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1.  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
2.  Neuroimaging for the Evaluation of Chronic Headaches 
Executive Summary
Objective
The objectives of this evidence based review are:
i) To determine the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) scans in the evaluation of persons with a chronic headache and a normal neurological examination.
ii) To determine the comparative effectiveness of CT and MRI scans for detecting significant intracranial abnormalities in persons with chronic headache and a normal neurological exam.
iii) To determine the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Clinical Need: Condition and Target Population
Headaches disorders are generally classified as either primary or secondary with further sub-classifications into specific headache types. Primary headaches are those not caused by a disease or medical condition and include i) tension-type headache, ii) migraine, iii) cluster headache and, iv) other primary headaches, such as hemicrania continua and new daily persistent headache. Secondary headaches include those headaches caused by an underlying medical condition. While primary headaches disorders are far more frequent than secondary headache disorders, there is an urge to carry out neuroimaging studies (CT and/or MRI scans) out of fear of missing uncommon secondary causes and often to relieve patient anxiety.
Tension type headaches are the most common primary headache disorder and migraines are the most common severe primary headache disorder. Cluster headaches are a type of trigeminal autonomic cephalalgia and are less common than migraines and tension type headaches. Chronic headaches are defined as headaches present for at least 3 months and lasting greater than or equal to 15 days per month. The International Classification of Headache Disorders states that for most secondary headaches the characteristics of the headache are poorly described in the literature and for those headache disorders where it is well described there are few diagnostically important features.
The global prevalence of headache in general in the adult population is estimated at 46%, for tension-type headache it is 42% and 11% for migraine headache. The estimated prevalence of cluster headaches is 0.1% or 1 in 1000 persons. The prevalence of chronic daily headache is estimated at 3%.
Neuroimaging
Computed Tomography
Computed tomography (CT) is a medical imaging technique used to aid diagnosis and to guide interventional and therapeutic procedures. It allows rapid acquisition of high-resolution three-dimensional images, providing radiologists and other physicians with cross-sectional views of a person’s anatomy. CT scanning poses risk of radiation exposure. The radiation exposure from a conventional CT scanner may emit effective doses of 2-4mSv for a typical head CT.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used to aid diagnosis but unlike CT it does not use ionizing radiation. Instead, it uses a strong magnetic field to image a person’s anatomy. Compared to CT, MRI can provide increased contrast between the soft tissues of the body. Because of the persistent magnetic field, extra care is required in the magnetic resonance environment to ensure that injury or harm does not come to any personnel while in the environment.
Research Questions
What is the effectiveness of CT and MRI scanning in the evaluation of persons with a chronic headache and a normal neurological examination?
What is the comparative effectiveness of CT and MRI scanning for detecting significant intracranial abnormality in persons with chronic headache and a normal neurological exam?
What is the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Research Methods
Literature Search
Search Strategy
A literature search was performed on February 18, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January, 2005 to February, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Systematic reviews, randomized controlled trials, observational studies
Outpatient adult population with chronic headache and normal neurological exam
Studies reporting likelihood ratio of clinical variables for a significant intracranial abnormality
English language studies
2005-present
Exclusion Criteria
Studies which report outcomes for persons with seizures, focal symptoms, recent/new onset headache, change in presentation, thunderclap headache, and headache due to trauma
Persons with abnormal neurological examination
Case reports
Outcomes of Interest
Primary Outcome
Probability for intracranial abnormality
Secondary Outcome
Patient relief from anxiety
System service use
System costs
Detection rates for significant abnormalities in MRI and CT scans
Summary of Findings
Effectiveness
One systematic review, 1 small RCT, and 1 observational study met the inclusion and exclusion criteria. The systematic review completed by Detsky, et al. reported the likelihood ratios of specific clinical variables to predict significant intracranial abnormalities. The RCT completed by Howard et al., evaluated whether neuroimaging persons with chronic headache increased or reduced patient anxiety. The prospective observational study by Sempere et al., provided evidence for the pre-test probability of intracranial abnormalities in persons with chronic headache as well as minimal data on the comparative effectiveness of CT and MRI to detect intracranial abnormalities.
Outcome 1: Pre-test Probability.
The pre-test probability is usually related to the prevalence of the disease and can be adjusted depending on the characteristics of the population. The study by Sempere et al. determined the pre-test probability (prevalence) of significant intracranial abnormalities in persons with chronic headaches defined as headache experienced for at least a 4 week duration with a normal neurological exam. There is a pre-test probability of 0.9% (95% CI 0.5, 1.4) in persons with chronic headache and normal neurological exam. The highest pre-test probability of 5 found in persons with cluster headaches. The second highest, that of 3.7, was reported in persons with indeterminate type headache. There was a 0.75% rate of incidental findings.
Likelihood ratios for detecting a significant abnormality
Clinical findings from the history and physical may be used as screening test to predict abnormalities on neuroimaging. The extent to which the clinical variable may be a good predictive variable can be captured by reporting its likelihood ratio. The likelihood ratio provides an estimate of how much a test result will change the odds of having a disease or condition. The positive likelihood ratio (LR+) tells you how much the odds of having the disease increases when a test is positive. The negative likelihood ratio (LR-) tells you how much the odds of having the disease decreases when the test is negative.
