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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.  How do patients referred to neurologists for headache differ from those managed in primary care? 
Background
Headache is the neurological symptom most frequently presented to GPs and referred to neurologists, but little is known about how referred patients differ from patients managed by GPs.
Aim
To describe and compare headache patients managed in primary care with those referred to neurologists.
Design of study
Prospective study.
Setting
Eighteen general practices in south-east England.
Method
This study examined 488 eligible patients consulting GPs with primary headache over 7 weeks and 81 patients referred to neurologists over 1 year. Headache disability was measured by the Migraine Disability Assessment Score, headache impact by the Headache Impact Test, emotional distress by the Hospital Anxiety and Depression Scale and illness perception was assessed using the Illness Perception Questionnaire.
Results
Participants were 303 patients who agreed to participate. Both groups reported severe disability and very severe impact on functioning. Referred patients consulted more frequently than those not referred in the 3 months before referral (P = 0.003). There was no significant difference between GP-managed and referred groups in mean headache disability, impact, anxiety, depression, or satisfaction with care. The referred group were more likely to link an increased number of symptoms to their headaches (P = 0.01), to have stronger emotional representations of their headaches (P = 0.006), to worry more (P = 0.001), and were made anxious by their headache symptoms (P = 0.044).
Conclusion
Patients who consult for headache experience severe disability and impact, and up to a third report anxiety and/or depression. Referral is not related to clinical severity of headaches, but is associated with higher consultation frequency and patients' anxiety and concern about their headache symptoms.
PMCID: PMC2047014  PMID: 17504590
headache; migraine disorders; neurology; primary health care; referral and consultation
3.  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
4.  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
5.  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
6.  Psychological Risk Factors in Headache 
Headache  2007;47(3):413-426.
Headache is a chronic disease that occurs with varying frequency and results in varying levels of disability. To date, the majority of research and clinical focus has been on the role of biological factors in headache and headache-related disability. However, reliance on a purely biomedical model of headache does not account for all aspects of headache and associated disability. Using a biopsychosocial framework, the current manuscript expands the view of what factors influence headache by considering the role psychological (i.e., cognitive and affective) factors have in the development, course, and consequences of headache. The manuscript initially reviews evidence showing that neural circuits responsible for cognitive–affective phenomena are highly interconnected with the circuitry responsible for headache pain. The manuscript then reviews the influence cognitions (locus of control and self-efficacy) and negative affect (depression, anxiety, and anger) have on the development of headache attacks, perception of headache pain, adherence to prescribed treatment, headache treatment outcome, and headache-related disability. The manuscript concludes with a discussion of the clinical implications of considering psychological factors when treating headache.
doi:10.1111/j.1526-4610.2006.00716.x
PMCID: PMC2408884  PMID: 17371358
headache; self-efficacy; locus of control; biopsychosocial; psychological; negative affect
7.  Symptomatic cluster headache: a review of 63 cases 
SpringerPlus  2014;3:64.
Cluster headache is a primary headache by definition not caused by any known underlying structural pathology. Symptomatic cases have been described, for example tumours, dissections and infections, but a causal relationship between the underlying lesion and the headache is difficult to determine in many cases. The proper diagnostic evaluation of cluster headache is an issue unresolved. The literature has been reviewed for symptomatic cluster headache or cluster headache-like cases in which causality was likely. The review also attempted to identify clinical predictors of underlying lesions in order to formulate guidelines for neuroimaging. Sixty-three cluster headache or "cluster headache-like"/"cluster-like headache" cases in the literature were identified which were associated with an underlying lesion. A majority of the cases had a non-typical presentation that is atypical symptomatology and abnormal examination (including Horner’s syndrome). A striking finding in this appraisal was that a significant proportion of CH cases were secondary to diseases of the pituitary gland or pituitary region. Another notable finding was that a proportion of cluster headache cases were associated with arterial dissection. Even typical cluster headaches can be caused by structural lesions and the response to typical cluster headache treatments does not exclude a secondary form. It is difficult to draw definitive conclusions from this retrospective review of case reports especially considering the size of the material. However, based on this review, I suggest that neuroimaging, preferably contrast-enhanced magnetic resonance imaging/magnetic resonance angiography should be undertaken in patients with atypical symptomatology, late onset, abnormal examination (including Horner’s syndrome), or those resistant to the appropriate medical treatment. The decision to perform magnetic resonance imaging in cases of typical cluster headache remains a matter of medical art.
doi:10.1186/2193-1801-3-64
PMCID: PMC3928394  PMID: 24570848
Cluster headache; Neuroimaging; Secondary; Symptomatic; Magnetic resonance imaging; Differential diagnosis
8.  Cluster headache and arachnoid cyst 
SpringerPlus  2013;2:4.
Background
Cluster headache is a primary headache by definition not caused by any known underlying structural pathology. However, symptomatic cases have been described, e.g. tumours, particularly pituitary adenomas, malformations, and infections/inflammations. The evaluation of cluster headache is an issue unresolved.
