Cluster Headache Impact Questionnaire (CHIQ) – a short measure of cluster headache related disability

Background Cluster headache (CH) is a severe, highly disabling primary headache disorder. However, there is little research on CH-related disability, and most of it is based on non CH-specific questionnaires. The aim of this study was to develop a short, CH-specific disability questionnaire. Methods The 8-item Cluster Headache Impact Questionnaire (CHIQ) was developed based on a literature review and patient and expert interviews. The questionnaire was tested in 254 CH patients (171 males; 47.5 ± 11.4 years; 111 chronic CH, 85 active episodic CH, 52 episodic CH in remission) from our tertiary headache center or from a German support group. Results Reliability and validity of the CHIQ was evaluated in active episodic and chronic CH patients ( n = 196). Internal consistency (Cronbach’s α = 0.88) and test-retest reliability (ICC 0.91, n = 41) were good. Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test (HIT-6, r = 0.58, p < 0.001), subscales of the depression, anxiety and stress scales (DASS, r = 0.46–0.62; p < 0.001) and with CH attack frequency ( r = 0.41; p < 0.001). CHIQ scores significantly differentiated between chronic CH (25.8 ± 6.5), active episodic CH (23.3 ± 6.9) and episodic CH patients in remission (13.6 ± 11.9, p < 0.05 for all 3 comparisons). Conclusions The CHIQ is a short, reliable, valid, and easy to administer measure of CH-related disability, which makes it a useful tool for clinical use and research

Test-retest reliability of visual-evoked potential habituation

Objective Habituation of visual-evoked potentials (VEPs) is typically described as deficient interictally in migraine patients, supposedly indicating altered cortical excitability. Use of this parameter for monitoring changes over time, e.g. under treatment, requires demonstration of test-retest reliability. Methods VEPs were recorded interictally in 41 episodic migraine patients and 40 controls. N75-P100 amplitudes were measured over six consecutive blocks of 75 VEPs each. Amplitude regression slopes and block ratios were used to quantify VEP habituation. Test-retest reliability was assessed over 15 minutes and two to three weeks. Results Controls showed significantly more negative VEP habituation slopes than migraine patients (-0.210.40 vs. 0.04 +/- 0.46 mu V/block, p<0.05). Results were similar for block ratios, though, in the migraine group, VEP habituation significantly increased from test to two- to three-week retest (p<0.05). In addition, VEP habituation test-retest correlations were mostly poor both in migraine patients and controls (intraclass correlation coefficients, 15 minutes: -0.13 to 0.30, two to three weeks: 0.07 to 0.59). Conclusions Deficient VEP habituation in migraine was confirmed. However, the test-retest reliability of VEP habituation was rather weak. Therefore, we suggest that VEP habituation should be used for evaluation of cortical excitability under treatment only at the group level and only when a control group with sham treatment is included

Magnetic suppression of perceptual accuracy is not reduced in episodic migraine without aura

Background: Altered cortical excitability is thought to be part of migraine pathophysiology. Reduced magnetic suppression of perceptual accuracy (MSPA) has been found in episodic migraine with aura and in chronic migraine, and has been interpreted as reduced inhibition of the occipital cortex in these migraine subtypes. Results are less clear for episodic migraine without aura. In the present study we compared MSPA between 24 healthy controls and 22 interictally measured episodic migraine patients without aura. In addition, we investigated test-retest reliability in 33 subjects (24 controls, 9 migraine). Findings: Visual accuracy was assessed by letter recognition and modulated by transcranial magnetic stimulation delivered to the occipital cortex at different intervals to the letter presentation (40, 100 and 190 ms). The results confirm suppression of visual accuracy at the 100 ms interval (p &lt; 0.001), but there were no significant group differences (percentage of correctly recognized letters, control: 36.1 +/- 36.2; migraine: 44.0 +/- 32.3, p = 0.44). Controls and migraine patients were pooled for assessment of test-retest reliability (n = 33). Levels of suppression at 100 ms were similar at test (percentage of correctly recognized letters: 42.3 +/- 32.6) and retest (41.9 +/- 33.8, p = 0.90) and test-retest correlations were good (r = 0.82, p &lt; 0.001). Conclusions: The results demonstrate that occipital cortex inhibition as assessed with MSPA is not reduced in episodic migraine without aura. This suggests a larger role of occipital cortex excitability in episodic migraine with aura and in chronic migraine compared to episodic migraine without aura. Test-retest reliability of MSPA was good