Detsky et al., determined the likelihood ratio for specific clinical variable from 11 studies. There were 4 clinical variables with both statistically significant positive and negative likelihood ratios. These included: abnormal neurological exam (LR+ 5.3, LR- 0.72), undefined headache (LR+ 3.8, LR- 0.66), headache aggravated by exertion or valsalva (LR+ 2.3, LR- 0.70), and headache with vomiting (LR+ 1.8, and LR- 0.47). There were two clinical variables with a statistically significant positive likelihood ratio and non significant negative likelihood ratio. These included: cluster-type headache (LR+ 11, LR- 0.95), and headache with aura (LR+ 12.9, LR- 0.52). Finally, there were 8 clinical variables with both statistically non significant positive and negative likelihood ratios. These included: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, and migraine type headache.
Outcome 2: Relief from Anxiety
Howard et al. completed an RCT of 150 persons to determine if neuroimaging for headaches was anxiolytic or anxiogenic. Persons were randomized to receiving either an MRI scan or no scan for investigation of their headache. The study population was stratified into those persons with a Hospital Anxiety and Depression scale (HADS) > 11 (the high anxiety and depression group) and those < 11 (the low anxiety and depression) so that there were 4 groups:
Group 1: High anxiety and depression, no scan group
Group 2: High anxiety and depression, scan group
Group 3: Low anxiety and depression, no scan group
Group 4: Low anxiety and depression, scan group
Anxiety
There was no evidence for any overall reduction in anxiety at 1 year as measured by a visual analogue scale of ‘level of worry’ when analysed by whether the person received a scan or not. Similarly, there was no interaction between anxiety and depression status and whether a scan was offered or not on patient anxiety. Anxiety did not decrease at 1 year to any statistically significant degree in the high anxiety and depression group (HADS positive) compared with the low anxiety and depression group (HADS negative).
There are serious methodological limitations in this study design which may have contributed to these negative results. First, when considering the comparison of ‘scan’ vs. ‘no scan’ groups, 12 people (16%) in the ‘no scan group’ actually received a scan within the follow up year. If indeed scanning does reduce anxiety then this contamination of the ‘no scan’ group may have reduced the effect between the groups results resulting in a non significant difference in anxiety scores between the ‘scanned’ and the ‘no scan’ group. Second, there was an inadequate sample size at 1 year follow up in each of the 4 groups which may have contributed to a Type II statistical error (missing a difference when one may exist) when comparing scan vs. no scan by anxiety and depression status. Therefore, based on the results and study limitations it is inconclusive as to whether scanning reduces anxiety.
Outcome 3: System Services
Howard et al., considered services used and system costs a secondary outcome. These were determined by examining primary care case notes at 1 year for consultation rates, symptoms, further investigations, and contact with secondary and tertiary care.
System Services
The authors report that the use of neurologist and psychiatrist services was significantly higher for those persons not offered as scan, regardless of their anxiety and depression status (P<0.001 for neurologist, and P=0.033 for psychiatrist)
Outcome 4: System Costs
System Costs
There was evidence of statistically significantly lower system costs if persons with high levels of anxiety and depression (Hospital Anxiety and Depression Scale score >11) were provided with a scan (P=0.03 including inpatient costs, and 0.047 excluding inpatient costs).
Comparative Effectiveness of CT and MRI Scans
One study reported the detection rate for significant intracranial abnormalities using CT and MRI. In a cohort of 1876 persons with a non acute headache defined as any type of headache that had begun at least 4 weeks before enrolment Sempere et al. reported that the detection rate was 19/1432 (1.3%) using CT and 4/444 (0.9%) using MRI. Of 119 normal CT scans 2 (1.7%) had significant intracranial abnormality on MRI. The 2 cases were a small meningioma, and an acoustic neurinoma.
Summary
The evidence presented can be summarized as follows:
Pre-test Probability
Based on the results by Sempere et al., there is a low pre-test probability for intracranial abnormalities in persons with chronic headaches and a normal neurological exam (defined as headaches experiences for a minimum of 4 weeks). The Grade quality of evidence supporting this outcome is very low.
Likelihood Ratios
Based on the systematic review by Detsky et al., there is a statistically significant positive and negative likelihood ratio for the following clinical variables: abnormal neurological exam, undefined headache, headache aggravated by exertion or valsalva, headache with vomiting. Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al. there is a statistically significant positive likelihood ratio but non statistically significant negative likelihood ratio for the following clinical variables: cluster headache and headache with aura. The Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al., there is a non significant positive and negative likelihood ratio for the following clinical variables: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, migraine type headache. The Grade quality of evidence supporting this outcome is very low.
Relief from Anxiety
Based on the RCT by Howard et al., it is inconclusive whether neuroimaging scans in persons with a chronic headache are anxiolytic. The Grade quality of evidence supporting this outcome is low.
System Services
Based on the RCT by Howard et al. scanning persons with chronic headache regardless of their anxiety and/or depression level reduces service use. The Grade quality of evidence is low.
System Costs
Based on the RCT by Howard et al., scanning persons with a score greater than 11 on the High Anxiety and Depression Scale reduces system costs. The Grade quality of evidence is moderate.
Comparative Effectiveness of CT and MRI Scans
There is sparse evidence to determine the relative effectiveness of CT compared with MRI scanning for the detection of intracranial abnormalities. The Grade quality of evidence supporting this is very low.
Economic Analysis
Ontario Perspective
Volumes for neuroimaging of the head i.e. CT and MRI scans, from the Ontario Health Insurance Plan (OHIP) data set were used to investigate trends in the province for Fiscal Years (FY) 2004-2009.