Case description
We present a case of a 43-year-old patient who presented with a 2-month history of side-locked attacks of pain located in the left orbit. He satisfied the revised International Classification of Headache Disorders criteria for cluster headache. His medical and family histories were unremarkable. There was no history of headache. A diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Computer tomography and enhanced magnetic resonance imaging after 1 month displayed a supra- and intrasellar arachnoid cyst with mass effect on adjacent structures. After operation, the headache attacks resolved completely.
Discussion and evaluation
Although we cannot exclude an unintentional comorbidity, in our opinion, the co-occurrence of an arachnoid cyst with mass effect with unilateral headache, in a hitherto headache-free man, points toward the fact that in this case the CH was caused or triggered by the AC. The headache attacks resolved completely after the operation and the patient also remained headache free at the follow-up. The response of the headache to sumatriptan and other typical CH medications does not exclude a secondary form. Symptomatic CHs responsive to this therapy have been described. Associated cranial lesions such as tumours have been reported in CH patients and the attacks may be clinically indistinguishable from the primary form.
Conclusions
Neuroimaging, preferably contrast-enhanced magnetic resonance imaging should always be considered in patients with cluster headache despite normal neurological examination. Late-onset cluster headache represents a condition that requires careful evaluation. Supra- and intrasellar arachnoid cyst can present as cluster headache.
doi:10.1186/2193-1801-2-4
PMCID: PMC3568463  PMID: 23419954
Cluster headache; Arachnoid cyst; Neuroimaging; Secondary; Symptomatic; Magnetic resonance imaging; Computer tomography
9.  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
10.  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
11.  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
12.  Spinal Cord Stimulation for Neuropathic Pain 
Executive Summary
Objective
The objective of this health technology policy assessment was to determine the effectiveness of spinal cord stimulation (SCS) to manage chronic intractable neuropathic pain and to evaluate the adverse events and Ontario-specific economic profile of this technology.
Clinical Need
SCS is a reversible pain therapy that uses low-voltage electrical pulses to manage chronic, intractable neuropathic pain of the trunk or limbs. Neuropathic pain begins or is caused by damage or dysfunction to the nervous system and can be difficult to manage.
The prevalence of neuropathic pain has been estimated at about 1.5% of the population in the United States and 1% of the population in the United Kingdom. These prevalence rates are generalizable to Canada.
Neuropathic pain is extremely difficult to manage. People with symptoms that persist for at least 6 months or who have symptoms that last longer than expected for tissue healing or resolution of an underlying disease are considered to have chronic pain. Chronic pain is an emotional, social, and economic burden for those living with it. Depression, reduced quality of life (QOL), absenteeism from work, and a lower household income are positively correlated with chronic pain.
Although the actual number is unknown, a proportion of people with chronic neuropathic pain fail to obtain pain relief from pharmacological therapies despite adequate and reasonable efforts to use them. These people are said to have intractable neuropathic pain, and they are the target population for SCS.
The most common indication for SCS in North America is chronic intractable neuropathic pain due to failed back surgery syndrome (FBSS), a term that describes persistent leg or back and leg pain in patients who have had back or spine surgery. Neuropathic pain due to complex regional pain syndrome (CRPS), which can develop in the distal aspect of a limb a minor injury, is another common indication. To a lesser extent, chronic intractable pain of postherpetic neuralgia, which is a persistent burning pain and hyperesthesia along the distribution of a cutaneous nerve after an attack of herpes zoster, is also managed with SCS.
For each condition, SCS is considered as a pain management therapy only after conventional pain therapies, including pharmacological, nonpharmacological, and surgical treatments, if applicable, have been attempted and have failed.
The Technology
The SCS technology consists of 3 implantable components: a pulse generator, an extension cable, and a lead (a small wire). The pulse generator is the power source for the spinal cord stimulator. It generates low-voltage electrical pulses. The extension cable connects the pulse generator to the lead. The lead is a small, insulated wire that has a set of electrodes at one end. The lead is placed into the epidural space on the posterior aspect of the spinal cord, and the electrodes are positioned at the level of the nerve roots innervating the painful area. An electrical current from the electrodes induces a paresthesia, or a tingling sensation that masks the pain.
Before SCS is initiated, candidates must have psychological testing to rule out major psychological illness, drug habituation, and issues of secondary gain that can negatively influence the success of the therapy. Successful candidates will have a SCS test stimulation period (trial period) to assess their responsiveness to SCS. The test stimulation takes about 1 week to complete, and candidates who obtain at least 50% pain relief during this period are deemed suitable to receive a permanent implantation of a spinal cord stimulator
Review Strategy
The Medical Advisory Secretariat (MAS) reviewed all published health technology assessments of spinal cord stimulation. Following this, a literature search was conducted from 2000 to January, 2005 and a systematic review of the literature was completed. The primary outcome for the systematic review was pain relief. Secondary outcomes included functional status and quality of life. After applying the predetermined inclusion and exclusion criteria, 2 randomized controlled trials (MAS level 2 evidence), and 2 prospective non-randomized controlled trials with a before-and-after-treatment study design (MAS level 3a evidence) were retrieved and reviewed.
