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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.  Line bisection performance in patients with generalized anxiety disorder and treatment-resistant depression 
Background and Objectives The line bisection error to the left of the true center has been interpreted as a relative right hemisphere activation, which might relate to the subject's emotional state. Considering that patients with generalized anxiety disorder (GAD) or treatment-resistant depression (TRD) often have negative emotions, we hypothesized that these patients would bisect lines significantly leftward. Methods We tried the line bisection task in the right-handed healthy volunteers (n = 56), GAD (n = 47) and TRD outpatients (n = 52). Subjects also completed the Zuckerman - Kuhlman Personality Questionnaire, the Zuckerman Sensation Seeking Scales, and the Plutchik-van Praag Depression Inventory. Results GAD patients scored highest on the Neuroticism-Anxiety trait, TRD patients scored highest on depression, and both patients scored lower on the Sociability trait. Patients with GAD also bisected lines significantly leftward compared to the healthy subjects. The Frequency of the bisection error was negatively correlated with Disinhibition-Seeking in the healthy subjects, and with Total sensation-seeking and Experience-Seeking in GAD patients, while the Magnitude of the line bisection error was negatively correlated with depression in TRD patients. Conclusions The study suggests a stronger right hemispheric activation, a weaker left activation, or both in the GAD, instead of TRD patients.
PMCID: PMC2899451  PMID: 20617126
Generalized Anxiety Disorder; hemispheric activation; line bisection; treatment-resistant depression
4.  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
5.  Psychosocial Correlates and Impact of Chronic Tension-type Headaches 
Headache  2000;40(1):3-16.
Objectives
To examine the psychosocial correlates of chronic tension-type headache and the impact of chronic tension-type headache on work, social functioning, and well-being.
Methods
Two hundred forty-five patients (mean age=37.0 years) with chronic tension-type headache as a primary presenting problem completed an assessment protocol as part of a larger treatment outcome study. The assessment included a structured diagnostic interview, the Medical Outcomes Study Short Form, Disability Days/Impairment Ratings, Recurrent Illness Impact Profile, Beck Depression Inventory, State-Trait Anxiety Inventory—Trait Form, Primary Care Evaluation for Mental Disorders, and the Hassles Scale Short Form. Comparisons were made with matched controls (N=89) and, secondarily, with Medical Outcomes Study data for the general population, arthritis, and back problem samples.
Results
About two thirds of those with chronic tension-type headache recorded daily or near daily (≥25 days per month) headaches with few (12%) recording headaches on less than 20 days per month. Despite the fact that patients reported that their headaches had occurred at approximately the present frequency for an average of 7 years, chronic tension-type headache sufferers were largely lapsed consulters (54% of subjects) or current consulters in primary care (81% of consulters).
Significant impairments in functioning and well-being were evident in chronic tension-type headache and were captured by each of the assessment devices. Although headache-related disability days were reported by 74% of patients (mean=7 days in previous 6 months), work or social functioning was severely impaired in only a small minority of patients. Sleep, energy level, and emotional well-being were frequently impaired with about one third of patients recording impairments in these areas on 10 or more days per month. Most patients with chronic tension-type headache continued to carry out daily life responsibilities when in pain, although role performance at times was clearly impaired by headaches and well-being was frequently impaired.
Chronic tension-type headache sufferers were 3 to 15 times more likely than matched controls to receive a diagnosis of an anxiety or mood disorder with almost half of the patients exhibiting clinically significant levels of anxiety or depression. Affective distress and severity of headaches (Headache Index) were important determinants of headache impact/impairment.
Conclusions
Chronic tension-type headache has a greater impact on individuals' lives than has generally been realized, with affective distress being an important correlate of impairment. If treatment is to remedy impairment in functioning, affective distress, as well as pain, thus needs to be addressed.
PMCID: PMC2128255  PMID: 10759896
chronic tension-type headache; disability; impairment; affective distress
6.  Homeopathic Treatment of Headaches: A Systematic Review of the Literature 
Abstract
Objective
To systematically review published prospective trials relating to the homeopathic treatment of tension type, cervicogenic, and migraine headache.
Data Sources
Pre-MEDLINE, MEDLINE, MANTIS, Cochrane Database of Systematic Reviews, and AMED were searched from the initial indexing year of each database through May 2002. Studies were further identified through a manual search of obtained article references.
