www.neurologyindia.com Case Report Hyper insulinemia in an hemicrania continua patient with sexual headache: Hypothesizing the basis for this unusual association Sanjay Prakash Department of Neurology, Medical College, Baroda, Gujarat-390 001, India Abstract Address for correspondence: Dr. Sanjay Prakash, The coexistence of hemicrania continua with another primary headache disorder is a O-19, Doctor’s Quarter, Jail Road, Baroda, Gujarat-390 001, India. very rare event. We report a male patient with both hemicrania continua of 16- year E-mail: [email protected] duration and pre-orgasmic headache of three-year duration. Both headache disorders responded to indomethacin. The patient had also in addition persistent elevation of fasting serum insulin. PMID: *** Hemicrania continua, hyperinsulinemia, sexual headache DOI: 10.4103/0028-3886.68689 Key words: Introduction seven times a week. The exacerbations were associated with lacrimation and rhinorrhea. The patient denied The coexistence of different types of primary headache the presence of aura, nausea, vomiting, photophobia, disorders in the patient is rare, but not uncommon. phonophobia or agitation during the exacerbations. He “Other primary headache disorders” are included in developed another type of headache since two to three Group 4 of International Headache Society Classification years. The headache, exclusively felt during sexual (HIS). Some of the common other primary headache activity, was band-like and holocranial, especially disorders include cluster headache, paroxysmal localized to occipital and neck areas. The headache was hemicrania, short-lasting unilateral neuralgiform noted in about 50% of sexual activities and used to start headache with conjunctival injection and tearing gradually after a few minutes of foreplay. The severity (SUNCT), and headache associated with sexual activity of the headache used to increase gradually, reaching (HSA).[1] The prevalence of these headache disorders maximum at the time of orgasm. The stopping of the is low in the general population and the coexistence sexual activity (on achieving orgasm or voluntarily of these headache disorders in the same individual is because of the unbearable headache) used to cease a very unusual phenomenon. We report a patient with the progression of headache. However, he used to hemicrania continua who, later developed pre-orgasmic get complete relief of headache 5-30 minutes after headache. stopping the sexual activity. He was a known case of hypertension. Physical and neurological examinations Case Report were normal A 48-year-old man presented with a 16-year history Magnetic resonance image (MRI) of the brain and MR of continuous right-sided headache. The pain was a angiography were essentially normal. Other laboratory constant ache of mild to moderate severity with episodic workup was normal, except for high fasting serum insulin exacerbations of severe pulsating pain lasting for 10-60 levels (120 to 148 m U/l). The oral glucose tolerance test minutes in supra-orbital, retro-orbital and temporo- (OGTT) done on a few occasions was within normal parietal areas. The frequency of exacerbation was two to limit. The reasons for serum insulin testing (by previous 642 Neurology India | Jul-Aug 2010 | Vol 58 | Issue 4 Prakash: Hemicrania continua, sexual headache and hyperinsulinemia treating physician) was not clear from the history. His and HSA has been speculated. Response of both headache father has hypertension and diabetes mellitus.. disorders to indomethacin may suggest a common pathophysiology. Mateo et al.[12] reported a patient with A diagnosis of hemicrania continua (HC) and headache chronic paroxysmal hemicrania (CPH) in association associated with sexual activity (HSA) (pre orgasmic with benign cough headache. Both the headaches headache) was made. Treatment with indomethacin (50 responded to indomethacin. Evers et al.[13] demonstrated mg q8) resulted in complete remission of HC and he had impaired cerebrovascular autoregulation in patients decrease in the frequency and intensity of pre orgasmic with HSA and suggested a possibility of stretching of headaches. He could prevent pre orgasmic headache small intracranial arteries to induce the activation of by taking additional 50 mg of indomethacin, one to two pain- processing trigemino- vascular system. They also hours before the sexual activity. In the 15-month follow considered the possibility of primary dysbalance of the up he was headache free except for the days of drug trigemino-vascular system and impaired cerebrovascular default. On each occasion, it resulted in recurrence of autoregulation as a secondary effect. [13] This may be an both types of headache. Repeat serum insulin testing explanation for HSA in a patient with HC. Activation of on two more occasions during the remission phase the hypothalamus has been observed in patients with remained elevated (126 and 132 m U/l). HC. In the same way, activation of the hypothalamus has been demonstrated during sexual activity and orgasm. [14] Discussion Therefore, the possibility of HSA can be speculated in a patient with HC. Clinical characteristics of headaches in our patient fulfilled the diagnostic criteria of HC and HSA.