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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.  The effects of sodium valproate with fish oil supplementation or alone in migraine prevention: A randomized single-blind clinical trial 
Iranian Journal of Neurology  2012;11(1):21-24.
Background
Omega-3 polyunsaturated fatty acids (PUFA) have beneficial effects on both specific and non-specific inflammatory reactions. The aim of this study was to evaluate the effect of dietary supplementation with fish oil in migraine prevention.
Methods
A 12-week, randomized, single-blind clinical trial was conducted from October 2008 to June 2009. A total of 67 patients (52 women, 15 men) with migraine headache were randomly allocated to 2 groups. In the first group, 38 patients (30 females with a mean age of 35 ± 9 year) received 400 mg/day sodium valproate. In the second group, 29 patients (22 females with a mean age of 36 ± 9 years) received sodium valproate 400 mg daily plus fish oil supplementation (180 mg). Response to the treatment was assessed at 0, 1, 2, and 3 months after start of the therapy.
Results
A significant decrease in duration, monthly frequency, and severity of headache after month 1, 2, and 3 in comparison with month 0 occurred in both groups. There was a significant reduction in headache severity (P = 0.046) and frequency (P = 0.044) in the group with fish oil supplementation after month 1 in comparison with sodium valproate alone. In contrast, there was no significant difference between two treatment groups in duration of the headache after month 1. Mean intensity, mean duration and mean frequency of the attacks after month 2 and 3 were not significantly different between the two groups.
Conclusion
This study demonstrated that sodium valproate plus fish oil supplementation significantly reduces migraine headache more than sodium valproate alone but only at the beginning of the treatment.
PMCID: PMC3829229  PMID: 24250854
Fish Oil; Migraine; Sodium Valproate; Pain
3.  Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia: Coenzyme Q10 Effect on Clinical Improvement 
PLoS ONE  2012;7(4):e35677.
Background
Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q10 (CoQ10) supplementation on biochemical markers and clinical improvement were also evaluated.
Methods
We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ10, catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs.
Results
We found decreased CoQ10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P<0.05 and P<0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P<0.001). Significant negative correlations between CoQ10 or catalase levels in BMCs and headache parameters were observed (r = −0.59, P<0.05; r = −0.68, P<0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05). Oral CoQ10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P<0.001).
Discussion
The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.
doi:10.1371/journal.pone.0035677
PMCID: PMC3330812  PMID: 22532869
4.  Nutrition intervention for migraine: a randomized crossover trial 
Background
Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.
Methods
Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests.
Results
Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001).
Conclusions
These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research.
Trial registration
Clinicaltrials.gov, NCT01699009 and NCT01547494.
doi:10.1186/1129-2377-15-69
PMCID: PMC4227630  PMID: 25339342
Migraine; Headache; Nutrition; Diet; Plant-based; Vegan
5.  28B. Interdisciplinary Approach to Chronic Headaches 
Focus Areas: Experiential Workshop, Alleviating Pain
Chronic headaches are a common complaint, affecting millions of people worldwide. Underlying causes are varied, and many individuals suffer from multiple types of head pain, including migraines, tension headaches, and temporomandibular joint dysfunction. Many factors can affect pain intensity and frequency including dietary components, physical activity, stress, medications, and emotional events. Because of the varied causes, a single therapeutic approach is unlikely to be successful in treating the majority of patients. Conventional therapies often rely heavily on oral medication, which may provide insufficient pain control or be poorly tolerated.
This presentation will bring together a variety of alternative treatment options for chronic headaches. The foundations of health will be reviewed in the context of headache care, including a focus on dietary factors. The evidence basis for treatment with supplements, botanicals, hormonal intervention, and energy therapies will be addressed. We will look at available manual techniques with a focus on massage therapy. We will explore the diagnosis of mind-body pain syndrome and its overlap with chronic headaches. Commonly prescribed oral pain medication often results in intolerable side effects. We will discuss the options for topical application of these same pain medications with a much more favorable side effect profile. Participants will gain an understanding of how different types of providers can work together to provide optimal care to treat this common problem.
doi:10.7453/gahmj.2013.097CP.S28B
PMCID: PMC3875052
6.  Improving quality in population surveys of headache prevalence, burden and cost: key methodological considerations 
Population-based studies of headache disorders are important. They inform needs assessment and underpin service policy for a set of disorders that are a public-health priority. On the one hand, our knowledge of the global burden of headache is incomplete, with major geographical gaps; on the other, methodological differences and variable quality are notable among published studies of headache prevalence, burden and cost.
