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1.  Optimal management of severe nausea and vomiting in migraine: improving patient outcomes 
Migraine is a common and potentially disabling disorder for patients, with wide-reaching implications for health care services, society, and the economy. Nausea and vomiting during migraine attacks are common symptoms that affect at least 60% of patients suffering from migraines. These symptoms are often more disabling than the headache itself, causing a great burden on the patient’s life. Nausea and vomiting may delay the use of oral abortive medication or interfere with oral drug absorption. Therefore, they can hinder significantly the management and treatment of migraine (which is usually given orally). The main treatment of pain-associated symptoms of migraine (such as nausea and vomiting) is to stop the migraine attack itself as soon as possible, with the effective drugs at the effective doses, seeking if necessary alternative routes of administration. In some cases, intravenous antiemetic drugs are able to relieve a migraine attack and associated symptoms like nausea and vomiting. We performed an exhaustive PubMed search of the English literature to find studies about management of migraine and its associated symptoms. Search terms were migraine, nausea, and vomiting. We did not limit our search to a specific time period. We focused on clinical efficacy and tolerance of the various drugs and procedures based on data from human studies. We included the best available studies for each discussed drug or procedure. These ranged from randomized controlled trials for some treatments to small case series for others. Recently updated books and manuals on neurology and headache were also consulted. We herein review the efficacy of the different approaches in order to manage nausea and vomiting for migraine patents.
doi:10.2147/PROM.S31392
PMCID: PMC3798203  PMID: 24143125
migraine; nausea; vomiting; management; treatment
2.  Involvement of gap junction channels in the pathophysiology of migraine with aura 
Migraine is a common, recurrent, and disabling primary headache disorder with a genetic component which affects up to 20% of the population. One third of all patients with migraine experiences aura, a focal neurological disturbance that manifests itself as visual, sensitive or motor symptoms preceding the headache. In the pathophysiology of migraine with aura, activation of the trigeminovascular system from the meningeal vessels mediates migraine pain via the brainstem and projections ascend to the thalamus and cortex. Cortical spreading depression (CSD) was proposed to trigger migraine aura and to activate perivascular trigeminal nerves in the cortex. Quinine, quinidine and the derivative mefloquine are able to inhibit CSD suggesting an involvement of neuronal connexin36 channels in CSD propagation. More recently, CSD was shown to induce headache by activating the trigeminovascular system through the opening of stressed neuronal Pannexin1 channels. A novel benzopyran compound, tonabersat, was selected for clinical trial on the basis of its inhibitory activity on CSD and neurogenic inflammation in animal models of migraine. Interestingly, in the time course of animal model trials, tonabersat was shown to inhibit trigeminal ganglion (TGG) neuronal-glial cell gap junctions, suggesting that this compound could prevent peripheral sensitization within the ganglion. Three clinical trials aimed at investigating the effectiveness of tonabersat as a preventive drug were negative, and conflicting results were obtained in other trials concerning its ability to relieve attacks. In contrast, in another clinical trial, tonabersat showed a preventive effect on attacks of migraine with aura but had no efficacy on non-aura attacks. Gap junction channels seem to be involved in several ways in the pathophysiology of migraine with aura and emerge as a new promising putative target in treatment of this disorder.
doi:10.3389/fphys.2014.00078
PMCID: PMC3933780  PMID: 24611055
aura; connexin; cortical spreading depression; gap junction; pannexin; tonabersat; trigeminovascular
3.  Migraine management: How do the adult and paediatric migraines differ? 
Migraine is one of the common causes of severe and recurring headache. It may be difficult to manage in primary care settings, where it is under diagnosed and medically treated. Migraine can occur in children as well as in adults and it is three times more common in women than in men. Migraine in children is different from adults in various ways. Migraine management depends on the various factors like duration and severity of pain, associated symptoms, degree of disability, and initial response to treatment. The therapy of children and adolescents with migraines includes treatment modalities for acute attacks, prophylactic medications when the attacks are frequent, and biobehavioural modes of treatment to aid long-term management of the disorder. The long lasting outcome of childhood headaches and progression into adult headaches remains largely unknown. However, it has been suggested that adult migraine may represent a progressive disorder. In children, the progressive nature is uncertain and further investigations into longitudinal outcome and phenotypic changes in childhood headaches have yet to be recognized. Even though paediatric and adult migraines seem to be slightly different from one another, but not enough to categorize either as sole.
