Table 1.

Demographic characteristics and main outcomes of the current literature regarding headache attributed to airplane travel

Year, Author (reference)	Number of AH-patients	Gender (number of M/F)	Mean diagnosis age (mean ± SD) years	Publication type	Main outcomes
2004, Atkinson et al. [8]	1	1 M	28	Case report	• Patient developed a severe headache during ascent and descent. The pain was described as jabbing in the unilateral fronto-orbital region and lasted within 20 min. • Patient had no relevant medical history, used no medication and had no symptoms of sinus disease. • Neurological examinations were performed, CT and MRI, with normal findings.
2006, Berilgen et al. [7]	6	6 M	37.3 ± 2.9	Case reports	• All 6 patients experienced a severe headache when the airplane was taking off or landing. The pain was described as jabbing and stabbing in the orbital and/or supraorbital region. The headaches resolved within 15–20 min. • Three patients reported a history of migraine without aura, retinal migraine and exercise headache. • The authors suggested sinus barotrauma as the main cause of the headache. The pressure changes during the ascent and descent would potentially activate the trigeminovascular system and thereby induce the headache attack. • Examinations of neurological, ENT, blood analyses, MRI and paranasal sinus tomography showed normal findings.
2007, Evans et al. [9]	4	2 M/2 F	26.8 ± 3.9	Case reports	• All patients developed severe headache during the descent that lasted about 15–30 min. The pain intensity was rated as 10/10 and located in parietal and ethmoid regions. • Two patients experienced a second mild/moderate headache after the AH. • Ibuprofen was used by two patients; one patient experienced a mild reduction in pain and one did not experience any relieving effect. • The authors stated that sinus barotraume might be an explanation for the cause of the AH. • Examinations of CT, MRI and ENT showed normal findings.
2007, Mainardi et al. [5]	1	1 M	23	Case report	• The patient developed a severe pulsating headache after the take-off in the retro-orbital and frontal region. The headache lasted about 10–15 min. • Patient had no relevant medical history. • Authors believed that sinus barotrauma might not explain the cause of the headache as this patient developed the headache after the take-off. • Neurological and neuroradiological examinations (MRI and MRA) showed normal findings.
2008, Marchioretto et al. [15]	1	1 M	29	Letter to the editor	• The patient developed a highly sharp intense headache pain during the landing in the periorbital region. The pain resolved after 5 min. • Sodium naproxen 550 mg, one tablet, was taken by the patient after the first incidence of headache. He did not experience any headache after the use of the medication. • Neuroradiological examinations (MRI and MRA) showed normal findings.
2008, Coutinho et al. [17]	1	1 M	57	Case report	• The patient always developed an intense headache pain in the left frontal region during the landing. The headache often lasted between 5 and 10 min. • There was no relevant medical history and no history of sinus pathology. • Neurological examination, ENT and MRI, showed normal findings. • The authors excluded sinus barotrauma as a possible explanation of the headache due to the normal findings of the MRI.
2008, Potasman et al. [4]	52	18 M/34 F	33.3 ± 13.8	Journal article	• The travelers developed headache during the ascent and descent. The pain was often described as a unilateral or bilateral pressuring sensation with a pain intensity of 6 (on a scale of 1–10). • The headache lasted 4.0 h after take-off and 5.7 h after landing. • In the headache group, 23 passengers were diagnosed with migraine, 3 passengers reported sinusitis as the cause of the headache and 3 passengers reported hypertension as the cause. • Medications such as paracetamol, dipyrone and triptans, were taken by 25 travelers. The effects were not reported.
2008, Kim et al. [27]	1	1 M	38	Case report	• The patient developed a severe headache during the landing. The pain was described as jabbing and located in the supraorbital area. The headache lasted about 30 min. • Neurological examinations, x-ray of paranasal sinuses and cranial CT showed overall normal findings, except for mucosal thickening of the right ethmoid sinus. • Authors stated that the results of the thickening ethmoid sinus mucosa might be an incidental finding.
