Sentinel Headache in Subarachnoid Hemorrhage

An unusual, sudden and severe headache, during the days, or even weeks, before bleeding event has been reported in 15% to 60% of patients with aneurysmal subarachnoid hemorrhage (aSAH). It is referred to as “warning leak”, “minor leak” or “sentinel headache” (SH)¹.

Clinical relevance of SH is a matter of debate. Some authors suggested an active diagnostic attitude towards patients experiencing an unusual headache, as it offers a means of improving the overall outcome in patients with aSAH, while others even questioned the existence of the SH, attributing its high incidence to a “recall bias”². Indeed, older studies assessing the prognostic value of SH^1,3,4 collected retrospective data, asking patients with aSAH whether they had experienced any episodes of acute, sudden-onset severe headache in the 2 weeks preceding the most recent bleeding event. Insofar, results might be altered by the foregone exclusion of cases with poor outcome and by the lack of clinical features to distinguish SH from other types of headache.

Most recent studies tried to overcome this diagnostic problem, showing that the concept of SH can be supported by using MRI techniques^5,6,7:

Firstly, using the susceptibility weighted imaging (SWI)⁵ and the quantitative susceptibility mapping (QSM)⁶, an advancement of the previous technique that provides quantitative maps. SWI and QSM may show the iron deposit caused by microbleeds of the aneurysm and correlated with the headache. They seem particularly effective in aneurysms of the middle cerebral arteries or posterior circulation, which do not have the limit of the skull-base bone artifacts.

Secondly, with the T1 weighted imaging (T1WI)-FLAIR mismatch⁷. It is defined as the presence of bright hyperintense subarachnoid blood (BHSB) in T1 images, although less widespread compared to the BHSB detected in FLAIR images. The BHSB of T1WI represents the subacute blood of the minor leak, while the BHSB of FLAIR images the subsequent re-bleeding.

Finally, with the aneurysm wall enhancement (AWE) of the Vascular Wall Imaging (VWI)⁸. It may predict symptomatic presentation (SH or III nerve palsy), growth or rupture of intracranial aneurysms (IA). It is associated with increased proinflammatory markers and might identify areas of increased vasa vasorum, neovascularization and macrophage infiltration. Hence, the AWE could be considered a surrogate biomarker of aneurysm instability, even in patients with SH and no minor leak.

In conclusion, these studies support the existence of SH . These studies also pointed out that SH could be caused by a minor bleeding from a leak of a berry aneurysm or by a warning inflammatory process that can precede the aSAH. Hence, in patients with unruptured IA whether the headache comes from the aneurysm might potentially be clarified.

—

References:

1.F H Linn, E F Wijdicks, Y van der Graaf, F A Weerdesteyn-van Vliet, A I Bartelds, J van Gijn. Prospective study of sentinel headache in aneurysmal subarachnoid haemorrhage. Lancet. 1994 Aug 27;344(8922):590-3. doi: 10.1016/s0140-6736(94)91970-4.

2.K E Jakobsson, H Säveland, J Hillman, G Edner, S Zygmunt, L Brandt, L Pellettieri. Warning leak and management outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg. 1996 Dec;85(6):995-9. doi: 10.3171/jns.1996.85.6.0995.

3.Jürgen Beck, Andreas Raabe, Andrea Szelenyi, Joachim Berkefeld, Rüdiger Gerlach, Matthias Setzer, Volker Seifert. Sentinel headache and the risk of rebleeding after aneurysmal subarachnoid hemorrhage. Stroke. 2006 Nov;37(11):2733-7. doi: 10.1161/01.STR.0000244762.51326.e7. Epub 2006 Sep 28.

4. Viarasilpa T, Ghosh P, Gidwani S, Lantigua H, De Marchis GM, Panyavachiraporn N, Schmidt JM, Lee K, Badjatia N, Agarwal S, Claassen J, Mayer SA. Prognostic Significance of Sentinel Headache Preceding Aneurysmal Subarachnoid Hemorrhage. World Neurosurg. 2020 Jul;139:e672-e676. doi: 10.1016/j.wneu.2020.04.097. Epub 2020 Apr 24. PMID: 32339738.
5. Wan Z, Meng H, Xu N, Liu T, Chen Z, Sun Y, Wang H. Clinical characteristics associated with sentinel headache in patients with unruptured intracranial aneurysms. Interv Neuroradiol. 2021 Aug;27(4):497-502. doi: 10.1177/1591019920971977. Epub 2020 Nov 4. PMID: 33148104; PMCID: PMC8580530.
6. Nakagawa D, Kudo K, Awe O, Zanaty M, Nagahama Y, Cushing C, Magnotta V, Hayakawa M, Allan L, Greenlee J, Awad IA, Carroll T, Torner J, Raghavan ML, Hasan DM. Detection of microbleeds associated with sentinel headache using MRI quantitative susceptibility mapping: pilot study. J Neurosurg. 2018 May 1:1-7. doi: 10.3171/2018.2.JNS1884. Epub ahead of print. PMID: 29799347; PMCID: PMC6773513.
7. Oda S, Shimoda M, Hirayama A, Imai M, Komatsu F, Shigematsu H, Nishiyama J, Hotta K, Matsumae M. Retrospective review of previous minor leak before major subarachnoid hemorrhage diagnosed by MRI as a predictor of occurrence of symptomatic delayed cerebral ischemia. J Neurosurg. 2018 Feb;128(2):499-505. doi: 10.3171/2016.10.JNS161964. Epub 2017 Feb 10. PMID: 28186448.
8. Raghuram A, Sanchez S, Wendt L, Cochran S, Ishii D, Osorno C, Bathla G, Koscik TR, Torner J, Hasan D, Samaniego EA. 3D aneurysm wall enhancement is associated with symptomatic presentation. J Neurointerv Surg. 2022 Jul 19:neurintsurg-2022-019125. doi: 10.1136/jnis-2022-019125. Epub ahead of print. PMID: 35853699.