Summary of Findings
The authors of 6 health technology assessments concluded that evidence exists to support the effectiveness of SCS to decrease pain in various neuropathic pain syndromes. However, the quality of this evidence varied among reports from weak to moderate.
The systematic review completed by MAS found high quality level 2 evidence that SCS decreases pain and level 3a evidence that it improves functional status and quality of life in some people with neuropathic pain conditions. The rate of technical failures was approximately 11%, which included electrode lead migration and/or malposition. Procedural complications included infection and dural puncture; each occurred at a rate of 1.2%.
Conclusions
SCS may be considered for patients with chronic, neuropathic pain for whom standard pain treatments have failed and when there is no indication for surgical intervention to treat the underlying condition.
PMCID: PMC3382299  PMID: 23074473
13.  Headache as the sole presentation of cerebral venous thrombosis: a prospective study 
The Journal of Headache and Pain  2012;13(6):487-490.
Headache is the most frequent presenting symptom of cerebral venous thrombosis (CVT), most commonly associated with other manifestations. It has been described as its only clinical presentation in 15 % of patients. There is no typical pattern of headache in CVT. The objective of this study was to study the characteristics of headache as the sole manifestation of CVT. From a prospective study of 30 consecutive patients diagnosed with CVT over 18 months, we selected those who presented with headache only: they had a normal neurological examination, no papilloedema and no blood or any parenchymal lesion on CT scan. All were submitted to a systematic etiological workup and a structured questionnaire about the characteristics of headache was provided. Headache was the sole manifestation of CVT in 12 patients; it was diffuse or bilateral in the majority. Seven patients referred worsening with sleep/lying down, Valsalva maneuvers or straining. There was no association between the characteristics of headache and extension of CVT. Time from onset to diagnosis was significantly delayed in these patients presenting only with headache. In our series, 40 % of patients presented only with headache. There was no uniform pattern of headache apart from being bilateral. There was a significant delay of diagnosis in these patients. Some characteristics of headache should raise the suspicion of CVT: recent persistent headache, thunderclap headache or pain worsening with straining, sleep/lying down or Valsalva maneuvers even in the absence of papilloedema or focal signs.
doi:10.1007/s10194-012-0456-3
PMCID: PMC3464467  PMID: 22592865
Headache; Sinus thrombosis; Lateral sinus; Cerebral veins
14.  Headaches of otolaryngological interest: current status while awaiting revision of classification. Practical considerations and expectations 
SUMMARY
In 1988, diagnostic criteria for headaches were drawn up by the International Headache Society (IHS) and is divided into headaches, cranial neuralgias and facial pain. The 2nd edition of the International Classification of Headache Disorders (ICHD) was produced in 2004, and still provides a dynamic and useful instrument for clinical practice. We have examined the current IHC, which comprises 14 groups. The first four cover primary headaches, with "benign paroxysmal vertigo of childhood" being the forms of migraine of interest to otolaryngologists; groups 5 to 12 classify "secondary headaches"; group 11 is formed of "headache or facial pain attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cranial structures"; group 13, consisting of "cranial neuralgias and central causes of facial pain" is also of relevance to otolaryngology. Neither the current classification system nor the original one has a satisfactory collocation for migraineassociated vertigo. Another critical point of the classification concerns cranio-facial pain syndromes such as Sluder's neuralgia, previously included in the 1988 classification among cluster headaches, and now included in the section on "cranial neuralgias and central causes of facial pain", even though Sluder's neuralgia has not been adequately validated. As we have highlighted in our studies, there are considerable similarities between Sluder's syndrome and cluster headaches. The main features distinguishing the two are the trend to cluster over time, found only in cluster headaches, and the distribution of pain, with greater nasal manifestations in the case of Sluder's syndrome. We believe that it is better and clearer, particularly on the basis of our clinical experience and published studies, to include this nosological entity, which is clearly distinct from an otolaryngological point of view, as a variant of cluster headache. We agree with experts in the field of headaches, such as Olesen and Nappi who contributed to previous classifications, on the need for a revised classification, particularly with regards to secondary headaches. According to the current Committee on headaches, the updated version of the classification, presently under study, is due to be published soon; it is our hope that this revised version will take into account some of the above considerations.
PMCID: PMC3383075  PMID: 22767967
Headache;  Migraine;  Facial pain;  Cranial neuralgias ;  International Headache Classification;  Sluder's neuralgia;  Charlin's neuralgia;  Vestibular migraine;  ENT
15.  Cluster headache associated with a clinically non-functioning pituitary adenoma: a case report 
Introduction
Cluster headache belongs to a group of primary headache entities: the trigeminal autonomic cephalalgias. Cluster headache is the most common variant. The headache is usually severe and it is also associated with autonomic symptoms. Secondary causes of cluster headache have been reported, such as intracranial artery aneurysms and tumors. The question of when to carry out neuroimaging in patients with cluster headache is yet unsettled. To the best of the author's knowledge, cluster headache associated with a clinically non-functioning pituitary adenoma (chromophobe adenoma) has not been described. This case report describes the case of a man with cluster headache where the evaluation showed a clinically non-functioning pituitary adenoma.
