Autonomic Function Testing in Patients with Migraine

SYNOPSIS
Autonomic nervous system function was studied in 62 patients with migraine. The Valsalva maneuver, deep breathing test, sustained handgrip test, orthostatic test and spectral analysis of heart rate variability in the supine and standing positions were performed in a group of 62 patients of both sexes, aged 21 to 50 years, and in an age-matched control group of 45 healthy volunteers.
Heart rate increase during sustained handgrip was significantly reduced in the headache group, when compared to the control group, while the results of the remaining cardiovascular tests did not significantly differ between the control and headache groups. In standing patients, the integrals of middle frequency bands of amplitude spectra were smaller in patients than in controls because the increase induced by standing was smaller in migraine patients. The results in patients with migraine with aura (21 patients) and migraine without aura (41 patients) did not differ significantly from each other. The same was true for the results of the female and male patients.
It is concluded that sympathetic function is impaired in migraine patients.     

Initiating mechanisms of experimentally induced tension-type headache

To elucidate possible myofascial mechanisms of tension-type headache, the effect of 30 min of sustained tooth clenching (10% of maximal EMG-signal) was studied in 58 patients with tension-type headache and in 30 age- and sex-matched controls. Pericranial tenderness, mechanical and thermal pain detection and tolerance thresholds and FMG levels were recorded before and after the clenching procedure. Within 24 h, 69% of patients and 17% of controls developed a tension-type headache. Shortly after clenching, tenderness was increased in the group who subsequently developed headache, whereas tenderness was stable in the group of patients who remained headache free. Mechanical pain thresholds evaluated by pressure algometry remained unchanged in the group which developed headache, whereas thresholds increased in the group which did not develop headache Thermal pain detection and tolerance thresholds remained unchanged in both groups. These findings indicate that, though there may be several different mechanisms of tension-type headache, one of them is sustained muscle contraction. A peripheral mechanism of tension-type headache is therefore possible, whereas a secondary segmental central sensitization seems to be involved in subjects with frequent, tension-type headache. Finally, the increase in pressure pain thresholds in patients who did not develop headache suggested that clenching activated their antinociceptive system, whereas those developing headache were, unable to do so.     

The wavelength of light causing photophobia in migraine and tension-type headache between attacks

OBJECTIVE: To ascertain the wavelength of light that patients with migraine and tension-type headache find uncomfortable between attacks. BACKGROUND: Photophobia is an abnormal perceptual sensitivity to light experienced by most patients with headache during and, also, between attacks. METHODS: We examined the discomfort threshold to light of low, medium, and high wavelengths in a group of patients with migraine (n=21), patients with tension-type headache (n=19), and healthy controls (n=21). RESULTS: The results indicate that the migraine group had significantly lower discomfort thresholds at the low (P=.001) and high (P=.031) wavelengths compared with both the tension-type headache and control groups; the latter two groups had similar average discomfort levels at these two wavelengths. With the medium wavelength, the control group had significantly higher discomfort thresholds than the migraine (P=.002) and tension-type headache (P=.031) groups; the latter two groups had similar discomfort levels at this wavelength. With unfiltered (white) light, the migraine group had the lowest discomfort threshold and the control group the highest (P=.026), whereas the tension-type headache group had an intermediate discomfort threshold. CONCLUSIONS: There were significant differences between migraineurs, patients with tension-type headache, and healthy controls in the wavelengths that are uncomfortable between attacks.     

Adrenergic responses to sustained handgrip in patients with juvenile-onset-type diabetes mellitus.

1. The response of plasma noradrenaline, arterial blood pressure and heart rate to sustained handgrip at 30% of maximal voluntary contraction was studied in patients with long-term juvenile-onset-type diabetes millitus and healthy subjects of comparable age. 2. There was no significant difference between the intensity and duration of handgrip in diabetic patients and healthy subjects. 3. Sustained handgrip produced an increase in plasma concentration of noradrenaline both in diabetic and healthy subjects but the response in the diabetic subjects was significantly less. 4. The increase in systolic blood pressure during handgrip was significantly greater in diabetic subjects than in normal subjects. The increases in diastolic and mean blood pressure did not differ significantky. 5. The increase in heart rate during handgrip was greater in healthy subjects than in diabetic subjects. The response was smaller in diabetic patients with retinopathy than in the patients without retinopathy. 6. The sustained handgrip test may be useful for the diagnosis of abnormal sympathetic nervous system and haemodnynamic responsiveness in diabetic patients.     