The purpose here was to start the process of developing standardized and better methodology in these studies. An expert consensus group was assembled to identify the key methodological issues, and areas where studies might fail. Members had competence and practical experience in headache epidemiology or epidemiology in general, and were drawn from all WHO world regions. We reviewed the relevant literature, and supplemented the knowledge gathered from this exercise with experience gained from recent Global Campaign population-based studies, not all yet published. We extracted methodological themes and identified issues within them that were of key importance.
We found wide variations in methodology. The themes within which methodological shortcomings had adverse impact on quality were the following: study design; selection and/or definition of population of interest; sampling and bias avoidance; sample size estimation; access to selected subjects (managing and reporting non-participation); case definition (including diagnosis and timeframe); case ascertainment (including diagnostic validation of questionnaires); burden estimation; reporting (methods and results). These are discussed.
doi:10.1186/1129-2377-14-87
PMCID: PMC4231353  PMID: 24160915
Epidemiology; Burden of headache; Methodology; Global Campaign against Headache
7.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
8.  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
9.  Recurrent and chronic headaches in children below 6 years of age 
The Journal of Headache and Pain  2005;6(3):135-142.
The objective was to determine the frequency of headache subtypes, according to International Headache Society (IHS) criteria, in a population of children below 6 years visiting a Center for Diagnosis and Treatment of Headache in Youth. Medical records of the children below 6 years at their first visit, admitted for headache between 1997 and 2003, were studied. Headache was classified according to the IHS criteria 2004. Children with less than three headache attacks or less than 15 days of daily headache were excluded. We found 1598 medical records of children who visited our Headache Center in the study period. One hundred and five (6.5%) were children younger than 6 years. The mean age at the first medical control was 4.8±1.3 years (range 17–71 months). There were 59 males (56.1%) and 46 females (43.9%). The mean age at onset of headaches was 4.3 years (range 14–69 months). According to the IHS criteria we found 37 cases (35.2%) with migraine, 19 cases (18%) with episodic tension headache, 5 cases (4.8%) with chronic daily headache, 13 cases (12.4%) with primary stabbing headache, 18 cases (17.1%) with post–traumatic headache, 7 cases (6.6%) with other non–dangerous secondary headaches (otorhinolaryngological diseases, post–infectious headaches), 3 cases (2.85%) with dangerous headaches (Arnold–Chiari type 1 malformation, brain tumour) and 9 cases (8.6%) with unclassifiable headaches. Six children (5.7%) reported more than one headache subtype. The prevalence of dangerous headaches was higher than those in school age (χ2=4.70, p<0.05). Our study shows some differences in headaches in this population vs. school children. In fact at this age migraine is the most common headache, but we also found an increase of secondary causes among the chronic/recurrent and daily headaches, especially posttraumatic disorders and potentially dangerous headaches. Finally our study shows the highest prevalence of the idiopathic stabbing headache in pre–school children in comparison with other ages.
doi:10.1007/s10194-005-0168-z
PMCID: PMC3451630  PMID: 16355294
Children; Migraine; Secondary headaches; Stabbing headaches
10.  A Primary Care Migraine Education Program has Benefit on Headache Impact and Quality of Life: Results from the Mercy Migraine Management Program 
Headache  2010;50(4):600-612.
Objective
The objective of this study was to evaluate the effectiveness of the Mercy Migraine Management Program (MMMP), an educational program for physicians and patients. The primary outcome was change in headache days from baseline at 3, 6, and 12 months. Secondary outcomes were changes in migraine-related disability and quality of life, worry about headaches, self-efficacy for managing migraines, ER visits for headache, and satisfaction with headache care.
Background
Despite progress in the understanding of the pathophysiology of migraine and development of effective therapeutic agents, many practitioners and patients continue to lack the knowledge and skills to effectively manage migraine. Educational efforts have been helpful in improving the quality of care and quality of life for migraine sufferers. However, little work has been done to evaluate these changes over a longer period of time. Also, there is a paucity of published research evaluating the influence of education about migraine management on cognitive and emotional factors (e.g., self-efficacy for managing headaches, worry about headaches).