doi:10.1016/j.jsps.2011.07.001
PMCID: PMC3745030  PMID: 23960771
Adult; Headache; Migraine; Paediatrics
4.  Migraine and Obesity: Epidemiology, Possible Mechanisms, and the Potential Role of Weight Loss Treatment 
Migraine and obesity are two public health problems of enormous scope that are responsible for significant quality of life impairment and financial cost. Recent research suggests that these disorders may be directly related, with obesity exacerbating migraine in the form of greater headache frequency and severity, or possibly increasing the risk for having migraine. The relationship between migraine and obesity may be explained through a variety of physiological, psychological, and behavioral mechanisms, many of which are affected by weight loss. Given that weight loss might be a viable approach for alleviating migraine in obese individuals, randomized controlled trials are needed to test the effect of weight loss interventions in obese migraineurs. Large-scale weight loss trials have shown that behavioral interventions, in particular, can produce sustained weight losses and related cardiovascular improvements in patients who are diverse in body weight, age, and ethnicity. Consequently, these interventions may provide a useful treatment model for showing whether weight loss reduces headache frequency and severity in obese migraineurs, and offering further insight into pathways through which weight loss might exert an effect.
doi:10.1111/j.1467-789X.2010.00791.x
PMCID: PMC2974024  PMID: 20673279
migraine; obesity; mechanisms; weight loss
5.  Clinical features, anger management and anxiety: a possible correlation in migraine children 
Background
Psychological factors can increase severity and intensity of headaches. While great attention has been placed on the presence of anxiety and/or depression as a correlate to a high frequency of migraine attacks, very few studies have analyzed the management of frustration in children with headache. Aim of this study was to analyze the possible correlation between pediatric migraine severity (frequency and intensity of attacks) and the psychological profile, with particular attention to the anger management style.
Methods
We studied 62 migraineurs (mean age 11.2 ± 2.1 years; 29 M and 33 F). Patients were divided into four groups according to the attack frequency (low, intermediate, high frequency, and chronic migraine). Pain intensity was rated on a 3-levels graduate scale (mild, moderate and severe pain). Psychological profile was assessed by Picture Frustration Study test for anger management and SAFA-A scale for anxiety.
Results
We found a relationship between IA/OD index (tendency to inhibit anger expression) and both attack frequency (r = 0.328, p = 0.041) and intensity (r = 0.413, p = 0.010). When we analyzed the relationship between anxiety and the headache features, a negative and significant correlation emerged between separation anxiety (SAFA-A Se) and the frequency of attacks (r = −0.409, p = 0.006). In our patients, the tendency to express and emphasize the presence of the frustrating obstacle (EA/OD index) showed a positive correlation with anxiety level (“Total anxiety” scale: r = 0.345; p = 0.033).
Conclusions
Our results suggest that children suffering from severe migraine tend to inhibit their angry feelings. On the contrary, children with low migraine attack frequency express their anger and suffer from separation anxiety.
doi:10.1186/1129-2377-14-39
PMCID: PMC3653764  PMID: 23651123
Migraine; Anger; Anxiety; Children
6.  Comorbid neuropathologies in migraine 
The Journal of Headache and Pain  2006;7(4):222-230.
