Smell Sensitivity in Chronic Migraine: A Case-Control Study

• difference in UPSIT scores between subjects and controls [ Time Frame: Chronic migraineurs up to 12 months. Controls up to 2 weeks. ] [ Designated as safety issue: No ]

  Migraineurs and controls will take the University of Pennsylvania Smell Identification Test (UPSIT) in the office. After the first visit, migraineurs will self-administer the UPSIT during a migraine attack day at home.

  Age and sex matched controls will also take the first UPSIT in the office. They will take second UPSIT 2 weeks later at home.

  
  

We will interview subjects and controls to ensure that they meet inclusion criteria and do not meet exclusion criteria. After obtaining informed consent, subjects and controls will complete a questionnaire survey with the interviewer regarding their history of headaches, smell sensitivity, osmophobia and current medication use. Subjects will also answer questions about attack frequency, location of headache, duration of disease, use of medication for pain, and disability.

After completing the questionnaire survey, migraineurs and controls will take the University of Pennsylvania Smell Identification Test (UPSIT) in the office. During this visit we will demonstrate and give instructions on how to perform UPSIT at home.

After the first visit, migraineurs will self-administer the UPSIT during a migraine attack day at home. They will be required to mail or drop off the second test at the Jefferson Headache Center.

Age and sex matched controls will take the first UPSIT in the office. They will take second UPSIT 2 weeks later at home and call the Headache Center to notify the staff that they have completed the second UPSIT. They will be asked to mail or drop off the test at the Jefferson Headache Center.

The UPSIT is a standardized, validated test for olfaction. There are a total of 40 odorants, with four booklets each containing ten odorants. The stimuli are embedded in "scratch and sniff" microcapsules at the bottom of each page. Subjects must choose one answer among four possible answers for each odorant - a forced choice test. The validity and reliability of the UPSIT, as well as the basis for using these particular odorants, has been demonstrated in multiple studies. The tests kits will be supplied by Dr. Richard Doty at University of Pennsylvania.

We will use analysis of variance (ANOVA) to determine variance in UPSIT scores between subjects and controls. We will also use ANOVA to examine differences based on subject characteristics, including attack frequency, duration of illness, osmophobia during attacks, and if odors trigger headaches. We will also use Chi-square and the Wilcoxon rank sum test to determine categorical outcomes such as gender and statistical significance between groups.

To achieve a 90% power that the study will detect a statistically significant difference between the mean UPSIT scores at a two-sided 5 percent significance level, our sample size for both subjects and controls is 50. This is based on the assumption that the standard deviation of the response variable is 3 units. Our assumptions about effect size are based on previous studies using the UPSIT to detect differences in subjects and controls in other neurologic disorders, such as schizophrenia.