Giorgio Zanchin

A history of the therapeutic use of liquorice in Europe

Abstract Liquorice root has been used in Europe since prehistoric times, and is well documented in written form starting with the ancient Greeks. In this review we compare the independent development of medical uses of this botanical drug in several ancient cultures, attempting to show the rationality of specific indications across different ethnic groups with different cultural backgrounds. Identical specific indications in different cultures highlight universally reproducible therapeutic effects that are beyond those of a mere placebo. In the first part of the review, historical sources dealing with liquorice (Scythian, Greek, Roman, and from the Middle Ages in Germany, Italy, Spain, England) have been considered. In the second part, the historical records of diseases treated with liquorice have been presented. Finally, a comparison between traditional use in and outside Europe, with the most important recent scientific studies concerning its use, is presented.

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.

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version.

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 intracranial tumours: A prospective cohort study

Between January 2007 and March 2008, we prospectively studied all patients operated on for intracranial tumours in our Department of Neurosurgery. Preoperatively, all patients were interviewed by a neurologist to collect headache characteristics. Measurements of tumour and oedema volume were made using dedicated software for magnetic resonance imaging studies. Tumour histopathology was established by histological examination postoperatively. If headache improved postoperatively, a diagnosis of ‘headache attributed to intracranial neoplasm’ was made, according to the 2004 International Classification of Headache Disorders (ICHD-II). A multivariate logistic regression model was used to evaluate the association of headache with potential risk factors. We studied 206 subjects. The prevalence of tumour headache was 47.6%. Intracranial tumour headache was non-specific and in most cases could not be classified by current ICHD-II diagnostic criteria for primary headache syndromes. Its prevalence varied depending on volume, location and type of tumour, as well as on the patients previous headache history.

Osmophobia in juvenile primary headaches

This study was planned to investigate the prevalence of osmophobia in juvenile headache sufferers and to analyse the diagnostic utility of osmophobia in order to distinguish migraine without aura from episodic tension-type headache. We examined 305 consecutive patients presenting at our Paediatric Headache Centre. A semistructured questionnaire was given to 275 selected patients affected by migraine or tension-type headache. The prevalence of osmophobia during attacks was 18.5%, mainly in migraine patients (25.1%) vs. those with tension-type headache (8.3%). Osmophobia showed more specificity than phonophobia or photophobia in the differential diagnosis between migraine and tension-type headache. In conclusion, this study demonstrates that osmophobia resulted in a symptom with poor sensitivity (27.1%) but high specificity (92%) that could become a supportive diagnostic criterion even in children for the differential diagnosis between migraine without aura and tension-type headache.