The identification of comorbid disorders in migraineurs is important since it may impose therapeutic challenges and limit treatment options. Moreover, the study of comorbidity might lead to improve our knowledge about causes and consequences of migraine. Comorbid neuropathologies in migraine may involve mood disorders (depression, mania, anxiety, panic attacks), epilepsy, essential tremor, stroke, and white matter abnormalities. Particularly, a complex bidirectional relation exists between migraine and stroke, including migraine as a risk factor for cerebral ischemia, migraine caused by cerebral ischemia, migraine as a cause of stroke, migraine mimicking cerebral ischemia, migraine and cerebral ischemia sharing a common cause, and migraine associated with subclinical vascular brain lesions.
doi:10.1007/s10194-006-0300-8
PMCID: PMC3476070  PMID: 16767530
Migraine; Depression; Epilepsy; Tremor; Stroke; White matter lesions; Patent foramen ovale
7.  Common hippocampal structural and functional changes in migraine 
Brain structure & function  2012;218(4):903-912.
The hippocampus is classically involved in memory consolidation, spatial navigation and is involved in the stress response. Migraine is an episodic disorder characterized by intermittent attacks with a number of physiological and emotional stressors associated with or provoking each attack. Given that migraine attacks can be viewed as repeated stressors, alterations in hippocampal function and structure may play an important role in migraine pathophysiology. Using high-resolution magnetic resonance imaging, hippocampal morphometric and functional differences (in response to noxious heat stimulation) were compared in age and gender-matched acute episodic migraineurs with high (HF) versus low (LF) frequency of migraine attacks. Morphometric results were compared with age and gender-matched healthy control (HC) cohort. Significant larger bilateral hippocampal volume was found in LF group relative to the HF and HC groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency. Functional correlates of greater deactivation (LF > HF) in the same hippocampal regions in response to noxious stimulation was also accompanied by overall reduction in functional connectivity of the hippocampus with other brain regions involved in pain processing in the HF group. The results implicate involvement of hippocampus in the pathophysiology of the migraine.
doi:10.1007/s00429-012-0437-y
PMCID: PMC3711530  PMID: 22760159
Headache; Pain; Migraine; fMRI; Functional connectivity; Morphometry
8.  Studies on the Pathophysiology and Genetic Basis of Migraine 
Current Genomics  2013;14(5):300-315.
Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies.
doi:10.2174/13892029113149990007
PMCID: PMC3763681  PMID: 24403849
Migraine; Migraine with aura; Migraine without aura; Familial hemiplegic migraine; Molecular genetics; Genes
9.  Epigone migraine vertigo (EMV): a late migraine equivalent 
SUMMARY
Migrainous headache is determined by pathogenetic mechanisms that are also able to affect the peripheral and/or central vestibular system, so that vestibular symptoms may substitute and/or present with headache. We are convinced that there can be many different manifestations of vestibular disorders in migrainous patients, representing true different clinical entities due to their different characteristics and temporal relashionship with headache. Based on such considerations, we proposed a classification of vertigo and other vestibular disorders related to migraine, and believe that a particular variant of migraine-related vertigo should be introduced, namely "epigone migraine vertigo" (EMV): this could be a kind of late migraine equivalent, i.e. a kind of vertigo, migrainous in origin, starting late in the lifetime that substitutes, as an equivalent, pre-existing migraine headache. To clarify this particular clinical picture, we report three illustrative clinical cases among 28 patients collected during an observation period of 13 years (November 1991 - November 2004). For all patients, we collected complete personal clinical history. All patients underwent standard neurotological examination, looking for spontaneous-positional, gaze-evoked and caloric induced nystagmus, using an infrared video camera. We also performed a head shaking test (HST) and an head thrust test (HTT). Ocular motility was tested looking at saccades and smooth pursuit. To exclude other significant neurological pathologies, a brain magnetic resonance imaging (MRI) with gadolinium was performed. During the three months after the first visit, patients were invited to keep a diary noting frequency, intensity and duration of vertigo attacks. After that period, we suggested that they use prophylactic treatment with flunarizine (5 mg per day) and/or acetylsalicylic acid (100 mg per day), or propranolol (40 mg twice a day). All patients were again recommended to note in their diary the frequency and intensity of both headache and vertigo while taking prophylactic therapy. Control visits were programmed after 4, 12 and 24 months of therapy. All patients considerably improved symptoms with therapy: 19 subjects (68%) reported complete disappearance of vestibular symptoms, while 9 (32%) considered symptoms very improved. The subjective judgement was corroborated by data from patients diaries. We conclude that EMV is a clinical variant of typical migraine-related vertigo: a migraineassociated vertigo, headache spell independent, following a headache period, during the lifetime of a patient.