Assumptions were made in order to investigate neuroimaging of the head for the indication of headache. From the literature, 27% of all CT and 13% of all MRI scans for the head were assumed to include an indication of headache. From that same retrospective chart review and personal communication with the author 16% of CT scans and 4% of MRI scans for the head were for the sole indication of headache. From the Ministry of Health and Long-Term Care (MOHLTC) wait times data, 73% of all CT and 93% of all MRI scans in the province, irrespective of indication were outpatient procedures.
The expenditure for each FY reflects the volume for that year and since volumes have increased in the past 6 FYs, the expenditure has also increased with a pay-out reaching 3.0M and 2.8M for CT and MRI services of the head respectively for the indication of headache and a pay-out reaching 1.8M and 0.9M for CT and MRI services of the head respectively for the indication of headache only in FY 08/09.
Cost per Abnormal Finding
The yield of abnormal finding for a CT and MRI scan of the head for the indication of headache only is 2% and 5% respectively. Based on these yield a high-level estimate of the cost per abnormal finding with neuroimaging of the head for headache only can be calculated for each FY. In FY 08/09 there were 37,434 CT and 16,197 MRI scans of the head for headache only. These volumes would generate a yield of abnormal finding of 749 and 910 with a CT scan and MRI scan respectively. The expenditure for FY 08/09 was 1.8M and 0.9M for CT and MRI services respectively. Therefore the cost per abnormal finding would be $2,409 for CT and $957 for MRI. These cost per abnormal finding estimates were limited because they did not factor in comparators or the consequences associated with an abnormal reading or FNs. The estimates only consider the cost of the neuroimaging procedure and the yield of abnormal finding with the respective procedure.
PMCID: PMC3377587  PMID: 23074404
3.  Course of adolescent headache: 4-year annual face-to-face follow-up study 
The Journal of Headache and Pain  2010;11(4):327-334.
The objective of this study is to investigate the course of the diagnosis and characteristics of headache in 12- to 17-year-old adolescents during a follow-up period of 4 years. Headache prevalence and characteristics, and even the type of headache show important changes during adolescence. The course of adolescent headache might reveal important insight into the pathophysiology of headache. Subjects who received a single headache diagnosis were invited to participate in a follow-up study consisting of annual face-to-face evaluation of the subjects for 4 years. Subjects who had only one type of headache and who agreed to participate were included in the study. Each subject had four annual semi-structured interviews with a neurology resident. The International Classification of Headache Disorders second edition was used for case definitions. A total of 87 subjects completed the study: 64 girls (73.56%) and 23 boys (26.44%) (p = 0.016). The headache type included migraine in 50 adolescents (57.47%), tension type headache in 24 (27.59%), secondary headache in 5 (5.7%), and non-classifiable headache in 8 (9.2%). Headache has not remitted in any of the subjects. Headache diagnosis has changed in eighteen (20.69%) subjects at least once during the follow-up period. There was transformation of headache type in 4 of 50 with migraine (8%), 10 of 24 with tension-type headache (TTH) (41.7%), and 4 of 13 with other headaches (30.8%). In conclusion, transition of headache types from one type to another (more than once in some adolescents) and variability of diagnosis throughout the years strongly support the continuum theory of headaches.
doi:10.1007/s10194-010-0228-x
PMCID: PMC3476353  PMID: 20526648
Adolescent; Headache; Migraine; Tension-type headache; Course; Transformation
4.  Cluster headache associated with acute maxillary sinusitis 
SpringerPlus  2013;2:509.
Background
Cluster headache is a primary headache by definition not caused by any known underlying structural pathology. However, symptomatic cases have been described, for example tumours, particularly pituitary adenomas, malformations, and infections/inflammations. The evaluation of cluster headache is an issue unresolved.
Case description
I present a case of a 24-year-old patient who presented with a 4-week history of side-locked attacks of pain located in the left orbit. He satisfied the revised International Classification of Headache Disorders criteria for cluster headache. His medical and family histories were unremarkable. There was no history of headache. A diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Low-dose computer tomography scan after 2 weeks displayed a left-sided acute maxillary sinusitis. The headache attacks resolved completely after treatment with antibiotics and sinus puncture.
Discussion and evaluation
Although I cannot exclude an unintentional comorbidity, in my opinion, the co-occurrence of an acute maxillary sinusitis with unilateral headache, in a hitherto headache-free man, points toward the fact that in this case the cluster headache was caused or triggered by the sinusitis. The headache attacks resolved completely after the treatment and the patient also remained headache free at the follow-up. The response of the headache to sumatriptan and other typical cluster headache medications does not exclude a secondary form. Symptomatic cluster headaches responsive to this therapy have been described. Associated cranial lesions such as infections have been reported in cluster headache patients and the attacks may be clinically indistinguishable from the primary form.
Conclusions
Neuroimaging, preferably contrast-enhanced magnetic resonance imaging including sinuses should always be considered in patients with cluster headache despite normal neurological examination. Acute maxillary sinusitis can present as cluster headache.
doi:10.1186/2193-1801-2-509
PMCID: PMC3795873  PMID: 24133652
Cluster headache; Acute maxillary sinusitis; Secondary; Symptomatic; Infection
5.  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
6.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
7.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
8.  Cluster headache and arachnoid cyst 
SpringerPlus  2013;2:4.
