headache is a notable and common somatic complaint in paediatric age [ 1 , 2 ] .
although migraine and tension - type headache show the highest incidence , other primary headaches are much rarer and poorly recognised , thus representing a clinical and therapeutic challenge .
chronic paroxysmal hemicrania ( cph ) is a rare and well - characterised headache , classified amongst the trigeminal autonomic cephalgias ( tacs ) .
cph is characterised by short - lasting ( 230  min ) and multiple pain attacks , with a typical attack frequency of more than 5 per day [ 36 ] .
pain is unilateral , located on the fronto - orbital - temporal region , it has rapid onset and it is described as excruciating .
attacks occur in combination with al least one ipsilateral autonomic symptom , such as conjunctival injection , lachrymation , miosis , ptosis , eyelid oedema , and nasal congestion or rhinorrhea [ 3 , 7 ] .
the standard cph treatment is based on the use of indomethacin . the absolute pain responsiveness
to indomethacin represents one of the diagnostic criteria for cph   ( table  1).table  1diagnostic criteria for paroxysmal hemicrania ( ichd - ii)a .
attacks completely prevented by therapeutic doses of indomethacin ( mg  kg  day)f . not attributed to another disorder diagnostic criteria for paroxysmal hemicrania ( ichd - ii ) because of its typical onset between 20 and 30  years of age [ 5 , 6 ] , cph has been extensively studied in adult population .
the disease can occur , although more rarely , also in children [ 816 ] , as early as from the age of 3 [ 9 , 12 ] .
however , few reports in paediatric age fulfilled the diagnostic criteria for cph [ 9 , 10 , 12 ] according to the international classification of headache disorders , 2nd edition ( ichd - ii )   ( table  2 ) .
in particular , the presence of autonomic signs and response to indomethacin has not been discussed adequately [ 11 , 14 , 15 , 18 ] .
some unilateral short - lasting paediatric headaches without autonomic signs have been diagnosed as cph [ 15 , 18 ] .
moorjani described a case of unilateral , short - lasting and severe headache responsive to indomethacin , but the attack duration and the autonomic symptoms were not specified . despite the complete response to indomethacin
is one of the diagnostic criteria , in some cph children , the response to indometachin was not tested [ 11 , 14 ] or this was done only in part . moreover , even one case of headache symptomatic of a cerebral infarction has been reported as cph .table  2characteristics of previously described children with paroxysmal hemicraniacase reportvieira talvik almeida gladstein klassen kudrow shabbir   ( 2 cases)moorjani broeske seidel blankenbug   ( 8 cases)age ( years)/gender9/m3/f10/f8/m6/m9/m13/f14/f4/f3/f17/m7 mean3f/5mattack duration ( min)53051515401530<101020 several min < 15not specified>4510151545attack frequency / daynot specified520not specified313 in a weekevery 1.5  h8922510520autonomic signs : absentyesyesyesyesyesnot specifiednot specifiedyesyesyes  1
miosis / ptosisabsentnononoyesyesnot specifiednot specifiedyesnoyestriggerabsentnot specifiednot specifiednot specifiedstressnot specifiednot specifiednot specifiednot specifiedquick head movementsstresssymptomatic phnonononononononocerebral infarctionnonoindomethacin responsenot administeredyesyesyesnot administerednot administered ( baby aspirin)incomplete ( + verapamil)yesyesyesyesf female , m malecph cases fulfilling the ichd - ii criteria characteristics of previously described children with paroxysmal hemicrania cph cases fulfilling the ichd - ii criteria here , we describe two children , referred to our headache centre , with typical cph features and a positive response to indomethacin therapy .
l. , a 7-year - old boy , was referred to our headache center because of a headache that had started 1-year earlier .
he suffered from unilateral pain , located in the right orbito - frontal region without side shift ; pain intensity was excruciating , and its quality was described as throbbing .
headache occurred 13 times per day , during daytime and night - time , without circadian rhythm .
pain was combined with ipsilateral autonomic symptoms , such as conjunctival injection , eyelid oedema and rhinorrhea . during the attacks , the patient cried and found difficult to lie still showing marked agitation and restlessness . moreover ,
skull ct scan , brain mri , also including the angiographic sequences , and eeg , were normal .
