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Atypical Causes of Stroke: Mimics & Chameleons

By: | Tags: , , , , , , , , | September 24th, 2020

Dr. Saha is a Board-certified TeleNeurologist with TeleSpecialists and has expertise in the fields of stroke neurology, general neurology and acute care telemedicine.  He earned his medical degree at Albany Medical College and completed residency training in neurology at the University of Cincinnati Medical Center. In addition to Telemedicine, Dr. Saha serves as a Regional Medical Director within the TeleSpecialists Quality and Performance Improvement Division and provides neurohospitalist coverage at area hospitals.

Typical Stroke Symptoms:

Neurology is an essential yet diagnostically challenging field of medicine due to limited availability of sensitive diagnostic testing and scarcity of expert neurologists, especially at rural “spoke” hospitals across the country. The most prevalent and permanently disabling neurological condition is a stroke.  Strokes occur abruptly and result in permanent damage to millions of brain cells every minute once blood flow to part of the brain is interrupted as a result of a blood vessel blockage (Ischemic Stroke) or blood vessel bleeding (Hemorrhagic Stroke).  If an Ischemic Stroke is suspected, thrombolytics (blood clot busters) may be necessary.

As a neurologist working heavily in the stroke/TeleStroke field, we must address that when stroke symptoms occur, they are not always as they seem. Stroke neurologists integrated as part of a greater emergency care team expedites recognition and decision making for all patients with sudden stroke-like symptoms. Taken together, these stroke-like symptoms may be characterized as one of three conditions: a typical stroke, a non-stroke condition mimicking stroke, or an atypical stroke mimicking a non-stroke condition. Our focus will be on the latter two presentations respectively known as Stroke Mimics and Chameleons.  Misdiagnosis of Mimics and Chameleons impact emergency treatment decisions daily. Surprisingly, many medical providers and patients alike are unaware of Mimics and Chameleons, and how they can impact the care of all stroke patients.

With  “typical” Ischemic Strokes, a patient experiences the sudden onset of symptoms such as facial drooping, arm weakness or drift, and speech issues (FAST). Further, patients can sometimes experience vision loss, numbness or tingling. These are all typical and easily identifiable stroke symptoms. Less “typical” symptoms include headaches, confusion, falls, vertigo and unsteadiness.

But what happens when stroke symptoms are present, but there’s no stroke? Conversely, and more dangerously, how do we identify a stroke with atypical symptoms?

When typical stroke symptoms present as a stroke, but there is no actual stroke, it is called a Stroke Mimic. A Mimic is a non-stroke condition presenting with stroke-like symptoms. Typically, Mimics lead to an over-diagnosis and occasional over-treatment of strokes, rather than identifying and treating the true cause of the symptoms.

Alternatively, there are Stroke Chameleons. These are actual stroke conditions presenting with atypical or under-recognized stroke symptoms masquerading as non-stroke medical conditions.  Misdiagnosing Chameleons lead to significant delays in identifying and treating patients with actual strokes.

One major differentiator to understand is that with Ischemic Strokes, symptoms are often negative or absent (i.e. the loss of strength, sensation, vision or speech). Meanwhile with Mimics and Chameleons, patients experience positive or new symptoms (visual hallucinations, abnormal movements, spreading pain) with or without the negative symptoms of stroke.

The Mimic:
Stroke Mimics can present in a variety of ways:

      • Recrudescence of Prior Stroke
      • Seizure/Post-Ictal Todd Paralysis
      • Complicated migraine
      • Functional Neurological or Conversion Disorders
      • Subarachnoid Hemorrhage/ICH
      • Hypoglycemia/Hyperglycemia/Severe Hyponatremia/Metabolic Encephalopathy
      • Hypertensive Encephalopathy/PRES
      • Peripheral Vertigo: BPPV, Labyrinthitis, Vestibular Neuronitis
      • Bell’s Palsy
      • Other: Guillain Barre, Myasthenia Gravis, MS, Brain Tumor/Abscess, Encephalitis, Sepsis, Syncope

For example, recognizing symptoms such as stuttering speech, variable examination findings and astasia-abasia gait clue neurologists in to diagnoses of a Stroke Mimic such as conversion disorder since these are not caused by true strokes.

So, how do we identify these Mimics then?

The most sensitive and specific test is an MRI of the brain.  If a brain MRI is performed while a patient is experiencing stroke-like symptoms but does not show any injury or bleeding, it is extremely likely to be a Mimic, especially if a Mimic was already suspected. The limitation with diagnosing by negative imaging is that MRI can be falsely negative in cases of small or early Ischemic Strokes. Thus, advanced imaging alone cannot be used to identify a Stroke Mimic.

Clinical factors including demographics (younger age, women, minorities) have been observed more often in Mimics than true Ischemic Strokes. Ischemic Strokes can happen at ANY age but tend to be less prevalent under the age of 50, especially if there are no obvious risk factors. Finally, consider patients with a psychiatric disorder, pre-existing neurological illness, or even a new life event/stressor (moving, new job, death of a loved one).

Identifying Mimics is challenging since stroke treatment is extremely time sensitive.  The decision to administer thrombolytics (blood-clot busters) such as alteplase (tPA) needs to be made clinically, well before time-consuming diagnostic testing or additional histories can be obtained.  The take home point is that if an Ischemic Stroke cannot be ruled out (even if a Stroke Mimic is suspected), a patient must be treated as if he or she is experiencing an Ischemic Stroke.

The Chameleon:

Stroke Chameleons are true Ischemic Strokes with atypical, vague, or subtle stroke-like signs and symptoms. Symptoms such as malaise, loss of consciousness, unsteady gait, generalized weakness, altered mental status, psychosis and vomiting are all Chameleon symptoms which could easily be attributed to another medical condition.

What non-stroke medical conditions are atypical stroke symptoms most often attributed to?

      • Altered mental status/toxic metabolic encephalopathy
      • Syncope Hypertensive emergency
      • Systemic infection/sepsis
      • Acute coronary syndrome/NSTEMI
      • Other: Vertigo, Dementia, Focal Motor Seizure, Cauda Equina Syndrome

Diagnosing the Real Strokes

As discussed earlier, the most efficient way to confirm a stroke is through imaging, though each type serves a different purpose with different limitations.

      • Non-Contrast Head CT – rules out acute bleeding and already present stroke (>6-12 hours). Not as reliable in ruling out early stroke/back of the brain stroke. Since CT rapidly rules out bleeding in the brain, this is the only imaging test needed to determine if a patient can safely receive alteplase.
      • CT Angiogram –confirms Large Vessel Occlusions (major blood vessel clots) accounting for 25-50% of Ischemic Strokes. Necessary to determine if mechanical thrombectomy (blood clot retrieval) is needed
      • CT Perfusion – determines amount of salvageable brain (penumbra) from irreversibly damaged brain (infarct core) in patients with Large Vessel Occlusions. This helps determine good candidates for mechanical thrombectomy to remove blood clots before more irreversible damage occurs
      • MRI Brain – Identifies diffusion restriction (areas of brain cell death) which occurs in Ischemic Strokes. Diffusion restriction can be seen in some Stroke Mimics such as infections, tumors and after seizures/status epilepticus, but are typically easy to distinguish from true strokes

Stroke Mimics and Chameleons: Is Treatment Appropriate?

When in doubt, if an Ischemic Stroke cannot be expeditiously ruled out, even though a Stroke Mimic or potential Chameleon is suspected, it is recommended to administer alteplase (tPA) if there are no contraindications.

Why is it acceptable to administer alteplase in Stroke Mimics or Chameleons? Consider the following: Numerous studies in the past 2 decades demonstrate increased recognition of Stroke Mimics via clinical and radiological information.  The number of Mimics identified is rising with more TeleStroke consultation requests from emergency departments. In hindsight, anywhere from 15-30%+ patients admitted for stroke may be diagnosed with a Stroke Mimic or non-stroke diagnosis at discharge.

Recently, 2 studies have demonstrated increased recognition of Mimics by stroke providers, as well as the implications of treating Mimics with alteplase.  A retrospective study in 2018 to externally validate the TeleStroke Mimic Score identified common characteristics of Mimics, including younger age, fewer cardiovascular risk factors, lack of facial droop and NIHSS score <14.[i]

Analysis of Get With The Guidelines Stroke Registry data (72,582 patients across 485 US hospitals) showed that despite the rising consultations for Stroke Mimics, only 3.5% of patients who received alteplase were designated as Mimics at centers that use alteplase more often.[ii]

Even if a Stroke Mimic is suspected, stroke alerts should be activated as soon as possible. Early stroke consultations allow neurologists to determine whether an Ischemic Stroke could explain sudden stroke-like symptoms. Unless the patient has an easy to exclude Mimic (ie. hemorrhage on CT or hypoglycemia with low blood glucose), a neurologist will offer alteplase in an eligible patient as soon as possible.

Time is brain. Alteplase significantly reduces long term disability if administered as soon as possible. If alteplase is administered early, there is a net benefit of treatment within the first 4.5 hours, already taking into account the low but potential risk of harm (2-7% risk of brain bleeding).[iii]  Although alteplase does not directly benefit a treated Mimic, outcomes for Mimics are better than true Ischemic Strokes, and the risk of harm is significantly less (<1%).

It is important to note that within the first 90 minutes from stroke symptom onset, less than 4 patients need to be treated with alteplase for 1 true stroke patient to avoid life-altering disability.  Extended up to 4.5 hours, the number of patients needed to treat for net benefit is less than 8.[iv] Therefore, even if 3.5% of the 4 patients receiving alteplase is a Mimic, at least 1 true Ischemic Stroke patient will benefit  by avoiding major disability .

