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
encountered in the paediatric population include migraine and
tension-type headaches. The trigeminal autonomic cephalalgias
(TACs), which includes cluster headache (CH), paroxysmal
hemicrania (PH) and short-lasting unilateral neuralgiform
headache attacks with conjunctival injection and tearing
(SUNCT), are rarely reported in the paediatric population.
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
restlessness seem to less prominent in children than in adults.
When restlessness is present, it often manifests as thrashing
around in children and can distract attention from the headache,
thereby contributing to a delay in diagnosis. The frequency of
cluster periods seems to be lower in childhood. Similarly, the
duration of the single cluster period seems to be shorter. The
temporal pattern shows a trend towards a gradual increase of
frequency and duration of symptoms in adult life. In terms of
management of paediatric CH, oxygen has been used success-
fully in several paediatric CH patients, and given its good side-
effect profile, it is considered the abortive agent of choice for
paediatric CH. Verapamil is the preventative drug of choice in
both episodic and chronic CH, though paediatric patients
should be started on lower doses and titrated according to
age. Paediatric-onset PH and SUNCT are very rarely reported.
The clinical phenotype and response to treatment seem to
resemble the adult-onset form. Paediatric-onset TACs are poor-
ly recognized and there is often a delay of several months or
This article is part of the Topical Collection on Trigeminal Autonomic
Cephalalgias
G. Lambru : M. Matharu (*)
Headache Group, Institute of Neurology, The National Hospital
for Neurology and Neurosurgery, Queen Square, London
WC1N 3BG, UK
e-mail: m.matharu@uclmail.net
years before the diagnosis is made. Awareness of typical clin-
ical pictures of these excruciating headaches is essential to
allow prompt initiation of the appropriate management.
Keywords Childhood onset headache . Cluster headache .
Paroxysmal hemicrania . SUNCT . Paediatric headache .
Trigeminal autonomic cephalalgias
Introduction
The trigeminal autonomic cephalalgias (TACs) are a
group of primary headache disorders characterized by
unilateral head pain that occurs in association with prom-
inent ipsilateral cranial autonomic features. The TACs
include cluster headache (CH), paroxysmal hemicrania
(PH) and short-lasting unilateral neuralgiform headache
attacks with conjunctival injection and tearing (SUNCT).
CH, PH and SUNCT are currently grouped into section 3 of
the revised International Classification of Headache Disorders
(ICHD-II).
The TACs are relatively rare in the adult population and are
considered to be even more rare in the pediatric population.
Childhood and adolescent onset TACs resemble the adult forms
of the disorders with regard to the characteristics of the pain, the
associated symptoms and response to treatments. Nonetheless,
pediatric-onset TACs are poorly recognized and there is often a
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
attack duration and frequency. The differentiation between
the TACs is essential, since the treatments are very different.
These syndromes are considered to be some of the most
painful known to humankind, thereby underlining the im-
portance of early recognition and initiation of the excellent
but highly selective treatments.
323, Page 2 of 10
Cluster Headache
CH is a strictly unilateral headache that occurs in association
with cranial autonomic features and, in most patients, has a
striking circannual and circadian periodicity. It is an excru-
ciating syndrome, with female patients describing each at-
tack as being worse than childbirth.
Epidemiology
The prevalence of adult CH is estimated to be 0.1 % [1]. CH
can begin at any age, though the most common age of onset is
the third or fourth decade of life. The first publications about
cluster headache in childhood were in the early 1970s [2, 3]. In
1981, an interesting description of cluster headache symptoms
in an infant was reported [4]. At the beginning of the attack, the
infant became irritable and unmanageable, touching and rub-
bing his forehead at the region of his right eye. The eye then
began watering; the right eye demonstrated ptosis, and the skin
in the region involved with pain was warm to the touch. The
infant had one to two attacks daily, almost all of them occurring
in the daytime, with spontaneous remission lasting no more
than three days. When the child was three years of age, the
attacks ceased spontaneously.
The onset of CH in the paediatric population is well
reported, though the prevalence seems to be relatively low.
A multicentre paediatric study in 27 Italian headache centres
on 6,629 headache patients less than 18 years of age
reported the 1-year prevalence of CH to be 0.03 % [5].
Childhood-onset CH shows a male preponderance with a
ratio of 2.5:1 [6•], similar to that observed in the adult population
[7]. The mean age of onset of CH in childhood and adolescence
is 11–14 years, with a wide range of 3–18 years [8].
Genetic factors appear to be involved in the same pro-
portion of the paediatric population as in the adult popula-
tion. In a recent review [6•], a positive family history for CH
has been found in approximately 10 % of pediatric CH
cases, whereas a positive family history for migraine was
found in 25 %.
Clinical Features
The Cluster Attack
Cluster attacks are strictly unilateral, though the headache
may alternate sides. It is centred around the orbital and
temporal regions, though any part of the head can be affect-
ed. The pain is excruciatingly severe. The headache can
range from 15 minutes to 3 hours. The signature feature of
CH is the association with cranial autonomic symptoms [9].
The autonomic features are transient, lasting only for the
duration of the attack, with the exception of partial Horner’s
syndrome.
