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Curr Pain Headache Rep (2013) 17:323

DOI 10.1007/s11916-013-0323-1

TRIGEMINAL AUTONOMIC CEPHALALGIAS (M MATHARU, SECTION EDITOR)

Management of Trigeminal Autonomic Cephalalgias


in Children and Adolescents
Giorgio Lambru & Manjit Matharu

Published online: 9 March 2013


# Springer Science+Business Media New York 2013

Abstract Primary headache disorders that are more frequently years before the diagnosis is made. Awareness of typical clin-
encountered in the paediatric population include migraine and ical pictures of these excruciating headaches is essential to
tension-type headaches. The trigeminal autonomic cephalalgias allow prompt initiation of the appropriate management.
(TACs), which includes cluster headache (CH), paroxysmal
hemicrania (PH) and short-lasting unilateral neuralgiform Keywords Childhood onset headache . Cluster headache .
headache attacks with conjunctival injection and tearing Paroxysmal hemicrania . SUNCT . Paediatric headache .
(SUNCT), are rarely reported in the paediatric population. Trigeminal autonomic cephalalgias
The 1-year prevalence of CH seems to be 0.03 %. The clinical
features of childhood and adolescence onset CH seem to be
similar to those of adult onset. Cranial autonomic features and Introduction
restlessness seem to less prominent in children than in adults.
When restlessness is present, it often manifests as thrashing The trigeminal autonomic cephalalgias (TACs) are a
around in children and can distract attention from the headache, group of primary headache disorders characterized by
thereby contributing to a delay in diagnosis. The frequency of unilateral head pain that occurs in association with prom-
cluster periods seems to be lower in childhood. Similarly, the inent ipsilateral cranial autonomic features. The TACs
duration of the single cluster period seems to be shorter. The include cluster headache (CH), paroxysmal hemicrania
temporal pattern shows a trend towards a gradual increase of (PH) and short-lasting unilateral neuralgiform headache
frequency and duration of symptoms in adult life. In terms of attacks with conjunctival injection and tearing (SUNCT).
management of paediatric CH, oxygen has been used success- CH, PH and SUNCT are currently grouped into section 3 of
fully in several paediatric CH patients, and given its good side- the revised International Classification of Headache Disorders
effect profile, it is considered the abortive agent of choice for (ICHD-II).
paediatric CH. Verapamil is the preventative drug of choice in The TACs are relatively rare in the adult population and are
both episodic and chronic CH, though paediatric patients considered to be even more rare in the pediatric population.
should be started on lower doses and titrated according to Childhood and adolescent onset TACs resemble the adult forms
age. Paediatric-onset PH and SUNCT are very rarely reported. of the disorders with regard to the characteristics of the pain, the
The clinical phenotype and response to treatment seem to associated symptoms and response to treatments. Nonetheless,
resemble the adult-onset form. Paediatric-onset TACs are poor- pediatric-onset TACs are poorly recognized and there is often a
ly recognized and there is often a delay of several months or delay of several years before the diagnosis is made.
While the TACs can be recognized by distinctive short-
lasting headaches with autonomic features, they differ in
This article is part of the Topical Collection on Trigeminal Autonomic attack duration and frequency. The differentiation between
Cephalalgias
the TACs is essential, since the treatments are very different.
G. Lambru : M. Matharu (*) These syndromes are considered to be some of the most
Headache Group, Institute of Neurology, The National Hospital
painful known to humankind, thereby underlining the im-
for Neurology and Neurosurgery, Queen Square, London
WC1N 3BG, UK portance of early recognition and initiation of the excellent
e-mail: m.matharu@uclmail.net but highly selective treatments.
323, Page 2 of 10 Curr Pain Headache Rep (2013) 17:323