2010, Baldacci et al. [13]	1	1 F	20	Case report	• The patient experienced a sharp pain in the right retro-orbital and frontal regions during the take-offs. The pain sensation was severe with the rating 10/10 and the headache disappeared within 10 min. • There was no relevant medical history; but, every headache attack was preceded with a characteristic sensory aura. She always experienced a sensation of paraesthesias starting from the left thumb accompanied by spread to her hand and to the perioral region. These symptoms lasted 5–10 min before the start of the headache attack. • Neurological examinations, ENT, EEG, CT and MRA showed normal findings. • The authors stated that sinus barotrauma might explain the mechanism for the headache and suggest that the reported aura might be related to the pressure changes in the cabin.
2010, Domitrz [10]	1	1 M	29	Case report	• The patient developed a sudden jabbing headache during the take-off and landing – but only when he was travelling with airplane and not with jumbo jet. The pain was located in the left frontal region with radiation into the left eye. The intensity of the pain was severe and the patient could not move until the headache disappeared. • Medical history was not relevant. Neurological-, ophtolaryngological-, and ophthalmological examinations and MRA showed normal findings. • The author stated that sinus barotrauma might be a possible cause of the headache.
2010, Ipekdal et al. [28]	2	1 M/ 1 F	12 ± 1	Conference abstract	• Two children suffered from severe headaches during the landing phase. • Blood sample analyses, cerebral MRI and MRA showed normal findings. However, paranasal sinus tomography revealed pansinusitis in the male patient and bilateral maxillary sinusitis in the female patient. • Both patients were given antibiotic and anti-inflammatory medications and experienced afterwards headache-free airplane travels.
2010, Ipekdal et al. [16]	3	1 M/ 2 F	13 ± 0.8	Case reports	• Three children developed severe headaches during the ascent and descent. The pain was located in the unilateral periorbital and orbito-frontal region and lasted between 10 and 25 min. • One patient had a history of allergy rhinitis and allergy to pollens. • Paranasal sinus tomography and MRI showed nasal mucosal wall thickening and inflammation in all 3 patients. ENT showed adenoidal and tonsillar hypertrophy in one patient. • The patient with adenoidal and tonsillar hypertrophy underwent adenotonsillectomy surgery and experienced headache-free airplane travels after recovery. • The 2 other patients with inflamed nasal mucosal walls were given antihistamine and anti-inflammatory medications and were completely headache-free after treatment. • The authors stated that their effective treatment with antihistamine and anti-inflammatory medications support the theory that sinus barotrauma plays a central role in the mechanism of AH.
2010, Pfund et al. [19]	1	1 F	27	Case report	• The patient developed bilateral headache located in her ear, cheek, forehead, and on the top of the head. The pain was described as stabbing, jabbing and rated as 10/10. • The severe headache pain disappeared after landing, but was followed by a mild headache that lasted two weeks after the flight travel. • MRI and paranasal sinus computed tomography and revealed bilateral inflammation in the sphenoid, maxillary and ethmoid sinuses. Furthermore, the patient had increased number of eosinophilic cells and swelled nasal mucosa. These findings supported the diagnosis of chronic non-allergic rhinosinusitis. • Patient was given antihistamine and experienced almost painless airplane travels. • The authors supported the sinus barotrauma as a central role in the mechanism of AH.
2011, Berilgen et al. [26]	18	16 M/ 2 F	34.25 ± 7.7	Case reports	• All patients developed a severe headache during the landing phase. The pain was located in the frontal and orbital region and described as jabbing and stabbing with a duration of 15–30 min. • All ENT and neurological examinations showed normal findings. • The authors supported the hypothesis of sinus barotrauma as a possible mechanism of AH.
2011, Mainardi et al. [29]	N/A	N/A	N/A	Letter to the editor	• The authors stated that the findings from the paper by Pfund et al. [19] differ from the stereotypical AH-attacks: 1) The AH-attack does not exceed 30 min, 2) the pain is not strictly bilateral and 3) neuroradiological examinations do not show signs of sinus inflammation. • They suggested that “pure” AH should be considered as a separated headache from the flight-related headache in patients with organic condition.