Curr Pain Headache Rep (2013) 17:323
The clinical features of childhood and adolescence onset
CH attack seem to be similar to those of adult onset CH.
Maytal et al. reviewed the phenotype of 35 paediatric-onset
CH patients. Pain was felt in and around the eye in 31
patients (88 %). It commonly radiated to the temple
(43 %), to the ipsilateral maxilla (40 %) and to the ipsilateral
forehead (20 %). Common descriptions of the pain used
were: burning, piercing, tearing, and boring. The majority
of patients described their pain as severe [8]. Although it has
been suggested that cranial autonomic features may be less
prominent in children than in adults [6•], the distribution of
ocular, nasal and facial autonomic symptoms reflects the
distribution in adult onset forms of CH. Lacrimation of the
eye has been reported to be the most common symptom in
childhood CH, followed by conjunctival injection and nasal
discharge. Ptosis and nasal congestion were reported less
frequently, whereas meiosis and flushing and sweating of
the face and/or body were reported only in few patients [8].
Restlessness during CH seems to be less frequently reported
during CH attacks compared to adult onset CH [10]. In a
retrospective phenotyping study of paediatric onset CH
patients, restlessness has been noted in nine out of 14
patients (64 %) [11•]. Subsequently, another three cases of
paediatric CH, with a long follow-up, were described. The
authors noted prominent cranial autonomic features in all of
them, though only one patient was agitated during attacks
[12]. When present, restlessness often manifests as thrashing
around in children and can distract attention from the head-
ache, thereby contributing to a delay in diagnosis [13].
Other associated symptoms normally occurring in migraine,
such as nausea, vomiting, photophobia and phonophobia have
been reported in paediatric CH patients. In a retrospectively
analysed series, seven out of 35 patients reported nausea during
CH attacks (20 %) [8]. Photophobia and phonophobia were
also reported in another retrospective series of paediatric onset
CH [14]. Aura is now recognized as a clinical symptom of CH
[15]. Up to 20 % of CH patients can experience aura symp-
toms, a similar percentage of migraine sufferers who have aura.
Awareness that focal transient neurological symptoms can
accompany CH attacks and not only migraine is very helpful
for the differential diagnosis of these two conditions in paedi-
atric patients.
The cluster attack frequency varies between one every
alternate day to three daily, although some have up to eight
daily. In two series of pediatric onset CH, the majority of
patients reported one or less than one attack a day [8, 11•].
Circadian rhythmicity, which is a cornerstone feature of CH,
has been reported also in pediatric patients.
Alcohol, exercise, elevated environmental temperature
and the smell of volatile agents are recognised precipitants
of acute cluster attacks. Alcohol induces acute attacks, usu-
ally within an hour of intake, in the vast majority of suffer-
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-

CH is classified according to the duration of the bout. About
80–90 % of patients have episodic cluster headache (ECH),
which is diagnosed when they experience recurrent bouts,
each with a duration of more than a week and separated by
remissions lasting more than four weeks. The bouts typical-
ly occur once or twice a year. Often, a striking circannual
periodicity is seen with the cluster periods, with the bouts
occurring in the same month of the year. The remaining 10–
20 % of patients have chronic cluster headache (CCH), in
which either no remission occurs within one year, or the
remissions last less than one month [9].
The frequency of cluster periods seems to be lower in
childhood. Similarly, the duration of the single cluster peri-
od seems to be shorter [6•]. It has also been observed that
the temporal pattern shows a trend towards a gradual in-
crease of frequency and duration of symptoms in adult life.
In a series of 35 childhood onset CH patients, 13 (37 %) and
14 patients (40 %) reported an increase of frequency and
versely, only four patients (11 %) reported a decrease in
frequency and two patients (6 %) reported a decrease in
duration of their cluster periods during their adulthood [8].
Differential Diagnosis
The main differential diagnoses to consider are: secondary
causes of CH, other TACs (see Table 1) and migraine.
Symptomatic CH has been described with infectious, vas-
cular and neoplastic intracranial lesions. However, the true
prevalence of symptomatic causes of CH is unknown, as there
are no prospective population-based neuroimaging studies. A
review of retrospective case reports published in the medical
literature suggests that the TACs may be associated with
pituitary tumours, though this most likely reflects a consider-
able element of publication bias [16].
Differentiating between migraine and CH can be difficult in
some cases, as unilaterality of pain and presence of migrainous
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
323, Page 4 of 10
features that can be useful in distinguishing CH from migraine
include: relatively short duration of headache, rapid onset and
cessation, circadian periodicity, precipitation within an hour by
alcohol, restlessness or agitation during the attack and cluster-
ing of attacks with intervening remissions in ECH.
Investigations
The diagnosis of CH is made entirely on the basis of a good
clinical history and a detailed neurological examination.
Any atypical features in the history or abnormalities on
neurological examination (with the exception of partial
Horner’s syndrome) warrant further investigations to search
for organic causes. It remains unclear whether every TAC
patient requires neuroimaging; if it is considered, then mag-
netic resonance imaging (MRI) is the preferred modality.
Given the rarity of CH in childhood and adolescence, it
seems reasonable to offer neuroimaging to all paediatric
patients to exclude a symptomatic cause.
