Tag Archives: neurology

Posterior Circulation Strokes and Dizziness: Pearls and Pitfalls

Authors: Alec Pawlukiewicz, BA (Vanderbilt University School of Medicine) and Drew A. Long, BS (@drewlong2232, Vanderbilt University School of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Case Presentation

You are working the night shift in the ED, and you see the next patient is a 38-year-old female complaining of dizziness.  Her vital signs include HR 82, BP 115/70, RR 12, O2 saturation 99%, and T 37 C.  She describes her dizziness as a sensation of the room spinning, and her dizziness began yesterday and has worsened today.  It is associated with severe nausea and vomiting. Her past medical history is notable for type I diabetes.  She has never had any previous episodes of dizziness.  Is she having a posterior stroke? How can you evaluate this patient for a life-threatening cause of dizziness?


Worldwide, stroke is a major cause of disability and mortality.1  In the U.S., around 795,000 strokes occur every year.2 Posterior circulation strokes account for approximately 20% of ischemic strokes.3 Unfortunately, many of these posterior strokes are initially misdiagnosed or remain undiagnosed.4 Misdiagnosis of posterior circulation strokes presenting with dizziness is common, occurring in up to 35% of cases.5 The common causes of posterior circulation strokes include embolic causes, atherosclerosis (and subsequent stenosis), small vessel disease, and arterial dissection.6-9 The posterior circulation supplies approximately 20% of the brain.10  See Figure 1 for the anatomy of the posterior circulation and Table 1 for the areas supplied.

Screen Shot 2017-03-10 at 5.13.27 PM

Table 1: Areas Supplied by Posterior Circulation11

Artery Area Supplied
Vertebral Artery Brainstem
PICA Cerebellum
Basilar Artery Thalamus
Posterior cerebral Auditory/vestibular structures
Medial temporal lobe Visual occipital cortex

Clinical Presentation

The clinical presentation of posterior circulation strokes can vary widely and depends on the location of the infarct. Posterior circulation strokes commonly present with symptoms of altered mental status, vision changes, speech changes, nystagmus, vertigo, ataxia, limb weakness, headache, and a variety of other focal neurological deficits.12,13 Of note, these focal neurological deficits may be absent or subtle, leading to difficulty diagnosing posterior strokes.13,14 One particularly challenging presentation of posterior circulation stroke is patients with acute vestibular syndrome (AVS), which often manifests with vertigo or “dizziness.”  This review will focus on dizziness or vertigo and the posterior circulation.

Categorizing Dizziness

A common, classic first step in evaluating a patient with dizziness is to have them characterize what they mean by “dizzy,” as dizziness is an imprecise descriptor.  Dizziness is often used by patients to describe a wide variety of experiences, which can be categorized into one of four categories.  These include vertigo (illusion of motion, often spinning), near syncope (feeling of impending fainting), disequilibrium (loss of balance while walking), and nonspecific dizziness.15  Unfortunately, having the patient describe what they mean by “dizzy” has been shown to be an unreliable indicator of the underlying pathology.16,17  A study by Newman-Toker et al. found that patients frequently changed their descriptors of the type of dizziness if questioned in a different manner after only 10 minutes.18 These studies bring into question the utility of a patient’s description and characterization of “dizziness.”

A newer method of categorizing “dizziness” deals with the timing and triggers of its onset.14 One study has shown that despite the unreliability of the description of the dizziness, patients often reliably relate the context and timing of its onset.19 These categories are displayed in Table 2.

Table 2.  Categories of Timing and Triggered Based Vestibular Syndromes14

Vestibular Syndrome  Duration Asymptomatic Periods Triggers?
Acute Vestibular Syndrome > 24 Hours No No
Triggered Episodic Vestibular Syndrome < 1 minute Yes Yes
Spontaneous Episodic Vestibular Syndrome Minutes to hours Yes No, but may have exacerbating factors

Vestibular Syndromes include Acute Vestibular Syndrome (AVS), Triggered Episodic Vestibular Syndrome, and Spontaneous Episodic Vestibular Syndrome.  Table 2 lists defining characteristics of these syndromes. Table 3 lists common benign and dangerous causes of these categories of dizziness. The dizziness associated with posterior circulation strokes often falls into the category of AVS.  AVS is characterized by a rapid onset of vertigo, in addition to nausea/vomiting and gait unsteadiness.  AVS is often associated with head motion intolerance and nystagmus that can last for days to weeks.20

Table 3. Benign and Dangerous Causes of Dizziness14

Vestibular Syndrome Common Benign Cause Dangerous Cause(s)
Acute Vestibular Syndrome Vestibular neuritis Stroke
Triggered Episode Vestibular Syndrome BPPV Posterior Fossa Tumor
Spontaneous Episodic Vestibular Syndrome Vestibular migraine TIA, Cardiac Dysrhythmia

Peripheral vs. Central Causes of AVS

The differential diagnosis of AVS can be broken into peripheral and central causes. It is imperative the Emergency Physician consider central causes of vertigo. Central causes include those disorders that affect the structures of the central nervous system such as the cerebellum and the brainstem. The most common, dangerous central cause of AVS is a posterior circulation stroke. Peripheral causes are those that affect CN VIII and the vestibular apparatus.  The most common peripheral causes of AVS are vestibular neuritis and labyrinthitis.20 A list of signs and symptoms associated with peripheral and central causes is shown in Table 4. The Emergency Physician (EP) must keep in mind many of the distinguishing features of peripheral lesions may also be present in central lesions. For example, while auditory symptoms are typically associated with peripheral processes, their presence does not exclude a central process.21

The evaluation for stroke in AVS is particularly important in those patients who are older, have hypertension or cardiovascular disease, are on anticoagulation, or have other classic stroke risk factors.22 However, the EP must keep in mind younger age is not sufficient reason to exclude the potential diagnosis of stroke. It is estimated one in five strokes causing AVS affects a patient less than 50 years of age and one in ten patients less than 40 years of age.20 One study found 50% of patients misdiagnosed after suffering a posterior circulation stroke were under the age of 50.23 The overall mortality described by this study was 40%, with a 50% prevalence of significant neurological disability among the survivors.23 These findings convey the significance of thorough assessment for central pathologies in patients with AVS.

Table 4: Signs/ Symptoms Differentiating Peripheral and Central Vertigo22

Peripheral Central
Onset Sudden or Insidious Sudden
Severity of Vertigo Intense Spinning Ill-defined, may be severe or less intense
Prodromal Dizziness Occurs in up to 25%, often single episode Occurs in up to 25%, recurrent episodes suggest TIA’s
Intolerant of head movements/Dix-Hallpike Maneuver Yes Varies, but often intolerant
Associated Nausea/Diaphoresis Frequent Variable, but often frequent
Auditory Symptoms Points to peripheral causes May be present
Proportionality of Symptoms Usually proportional Often disproportionate
Headache/Neck Pain Unusual More likely
CNS signs/symptoms Absent Usually present
Head Impulse Test Abnormal Often normal
Nystagmus Horizontal Vertical/direction-changing
HINTS Testing Negative Abnormal in at least 1 out of 3 tests

Physical Exam

A focused neurological exam, including gait assessment, speech, and cranial nerves, in patients presenting with AVS is needed. Focal neurological deficits are consistent with a central cause of AVS. However, the absence of neurological deficits does not exclude a central cause. One review of AVS secondary to strokes found focal neurological deficits were present in 80% of cases.24 Additionally, Dix-Hallpike testing, while effective in diagnosing BPPV (a cause of triggered episodic vestibular syndrome), provides no diagnostic utility in the assessment of AVS.14 A potential tool for the Emergency Physician in evaluating patients with AVS is the HINTS examination.

HINTS Testing

HINTS testing is a three-part examination that consists of head impulse testing, nystagmus assessment, and test of skew. This test is the gold standard for diagnosis of posterior circulation strokes, as its sensitivity is higher than any imaging modality in the first 24-48 hours after symptom onset.  The HINTS test should  be used in patient complaining of continuous feelings of vertigo or dizziness, where concern for AVS is present.  It is not useful in patients with momentary position-related vertigo or patients with TIAs who are not dizzy when examined.25 For a great overview, see EMCrit at https://emcrit.org/podcasts/posterior-stroke/.

The first component of the HINTS test is head impulse testing.  Head impulse testing consists of having the patient visually fixate on a target followed by a rapid 40 degree head turn. This process is then repeated in the other direction. A unilateral abnormal finding (saccade) is consistent with a peripheral process and a normal response (no saccade) to this testing is consistent with a central process (Kattah, Edlow).14,20  This test is depicted in Figure 2 and an abnormal response is shown in Video 1.

Video 1: Abnormal Head Impulse Test

Screen Shot 2017-03-10 at 5.14.10 PM

The second component of the HINTS test is assessment of nystagmus, which analyzes the characteristics of nystagmus during lateral gaze at 45-60 degrees, not at end-gaze. Direction changing nystagmus is consistent with a central cause of AVS and unidirectional horizontal nystagmus is more consistent with a peripheral cause. Assessment of nystagmus is specific but not sensitive for a central cause of AVS.22 Vertical or torsional nystagmus in a patient with AVS is a sign of a central etiology.  However, strokes presenting with AVS may have a normal (horizontal) finding of nystagmus.20 A study by Lee et al. found that approximately half of pseudolabyrinthine strokes present with unilateral, horizontal findings of nystagmus.26

The final component of the HINTS test is the test of skew, which assesses ocular misalignment. This is determined using the alternating cover test, which consists of covering one eye and then assessing for any movement/re-fixation when the eye is uncovered. Any realignment is consistent with a central process. An abnormal test of skew is shown in Video 2. This test is also specific but not sensitive for central causes of AVS.22

Video 2: Abnormal Test of Skew

A helpful mnemonic for the HINTS testing results that are consistent with central causes is INFARCT (Impulse Normal, Fast-phase Alternating, Refixation on Cover Test).20

Table 5.  INFARCT mnemonic for HINTS findings suggestive of central cause of vertigo.20

INFARCT mnemonic
Impulse Normal
Fast-phase Alternating
Refixation on Cover Test

Buyers Beware…

Many of the studies evaluating the HINTS exam utilized neuro-ophthalmologists with specialized equipment and training, often in patients not in the ED. Thus, translating this to regular ED practice must be done with caution. A slow-motion camera (there are several apps available for phone use) can assist in detecting subtle ocular findings. More studies are needed evaluating the HINTS exam conducted by emergency physicians on ED patients. For more potential pitfalls in the ED, please see EMCrit at https://emcrit.org/emnerd/adventure-veiled-lodger/.


What is the role of imaging in the ED evaluation of patients with vertigo?  Patients with physical exam findings concerning for a central process require urgent imaging to assess for hemorrhage, infarction, or tumor.22 In regards to the type of imaging, MRI in addition to CT is preferred due to poor visualization of the posterior fossa with CT.27 The sensitivity of brain CT for posterior circulation infarcts is only 7-42%.28-31 However, even a negative MRI does not rule out a posterior circulation stroke in patients with a high clinical suspicion for a central cause.  MRI with DWI within the first 48 hours of infarction may miss up to 10-20% of posterior circulation strokes.32

The most important tool to evaluate for a central cause in patients with AVS is the HINTS exam performed by an experienced physician.  In the evaluation of posterior circulation stroke, Kattah et al. examined the various methods for diagnosis, shown in Figure 3.20 An abnormal HINTS test has been shown to be 100% sensitive and 96% specific for the detection of central causes of AVS, making it more sensitive than even MRI in the first 24-48 hours.20  Furthermore, a brain MRI takes at least 5-10 minutes to conduct not considering wait time, in addition to thousands of dollars in cost.  The HINTS test can be done in minutes at no additional cost.

Figure 3.  Diagnostic Modalities for Posterior Circulation Stroke20

Screen Shot 2017-03-10 at 5.14.30 PM


In considering the disposition of these patients, Edlow et al. in 2015 recommended disposition criteria.14 They recommended a patient presenting with AVS is likely safe to go home if:

  • Patient is able to sit and stand independently
  • Patient has no cranial or cerebellar signs
  • Patient has HINTS testing suggestive of a peripheral process

 HINTS exam results indicative of peripheral vertigo are unidirectional, horizontal nystagmus, unilaterally abnormal head impulse test, and normal vertical eye alignment (no skew).  Together, these findings reduce the odds of a stroke by at least 50 fold.24

Pearls and Pitfalls


  • Clarify what the patient means by dizziness regarding timing and triggers of the onset of symptoms. Distinguish dizziness from syncope or other mimicking conditions, as these will require a different work-up.
  • Suspect a central etiology in patients with acute vestibular syndrome. Evaluate with the HINTS exam.
  • Use the HINTS test in patients presenting with Acute Vestibular Syndrome, as this is more sensitive than both CT and MRI for posterior circulation strokes.
  • Nystagmus is assessed during lateral gaze at 45-60 degrees, not at end-gaze. An abnormal response in a patient with AVS is vertical or torsional nystagmus. 
  • The HINTS exam should only be used in patients presenting with Acute Vestibular Syndrome, not patients with Triggered or Spontaneous Episodic Vertigo Syndrome.


  • Symptoms that worsen with movement do not confirm a peripheral process. Symptoms with movement may also exacerbate symptoms from a central process.
  • A normal head CT is not sufficient in excluding ischemic stroke.
  • MRI should not be relied upon in the initial 24-48 hours after symptom onset to rule out a posterior circulation stroke, as it may miss up to 10-20% of posterior circulation strokes.
  • Younger age does not exclude central causes of Acute Vestibular Syndrome. A stroke should still be suspected in patients younger than 50 if the physical exam is concerning for a central process.
  • Many of the classic distinguishing features of peripheral lesions are also found in central lesions.

Case Resolution

You return to the room of the 38 y/o female with dizziness to gather a more detailed history and physical.  You determine that the patient’s dizziness began yesterday morning after she awoke, was constant all day yesterday, and has not resolved today.  She has experienced difficulty walking since yesterday and is still feeling dizzy currently.  Astutely categorizing this patient as exhibiting AVS, you conduct a HINTS exam in addition to a neurologic exam.  The HINTS exam is notable for direction-changing nystagmus and a positive test of skew.  Concerned for a central etiology of this patient’s vertigo, you order a brain MRI in addition to consulting neurology for further workup and management.


This post is sponsored by www.ERdocFinder.com, a supporter of FOAM and medical education, who with their sponsorship are making FOAM material more accessible to ER physicians around the world.

Screen Shot 2017-03-12 at 5.28.13 PM

References/Further Reading

  1. Lozano R, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.
    Lancet. 2012 Dec;380(9859):2095-128.
  2. Mozaffarian D et al.  Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association
  3. Savitz S, Caplan L. Vertebrobasilar Disease. N Engl J Med 2005;352:2618-26
  4. Ferro JM, Pinto AN, Falcao I, et al. Diagnosis of stroke by the nonneurologist: a validation study. Stroke 1998;29:1106-9.
  5. Kerber KA, Brown DL, Lisabeth LD, Smith MA, Morgenstern LB. Stroke among patients with dizziness, vertigo, and imbalance in the emergency department: a population-based study. Stroke. 2006;37: 2484–2487.
  6. Caplan LR, Wityk RJ, Glass TA, et al. New England Medical Center Posterior Circulation Registry. Ann Neurol 2004;56:389-98.
  7. Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 1988;19:1083-92.
  8. Moulin T, Tatu L, Vuillier F, Berger E, Chavot D, Rumbach L. Role of a stroke data bank in evaluating cerebral infarction subtypes: patterns and outcome of 1,776 consecutive patients from the Besancon Stroke Registry. Cerebrovasc Dis 2000;10:261-71.
  9. Vemmos K, Takis C, Georgilis K, et al. The Athens Stroke Registry: results of a five-year hospital-based study. Cerebrovasc Dis 2000;10:133-41.
  10. Crocco T, Goldstein J. Stroke. In Marx J, Hockberger R, Walls R. Rosen’s Emergency Medicine. 2014; 8: 1363-1374.
  11. Go S, Worman D. Stroke Syndromes. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill; 2016.
  12. Searls  DE, Pazdera  L, Korbel  E, Vysata  O, Caplan  LR: Symptoms and signs of posterior circulation ischemia in the New England Medical Center Posterior Circulation Registry. Arch Neurol. 2012; 69: 346.
  13. Bradley  WG, Daroff  RB, Fenichel  GM, Marsden  CD (eds): Neurology in Clinical Practice, 4th ed. Philadelphia, PA: Butterworth-Heinemann; 2004.
  14. Edlow JA, Newman-Toker D.  Using the Physical Exam to Diagnose Patients with Acute Dizziness and Vertigo.  J Emerg Med.  2016 Apr 50(4):  617-28.
  15. Drachman DA, and Hart CW: An approach to the dizzy patient. Neurology 1972; 22: pp. 323-334
  16. Kerber KA, Newman-Toker DE. Misdiagnosing dizzy patients: common pitfalls in clinical practice. Neurol Clin 2015;33:564–76
  17. Newman-Toker DE, Edlow JA. TiTrATE: a novel approach to diagnosing acute dizziness and vertigo. Neurol Clin 2015;33:577–99.
  18. Newman-Toker DE, Cannon LM, Stofferahn ME, Rothman RE, Hsieh YH, Zee DS. Imprecision in patient reports of dizziness symptom quality: a cross-sectional study conducted in an acute care setting. Mayo Clin Proc 2007;82:1329–40.
  19. Bisdorff A, Staab J, Newman-Toker D. Overview of the international classification of vestibular disorders. Neurol Clin 2015;33: 541–50.
  20. Kattah  JC, Talkad  AV, Wang  DZ, et al.: HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009; 40: 3504.
  21. Lee  H, Kim  JS, Chung  EJ, et al.: Infarction in the territory of anterior inferior cerebellar artery: spectrum of audiovestibular loss. Stroke. 2009; 40: 3745.
  22. Goldman B. Vertigo. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e. New York, NY: McGraw-Hill; 2016.
  23. Savitz  SI, Caplan  LR, Edlow  JA: Pitfalls in the diagnosis of cerebellar infarction. Acad Emerg Med. 2007; 14: 63.
  24. Tarnutzer  AA, Berkowitz  AL, Robinson  KA, et al.: Does my dizzy patient have a stroke? A systematic review of bedside diagnosis in acute vestibular syndrome. CMAJ. 2011; 183: E571.
  25. Caplan LR. Posterior circulation cerebrovascular syndromes. https://www.uptodate.com/contents/posterior-circulation-cerebrovascular-syndromes. Accessed February 22, 2017.
  26. Lee H, Sohn SI, Cho YW, et al. Cerebellar infarction presenting isolated vertigo: frequency and vascular topographical patterns. Neurology 2006;67:1178–1183.
  27. Kerber  KA, Schweigler  L, West  BT, et al.: Value of computed tomography scans in ED dizziness: analysis from a nationwide representative sample. Am J Emerg Med. 2010; 28: 1030.
  28. Chalela JA, Kidwell CS, Nentwich LM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet 2007;369:293–8.
  29. Hwang DY, Silva GS, Furie KL, Greer DM. Comparative sensitivity of computed tomography vs. magnetic resonance imaging for detecting acute posterior fossa infarct. J Emerg Med 2012;42:559–65.
  30. Kabra R, Robbie H, Connor SE. Diagnostic yield and impact of MRI for acute ischaemic stroke in patients presenting with dizziness and vertigo. Clin Radiol 2015;70:736–42.
  31. Ozono Y, Kitahara T, Fukushima M, et al. Differential diagnosis of vertigo and dizziness in the emergency department. Acta Otolaryngol 2014;134:140–5.
  32. Saber Tehrani AS, Kattah JC, Mantokoudis G, et al. Small strokes causing severe vertigo: frequency of false-negative MRIs and nonlacunar mechanisms. Neurology 2014;83:169–73.


