Stroke mimics: the acute deficit that is not vascular

A 58-year-old man is brought in by the prehospital care team with right arm weakness and slurred speech. The symptoms started less than an hour ago. The stroke code is activated, the CT scan is ordered, and the neurology team is already on the way. While the technician positions the patient, his wife says he had "an attack" a few years ago and that since then he has been taking seizure medication. She thinks he forgot his dose yesterday.

The scene is common in any emergency department that treats acute stroke. Sudden focal deficit is the entry point, but not every sudden focal deficit comes from an occluded or ruptured artery. Seizures with postictal paresis, hypoglycemia, migraine with aura, functional disorders, tumors and infections can present exactly like a stroke in the first minutes. These conditions are called stroke mimics, or stroke mimics.

This text shows what studies from several countries say about how often mimics occur, which diagnoses appear most often, how scores help and where they fail, and why the urgency of door-to-needle time coexists with the risk of treating something that is not vascular.

Key points

• A relevant share of stroke codes ends with another diagnosis, and that share varies widely between services.
• Seizure, functional disorder, metabolic disturbance, migraine and peripheral vertigo are among the most frequent mimics.
• Younger patients have a higher proportion of mimics than older patients.
• Clinical scores help you think, but none of them is accurate enough to decide on its own.
• Thrombolysis in mimics seems to carry little bleeding risk in the available studies, but that depends on careful reasoning before the decision.

What a stroke mimic is

A stroke mimic is any nonvascular condition that presents with signs and symptoms suggestive of acute stroke. The term covers a heterogeneous group of diseases, ranging from simple metabolic causes to structural diseases of the nervous system. A review on the topic notes that mimics account for nearly half of admissions for suspected stroke and that up to 40 out of every 100 patients with an initial suspicion receive an alternative diagnosis (Buck et al., 2021).

In practice, the term brings together very different situations:

• conditions that cause a true but reversible focal deficit, such as hypoglycemia and postictal paresis;
• conditions with nonvascular structural injury, such as tumors and abscesses;
• conditions without structural injury, such as migraine with aura and functional disorder;
• conditions that worsen an old deficit, such as infection and metabolic disturbance in someone who has already had a stroke.

This division helps remind you that each group calls for a different clue in the history and the examination. The concept matters for two reasons. The first is clinical: the real cause of the deficit needs its own treatment, and a patient with hypoglycemia or a seizure loses time if kept only in the vascular protocol. The second is safety: reperfusion treatment carries risks, and exposing a patient without stroke to that treatment only makes sense when the benefit of acting fast outweighs the diagnostic uncertainty.

There is also the opposite problem. The so-called chameleons are strokes that present atypically, such as isolated confusion, vertigo or a fall, and end up labeled as something else. This text focuses on mimics, but both situations come from the same reasoning error: trusting the first impression without testing competing hypotheses. The text on differential diagnosis and clues goes deeper into this exercise.

How often a stroke code is not a stroke

The proportion of mimics changes with the setting, the timing of the assessment and the definition used. In a series of 206 patients assessed by telemedicine for stroke over nine months, 22 out of every 100 were classified as mimics (Tobin and colleagues, 2009). In a hospital in Qatar, among 1961 patients admitted with suspected stroke from June 2015 to September 2016, 161 had a functional diagnosis and 390 had another clinical diagnosis (Wilkins and colleagues, 2018).

Other services found different numbers. In Japan, among 1557 suspected strokes, 137 were mimics, the equivalent of 8.8 out of every 100 (Okano and colleagues, 2018). In Iran, among 1985 patients, 295 were mimics, or 14.9 out of every 100 (Hosseininezhad and Sohrabnejad, 2017). In Saudi Arabia, among 1063 patients seen from February 2016 to July 2018, 131 were mimics, or 12.3 out of every 100 (Al Khathaami and colleagues, 2020).

When the filter is broader, the proportion rises. In a Korean service, among 409 patients with a stroke code activated in 2019, 125 were mimics, which corresponds to 31 out of every 100 (Kim and colleagues, 2022). In Stockholm, a study of 2905 patients seen from October 2017 to October 2018 found mimics in 44 out of every 100 prehospital stroke codes (Sjöö and colleagues, 2022).

This variation has an explanation. The earlier and broader the code activation, the greater the chance of including people without stroke. The more the patient goes through triage before registration, the lower the proportion. Comparing services requires looking at who was included and at what moment, a precaution that applies to any estimate of pretest probability.

Why the definition changes the number

This difference appears even within the same country, between hospitals with different workflows, and that is why each service needs to know its own numbers before comparing them with the literature.

Some studies count as a mimic only those who went on to receive thrombolysis. Others include every patient with a suspicion raised by the ambulance team. There are also studies that separate transient ischemic attack from mimic, while others combine the two. Each choice changes the denominator and therefore the result. When reading a number about mimics, the first question is always: mimic among whom, assessed where and at what stage of care?

The most common mimics

The list of alternative diagnoses repeats across studies, in varying order. In the American series assessed by telemedicine, epileptic seizure, encephalopathy, syncope and migraine were the most common mimics (Tobin and colleagues, 2009). In the Japanese study, epilepsy accounted for 28 of the 137 mimics, or 20.4 out of every 100, and hypoglycemia for 15, or 10.9 out of every 100 (Okano and colleagues, 2018).

In the Korean service, among the 125 mimics, epileptic seizures accounted for 21.7 out of every 100, drug toxicity for 12.0, metabolic disorders for 11.2, tumors for 8.8 and peripheral vertigo for 7.2 (Kim and colleagues, 2022). In the Iranian study, tumors accounted for 10.5 out of every 100 mimics, hypoglycemia for 9.2 and intoxications for 8.5 (Hosseininezhad and Sohrabnejad, 2017). In the Saudi study, peripheral vertigo accounted for 27.4 out of every 100 mimics and the psychogenic condition for 24.4 (Al Khathaami and colleagues, 2020).

The main groups can be summarized as follows:

• Epileptic seizures and postictal paresis: the deficit usually appears after an event, sometimes unwitnessed, and improves within hours.
• Metabolic disorders: hypoglycemia, hyperglycemia and sodium disorders can cause a true focal deficit.
• Functional conditions: weakness or speech change without a structural lesion, with positive signs on examination.
• Migraine with aura: symptoms that spread progressively, often visual, with headache before or after.
• Nonvascular structural lesions: tumors, abscesses and subdural hematomas.
• Peripheral vertigo and syncope: intense dizziness or transient loss of consciousness mistaken for a posterior circulation event.
• Toxicity and infection: drug intoxication, sepsis and encephalopathies that worsen an old deficit.

The role of the old deficit

Many mimics appear in people who have already had a stroke. A urinary infection, hypoglycemia or a seizure can bring back a deficit that had been compensated. For whoever arrives at that moment, the picture looks new. Asking about previous deficits, checking old tests and talking to people who know the patient avoids confusing recrudescence with a new lesion.

Functional disorder: the mimic that confuses the most

Functional symptoms deserve special attention because they can closely resemble a real stroke and because the label carries stigma. In the Qatar study, the 161 patients with a functional diagnosis accounted for 8.2 per 100 of the 1961 admitted (Wilkins et al., 2018). Thrombolysis was given in 9.9 per 100 functional mimics, against 0.5 per 100 clinical mimics and 16.4 per 100 patients with ischemic stroke (Wilkins et al., 2018).

The data show that the functional disorder deceives more than the clinical mimics. Hypoglycemia shows up on the capillary glucose; a witnessed seizure is usually reported. The functional disorder, on the other hand, requires a careful exam and time, and time is exactly what is missing in the stroke code.

In Stockholm, functional paresis accounted for 18 of 55 thrombolysed mimics, or 32.7 per 100, against 82 of 1221, or 6.7 per 100, among the non-thrombolysed mimics (Sjöö et al., 2022). This pattern reinforces the idea that the functional disorder is the mimic with the greatest chance of reaching reperfusion treatment.

Care with language is part of the reasoning. Calling the patient a "simulator" or recording that "it is psychological" changes the way the team looks at the next symptoms, as the text on stigma and language discusses. The functional diagnosis rests on positive signs at the exam, and whoever makes it must keep structural hypotheses open until they are actually ruled out.

Signs that raise the functional hypothesis

Some findings at the exam suggest functional weakness, such as inconsistency between tests, variation in effort and discrepancy between the observed deficit and what the patient can do when distracted. These signs help, but the decision in the stroke code can rarely wait for a complete assessment. That is why the functional hypothesis is usually recorded as a possibility, and the reperfusion decision is made based on the overall risk.

Mimics in young people

Age changes the probability. In the Norwegian NOR-TEST study, among 1091 patients included, 211 were under 60; 69 of these young people were mimics, the equivalent of 32.7 per 100, against 12.8 per 100 among older patients (Jacobsen et al., 2023). Migraine accounted for 11.8 per 100 diagnoses among the young, and the study recorded no hemorrhage among the young mimics (Jacobsen et al., 2023).

The explanation is intuitive. The base rate of stroke in a 35-year-old is much lower than in an 80-year-old, while migraine, seizure and functional disorder are relatively more common in this age range. The reasoning that uses the base rate in diagnosis understands that the same deficit has different probabilities of being vascular depending on who presents it.

This does not mean that a young person with an acute deficit should be treated with less attention. Stroke in young people exists, has its own causes, such as arterial dissection, and can be devastating. Age changes the list of hypotheses, but the investigation of a vascular cause remains mandatory.

Scores to separate mimics

Several scores attempt to estimate the chance of a mimic at the moment of decision. The TM score was derived in 829 patients assessed by telemedicine from January 2004 to April 2013 and validated in 332 inpatients and 226 outpatients (Ali and colleagues, 2014). The proportion of mimics was 23, 24 and 22 per 100 in the three cohorts, and the area under the curve was 0.75, 0.71 and 0.77, respectively (Ali and colleagues, 2014).

A study from Singapore compared four scales in thrombolysed patients from January 2015 to October 2017 (Tu and colleagues, 2020). The TM score had an area under the curve of 0.75 and sensitivity of 91.3 per 100, the Khan scale had specificity of 88.2 per 100, and a decision tree proposed by the authors reached an area under the curve of 0.80 (Tu and colleagues, 2020).

In the series assessed by telemedicine over nine months, the authors tested scores and concluded that they were not useful for separating mimics (Tobin and colleagues, 2009). This result matches the experience of those who work in the emergency department: the score organizes data collection, but it rarely decides on its own.

Study	Context	Main finding
Ali and colleagues, 2014	Telemedicine, 829 patients in derivation	TM score with area under the curve between 0.71 and 0.77
Tu and colleagues, 2020	Thrombolysed patients in Singapore	Decision tree with area under the curve of 0.80
Tobin and colleagues, 2009	Telemedicine, 206 patients	Scores of little use for separating mimics
Kim and colleagues, 2022	Stroke code, 409 patients	125 mimics, seizure as the most frequent cause
Jacobsen and colleagues, 2023	NOR-TEST, 211 under 60 years old	32.7 per 100 young people were mimics

Why no score solves it

An area under the curve between 0.70 and 0.80 indicates moderate discrimination. In practical terms, the score gets a relevant fraction of patients wrong, and the consequences of that error are asymmetric: failing to treat a real stroke has a very different consequence from treating a mimic. Scores are useful for training the eye and for auditing the service, but the individual decision still depends on history, examination and imaging. The logic of deciding with diagnostic uncertainty applies here.

Thrombolysis in mimics: risk and decision

The fear of treating a mimic is understandable, but the available data suggest a low bleeding risk. In a Swedish registry with 674 thrombolysed patients from January 1, 2008 to December 1, 2013, 48 were mimics, equivalent to 7 per 100 (Kostulas and colleagues, 2017). Mimics had an excellent outcome in 87.5 per 100, against 50 per 100 in patients with stroke, and no mimic had symptomatic hemorrhage (Kostulas and colleagues, 2017).

In the same registry, being under 40 years old increased the chance of being a mimic, with an odds ratio of 8.7 (Kostulas and colleagues, 2017). This finding connects with the Norwegian study on young people and with the idea that age should weigh in the reasoning.

The review on mimics also discusses this balance and recalls that the rapid assessment of a patient with suspected stroke must live with a share of alternative diagnoses (Buck and colleagues, 2021). The practical conclusion is that the fear of treating a mimic should not delay reperfusion in someone with stroke, but it also does not justify ignoring clear clues of another diagnosis.

How to think before the decision

Some questions help reduce the error without delaying care:

1. Was the capillary glucose measured before any decision?
2. Was there an event suggestive of seizure before the deficit, witnessed or reported?
3. Does the patient have an old deficit that may have reappeared with infection or metabolic disturbance?
4. Did the symptoms spread progressively, as in a migraine aura?
5. Does the examination show positive signs of a functional disorder or inconsistency between tests?
6. Do the age and the vascular risk profile fit with stroke?