Background
Cluster headache is a primary headache by definition not caused by any known underlying structural pathology. However, symptomatic cases have been described, e.g. tumours, particularly pituitary adenomas, malformations, and infections/inflammations. The evaluation of cluster headache is an issue unresolved.
Case description
We present a case of a 43-year-old patient who presented with a 2-month history of side-locked attacks of pain located in the left orbit. He satisfied the revised International Classification of Headache Disorders criteria for cluster headache. His medical and family histories were unremarkable. There was no history of headache. A diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Computer tomography and enhanced magnetic resonance imaging after 1 month displayed a supra- and intrasellar arachnoid cyst with mass effect on adjacent structures. After operation, the headache attacks resolved completely.
Discussion and evaluation
Although we cannot exclude an unintentional comorbidity, in our opinion, the co-occurrence of an arachnoid cyst with mass effect with unilateral headache, in a hitherto headache-free man, points toward the fact that in this case the CH was caused or triggered by the AC. The headache attacks resolved completely after the operation and the patient also remained headache free at the follow-up. The response of the headache to sumatriptan and other typical CH medications does not exclude a secondary form. Symptomatic CHs responsive to this therapy have been described. Associated cranial lesions such as tumours have been reported in CH patients and the attacks may be clinically indistinguishable from the primary form.
Conclusions
Neuroimaging, preferably contrast-enhanced magnetic resonance imaging should always be considered in patients with cluster headache despite normal neurological examination. Late-onset cluster headache represents a condition that requires careful evaluation. Supra- and intrasellar arachnoid cyst can present as cluster headache.
doi:10.1186/2193-1801-2-4
PMCID: PMC3568463  PMID: 23419954
Cluster headache; Arachnoid cyst; Neuroimaging; Secondary; Symptomatic; Magnetic resonance imaging; Computer tomography
9.  Application of ICHD-II Criteria in a Headache Clinic of China 
PLoS ONE  2012;7(12):e50898.
Background
China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II).
Methods and Results
Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001). The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004). The peak age at onset of TTH for male and female were both in the 3rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2nd decade for females and the 1st decade for males.
Conclusions/Significance
This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria.
doi:10.1371/journal.pone.0050898
PMCID: PMC3519829  PMID: 23239993
10.  Migraine and Tension-Type Headache in Children and Adolescents Presenting to Neurology Clinics 
Iranian Journal of Pediatrics  2013;23(5):536-540.
Objective
Headache is one of the most common neurologic problems in children and adolescents. Primary headache including migraine and tension-type headache comprises the vast majority of headaches and are associated with marked incidence, prevalence, and individual and social cost. We aimed to assess demographic characteristics and to compare some factors related to primary headaches in children/ adolescents presented to neurology clinics of Tabriz University of Medical Sciences.
Methods
Children from 4 to 15 years of age with the diagnosis of primary headache (migraine or tension-type headaches) who presented to the neurology clinics affiliated to Tabriz University of Medical Sciences, Tabriz, Iran from March 2009 to October 2011 are included in this cross-sectional study. Data regarding the type of headache, history of atopy, peripartum asphyxia, and breast feeding, family history of headache and the socioeconomic status of the family were collected. The diagnosis was based on the international headache society diagnostic criteria for the primary headache disorders.
Findings
One hundred ninety children (107 females) with primary headache (88 patients with migraine and 102 patients with tension type headache) enrolled in the study. Peripartum asphyxia, history of atopy, family history of headache and low socioeconomic status (SES) were more common in patients with migraine (P-values: 0.007, 0.01, 0.001, 0.003; respectively).
Conclusion
Physicians need to extent their knowledge regarding the primary headaches. Peripartum asphyxia, history of atopy, headache in parents and low SES have been shown in the present study to be more prevalent in patients with migraine as compared to tension-type headache.
PMCID: PMC4006502  PMID: 24800013
Asphyxia; Atopy; Children; Migraine; Tension-Type Headache
11.  Recurrent and chronic headaches in children below 6 years of age 
The Journal of Headache and Pain  2005;6(3):135-142.
The objective was to determine the frequency of headache subtypes, according to International Headache Society (IHS) criteria, in a population of children below 6 years visiting a Center for Diagnosis and Treatment of Headache in Youth. Medical records of the children below 6 years at their first visit, admitted for headache between 1997 and 2003, were studied. Headache was classified according to the IHS criteria 2004. Children with less than three headache attacks or less than 15 days of daily headache were excluded. We found 1598 medical records of children who visited our Headache Center in the study period. One hundred and five (6.5%) were children younger than 6 years. The mean age at the first medical control was 4.8±1.3 years (range 17–71 months). There were 59 males (56.1%) and 46 females (43.9%). The mean age at onset of headaches was 4.3 years (range 14–69 months). According to the IHS criteria we found 37 cases (35.2%) with migraine, 19 cases (18%) with episodic tension headache, 5 cases (4.8%) with chronic daily headache, 13 cases (12.4%) with primary stabbing headache, 18 cases (17.1%) with post–traumatic headache, 7 cases (6.6%) with other non–dangerous secondary headaches (otorhinolaryngological diseases, post–infectious headaches), 3 cases (2.85%) with dangerous headaches (Arnold–Chiari type 1 malformation, brain tumour) and 9 cases (8.6%) with unclassifiable headaches. Six children (5.7%) reported more than one headache subtype. The prevalence of dangerous headaches was higher than those in school age (χ2=4.70, p<0.05). Our study shows some differences in headaches in this population vs. school children. In fact at this age migraine is the most common headache, but we also found an increase of secondary causes among the chronic/recurrent and daily headaches, especially posttraumatic disorders and potentially dangerous headaches. Finally our study shows the highest prevalence of the idiopathic stabbing headache in pre–school children in comparison with other ages.
doi:10.1007/s10194-005-0168-z
PMCID: PMC3451630  PMID: 16355294
Children; Migraine; Secondary headaches; Stabbing headaches
12.  Serious neurological disorders in children with chronic headache 
Archives of Disease in Childhood  2005;90(9):937-940.