2011, Ipekdal et al. [11]	5	1 M/ 4 F	29.6 ± 1.9	Case reports	• All the patients developed a severe headache during the ascending or the descending phase. The pain was located in the unilateral fronto-orbital region and lasted between 15 and 25 min. • Triptans were prescribed to all patients and they were instructed to take a triptan (either naratriptan, zolmitriptan, eletriptan or sumatriptan) 30 min before the start of the airplane travel. There was a follow-up period of 2–4 years and all patients were completely headache-free in all their airplane travels. • The authors indicated that sinus barotrauma might play a role in the mechanism of AH. They also hypothesized that the use of triptans may cause vasospasm in cerebral arteries and thereby prevent the AH-attack.
2011, Mainardi et al. [30]	N/A	N/A	N/A	Letter to the editor	• The authors suggested that AH should be included in the forthcoming revision of the “International Classification of Headache Disorders” in the section of “Headache attributed to disorder of homoeostasis”. • They stated that the criteria set by Berilgen et al. [26] are broadened. The criteria of AH should be restrictive and clearly defined in order to properly diagnose the headache.
2011, Mainardi et al. [31]	63	41 M/ 22 F	29.5	Conference abstract	• The headache occurred mainly at landing and in the fronto-orbital region. Pain intensity was severe and lasted about 20 min. • Prophylactic use of NSAIDs prevented the AH-attacks. • The authors stated that their findings confirm the stereotypical features of AH and that the headache should be recognized by The International Headache Society.
2011, Kararizou et al. [12]	1	1 F	27	Case report	• The patient experienced an intense headache in the frontotemporal and retro-orbital area of the skull. The pain was described as jabbing and lasted about 15–20 min. • She had a history of tension type headache. ENT, CT, MRI and MRA showed normal findings. A test for anxiety and depression was performed with a score of 14 on the Hamilton anxiety scale (mild anxiety ≥14) and 12 on the Hamilton depression scale (mild depression >7). • Paracetamol and ibuprofen were taken by the patient, but there was no relieving effect. • The authors stated that psychiatric disorders should be investigated for future studies in order to establish a possible signification to AH. This might clarify the mechanism of AH and specify effective therapeutic strategies.
2012, Mohamad [24]	N/A	N/A	N/A	Letter to the editor	• The author ascertained that the clinical features of AH are similar with the symptoms of sinus barotrauma. According to author, the pressure changes during the landing phase might be a key player in the pathophysiology of AH. • According to author, sinus barotrauma could be prevented by surgical or medical intervention.
2012, Purdy [14]	N/A	N/A	N/A	Editorial	• The author postulated that sinus barotrauma might be the main mechanism in the pathophysiology of AH. • According to the author, the increasing number of case reports on AH is important for the further research for this headache that will allow future studies to examine the mechanism and thereby develop specific therapeutic strategies.
2012, Shevel [32]	N/A	N/A	N/A	Letter to the editor	• The author stated that it does not seem plausible that the changes in the barometric pressure should trigger the AH-attack during the ascending or descending phases. The pressure in the sinus is low during the whole flight travel and will not be affected by the increasing ambient pressure during the descending phase. • The pressure in the cabin and the intra-sinus pressure is the lowest during the whole flight travel. The pain is expected to occur during this phase, which is not the case.
2012, Mainardi et al. [6]	75	29 M/ 46 F	36.5 ± 10.2	Journal article	• The majority of the patients developed a headache during the landing. The headache lasted less than 30 min. In most of the cases, the pain was described as jabbing, stabbing and located in the fronto-orbital region. The intensity of pain was severe and rated as 8.8/10. • A subgroup, consisting 29 AH-patients, took medications. Only 11 of the patients were completely headache-free when they used ibuprofen, naproxen, aspirin and nasal decongestant. • A minority of the patients used non-pharmacological methods such as Valsalva manoeuvre, pressure on pain site chewing. These methods showed an unremarkable efficacy. • The authors did not think that the change in pressure is the only trigger for the AH-attack. Other factors such as environmental factors (aircraft speed, angle of ascent/descent, maximum altitude) and anatomic factors (acquired or congenital abnormalities of sinus outlet might contribute to the development of AH.