[1] The Another unique observation in our patient was first report of two primary headache disorders occurring persistent hyper insulinemia. Insulin levels are tested in the same patient was HC with cluster headache in the presence of risk factors for metabolic syndrome (CH). [2] Subsequently cases of HC in association with or cardiovascular syndrome.[15] There was no risk other primary headache disorders have been reported factor for metabolic syndrome (or hyper insulinemia) [Table 1].[2-9] In most of these cases, HC evolved from in our patient. The family history of diabetes mellitus another primary headache disorder. There are only two and hypertension may be a reason for testing insulin case reports in whom HC and another primary headache level. Hyper insulinemia may be related to both disorder occurred concurrently, similar to our patient. [3, 4] normal and abnormal glucose levels. In patients with Migraine and benign exertional headache are the two insulin resistant state, abnormally high insulin level most common headache disorders associated with HSA. may have either normal or low glucose level. Normal A few reports described HSA in association with another OGTT supports the presence of insulin resistant state. primary headache disorder: HSA in association with The presence of hyper insulinemia in our patient CH[10] and HSA in association with hypnic headache. [11] is largely unexplained. However, impaired insulin sensitivity has been demonstrated in patients with It is difficult to determine, on the basis of case reports, migraine.[16] McCarthy et al. [17] have demonstrated an whether the occurrence of this rare association (HC association between insulin receptor gene and migraine, with HSA) in the same patient is just a coincidence or and suggested a role of insulin receptor in migraine whether they have a common pathophysiology. The pathogenesis. The clinical feature of the exacerbation clinical characteristics of HC and HSA are totally different. of HC is similar to that of migraine. [18] Therefore, a This suggests that the association is more a coincidence. similar type of association is possible in patients with However, a common pathogenic relationship between HC HC. However, a single case report is not sufficient to Table 1: Literature review of co-occurrence of hemicrania continua with other primary headache disorders Author Age/ sex Other primary Interrelation between Notes (year) headache HC and other headache Centonze et al. (1987) 53 Y/F CH HC evolved from CH HC evolved after 10 months of CH pain-free period. Evers et al. (1999) 39Y/ F FHM Both at the same time Family history of different types of migraine Lisotto et al. (2003) 32Y/M CH Both at the same time CH was on the contralateral side Palmieri et al. (2004) 40 Y/ F Migraine with HC evolved from Migraine Indomethacin was successfully tapered off after one aura month Saito et al. (2005) 36 Y/M CH HC evolved from CH Rozen (2006) 24Y/F CH HC evolved from CH HC responded to verapamil Castellanos-Pinedo et al. 43 Y /F PH HC evolved from PH. Past history of migraine (2006) Indomethacin was successfully tapered off Lambru et al. (2008) 51Y/F CH HC evolved from CH HC responded to valproic acid CH - Cluster headache; F - Female; FHM - Familial hemiplegic migraine; HC - Hemicrania continua; PH - Paroxysmal hemicrania; Y - Years Neurology India | Jul-Aug 2010 | Vol 58 | Issue 4 643 Prakash: Hemicrania continua, sexual headache and hyperinsulinemia say that hyper insulinemia predisposes such a type of episodic cluster headache. Cephalalgia 2006;26:351-3. headache, and at this point of time in clinical practice, 8. Castellanos-Pinedo F, Zurdo M, Martínez-Acebes E. Hemicrania continua evolving from episodic paroxysmal hemicrania. Cephalalgia a routine estimation of serum insulin level cannot be 2006;26:1143-5. suggested. However, because of the marked similarity 9. Lambru G, Castellini P, Bini A, Evangelista A, Manzoni GC, Torelli in clinical profiles of HC to that of migraine, we suggest P. Hemicrania continua evolving from cluster headache responsive to further observational studies to confirm it. If it is valproic acid. Headache 2008;48:1374-6. 10. Maliszewski M, Diamond S, Freitag FG. Sexual headaches occurring confirmed in other patients with HC, it may help in in cluster headache patients. Clin J Pain 1989;5:45-7. understanding the pathophysiolgy of this uncommon 11. Porta-Etessam J, García-Morales I, Di Capua D, García-Cobos R. A primary headache disorder. patient with primary sexual headache associated with hypnic headaches. J Headache Pain 2009;10:135. 12. Mateo I, Pascual J. Coexistence of chronic paroxysmal hemicrania and References benign cough headache. Headache 1999;39:437-8. 13. Evers S, Schmidt O, Frese A, Husstedt IW, Ringelstein EB. The 1. Headache Classification Committee of the International Headache cerebral hemodynamics of headache associated with sexual activity. Society. Classification and diagnostic criteria for headache disorders, Pain 2003;102:73-8.