PMCID: PMC3970230  PMID: 24711685
Headache; Migraine vertigo; Epigone migraine vertigo; Motion sickness; Aura
10.  Migraine management in pregnancy 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 78.
Abstract:
Background:
Migraine and tension-type headache are primary headache disorders that occur during pregnancy. Most women with migraine improve during pregnancy. Some women have their first attack during pregnancy. Migraine can recur postpartum; it can also begin at that time. Women who have had menstrual migraine and migraine onset at menarche tend to experience no migraine during pregnancy. Not all migraines improve during pregnancy, however. Some women experience migraine for the first time during pregnancy.
Etiology:
Headaches caused by cerebral arteriovenous malformations often present as migraine with aura. Cerebral venous thrombosis (common during pregnancy and the puerperium) may manifest with migraine-like visual disturbance and headache.
Treatment:
Nondrug therapies (relaxation, sleep, massage, ice packs and biofeedback) should be tried first to treat migraine in women who are pregnant. For treatment of acute migraine attacks 1000 mg of paracetamol (acetaminophen) preferably as a suppository is considered the first choice drug treatment.
Conclusions:
Migraine has also been recently postulated as one of the major risk factors for stroke during pregnancy and the puerperium. There is thus an urgent need for prospective studies of large numbers of pregnant women to determine the real existence and extent of the risks posed by migraine during pregnancy.
Keywords:
Migraine, Pregnancy, Headache
PMCID: PMC3571604
11.  The primary headaches: genetics, epigenetics and a behavioural genetic model 
The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research.
doi:10.1007/s10194-008-0026-x
PMCID: PMC2276243  PMID: 18345478
Migraine; Tension-type headache; Cluster headache; Genetics; Epigenetics
12.  The primary headaches: genetics, epigenetics and a behavioural genetic model 
The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research.
doi:10.1007/s10194-008-0026-x
PMCID: PMC2276243  PMID: 18345478
Migraine; Tension-type headache; Cluster headache; Genetics; Epigenetics
13.  Migraine: Maladaptive Brain Responses to Stress 
Headache  2012;52(Suppl 2):102-106.
Migraine offers a unique model to understand the consequences of repeated stressors on the brain. Repeated stressors can alter the normal response of physiological systems and this concept has been termed ‘allostatic load’. In the case of the brain, the effects of repeated stress may lead to alteration in brain networks both functionally and structurally. As a result the brain responds abnormally to environmental conditions (psychological or physiological). Here we present an alternative perspective on migraine disease and propose that changes in brain states may occur as a result of repeated migraine attacks through maladaptive coping mechanisms. The cascade of these effects can lead to further deterioration of adaptation and thus lead to transformation or chronification of the disease.
doi:10.1111/j.1526-4610.2012.02241.x
PMCID: PMC3475609  PMID: 23030541
14.  Chronic pain and fatigue: Associations with religion and spirituality 
BACKGROUND:
Conditions with chronic, non-life-threatening pain and fatigue remain a challenge to treat, and are associated with high health care use. Understanding psychological and psychosocial contributing and coping factors, and working with patients to modify them, is one goal of management. An individual’s spirituality and/or religion may be one such factor that can influence the experience of chronic pain or fatigue.
METHODS:
The Canadian Community Health Survey (2002) obtained data from 37,000 individuals 15 years of age or older. From these data, four conditions with chronic pain and fatigue were analyzed together – fibromyalgia, back pain, migraine headaches and chronic fatigue syndrome. Additional data from the survey were used to determine how religion and spirituality affect psychological well-being, as well as the use of various coping methods.