Treatment
Management of paediatric CH (and other TACs) is not well
substantiated by appropriate studies and is derived almost
exclusively from experience in adult patients. Currently, there
are both medical and surgical interventions available for these
patients. Medical management falls into one of three catego-
ries; acute, preventive or transitional therapies. Acute or abor-
tive treatment is given at the onset of an attack and is aimed at
aborting the attack itself, whilst the aim of preventive medica-
tion is to produce a rapid suppression of attacks and maintain
that remission while the patient is still in a bout. However,
preventive treatments generally need to be titrated to an opti-
mum dose, and therefore there can be a delay of a few days to
weeks before their beneficial effect emerges. Transitional treat-
ments are therapies that can be used to rapidly suppress the
attacks, but are only effective for a few days to weeks and can
therefore be very helpful while waiting for the preventive
treatments to work. Surgical treatments are generally avoided
until the medical treatments are exhausted.
Abortive Agents
Because the pain of CH builds up so rapidly, the most
efficacious agents are those that involve parenteral or pul-
monary administration.
Oxygen. Inhalation of 100 % oxygen, at 7–12L/min, is rapidly
effective in relieving pain in the majority of sufferers [17]. It
should be inhaled continuously for 15–30 minutes via a non-
rebreathing facial mask. Oxygen has been used successfully in
several paediatric CH patients [6•], and given its good side-
effect profile, it is the abortive agent of choice for paediatric CH.
Curr Pain Headache Rep (2013) 17:323
Subcutaneous and Intranasal Triptans. Subcutaneous suma-
triptan is the most effective abortive treatment for cluster
headache [18]. In CH, unlike in migraine, subcutaneous suma-
triptan can be prescribed at a frequency of twice daily, on a
long-term basis if necessary, without risk of tachyphylaxis or
rebound [19, 20]. Sumatriptan and zolmitriptan nasal spray are
both more effective than placebo [21, 22]. While experience
with the use of subcutaneous sumatriptan in the pediatric
population is limited, Sumatriptan nasal spray has been shown
to be well tolerated in children between 12 and 17 years old at
the dose of 20 mg, in randomized, placebo-controlled studies
in migraine [23].
Transitional Treatments
Corticosteroids. Corticosteroids are highly efficacious and
the most rapid acting of the preventative agents [24]. Cau-
tion has to be exercised in their use because of the potential
for serious side effects. Treatment is usually limited to a
short intensive course of 2–3 weeks in tapering doses be-
cause of the potential for side effects [25]. Unfortunately,
relapse almost invariably occurs as the dose is tapered. For
this reason, steroids are used as an initial therapy in con-
junction with preventives, until the latter are effective.
In adolescence, a marked relief of cluster headache in 59
(77 %) of 77 ECH patients, and a partial relief in another
12 % of patients treated with prednisone was reported [26].
A report of sustained efficacy of intravenous (IV) prednis-
olone in a 7-year-old female has been reported. In this case,
prednisolone was started at 50 mg IV and reduced every
fourth day (50 mg IV for 3 days, 25 mg for the next 3 days,
15 mg IV for the following 3 days, and 5 mg for the last
3 days of the therapy), leading to the termination of attacks
on the third day of the treatment and allowing a subsequent
pain-free period for several months [27].
Greater Occipital Nerve (GON) Block. Injection of local
anaesthetic and corticosteroid around the GON on the af-
fected side can abort a bout of cluster headache [28].
Though there are no reports on the use of GON blocks in
paediatric CH, it is an excellent short-term strategy, with
only very modest, infrequent side effects.
Preventive Treatments
The preventive agents used in the management of CH in-
clude verapamil, lithium, topiramate, methysergide, gaba-
pentin, melatonin and valproate. Verapamil is the agent of
choice. While the other agents are often used, the evidence
base for their use is poor. Table 2 provides an overview of
the recommendations for CH preventive treatments by the
European Federation of Neurological Societies (EFNS) [29]
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
both episodic and chronic CH [31]. There are reports of
efficacy of verapamil in children at doses between 120 mg
and 240 mg, though this agent is often used at doses of up to
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
development of heart block. There is only one formal guide-
line in the literature for the titration of the verapamil dose in
adults [25], which recommends starting patients on 240 mg
daily and incrementing the dose in steps of 80 mg every
2 weeks under ECG guidance. The dose is increased until
the cluster attacks are suppressed, side effects intervene or
the maximum dose of 960 mg daily is achieved. In the
paediatric population, we recommend starting at a lower
dose of 40–80 mg daily and titrating the dose in steps of
40 mg, up to 360 mg a day in total.
Surgery
In adults, medically intractable CCH is a rare but highly
disabling disorder, and it is therefore appropriate to consider
surgical interventions in these patients. There are no reports of
surgical intervention for the management of pediatric CH,
though medically refractory CCH cases are described [6•].
Surgery is a last-resort measure in treatment–resistant patients,
and should only be considered when the pharmacological
options have been exploited to the fullest. Historically, de-
structive procedures involving the trigeminal nerve have been
tried in CH. However, they are associated with considerable
morbidity and therefore have largely been abandoned. Most
recently, neurostimulation therapies with either hypothalamic
deep brain stimulation or occipital nerve stimulation (ONS)
have emerged. These approaches are very promising, and
ONS especially offers a more acceptable side effect profile
than destructive and invasive approaches [32•].
Paroxysmal Hemicrania
PH, like CH, is characterized by strictly unilateral, brief
headaches that occur in association with cranial autonomic
features. PH differs from CH mainly in the higher frequency
and shorter duration of individual attacks, though there is a
considerable overlap in these characteristics. However, un-
like CH, PH responds in a dramatic and absolute fashion to
indometacin [9], thereby underlining the importance of dis-
tinguishing it from CH.
Epidemiology
PH is a very rare syndrome. The prevalence of PH is not
known, but the relationship compared to CH is reported to
be approximately 1–3 %. The most common age of onset is
the second or third decade of life, though there is a wide
range of age of onset (1–68 years), with several case reports
of onset before the age of 18 years [33–40]. PH seems to be
equally prevalent in females and males [33].
Clinical Features
The clinical phenotype of PH is highly characteristic [33, 41].
The pain is strictly unilateral and centred around the orbital
and temporal regions, though any part of the head can be
323, Page 6 of 10
affected. It is excruciatingly severe. The headache usually
lasts 2–30 minutes. Attacks of PH invariably occur in associ-
ation with ipsilateral cranial autonomic features. Up to 85 % of
patients report at least one migrainous feature of photophobia,
nausea or vomiting during an attack. Similar to CH, patients
are often restless or agitated during an attack. The attacks
occur at a high frequency. Typically, patients have more than
five attacks daily, though the frequency of attacks shows a
considerable fluctuation, ranging between one and 40 daily.
The attacks occur randomly throughout the 24-hour period,
without a preponderance of nocturnal attacks as in cluster
headache. While the majority of attacks are spontaneous,
common triggers include stress, release from stress, exercise,
alcohol ingestion and neck movement [33].
PH is classified depending on the presence of a remission
period. About 35 % of patients have episodic paroxysmal
hemicrania (EPH), which is diagnosed when there are clear
remission periods between bouts of attacks. The remaining
65 % of patients have chronic paroxysmal hemicrania (CPH)
(26), which is diagnosed when patients have either no remis-
sion within one year, or the remissions last less than one
month [9].
Differential Diagnosis
The differential diagnoses that need to be considered are:
secondary causes of PH, other TACs and hemicrania con-
tinua (HC). A large number of symptomatic cases of PH,
caused by diverse pathological processes at various intracranial
sites, have been described, though a causal relationship is
difficult to ascertain in most of these cases [16]. PH can be
differentiated from CH and SUNCT with a trial of indometa-
cin. HC is a strictly unilateral headache that is continuous and
associated with ipsilateral cranial autonomic symptoms. Both
PH and HC are exquisitely responsive to indomethacin, and
can be differentiated on the basis of the clinical phenotype [42].
Investigations
As a relatively high number of symptomatic cases have been
reported, an MRI brain scan should be routinely performed
in all PH patients.
Treatment
The treatment of PH is entirely preventive, as attacks are too
short and intense for any acute oral treatment to be effective.
Indometacin
Indometacin is the treatment of choice and, in fact, has been
deemed the sine qua non for establishing the diagnosis [9].
Complete resolution of the headache is prompt, usually
Curr Pain Headache Rep (2013) 17:323
occurring within 1–2 days of initiating the effective dose.
The typical maintenance dose ranges from 25 to 100 mg
daily, but doses up to 300 mg daily are occasionally required
[43]. In children from 1 month to 18 years of age, the dose
of 0.5–1 mg/kg twice daily should be used. Talvik et al.
described a 3-year-old female with a year history of CPH
who responded dramatically to 50 mg of indometacin, be-
coming pain-free. Interestingly, although the symptoms
were typical for PH, she has been diagnosed 10 months after
the onset of the symptoms [40]. This case highlights the
importance of recognising the possible childhood onset of
this disorder.
Other Medications
For patients who cannot tolerate indomethacin, one faces a
difficult challenge. No other drug is consistently effective in
PH. Other drug therapies that have been reported to be
effective in PH include cyclooxygenase-2 inhibitors, calci-
um channel antagonists (verapamil, Flunarizine), topiramate
or greater occipital nerve blocks [43].
SUNCT
Short-lasting unilateral neuralgiform headache attacks
with conjunctival injection and tearing (SUNCT), as its
name implies, is a disorder characterised by strictly
unilateral, severe, neuralgic attacks centred on the oph-
thalmic trigeminal distribution that are brief in duration
and occur in association with both conjunctival injection
and lacrimation [9].
Epidemiology
SUNCT is relatively rare, with a recent study showing a
prevalence of 6.6 per 100,000 population [44]. SUNCT has
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
mean age of onset of 48 years and a range between 2 and
77 years. Pediatric-onset SUNCT is very rare, with only five
case reports in the literature [46–50].
Clinical Features
The attacks are strictly unilateral, though may alternate
sides. The pain is usually maximal in the ophthalmic
distribution of the trigeminal nerve, but can radiate to
any part of the head. The pain has an excruciating
intensity and a neuralgic quality. The individual attacks
are relatively brief, lasting between 5 and 240 seconds.