Case presentation
This case involved a 49-year-old Caucasian man who presented with a one-month history of side-locked attacks of pain located in the right orbit. His symptoms fulfilled the criteria for cluster headache and a diagnosis of cluster headache was made. The patient responded to symptomatic treatment. Enhanced magnetic resonance imaging showed a pituitary adenoma. Further evaluations including hormonal screening revealed a clinically non-functioning pituitary adenoma (chromophobe adenoma). After surgery to remove the tumor, his headache attacks resolved totally.
Conclusion
Tumors have been reported in patients with cluster headache whose clinical attacks are identical to genuine cluster headache. A clinically non-functioning pituitary adenoma can present as cluster headache. This case emphasizes the need of imaging procedures in patients with cluster headache. Contrast-enhanced magnetic resonance imaging including the sella turcica should always be done in patients with cluster headache.
doi:10.1186/1752-1947-8-451
PMCID: PMC4307905  PMID: 25526868
Cluster headache; Neuroimaging; Pituitary adenoma; Secondary; Symptomatic
16.  Headache associated with moyamoya disease: a case story and literature review 
Headache associated with moyamoya disease (HAMD) is common in moyamoya disease. However, the characteristics and classification of HAMD are largely unknown. We present a case of a 39-year-old woman with HAMD. To characterize and classify the features of this syndrome, the patient was asked to complete a 4-month diagnostic headache diary. There was a total of 15 ictal days. All episodes were without aura. The headache was more commonly pressing (10/15), mild to moderate in severity (14/15), unchanged by physical activity (11/15), and associated with photophobia (10/15). The International Headache Society Classification was utilized to determine that eight episodes met criteria for probable migraine without aura, while seven episodes met criteria for probable frequent episodic tension-type headache. We identified four other case reports of HAMD with partial descriptions of the characteristics. When combined with our patient, the median age was 34 years old (range 6–49, SD 16). Four were female, while the patient with cluster headache was male. The median time from headache onset to diagnosis with moyamoya disease was 9.5 months (range 0–192, SD 88.0). Headaches were described as migraine with aura in two of five cases, hemiplegic migraine in one of five, and cluster headache in one of five. The highest intensity was described as severe in three of three cases, in which headache intensity was reported. Meanwhile, nausea, vomiting, and photophobia were present in two of three cases, where these features were reported, while nausea without vomiting was seen in one of three cases. In all five cases, patients had other neurological symptoms, such as paresis, seizures, visual disturbances, dysarthria, allodynia, ptosis, and unilateral restless leg syndrome. In conclusion, HAMD can present as migraine without aura. It can be the first presenting symptom of moyamoya disease. The headache features are not diagnostic; hence, early neurovascular imaging should be considered in patients with new onset, refractory migraine-like headache, especially in the setting of other neurological symptoms to exclude underlying moyamoya disease. Further reports using headache diaries are needed to better characterize HAMD as well as to determine whether headache with tension-type features is also part of this condition.
doi:10.1007/s10194-009-0181-8
PMCID: PMC3452187  PMID: 20012551
Moyamoya; Headache; Migraine; Cluster; Diagnosis
17.  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
18.  Placebo and other psychological interactions in headache treatment 
The Journal of Headache and Pain  2012;13(3):191-198.
We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth century. Controversies about its effect came from an excessive interpretation due to methodological bias, inadequate consideration of the variation of the measure (regression to the mean) and of the natural course of the disease. Several powerful studies on placebo effect showed that the nature of the treatment, the associated announce, the patients’ expectancy, and the repetition of the procedures are of paramount importance. The placebo expectancy is associated with an activation of pre-frontal, anterior cingular, accumbens, and periacqueducal grey opioidergic neurons possibly triggered by the dopaminergic meso-limbic system. In randomized control trials, several arms design could theoretically give information concerning the respective part of the different component of the outcome and control the natural course of the disease. However, for migraine and tension type headache attacks treatment, no three arm (verum, placebo, and natural course) trial is available in the literature. Indirect evidence of a placebo effect in migraine attack treatment, comes from the high amplitude of the improvement observed in the placebo arms (28% of the patients). This figure is lower (6%) when using the harder criterium of pain free at 2 h. But these data disregard the effect of the natural course. For prophylactic treatment with oral medication, the trials performed in the last decades report an improvement in 21% of the patients in the placebo arms. However, in these studies the duration of administration was limited, the control of attacks uncertain as well as the evolution of the co-morbid psycho-pathology. Considering the reviews and meta-analysis of complex prophylactic procedures, it must be concluded that their effect is mostly linked to a placebo and non-specific psychological effects. Acupuncture may have a slight specific effect on tension type headache, but not on migraine. Manual therapy studies do not exhibit difference between manipulation, mobilization, and controls; touch has no proven specific effect. A comprehensive efficacy review of biofeedback studies concludes to a small specific effect on tension type headache but not on migraine. A review of behavioral treatment conclude to an interesting mean improvement but did not demonstrated a specific effect with the exception of a four arm study including a pseudo meditation control group. Expectation-linked placebo, conditioning, and non-specific psychological effects vary according clinical situations and psychological context; likely low in RCT, high after anempathic medical contact, and at its maximum with a desired charismatic healer. The announcements of doctors strongly influence the beliefs of patients, and in consequence their pain and anxiety sensibilities; this modulates the amplitude of the placebo and the non-specific psychological effects and is therefore a major determinant of the therapeutic success. Furthermore, any repetitive contact, even through a placebo, may interfere positively with the psychopathological co-morbidity. One has to keep in mind that the non-specific psychological interactions play a major role in the improvement of the majority of the headache sufferers.