Cluster Headache The clinical features of childhood and adolescence onset


CH attack seem to be similar to those of adult onset CH.
CH is a strictly unilateral headache that occurs in association Maytal et al. reviewed the phenotype of 35 paediatric-onset
with cranial autonomic features and, in most patients, has a CH patients. Pain was felt in and around the eye in 31
striking circannual and circadian periodicity. It is an excru- patients (88 %). It commonly radiated to the temple
ciating syndrome, with female patients describing each at- (43 %), to the ipsilateral maxilla (40 %) and to the ipsilateral
tack as being worse than childbirth. forehead (20 %). Common descriptions of the pain used
were: burning, piercing, tearing, and boring. The majority
Epidemiology of patients described their pain as severe [8]. Although it has
been suggested that cranial autonomic features may be less
The prevalence of adult CH is estimated to be 0.1 % [1]. CH prominent in children than in adults [6•], the distribution of
can begin at any age, though the most common age of onset is ocular, nasal and facial autonomic symptoms reflects the
the third or fourth decade of life. The first publications about distribution in adult onset forms of CH. Lacrimation of the
cluster headache in childhood were in the early 1970s [2, 3]. In eye has been reported to be the most common symptom in
1981, an interesting description of cluster headache symptoms childhood CH, followed by conjunctival injection and nasal
in an infant was reported [4]. At the beginning of the attack, the discharge. Ptosis and nasal congestion were reported less
infant became irritable and unmanageable, touching and rub- frequently, whereas meiosis and flushing and sweating of
bing his forehead at the region of his right eye. The eye then the face and/or body were reported only in few patients [8].
began watering; the right eye demonstrated ptosis, and the skin Restlessness during CH seems to be less frequently reported
in the region involved with pain was warm to the touch. The during CH attacks compared to adult onset CH [10]. In a
infant had one to two attacks daily, almost all of them occurring retrospective phenotyping study of paediatric onset CH
in the daytime, with spontaneous remission lasting no more patients, restlessness has been noted in nine out of 14
than three days. When the child was three years of age, the patients (64 %) [11•]. Subsequently, another three cases of
attacks ceased spontaneously. paediatric CH, with a long follow-up, were described. The
The onset of CH in the paediatric population is well authors noted prominent cranial autonomic features in all of
reported, though the prevalence seems to be relatively low. them, though only one patient was agitated during attacks
A multicentre paediatric study in 27 Italian headache centres [12]. When present, restlessness often manifests as thrashing
on 6,629 headache patients less than 18 years of age around in children and can distract attention from the head-
reported the 1-year prevalence of CH to be 0.03 % [5]. ache, thereby contributing to a delay in diagnosis [13].
Childhood-onset CH shows a male preponderance with a Other associated symptoms normally occurring in migraine,
ratio of 2.5:1 [6•], similar to that observed in the adult population such as nausea, vomiting, photophobia and phonophobia have
[7]. The mean age of onset of CH in childhood and adolescence been reported in paediatric CH patients. In a retrospectively
is 11–14 years, with a wide range of 3–18 years [8]. analysed series, seven out of 35 patients reported nausea during
Genetic factors appear to be involved in the same pro- CH attacks (20 %) [8]. Photophobia and phonophobia were
portion of the paediatric population as in the adult popula- also reported in another retrospective series of paediatric onset
tion. In a recent review [6•], a positive family history for CH CH [14]. Aura is now recognized as a clinical symptom of CH
has been found in approximately 10 % of pediatric CH [15]. Up to 20 % of CH patients can experience aura symp-
cases, whereas a positive family history for migraine was toms, a similar percentage of migraine sufferers who have aura.
found in 25 %. Awareness that focal transient neurological symptoms can
accompany CH attacks and not only migraine is very helpful
Clinical Features for the differential diagnosis of these two conditions in paedi-
atric patients.
The Cluster Attack The cluster attack frequency varies between one every
alternate day to three daily, although some have up to eight
Cluster attacks are strictly unilateral, though the headache daily. In two series of pediatric onset CH, the majority of
may alternate sides. It is centred around the orbital and patients reported one or less than one attack a day [8, 11•].
temporal regions, though any part of the head can be affect- Circadian rhythmicity, which is a cornerstone feature of CH,
ed. The pain is excruciatingly severe. The headache can has been reported also in pediatric patients.
range from 15 minutes to 3 hours. The signature feature of Alcohol, exercise, elevated environmental temperature
CH is the association with cranial autonomic symptoms [9]. and the smell of volatile agents are recognised precipitants
The autonomic features are transient, lasting only for the of acute cluster attacks. Alcohol induces acute attacks, usu-
duration of the attack, with the exception of partial Horner’s ally within an hour of intake, in the vast majority of suffer-
syndrome. ers, though in paediatric age this trigger is less helpful.
Curr Pain Headache Rep (2013) 17:323 Page 3 of 10, 323