Psychological factors associated with headache frequency, intensity, and headache-related disability in migraine patients

BACKGROUND Several psychological cofactors of migraine have been identified, but relationships to different headache parameters (e.g., headache frequency vs. headache-related disability) are only incompletely understood. METHODS We cross-sectionally assessed 279 migraine patients at their first presentation at our tertiary headache center. We obtained headache and acute medication frequency, pain intensity, the Migraine Disability Assessment Scale (MIDAS), and the Pain Disability Index (PDI) as headache-related outcomes as well as scores of the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), Pain-Related Control Scale (PRCS), and Avoidance Endurance Questionnaire (AEQ) as psychological factors. RESULTS Linear regression models revealed the highest associations of the psychological factors with the PDI (adjusted R2 = 0.296, p < 0.001, independent predictors: PCS, AEQ social avoidance, depression) followed by the MIDAS (adjusted R2 = 0.137, p < 0.001, predictors: depression, AEQ social avoidance) and headache frequency (adjusted R2 = 0.083, p < 0.001, predictors: depression, AEQ humor/distraction). Principal component analysis corroborated that psychological factors were preferentially associated with the PDI, while the MIDAS loaded together with headache frequency. CONCLUSION Our results suggest that psychological factors are more strongly associated with the subjective degree of headache-related disability measured by the PDI than with the days with disability (MIDAS) or the more objective parameter of headache frequency. This once again highlights the need for comprehensive assessment of migraine patients with different headache parameters and the need for considering psychological treatment, especially in patients with high disability

Test-retest reliability of visual-evoked potential habituation

Objective Habituation of visual-evoked potentials (VEPs) is typically described as deficient interictally in migraine patients, supposedly indicating altered cortical excitability. Use of this parameter for monitoring changes over time, e.g. under treatment, requires demonstration of test-retest reliability. Methods VEPs were recorded interictally in 41 episodic migraine patients and 40 controls. N75-P100 amplitudes were measured over six consecutive blocks of 75 VEPs each. Amplitude regression slopes and block ratios were used to quantify VEP habituation. Test-retest reliability was assessed over 15 minutes and two to three weeks. Results Controls showed significantly more negative VEP habituation slopes than migraine patients (-0.210.40 vs. 0.04 +/- 0.46 mu V/block, p<0.05). Results were similar for block ratios, though, in the migraine group, VEP habituation significantly increased from test to two- to three-week retest (p<0.05). In addition, VEP habituation test-retest correlations were mostly poor both in migraine patients and controls (intraclass correlation coefficients, 15 minutes: -0.13 to 0.30, two to three weeks: 0.07 to 0.59). Conclusions Deficient VEP habituation in migraine was confirmed. However, the test-retest reliability of VEP habituation was rather weak. Therefore, we suggest that VEP habituation should be used for evaluation of cortical excitability under treatment only at the group level and only when a control group with sham treatment is included

The Contribution of Psychological Factors to Inter-Individual Variability in Conditioned Pain Modulation Is Limited in Young Healthy Subjects