Three different types of pain have been described in
SUNCT syndrome: single stabs; groups of stabs and a
Curr Pain Headache Rep (2013) 17:323
Table 3 Differentiating Features of SUNCT and trigeminal neuralgia
Feature SUNCT Trigeminal neuralgia
Male: female ratio 1.5:1 1:2
Site of pain V1 V2/3
Duration (seconds) 5–240 <5
Autonomic features Prominent Sparse or none
Refractory period Absent Present
SUNCT Short-lasting unilateral neuralgiform headache attacks with
conjunctival injection and tearing
saw-tooth pattern in which repetitive spike-like parox-
ysms occur without reaching the pain-free baseline be-
tween the individual spikes. By definition, all SUNCT
patients had both ipsilateral conjunctival injection and
lacrimation associated with their attacks [9]. Patients are
often restless or agitated during the attacks [45]. The
attack frequency during the symptomatic phase varies
immensely between sufferers and within an individual
sufferer. Attacks may be as infrequent as once a day, or
less to more than 60 per hour.
The majority of patients can precipitate attacks by touch-
ing certain trigger zones within trigeminal innervated distri-
bution and, occasionally, even from an extra-trigeminal
territory. Precipitants include touching the face or scalp,
washing, shaving, eating, chewing, brushing teeth, talking
and coughing. Unlike in trigeminal neuralgia, most patients
have no refractory period.
The temporal pattern is quite variable, with the symp-
tomatic periods alternating with remissions in an erratic
manner. Symptomatic periods generally last from a few days
to several months and occur once or twice annually. Remis-
sions typically last a few months, yet can range from 1 week
to 7 years. Symptomatic periods appear to increase in fre-
quency and duration over time [51].
Paediatric onset SUNCT syndrome has been reported
only in four children (three idiopathic and one secondary),
aged from 5 to 11 years [46–50]. In all of them, the clinical
phenotype of the headache resembled the adult-onset
form. The first case was reported by D’Andrea and
Granella. They described a 10-year-old female with
Table 4 Management of short-
lasting unilateral neuralgiform Preventive treatments
headache attacks with conjunc-
tival injection and tearing
(SUNCT)
Transitional treatments
Surgery
Page 7 of 10, 323
very short-lasting, spontaneous, strictly unilateral but
alternating side attacks, associated with lacrimation
and conjunctival injection. The patient did not require
any treatment, since the headache disappeared sponta-
neously a few months after the onset [46]. Subsequent-
ly, a second case of young onset SUNCT was reported
in a 5-year-old male. His bout lasted five months and
no relapses were reported after a year of follow-up
[48]. More recently, a 6-year-old male with idiopathic
SUNCT was described. Compared to the previous
cases, the headache lasted for 4 years and responded
to lamotrigine [49].
Differential Diagnosis
The differential diagnosis of very brief headaches includes:
SUNCT (primary and secondary forms), trigeminal neural-
gia, primary stabbing headache and PH.
Secondary SUNCT is typically seen with either pos-
terior fossa or pituitary gland lesions [51]. A case of
secondary SUNCT in an 11-year-old girl, due to an
astrocytoma of the ipsilateral pontocerebellar angle was
reported. After the partial removal, the pain attacks
persisted, but were shorter and less intense [47]. The
case emphasizes the need for brain MRI, even in
patients presenting with typical SUNCT and without
neurologic deficits, as in the aforementioned case.
In addition, a recent study systematically looked for tri-
geminal neurovascular conflict with dedicated trigeminal MRI
scans, and found a high proportion of ipsilateral vascular
loops in contact with the trigeminal nerve in SUNCT [44].
Differentiating SUNCT from trigeminal neuralgia can
be challenging in some cases, as there is a considerable
overlap in the clinical phenotypes of the two syn-
dromes. Table 3 outlines the useful differentiating fea-
tures. Primary stabbing headache refers to brief, sharp
or jabbing pain in the head that occurs either as a single
episode or in brief repeated volleys. The pain usually
lasts a fraction of a second, but can persist for up to
1 min. These headaches are generally easily distinguish-
able from SUNCT, as they differ in several respects: in
primary stabbing headache, the site and radiation of
Lamotrigine
Topiramate
Gabapentin
Local blocks (including greater occipital nerve block)
Intravenous lidocaine
Microvascular decompression of the trigeminal nerve
Occipital nerve stimulation
Hypothalamic deep brain stimulation
323, Page 8 of 10
pain often varies between attacks; the majority of the
attacks tend to be spontaneous; and cranial autonomic
features are absent. PH can be differentiated from
SUNCT with a trial of indometacin.
Investigations
The association of secondary SUNCT with pituitary disor-
ders, posterior fossa abnormalities and trigemino-vascular
conflict emphasizes the need for a cranial MRI, including an
adequate view of the pituitary and the trigeminal nerves.
Treatment
In view of the rarity of this condition, there are no published
placebo-controlled trials of treatments in SUNCT. The man-
agement of SUNCT is entirely based on case reports or very
small case series. The treatment options are outlined in Table 4.
