Abstract
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare type of primary headache. In this report we describe the occurrence of SUNCT in a family. Unfortunately, one of the siblings was already dead. However, clear and detailed information from close relatives and her general practitioner confirmed the diagnosis of SUNCT. It is likely that genetic factors contribute to all types of trigeminal autonomic cephalalgias.
Introduction
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) (1) is a rare type of primary headache classified among the trigeminal autonomic cephalalgias (TACs) (2). The prevalence is very difficult to estimate since formal diagnostic criteria have only recently been agreed (3). There are only about 50 case reports published in English literature to date (4). The prevalence of SUNCT is almost certainly less than the prevalence of cluster headache, which is about 0.2% (5). A fundamental question in headache is why primary headache syndromes occur at all. For migraine (6) and cluster headache (7, 8) the evidence for an important familial component is relatively clear. For rarer headache types this becomes a more problematic question.
In this report we describe for the first time the occurrence of SUNCT in the same family. Unfortunately, one of the two siblings deceased 6 years before we saw the index case. However, we were able to speak to a close relative and her general practitioner who gave a clear account of her symptoms.
Cases
Case 1—P.F.
This 65-year-old male presented in 2003 with a 10-year history of left-sided facial pain (Fig. 1). His pain involved the vertex with radiation behind the eye, to the nasal inner canthus and naso-labial fold. The character was described as sharp and stabbing. Typically the pain lasted 3 min but with a range from a few seconds up to 10 min. The severe attacks occurred every 10–30 min, mostly during the day but also at night. The pain was associated with ipsilateral lacrimation, conjunctival injection, periorbital swelling, ptosis, rhinorrhoea and facial flushing. There were no aura symptoms, but occasional nausea and left-sided photophobia. He felt restless during attacks. Triggers included touch in the parietal, temporal and naso-ocular region, wind, chewing, bright lights, loud sounds and heat, and there was no refractory period. He could get a little relief by blowing the nose, sneezing and rubbing left-sided on the back of the head. Alcohol did not trigger attacks. He was on Carbamazepine 1600 mg and Temazepam 10 mg at night.
The family tree of the cases described. The proband, a male (□), is indicated (arrow), as is his affected sister (○), who is deceased.
Previous medication and therapy included, with daily doses, morphine (20 mg), nabilone, cannabis, amitriptyline (25 mg), sertraline, gabapentin (1800 mg), amantadine, mexiletine, baclofen, intravenous ketamine, intravenous and intranasal lidocaine, intranasal EMLA, TENS to the forehead, acupuncture, left infra-orbital and greater occipital nerve injections. The latter gave him his longest remission of 1 day. None of these had a particular or longer lasting effect. He had been reviewed in ophthalmology and ENT departments with no diagnosis to account for his symptoms. Computed tomography (CT) scans in 1995 were normal but magnetic resonance imaging (MRI) of the brain in 1996 suggested an enlarged blood vessel on the left.
On examination he had reduced sensation to light touch and pinprick in the distribution of the infra-orbital nerve on the left and no corneal reflex on the left.
He was admitted to the ward for further investigation. Glycerol trinitrate (GTN), high-flow oxygen (100% at 12 l/min), intravenous lidocaine (discontinued on 45 ml/h because of side-effects) and intramuscular indometacin (100 mg) did not have any effect on his headache. MR-angiography and MRI with views of the trigeminal nerve did not reveal any abnormalities and several blood tests did not show significant changes, apart from high cholesterol.
An out-patient trial with lamotrigine up to 175 mg did not reduce attack frequency, but reduced intensity from 8 to 10 out of 10 on a verbal rating scale to 3–5. However, the drug was not tolerated because of severe side-effects, such as nausea, rashes, paraesthesia and cramps.
Case 2—E.C.
This female patient died in 1997 at the age of 79 from ischaemic heart disease, approximately 2–3 years after her headache problem ceased. The history is based on information from her brother case 1, her daughter and her GP.
The headache was described as severe right-sided sharp electric-shock-like pain. For more than 9 years she suffered several attacks a day which could last 1–2 min. The pain was associated with ipsilateral conjunctival injection and tearing as well as rhinorrhoea, each of which was noted by her daughter. Her daughter commented that she had thought that her mother was crying but considered it odd that she cried from only one eye. Her daughter noted trigger factors of wind, cold temperature and sun. She did not complain of nausea, photophobia or phonophobia and did not have any obvious changes in pupil diameter. Her other medical history, obtained from her GP's records, included: coronary heart disease, renal dysfunction, a minor stroke in 1987 with persistent left facial weakness, glaucoma with visual field constrictions, and in her later years probable Parkinson's disease.
In 1985 she was seen by anaesthetists in a pain clinic and her problem was diagnosed as trigeminal neuralgia. CT scans of the brain showed no abnormality.
Discussion
Two cases of short-lasting unilateral headache attacks with ipsilateral conjunctival injection and tearing are presented. The index case fulfils current criteria for SUNCT (3) and the diagnosis seems safe. We postulate that the infra-orbital sensory loss is iatrogenic and is a traumatic neuropathy. For his sister the history, although obtained second hand, would also fulfil these criteria. If the diagnosis is accepted in case 2 then it seems improbable that two cases occurred in the same family by chance and we would submit this as the first description of familial SUNCT.
While it is widely accepted that migraine has a significant (6), if not determining genetic component (9), the genetics of other primary headaches is less clear. The description of clear genetic mutations in familial hemiplegic migraine (10, 11) has certainly spurred a search for genes in migraine. For the TACs (2) this question is in its infancy. It seems to us unlikely that the TACs will not have some predisposing component, and this seems logically to be genetic.
For cluster headache there are clinical data to suggest a genetic predisposition. There have been clinical reports of cluster headache in families (12, 13), as well as in several twin pairs (14–16). There is a strong risk of cluster headache in the first-degree relatives of patients with the condition (17). One large recent study reported a 39-fold increase risk (18), while another reported a positive family history of cluster headache in 20 index patients (10.8%) with 22 affected first-degree relatives (3.4%) (8). Taken together, these observations suggest that a genetic component will be identified for cluster headache. There are no similar data for paroxysmal hemicrania.
The major limitation of this report is that the second case was dead and we can rely only on her GP's records, and her daughter's recollection. We were impressed by her unprompted comment concerning the ‘unilateral crying’. Furthermore, she had been diagnosed as having trigeminal neuralgia by pain specialists; this is a common misdiagnosis in SUNCT patients in our experience. Cranial autonomic symptoms are seem in first division trigeminal neuralgia (19), but in our experience these are minor. Prominent cranial autonomic symptoms, particularly lacrimation, are an important diagnostic marker of SUNCT and often assist in the differential diagnosis from trigeminal neuralgia (20). Considering all the clinical features it seems more than likely that case 2 had SUNCT.
These cases represent the first description of familial SUNCT. We think it likely that the general principle will be extended to paroxysmal hemicrania, and that TACs will ultimately be shown to be primarily determined on a genetic basis.