Conditioned pain modulation (CPM) describes the decrease in pain perception of a test stimulus (TS) when presented together with a heterotopic painful conditioning stimulus (CS). Inter-individual differences in CPM are large and have been suggested to reflect differences in endogenous pain modulation. In a previous analysis, we demonstrated that in young, healthy participants, inter-individual differences account for about one-third of CPM variance, with age and sex together explaining only 1%. Here, we investigated if psychological factors explain significant amounts of inter-individual variance in CPM. Using the same dataset as before, we performed both cross-sectional (n = 126) and repeated measures (n = 52, 118 observations) analysis and the corresponding variance decompositions, using results of psychological questionnaires assessing depression, trait anxiety and pain catastrophizing. Psychological factors did not significantly predict CPM magnitude, neither directly nor when interactions with the CPM paradigm were assessed;however, the interaction between depression and the paradigm approached significance. Variance decomposition showed that the interaction between depression and the CPM paradigm explained an appreciable amount of variance (3.0%), but this proportion seems small when compared to the residual inter-individual differences (35.4%). The main effects of the psychological factors and the interactions of anxiety or catastrophizing with the CPM paradigm are explained at <0.1% each. These results show that the contribution of psychological factors to inter-individual CPM differences in healthy participants is limited and that the large inter-individual variability in the CPM effect remains largely unexplained

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents

A Randomized Sham‐Controlled Cross‐Over Study on the Short‐Term Effect of Non‐Invasive Cervical Vagus Nerve Stimulation on Spinal and Supraspinal Nociception in Healthy Subjects

Objective The aim of the present study was to test the effects of vagus nerve stimulation (VNS) on the descending pain inhibition, quantified by the nociceptive flexor (RIII) reflex and the conditioned pain modulation (CPM) paradigm, and on supraspinal nociceptive responses, assessed by pain intensity and unpleasantness ratings and late somatosensory evoked potentials (SEPs), in healthy subjects. Background Non‐invasive vagus nerve stimulation (nVNS) showed promising effects on headache and pain treatment. Underlying mechanisms are only incompletely understood but may include the activation of the descending pain inhibitory system and/or the modification of emotional responses to pain. Methods Twenty‐seven adult, healthy, and pain‐free subjects participated in this double‐blind cross‐over study conducted at a university research center. They received 4 minutes of cervical nVNS or sham stimulation in randomized order. RIII reflexes, pain ratings, and SEPs were assessed before, during, and 5, 15, 30, and 60 minutes after nVNS/sham stimulation, followed by CPM testing. The primary outcome was the nVNS effect on the RIII reflex size. Three subjects were excluded after the preparatory session (before randomization), 1 subject was excluded after outlier analysis, leaving 23 for analysis. Results RIII reflex areas were 917.1 ± 563.8 µV × ms (mean ± SD) before, 952.4 ± 467.4 µV × ms during and 929.2 ± 484.0 µV × ms immediately after nVNS and 858.4 ± 489.2 µV × ms before, 913.9 ± 539.7 µV × ms during and 862.4 ± 476.0 µV × ms after sham stimulation, revealing no differences between the immediate effects of nVNS and sham stimulation (F [3,66] = 0.67, P = .574). There also were no effects of nVNS over sham on RIII reflex areas up to 60 minutes after nVNS (F [1.7,37.4] = 1.29, P = .283). Similarly, there was no statistically significant effect of nVNS on pain intensity ratings and thresholds, RIII reflex thresholds, late SEP amplitudes, and the CPM effect, compared to sham. Pain unpleasantness ratings statistically significantly decreased from 4.4 ± 2.4 (NRS 0‐10) to 4.1 ± 2.5 during nVNS compared to sham stimulation (F [1,22] = 8.74, P = .007), but there were no longer lasting effects (5‐60 minutes after stimulation). Conclusions The present study does not support an acute effect of nVNS on descending pain inhibition, pain intensity perception or supraspinal nociception in healthy adults. However, there was a small effect on pain unpleasantness during nVNS, suggesting that nVNS may preferentially act on affective, not somatosensory pain components

Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with similar to 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 +/- 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis

Age- and frequency-dependent changes in dynamic contrast perception in visual snow syndrome

OBJECTIVE Patients with visual snow syndrome (VSS) suffer from a debilitating continuous (\textquotedblTV noise-like\textquotedbl) visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient's history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds. METHODS Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases. RESULTS The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20). CONCLUSIONS This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS