Not All Headaches are Due to Migraine: Red Flags, Don’t Miss Diagnoses, and Diagnostic Pitfalls

The Cases

Case #1: A 22-year-old physically active man went to his family physician complaining of severe headaches and left eye pain. He was treated for a presumed migraine, but the headache persisted without remission. Three days after this outpatient visit, the patient’s parents took him to the emergency department (ED), where he was found to have a low-grade fever and leukocytosis, but he was again treated for a presumed migraine.

Two days after the ED visit, the patient’s mother mentioned his symptoms to a physician friend. This friend suggested that the patient should be taken back to an ED and computed tomography (CT) of the head should be requested. On this second ED visit, the patient remained febrile with increasing leukocytosis and a Glasgow coma score of 10-13, indicating somnolence, confusion, and difficulty following commands. Head CT revealed brain abscess, meningitis and encephalitis, apparently originating from sinusitis. The patient required craniotomy and surgical drainage of his cerebral abscess; he gradually improved with intravenous antibiotics over several weeks in neurosurgical intensive care.

Case #2: A 33-year-old woman was admitted to the hospital with severe headaches, blurry vision, and numbness in her left arm. A neurologist examined the patient and diagnosed migraine headaches. The neurologist ordered magnetic resonance imaging (MRI), which revealed nonspecific abnormalities in the patient’s right frontal lobe, but did not refer the patient for further evaluation. The neurologist continued to treat the patient for migraines over the subsequent four years.   

Approximately five years after the first hospitalization, the patient suffered a head injury at work. She was treated at a different hospital’s ED, received CT imaging, and was diagnosed with a brain tumor. By this time, the tumor had grown with significant compression of brain tissue. She received whole brain radiation treatment, and is currently in remission, but she suffers from severe short-term memory loss that impedes her ability to drive or work. 

The Commentary

By Andrew P.J. Olson, MD

Background

Headache is a commonly encountered condition in both primary and acute care. The vast majority of patients who present with headache do not have a life-threatening condition, and most have conditions – such as migraine and tension headache – that can be diagnosed by clinicians based on the history and physical examination alone, without imaging. There have been many initiatives aimed at improving the appropriateness of imaging (such as computed tomography [CT] or magnetic resonance imaging [MRI]) for patients with headache, as imaging is overused at the population level. However, as these two cases demonstrate, there are serious causes of headache that must be considered, and imaging performed, to make a safe and timely diagnosis.

There are many reasons that the approach to headache is challenging, including the prevalence of headaches, the fact that most patients with headaches do not require imaging or advanced testing, and the use of clinical criteria to assign most diagnostic labels in patients presenting with headache. In most cases, there are no definitive tests to determine a specific etiology for a patient’s headache, and the diagnostic approach involves considering serious causes requiring further investigation and/or intervention before applying clinical criteria to categorize the headache. As the above cases exemplify, there are serious, life-threatening causes of headache that are only diagnosed when a patient and their clinician have enough suspicion to pursue further diagnostic evaluation, including imaging, applicable laboratory testing, and other tests such as lumbar puncture. However, pursuing such tests in most patients with headache is unnecessary, leading to excessive testing, potential harms, and waste.

This challenge - balancing testing and interventions with a parsimonious approach - is common in many areas of medicine and can confound patients and clinicians alike. There are many different approaches that clinicians and patients can consider in such situations and further research is certainly needed. However, a well-known and helpful framework, developed by Dr. Gordon Schiff,^1,2 for approaching such diagnostically challenging situations is to consider three ideas when evaluating a patient:

• Diagnostic pitfalls
• Red flags
• Don’t miss diagnoses

In this commentary, this framework will be discussed in the context of the two cases of headache presented, and considerations for application in other cases will be discussed.

Approach to Improving Safety

Diagnostic excellence is an emerging idea in the field of diagnostic quality and safety.  This means moving from reducing errors alone (which is certainly valuable) to moving toward a world where diagnosis is “safe, effective, patient-centered, timely, efficient, and equitable.”³ This means identifying strategies that improve diagnostic safety and quality while optimally using resources; more diagnostic testing isn’t necessarily better. Diagnostic excellence, instead, includes using the best diagnostic resources and interventions in situations where they are necessary and not using them in situations where they are not.

Given this tension, the tripartite framework of diagnostic pitfalls, red flags, and “don’t miss diagnoses” can help clinicians and patients partner in their diagnostic approach. 

