICP and therefore treat headaches or visual problems. There are limited data to support the safety and effectiveness of CSF diversion procedures in pregnancy, however, the data that is available suggests LPS are not contraindicated in pregnancy and can be safe for both mother and fetus. 
Modes of Delivery
IIH in pregnancy is not a specific indication for a cesarean delivery and active labor is not contraindicated. Active labor does not place the pregnant woman at an increased risk for vision loss. During delivery no special analgesic requirements are necessary except for epidural anesthesia in patients with a LPS, as the anesthesia may move into the peritoneum and not be as effective. The increased ICP during labor is not harmful to the mother or the baby because it is transient.
The prognosis for pregnant women with IIH is excellent for both mother and child. Visual outcomes in women with IIH in pregnancy are the same as non-pregnant women. There is no greater risk of recurrence of IIH for subsequent pregnancies when compared to the general population. The spontaneous abortion rate for women with IIH in pregnancy is the same as women without IIH in pregnancy.  Therefore, IIH is generally not an indication for medical termination of pregnancy.
- Thirumalaikumar, L, Ramalingam, K, Heafield, T. Idiopathic intracranial hypertension in pregnancy. The Obstetrician & Gynaecologist 2014; 16: 93– 97.
- Tang RA. Management of idiopathic intracranial hypertension in pregnancy. MedGenMed. 2005;7(4):40. Published 2005 Nov 10.
- Digre KB, Varner MW, Corbett JJ: Pseudotumor cerebri and pregnancy. Neurology 1984, 34:721–729.
- Huna-Baron, R. & Kupersmith, M. J Neurol (2002) 249: 1078. https://doi.org/10.1007/s00415-002-0791-4
- Kesler A, Kupferminc M. Idiopathic intracranial hypertension and pregnancy. Clin Obstet Gynecol. 2013;56(2):389–96.
- AG. Lee, Andrew & Sinclair, Alexandra & Sadaka, Ama & Berry, Shauna & Mollan, Susan. (2019). Neuro-Ophthalmology Global Trends in Diagnosis, Treatment and Management: Global Trends in Diagnosis, Treatment and Management. 10.1007/978-3-319-98455-1.
- Smith JL. Whence pseudotumor cerebri? J Clin Neuroophthalmol. 1985;5:55–6.
- Chung SM: Safety issues in magnetic resonance imaging. J Neuro-ophthalmol 2002, 22:35–39.
- Evans RW, Friedman DI. Expert opinion: the management of pseudotumor cerebri during pregnancy. Headache 2000;40:495–7.
- Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling. Federal Register/Vol. 73, No. 104/Thursday, May 29, 2008.
- Satti SR, Leishangthem L, Spiotta A, Chaudry MI. Dural venous sinus stenting for medically and surgically refractory idiopathic intracranial hypertension. Interv Neuroradiol. 2017;23(2):186–193. doi:10.1177/1591019916680110
- Landwehr JB, Isada NB, Pryde PG, et al.: Maternal neurosurgical shunts and pregnancy outcome. Obstet Gynecol 1994, 83:134–137.