Study Selection
English and non-English randomized clinical trials and prospective observational trials were included if there were at least ten subjects in the homeopathic portion of the trial and, for randomized clinical trials, if there was a placebo group. Treatment in these studies included single dose and individualized homeopathic prescription. Case studies, homeopathic provings, unpublished material, non-peer reviewed papers, and studies that combined multiple homeopathic remedies, introduced other complementary and alternative medicine therapies and/or introduced additional medical therapy for patients in the homeopathic treatment groups were excluded.
Data Extraction
Qualitative data were extracted from each paper and entered into an evidence table.
Data Synthesis
A critical evaluation list of 20 methodological items and their operational definitions was used, resulting in a validity score determined for each paper.
Results
Six papers met criteria for inclusion. Three out of the six papers studied migraine headache, two studied cervicogenic and tension type headache, and one included all types of headaches. Four studies were randomized clinical trials, and two were prospective observational studies. Validity scores ranged from 25.0% to 63.4%. Homeopathy was superior to placebo in one randomized clinical trial and equal to placebo in three randomized trials. In no study was homeopathy less effective than placebo in treating headache, or harmful. Two prospective observational studies demonstrated improvement in patients receiving homeopathic care.
Conclusion
There is insufficient evidence to support or refute the use of homeopathy for managing tension type, cervicogenic, or migraine headache. The studies reviewed possessed several flaws in design. Given these findings, further research is warranted to better investigate the effectiveness of homeopathic treatment of headaches.
doi:10.1016/S0899-3467(07)60085-8
PMCID: PMC2646987  PMID: 19674623
Homeopathy; Headache; Review of the Literature
7.  GREATER FREQUENCY OF DEPRESSION ASSOCIATED WITH CHRONIC PRIMARY HEADACHES THAN CHRONIC POST-TRAUMATIC HEADACHES 
Objective
To compare the prevalence of co-morbid depression between patients with chronic primary headache syndromes and chronic post-traumatic headaches.
Method
A prospective cross-sectional analysis of all patients presenting sequentially to a community-based general neurology clinic during a 2-year period for evaluation of chronic headache pain was conducted. Headache diagnosis was determined according to the International Headache Society’s Headache Classification criteria. Depression was determined through a combination of scores on the clinician administered Hamilton Rating Scale for Depression and patients’ self-report. An additional group of patients who suffered traumatic brain injuries (TBI) but did not develop post-traumatic headaches was included for comparison.
Results
A total of 83 patients were included in the study: 45 with chronic primary headaches (24 with chronic migraine headaches, 21 with chronic tension headaches), 24 with chronic post-traumatic headaches, and 14 with TBI but no headaches. Depression occurred less frequently among those with chronic post-traumatic headaches (33.3%) compared to those with chronic migraine (66.7%) and chronic tension (52.4%) headaches (Chi-Square = 7.68; df = 3; p = 0.053), and did not significantly differ from TBI patients without headaches. A multivariate logistic regression model using depression as the outcome variable and including headache diagnosis, gender, ethnicity, and alcohol and illicit substance use was statistically significant (Chi-Square = 27.201; df = 10; p < 0.01) and identified primary headache (migraine and tension) diagnoses (Score = 7.349; df = 1; p = 0.04) and female gender (Score = 15.281; df = 1; p < 0.01) as significant predictor variables. The overall model accurately predicted presence of co-morbid depression in 74.7% of the cases.
Conclusions
Co-morbid depression occurs less frequently among patients with chronic post-traumatic headaches and TBI without headaches than among those with chronic primary headaches.
PMCID: PMC4326262  PMID: 24066406
chronic pain; depression; headache
8.  Assessing personality traits by questionnaire: psychometric properties of the Greek version of the Zuckerman-Kuhlman personality questionnaire and correlations with psychopathology and hostility 
Hippokratia  2013;17(4):342-350.
Background: The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) was developed in an attempt to define the basic factors of personality or temperament. We aimed to assess the factor structure and the psychometric properties of its Greek version and to explore its relation to psychopathological symptoms and hostility features.
Methods: ZKPQ was translated into Greek using back-translation and was administered to 1,462 participants (475 healthy participants, 619 medical patients, 177 psychiatric patients and 191 opiate addicts). Confirmatory and exploratory factor analyses were performed. Symptoms Distress Check-List (SCL-90R) and Hostility and Direction of Hostility Questionnaire (HDHQ) were administered to test criterion validity.