doi:10.1007/s10194-012-0422-0
PMCID: PMC3311834  PMID: 22367630
Migraine; Placebo; Headache treatment
19.  Placebo and other psychological interactions in headache treatment 
The Journal of Headache and Pain  2012;13(3):191-198.
We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth century. Controversies about its effect came from an excessive interpretation due to methodological bias, inadequate consideration of the variation of the measure (regression to the mean) and of the natural course of the disease. Several powerful studies on placebo effect showed that the nature of the treatment, the associated announce, the patients’ expectancy, and the repetition of the procedures are of paramount importance. The placebo expectancy is associated with an activation of pre-frontal, anterior cingular, accumbens, and periacqueducal grey opioidergic neurons possibly triggered by the dopaminergic meso-limbic system. In randomized control trials, several arms design could theoretically give information concerning the respective part of the different component of the outcome and control the natural course of the disease. However, for migraine and tension type headache attacks treatment, no three arm (verum, placebo, and natural course) trial is available in the literature. Indirect evidence of a placebo effect in migraine attack treatment, comes from the high amplitude of the improvement observed in the placebo arms (28% of the patients). This figure is lower (6%) when using the harder criterium of pain free at 2 h. But these data disregard the effect of the natural course. For prophylactic treatment with oral medication, the trials performed in the last decades report an improvement in 21% of the patients in the placebo arms. However, in these studies the duration of administration was limited, the control of attacks uncertain as well as the evolution of the co-morbid psycho-pathology. Considering the reviews and meta-analysis of complex prophylactic procedures, it must be concluded that their effect is mostly linked to a placebo and non-specific psychological effects. Acupuncture may have a slight specific effect on tension type headache, but not on migraine. Manual therapy studies do not exhibit difference between manipulation, mobilization, and controls; touch has no proven specific effect. A comprehensive efficacy review of biofeedback studies concludes to a small specific effect on tension type headache but not on migraine. A review of behavioral treatment conclude to an interesting mean improvement but did not demonstrated a specific effect with the exception of a four arm study including a pseudo meditation control group. Expectation-linked placebo, conditioning, and non-specific psychological effects vary according clinical situations and psychological context; likely low in RCT, high after anempathic medical contact, and at its maximum with a desired charismatic healer. The announcements of doctors strongly influence the beliefs of patients, and in consequence their pain and anxiety sensibilities; this modulates the amplitude of the placebo and the non-specific psychological effects and is therefore a major determinant of the therapeutic success. Furthermore, any repetitive contact, even through a placebo, may interfere positively with the psychopathological co-morbidity. One has to keep in mind that the non-specific psychological interactions play a major role in the improvement of the majority of the headache sufferers.
doi:10.1007/s10194-012-0422-0
PMCID: PMC3311834  PMID: 22367630
Migraine; Placebo; Headache treatment
20.  The Impact of Dyspepsia on Symptom Severity and Quality of Life in Adults with Headache 
PLoS ONE  2015;10(1):e0115838.
Background
Dyspepsia and headache frequently co-exist, but the clinical implication of this association is uncertain. We planned to examine the prevalence and impact of dyspepsia in adults with headache.
Methods
A cross-sectional study was conducted in a secondary care setting. Clinical, psychological and health-related quality of life (HRQOL) data were compared between subjects with headache and controls (non-headache subjects). The impact of dyspepsia was analysed further in subjects with headache alone.
Results
280 subjects (93 cases with headache and 187 matched controls) were recruited. The following baseline characteristics of subjects were as follows: mean age 45.0±17.3 years, 57.0% females and ethnic distribution—Malaysian = 45 (48.4%), Chinese n = 24 (25.8%) and Indians n = 24 (25.8%). Headache sub-types among cases with headache were as follows: tension-type headache (TTH) n = 53 (57.0%) and migraine n = 40 (43.0%). Dyspepsia was more prevalent in cases with headache compared to controls (25.8% vs 12.8%, p = 0.011), and headache was independently associated with dyspepsia (OR 2.75, 95% CI 1.39–5.43). Among cases with headache, there was a trend towards a higher prevalence of dyspepsia in those with migraine (27.5%) compared to TTH (24.5%). Subjects with headache and dyspepsia, compared to those with headache alone, had a greater severity of headache symptoms (63.67±22.85 mm vs 51.20 ±24.0 mm VAS, p = 0.029). Overall HRQOL scores were lower in headache subjects with dyspepsia (EQ-5D summary score 0.82±0.18 vs 0.90 ±0.16, p = 0.037 and EQ-5D VAS 62.08±17.50 mm vs 72.62 ±18.85 mm, p = 0.018), compared to those without dyspepsia.