Seizure Mimics: Pearls & Pitfalls

Authors: James L Webb, MD (Internal Medicine, SAUSHEC, USAF) and Brit Long, MD (@long_brit) // Edited by: Erica Simon, DO, MHA (@E_M_Simon) & Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

A 20 year-old female presents to the ED after a witnessed fall. According to bystanders, the young woman was walking towards a gym treadmill when she collapsed to the floor below, convulsing for approximately1-2 minutes. Upon EMS arrival VS were within normal limits, GCS was noted as 14 (confusion, orientation only to self), EKG revealed NSR, and accucheck demonstrated a blood glucose of 134. Intravenous access was obtained en route to your facility.

As you interview and examine the patient, you note ABCs intact, a GCS of 15, an ample history remarkable only for report of a “rising feeling in the abdomen” prior to the event, and a secondary survey without obvious signs of trauma. ED evaluation, to include a CBC, CMP, EKG, and non-contrasted head CT are all within normal limits. Urine Hcg is negative.

Was this a seizure? What’s the appropriate patient disposition? If you’ve got questions, we’ve got important details on seizures and their mimics.



Current data indicate that nearly 2 million U.S. residents are affected by Epilepsy.1-2 In addition to this population, approximately 150,000 Americans (age >18 years) present to healthcare providers annually following an apparent first seizure.1-2 As assigning a diagnosis a seizure or seizure disorder is not without significant health and quality of life implications (employment repercussions, driving restrictions, etc.1-5), emergency physicians must be aware of conditions that may mimic seizure activity: syncope, psychogenic non-epileptic seizures, metabolic derangements, stroke or TIA, sleep disorders, and migraines.


Seizures – A Review

Seizures result from abnormal neurologic electrical activity. This abnormal activity can occur in both hemispheres (generalized seizure) or within one hemisphere (focal seizure), which may spread to the entire brain. Generalized seizures are more common than focal seizures, and often have a genetic association.6 Generalized tonic-clonic seizures most frequently occur in adults – the motions of which consist of a tonic phase with muscle stiffening, followed by a clonic phase with rhythmic muscle contractions.6-7 Focal seizures often occur in the setting of cerebral insult.7 Unlike generalized seizures, symptoms of focal seizures vary according to the anatomic location of the abnormal electrical activity.6,8

Seizures can be classified as provoked or unprovoked. Provoked seizures are those with identifiable causes, which can be isolated to the brain, or are thought to occur secondary to a systemic disorder or illness. Such causes include: brain trauma, CNS infection (i.e. meningitis, encephalitis, brain abscess), anoxic brain injury, intracranial hemorrhage or surgery, metabolic disorders, illicit drug abuse or intoxication (most commonly tricyclic antidepressants and isoniazid), or alcohol withdrawal.9,10  Seizures may also occur in the setting of metabolic derangements (hypoglycemia or hyponatremia).9-12

 Unprovoked seizures are those with no discernible cause, or those occurring greater than seven days following precipitating factors or events. What factors or events might the emergency physician identify through the H&P?

  • Pregnant patient with a seizure –>evaluate for eclampsia
  • Child with an recent illness –>evaluate for personal and familial history of febrile seizures
  • In all patients –>inquire regarding a history of recent head trauma (occurring within 1 week prior to presentation)

It is particularly important to perform a thorough H&P in this patient population, as 50% of individuals experiencing an unprovoked seizure will experience a recurrence.11



Patients presenting with altered mental status (AMS)/seizure concern should be quickly assessed10,13-15,17:

  • ABCs
  • Consider obtaining a POC glucose level
  • First line treatment for seizure activity: benzodiazepines (lorazepam 0.1 mg/kg IV)
    • Second line agents: phenytoin, fosphenytoin, levetiracetam, or valproic acid
      • Intubation with propofol or ketamine with contiguous EEG (in consultation with neurology) may be required.14-17
    • After addressing ABCs, perform an H&P, complete a physical examination (PE), and obtain IV access. Consider: CBC, CMP, EKG, serum Hcg, anticonvulsant level if applicable, imaging as appropriate (CT recommended in the setting of new focal deficits, head trauma, continued AMS, immunocompromised state, history of cancer, persistent fever, focal seizures, history of stroke, or anticoagulation), +/- an LP.13,15-19
      • Note: neuroimaging should be performed in patients with suspected new-onset seizures, but may occur in the outpatient setting for those with a first time generalized tonic-clonic seizure with a normal neurologic exam. MRI is preferable with a higher yield of identifying abnormalities in the non-emergent setting.13,15-19
    • Disposition is often determined in conjunction with specialty consultation. Admission may be required in the setting of persistent neurologic deficit, persistent AMS, or poor social situation.13,15-19 Patients who return to mental status baseline, possess a normal neurologic exam, and whose labs and imaging are without pathology, may be discharged with outpatient follow-up.13,19

 For an in-depth discussion of seizure evaluation and management, see:  http://www.emdocs.net/treatment-of-seizures-in-the-emergency-department-pearls-and-pitfalls/


Evaluating Seizure Activity in Patients with Return to Mental Status Baseline

 A definitive diagnosis of seizure is made by EEG interpretation during seizure activity. As this is often times impossible in the ED setting, the emergency physician must seek out signs and symptoms commonly associated with seizure activity9,13,20:

  • HPI significant for aura: déjà vu, a rising sensation in the abdomen, abnormal taste or smell, or autonomic changes.
    • Activity commonly associated with a true seizure: witnessed tonic/clonic movements or observed head turning in the setting of a generalized seizure, or the abrupt onset of limb movements, abnormal sensations, or hallucinations in the setting of a focal seizure. 6,7,20
    • A postictal period occurring for minutes to hours with confusion, disorientation, and drowsiness.
  • Physical exam remarkable for tongue biting.

See Table 1 for signs and symptoms related to seizure activity in studies comparing seizures versus syncope. *Urinary incontinence was demonstrated to lack clinical significance.


What about laboratory studies?

 A lactate level may be useful in differentiating seizures from psychogenic non-epileptic seizures and syncope (sensitivity of 88%, specificity 87% for true seizure activity), 24 while an elevated CK is suggestive of epileptic seizures (specificity 85-100%), but demonstrates variable sensitivity (15-88%).25


Seizure Mimics

Studies indicate that approximately 20% of patients presenting for evaluation of seizure are misdiagnosed as having epilepsy.26  Conditions most commonly mistaken for epitileptiform seizure activity include syncope and psychogenic non-epileptic seizures.5 Detailed below is a review of seizure mimics with tips and tricks for ED evaluation and disposition.


Syncope is a sudden loss of consciousness (LOC) due to decreased cerebral perfusion, resulting in loss of postural tone, with rapid return to mental status baseline. Syncope may be cardiac, orthostatic, or neurocardiogenic (vasovagal) in origin.

Historical evidence favoring a syncopal episode versus a seizure27-34:

  • Presentation –>LOC with rapid return to mental status baseline.
  • History –>Remarkable for precipitating factors: recent illness (emesis/diarrhea – hypovolemia), recent medication changes (i.e. B-blockers and bradycardia, diuretics causing hypovolemia, etc.), LOC following increased vagal tone (coughing, defecation, shaving).  LOC during physical exertion. In obtaining the HPI, it is important to note that myoclonic jerking occurs in up to 90% of patients experiencing syncope.27

Management and Disposition Pearls:

  • Evaluation –> EKG for dysrhythmias, consider a CBC and CMP to assess for anemia and electrolyte derangement, consider cardiac markers as indicated.
  • Disposition–>As appropriate. Referral for tilt-table testing in the setting of neurocardiogenic syncope may be considered after ruling out life-threatening conditions.

Notes on Syncope of Cardiac Origin

Syncope secondary to cardiac dysrhythmias or structural heart disease may present similarly to a seizure, however, the following suggest cardiac origin27-29, 33,34:

  • Presentation –>Most commonly an elderly patient.
  • History –>The absence of a prodrome; ROS positive for palpitations prior to LOC; CP or LOC during exertion.

Management and Disposition Pearls:

  • Evaluation –>PE for murmurs, rubs, gallops and s/s of heart failure (JVD, peripheral edema, hepatojugular reflex, etc.); EKG for dysrhythmias: SVT, VT, Mobitz type II second-degree, or third-degree AV block, bundle branch blocks, Long QT Syndrome, Brugada Syndrome, WPW Syndrome, Right Ventricular Dysplasia, and pacemaker malfunction have all been associated with syncopal episodes.33 Consider bedside POCUS or formal echocardiogram to evaluate for cardiac structural anomalies.
  • Disposition –>As appropriate. In the large majority of cases admission is required for adjunct testing.


Psychogenic Non-Epileptic Seizure (PNES) Disorder

PNES, a condition characterized by the presence of seizure-like activity occurring in the absence of EEG changes, is difficult to differentiate from a true seizure in the emergency setting; even more so as nearly 40% of patients with epilepsy suffer from the disorder.35 Characteristics that make PNES more likely include35-39:

  • Presentation –>Patient in their 20s-30s,35 experiencing an event characterized by asynchronous extremity movements, rapid head turning, pelvic thrusting, eye closing, or geotropic eye movements. Clinical clues useful for the provider: the absence of tongue biting, a prolonged duration (>2 mins), a patient who can recall the event, or a patient who was witnessed to have been crying during the seizure-like activity.
  • History –>Approximately 70% have a PMHx of a psychiatric disorder (depression, PTSD, personality disorder).36,37

Management and Disposition Pearls:

  • Evaluation –>When in doubt: treatment as appropriate (ABCs +/- benzodiazepines). Video EEG is the gold standard for diagnosis, therefore specialty consultation is required.
  • Disposition –>In consultation with neurology/neuropsychiatry. Treatment is often targeted to the underlying psychiatric disorder.39


Metabolic Derangements

Metabolic disorders are identified in 2.4-8% of patients presenting with first generalized seizure.9,10,13 Hypoglycemia and hyponatremia are the most common, but other disorders may include hypernatremia, hyperglycemia, hypercalcemia, and uremia.9,10,13

 Management and Disposition Pearls:

  • Evaluation –>Accucheck for all patients with AMS/seizure activity. CMP as appropriate.
  • Disposition –>Treatment and admission requirements based upon laboratory findings.


Stroke and TIA 

Stroke/TIA can be confused with a seizure when there is resolution of the neurologic deficit previously caused by cerebral ischemia. Characteristics of Stroke/TIA18,40,41:

  • Presentation –>Most commonly a middle-aged or elderly patient. HPI remarkable for negative symptoms: numbness, weakness, or blindness.
  • History –>PMHx significant for HTN, HLD, cardiac arrhythmia, family history of CVA

Management and Disposition Pearls:

  • Evaluation –>PE: focused neurological examination, accucheck, EKG for dysrhythmias, performance of risk stratification to determine the requirement for cerebral vasculature imaging.
  • Disposition –>As appropriate. Inpatient admission may be required for MRI, carotid ultrasonography, echocardiography, and medication optimization.


Sleep Disorders

Narcolepsy with cataplexy may present similarly to seizures. Narcolepsy is defined by excessive daytime sleepiness, lapses into sleep, or multiple naps during the same day at least 3 times per week for a duration of 3 months time. Cataplexy is the sudden loss of tone in response to emotion. 42-45

  • Presentation –>Patient suddenly collapses, but rapidly recovers to mental status baseline with complete recollection of the  event. 42-45

Management and Disposition Pearls:

  • Evaluation –>Thorough history-taking often allows differentiation from seizure activity.
  • Disposition –>Specialty referral for overnight polysomnography and sleep latency testing. Driving restriction is often state-mandated if the condition is suspected. 42-45



 Migraines are recurrent headaches with or without aura (visual or sensory symptoms). Symptoms include throbbing headache, nausea, vomiting, and sensitivity to light and sound. Auras are often positive visual symptoms. Migraines with aura are similar to certain focal seizures with visual symptoms (hallucinations) or generalized seizure prodrome (aura). Signs and symptoms making a diagnosis of migraine more likely19, 50-52:

  • Presentation –>headache characterized by unilateral pain, throbbing pain, moderate-severe pain, and aggravated by physical activity, +/- nausea/vomiting or photo-/phonophobia
  • History –>PMHx significant for migraines.

Keep in mind, complex migraines may present with neurologic symptoms causing weakness, alteration in consciousness, or LOC.

Management and Disposition Pearls:

  • Evaluation –>PE: focused neurological examination. Rule out intracranial pathology as appropriate (CVA/SAH/meningitis/encephalitis – CT, LP, etc.)
  • Disposition –>As appropriate. In the setting of negative imaging (+/- negative LP), neurology consultation is appropriate as prophylactic medications (TCAs, B-blockers, anti-epileptics) may be considered for outpatient therapy.



– Seizures are caused by abnormal neurologic electrical activity resulting in motor, sensory, and behavioral symptoms.
In all patients presenting with AMS or actively seizing: ABCs, accucheck, initiate therapy as appropriate (benzodiazepines first line).
– For patients presenting after return to baseline mental status: a thorough history and physical examination are key to differentiating between a true seizure and its mimic.
– If a seizure is not suspected, consider syncope, psychogenic non-epileptic seizures, stroke or TIA, sleep disorders, and migraines.