The Cluster Bout duration of CH periods, respectively, in adulthood. Con-


versely, only four patients (11 %) reported a decrease in
CH is classified according to the duration of the bout. About frequency and two patients (6 %) reported a decrease in
80–90 % of patients have episodic cluster headache (ECH), duration of their cluster periods during their adulthood [8].
which is diagnosed when they experience recurrent bouts,
each with a duration of more than a week and separated by Differential Diagnosis
remissions lasting more than four weeks. The bouts typical-
ly occur once or twice a year. Often, a striking circannual The main differential diagnoses to consider are: secondary
periodicity is seen with the cluster periods, with the bouts causes of CH, other TACs (see Table 1) and migraine.
occurring in the same month of the year. The remaining 10– Symptomatic CH has been described with infectious, vas-
20 % of patients have chronic cluster headache (CCH), in cular and neoplastic intracranial lesions. However, the true
which either no remission occurs within one year, or the prevalence of symptomatic causes of CH is unknown, as there
remissions last less than one month [9]. are no prospective population-based neuroimaging studies. A
The frequency of cluster periods seems to be lower in review of retrospective case reports published in the medical
childhood. Similarly, the duration of the single cluster peri- literature suggests that the TACs may be associated with
od seems to be shorter [6•]. It has also been observed that pituitary tumours, though this most likely reflects a consider-
the temporal pattern shows a trend towards a gradual in- able element of publication bias [16].
crease of frequency and duration of symptoms in adult life. Differentiating between migraine and CH can be difficult in
In a series of 35 childhood onset CH patients, 13 (37 %) and some cases, as unilaterality of pain and presence of migrainous
14 patients (40 %) reported an increase of frequency and and autonomic symptoms are features common to both. The

Table 1 Clinical features of the


trigeminal autonomic Cluster Paroxysmal SUNCT
cephalalgias headache hemicrania

Sex M:F 2.5–7.2:1 1:1 1.5:1


Pain:
Type Sharp, throbbing Sharp, throbbing Stabbing, burning
Severity Very severe Very severe Very severe
Site Orbit, temple Orbit, temple Periorbital
Attack frequency 1/alternate day −8/day 1–40/day (> 5/day 3–200/day
for more than half
the time)
Duration of attack 15–180 min 2–30 min 5–240 sec
Circadian periodicity 70 % 45 % Absent
Autonomic features Yes Yes Yesa
Restless or agitated 90 % 80 % 65 %
Migrainous features Yes Yes Rare
Triggers:
Alcohol Consistent Less consistent Never
Cutaneous Never Never Consistent
Indometacin effect – ++ –
Abortive treatment Sumatriptan injection Nil Nil
++ indicates absolute response Sumatriptan or Zolmitriptan
to Indometacin, + indicates some nasal spray
response, – indicates no
Oxygen
response
Prophylactic treatment Verapamil Indometacin Lamotrigine
SUNCT Short-lasting unilateral
neuralgiform headache attacks Methysergide Topiramate
with conjunctival injection and Lithium Gabapentin
tearing; IV intravenous; GONB Topiramate
Greater occipital nerve block
a
Transitional treatment Corticosteroids GONB GONB
Prominent conjunctival injection GONB
and lacrimation by definition
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features that can be useful in distinguishing CH from migraine Subcutaneous and Intranasal Triptans. Subcutaneous suma-
include: relatively short duration of headache, rapid onset and triptan is the most effective abortive treatment for cluster
cessation, circadian periodicity, precipitation within an hour by headache [18]. In CH, unlike in migraine, subcutaneous suma-
alcohol, restlessness or agitation during the attack and cluster- triptan can be prescribed at a frequency of twice daily, on a
ing of attacks with intervening remissions in ECH. long-term basis if necessary, without risk of tachyphylaxis or
rebound [19, 20]. Sumatriptan and zolmitriptan nasal spray are
Investigations both more effective than placebo [21, 22]. While experience
with the use of subcutaneous sumatriptan in the pediatric
The diagnosis of CH is made entirely on the basis of a good population is limited, Sumatriptan nasal spray has been shown
clinical history and a detailed neurological examination. to be well tolerated in children between 12 and 17 years old at
Any atypical features in the history or abnormalities on the dose of 20 mg, in randomized, placebo-controlled studies
neurological examination (with the exception of partial in migraine [23].
Horner’s syndrome) warrant further investigations to search
for organic causes. It remains unclear whether every TAC Transitional Treatments
patient requires neuroimaging; if it is considered, then mag-
netic resonance imaging (MRI) is the preferred modality. Corticosteroids. Corticosteroids are highly efficacious and
Given the rarity of CH in childhood and adolescence, it the most rapid acting of the preventative agents [24]. Cau-
seems reasonable to offer neuroimaging to all paediatric tion has to be exercised in their use because of the potential
patients to exclude a symptomatic cause. for serious side effects. Treatment is usually limited to a
short intensive course of 2–3 weeks in tapering doses be-
Treatment cause of the potential for side effects [25]. Unfortunately,
relapse almost invariably occurs as the dose is tapered. For
Management of paediatric CH (and other TACs) is not well this reason, steroids are used as an initial therapy in con-
substantiated by appropriate studies and is derived almost junction with preventives, until the latter are effective.
exclusively from experience in adult patients. Currently, there In adolescence, a marked relief of cluster headache in 59
are both medical and surgical interventions available for these (77 %) of 77 ECH patients, and a partial relief in another
patients. Medical management falls into one of three catego- 12 % of patients treated with prednisone was reported [26].
ries; acute, preventive or transitional therapies. Acute or abor- A report of sustained efficacy of intravenous (IV) prednis-
tive treatment is given at the onset of an attack and is aimed at olone in a 7-year-old female has been reported. In this case,
aborting the attack itself, whilst the aim of preventive medica- prednisolone was started at 50 mg IV and reduced every
tion is to produce a rapid suppression of attacks and maintain fourth day (50 mg IV for 3 days, 25 mg for the next 3 days,
that remission while the patient is still in a bout. However, 15 mg IV for the following 3 days, and 5 mg for the last
preventive treatments generally need to be titrated to an opti- 3 days of the therapy), leading to the termination of attacks
mum dose, and therefore there can be a delay of a few days to on the third day of the treatment and allowing a subsequent
weeks before their beneficial effect emerges. Transitional treat- pain-free period for several months [27].
ments are therapies that can be used to rapidly suppress the
attacks, but are only effective for a few days to weeks and can Greater Occipital Nerve (GON) Block. Injection of local
therefore be very helpful while waiting for the preventive anaesthetic and corticosteroid around the GON on the af-
treatments to work. Surgical treatments are generally avoided fected side can abort a bout of cluster headache [28].
until the medical treatments are exhausted. Though there are no reports on the use of GON blocks in
paediatric CH, it is an excellent short-term strategy, with
Abortive Agents only very modest, infrequent side effects.