Neuropeptide Y in Juvenile Migraine and Tension-Type Headache

SYNOPSIS
Neuropeptide Y (NPY) is widely distributed throughout sympathetic nerve endings where it is co-stored and co-secreted with noradrenaline. It is considered a marker of noradrenergic function. To determine the role of NPY in the pathogenesis of juvenile headache, we determined its plasma levels in two groups of young migraine patients (with and without aura), in a group of episodic tension-type headache patients and in a group of age and sex-matched healthy subjects. Significantly lower plasma levels of NPY were evident in the migraine patients with aura (P<0.001) and, to lesser extent, in the migraine patients without aura (P<0.02), both assessed in the interictal period, with respect to the control group. Plasma NPY levels tended to significantly increase during attacks in migraine patients with aura (P<0.0009). A less evident, though significant increase was also present during attacks in migraine patients without aura (P<0.02). No significant variations were observed between headache-free periods and attacks in tension-type headache patients. Reduced NPY levels in the interictal period can be considered further evidence of the derangement of the sympathetic function in the course of migraine, particularly that with aura. The increase in NPY levels during migraine attacks could be an expression of sympathetic activation, even though the functional status of this system is less efficient.     

Cervical musculoskeletal impairment in frequent intermittent headache. Part 1: Subjects with single headaches

Musculoskeletal disorders are considered the underlying cause of cervicogenic headache, but neck pain is commonly associated with migraine and tension-type headaches. This study tested musculoskeletal function in these headache types. From a group of 196 community-based volunteers with headache, 73 had a single headache classifiable as migraine (n = 22), tension-type (n = 33) or cervicogenic headache (n = 18); 57 subjects acted as controls. Range of movement, manual examination of cervical segments, cervical flexor and extensor strength, the cranio-cervical flexion test (CCFT), cross-sectional area of selected extensor muscles at C2 (ultrasound imaging) and cervical kinaesthetic sense were measured by a blinded examiner. In all but one measure (kinaesthetic sense), the cervicogenic headache group were significantly different from the migraine, tension-type headache and control groups (all P < 0.001). A discriminant function analysis revealed that collectively, restricted movement, in association with palpable upper cervical joint dysfunction and impairment in the CCFT, had 100% sensitivity and 94% specificity to identify cervicogenic headache. There was no evidence that the cervical musculoskeletal impairments assessed in this study were present in the migraine and tension-type headache groups. Further research is required to validate the predictive capacity of this pattern of impairment to differentially diagnose cervicogenic headache.     

Blood pool scintigraphy of the skull in relation to head-down tilt provocation in patients with chronic tension-type headache and controls

OBJECTIVE: To investigate the mechanisms behind the increase of chronic tension-type headache during head-down tilt. BACKGROUND: The pathophysiology of chronic tension-type headache is unknown. DESIGN AND METHODS: Ten patients suffering from chronic tension-type headache and 10 age- and sex-matched controls were studied with respect to pain intensity and alterations in cranial blood volume using planar scintigraphy and radiolabeled autologous erythrocytes before, during, and after head-down tilt, a procedure known to increase chronic tension-type headache. RESULTS: Four of 8 patients with chronic tension-type headache studied had increased cerebrospinal fluid pressure. During head-down tilt, the pain increased significantly in the group with chronic tension-type headache (P <.001) while the procedure did not cause headache in the controls. Blood volume significantly increased extracranially and decreased intracranially in both groups during head-down tilt. The extracranial nasal blood volume was significantly related to the pain experienced by the patients with chronic tension-type headache before and during head-down tilt. CONCLUSIONS: Although the changes in blood volume and, presumably, the increase of intracranial pressure were similar in the patients with chronic tension-type headache and the controls, only the patients experienced pain and pain increase during head-down tilt. This indicates that the pre-head-down tilt conditions must be different in the 2 groups and should be related to increased cerebrospinal fluid pressure/intracranial venous pressure in patients with chronic tension-type headache compared with controls. A difference in central mechanisms may, however, also be of importance for the difference in headache provocation in the 2 groups during head-down tilt.     

