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1.  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
2.  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
3.  Personality Characteristics of Male Sufferers of Chronic Tension-Type and Cervicogenic Headache 
Background and Purpose
Chronic tension-type headache (a primary headache disorder) and cervicogenic headache (a secondary headache disorder that is attributable to upper cervical spine pathology) share similar clinical manifestations, but their associated personality traits may differ. We evaluated the personality differences between sufferers of chronic tension-type headache and cervicogenic headache.
Methods
We administered the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) and the Zuckerman Sensation-Seeking Scale (SSS) to 18 patients suffering from chronic tension-type headache, 19 suffering from cervicogenic headache, and 26 healthy volunteers. Depressive trends were measured with the Plutchik-van-Praag Depression Inventory (PVP).
Results
Compared to healthy controls, the chronic tension-type headache group scored significantly higher on ZKPQ Neuroticism-Anxiety and on the PVP, while the cervicogenic headache group scored significantly lower on SSS Thrill and Adventure Seeking. In addition, the total SSS score was significantly lower in the cervicogenic headache group than in both the chronic tension-type headache group and the healthy controls.
Conclusions
The results of this study indicate that higher scores for neuroticism-anxiety and depression were associated with chronic tension-type headache, while lower sensation-seeking scores were associated with cervicogenic headache.
doi:10.3988/jcn.2012.8.1.69
PMCID: PMC3325435  PMID: 22523516
cervicogenic headache; chronic tension-type headache; personality traits
4.  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
Chronic daily headache; Differential diagnosis; Strategy
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
Chronic daily headache; Differential diagnosis; Strategy
6.  Primary meningeal melanocytoma of the anterior cranial fossa: a case report and review of the literature 
Background
Primary meningeal melanocytoma is a rare neurological disorder. Although it may occur at the base of the brain, it is extremely rare at the anterior cranial fossa.
Case presentation
A 27-year-old man presented with headache and diplopia at our department. Fundoscopy showed left optic nerve atrophy and right papilledema consistent with Foster-Kennedy syndrome. Neurological exams were otherwise normal. A left frontal irregular space-occupying lesion was seen on magnetic resonance imaging (MRI), and enhancement was shown on contrast-enhanced computed tomography (CT) scan. CT angiography (CTA) revealed vascular compression around the lesion. Prior to surgery, meningioma was diagnosed and gross tumor removal was performed. On postoperative pathohistological exam, the tumor proved to be a meningeal melanocytoma, WHO grade I. No skin melanoma was found. After surgery, the patient received radiation therapy. No tumor was seen on follow-up MR images six months after surgery. The patient was well after two and a half years, and there was no tumor recurrence on the follow-up CT.
Conclusions
This case of primary meningeal melanocytoma located at the anterior cranial fossa is very rare. Although primary meningeal melanocytoma is benign, it may behave aggressively. Complete surgical resection is curative for most cases. Radiation therapy is important to prevent relapse of the tumor, especially in cases of incomplete surgical resection.
doi:10.1186/1477-7819-10-135
PMCID: PMC3433350  PMID: 22759717
7.  Primary care access to computed tomography for chronic headache 
Background
The diagnostic yield of neuroimaging in chronic headache is low, but can reduce the use of health services.
Aim
To determine whether primary care access to brain computed tomography (CT) referral for chronic headache reduces referral to secondary care.
Design of study
Prospective observational analysis of GP referrals to an open access CT brain scanning service.
Setting
Primary care, and outpatient radiology and neurology departments.
Method
GPs in Tayside and North East Fife, Scotland were given access to brain CT for patients with chronic headache. All referrals were analysed prospectively over 1 year, and questionnaires were sent to referrers to establish whether imaging had resulted in or stopped a referral to secondary care. The Tayside outpatient clinic database identified scanned patients referred to the neurology clinic for headache from the start of the study period to at least 1 year after their scan.
Results
There were 232 referrals (55.1/100 000/year, 95% confidence interval = 50.4 to 59.9) from GPs in 59 (82%) of 72 primary care practices. CT was performed on 215 patients. Significant abnormalities were noted in 3 (1.4%) patients; there were 22 (10.2%) non-significant findings, and 190 (88.4%) normal scans. Questionnaires of the referring GPs reported that 167 (88%) scans stopped a referral to secondary care. GPs referred 30 (14%) scanned patients to a neurologist because of headache. It is estimated that imaging reduced referrals to secondary care by 86% in the follow-up period.