Because the pain of CH builds up so rapidly, the most Preventive Treatments


efficacious agents are those that involve parenteral or pul-
monary administration. The preventive agents used in the management of CH in-
clude verapamil, lithium, topiramate, methysergide, gaba-
Oxygen. Inhalation of 100 % oxygen, at 7–12L/min, is rapidly pentin, melatonin and valproate. Verapamil is the agent of
effective in relieving pain in the majority of sufferers [17]. It choice. While the other agents are often used, the evidence
should be inhaled continuously for 15–30 minutes via a non- base for their use is poor. Table 2 provides an overview of
rebreathing facial mask. Oxygen has been used successfully in the recommendations for CH preventive treatments by the
several paediatric CH patients [6•], and given its good side- European Federation of Neurological Societies (EFNS) [29]
effect profile, it is the abortive agent of choice for paediatric CH. and the American Academy of Neurology (AAN) [30].
Curr Pain Headache Rep (2013) 17:323 Page 5 of 10, 323

Table 2 Preventive treatments of cluster headache

Level of evidence Level of evidence Monitoring Common side effects


(EFNS)(19) (AAN)(20)

Verapamil A C ECG monitoring for cardiac Hypotension, constipation,


arrhythmias peripheral oedema
Lithium B C Lithium levels, renal function, Diarrhoea, tremor, polyuria
thyroid function
Topiramate B Not rated Paraesthesias, weight loss, cognitive
dysfunction, fatigue, dizziness,
taste alteration
Methysergide B Not rated Annual visceral fibrosis screening: Nausea/vomiting Muscle cramps,
Echocardiogram, Chest x-ray Abdominal pain, Peripheral oedema,
Abdominal and pelvis MRI Retroperitoneal fibrosis (rare)
scan Relevant blood tests
Gabapentin Not rated Not rated Somnolence, fatigue, dizziness,
weight gain, peripheral oedema, ataxia
Melatonin C C Fatigue, sedation
Sodium C B Full blood count, liver function Weight gain, fatigue, tremor,
valproate hair loss, nausea

ECG electrocardiogram; MRI magnetic resonance imaging

Verapamil. Verapamil is the preventative drug of choice in deep brain stimulation or occipital nerve stimulation (ONS)
both episodic and chronic CH [31]. There are reports of have emerged. These approaches are very promising, and
efficacy of verapamil in children at doses between 120 mg ONS especially offers a more acceptable side effect profile
and 240 mg, though this agent is often used at doses of up to than destructive and invasive approaches [32•].
960 mg daily in adults. Verapamil can cause heart block by
slowing conduction in the atrioventricular node. Observing
for PR interval prolongation on ECG can monitor potential Paroxysmal Hemicrania
development of heart block. There is only one formal guide-
line in the literature for the titration of the verapamil dose in PH, like CH, is characterized by strictly unilateral, brief
adults [25], which recommends starting patients on 240 mg headaches that occur in association with cranial autonomic
daily and incrementing the dose in steps of 80 mg every features. PH differs from CH mainly in the higher frequency
2 weeks under ECG guidance. The dose is increased until and shorter duration of individual attacks, though there is a
the cluster attacks are suppressed, side effects intervene or considerable overlap in these characteristics. However, un-
the maximum dose of 960 mg daily is achieved. In the like CH, PH responds in a dramatic and absolute fashion to
paediatric population, we recommend starting at a lower indometacin [9], thereby underlining the importance of dis-
dose of 40–80 mg daily and titrating the dose in steps of tinguishing it from CH.
40 mg, up to 360 mg a day in total.
Epidemiology
Surgery
PH is a very rare syndrome. The prevalence of PH is not
In adults, medically intractable CCH is a rare but highly known, but the relationship compared to CH is reported to
disabling disorder, and it is therefore appropriate to consider be approximately 1–3 %. The most common age of onset is
surgical interventions in these patients. There are no reports of the second or third decade of life, though there is a wide
surgical intervention for the management of pediatric CH, range of age of onset (1–68 years), with several case reports
though medically refractory CCH cases are described [6•]. of onset before the age of 18 years [33–40]. PH seems to be
Surgery is a last-resort measure in treatment–resistant patients, equally prevalent in females and males [33].
and should only be considered when the pharmacological
options have been exploited to the fullest. Historically, de- Clinical Features
structive procedures involving the trigeminal nerve have been
tried in CH. However, they are associated with considerable The clinical phenotype of PH is highly characteristic [33, 41].
morbidity and therefore have largely been abandoned. Most The pain is strictly unilateral and centred around the orbital
recently, neurostimulation therapies with either hypothalamic and temporal regions, though any part of the head can be
323, Page 6 of 10 Curr Pain Headache Rep (2013) 17:323