Pathophysiology
Any pathophysiological construct for TACs must ac-
count for the three major clinical features characteristic
of the various conditions that comprise this group: tri-
geminal distribution pain, ipsilateral autonomic features,
and the circadian periodicity of the attacks. The pain-
producing innervation of the cranium projects through
branches of the trigeminal and upper cervical nerves to
the trigeminocervical complex, from whence nociceptive
pathways project to higher centers. This implies an
integral role for the ipsilateral trigeminal nociceptive
pathways in TACs. The ipsilateral autonomic features
suggest cranial parasympathetic activation (lacrimation,
rhinorrhoea, nasal congestion and eyelid oedema) and
sympathetic hypofunction (ptosis and meiosis). It has
been suggested that the pathophysiology of the TACs revolves
around the trigeminal-autonomic reflex [52]. There is consid-
erable experimental animal literature to document that stimu-
lation of trigeminal afferents can result in cranial autonomic
outflow, the trigeminal-autonomic reflex [53]. In fact, some
degree of cranial autonomic symptomatology is a normal
physiologic response to cranial nociceptive input, and patients
with other headache syndromes often report these symptoms.
The distinction between the TACs and other headache syn-
dromes is the degree of cranial autonomic activation, not its
presence [54, 55].
The cranial autonomic symptoms may be prominent in
the TACs due to a central disinhibition of the trigeminal-
autonomic reflex [56]. Supporting evidence is emerging
from functional imaging studies: positron emission tomog-
raphy studies in CH [57] and PH [58], and functional MRI
studies in SUNCT syndrome [59] have demonstrated
Curr Pain Headache Rep (2013) 17:323
hypothalamic activation. Importantly, the involvement of
posterior hypothalamic structures may account for the rhyth-
micity or periodicity that is such a hallmark of these con-
ditions. Hypothalamic activation is not seen in experimental
trigeminal distribution head pain [60]. Furthermore, there is
abundant evidence for a role of the hypothalamus in medi-
ating anti-nociceptive [61] and autonomic responses [62]. In
view of the presence of direct hypothalamic-trigeminal con-
nections [63], the TACs may be due to an abnormality in the
hypothalamus with subsequent trigeminovascular and cra-
nial autonomic activation.
Conclusions
The TACs are a group of primary headache disorders char-
acterized by unilateral head pain that occurs in association
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-
istics of the pain, the associated symptoms and response to
treatments. Nonetheless, pediatric-onset TACs are poorly
recognized and there is often a delay of several months or
years before the diagnosis is made. Awareness of typical
clinical pictures of these excruciating headaches expedites
the diagnosis and allows prompt initiation of the appropriate
management.
Conflict of interest Dr. Giorgio Lambru declares that he has no
conflict of interest.
Dr. Manjit Matharu is a section editor for Current Pain and Headache
Reports. He is a board member for Allergan Ltd. He has received a grant
from St. Jude Medical and honoraria from Merck Sharpe Dohme. He has
also received payment for development of educational presentations
including service on speakers’ bureaus from St. Jude Medical and Aller-
gan Ltd.
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
1. Tonon C, Guttmann S, Volpini M, Naccarato S, Cortelli P,
D’Alessandro R. Prevalence and incidence of cluster headache in
the Republic of San Marino. Neurology. 2002;58(9):1407–9.
2. Ekbom K. A clinical comparison of cluster headache and migraine.
Acta Neurol Scand. 1970;Suppl 41:1.
3. Lance JW, Anthony M. Migrainous neuralgia or cluster headache? J
Neurol Sci. 1971;13(4):401–14.
4. Terzano MG, Manzoni GC, Maione R. Cluster headache in one
year old infant? Headache. 1981;21(6):255–6.
5. Gallai B, Mazzotta G, Floridi F, Mattioni A, Baldi A, Sarchielli P, et
al. Cluster headache in childhood and adolescence: one-year preva-
lence in an out-patient population. J Headache Pain. 2003;4:132–7.
Curr Pain Headache Rep (2013) 17:323
6. • Antonaci F, Alfei E, Piazza F, De Cillis I, Balottin U. Therapy-
resistant cluster headache in childhood: case report and literature
review. Cephalalgia. 2010;30(2):233–8. The article presents three
challenging cases of childhood onset cluster headache refractory
to many medical treatments.
7. Russell MB. Epidemiology and genetics of cluster headache.
Lancet Neurol. 2004;3(5):279–83.
8. Maytal J, Lipton RB, Solomon S, Shinnar S. Childhood onset
cluster headaches. Headache. 1992;32(6):275–9.
9. Headache Classification Committee of The International Headache
Society. The international classification of headache disorders 2nd
edition. Cephalalgia. 2004;24(Supplement 1):1–195.
10. Bahra A, May A, Goadsby PJ. Cluster headache: a prospec-
tive clinical study with diagnostic implications. Neurology.
2002;58(3):354–61.
11. • Majumdar A, Ahmed MA, Benton S. Cluster headache in chil-
dren—experience from a specialist headache clinic. Eur J Paediatr
Neurol. 2009;13(6):524–9. This interesting retrospective analysis
of a group of childhood onset CH outilnes the clinical charater-
istics of this disorder in the pediatric age.
