HC was first described in 1981 and officially named by Sjaastad and Spierings in 1984 [9, 10]. There are now more than 100 reports of HC in the literature. HC was originally believed to be a rare primary headache disorder but more recent evidence suggests that HC is not rare, just under recognized [2]. In the clinical setting, HC is characterized by a unilateral headache that is continuous and of mild to moderate severity. The pain is usually reported as dull, aching, or pressure-like pain without associated symptoms. Exacerbations or more severe pain, lasting anywhere from 20 min to several days, are experienced in the majority of those with HC, and when present are associated with one or more autonomic symptoms on the ipsilateral side. Migrainous features, such as photophobia, phonophobia, nausea, and vomiting commonly occur during exacerbations of pain. Many patients will experience a sensation of a foreign body in their eye similar to sand or an eyelash on the affected side. The pathophysiology of HC is not known, some scientist believe it is a subtype of migraine, while others believe it is more closely related to the trigeminal autonomic cephalalgias (TAC). It was hoped that functional brain imaging would help to clarify our understanding of HC, but it revealed that HC is a distinct headache syndrome, not belonging to the migraine or TAC group. The scans revealed activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons, as well as activation of the ipsilateral ventrolateral midbrain, extending over the red nucleus and substania nigra and the bilateral pontomedullary junction [11]. These areas have been previously demonstrated to be the sites of activation in the TACs and migraine, ipsilateral activation hypothalamic activation in short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and cluster; in HC the findings are reversed. HC was not included in the first edition of the ICHD-I [12], but is included within the other primary headaches section of the second edition of the ICHD-II [5].
Hemicrania continua presents as two temporal profiles: an episodic form with distinct headache phases separated by periods of pain-free remissions, and a chronic form in which the headache persists without remission for years [3]. HC is chronic from onset in 53% of patients; the disorder began in the episodic form and evolved into the chronic form in 35%, and it begins and remains episodic in 12% of patients [2].
Hemicrania continua may be incorrectly diagnosed as cluster headache. This can occur by focusing exclusively on the ipsilateral autonomic features that accompany the painful exacerbations of HC. Similarly, focusing on the associated photophobia, phonophobia, nausea, and vomiting that may occur during exacerbations of HC may lead to misdiagnosing HC as migraine. An absolute response to therapeutic doses of indomethacin helps distinguish HC from chronic migraine. Autonomic features on the ipsilateral side, which are present during exacerbations of HC, are at times also present during acute attacks of migraine. HC is also distinguished from cluster headache and migraine by the presence of a continuous baseline headache that is usually unilateral and mild to moderate in severity. The associated features of photophobia, phonophobia, nausea, and vomiting, as well as the ipsilateral autonomic features of cluster are absent with the continuous baseline pain of HC.
Some patients are unable to tolerate indomethacin due to GI distress, renal disease, or concurrent anticoagulation therapy, and alternative types of therapy must be considered. Peres and Silberstein demonstrated in a study using cyclooxygenase-2 inhibitors (COX-2), efficacy of celecoxib and rofecoxib, the latter of which has since been removed from the market. They found 60% of patients who received celecoxib and 33% who received rofecoxib experienced a complete response [13]. There is one case in the literature of a unilateral headache similar to HC that did not respond to indomethacin, and many other standard headache agents, but was responsive to gabapentin at 1,200 mg per day. That patient had complete pain relief after 17 years of continuous headache. [6]. There have also been two separate reports of melatonin being efficacious for HC, one case reported by Spears [14], and three cases by Rozen [15]. There have also been four cases in the literature of patients responding to topiramate, one by Camarda et al. [16], one by Matharu et al. [7], and two cases by Brighina et al. [8]. Rozen also reported one case responsive to verapamil [17].
Gabapentin is an antiepileptic drug that is approved for use in the adjunctive treatment of partial seizures with and without secondary generalization in patients over 12 years of age. Gabapentin is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3–12 years of age. Gabapentin is also indicated for the management of post herpetic neuralgia in adults. Benefit has been reported in gabapentin treatment for hypobaric hypoxia-induced headache, high altitude headache, nummular headache, SUNCT syndrome, chronic cluster headache, post-dural puncture headache, and primary thunderclap headache just to mention headaches disorders [18–26].
The mechanism by which gabapentin exerts its analgesic action is unknown, but in animal models of analgesia, gabapentin prevents allodynia (pain related behavior in response to a normally innocuous stimulus) and hyperalgesia (exaggerated response to painful stimuli). Gabapentin also decreases pain related responses after peripheral inflammation [27].
The mechanism by which gabapentin exerts its anticonvulsant action is unknown, but in animal test systems designed to detect anticonvulsant activity, gabapentin prevents seizures. Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA) but does not modify GABA a or GABA b radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. Gabapentin was tested in radioligand binding assays and did not exhibit affinity for a number of other common receptor sites including benzodiazepine, glutamate, N-methyl-d-aspartate (NMDA), quisqualate, kainate, strychnin-insensitive glycine, alpha 1, alpha 2, or beta adrenergic, adenosine A1 or A2, cholinergic muscarinic or nicotinic, dopamine D1 or D2, histamine H1, serotonin S1 or S2, opiate mu, delta or kappa, cannabinoid 1, voltage sensitive calcium channel sites labeled with nitrendipine or diltiazem, or at voltage sensitive sodium channel sites labeled with batrachotoxinin A 20 alpha benzoate. Gabapentin also did not alter the cellular uptake of dopamine, noradrenaline or serotonin.
One patient reported an 80% reduction of pain on 2,400 mg of gabapentin but was also on the fentanyl patch. There have been reports in the literature of enhancement of pain control on the combination of opioids and gabapentin [28, 29]. It should be noted that this patient was taking opioids for a concomitant condition. This patient met the primary endpoint, but the concomitant use of an opioid is a confounding factor.