References/Further Reading

  1. Hauser WA, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia. 2008;49 Suppl 1:8-12.
  2. Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-Based Guideline: Management of an Unprovoked First Seizure in Adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsy Curr. 2015 May-Jun;15(3):144-52.
  3. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998 Apr 2;338(14):970-6.
  4. England MJ, Livermari CT, Schultz AM, Strawbridge LM Institute of Medicine (US) Committee on the Public Health Dimensions of the Epilepsies; England MJ, Livermari CT, Schultz AM, Strawbridge LM, editors. Epilepsy Across the Spectrum: Promoting Health and Understanding. Washington, DC: The National Academies Press; 2012.
  5. Xu Y, Nguyen D, Mohamed A, et al. Frequency of a false positive diagnosis of epilepsy: A systematic review of observational studies. 2016 Aug 23;41:167-174.
  6. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010 Apr;51(4):676-85.
  7. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med. 2003 Sep 25;349(13):1257-66.
  8. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475.
  9. Beghi E, Carpio A, Forsgren L, et al. Recommendation for a definition of acute symptomatic seizure. Epilepsia. 2010;51(4):671.
  10. Fields MC, Labovitz DL, French JA. Hospital-onset seizures: an inpatient study. JAMA Neurol. 2013 Mar;70(3):360-4.
  11. Riggs JE. Neurologic manifestations of electrolyte disturbances. Neurol Clin. 2002 Feb;20(1):227-39.
  12. D’Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999 Mar 25;340(12):915-9.
  13. Dunn MJ, Breen DP, Davenport RJ, Gray AJ. Early management of adults with an uncomplicated first generalised seizure. Emerg Med J. 2005 Apr;22(4):237-42.
  14. Pillow MT. Seizure Assessment in the Emergency Department. Emedicine: Medscape. http://emedicine.medscape.com/article/1609294-overview. Accessed 11 August 2016.
  15. American College of Emergency Physicians. Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2014 Apr;63(4):437-47.e15.
  16. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011 Oct;134(Pt 10):2802-18.
  17. Brophy, Gretchen M., Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012 Aug;17(1):3-23.
  18. Harden CL, Huff JS, Schwartz TH, et al. Reassessment: neuroimaging in the emergency patient presenting with seizure (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2007 Oct 30;69(18):1772-80.
  19. French JA, Pedley TA. Clinical practice. Initial management of epilepsy. N Engl J Med. 2008 Jul 10;359(2):166-76.
  20. Manford M. Assessment and investigation of possible epileptic seizures. J Neurol Neurosurg Psychiatry. 2001;70(Suppl 2):ii3–ii8.
  21. Brigo F, Nardone R, Bongiovanni LG. Value of tongue biting in the differential diagnosis between epileptic seizures and syncope. Seizure. 2012 Oct;21(8):568-72.
  22. Brigo F, Nardone R, Ausserer H, et al. The diagnostic value of urinary incontinence in the differential diagnosis of seizures. Seizure. 2013 Mar;22(2):85-90.
  23. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol. 2002 Jul 3;40(1):142-8.
  24. Matz O, Zdebik C, Zechbauer S, et al. Lactate as a diagnostic marker in transient loss of consciousness. Seizure. 2016 Aug;40:71-5.
  25. Brigo F, Igwe SC, Erro R, Bongiovanni LG, et al. Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review. J Neurol. 2015 Feb;262(2):251-7.
  26. Smith PE. Epilepsy: mimics, borderland and chameleons. Pract Neurol. 2012 Oct;12(5):299-307.
  27. Chen LY, Benditt DG, Shen WK. Management of syncope in adults: an update. Mayo Clin Proc. 2008 Nov;83(11):1280-93.
  28. Walsh K, Hoffmayer K, Hamdan MH. Syncope: diagnosis and management. Curr Probl Cardiol. 2015 Feb;40(2):51-86.
  29. Huff JS, Decker WW, Quinn JV, et al.; American College of Emergency Physicians. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with syncope. Ann Emerg Med. 2007 Apr;49(4):431-44.
  30. Grubb BP. Clinical practice. Neurocardiogenic syncope. N Engl J Med. 2005 Mar 10;352(10):1004-10.
  31. Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol 1994 Aug;36(2):233–7.
  32. McKeon A, Vaughan C, Delanty N. Seizure versus syncope. Lancet Neurol. 2006 Feb;5(2):171-80.
  33. Morag R. Syncope. Emedicine: Medscape. http://emedicine.medscape.com/article/811669-overview. Accessed 15 August 2016.
  34. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009). the task force for the diagnosis and management of syncope of the European Society of Cardiology (ESC). Eur Heart J. 2009 Nov;30(21):2631-71.
  35. Alsaadi TM, Marquez AV. Psychogenic nonepileptic seizures. Am Fam Physician. 2005 Sep 1;72(5):849-56.
  36. Panagos PD, Merchant RC, Alunday RL. Psychogenic seizures: a focused clinical review for the emergency medicine practitioner. Postgrad Med. 2010 Jan;122(1):34-8.
  37. Shaibani A, Sabbagh MN. Pseudoneurologic syndromes: recognition and diagnosis. Am Fam Physician. 1998 May 15;57(10):2485-94.
  38. LaFrance WC Jr, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. 2013 Nov;54(11):2005-18.
  39. Siket MS, Merchant RC. Psychogenic seizures: A review and description of pitfalls in their acute diagnosis and management in the emergency department. Emerg Med Clin North Am. 2011 Feb;29(1):73-81.
  40. Johnston SC. Clinical practice. Transient ischemic attack. N Engl J Med 2002 Nov 21; 347(21):1687-92.
  41. Nanda A. Transient Ischemic Attack. Emedicine: Medscape. http://emedicine.medscape.com/article/1910519-overview. Accessed 22 August 2016.
  42. American Academy of Sleep Medicine. The International Classification of Sleep Disorders-Revised: Diagnostic and Coding Manual. 3rd ed. Rochester, MN: American Academy of Sleep Medicine; 2014.
  43. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013. 372-78.
  44. Bozorg, A. Narcolepsy. Emedicine: Medscape. http://emedicine.medscape.com/article/1188433-overview. Accessed 22 August 2016.
  45. Scammell TE. Narcolepsy. N Engl J Med. 2015 Dec 31;373(27):2654-62.
  46. Tarsy D, Simon D. Dystonia. N Engl J Med. 2006 Aug 24;355(8):818-29.
  47. Smith PE. If it’s not Epilepsy. J Neurol Neurosurg Psychiatry 2001;70:9-14.
  48. Moberg-Wolff EA. Dystonias. Emedicine: Medscape. http://emedicine.medscape.com/article/312648-overview. Accessed 22 August 2016.
  49. Albanese A, Barnes MP, Bhatia KP, et al. A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force. Eur J Neurol. 2006 May;13(5):433-44.
  50. Sances G, Guaschino E, Perucca P, et al. Migralepsy: a call for a revision of the definition. Epilepsia 2009;50:2487–96.
  51. Goadsby PJ, Lipton RB, Ferrari MD. Migraine–current understanding and treatment. N Engl J Med. 2002 Jan 24;346(4):257-70.
  52. Chawla J. Migraine. Emedicine: Medscape. http://emedicine.medscape.com/article/1142556-overv



Thunderclap Headache – Pearls and Pitfalls

Authors: Drew A. Long, BS (@drewlong2232, Vanderbilt University School of Medicine) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

You are working in the ED and see that your next patient is a 38 y/o female complaining of headache.  As soon as you enter the room, you notice the patient appears to be in pain, holding her hand to her left temple and wincing.  She states she was going on a run about an hour earlier when she experienced a 10/10 intensity headache.  When you ask about the onset of the headache, she states “One moment I was running, and suddenly I was bent over in pain.”  She also complains of dizziness, nausea, and tingling and numbness of her left hand and foot.  The patient has no history of headaches and no pertinent past medical history.  She recently gave birth 6 weeks prior via spontaneous vaginal delivery.  Her vitals include HR 110, RR 16, BP 173/100, oxygen saturation of 98%, and a normal temperature.  As you gather the rest of the history and move to the physical examination, what must you consider in this patient?

What is a thunderclap headache?

A thunderclap headache (TCH) has been defined as a “headache that reaches 7 (out of 10) or more in intensity within less than one minute.”1 TCH is often unexpected and not preceded by any warning signs or symptoms.  While the duration and location of the headache are important parts of the history, they do not have a role in defining TCH and are nonspecific for TCH.1 When evaluating a patient with a headache, it is vital the Emergency Physician (EP) determine both the intensity and time it took the headache to reach maximum severity.  The EP must keep in mind that a normal neurological exam and absence of any associated symptoms does not exclude a serious cause in a patient with a TCH, and the patient still requires a diagnostic workup for potentially deadly pathologic conditions.1 Additionally, pain relief with treatment does not exclude a serious cause.2-4

The classic teaching in medical school is that a “thunderclap” headache is pathognomonic for subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm.  However, only 11-25% of TCHs are due to SAH.5,6 What else should the EP think of when a patient presents with a TCH?

Differential Diagnosis

Table 1 depicts conditions that may manifest as a TCH.1,7,8

Subarachnoid Hemorrhage
Cerebral Venous Thrombosis
Cervical Artery Dissection
Acute Hypertensive Crisis/

Posterior Reversible Encephalopathy Syndrome

Ischemic Stroke
Intracranial Hypotension
Pituitary Apoplexy
Retroclival Hematoma
Third Ventricle Colloid Cyst
Temporal Arteritis
Reversible Cerebral Vasoconstriction Syndrome

Subarachnoid Hemorrhage

Most cases of SAH occur from a ruptured cerebral aneurysm (about 85% of cases), which occur most commonly at branch points in the Circle of Willis.9 The typical presentation of SAH is a sudden, severe headache that the patient describes as “the worst headache of my life.”  A headache will be the primary symptom of SAH in 70% of patients, of which 50% will present with a TCH.6,10-12 The headache usually lasts for several days and very rarely resolves within a few hours.13 Accompanying signs and symptoms include loss of consciousness (one third of patients), seizures (6-9%), delirium (16%), stroke, visual disturbances, N/V, dizziness, neck stiffness, and photophobia.14-16

As TCH is a common presentation of a SAH, any patient that presents with TCH must be evaluated for SAH due to high morbidity and mortality.  According to literature, the average fatality rate of SAH is 51%.17 About 10% of patients with aneurysmal SAH die prior to hospital arrival, 25% die within the first 24 hours of SAH onset, and 45% die within 30 days.18

In evaluating for SAH it is helpful to consider a sentinel headache.  A sentinel headache is a headache that occurs days or weeks prior to a ruptured cerebral aneurysm.  This is thought to arise from a small leak of blood into the subarachnoid space.8 About 10-43% of patients with aneurysmal SAH report a prior similar warning headache.19 Importantly, signs often accompanying SAH, such as a stiff neck, altered mental status, and focal neurological deficits, are usually absent in a sentinel headache.7 However, even if these signs are absent the patient still requires evaluation for a SAH.  For more on evaluation of SAH, see http://www.emdocs.net/controversies-in-the-diagnosis-of-subarachnoid-hemorrhage/.

Cerebral Venous Thrombosis

A headache occurs in 75-95% of patients with cerebral venous thrombosis (CVT).20,21 While the onset of headache in CVT is usually gradual, about 2-13% of patients experience a TCH as the primary symptom.22 Additionally, patients may experience accompanying neurological symptoms from several vascular territories.  Other signs and symptoms include seizures (more commonly focal), papilledema, altered mental status, and focal neurological deficits.7,8 The symptoms can be associated with thrombus location.23,24 Importantly, patients with CVT presenting with TCH as their main symptom are clinically indistinguishable from patients with SAH presenting with TCH.7

While CVT is a relatively rare disorder, 80% of patients with CVT are younger than 50.23,25,26 CVT is more common in women, especially in the peripartum period and in patients with recent surgery.27 CVT is also associated with hypercoagulable states including the use of oral contraceptives, hematologic disorders, factor V Leiden, protein C or S deficiency, and anti-thrombin III deficiency.25,28

For more information about CVT, check out a previous post here:  http://www.emdocs.net/cerebral-venous-thrombosis-pearls-and-pitfalls/

Cervical Artery Dissection

A cervical artery dissection can result in an ischemic stroke, transient ischemic attack, or more rarely a SAH.8 Carotid or vertebral artery dissections are an especially important cause of strokes to consider in young and middle aged patients.29-32 A significant risk factor is a history of neck trauma, which can be minor (e.g. manipulation therapy of the neck or sports-related trauma).33 Other risk factors include connective tissue disease, large vessel arteriopathies, hypertension, and a history of migraines.34-36

Headaches are reported in 60-95% of patients with carotid artery dissections and 70% of patients with vertebral artery dissections.36 While headache onset is typically gradual, TCH occurs in about 20% of patients with a cervical artery dissection.38,39 According to the International Headache Society’s diagnostic criteria, headaches from cervical artery dissection must be ipsilateral to the dissected artery.40 The typical first symptom of a cervical artery dissection is unilateral headache (68%), neck pain (39%), or facial pain (10%).41 The headache from a carotid artery dissection is found most commonly in the frontotemporal region.42 Additionally, about 25% of patients will experience a partial Horner’s syndrome (miosis and ptosis).43 A vertebral artery dissection presents with neck pain (66%) and headache (65%), which can be unilateral or bilateral.44 The headache is more commonly posterior in location.  Many other symptoms may be present, including facial paresthesia, dizziness, vertigo, nausea/vomiting, visual disturbances (such as diplopia), ataxia, limb weakness or numbness, dysarthria, and hearing loss.42

Acute Hypertensive Crisis/Posterior Reversible Encephalopathy Syndrome

Two case reports describe patients who presented with TCH from either a hypertensive crisis or posterior reversible encephalopathy syndrome (PRES).45,46 In a hypertensive emergency, while the diastolic pressure is often ≥ 120 mmHg, there is no specific threshold, as different patients will manifest signs of end-organ damage at varying blood pressures.47 While about 20% of patients with hypertensive crises have associated headaches, most of these are not a TCH but rather a throbbing headache.48 Additionally, a hypertensive crisis may present with symptoms in addition to headache consistent with end-organ damage.  These may include dizziness, dyspnea, vision change, chest pain, psychomotor agitation, change in urine output, fluid overload state, or focal neurological deficits.8

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with radiographic findings that presents with headache, seizures, and visual loss often with extreme hypertension.49 Other symptoms include nausea/vomiting, focal neurological signs, or altered mental status.49,50 Specific radiographic findings are necessary for the diagnosis, most commonly symmetric white matter edema in the posterior cerebral hemispheres.51 The headache associated with PRES generally has an acute onset.7 PRES may occur in conjunction with other disorders including eclampsia, thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, and immunosuppressive therapy.52

It is important to determine whether a patient with TCH is hypertensive due to a stress response to the severe headache or if the TCH is the result of the hypertension.  In patients with TCH and extreme hypertension, it is vital to evaluate for signs of end-organ damage suggesting an acute hypertensive crisis and to consider PRES in patients presenting with headache, seizures, and visual loss.

Ischemic Stroke

About 25-34% of patients with stroke develop an associated headache.53,54 In 50% of these patients, the headache precedes any other neurological signs or symptoms.54 Typically, the headache is throbbing and ipsilateral to the side of the stroke.54  TCH associated with stroke is rare, but several case reports document patients presenting with TCH due to stroke.5,55,56

Spontaneous Intracranial Hypotension

The most common cause of spontaneous intracranial hypotension is CSF leakage from spinal meningeal defects or dural tears.57 This most commonly occurs after lumbar puncture, but can occur from minor trauma such as falls, lifting, coughing, or sports.1,7 Most commonly intracranial hypotension presents with a positional headache that improves after lying down and worsens when upright.58 However, 15% of patients will present with TCH.59,60  Other symptoms associated with spontaneous intracranial hypotension are nausea/vomiting, dizziness, auditory changes, diplopia, visual blurring, interscapular pain, or upper extremity pain.7,8


Meningitis can very rarely present with TCH.  A prospective study of patients presenting with TCH found 2.7% to have an infectious etiology.6 Consider meningitis if the patient is febrile, at increased risk for infection (immunocompromised), or has features of meningitis (e.g. stiff neck).

Pituitary Apoplexy

Pituitary apoplexy occurs with hemorrhage or infarction of the pituitary gland.1,7,8 This most commonly occurs in the setting of a pituitary adenoma, but may occur in association with pregnancy, general anesthesia, bromocriptine therapy, or pituitary irradiation.61 Pituitary apoplexy usually presents with a combination of acute headache, ophthalmoplegia, decreased visual acuity, reduction in visual fields, and altered mental status.62 The headache is usually sudden and severe.62

Retroclival hematoma

A retroclival hematoma is usually seen as a rare manifestation of severe head and neck injuries in which there is atlantoaxial dislocation.63,64 Patients with retroclival hematomas may present with TCH, which has been described in several patients.65,66

Third Ventricle Colloid Cyst

A colloid cyst of the third ventricle can impede the flow of CSF leading to obstructive hydrocephalus.  Third ventricle colloid cysts account for 0.5% of intracranial tumors and are most commonly diagnosed between the third and fifth decades of life.67 The most common symptom is headache, which occurs in 68-100% of patients.68 The headache of a third ventricle colloid cyst usually begins abruptly, lasts for seconds up to one day, and resolves quickly.69 The headache may be relieved with a supine position. Additionally, 50% of patients have associated nausea/vomiting.  They can also experience loss of consciousness, altered mental status, seizures, coma, or death.68

Temporal Arteritis

Temporal arteritis is a very rare cause of TCH.  Temporal arteritis should be suspected in older patients (>50) complaining of a new onset headache, temporal pain, visual symptoms, or jaw claudication.  It is also associated with polymyalgia rheumatica, which occurs in 40-50 percent of patients with temporal arteritis.70 For more information on temporal arteritis, check out this previous post:  http://www.emdocs.net/can-giant-cell-arteritis-be-ruled-out-in-the-ed/.

Reversible Cerebral Vasoconstriction Syndrome

Reversible Cerebral Vasoconstriction Syndrome (RCVS) includes conditions associated with TCH and diffuse, segmental, reversible vasospasm.71,72 RCVS is thought to account for most cases of TCH that are termed “benign,” or unexplained.1 Risk factors for RCSV include the postpartum period, history of migraine, and use of pharmacologic agents including ergotamine, triptans, SSRIs, pseudoephedrine, cocaine, amphetamines, ecstasy, cannabis, and bromocriptine.73-81 Half of RCVS cases occur during the postpartum period or after exposure to serotoninergic agents, adrenergic agents, or cannabis.81-83

The hallmark of RCVS is multiple thunderclap headaches that recur every day or every few days.  These headache recurrences can occur for up to four weeks.72,81 Other symptoms include altered mental status, motor or sensory deficits, seizures, visual changes, ataxia, speech abnormalities, and N/V.7

While RCVS is usually self-limiting, it is not always benign.  A minority of patients can experience residual effects including seizures or strokes.72,82,84

Other causes of TCH

Other conditions that have been reported in association with TCH include complicated sinusitis; cluster headache; primary cough, exertional, and sexual headaches; and primary TCH.1,7,8


What is the workup of TCH?

