Abstract
An estimated 1–6% of the adult population harbor an unruptured intracranial aneurysm (UIA) with a 0.5–1% yearly risk of subarachnoid hemorrhage in aneurysms between 7 and 10 mm in diameter (1,2). Current guidelines for the surgical management of UIAs rely mainly on aneurysm size and patient age, with surgical intervention indicated for nearly all patients under the age of 70 with aneurysms 10 mm in diameter or greater (1). Moreover, the presence of symptoms attributable to a UIA is also a key determinant in surgical candidacy (1).
Issues surrounding the management of UIAs are of particular significance to clinicians caring for headache patients, as headache is the presenting complaint in approximately one-third of patients with a UIA (1,3,4). In the context of new headaches, many patients (and clinicians alike) may fear more sinister underlying causes and may be quick to make associations between severe headaches and the presence of UIAs as a possible secondary cause (5). This is especially evident in the evaluation of sentinel headaches, which often present as thunderclap headache or other headaches of abrupt onset and may occur in up to 43% of individuals found to have a subarachnoid hemorrhage. Adding to these fears is the knowledge that nearly three-quarters of sentinel headaches will be complicated by a major aneurysmal rupture within the ensuing month (6).
The 2nd edition of the International Classification of Headache Disorders (ICHD-II) outlines established criteria for the diagnosis of headache secondary to intracranial aneurysm and requires the presence of either thunderclap headache or any other new acute headache determined to be caused by an aneurysm. Additionally, headache must resolve within 72 hours (7). A great deal of diagnostic and therapeutic uncertainty exists, however, in scenarios where the clinician is faced with the discovery of a UIA and headache of a less distinct and more chronic nature. This is especially problematic when the headache exhibits features of migraine or tension-type headache – phenotypes not commonly associated with UIA. The decision to recommend surgery may be further influenced by numerous psychosocial stressors which take an emotional toll in patients with untreated UIAs, as many of them fear that they are ‘ticking time bombs’ and that each successive headache may portend an eventual aneurysmal rupture with a potentially fatal outcome (8).
Little guidance exists with regard to the treatment of otherwise ‘non-surgical’ UIAs and headache outcomes. Additionally, prior to UIA repair, it is difficult to prognosticate which patients will improve, which will worsen, and which will have no change. At this point, the data regarding headache improvement following surgical repair of UIAs has been limited to retrospective studies and ranges from 60% to 90% (4,9). Within these studies, there is a paucity of objective data regarding the true impact on headache frequencies, anxiety, depression, and headache-related disability.
In the first prospective study to assess headache outcomes after surgical UIA repair, Schwedt and colleagues address many of these questions. Pre- and post-operative data were obtained from 44 patients with a UIA (28 of whom had active headache, defined as ≥ 3 headache attacks per 90 days) including phenotypic headache characteristics, as well as responses to clinical scales screening for headache disability, cutaneous allodynia, depression, and anxiety. Based on the hypothesis that new or worsened headache after UIA repair may be secondary to central sensitization, quantitative sensory tests followed by manual assessments of pain thresholds with von Frey filaments were also conducted pre- and post-operatively. Follow-up data was then obtained at regular time intervals of 1 month, 3 months, and 6 months.
Key findings included the significant decrease in mean 90-day headache frequencies 6 months after surgery from 49/90days to 24/90 days among the 28 patients with active headache. Within the same time frame, a ≥ 50% decrease in headache frequency in 68% and a ≥ 50% worsening of headache frequency in 11% of this population was also noted. No significant changes were noted in headache severities, nor were there any significant changes in Migraine Disability Assessment Scale (MIDAS), Allodynia Symptom Checklist (ASC-12), or Beck Depression Inventory (BDI) in this population of active headache sufferers; however both state and trait anxiety scores decreased significantly (3).
Interesting similarities were also noted among those without improvement of their headache, including pre-operative elevations in trait anxiety, increased headache severity, and a diagnosis of migraine. No evidence of central sensitization was found in the 21 patients who completed cutaneous sensory testing (3).
Prima facie, the prognosis for headache improvement after UIA repair appears favorable; however the data should be interpreted with caution as other factors which may contribute to the expression of headache (i.e. anxiety) were also found to decrease significantly. The knowledge that one is harboring a UIA may have a marked psychosocial impact and precipitate an anxiety level of enough significance to amplify the perception of headache pain through activation of the entorhinal cortex in the hippocampal formation (8,10). Simply put, the sheer act of repairing the UIA may exert a placebo response of a magnitude great enough to produce a decrease in a patient’s perception of headache pain. Schwedt and colleagues allude to this possibility in their discussion of possible explanations for post-operative headache improvement. This phenomenon would be difficult to rule out as the ethics of conducting sham UIA repair in symptomatic patients is questionable. In future studies, however, it would be interesting to quantify the strength of association that a patient makes between their UIA and their headaches. Of particular note, the observation that headache outcomes differed between surgical techniques (with a lack of headache improvement after stent-assisted coiling compared to clipping or coiling) suggests that placebo effect may not play a significant role in post-operative headache improvement.
There are also a number of other possible explanations for the improvement of headache in the presence of UIA repair, including the hypothesis that disruptions in the normal flow and structure of intracranial arteries may lead to activation of afferent nociceptive fibers which then become quiescent after surgery (3). A small number of patients in this study also had alterations in their medication regimens that may have influenced their outcome. Moreover, completion of the MIDAS questionnaire is subject to recall bias in the absence of a daily headache diary.
The identification of underlying pathology is paramount in the evaluation of headache. The diagnostic workup occasionally reveals abnormalities which are coincidental, but which may give patients and healthcare providers pause, as their significance may be unclear. The discovery of a UIA presents a distinct quandary for the clinician – especially when in the context of headache disorders meeting criteria for migraine or tension-type headache as little data exist regarding the impact of surgery on headache outcomes. The recent work of Dr Schwedt and colleagues not only supports previous observations regarding UIA repair and headache improvement but also provides novel data that may help in the prognostication of which patient populations are most likely to have favorable outcomes.
The lack of complete headache resolution in a number of patients supports the commonly held belief that headache is a complex and multifactorial disorder. It is therefore reasonable to counsel patients that UIA repair may address only one of several possible triggers and that, in many cases, additional medical management may be necessary. Clearly, more research is required to fully understand the full breadth of the impact of UIAs in headache management.