Conclusion
Dyspepsia is associated with more severe headache symptoms and results in a lower HRQOL in patients with headache.
doi:10.1371/journal.pone.0115838
PMCID: PMC4309562  PMID: 25629323
21.  Delayed-onset post-traumatic headache after a motor vehicle collision: a case report 
Introduction
Headaches are common after a motor vehicle accident (MVA). Post-traumatic headaches share many clinical symptoms including the clinical course of primary headaches. Secondary headaches (including those resulting from a subdural hematoma) are not as common, but should be considered in cases of post-traumatic events particularly if clinical symptoms progress.
Clinical Features
A case of a patient with a post-traumatic subdural hematoma demonstrates the importance of carefully examining, properly diagnosing and managing patients that experience headaches after MVAs. This patient presented with uncomplicated low back pain, neck pain and headache which progressed at one month to include focal neurological deficits. Since clinical examination alone may not be sufficient to diagnose secondary headaches, immediate referral to the emergency department may be required.
Conclusion
Primary contact practitioners should be aware of the various causes of headaches that result after a MVA. Headaches, which do not respond or progress, should be followed aggressively to determine their source.
PMCID: PMC1924661  PMID: 17657301
headache; subdural hematoma; post-traumatic; migraine; sous-dural; hématome; post-traumatique
22.  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
23.  Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis 
PLoS Medicine  2013;10(5):e1001454.
Jürgen Barth and colleagues use network meta-analysis - a novel methodological approach - to reexamine the comparative efficacy of seven psychotherapeutic interventions for adults with depression.
Please see later in the article for the Editors' Summary
Background
Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression.
Methods and Findings
We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = −0.62 to d = −0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = −0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = −0.30, 95% credibility interval [CrI] [−0.54 to −0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [−0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [−0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions.
Conclusions
Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Depression is a very common condition. One in six people will experience depression at some time during their life. People who are depressed have recurrent feelings of sadness and hopelessness and might feel that life is no longer worth living. The condition can last for months and often includes physical symptoms such as headaches, sleeping problems, and weight gain or loss. Treatment of depression can include non-drug treatments (psychotherapy), antidepressant drugs, or a combination of the two. Especially for people with mild or intermediate depression, psychotherapy is often considered the preferred first option. Psychotherapy describes a range of different psychotherapies, and a number of established types of psychotherapies have all shown to work for at least some patients.
Why Was This Study Done?
While it is broadly accepted that psychotherapy can help people with depression, the question of which type of psychotherapy works best for most patients remains controversial. While many scientific studies have compared one psychotherapy with control conditions, there have been few studies that directly compared multiple treatments. Without such direct comparisons, it has been difficult to establish the respective merits of the different types of psychotherapy. Taking advantage of a recently developed method called “network meta-analysis,” the authors re-examine the evidence on seven different types of psychotherapy to see how well they have been shown to work and whether some work better than others.
What Did the Researchers Do and Find?
The researchers looked at seven different types of psychotherapy, which they defined as follows. “Interpersonal psychotherapy” is short and highly structured, using a manual to focus on interpersonal issues in depression. “Behavioral activation” raises the awareness of pleasant activities and seeks to increase positive interactions between the patient and his or her environment. “Cognitive behavioral therapy” focuses on a patient's current negative beliefs, evaluates how they affect current and future behavior, and attempts to restructure the beliefs and change the outlook. “Problem solving therapy” aims to define a patient's problems, propose multiple solutions for each problem, and then select, implement, and evaluate the best solution. “Psychodynamic therapy” focuses on past unresolved conflicts and relationships and the impact they have on a patient's current situation. In “social skills therapy,” patients are taught skills that help to build and maintain healthy relationships based on honesty and respect. “Supportive counseling” is a more general therapy that aims to get patients to talk about their experiences and emotions and to offer empathy without suggesting solutions or teaching new skills.
The researchers started with a systematic search of the medical literature for relevant studies. The search identified 198 articles that reported on such clinical trials. The trials included a total of 15,118 patients and compared one of the seven psychotherapies either with another one or with a common “control intervention”. In most cases, the control (no psychotherapy) was deferral of treatment by “wait-listing” patients or continuing “usual care.” With network meta-analysis they were able to summarize the results of all these trials in a meaningful way. They did this by integrating direct comparisons of several psychotherapies within the same trial (where those were available) with indirect comparisons across all trials (using no psychotherapy as a control intervention).
Based on the combined trial results, all seven psychotherapies tested were better than wait-listing or usual care, and the differences were moderate to large, meaning that the average person in the group that received therapy was better off than about half of the patients in the control group. When comparing the therapies with each other, the researchers saw small or no differences, meaning that none of them really stood out as much better or much worse than the others. They also found that the treatments worked equally well for different patient groups with depression (younger or older patients, or mothers who had depression after having given birth). Similarly, they saw no big differences when comparing individual with group therapy, or person-to-person with internet-based interactions between therapist and patient.