Is chronic tension-type headache a vascular headache? The relation between chronic tension-type headache and cranial hemodynamics

Twenty-seven patients with chronic tension-type headache were studied as to end-tidal PCO2, heart rate, mean blood pressure, diameter and blood flow of the common carotid arteries, cranial vascular resistance, and headache intensity at supine rest, after administration of nitroglycerin, and at head down tilt. The results were compared to the results of nitroglycerin and head down tilt provocations in age- and sex-matched controls. During supine rest, no change in chronic tension-type headache occurred. Nitroglycerin and tilting induced significant increase of the headache intensity compared to baseline in patients with chronic tension-type headache (P=0.01 and P<0.05, respectively) in contradistinction to controls who did not develop significant headache. Common carotid artery blood flow changes were similar during nitroglycerin provocations in the two groups, but greater (P<0.05) during head down tilt in patients than in controls. Lumbar cerebrospinal fluid pressure was found to be greater than 20 but less than 26 cm H2O in 45% of the 22 patients studied with chronic tension-type headache. The results indicate that the pain in chronic tension-type headache is related to cranial hemodynamics, presumably to distention of intracranial veins.     

Specificity and Sensitivity of Temporalis ES2 Measurements in the Diagnosis of Chronic Primary Headaches

We have evaluated the specificity and sensitivity of temporalis ES2 measurements for the diagnosis of primary headaches. Ninety-four outpatients diagnosed according to IHS criteria were prospectively included: 25 had chronic tension-type headache (code 2.2.), 15 episodic tension-type headache (code 2.1.), 20 migraine without aura (code 1.1.) and 34 chronic daily headaches with daily analgesics/ergotamine abuse (code 8.2.). In chronic tension-type, the sensitivity of the ES2 test was 84% at the 0.1 and the 0.5 Hz, but only 56% at the 2Hz stimulation rates. Its specificity was 100% at 0.1Hz, 90% at 0.5Hz and 95% at 2Hz compared to migraine; positive predictive values were at similar levels. Sensitivity of ES2 at 0.1 Hz was 67% in episodic tension-type headache, but its positive predictive value versus migraine was excellent. Comparing chronic tension-type headache and analgesic abusers, the specificity and positive predictive value of the ES2 test for diagnosing chronic tension-type headache were less satisfactory (60%) while the negative predictive values, however, remained good (83% at 0.1Hz).
The results confirm that the temporalis ES2 test has a higher diagnostic sensitivity in chronic and episodic tension-type headache, but that it has a high negative predictive value for both types of tension-type headache compared to other primary headaches. For diagnostic purposes, the 0.1Hz stimulation rate seems optimal. The 2Hz stimulation rate is the least sensitive, although it may induce total disappearance of ES2 in up to 40% of patients. ES2 is of limited usefulness for separating chronic tension-type headache and chronic drug-abuse headache, possibly because the latter group comprises both tension-type headache and migraine patients.     

Quality of life of patients with cervicogenic headache: a comparison with control subjects and patients with migraine or tension-type headache

OBJECTIVE: To establish the health-related quality of life of patients with cervicogenic headache and to compare it with a random Dutch sample of control subjects and with patients with migraine without aura or with episodic tension-type headache. METHODS: Thirty-seven patients with cervicogenic headache, 42 patients with episodic tension-type headache, and 39 patients with migraine without aura completed a Medical Outcomes Study 36-Item Short Form questionnaire. RESULTS: Domain scores for "physical functioning" of patients with cervicogenic headache were worse than those of patients with migraine or tension-type headache. Physical functioning scores were lower for patients with tension-type headache than for those with migraine. Migraineurs reported a diminished score for "social functioning" compared to patients with tension-type headache. All Medical Outcomes Study 36-Item Short Form domain scores were significantly lower for patients with cervicogenic headache relative to the control group. CONCLUSIONS: Patients with cervicogenic headache have a quality of life burden that is substantial. Although impairment in the quality of life of patients with cervicogenic headache is comparable to patients with migraine without aura and those with episodic tension-type headache, there are some specific differences.     

