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2.  Chronic migraine classification: current knowledge and future perspectives 
The Journal of Headache and Pain  2011;12(6):585-592.
In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days).
doi:10.1007/s10194-011-0393-6
PMCID: PMC3208036  PMID: 22028184
Chronic migraine; Transformed migraine; Chronic daily headache; Chronic headache; Headache; Migraine
3.  Chronic migraine classification: current knowledge and future perspectives 
The Journal of Headache and Pain  2011;12(6):585-592.
In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days).
doi:10.1007/s10194-011-0393-6
PMCID: PMC3208036  PMID: 22028184
Chronic migraine; Transformed migraine; Chronic daily headache; Chronic headache; Headache; Migraine
4.  Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study 
The Journal of Headache and Pain  2011;12(4):427-433.
Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0339-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0339-z
PMCID: PMC3139089  PMID: 21499747
Botulinum toxin type-A; Medication-overuse headache; Prophylactic treatment; Migraine; Pericranial muscle tenderness
5.  Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study 
The Journal of Headache and Pain  2011;12(4):427-433.
Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0339-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0339-z
PMCID: PMC3139089  PMID: 21499747
Botulinum toxin type-A; Medication-overuse headache; Prophylactic treatment; Migraine; Pericranial muscle tenderness
6.  Headache, anxiety and depressive disorders: the HADAS study 
The Journal of Headache and Pain  2010;11(2):141-150.
The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tension-type headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (p = 0.009) for obsessive–compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2–7.0). The association was higher (OR 6.3; 95% CI 1.4–28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive–compulsive disorder (OR 4.8; 95% CI 1.1–20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden.
doi:10.1007/s10194-010-0187-2
PMCID: PMC3452290  PMID: 20108021
Migraine; Tension-type headache; Depression; Anxiety; Prevalence
7.  Cardiac cephalgia 
The purpose of this review was to provide a critical evaluation of medical literature on so-called “cardiac cephalgia” or “cardiac cephalalgia”. The 2004 International Classification of Headache Disorders codes cardiac cephalgia to 10.6 in the group of secondary headaches attributed to disorder of homoeostasis. This headache is hardly recognizable and is associated to an ischaemic cardiovascular event, of which it may be the only manifestation in 27% of cases. It usually occurs after exertion. Sometimes routine examinations, cardiac enzymes, ECG and even exercise stress test prove negative. In such cases, only a coronary angiogram can provide sufficient evidence for diagnosis. Cardiac cephalgia manifests itself without a specific pattern of clinical features: indeed, in this headache subtype there is a high variability of clinical manifestations between different patients and also within the same patient. It “mimics” sometimes a form of migraine either accompanied or not by autonomic symptoms, sometimes a form of tension-type headache; on other occasions, it exhibits characteristics that can hardly be interpreted as typical of primary headache. Pain location is highly variable. When the headache occurs as the only manifestation of an acute coronary event, the clues for suspicion are a) older age at onset, b) no past medical history of headache, c) presence of risk factors for vascular disorders and d) onset of headache under stress. Knowledge of cardiac cephalgia is scarce, due to its rare clinical occurrence and to the scant importance given to headache as a symptom concomitantly with an ischaemic cardiac event.
doi:10.1007/s10194-008-0087-x
PMCID: PMC3451760  PMID: 19139804
Cardiac cephalgia; Exertional headache; Secondary headache; Headache attributed to disorder of homoeostasis; Acute myocardial ischemia
8.  Epidemiology of migraine 
The Journal of Headache and Pain  2003;4(Suppl 1):s18-s22.
One-year migraine prevalence rates in the general population for Western countries vary from 4% to 9% in men and from 11% to 25% in women. Non-Western countries report lower figures. Incidence rates for people under 30 years of age vary from 1.5 to 6 per 1000 person-years in men and from 3 to 24 per 1000 person-years in women. Data on the prevalence of migraine in general, on the gender ratio and on the variations in prevalence in the different age ranges are fairly comparable and can be regarded as very close to reality. On the contrary, data on the incidence of migraine, on the prevalence of different migraine subtypes, such as migraine with aura and the so-called migrainous disorder, and on the frequency of migraine attacks show a striking discordance that somewhat undermines their reliability. The main critical points in prevalence and incidence studies are migraine definition and the methodological approaches used for case screening. Even if International Headache Society (IHS) classification is certainly an improvement over previous tools used in epidemiological studies, the diagnostic criteria for migraine without aura are quite scanty and not easily remembered by subjects belonging to the general population, and those for migraine with aura appear not only difficult to translate for use in a questionnaire or an interview, but also too loose. In particular, the lack of any low-end limit for aura duration may cause an overestimation of migraine with aura prevalence.
doi:10.1007/s101940300003
PMCID: PMC3611683
Key words Migraine; Migraine without aura; Migraine with aura; Epidemiology; Headache
9.  Epidemiology of migraine 
The Journal of Headache and Pain  2001;2(Suppl 1):s11-s13.
The 1988 International Headache Society (IHS) classification has greatly contributed to overcoming the obstacles that had made it difficult in the past to compare results of surveys on headache epidemiology. For migraine without aura, the more recent studies of the general adult population indicate lifetime prevalence rates between 6% and 10% for men and between 15% and 26% for women. One–year prevalence rates are between 2% and 15% for men and between 4% and 35% for women. Rates of frequent migraine are 6% in men and 14% in women. Migraine occurs in 3%–6% of prepubertal children with no significant differences between girls and boys. The prevalence of migraine without aura increases progressively from the age of 12 years up to about the age of 40, when it begins to record a gradual, progressive decrease down to 1%–4% in the elderly. For migraine with aura, recent epidemiological investigations by Rasmussen and Olesen indicate a lifetime prevalence rate of 6% and a one-year prevalence rate of 4%.
doi:10.1007/s101940170002
PMCID: PMC3451821
Migraine; Migraine without aura; Migraine with aura; Epidemiology

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