Abstract
We report two cases of cluster headache sine headache occurring in a family of cluster headache sufferers. A 54-year-old female, suffered for 15 years from short-lasting, right-sided attacks of eye reddening, lacrimation, rhinorrea, palpebral oedema and miosis, seven to eight times per day, in periods of 20-30 days. She did not experience headache, either with or without these phenomena. Her son suffers from periorbital, short-lasting, right-sided painful attacks accompanied by eye reddening, lacrimation, rhinorrea and nasal stiffnesss, occurring in periods of 30-35 days. Soon after the end of the current cluster period he still had daily attacks lasting 10-15 min, with the oculo-nasal autonomic phenomena only. The occurrence of cluster headache sine headache and cluster headache in the same family strongly suggests that the first condition is related to the cluster headache syndrome. Cluster headache sine headache should be considered as a subtype of the cluster headache syndrome.
Introduction
Cluster headache attacks are characterized by excruciating unilateral orbitofrontotemporal pain, lasting 15–180 min, associated with ipsilateral lacrimation, conjunctival injection, nasal congestion, rhinorrhea, ptosis, miosis and eyelid oedema (1). Seven per cent of these patients experience typical pain crises without autonomic phenomena (2); by contrast, only one case characterized by autonomic crises but no pain has been reported (3). We describe a family of cluster headache sufferers, in whom two of the three probands present typical autonomic attacks without pain.
Case reports
Proband 1
A 54-year-old woman has, since age 39, experienced right-sided attacks characterized by eye reddening, lacrimation, nasal obstruction, rhinorrhea, palpebral oedema and, sometimes, miosis (see Fig. 1), occurring seven to eight times a day, often at fixed times, and lasting about 20 min. The patient reports never having experienced headache, either during or outside these crises. These attacks occur in periods lasting 20–30 days, in autumn or summer. General and neurological examination and brain MRI are normal.
Proband one during a right-sided attack of ocular autonomic phenomena without pain.
Proband 2
A 30-year-old physician is the son of the proband 1. Since the age of 19 he has suffered from severe right periorbital pain crises lasting about 30 min, accompanied by eye reddening, lacrimation, nasal obstruction and rhinorrhea, ipsilateral to the pain, two or three times a day, over periods lasting 30–35 days. Once the cluster period has resolved it is followed over the next 40 or so days by the occurrence of attacks of right-sided massive lacrimation and rhinorrhea, lasting 10–15 min, at the same regular times as the previous painful attacks. General and neurological examination and brain MRI are normal.
Proband 3
Proband 1 reported that her deceased father suffered from headache attacks from the age of 18 until he was 35. These crises were excruciatingly painful, located in the right periorbital region, lasted 15–30 min, and were not accompanied by autonomic phenomena. There were two to three pain episodes a day and no significant pain-free intervals, not occurring in cluster periods but in a chronic fashion.
Discussion
In proband 1 both the autonomic attacks and their periodicity are strongly reminiscent of cluster headache, except that the headache is absent. It would seem, in fact, that we are dealing with a rare form of cluster headache in which the pain crises are totally lacking.
Salvesen (3) recently described a patient who, for a few weeks, developed daily left-sided attacks of miosis, ptosis and nasal obstruction, but without pain. Six years later the patient developed left-side headaches accompanied by autonomic manifestations that were typical cluster headaches. The author proposed the term cluster headache sine headache for these episodes without pain. Although our proband 1 may develop typical cluster headache in the future, it seems likely that she maybe the first true case of cluster headache sine headache. The suggestion that cluster headache sine headache should be considered a variant of cluster headache is reinforced by the fact that our proband has two close relatives who suffer or suffered from cluster headache. In fact her son (proband 2), who suffers from otherwise typical episodic cluster headache, regularly experiences attacks of cluster headache sine headache as soon as his normal cluster period is over. Proband 3 suffered from short-lasting unilateral periorbital pain crisis without autonomic phenomena. The markedly increased risk of CH in the relatives of patients with the condition strongly suggests a genetic component (4). In the present family the occurrence of typical cluster headache, chronic pain episodes without autonomic manifestations, and episodic oculo-nasal autonomic outbursts without pain, suggest a common pathogenetic background, probably subserved by the same genetic defect. Episodic and chronic cluster headache have been reported previously in a single family (5).
The increased levels of calcitonin-gene-related-peptide and vasoactive intestinal polypeptide in jugular vein blood on the pain side during cluster headache attacks (6) indicate, respectively, trigeminal and facial nerve parasympathetic activation, i.e. activation of the so-called trigemino-facial reflex (7). In addition, the activation of posterior inferior hypothalamic grey matter homolateral to the pain has been shown during cluster headache attacks (8) and this finding appears to be specific to the condition (9). These observations and the anatomical connections between the hypothalamus and both trigeminal nucleus caudalis (10) and parasympathetic nuclei in the brainstem (11) suggest the hypothalamus as the cluster generator (8, 9). Different activation thresholds for the trigeminal and parasympathetic pathways to hypothalamic stimuli might explain the different combinations of pain and autonomic phenomena observed.
As early as 1988 Sjaastad (12) discussed a possible dichotomy of pain and autonomic symptoms. Thus, in cluster headache sine headache the parasympathetic component of the trigemino-facial circuit would be activated and the trigeminal quiescent. In cluster headache variants characterized by pain only, the trigeminal component would be activated and the parasympathetic component un-activated or perhaps only subclinically activated. The existence of cluster headache sine headache indicates that the autonomic manifestations typically accompanying the pain in cluster headache are not a reaction to that pain, as is also suggested by the fact that they may appear before pain onset (12). So far only three cases of cluster headache sine headache have been reported (3). If new cases are found, the form should be considered for inclusion in the International Headache Society classification as a subtype of cluster headache.