Results: Five factors were identified, largely corresponding to the original version’s respective factors. Retest reliabilities were acceptable (rli’s: 0.79-0.89) and internal consistency was adequate for Neuroticism-Anxiety (0.87), Impulsive Sensation Seeking (0.80), Aggression-Hostility (0.77) and Activity (0.72), and lower for Sociability (0.64). Most components were able to discriminate psychiatric patients and opiate addicts from healthy participants. Opiate addicts exhibited higher rates on Impulsive Sensation Seeking compared to healthy participants. Neuroticism-Anxiety (p<0.001) and Impulsive Sensation Seeking (p<0.001) were significantly associated with psychological distress and Aggression-Hostility was the most powerful correlate of Total Hostility (p<0.001), and Neuroticism-Anxiety was the stronger correlate of introverted hostility (p<0.001), further supporting the instrument’s concurrent validity.
Conclusions: Present findings support the applicability of the Greek version of ZKPQ within the Greek population. Future studies could improve its psychometric properties by finding new items, especially for the Sociability scale.
PMCID: PMC4097416  PMID: 25031514
Zuckerman-Kuhlman Personality Questionnaire; ZKPQ; alternative Five-Factor personality model; psychological distress; SCL-90; hostility; sensation seeking
9.  Symptomatic approach to posttraumatic headache and its possible implications for treatment 
European Spine Journal  2001;10(5):403-407.
Abstract.
We investigated 112 patients [mean age 39.5±10.5 years, 59% women (n=66)] with chronic posttraumatic headache following cranio-cervical acceleration/deceleration trauma after an average time interval of 2.5±1.9 years from trauma. Headache following minor head injury or whiplash is one of the most prominent problems in neurotraumatology. Previous research is inconclusive regarding the symptomatic approach of this type of headache. Details of the phenomenology of posttraumatic headache in the previous literature are inconclusive. This may lead to inappropriate treatment strategies, because recent advances in therapy of different headache types may be neglected. Patients were investigated at the outpatient service of the Department of Psychiatry. Headache was analyzed according to its principal location, laterality, projection, quality, precipitation or aggravation and possible additional symptoms. For this analysis, headache was diagnosed according to the classification of the International Headache Society. The results showed that 42 patients (37%) had tension-type headache, 30 (27%) were identified as suffering from migraine, whereas 20 patients (18%) had cervicogenic headache. An additional 18% of patients suffered from headache that did not fulfill criteria of a particular category. In 104 patients (93%), neck pain was associated in time with headache. Each of the diagnosed headache types in this study may require specific treatment strategies based upon empirical studies of non-traumatic headache types. For these reasons a detailed analysis of headache following cranio-cervical acceleration/deceleration trauma is necessary.
doi:10.1007/s005860000227
PMCID: PMC3611524  PMID: 11718194
Head trauma Whiplash injury Chronic posttraumatic headache Migraine Tension headache
10.  Classification and Clinical Features of Headache Disorders in Pakistan: A Retrospective Review of Clinical Data 
PLoS ONE  2009;4(6):e5827.
Background
Morbidity associated with primary headache disorders is a major public health problem with an overall prevalence of 46%. Tension-type headache and migraine are the two most prevalent causes. However, headache has not been sufficiently studied as a cause of morbidity in the developing world. Literature on prevalence and classification of these disorders in South Asia is scarce. The aim of this study is to describe the classification and clinical features of headache patients who seek medical advice in Pakistan.
Methods and Results
Medical records of 255 consecutive patients who presented to a headache clinic at a tertiary care hospital were reviewed. Demographic details, onset and lifetime duration of illness, pattern of headache, associated features and family history were recorded. International Classification of Headache Disorders version 2 was applied.
66% of all patients were women and 81% of them were between 16 and 49 years of age. Migraine was the most common disorder (206 patients) followed by tension-type headache (58 patients), medication-overuse headache (6 patients) and cluster headache (4 patients). Chronic daily headache was seen in 99 patients. Patients with tension-type headache suffered from more frequent episodes of headache than patients with migraine (p<0.001). Duration of each headache episode was higher in women with menstrually related migraine (p = 0.015). Median age at presentation and at onset was lower in patients with migraine who reported a first-degree family history of the disease (p = 0.003 and p<0.001 respectively).
Conclusions/Significance
Patients who seek medical advice for headache in Pakistan are usually in their most productive ages. Migraine and tension-type headache are the most common clinical presentations of headache. Onset of migraine is earlier in patients with first-degree family history. Menstrually related migraine affects women with headache episodes of longer duration than other patients and it warrants special therapeutic consideration. Follow-up studies to describe epidemiology and burden of headache in Pakistan are needed.
doi:10.1371/journal.pone.0005827
PMCID: PMC2688080  PMID: 19503794
11.  Individual differences in drug abuse vulnerability: d-Amphetamine and sensation-seeking status 
Psychopharmacology  2006;189(1):17-25.