12. Arruda MA, Bonamico L, Stella C, Bordini CA, Bigal ME. Cluster
headache in children and adolescents: ten years of follow-up in
three pediatric cases. Cephalalgia. 2011;31(13):1409–14.
13. Del Bene E, Poggioni M. Typical and atypical cluster headache in
childhood. Cephalalgia. 1987;7 Suppl 6:128–30.
14. McNabb S, Whitehouse W. Cluster headache-like disorder in
childhood. Arch Dis Child. 1999;81(6):511–2.
15. Rozen TD. Cluster headache with aura. Curr Pain Headache Rep.
2011;15(2):98–100.
16. Cittadini E, Matharu MS. Symptomatic trigeminal autonomic
cephalalgias. Neurologist. 2009;15(6):305–12.
17. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of
cluster headache: a randomized trial. JAMA. 2009;302(22):2451–7.
18. Ekbom K, Monstad I, Prusinski A, Cole JA, Pilgrim AJ, Noronha
D. Subcutaneous sumatriptan in the acute treatment of cluster
headache: a dose comparison study. The Sumatriptan Cluster
Headache Study Group. Acta Neurol Scand. 1993;88(1):63–9.
19. Ekbom K, Waldenlind E, Cole J, Pilgrim A, Kirkham A.
Sumatriptan in chronic cluster headache: results of continuous
treatment for eleven months. Cephalalgia. 1992;12(4):254–6.
20. Gobel H, Lindner V, Heinze A, Ribbat M, Deuschl G. Acute
therapy for cluster headache with sumatriptan: findings of a one-
year long-term study. Neurology. 1998;51(3):908–11.
21. Van Vliet JA, Bahra A, Martin V, Ramadan N, Aurora SK, Mathew
NT, et al. Intranasal sumatriptan in cluster headache: randomized
placebo-controlled double-blind study. Neurology. 2003;60(4):630–3.
22. Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ.
Effectiveness of intranasal zolmitriptan in acute cluster headache: a
randomized, placebo-controlled, double-blind crossover study.
Arch Neurol. 2006;63(11):1537–42.
23. Winner P, Rothner AD, Saper J, et al. A randomized, double-blind,
placebo-controlled study of sumatriptan nasal spray in the treatment
of acute migraine in adolescents. Pediatrics. 2000;106(5):989–97.
24. Couch Jr JR, Ziegler DK. Prednisone therapy for cluster headache.
Headache. 1978;18(4):219–21.
25. Matharu MS, Goadsby PJ. Trigeminal autonomic cephalgias. J
Neurol Neurosurg Psychiatry. 2002;72 Suppl 2:19–26.
26. Linet MS SW. Migraine headache: epidemiologic perspectives. In:
Nathanson N, Gordis L, Gregg M, Szklo M, editors. Epidemiology
review, vol. 6. Baltimore: John Hopkins School of Hygiene and
Public Health; 1984. p. 107–29.
27. Lampl C. Childhood-onset cluster headache. Pediatr Neurol.
2002;27(2):138–40.
28. Ambrosini A, Vandenheede M, Rossi P, et al. Suboccipital injection
with a mixture of rapid- and long-acting steroids in cluster headache:
A doubleblind placebo-controlled study. Pain. 2005;118:92–6.
Page 9 of 10, 323
29. May A, Leone M, Afra J, Linde M, Sandor PS, Evers S, et al. EFNS
guidelines on the treatment of cluster headache and other trigeminal-
autonomic cephalalgias. Eur J Neurol. 2006;13(10):1066–77.
30. Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharma-
cologic treatment of cluster headache. Neurology. 2010;75(5):463–73.
31. Leone M, D’Amico D, Frediani F, Moschiano F, Grazzi L,
Attanasio A, et al. Verapamil in the prophylaxis of episodic cluster
headache: a double-blind study versus placebo. Neurology.
2000;54(6):1382–5.
32. • Lambru G, Matharu MS. Occipital nerve stimulation in primary
headache syndromes. Ther Adv Neurol Disord. 2012;5(1):57–67.
This is a comprehensive review of the latest developments in
peripheral neuromodulation in primary headaches. This article
highlights the safety of this procedure, suggesting the potential
use also in paediatric age medically intractable TACs.
33. Cittadini E, Matharu MS, Goadsby PJ. Paroxysmal hemicrania: a
prospective clinical study of 31 cases. Brain. 2008;131(Pt 4):1142–55.
34. Kudrow DB, Kudrow L. Successful aspirin prophylaxis in a child
with chronic paroxysmal hemicrania. Headache. 1989;29(5):280–1.
35. Gladstein J, Holden EW, Peralta L. Chronic paroxysmal hemi-
crania in a child. Headache. 1994;34(9):519–20.
36. Shabbir N, McAbee G. Adolescent chronic paroxysmal hemicrania
responsive to verapamil monotherapy. Headache. 1994;34(4):209–10.
37. Klassen BD, Dooley JM. Chronic paroxysmal hemicrania-like
headaches in a child: response to a headache diary. Headache.
2000;40(10):853–5.
38. Moorjani BI, Rothner AD. Indomethacin-responsive headaches in
children and adolescents. Semin Pediatr Neurol. 2001;8(1):40–5.
