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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.  Osmophobia in primary headaches 
The Journal of Headache and Pain  2005;6(4):213-215.
This study evaluates osmophobia (defined as an unpleasant perception, during a headache attack, of odours that are non–aversive or even pleasurable outside the attacks) in connection with the diagnosis of primary headaches. We recruited 775 patients from our Headache Centre (566 females, 209 males; age 38±12 years), of whom 477 were migraineurs without aura (MO), 92 with aura (MA), 135 had episodic tension–type headache (ETTH), 44 episodic cluster headache (ECH), 2 chronic paroxysmal hemicrania (CPH) and 25 other primary headaches (OPHs: 12 primary stabbing headaches, 2 primary cough headaches, 3 primary exertional headaches, 2 primary headaches associated with sexual activity, 3 hypnic headaches, 2 primary thunderclap headaches and 1 hemicrania continua). Among them, 43% with MO (205/477), 39% with MA (36/92), and 7% with CH (3/44) reported osmophobia during the attacks; none of the 135 ETTH and 25 OPH patients suffered this symptom. We conclude that osmophobia is a very specific marker to discriminate adequately between migraine (MO and MA) and ETTH; moreover, from this limited series it seems to be a good discriminant also for OPHs, and for CH patients not sharing neurovegetative symptoms with migraine. Therefore, osmophobia should be considered a good candidate as a new criterion for the diagnosis of migraine.
doi:10.1007/s10194-005-0188-8
PMCID: PMC3451998  PMID: 16362667
Osmophobia; Migraine; Primary headaches; International Headache Classification
3.  Headaches precipitated by cough, prolonged exercise or sexual activity: a prospective etiological and clinical study 
The Journal of Headache and Pain  2008;9(5):259-266.
Headaches provoked by cough, prolonged physical exercise and sexual activity have not been studied prospectively, clinically and neuroradiologically. Our aim was to delimitate characteristics, etiology, response to treatment and neuroradiological diagnostic protocol of those patients who consult to a general Neurological Department because of provoked headache. Those patients who consulted due to provoked headaches between 1996 and 2006 were interviewed in depth and followed-up for at least 1 year. Neuroradiological protocol included cranio-cervical MRI for all patients with cough headache and dynamic cerebrospinal functional MRI in secondary cough headache cases. In patients with headache provoked by prolonged physical exercise or/and sexual activity cranial neuroimaging (CT and/or MRI) was performed and, in case of suspicion of subarachnoid bleeding, angioMRI and/or lumbar tap were carried out. A total of 6,412 patients consulted due to headache during the 10 years of the study. The number of patients who had consulted due to any of these headaches is 97 (1.5% of all headaches). Diagnostic distribution was as follows: 68 patients (70.1%) consulted due to cough headache, 11 (11.3%) due to exertional headache and 18 (18.6%) due to sexual headache. A total of 28 patients (41.2%) out of 68 were diagnosed of primary cough headache, while the remaining 40 (58.8%) had secondary cough headache, always due to structural lesions in the posterior fossa, which in most cases was a Chiari type I malformation. In seven patients, cough headache was precipitated by treatment with angiotensin-converting enzyme inhibitors. As compared to the primary variety, secondary cough headache began earlier (average 40 vs. 60 years old), was located posteriorly, lasted longer (5 years vs. 11 months), was associated with posterior fossa symptoms/signs and did not respond to indomethacin. All those patients showed difficulties in the cerebrospinal fluid circulation in the foramen magnum region in the dynamic MRI study and preoperative plateau waves, which disappeared after posterior fossa reconstruction. The mean age at onset for primary headaches provoked by physical exercise and sexual activity began at the same age (40 years old), shared clinical characteristics (bilateral, pulsating) and responded to beta-blockers. Contrary to cough headache, secondary cases are rare and the most frequent etiology was subarachnoid bleeding. In conclusion, these conditions account for a low proportion of headache consultations. These data show the total separation between cough headache versus headache due to physical exercise and sexual activity, confirm that these two latter headaches are clinical variants of the same entity and illustrate the clinical differences between the primary and secondary provoked headaches.
doi:10.1007/s10194-008-0063-5
PMCID: PMC3452197  PMID: 18751938
Chiari malformation; Cough headache; Exertional headache; Sexual headache
4.  Recurrent and chronic headaches in children below 6 years of age 
The Journal of Headache and Pain  2005;6(3):135-142.
