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1.  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
2.  Anger and emotional distress in patients with migraine and tension–type headache 
The Journal of Headache and Pain  2005;6(5):392-399.
The objective was to evaluate the prevalence and the characteristics of anger and emotional distress in migraine and tension– type headache patients. Two hundred and one headache patients attending the Headache Center of the University of Turin were selected for the study and divided into 5 groups: (1) migraine, (2) episodic tension–type headache, (3) chronic tension–type headache, (4) migraine associated with episodic tension–type headache and (5) migraine associated with chronic tension–type headache. A group of 45 healthy subjects served as controls. All the subjects completed the State–Trait Anger Expression Inventory, the Beck's Depression Inventory and the Cognitive Behavioral Assessment. Anger control was significantly lower in all headache patients (p<0.05) except in migraineurs. Patients with migraine and tension–type headache showed a significantly higher level of angry temperament and angry reaction (p<0.05). In addition, chronic tension–type headache and migraine associated with tension–type headache patients reported a higher level of anxiety (p<0.05), depression (p<0.001), phobias (p<0.001) and obsessive–compulsive symptoms (p<0.01), emotional liability (p<0.001) and psychophysiological disorders (p<0.001). Our study shows that chronic tension–type headache and migraine associated with tension–type headache patients present a significant impairment of anger control and suggests a connection between anger and the duration of headache experience.
doi:10.1007/s10194-005-0240-8
PMCID: PMC3452065  PMID: 16362712
Migraine; Tension–type headache; Anger; Depression
3.  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
4.  Personality traits in chronic daily headache patients with and without psychiatric comorbidity: an observational study in a tertiary care headache center 
Background
Previous studies suggest that patients with Chronic Daily Headache (CDH) have higher levels of anxiety and depressive disorders than patients with episodic migraine or tension-type headache. However, no study has considered the presence of psychiatric comorbidity in the analysis of personality traits. The aim of this study is to investigate the prevalence of psychiatric comorbidity and specific personality traits in CDH patients, exploring if specific personality traits are associated to headache itself or to the psychiatric comorbidity associated with headache.
Methods
An observational, cross-sectional study. Ninety-four CDH patients with and without medication overuse were included in the study and assessed by clinical psychiatric interview and Mini International Neuropsychiatric Interview (M.I.N.I.) as diagnostic tools. Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Hamilton Depression Rating Scale (HAM-D) were afterwards administered. Patients with and without psychiatric comorbidity were compared. Further analyses were made by splitting the whole group according to the headache diagnosis and the presence or not of medication overuse.
Results
Psychiatric comorbidity was detected in 44 patients (46.8%) (group A) and was absent in the remaining 50 patients (53.2%) (group B). Mood and anxiety disorders were the most frequently diagnosed (43.6%).
In the overall group, mean scores of MMPI-2 showed a high level in the so-called neurotic triad; in particular the mean score in the Hypochondriasis subscale was in the pathologic area (73.55 ± 13.59), while Depression and Hysteria scores were moderate but not severe (62.53 and 61.61, respectively). In content scales, score in Health Concern was also high (66.73).
Group A presented higher scores compared to Group B in the following MMPI-2 subscales: Hypochondriasis (p = .036), Depression (p = .032), Hysteria (p < .0001), Hypomania (p = .030). Group B had a high score only in the Hypochondriasis subscale. No significant differences were found between chronic migraine (CM)-probable CM (pCM) plus probable medication overuse headache (pMOH) and chronic tension-type headache (CTTH)-probable CTTH (pCTTH) plus pMOH patients or between patients with and without drug overuse.
Conclusions
The so-called “Neurotic Profile” reached clinical level only in CDH patients with psychiatric comorbidity while a high concern about their general health status was a common feature in all CDH patients.
doi:10.1186/1129-2377-14-22
PMCID: PMC3620450  PMID: 23566048
Chronic daily headache; Medication overuse headache; Psychiatric comorbidity; MMPI-2
5.  Study of psychiatric comorbidity in patients with headache using a short structured clinical interview in a rural neurology clinic in Western India 
Background:
Psychiatric disorders are common in patients attending neurology clinics with headache. Evaluation of psychiatric comorbidity in patients with headache is often missed in the busy neurology clinics.
Aims:
To assess the prevalence of Axis-I DSM-IV psychiatric disorders in patients with primary headache disorders in a rural-based tertiary neurology clinic in Western India.
Settings and Design
: A cross-sectional observation survey was conducting assessing all patients with migraine, tension-type headache and chronic daily headache attending the Neurology Clinic of Shree Krishna Hospital, a rural medical teaching hospital in Karamsad, in Gujarat in Western India.
Materials and Methods:
A total of 101 consecutive consenting adults with headache were interviewed using Mini International Neuropsychiatric Interview (M.I.N.I.), a structured diagnostic clinical interview to assess prevalence of Axis-I DSM-IV psychiatric disorders.