Delaying alteplase treatment in order to identify and exclude Mimics up front by waiting for additional imaging results (CTP, MRI) or overemphasizing the harms of alteplase is impractical and harmful for the 25% of stroke patients that could have benefitted by receiving treatment sooner. The repercussions of missed or untreated stroke (either excluding an Ischemic Stroke patient due to the suspicion of a Stroke Mimic, or misdiagnosing Chameleons as another non-stroke condition) are significant from both a patient care and medicolegal standpoint. For example, 20% of misdiagnosed strokes in the ED are Chameleons.

Regardless of whether stroke-like symptoms are due to an Ischemic Stroke, Stroke Mimic or Stroke Chameleon, the sooner a stroke alert is activated and alteplase is administered, the greater the net benefit to stroke patients compared to delayed treatment or no treatment at all.

How can you ensure that patients receive the best and most efficient care possible?

        • When in doubt, activate a Stroke Alert. Consult with neurology early; it’s better to over-call as each case is a learning point. A second set of experienced eyes makes a difference.
        • Always seek the last known normal. How suddenly did these symptoms present?
        • Educate your team (including EMS) on tools to identify stroke symptoms Comprehensive symptom exam like SAVES.
        • Understand the limitation of NIHSS: Designed as research tool to reliably screen patients for stroke and predict stroke volume. However, it favors identification of left anterior hemispheric strokes, and is not as sensitive for right hemispheric or posterior circulation strokes
        • HINTS (Head Impulse, Nystagmus, Test of Skew) for vertigo
        • INFARCT (Impulse Normal, Fast-phase Alternating, Refixation on Cover Test) suggests Ischemic Stroke
        • Partner with a reputable comprehensive TeleNeurology company with substantial clinical and telemedicine stroke experience. This will ensure that your patients will get the best stroke or emergent neurology care quickly and efficiently.

With the inclusion of telemedicine, more specifically TeleStroke services, into more hospitals and EDs expert neurologists can help recognize a suspected Mimic or Chameleon and treat appropriately. Unlike most medical conditions that require a definitive diagnosis before deciding on treatment, the moderate to high clinical suspicion of Ischemic Stroke alone is necessary to decide if alteplase should be offered.  Once alteplase is administered, additional investigations will either confirm an Ischemic Stroke, rule out a Mimic or confirm whether the patient was a Chameleon after all.

Have questions on how TeleSpecialists works with hospitals to create a strong TeleStroke program?

[i] Ali SF, Hubert GJ, Switzer JA, Majersik JJ, Backhaus R, Shepard LW, Vedala K, Schwamm LH. Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks. Stroke. 2018 Mar;49(3):688-692. doi: 10.1161/STROKEAHA.117.018758. Epub 2018 Jan 26. PMID: 29374105; PMCID: PMC5829006.

[ii] Ali-Ahmed F, Federspiel JJ, Liang L, Xu H, Sevilis T, Hernandez AF, Kosinski AS, Prvu Bettger J, Smith EE, Bhatt DL, Schwamm LH, Fonarow GC, Peterson ED, Xian Y. Intravenous Tissue Plasminogen Activator in Stroke Mimics. Circ Cardiovasc Qual Outcomes. 2019 Aug;12(8):e005609. doi: 10.1161/CIRCOUTCOMES.119.005609. Epub 2019 Aug 15. PMID: 31412730; PMCID: PMC6699639.

[iii] Yaghi S, Willey JZ, Cucchiara B, Goldstein JN, Gonzales NR, Khatri P, Kim LJ, Mayer SA, Sheth KN, Schwamm LH; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Quality of Care and Outcomes Research. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2017 Dec;48(12):e343-e361. doi: 10.1161/STR.0000000000000152. Epub 2017 Nov 2. PMID: 29097489.

[iv] Lansberg MG, Schrooten M, Bluhmki E, Thijs VN, Saver JL. Treatment time-specific number needed to treat estimates for tissue plasminogen activator therapy in acute stroke based on shifts over the entire range of the modified Rankin Scale. Stroke. 2009 Jun;40(6):2079-84. doi: 10.1161/STROKEAHA.108.540708. Epub 2009 Apr 16. PMID: 19372447; PMCID: PMC2881642.

Nattasha Acevedo, MD

Dr. Acevedo received her medical degree from the Ponce School of Medicine in Puerto Rico and did her neurology residency at Montefiore Medical Center in New York. She went on to do a clinical neurophysiology fellowship at Emory School of Medicine in Atla nta, Georgia and then joined private practice in Fort Myers, Florida. She currently resides in San Juan, Puerto Rico. She likes running, paddle boarding and spending time with family.