Methods
In this open-label, prospective study, 284 individuals with migraine (92% female, mean age = 41.6) participated in the MMMP, an educational and skills based program. Of the 284 who participated in the program, 228 (80%) provided data about their headache frequency, headache-related disability (as measured by the Headache Impact Test-6 (HIT-6), migraine-specific quality of life (MSQ), worry about headaches, self-efficacy for managing headaches, ER visits for headaches, and satisfaction with care at four time points over 12 months (baseline, 3 months, 6 months, 12 months).
Results
Overall, 46% (106) of subjects reported a 50% or greater reduction in headache frequency. Over 12 months, patients reported fewer headaches and improvement on the HIT-6 and MSQ (all p < .001). The improvement in headache impact and quality of life was greater among those who had more worry about their headaches at baseline. There were also significant improvements in ‘worry about headaches’, ‘self-efficacy for managing headaches’, and ‘satisfaction with headache care’.
Conclusion
The findings demonstrate that patients participating in the MMMP reported improvements in their headache frequency as well as the cognitive and emotional aspects of headache management. This program was especially helpful among those with high amounts of worry about their headaches at the beginning of the program. The findings from this study are impetus for further research that will more clearly, through evaluate the effects of education and skill development not only on headache but also emotional and cognitive influences.
doi:10.1111/j.1526-4610.2010.01618.x
PMCID: PMC2872510  PMID: 20148982
11.  Headaches precipitated by cough, prolonged exercise or sexual activity: a prospective etiological and clinical study 
The Journal of Headache and Pain  2008;9(5):259-266.
Headaches provoked by cough, prolonged physical exercise and sexual activity have not been studied prospectively, clinically and neuroradiologically. Our aim was to delimitate characteristics, etiology, response to treatment and neuroradiological diagnostic protocol of those patients who consult to a general Neurological Department because of provoked headache. Those patients who consulted due to provoked headaches between 1996 and 2006 were interviewed in depth and followed-up for at least 1 year. Neuroradiological protocol included cranio-cervical MRI for all patients with cough headache and dynamic cerebrospinal functional MRI in secondary cough headache cases. In patients with headache provoked by prolonged physical exercise or/and sexual activity cranial neuroimaging (CT and/or MRI) was performed and, in case of suspicion of subarachnoid bleeding, angioMRI and/or lumbar tap were carried out. A total of 6,412 patients consulted due to headache during the 10 years of the study. The number of patients who had consulted due to any of these headaches is 97 (1.5% of all headaches). Diagnostic distribution was as follows: 68 patients (70.1%) consulted due to cough headache, 11 (11.3%) due to exertional headache and 18 (18.6%) due to sexual headache. A total of 28 patients (41.2%) out of 68 were diagnosed of primary cough headache, while the remaining 40 (58.8%) had secondary cough headache, always due to structural lesions in the posterior fossa, which in most cases was a Chiari type I malformation. In seven patients, cough headache was precipitated by treatment with angiotensin-converting enzyme inhibitors. As compared to the primary variety, secondary cough headache began earlier (average 40 vs. 60 years old), was located posteriorly, lasted longer (5 years vs. 11 months), was associated with posterior fossa symptoms/signs and did not respond to indomethacin. All those patients showed difficulties in the cerebrospinal fluid circulation in the foramen magnum region in the dynamic MRI study and preoperative plateau waves, which disappeared after posterior fossa reconstruction. The mean age at onset for primary headaches provoked by physical exercise and sexual activity began at the same age (40 years old), shared clinical characteristics (bilateral, pulsating) and responded to beta-blockers. Contrary to cough headache, secondary cases are rare and the most frequent etiology was subarachnoid bleeding. In conclusion, these conditions account for a low proportion of headache consultations. These data show the total separation between cough headache versus headache due to physical exercise and sexual activity, confirm that these two latter headaches are clinical variants of the same entity and illustrate the clinical differences between the primary and secondary provoked headaches.