Statistical Analysis:
Descriptive statistics were calculated using SPSS software version 16 and a binomial regression model was used to study the relationship of psychiatric co-morbidity with patient-related factors.
Results:
49 out of 101 (48.5%) patients with headache suffered from depressive disorders (dysthymia or depression or suicidality), 18 out of 101 patients with headache (17.90%) suffered from anxiety related disorders (generalized anxiety disorder or agoraphobia or social phobia or panic disorder).
Conclusions:
Axis-I psychiatric disorders are a significant comorbidity among patients with headache disorders. M.I.N.I. can be used as a short, less time consuming instrument to assess all patients with headache disorders.
doi:10.4103/0976-3147.145199
PMCID: PMC4271380  PMID: 25540537
Anxiety; depression; headache; migraine; tension-type headache
6.  Anxiety, depression and school absenteeism in youth with chronic or episodic headache 
Chronic daily headache (CDH) is relatively common among children. Although comorbid conditions have been extensively studied in adults, they have not been assessed in the pediatric CDH population. Accordingly, the authors assessed several conditions known to be associated with CDH in adult patients in children with either CDH or episodic headache. The influence of CDH or episodic headache on the number of school days missed was also assessed.
BACKGROUND:
Chronic daily headache (CDH) in children has been documented in general and clinical populations. Comorbid psychological conditions, risk factors and functional outcomes of CDH in children are not well understood.
OBJECTIVES:
To examine anxiety and depression, associated risk factors and school outcomes in a clinical population of youth with CDH compared with youth with episodic headache (EH).
METHODS:
Data regarding headache characteristics, anxiety, depression and missed school days were collected from 368 consecutive patients eight to 17 years of age, who presented with primary headache at a specialized pediatric headache centre.
RESULTS:
A total of 297 patients (81%) were diagnosed with EH and 71 were diagnosed with CDH. Among those with CDH, 78.9% presented with chronic tension-type headache and 21.1% with chronic migraine (CM). Children with CDH had a higher depression score than the standardized reference population. No difference was observed for anxiety or depression scores between children with CDH and those with EH. However, children with CM were more anxious and more depressed than those with chronic tension-type headache. Youth experiencing migraine with aura were three times as likely to have clinically significant anxiety scores. Headache frequency and history were not associated with psychopathological symptoms. Children with CDH missed school more often and for longer periods of time.
CONCLUSIONS:
These findings document the prevalence of anxiety, depression and school absenteeism in youth with CDH or EH. The present research also extends recent studies examining the impact of aura on psychiatric comorbidity and the debate on CM criteria.
PMCID: PMC4197750  PMID: 24911174
Adolescents; Anxiety; Children; Chronic headache; Depression
7.  Migraine may be a risk factor for the development of complex regional pain syndrome 
The aim was to assess the relative frequency of migraine and the headache characteristics of complex regional pain syndrome (CRPS) sufferers. CRPS and migraine are chronic, often disabling pain syndromes. Recent studies suggest that headache is associated with the development of CRPS. Consecutive adults fulfilling International Association for the Study of Pain criteria for CRPS at a pain clinic were included. Demographics, medical history, and pain characteristics were obtained. Headache diagnoses were made using International Classification of Headache Disorders, 2nd edn criteria. Migraine and pain characteristics were compared in those with migraine with those without. ANOVA with Tukey post hoc tests was used to determine the significance of continuous variables and Fisher’s exact or χ2 tests for categorical variables. The expected prevalence of migraine and chronic daily headache (CDH) was calculated based on age- and gender-stratified general population estimates. Standardized morbidity ratios (SMR) were calculated by dividing the observed prevalence of migraine by the expected prevalence from the general population. The sample consisted of 124 CRPS participants. The mean age was 45.5 ± 12.0 years. Age-and gender-adjusted SMRs showed that those with CRPS were 3.6 times more likely to have migraine and nearly twice as likely to have CDH as the general population. Aura was reported in 59.7% (74/124) of participants. Of those CRPS sufferers with migraine, 61.2% (41/67) reported the onset of severe headaches before the onset of CRPS symptoms Mean age of onset of CRPS was earlier in those with migraine (34.9 ± 11.1 years) and CDH (32.5 ± 13.4 years) compared with those with no headaches (46.8 ± 14.9 years) and those with tension-type headache (TTH) (39.9 ± 9.9 years), P < 0.05. More extremities were affected by CRPS in participants with migraine (median of four extremities) compared with the combined group of those CRPS sufferers with no headaches or TTH (median 2.0 extremities), P < 0.05. The presence of static, dynamic and deep joint mechanoallodynia together was reported by more CRPS participants with migraine (72.2%) than those with no headaches or TTH (46.2%), P ≤ 0.05. Migraine may be a risk factor for CRPS and the presence of migraine may be associated with a more severe form of CRPS. Specifically: (i) migraine occurs in a greater percentage of CRPS sufferers than expected in the general population; (ii) the onset of CRPS is reported earlier in those with migraine than in those without; and (iii) CRPS symptoms are present in more extremities in those CRPS sufferers with migraine compared with those without. In addition, as we also found that the presence of aura is reported in a higher percentage of those CRPS sufferers with migraine than reported in migraineurs in the general population, further evaluation of the cardiovascular risk profile of CRPS sufferers is warranted.
