Principal Investigator: Melissa Cortez
Keywords: Headache , Migraine , Migraine with Aura , Concussion , Post Traumatic Headache , Post-concussive syndrome , autonomic dysfunction , Trigeminal Cephalgia , POTS , Postural Orthostatic Tachycardic Syndrome Department: Neurology
IRB Number: 00085309
Specialty: Neurology, Neurology, Neurology
Sub Specialties: Traumatic Brain Injury, Migraine, Headache
Recruitment Status: Recruiting

Contact Information

Leah Millsap
leah.millsap@utah.edu
801-581-7978

Simple Summary

This research study is designed to assess whether a series of physiologic tests can distinguish between normal participants, patients with certain types of headache, and participants with migraine related symptoms. This distinction will help guide routine neurological treatment of headache. Physiologic testing includes measurement of a person’s pupil function, heart rate and blood pressure during changes in position and breathing, sensitivity to smells, light (via a test technique called “psychophysics”), facial sensation to touch and temperature, and reaction to smelling salts. Clinical testing includes a neurological exam, history and neuropsychometric tests to fully characterize an individual’s clinical headache history and symptoms. You may have two or more separate visits composed of one or more of the following: 1) clinical assessment and questionnaires; 2) psychophysics (motion, smell, and light sensitivity testing); 2) pupil testing; 3) physiology (facial autonomic and blood pressure/heart rate monitoring). In the context of this study, these procedures are considered non-standard, and are not required for your routine medical care. Each participant may consent to all or none, and test schedule can be customized to fit the participant’s scheduling needs, though some of the testing should ideally take place between the hours of 7:30 am and 4 pm. You will be given specific instructions at the start of each task. Please ask the experimenter any questions that may arise during each task.During the clinical assessment visit, you will be asked a series of questions about your medical history and medication use, as well as to fill out a series of medical questionnaires, requiring approximately 20 minutes to complete. For the psychophysics testing, you will be asked to report detection of certain smells (odor sensitivity testing), or a bright light (photophobia testing), each of which will last 15 – 20 minutes.For the physiological testing, you will be asked to report the sensation of touch and temperature to your face before and after facial autonomic testing. Facial autonomic testing will involve lying still while being photographed with a mounted camera under green lighting. Smelling salts are used to stimulate the nasal mucosa and generate a noxious sensation that triggers the facial nerves. You will be asked to hold still during the administration of the smelling salts (which are directed into one nostril using tubing attached to an air pump), and will receive instructions on how to control/stop your exposure to the smell. The camera will record facial responses for 30 seconds prior to and 90 seconds following smelling salt administration. Heart rate, blood pressure and pupil responses are measured during this phase of the study.

Inclusion Criteria

A total of 420 pairwise participants, ages 12+, will be recruited, divided among the following groups:

minimum of 30 each group:

  • episodic migraine with and without aura (EM)
  • chronic migraine (CM)
  • trigeminal autonomic cephalgias (TAC)
  • post-traumatic headache (PTH)
  • age and sex-matched non-headache controls (NH)
  • orthostatic intolerance with headache (OIH)
  • orthostatic intolerance without headache (OI)
  • Chiari malformation with headache (CHMH)
  • Chiari malformation without headache (CHM)

A minimum of 60 subjects at high risk (AR) for development of PTH meeting one of the following categories. Specifically, those who are at risk due to high-impact sport play or recent concussion as defined below.

Subjects will be screened using a standard clinical questionnaire; diagnostic characterization is determined based on this questionnaire. Symptoms and relevant comorbidities are also obtained via the questionnaire. 

Inclusion criteria for each headache group are defined by the recently updated ICHD-III beta diagnostic criteria[5], summarized in brief below.

The criteria for the diagnosis of migraine are as follows:

  1. Episodic migraine (EM): either of the following allowed.
    1. Migraine with aura (MA): At least 2 episodes of aura symptoms including visual disturbances prior to the onset of headache and fulfilling criteria for migraine, as in migraine without aura below.
    2. Migraine without aura (MO):  At least 5 episodes of moderate to severe headache with all of the following:
      1. Pulsating or one-sided headache
      2. Associated with nausea and/or vomiting and/or hypersensitivity to light or sound
      3. Headache exacerbated by movement or similar physical activity
      4. Headache lasting 4-72 hours
  1. Chronic migraine (CM). Those meeting diagnostic criteria for #1 or #2 above, with headache occurring >15 days per month.

Trigeminal autonomic cephalgia (TAC): recurrent headache or facial pain occurring with at least one or more craniofacial autonomic symptom ipsilateral to the head pain.

Post-traumatic headache (PTH) as follows:

  1. Headache fulfilling criteria 2 and/or 3, no typical characteristics required
  2. Head trauma with all the following:
    1. Either no loss of consciousness, or loss of consciousness of less than 30 minutes’ duration
  3. Symptoms and/or signs diagnostic of concussion
  4. Headache develops within 7 days after head trauma
  5. One or other of the following:
    1. Headache resolves within 3 months after head trauma
    2. Headache persists but 3 months have not yet passed since head trauma

Orthostatic Intolerance with headache (OIH) criteria as follows [7]: OI is again defined as the inability to tolerate upright posture because of signs and symptoms which can be relieved upon lying down, but will explicitly include headache as one of the key recurrent symptoms. 

  1. Hypotension or hypertension upon change of upright posture during which BP 
  2. May or may not include reflex tachycardia upon change of upright posture 
  3. Headache with or without one or more of the following symptoms upon changing to an upright position:
    1. Lightheadedness upon change to upright posture. 
    2. Nausea or abdominal pain
    3. Sweating
    4. Tremulousness 
    5. Fatigue

Improvement of symptoms with recumbence to supine position.

Chiari malformation criteria as follows: Previously diagnosed with Chiari malformation type I or type II via MRI brain imaging. 

Inclusion criteria for the at-risk (AR) group will include:

  1. At-risk individuals (recreational sport participants)
  2. Acute concussion - individuals presenting for medical evaluation within 24 hours of concussion (can result from any mechanism, including sports related, fall, etc)
  3. Subacute, persistent post-concussive symptoms - individuals presenting for medical evaluation within 30-45 days of concussion (can result from any mechanism, including sports related, fall, etc)

References:

5.         The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia, 2013. 33(9): p. 629-808.

7.         Stewart, Julian M. “Common Syndromes of Orthostatic Intolerance.” Pediatrics131.5 (2013): 968–980. PMC. Web. 28 Aug. 2018.

 

Exclusion Criteria

Subjects will be permitted to use acute headache-specific treatment up to 48 hours prior to study, but testing must take place at least 48 hours after an acute attack, as this is an inter-ictal study. 

Chronic headache related medications will be permitted for those enrolled. Subjects enrolled for Aim 2 do not have medication restrictions, though subjects will be asked to keep a headache and/or medication diary for the period of study.

Those who cannot provide consent, or where follow-up visits would not be feasible.

Participant Reimbursement

In return for your time and effort, you will be offered monetary compensation at the rate of $10 per hour (not to exceed $100). This includes time spent undergoing clinical assessment and testing modules as described above, but does not include travel or telephone time, and will be rendered in a single sum at the completion of your involvement in the study. Participants are not required to complete all study modules, though will receive compensation only after completing the study visits.