doi:10.1007/s10194-008-0063-5
PMCID: PMC3452197  PMID: 18751938
Chiari malformation; Cough headache; Exertional headache; Sexual headache
12.  Other primary headaches 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S66-S71.
The ‘Other Primary Headaches’ include eight recognised benign headache disorders. Primary stabbing headache is a generally benign disorder which often co-exists with other primary headache disorders such as migraine and cluster headache. Primary cough headache is headache precipitated by valsalva; secondary cough has been reported particularly in association with posterior fossa pathology. Primary exertional headache can occur with sudden or gradual onset during, or immediately after, exercise. Similarly headache associated with sexual activity can occur with gradual evolution or sudden onset. Secondary headache is more likely with both exertional and sexual headache of sudden onset. Sudden onset headache, with maximum intensity reached within a minute, is termed thunderclap headache. A benign form of thunderclap headache exists. However, isolated primary and secondary thunderclap headache cannot be clinically differentiated. Therefore all headache of thunderclap onset should be investigated. The primary forms of the aforementioned paroxysmal headaches appear to be Indomethacin sensitive disorders. Hypnic headache is a rare disorder which is termed ‘alarm clock headache’, exclusively waking patients from sleep. The disorder can be Indomethacin responsive, but can also respond to Lithium and caffeine. New daily persistent headache is a rare and often intractable headache which starts one day and persists daily thereafter for at least 3 months. The clinical syndrome more often has migrainous features or is otherwise has a chronic tension-type headache phenotype. Management is that of the clinical syndrome. Hemicrania continua straddles the disorders of migraine and the trigeminal autonomic cephalalgias and is not dealt with in this review.
doi:10.4103/0972-2327.100012
PMCID: PMC3444217  PMID: 23024566
Cough headache; exertional headache; hypnic headache; primary headache disorders; stabbing headache
13.  Predictors of Headache Before, During, and After Pregnancy: A Cohort Study 
Headache  2012;52(3):348-362.
Objective
The present study endeavored to identify predictors of headache during pregnancy, shortly after delivery, and at 8-week follow-up.
Background
Many women suffer from headaches during pregnancy and the postpartum period. However, little is known about factors that predict headache surrounding childbirth.
Methods
Secondary analysis of longitudinal cohort study of 2434 parturients hospitalized for cesarean or vaginal delivery in four university hospitals in the United States and Europe. Data were gathered from interviews and review of medical records shortly after delivery; 972 of the women were contacted 8 weeks later to assess persistent headache. The primary outcome measures were experiencing headache during pregnancy, headache within 72 hours after delivery, and headache at 8 weeks after delivery.
Results
Of the parturients, 10% experienced headache during pregnancy, 3.7% within 72 hours after delivery, and 3.6% at 8 weeks post delivery. Compared to those without a history of headache, a history of headache prior to pregnancy was the strongest predictor of headache during pregnancy (9.8% versus 23.5%; RR 2.4; 95% CI: 1.4 to 4.0). Experiencing headache during pregnancy (adjusted HR 3.8; 95% CI: 2.4 to 6.2) and receiving needle-based regional anesthesia for pain treatment (adjusted HR 2.2; 95% CI: 1.1 to 4.5) were independently associated with headache within 72 hours after delivery with event rates of 11.1% and 10.5%, respectively. Compared to those without such a history, headache before pregnancy was significantly associated with experiencing headache 8 weeks after delivery (4.0% versus 23.8%; RR = 6.0; 95% CI: 2.0 to 8.0), but headache during pregnancy or shortly after delivery was not. Several other psychosocial predictors (e.g., somatization, smoking before pregnancy) were statistically associated with at least one headache outcome.
Conclusions
A history of headache prior to pregnancy is a strong predictor of headache during and after pregnancy, the latter independent of but compounded by spinal injection. Physicians should attend to prior headache history when making decisions about pain management during and after childbirth. As the lack of formal ICHD-II headache diagnoses is a limitation of this study, future longitudinal studies should replicate the present design while including headache subtyping consistent with ICHD-II nosology.
doi:10.1111/j.1526-4610.2011.02066.x
PMCID: PMC3299832  PMID: 22268840
Pregnancy; migraine; spinal anesthesia
14.  Frovatriptan vs. transdermal oestrogens or naproxen sodium for the prophylaxis of menstrual migraine 
The Journal of Headache and Pain  2007;8(5):283-288.