39. de Almeida DB, Cunali PA, Santos HL, Brioschi M, Prandini M.
Chronic paroxysmal hemicrania in early childhood: case report.
Cephalalgia. 2004;24(7):608–9.
40. Talvik I, Koch K, Kolk A, Talvik T. Chronic paroxysmal hemicrania
in a 3-year, 10-month-old female. Pediatr Neurol. 2006;34(3):225–7.
41. Antonaci F, Sjaastad O. Chronic paroxysmal hemicrania (CPH): a
review of the clinical manifestations. Headache. 1989;29(10):648–56.
42. Matharu M, Goadsby P. Trigeminal autonomic cephalalgias: diag-
nosis and management. In: Silberstein S, Lipton R, Dodick D,
editors. Wolff’s headache and other head pain Eighth Edition. 8th
ed. New York: Oxford University Press; 2007. p. 379–430.
43. Matharu MS, Boes CJ, Goadsby PJ. Management of trigemi-
nal autonomic cephalgias and hemicrania continua. Drugs.
2003;63(16):1637–77.
44. Williams MH, Broadley SA. SUNCT and SUNA: clinical features
and medical treatment. J Clin Neurosci. 2008;15(5):526–34.
45. Cohen AS, Matharu MS, Goadsby PJ. Short-lasting unilateral neu-
ralgiform headache attacks with conjunctival injection and tearing
(SUNCT) or cranial autonomic features (SUNA)—a prospective
clinical study of SUNCT and SUNA. Brain. 2006;129(Pt 10):2746–
60.
46. D’Andrea G, Granella F. SUNCT syndrome: the first case in child-
hood. Short-lasting unilateral neuralgiform headache attacks with
conjunctival injection and tearing. Cephalalgia. 2001;21(6):701–2.
47. Blattler T, Capone Mori A, Boltshauser E, Bassetti C. Symptomatic
SUNCT in an eleven-year-old girl. Neurology. 2003;60(12):2012–3.
48. Sekhara T, Pelc K, Mewasingh LD, Boucquey D, Dan B. Pediatric
SUNCT syndrome. Pediatr Neurol. 2005;33(3):206–7.
49. Unalp A, Ozturk AA. SUNCT syndrome in a child: a rare cause of
paroxysmal headache. Ann Saudi Med. 2008;28(5):386–7.
50. Sciruicchio V, Sardaro M, Gagliardi D, Trabacca A, Galeone D, de
Tommaso M. A case of early-onset and monophasic trigeminal
autonomic cephalalgia: could it be a SUNCT? J Headache Pain.
2010;11(4):363–5.
51. Matharu MS, Cohen AS, Boes CJ, Goadsby PJ. Short-lasting
Unilateral Neuralgiform headache with Conjunctival Injection
and Tearing Syndrome: A Review. Curr Pain Headache Rep.
2003;7(4):308–18.
323, Page 10 of 10
52. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias,
SUNCT syndrome and other short-lasting headaches with auto-
nomic feature, including new cases. Brain. 1997;120(Pt 1):193–
209.
53. May A, Goadsby PJ. The trigeminovascular system in humans:
pathophysiologic implications for primary headache syndromes of
the neural influences on the cerebral circulation. J Cereb Blood
Flow Metab. 1999;19(2):115–27.
54. Goadsby PJ, Matharu MS, Boes CJ. SUNCT syndrome or trigem-
inal neuralgia with lacrimation. Cephalalgia. 2001;21:82–3.
55. Goadsby PJ. Trigeminal autonomic cephalalgias: fancy term or con-
structive change to the IHS classification? J Neurol Neurosurg
Psychiatry. 2005;76(3):301–5.
56. Leone M, Bussone G. Pathophysiology of trigeminal autonomic
cephalalgias. Lancet Neurol. 2009;8(8):755–64.
57. May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ.
Hypothalamic activation in cluster headache attacks. Lancet.
1998;352(9124):275–8.
Curr Pain Headache Rep (2013) 17:323
58. Matharu MS, Cohen AS, Frackowiak RS, Goadsby PJ. Posterior
hypothalamic activation in paroxysmal hemicrania. Ann Neurol.
2006;59(3):535–45.
59. May A, Bahra A, Buchel C, Turner R, Goadsby PJ. Functional
magnetic resonance imaging in spontaneous attacks of SUNCT:
short-lasting neuralgiform headache with conjunctival injection
and tearing. Ann Neurol. 1999;46(5):791–4.
60. May A, Kaube H, Buchel C, Eichten C, Rijntjes M, Juptner M, et al.
Experimental cranial pain elicited by capsaicin: a PET study. Pain.
1998;74(1):61–6.
61. Dafny N, Dong WQ, Prieto-Gomez C, Reyes-Vazquez C, Stanford
J, Qiao JT. Lateral hypothalamus: site involved in pain modulation.
Neuroscience. 1996;70(2):449–60.
62. Lumb BM, Lovick TA. The rostral hypothalamus: an area for
the integration of autonomic and sensory responsiveness. J
Neurophysiol. 1993;70(4):1570–7.
63. Malick A, Burstein R. Cells of origin of the trigeminohypothala-
mic tract in the rat. J Comp Neurol. 1998;400(1):125–44.