affected. It is excruciatingly severe. The headache usually occurring within 1–2 days of initiating the effective dose.
lasts 2–30 minutes. Attacks of PH invariably occur in associ- The typical maintenance dose ranges from 25 to 100 mg
ation with ipsilateral cranial autonomic features. Up to 85 % of daily, but doses up to 300 mg daily are occasionally required
patients report at least one migrainous feature of photophobia, [43]. In children from 1 month to 18 years of age, the dose
nausea or vomiting during an attack. Similar to CH, patients of 0.5–1 mg/kg twice daily should be used. Talvik et al.
are often restless or agitated during an attack. The attacks described a 3-year-old female with a year history of CPH
occur at a high frequency. Typically, patients have more than who responded dramatically to 50 mg of indometacin, be-
five attacks daily, though the frequency of attacks shows a coming pain-free. Interestingly, although the symptoms
considerable fluctuation, ranging between one and 40 daily. were typical for PH, she has been diagnosed 10 months after
The attacks occur randomly throughout the 24-hour period, the onset of the symptoms [40]. This case highlights the
without a preponderance of nocturnal attacks as in cluster importance of recognising the possible childhood onset of
headache. While the majority of attacks are spontaneous, this disorder.
common triggers include stress, release from stress, exercise,
alcohol ingestion and neck movement [33]. Other Medications
PH is classified depending on the presence of a remission
period. About 35 % of patients have episodic paroxysmal For patients who cannot tolerate indomethacin, one faces a
hemicrania (EPH), which is diagnosed when there are clear difficult challenge. No other drug is consistently effective in
remission periods between bouts of attacks. The remaining PH. Other drug therapies that have been reported to be
65 % of patients have chronic paroxysmal hemicrania (CPH) effective in PH include cyclooxygenase-2 inhibitors, calci-
(26), which is diagnosed when patients have either no remis- um channel antagonists (verapamil, Flunarizine), topiramate
sion within one year, or the remissions last less than one or greater occipital nerve blocks [43].
month [9].

Differential Diagnosis SUNCT

The differential diagnoses that need to be considered are: Short-lasting unilateral neuralgiform headache attacks
secondary causes of PH, other TACs and hemicrania con- with conjunctival injection and tearing (SUNCT), as its
tinua (HC). A large number of symptomatic cases of PH, name implies, is a disorder characterised by strictly
caused by diverse pathological processes at various intracranial unilateral, severe, neuralgic attacks centred on the oph-
sites, have been described, though a causal relationship is thalmic trigeminal distribution that are brief in duration
difficult to ascertain in most of these cases [16]. PH can be and occur in association with both conjunctival injection
differentiated from CH and SUNCT with a trial of indometa- and lacrimation [9].
cin. HC is a strictly unilateral headache that is continuous and
associated with ipsilateral cranial autonomic symptoms. Both Epidemiology
PH and HC are exquisitely responsive to indomethacin, and
can be differentiated on the basis of the clinical phenotype [42]. SUNCT is relatively rare, with a recent study showing a
prevalence of 6.6 per 100,000 population [44]. SUNCT has
Investigations a slight male predominance, with a sex ratio of 1.5:1 [45].
The typical age of onset is between 40 and 70 years, with a
As a relatively high number of symptomatic cases have been mean age of onset of 48 years and a range between 2 and
reported, an MRI brain scan should be routinely performed 77 years. Pediatric-onset SUNCT is very rare, with only five
in all PH patients. case reports in the literature [46–50].