RESULTS:
Religious persons were less likely to have chronic pain and fatigue, while those who were spiritual but not affiliated with regular worship attendance were more likely to have those conditions. Individuals with chronic pain and fatigue were more likely to use prayer and seek spiritual support as a coping method than the general population. Furthermore, chronic pain and fatigue sufferers who were both religious and spiritual were more likely to have better psychological well-being and use positive coping strategies.
INTERPRETATION:
Consideration of an individual’s spirituality and/or religion, and how it may be used in coping may be an additional component to the overall management of chronic pain and fatigue.
PMCID: PMC2799261  PMID: 18958309
Chronic pain; Coping; Psychophysiological; Psychosomatic; Religion; Spirituality
15.  Physical and psychological correlates of primary headache in young adulthood: A 26 year longitudinal study 
Objectives: To determine if physical and/or psychological risk factors could differentiate between subtypes of primary headache (migraine, tension-type headache (TTH), and coexisting migraine and TTH (combined)) among members of a longitudinal birth cohort study.
Methods: At age 26, the headache status of members of the Dunedin Multidisciplinary Health and Development Study (DMHDS) was determined using International Headache Society criteria. Headache history and potential physical and psychological correlates of headache were assessed. These factors included perinatal problems and injuries sustained to age 26; and behavioural, personality, and psychiatric disorders assessed between ages 5 to 21.
Results: The 1 year prevalences for migraine, TTH, and combined headache at the age of 26 were 7.2%, 11.1%, and 4.3%, respectively. Migraine was related to maternal headache, anxiety symptoms in childhood, anxiety disorders during adolescence and young adulthood, and the stress reactivity personality trait at the age of 18. TTH was significantly associated with neck or back injury in childhood (before the age of 13). Combined headache was related to maternal headache and anxiety disorder at 18 and 21 only among women with a childhood history of headache. Headache status at the age of 26 was unrelated to a history of perinatal complication, neurological disorder, or mild traumatic head injury.
Conclusions: Migraine and TTH seem to be distinct disorders with different developmental characteristics. Combined headache may also have a distinct aetiology.
doi:10.1136/jnnp.72.1.86
PMCID: PMC1737678  PMID: 11784831
16.  Topiramate: Safety and Efficacy of its Use in the Prevention and Treatment of Migraine 
Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramate’s role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports have demonstrated topiramate as a cause of cognitive and behavioural changes. The use of topiramate in migraine prevention can improve a patient’s quality of life and is a cost-effective option for migraine prevention.
doi:10.4137/JCNSD.S4365
PMCID: PMC3663617  PMID: 23861645
topiramate; migraine; prophylaxis
17.  Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache 
The Journal of Headache and Pain  2007;8(3):157-166.
The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.
doi:10.1007/s10194-007-0384-9
PMCID: PMC3476146  PMID: 17568991
Catecholamines; Cortisol; Migraine; Tension-type headache; Stress
18.  Prophylaxis of migraine: general principles and patient acceptance 
Migraine is a chronic neurological condition with episodic exacerbations. Migraine is highly prevalent, and associated with significant pain, disability, and diminished quality of life. Migraine management is an important health care issue. Migraine management includes avoidance of trigger factors, lifestyle modifications, non-pharmacological therapies, and medications. Pharmacological treatment is traditionally divided into acute or symptomatic treatment, and preventive treatment or prophylaxis. Many migraine patients can be treated using only acute treatment. Patients with severe and/or frequent migraines require long-term preventive therapy. Prophylaxis requires daily administration of anti-migraine compounds with potential adverse events or contraindications, and may also interfere with other concurrent conditions and treatments. These problems may induce patients to reject the idea of a preventive treatment, leading to poor patient adherence. This paper reviews the main factors influencing patient acceptance of anti-migraine prophylaxis, providing practical suggestions to enhance patient willingness to accept pharmacological anti-migraine preventive therapy. We also provide information about the main clinical characteristics of migraine, and their negative consequences. The circumstances warranting prophylaxis in migraine patients as well as the main characteristics of the compounds currently used in migraine prophylaxis will also be briefly discussed, focusing on those aspects which can enhance patient acceptance and adherence.