Every patient with TCH must be assumed to have a life-threatening intracranial condition.  Management of patients presenting with TCH starts with the ABCs.  Once the patient is stabilized, diagnostic evaluation is initiated beginning with specific evaluation for SAH.  Schwedt, Matharu, and Dodick proposed an algorithm for TCH evaluation in 2005, beginning with head CT:7


Figure 1.  Diagnostic Evaluation of TCH.7 (CVST:  cerebral venous sinus thrombosis; SIH:  spontaneous intracranial hypotension; PRES:  posterior reversible encephalopathy syndrome; RCVS:  reversible cerebral vasoconstriction syndrome)

The initial imaging modality is a noncontrast head CT.  CT scan has a high sensitivity and specificity for SAH.  When conducted within 6 hours of onset of TCH, CT has a specificity of 98% and sensitivity nearing 100%.11 As time from headache onset increases, the sensitivity of CT for SAH declines:  86% on day two, 76% after two days, and 58% after five days.85 However, these numbers are based on head CTs interpreted by neuroradiologists, and the scanners utilized were at least third generation.

Unfortunately, CT can miss many causes of TCH including SAH (especially if after 12 hours), CVT, CVA dissection, acute hypertensive crisis/PRES, intracranial hypotension, meningitis, pituitary apoplexy, and retroclival hematoma.  For CVT, the initial CT may be normal in up to 25-30% of patients.86 In a patient with CVA dissection without an ischemic stroke, head CT is usually normal.1,7 Similarly, CT is typically unrevealing in patients with acute hypertensive crisis, intracranial hypotension, meningitis, pituitary apoplexy, and retroclival hematoma.1,7,8 For patients with an acute hypertensive crisis or PRES, while neuroradiographic changes may be apparent on CT, they are best visualized on MRI.87,88

Some authors recommend always performing a CTA or MRA after negative CT noncontrast.1,7,72,89 If the patient has a SAH, a CTA can detect a ruptured aneurysm.  One method is for the TCH patient to receive a CT and CTA, as CTA will additionally further evaluate for SAH or an aneurysm, CVA dissection, stroke, and RCVS.

An LP with opening pressure can aid in diagnosis.  LP is the gold standard for the diagnosis of SAH, especially if the patient presents after 12 hours of headache onset.11,89,90 CSF studies including glucose, protein, white cells, and differential are used for diagnosing viral and bacterial meningitis.  Additionally, opening pressure can be utilized to detect increased or decreased pressures.  CVT may be associated with an elevated opening pressure, while intracranial hypotension is associated with a low opening pressure.1,22 Finally, the CSF should be visually inspected for xanthochromia.

The majority of evidence states that conventional angiography is not necessary in patients with a normal head CT and LP.91 Angiography has a small risk of transient and permanent neurological complications.92 In evaluating patients with TCH and normal head CT and LPs, prospective studies have found no subsequent development of SAH or sudden death in patients with normal head CT and normal LP, supporting the viewpoint that conventional angiography may be more harmful than helpful.93-96

The role of MRI for imaging of the brain and cerebral vasculature has not yet been defined in patients with TCH, especially in the setting of the Emergency Department.  Schwedt, Matharu, and Dodick in 2005 recommended that patients presenting with TCH and a normal head CT and LP receive further evaluation with MRI.7 An MRI can help further evaluate for CVT, pituitary apoplexy, PRES, or intracranial hypotension.7 If MRI is normal, Schwedt et al. recommends evaluation with either an MRA or MRV.  Ducros and Bousser in 2012 have similar recommendations and state that all patients with TCH and a normal head CT and LP should receive a CTA or MRA.1 If these are normal, they recommend a brain MRI for further evaluation.

Even with a thorough workup, studies estimate that a diagnosis is made in only 27-71% of patients with TCH.5,6,10,95 The most common diagnosed cause of TCH is SAH.5,6,10,95 Other vascular causes are the second most common diagnosed cause, which includes cervical artery dissection, CVT, and RCVS.1,97

In determining workup of patients with TCH, the patient history is essential in determining the necessary diagnostic evaluation.  Table 2 provides several suspicious features associated with TCH that may help an Emergency Physician suspect a specific diagnosis.  While the physical exam is useful, patients with TCH and a normal exam (specifically a neurological exam) may still have a deadly intracranial condition.  The decision to pursue further measures beyond a head CT and/or LP should be made in conjunction with a neurologist, so early consultation is warranted. Neurosurgery may also need to be on board.  The ideal mechanism of imaging for each potential condition is shown in Table 3.

Table 2.  Features of TCH that aid with diagnostic evaluation1,7,8,42

Diagnosis Suspect with…
Subarachnoid Hemorrhage Any patient with TCH; also a/w neck stiffness, transient loss of consciousness, and focal neurological symptoms
Cerebral Venous Thrombosis Nonanatomic neurologic deficits, women in peripartum period, recent surgical history, clotting disorders, use of OCPs
Cervical Artery Dissection Young/middle-age patient presenting with stroke S/S, neck trauma
Acute Hypertensive Crisis/

Posterior Reversible Encephalopathy Syndrome

-Hypertensive Crisis:  extreme HTN with S/S of end-organ damage

-PRES:  extreme HTN with headache, seizures, and visual loss

Ischemic Stroke Patients with risk factors for stroke with focal neurological S/S in anatomic distribution
Intracranial Hypotension S/P lumbar puncture or mild trauma with orthostatic headache
Infectious Patient with fever, immunocompromise, or S/S of meningitis
Pituitary Apoplexy Patient with hx of pituitary adenoma, or currently pregnant, with headache, visual S/S, and AMS
Retroclival Hematoma Severe head and neck injury
Third Ventricle Colloid Cyst TCH that resolves quickly, pain often relieved with supine position
Temporal Arteritis Older patient with HA, pain in temporal distribution, visual sx, or jaw claudication.  A/w PMR
Reversible Cerebral Vasoconstriction Syndrome Recurrent TCH over several weeks; history of migraine; postpartum; or use of ergotamine, triptans, SSRIs, pseudoephedrine, cocaine, amphetamines, ecstasy, cannabis, or bromocriptine

Table 3.  Gold-Standard Diagnostic Modality for Conditions resulting in TCH1,7,8,42

Diagnosis Gold-standard diagnosing modality
Subarachnoid Hemorrhage Head CT and Lumbar Puncture
Cerebral Venous Thrombosis MR Venography
Cervical Artery Dissection Brain MRI with MRA or head CT with CTA
Acute Hypertensive Crisis/

Posterior Reversible Encephalopathy Syndrome

Brain MRI
Ischemic Stroke Brain MRI
Intracranial Hypotension Brain MRI
Infectious LP
Pituitary Apoplexy Brain MRI
Retroclival Hematoma MRI
Third Ventricle Colloid Cyst CT or brain MRI
Temporal Arteritis Temporal Artery Biopsy
Reversible Cerebral Vasoconstriction Syndrome CTA or MRA

Case Conclusion

Upon further questioning, the patient remembers that she was in a minor car accident several days prior.  She states she was not injured other than minor neck pain from “whiplash.”  However, the pain had been decreasing over the past several days and was barely noticeable prior to today.  When asked about neck pain, she admits she is experiencing left sided neck pain, but not nearly as severe as her headache.  Now suspicious for a CVA dissection, you order a head CT and CTA.  CTA demonstrates a left sided vertebral artery dissection, revealing the cause of this patient’s thunderclap headache.


A thunderclap headache (TCH) is a headache that reaches 7 (out of 10) or more in intensity within less than one minute.  Every patient presenting with TCH must be assumed to have a life-threatening intracranial condition.  As many conditions can present with TCH (most commonly SAH or RCVS), a thorough history is essential in evaluating for risk factors for other conditions.  The Emergency Physician must keep in mind that the absence of associated symptoms and a normal physical and neurological exam does not exclude a serious cause in a patient with a TCH; the patient still requires a diagnostic workup.  Due to the high morbidity and mortality of subarachnoid hemorrhage, any patient that presents with TCH must be evaluated for SAH.  A noncontrast head CT has a sensitivity for SAH nearing 100% if performed within 6 hours of headache onset.  We recommend TCH patients to receive a CTA with the initial head CT, as this will further evaluate for an aneurysm, cervical artery dissection, stroke, or RCVS.  Decisions on further imaging and diagnostic evaluation should be made in conjunction with neurology and possibly neurosurgery.


References/Further Reading:

  1. Ducros A, Bousser MG. Thunderclap Headache.  BMJ 2013 Jan 8;346:e8557.
  2. Pope JV, Edlow JA. Favorable Response to Analgesics does not predict a benign etiology of headache.  Headache 2008;48:944-950.
  3. Rosenberg JH, Silberstein SD. The Headache of SAH responds to Sumatriptan.  Headache 2005;45:597-598.
  4. Seymour JJ, Moscati RM, Jehle DV. Response of headaches to nonnarcotic analgesics resulting in missed intracranial hemorrhage.  Am J Emerg Med 1995;13:43-45.
  5. Landtblom AM, Fridriksson S, Boivie J, et al. Sudden onset headache:  a prospective study of features, incidence and causes.  Cephalalgia 2002;22:354-60.
  6. Linn FJ, Wijdicks EF, van der Graff Y, Weerdesteyn-van Vliet FA, Bartelds AI, van Gijn J. Prospective study of sentinel headache in aneurysmal subarachnoid hemorrhage.  Lancet 1994:344:590-93.
  7. Schwedt TJ, Matharu MS, Dodick DW. Thunderclap headache.  Lancet Neurol 2006 Jul;5(7):621-31.
  8. Schwedt TJ, Dodick DW. Thunderclap Headache.  UpToDate 2014 Dec 10.
  9. van Gijn J, Rinkel GJ. Subarachnoid hemorrhage:  diagnosis, causes and management.  Brain 2001;124:249-78.
  10. Linn FJ, Rinkel GJ, Algra A, van Gijn J. Headache characteristics in subarachnoid hemorrhage and benign thunderclap headache.  J Neurol Neurosurg Psychiatry 1998;65:791-3.
  11. Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage.  N Engl J Med 2000;344:29-36.
  12. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid hemorrhage.  Lancet 2007;369:306-18.
  13. Sandercock PAG, Hankey GJ, van Gijn J, et al. Stroke:  a practical guide to management.  2nd  Oxford:  Blackwell Science Ltd;2000.
  14. Hasan D, Schonck RS, Avezaat CJ, Tanghe HL, van Gijn J, van der Lugt PJ. Epileptic seizures after subarachnoid hemorrhage.  Ann Neurol 1993;33:286-91.
  15. Pinto AN, Canhao P, Ferro JM. Seizures at the onset of subarachnoid hemorrhage.  J Neurol 1996;243:161-164.
  16. Caeiro L, Menger C, Ferro JM, Albuquerque R, Figueira ML. Delirium in acute subarachnoid hemorrhage.  Cerebrovasc Dis 2005;19:31-38.
  17. Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional outcome after subarachnoid hemorrhage:  a systematic review.  Stroke 1997;28(3):660.
  18. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.  Stroke 1994;25(7):1342.
  19. Polmear A. Sentinel headaches in aneurysmal subarachnoid hemorrhage:  what is the true incidence?  A systemic review.  Cephalalgia 2003;23:935.
  20. Terazzi E, Mittino D, Ruda R, et al. Cerebral venous thrombosis:  a retrospective multicenter study of 48 patients.  Neurol Sci 2005;25:311-315.
  21. de Bruijn SFTM, de Hann RJ, Stam J, et al. Clinical features and prognostic factors of cerebral venous sinus thrombosis in a prospective series of 59 patients.  J Neurol Neurosurg Psychiatry 2001;70:105-8.
  22. de Bruijn SF, Stam J, Kappelle LJ. Thunderclap headache as first symptom of cerebral venous sinus thrombosis.  CVST Study Group.  Lancet 1996;348(9042):
  23. Bousser MG, Ferro JM. Cerebral venous thrombosis:  an update.  Lancet Neurol 2007;6:162-70.
  24. Stam J. Thrombosis of the cerebral veins and sinuses.  N Engl J Med 2005;352:1791-8.
  25. Piazza G. Cerebral venous thrombosis.  Circulation 2012;125:1704-1709.
  26. Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. Cerebral venous thrombosis – A primer for the haematologist.  Blood Reviews 2015;29:45-50.
  27. Alvis-Miranda HR, Milena Castellar-Leones S, Alcala-Cerra G, Rafael Moscote-Salazar L: Cerebral sinus venous thrombosis.  J Neurosci Rural Pract 4:427,2013.
  28. Canhao P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F, et al. Causes and predictors of death in cerebral venous thrombosis.  Stroke 2005;36:1720-5.
  29. Leys D, Bandu L, Henon H, Lucas C, Mounier-Vehier F, Rondepierre P, Godefroy O. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke.  Neurology 2002;59(1):26.
  30. Rasura M, Spalloni A, Ferrari M, De Castro S, Patella R, Lisi F, Beccia M. A case series of young stroke in Rome.  Eur J Neurol 2006;13(2):146.
  31. Cerrato P, Grasso M, Imperiale D, Priano L, Baima C, Giraudo M et al. Stroke in young patients: etiopathogenesis and risk factors in different age classes.  Cerebrovasc Dis 2004;18(2):154.
  32. Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP et al. Ischaemic stroke in young adults:  predictors of outcome and recurrence.  J Neurol Neurosurg Psychiatry 2005;76(2):191.
  33. Debate S. Pathophysiology and risk factors of carotid artery dissection: what have we learnt from large hospital-based cohorts?  Curr Opin Neurol 2014;27:20
  34. Grond-Ginsbach C, Debette S. The association of connective tissue disorders with cervical artery dissections.  Curr Mol Med 2009;9(2):210
  35. Southerland AM, Meschia JF, Worrall BB. Shared associations of nonatherosclerotic, large-vessel, cerebrovascular arteriopathies:  considering intracranial aneurysms, cervical artery dissection, moyamoya disease and fibromuscular dysplasia.  Curr Opin Neurol 2013;26:13.
  36. Arnold M, Pannier B, Chabriat H et al. Vascular risk factors and morphometric data in cervical artery dissection: a case-control study.  J Neurol Neurosurg Psychiatry 2009;80:232.
  37. Silbert PL, Mokri B, Schievink WI.  Headache and neck pain in spontaneous internal carotid and vertebral artery dissections.  Neurology 1995;45:1517-22.
  38. Mitsias P, Ramadan NM.  HA in ischemic cerebrovascular disease.  Part I:  Clinical features.  Cephalalgia 1992;12(5):269.
  39. Maruyama H, Nagoya H, Kato Y, Deguchi I, Fukuoka T, Ohe Y, et al.  Spontaneous cervicocephalic arterial dissection with headache and neck pain as the only symptom.  J Headache Pain  2012 Apr;13(3):247-53.
  40. Headache Classification Committee of the International Headache Society.  The international classification of headache disorders.  Cephalalgia 2004;24:1-151.
  41. Schievink WI.  Spontaneous dissection of the carotid and vertebral arteries.  N Engl J Med 2001;344:898.
  42. Tintinalli JE, Stapczynski JS, Ma OJ, Yearly GD, Meckler GD, Cline DM. Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  8th  New York:  McGraw-Hill, 2016.
  43. Lee VH, Brown RD Jr, Mandrekar JN, Mokri B. Incidence and outcome of cervical artery dissection:  a population-based study.  Neurology 2006;67:1809.
  44. Debette S, Grond-Ginsbach C, Bodenant M et al.  Differential features of carotid and vertebral artery dissections:  the CADISP study.  Neurology 2011;77:1174.
  45. Tang-Wai DF, Phan TG, Wijdicks EFM. Hypertensive encephalopathy presenting with thunderclap headache.  Headache 2001;41:198-2000.
  46. Dodick DW, Eross EJ, Drazkowski JF, et al. Thunderclap headache associated with reversible vasospasm and posterior leukoencephalopathy syndrome.  Cephalalgia 2003;23:994-97.
  47. Lenfant C, Chobanian AV, Jones DW, Roccella EJ. Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7):  resetting the hypertension sails.  Hypertension 2003;41(6):1178-9.
  48. Zampaglione B, Pascale C, Marchisio M, et al.  Hypertensive urgencies and emergencies:  Prevalence and clinical presentation.  Hypertension 1996;27:144-147.
  49. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al.  A reversible posterior leukoencephalopathy syndrome.  N Engl J Med 1996;334(8):494
  50. Healton E, Burst J, Feinfield D, Thompson G. Hypertensive encephalopathy and the neurologic manifestations of malignant hypertension.  Neurology 1982;32:127-32.
  51. Lamy C, Oppenheim C, Meder JF, Mas JL.  Neuroimaging in posterior reversible encephalopathy syndrome.  J Neuroimaging 2004;14(2):89.
  52. Stott, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome:  a misnomer reviewed.  Intern Med J 2005;35:83-90.
  53. Ferro JM, Melo TP, Oliveira V, Salgado AV, Crespo M, Canhao P, Pinto AN. A multivariate study of headache associated with ischemic stroke.  Headache 1995;35(6):315.
  54. Vestergaard K, Andersen G, Nielsen MI, Jensen TS. Headache in stroke.  Stroke 1993;24(11):1621.
  55. Schwedt TJ, Dodick DW. Thunderclap stroke:  embolic cerebellar infarcts presenting as thunderclap headache.  Headache 2006;46(3):520.
  56. Edvardsson BA, Persson S. Cerebral infarct presenting with thunderclap headache.  J Headache Pain 2009 Jun;10(3):207-9.
  57. Rando TA, Fishman RA. Spontaneous intracranial hypotension:  report of two cases and review of the literature.  Neurology 1992;42(3 Pt 1):481.
  58. Mokri B. Headaches caused by decreased intracranial pressure:  diagnosis and management.  Curr Opin Neurol 2003;16:319-26.
  59. Schievink WI, Wijdicks EF, Meyer FB, et al. Spontaneous intracranial hypotension mimicking aneurysmal subarachnoid hemorrhage.  Neurosurgery 2001;48:513-7.
  60. Ferrante E, Savino A. Thunderclap headache caused by spontaneous intracranial hypotension.  Neurol Sci 2005;26:S155-57.
  61. Mohr G, Hardy J. Hemorrhage, necrosis, and apoplexy in pituitary adenomas.  Surg Neurol 1982;18:181-189.
  62. Randeva HS, Schoebel J, Byrne J, et al. Classical pituitary apoplexy:  clinical features, management and outcome.  Clin Endocrinol (Oxf) 1999;51:181-88.
  63. Kuroso A, Amano K, Kubo O, et al. Clivus epidural hematoma.  J Neurosurg 1990;72:660-62.
  64. Orrison WW, Rogde S, Kinard RE, et al. Clivus epidural hematoma:  a case report.  Neurosurgery 1986;18:194-6.
  65. Tomaras C, Horowitz BL, Harper RL. Spontaneous clivus hematoma:  case report and literature review.  Neurosurgery 1995;37:123-24.
  66. Schievink WI, Thompson RC, Loh CT, Maya MM. Spontaneous retroclival hematoma presenting as thunderclap headache.  J Neurosurg 2001;95:522-24.
  67. Spears RC. Colloid cyst headache.  Curr Pain Headache Rep 2004;8:297-300.
  68. Young WB, Silberstein SD. Paroxysmal headache caused by colloid cyst of the third ventricle:  case report and review of the literature.  Headache 1997;37:15-20.
  69. Kelly R. Colloid cysts of the third ventricle; analysis of twenty-nine cases.  Brain 1951;74:23-65.
  70. Gonzalez-Gay MA, Barros S, Lopez-Diaz MJ, Garcia-Porrua C, Sanchez-Andrade A, Llorca J.  Giant cell arteritis:  disease patterns of clinical presentation in a series of 240 patients.  Medicine (Baltimore) 2005;84(5):269.
  71. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review:  reversible cerebral vasoconstriction syndromes.  Ann Intern med 2007;146(1):34.
  72. Ducros A. Reversible cerebral vasoconstriction syndrome.  Lancet Neurol 2012 Oct;11(10):906-17.
  73. Schluter A, Kissig B. MR angiography in migrainous vasospasm.  Neurology 2002;59(11):1772.
  74. Farine D, Andreyko J, Lysikiewicz A, Simha S, Addison A. Isolated angiitis of brain in pregnancy and puerperium.  Obstet Gynecol 1984;63(4):586.
  75. Janssens E, Hommel M, Mounier-Vehier F, Leclerc X, Guerin du Masgenet B, Leys D. Postpartum cerebral angiopathy possibly due to bromocriptine therapy.  Stroke 1995;26(1):128.
  76. Henry PY, Larre P, Aupy M, Lafforgue JL, Orgogozo JM. Reversible cerebral arteriopathy associated with the administration of ergot derivatives.  Cephalalgia 1984;4(3):171.
  77. Meschia JF, Malkoff MD, Biller J. Reversible segmental cerebral arterial vasospasm and cerebral infarction:  possible association with excessive use of sumatriptan and Midrin.  Arch Neurol 1998;55(5):712.
  78. Singhal AB, Caviness VS, Begleiter AF, Mark EJ, Rordorf G, Koroshetz WJ. Cerebral vasoconstriction and stroke after use of serotonergic drugs.  Neurology 2002;58(1):130.
  79. Levine SR, Washington JM, Jefferson MF, Kieran SN, Moen M, Feit H, Welch KM. “Crack” cocaine-associated stroke.  Neurology 1987;37(12):1849.
  80. Reneman L, Habraken JB, Majoie CB, Booij J, den Heeten GJ. MDMA (“ecstasy”) and its association with cerebrovascular accidents:  preliminary findings.  AJNR Am J Neuroradiol 2000;21(6):1001.
  81. Ducros A, Boukobza M, Porcher R, Sarov M, Valade D, Bousser MG. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome.  A prospective series of 67 patients.  Brain 2007;130(Pt 12):3091.
  82. Singhal AB, Hajj-Ali RA, Topcuoglu MA, Fok J, Bena J, Tang D, et al. Reversible cerebral vasoconstriction syndrome:  analysis of 139 cases.  Arch Neurol 2011;68:1005-12.
  83. Fugate JE, Ameriso SF, Ortiz G, Schottlaender LV, Wijdicks EF, Flemming KD, et al. Variable presentations of postpartum angiopathy.  Stroke 2012;43:670-6.
  84. Ducros A, Fiedler U, Porcher R, Boukobza M, Stapf C, Bousser MG. Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome.  Frequency, features, and risk factors.  Stroke 2010;41:2505-11.
  85. van Gijn J, van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms.  Neuroradiology 1982;23(3):153.
  86. Rao KC, Knipp HC, Wagner EJ. Computed tomographic findings in cerebral sinus and venous thrombosis.  Radiology 1981;140(2):391.
  87. Oppenheim C, Logak M, Dormont D, Lehericy S, Manai R, Samson Y, Marsault C, Rancurel G. Diagnosis of acute ischemic stroke with fluid-attenuated inversion recovery and diffusion-weighted sequences.  Neuroradiology 2000;42(8):602.
  88. Schwartz RB, Jones KM, Kalina P, Bajakian RL, Mantello MT, Garada B, Holman BL. Hypertensive encephalopathy:  findings on CT, MR imaging, and SPECT imaging in 14 cases.  AJR Am J Roentgenol 1992;159(2):379.
  89. Moussouttas M, Mayer SA. Thunderclap headache with normal CT and lumbar puncture:  further investigations are unnecessary:    Stroke 2008;39:1394-5.
  90. Savitz SI, Edlow J. Thunderclap headache with normal CT and lumbar puncture:  further investigations are unnecessary:    Stroke 2008;39:1392-3.
  91. Savitz SI, Levitan EB, Wears R, Edlow JA. Pooled analysis of patients with thunderclap headache evaluated by CT and LP:  is angiography necessary in patients with negative evaluations?  J Neurol Sci 2009 Jan;276(1-2):123-5.
  92. Warnock NG, Gandhi MR, Bergvall U, Powell T. Complications of intraarterial digital subtraction angiography in patients investigated for cerebral vascular disease.  Br J Radiol 1993;66(790):855.
  93. Markus HS. A prospective follow up of thunderclap headache mimicking subarachnoid hemorrhage.  J Neurol Neurosurg Psychiatry 1991;54(12):1117.
  94. Linn FJ, Rinkel GJ, Algra A, van Gijn J. Follow-up of idiopathic thunderclap headache in general practice.  J Neurol 1999;246(10):946.
  95. Harling DW, Peatfield RC, Van Hile PT, Abbott RJ. Thunderclap headache:  is it a migraine?  Cephalalgia 1989;9(2):87.
  96. Landtblom AM, Boivie J, Fridriksson S, et al. Thunderclap headache:  final results form a prospective study of consecutive cases.  Acta Neurol Scand 1996;167(Suppl 94):23.
  97. Schwedt TJ. Clinical spectrum of thunderclap headache.  Expert Rev Neurother 2007 Sep;7(9):1135-44.