Treatment Clinical Features

The treatment of PH is entirely preventive, as attacks are too The attacks are strictly unilateral, though may alternate
short and intense for any acute oral treatment to be effective. sides. The pain is usually maximal in the ophthalmic
distribution of the trigeminal nerve, but can radiate to
Indometacin any part of the head. The pain has an excruciating
intensity and a neuralgic quality. The individual attacks
Indometacin is the treatment of choice and, in fact, has been are relatively brief, lasting between 5 and 240 seconds.
deemed the sine qua non for establishing the diagnosis [9]. Three different types of pain have been described in
Complete resolution of the headache is prompt, usually SUNCT syndrome: single stabs; groups of stabs and a
Curr Pain Headache Rep (2013) 17:323 Page 7 of 10, 323

Table 3 Differentiating Features of SUNCT and trigeminal neuralgia very short-lasting, spontaneous, strictly unilateral but
Feature SUNCT Trigeminal neuralgia alternating side attacks, associated with lacrimation
and conjunctival injection. The patient did not require
Male: female ratio 1.5:1 1:2 any treatment, since the headache disappeared sponta-
Site of pain V1 V2/3 neously a few months after the onset [46]. Subsequent-
Duration (seconds) 5–240 <5 ly, a second case of young onset SUNCT was reported
Autonomic features Prominent Sparse or none in a 5-year-old male. His bout lasted five months and
Refractory period Absent Present no relapses were reported after a year of follow-up
[48]. More recently, a 6-year-old male with idiopathic
SUNCT Short-lasting unilateral neuralgiform headache attacks with SUNCT was described. Compared to the previous
conjunctival injection and tearing
cases, the headache lasted for 4 years and responded
to lamotrigine [49].
saw-tooth pattern in which repetitive spike-like parox-
ysms occur without reaching the pain-free baseline be- Differential Diagnosis
tween the individual spikes. By definition, all SUNCT
patients had both ipsilateral conjunctival injection and The differential diagnosis of very brief headaches includes:
lacrimation associated with their attacks [9]. Patients are SUNCT (primary and secondary forms), trigeminal neural-
often restless or agitated during the attacks [45]. The gia, primary stabbing headache and PH.
attack frequency during the symptomatic phase varies Secondary SUNCT is typically seen with either pos-
immensely between sufferers and within an individual terior fossa or pituitary gland lesions [51]. A case of
sufferer. Attacks may be as infrequent as once a day, or secondary SUNCT in an 11-year-old girl, due to an
less to more than 60 per hour. astrocytoma of the ipsilateral pontocerebellar angle was
The majority of patients can precipitate attacks by touch- reported. After the partial removal, the pain attacks
ing certain trigger zones within trigeminal innervated distri- persisted, but were shorter and less intense [47]. The
bution and, occasionally, even from an extra-trigeminal case emphasizes the need for brain MRI, even in
territory. Precipitants include touching the face or scalp, patients presenting with typical SUNCT and without
washing, shaving, eating, chewing, brushing teeth, talking neurologic deficits, as in the aforementioned case.
and coughing. Unlike in trigeminal neuralgia, most patients In addition, a recent study systematically looked for tri-
have no refractory period. geminal neurovascular conflict with dedicated trigeminal MRI
The temporal pattern is quite variable, with the symp- scans, and found a high proportion of ipsilateral vascular
tomatic periods alternating with remissions in an erratic loops in contact with the trigeminal nerve in SUNCT [44].
manner. Symptomatic periods generally last from a few days Differentiating SUNCT from trigeminal neuralgia can
to several months and occur once or twice annually. Remis- be challenging in some cases, as there is a considerable
sions typically last a few months, yet can range from 1 week overlap in the clinical phenotypes of the two syn-
to 7 years. Symptomatic periods appear to increase in fre- dromes. Table 3 outlines the useful differentiating fea-
quency and duration over time [51]. tures. Primary stabbing headache refers to brief, sharp
Paediatric onset SUNCT syndrome has been reported or jabbing pain in the head that occurs either as a single
only in four children (three idiopathic and one secondary), episode or in brief repeated volleys. The pain usually
aged from 5 to 11 years [46–50]. In all of them, the clinical lasts a fraction of a second, but can persist for up to
phenotype of the headache resembled the adult-onset 1 min. These headaches are generally easily distinguish-
form. The first case was reported by D’Andrea and able from SUNCT, as they differ in several respects: in
Granella. They described a 10-year-old female with primary stabbing headache, the site and radiation of