Acute treatment of menstrual migraine (MM) attacks is often incomplete and unsatisfactory, and perimenstrual prophylaxis with triptans, oestrogen supplementation or naproxen sodium may be needed for decreasing frequency and severity of the attack. In this pilot, open-label, non-randomised, parallel group study we evaluated, in 38 women with a history of MM, the efficacy of frovatriptan (n=14) 2.5 mg per os or transdermal oestrogens (n=10) 25 μg or naproxen sodium (n=14) 500 mg per os once-daily for the short-term prevention of MM. All treatments were administered in the morning for 6 days, beginning 2 days before the expected onset of menstrual headache. All women were asked to fill in a diary card, in the absence of (baseline) and under treatment, in order to score headache severity. All women reported at least one episode of MM at baseline. During treatment all patients taking transdermal oestrogens or naproxen sodium and 13 out of the 14 patients (93%) taking frovatriptan had at least one migraine attack (p=0.424). Daily incidence of migraine was significantly (p=0.045) lower under frovatriptan than under transdermal oestrogens or NS. At baseline, the overall median score of headache severity was 4.6, 4.2 and 4.3 in the group subsequently treated with frovatriptan, transdermal oestrogens and naproxen sodium, respectively (p=0.819). During treatment the median score was significantly lower under frovatriptan (2.5) than under transdermal oestrogens (3.0) and naproxen sodium (3.9, p=0.049). This was evident also for each single day of observation (p=0.016). Among treatments differences were particularly evident for the subgroup of patients with true MM (n=22) and for frovatriptan vs. naproxen sodium. This study suggests that short-term prophylaxis of MM with frovatriptan may be more effective than that based on transdermal oestrogens or naproxen sodium.
doi:10.1007/s10194-007-0417-4
PMCID: PMC3476156  PMID: 17955167
Frovatriptan; Menstrual migraine; Transdermal oestrogens; Naproxen sodium; True menstrual migraine; Menstrually related migraine
15.  13C. The Effectiveness of Dietary Supplements for Pain Management 
Focus Areas: Integrative Approaches to Care, Alleviating Pain
Pain is often the most common medical condition for which patients choose complementary and alternative medicine (CAM), with dietary supplements representing the most common self-directed CAM treatment choice. However, with numerous dietary supplement choices on the market it often can be difficult for patients and clinicians to identify those with proven effectiveness for pain. This presentation will initially examine pain scenarios for which dietary supplements are commonly used (headache, joint pain, low back pain, and abdominal pain).
Subsequently, the presentation will examine the rationale for dietary supplements including the purported mechanism(s) of action and indirect benefit on pain sequelea such as depression and fatigue. Finally, the presentation will provide the rationale for use and overview of currently available dietary supplement formulations that have demonstrated clinical effectiveness in various pain states. At the conclusion of this session, clinicians should gain great understanding of the importance of clinically tested dietary supplement formulations as well as counseling strategies for guiding patients toward evidence-based choices to optimize pain care.
doi:10.7453/gahmj.2013.097CP.S13C
PMCID: PMC3875034
16.  Vitamin D3 Supplementation and Upper Respiratory Tract Infections in a Randomized, Controlled Trial 
In a trial substudy of 1000 IU vitamin D3 supplementation, 759 participants completed daily health diaries for up to 17 months. Supplementation provided no significant reduction in upper respiratory tract infections, colds, or influenza-like illness during winter or overall.
Background. Randomized controlled trials testing the association between vitamin D status and upper respiratory tract infection (URTI) have given mixed results. During a multicenter, randomized controlled trial of colorectal adenoma chemoprevention, we tested whether 1000 IU/day vitamin D3 supplementation reduced winter episodes and duration of URTI and its composite syndromes, influenza-like illness (ILI; fever and ≥2 of sore throat, cough, muscle ache, or headache) and colds (no fever, and ≥2 of runny nose, nasal congestion, sneezing, sore throat, cough, swollen or tender neck glands).
Methods. The 2259 trial participants were aged 45–75, in good health, had a history of colorectal adenoma, and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were randomized to vitamin D3 (1000 IU/day), calcium (1200 mg/day), both, or placebo. Of these, 759 participants completed daily symptom diaries. Secondary data included semiannual surveys of all participants.
Results. Among those who completed symptom diaries, supplementation did not significantly reduce winter episodes of URTI (rate ratio [RR], 0.93; 95% confidence interval [CI], .79–1.09) including colds (RR, 0.93; 95% CI, .78–1.10) or ILI (RR, 0.95; 95% CI, .62–1.46), nor did it reduce winter days of illness (RR, 1.13; 95% CI, .90–1.43). There was no significant benefit according to adherence, influenza vaccination, body mass index, or baseline vitamin D status. Semiannual surveys of all participants (N = 2228) identified no benefit of supplementation on ILI (odds ratio [OR], 1.14; 95% CI, .84–1.54) or colds (OR, 1.03; 95% CI, .87–1.23).