These questions fit into a few minutes and organize the main hypothesis and the competing ones. A brief diagnostic pause before the decision, discussed later in review sessions, helps the team learn from the mimic cases that reached treatment.

How the reasoning works in practice

Returning to the 58-year-old man with right arm weakness, the history of epilepsy and the possible medication failure increase the probability of postictal paresis. Even so, he is of an age and possibly has risk factors for stroke, and a seizure can be a symptom of a new vascular lesion. Both hypotheses remain open.

The safest path is to record the hypotheses in order of probability, measure blood glucose, complete the imaging and reassess the deficit within a short interval. A clear record in the chart, as discussed in the text about organizing clinical reasoning in the chart, makes it visible to the whole team why the decision was made and what could change it.

What to watch for on reassessment.

Reassessment is a diagnostic tool. Postictal paresis tends to improve over hours, corrected hypoglycemia improves within minutes and a migraine aura usually has a course of its own. Stroke, on the other hand, can fluctuate, but tends to leave signs on delayed imaging. Comparing the neurological exam at different moments helps separate the hypotheses.

The conversation with whoever brought the patient in.

Family members and prehospital teams bring clues that the patient cannot always report. The exact time of the last moment he was well, the presence of abnormal movements, loss of urine and medication use change the leading hypothesis. Valuing signs, symptoms and history is as important as the imaging.

Cognitive traps in the stroke code

The stroke code creates an environment that favors some biases. The first is premature closure: once the protocol starts, everyone looks for stroke, and contrary clues fall into the background. The second is anchoring on the ambulance information, which arrives as a ready-made diagnosis. The third is the opposite, when the team discovers a psychiatric history and starts seeing any symptom as functional, in an example of diagnostic overshadowing.

A simple antidote is to name the leading hypothesis and at least one alternative out loud. Another is to ask someone on the team to play the role of the dissenter, asking what else could explain that deficit. These practices take little time and reduce the risk of the whole team following the same track without reviewing the path.

Feedback is also part of learning. Knowing, days later, that the patient had another diagnosis helps calibrate the intuition of those who were on shift. Services that routinely review stroke codes that ended as mimics, without a tone of blame, build a collective memory of patterns that no score can capture on its own.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code.

The limits on using the game are described on the NEXO Economy page. If you research the teaching of clinical reasoning, the page for Researchers explains how to get in touch. Professionals who write or review cases find information under Curator and Creators, and institutions can learn about the proposal on the partnerships page. Training clinical decision-making and searching for the right ICD-10 code complete this practice.

Frequently asked questions

What is a stroke mimic?

It is a nonvascular condition that presents as a stroke, and a review points out that up to 40 out of every 100 patients with an initial suspicion receive an alternative diagnosis (Buck et al., 2021).

What are the most common mimics?

Seizure, metabolic disorder, functional presentation, migraine, peripheral vertigo and tumors appear frequently, and in a Korean service seizures accounted for 21.7 out of every 100 mimics (Kim et al., 2022).

Do younger people have more stroke mimics?

The data point in that direction: in NOR-TEST, 32.7 out of every 100 patients under 60 were mimics, versus 12.8 out of every 100 among older patients (Jacobsen et al., 2023).

Do clinical scores settle the doubt?

They help organize reasoning, but the TM score had an area under the curve between 0.71 and 0.77 in the validation and derivation cohorts (Ali et al., 2014), which indicates moderate discrimination.

Is it dangerous to treat a mimic with thrombolysis?

The available data suggest a low risk: in a Swedish registry, none of the 48 thrombolysed mimics had symptomatic hemorrhage (Kostulas et al., 2017).

Take-home messages

• Stroke mimics appear in a relevant share of stroke codes, with wide variation between services.
• Seizure, metabolic disorders, functional disorder, migraine and peripheral vertigo lead the list.
• The functional disorder is the mimic most likely to reach thrombolysis.
• Young people have a higher proportion of mimics, but stroke in young people remains a mandatory hypothesis.
• Scores organize the reasoning, but none decides alone.
• Glucose, history with witnesses and serial reassessment are the simplest tools against error.

References

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