Nicorandil induced ophthalmoplegic migraine

A previously healthy 45-year-old male patient seen in the Chest Pain Clinic giving a classical history for angina having developed exertional central chest/left arm discomfort while training for a marathon. He had a past history of infrequent migraines but nil else of note. He had a family history of ischaemic heart disease in first degree relatives and was an ex-smoker, he was just on aspirin. Physical examination showed no clinical abnormality, with a BMI of 24, BP was 135/ 60 mmHg and HR 58 bpm. Resting ECG showed sinus rhythm and an exercise stress test was stopped prematurely because of ST depression in anterior leads, achieving Bruce protocol of 10.4 mets before experiencing exertional chest pain. A diagnosis of exertional angina was made and an outpatient coronary angiogram was requested. Given his good history of angina, he was prescribed simvastatin 40 mg nocte (with initial pretreatment total cholesterol of 4.7 mmol/L and LDL 3.0 mmol/L) and nicorandil 10 mg twice daily, which he started 4 days later. The patient developed a headache immediately on starting nicorandil, which at times was extremely severe, having some ‘thunderclap’ elements. This resulted in him being admitted 6 days after starting his nicorandil. The headache was bilateral in nature, no preceding aura or flashing lights and no abdominal symptoms, however he did have double vision for 2 days preceding the admission. Clinical examination showed a total left 6th nerve palsy and no other abnormal findings (Figures 1, 2 and 3). Blood pressure on admission was 138/ 70 mmHg. Investigations for his headache showed a normal CT head, MRI brain and MRA head/neck (including post-gadolinium). Lumbar puncture was performed to exclude a subarrachnoid haemorrhage, opening pressure was 9 cm H2O and there was no xathochromia. An autoimmune profile to exclude vasculitidies was also normal (Rheumatoid factor negative, ANA negative and ANCA negative). Clinical review by consultant ophthalmologists and neurologists confirmed a severe isolated sixth nerve palsy (Figure 1). His nicorandil was stopped whilst he was an inpatient, simvastatin was continued as it was not felt to be causal in his symptoms. The sixth nerve palsy fully resolved within 6 weeks with no further ophthalmoplegic symptoms and the patient has had no further headache. He went on to have a successful coronary angioplasty for a very tight stenosis to his proximal LAD and was commenced on dual anti-platelet therapy.