Conclusions. Supplementation with 1000 IU/day vitamin D3 did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12 ng/mL.
doi:10.1093/cid/cit549
PMCID: PMC3805175  PMID: 24014734
upper respiratory tract infection; vitamin D; randomized controlled trial
17.  The Effect of Acclydine in Chronic Fatigue Syndrome: A Randomized Controlled Trial 
PLoS Clinical Trials  2007;2(5):e19.
Objectives:
It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio).
Design:
A randomized, placebo-controlled, double-blind clinical trial.
Setting:
Radboud University Nijmegen Medical Centre, The Netherlands.
Participants:
Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals.
Intervention:
Acclydine or placebo for 14 wk.
Outcome measures:
Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis.
Results:
There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI −4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI −201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio −0.5 (95% CI −2.8 to +1.7, p = 0.63).
Conclusion:
We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS.
Editorial Commentary
Background: Chronic fatigue syndrome is a complicated and poorly understood illness. People with the condition experience tiredness that carries on for a long period of time and does not get better with rest. Other symptoms include sleeping problems, muscle and joint pains, concentration difficulties, and headaches. The causes of chronic fatigue syndrome are not known. There is evidence for the effectiveness of certain behavioral interventions, such as exercise therapy and cognitive behavioral therapy, in improving certain symptoms. However, some doctors are concerned that a food supplement called Acclydine, derived from a plant called Solanum dulcamara, is being used and promoted as a treatment for chronic fatigue syndrome when there is little evidence about the efficacy or safety of this supplement.
The researchers here carried out a randomized trial in The Netherlands, recruiting adult patients who met the internationally accepted criteria for chronic fatigue syndrome. The participants were allocated by chance to receive either 14 weeks of treatment with Acclydine together with amino acid supplements or, alternatively, placebo versions of the Acclydine and amino acid tablets. The researchers then measured participants' responses with respect to two primary outcome measures. One of these was how tired participants felt, which was measured using a subscale on a questionnaire called the Checklist Individual Strength scale (CIS-fatigue). The other primary outcome measure was “functional impairment,” which examines how well someone carries out their daily life, using the Sickness Impact Profile (SIP-8) scale. The secondary outcome measures included physical activity levels, day-to-day fatigue levels, and the levels of insulin-like growth factor 1 (IGF1) in blood, a hormone that's thought by some researchers to be related to the severity of chronic fatigue.
What the trial shows: In the trial, 57 people were randomized to receive either Acclydine plus amino acid supplements, or placebo tablets. When comparing scores on the primary outcome measures at the end of the trial, the researchers did not see significant differences between the treatment and placebo groups. Similarly, the results for secondary outcome measures in this trial did not show any significant differences between the treatment and placebo groups.
Strengths and limitations: Strengths of this study include the fact that it is one of the few properly designed studies of a product for which claims have been made of effectiveness in chronic fatigue syndrome. The study was designed as a double-blind trial, in which participants and investigators (those collecting the outcome data) did not know whether an individual received Acclydine or placebo. This procedure should help to minimize bias in assessing outcomes. A key limitation of this study is the relatively small number of participants. However, the investigators considered it unlikely that a larger trial would detect a clinically meaningful effect of Acclydine on these outcome measures for patients with chronic fatigue syndrome.
Contribution to the evidence: Systematic reviews of interventions for the treatment of chronic fatigue syndrome have found evidence for the efficacy of exercise therapy and cognitive behavioral therapy. This trial shows no evidence of efficacy of Acclydine plus amino acid supplements for the treatment of chronic fatigue.
doi:10.1371/journal.pctr.0020019
PMCID: PMC1876596  PMID: 17525791
18.  Overview of diagnosis and management of paediatric headache. Part I: diagnosis 
Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life.
doi:10.1007/s10194-011-0297-5
PMCID: PMC3056001  PMID: 21359874
Headache; Childhood; Paediatric headaches; Diagnosis; Epidemiology; Defining features
19.  Overview of diagnosis and management of paediatric headache. Part I: diagnosis 
Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life.