Critical Intracranial Hemorrhage: Pearls and Pitfalls in Evaluation and Management

Authors: Cosby Arnold, MD, MPH (EM Resident Physician, University of Tennessee at Memphis) and Mark Brady, MD, MPH (Affiliate Assistant Professor, Department of Emergency Medicine, University of Tennessee at Memphis) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

A 61-year-old man presents to the Emergency Department with severe headache and left arm and leg weakness. He states the headache began a few hours ago. It was initially mild but has become progressively worse while he has been working at his desk job. Past medical history is significant for uncontrolled hypertension. Vital signs are: HR 90, RR 10, BP 215/110, T 99º F. Physical exam reveals decreased left-sided grip strength and inability to lift his left leg without assistance. The remainder of his neurological exam is normal.


Intracranial hemorrhage (ICH) is the second most common cause of stroke, accounting for 10 to 15% of all acute strokes and affecting about 65,000 patients per year.1 Long-standing hypertension, resulting in hypertensive vasculopathy, is the most significant risk factor.2 Other causes include cerebral amyloid angiopathy, underlying vascular malformations (including arteriovenous malformations (AVMs) and aneurysms), hemorrhagic infarction (including venous sinus thrombosis), septic or mycotic aneurysm, tumors, blood dyscrasias, hemorrhagic transformation of ischemic stroke, Moyamoya disease, and drug intoxication (particularly sympathomimetics, such as cocaine and amphetamines).3

How does ICH present? Unlike subarachnoid hemorrhage, symptoms are not classically maximal at onset. Headache and nausea/ vomiting only occur in about half of cases, and when they do they are typically gradual in onset rather than “thunderclap.” Patients with ICH may present identically to those with ischemic stroke, and these two processes cannot be reliably differentiated from each other without imaging.

Neurologic signs reflect hemorrhage location (Table 1). Bleeding into the putamen is the most common, followed by the subcortex, cerebellum, thalamus, and pons.1,3

Table 1. Clinical presentation corresponding to intracranial hemorrhage location

Putamen Hemiplegia, hemisensory loss, homonymous hemianopsia, gaze palsy, stupor, coma
Cerebellum Gait imbalance, vomiting, headache, neck stiffness, gaze palsy, facial weakness
Thalamus Hemiplegia, hemisensory loss, transient homonymous hemianopsia, aphasia or neglect, upgaze palsy with miotic unreactive pupils that look toward tip of nose, are skewed, or point toward the weak side
Pons Total paralysis, pinpoint reactive pupils, absent horizontal eye movements, deep coma within minutes of onset
Subcortex Most commonly affect parietal (contralateral lower extremity hemiplegia) or occipital (contralateral homonymous hemianopsia) lobe; highest incidence of seizure




The differential diagnosis for ICH is broad and includes:

  • Migraine
  • Seizure
  • Bell’s palsy
  • Labyrinthitis
  • Vestibular neuronitis
  • Peripheral nerve palsy
  • Demyelinating diseases
  • Meniere’s disease
  • Giant cell arteritis
  • Tumor
  • Abscess
  • Hypertensive encephalopathy
  • Ischemic stroke
  • Subarachnoid hemorrhage
  • Cavernous sinus thrombosis
  • Carotid or aortic dissection
  • Air embolism
  • Metabolic abnormalities
  • Trauma


While the history and clinical findings may suggest the diagnosis of ICH, imaging is required for confirmation. Either CT or MRI can detect ICH,4,5 but noncontrast head CT is faster and is the usual initial imaging modality in the ED. CT can demonstrate hemorrhage size and location, extension into the ventricles, surrounding edema, and herniation. Density is inversely related to timing of the bleed, with chronic blood appearing hypodense on CT. A patchy appearance of hyperdensity with a larger area of iso- or hypodensity suggests hemorrhagic transformation of ischemic stroke. MRI is superior for evaluating for underlying structural malformations. Alternatively, CT angiography or conventional angiography are useful adjuncts to demonstrate underlying macrovascular causes.6

The optimal approach to exclude ICH with a normal noncontrast head CT is debatable.  The sensitivity of noncontrast head CT is inversely proportional to the time from onset of symptoms.  Options for further studies include lumbar puncture, CTA, or MRI/ MRA. It is prudent to document whether a patient declines further workup if there is an unremarkable noncontrast CT head.7 You can read more about the controversies here: http://www.emdocs.net/controversies-in-the-diagnosis-of-subarachnoid-hemorrhage/.

Obtain platelet count, prothrombin time, and partial thromboplastin time to evaluate for bleeding disorders in all patients with ICH. A drug screen to evaluate for sympathomimetic use may be performed in patients in whom substance abuse is suspected. Underlying vascular malformations are relatively common in patients with ICH after cocaine use and require vascular imaging (e.g., CTA, MRA, angiography) for detection.


All patients with ICH require ICU admission and neurosurgery consult for possible surgical intervention. These patients are at especially high risk of deterioration in mental status requiring endotracheal intubation. Short-acting sedatives are advisable in intubated patients to facilitate serial neurological examinations. Treat hyperthermia with antipyretics, titrate insulin dosing to maintain a target serum glucose level to avoid both hyper- and hypoglycemia (optimal glucose level is not agreed upon), administer antiepileptics if seizure occurs, and keep the head of the bed elevated 30 degrees to decrease intracranial pressure. Discontinue all anticoagulant and antiplatelet drugs, and administer appropriate agents for anticoagulant reversal.6

Blood pressure control after ICH is controversial. Hypertension may exacerbate bleeding, but an elevated mean arterial pressure (MAP) may be required to maintain cerebral blood flow (CBF) in patients who are chronically hypertensive.8 The INTERACT II trial found that patients randomly assigned to rapid reduction in blood pressure to <140 mm Hg within 1 hour demonstrated better functional outcomes when compared to those patients who underwent traditional management of target systolic blood pressure <180 mm Hg; however, there was no significant difference in rate of mortality or disability between the two groups.9 The ATACH II trial, just released in 2016, found no difference in death, disability, or hematoma size when targeting systolic blood pressure of 110-139 mm Hg or 140-179 mm Hg.10 Of note, investigators used nicardipine for BP lowering.10  Several agents can be used for BP control. For proper use of nicardipine, please see http://emcrit.org/wp-content/uploads/2014/07/bolus-dose-nicardipine.pdf. Labetalol is another option. Current guidelines for managing hypertension in ICH patients are presented in Table 2.6

Table 2. Management of hypertension in ICH

SBP 150-220 mm Hg Aggressive lowering to SBP <140 mm Hg is safe
SBP >220 mm Hg Aggressive lowering to SBP < 140 mm Hg may be reasonable, but fewer data are available regarding safety and efficacy

Current guidelines recommend IV fosphenytoin or phenytoin as the first-line anti-epileptic drug in the treatment of seizure; prophylactic use of anti-epileptic drugs may be harmful and is not recommended by current AHA ICH guidelines.3,6

Medical measures to reduce ICP in patients with clinical or radiographic findings suggestive of elevated ICP include elevating the head of the bed to 30 degrees and appropriate analgesia and sedation. Recommended IV sedatives include propofol, etomidate, or midazolam; morphine or alfentanil are recommended for analgesia. Fentanyl is an option as well. Normal saline is considered the fluid of choice; hypotonic fluids are contraindicated due to risk of cerebral edema. Mannitol is the treatment of choice to lower ICP. Hypertonic saline may be used as an adjunct or alternative. Hyperventilation may dramatically lower ICP, but the effect only lasts minutes to hours. This approach may be utilized in the interim until definitive treatment.


  • Imaging needs to be considered in all patients with undifferentiated headache because ICH often has an indolent presentation
  • Follow-up angiography to determine source of bleed
  • Control blood pressure and reverse anticoagulation in conjunction with local standard of care


  • Failure to obtain imaging in a patient with atypical presentation of cerebral bleed (e.g., gradual onset headache)
  • With a normal noncontrast head CT, consider LP and further neuroimaging; if you do not pursue further testing document that a patient declines further workup or that in your judgment the risk is greater than benefit of further workup for ICH


References / Further Reading

  1. Marx J, Hockberger R, Walls R. Rosens Emergency Medicine Concepts and Clinical Practice. Philadelphia: Mosby/Elsevier; 2013.
  2. Woo D, Sauerbeck LR, Kissela BM, et al. Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study. Stroke; a journal of cerebral circulation. 2002;33(5):1190-1195.
  3. de Oliveira Manoel AL, Goffi A, Zampieri FG, et al. The critical care management of spontaneous intracranial hemorrhage: a contemporary review. Critical care (London, England). 2016;20:272.
  4. Kidwell CS, Wintermark M. Imaging of intracranial haemorrhage. The Lancet Neurology. 2008;7(3):256-267.
  5. Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM. Tintinalli’s Emergency Medicine A Comprehensive Study Guide. New York: McGraw Hill; 2016.
  6. Hemphill JC, 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation. 2015;46(7):2032-2060.
  7. Farzad A, Radin B, Oh JS, et al. Emergency diagnosis of subarachnoid hemorrhage: an evidence-based debate. The Journal of emergency medicine. 2013;44(5):1045-1053.
  8. Garg RK, Liebling SM, Maas MB, Nemeth AJ, Russell EJ, Naidech AM. Blood pressure reduction, decreased diffusion on MRI, and outcomes after intracerebral hemorrhage. Stroke; a journal of cerebral circulation. 2012;43(1):67-71.
  9. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. The New England journal of medicine. 2013;368(25):2355-2365.
  10. Qreshi et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. New England journal of medicine. 2016;375:1033-1043.

Current Controversies in TIA Evaluation

Author: Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

A 58-year-old male with a history of coronary artery disease, hypertension, and diabetes presents after experiencing right arm weakness for less than one hour. The symptoms resolved with no further episodes. This has never happened before and frightened him. His initial vital signs reveal mild hypertension, with a completely normal neurologic exam including cranial nerves, motor, sensory, cerebellar, gait, and reflexes. ECG, head CT, and labs are unrevealing. You diagnose him with TIA, but what now? Does he need further testing? Does he require admission?

Transient ischemic attack (TIA) affects over 200,000 U.S. patients per year, which increases with age.1-3 TIA may precede 14% to 23% of strokes.3-8 The risk of stroke after TIA may be as high as 10% at 7 days and 17% at 90 days.1-8 Due to this risk and the mortality and morbidity from stroke, TIA requires management and evaluation for high risk conditions such as atrial fibrillation and carotid stenosis.