. l. was submitted to psychological screening tests ( safa a , d , s scales ) which showed normal anxiety , depression and somatization indices . during the headache attack , pain intensity was not affected by most non - steroidal anti - inflammatory drugs ( nsaids ) , including acetaminophen , ketoprofen , and aspirin .
a prophylactic treatment with amitriptyline 16  mg / day was attempted , with no improvement in attack frequency , nor in pain intensity .
when considering the headache characteristics , the clinical history and the failure of most analgesic drugs , a prophylactic treatment with indomethacin was started , at the initial dose of 25  mg / day .
the attack frequency immediately showed a strong reduction , decreasing from 1 to 3 attack / day to 23  attacks / month .
moreover , the child s parents were invited to use indomethacin 25  mg for each single pain attack , and they reported a strong pain relief .
after 6  months , the parents discontinued the treatment voluntarily , and the headache worsened considerably . over the following 9  months , flunarizine 5  mg / day was attempted , as suggested by another headache centre , without any amelioration .
conversely , a satisfactory improvement was obtained after the resumption of indomethacin 25  mg / day ( attack frequency of 34 per months ) . a further reduction in headache attack frequency up to 12  months
was obtained when topiramate was added at the dose of 45  mg / day ( corresponding to 1.5  mg / kg / day ) . however , due to an attentive performance reduction , probably caused by topiramate , this drug was discontinued and replaced by sodium valproate at the dose of 600  mg / day .
when l. was 9  years , the dose of indomethacin was increased up to 50  mg / day , with a mean attack frequency of 1 per month and without any side effect , as also confirmed by periodic blood examinations .
a. , a 11-year - old romanian boy , presented with a 3-year history of recurrent daily headache .
he described episodes of severe throbbing pain attacks in the left fronto - orbital - temporal region .
attacks were short - lasting ( ranging from 5 to 40  min ) , and they occurred 34 times per day .
attacks occurred during daytime and night - time , without nocturnal predominance , nor circadian rhythm , and most of them were combined with ipsilateral lachrymation , conjunctival injection , ptosis and nasal congestion . pain was not accompanied by nausea , vomit nor other migraine - like features , but the child reported osmophobia during some headache attacks . owing to his headache ,
the child had stopped practicing sport . at the time of the first consultation in our centre , a. was assuming paracetamol 500  mg / day as a prophylactic treatment , without any positive effect . moreover , his parents referred that other nsaids were attempted , unsuccessfully .
neurological examination was normal ; brain mri and blood tests did not show any abnormality .
a. had a positive familiar history of headache , as his mother suffered from migraine attacks .
paracetamol and ibuprophen treatment were attempted without any positive effect , because pain resolved in 3040  min also without medication . to reduce the frequency of pain attacks , a prophylactic treatment with topiramate ( 50  mg / day )
the clinical characteristics of our child s headache and the failure of the traditional symptomatic and prophylactic treatments led us to consider the diagnosis of cph .
therefore , indomethacin 50  mg / day was started , soon affecting the frequency of the attacks , which were no longer present after the second administration .
a. , who is continuing the indomethacin therapy at the same dose , has not suffered from any headache attack for the last 6  months .
clinical symptoms and pain characteristics of our children are similar to those found in typical adult cph .
l. and a. presented with a long history of severe and unilateral pain , which occurred in the fronto - orbital region without side shift . as required by the current cph definition , attacks were accompanied by at least one autonomic symptom , ipsilateral to pain . during the attacks , besides conjunctival injection , eyelid oedema and rhinorrhea , l. also presented vomiting and bilateral photophobia , which are typical migraine features , common in cph [ 5 , 7 , 10 ] .