The objective was to determine the frequency of headache subtypes, according to International Headache Society (IHS) criteria, in a population of children below 6 years visiting a Center for Diagnosis and Treatment of Headache in Youth. Medical records of the children below 6 years at their first visit, admitted for headache between 1997 and 2003, were studied. Headache was classified according to the IHS criteria 2004. Children with less than three headache attacks or less than 15 days of daily headache were excluded. We found 1598 medical records of children who visited our Headache Center in the study period. One hundred and five (6.5%) were children younger than 6 years. The mean age at the first medical control was 4.8±1.3 years (range 17–71 months). There were 59 males (56.1%) and 46 females (43.9%). The mean age at onset of headaches was 4.3 years (range 14–69 months). According to the IHS criteria we found 37 cases (35.2%) with migraine, 19 cases (18%) with episodic tension headache, 5 cases (4.8%) with chronic daily headache, 13 cases (12.4%) with primary stabbing headache, 18 cases (17.1%) with post–traumatic headache, 7 cases (6.6%) with other non–dangerous secondary headaches (otorhinolaryngological diseases, post–infectious headaches), 3 cases (2.85%) with dangerous headaches (Arnold–Chiari type 1 malformation, brain tumour) and 9 cases (8.6%) with unclassifiable headaches. Six children (5.7%) reported more than one headache subtype. The prevalence of dangerous headaches was higher than those in school age (χ2=4.70, p<0.05). Our study shows some differences in headaches in this population vs. school children. In fact at this age migraine is the most common headache, but we also found an increase of secondary causes among the chronic/recurrent and daily headaches, especially posttraumatic disorders and potentially dangerous headaches. Finally our study shows the highest prevalence of the idiopathic stabbing headache in pre–school children in comparison with other ages.
doi:10.1007/s10194-005-0168-z
PMCID: PMC3451630  PMID: 16355294
Children; Migraine; Secondary headaches; Stabbing headaches
5.  The differential diagnosis of chronic daily headaches: an algorithm-based approach 
The Journal of Headache and Pain  2007;8(5):263-272.
Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review.
doi:10.1007/s10194-007-0418-3
PMCID: PMC2793374  PMID: 17955166
Chronic daily headache; Differential diagnosis; Strategy
6.  The differential diagnosis of chronic daily headaches: an algorithm-based approach 
The Journal of Headache and Pain  2007;8(5):263-272.
Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review.
doi:10.1007/s10194-007-0418-3
PMCID: PMC2793374  PMID: 17955166
Chronic daily headache; Differential diagnosis; Strategy
7.  Application of ICHD-II Criteria in a Headache Clinic of China 
PLoS ONE  2012;7(12):e50898.
Background
China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II).
Methods and Results
Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001). The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004). The peak age at onset of TTH for male and female were both in the 3rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2nd decade for females and the 1st decade for males.
Conclusions/Significance
This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria.
doi:10.1371/journal.pone.0050898
PMCID: PMC3519829  PMID: 23239993
8.  Incidence and influence on referral of primary stabbing headache in an outpatient headache clinic 
The Journal of Headache and Pain  2011;12-12(3):311-313.