Conclusion
An open access brain CT service for patients with chronic headache was used by most GP practices in Tayside, and reduced the number of referrals to secondary care.
doi:10.3399/bjgp10X502146
PMCID: PMC2880741  PMID: 20529496
headache disorders; computed tomography; open access; primary health care
8.  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
9.  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
10.  Serious neurological disorders in children with chronic headache 
Archives of Disease in Childhood  2005;90(9):937-940.
Methods: All children presenting to a specialist headache clinic over seven years with headache as their main complaint were assessed by clinical history, physical and neurological examination, neuroimaging where indicated, and by follow up using prospective headache diaries. Results: A total of 815 children and adolescents (1.25–18.75 years of age, mean 10.8 years (SD 2.9); 432 male) were assessed. Mean duration of headache was 21.2 months (SD 21.2). Neuroimaging (brain CT or MRI) was carried out on 142 (17.5%) children. The vast majority of patients had idiopathic headache (migraine, tension, or unclassified headaches). Fifty one children (6.3%) had other chronic neurological disorders that were unrelated to the headache. The headache in three children (0.37%, 95% CI 0.08% to 1.1%) was related to active intracranial pathology which was predictable on clinical findings in two children but was unexpected until a later stage in one child (0.12%, 95% CI 0.006% to 0.68%).
Conclusions: Chronic headache in childhood is rarely due to serious intracranial pathology. Careful history and thorough clinical examination will identify most patients with serious underlying brain abnormalities. Change in headache symptomatology or personality change should lower the threshold for imaging.
doi:10.1136/adc.2004.067256
PMCID: PMC1720577  PMID: 16113128
11.  Psychopathology and quality of life burden in chronic daily headache: influence of migraine symptoms 
The Journal of Headache and Pain  2010;11(3):247-253.
The aim of this study is to compare the psychopathology and the quality of life of chronic daily headache patients between those with migraine headache and those with tension-type headache. We enrolled 106 adults with chronic daily headache (CDH) who consulted for the first time in specialised centres. The patients were classified according to the IHS 2004 criteria and the propositions of the Headache Classification Committee (2006) with a computed algorithm: 8 had chronic migraine (without medication overuse), 18 had chronic tension-type headache (without medication overuse), 80 had medication overuse headache and among them, 43 fulfilled the criteria for the sub-group of migraine (m) MOH, and 37 the subgroup for tension-type (tt) MOH. We tested five variables: MADRS global score, HAMA psychic and somatic sub-scales, SF-36 psychic, and somatic summary components. We compared patients with migraine symptoms (CM and mMOH) to those with tension-type symptoms (CTTH and ttMOH) and neutralised pain intensity with an ANCOVA which is a priori higher in the migraine group. We failed to find any difference between migraine and tension-type groups in the MADRS global score, the HAMA psychological sub-score and the SF36 physical component summary. The HAMA somatic anxiety subscale was higher in the migraine group than in the tension-type group (F(1,103) = 10.10, p = 0.001). The SF36 mental component summary was significantly worse in the migraine as compared with the tension-type subgroup (F(1,103) = 5.758, p = 0.018). In the four CDH subgroups, all the SF36 dimension scores except one (Physical Functioning) showed a more than 20 point difference from those seen in the adjusted historical controls. Furthermore, two sub-scores were significantly more affected in the migraine group as compared to the tension-type group, the physical health bodily pain (F(1,103) = 4.51, p = 0.036) and the mental health (F(1,103) = 8.17, p = 0.005). Considering that the statistic procedure neutralises the pain intensity factor, our data suggest a particular vulnerability to somatic symptoms and a special predisposition to develop negative pain affect in migraine patients in comparison to tension-type patients.
doi:10.1007/s10194-010-0208-1
PMCID: PMC3451907  PMID: 20383733
Psychopathology; Quality of life; Chronic daily headache; Migraine symptoms; Tension type headache symptoms
12.  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
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.  New daily persistent headache 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S62-S65.
