Ferdinando Maggioni

Headache during pregnancy.

A questionnaire was submitted to 430 women 3 days after delivery, asking mainly about features of headache before and during pregnancy and their possible modification or recurrence; moreover, delivery modalities and the condition of the newborn were evaluated. One-hundred-and-twenty-six (29.3%) were found to be primary headache sufferers (IHS criteria, 1988), 81 of whom had migraine without aura (MO), 12 migraine with aura (MA), and 33 tension-type headache (TH). In all three groups, about 80% showed complete remission or a higher than 50% decrease in the number of attacks. The improvement was more evident after the end of the first trimester; this trend was common to the three primary headaches considered. In our series of primary headaches, there was only one case (MO) which began during pregnancy. In a subgroup of pluripara, headache maintained the improvement presented in the first pregnancy also during the following gravidic periods in about 50% of cases, whereas in the remaining 50% a worsening in parallel with successive pregnancies was found. Primary headaches “per se” do not seem to increase the pregnancy or delivery risks, nor the vitality of the newborn. During pregnancy, drug use was very much reduced and was restricted to a limited number of compounds.

Chronic paroxysmal hemicrania, hemicrania continua and SUNCT syndrome in association with other pathologies: a review.

We present a review of 22 cases of headache mimicking chronic paroxysmal hemicrania (CPH) (17 female and five male; F : M ratio 3.4), nine cases mimicking hemicrania continua (HC) (seven female and two male) and seven cases mimicking SUNCT syndrome (five male and two female) found in association with other pathologies published from 1980 up to the present. All case reports were discussed with respect to diagnostic criteria proposed by International Headache Society (IHS) for CPH, by Goadsby and Lipton for HC and SUNCT, and evaluated to identify a possible causal relationship between the pathology and the onset of headache. The aim of the present review was to evaluate if the presence of associated lesions and their location could help elucidate the pathogenesis of trigeminal autonomic cephalalgias (TACs).

Osmophobia in Migraine and Tension-Type Headache and Its Clinical Features in Patients With Migraine

Intolerance to smell is often reported by migraine patients. This study evaluates osmophobia in connection with the diagnosis of migraine and episodic tension-type headache (ETTH). The characteristics of this symptom are also investigated. We recruited from our Headache Centre 1005 patients (772 female, 233 male; age 37 ± 11 years), of whom 677 were migraine without aura (MoA), 130 migraine with aura (MA) and 198 TTH. Patients with two or more forms of primary headache were excluded. Among migraine patients, 43.9% with MoA and 38.5% with MA reported osmophobia during the attacks; none of the 198 TTH patients suffered this symptom. Most frequently offending odours were scents (63.9%), food (55.2%) and cigarette smoke (54.8%). Osmophobia appears structurally integrated into the migraine history of the patient. It seems to be a peculiar symptom favouring the diagnosis of migraine (MoA and MA) in the differential diagnosis with ETTH.

Cluster-like headache. A comprehensive reappraisal

Among the primary headaches, cluster headache (CH) presents very particular features allowing a relatively easy diagnosis based on criteria listed in Chapter 3 of the International Classification of Headache Disorders (ICHD-II). However, as in all primary headaches, possible underlying causal conditions must be excluded to rule out a secondary cluster-like headache (CLH). The observation of some cases with clinical features mimicking primary CH, but of secondary origin, led us to perform an extended review of CLH reports in the literature. We identified 156 CLH cases published from 1975 to 2008. The more frequent pathologies in association with CLH were the vascular ones (38.5%, n = 57), followed by tumours (25.7%, n = 38) and inflammatory infectious diseases (13.5%, n = 20). Eighty were excluded from further analysis, because of inadequate information. The remaining 76 were divided into two groups: those that satisfied the ICHD-II diagnostic criteria for CH, ‘fulfilling’ group (F), n = 38; and those with a symptomatology in disagreement with one or more ICHD-II criteria, ‘not fulfilling’ group (NF), n = 38. Among the aims of this study was the possible identification of clinical features leading to the suspicion of a symptomatic origin. In the differential diagnosis with CH, red flags resulted both for F and NF, older age at onset; for NF, abnormal neurological/general examination (73.6%), duration (34.2%), frequency (15.8%) and localization (10.5%) of the attacks. We stress the fact that, on first observation, 50% of CLH presented as F cases, perfectly mimicking CH. Therefore, the importance of accurate, clinical evaluation and of neuroimaging cannot be overestimated.

Osmophobia in primary headaches

This study evaluates osmophobia (defined as an unpleasant perception, during a headache attack, of odours that are non–aversive or even pleasurable outside the attacks) in connection with the diagnosis of primary headaches. We recruited 775 patients from our Headache Centre (566 females, 209 males; age 38±12 years), of whom 477 were migraineurs without aura (MO), 92 with aura (MA), 135 had episodic tension–type headache (ETTH), 44 episodic cluster headache (ECH), 2 chronic paroxysmal hemicrania (CPH) and 25 other primary headaches (OPHs: 12 primary stabbing headaches, 2 primary cough headaches, 3 primary exertional headaches, 2 primary headaches associated with sexual activity, 3 hypnic headaches, 2 primary thunderclap headaches and 1 hemicrania continua). Among them, 43% with MO (205/477), 39% with MA (36/92), and 7% with CH (3/44) reported osmophobia during the attacks; none of the 135 ETTH and 25 OPH patients suffered this symptom. We conclude that osmophobia is a very specific marker to discriminate adequately between migraine (MO and MA) and ETTH; moreover, from this limited series it seems to be a good discriminant also for OPHs, and for CH patients not sharing neurovegetative symptoms with migraine. Therefore, osmophobia should be considered a good candidate as a new criterion for the diagnosis of migraine.

Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders.

The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radio-immunoassay methods in external jugular blood] between responders and nonresponders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a lesser degree of trigeminal activation, lower variations of trigeminal neuropeptides after triptan administration, and no evidence of parasympathetic activation at baseline.

Headache attributed to airplane travel (“airplane headache”: first italian case

A new form of headache, whose attacks seem to be stereotyped, has been recently reported; because of the peculiarity of its onset, strictly related to airplane travel, the name of “Airplane headache” was proposed. A total of 7 cases have been published. Here we present the first Italian one. Furthermore the revision of the clinical characteristics of each patient leads us to propose provisional diagnostic criteria.

Weight variations in the prophylactic therapy of primary headaches: 6-month follow-up.

We conducted a study on 367 patients (86% female, 14% male; mean age 37±15 years) suffering from migraine with and without aura and chronic tension–type headache to evaluate the incidence of weight gain, an undesirable side effect observed during prophylactic therapy in primary headaches. Patients treated with amitriptyline (20 and 40 mg), pizotifen (1 mg), propranolol (80–160 mg), atenolol (50–100 mg), verapamil (160–240 mg), valproate (600 mg) and gabapentin (900–1200 mg) were evaluated after a period of 3 and 6 months. In particular, 89 patients were assessed (78% female, 22% male) at 6 months, of whom 10 were in treatment with amitriptyline 20 mg, 19 with amitriptyline 40 mg, 7 with pizotifen (1 mg), 13 with propranolol (80–160 mg), 4 with verapamil (160 mg), 10 with valproate (600 mg), 15 with atenolol (50 mg) and 11 with gabapentin (900–1200 mg). The control group consisted of 97 patients with migraine (79% female, 21% male; mean age 35±16 years) without indication for prophylactic therapy. Weight variations ≥1 kg were considered. After 6 months of therapy, the percentage of patients with weight gain was 86% with pizotifen (6/7; mean weight increase 4.4±2.5 kg), 60% with amitriptyline 20 mg (6/10; 3.1±1.6), 47% with amitriptyline 40 mg (9/19; 5.4±2.7), 25% with valproate 600 mg (2/8, 3.0±2.8 kg), 25% with verapamil (1/4, 2.5 kg), 20% with atenolol (3/15, 1.7±0.6 kg), 9% with gabapentin (1/11, 1.5 kg) and 8% with propranolol (1/13; 6 kg). We conclude that propranolol, gabapentin, atenolol, verapamil and valproate affect body weight in a modest percentage of patients at 6 months. A greater mean weight gain at 6 months was found in patients treated with pizotifen, amitriptyline, and, in one patient out of 13, with propranolol.

Episodic hypnic headache

Hypnic headache is a primary headache disorder, which occurs exclusively during sleep and usually begins after the age of 60 years. It was first described by Raskin in 1988 (1), as a sleep-related headache, that regularly awakened patients at a consistent time of night; the pain was diffuse, persisting for 30–60 min, without autonomic symptoms. Hypnic headache was not included in the first edition of the International Headache Society (IHS) classification. In the second edition this headache was classified in section 4.5, included in the group of ‘Other primary headaches’ (2). At the time of this writing 82 patients with this disorder have been described (3–29). The possible pathophysiology and the pharmacological treatment of this headache have been recently discussed and analysed (30, 31), as well as its relationship with REM sleep (14, 27, 28). A symptomatic case that developed after an ischaemic stroke in the pontine reticular formation was also reported (29). The natural history of hypnic headache is not well known. The review of the published cases suggests that hypnic headache tends to be a chronic unremitting disorder. To better understand the natural history of hypnic headache, we have prospectively followed 4 patients with this disorder since 1998. The first two cases, diagnosed in 1998 and 1999, respectively, were published previously (13, 17); the other two cases, of new description, were first seen in 2000. Hypnic headache was the main diagnosis in 0.09% of all headache patients and notably in 1.4% of geriatric patients (above the age of 65 years) seen in our Headache Centre from 1998 to 2002.

Headache attributed to airplane travel ('airplane headache'): clinical profile based on a large case series.

Background: The ‘headache attributed to airplane travel’, also named ‘airplane headache’ (AH), is a recently described headache disorder that appears exclusively in relation to airplane flights, in particular during the landing phase. Based on the stereotypical nature of the attacks in all reported cases, we proposed provisional diagnostic criteria for AH in a previously published paper. Up to now 37 cases have been described in the literature. Methods: After our paper was disseminated via the Internet, we received several email messages from subjects around the world who had experienced such a peculiar headache. Their cooperation, by completing a structured questionnaire and allowing the direct observation of three subjects, enabled us to carry out a study on a total of 75 patients suffering from AH. Results: Our survey confirmed the stereotypical nature of the attacks, in particular with regard to the short duration of the pain (lasting less than 30 minutes in up to 95% of the cases), the clear relationship with the landing phase, the unilateral pain, the male preponderance, and the absence of accompanying signs and/or symptoms. It is conceivable to consider barotrauma as one of the main mechanisms involved in the pathophysiology of AH. The observation that the pain appears inconstantly in the majority of cases, without any evident disorder affecting the paranasal sinuses, could be consistent with a multimodal pathogenesis underlying this condition, possibly resulting in the interaction between anatomic, environmental and temporary concurrent factors. Conclusions: This is by far the largest AH case series ever reported in the literature. The diagnostic criteria that we previously proposed proved to be valid when applied to a large number of patients suffering from this condition. We support its recognition as a new form of headache, to be included in the forthcoming update of the International Headache Society Classification, within ‘10. Headache attributed to disorder of homoeostasis’. Its formal validation would favour further studies aimed at improving the understanding of its pathophysiology and implementing preventative measures.