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1.  Headache in juvenile myoclonic epilepsy 
The Journal of Headache and Pain  2011;12(2):227-233.
The objective of this study was to assess the prevalence of and risk factors for primary headaches in juvenile myoclonic epilepsy (JME). Headache was classified in 75 patients with JME using a questionnaire, and its prevalence was correlated with the literature on the general population and clinical data. Headache was present in 47 patients. Thirty-one had migraine [20 migraine without aura (MO), 11 migraine with aura (MA)]. Fourteen patients with migraine had tension-type headache (TTH) in addition. Sixteen had only TTH. Comparison with the general population revealed a significantly higher prevalence of migraine (RR 4.4), MO (3.6), MA (7.3) and TTH (3.4) in JME. Risk factors for migraine and MO were female gender and for MA family history of migraine in first-degree relatives. Migraine and MA were associated with fairly controlled generalized tonic clonic seizures, MO with absences. Together with its strong genetic background, JME appears to be an attractive homogenous subtype of epilepsy for genetic research on migraine.
doi:10.1007/s10194-011-0332-6
PMCID: PMC3072490  PMID: 21437711
Juvenile myoclonic epilepsy; Headache; Migraine; Prevalence
2.  Headache in juvenile myoclonic epilepsy 
The Journal of Headache and Pain  2011;12(2):227-233.
The objective of this study was to assess the prevalence of and risk factors for primary headaches in juvenile myoclonic epilepsy (JME). Headache was classified in 75 patients with JME using a questionnaire, and its prevalence was correlated with the literature on the general population and clinical data. Headache was present in 47 patients. Thirty-one had migraine [20 migraine without aura (MO), 11 migraine with aura (MA)]. Fourteen patients with migraine had tension-type headache (TTH) in addition. Sixteen had only TTH. Comparison with the general population revealed a significantly higher prevalence of migraine (RR 4.4), MO (3.6), MA (7.3) and TTH (3.4) in JME. Risk factors for migraine and MO were female gender and for MA family history of migraine in first-degree relatives. Migraine and MA were associated with fairly controlled generalized tonic clonic seizures, MO with absences. Together with its strong genetic background, JME appears to be an attractive homogenous subtype of epilepsy for genetic research on migraine.
doi:10.1007/s10194-011-0332-6
PMCID: PMC3072490  PMID: 21437711
Juvenile myoclonic epilepsy; Headache; Migraine; Prevalence
3.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
4.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
5.  Headache-related work disability in young men 
Based on the knowledge that migraine and tension-type headache (TTH) are associated with reduced effectiveness at work and impairment of function in social roles, we studied the different influences that these primary headaches have on work in a specialized and homogeneous population. We studied 140 consecutive male patients, aged 18–35 years, attending an outpatient headache clinic at the Neurology Department of an Army General Hospital. Using International Headache Society (IHS) criteria, 60 patients were diagnosed with migraine and 80 patients with TTH. The impact of headache on work during the preceding 2 months was assessed using a selfadministered questionnaire, based on MIDAS. Two parameters of work disability were derived: the lost work days (LWD) and the days with reduced effectiveness while being at work (REWD). Of 142 LWD due to headaches, 95 (66.9%) were attributable to migraine and 47 (33.1%) to TTH (plt;0.001). Of 490 REWD, 120 (24.4%) were reported by migraineurs and 370 (75.5%) by TTH patients (p<0.001). The number of LWD in migraine was significantly higher (p<0.001) than in TTH group; the number of REWD in TTH group was significantly higher (p<0.001) than in migraine group. Pain intensity was the main factor contributing to disability at work in migraine group (plt;0.001), in contrast with TTH group in which there was no statistical difference (p>0.05) between pain intensity and duration of pain. Patients with migraine were much more likely to report actual lost workdays because of headache whereas TTH was responsible for the largest proportion of decreased work effectiveness. Assessing headache severity with an objective method (i.e. questionnaire) may improve headache care and lead to proper treatment decisions. Special attention must be given to particular populations.
doi:10.1007/s101940200023
PMCID: PMC3613233
Key words Migraine; Tension-type headache; Worn effectiveness
6.  Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study 
The Journal of Headache and Pain  2012;13(7):521-529.