TIA was previously defined as a transient neurologic deficit with symptom resolution in less than 24 hours. The American Heart Association (AHA) updated definition includes a brief neurologic deficit due to cerebral ischemia, with no permanent infarction.3-9 No time restriction is present in the new definition. Up to 30% to 50% of patients diagnosed with TIA have infarction on neuroimaging, which is one of the reasons the definition was changed.7,9 Symptoms associated with transient ischemia resolve within one hour in 60% of patients and 2 hours in 70%.7-9 This updated definition increases the annual rate of ischemic stroke by 50,000 annually, while decreasing the 90 day stroke rate in those diagnosed with TIA.10

Significant variation exists in ED imaging, laboratory investigation, and disposition.16,17 Historically, patients have been admitted for evaluation of suspected TIA.  A study by Johnson et al. demonstrated 5% of patients with TIA go on to have stroke within 2 days, with 10% suffering acute stroke within 3 months.1 However, a 2016 study found a stroke rate of 2.1% at 7 days and 6.2% at one year.18 The American Heart Association (AHA) and National Stroke Association (NSA) possess several criteria for which patients require admission:3-6,8

AHA and NSA Recommendations

Association Admission Criteria
AHA ABCD2 score of > 3, ABCD2 score of 0-2 and uncertain follow up, or ABCD2 score of 0-2 and evidence that focal ischemia occurred.
NSA Consider admission if first TIA within 24-48 hours. For recent TIA within one week, hospitalization is needed for crescendo TIA (worsening TIA’s), duration of symptoms longer than 1 hour, internal carotid stenosis greater than 50% with symptoms, known cardiac source of embolus, or hypercoagulable state.

Assessment of patients with suspected TIA should be conducted in a rapid manner, and this evaluation of TIA can also determine patient disposition. Several factors associated with higher stroke risk include age over 60 years, infarct discovered on imaging, cardiogenic emboli, and modified Rankin score greater than 2.1,2,16-18 The evaluation of suspected TIA centers on neuroimaging and the use of clinical risk scores for risk stratification. The specific imaging required in the ED and patient disposition based on risk scores are controversial topics.


Neuroimaging within 24 hours of suspected TIA is recommended by the AHA/ASA, and MRI with DWI is preferred.3-6,8 CT is most commonly available in the ED, as 56% to 92% of patients receive imaging with this modality in the ED.19

Head CT

Head CT noncontrast can rapidly identify other conditions and is the primary ED modality, with sensitivities ranging from 12% to 52%.3-6,8,17,19-21 Forster et al. in 2012 finds 95.7% of initial head CT examinations are negative for acute infarction.19 A study from Germany evaluating head CT noncontrast in 1533 patients with suspected TIA finds a 3.1% rate of acute CVA, despite complete resolution of symptoms.20 Another study in 2003 finds the frequency of stroke does not differ at 90 days in those receiving head CT versus those who do not.21 This same study does endorse the use of CT to evaluate for other etiologies of symptoms, as 1.2% of patients have an alternative condition found on head CT.21


The best test is magnetic resonance imaging (MRI) in acute ischemic stroke and TIA evaluation, specifically the use of MRI with diffusion-weighted imaging (DWI). This modality has a Class I, Level B recommendation for suspected TIA.6,8 DWI will demonstrate hyperintense signals due to cytotoxic edema.23-25 One third of patients with normal CT and MRI noncontrast demonstrate acute lesions on DWI.23 Close to 39% of patients have ischemic lesions on imaging, and follow-up scanning past 24 hours reveals involvement in up to 100% of patients.24,25 Ischemic lesions on MRI predict future stroke (up to fifteen-fold increase).26-28

This test may not be available in the ED (available in 15% of centers at any one time).29,30 MRI displays greater diagnostic capabilities for ischemic lesions than CT, as 35.2% of patients with negative CT display ischemic lesions on MRI.19 Within 12 hours of acute stroke symptom onset, MRI with DWI demonstrates odds ratio (OR) of 25 (95% CI 8-79) if ischemia is found, while another study finds an OR 10.1 for acute stroke within 7 days with positive DWI.23,24,27,28  Sensitivity ranges from 83% to 97% for early ischemia.31-33 Stroke risk in negative DWI ranges from 0 to 2.9% at 2 and 7 days, while patients with scans positive for ischemia possess a stroke rate of 14.3% at 2 days and 23.8% at 7 days.23,27,31-37 However, intermediate to high risk scores from clinical rules are not associated with abnormalities found on DWI.34-36

Patients with positive DWI remain at high risk for stroke, no matter the predicted risk on clinical scoring. Calvet et al. found positive DWI in 40% of patients, and factors associated with positive imaging included weakness, duration of symptoms greater than 60 minutes, atrial fibrillation, and large artery atherosclerosis.28 Negative MRI with DWI is associated with low risk of stroke, especially when used in conjunction with risk stratification.25,27,28,38 Asimos et al. found patients with negative MRI and low ABCD2 are extremely low risk for stroke.38

Vascular Imaging

A major risk for stroke and recurrent TIA includes significant carotid stenosis (occlusion greater than 70% and greater than 50% with symptoms in males).5 The AHA/ASA provides a Class 1, Level A recommendation for intracranial and extracranial vascular imaging in evaluation of suspected TIA.3-5,8 Up to 31% of patients with TIA have carotid disease, and in the setting of significant disease, 90 day stroke risk can reach 20.1%.39,40-43  Carotid disease alone is a significant risk factor for adverse outcome including recurrent stroke, with a hazard ratio (HR) of 4.9.25 Close to half of patients with positive lesions on DWI have significant stenosis of at least one large intra/extracranial vessel.25

Noninvasive testing includes carotid ultrasound, CTA, and magnetic resonance angiography (MRA).44-46 Negative likelihood ratio (LR) for MRA and US is 0.07.47 US sensitivity ranges from 70% to 90%, MRA sensitivity 82% to 94%, and CTA sensitivity 77% to 90%.49-54 Literature suggests that stenosis less than 50% on Doppler US or MRA is associated with low likelihood of significant disease. However, stenosis greater than 50% requires further imaging with MRA or CTA.3-6,8,51-54

Doppler US and MRA possess adequate sensitivity and specificity for diagnosis of significant carotid disease. CTA is likely easier to obtain in most emergency departments, but this test alone may miss significant disease.

Atrial Fibrillation

Atrial fibrillation is a major risk factor for stroke, independent of imaging and risk prediction tools.3-6,8,55 Close to 2% of patients with TIA will be diagnosed with new onset atrial fibrillation.55,56  Risk scores, including the ABCD and ABCD2 scores, are not correlated with atrial fibrillation.57 The diagnosis and acute management of atrial fibrillation including anticoagulation may reduce short and long-term risk of stroke.3-6,8

Risk Scores

Providers have sought tools to predict stroke risk after TIA, shown in Table 2.1-6,8,10,26,28,35,37,57,58 Risk stratification tools may identify patients at low risk for whom further workup may be deferred, while identifying patients at short and long term risk of stroke.

Table 2 – Clinical Risk Scores1-6,8,10,26,28,35,37,57,58

Prediction Rule Components Points
California rule Age > 60 years


Unilateral weakness

Impaired speech

Symptoms > 10 minutes








ABCD rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)

Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes










ABCD2 rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)


Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes











ABCD3 rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)


Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes

Dual TIA












ABCD3-I rule Age > 60 years

Elevated blood pressure (>140/90 mm Hg)


Unilateral weakness

Impaired speech

Symptoms > 60 minutes

Symptoms 10-59 minutes

Symptoms < 10 minutes

Dual TIA

Positive imaging (Internal carotid stenosis > 50%, DWI)













One of the first evaluations for stroke risk is the ABCD score, shown above.1,16,22,35-37,58-66 Patients with score 0-3 are considered low risk, while those greater than 3 points are considered moderate to high risk. Low risk scores demonstrate 2-day, 7-day, 30-day, and 90-day risks of 1.2%, 5.9%, 5.4%, and 3.2%, respectively, with the moderate to high risk patients demonstrating risks of 4.9-7.9%, 4.2-15.9%, 6.9-17.6%, and 11.3-18.9%, respectively.1,22,60-66 The California rule is similar to the ABCD score. However, it does not use hypertension, but diabetes.1,22,35,58,60,61 Both the ABCD and California scores categorize over 54% to 85% as at least intermediate risk.1,16,22,35-37,58-66 The ABCD and California scores demonstrate AUC curves of 0.62 to 0.81, with the majority of studies demonstrating values of less than 0.70.28,58,69 This value correlates with fair accuracy for predicting stroke in these patients, but the scores place a significant number of patients at or above intermediate risk.

The most commonly used tool is the ABCD2 score, which adds diabetes. Initial studies validating this score suggest strong predictive attributes for stroke risk at 24 hours.58,60,64,65,69 Using this score for stratification, 33%, 48%, and 19% are categorized as low, moderate, and high risk, respectively.27,28,35,58,60,61,63-75 The score demonstrates sensitivities of 86% in moderate to high risk patients, with specificity 35%. Close to 1% of this group experience stroke at 2 days, with 1.2% at 7 days. AUC is 0.66-0.74 for 2 and 7 day stroke risk. Initial results show stroke occurs in 3.2% of patients at 90 days. However, positive likelihood ratios never reach higher than 1.54.28,35,58,63-75

These scores demonstrate limited predictive ability. Schrock et al. in 2009 suggests high risk ABCD2 score is not beneficial for guidance on obtaining other diagnostic testing including MRI, ECG, head CT.58,69 Perry et al. suggests it is not a reliable tool, as a cutoff of 5 points results in misclassification of approximately 8% of patients as low risk.75 This cutoff displays a sensitivity of 94.7%, but a specificity of 12.%.75 Stead et al. in 2011 finds no difference between different classifications based on the ABCD2 score, as the low, moderate, and high risk groups display stroke rates of 1.1%, 0.3%, 2.7% at 7 days.75 A study by Ghia in 2012 finds stroke rates in low risk ABCD2 patients to be 1.2% at 30 days and 0.8% in moderate and high risk groups, questioning ability for risk stratification and stroke prediction.77

An Australian study suggests patients in all risk categories possess similar stroke rates, while at the same time having poor predictive ability.28,58,65,77 When used in combination with other imaging modalities evaluating the brain and carotid systems, the ABCD2 score does not provide additional risk stratification information, with sensitivity in high risk patients only 30% to 40%.65,69,70,71,75-77 Schrock et al. suggests the use of this test alone misses patients with high grade carotid stenosis.69 A 2012 meta-analysis of 33 studies finds a positive likelihood ratio of 1.4 for scores > 3, with sensitivities of 89% at days 2 and 7 and 87% at day 90 post TIA.65 This score does not have predictive capability likely to change management in the ED.65

Can you add imaging? The ABCD2-I score added CT or MRI with DWI, which results in an AUC value of 0.78 at 7 days, versus 0.66 for the original ABCD2 score.67 The ABCD3-I score, has a third “D” representing a TIA occurring within one week of the first TIA.74 The “I” component refers to carotid stenosis greater than 50% discovered on carotid imaging or any abnormality discovered on MRI with DWI. It does demonstrate better ability when compared to the original ABCD2 score.28,58,74 The C-statistic for the modified score is 0.66, while the ABCD2 score demonstrates a C-statistic of 0.54, neither over the threshold of 0.7 for moderate prediction. When imaging involves MRI with DWI, this values reaches 0.81.28,58,74,75

Another rule is the Canadian TIA Score.  Scores range from -3 to 23, and stroke rate within 7 days ranges from 0.01% to greater than 27%. Patients with less than 6 points demonstrate less than 1% chance of stroke, with sensitivity approaching 98%. Scores greater than 10 demonstrate 5.1% stroke risk, with scores greater than 12 possessing a 12.6% risk. The discriminatory capability of this test possesses a C-statistic of 0.77.78 However, this score requires multiple variables and has not been validated.

Table 3 – Canadian TIA Score78

Item Points
Clinical Findings

First TIA (in lifetime)

Symptoms > 10 min

History of carotid stenosis

Already on antiplatelet therapy

History of gait disturbance

History of unilateral weakness

History of vertigo

Initial diastolic blood pressure > 110 mm Hg

Dysarthria or aphasia


Investigations in the ED

Atrial fibrillation on ECG

Infarction on CT (new or old)

Platelet count > 400×109/L

Glucose > 15 mmol/L

Total score (-3 to 23)


















Role of Risk Scores

The use of prediction scores alone for risk stratification is not recommended, as they are not reliable.58,65,69,75,77 Over 40% of patients with greater than 4 on the ABCD2 score are experiencing mimic.37 Scores do not allow recognition of stroke subtype such as lacunar, cardioembolic, or large vessel or the specific vascular territory affected.58,65,69,75,77 MRI with DWI and clinical features may predict risk. Cucchiara et al. finds scores 0-3 have significant risk of stroke (up to 20%).37 Close to 1/3 of patients in the ED are not categorized appropriately into low, intermediate, or high risk.76,80 Risk scores are a tool that may assist in gauging short term risk of stroke, but this should not take precedence over physician gestalt.4-8,58

The combination of MRI with risk stratification significantly improves the diagnostic and predictive values of the provider. The addition of MRI with DWI to the ABCD2 score possesses a higher 7 day stroke risk prognostic ability after TIA.26-28,38,58 One study demonstrates the absence of lesion on MRI with DWI and ABCD < 4 reaches 100% sensitivity for excluding stroke at 7 days, while those with infarction on imaging show a 20-fold increase in stroke risk.38

ED Directed Protocols and Observation Units

ED diagnostic protocols and observation units can reduce length of stay and total cost, while improving patient compliance with AHA and NSA recommended treatments.3-8,58,80-85 Studies demonstrate faster time to risk stratification and treatment, as well as a significant reduction in stroke from 10% to approximately 1 to 2% with use of these clinics.85-87

Stead et al. evaluated TIA patients in an ED unit, with the use of a standardized protocol including patients with no symptoms and negative head CT noncontrast.80 This study finds approximately 30% of patients can be discharged directly from an observation unit, with no difference in rate of strokes at 2 and 7 days.80 Ross et al. in 2007 evaluated 149 patients with suspected TIA in the ED with a diagnostic protocol with carotid imaging, echocardiography, repeat neurologic examination, and cardiac monitoring for a period of at least 12 hours.85 No increase in adverse outcomes are present in those patients in the protocol, as well as shorter length of stay and total cost in the observation patients.85 Oostema et al. investigated an ED observation unit that combined the use of MRI with DWI and a diagnostic protocol.84 In this study, 94% of patients underwent MRI with DWI, and 97% of patients in the accelerated protocol underwent imaging of the cervical vessels. Close to 14% of patients have infarct on DWI, and these patients demonstrate a 6.3% risk of stroke at 30 days compared to 1.2% in patients with negative DWI.84

How about an outpatient clinic? Mijalski in the OTTAWA trial obtained ECG and head CT in the ED, followed by carotid Doppler, echocardiogram, 24 hours telemetry, and neurology follow up.87 This study found a 2 day stroke rate with use of this clinic of 1%, with a 3.2% risk at 90 days.87 Lavallee et al. finds a 90 day stroke rate of 1.24% in patients managed in a hospital-based clinic staffed with neurologists, with imaging including MRI or head CT, carotid ultrasound, ECG, and ankle-brachial index (ABI).81,88 Close to 74% of patients can be evaluated and discharged upon presentation to the ED with the use of this clinic.88 Olivot et al. discharged patients with ABCD2 scores of 0 to 3 to an outpatient TIA clinic, while patients with scores of 4 or 5 underwent imaging of the intracranial and carotid vasculature.89 Approximately 70% of patients can be discharged from the ED in this study to follow-up at the TIA clinic, with low stroke rate.89 Wasserman et al. evaluated 982 patients, with 32% categorized as low risk, 49% as medium risk, and 19% as high risk.90 All patients underwent head CT and ECG in the ED and follow-up care in a stroke clinic where they received carotid Doppler, echocardiogram, and laboratory testing. Stroke rate was less than 1% risk for those with scores 0-4.90

Stroke rate at 90 days can be reduced by 80% with the use of these diagnostic protocols or dedicated clinics.90-94 This requires an ED system with resources available including a protocol or TIA clinic.58

What should the EM provider do?

A summary of the 2016 ACEP clinical policy on TIA is below, released in 2016.58

American College of Emergency Physicians Recommendations for TIA58

Question Recommendation Level
In adult patients with suspected TIA, are there clinical decision rules that can identify patients at very low short-term risk for stroke who can be safely discharged from the ED? In adult patients with suspected TIA, do not rely on current existing risk stratification instruments (eg, ABCD2 score) to identify TIA patients who can be safely discharged from the ED. B
In adult patients with suspected TIA, what imaging can be safely delayed from the initial ED workup? (1) The safety of delaying neuroimaging from the initial ED workup is unknown. If noncontrast brain MRI is not readily available, it is reasonable for physicians to obtain a noncontrast head CT as part of the initial TIA workup to identify TIA mimics (eg, intracranial hemorrhage, mass lesion). However, noncontrast head CT should not be used to identify patients at high short-term risk for stroke.

(2) When feasible, physicians should obtain MRI with DWI to identify patients at high short-term risk for stroke.

(3) When feasible, physicians should obtain cervical vascular imaging (carotid ultrasonography, CTA, or MRA) to identify patients at high short-term risk for stroke.

In adult patients with suspected TIA, is carotid ultrasonography as accurate as neck CTA or MRA in identifying severe carotid stenosis?