doi:10.1007/s10194-011-0297-5
PMCID: PMC3056001  PMID: 21359874
Headache; Childhood; Paediatric headaches; Diagnosis; Epidemiology; Defining features
20.  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
21.  Sport and exercise headache: Part 2. Diagnosis and classification. 
A group of 129 subjects (67 men and 62 women) experiencing sports headache was established using a questionnaire. A wide range of information was gathered, focusing on the mode of onset, time course, characteristic features and associated symptoms of sports-related headache. Criteria for the varieties of sports headaches were established using head trauma and then migraine to divide subgroups of sports headaches. Cases were classified into four categories: effort migraine, trauma-triggered migraine, effort-exertion headache, and post-traumatic headache. The percentages of each sports-related headache found were: effort migraine 9%, trauma-triggered migraine 6%, effort-exertion headache 60%, post-traumatic headache 22% and miscellaneous 3%. Sports migraine accounted for 15% of the total sports headache sample. Effort-exertion headache was the most common type of sports headache. Although effort-exertion headache could be separated into subjects who had an acute severe headache induced by anaerobic exercise (exertion headache) from those having a substantial headache lasting hours initiated by aerobic exercise (effort headache), most subjects with effort-exertion headache in this study appeared not to fall into any discrete subgroups. Trauma-related headaches were experienced mainly by men in contact sports, while women more commonly had non-trauma-related headache in running and jogging.
PMCID: PMC1332039  PMID: 7921916
22.  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
23.  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
24.  Course of adolescent headache: 4-year annual face-to-face follow-up study 
The Journal of Headache and Pain  2010;11(4):327-334.
The objective of this study is to investigate the course of the diagnosis and characteristics of headache in 12- to 17-year-old adolescents during a follow-up period of 4 years. Headache prevalence and characteristics, and even the type of headache show important changes during adolescence. The course of adolescent headache might reveal important insight into the pathophysiology of headache. Subjects who received a single headache diagnosis were invited to participate in a follow-up study consisting of annual face-to-face evaluation of the subjects for 4 years. Subjects who had only one type of headache and who agreed to participate were included in the study. Each subject had four annual semi-structured interviews with a neurology resident. The International Classification of Headache Disorders second edition was used for case definitions. A total of 87 subjects completed the study: 64 girls (73.56%) and 23 boys (26.44%) (p = 0.016). The headache type included migraine in 50 adolescents (57.47%), tension type headache in 24 (27.59%), secondary headache in 5 (5.7%), and non-classifiable headache in 8 (9.2%). Headache has not remitted in any of the subjects. Headache diagnosis has changed in eighteen (20.69%) subjects at least once during the follow-up period. There was transformation of headache type in 4 of 50 with migraine (8%), 10 of 24 with tension-type headache (TTH) (41.7%), and 4 of 13 with other headaches (30.8%). In conclusion, transition of headache types from one type to another (more than once in some adolescents) and variability of diagnosis throughout the years strongly support the continuum theory of headaches.
doi:10.1007/s10194-010-0228-x
PMCID: PMC3476353  PMID: 20526648
Adolescent; Headache; Migraine; Tension-type headache; Course; Transformation
25.  Cluster headache associated with acute maxillary sinusitis 
SpringerPlus  2013;2:509.
Background
Cluster headache is a primary headache by definition not caused by any known underlying structural pathology. However, symptomatic cases have been described, for example tumours, particularly pituitary adenomas, malformations, and infections/inflammations. The evaluation of cluster headache is an issue unresolved.
Case description
I present a case of a 24-year-old patient who presented with a 4-week history of side-locked attacks of pain located in the left orbit. He satisfied the revised International Classification of Headache Disorders criteria for cluster headache. His medical and family histories were unremarkable. There was no history of headache. A diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Low-dose computer tomography scan after 2 weeks displayed a left-sided acute maxillary sinusitis. The headache attacks resolved completely after treatment with antibiotics and sinus puncture.
Discussion and evaluation
Although I cannot exclude an unintentional comorbidity, in my opinion, the co-occurrence of an acute maxillary sinusitis with unilateral headache, in a hitherto headache-free man, points toward the fact that in this case the cluster headache was caused or triggered by the sinusitis. The headache attacks resolved completely after the treatment and the patient also remained headache free at the follow-up. The response of the headache to sumatriptan and other typical cluster headache medications does not exclude a secondary form. Symptomatic cluster headaches responsive to this therapy have been described. Associated cranial lesions such as infections have been reported in cluster headache patients and the attacks may be clinically indistinguishable from the primary form.
Conclusions
Neuroimaging, preferably contrast-enhanced magnetic resonance imaging including sinuses should always be considered in patients with cluster headache despite normal neurological examination. Acute maxillary sinusitis can present as cluster headache.
doi:10.1186/2193-1801-2-509
PMCID: PMC3795873  PMID: 24133652
Cluster headache; Acute maxillary sinusitis; Secondary; Symptomatic; Infection

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