This prospective study investigated the effectiveness of a three-tier modularized out- and inpatient multidisciplinary integrated headache care program. N = 204 patients with frequent headaches (63 migraine, 11 tension-type headache, 59 migraine + tension-type headache, 68 medication-overuse headache and 3 with other primary headaches) were enrolled. Outcome measures at baseline, 6- and 12-month follow-ups included headache frequency, Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), standardized headache diary and a medication survey. Mean reduction in headache frequency was 5.5 ± 8.5 days/month, p < 0.001 at 6 months’ follow-up and 6.9 ± 8.3 days/month, p < 0.001 after 1 year. MIDAS decreased from 53.0 ± 60.8 to 37.0 ± 52.4 points, p < 0.001 after 6 months and 34.4 ± 53.2 points, p < 0.001 at 1 year. 44.0 % patients demonstrated at baseline an increased HAD-score for anxiety and 16.7 % of patients revealed a HAD-score indicating a depression. At the end of treatment statistically significant changes could be observed for anxiety (p < 0.001) and depression (p < 0.006). The intake frequency of attack-aborting medication decreased from 10.3 ± 7.3 days/month at admission to 4.7 ± 4.1 days/month, p < 0.001 after 6 months and reached 3.8 ± 3.5 days/month, p < 0.001 after 1 year. At baseline 37.9 % of patients had experience with non-pharmacological treatments and 87.0 % at 12-month follow-up. In conclusion, an integrated headache care program was successfully established. Positive health-related outcomes could be obtained with a multidisciplinary out- and inpatient headache treatment program.
doi:10.1007/s10194-012-0469-y
PMCID: PMC3444539  PMID: 22790281
Integrated; Care; Multidisciplinary treatment program; Outcome study; Headache-related disability; Headache-related quality of life; Chronic headache
7.  Association between lifestyle factors and headache 
The Journal of Headache and Pain  2011;12(2):147-155.
Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-010-0286-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-010-0286-0
PMCID: PMC3072498  PMID: 21222138
Migraine; Tension-type headache; Alcohol consumption; Body mass index; Physical activity; Smoking
8.  Association between lifestyle factors and headache 
The Journal of Headache and Pain  2011;12(2):147-155.
Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-010-0286-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-010-0286-0
PMCID: PMC3072498  PMID: 21222138
Migraine; Tension-type headache; Alcohol consumption; Body mass index; Physical activity; Smoking
9.  Drug and Nondrug Treatment in Tension-type Headache 
Tension-type headache (TTH) is a common primary headache with tremendous socioeconomic impact. Establishment of an accurate diagnosis is important before initiation of any treatment. Nondrug management is crucial. Information, reassurance and identification of trigger factors may be rewarding. Psychological treatments with scientific evidence for efficacy include relaxation training, EMG biofeedback and cognitive-behavioural therapy. Physical therapy and acupuncture are widely used, but the scientific evidence for efficacy is sparse. Simple analgesics are the mainstays for treatment of episodic TTH. Combination analgesics, triptans, muscle relaxants and opioids should not be used, and it is crucial to avoid frequent and excessive use of simple analgesics to prevent the development of medication-overuse headache. The tricyclic antidepressant amitriptyline is drug of first choice for the prophylactic treatment of chronic TTH. The efficacy is modest and treatment is often hampered by side effects. Thus, treatment of frequent TTH is often difficult and multidisciplinary treatment strategies can be useful. The development of specific nonpharmacological and pharmacological managements for TTH with higher efficacy and fewer side effects is urgently needed. Future studies should also examine the relative efficacy of the various treatment modalities; for example, psychological, physical and pharmacological treatments, and clarify how treatment programs should be optimized to best suit the individual patient.
doi:10.1177/1756285609102328
PMCID: PMC3002628  PMID: 21179525
tension-type headache; treatment; amitriptyline
10.  Potentially traumatic interpersonal events, psychological distress and recurrent headache in a population-based cohort of adolescents: the HUNT study 
BMJ Open  2013;3(7):e002997.
Objectives
Recurrent headache co-occurs commonly with psychological distress, such as anxiety or depression. Potentially traumatic interpersonal events (PTIEs) could represent important precursors of psychological distress and recurrent headache in adolescents. Our objective was to assess the hypothesised association between exposure to PTIEs and recurrent migraine and tension-type headache (TTH) in adolescents, and to further examine the potential impact of psychological distress on this relationship.
Design
Population-based, cross-sectional cohort study. The study includes self-reported data from youth on exposure to potentially traumatic events, psychological distress and a validated interview on headache.
Setting
The adolescent part of the Nord-Trøndelag Health Study 2006–2008 (HUNT), conducted in Norway.
