In cluster headache (CH), autonomic signs are usually reported as ipsilateral to the painful side. However, quantitative studies1 have proven bilateral increase of both lacrimation and nasal secretion during attacks, predominantly on the symptomatic side. Although conjunctival injection also seems bilateral but predominant on the side of the pain,2 no objective estimation of ictal conjunctival injection has been performed.
Therefore, we sought to witness CH attacks and study the pattern of ictal conjunctival injection in both eyes.
Methods.
Over 1 year we studied all consecutive patients who met IHS diagnostic criteria for CH3 and agreed to participate and sign informed consent. All patients had normal neurologic and ophthalmologic examinations. Routine blood and urine analysis and brain MRI examinations were also normal. Patients were asked not to take any medication before the study was performed.
Interictally and during attacks, high quality pictures centered in both eyes were taken under the same conditions of light, magnification, and exposure parameters using a high-resolution camera (ZEISS FF 450 IR plus Fundus camera, 786 × 576 pixels resolution) and digital image archiving system (Visupac 451 Digital 3.2.1 version). All images were obtained in a blinded way by the same investigator, always with the same sequence: right/left. Two ophthalmologists (P.G., J.Y.), blinded regarding to diagnosis and laterality of symptoms and signs, independently scored conjunctival injection according to a semiquantitative scale.4 Inter-rater reliability was 100%.
Results.
Nine patients were included, all with episodic CH. Eight of them developed ictal conjunctival injection, always bilaterally (table). In 100% of witnessed attacks, conjunctival injection was dependent on the peripheral conjunctival vessels feeding the bulbar and tarsal conjunctiva without noticeable participation of the pericorneal territory (ciliary vessels). The intensity of the conjunctival injection ranged from mild to intense, regardless to pain, but was always symmetric in both eyes. When specifically asked, eight of the patients mentioned having conjunctival injection during attacks, always ipsilateral to pain, except Patient 1, who reported bilateral injection (figures E-1 and E-2 on the Neurology Web site at www.neurology.org). There was a difference between subjective perception and objective registration in this group of patients (Wilcoxon test, p = 0.035).
Table Results
Discussion.
CH along with paroxysmal hemicrania (PH) and SUNCT belong to the group of trigeminoautonomic cephalalgias (TACs), Group 3 of the IHS classification.3 TACs are thought to essentially depend on the activation of the trigeminal system with pain felt in the area supplied by the first branch (V-1) of the trigeminal nerve, together with a disinhibition of a trigeminofacial (parasympathetic) reflex responsible for the autonomic signs, as has recently been discussed.5
We found that conjunctival injection is bilateral during CH attacks. If these autonomic signs were to be the result of a trigeminofacial reflex, it would be direct and consensual in CH. This feature has important clinical and pathophysiologic consequences since in SUNCT ocular/nasal congestion seems to be unilateral (only direct reflex), and V-1 trigeminal neuralgia is not accompanied by conjunctival injection (untriggered reflex).4,6
Since trigeminal pain is intense in the three conditions, we postulate that the efferent autonomic responses essentially vary owing to differences in central processing of the reflex. In this regard there would be pathogenic and clinical support to distinguish among TACs and differentiate TACs and V-1 neuralgia from the autonomic point of view. There is reason to believe that PH would behave similar to CH in regards to autonomic signs.3
The discrepancy between objective/subjective data may have to do with attention focusing on the symptomatic side, thus possibly disregarding manifestations in the pain-free side. Otherwise, since conjunctival injection is a sign, it should be objectively assessed if pathophysiologic implications are to be considered.
The observed pattern of conjunctival injection involving the peripheral territory of the bulbar and tarsal conjunctiva (but not the ciliary vessels) bears clinical importance. In fact, witnessing this sign may help differentiate CH attacks from pain arising from disorders of the anterior chamber of the eye, such as glaucoma, uveitis, or cheratitis, that are regularly accompanied by pericorneal (ciliary) injection.
CH is a unilateral headache disorder with two symptomatic sides: the usual symptomatic side, where the pain and autonomic signs are full blown developed, and the oligo-symptomatic—painless—side, where a certain degree of autonomic signs can also be frequently observed. The clinical manifestations of the painless side may seem to inherently carry important pathophysiologic differences between TACs and V-1 trigeminal neuralgia, with clinical implications.
Footnotes
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Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the January 2 issue to find the title link for this article.
Commentary, see page 3
Disclosure: The authors report no conflicts of interest.
Received March 7, 2006. Accepted in final form August 28, 2006.
References
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