帕罗西汀联合安定在预防紧张型头痛临床效果分析

目的探讨和分析神经内科门诊中帕罗西汀联合安定预防紧张型头痛的临床效果。方法随机性选取我院86例紧张型头痛患者分成联合组和对照组。联合组(46例)使用帕罗西汀(30 mg/d)联合安定进行抗焦虑治疗,对照组(40例)使用常规抗抑郁药联合安定治疗。分析对比两组对头痛的疗效和不良反应情况。结果联合组头痛疗效有效率为89.1%,头痛明显缓解,基本没有不良反应;与对照组治疗效果比较,差异均有统计学意义(P<0.05)。结论帕罗西汀联合安定预防和治疗紧张型头痛有显著的疗效,且不良反应少。     

Steady-state visual-evoked potentials in headache: diagnostic value in migraine and tension-type headache patients

We tested the hypothesis that migraine and tension-type headache are separate disorders based on visual evoked potentials. We recruited 120 migraine without aura patients (MwoA), 64 tension-type headache patients (TTH), and 51 healthy controls. We performed discriminant analysis combined with a stepwise selection of predictors. Mean values of the F1 component were significantly increased over Fp1, C3, P4, O2 and O1 electrodes in MwoA and TTH patients compared with normal subjects. Only the control subjects were correctly distinguished. The increased brain response to visual stimulation detected in both MwoA and TTH may suggest a common neuronal dysfunction in the two headache subtypes.     

Serum levels of N-acetyl-aspartate in migraine and tension-type headache

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography–mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.     

beta-Thromboglobulin and 11-dehydrothromboxane B in tension-type headache

Platelet factor 4, beta-thromboglobulin, thromboxane B2, and 11-dehydrothromboxane B2 were investigated in tension-type headache. Ten cases of episodic tension-type headache (mean age 42.5 years), 10 cases of chronic tension-type headache (mean age 45.3 years), and 10 age-matched healthy controls were studied. The platelet factor 4, beta-thromboglobulin, thromboxane B2 and 11-dehydrothromboxane B2 concentrations in the plasma were significantly higher in the episodic tension-type headache group than in the chronic tension-type headache and healthy control groups. Platelets may be involved in episodic tension-type headache.     

Neck flexor muscle fatigue in adolescents with headache: an electromyographic study.

BACKGROUND: Muscular disorders of the neck region may be of importance for the etiology of tension-type headache. However, in adolescents, there are no data on the association between neck muscle fatigue and headache. AIM: To study differences in fatigue characteristics of the neck flexor muscles in adolescents with and without headache. METHODS: A population-based sample of 17-year-old adolescents with migraine-type headache (N=30), tension-type headache (N=29) and healthy controls without headache (N=30) was examined. Surface EMG data were recorded from the sternocleidomastoid (SCM) muscles bilaterally during an isometric neck flexor endurance test. The spectral median frequency (MF) change during the total endurance time (TMF) and the initial time of 30s (IMF) was calculated. The intensity of discomfort in the neck area was assessed with the visual analogue scale (VAS). RESULTS: The rate of decline in TMF of both SCM muscles was significantly increased in the tension-type headache group compared with controls (right SCM, P=0.030, OR 2.0, 95% 1.2-3.7; left SCM, P=0.009, OR 2.5, 95% 1.4-4.9), while no significant differences were found between controls and subjects with migraine. The rate of decline in IMF, the total endurance time (P=0.050), and VAS did not differ significantly among the study groups. CONCLUSIONS: This preliminary finding shows that increased neck flexor muscle fatigue in adolescents seems to be associated with tension-type headache.     

Platelet-rich plasma serotonin levels in tension-type headache and depression

We measured platelet-rich plasma (PRP) serotonin in patients suffering from tension-type headache, before and after treatment with amitriptyline, comparing them with a healthy control group and patients with untreated depression. We evaluated the severity of headache and depression in each group. PRP serotonin levels were higher in patients with headache than in controls and depressed patients. We observed a fall of PRP serotonin in patients with tension-type headache to similar levels after treatment as the depressed group. This fall was correlated with the improvement of headache but not with depression scales. Our data suggest that the rise of platelet serotonin levels in tension-type headache is related to pain and not depression.     

Musculoskeletal abnormalities in chronic headache: a controlled comparison of headache diagnostic groups

The presence of postural, myofascial, and mechanical abnormalities in patients with migraine, tension-type headache, or both headache diagnoses was compared to a headache-free control sample. Twenty-four control subjects were obtained from a convenience sampling and each was matched by age and sex to three patients with headache (one with migraine [with or without aura], one with tension-type headache, and one with diagnoses of both migraine and tension-type headache [combined diagnosis]) who had been previously assessed by a physical therapist at a headache clinic. Physical therapy assessment findings were compared among the four groups.
There was a significant difference in the presence of postural abnormalities between the controls and the patients, with posture abnormalities more likely to be present in those with headache. The patients were also significantly more likely to have active trigger points and trigger points in the neck than were the control subjects. There were no significant group differences identified in the mechanical measures, nor were there any significant differences among the three headache categories. Determination of the clinical significance of these musculoskeletal abnormalities in patients with headache will require the development and testing of further standardized assessments as well as physical therapy treatment programs.     

