A Computational Analysis of Diagnostic Misrecognition in Co-Occurring Primary Headache Disorders: Prime Encoding of ICHD3 Criteria Reveals 72 Potentially Spurious Diagnoses

Background/Objectives: In clinical circumstances with more than one headache disorder, misrecognition can occur if each headache disorder is not separately and individually evaluated. For example, consider the case of a patient with baseline tension-type headaches lasting hours who now develops cluster headaches with nausea. Merging the characteristics of both disorders may yield the illusion of migraine. Do these types of misrecognitions occur necessarily because of ICHD3 criteria? Are there combinations of ICHD3 criteria, if any, which yield this type of misrecognition? This work seeks to determine whether a new, unintended diagnosis can be arrived at when one merges two primary ICHD3 diagnoses. Methods: ICHD3 primary headache disorders, as well as headache phenotypes closely mimicking ICHD3 criteria, were translated as numerical data using the prime encoding method. The encoding of two concurrent diagnoses in an individual was then modeled by multiplying all pairings of the ICHD3 encoding. The results were algorithmically diagnosed to see which pairings, if any, generate logically spurious diagnoses. Results: A total of 117,526 phenotypes were generated. After duplicate pairings of diagnoses were removed, a total of 72 pairings of unique ICHD3 diagnoses were derived that yield a “new” diagnosis. Thirty-seven (51%) of these pairings arise from our model’s idiosyncrasy of encoding chronic migraine without encoding migraine with or without aura explicitly. Of the rest, 23 pairings involve combining paroxysmal hemicrania with either a longer- or shorter-duration headache. I further generalize the condition under which the above logically spurious diagnosis occurs as a mathematical observation. Conclusions: Misrecognition arises naturally if diagnostic criteria consist solely of characteristics from another headache disorder or a combination of two headache disorders. Specifically, combining headaches with different duration and/or frequency is most likely to yield these “logically spurious” diagnoses.