PMCID: PMC2646645  PMID: 19337456
migraine; prophylaxis; preventive therapy; acceptance; adherence
19.  Serotonin Effects on Sleep and Emotional Disorders in Adolescent Migraine 
Headache  2009;49(10):1486-1492.
Objective
To determine frequency of emotional disorders and sleep disturbances in adolescent migraineurs with episodic and chronic headaches. To determine the relationship of whole blood serotonin, caffeine consumption, and frequency of sleep and mood disorders.
Background
The neurotransmitter serotonin has been implicated to play a role in the initiation and maintenance of sleep and in modulating mood. A putative role in migraine pathophysiology is also known.
Methods
Adolescents from 13 to 17 years of age were identified from our headache clinic with episodic or chronic migraine (according to International Classification of Headache Disorders-Second Edition criteria) and healthy controls enrolled. Psychological rating scales were completed, including Adolescent Symptom Inventory (4th Edition) and Child Depression Inventory. Sleep questionnaires (Pediatric Sleep Questionnaire and Child Sleep Habit Questionnaire) were completed by the teenager’s parents/guardian. Whole blood serotonin levels were drawn and analyzed and caffeine consumption obtained by history.
Results
A total of 18 controls (8 girls) and 15 patients each with episodic migraines (9 girls) and chronic migraine (10 girls) were studied.
Patients with headache had significantly more sleep problems than controls. Patients with chronic migraines had increased daytime sleepiness and dysthymia compared with teenagers with episodic migraines. Serotonin levels were not significantly different, and no association was noted between serotonin levels and sleep abnormalities or emotional rating scales. Increased caffeine intake was related to sleep and depressive complaints.
Conclusions
Sleep and emotional disorders were common in adolescents with migraine. Sleep disorders and dysthymia were more prevalent with increased headache frequency. No correlation was noted with whole blood serotonin levels.
doi:10.1111/j.1526-4610.2009.01392.x
PMCID: PMC3777568  PMID: 19486363
migraine; serotonin; sleep; depression; pediatrics
20.  Psychological and social stressors and psychiatric comorbidity in patients with migraine without aura from headache centers in Italy: a comparison with tension-type headache patients 
A multicenter study was carried out to investigate the prevalence of psychosocial stressors and psychiatric comorbidity in patients suffering from migraine without aura (MWO) according to the International Headache Society criteria. Two hundred four adult MWO outpatients underwent a structured psychiatric interview (CIDI-c) to determine the presence of anxiety, and mood and somatoform disorders according to DSM-III-R criteria. An ad hoc questionnaire was used to assess psychosocial stress events. Anxiety disorders were found in 39.2% of the sample, mood disorders occurred in 23.0% and somatoform disorders in 21.6%. Psychosocial stressors were identified in 22.5% of the migraineurs without any difference between patients with and without psychiatric comorbidity. No correlation was found between psychiatric comorbidity and migraine duration or frequency. When the migraine patients were compared with a homogeneous group of tension-type headache sufferers, a higher frequency of psychiatric comorbidity was found in the latter group (56.4% vs. 77.8%, p = 0.01). These data suggest that migraine as well as tension-type headache are associated with an increased vulnerability to psychiatric disorders. Whether this is related to a common genetic susceptibility or is the effect of a psychoneurobiological loop related to the stress response activation remains to be investigated.
doi:10.1007/s101940050005
PMCID: PMC3611697
Key words Migraine without aura; Tension-type headache; Psychiatric comorbidity; DSM-III-R; IHS classification; Psychological stressors; Social stressors; Stress response
21.  Ophthalmoplegia starting with a headache circumscribed in a line-shaped area: a subtype of ophthalmoplegic migraine? 