Participants
A cohort of 10 464 adolescents were invited to the study. Age ranged from 12 to 20 years. The response rate was 73% (7620), of whom 50% (3832) were girls.
Main outcome measures
Data from the headache interview served as the outcome. Recurrent headache was defined as headache recurring at least monthly during the past year, and was subclassified into monthly, weekly and daily complaints. Subtypes were classified as TTH, migraine, migraine with TTH and/or non-classifiable headache, in accordance with the International Classification of Headache Disorders criteria, second edition.
Results
Multiple logistic regression analysis, adjusted for sociodemographics, showed consistently significant associations between exposure to PTIEs and recurrent headache, regardless of the frequency or subtype of headache. Increasing exposure to PTIEs was associated with higher prevalence of recurrent headache, indicating a dose–response relationship. The strength of associations between exposure to PTIEs and all recurrent headache disorders was significantly attenuated when psychological distress was entered into the regression equation.
Conclusions
The empirical evidence of a strong and cumulative relationship between exposure to PTIEs, psychological distress and recurrent headache indicates a need for the integration of somatic and psychological healthcare services for adolescents in the prevention, assessment and treatment of recurrent headache. Prospective studies are needed.
doi:10.1136/bmjopen-2013-002997
PMCID: PMC3731723  PMID: 23901028
Public Health
11.  Comparison of oxidative stress among migraineurs, tension-type headache subjects, and a control group 
Background:
A primary headache, particularly migraine, is associated with oxidative stress during the attack. However, data regarding the interictal state in migraineurs and in those with tension-type headache (TTH) is limited.
Objectives:
(1) To assess the oxidative stress in migraineurs and TTH subjects in between the episodes and (2) to see if there is a difference in the degree of oxidative stress in the different subtypes of migraine and TTH.
Materials and Methods:
Fifty migraineurs, 50 patients with TTH, and 50 control subjects were included in this study after screening for the exclusion criteria. Diagnosis of headache was made according to the International Classification of Headache Disorders (ICHD)-2 criteria. A venous blood sample was collected from the antecubital vein at least 3 days after the last attack of headache. The sample was centrifuged immediately and the plasma was stored at –70°C. The ferric reducing activity of plasma (FRAP) and the malondialdehyde (MDA) levels were assessed using colorimetric methods. Statistical analysis was done with the help of SPSS for Windows, v 11.0. One way ANOVA with post hoc Tukey test, independent sample t test, univariate regression, and multivariate regression analysis were done as indicated.
Results:
Migraineurs had higher values of MDA and FRAP than the subjects in the other two groups (P<0.001). No difference was observed between the TTH group and the control group. FRAP levels were significantly higher in subjects who had mixed migraine (migraine with aura and without aura) as compared to those with only migraine without aura (mean difference 196.1; 95% CI = 27.3 to 364.9; P = 0.01). Similarly, oxidative stress was significantly higher in patients with episodic TTH as compared to those with chronic TTH (FRAP t = 3.16; P = 0.003 and MDA t = 2.75; P = 0.008).
Conclusions:
This study suggests that oxidative stress continues even between headache episodes in migraineurs but not in those with TTH. This could probably be consequent to the different pathophysiological mechanisms of TTH and migraine.
doi:10.4103/0972-2327.56316
PMCID: PMC2824933  PMID: 20174497
Migraine; tension type headache; oxidative stress; ferric reducing activity of plasma; malondialdehyde
12.  Reliability and Validity of the Migraine Disability Assessment Scale among Migraine and Tension Type Headache in Iranian Patients 
BioMed Research International  2014;2014:978064.
Introduction. MIDAS is a valid and reliable short questionnaire for assessment of headache related disability. Linguistic validation of Persian MIDAS and assessment of psychometric properties between tension type headache (TTH) and migraine were the aims of this study. Methods. Patients with migraine or TTH were included. At the first visit, we administered a headache symptom questionnaire, MIDAS, and SF-36. Patients filled out MIDAS in second and third visit within three and eight weeks after base line visit. Internal consistency (Cronbach α) and test-retest reproducibility (Spearman correlation coefficient) were used to assess reliability. Convergent validity and MIDAS capability to differentiate between chronic and episodic headaches (migraine and TTH) were also assessed. Results. The 267 participants had episodic migraine (EM-64%), chronic migraine (CM-13.5%), episodic TTH (ETTH-13.5%), and chronic TTH (CTTH-9). Internal consistency reliability was 0.8 for the entire sample, 0.72 for TTH, and 0.82 for migraine. Test-retest reliability for all questions between visit 1 and visit 2 varied from 0.54 to 0.71. Convergent validity was assessed using SF-36 as an external referent. Patients with episodic headaches (EM and ETTH) had significantly lower MIDAS scores than chronic headaches (CM and CTTH). Conclusion. Persian MIDAS is a valid and reliable questionnaire for migraine and TTH that can differentiate between episodic headache and chronic headache.