In adult patients with suspected TIA, carotid ultrasonography may be used to exclude severe carotid stenosis because it has accuracy similar to that of MRA or CTA. C
In adult patients with suspected TIA, can a rapid ED-based diagnostic protocol safely identify patients at short-term risk for stroke? In adult patients with suspected TIA without high-risk conditions,* a rapid ED- based diagnostic protocol may be used to evaluate patients at short-term risk for stroke.

*High-risk conditions include abnormal initial head CT result (if obtained), suspected embolic source (presence of atrial fibrillation, cardiomyopathy, or valvulopathy), known carotid stenosis, previous large stroke, and crescendo TIA.


Patients should be evaluated within 24 hours from the time of event, whether as inpatient, in an ED observation unit/diagnostic protocol, or specialized outpatient TIA clinic. A detailed and accurate history is important, as misdiagnosis by emergency providers occurs in close to 60% of cases.12,13,28,95,96 The provider should assess for focal neurologic symptoms. Symptoms associated with loss of function such as motor weakness, altered speech, or vision abnormalities suggest TIA, while symptoms including tingling, increased speech, involuntary motions, and flashing lights suggest alternative diagnosis.11-13,97 An ECG should be obtained to evaluate for atrial fibrillation. MRI with DWI is the first line modality per the AHA/ASA.3-8 However, in most emergency departments, head CT noncontrast is rapidly available at all times. Any focal lesion found on neuroimaging warrants admission.2-8,28,58

Patient assessment and availability of local resources will determine the disposition. Admission criteria include crescendo neurologic symptoms or continued symptoms, atrial fibrillation on ECG, vascular disease on imaging, ischemic focus on neuroimaging, poor social situation, inability to follow-up, and poor compliance. 2-8,28,58 If these are not present, a rapid diagnostic protocol or rapid follow-up clinic can be beneficial. MRI with DWI and carotid imaging are cornerstones of evaluation. Evaluation with these studies should occur within 24 hours. ED-focused diagnostic protocols and rapid follow-up clinics decrease stroke risk and patient cost. Stratification tools may be used in conjunction with neuroimaging such as MRI with DWI, but these scores alone do not sufficiently identify patients at low-risk for stroke.



– TIA is defined as a brief episode of neurologic dysfunction with no permanent infarction. Over 200,000 patients per year in the U.S. are affected, and this disease may precede approximately 20% of strokes.

– Patients are typically admitted for inpatient management due to this risk of future stroke. A great deal of literature has evaluated the use of imaging, clinical risk scores, and diagnostic protocols in the evaluation of TIA.

– Head CT noncontrast is not reliable for acute ischemia, but it can find alternative conditions necessitating management. MRI with DWI displays greater diagnostic ability. Carotid imaging includes MRA, CTA, and Doppler with US. MRA and Doppler US demonstrate similar test characteristics.

– Risk scores that predict future stroke are not reliable when used alone.

– The use of ED diagnostic protocols and observation units can reduce length of stay while improving patient treatment and reducing stroke rate.

– Careful evaluation of risk factors and imaging may allow the patient to be discharged with follow up within 24 hours for further evaluation.


References/Further Reading

  1. Johnston SC, Fayad PB, Gorelick PB, et al. Prevalence and knowledge of transient ischemic attack among US adults. Neurology 2003;60(9):1429-1434.
  2. Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke 2005;36(4):720-723.
  3. Kernan WN, Ovbiagele B, Black HR, et al. American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160-2236.
  4. Sacco RL, Kasner SE, Broderick JP, et al. American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:2063-89.
  5. Jauch EC, Saver JL, Adams HP Jr, et al, American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947.
  6. Mozaffarian D, Benjamin EJ, Go AS, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 2016;133:e38-e360.
  7. Shah SH, Saver JL, Kidwell CS, et al. A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients. Stroke 2007;38:463.
  8. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack. A scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke 2009;40(6):2276-2293.
  9. Levy DE. How transient are transient ischemic attacks? Neurology 1988;38(5):674-677.
  10. Mullen MT, Cucchiara BL. Redefinition of transient ischemic attack improves prognosis of transient ischemic attack and ischemic stroke: an example of the will rogers phenomenon. Stroke 2011 Dec;42(12):3612-3.
  11. Nadarajan V, Perry RJ, Johnson J, et al. Transient ischaemic attacks: mimics and chameleons. Pract Neurol 2014;14:23-31.
  12. Castle J, Mlynash M, Lee K, et al. Agreement regarding diagnosis of transient ischemic attack fairly low among stroke-trained neurologists. Stroke 2010;41:1367-1370.
  13. Prabhakaran S, Silver AJ, Warrior L, et al. Misdiagnosis of transient ischemic attacks in the emergency room. Cerebrovasc Dis 2008;26:630-635.
  14. Tsivgoulis G, Zand R, Katsanos AH, Goyal N, Uchino K, Chang J, et al. Safety of Intravenous Thrombolysis in Stroke Mimics: Prospective 5-Year Study and Comprehensive Meta-Analysis. Stroke 2015;46:1281-1287.
  15. Dolmans LS, Rutten FH, El Bartelink ML, et al. Serum biomarkers for the early diagnosis of TIA: the MIND-TIA study protocol. BMC Neurol 2015;15:119.
  16. Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol 2007;6:1063-1072.
  17. Panagos PD. Transient ischemic attack (TIA): the initial diagnostic and therapeutic dilemma. American Journal of Emergency Medicine 2012;30:794-799.
  18. Amarenco P, Lavallée PC, Labreuche J, Albers GW, Bornstein NM, et al.; TIAregistry.org Investigators. One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke. N Engl J Med 2016 Apr 21;374(16):1533-42.
  19. Förster A, Gass A, Kern R, et al. Brain Imaging in Patients with Transient Ischemic Attack: A Comparison of Computed Tomography and Magnetic Resonance Imaging. European Neurology 2012;67(3):136-141.
  1. Al-Khaled M, Matthis C, Munte TF, et al. Use of cranial CT to identify a new infarct in patients with a transient ischemic attack. Brain Behav 2012;2:377-381.
  2. Douglas VC, Johnston CM, Elkins J, et al. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003;34:2894-2899.
  3. Sciolla R, Melis F, for the SINPAC Group. Rapid identification of high- risk transient ischemic attacks. Prospective validation of the ABCD score. Stroke. 2008;39:297-302.
  4. Ay H, Oliveira-Filho J, Buonanno FS, et al. ‘Footprints’ of transient ischemic attacks: a diffusion-weighted MRI study. Cerebrovasc Dis. 2002;14(3-4):177-186.
  5. Nah HW, Kwon SU, Kang DW, et al. Diagnostic and prognostic value of multimodal MRI in transient ischemic attack. Int J Stroke 2014;9:895-901.
  6. Calvet D, Lamy C, Touze E, Oppenheim C, Meder JF, Mas JL. DWI lesions and TIA etiology improve the prediction of stroke after TIA. Stroke 2009;40(1):187-192.
  7. Ay H, Gungor L, Arsava EM, et al. A score to predict early risk of recurrence after ischemic stroke. Neurology 2010;74(2):128-135.
  8. Ay H, Arsava EM, Johnston SC, et al. Clinical-and Imaging-based Prediction of stroke risk after transient ischemic attack. The CIP model. Stroke 2009;40:181-186.
  9. Bhatt A, Jani V. The ABCD and ABCD2 scores and the risk of stroke following a TIA: a narrative review. ISRN Neurology 2011;2011:1-12.
  10. Edlow JA, Kim S, Pelletier AJ, et al. National study on emergency department visits for transient ischemic attack, 1992-2001. Acad Emerg Med 2006;13(6):666-672.
  11. Ginde AA, Foianini A, Renner DM, et al. Availability and quality of computed tomography and magnetic resonance imaging equipment in U.S. emergency departments. Acad Emerg Med 2008;15(8):780-783.
  12. Chalela JA, Kidwell CS, Nentwich LM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet 2007;369(9558):293-298.
  13. Fiebach JB, Schellinger PD, Jansen O, et al. CT and diffusion-weighted MR imaging in randomized order: diffusion- weighted imaging results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke. Stroke 2002;33(9):2206-2210.
  14. Mullins ME, Schaefer PW, Sorensen AG, et al. CT and conventional and diffusion-weighted MR imaging in acute stroke: study in 691 patients at presentation to the emergen- cy department. Radiology 2002;224(2):353-360.
  15. Redgrave JN, Schulz UG, Briley D, Meagher T, Rothwell PM. Presence of acute ischaemic lesions on diffusion-weighted imaging is associated with clinical predictors of early risk of stroke after transient ischaemic attack. Cerebrovasc Dis 2007;24(1):86-90.
  16. Purroy F, Begué R, Quílez A, Piñol-Ripoll G, Sanahuja J, Brieva L, et al. The California, ABCD, and unified ABCD2 risk scores and the presence of acute ischemic lesions on diffusion-weighted imaging in TIA patients. Stroke 2009 Jun;40(6):2229-32.
  17. Purroy F, Pinol-Ripoll G, Quilez A, Sanahuja J, Brieva L, Suarez Luiz I. Validation of the ABCDI and ABCD2I scales in the registry of patients with transient ischemic attacks from Lleida (REGITELL) Spain. Med Clin (Barc) 2010 Sep 11;135(8):351-6.
  18. Cucchiara BL, Messe SR, Taylor RA, Pacelli J, Maus D, Shah Q, Kasner SE. Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack? Stroke 2006 Jul;37(7):1710-4.
  19. Asimos AW, Rosamond WD, Johnson AM, et al. Early diffusion weighted MRI as a negative predictor for disabling stroke after ABCD2 score risk categorization in transient ischemic attack patients. Stroke. 2009;40: 3252-3257.
  20. Widjaja E, Manuel D, Hodgson TJ, et al. Imaging findings and referral outcomes of rapid assessment stroke clinics. Clin Radiol. 2005;60(10):1076-1082.
  21. Carroll BA. Duplex sonography in patients with hemispheric 
 J Ultrasound Med. 1989;8(10):535-540.
  22. Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett JHM. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. CMAJ 2004;170(7):1105-1109.
  23. Purroy F, Molina CA, Montaner J, Alvarez-Sabrin A. Absence of usefulness of ABCD score in the early risk of stroke of transient ischemic attack patients. Stroke 2007;38(3):8855-856.
  24. Koton S, Rothwell PM. Performance of the ABCD and ABCD2 scores in TIA patients with carotid stenosis and atrial fibrillation. Cerebrovascular Diseases 2007;24(2-3):231-235.
  25. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-453.
  26. Rerkasem K, Rothwell PM. Carotid endarterectomy for symptomatic carotid stenosis (review). Cochrane Database Syst Rev 2011;(4): CD001081.
  27. D’Onofrio M, Mansueto G, Faccioli N, Guarise A, Tamellini P, Bogina G, et al. Doppler ultrasound and contrast-enhanced magnetic resonance angiography in assessing carotid artery stenosis. Radiol Med (Torino) 2006;111(1):93-103.
  28. Heijenbrok-Kal MH, Buskens E, Nederkoorn PJ, et al. Optimal peak systolic velocity threshold at duplex US for determining the need for carotid endarterectomy: a decision analytic approach. Radiology 2006;238:480-488.
  29. Buskens E, Nederkoorn PJ, Buijs-Van Der Woude T, et al. Imaging of carotid arteries in symptomatic patients: cost-effectiveness of diagnostic strategies. Radiology 2004;233(1):101-112.
  30. Nederkoorn PJ, Mali WP, Eikelboom BC, et al. Preoperative diagnosis of carotid artery stenosis. Accuracy of noninvasive testing. Stroke 2002;33:2003-2008.
  31. Nonent M, Salem DB, Serfaty JM, et al. Overestimation of moderate carotid stenosis assessed by both Doppler US and contrast enhanced 3D-MR angiography in the CARMEDAS study. J Neuroradiol 2011;38:148-155.
  32. Blakeley DD, Oddone EZ, Hasselblad V, et al. Noninvasive carotid artery testing. A meta-analytic review. Ann Intern Med 1995;122:360-367.
  33. Nederkoorn PJ, van der Graaf Y, Hunink MG. Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis. A systematic review. Stroke 2003;34:1324-1332.
  34. Jahromi AS, Cina CS, Liu Y, et al. Sensitivity and specificity of color duplex ultrasound measurement in the estimation of internal carotid artery stenosis: a systematic review and meta-analysis. J Vasc Surg 2005;41:962-972.
  35. Wardlaw JM, Chappell FM, Best JJ, et al, on behalf of the NHS Research and Development Health Technology Assessment Carotid Stenosis Imaging Group. Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis. Lancet 2006;367:1503-1512.
  36. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22(8):983-988.
  37. Elkins JS, Sidney S, Gress DR, et al. Electrocardiographic findings predict short-term cardiac morbidity after transient ischemic attack. Arch Neurol 2002;59(9):1437-1441.
  38. Bray JE, Coughlan K, Bladin C. Can the ABCD Score be dichotomised to identify high-risk patients with transient ischaemic attack in the emergency department? EMJ 2007;24(2):92-95.
  39. Lo BM, Carpenter CR, Hatten BW, Wright BJ, Brown MD, et al. Clinical Policy: Critical Issues in the Evaluation of Adult Patients With Suspected Transient Ischemic Attack in the Emergency Department. Ann Emerg Med 2016 Sep;68(3):354-370.e29.
  40. Sanossian N, Ovbiagele B. The risk of stroke within a week of minor stroke or transient ischemic attack. Expert Opin Pharmacother 2008 Aug;9(12):2069-76.
  41. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007;369:283-292.
  42. Nguyen H, Kerr D, Kelly AM. Comparison of prognostic performance of scores to predict risk of stroke in ED patients with transient ischaemic attack. Eur J Emerg Med. 2010;17:346-348.
  43. Tsivgoulis G, Spengos K, Manta P, Karandreas N, Zambelis T, Zakopoulos N, Vassilopoulos D. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke 2006 Dec;37(12):2892-7.
  44. Fothergill A, Christianson TJ, Brown RD, Rabinstein AA. Validation and Refinement of the ABCD2 Score: a population-based analysis. Stroke; a journal of cerebral circulation. 2009;40(8):2669-2673.
  45. Josephson SA, Sidney S, Pham TN, Bernstein AL, Johnston SC. Higher ABCD score predicts patients most likely to have true transient ischemic attack. Stroke 2008;29(11):3096-3098.
  46. Sanders LM, Srikanth VK, Blaker DJ, et al. Performance of the ABCD2 score for stroke risk post TIA: meta-analysis and probability modeling. Neurology 2012;79:971-980.
  47. Giles MF, Rothwell PM. Systematic review and pooled analysis of published and unpublished validations of the ABCD and ABCD2 transient ischemic attack risk scores. Stroke 2010;41:667-673.
  48. Giles MF, Albers GW, Amarenco P, et al. Addition of brain infarction to the ABCD2 Score (ABCD2I): a collaborative analysis of unpublished data on 4574 patients. Stroke 2010;41(9):1907–13.
  49. Harrison JK, Sloan B, Dawson J, Lees KR, Morrison DS. The ABCD and ABCD2 as predictors of stroke in transient ischemic attack clinic outpatients: a retrospective cohort study over 14 years. QJM 2010;103:679-685.
  50. Schrock JW, Victor A, Losey T. Can the ABCD2 risk score predict positive diagnostic testing for emergency department patients admitted for transient ischemic attack? Stroke. 2009 Oct;40(10):3202-5.
  51. Amarenco P, Labreuche J, Lavallee PC, et al. Does ABCD2 score below 4 allow more time to evaluate patients with a transient ischemic attack? Stroke 2009;40:3091–3095.
  52. Chandratheva A, Geraghty OC, Luengo-Fernandez R, et al; for the Oxford Vascular Study. ABCD2 score predicts severity rather than risk of early recurrent events after transient ischemic attack. Stroke 2010;41:851-856.
  53. Chatzikonstantinou A, Wolf ME, Schaefer A, et al. Risk prediction of subsequent early stroke in patients with transient ischemic attacks. Cerebrovasc Dis 2013;36:106-109.
  54. Purroy F, Jimenez Caballero PE, Gorospe A, et al; on behalf of the Stroke Project of the Spanish Cerebrovascular Diseases Study Group. Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores. Cerebrovasc Dis 2012;33:182-189.
  55. Kiyohara T, Kamouchi M, Kumai Y, Ninomiya T, Hata J, Yoshimura S, et al. ABCD3 and ABCD3-I scores are superior to ABCD2 score in the prediction of short- and long-term risks of stroke after transient ischemic attack. Stroke 2014 Feb;45(2):418-25.
  56. Perry JJ, Sharma M, Sivilotti MLA, et al. Prospective validation of the ABCD2 score for patients in the emergency department with transient ischemic attack. CMAJ : Canadian Medical Association Journal 2011;183(10):1137-1145.
  57. Stead LG, Suravaram S, Bellolio MF, et al. An Assessment of the Incremental Value of the ABCD2 Score in the Emergency Department Evaluation of Transient Ischemic Attack. Annals of emergency medicine 2011;57(1):46-51.
  58. Ghia D, Thomas P, Cordato D, Epstein D, Beran RG, Cappelen-Smith C, et al. Low positive predictive value of the ABCD2 score in emergency department transient ischaemic attack diagnoses: the South Western Sydney transient ischaemic attack study. Intern Med J 2012 Aug;42(8):913-8.
  59. Perry JJ, Sharma M, Sivilotti ML, et al. A prospective cohort study of patients with transient ischemic attack to identify high-risk clinical characteristics. Stroke 2014;45:92-100.
  60. Wardlaw JM, Brazzelli M, Chappell FM, et al. ABCD2 score and secondary stroke prevention: meta-analysis and effect per 1,000 patients triaged. Neurology 2015;85(4):373–80.
  61. Stead LG, Bellolio MF, Suravaram S, Brown Jr RD, Bhagra A, Gilmore RM, et al. Evaluation of transient ischemic attack in an emergency department observation unit. Neurocrit Care 2009;10:204-8.
  62. Hörer S, Schulte-Altedorneburg G, Haberl RL. Management of patients with transient ischemic attack is safe in an outpatient clinic based on rapid diagnosis and risk stratification. Cerebrovasc Dis 2011;32(5):504-10.
  63. Engelter ST, Amort M, Jax F, et al. Optimizing the risk estimation after a transient ischaemic attack – the ABCDE+ score. Eur J Neurol 2012;19(1):55-61.
  64. Sorensen AG, Ay H. Transient ischemic attack: definition, diagnosis, and risk stratification. Neuroimaging Clin N Am. 2011;21(2):303-313.
  65. Oostema JA, DeLano M, Bhatt A, et al. Incorporating diffusion-weighted magnetic resonance imaging into an observation unit transient ischemic attack pathway: a prospective study. Neurohospitalist. 2014;4:66-73.
  66. Ross MA, Compton S, Medado P, et al. An emergency department diagnostic protocol for patients with transient ischemic attack: a randomized controlled trial. Ann Emerg Med. 2007;50: 109-119.
  67. SPS3 Investigators; Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367(9):817-825.
  68. Mijalski C, Silver B. TIA management: should TIA patients be admitted? Should TIA patients get combination antiplatelet therapy? Neurohospitalist 2015;5(3): 151–60.
  69. Lavalle ́e P, Meseguer E, Abboud H, et al. A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects. Lancet Neurol. 2007;6(11):953-960.
  70. Olivot JM, Wolford C, Castle J, et al. Two aces. Transient ischemic attack work-up as outpatient assessment of clinical evaluation and safety. Stroke. 2011;42:1839-1843,
  71. Wasserman J, Perry J, Dowlatshahi D, et al. Stratified, urgent care for transient ischemic attack results in low stroke rates. Stroke. 2010;41(11):2601-2605.
  72. Martinez-Martinez MM, Martinez-Sanchez P, Fuentes B, et al. Transient ischaemic attacks clinics provide equivalent and more efficient care than early in-hospital assessment. Eur J Neurol 2013;20:338-343.
  73. Sanders LM, Srikanth VK, Jolley DJ, et al. Monash transient ischemic attack triaging treatment. Safety of a transient ischemic attack mechanism-based outpatient model of care. Stroke. 2012;43:2936-2941.
  74. Webster F, Saposnik G, Kapral MK, Fang J, O’Callaghan C, Hachinski V. Organized outpatient care: stroke prevention clinic referrals are associated with reduced mortality after transient ischemic attack and ischemic stroke. Stroke. 2011 Nov; 42(11):3176-82.
  75. Wu CM, Manns BJ, Hill MD, Ghali WA, Donaldson C, Buchan AM. Rapid evaluation after high-risk TIA is associated with lower stroke risk. Can J Neurol Sci. 2009 Jul; 36(4):450-5.
  76. Kraaijeveld CL, van Gijn J, Schouten HJ, et al. Interobserver agreement for the diagnosis of transient ischemic attacks. Stroke 1984;15(4):723-725.
  77. Tomasello F, Mariani F, Fieschi C, et al. Assessment of inter-observer differences in the Italian multicenter study on reversible cerebral ischemia. Stroke 1982;13(1):32-35.
  78. Landi G. Clinical diagnosis of transient ischaemic attacks. Lancet 1992;339(8790):402-405.