Recurrent painful ophthalmoplegic neuropathy (RPON), formerly named ophthalmoplegic migraine (OM), is a rare condition characterized by the association of unilateral headaches and the ipsilateral oculomotor nerve palsy. The third cranial nerve is most commonly involved in the recurrent attacks. But it is still debated whether a migraine or an oculomotor neuropathy may be the primary cause of this disorder. Here, we report an elder patient who had a recurrent ophthalmoplegia starting with an unilateral headache circumscribed in an area shaped in a line linking the posterior-parietal region and the ipsilateral eye. And the headache had couple of features similar to that of migraine, such as past history of recurrent migraine attacks, accompaniments of nausea, vomiting, and phonophobia, response to flunarizine and sodium valproate. We may herein report a subtype of OM but not a RPON. This case report indicates that OM may exist as an entity and some OM may be wrongly grouped under the category of RPON in the current international headache classification.
doi:10.1186/1129-2377-15-19
PMCID: PMC3996493  PMID: 24739597
Recurrent painful ophthalmoplegic neuropathy; Ophthalmoplegic migraine; Migraine; Epicrania fugax; Neuralgia
22.  Sex Matters: Evaluating Sex and Gender in Migraine and Headache Research 
Headache  2011;51(6):839-842.
Significant sex differences exist in migraine and other headache disorders. Several hypotheses have been proposed to explain these differences, including fluctuations in sex hormones and receptor binding, genetic factors, differences in exposure to environmental stressors, as well as differences in response to stress and pain perception; but how valid are some of these findings and can we improve the quality of research in this field? It is notable that the preponderance of animal pain studies use male subjects to study a predominantly female disorder. Furthermore, with respect to headache and migraine sex differences, limited data have been derived from animal models. Additionally, although sex differences (based on the categorization of male vs female) may be more routinely evaluated in clinical headache research than in the basic science research, greater attention to potential differences across the life cycle of women (ie, premenopausal vs postmenopausal differences) and menstrual cycle is warranted. In this manuscript we define the differences between “sex” and “gender” and highlight the importance of their application and use in headache research. The enhanced recognition and implementation of attention to sex differences throughout the hormonal and life-cycle phase in both human and animal research will only help to strengthen and further our understanding of migraine and may help guide the direction of future headache research.
doi:10.1111/j.1526-4610.2011.01900.x
PMCID: PMC3975603  PMID: 21631471
sex; gender; headache; animal models; research; reproductive
23.  Overview of diagnosis and management of paediatric headache. Part I: diagnosis 
Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life.
doi:10.1007/s10194-011-0297-5
PMCID: PMC3056001  PMID: 21359874
Headache; Childhood; Paediatric headaches; Diagnosis; Epidemiology; Defining features
24.  Overview of diagnosis and management of paediatric headache. Part I: diagnosis 
Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life.
doi:10.1007/s10194-011-0297-5
PMCID: PMC3056001  PMID: 21359874
Headache; Childhood; Paediatric headaches; Diagnosis; Epidemiology; Defining features
25.  Clinical diagnosis and computer analysis of headache symptoms. 
The headache histories obtained from clinical interviews of 600 patients were analysed by computer to see whether patients could be separated systematically into clinical categories and to see whether sets of symptoms commonly reported together differed in distribution among the categories. The computer classification procedure assigned 537 patients to the same category as their clinical diagnosis, the majority of discrepancies between clinical and computer classifications involving common migraine, tension-vascular and tension headache. Cluster headache emerged as a clearly-definable syndrome, and neurological symptoms during headache were most prevalent in the classical migraine group. However, the classical migraine, common migraine, tension-vascular and tension headache categories differed in terms of the number, rather than the nature, of common migraine features. Whether the two extremes of this migraine-tension headache spectrum are different disorders can be determined only by studies of their pathophysiology.
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PMCID: PMC1027680  PMID: 6707652

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