New daily persistent headache (NDPH) is a chronic headache developing in a person who does not have a past history of headaches. The headache begins acutely and reaches its peak within 3 days. It is important to exclude secondary causes, particularly headaches due to alterations in cerebrospinal fluid (CSF) pressure and volume. A significant proportion of NDPH sufferers may have intractable headaches that are refractory to treatment. The condition is best viewed as a syndrome rather than a diagnosis. The headache can mimic chronic migraine and chronic tension-type headache, and it is also important to exclude secondary causes, particularly headaches due to alterations in CSF pressure and volume. A large proportion of NDPH sufferers have migrainous features to their headache and should be managed with treatments used for treating migraine. A small group of NDPH sufferers may have intractable headaches that are refractory to treatment.
doi:10.4103/0972-2327.100011
PMCID: PMC3444222  PMID: 23024565
Chronic daily headache; new daily persistent headache; intractable headache
15.  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
16.  Headache (chronic tension-type) 
Clinical Evidence  2009;2009:1205.
Introduction
Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes of headache lasting minutes to days. It affects 4.1% of the general population in the USA, and is more prevalent in women (up to 65% of cases).
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for chronic tension-type headache? What are the effects of non-drug treatments for chronic tension-type headache? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 50 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture; amitriptyline; analgesics; anticonvulsant drugs; benzodiazepines; botulinum toxin; chiropractic and osteopathic manipulations; cognitive behavioural therapy (CBT); Indian head massage; mirtazapine; relaxation and electromyographic biofeedback; selective serotonin reuptake inhibitor antidepressants (SSRIs); and tricyclic antidepressants (other than amitriptyline).
Key Points
Chronic tension-type headache (CTTH) is a disorder that evolves from episodic tension-type headache, with daily or very frequent episodes, lasting minutes to days. It affects 4.1% of the general population in the USA, and is more prevalent in women (up to 65% of cases).
We found only limited evidence about the treatment of CTTH. Regular analgesics may lead to chronic headache symptoms and reduce the effectiveness of prophylactic treatment. Amitriptyline and mirtazapine may be equally effective in reducing the duration and frequency of CTTH, although amitriptyline may be associated with a less favourable adverse-effect profile.We don't know whether tricyclic antidepressants other than amitriptyline are effective in treating CTTH.We found no evidence examining the effectiveness of noradrenergic and specific serotonergic antidepressants, other than mirtazapine, in CTTH.We don't know whether SSRIs are effective in treating CTTH.We don't know whether benzodiazepines are effective in treating CTTH, and they are commonly associated with significant adverse effects.We found no evidence examining the effectiveness of anticonvulsants, such as sodium valproate, topiramate, and gabapentin, in CTTH. Botulinum toxin does not seem to be a useful treatment for CTTH. It may be associated with several adverse effects, including facial weakness, difficulty in swallowing, and disturbed local sensation.
We don't know whether non-drug treatments, such as CBT, relaxation or electromyographic biofeedback, or acupuncture, are effective in treating CTTH. We don’t know whether chiropractic and osteopathic manipulations are effective in treating CTTH. These treatments have been associated with rare, but very serious, adverse effects; for example, arterial dissection causing stroke, other stroke syndromes, and cerebellar and spinal cord injuries.
PMCID: PMC2907789  PMID: 21696647
17.  Imaging patients with suspected brain tumour: guidance for primary care 
The number of referrals by primary care practitioners to secondary care neurology services, particularly for headache, may be difficult to justify. Access to imaging by primary care practitioners could avoid referral without compromising patient outcomes, but the decision to refer is based on a number of complex factors. Due to the paucity of rigorous evidence in this area, available data are combined with expert opinion to offer support for GPs. The study suggests management for three levels of risk of tumour: red flags >1%; orange flags 0.1–1%; and yellow flags <0.1% but above the background population rate of 0.01%. Clinical presentations are stratified into these three groups. Important secondary causes of headache where imaging is normal should not be overlooked, and normal investigation does not eliminate the need for follow-up or appropriate management of headache.
doi:10.3399/bjgp08X376203
PMCID: PMC2593538  PMID: 19068162
brain tumour; diagnosis; imaging; primary care
18.  Validation of criterion-based patient assignment and treatment effectiveness of a multidisciplinary modularized managed care program for headache 
The Journal of Headache and Pain  2012;13(5):379-387.