Primary stabbing headache (PSH) is a pain, as brief, sharp, jabbing stabs, predominantly felt in the first division of trigeminal nerve. Population studies have shown that PSH is a common headache. However, most people suffer attacks of low frequency or intensity and seldom seek for medical assistance. There are few clinic-based studies of PSH, and its real influence as a primary cause for referral to neurology outpatient offices is to be determined. We aim to investigate the burden of PSH as main complaint in an outpatient headache clinic. We reviewed all patients with PSH (ICHD-II criteria), attended in an outpatient headache clinic in a tertiary hospital during a 2.5-year period (January 2008–June 2010). We considered demographic and nosological characteristics and if PSH was main cause of submission. 36 patients (26 females, 10 males) out of 725 (5%) were diagnosed of PSH. Mean age at onset 34.1 ± 2.9 years (range 10–72). Mean time from onset to diagnosis 68.8 ± 18.3 months. Twenty-four patients fulfilled ICHD-II criteria for other headaches (14 migraine, 6 tension-type headache, 2 hemicrania continua, 1 primary cough headache and 1 primary exertional headache). 77.7% of patients were submitted from primary care. In 14 patients (39%), PSH was main reason for submission, its intensity or frequency in 5 (35.7%) and fear of malignancy in 9 (74.3%). Only two patients of those who associated other headaches were submitted due to PSH. In conclusion, PSH is not an uncommon diagnosis in an outpatient headache office. However, and according to our data, it is not usually the main cause of submission to a headache clinic.
doi:10.1007/s10194-010-0283-3
PMCID: PMC3094672  PMID: 21210176
Primary stabbing headache; Headache clinic; Primary care
9.  Incidence and influence on referral of primary stabbing headache in an outpatient headache clinic 
The Journal of Headache and Pain  2011;12(3):311-313.
Primary stabbing headache (PSH) is a pain, as brief, sharp, jabbing stabs, predominantly felt in the first division of trigeminal nerve. Population studies have shown that PSH is a common headache. However, most people suffer attacks of low frequency or intensity and seldom seek for medical assistance. There are few clinic-based studies of PSH, and its real influence as a primary cause for referral to neurology outpatient offices is to be determined. We aim to investigate the burden of PSH as main complaint in an outpatient headache clinic. We reviewed all patients with PSH (ICHD-II criteria), attended in an outpatient headache clinic in a tertiary hospital during a 2.5-year period (January 2008–June 2010). We considered demographic and nosological characteristics and if PSH was main cause of submission. 36 patients (26 females, 10 males) out of 725 (5%) were diagnosed of PSH. Mean age at onset 34.1 ± 2.9 years (range 10–72). Mean time from onset to diagnosis 68.8 ± 18.3 months. Twenty-four patients fulfilled ICHD-II criteria for other headaches (14 migraine, 6 tension-type headache, 2 hemicrania continua, 1 primary cough headache and 1 primary exertional headache). 77.7% of patients were submitted from primary care. In 14 patients (39%), PSH was main reason for submission, its intensity or frequency in 5 (35.7%) and fear of malignancy in 9 (74.3%). Only two patients of those who associated other headaches were submitted due to PSH. In conclusion, PSH is not an uncommon diagnosis in an outpatient headache office. However, and according to our data, it is not usually the main cause of submission to a headache clinic.
doi:10.1007/s10194-010-0283-3
PMCID: PMC3094672  PMID: 21210176
Primary stabbing headache; Headache clinic; Primary care
10.  Treatment of Headache in the Elderly 
Opinion statement
Most primary headaches in the elderly are similar to those in younger patients (tension, migraine, and cluster), but there are some differences, such as late-life migraine accompaniments and hypnic headaches. Although migraine in younger persons usually presents with headache, migraine in older persons may initially appear with visual or sensory phenomena, instead of headache (“migraine accompaniments”). Hypnic headaches awaken patients from sleep, are short-lived, and occur only in the elderly. The probability of secondary headache increases steadily with age. Secondary headaches include those associated with temporal arteritis, trigeminal neuralgia, sleep apnea, post- herpetic neuralgia, cervical spondylosis, subarachnoid hemorrhage, intracerebral hemorrhage, intracranial neoplasm, and post-concussive syndrome. Certain rescue treatments for migraine headache in younger individuals (triptans or dihydroergotamine, for example) should not be used in elderly patients because of the risk of coronary artery disease. Naproxen and hydroxyzine are commonly used oral rescue therapies for older adults who have migraine or tension headaches. Intravenous magnesium, valproic acid, and metoclopramide are all effective rescue therapies for severe headaches in the emergency room setting. Some effective prophylactic agents for migraine in younger patients (amitriptyline and doxepin) are not usually recommended for older individuals because of the risks of cognitive impairment, urinary retention, and cardiac arrhythmia. For these reasons, the recommended oral preventive agents for migraine in older adults include divalproex sodium, topiramate, metoprolol, and propranolol. Oral agents that can prevent hypnic headaches include caffeine and lithium. Cough headaches respond to indomethacin or acetazolamide.