However, they did find that smaller and less rigorous studies generally found larger benefits of psychotherapies, and most of the studies included in the analysis were small. Only 36 of the studies had at least 50 patients who received the same treatment. When they restricted their analysis to those studies, the researchers still saw clear benefits of cognitive-behavioral therapy, interpersonal therapy, and problem-solving therapy, but not for the other four therapies.
What Do these Findings Mean?
Similar to earlier attempts to summarize and make sense of the many study results, this one finds benefits for all of the seven psychotherapies examined, and none of them stood as being much better than some or all others. The scientific support for being beneficial was stronger for some therapies, mostly because they had been tested more often and in larger studies.
Treatments with proven benefits still do not necessarily work for all patients, and which type of psychotherapy might work best for a particular patient likely depends on that individual. So overall this analysis suggests that patients with depression and their doctors should consider psychotherapies and explore which of the different types might be best suited for a particular patient.
The study also points to the need for further research. Whereas depression affects large numbers of people around the world, all of the trials identified were conducted in rich countries and Western societies. Trials in different settings are essential to inform treatment of patients worldwide. In addition, large high-quality studies should further explore the potential benefits of some of therapies for which less support currently exists. Where possible, future studies should compare psychotherapies with one another, because all of them have benefits, and it would not be ethical to withhold such beneficial treatment from patients.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001454.
The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish); information on psychotherapy includes information on its most common forms
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
The UK nonprofit Mind provides information on depression, including an explanation of the most common psychotherapies in the UK
MedlinePlus provides links to other resources about depression (in English and Spanish)
The UK nonprofit healthtalkonline.org has a unique database of personal and patient experiences on depression
doi:10.1371/journal.pmed.1001454
PMCID: PMC3665892  PMID: 23723742
24.  Psychological therapies for the management of chronic and recurrent pain in children and adolescents 
Background
Chronic pain affects many children, who report severe pain, distressed mood, and disability. Psychological therapies are emerging as effective interventions to treat children with chronic or recurrent pain. This update adds recently published randomised controlled trials (RCTs) to the review published in 2009.
Objectives
To assess the effectiveness of psychological therapies, principally cognitive behavioural therapy and behavioural therapy, for reducing pain, disability, and improving mood in children and adolescents with recurrent, episodic, or persistent pain. We also assessed the risk of bias and methodological quality of the included studies.
Search methods
Searches were undertaken of MEDLINE, EMBASE, and PsycLIT. We searched for RCTs in references of all identified studies, meta-analyses and reviews. Date of most recent search: March 2012.
Selection criteria
RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment were eligible for inclusion (waiting list or standard medical care) for children or adolescents with episodic, recurrent or persistent pain.
Data collection and analysis
All included studies were analysed and the quality of the studies recorded. All treatments were combined into one class: psychological treatments; headache and non-headache outcomes were separately analysed on three outcomes: pain, disability, and mood. Data were extracted at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (at least three months after the post-treatment assessment point, but not more than 12 months).
Main results
Eight studies were added in this update of the review, giving a total of 37 studies. The total number of participants completing treatments was 1938. Twenty-one studies addressed treatments for headache (including migraine); seven for abdominal pain; four included mixed pain conditions including headache pain, two for fibromyalgia, two for pain associated with sickle cell disease, and one for juvenile idiopathic arthritis. Analyses revealed five significant effects. Pain was found to improve for headache and non-headache groups at post-treatment, and for the headache group at follow-up. Mood significantly improved for the headache group at follow-up, although, this should be interpreted with caution as there were only two small studies entered into the analysis. Finally, disability significantly improved in the non-headache group at post-treatment. There were no other significant effects.
Authors’ conclusions
Psychological treatments are effective in reducing pain intensity for children and adolescents (<18 years) with headache and benefits from therapy appear to be maintained. Psychological treatments also improve pain and disability for children with non-headache pain. There is limited evidence available to estimate the effects of psychological therapies on mood for children and adolescents with headache and non-headache pain. There is also limited evidence to estimate the effects on disability in children with headache. These conclusions replicate and add to those of the previous review which found psychological therapies were effective in reducing pain intensity for children with headache and non-headache pain conditions, and these effects were maintained at follow-up.
doi:10.1002/14651858.CD003968.pub3
PMCID: PMC3715398  PMID: 23235601
*Pain Management; Abdominal Pain [therapy]; Chronic Disease; Cognitive Therapy; Fibromyalgia [therapy]; Headache [therapy]; Hemoglobin SC Disease [complications]; Mood Disorders [therapy]; Pain [psychology]; Psychotherapy [*methods]; Randomized Controlled Trials as Topic; Recurrence; Adolescent; Child; Humans
25.  A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study 
PLoS Medicine  2014;11(1):e1001589.
