A 40-year-old woman with a history of migraine with aura dating back 6 years has been treated for the last 4 years at the Chulalongkorn Comprehensive Headache Center, King Chulalongkorn Memorial Hospital, a tertiary care hospital in Bangkok, Thailand. Her visual aura involves blurring of the whole visual field for 5 min during the headache phase. She also reported rare difficulties in understanding people who were talking to her for about 1 min during the headache phase. She had comorbid allergic rhinitis and took cetirizine 10 mg/day but did not take any stimulant medications. Her migraine attacks were initially present at most two times per month, with symptoms lasting from 1 to 2 days. Her headache characteristics were non-throbbing pain with a unilateral location that side shifts in the periorbital, forehead, temporal, occipital, and neck regions, accompanied by nausea, photophobia, phonophobia, dizziness, and osmophobia and exacerbated by strong smells and hot weather.

Three years ago, she took propranolol 80 mg/day, topiramate 50 mg/day, and nortriptyline 10 mg/day for migraine prevention but stopped taking nortriptyline because of constipation. After the cessation of nortriptyline treatment, the frequency of migraine attacks increased to 5–7 days per month. The dose of topiramate was increased to 75 mg/day and then 100 mg/day. She responded to topiramate 100 mg/day and propranolol 80 mg/day with 3 headache days per month. For acute treatment, she took acetaminophen 500 mg, etoricoxib 60 mg, or naproxen sodium 250 mg plus eletriptan 40 mg. She never had any side effects from these medications.

Two years ago, she stopped all migraine prevention as her headaches were well controlled. One month after discontinuation of the migraine prevention, she developed near daily headaches. Topiramate 100 mg/day for migraine prevention was restarted, and her headache frequency improved.

One year ago, she developed chronic migraine with headache on > 15 days a month associated with medication overuse of eletriptan 40 mg, which was taken an average of 10–15 days per month, and did not respond to topiramate 100 mg/days. Amitriptyline 10 mg/day for migraine prevention was combined, but her headache frequency did not respond. As a result, the treatment plan was to combine anti-CGRP monoclonal antibodies with her oral migraine prevention. Two months before her loading dose of anti-CGRP monoclonal antibodies, her monthly migraine days were nine headache days per month, and 1 month before her loading dose her headache frequency was seven headache days a month. In her logbook headache diary, in the last 28 days before the loading dose, she had headache days on 28, 27, 22, 11, 10, 9, and 1 day before the injection. She took acetaminophen 500 mg plus eletriptan 40 mg once a day only on days 28, 27, and 22 before the injection, and the last day of taking acetaminophen 500 mg plus eletriptan 40 mg was 22 days before the injection. On the four recent headache days before the injection, she did not take any analgesics or triptans as her headache severity was mild. Her Thai version of the Migraine Disability Scale (MIDAS) score and the Migraine Specific Quality of Life Questionnaire version 2.1 (MSQ 2.1) score were 23 days and 67.2, respectively. She was a candidate for anti-CGRP monoclonal antibodies, according to the Thai guidelines [4], with no response to oral migraine prevention in at least two out of four classes of preventive medications and monthly migraine days of 4–7 days with severe disability (MIDAS score at least 21 days). On the evening before the planned loading dose of galcanezumab, she had a headache with very mild pain severity and did not take any medications.

On the day of the injection, her blood pressure, pulse rate, and body mass index were 119/66 mmHg, 90 bpm, and 20.3 kg/m2, respectively. She received a loading dose of galcanezumab, 120 mg × 2, which was injected subcutaneously in both deltoid regions. Ten minutes later, she developed numbness in her right buttock, spreading to the right knee, lateral aspect of the right thigh, right shoulder, lateral aspect of the right arm, right side of the tongue, and right side of the cheek. Twenty minutes later, the numbness spread to her right foot. Neurological examinations revealed normal findings including pinprick sensation, motor functions, and deep tendon reflexes. Thirty minutes later, her numbness slightly improved but did not resolve. She did not experience any headaches during the numbness. She was discharged and subsequently observed at home. On the day of the injection, she neither had a headache nor took any analgesics. The next day, she developed transient bilateral non-pulsatile tinnitus in the morning, and it resolved in the evening. The tinnitus occurred every day. The second day after the injection, she developed a headache and took one tablet of eletriptan 40 mg. Her numbness resolved over 2 days, and bilateral non-pulsatile tinnitus resolved over 2 weeks. Magnetic resonance angiography (MRA) brain imaging was performed 24 days after the loading dose and revealed segmental arterial constriction of both middle cerebral arteries (MCA) in the M1–2 segments and both posterior cerebral arteries (PCA) in the P1–2 segments (Fig. 1A,B). She had not had any triptans just prior to this. Four weeks after the injection, she visited the clinic with a scheduled follow-up and reported migraine days for 2 days, the 2nd and 15th days after the injection. She took one tablet of eletriptan 40 mg for each headache.

Magnetic resonance angiography (MRA) brain imaging performed 24 days after the injection of galcanezumab (A, B) revealed segmental arterial constriction of M1–2 segments of bilateral middle cerebral arteries (MCAs) and P1-2 segments of bilateral posterior cerebral arteries (PCAs), which suggested cerebral vasoconstriction (A, B, arrows). The sequential MRA brain imaging performed about 1 month after the injection (C, D) revealed complete resolution of the vasoconstriction of M1 segments of bilateral MCAs and P1–2 segments of bilateral PCAs (C) with remaining mild narrowing at the proximal M2 segment of the right MCA (D, arrowhead)

The day the MRA brain imaging was done was 9 days after the last dose of eletriptan treatment. Neurological findings were normal. She was diagnosed with possible RCVS related to galcanezumab and was advised to discontinue galcanezumab injections and not to take triptans. One month after the injection, sequential MRA brain imaging revealed an improvement in the previously observed vasoconstriction of the M1–2 segments of both MCAs and the P1–2 segments of both PCAs, remaining as mild narrowing at the proximal M2 segment of the right MCA (Fig. 1C,D). Three months after the injection, MRA brain imaging revealed an improvement in the previously observed mild narrowing at the proximal M2 segment of the right MCA (Fig. 2A). Six months after the injection, MRA brain imaging revealed further improvement of the mild stenosis at the proximal M2 segment of the right MCA (Fig. 2B) but was still not back to normal. She did not receive any specific medications for RCVS.

Magnetic resonance angiography (MRA) brain imaging performed 3 months after the injection of galcanezumab (A) revealed an improvement in the previously observed mild narrowing at the proximal M2 segment of the right middle cerebral artery (MCA) (arrows). MRA brain imaging performed 6 months later (B) revealed further improvement of the mild stenosis at the proximal M2 segment of the right MCA (arrowhead)