Diagnostic Pitfalls

Diagnostic pitfalls are common “traps” that clinicians and teams fall into during the diagnostic process, leading to missed, delayed, or wrong diagnoses. A recent study demonstrated both condition-specific pitfalls as well as generic pitfalls across conditions.¹ For example, patients with nausea and vomiting may be misdiagnosed as having the common condition of gastroenteritis when these symptoms are actually caused by a posterior circulation stroke. Another condition-specific pitfall is that Parkinson disease may be misdiagnosed as chronic fatigue syndrome. Generic pitfalls include one condition repeatedly mistaken for another and a chronic disease mistakenly considered to be the cause of a patient’s new symptoms. There are many condition-specific pitfalls that clinicians and patients can consider when approaching a patient with headache; in general, these involve not appropriately considering a serious (even life-threatening) cause of headache before making a diagnosis of a benign cause. Of course, there are also pitfalls in over-evaluation of benign headaches.

Red Flag Conditions

As one attempts to avoid diagnostic pitfalls, it can be helpful to proactively consider “red flags” during the diagnostic process. Red flags are clinical findings that point toward a serious condition and must be consciously considered before dismissing them. It is important to note that red flags do not always mandate further testing but instead suggest the need to proactively consider and discuss these clinical findings before moving on. For example, in patients with headache, important red flags that portend a serious diagnosis include a new headache after 50 years of age, loss of consciousness, a “thunderclap” onset, alteration in mental status, persistent or progressive visual symptoms, nausea with vomiting, fever, weight loss, and others.⁴ Of course, many of these symptoms may be present in patients with benign causes of headache; proactively addressing these symptoms and asking, “Could this symptom be a sign of a serious cause of headache?” is an important consideration to avoid diagnostic error. When such questions are addressed, clinicians and patients can use a combination of expertise and shared decision making to make safer diagnostic choices.  

Don’t Miss Diagnoses

Lastly, considering both diagnostic pitfalls and “red flag” clinical findings can lead clinicians and patients to rule out “don’t miss diagnoses” during the diagnostic process.  Such conditions may have relatively low prevalence but are serious enough that they must be considered as part of the diagnostic process. Approaches to crafting and revising a differential diagnosis such as structured reflection have been shown to improve diagnostic performance.⁵ These approaches encourage clinicians to consider clinical factors that argue for and/or against certain conditions in the differential diagnosis, while explicitly considering “don’t miss diagnoses". Such conditions (etiologies) in patients with headache include intracranial hemorrhage, CNS infections, neoplasms, as well as others. While the vast majority of patients with headache do not have one of these conditions, it is helpful and important to actively consider such conditions on the differential diagnosis to determine if further diagnostic evaluation is warranted.

Conclusion

It is important to emphasize that proactive consideration of pitfalls, red flags, and don’t miss diagnoses does not mean that every patient should receive testing for these conditions; most patients with headache can safely be managed expectantly and conservatively.  While being mindful of the false clarity that retrospective case review and thus hindsight bias can provide, it is illustrative to consider what might have been different had pitfalls, red flags, and “don’t miss diagnoses” been proactively considered in the cases summarized above. Considering these ideas prompts clinicians and patients to break out of diagnostic momentum that could be driving toward errors and harms, and instead to invite discussion about whether a different path is needed. 

As we have previously described, the tripartite framework of diagnostic pitfalls, red flags, and don’t miss diagnoses may be very helpful, but to achieve diagnostic excellence, we also “need to ensure diagnosticians are equipped with the necessary factors—time, tools, teams, training, and technologies-to make high-quality, safe diagnostic decisions.”² If we can better define these factors through ongoing and future research, then clinicians can be supported and empowered through targeted education, interdisciplinary collaborations, online resources, and potentially artificial intelligence (AI) tools.

Take Home Points

• Considering diagnostic pitfalls, red flags, and don’t miss diagnoses may help avoid diagnostic error
• Proactively discussing the diagnostic process (as well as potential wrong directions in that process) is helpful to improve diagnostic performance

Andrew P.J. Olson, MD
Professor of Medicine and Pediatrics
University of Minnesota Medical School
apjolson@umn.edu 

References 

1. Schiff GD, Volodarskaya M, Ruan E, et al. Characteristics of Disease-Specific and Generic Diagnostic Pitfalls: A Qualitative Study. JAMA Netw Open. 2022;5(1):e2144531. [Free full text] 
2. Olson APJ, Linzer M, Schiff GD. Measuring and Improving Diagnostic Safety in Primary Care: Addressing the “Twin” Pandemics of Diagnostic Error and Clinician Burnout. J Gen Intern Med. 2021;36(5):1404-1406. [Free full text]
3. Yang D, Fineberg HV, Cosby K. Diagnostic Excellence. JAMA. 2021;326(19):1905-1906. [Available at]
4. Smith DE, Siket MS. High-Risk Chief Complaints III: Neurologic Emergencies. Emerg Med Clin North Am. 2020;38(2):523-537. [Free full text]
5. Mamede S, van Gog T, Sampaio AM, de Faria RMD, Maria JP, Schmidt HG. How can students’ diagnostic competence benefit most from practice with clinical cases? The effects of structured reflection on future diagnosis of the same and novel diseases. Acad Med. 2014;89(1):121-127. [Free full text]