A 48-year-old Korean man presented to emergency room with recurrent severe left-sided headache attacks involving the orbit and periorbital areas accompanied by abnormal lacrimation which started 2 days prior to the visit. He was an otherwise healthy individual with no previous medical history except occasional migraine attacks and dental caries and took no medications for the migraine attacks. His headache attacks, with a numeric rating scale (NRS) of 8-9, occurred once or twice a day and each attack lasted for an hour. Between headache attacks, patient did not report any headache. During his emergency room visit, brain computed tomography and ophthalmologic examination revealed normal findings. He was treated with intravenous (IV) analgesics at the outpatient clinic, the patient complained of an aggravation of the same left-sided headache attacks with NRS of 5, accompanied by abnormal lacrimation, involving the orbital and periorbital regions.

He was diagnosed as having CH, fulfilling the criteria for CH according to the 3rd edition of the International Classification of Headache Disorder, and was admitted to our neurology service for pain and medication control and to evaluate for possible secondary causes of headache. On admission, his contrast-enhanced brain magnetic resonance imaging (MRI) and cerebrospinal fluid examination showed no abnormal findings (Fig. A). He was prescribed oral prednisolone 60 mg/day, verapamil 320 mg/day, and valproate 500 mg/day as preventive treatment for the headache, and oral zolmitriptan 2.5 mg for acute treatment of CH. After starting the medications, the headache attacks slowly abated with shorter duration of headaches from 1 hour to 10 minutes, and a reduced NRS of 1-2 during attacks. He was discharged 4 days after admission.

A week from discharge, he was readmitted for worsened left-sided headache with an NRS of 10. On the day of admission, his headache responded well (with NRS 6) to nasal oxygen 10 L/min. On the 3rd day, contrast-enhanced brain MRI revealed a left cavernous sinus thrombophlebitis and empirical antibiotic treatment was started promptly: ceftriaxone (4 g/day), vancomycin (2 g/day), and metronidazole (1.5 g/day). On the 4th day, while the patient’s left sided headache slowly showed reduction in pain intensity (NRS 3) in response to intravenous antibiotics, he started complaining of a new-onset right-sided headache (NRS 6) accompanied by a right third nerve palsy including anisocoria (6 mm/3 mm) and right ptosis. To prevent neurologic deterioration, methylprednisolone (1 g/day) pulse treatment was started.

On the 14th day of admission, follow-up contrast-enhanced brain MRI revealed progression of bilateral thrombophlebitis, right side internal carotid arteritis and carotid-cavernous fistula (Fig. B).

On the 17th day of admission, the patient expired from subarachnoid hemorrhage that was caused by an internal carotid artery rupture (Fig. C).

Isolated headache can be the only clinical symptom of a cavernous sinus thrombophlebitis [2]. Previously reported cases of cavernous sinus thrombophlebitis were accompanied by intracranial hemorrhages (25%), non-hemorrhagic infarcts (27%), hydrocephalus (3%), mass effect (13%), midline shift (6%), and vasogenic or diffuse cerebral edema (9%) [3]. While intracranial hemorrhages, mass effect or diffuse cerebral edema could be the cause of an acute progressively worsening headache, it is important to recognize that cavernous sinus thrombophlebitis can present as cluster-like headache with a normal neurological examination and a normal non-contrast brain computed tomography [2]. Regarding the use of contrast-enhanced MRI for first-onset cluster headache evaluation, American College of Radiology appropriateness criteria recommends that contrast-enhanced MRI be performed at follow-up if the patient does not respond adequately to medication [4]. Regardless of the response to the initial treatment of CH, an initial neuroimaging protocol of brain MRI with contrast-enhanced imaging should strongly be recommended. In cases with worsened headaches after conventional first-line headache medications have been tried, a follow-up repeat high-resolution imaging should be considered to search for secondary causes of headache such as cavernous sinus thrombophlebitis so that life-threatening complications can be prevented.