Abstract
Primary headache provoked by exertional factors encompasses a series of conditions where headache is precipitated by an activity that may increase intracranial pressure (ICP) such as exercise, cough and sexual activity (1). Intracranial lesions and cerebrospinal fluid pathway obstructions must be ruled out in order to consider the headache as a benign condition. Although they share some characteristics, the International Headache Society recognizes them as distinct conditions (2). Primary cough headache is described as shortlasting attacks of pain triggered by coughing. It commonly affects middle-aged men and may persist for years (3). Treatment strategies typically include daily indomethacin and other drugs that may lower ICP, such as acetazolamide (4). Lumbar puncture has occasionally been reported effective in treating this condition (5).
We describe three patients with primary cough headache not adequately controlled with standard therapies that were responsive to topiramate.
Case reports
Case 1
A 68-year-old man with a previous history of hypertension, dyslipidaemia and mild left heart failure, treated with warfarin, digoxin, furosemide, valsartan and lovastatine, referred a 4-month history of headache triggered by cough and Valsalva manoeuvres. Headache was of short duration (4–5 min), intense and bilateral, without any autonomic or vegetative manifestations. The mean frequency of headache attacks was 20 per month. Magnetic resonance imaging (MRI) showed no intracranial lesions. A trial with indomethacin 100 mg/day for a week clearly alleviated the headache but was stopped because of potential interactions with warfarin. Topiramate was prescribed up to 50 mg/day. At 2 months, the patient had a clear reduction in the intensity and duration of the headache and only sneezing or heavy cough triggered headache. The headache frequency was reduced by 60%. The patient could not tolerate topiramate at a dose of 100 mg/day and he stayed with 50 mg/day. Warfarin controls and digoxin plasmatic levels were unchanged during topiramate therapy.
Case 2
A 54-year-old woman with a previous history of hypertension, Type 2 diabetes mellitus and depression, and treated with amlodipine, glumide and sertraline, referred a 3-year history of hemicranial headache precipitated by cough and Valsalva manoeuvres. She denied conjuntival injection, lacrimation, nasal congestion, rhinorrhoea, facial sweating and other symptoms. The pain was intense, non-pulsatile and lasted 5–15 min. The mean frequency of headache attacks was 12 per month. Neurological examination was normal and MRI showed no intracranial lesions. Indomethacin, 75 mg/day, was effective but it was withdrawn due to gastrointestinal side-effects. Topiramate was prescribed instead at a dose of 50 mg/day. With topiramate, headache frequency and intensity were reduced by 50% and its duration did not exceed 3 min. Headache was precipitated only by intense physical effort.
Case 3
An 18-year-old woman with no previous history or family history of migraine referred to us for a 1-year history of daily exertional headache. The headache was precipitated by minimal exertion such as coughing, defaecation or lifting weights. Headache was bilateral, non-pulsatile and of short duration and high intensity that created interference with daily activities. Two years later she developed another episodic pulsatile headache and a diagnosis of migraine headache was made. The patient referred this exertional headache as not related to her migraines in terms of headache duration or pain characteristics. When she started her cough headache, there was no evidence of migraine. Neurological examination revealed no abnormalities and neuroimaging studies (MRI) were normal. A diagnosis of primary cough headache was made although age of onset and sex were not characteristic for this condition. Indomethacin 75 mg/day was prescribed with partial relief. Adding a calcium channel blocker was of no value. Topiramate up to 50 mg/day was added to indomethacin with clear relief of the headache. Indomethacin was withdrawn and topiramate increased to 75 mg/day. The mean frequency of headache attacks was reduced to one to two per month. Apart from a 3-kg weight loss, the patient referred no other side-effects with topiramate. At the time of writing, the dosage of topiramate was 100 mg/day, and this patient described only attacks of episodic migraine headache, not the exertional headache.
Discussion
Indomethacin is usually effective in the treatment of primary cough headache. Indomethacin decreases intracranial pressure (6) and that may be why it is effective in this condition compared with other non-steroidal anti-inflammatories (3). Other carbonic anhydrase inhibitors (e.g. acetazolamide), by reducing cerebral spinal fluid production (7), decreases the pressure gradient and therefore relieves the headaches. Acetazolamide has been reported to be effective in open-label trials of management of the primary cough headache. We report the utility of topiramate as a treatment for primary cough headache, based on the inhibitory actions of topiramate over carbonic anhydrase. Recently, Palacio et al. (8) reported a patient with Behçet's syndrome and headache secondary to idiopathic intracranial hypertension with a good response to topiramate at dose of 75 mg/day, in line with the dose we found effective. Topiramate was efficacious at a dose lower than that used for epilepsy and the effect over headache was noted in the first weeks; therefore, if there is no effect over headache, it should be noted very early on in the course of treatment.
We report three patients with primary cough headache treated with topiramate after patients were intolerant to indomethacin. One patient responded well to topiramate and two others had a partial response. Further reports are needed to evaluate topiramate as an effective option in patients not responsive to indomethacin, and other studies are necessary to compare the efficacy of topiramate and indomethacin for primary cough headache, and in patients with other indomethacin-responsive headache disorders.