doi:10.1111/j.1468-2982.2009.01916.x
PMCID: PMC3979276  PMID: 19614690
Migraine; chronic daily headache; complex regional pain syndrome; allodynia; aura
8.  Prevalence and burden of primary headache disorders among a local community in Addis Ababa, Ethiopia 
Background
Headache disorders are the most common complaints worldwide. Migraine, tension type and cluster headaches account for majority of primary headaches and improvise a substantial burden on the individual, family or society at large. There is a scanty data on the prevalence of primary headaches in sub-Saharan Africa in general and Ethiopia in particular. Moreover there is no population based urban study in Ethiopia. The purpose of this study is to determine the prevalence and burden of primary headaches in local community in Addis Ababa, Ethiopia.
Methods
Cross-sectional sample survey was carried out in Addis Ketema sub city, Kebele 16/17/18 (local smallest administrative unit). Using systematic random sampling, data were collected by previously used headache questionnaire, over a period of 20 days.
Results
The study subjects were 231 of which 51.5% were males and 48.5% were females. The overall one year prevalence of primary headache disorders was 21.6% and that for migraine was 10%, migraine without aura 6.5% migraine with aura was 2.6% and probable migraine was 0.9%. The prevalence of tension type of headache was found to be 10.4%, frequent episodic tension type headache was 8.2% followed by infrequent tension type headache of 2.2%. The prevalence of cluster headache was 1.3%. The burden of primary headache disorders in terms of missing working, school or social activities was 68.0%. This was 78.3% for migraineurs and 66.7% for tension type headache. Majority 92.0% of primary headache cases were not using health services and 66.0% did not use any drug or medications during the acute attacks and none were using preventive therapy.
Conclusion
Prevalence and burden of primary headache disorders was substantial in this community. Health service utilization of the community for headache treatment was poor.
doi:10.1186/1129-2377-14-30
PMCID: PMC3620379  PMID: 23574933
Prevalence; Primary headaches; Burden; Addis Ababa; Ethiopia
9.  Magnitude, impact, and stability of primary headache subtypes: 30 year prospective Swiss cohort study 
Objective
To determine the prevalence, impact, and stability of different subtypes of headache in a 30 year prospective follow-up study of a general population sample.
Design
Prospective cohort study.
Setting
Canton of Zurich, Switzerland.
Participants
591 people aged 19–20 from a cohort of 4547 residents of Zurich, Switzerland, interviewed seven times across 30 years of follow-up.
Main outcome measures
Prevalence of headache; stability of the predominant subtype of headache over time; and age of onset, severity, impact, family history, use of healthcare services, and drugs for headache subtypes.
Results
The average one year prevalences of subtypes of headache were 0.9% (female:male ratio of 2.8) for migraine with aura, 10.9% (female:male ratio of 2.2) for migraine without aura, and 11.5% (female:male ratio of 1.2) for tension-type headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type headache. Despite the high prevalence of migraine without aura, most cases were transient and only about 20% continued to have migraine for more than half of the follow-up period. 69% of participants with migraine and 58% of those with tension-type headache manifested the same predominant subtype over time. However, the prospective stability of the predominant headache subtypes was quite low, with substantial crossover among the subtypes and no specific ordinal pattern of progression. A gradient of severity of clinical correlates and service use was present across headache subtypes; the greatest effect was for migraine with aura followed by migraine without aura, and then tension-type headache and unclassified headaches.
Conclusions
These findings highlight the importance of prospective follow-up of people with headache. The substantial longitudinal overlap among subtypes of headache shows the developmental heterogeneity of headache syndromes. Studies of the causes of headache that apply diagnostic nomenclature based on distinctions between discrete headache subtypes may not capture the true nature of headache in the general population.
PMCID: PMC3161722  PMID: 21868455
10.  Magnitude, impact, and stability of primary headache subtypes: 30 year prospective Swiss cohort study 
Objective To determine the prevalence, impact, and stability of different subtypes of headache in a 30 year prospective follow-up study of a general population sample.
Design Prospective cohort study.
Setting Canton of Zurich, Switzerland.
Participants 591 people aged 19-20 from a cohort of 4547 residents of Zurich, Switzerland, interviewed seven times across 30 years of follow-up.