, there is a considerable overlapping between the diagnostic criteria for cph and ch , mostly concerning headache duration ( from 15 to 30  min ) and attack frequency ( from 5 to 8) , thus complicating the differential diagnosis .
moreover , also the behavioural characteristics may not be useful in distinguishing cph from ch , since agitation , restlessness and aggressive behaviour during pain attacks , typical of ch , have been described also in some cph cases [ 7 , 12 ] .
pain site and associated autonomic phenomena are similar in both headaches , but the higher frequency of the attacks , their shorter duration and the absolute response to indomethacin may help in distinguishing cph from ch . although cph is commonly considered to prevail amongst female patients , many cph cases in paediatric age are males [ 911 , 13 ] , as the children we described . in line with the previous cases of cph reported during developmental age
, our patients showed some atypical features , not fully meeting the ichd - ii criteria .
first , although the ichd - ii criteria require an attack frequency higher than 5 attacks per day , in our patients , the attack frequency was lower
. this could be in favour of a diagnosis of ch , but an attack frequency lower than the one required by the ichd - ii criteria has been described in cph of both childhood [ 11 , 13 , 18 ] and adulthood [ 46 ] . moreover , according to icdh - ii criteria , the attack frequency needed for diagnosing cph should be higher than 5 per day , not constantly , but for at least half the time of observation .
second , attack duration was variable in both our children , but in a. it was sometimes longer than 30  min , which represents the maximal duration for a cph attack , according to the ichd - ii criteria .
however , several reports showed cph patients with attack duration longer than 30  min in both adults [ 5 , 7 ] and children [ 8 , 9 ] .
frequency and duration of the attacks , nevertheless , are commonly different between paediatric and adult population also in more common primary headaches , such as migraine and tension - type headache . if attack duration and frequency can make the diagnosis more difficult , especially in paediatric age , the absolute response to indomethacin represents the diagnostic key for cph in both adults and children ( indotest ) [ 3 , 21 ] .
indeed , it is noteworthy that our children showed a dramatic response to indomethacin . in particular
, l. did not respond to amitriptyline , as a prophylactic drug , nor to common nsaids .
moreover , after an initial response to indomethacin , the headache attacks increased their frequency after the voluntary discontinuation of the drug .
they were markedly reduced when indomethacin was resumed . to avoid a prolonged treatment with a high indomethacin dose ,
topiramate was added , with a satisfactory clinical response , as suggested by previous studies on cph [ 9 , 22 , 23 ] .
owing to cognitive adverse events , topiramate was replaced with valproate , which was effective , as well . to our knowledge , there are no studies showing the efficacy of valproate in cph .
a. did not show any improvement when treated with paracetamol and topiramate , whereas headache attacks disappeared after indomethacin was started . in none of the patients
, triptans were tested , since both of them are under 12 , and at their age the use of triptans is not allowed in italy .
long - term therapy with indomethacin is generally well tolerated , but adverse side effects may occur both in adulthood and childhood [ 9 , 22 ] .
the characteristics of our children s headache , particularly the positive response to indomethacin , led us to consider the diagnosis of cph .
however , the frequency and duration of our patient attacks did not fulfil the ichd - ii criteria .
cph diagnosis can be difficult in developmental age , due to the frequency and duration of attacks .
although attacks should not be longer than 30  min , in children s cph , the headache duration can exceed 40  min [ 8 , 9 , 16 ] .
moreover , although the ichd - ii criteria for cph require an attack frequency higher than 5 per day , many cph children show a lower attack frequency ( 23 per day or less ) [ 8 , 11 , 13 , 18 ] .
these elements suggest that a revision of the current cph diagnostic criteria , possibly with the inclusion of special notes for developmental age , would be necessary .
 chronic paroxysmal hemicrania ( cph ) is a rare primary headache syndrome , which is classified along with hemicrania continua and short - lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing ( sunct ) as trigeminal autonomic cephalalgia ( tacs ) . 
 cph is characterised by short - lasting ( 230  min ) , severe and multiple ( more than 5/day ) pain attacks . 
 headache is unilateral , and fronto - orbital - temporal pain is combined with cranial autonomic symptoms . according to the international classification of headache disorders , 2nd edition , the attacks are absolutely responsive to indomethacin . 
 cph has been only rarely and incompletely described in the developmental age . here , we describe two cases concerning a 7-year - old boy and a 11-year - old boy with short - lasting , recurrent headache combined with cranial autonomic features . pain was described as excruciating , and was non - responsive to most traditional analgesic drugs . 
 the clinical features of our children s headache and the positive response to indomethacin led us to propose the diagnosis of cph . 
 therefore , our children can be included amongst the very few cases of this trigeminal autonomic cephalgia described in the paediatric age . 
Introduction
Case 1
Case 2
Discussion