Related Experiment Video
Updated: Aug 11, 2025
3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache
Published on: June 2, 2014
Intra- and interindividual attack frequency variability of chronic cluster headache
Roemer B Brandt1, Wim Mulleners2, Leopoldine A Wilbrink3
1Department of Neurology, 4501, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Accurate chronic cluster headache attack frequency can be recorded weekly, not just instantly. Seven weeks of baseline data provide a reliable estimate, with higher attack frequency in spring.
Area of Science:
- Neurology
- Clinical Trials
Background:
- Chronic cluster headache attack frequency variability complicates clinical trial design.
- Optimal baseline period duration for trials remains unclear.
Purpose of the Study:
- To assess intra- and interindividual attack frequency variability in chronic cluster headache.
- To determine the optimal baseline period duration for clinical trials.
- To compare weekly versus instantaneous attack frequency recording methods.
Main Methods:
- Analysis of a 12-week baseline period from the ICON trial (occipital nerve stimulation for chronic cluster headache).
- Comparison of weekly and instantaneous attack frequency recording.
- Assessment of intra-individual and seasonal attack frequency variability.
- Determination of the shortest reliable baseline observation period.
Main Results:
- Weekly and instantaneous attack frequency recordings showed similar median values.
- Attack frequency was significantly higher in spring.
- Higher attack frequency (≥3 attacks/day) correlated with lower variability.
- Seven weeks of baseline data achieved a 90% accuracy for attack frequency estimation.
Conclusions:
- Weekly retrospective recording of attack frequency is a convenient and valid method.
- Seven weeks is an optimal baseline period for chronic cluster headache trials, balancing accuracy and feasibility.
- Understanding attack frequency variability aids in trial design and power calculations.
Background:
The lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration.
Methods:
We analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency.
Results:
Weekly median (14.4 [8.2-24.0]) and instantaneous (14.2 [8.0-24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2-140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period.
Conclusion:
Weekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those with <3 daily attacks. An optimal balance between 90% accuracy and feasibility is achieved at a baseline period of seven weeks.The ICON trial is registered in ClinicalTrials.gov under number NCT01151631.
Related Concept Videos
01:11Variability: Analysis
The range is a simple measure of variability, indicating the difference between the highest and...
01:26Patterns of Fever
01:27Panic Disorder
01:15Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...