doi:10.1007/s11940-012-0205-6
PMCID: PMC3553408  PMID: 23054583
Cluster; Headache; Treatment; Elderly; Divalproex; Hydroxyzine; Hypnic; Lithium; Magnesium; Medication overuse; Metoclopramide; Metoprolol; Migraine accompaniment; Naproxen; Propranolol; Sleep apnea; Subarachnoid hemorrhage; Temporal arteritis; Tension; Thunderclap; Topiramate; Trigeminal neuralgia
11.  New daily persistent headache with a thunderclap headache onset and complete response to Nimodipine (A new distinct subtype of NDPH) 
At present new daily persistent headache is just a group of conditions that are connected based on the temporal profile of their mode of onset. If new daily persistent headache is a true distinct syndrome like migraine then we need to start to define subtypes that have specific effective treatments such has been noted for migraine sub-forms. We present what we believe is the first recognized subtype of new daily persistent headache that which starts with a thunderclap headache onset. A patient presented with a 13 month history of a daily headache from onset which initiated as a thunderclap headache along with persistent acalculia. All neuroimaging studies for secondary causes were negative. Nimodipine rapidly and completely alleviated her headache and associated neurologic symptoms. We propose that this subtype of new daily persistent headache is caused by a very rapid increase in CSF tumor necrosis factor alpha levels leading to cerebral artery vasospasm with a subsequent thunderclap headache, then continuous or near continuous cerebral artery vasospasm leading to a persistent daily headache. Nimodipine which not only inhibits cerebral artery vasospasm but also tumor necrosis factor alpha production appears to be a specific treatment for this distinct subtype of new daily persistent headache.
doi:10.1186/1129-2377-14-100
PMCID: PMC3878041  PMID: 24364890
New daily persistent headache; Thunderclap headache; Vasospasm; Nimodipine; Reversible cerebral vasoconstriction syndrome; Acalculia
12.  Cardiac cephalgia 
The purpose of this review was to provide a critical evaluation of medical literature on so-called “cardiac cephalgia” or “cardiac cephalalgia”. The 2004 International Classification of Headache Disorders codes cardiac cephalgia to 10.6 in the group of secondary headaches attributed to disorder of homoeostasis. This headache is hardly recognizable and is associated to an ischaemic cardiovascular event, of which it may be the only manifestation in 27% of cases. It usually occurs after exertion. Sometimes routine examinations, cardiac enzymes, ECG and even exercise stress test prove negative. In such cases, only a coronary angiogram can provide sufficient evidence for diagnosis. Cardiac cephalgia manifests itself without a specific pattern of clinical features: indeed, in this headache subtype there is a high variability of clinical manifestations between different patients and also within the same patient. It “mimics” sometimes a form of migraine either accompanied or not by autonomic symptoms, sometimes a form of tension-type headache; on other occasions, it exhibits characteristics that can hardly be interpreted as typical of primary headache. Pain location is highly variable. When the headache occurs as the only manifestation of an acute coronary event, the clues for suspicion are a) older age at onset, b) no past medical history of headache, c) presence of risk factors for vascular disorders and d) onset of headache under stress. Knowledge of cardiac cephalgia is scarce, due to its rare clinical occurrence and to the scant importance given to headache as a symptom concomitantly with an ischaemic cardiac event.
doi:10.1007/s10194-008-0087-x
PMCID: PMC3451760  PMID: 19139804
Cardiac cephalgia; Exertional headache; Secondary headache; Headache attributed to disorder of homoeostasis; Acute myocardial ischemia
13.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
14.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
15.  Chronic daily headaches 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S40-S50.
Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches.
doi:10.4103/0972-2327.100002
PMCID: PMC3444216  PMID: 23024563
Chronic daily headache; chronic migraine; chronic tension type headache; hemicrania continua; new daily persistent headache
16.  Chronic headaches: from research to clinical practice 
The Journal of Headache and Pain  2005;6(4):175-178.
Chronic daily headache (CDH) is a heterogeneous group of headaches that includes primary and secondary varieties. Primary CDH is a frequent entity that probably affects 4–5% of the population. It can be subdivided into headaches of short duration (<4 h/attack) like chronic cluster headache, and disorders of long duration (>4 h/attack). Primary CDH of long duration includes transformed migraine, chronic tension–type headache, and new daily persistent headache and hemicrania continua. Analgesics, ergots and triptan overuse are frequent in all types of CDH. We revise recent insights into the epidemiology, pathophysiology, clinical characteristics and prognosis of CDH.
doi:10.1007/s10194-005-0177-y
PMCID: PMC3452019  PMID: 16362656
Chronic migraine; Chronic tension–type headache; New persistent daily headache; Physiopathology; Epidemiology
17.  Validation of a guideline-based decision support system for the diagnosis of primary headache disorders based on ICHD-3 beta 
Background
China may have the largest population of headache sufferers and therefore the most serious burden of disease worldwide. However, the rate of diagnosis for headache disorders is extremely low, possibly due to the relative complexity of headache subtypes and diagnostic criteria. The use of computerized clinical decision support systems (CDSS) seems to be a better choice to solve this problem.
Methods
We developed a headache CDSS based on ICHD-3 beta and validated it in a prospective study that included 543 headache patients from the International Headache Center at the Chinese PLA General hospital, Beijing, China.
Results
We found that the CDSS correctly recognized 159/160 (99.4%) of migraine without aura, 36/36 (100%) of migraine with aura, 20/21 (95.2%) of chronic migraine, and 37/59 (62.7%) of probable migraine. This system also correctly identified 157/180 (87.2%) of patients with tension-type headache (TTH), of which infrequent episodic TTH was diagnosed in 12/13 (92.3%), frequent episodic TTH was diagnosed in 99/101 (98.0%), chronic TTH in 18/20 (90.0%), and probable TTH in 28/46 (60.9%). The correct diagnostic rates of cluster headache and new daily persistent headache (NDPH) were 90.0% and 100%, respectively. In addition, the system recognized 32/32 (100%) of patients with medication overuse headache.
Conclusions
With high diagnostic accuracy for most of the primary and some types of secondary headaches, this system can be expected to help general practitioners at primary hospitals improve diagnostic accuracy and thereby reduce the burden of headache in China.
doi:10.1186/1129-2377-15-40
PMCID: PMC4074417  PMID: 24934331
Headache; Computer-assisted diagnosis; Clinical decision support; ICHD-3 beta; SAGE
18.  A common cause of sudden and thunderclap headaches: reversible cerebral vasoconstriction syndrome 
Background
Thunderclap headache (TCH) is a sudden headache (SH) with accepted criteria of severe intensity and onset to peak within one minute. It is a well-known presentation for subarachnoid hemorrhage (SAH) but most patients with TCH or SH run a benign course without identifiable causes. Reversible cerebral vasoconstriction syndrome (RCVS), a recently recognized syndrome characterized by recurrent TCH attacks, has been proposed to account for most of these patients.
Methods
We recruited consecutive patients presenting with SH at our headache clinic. Computed tomography and/or magnetic resonance imaging with angiography were performed to exclude structural causes and to identify vasoconstriction. Catheter angiography and lumbar puncture were performed with patients consent. Reversibility of vasoconstriction was confirmed by follow-up study.
Results
From July 2010 to June 2013, 31 patients with SH were recruited. Twenty-four (72.7%) of these SH patients exhibited headache fulfilling the TCH criteria. The diagnosis of RCVS was confirmed in 14 (45.2%) of patients with SH and 11 (45.8%) of patients with TCH. Other diagnoses were as follows: primary headaches (SH: 41.9%, TCH: 45.8%) and other secondary causes (SH: 12.9%, TCH: 8.3%). Compared with non-RCVS patients, patients with RCVS were older (50.8 ± 9.3 years vs. 40.8 ± 10.0 years, P = 0.006) and less likely to experience short headache duration of < 1 hour (23.1% vs. 78.6%, P = 0.007). Patients with RCVS were more likely to cite bathing (42.9% vs. 0%, P = 0.004) and less likely to cite exertion (0% vs. 29.4%, P = 0.048) as headache triggers.
Conclusions
Reversible cerebral vasoconstriction syndrome is a common cause of SH and TCH. Considering the potential mortality and morbidity of RCVS, systemic examination of cerebral vessels should be performed in these patients.
doi:10.1186/1129-2377-15-13
PMCID: PMC3973996  PMID: 24580731
Bath-related thunderclap headache; Orgasmic headache; Primary cough headache; Primary exertional headache; Primary headache associated with sexual activity; Reversible cerebral vasoconstriction syndrome; Sentinel headache; Sudden headache; Subarachnoid hemorrhage; Thunderclap headache
19.  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
20.  Focus on therapy: hemicrania continua and new daily persistent headache 
The Journal of Headache and Pain  2010;11(3):259-265.
Hemicrania continua (HC) and new daily-persistent headache (NDPH) represent the only two forms of chronic daily headache in Chap. IV “Other Primary Headaches” of the second edition of the International Classification of Headache Disorders. HC and NDPH are rare and poorly defined from a pathophysiological point of view; as a consequence, their management is largely empirical. Indeed, there is a lack of prospective, controlled trials in this field, and treatment effectiveness is basically inferred from the results of sparse open-label trials, retrospective case series, clinical experience and expert opinions. In this narrative review we have summarised the information collected from an extensive analysis of the literature on the treatment of HC and NDPH in order to provide the best available and up-to-date evidence for the management of these two rare forms of primary headache. Indomethacin is the mainstay of HC management. The reported effective dose of indomethacin ranges from 50 to 300 mg/day. Gabapentin 600–3,600 mg tid, topiramate 100 mg bid, and celecoxib 200–400 mg represent the most interesting alternative choices in the patients who do not tolerate indomethacin or who have contraindications to its use. NDPH is very difficult to treat and it responds poorly only to first-line options used for migraine or tension-type headache.
doi:10.1007/s10194-010-0194-3
PMCID: PMC3451920  PMID: 20186563
Hemicrania continua; New daily persistent headache; Chronic daily headache; Therapy; Management
21.  Benign vascular sexual headache and exertional headache: interrelationships and long term prognosis. 
There is a definite relationship between the vascular type of benign sexual headache and benign exertional headache. Forty five patients with benign vascular sexual headache were reviewed. Twenty seven (60%) experienced benign vascular sexual headache alone and eighteen (40%) had experienced both benign vascular sexual headache and benign exertional headache on at least one occasion. The mean age was 34.3 years with a male:female ratio of 5.4:1. Thirty patients with a history of benign vascular sexual headache were followed for an average of 74 months. A personal history of migraine was found in 47% of cases and a family history of migraine in 30%. Forty one per cent of patients with benign vascular sexual headache alone had recurrences after diagnosis, and stress and fatigue were considered major contributing factors to the initial and recurrent headache. Nine patients had experienced benign vascular sexual headache and benign exertional headache within 72 hours of each other on at least one occasion, often with a residual headache between the two. Four patients experienced their benign vascular sexual headache and benign exertional headache separated by months to years. The prognosis of benign vascular sexual headache and the clinical and possible pathophysiological relationships between benign vascular sexual headache and benign exertional headache are discussed. Knowledge of the interrelationships of these varieties of headache is valuable in the counselling of patients.