Methods: All children presenting to a specialist headache clinic over seven years with headache as their main complaint were assessed by clinical history, physical and neurological examination, neuroimaging where indicated, and by follow up using prospective headache diaries. Results: A total of 815 children and adolescents (1.25–18.75 years of age, mean 10.8 years (SD 2.9); 432 male) were assessed. Mean duration of headache was 21.2 months (SD 21.2). Neuroimaging (brain CT or MRI) was carried out on 142 (17.5%) children. The vast majority of patients had idiopathic headache (migraine, tension, or unclassified headaches). Fifty one children (6.3%) had other chronic neurological disorders that were unrelated to the headache. The headache in three children (0.37%, 95% CI 0.08% to 1.1%) was related to active intracranial pathology which was predictable on clinical findings in two children but was unexpected until a later stage in one child (0.12%, 95% CI 0.006% to 0.68%).
Conclusions: Chronic headache in childhood is rarely due to serious intracranial pathology. Careful history and thorough clinical examination will identify most patients with serious underlying brain abnormalities. Change in headache symptomatology or personality change should lower the threshold for imaging.
doi:10.1136/adc.2004.067256
PMCID: PMC1720577  PMID: 16113128
13.  The evaluation and management of paediatric headaches 
Paediatrics & Child Health  2009;14(1):24-30.
The management of patients with headaches is a major component of every paediatric practice. In a nationally representative sample of Canadian adolescents, it was found that 26.6% of those 12 to 13 years of age and 31.2% of those 14 to 15 years of age reported that they experienced headaches at least once per week.
The diagnosis of headaches in children and adolescents is established through a headache history in the vast majority of patients. Specific questions can identify those at most risk for headaches secondary to underlying pathology. Similarly, the examination should be tailored to identify those who require further investigation. Investigations are not routinely indicated for paediatric headache, but neuroimaging should be considered in children whose headaches do not meet the criteria for one of the primary headache syndromes and in those with an abnormal neurological examination.
The optimal treatment of primary headaches should begin with nonpharmacological methods. Preventive pharmacological therapy should be considered when headaches significantly impair the patient’s quality of life. Flunarizine may be valuable in paediatric headache prevention, and ibuprofen, acetaminophen and nasal sumatriptan may be effective in the acute management of headaches.
PMCID: PMC2661331  PMID: 19436460
Headaches; Ibuprofen; Migraine
14.  OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program 
Acta Neurologica Scandinavica  2013;129(1):61-70.
Objective
Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX®) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study.
Materials and methods
PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported.
Results
Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (−12.0 O/O, −11.1 P/O; P = 0.035), migraine days (−11.6 O/O, −10.7 P/O; P = 0.038), and moderate/severe headache days (−11.0 O/O, −10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials.
Conclusions
This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.
doi:10.1111/ane.12171
PMCID: PMC4033567  PMID: 24107267
chronic migraine; headache; long term; onabotulinumtoxinA; PREEMPT; prophylaxis
15.  Reference programme: Diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 2nd Edition, 2012 
The Journal of Headache and Pain  2012;13(Suppl 1):1-29.
Headache and facial pain are among the most common, disabling and costly disorders in Europe. Correct diagnosis and treatment is important for achieving a high quality of care. As a national organisation whose role is to educate and advocate for the needs of patients with primary headaches, the Danish Headache Society has set up a task force to develop a set of guidelines for the diagnosis, organisation and treatment of the most common types of headaches and for trigeminal neuralgia in Denmark. The guideline was published in Danish in 2010 and has been a great success. The Danish Headache Society decided to translate and publish our guideline in English to stimulate the discussion on optimal organisation and treatment of headache disorders and to encourage other national headache authorities to produce their own guidelines. The recommendations regarding the most common primary headaches and trigeminal neuralgia are largely in accordance with the European guidelines produced by the European Federation of Neurological Societies. The guideline provides a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organised in Denmark. This description is followed by individual sections on the characteristics, diagnosis, differential diagnosis and treatment of each of the major headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular problems regarding headache in children and headache in relation to female hormones and pregnancy are described.
doi:10.1007/s10194-011-0402-9
PMCID: PMC3266527  PMID: 22270537
16.  Reference programme: Diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 2nd Edition, 2012 
The Journal of Headache and Pain  2012;13(Suppl 1):1-29.