Beth Payne and colleagues use a risk prediction model, the Pre-eclampsia Integrated Estimate of RiSk (miniPIERS) to help inform the clinical assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings.
Please see later in the article for the Editors' Summary
Background
Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications.
Methods and Findings
From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735–0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658–0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability.
Conclusions
The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Each year, ten million women develop pre-eclampsia or a related hypertensive (high blood pressure) disorder of pregnancy and 76,000 women die as a result. Globally, hypertensive disorders of pregnancy cause around 12% of maternal deaths—deaths of women during or shortly after pregnancy. The mildest of these disorders is gestational hypertension, high blood pressure that develops after 20 weeks of pregnancy. Gestational hypertension does not usually harm the mother or her unborn child and resolves after delivery but up to a quarter of women with this condition develop pre-eclampsia, a combination of hypertension and protein in the urine (proteinuria). Women with mild pre-eclampsia may not have any symptoms—the condition is detected during antenatal checks—but more severe pre-eclampsia can cause headaches, blurred vision, and other symptoms, and can lead to eclampsia (fits), multiple organ failure, and death of the mother and/or her baby. The only “cure” for pre-eclampsia is to deliver the baby as soon as possible but women are sometimes given antihypertensive drugs to lower their blood pressure or magnesium sulfate to prevent seizures.
Why Was This Study Done?
Women in low- and middle-income countries (LMICs) are more likely to develop complications of pre-eclampsia than women in high-income countries and most of the deaths associated with hypertensive disorders of pregnancy occur in LMICs. The high burden of illness and death in LMICs is thought to be primarily due to delays in triage (the identification of women who are or may become severely ill and who need specialist care) and delays in transporting these women to facilities where they can receive appropriate care. Because there is a shortage of health care workers who are adequately trained in the triage of suspected cases of hypertensive disorders of pregnancy in many LMICs, one way to improve the situation might be to design a simple tool to identify women at increased risk of complications or death from hypertensive disorders of pregnancy. Here, the researchers develop miniPIERS (Pre-eclampsia Integrated Estimate of RiSk), a clinical risk prediction model for adverse outcomes among women with hypertensive disorders of pregnancy suitable for use in community and primary health care facilities in LMICs.
What Did the Researchers Do and Find?
The researchers used data on candidate predictors of outcome that are easy to collect and/or measure in all health care settings and that are associated with pre-eclampsia from women admitted with any hypertensive disorder of pregnancy to participating centers in five LMICs to build a model to predict death or a serious complication such as organ damage within 48 hours of admission. The miniPIERS model included parity (whether the woman had been pregnant before), gestational age (length of pregnancy), headache/visual disturbances, chest pain/shortness of breath, vaginal bleeding with abdominal pain, systolic blood pressure, and proteinuria detected using a dipstick. The model was well-calibrated (the predicted risk of adverse outcomes agreed with the observed risk of adverse outcomes among the study participants), it had a good discriminatory ability (it could separate women who had a an adverse outcome from those who did not), and it designated women as being at high risk (25% or greater probability of an adverse outcome) with an accuracy of 85.5%. Importantly, external validation using data collected in fullPIERS, a study that developed a more complex clinical prediction model based on data from women attending tertiary hospitals in high-income countries, confirmed the predictive performance of miniPIERS.
What Do These Findings Mean?
These findings indicate that the miniPIERS model performs reasonably well as a tool to identify women at increased risk of adverse maternal outcomes associated with hypertensive disorders of pregnancy. Because miniPIERS only includes simple-to-measure personal characteristics, symptoms, and signs, it could potentially be used in resource-constrained settings to identify the women who would benefit most from interventions such as transportation to a higher level of care. However, further external validation of miniPIERS is needed using data collected from women living in LMICs before the model can be used during routine antenatal care. Moreover, the value of miniPIERS needs to be confirmed in implementation projects that examine whether its potential translates into clinical improvements. For now, though, the model could provide the basis for an education program to increase the knowledge of women, families, and community health care workers in LMICs about the signs and symptoms of hypertensive disorders of pregnancy.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001589.
The World Health Organization provides guidelines for the management of hypertensive disorders of pregnancy in low-resourced settings
The Maternal and Child Health Integrated Program provides information on pre-eclampsia and eclampsia targeted to low-resourced settings along with a tool-kit for LMIC providers
The US National Heart, Lung, and Blood Institute provides information about high blood pressure in pregnancy and a guide to lowering blood pressure in pregnancy
The UK National Health Service Choices website provides information about pre-eclampsia
The US not-for profit organization Preeclampsia Foundation provides information about all aspects of pre-eclampsia; its website includes some personal stories
The UK charity Healthtalkonline also provides personal stories about hypertensive disorders of pregnancy
MedlinePlus provides links to further information about high blood pressure and pregnancy (in English and Spanish); the MedlinePlus Encyclopedia has a video about pre-eclampsia (also in English and Spanish)
More information about miniPIERS and about fullPIERS is available
doi:10.1371/journal.pmed.1001589
PMCID: PMC3897359  PMID: 24465185

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