PMCID: PMC488541  PMID: 1865204
22.  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
23.  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
24.  Thunderclap headache attributed to reversible cerebral vasoconstriction: view and review 
The Journal of Headache and Pain  2008;9(5):277-288.
Thunderclap headache attributed to reversible cerebral vasoconstriction (THARCV) is a syndrome observed in a number of reported cases. In this article we reviewed this new headache entity (idiopathic form) using the clinical-radiological findings of 25 reported patients. In this series of patients 72% were women, the mean age at the onset of first headache episode was 39.4 ± 2.3 years. In addition to the sine qua non condition of being abrupt and severe (thunderclap) at the onset, the headache was usually described as being explosive, excruciating, or crushing. The feature of pulsatility, accompanied or not by nausea was described by 80% of the patients. Forty percent of the cases manifested vomiting and 24% photophobia. Usually the headache was generalized, and in three cases it was unilateral at least at the onset. In 21 of 25 patients (84%) there was at least one recurrence or a sudden increase in the intensity of the headache. A past history of migraine was present in 52% of the patients. Precipitating factors were identified in 56% of the patients. Sexual intercourse was described by six patients. Of the 25 patients with THARCV syndrome studied, 12 (48%) developed focal neurological signs, transitory ischemic attack (n = 1), or ischemic stroke (n = 11, 44%), and two (8%) of them manifested seizures. The THARCV syndrome is a neurological disturbance perhaps more frequent than expected, preferentially affecting middle aged female migraineurs, and having an unpredictable prognosis, either showing a benign course or leading to stroke.
doi:10.1007/s10194-008-0054-6
PMCID: PMC3452202  PMID: 18668199
Headache; Vasospasm; Stroke; Thunderclap headache; Pathophysiology; Criteria
25.  Hemicrania continua in a headache clinic: referral source and diagnostic delay in a series of 22 patients 
The Journal of Headache and Pain  2012;13(7):567-569.
Hemicrania continua (HC) is a unilateral and continuous primary headache with superimposed exacerbations frequently associated with autonomic features. Diagnostic criteria of HC, according to II Edition of International Classification of Headache Disorders require complete response to indomethacin. HC is probably misdiagnosed more often than other primary headaches. We aim to analyze characteristics of a series of 22 consecutive cases of HC. We recruited patients from a headache outpatient clinic in a tertiary hospital over a 3-year period (January 2008 to January 2011). We prospectively gathered demographic and nosological characteristics and considered referral source and delay between onset of headache and diagnosis of HC. Twenty-two patients (14 females, 8 males) out of 1,150, who attended the mentioned clinic during the inclusion period (1.9 %) were diagnosed with HC. All cases responded to indomethacin. No patient received a diagnosis of HC before attending our headache office. Mean latency of diagnosis was 86.1 ± 106.5 months (range 3–360). 11 patients (50 %) were referred from primary care, with 9 (40.9 %) from other neurology clinics and 2 (9.1 %) from other specialities offices. According to our series, HC is not an infrequent diagnosis in a headache outpatient clinic. Diagnostic delay is comparable to data collected in previous studies. As HC is frequently misdiagnosed, we thing there is a need for increasing the understanding of this entity, potentially responsive to indomethacin.
doi:10.1007/s10194-012-0471-4
PMCID: PMC3444545  PMID: 22821619
Hemicrania continua; Indomethacin; Diagnostic delay; Headache office; Referral source

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