Case Report
A case of postpartum reversible cerebral vasoconstriction syndrome due to excessive use of vasoconstrictive nasal spray
2024 Volume 12 Issue 3 Pages 64-68
Details
2024 Volume 12 Issue 3 Pages 64-68
Reversible cerebral vasoconstriction syndrome is characterized by sudden severe headaches, imaging evidence of vasoconstriction, and resolution of symptoms within three months. Reversible cerebral vasoconstriction syndrome is common in women of reproductive age and can be triggered by pregnancy, postpartum conditions, migraine, vasoactive drugs, and vascular injuries. In this case report, we describe a 32-year-old postpartum woman with a history of migraines and smoking who developed reversible cerebral vasoconstriction syndrome after excessive use of a self-administered over-the-counter nasal spray containing naphazoline hydrochloride. Onset of the patient’s headaches occurred after administration of the spray at a dose and frequency significantly exceeding the recommendations in the package insert. Chronic smoking and postpartum vascular changes likely contributed to her condition. Careful monitoring of vasoconstrictive medication use and vascular risk factors during the perinatal period is essential to prevent reversible cerebral vasoconstriction syndrome.
Reversible cerebral vasoconstriction syndrome (RCVS) is diagnosed based on the following main clinical features: thunderclap headache (a type of headache that has a sudden onset and reaches peak intensity in less than one minute) or severe recurrent headaches, imaging evidence of vasoconstriction in at least two arteries, and resolution of vasoconstriction within three months in the absence of primary central nervous system vasculitis or aneurysmal subarachnoid hemorrhage.1) RCVS is most common in women of reproductive age, with one study indicating that 7% to 9% of patients developed RCVS during the postpartum period within one month after childbirth.2) The causes of RCVS include not only pregnancy or the postpartum state, but also sexual intercourse, smoking, exercise, emotional stress, the Valsalva maneuver, a history of migraines, use of vasoactive medications, eclampsia, and direct vascular injury due to dissection or surgical procedures.1,2,3,4,5) In this report, we present a case of RCVS suspected to have been caused by the adverse effects of excessive nasal spray use.
The patient was a 32-year-old woman (gravida 2, para 1) with a history of paternal hypertension. At the age of 16 years, she had experienced syncope and vertigo, which led to outpatient consultation with a neurosurgeon. However, no significant abnormalities were identified on CT or MRI, and she was diagnosed with migraine. She subsequently experienced similar headaches on an intermittent basis, and oral analgesics effectively reduced the pain.
At the age of 26 years, the patient became pregnant for the first time by spontaneous conception and began antenatal care at our facility. Before her pregnancy, she had been a heavy smoker (≥20 cigarettes/day), but she ceased smoking early in pregnancy. Her pregnancy course was uneventful, and labor was induced with oxytocin at 40 weeks 3 days of gestation because her due date had been exceeded. This culminated in an uneventful vaginal delivery on the same day. The neonate was a male weighing 3,190 g; his Apgar scores were 8 at 1 minute and 9 at 5 minutes, and his umbilical artery blood gas pH was 7.287.
On postpartum day 25, after being discharged from the hospital and returning home, the patient presented with symptoms of rhinitis for which she had used a self-administered over-the-counter nasal spray (Sutto nose nasal spray α-plus; Okuda Seiyaku Co., Ltd., Osaka, Japan). Concurrently, she sought medical attention in the internal medicine department for headache, and her blood pressure was 155/80 mmHg on admission. Cranial CT demonstrated no intracranial hemorrhage or mass lesions, and sinusitis was ruled out. Symptomatic relief was achieved with intravenous acetaminophen, and sumatriptan nasal spray was prescribed for migraine prior to discharge. The following day (postpartum day 26), she re-presented with a throbbing headache from the vertex to the occiput; this was accompanied by nausea and neck stiffness, but she had no clinical evidence of hypertension or hypotension (blood pressure, 119/78 mmHg). A muscle tension headache was suspected, and she was treated with lornoxicam and eperisone hydrochloride. Inadequate headache resolution by postpartum day 30 prompted a subsequent outpatient visit, with a plan for cranial MRI with magnetic resonance angiography (MRA). On postpartum day 34, the routine one-month obstetric checkup revealed a blood pressure of 141/89 mmHg and lower limb edema with no significant obstetric findings. Concurrent MRI demonstrated the absence of intracranial mass lesions or ventricular asymmetry; however, MRA revealed multifocal cerebrovascular stenosis with post-stenotic dilatation exhibiting a “string of beads” appearance, suggesting RCVS (Figure 1). Therefore, the patient was referred to the neurosurgery department to undergo evaluation for suspected RCVS. On postpartum day 59, repeat MRA demonstrated resolution of the vasospasm, prompting conservative management (Figure 2).
