Letters to the Editor

Spontaneous Unwelcome Orgasms: A Novel Case of an Aura Symptom Observed in Migraine Headache

was gradually increased to 150 mg according to clinical response. Wolff proposed that the neurologic symptoms of the migraine aura were caused by cerebral vasoconstriction and the headache by vasodilatation of the arteries of the scalp.1 Experimental data have suggested that the preceding aura symptoms may reflect a cortical spreading depression associated with local blood flow changes and transient clinical signs.1,2 Several studies have suggested either a reduced cortical inhibition or an increased neuronal excitability and responsiveness of the primary visual cortical areas, possibly precipitating migraine aura.2 A significant amount of data suggests the role of the right hemisphere in human sexual functions and the production of hormones mediating sexual functions shows a predilection for the right side.3 It is uncommon but well known that sexual arousal and orgasm may occur as part of a partial seizure; usually the auras or the epileptic discharges may induce general sexual or genital arousal, which may sometimes progress to orgasmic activity.3 In most of the published cases dealing with this seizure-related sexual phenomenon, the epileptogenic zones were located on the right hemispheres. To our knowledge, no other aura symptoms observed as spontaneous unwelcome orgasms have been reported previously in the literature. It is difficult to present the precise mechanism between spontaneous unwelcome orgasms and migraine aura. Topiramate is a widely used agent for migraine prevention. At recommended migraine prophylactic doses, it is also generally well tolerated, and common adverse effects of this medication include paresthesia, fatigue, anorexia, weight loss, and cognitive impairment.4 To our knowledge, however, sexual dysfunction in women, and anorgasmia, in general, has only recently been reported as a side effect of this medication.4 Our patient started topiramate prophylactically, with this side effect in mind. The patient was followed for 6 months with the same dosage and medication and showed a good clinical response. After the onset of drug treatment, so far she has not experienced any episode

Migraine is one of the most common neurological disorders and one of the most frequent causes of primary headaches. Recurrent episodes of transient focal neurologic symptoms, also known as aura, may be seen before migraine headache. Migraine aura is characterized by focal neurologic features of visual and/or sensory and/or speech disturbance preceding/accompanying a headache attack gradually developing over 5 to 20 minutes lasting no longer than 1 hour. We describe a 35-year-old woman having spontaneous unwelcome orgasms as an aura of migraine headache. A 35-year-old woman had a 10-year history of migraine without aura; her first migraine attack emerged when she was 25 years old. She had since then experienced migraine without aura (attacks characterized by unilateral throbbing severe pain, accompanied by photophobia, phonophobia, nausea and vomiting, lasting 1 day, not precipitated by any trigger factor), with a frequency of 1 attack per month. The pain attacks started during the previous 3 months prior to presentation with 4 attacks per month that were different in nature: an aura lasting 10 to 30 minutes just before headache onset, characterized by seeing an ovoid area of flashing lights in the upper left hemi-field evolving to a zigzag-like, wavy-lined pattern expanding over the central part of her visual field, accompanied by spontaneous unwelcome orgasms. Orgasms occurred without any premonition, perceivable stimulation, or increased sexual desire. They were experienced as highly undesired and embarrassing. Pathological history of the patient was otherwise unremarkable; physical, psychiatric, gynecological, and neurological examinations were normal, as well as electroencephalography (EEG) and brain magnetic resonance imaging (MRI). However, MRI and EEG could not be performed during an attack. Routine blood and hormonal tests were also normal. Topiramate was started at a dose of 25 mg once daily and

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754 of headache or auras with spontaneous unwelcome orgasms. In this report, it was not possible to relate the actual positive response to treatment with the efficacy of topiramate in migraine prophylaxis, the side effect of causing anorgasmia, or a combination of the two. We conclude that new cases and treatment experience is needed. Ali Ulvi Uca, MD; Hasan Hüseyin Kozak, MD Department of Neurology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

April 2014 Table.—Summary of P Values (One-Sided) in One Randomized, Controlled Trial (RCT) With Guanfacine (Reproduced From Elkind et al3)

Migraines/month Migraine/month with nausea/vomiting Incidence of nausea/vomiting

0.5 mg vs Placebo

1.0 mg vs Placebo

.6208 .6422 .981

.0053 .0146 .0325

REFERENCES 1. Evans RW, Aurora SK. Migraine with persistent visual aura. Headache. 2012;52:494-501. 2. Griebe M, Flux F, Wolf ME, Hennerici MG, Szabo K. Multimodal assessment of optokinetic visual stimulation response in migraine with aura. Headache. 2014;54:131-141. 3. Ozkara C, Ozdemir S, Yilmaz A, Uzan M, Yeni N, Ozmen M. Orgasm-induced seizures: A study of six patients. Epilepsia. 2006;47:2193-2197. 4. Sun C, Lay C, Broner S, Silberstein S, Tepper S, Newman L. Reversible anorgasmia with topiramate therapy for headache: A report of 7 patients. Headache. 2006;46:1450-1453.

Why Is Guanfacine Recommended by AHS and ANN for Migraine Prevention? In the recent AHS/AAN guidelines for migraine prevention, the α-2-agonist guanfacine and 7 other drugs were recommended as possibly effective (Level C).1 A Level C requires one Class II study rated as such according to the AAN’s classification scheme.2 The available evidence for guanfacine is an extended abstract (536 words) from an International Headache Congress in 1989.3 The study3 was a double-blind, parallel group comparison of guanfacine at 0.5 mg (N = 13), 1 mg (N = 12) doses to placebo (N = 12) in the prevention of classical and/or common migraine. Each subject had at least 3 migraine attacks per month. After a 4-week baseline period, patients were treated for 12 weeks. There were 31 females and 6 males in this randomized, controlled trial (RCT). Three patients withdrew early because adverse events. Only P values were presented as shown in the Table. Guanfacine 1 mg seemingly significantly reduced migraine frequency, but no data for the results were presented.3 The authors concluded that “guanfacine may be an effective agent in migraine prophylaxis.”3 In addition, they

stated that “further studies with 1.0 mg or larger doses may be necessary to determine if guanfacine has a role in the prophylaxis.”3 There have been no further studies (no relevant hits in PubMed with “guanfacine” and “migraine”), and the RCT with guanfacine3 has never been published in a peer-reviewed journal. The RCT was a single site study of a 2-site multicenter study,3 and the results from the second site were not then or later published. There can be many causes for this lack of publication, but one possibility (we could speculate) is that it was due to “negative results” in this second part of the multicenter RCT. The panel of headache and methodology experts of AHS and AAN reviewed the evidence and classified the RCTs as Class I and Class II studies.1 The RCT on guanfacine was classified as a Class II study,1 but according to the classification scheme of AAN2 on can question whether is correct. Thus, one requirement for a Class II study is “relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.”2 In the guanfacine abstract, no such baseline characteristics are presented, and we are left unaware of what kind of migraine patients were studied in this RCT. Finally, presentation of results in a paper is not a requirement for classification as a Class II study2 but the usual custom when RCTs are reported. In my opinion, it is unusual to recommend a drug like guanfacine for which no data on results3 are available. Peer Tfelt-Hansen, MD, DMSc Department of Neurology, Danish Headache Center, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark

REFERENCES 1. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: Pharmacologic treatment for episodic

Spontaneous unwelcome orgasms: a novel case of an aura symptom observed in migraine headache.

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