Rationale
While the personality dimensions of novelty seeking and sensation seeking are associated with drug abuse vulnerability, the mechanisms associated with this vulnerability remain obscure.
Objective
This study examined the behavioral effects of d-amphetamine in healthy volunteers scoring in the upper and lower quartiles based on age- and gender-adjusted population norms on the impulsive Sensation-Seeking Scale (SSS) of the Zuckerman–Kuhlman personality questionnaire (ZKPQ).
Method
Participants completed 7-day outpatient studies examining the subjective, performance, and cardiovascular effects of d-amphetamine (0, 7.5, and 15 mg/70 kg, p.o.) under double-blind conditions according to a randomized block design. Performance tasks included behavioral measures of impulsivity, including attention, inhibition, and risk-taking behavior.
Results
No differences in baseline performance or d-amphetamine effects on measures of attention, inhibition, and risk-taking behavior were observed. High impulsive sensation seekers reported greater increases on several subjective report measures associated with drug abuse potential, including visual analog scales feel drug, like drug, and high.
Conclusions
Healthy adults scoring in the top quartile on the population of the impulsive SSS of the ZKPQ may be vulnerable to the abuse potential of d-amphetamine.
doi:10.1007/s00213-006-0487-z
PMCID: PMC3188427  PMID: 16972106
d-amphetamine; Sensation-seeking status; Vulnerability; Subjective effects; Performance effects; Abuse potential
12.  Prevalence and characteristics of allodynia in headache sufferers 
Neurology  2008;70(17):1525-1533.
Objective:
The authors estimated the prevalence and severity of cutaneous allodynia (CA) in individuals with primary headaches from the general population.
Methods:
We mailed questionnaires to a random sample of 24,000 headache sufferers previously identified from the population. The questionnaire included the validated Allodynia Symptom Checklist (ASC) as well as measures of headache features, disability, and comorbidities. We modeled allodynia as an outcome using headache diagnosis, frequency and severity of headaches, and disability as predictor variables in logistic regression. Covariates included demographic variables, comorbidities, use of preventive medication, and use of opioids.
Results:
Complete surveys were returned by 16,573 individuals. The prevalence of CA of any severity (ASC score ≥3) varied with headache type. Prevalence was significantly higher in transformed migraine (TM, 68.3%) than in episodic migraine (63.2%, p < 0.01) and significantly elevated in both of these groups compared with probable migraine (42.6%), other chronic daily headaches (36.8%), and severe episodic tension-type headache (36.7%). The prevalence of severe CA (ASC score ≥9) was also highest in TM (28.5%) followed by migraine (20.4%), probable migraine (12.3%), other chronic daily headaches (6.2%), and severe episodic tension-type headache (5.1%). In the migraine and TM groups, prevalence of CA was higher in women and increased with disability score. Among migraineurs, CA increased with headache frequency and body mass index. In all groups, ASC scores were higher in individuals with major depression.
Conclusions:
Cutaneous allodynia (CA) is more common and more severe in transformed migraine and migraine than in other primary headaches. Among migraineurs, CA is associated with female sex, headache frequency, increased body mass index, disability, and depression.
doi:10.1212/01.wnl.0000310645.31020.b1
PMCID: PMC2664547  PMID: 18427069
13.  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
14.  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
15.  Headache, anxiety and depressive disorders: the HADAS study 
The Journal of Headache and Pain  2010;11(2):141-150.
The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tension-type headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (p = 0.009) for obsessive–compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2–7.0). The association was higher (OR 6.3; 95% CI 1.4–28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive–compulsive disorder (OR 4.8; 95% CI 1.1–20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden.
doi:10.1007/s10194-010-0187-2
PMCID: PMC3452290  PMID: 20108021
Migraine; Tension-type headache; Depression; Anxiety; Prevalence
16.  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
17.  Clinical features of headache patients with fibromyalgia comorbidity 
The Journal of Headache and Pain  2011;12(6):629-638.
Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
doi:10.1007/s10194-011-0377-6
PMCID: PMC3208047  PMID: 21847547
Primary headache; Fibromyalgia; Comorbidity
18.  Clinical features of headache patients with fibromyalgia comorbidity 
The Journal of Headache and Pain  2011;12(6):629-638.
Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
doi:10.1007/s10194-011-0377-6
PMCID: PMC3208047  PMID: 21847547
Primary headache; Fibromyalgia; Comorbidity
19.  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
20.  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
21.  Migraine headaches in Chronic Fatigue Syndrome (CFS): Comparison of two prospective cross-sectional studies 
BMC Neurology  2011;11:30.
Background
Headaches are more frequent in Chronic Fatigue Syndrome (CFS) than healthy control (HC) subjects. The 2004 International Headache Society (IHS) criteria were used to define CFS headache phenotypes.
Methods
Subjects in Cohort 1 (HC = 368; CFS = 203) completed questionnaires about many diverse symptoms by giving nominal (yes/no) answers. Cohort 2 (HC = 21; CFS = 67) had more focused evaluations. They scored symptom severities on 0 to 4 anchored ordinal scales, and had structured headache evaluations. All subjects had history and physical examinations; assessments for exclusion criteria; questionnaires about CFS related symptoms (0 to 4 scale), Multidimensional Fatigue Inventory (MFI) and Medical Outcome Survey Short Form 36 (MOS SF-36).
Results
Demographics, trends for the number of diffuse "functional" symptoms present, and severity of CFS case designation criteria symptoms were equivalent between CFS subjects in Cohorts 1 and 2. HC had significantly fewer symptoms, lower MFI and higher SF-36 domain scores than CFS in both cohorts. Migraine headaches were found in 84%, and tension-type headaches in 81% of Cohort 2 CFS. This compared to 5% and 45%, respectively, in HC. The CFS group had migraine without aura (60%; MO; CFS+MO), with aura (24%; CFS+MA), tension headaches only (12%), or no headaches (4%). Co-morbid tension and migraine headaches were found in 67% of CFS. CFS+MA had higher severity scores than CFS+MO for the sum of scores for poor memory, dizziness, balance, and numbness ("Neuro-construct", p = 0.002) and perceived heart rhythm disturbances, palpitations and noncardiac chest pain ("Cardio-construct"; p = 0.045, t-tests after Bonferroni corrections). CFS+MO subjects had lower pressure-induced pain thresholds (2.36 kg [1.95-2.78; 95% C.I.] n = 40) and a higher prevalence of fibromyalgia (47%; 1990 criteria) compared to HC (5.23 kg [3.95-6.52] n = 20; and 0%, respectively). Sumatriptan was beneficial for 13 out of 14 newly diagnosed CFS migraine subjects.
Conclusions
CFS subjects had higher prevalences of MO and MA than HC, suggesting that mechanisms of migraine pathogenesis such as central sensitization may contribute to CFS pathophysiology.
Clinical Trial Registration
Georgetown University IRB # 2006-481
ClinicalTrials.gov NCT00810329
doi:10.1186/1471-2377-11-30
PMCID: PMC3058027  PMID: 21375763
22.  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
23.  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
24.  Genome-wide association study of personality traits in bipolar patients 
Psychiatric genetics  2011;21(4):190-194.
Objective
Genome-wide association study was carried out on personality traits among bipolar patients as possible endophenotypes for gene discovery in bipolar disorder.
Methods
The subscales of Cloninger’s Temperament and Character Inventory (TCI) and the Zuckerman–Kuhlman Personality Questionnaire (ZKPQ) were used as quantitative phenotypes. The genotyping platform was the Affymetrix 6.0 SNP array. The sample consisted of 944 individuals for TCI and 1007 for ZKPQ, all of European ancestry, diagnosed with bipolar disorder by Diagnostic and Statistical Manual of Mental Disorders-IV criteria.
Results
Genome-wide significant association was found for two subscales of the TCI, rs10479334 with the ‘Social Acceptance versus Social Intolerance’ subscale (Bonferroni P = 0.014) in an intergenic region, and rs9419788 with the ‘Spiritual Acceptance versus Rational Materialism’ subscale (Bonferroni P = 0.036) in PLCE1 gene. Although genome-wide significance was not reached for ZKPQ scales, lowest P values pinpointed to genes, RXRG for Sensation Seeking, GRM7 and ITK for Neuroticism Anxiety, and SPTLC3 gene for Aggression Hostility.
Conclusion
After correction for the 25 subscales in TCI and four scales plus two subscales in ZKPQ, phenotype-wide significance was not reached.
doi:10.1097/YPG.0b013e3283457a31
PMCID: PMC3125400  PMID: 21368711
bipolar; genome-wide association study; GRM7; personality; RXRG; Temperament and Character Inventory; Zuckerman–Kuhlman Personality Questionnaire
25.  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

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