Headache and facial pain are among the most common, disabling and costly disorders in Europe. Correct diagnosis and treatment is important for achieving a high quality of care. As a national organisation whose role is to educate and advocate for the needs of patients with primary headaches, the Danish Headache Society has set up a task force to develop a set of guidelines for the diagnosis, organisation and treatment of the most common types of headaches and for trigeminal neuralgia in Denmark. The guideline was published in Danish in 2010 and has been a great success. The Danish Headache Society decided to translate and publish our guideline in English to stimulate the discussion on optimal organisation and treatment of headache disorders and to encourage other national headache authorities to produce their own guidelines. The recommendations regarding the most common primary headaches and trigeminal neuralgia are largely in accordance with the European guidelines produced by the European Federation of Neurological Societies. The guideline provides a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organised in Denmark. This description is followed by individual sections on the characteristics, diagnosis, differential diagnosis and treatment of each of the major headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular problems regarding headache in children and headache in relation to female hormones and pregnancy are described.
doi:10.1007/s10194-011-0402-9
PMCID: PMC3266527  PMID: 22270537
17.  Sinusitis in children and adolescents with chronic or recurrent headache: a case–control study 
The aim of this study was to determine the frequency of misdiagnosis of sinus headache in migraine and other primary headache types in the children and adolescents with chronic or recurrent headaches. Children with chronic or recurrent headaches (n = 310) were prospectively evaluated. Data collection for each patient included history of previously diagnosed sinusitis due to headache, and additional sinusitis complaints (such as fever, cough, nasal discharge, postnasal discharge) at the time of sinusitis diagnosis, and improvement of the headache following treatment of sinusitis. If sinus radiographs existed they were recorded. The study included 214 patients with complete data. One hundred and sixteen (54.2%) patients have been diagnosed as sinusitis previously and 25% of them had at least one additional complaint, while 75% of them had none. Sinusitis treatment had no effect on the headaches in 60.3% of the patients. Sinus graphy had been performed in 52.8%, and 50.4% of them were normal. The prevalence of sinus headache concomitant with primary headache, and only sinus headache was detected in 7 and 1%, respectively, in our study. Approximately 40% of the patients with migraine and 60% of the patients with tension-type headache had been misdiagnosed as “sinus headache”. Children with chronic or recurrent headaches are frequently misdiagnosed as sinus headache and receive unnecessary sinusitis treatment and sinus graphy.
doi:10.1007/s10194-008-0007-0
PMCID: PMC3476172  PMID: 18219442
Headache; Migraine; Sinusitis
18.  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
19.  Headache in an Italian pediatric emergency department 
The objective of this study was to assess epidemiology, diagnostic work-up, treatment and follow-up of children presenting to emergency department (ED) with headache. Records of visits for non-traumatic headache to the ED of a pediatric hospital over a period of 12 months were retrospectively reviewed. Headache center charts were analyzed one year after. Five-hundred and fifty patients (1% of all ED visits) were included. Spectrum of diagnoses was: primary headache (56.7%), with 9.6% of migraine; secondary headache (42%); unclassified headache (1.3%). Viral illnesses accounted for 90.5% of secondary headaches. A serious disorder was found in 4% of patients. Forty-four patients (8%) underwent neuroimaging studies, with 25% of abnormal findings. Only 223 patients (40.5%) received pharmacological treatment. On discharge, 212 patients (38.5%) were referred to headache center and 114 (20.7% of all patients) attended it. ED diagnosis was confirmed in 74.6% of cases. Most of ED repeated visits (82.6%) occurred in patients not referred to headache center at discharge from first ED visit. The most frequent diagnosis was primary headache; viral illnesses represented the majority of secondary headaches. Underlying serious disorders were associated with neurological signs, limiting the need of diagnostic investigations. Well structured prospective studies are needed to evaluate appropriate diagnostic tools, as well as correct therapeutic approach of pediatric headache in emergency. Collaboration with headache center might limit repeated visits and provide a correct diagnostic definition.
doi:10.1007/s10194-008-0014-1
PMCID: PMC3476181  PMID: 18250964
Headache; Migraine; Emergency department; Childhood
20.  Sturge-weber syndrome: a case report with persistent headache 
Sturge-Weber syndrome (SWS) is a rare congenital disorder characterized by a facial vascular nevus associated with an ipsilateral leptomeningeal angioma. Headache is a rare component of SWS and when it occurs it usually occurs as a migraine-like headache. We aimed to present a SWS patient with episodic tension type headache and to draw attention in different types of headaches that can be seen in SWS. A 21 year old female patient with the diagnosis of SWS was suffering from severe headaches. At her physical examination a facial nevus -occurred due to choroid angioma- was observed. On her neurological examination a mild asymmetry of upper extremities was visible. She had a 2 year history of frequent non-pulsating headaches. There was no nausea or aura like symptoms accompanying the headache. Headaches were lasting for hours. The pain was bilateral and pressing in quality. SWS are a very rare and challenging disease for both the patients and their families. Usually migraine type headache is seen in SWS but it should not be forgotten that more generalized headaches like tension type may also be seen.
doi:10.11604/pamj.2014.18.87.3346
PMCID: PMC4231313  PMID: 25400854
Sturge-weber syndrome; congenital disorder; vascular nevus; angioma
21.  Traumatic-event headaches 
BMC Neurology  2004;4:17.
Background
Chronic headaches from head trauma and whiplash injury are well-known and common, but chronic headaches from other sorts of physical traumas are not recognized.
Methods
Specific information was obtained from the medical records of 15 consecutive patients with chronic headaches related to physically injurious traumatic events that did not include either head trauma or whiplash injury. The events and the physical injuries produced by them were noted. The headaches' development, characteristics, duration, frequency, and accompaniments were recorded, as were the patients' use of pain-alleviative drugs. From this latter information, the headaches were classified by the diagnostic criteria of the International Headache Society as though they were naturally-occurring headaches. The presence of other post-traumatic symptoms and litigation were also recorded.
