What is causing this woman's migraine, polycythemia, and hypoxemia?

A 31-year-old Korean woman with migraine headaches during menstruation was found to have a hemoglobin level of 16 g/dL as part of routine blood work. This was confirmed by a repeated complete blood cell count. The patient was referred to a hematologist, who discovered her arterial oxygen saturation (SaO₂) on room air was 92% at rest and 81% after exercise. The patient was sent for a pulmonary consultation.

She denied dyspnea at rest or on exertion, as well as angina, dizziness, and syncopal episodes. She has smoked 5 cigarettes per day for 16 years and worked as a fashion designer. On physical examination, the patient's blood pressure was 116/80 mm Hg, pulse rate was 80 beats per minute, and SaO₂ on room air was 91%. Findings on heart and lung examinations were normal. There was no clubbing, edema, cyanosis, or skin lesions. The results of chest radiography and echocardiography were normal.

Blood gas analysis showed a PaO₂ of 52 mm Hg, PaCO₂ of 35 mm Hg, and SaO₂ of 88%. The patient's hemoglobin level was 16.8 g/dL. The rest of the blood count and basic metabolic panel findings were normal. The results of pulmonary function studies, including carbon monoxide- diffusing capacity, were normal. The patient's methemoglobin level was normal at 1.1%, but the carboxyhemoglobin level was mildly elevated at 6.5%, which was probably due to cigarette smoking. A hemoglobin electrophoresis did not reveal any abnormalities.

Another chest radiograph was obtained (Figure 1), followed by CT angiography (Figure 2).

What is the likely diagnosis?

Answer on next page.

What is causing this woman's migraine, polycythemia, and hypoxemia? The chest radiograph showed increased vascular markings on the right lung base. This suggested the possibility of pulmonary arteriovenous malformation (PAVM) in the right lower lobe. CT angiography revealed dilation and communication of the right lower lobe pulmonary arteries and veins, confirming the diagnosis of PAVM. Magnetic resonance angiography of the brain did not reveal any vascular anomalies.

These results were discussed with the patient, and she was advised to stop smoking. The patient agreed to undergo pulmonary angiography with embolotherapy. Complex PAVMs of the subdivisions of the right lower lobe artery were embolized with 11 coils of multiple sizes (Figure 3). The patient's SaO₂₂₂₂ improved from 90% to 98% by the end of the procedure. She tolerated the procedure well without complications. At 1- and 6-month follow-up, she reported complete resolution of migraine headaches.

Discussion

PAVM is an abnormal communication between a pulmonary artery and a pulmonary vein. These malformations are usually congenital; they are infrequently acquired in cases of hepatic cirrhosis, schistosomiasis, mitral stenosis, trauma, actinomycosis, and metastatic thyroid carcinoma.

Rendu, Osler, and later, Weber described telangiectases and arteriovenous malformations as features of hereditary hemorrhagic telangiectasia (HHT). Approximately 70% of PAVMs are associated with HHT, and 15% to 30% of patients with HHT have PAVM. The incidence is 1 in 40,000, and PAVMs occur twice as often in women as in men.¹

PAVMs can be classified as simple, with a single feeding artery leading to single draining vein, or as complex. Approximately 79% of PAVMs are of the simple type and occur in lower lobes.¹ The remaining 21% are complex, with 2 or more feeding arteries or draining veins, and usually occur in the lingula and right middle lobe.

The clinical presentation of PAVM ranges from asymptomatic to massive hemoptysis and death. The most common symptom is epistaxis, followed by dyspnea with or without platypnea, hemoptysis, and infrequently, neurological symptoms.

A higher prevalence of migraine headaches has been reported in HHT patients with PAVMs² as well as in patients with intracardiac shunts.³ A few unproven hypotheses and a possible genetic predisposition have been suggested. Emboli of septic debris, thrombi, and air bubbles have been described as mechanisms,^4,5 but these do not explain the higher incidence of migraines in women with PAVMs.⁵

The timing of migraines and their resolution after embolotherapy strongly suggest an association between shunting and menstruation. We put forth the following 2 hypotheses as an attempt to better understand this phenomenon. First, a decrease of hemoglobin during menstruation and subsequent decline in the oxygen-carrying capacity and SaO₂₂ may cause further hypoxemia and lead to migraine headaches.

Second, menstruation-related vasoactive substances, such as prostaglandins, can increase shunting of deoxygenated blood by vasodilating the pulmonary vasculature and by increasing their own distribution into the arterial circulation; this may cause cerebral vasodilation, inflammation, and pain receptor sensitization, leading to migraine headaches. It would have been useful to know the patient's hemoglobin level and SaO₂₂₂ during her menstrual cycles; this information might have helped further our understanding of this phenomenon and perhaps validated or ruled out our hypotheses.

Case and figures provided by Vasilos Sierros, MD, and Rammohan Gumpeni, MD, of Weill Medical College of Cornell University, New York, and New York Hospital of Queens, Flushing, New York.

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