Status Migrainosus - Differentiating Between Responders and Non-responders

Recently, there has been a major focus on "evidence-based" treatments. Who could possibly
argue against basing decisions on data? Since the highest level of evidence is derived from
randomized double-blind controlled therapeutic trials that consider treatments rendered to
large groups of patients with general diagnoses (e.g., migraine) or from a systematic review
of several randomized controlled trials (meta analysis), physicians have always prided
themselves on applying some type of evidence in order to select treatment. One does not want
to imagine medical treatment that is purely subjective. The question, however, is how well
does the evidence from trials applies to the care of individual patients? The main problem
with such FDA-guided therapeutic trials is the issue of numbers vs specificity. For results
to be statistically and biologically valid and important, they must include hundreds and
often thousands of participants. To achieve numbers, a lumping strategy predominates over
splitting. The more a trial lumps together diverse subgroups, the less specific are the
results for individual patients. Given that trials have extensive inclusion and exclusion
criteria, often 5 to 10 patients are screened for each patient finally enrolled in the study.
Patients who are too ill, too old, too young, female and of childbearing age, incapable of
giving informed consent, too complex, or too full of coexisting illnesses are often excluded
from trials. Yet, these are the patients who frequently visit the headache center and to whom
individualized medicine can provide the most appropriate answers.

Trials that study migraine prevention measure pain intensity and duration, attack frequency,
functional disability, quality of life, number of working days lost, nausea, vomiting, and
hypersensitivity to light and noise. Whether these measures are those most representative of
the important aspects of a condition is an important consideration since not all end points
are comparable. Some patients make their living talking. How can their aphasia (difficulty
finding the right words) be compared to sensitivity to light or facial numbness? For some
patients, it is the sharp pain that continuously pierces through their eyes that makes the
headache impossible to tolerate whereas for others it is the ongoing nausea that prevents
them from the pleasure of enjoying food, or perhaps the extreme photophobia that makes
reading or working on a computer impossible and forces them to quit their jobs and seek the
comfort of darkness. How is it, then, that identical weights are assigned to various
patients? Physicians are not compelled to treat all patients with a given condition according
to identical guidelines, as is the case in therapeutic trials that follow strict protocols.
Randomized trials mandate that many patients with a general condition must be given treatment
A, and the results are then compared with those of patients given treatment B or C, or
placebo. Physicians, however, while caring for one patient at a time must consider several
variables, including:

(1) the patient's medical problem; (2) the patient's disease risks; (3) the background,
genetics, socioeconomic milieu, psychology, responsibilities, goals, and other
characteristics of the patient; and (4) the benefits and risks of potential therapeutic
strategies to treat the patient's conditions and to prevent conditions that he or she is at
risk of developing.

An inescapable conclusion is therefore that the results of FDA-approved clinical trials fall
short of allowing us to 'tailor' the right treatment to the right patient as it does not
allow us to predict whether the patient we treat today will or will not benefit from an
approved treatment. This conclusion questions the do-ability of translating the often stated
goal of individualizing medicine from words to deeds.

Accordingly, the main goal of this proposal is determine whether it is possible - in the
setup of routine clinical care - to identify in individual patients who are clear responders
to drug X, common denominators that are absent in individual patients who are non-responders
to the same drug, and vice versa. All currently available knowledge about migraine
pathophysiology will be utilized, using as much time as is needed to ask as many questions as
are necessary, in an attempt to profile clear responders and clear non-responders.

Inclusion Criteria:

- males and females

- ≥18 years old with no upper age limit

- patients with status migrainosus - defined as a severe migraine headache without aura
lasting longer than 72 hours and considered primarily as a complication of migraine

- patients who are willing and able to provide written, informed consent

Exclusion Criteria:

- <18 years old

- unable or unwilling to provide written, informed consent

- females who are pregnant, breastfeeding, or who are trying to become pregnant

- patients who do not speak English

- any medical condition or other reason that in the opinion of the investigators makes
the patient unfit or at risk to participate in the study