Table 4 Management of short-


lasting unilateral neuralgiform Preventive treatments Lamotrigine
headache attacks with conjunc- Topiramate
tival injection and tearing Gabapentin
(SUNCT)
Transitional treatments Local blocks (including greater occipital nerve block)
Intravenous lidocaine
Surgery Microvascular decompression of the trigeminal nerve
Occipital nerve stimulation
Hypothalamic deep brain stimulation
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pain often varies between attacks; the majority of the hypothalamic activation. Importantly, the involvement of
attacks tend to be spontaneous; and cranial autonomic posterior hypothalamic structures may account for the rhyth-
features are absent. PH can be differentiated from micity or periodicity that is such a hallmark of these con-
SUNCT with a trial of indometacin. ditions. Hypothalamic activation is not seen in experimental
trigeminal distribution head pain [60]. Furthermore, there is
Investigations abundant evidence for a role of the hypothalamus in medi-
ating anti-nociceptive [61] and autonomic responses [62]. In
The association of secondary SUNCT with pituitary disor- view of the presence of direct hypothalamic-trigeminal con-
ders, posterior fossa abnormalities and trigemino-vascular nections [63], the TACs may be due to an abnormality in the
conflict emphasizes the need for a cranial MRI, including an hypothalamus with subsequent trigeminovascular and cra-
adequate view of the pituitary and the trigeminal nerves. nial autonomic activation.

Treatment
Conclusions
In view of the rarity of this condition, there are no published
placebo-controlled trials of treatments in SUNCT. The man- The TACs are a group of primary headache disorders char-
agement of SUNCT is entirely based on case reports or very acterized by unilateral head pain that occurs in association
small case series. The treatment options are outlined in Table 4. with ipsilateral cranial autonomic features. Childhood and
adolescent onset TACs are even more rare than the adult-
onset forms, but resemble them with regard to the character-
Pathophysiology istics of the pain, the associated symptoms and response to
treatments. Nonetheless, pediatric-onset TACs are poorly
Any pathophysiological construct for TACs must ac- recognized and there is often a delay of several months or
count for the three major clinical features characteristic years before the diagnosis is made. Awareness of typical
of the various conditions that comprise this group: tri- clinical pictures of these excruciating headaches expedites
geminal distribution pain, ipsilateral autonomic features, the diagnosis and allows prompt initiation of the appropriate
and the circadian periodicity of the attacks. The pain- management.
producing innervation of the cranium projects through
branches of the trigeminal and upper cervical nerves to Conflict of interest Dr. Giorgio Lambru declares that he has no
the trigeminocervical complex, from whence nociceptive conflict of interest.
Dr. Manjit Matharu is a section editor for Current Pain and Headache
pathways project to higher centers. This implies an Reports. He is a board member for Allergan Ltd. He has received a grant
integral role for the ipsilateral trigeminal nociceptive from St. Jude Medical and honoraria from Merck Sharpe Dohme. He has
pathways in TACs. The ipsilateral autonomic features also received payment for development of educational presentations
suggest cranial parasympathetic activation (lacrimation, including service on speakers’ bureaus from St. Jude Medical and Aller-
gan Ltd.
rhinorrhoea, nasal congestion and eyelid oedema) and
sympathetic hypofunction (ptosis and meiosis). It has
been suggested that the pathophysiology of the TACs revolves
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