This prospective observational study evaluates the validity of an algorithm for assigning patients to a multidisciplinary modularized managed care headache treatment program. N = 545 chronic headache sufferers [migraine (53.8 %), migraine + tension type (30.1 %), tension type (8.3 %) or medication overuse headache (6.2 %), other primary headaches (1.5 %)] were assigned to one of four treatment modules differing with regard to the number and types of interventions entailed (e.g., medication, psychological intervention, physical therapy, etc.). A rather simple assignment algorithm based on headache frequency, medication use and psychiatric comorbidity was used. Patients in the different modules were compared with regard to the experienced burden of disease. 1-year follow-up outcome data are reported (N = 160). Headache frequency and analgesic consumption differed significantly among patients in the modules. Headache-related disability was highest in patients with high headache frequency with/without medication overuse or psychiatric comorbidity (modules 2/3) compared to patients with low headache frequency and medication (module 0). Physical functioning was lowest in patients with chronic headache regardless of additional problems (modules 1/2/3). Psychological functioning was lowest in patients with severe chronicity with/without additional problems (module 2/3) compared to headache suffers with no/moderate chronicity (module 0/1). Anxiety or depression was highest in patients with severe chronicity. In 1-year follow-up, headache frequency (minus 45.3 %), consumption of attack-aborting drugs (minus 71.4 %) and headache-related disability decreased (minus 35.9 %). Our results demonstrate the clinical effectiveness and the criterion validity of the treatment assignment algorithm based on headache frequency, medication use and psychiatric comorbidity.
doi:10.1007/s10194-012-0453-6
PMCID: PMC3381067  PMID: 22581187
Integrated care; Multidisciplinary modularized treatment program; Outcome study; Headache-related disability; Headache-related quality of life; Chronic headache
19.  Chronic daily headache 
The Journal of Headache and Pain  2003;4(3):111-124.
Chronic daily headache relates to the daily or almost daily occurrence of headache in a nonparoxysmal pattern. In this review, I discuss the presentation, development, outcome, and treatment of chronic daily headache. In the context of the development of chronic daily headache, a headache continuum is presented along with its underlying pathophysiology. The treatment section covers rebound headache, analgesic and vasoconstrictor withdrawal, and the use of long-acting opioids in intractable patients. The review concludes with a discussion of hemicrania continua, an indomethacin-responsive headache syndrome.
doi:10.1007/s10194-003-0045-6
PMCID: PMC3451772
Daily headache; Chronic daily headache; Presentation; Development; Tension-type headache; Migraine; Headache continuum; Outcome; Treatment; Rebound headache; Hemicrania continua
20.  Clinical features of headache patients with fibromyalgia comorbidity 
The Journal of Headache and Pain  2011;12(6):629-638.
Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
doi:10.1007/s10194-011-0377-6
PMCID: PMC3208047  PMID: 21847547
Primary headache; Fibromyalgia; Comorbidity
21.  Clinical features of headache patients with fibromyalgia comorbidity 
The Journal of Headache and Pain  2011;12(6):629-638.
Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
doi:10.1007/s10194-011-0377-6
PMCID: PMC3208047  PMID: 21847547
Primary headache; Fibromyalgia; Comorbidity
22.  Magnetic resonance imaging of craniovertebral structures: clinical significance in cervicogenic headaches 
This paper aims to investigate the relevance of morphological changes in the main stabilizing structures of the craniocervical junction in persons with cervicogenic headache (CEH). A case control study of 46 consecutive persons with CEH, 22 consecutive with headache attributed to whiplash associated headache (WLaH) and 19 consecutive persons with migraine. The criteria of the Cervicogenic Headache International Study Group (CHISG) were used for diagnosing CEH; otherwise the criteria of the International Classification of Headache Disorders (ICHD II) were applied. All participants had a clinical interview, and physical and neurological examination. Proton weighted magnetic resonance imaging (MRI) of the craniovertebral junction, and the alar and transverse ligaments were evaluated and blinded to clinical information. The MRI of the craniovertebral and the cervical junctions, the alar and transverse ligaments disclosed no significant differences between those with CEH, WLaH and or migraine. The site of CEH pain was not correlated with the site of signal intensity changes of the alar and transverse ligaments. In fact, very few had moderate or severe signal intensity changes in their ligaments. MRI shows no specific changes of cervical discs or craniovertebral ligaments in CEH.