Main outcome measures Prevalence of headache; stability of the predominant subtype of headache over time; and age of onset, severity, impact, family history, use of healthcare services, and drugs for headache subtypes.
Results The average one year prevalences of subtypes of headache were 0.9% (female:male ratio of 2.8) for migraine with aura, 10.9% (female:male ratio of 2.2) for migraine without aura, and 11.5% (female:male ratio of 1.2) for tension-type headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type headache. Despite the high prevalence of migraine without aura, most cases were transient and only about 20% continued to have migraine for more than half of the follow-up period. 69% of participants with migraine and 58% of those with tension-type headache manifested the same predominant subtype over time. However, the prospective stability of the predominant headache subtypes was quite low, with substantial crossover among the subtypes and no specific ordinal pattern of progression. A gradient of severity of clinical correlates and service use was present across headache subtypes; the greatest effect was for migraine with aura followed by migraine without aura, and then tension-type headache and unclassified headaches.
Conclusions These findings highlight the importance of prospective follow-up of people with headache. The substantial longitudinal overlap among subtypes of headache shows the developmental heterogeneity of headache syndromes. Studies of the causes of headache that apply diagnostic nomenclature based on distinctions between discrete headache subtypes may not capture the true nature of headache in the general population.
doi:10.1136/bmj.d5076
PMCID: PMC3161722  PMID: 21868455
11.  Psychopathology and quality of life burden in chronic daily headache: influence of migraine symptoms 
The Journal of Headache and Pain  2010;11(3):247-253.
The aim of this study is to compare the psychopathology and the quality of life of chronic daily headache patients between those with migraine headache and those with tension-type headache. We enrolled 106 adults with chronic daily headache (CDH) who consulted for the first time in specialised centres. The patients were classified according to the IHS 2004 criteria and the propositions of the Headache Classification Committee (2006) with a computed algorithm: 8 had chronic migraine (without medication overuse), 18 had chronic tension-type headache (without medication overuse), 80 had medication overuse headache and among them, 43 fulfilled the criteria for the sub-group of migraine (m) MOH, and 37 the subgroup for tension-type (tt) MOH. We tested five variables: MADRS global score, HAMA psychic and somatic sub-scales, SF-36 psychic, and somatic summary components. We compared patients with migraine symptoms (CM and mMOH) to those with tension-type symptoms (CTTH and ttMOH) and neutralised pain intensity with an ANCOVA which is a priori higher in the migraine group. We failed to find any difference between migraine and tension-type groups in the MADRS global score, the HAMA psychological sub-score and the SF36 physical component summary. The HAMA somatic anxiety subscale was higher in the migraine group than in the tension-type group (F(1,103) = 10.10, p = 0.001). The SF36 mental component summary was significantly worse in the migraine as compared with the tension-type subgroup (F(1,103) = 5.758, p = 0.018). In the four CDH subgroups, all the SF36 dimension scores except one (Physical Functioning) showed a more than 20 point difference from those seen in the adjusted historical controls. Furthermore, two sub-scores were significantly more affected in the migraine group as compared to the tension-type group, the physical health bodily pain (F(1,103) = 4.51, p = 0.036) and the mental health (F(1,103) = 8.17, p = 0.005). Considering that the statistic procedure neutralises the pain intensity factor, our data suggest a particular vulnerability to somatic symptoms and a special predisposition to develop negative pain affect in migraine patients in comparison to tension-type patients.
doi:10.1007/s10194-010-0208-1
PMCID: PMC3451907  PMID: 20383733
Psychopathology; Quality of life; Chronic daily headache; Migraine symptoms; Tension type headache symptoms
12.  Diagnostic criteria for CADASIL in the International Classification of Headache Disorders (ICHD-II): are they appropriate? 
The Journal of Headache and Pain  2010;11(3):181-186.
We reviewed the characteristics of headache in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to verify the appropriateness of the International Classification of Headache Disorders, second edition (ICHD-II) criteria. Available data were found through Medline/PubMed using the keyword “cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)”. The search was restricted to studies published in English in the years between 1993 and 2008. We excluded studies that did not report original data on CADASIL and information regarding the presence of headache. We found 34 studies reporting data on 749 patients overall; 387 (51.7%) patients had headache. According to the authors’ definition, 356 (92%) patients were reported as having migraine and 31 (8%) as having headache. Of the 356 patients who were defined as migraineurs, 125 (35.1%) had migraine with aura, 7 (2%) migraine without aura, 156 (43.8%) unspecified migraine and 68 (19.1%) had more than one type of migraine. Among the 31 patients reported as suffering from headache, the headache was not further detailed in 18 (58.1%) patients; it was defined as chronic in 6 (19.3%), as resembling migraine with aura in 4 (12.9%), as resembling migraine without aura in 2 (6.5%) and as tension type in 1 (3.2%) patient. In patients with CADASIL, the headache was usually referred to as migraine and mostly as migraine with aura. However, this referral is formally incorrect since the diagnostic criteria for any type of migraine in the ICHD-II require that the disturbance is not attributed to another disorder. For this reason, we suggest updating the ICHD-II in relation to CADASIL. Our suggestion is to insert a new category referred to as Headache attributed to genetic disorder including Headache attributed to CADASIL.