doi:10.1155/2014/978064
PMCID: PMC3914354  PMID: 24527462
13.  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
14.  Prevalence of headache in an elderly population: attack frequency, disability, and use of medication 
OBJECTIVES—To assess the 1 year prevalence of tension-type headache (TTH), migraine headache (MH), and chronic daily headache (CDH), as well as of headache in general in a rural elderly population.
METHODS—A door to door two phase survey was carried out on all elderly (⩾65 years) residents in three villages in central Italy. Participants completed a standardised headache questionnaire and underwent a clinical evaluation by a neurologist. Headache diagnosis was made according to the classification of the International Headache Society, with minor modifications for the classification of patients with MH with⩾15 attacks/month.
RESULTS—Eight hundred and thirty three (72.6%) of the 1147 eligible persons completed the study protocol. One year prevalence rates were respectively 44.5% for TTH, 11.0% for MH, 2.2% for symptomatic headaches, and 0.7% for the remaining types of headache. The prevalence of headache in general was 51.0% because 62 residents had both TTH and MH attacks. Prevalence rates of patients with headache were higher in women than men (62.1% and 36.6% respectively) and decreased steadily with age for the 65-74, 75-84, and 85-96 age groups (56.7%, 45.2% and 26.1% respectively). Prevalence rates were 20.4% for patients with moderate to severe attacks, 18.0% for those with ⩾1 attacks a month, and 4.4% for those with CDH. Of the 425 with headache 52 (12.2%) had not taken any drugs for their attacks in the previous year, 195 (45.9%) had taken them regularly, and 178 (41.9%) had taken them only when the headache pain interfered with activities that could not be postponed. Medication overuse was reported by 37.8% of patients with CDH with higher proportions for transformed migraine than for patients with chronic TTH (69.2% and 23.8% respectively, p=0.009)
CONCLUSIONS—A consistent proportion of elderly people have primary headaches and consultation with a specialist is particularly recommended for patients with moderate or severe attacks, or with CDH.


doi:10.1136/jnnp.70.3.377
PMCID: PMC1737286  PMID: 11181862
15.  Evaluating integrated headache care: a one-year follow-up observational study in patients treated at the Essen headache centre 
BMC Neurology  2011;11:124.
Background
Outpatient integrated headache care was established in 2005 at the Essen Headache Centre in Germany. This paper reports outcome data for this approach.
Methods
Patients were seen by a neurologist for headache diagnosis and recommendation for drug treatment. Depending on clinical needs, patients were seen by a psychologist and/or physical therapist. A 5-day headache-specific multidisciplinary treatment programme (MTP) was provided for patients with frequent or chronic migraine, tension type headache (TTH) and medication overuse headache (MOH). Subsequent outpatient treatment was provided by neurologists in private practice.
Results
Follow-up data on headache frequency and burden of disease were prospectively obtained in 841 patients (mean age 41.5 years) after 3, 6 and 12 months. At baseline mean headache frequency was 18.1 (SD = 1.6) days per month, compared to measurement at 1 year follow-up a mean reduction of 5.8 (SD = 11.9) headache days per month was observed in 486 patients (57.8%) after one year (TTH patients mean: -8.5 days per month; migraine mean: -3.2 days per month, patients with migraine and TTH mean: -5.9 days per month). A reduction in headache days ≥ 50% was observed in 306 patients (36.4%) independent of diagnosis, while headache frequency remains unchanged in 20.9% and increase in 21.3% of the patient.
Conclusion
Multidisciplinary outpatient headache centres offer an effective way to establish a three-tier treatment offer for difficult headache patients depending on clinical needs.
doi:10.1186/1471-2377-11-124
PMCID: PMC3203041  PMID: 21985562
16.  Cerebrovascular reactivity during the Valsalva maneuver in migraine, tension-type headache and medication overuse headache  
Functional Neurology  2012;26(4): 223 - 227 .