doi:10.1007/s10194-011-0387-4
PMCID: PMC3253147  PMID: 21947945
Cervicogenic headache; Alar ligaments; Transverse ligaments; Craniovertebral junction; Cervical junction; MRI
23.  Magnetic resonance imaging of craniovertebral structures: clinical significance in cervicogenic headaches 
This paper aims to investigate the relevance of morphological changes in the main stabilizing structures of the craniocervical junction in persons with cervicogenic headache (CEH). A case control study of 46 consecutive persons with CEH, 22 consecutive with headache attributed to whiplash associated headache (WLaH) and 19 consecutive persons with migraine. The criteria of the Cervicogenic Headache International Study Group (CHISG) were used for diagnosing CEH; otherwise the criteria of the International Classification of Headache Disorders (ICHD II) were applied. All participants had a clinical interview, and physical and neurological examination. Proton weighted magnetic resonance imaging (MRI) of the craniovertebral junction, and the alar and transverse ligaments were evaluated and blinded to clinical information. The MRI of the craniovertebral and the cervical junctions, the alar and transverse ligaments disclosed no significant differences between those with CEH, WLaH and or migraine. The site of CEH pain was not correlated with the site of signal intensity changes of the alar and transverse ligaments. In fact, very few had moderate or severe signal intensity changes in their ligaments. MRI shows no specific changes of cervical discs or craniovertebral ligaments in CEH.
doi:10.1007/s10194-011-0387-4
PMCID: PMC3253147  PMID: 21947945
Cervicogenic headache; Alar ligaments; Transverse ligaments; Craniovertebral junction; Cervical junction; MRI
24.  Are investigations anxiolytic or anxiogenic? A randomised controlled trial of neuroimaging to provide reassurance in chronic daily headache 
Objectives: Aims were to investigate (a) whether neuroimaging in patients with chronic daily headache reassures patients or fails to reassure them and/or worsens outcome, impacting on service use, costs, health anxieties, and symptoms, and (b) whether this reassurance process occurs differentially in patients with different levels of psychological morbidity.
Methods: Design: randomised controlled trial; setting: headache clinic in secondary care, South London; participants: 150 patients fulfilling criteria for chronic daily headache, stratified using the Hospital Anxiety and Depression Scale (HADS); intervention: treatment as usual or the offer of an MRI brain scan; main outcome measures: use of services, costs, and health anxiety.
Results: Seventy six patients were randomised to the offer of a brain scan and 74 patients to treatment as usual. One hundred and thirty seven (91%) primary care case notes were examined at 1 year, 103 (69%) patients completed questionnaires at 3 months and 96 (64%) at 1 year. Sixty six (44%) patients were HADS positive (scored >11 on either subscale). Patients offered a scan were less worried about a serious cause of the headaches at 3 months (p = 0.004), but this was not maintained at 1 year; other health anxiety measures did not differ by scan status. However, at 1 year HADS positive patients offered a scan cost significantly less, by £465 (95% confidence interval (CI): –£1028 to –£104), than such patients not offered a scan, due to lower utilisation of medical resources.
Conclusions: Neuroimaging significantly reduces costs for patients with high levels of psychiatric morbidity, possibly by changing subsequent referral patterns of the general practitioner.
doi:10.1136/jnnp.2004.057851
PMCID: PMC1739391  PMID: 16227551
25.  Pooled analysis of patients with thunderclap headache evaluated by CT and LP 
Journal of the neurological sciences  2008;276(1-2):123-125.
Background
Severe, abrupt onset headache raises concern for aneurysmal subarachnoid hemorrhage (SAH). The current standard work-up is brain CT scan followed by LP if the CT is non-diagnostic in patients with a normal neurological exam. Some have suggested that angiography is also indicated in this common clinical situation. Is evaluation with brain CT and LP for thunderclap headache to rule out SAH sufficient and is angiography needed?
Methods
We systematically searched for studies that followed neurologically-intact patients with thunderclap headache and normal CT and LP for at least 1 year. The primary outcome was SAH. We estimated the proportion of patients who developed SAH and the one-sided upper 95% confidence bound.
Results
Seven studies including 813 patients were identified. None of the patients developed SAH during follow-up (pooled proportion = 0, upper 95% confidence bound = 0.004).
Conclusion
Although our methods have important limitations, we believe this analysis will give clinicians better tools to decide whether or not to pursue further work-up with angiography in patients with thunderclap headache and normal neurological exam, CT, and LP.
doi:10.1016/j.jns.2008.09.019
PMCID: PMC2626143  PMID: 18945447

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