doi:10.1007/s10194-010-0203-6
PMCID: PMC3451909  PMID: 20224942
Migraine; Headache; CADASIL; International Classification of Headache Disorders
13.  The importance of anxiety and depression as factors in chronicization of primary headaches 
The Journal of Headache and Pain  2000;1(Suppl 1):S45-S48.
A multicenter study was carried out in 10 Italian headache centers to investigate the prevalence of anxiety and depression in patients with chronic daily headache(CDH). The study investigated 219 patients (171 F; 48 M) including 53 cases of chronic tension-type headache (CTTH), 99 cases of CTTH+ migraine and 67 cases of transformed migraine (TM). The type of headache diagnosed at the beginning was episodic tension-type headache (ETTH, n=32), ETTH + migraine (n=2), CDH ab initio (n=22), migraine with/without aura (n=151), not classifiable migraine (n=7) and not classifiable headache (n=3). The assessment of anxiety and depression was carried out using a Zung self-rating scale for anxiety (Zung A) and for depression (Zung D). The results show that anxiety and depression levels, in each group, were related to sex (F>M). Anxiety, but not depression, was related to the length of chronicization process. Anxiety and depression did not correlate with type of headache at onset, with ongoing headache or, surprisingly, with the abuse of anti-inflammatory drugs. These data suggest the chronicization is a biological and psychological trait.
doi:10.1007/s101940070025
PMCID: PMC3611803
Key words Chronic daily headache; Anxiety; Depression; Overuse of analgesics; Zung scale
14.  Migraine aura without headache compared to migraine with aura in patients with affective disorders 
The Journal of Headache and Pain  2005;6(5):378-386.
The characteristics of psychiatric comorbidity in migraine have been studied in migraine with aura (MA) and migraine without aura (MO). Little information is available concerning patients with migraine aura without headache. In a study of 201 patients with major affective disorders (DSM–IV) we have described the clinical characteristics of patients with these three sub–types of migraine (IHS criteria) and compared the MA and migraine aura without headache groups. Compared to patients having MA (n=57), the group with migraine aura without headache (n=18) had a higher age of onset of migraine (28.5 vs. 19.2, p=0.001), significantly lower prevalences of affective temperaments (28% vs. 56%, p=0.036), suicide attempts (17% vs. 53%, p=0.013) and Raynaud’s syndrome (0% vs. 25%, p=0.017). These results indicate that there seem to be differences in the clinical characteristics found in patients with migraine with aura when compared to those having the migraine subtype without a headache phase. This may convey new information concerning the comorbid expression of migraine and affective disorders or concerning the processes that differentiates the migraine types with and without a subsequent pain attack.
doi:10.1007/s10194-005-0236-4
PMCID: PMC3452069  PMID: 16362710
Affective disorders; Affective temperaments; Migraine; Suicide attempt; Raynaud's syndrome
15.  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
16.  Primary headaches in patients with generalized anxiety disorder 
The Journal of Headache and Pain  2011;12-12(3):331-338.
Although anxiety disorders and headaches are comorbid conditions, there have been no studies evaluating the prevalence of primary headaches in patients with generalized anxiety disorder (GAD). The aim of this study was to analyze the lifetime prevalence of primary headaches in individuals with and without GAD. A total of 60 individuals were evaluated: 30 GAD patients and 30 controls without mental disorders. Psychiatric assessments and primary headache diagnoses were made using structured interviews. Among the GAD patients, the most common diagnosis was migraine, which was significantly more prevalent among the GAD patients than among the controls, as were episodic migraine, chronic daily headache and aura. Tension-type headache was equally common in both groups. Primary headaches in general were significantly more common and more severe in GAD patients than in controls. In anxiety disorder patients, particularly those with GAD, accurate diagnosis of primary headache can improve patient management and clinical outcomes.
doi:10.1007/s10194-010-0290-4
PMCID: PMC3094648  PMID: 21298316
Migraine; Anxiety disorders; Generalized anxiety disorder; Comorbidity
17.  Primary headaches in patients with generalized anxiety disorder 
The Journal of Headache and Pain  2011;12(3):331-338.