Magnetic resonance angiography reveals multifocal angiostenosis and post-stenotic vasodilation characterized by a “string of beads” appearance.
The multiple vascular stenoses and dilatations that were observed during the onset of reversible cerebral vasoconstriction syndrome are no longer observed, and normal cerebral blood vessels are visualized.
The patient re-presented to our hospital for her second pregnancy at the age of 32 years. She reported that she had experienced frequent headaches since her last delivery. We also found that prior to the onset of headache, she had been using a nasal spray containing naphazoline hydrochloride at higher doses and more frequently than indicated in the package insert. Thus, she was advised to avoid using this nasal spray during her pregnancy. Her antenatal course was unremarkable, and planned labor induction with oxytocin at 38 weeks 1 day of gestation resulted in an uncomplicated vaginal delivery on the same day. The neonate was a male weighing 2,932 g; his Apgar scores were 8 at 1 minute and 9 at 5 minutes, and his umbilical artery blood gas pH was 7.338. The patient’s postpartum recovery progressed smoothly and uneventfully, and the headaches had not recurred at the time of the one-month checkup. She also reported no headaches thereafter.
The pregnancy and puerperium periods are recognized triggering factors for RCVS, and many cases have been reported to occur during the postpartum period.6) Eclampsia and posterior reversible encephalopathy syndrome are caused by cerebrovascular abnormalities that develop during the perinatal period, and they share similarities with RCVS. Vasoconstriction is thought to be one of the mechanisms underlying the development of these three syndromes. In RCVS, vasoconstriction leads to headaches, whereas eclampsia is characterized by generalized convulsions during pregnancy that are not attributable to epilepsy or other convulsive disorders. The acute neurologic manifestations of the vasospasm that occurs in eclampsia are thought to cause local anoxic damage to the capillary endothelium, leading to convulsions. Disruption of the blood–brain barrier causes reversible subcortical angiogenic brain edema (i.e., posterior reversible encephalopathy syndrome). These three syndromes are considered differential diagnoses, and a case of all three occurring simultaneously in the same patient has been reported.7) Among these differential diagnoses, the use of vasoconstrictors poses a risk of triggering RCVS.1,2,3,4,5) The present case involved a patient with a history of migraine and smoking who developed RCVS in the postpartum period triggered by excessive use of nasal spray.
The patient’s use of nasal spray was discovered during an interview in her second pregnancy. On the day her headache began, the patient had been using the nasal spray for allergic nasal symptoms at a dosage of three sprays in each nostril over a three-hour period, more than once per hour and each time she blew her nose. According to the medical package insert, one to two sprays should be administered up to six times per day at intervals of at least three hours. In this case, the patient exceeded the maximum daily dose within a short time frame. The ingredients of the nasal spray included naphazoline hydrochloride as a vasoconstrictor, chlorpheniramine maleate as an antihistamine, lidocaine as a local anesthetic, benzethonium chloride as a sterilization agent, and dipotassium glycyrrhizinate as an anti-inflammatory agent. Among these ingredients, naphazoline hydrochloride was considered the likely causative agent of the headaches. Naphazoline hydrochloride is commonly used as a vasoconstrictor for nasal and ocular blood vessels.8) The nasal spray contains 50 mg naphazoline hydrochloride per 100 ml. Each push of the nasal spray delivers approximately 0.1 ml (0.05 mg) of naphazoline hydrochloride. Assuming that the patient used the device approximately three times per hour, this amounts to a total of 54 sprays over a three-hour period, which is more than two times the maximum daily dose recommended in the package insert. We calculated that approximately 2.7 mg naphazoline hydrochloride may have been used at the time of onset; therefore, more vasoconstriction than necessary likely occurred. However, the dose at which RCVS occurs and whether the onset is dose-dependent remain unclear.
Smoking-induced narrowing of brain vessels may also serve as a trigger for RCVS development. The patient in this case continued smoking at a rate of ≥20 cigarettes per day until early pregnancy, potentially leading to chronic narrowing of brain vessels. Vascular narrowing is associated with risk factors such as smoking, hyperlipidemia, and prolonged hypertension, all of which contribute to atherosclerosis. Particularly in young patients with headaches who have underlying risk factors for atherosclerosis, there is a risk of developing RCVS if vasoconstrictive drugs are used without imaging confirmation.9)
The headaches in the present case were likely triggered by multiple factors including excessive use of nasal spray containing vasoconstrictors, the postpartum state, vascular narrowing due to smoking, and a history of migraine. The widespread use of over-the-counter medication has made it easy for the general public to obtain medications; however, some people use them without referring to the package inserts, which may lead to the occurrence of unexpected side effects. Clinicians must remain vigilant for RCVS risk factors, especially during pregnancy and the postpartum period, to ensure that triggering factors are assessed and not overlooked at the onset of headaches.
We thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
The authors have no conflicts to disclose.
