Familial SUNCT in mother and son

Abstract

Background

Trigeminal autonomic cephalalgias comprise a heterogeneous group of lateralized headaches associated with ipsilateral autonomic symptoms. They are usually localized within the territory of one or more rami of the trigeminal nerve, but may be localized outside its cutaneous territory. Although these headaches are considered primary disorders, the evidence supporting their genetic nature is lacking, particularly concerning their neuralgic forms, with the exception of a familial case described partly based on a historical account.

Case reports

We report on a mother and son with episodic, short-lasting, intense, paroxysmal headaches, with the same localization in the left retroauricular region, associated with prominent conjunctival injection and tearing, which are consistent with the diagnosis of SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing).

Discussion

These cases corroborate the existence of hereditary forms of this disorder, thus supporting its primary nature.

Introduction

Trigeminal autonomic cephalalgias (TACs) are a spectrum of intense, lateralized headaches associated with cranial autonomic symptoms (1). They are usually considered primary headache disorders, and are differentiated by their variable temporal profile (ranging from seconds to hours), type of associated autonomic symptoms and response to specific treatment. However, the primary nature of some of these entities has been questioned because of the increasing recognition of secondary forms and considerable overlap between diagnostic criteria. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) in particular has been interpreted as a possible variant of trigeminal neuralgia (TN) of the first division of the fifth cranial nerve (2). It has a brief duration, a shock-like quality, is sometimes associated with facial trigger factors and to neurovascular contacts of the trigeminal nerve and might be relieved by microvascular decompression (3). Also, in TN series, autonomic symptoms are reported in up to 31% of patients (4).

Here, we report on a mother and son with recurrent paroxysmal headaches that fit better the diagnosis of SUNCT. Their identical symptoms, normal neuroimaging and family history support the existence of primary and hereditary forms of this disorder.

Case reports

Patient 1

A 55-year-old female began experiencing headache attacks when she was 39 years of age. These were described as a very severe, sharp, stabbing or shooting pain, with maximal intensity in the left retroauricular temporoparietal region, occasionally radiating to the ipsilateral frontal, periorbital and internal nasal regions (Figure 1). Attacks were short-lasting, usually in the form of single stabs lasting about 10 seconds or series of stabs of up to 3 minutes’ duration, and occurred variably from every 5 to 10 minutes to a few episodes per day. They were associated with prominent ipsilateral lacrimation and conjunctival injection and, sometimes, watery rhinorrhea and facial sweating. Between attacks there was a low-intensity background headache in the same location. Trigger factors included exposure to cold wind, temperature changes, and drinking cold water. There were no aura symptoms, nausea, photophobia, or restlessness, and there was no refractory period. Attacks rarely occurred during the night or awakened her during sleep. The headache was episodic, with symptomatic periods lasting variably from 24 hours to three consecutive months, intercalated with longer (usually more than six months) symptom-free periods. She had a past medical history of arterial hypertension, type 2 diabetes and hyperlipidemia. Physical and neurologic examinations were normal, with no tenderness upon palpation of the occipital nerve, and cranial imaging (computed tomography (CT) and magnetic resonance imaging (MRI)) was unremarkable. During symptomatic periods there was some initial response to indomethacin (up to 225 mg/day), which reduced the intensity of the pain better than analgesics but did not abolish the attacks. Later she responded to lamotrigine (50 mg/day), which interrupted an episode in less than 24 hours, and she had no further attacks for the last five months under this therapy.

Figure 1.

Patients were asked to point to the exact location of their headache attacks (from left to right, Patient 2 and Patient 1). The patients allowed their picture to be published.

Patient 2

A 38-year-old male, one of two children of Patient 1 (Figure 2), reported a headache that started three years before and was described as intense to excruciating attacks of shooting or stabbing pain, localized in the left retroauricular and posterior temporal region, in the same localization as his mother (Figure 1), radiating, when more intense, to the ipsilateral frontal and periorbital regions. There was a low-intensity background pain between attacks. Episodes usually lasted from 30 seconds to one minute, and recurred variably between a few per day to more than 10 per hour. There was prominent lacrimation, conjunctival injection, and sometimes watery rhinorrhea. There were no migrainous symptoms, no restlessness, and attacks occurred only in daytime. The only trigger factor identified was exposure to cold wind. His symptomatic periods lasted from 24 hours to two weeks, and were usually followed by a long asymptomatic period. Neurologic examination and cranial CT were normal. He was prescribed ibuprofen (1800 mg per day) in another center without response.

Figure 2.

Relevant family history (index cases highlighted).

Discussion

We report two close relatives with an identical type of headache, consisting of unilateral, short-lasting, neuralgic paroxysmal attacks with cranial autonomic symptoms, whose temporal profile is better described as SUNCT. Symptoms began at similar ages, slightly earlier in the son, and were independently reported to different doctors.

Headache appeared in single stabs or groups of stabs of very brief duration (seconds to minutes), was strictly lateralized and localized to the retroauricular/inferior parietal region and was associated with conjunctival injection and lacrimation in both patients. Trigger factors included exposure to cold or changing temperature. The course was episodic in both with periods of frequent attacks separated by periods of remission. Therapeutic response was tested only in the mother since the son has been in remission. There was a partial but not dramatic benefit with indomethacin. This finding could suggest the diagnosis of paroxysmal hemicranias (PHs), yet the very short duration of episodes and prominent lacrimation/tearing are more suggestive of SUNCT (Table 1) (1). Also, there was a sustained response to lamotrigine in the mother, which has been more consistently described in SUNCT (5).

Table 1.

Clinical features of Patients 1 and 2, and comparison with other unilateral short-lasting episodic cephalalgias.