2013, Mainardi et al. [33]	11	5 M/6 F	37	Conference abstract	• All patients suffered from AH and experienced a similar headache when they were descending a mountain by car. Both headaches were described as a severe jabbing pain in the unilateral fronto-temporal region and lasted about 20 min. • General and neurological examination, brain MRI, MRA, and cranial CT-scan for sinuses showed normal findings. • The authors suggested that both headaches might share a possible common pathophysiology mechanism as both headaches are trigged by changes in the pressure.
2013, Mainardi et al. [34]	9	4 M/5 F	37 ± 12	Conference abstract	• All AH-patients experienced a similar headache when they were scuba diving. The headache pain started shortly after the ascent. • MRI, MRA and cranial CT-scan for sinuses showed normal findings. • The authors suggested that AH and headache attributed to scuba diving might share a common pathophysiology mechanism as both headaches are trigged by external pressure.
2013, Mainardi et al. [3]	N/A	N/A	N/A	Journal article	• The authors stated that AH might share a common physiological mechanism with the situations when you are descending from a mountain in car or diving as all these conditions are trigged the changes in the pressure. • Beside the pressure changes, other factors such as environmental factors (aircraft speed, angle of ascent/descent, maximum altitude) and anatomic factors (acquired or congenital abnormalities of sinus outlet might contribute to the development of AH. • According to the authors, AH should be considered as a formal headache by “International Headache Society”.
2013, Cherian et al. [35]	2	2 M	33 ± 1	Case reports	• Both patients developed headache during the descent. The pain was described as jabbing, stabbing and located in the unilateral supraorbital region. The intensity of pain was severe and rated as 9.5/10. • MRI and CT showed normal findings. Only one patient had a history of migraine without aura. • The patients took oxymetazoline nasal drops in combination with naproxen sodium which completely prevented the AH-attacks.
2013, Nagatani [21]	2	1 M/1 F	37.5 ± 11.5	Case reports	• Both patients developed a severe headache during the descent. The headache lasted 30–40 min and the pain was located in the fronto-orbital region. • Medical history was not relevant for the female patient, but male patient had had a past history of episodic tension-type headache. Intracranial and paranasal CT examinations showed normal findings. • For the male patient, the headache only occurred when he had mental stress or was suffering from a lack of sleep. • NSAIDs were taken by both patients, but did not show any relieving effect. • The authors pointed out that the prevalence of AH might be underestimated as many passengers, suffering from AH, do not seek a doctor.
2015, Rogers et al. [18]	1	1 F	11	Case report	• The patient experienced a severe headache during the ascent. The pain was described as sharp, stabbing, throbbing and located in the unilateral and frontal region. Every headache episode was associated with dizziness, but there were no additional accompanying symptoms. • Medical history was significant for episodic migraine and adenotonsillectomy only. • Blood test, MRI and EEG showed normal findings. • The authors stated that their data, in conjunction with the reignition of AH by the International Headache Society, contribute to the increasing evidence on AH.
2015, Mainardi et al. [36]	130	76 M/54 F	N/A	Conference abstract	• The majority of the patients developed AH during the landing phase. The pain was located in the frontal-orbital region and lasted less than 30 min. • The AH-attacks occurred more than 50% of the flight travels in 35 patients and 23 patients experienced AH in every flight travel. • Prophylactic use of NSAIDs showed a relieving or preventing effect in more than 50% of the cases. • The authors stated that these findings confirm the stereotypical clinical features of an AH-attack.
2015, Mainardi et al. [37]	140	83 M/ 87 F	N/A	Conference abstract	• The data from this publication are similar to the conference abstract by Mainardi et al. [36].