Bernadette Borte, MD

Dr. Borte received her medical degree from St. Matthew’s University School of Medicine in Grand Cayman. She completed her neurology residency at the University of Iowa Hospitals and Clinics in Iowa City, Iowa. Her areas of interest include inpatient neurology and acute stroke. When not working, she enjoys spending time outdoors with her family. Dr. Borte joined the TeleSpecialist family in March of 2019.

Mazen Almidani, MD

Dr. Almidani is board certified in pediatrics by the American Board of Pediatrics and board certified in epilepsy, as well as neurology with special  qualification in child neurology by the American Board of Psychiatry and Neurology.  Dr. Almidani is happily married with 4 children. His oldest son has autism and his daughter has complicated seizures; both were a drive for him to become a neurologist. Dr. Almidani enjoys soccer, running and spending time with his family. He is very involved with his sons’ therapy and helping with daily challenges. He is double board certified in Pediatric and Adult Neurology and Epilepsy. He sees children and adults. He also participates in charities for children in Syria who may be underprivileged and/or affected by the war. Dr. Almidani joined TeleSpecialists in August 2020.

Amanda Cheshire, MD

Dr. Cheshire received her medical degree from the University of Louisville School of Medicine in Louisville, Kentucky. She completed her neurology residency at the University of Cincinnati Medical Center in Cincinnati, Ohio. She did a fellowship in neurophysiology at the University of Michigan Medical School in Ann Arbor, Michigan. Dr. Cheshire is double board certified in neurology and clinical neurophysiology. She enjoys traveling, reading and music. She currently resides in Viera, Florida.  Dr. Cheshire joined TeleSpecialists in June 2019.

Jessica Floyd, MD

Dr. Floyd completed her neurology residency at Mayo Clinic in Jacksonville, Florida followed by fellowship training in clinical neurophysiology with focus in EEG and epilepsy at the Medical University of South Carolina in Charleston, South Carolina. She has particular interest in hospital neurology and patient education as well as the blossoming specialty of lifestyle medicine. She strives to take advantage of every encounter with patients and medical staff to empower them to do their own research into how daily thoughts, choices, and habits can add up to create greater and longer-lasting brain and neurologic health for ourselves and our loved ones. She lives in Florence, South Carolina with her awesome husband of 13 plus years and three beautiful children. She is an avid yogi, astrologer, and lover of food and all things neurology! Dr. Floyd joined the TeleSpecialist family in July 2017.

Nancy Futrell, MD

Dr. Futrell received her medical degree from the University of Utah in Salt Lake City, Utah. She also did her neurology residency at the University of Utah as well as a research fellowship in cerebral vascular disease at Jackson Memorial Hospital in Miami, Florida. She currently resides in Salt Lake City, Utah. She has authored 2 books and 50 peer reviewed papers. 

Rebecca Jimenez-Sanders, MD

Dr. Jimenez Sanders received her undergraduate degree from Emory University, and her medical degree from the San Juan Bautista School of Medicine in Puerto Rico. She completed her neurology residency at the University of South Florida in Tampa, Florida, where she also did a specialized headache medicine and facial pain fellowship. She currently resides in Tampa, Florida with her husband and her two daughters. She is also fluent in Spanish and Italian languages, and enjoys photography, baking, boating, and biking.

Cory Lamar, MD

Dr. Lamar received his medical degree from Meharry Medical College in Nashville, Tennessee. He completed his internship and residency at Wake Forest Baptist Health in Winston Salem, North Carolina. Following residency, he completed a clinical fellowship in neurophysiology, with a concentration in epilepsy. He currently resides in Florida and enjoys outdoor activities.

Clifford Meyers, MD

Dr. Meyers received his medical degree from Brown University in Providence, Rhode Island and his MBA from the Simon School of Business at the University of Rochester in Rochester, New York. He completed his neurology residency at the University of Rochester, where he also did a neurophysiology fellowship. Dr. Meyers resides in Webster, New York with his wife and daughter. When not doing teleneurology, he enjoys playing sports with his wife and daughter.

Tao Tong, MD

Dr. Tong received her medical degree from the University of Miami School of Medicine in Miami, Florida. She completed her neurology residency at Jackson Memorial Hospital in Miami, Florida, where she also did a neuromuscular/EMG fellowship.  She currently resides in College Station, Texas. Dr. Tong is married with two boys. She enjoys spending time with her family, traveling and reading.

Shubhangi Chumble, MD

Dr. Chumble attended BJ Medical School. She is a board certified neurologist with a subspeciality interest in sleep medicine. Dr. Chumble did her residency at Howard University in Washington DC and has practiced neurology since 2001 in private and corporate settings. She lives in Melbourne, Florida and loves the sunshine state. Her hobbies include yoga, meditation, cooking , traveling and meeting new people. She also loves to do stained glass, pottery and painting. She joined TeleSpecialists in June 2019.