	Intensity	Localization	Duration of attacks	Number of attacks	Conjunctival injection and tearing	Other CASa	Triggers	Background headache	Therapeutic response
Patient 1	Severe	Left retroauricular/ temporoparietal region, irradiates to the ipsilateral frontal, periorbital and nasal regions	10 sec–3 min (usually single stab)	>1 attack/day, up to every 5 min	Yes	Rhinorrhea, facial sweating	Sometimes	Yes (during symptomatic periods)	Indomethacin 225 mg/day (incomplete response)
Lamotrigine 50 mg/day
Patient 2	Severe to excruciating	Left retroauricular / temporoparietal region (same as Patient 1), radiates to ipsilateral frontal and periorbital regions	30 sec– 1 min (single stab)	>1 attack/day, up to 10/hour	Yes	No	Sometimes	Yes (during symptomatic periods)	Ibuprofen 600 mg tid (partial response)
SUNCT	Moderate or severe	Strictly unilateral; orbital, supraorbital, temporal and/or other trigeminal distribution	1 sec–10 min (single stabs, series of stabs or saw-tooth pattern)	>1 attack/day (> half the time when disorder active)	Both	Frequent	Usually	About 30%	Lamotrigine
SUNA	Moderate or severe	Strictly unilateral; orbital, supraorbital, temporal and/or other trigeminal distribution	1 sec–10 min (single stabs, series of stabs or saw-tooth pattern)	>1 attack/day (> half the time when disorder active)	Only one or neither	Frequent	Usually	About in 25%	Lamotrigine
Paroxysmal hemicrania	Severe	Strictly unilateral; orbital, supraorbital, temporal or any combination	2–30 min	>5 attacks/day (> half the time when disorder active)	Frequent	Frequent	Sometimes	Possible	Prevented by Indomethacin 150–300 mg (absolute response)
Primary stabbing headache	Stabbing	70% extratrigeminal; may move from one area to another, in either the same or opposite hemicranium; one-third of patients have a fixed location	Single stab or series of stabs	Generally low frequency (one, a few, to many/day)	No	No	No	No	NSAIDs
80% of stabs ≤3sec)
Trigeminal neuralgia	Severe, electric shock-like, shooting, stabbing or sharp	Distribution of one or more V divisions (no radiation beyond V distribution)	Fraction of a second to 2 min	Variable	May be present (mild)	No	Common	Possible	Medical and surgical
Occipital neuralgia	Severe, shooting, stabbing or sharp	Distribution of GON, LON, third ON; may reach fronto-orbital area	Few seconds to minutes	Variable	No	No	Frequent (nerve emergence)	Possible	Anesthetic bloc

CAS: cranial autonomic symptoms; GON: greater occipital nerve; LON: lesser occipital nerve; NSAIDs: nonsteroidal anti-inflammatory drugs; SUNA: short-lasting, unilateral, neuralgiform headache with cranial autonomic symptoms. ^aNasal congestion and/or rhinorrhea, eyelid edema, forehead and facial sweating, forehead and facial flushing, sensation of fullness in the ear, miosis and/or ptosis; SUNCT: short-lasting, unilateral, neuralgiform headache with conjunctival injection and tearing.

The absence of underlying structural pathology, the benign nature of the disorder and its family occurrence suggest a primary, eventually hereditary/genetically determined type of headache, thus reinforcing the primary nature of this TAC.

Another curious aspect of both cases is their identical initial and maximal intensity pain location, that is, the posterior temporal/retroauricular region. This retroauricular location is not acknowledged by the International Classification of Headache Disorders, third edition beta (ICHD-IIIb) criteria of SUNCT or PH (1), yet it is frequently reported (6–8). It raises questions regarding pain origin in our cases. If the origin is intracranial, it could correspond to meningeal rami of the trigeminal nerve, hence being of trigeminal origin. This would be in accordance with the fact that pain location in SUNCT, compared with other TACs, is more consistently in the trigeminal (mainly ophthalmic) territory (6). However, if one considers the pain origin to be extracranial, then this would more likely correspond to the cutaneous territory of the lesser occipital nerve (or posterior branch of the greater auricular nerve), then radiating to the frontal, periorbital and nasal regions, i.e. ophthalmic nerve. The overlap between the trigeminal nucleus caudalis and the dorsal horn of C1–C2 cervical roots, constituting the trigeminocervical complex, facilitates the radiation of pain between trigeminal and extratrigeminal regions.

A familial case of SUNCT has been described in the literature (9) in which one patient had trigeminal pain (left V1 territory) but the localization in not known in the sister whose data were taken retrospectively. SUNCT has also been described in a case series of 10 patients with simultaneous diagnosis of hemiplegic migraine, raising the question about the relation between these two disorders (10). Of these, only one patient had the diagnosis of familial hemiplegic migraine but there is no report of familial SUNCT in that family. There has also been a description of paroxysmal hemicrania in two family members, also with a (cutaneous) trigeminal location (11). Interestingly, Riederer et al. described three cases in a family with occipital and nervus intermedius neuralgia, in two of whom the location of the headache is strikingly similar to our cases (12). No cranial autonomic symptoms were present, however, ruling out TAC diagnosis.

While all TACs should be investigated by neuroimaging for the search of secondary causes, one must be aware that they are mostly primary headache disorders and can be familial, thus stressing the need of future genetic studies in such patients.

Clinical implications

A mother and son with identical headaches fitting the diagnosis of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) are described.

This report supports the familial, genetic nature of this rare form of headache whose cause is unknown.

It corroborates the construct of SUNCT as a distinct clinical entity, separate from secondary cranial neuralgias.