2016, Hiraga et al. [23]	N/A	N/A	N/A	Case report	• A 74-year old woman experienced a severe headache during the descent. The headache met the criteria of “International Classification of Headache Disorders 3 beta version” [1] for AH. • The headache pain continued for 48 h after landing. • MRA showed segmental vasoconstriction of brain vessels allowing the diagnosis reversible cerebral vasoconstriction syndrome (RCVS). • The authors suggested that RCVS may play a role in the pathophysiology of AH.
2016, Mainardi et al. [22]	N/A	N/A	N/A	Editorial	• The authors disagreed with the findings by Hiraga et al. [23] and ascertain that the clinical features of reversible cerebral vasoconstriction syndrome (RCVS) and AH are not comparable. By instance, the duration of an AH-attack does not exceed 30 min. The authors emphasized that patients who are suffering a second phase headache after an AH-attack should be investigated carefully in order to rule out secondary pathology, including RCVS.
2016, Hiraga et al. [38]	N/A	N/A	N/A	Editorial	• The authors agreed with Mainardi et al. [22] that AH and reversible cerebral vasoconstriction syndrome (RCVS) are two separated types of headache. • However, they suggested that RCVS might be a potential cause of AH in cases of second headaches arising after the resolution of the triggering factors such as the airplane descent. As a subgroup of AH sufferers do experience a second phase headache after the AH-attack, the authors believed that RCVS might be an overlooked condition and the physicians should be aware that airplane descent might be a trigger of RCVS.
2016, Mainardi et al. [20]	1	1 M	36	Case report	• The patient experienced a headache when she was descending from high altitude by car, called Mountain Descending Headache (MDH). The clinical features of the headache were identical to the stereotypical features of AH. • The authors suggested that MDH and AH might share a common pathophysiology mechanism as both headaches are trigged by the imbalance between the pressure in the sinuses and the changing environmental pressure.
2016, Zubero et al. [39]	1	1 F	34	Case report	• The patient developed a severe predominant right hemicranial headache with rhinorrhea and tearing during take-off and landing. • Medical history was not relevant. Neurological examinations showed normal findings.
2016, Bui et al. [2]	21	9 M/12 F	39 ± 14	Journal article	• All patients fulfilled the AH-criteria set by “International Classification of Headache Disorders 3 beta version” [1]. • Seven patients suffered from migraine and 13 patients suffered from High Altitude Headache. • The statistical analysis indicated that High Altitude Headache, but not migraine, might be a risk factor for AH. • Five patients took medication, i.e. paracetamol and triptans. These medications were effective to relieve and prevent the headache pain. • The authors supported the established hypothesis that changes in the pressure might play a key role in the mechanism of AH.
2017, Nath et al. [40]	2	2 M	45.5 ± 3.5	Case reports	• The patients experienced a bilateral occipital and parieto-occipital severe sharp shooting stabbing and piercing headache during the landing. The headache was associated with severe dizziness and lasted 40–50 min after landing. Both patients rated the intensity of pain as 8–9/10. • ENT, CT and MRI showed normal findings. Both patients had no history of tension headache, migraine or cluster headache. • The authors ascertained that the duration of the headache and the pain localization in the occipital and parieto-occipital area are not in accordance with the AH-criteria set by “International Classification of Headache Disorders 3 beta version” [1].
2017, Bui et al. [25]	7	1 M/ 6 F	29.7 ± 9.6	Journal article	• All patients fulfilled the AH-criteria set by “International Classification of Headache Disorders 3 beta version” [1]. • A pressure chamber was used as an experimental model to induce simulated AH in the patients. The clinical features of the headache were in accordance with an AH-attack in a real-time flight travel. • Saliva samples, saturation pulse oxygen, blood pressure and thermo imagining were collected and measured before, during and after their simulated flight in the pressure chamber. • The data showed that the values for saturation pulse oxygen, prostaglandin E2 and cortisol significant different in AH-patients in comparison with the healthy participants.

AH Airplane headache also called headache attributed to airplane travel. CT computerized tomography. MRI brain magnetic resonance imagining. MRA magnetic resonance angiography. ENT ear-nose-throat, EEG Electroencephalography, NSAIDs Non Steroidal Anti-Inflammatory Drugs