Although anxiety disorders and headaches are comorbid conditions, there have been no studies evaluating the prevalence of primary headaches in patients with generalized anxiety disorder (GAD). The aim of this study was to analyze the lifetime prevalence of primary headaches in individuals with and without GAD. A total of 60 individuals were evaluated: 30 GAD patients and 30 controls without mental disorders. Psychiatric assessments and primary headache diagnoses were made using structured interviews. Among the GAD patients, the most common diagnosis was migraine, which was significantly more prevalent among the GAD patients than among the controls, as were episodic migraine, chronic daily headache and aura. Tension-type headache was equally common in both groups. Primary headaches in general were significantly more common and more severe in GAD patients than in controls. In anxiety disorder patients, particularly those with GAD, accurate diagnosis of primary headache can improve patient management and clinical outcomes.
doi:10.1007/s10194-010-0290-4
PMCID: PMC3094648  PMID: 21298316
Migraine; Anxiety disorders; Generalized anxiety disorder; Comorbidity
18.  Validation of criterion-based patient assignment and treatment effectiveness of a multidisciplinary modularized managed care program for headache 
The Journal of Headache and Pain  2012;13(5):379-387.
This prospective observational study evaluates the validity of an algorithm for assigning patients to a multidisciplinary modularized managed care headache treatment program. N = 545 chronic headache sufferers [migraine (53.8 %), migraine + tension type (30.1 %), tension type (8.3 %) or medication overuse headache (6.2 %), other primary headaches (1.5 %)] were assigned to one of four treatment modules differing with regard to the number and types of interventions entailed (e.g., medication, psychological intervention, physical therapy, etc.). A rather simple assignment algorithm based on headache frequency, medication use and psychiatric comorbidity was used. Patients in the different modules were compared with regard to the experienced burden of disease. 1-year follow-up outcome data are reported (N = 160). Headache frequency and analgesic consumption differed significantly among patients in the modules. Headache-related disability was highest in patients with high headache frequency with/without medication overuse or psychiatric comorbidity (modules 2/3) compared to patients with low headache frequency and medication (module 0). Physical functioning was lowest in patients with chronic headache regardless of additional problems (modules 1/2/3). Psychological functioning was lowest in patients with severe chronicity with/without additional problems (module 2/3) compared to headache suffers with no/moderate chronicity (module 0/1). Anxiety or depression was highest in patients with severe chronicity. In 1-year follow-up, headache frequency (minus 45.3 %), consumption of attack-aborting drugs (minus 71.4 %) and headache-related disability decreased (minus 35.9 %). Our results demonstrate the clinical effectiveness and the criterion validity of the treatment assignment algorithm based on headache frequency, medication use and psychiatric comorbidity.
doi:10.1007/s10194-012-0453-6
PMCID: PMC3381067  PMID: 22581187
Integrated care; Multidisciplinary modularized treatment program; Outcome study; Headache-related disability; Headache-related quality of life; Chronic headache
19.  Relationship between insomnia and headache in community-based middle-aged Hong Kong Chinese women 
The Journal of Headache and Pain  2010;11(3):187-195.
Limited studies have investigated the prevalence of insomnia symptoms among individuals with different headache diagnoses and the association between insomnia and headache in subjects with comorbid anxiety and depression. A total of 310 community-dwelling Hong Kong Chinese women aged 40–60 years completed a self-administered questionnaire on headache, sleep difficulties, mood disturbances, and functional impairment. About 31% of the sample complained of recurrent headache unrelated to influenza and the common cold in the past 12 months. The percentages of women diagnosed to have migraine, tension-type headache (TTH), and headache unspecified were 8.4, 15.5 and 7.1%, respectively. The most frequent insomnia complaint was “problem waking up too early” (29.4%), followed by “difficulty staying asleep” (28.0%) and “difficulty falling asleep” (24.4%). Women with headaches were significantly more likely to report insomnia symptoms than those without headaches. There were no significant differences among women with migraine, TTH, and headache unspecified in the prevalence of insomnia symptoms. Logistic regression analysis showed that women with insomnia disorder as defined by an insomnia severity index total score ≥8 had 2.2-fold increased risk of reporting recurrent headache, 3.2-fold increased risk of migraine, and 2.3-fold increased risk of TTH, after adjusting for anxiety and depression. Individual insomnia symptoms were not independent predictors. The association between insomnia and headache was stronger in subjects with more frequent headaches. Our findings suggest that insomnia and the associated distress, but not insomnia symptoms alone, is an independent risk factor for recurrent headache in middle-aged women with mixed anxiety, depression and sleep disturbances.
doi:10.1007/s10194-010-0199-y
PMCID: PMC3451911  PMID: 20186559
Anxiety; Depression; Headache; Insomnia; Migraine; Tension-type headache
20.  The relation of sexual function to migraine-related disability, depression and anxiety in patients with migraine 
Background
Depression and anxiety are two phenomena that affect quality of life as well as sexual function. Depression and anxiety levels are reported to be high in migraine sufferers. We aimed to understand whether sexual function in women with migraine was associated to migraine-related disability and frequency of migraine attacks, and whether this relationship was modulated by depressive and anxiety symptoms.
