Hypnic Headaches in a Patient Post Coiling and Clipping of Intracranial Aneurysm

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Hypnic Headaches in a Patient Post Coiling and Clipping of Intracranial Aneurysm Molly P. Aldred, BSA, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Andrew G. Lee, MD H ypnic headache (HyH) is an uncommon headache phenotype that involves cyclical nocturnal headaches. HyHs typically occur in older adults and have an unknown pathophysiology. No correlation has been found between HyH and structural brain lesions, metabolic syndromes, or systemic diseases (1). We present a case of a young female who developed HyH after a subarachnoid hemorrhage with initial coiling, and then subsequent craniotomy and aneurysmal clipping. To the best of our knowledge, this is the first such case of HyH to be reported in the English language ophthalmic literature. CASE REPORT A 20-year-old white woman presented with a several-month history of retro-orbital left eye pressure. She also suffered from anxiety. Her family history and allergies were noncontributory. She was on no regular medications. She smoked one packet of cigarettes daily and drank 11 standard drinks of alcohol per week. She initially presented with a 3-week history of episodic sharp left retro-orbital pain. It would awaken her from sleep between 3 AM and 5 AM every night and was associated with blurred vision. Her other headache triggers included alcohol, excessive screen time (including Zoom for college classes), and sleep deprivation. Eighteen months before, computed tomography (CT) showed a subarachnoid hemorrhage for which she underwent endovascular coiling of a University of Texas Health Science Center (MA), Houston, Texas; Department of Ophthalmology (SR, PM, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology (AGL), Neurology, and Neurosurgery, Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, 450 Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Aldred et al: J Neuro-Ophthalmol 2022; 42: e415-e416 distal left internal carotid artery (ICA) aneurysm and subsequent craniotomy and clipping of the aneurysm after recanalization of the aneurysm. Postoperative angiography showed complete obliteration of the aneurysm. On neuro-ophthalmic examination, visual acuity was 20/25 at a distance in each eye (OU). Pupils were isocoric and normally reactive to light OU with no relative afferent pupillary defect. Ishihara plates were 14/14 OU. The lid height and ocular motility were normal and symmetrical OU. External and slitlamp examinations were unremarkable OU. CT and CT angiogram of the head and neck revealed only postoperative changes from the known left paraclinoid ICA aneurysm clipping and coiling. DISCUSSION HyH are rare, primary headaches that recur around the same time every night and may also be referred to as “clockwise” or “alarm clock” headaches (1). The diagnostic criteria according to the International Classification of Headache Disorders third edition (ICHD-3) published by the International Headache Society (IHS) is that they are (1) recurrent headache attacks that (2) develop only during sleep and awaken the patient, (3) occur greater than 10 days/month for greater than 3 months, (4) last from 15 minutes to 4 hours, (5) have no restlessness or cranial autonomic symptoms, and (6) do not fit the criteria of other headache diagnoses (2). The patient had nocturnal headaches almost every night for several months and met the ICHD-3 criteria for HyH. HyHs typically occur in older adults as dull, throbbing, or sharp pain within 2–8 hours after falling asleep (1). They can be bilateral or unilateral, and may occur with nausea and mild photophobia (1). No significant comorbidities have been found, but hypertension and previous headaches may be associated (1). MRI, CT, and electroencephalogram are normal, and there are typically no associated structural lesions (1). The underlying pathophysiology is unknown. A systematic review of 71 patients found a possible association with Rapid eye movements (REM) sleep, possibly from activation of the pyramidal motor systems, arterial hypertension, and low oxygenation (1). In addition, the dorsal raphe and locus coerulei nuclei are inactive during REM sleep—these areas are an important component of the antinociceptive e415 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence system and thus their diminished activity may lead to headache onset (1). Chronobiologic disturbances may also be related—the suprachiasmatic nuclei (SCN) sets the circadian rhythm through melatonin secretion, and connections to periaqueductal gray matter is also thought to be related to antinociception (1). Decreased SCN and melatonin activity may lead to headache onset. Both lithium, which indirectly increases melatonin, and melatonin have been efficacious in treatment of hypnic headaches (1). We hypothesize that her subarachnoid hemorrhage (SAH) and aneurysmal coiling and clipping may have disrupted her hypothalamic–pineal axis, causing decreased SCN function and secondary HyHs. Hypothalamopituitary dysfunction has been noted to occur after aneurysmal SAH, typically developing over weeks to months (3). A systematic review of 1,127 patients found that the prevalence of hypopituitarism after aneurysmal subarachnoid hemorrhage was 47% (95% confidence interval 37.4%–56.8%) (3). Hypopituitarism may occur at the level of the hypothalamus, pituitary, or the connecting stalk (3). Disruption in pituitary function is proposed to be from infarction and disruption in the hypothalamohypophysial portal blood supply (3). Hypothalamic dysfunction may occur from direct hypothalamic lesion, damage to hypothalamic arteries, and vasoconstriction (3). In addition, direct hypothalamic microhemorrhage may occur from the increased pressure in the chiasmatic cistern during SAH, which obstructs venous drainage (3). It is possible this patient’s SCN was damaged during or after her SAH. In theory, this event could have disrupted the hypothalamic–pineal axis, leading to decreased melatonin secretion and HyH. The absence of headaches when she takes sleeping medication e416 and her development of sleep disturbances 1 year after SAH provide further support for this hypothesis. HyH occurs most frequently in older adults but has been reported to occur in children infrequently (4). It is possible that the patient’s initial subarachnoid hemorrhage or her subsequent aneurysmal coiling and clipping could have led to diminished SCN function and decreased melatonin. To the best of our knowledge, this is the first reported case in the English language literature occurring after subarachnoid hemorrhage and aneurysmal repair. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. Aldred, S. Raviskanthan, P. W. Mortensen, and A. G. Lee; b. Acquisition of data: M. Aldred, S. Raviskanthan, P. W. Mortensen, and A. G. Lee; c. Analysis and interpretation of data: M. Aldred, S. Raviskanthan, P. W. Mortensen, and A. G. Lee. Category 2: a. Drafting the manuscript: M. Aldred, S. Raviskanthan, P. W. Mortensen, and A. G. Lee; b. Revising it for intellectual content: M. Aldred, S. Raviskanthan, P. W. Mortensen, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: M. Aldred, S. Raviskanthan, P. W. Mortensen, and A. G. Lee. REFERENCES 1. Evers S, Goadsby PJ. Hypnic headache: clinical features, pathophysiology, and treatment. Neurology. 2003;60:905–909. 2. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38:54–55. 3. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298:1429–1438. 4. Silva-Néto RP, Almeida KJ. Hypnic headache in childhood: a literature review. J Neurol Sci. 2015;356:45–48. Aldred et al: J Neuro-Ophthalmol 2022; 42: e415-e416 Copyright © North American Neuro-Ophthalmology Society. 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