Summary
The aim of this study was to investigate, by means of transcranial Doppler ultrasound (TCD), cerebrovascular reactivity during the Valsalva maneuver (VM) during the headache-free interval in patients with migraine (M), migraine plus tension-type headache (M+TTH), and migraine plus medication overuse headache (M+MOH). A total of 114 patients (n=60 M, n=38 M+TTH, n=16 M+MOH) and n=60 controls were investigated; diagnoses were made according to the International Headache Society criteria. All subjects underwent TCD monitoring and, simultaneously, non-invasive assessment of arterial blood pressure and end-tidal CO 2 . Two indices were determined: the cerebrovascular Valsalva ratio (CVR) was calculated as the maximum end-diastolic flow velocity acceleration during the late straining phase of the VM [cm/s 2 ] and the centroperipheral Valsalva ratio (CPVR) was defined as the quotient of CVR to the concomitant arterial blood pressure acceleration [cm/mmHg × s].
The dynamic cerebrovascular autoregulatory response to the VM, measured as CVR, was increased in patients with M and M+TTH compared to age-matched healthy subjects. By contrast, CPVR (i.e. the quotient of the cerebrovascular to the peripheral autonomic response), was increased in M patients compared to healthy subjects and all other headache conditions tested.
Cerebrovascular autoregulatory response during the VM was increased in M patients compared to age-matched normal healthy subjects, indicating a disturbed autonomic control of cerebral vasoreactivity. The CPVR seems to be a sensitive parameter for distinguishing between M patients and M+TTH or M+MOH patients.
PMCID: PMC3814561  PMID: 22364943
cerebral autoregulation ;  cerebral vasoreactivity ;  migraine ;  transcranial Doppler ;  Valsalva maneuver
17.  Clinical features of headache patients with fibromyalgia comorbidity 
The Journal of Headache and Pain  2011;12(6):629-638.
Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
doi:10.1007/s10194-011-0377-6
PMCID: PMC3208047  PMID: 21847547
Primary headache; Fibromyalgia; Comorbidity
18.  Clinical features of headache patients with fibromyalgia comorbidity 
The Journal of Headache and Pain  2011;12(6):629-638.
Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tension-type headache main group (35%, p < 0.0001) and chronic tension-type headache subtype (44.3%, p < 0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p < 0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.
doi:10.1007/s10194-011-0377-6
PMCID: PMC3208047  PMID: 21847547
Primary headache; Fibromyalgia; Comorbidity
19.  The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect 
Background and purpose
Anxiety is the most important precipitating factor of migraine attacks, and more than half of migraineurs have coexisting anxiety disorders. Paroxetine, an antidepressant, is one of the selective serotonin reuptake inhibitors (SSRIs) that has an anxiolytic effect, and is also known to be effective for migraine prophylaxis. The aim of this study was to determine the role of the anxiolytic effect of paroxetine on the prevention of migraine.
Methods
This study investigated migraineurs with a general anxiety disorder who visited the neurological clinic. The following efficacy variables were assessed at baseline and after taking paroxetine (20 for 12 weeks: headache frequency, Hamilton Anxiety Rating Scale (HAM-A), Headache Management Self-Efficacy Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between the headache responsiveness to paroxetine and improvement in anxiety levels was analyzed.
Results
Twenty-four patients (aged 54.96±12.09 years, mean±SD) were included in this study. Paroxetine reduced headache frequency by 49.1% within 12 weeks (p<0.05 vs baseline). HAM-A and HMSE scores also showed an improvement, whereas there was no significant change in HDI score. The baseline HAM-A scores did not differ between paroxetine responders and nonresponders. In addition, the improvement in HAM-A score was not correlated with the reduction in headache frequency.
Conclusions
Paroxetine decreased the headache frequency and reduced anxiety levels. However, the anxiolytic effect of paroxetine was not correlated with the migraine prevention effect. These observation indicate that the anxiolytic effect of paroxetine does not contribute strongly to its prophylactic effect on migraine frequency in migraineurs with anxiety disorder.
doi:10.3988/jcn.2006.2.4.246
PMCID: PMC2854974  PMID: 20396527
Paroxetine; Migraine; Anxiety disorder; Headache frequency
20.  Primary Headache Disorders at a Tertiary Health Facility in Lagos, Nigeria: Prevalence and Consultation Patterns 
BioMed Research International  2014;2014:782915.