Platelet 3H ketanserin binding in tension-type headache

OBJECTIVE: The present study was undertaken to investigate the alterations in platelet 5-HT2 receptor binding in patients with tension-type headache. BACKGROUND: Serotonin (5-HT) has an important but complex role in pain modulation. The involvement of serotonin in tension-type headache has been investigated by studying serotonin in peripheral blood, but results have been inconclusive. There are, however, only a few investigations in which the status of platelet serotonin transporters has been studied by 3H imipramine and 3H paroxetine. The present study was undertaken to investigate alterations in platelet 5-HT2A receptors using 3H ketanserin as a ligand. METHODS: Platelet 3H ketanserin binding was studied in 14 patients with tension-type headache and in 15 healthy controls. The binding characteristics, equilibrium dissociation constant and maximal number of binding sites were determined by Scatchard analysis. RESULTS: There was no change in the equilibrium dissociation constant in the patients with headache as compared to the control group, but subgroup analysis revealed that patients with tension-type headache with a headache index of less than 360 had a significantly lower equilibrium dissociation constant as compared to those with a headache index of more than 360; there was a significant correlation between the equilibrium dissociation constant and the headache index. A significant decrease was observed in the maximal number of binding sites in tension-type headache. No correlation was observed between the maximal number of binding sites and age, duration of illness, or headache intensity. CONCLUSIONS: The findings of the present study show that there is a decrease in the number of binding sites of 5-HT2A receptors in some patients with tension-type headache, suggesting postsynaptic serotonergic dysfunction and the involvement of serotonin in that group.     

Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies

In this present thesis I have discussed the epidemiology and possible pathophysiological mechanisms of tension-type headache. A population-based study of 1000 subjects randomly selected from a general population, two clinical studies, and a method study of EMG recordings, were conducted. Tension-type headache was the most prevalent form of headache, with a life-time prevalence of 78% in a general adult population. Thirty percent were affected more than 14 days per year and 3% were chronically affected, i.e. had headache at least every other day. Females were more frequently affected than males, and young subjects more frequently affected than older subjects. Females were more sensitive to mechanical pressure pain and revealed more tenderness from pericranial muscles and tendon insertions than males, and young subjects were more pain-sensitive than older subjects. Significantly higher tenderness in pericranial muscles was found in subjects with tension-type headache compared to migraineurs and to subjects without any experience of headache. Tenderness increased significantly with increasing frequency of tension-type headache in both males and females, whereas no such relation was found for mechanical pain thresholds. The applied EMG methodology was fairly reliable and nonpainful, but due to intersubject variability paired studies should be preferred. Subjects with chronic tension-type headache had slightly increased EMG levels during resting conditions and decreased levels during maximal voluntary contraction compared with headache-free subjects, indicating insufficient relaxation at rest and impaired recruitment at maximal activity. In a subsequent clinical, controlled study, the effect of 30 min of sustained tooth clenching was studied. Within 24 h, 69% of patients and 17% of controls developed a tension-type headache. Shortly after clenching, tenderness was increased in the group who subsequently developed headache, whereas tenderness was stable in the group of patients who remained headache-free, indicating that tenderness might be a causative factor of the headache. Likewise, psychophysical and EMG parameters were studied in 28 patients with tension-type headache, both during and outside of a spontaneous episode of tension-type headache. It was concluded that a peripheral mechanism of tension-type headache is most likely in the episodic subform, whereas a secondary, segmental central sensitization and/or an impaired supraspinal modulation of incoming stimuli seems to be involved in subjects with chronic tension-type headache. Prolonged nociceptive stimuli from myofascial tissue may be of importance for the conversion of episodic into chronic tension-type headache. The author emphasizes that tension-type headache is a multifactorial disorder with several concurrent pathophysiological mechanisms, and that extracranial myofascial nociception may constitute only one of them. The present thesis supplements the understanding of the balance between peripheral and central components in tension-type headache, and thereby, hopefully, leads us to a better prevention and treatment of the most prevalent type of headache.