Results
The intervals between the events and the onset of the headaches resembled those between head traumas or whiplash injuries and their subsequent headaches. The headaches themselves were, as a group, similar to those after head trauma and whiplash injury. Thirteen of the patients had chronic tension-type headache, two had migraine. The sustained bodily injuries were trivial or unidentifiable in nine patients. Fabrication of symptoms for financial remuneration was not evident in these patients of whom seven were not even seeking payments of any kind.
Conclusions
This study suggests that these hitherto unrecognized post-traumatic headaches constitute a class of headaches characterized by a relation to traumatic events affecting the body but not including head or whiplash traumas. The bodily injuries per se can be discounted as the cause of the headaches. So can fabrication of symptoms for financial remuneration. Altered mental states, not systematically evaluated here, were a possible cause of the headaches. The overall resemblance of these headaches to the headaches after head or whiplash traumas implies that these latter two headache types may likewise not be products of structural injuries.
doi:10.1186/1471-2377-4-17
PMCID: PMC529263  PMID: 15516263
22.  Anatomical Alterations of the Visual Motion Processing Network in Migraine with and without Aura 
PLoS Medicine  2006;3(10):e402.
Background
Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine.
Methods and Findings
To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing.
Conclusions
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a “silent” cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability seen in people who have migraine.
Editors' Summary
Background.
Migraine is a disabling brain disorder that affects more than one in ten people during their lifetimes. It is characterized by severe, recurrent headaches, often accompanied by nausea, vomiting, and light sensitivity. In some migraineurs (people who have migraines), the headaches are preceded by neurological disturbances known as “aura.” These usually affect vision, causing illusions of flashing lights, zig-zag lines, or blind spots. There are many triggers for migraine attacks—including some foods, stress, and bright lights—and every migraineur has to learn what triggers his or her attacks. There is no cure for migraine, although over-the-counter painkillers can ease the symptoms and doctors can prescribe stronger remedies or drugs to reduce the frequency of attacks. Exactly what causes migraine is unclear but scientists think that, for some reason, the brains of migraineurs are hyperexcitable. That is, some nerve cells in their brains overreact when they receive electrical messages from the body. This triggers a local disturbance of brain function called “cortical spreading depression,” which, in turn, causes aura, headache, and the other symptoms of migraine.
Why Was This Study Done?
Researchers need to know more about what causes migraine to find better treatments. One clue comes from the observation that motion perception is abnormal in migraineurs, even between attacks—they can be very sensitive to visually induced motion sickness, for example. Another clue is that aura are usually visual. So could brain regions that process visual information be abnormal in people who have migraines? In this study, the researchers investigated the structure of the motion processing parts of the brain in people who have migraine with aura, in people who have migraine without aura, and in unaffected individuals to see whether there were any differences that might help them understand migraine.
What Did the Researchers Do and Find?
The researchers used two forms of magnetic resonance imaging—a noninvasive way to produce pictures of internal organs—to examine the brains of migraineurs (when they weren't having a migraine) and healthy controls. They concentrated on two brain regions involved in motion processing known as the MT+ and V3A areas and first measured the cortical thickness of these areas—the cortex is the wrinkled layer of gray matter on the outside of the brain that processes information sent from the body. They found that the cortical thickness was increased in both of these areas in migraineurs when compared to healthy controls. There was no difference in cortical thickness between migraineurs who had aura and those who did not, but the area of cortical thickening in V3A corresponded to the source of cortical spreading depression previously identified in a person who had migraine with aura. The researchers also found differences between the white matter (the part of the brain that transfers information between different regions of the gray matter) immediately below the V3A and MT+ areas in the migraineurs and the controls but again not between the two groups of migraineurs.
What Do These Findings Mean?
This study provides new information about migraine. First, it identifies structural changes in the brains of people who have migraines. Until now, it has been thought that abnormal brain function causes migraine but that migraineurs have a normal brain structure. The observed structural differences might either account for or be caused by the hyperexcitability that triggers migraines. Because migraine runs in families, examining the brains of children of migraineurs as they grow up might indicate which of these options is correct, although it is possible that abnormalities in brain areas not examined here actually trigger migraines. Second, the study addresses a controversial question about migraine: Is migraine with aura the same as migraine without aura? The similar brain changes in both types of migraine suggest that they are one disorder. Third, the abnormalities in areas MT+ and V3A could help to explain why migraineurs have problems with visual processing even in between attacks. Finally, this study suggests that it might be possible to develop a noninvasive test to help doctors diagnose migraine.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030402.
The MedlinePlus encyclopedia has several pages on migraine
The US National Institute of Neurological Disorders and Stroke offers patient information on migraine and other headaches
The NHS Direct Online contains patient information on migraine from the UK National Health Service
MAGNUM provides information from The US National Migraine Association
The Migraine Trust is a UK charity that supports research and provides support for patients
The Migraine Aura Foundation is a site about aura that includes a section on art and aura
doi:10.1371/journal.pmed.0030402
PMCID: PMC1609120  PMID: 17048979
23.  Diagnostic and therapeutic guidelines for migraine. Italian Society for the Study of Headaches (SISC) 
The Journal of Headache and Pain  2001;2(Suppl 1):s125-s129.
The Italian Society for the Study of Headaches (SISC) published the first guidelines for diagnosis and treatment of migraine in 1993. In 2000, the Executive Committee of the SISC decided to provide updated diagnostic and therapeutic guidelines for migraine and cluster headache for headache experts and physicians dedicated to headaches. For this purpose an Ad Hoc Committee was formed, taking into consideration the multidisciplinary characteristics of the society, and was composed of prominent Italian researchers from various disciplines. The guidelines were published in 2001 and will be updated each year on the basis of new information concerning diagnostic and therapeutic strategies for migraine and cluster headache. The Ad Hoc Committee was organized into subcommittees, each responsible for a different topic: diagnosis of migraine; symptomatic treatment of migraine; prophylactic treatment of migraine; non–pharmacological treatment of migraine; diagnosis, symptomatic and prophylactic treatment of cluster headache; and lastly trigeminal autonomic cranial neuralgias (TACs) and unsolved questions. The present paper reports the major conclusions of the first three subcommittees only. From a methodological point of view, it was decided that all the information reported in the guidelines would be evidencebased. This involved a thorough research on Medline and Pubmed taking into consideration all the articles concerning clinical, laboratory and instrumental examinations and therapeutic approaches for migraine and cluster headache. As far as migraine is concerned, all studies available in the literature examining the sensitivity, specificity, predictive value of clinical history, neurological examination, laboratory tests and instrumental examination were evaluated to identify variables useful in the differential diagnosis of secondary headaches mimicking migraine attacks and to identify surrogate indicators of migraine. Four groups of recommendations, based on the levels of evidence, scientific effect and clinical assessment were defined for all symptomatic and prophylactic drugs. Information regarding clinical contraindications and pharmacological interactions for each class of symptomatic and prophylactic anti-migraine drugs were also reported.
doi:10.1007/s101940170025
PMCID: PMC3451830
Guidelines; Italian Society for the Study of Headaches; Migraine; Diagnosis; Treatment; Symptomatic drugs; Prophylactic drugs; Recommendations
24.  Prevalence and characteristics of migraine in medical students and its impact on their daily activities 
Background:
Migraine is a common neurological disorder with significant impact on quality of life. The aim of this study was to investigate the prevalence and characteristics of migraine headaches in medical students, to measure its impact on their life, and to assess their knowledge about the ailment. Information about lifestyle variables was also collected.
Materials and Methods:
All medical students who confirmed of having headache for more than 1 year formed the study group. Students filled a detailed questionnaire focusing on demographics, pain characteristics, accompanying factors, triggers, and family history of migraine. Lifestyle variables were enquired and migraine associated disability was assessed by MIDAS (Migraine Disability Assessment). The diagnosis of migraine was made according to the International Headache Society criteria. Results are expressed in n = numbers and percentage.
Results:
Sixty-eight percent of medical students had headache. The prevalence of migraine in the whole cohort was 28%; however, of the headache group, migraine constituted 42%. There was a female preponderance. One-fourth of the students had weekly or daily attacks with 31% students reporting increase in their headache intensity and frequency. Forty-four percent of students had severe headaches. Dizziness, allodynia, and neck stiffness were reported as accompanying symptoms. Trigger factors were identified in 99% students, predominant of which were poor sleep hygiene, environmental changes, head movements, and mental stress. Only 4% of students did regular exercise. Twenty-seven percent of students reported self-medication use of analgesics. One-fourth of the students had migraine-associated disability but only 6% realized that they had migraine.
Conclusion:
Our study found a high prevalence of headache with migraine in medical students. The students’ awareness of the disease was very low with one-fourth of the students resorting to self-medication. Our study identified previously less-recognized triggers like head movement and accompanying symptoms like neck stiffness. Migraine-attributed burden was high in medical students.
doi:10.4103/0972-2327.112472
PMCID: PMC3724079  PMID: 23956569
Impact on life; medical students; migraine
25.  Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study 
Objective To evaluate the association of overall and specific headaches with volume of white matter hyperintensities, brain infarcts, and cognition.
Design Population based, cross sectional study.
Setting Epidemiology of Vascular Ageing study, Nantes, France.
Participants 780 participants (mean age 69, 58.5% women) with detailed headache assessment.
Main outcome measures Brain scans were evaluated for volume of white matter hyperintensities (by fully automated imaging processing) and for classification of infarcts (by visual reading with a standardised assessment grid). Cognitive function was assessed by a battery of tests including the mini-mental state examination.
Results 163 (20.9%) participants reported a history of severe headache and 116 had migraine, of whom 17 (14.7%) reported aura symptoms. An association was found between any history of severe headache and increasing volume of white matter hyperintensities. The adjusted odds ratio of being in the highest third for total volume of white matter hyperintensities was 2.0 (95% confidence interval 1.3 to 3.1, P for trend 0.002) for participants with any history of severe headache when compared with participants without severe headache being in the lowest third. The association pattern was similar for all headache types. Migraine with aura was the only headache type strongly associated with volume of deep white matter hyperintensities (highest third odds ratio 12.4, 1.6 to 99.4, P for trend 0.005) and with brain infarcts (3.4, 1.2 to 9.3). The location of infarcts was predominantly outside the cerebellum and brain stem. Evidence was lacking for cognitive impairment for any headache type with or without brain lesions.
Conclusions In this population based study, any history of severe headache was associated with an increased volume of white matter hyperintensities. Migraine with aura was the only headache type associated with brain infarcts. Evidence that headache of any type by itself or in combination with brain lesions was associated with cognitive impairment was lacking.
doi:10.1136/bmj.c7357
PMCID: PMC3022913  PMID: 21245119

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