Methods
As migraine is more commonly seen in females, a total of 50 women with migraine were included. The diagnosis of migraine with or without aura was confirmed by two specialists in Neurology, according to the second edition of International Headache Society (IHS) International Classification of Headache Disorders (ICHD-II) in 2004. Migraine disability assessment scale score, female sexual function index scores, Beck depression inventory score and Beck anxiety inventory scores.
Results
Mean MIDAS score was 19.3 ± 12.8, and mean number of migraine attacks per month were 4.3 ± 2.7. Mean Female Sexual Function Index score was 20.9 ± 5.9 and 90% of patients had sexual dysfunction. Sexual dysfunction was not related to MIDAS score or frequency and severity of attacks. No relationship between sexual function and anxiety was found, whereas severity of depressive symptoms was closely related to sexual function. Depressive symptoms affected all dimensions of sexual function, except for pain.
Conclusion
Sexual dysfunction seemed to be very common in our patients with migraine, while not related to migraine related disability, frequency of attacks and migraine severity or anxiety. The most important factor that predicted sexual function was depression, which was also independent of disease severity and migraine related disability. While future larger scale studies are needed to clarify the exact relationship, depressive and sexual problems should be properly addressed in all patients with migraine, regardless of disease severity or disability.
doi:10.1186/1129-2377-15-32
PMCID: PMC4046390  PMID: 24884652
Migraine; Sexual dysfunction; Migraine related disability; Depression; Anxiety
21.  Migraine and psychiatric comorbidity: a review of clinical findings 
The Journal of Headache and Pain  2011;12(2):115-125.
Migraine is an extremely common disorder. The underlying mechanisms of this chronic illness interspersed with acute symptoms appear to be increasingly complex. An important aspect of migraine heterogeneity is comorbidity with other neurological diseases, cardiovascular disorders, and psychiatric illnesses. Depressive disorders are among the leading causes of disability worldwide according to WHO estimation. In this review, we have mainly considered the findings from general population studies and studies on clinical samples, in adults and children, focusing on the association between migraine and psychiatric disorders (axis I of the DSM), carried over after the first classification of IHS (1988). Though not easily comparable due to differences in methodology to reach diagnosis, general population studies generally indicate an increased risk of affective and anxiety disorders in patients with migraine, compared to non-migrainous subjects. There would also be a trend towards an association of migraine with bipolar disorder, but not with substance abuse/dependence. With respect to migraine subtypes, comorbidity mainly involves migraine with aura. Patients suffering from migraine, however, show a decreased risk of developing affective and anxiety disorders compared to patients with daily chronic headache. It would also appear that psychiatric disorders prevail in patients with chronic headache and substance use than in patients with simple migraine. The mechanisms underlying migraine psychiatric comorbidity are presently poorly understood, but this topic remains a priority for future research. Psychiatric comorbidity indeed affects migraine evolution, may lead to chronic substance use, and may change treatment strategies, eventually modifying the outcome of this important disorder.
doi:10.1007/s10194-010-0282-4
PMCID: PMC3072482  PMID: 21210177
Migraine; Comorbidity; Psychiatric disorders; Depression; Meta-analysis
22.  Migraine and psychiatric comorbidity: a review of clinical findings 
The Journal of Headache and Pain  2011;12(2):115-125.
Migraine is an extremely common disorder. The underlying mechanisms of this chronic illness interspersed with acute symptoms appear to be increasingly complex. An important aspect of migraine heterogeneity is comorbidity with other neurological diseases, cardiovascular disorders, and psychiatric illnesses. Depressive disorders are among the leading causes of disability worldwide according to WHO estimation. In this review, we have mainly considered the findings from general population studies and studies on clinical samples, in adults and children, focusing on the association between migraine and psychiatric disorders (axis I of the DSM), carried over after the first classification of IHS (1988). Though not easily comparable due to differences in methodology to reach diagnosis, general population studies generally indicate an increased risk of affective and anxiety disorders in patients with migraine, compared to non-migrainous subjects. There would also be a trend towards an association of migraine with bipolar disorder, but not with substance abuse/dependence. With respect to migraine subtypes, comorbidity mainly involves migraine with aura. Patients suffering from migraine, however, show a decreased risk of developing affective and anxiety disorders compared to patients with daily chronic headache. It would also appear that psychiatric disorders prevail in patients with chronic headache and substance use than in patients with simple migraine. The mechanisms underlying migraine psychiatric comorbidity are presently poorly understood, but this topic remains a priority for future research. Psychiatric comorbidity indeed affects migraine evolution, may lead to chronic substance use, and may change treatment strategies, eventually modifying the outcome of this important disorder.
doi:10.1007/s10194-010-0282-4
PMCID: PMC3072482  PMID: 21210177
Migraine; Comorbidity; Psychiatric disorders; Depression; Meta-analysis
23.  Serum levels of N-acetyl-aspartate in migraine and tension-type headache 
The Journal of Headache and Pain  2012;13(5):389-394.
Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography–mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.
doi:10.1007/s10194-012-0448-3
PMCID: PMC3381063  PMID: 22527035
Serum N-acetyl-aspartate; Migraine; Tension-type headache
24.  Anxiety, depression and behavioral problems among adolescents with recurrent headache: the Young-HUNT study 
Background
It is well documented that both anxiety and depression are associated with headache, but there is limited knowledge regarding the relation between recurrent primary headaches and symptoms of anxiety and depression as well as behavioral problems among adolescents. Assessment of co-morbid disorders is important in order to improve the management of adolescents with recurrent headaches. Thus the main purpose of the present study was to assess the relationship of recurrent headache with anxiety and depressive symptoms and behavioral problems in a large population based cross-sectional survey among adolescents in Norway.
Methods
A cross-sectional, population-based study was conducted in Norway from 1995 to 1997 (Young-HUNT1). In Young-HUNT1, 4872 adolescents aged 12 to 17 years were interviewed about their headache complaints and completed a comprehensive questionnaire that included assessment of symptoms of anxiety and depression and behavioral problems, i.e. conduct and attention difficulties.
Results
In adjusted multivariate analyses among adolescents aged 12–14 years, recurrent headache was associated with symptoms of anxiety and depression (OR: 2.05, 95% CI: 1.61-2.61, p < 0.001), but not with behavioral problems. A significant association with anxiety and depressive symptoms was evident for all headache categories; i.e. migraine, tension-type headache and non-classifiable headache. Among adolescents aged 15–17 years there was a significant association between recurrent headache and symptoms of anxiety and depression (OR: 1.64, 95% CI: 1.39-1.93, p < 0,001) and attention difficulties (OR: 1.25, 95% CI: 1.09-1.44, p =0.001). For migraine there was a significant association with both anxiety and depressive symptoms and attention difficulties, while tension-type headache was significantly associated only with symptoms of anxiety and depression. Non-classifiable headache was associated with attention difficulties and conduct difficulties, but not with anxiety and depressive symptoms. Headache frequency was significantly associated with increasing symptoms scores for anxiety and depressive symptoms as well as attention difficulties, evident for both age groups.
Conclusions
The results from the present study indicate that both anxiety and depressive symptoms and behavioral problems are associated with recurrent headache, and should accordingly be considered a part of the clinical assessment of children and adolescents with headache. Identification of these associated factors and addressing them in interventions may improve headache management.
doi:10.1186/1129-2377-15-38
PMCID: PMC4062897  PMID: 24925252
Recurrent headache; Migraine; Tension-type headache; Anxiety; Depression; Behavioral problems; Conduct difficulties; Attention difficulties; Adolescents
25.  Headaches in Multiple Sclerosis Patients Might Imply an Inflammatorial Process 
PLoS ONE  2013;8(8):e69570.
Recent studies on Multiple Sclerosis (MS) pathology mention the involvement of “tertiary B cell follicles” in MS pathogenesis. This inflammatory process, which occurs with interindividually great variance, might be a link between MS pathology and headaches. The aim of this study was to detect the prevalence of headaches and of subtypes of headaches (migraine, cluster, tension-type headache [TTH]) in an unselected MS collective and to compile possibly influencing factors. Unselected MS patients (n = 180) with and without headache were examined by a semi-structured interview using a questionnaire about headache, depression and the health status. Additionally clinical MS data (expanded disability state score [EDSS], MS course, medication, disease duration) were gathered. N = 98 MS patients (55.4%) reported headaches in the previous 4 weeks. We subsequently grouped headache patients according to the IHS criteria and detected 16 (16.3%) MS patients suffering from migraine (migraine with aura: 2 [2%]; migraine without aura: 14 [14.3%]), 23 (23.5%) suffering from TTH and none with a cluster headache. Thus, headaches of 59 (60.2%) MS patients remained unclassified. When comparing MS patients with and without headaches significant differences in age, gender, MS course, physical functioning, pain and social functioning occurred. MS patients with headaches were significantly younger of age (p = 0.001), female (p = 0.001) and reported more often of a clinically isolated syndrome (CIS) and relapsing/remitting MS (RRMS) instead of secondary chronic progressive MS (SCP). EDSS was significantly lower in MS patients suffering from headaches compared to the MS patients without headaches (p = 0.001). In conclusion headache in MS patients is a relevant symptom, especially in early stages of the MS disease. Especially unclassified headache seems to represent an important symptom in MS course and requires increased attention.
doi:10.1371/journal.pone.0069570
PMCID: PMC3734145  PMID: 23940524

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