Background. Primary headaches are underdiagnosed and undertreated, with a significant impact on social activities and work. Aim. To determine the last-year prevalence and health care utilization pattern of primary headaches at a tertiary centre. Methods. A cross-sectional study was carried out amongst staff of the Lagos State University Teaching Hospital in Lagos, Nigeria. 402 staff members were selected by simple random sampling and administered a detailed structured headache assessment questionnaire. Migraine and tension-type headache were diagnosed according to the criteria of the International Headache Society (2004). Results. The participants comprised 168 males and 234 females. The mean age was 36.9 ± 7.9 years. The overall headache prevalence was 39.3% with female predominance (P < 0.0001). Tension-type headache was the most prevalent at 72.8% and migraine at 18.9%. Unclassifiable headache constituted 8.2%. Migraine headache showed female preponderance (P = 0.000). 80.4% of participants did not seek medical consultation compared with 19.6% who did (P = 0.000). Of the latter, 83.9% consulted the general practitioner (GP), whilst 16.1% consulted the neurologist. Conclusions. Primary headache prevalence is high in our population. It is not recognised as that requiring care by most of the staff of this tertiary health facility; thus education is required to increase health care utilization.
doi:10.1155/2014/782915
PMCID: PMC3920920  PMID: 24587991
21.  The validity of questionnaire-based diagnoses: the third Nord-Trøndelag Health Study 2006–2008 
The Nord-Trøndelag Health Study (HUNT 3) performed in 2006–2008 is a replication of the cross-sectional survey from 1995 to 1997 (HUNT 2). The aim of the present study was to assess the sensitivity and specificity of questionnaire-based headache diagnoses using a personal interview by a neurologist as a gold standard. For the questionnaire-based status as headache sufferer, a sensitivity of 88%, a specificity of 86%, and a kappa statistic of 0.70 were found. Chronic headache, chronic tension-type headache (TTH), and medication overuse headache (MOH) were diagnosed with a specificity of ≥99%, and a kappa statistic of ≥0.73. Lower figures were found for the diagnoses of migraine and TTH. For individuals with headache ≥1 day per month, a sensitivity of 58% (migraine) and 96% (TTH), a specificity of 91 and 69%, and a kappa statistic of 0.54 and 0.44 were found, respectively. The specificity for migraine with aura was 95%. In conclusion, the HUNT 3-questionnaire is a valid tool for identifying headache sufferers, and diagnosing patients with chronic headache, including chronic TTH and MOH. The more moderate sensitivity for migraine and TTH makes the questionnaire-based diagnoses of migraine and TTH suboptimal for determining the prevalence. However, the high specificity of the questionnaire-based diagnosis of migraine, in particular for migraine with aura, makes the questionnaire a valid tool for diagnosing patients with migraine for genetic studies.
doi:10.1007/s10194-009-0174-7
PMCID: PMC3452179  PMID: 19946790
Headache; Migraine; Questionnaire; Survey; Population
22.  Trigger factors of migraine and tension-type headache: experience and knowledge of the patients 
The Journal of Headache and Pain  2006;7(4):188-195.
The objective was to examine potential trigger factors of migraine and tension-type headache (TTH) in clinic patients and in subjects from the population and to compare the patients’ personal experience with their theoretical knowledge. A cross-sectional study was carried out in a headache centre. There were 120 subjects comprising 66 patients with migraine and 22 with TTH from a headache outpatient clinic and 32 persons with headache (migraine or TTH) from the population. A semistructured interview covering biographic data, lifestyle, medical history, headache characteristics and 25 potential trigger factors differentiating between the patients’ personal experience and their theoretical knowledge was used. The most common trigger factors experienced by the patients were weather (82.5%), stress (66.7%), menstruation (51.4%) and relaxation after stress (50%). The vast majority of triggers occurred occasionally and not consistently. The patients experienced 8.9±4.3 trigger factors (range 0–20) and they knew 13.2±6.0 (range 1–27). The number of experienced triggers was smallest in the population group (p=0.002), whereas the number of triggers known did not differ in the three study groups. Comparing theoretical knowledge with personal experience showed the largest differences for oral contraceptives (65.0 vs. 14.7%, p<0.001), chocolate (61.7 vs. 14.3%, p>0.001) and cheese (52.5 vs. 8.4%, p<0.001). In conclusion, almost all trigger factors are experienced occasionally and not consistently by the majority of patients. Subjects from the population experience trigger factors less often than clinic patients. The difference between theoretical knowledge and personal experience is largest for oral contraceptives, chocolate and cheese.
doi:10.1007/s10194-006-0305-3
PMCID: PMC3476072  PMID: 16897622
Migraine; Tension-type headache; Weather; Stress; Menstruation
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.  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
25.  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

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