Seizures in the First Year of Life

Author: Erica Simon, DO, MHA (@E_M_Simon, EM Chief Resident at SAUSHEC, USAF) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Case 1:

A nine month-old female presents to the emergency department (ED) with an increased work of breathing. The patient’s mother states that she developed a cough three days prior.  Her past medical history is unremarkable and the patient’s immunizations are up to date.

Initial vital signs (VS) in the ED: Heart rate (HR) 166 beats per minute (bpm), respiratory rate (RR) 42/minute (min), Oxygen saturation 96% on room air (RA), Temperature (T) of 103.1° Fahrenheit (F). As you walk into the room, you note the patient exhibiting generalized tonic-clonic motions, which resolve approximately one minute after onset.  After rechecking the patient’s airway, breathing and circulation (ABCs), you verify that the patient is stable and you quickly move on to the next patient.

Case 2:

The nurse is triaging a well-appearing three week-old infant.  The baby’s VS are within normal limits.  However, the nurse pulls you aside to express her concern regarding the patient’s repetitive tongue movements and directional eye motions she witnessed prior to your arrival.

If you are scanning your memory bank for information regarding the evaluation and treatment of these pediatric seizures, look no further.  This post will discuss the epidemiology of pediatric seizures, and offer a review of the evaluation and treatment of seizures occurring within the first year of life.

Epidemiology of Pediatric Seizures

Seizures are the most common neurologic emergency of childhood, representing approximately 1.5% of pediatric emergency department (ED) visits annually.1-3  Each year, nearly 150,000 children in the United States experience new onset seizure activity and an estimated 25,000 to 40,000 of these are afebrile. In addition, up to 10% of these patients suffer from status epilepticus.1-5 Among individuals with unprovoked afebrile seizures, approximately 70% are idiopathic and nearly 88% experience a recurrence within two years of the initial event.5

Evaluation & Treatment

In all patients presenting with a chief complaint of seizure, a comprehensive history and physical examination should be performed.  The patient history should center on events immediately prior to seizure onset (cyanosis, LOC), length of the seizure, a description of seizure activity, the presence of bowel or bladder incontinence, evidence of a postictal period, and the presence or absence of a family history of seizure disorder.

Important historical information should be obtained in patients under the age of one year. This includes birth history (pre-term/term, maternal infection), immunizations, change in diet or formula (change in preparation), any time spent unsupervised (accidental ingestions), and home remedies or medications utilized to treat maladies.1,2,5

 If the patient has a known seizure disorder, details should be obtained regarding seizure frequency, any alterations in medication regimens such as missed doses, and changes in seizure pattern (s).5,6

Physical examination in infants should focus on:

Neurologic:  developmental stages appropriate for age (milestones: 2 months = social smile, coos, tracks faces; 4 months = babbles, reaches for toy, holds head unsupported, etc)7
HEENT: head circumference, bulging or sunken fontanelles, retinal hemorrhages (may indicate increased intracranial pressure (ICP) +/- non-accidental trauma (NAT) versus volume depletion

Cardiac: capillary refill >2 seconds (sec)

Abdominal: hepatosplenomegaly => metabolic derangement/glycogen storage disease

Integumentary: café-au-lait spots => neurofibromatosis; vitiliginous lesions => tuberous sclerosis; port-wine stains => Sturge-Weber Syndrome; excessive bruising => NAT5

 The evaluation and treatment of pediatric seizures within the first year of life varies according to seizure classification.

 Febrile Seizures

The American Academy of Pediatrics defines a febrile seizure as seizure activity associated with a temperature ≥ 100.4 °F or 38 °C, occurring in patients 6 through 60 months of age, in the absence of central nervous system (CNS) infection, metabolic abnormalities or a history of afebrile seizure.1-4  The incidence of simple febrile seizures peaks at 18 months of age.1

Risk Factors for Febrile Seizures

While the pathophysiology of seizures occurring in the setting of elevated core temperatures is poorly understood, several risk factors have been identified:

  • Family history of febrile seizures (no susceptibility gene identified, but family history reported in 25-40% of patients).1,8
  • Viral infections: human herpes virus (HHV) 6 and influenza.1,8
  • Vaccinations: diphtheria, tetanus toxoids, and whole cell pertussis (DTP), and measles, mumps, and rubella (MMR)1,8

To help aid in physician decision-making regarding the need for diagnostic testing and treatment, febrile seizures are identified as simple versus complex.

Table 1 summarizes the characteristics of simple and complex seizures.

Seizure Type
Simple Complex
Duration < 15 minutes ≥15 minutes
Motion Generalized, Tonic-Clonic Focal
Mental Status Return to baseline Persistent alteration in mental status
Episodes 1 episode within 24 hours > 1 episode within 24 hours

Neonatal seizures can be subtle and difficult to detect.  Generalized tonic-clonic and myoclonic activity is rarely seen in patients of this age group given their premature central nervous systems.1  Much more commonly, patients under 28 days of age present with motor automatisms (ocular deviations, repetitive limb movements, repetitive oral movements) or changes in heart rate, and/or respiratory rate (apneic episodes).6

Evaluation and Treatment of Simple Febrile Seizures

In 2011, the American Academy of Pediatrics (AAP) released an updated guideline for the management of simple febrile seizures.  In the setting of a simple febrile seizure, the AAP recommends the following:10

  • A lumbar puncture (LP) should be performed in pediatric patients presenting with meningeal signs or in any child whose history and/or examination suggest meningitis or intracranial infection (Level B recommendation based on overwhelming evidence from observational studies).
  • In infants 6-12 months of age who presents with a seizure and fever, a LP is an option when the child is deficient in Haemophilus influenza type b (Hib) or Streptococcus pneumoniae immunizations, or when immunization status is unknown (Level D recommendation that is based on expert opinion and case reports).
  • A LP is an option in a pediatric patient pre-treated with antibiotics, as antibiotics may mask signs and symptoms of meningitis (Level D recommendation based on expert opinion and case reports).
  • An electroencephalogram (EEG) should not be performed in a neurologically healthy child with a simple febrile seizure (Level B recommendation based on overwhelming evidence from observational studies).
  • Routine laboratory studies should not be routinely performed for the sole purpose of identifying the cause of a simple febrile seizure (Level B recommendation based on overwhelming evidence from observational studies).
  • Neuroimaging should not be performed in the setting of a simple febrile seizure (Level B recommendation based on overwhelming evidence from observational studies).

Note: The AAP’s recommendations are based on an academic review of literature published from 1996-2009.  Perhaps the most commonly cited studies include:

Green SM, Rothrock SG, Clem KJ, Zurcher RF, Mellick L. Can seizures be the sole manifestation of meningitis in febrile children? Pediatrics. 1993;92(4):527–534.

This is a retrospective review of 503 consecutive cases of meningitis in pediatric patients aged 2 months to 15 years seen at two referral hospitals over a 20 year period. None of the 503 patients noted to have meningitis manifested with seizure as a sole symptom.

Kimia AA, Capraro AJ, Hummel D, Johnston P, Harper MB. Utility of lumbar puncture for first simple febrile seizure among children 6 to 18 months of age. Pediatrics. 2009;123(1):6–12.

  • Retrospective cohort review of patients aged 6 to 18 months who were evaluated for first simple febrile seizure in a pediatric emergency department between October 1995 and October 2006: no patient was diagnosed as having bacterial meningitis (number undergoing LP: 360)

Ultimately, evaluation of a febrile patient experiencing a simple febrile seizure should focus on identifying the underlying etiology of the fever. Laboratory studies and imaging should be ordered at physician discretion and according to institutional policy.  Please review the Philadelphia, Rochester, & Boston criteria for further information on how to identify febrile infants who are at risk for serious bacterial infections.  Despite thorough evaluation, approximately 30% of patients experiencing a simple febrile seizure will leave the ED without an identified etiology.11

Evaluation of Complex Febrile Seizures

Given the heterogeneity of patient presentations and relatively little knowledge regarding their etiologies, no standard algorithm or clinical practice guideline exist for the evaluation and management of complex febrile seizures.1,4

 However, a recent retrospective, cohort review by Kimia et al. did present data on this patient population:

  • From 1995 to 2008, 526 pediatric ED patients aged 6 to 60 months (median age 17 months) were evaluated for a first complex febrile seizure. Of the 526 patients, 340 underwent LP. Ultimately, 3 patients were discovered to have acute bacterial meningitis (0.5% of patients experiencing a complex febrile seizure). An additional patient was hospitalized and treated with antibiotics based upon a positive blood culture result.

In terms of complex febrile seizures, further studies are warranted.  Determining the need for neuroimaging, lumbar puncture, laboratory studies, and EEG must be determined on a case-by-case basis.4 CT can be considered if there is a concern for increased ICP or a mass, while MRI may demonstrate hippocampal injury or temporal sclerosis in the setting of febrile seizures. A neurology consultation and admission are likely in the best interest of any of these patients.

Afebrile Seizures

The differential diagnosis for new onset afebrile seizures within the first year of life is broad (Table 2).  The emergency physician primarily plays a role in stabilizing patients and in initiating preliminary evaluation.

Etiologies of New-Onset Afebrile Seizures
Time of Onset  
24 Hours Direct Drug Effects Intraventricular Hemorrhage
  Hypoxic-ischemic Encephalopathy Laceration of Tentorium or Falx
  Intrauterine Infection Pyridoxine Dependency
  Subarachnoid Hemorrhage (SAH)
24-72 Hours Cerebral Contusion/Subdural Glycogen Synthase Deficiency
Cerebral Dysgenesis Glycine Encephalopathy
Cerebral Infarction Pyridoxine Dependency
Drug Withdrawal SAH
Hypoparathyroidism Tuberous Sclerosis
Intracranial Hemorrhage (ICH) Urea-cycle Disturbances
Intraventricular Hemorrhage  Electrolyte Disturbances
72 Hours – 1 Week Familial Neonatal Seizures Kernicterus
Cerebral Dysgenesis Methylmalonic Acidemia
Cerebral Infarction Nutritional Hypocalcemia
Hypoparathyroidism Propionic Acidemia
ICH Tuberous Sclerosis
Urea-cycle Disturbances  Electrolyte Disturbances
> 1 Week Adrenoleukodystrophy Gm1 Gangliosidosis Type 1
Cerebral Dysgenesis HSV Encephalitis
Fructose Dysmetabolism Ketotic Hyperglycinemias
Gaucher Type 2 Maple Syrup Urine Disease
Tuberous Sclerosis Urea-cycle Disturbances
Electrolyte Disturbances

New-Onset Neonatal Afebrile Seizures5,6

Based upon patient presentation and a comprehensive history and physical examination, the following laboratory studies/imaging may or may not be warranted:6

  • Inborn errors of metabolism: accucheck, ammonia levels, serum organic acids, urine organic acids, metabolic panel, lactate, pyruvate
  • NAT/cerebral anomalies: Cerebral US vs. CT vs. MRI, skeletal survey
  • Meningitis/meningoencephalitis: LP
  • Toxic ingestions: serum heavy metal screen, serum toxicology levels

It is important to note that experts recommend emergent neuroimaging in the following patient populations:13,14

  • Patients with a prolonged seizure (> 15 minutes)
  • Focal seizure in patients < 33 months
  • Patients with a persistent postictal focal deficit
  • Patients with alterations in baseline mental status post seizure activity
  • Patients with conditions pre-disposing to intracranial pathology (sickle cell, bleeding diathesis, neurocutaneous disorder, HIV, hydrocephalus, VP shunt, or closed head injury)

Ultimately, the decision between outpatient and inpatient evaluation should be based upon the clinical scenario and in consultation with a neurologist.  In general, stable, well-appearing children who have experienced a first unprovoked seizure and are in the low risk category (not requiring emergent neuroimaging as detailed above), may undergo outpatient evaluation if expedited follow-up for EEG is arranged.1,5

All patients experiencing a new-onset afebrile seizure should undergo EEG evaluation as soon as possible because EEG abnormalities may predict seizure recurrence.5 Overall, the recurrent seizure rate in this group is 54% and the majority of seizures recur within two years of the initial event.1  Patients with developmental delays or those with an abnormal EEG are more likely to eventually develop an epileptiform disorder.15

 Seizure Treatment

Addressing the patient’s airway and providing benzodiazepines are the mainstays of ED management.  The authors Abend and Loddenkemper provide an excellent example of a protocol created for the management of pediatric seizures:16

 PIC1 seizures

 PIC2 seizures

A quick word on status epilepticus: As mentioned previously, nearly 10% of all pediatric patients with new-onset seizure activity present to the ED in status epilepticus, which is defined as seizure activity > 5 minutes without return to mental status baseline.1  Unlike adults in which cerebral vascular accidents (CVAs) are the most common etiology of status epilepticus, febrile seizures are the most common etiology in pediatric patients, representing 1/3 of all episodes.17


Seizure Mimics

There are a number of seizure mimics that can present during the first year of life:

  • Neonatal reflexes – the startle reflex can often be misinterpreted as seizure activity.1
  • Benign sleep myoclonus – migrating myoclonic movements that do not wake the child.18
  • Shuddering attacks – rapid shivering of the head, shoulders, and trunk.19
  • Sandifer syndrome – arching of the back, crying, and writhing secondary to severe gastroesophageal reflux.1
  • Breath holding spells – seen in 5% of pediatric patients 6 months – 5 years of age (presentation variable but often times mistaken for a seizure or brief resolved unexplained event).1

 These seizure mimics are diagnoses of exclusion.  Every effort should be made to obtain an accurate history of events to aid in clinical decision-making.

Seizure Syndromes Unique to Patients in the First Year of Life

The differential diagnosis of a patient experiencing an unprovoked afebrile seizure in the first year of life should include the following:

Syndrome Onset Characteristics
Benign Convulsions Associated with Gastroenteritis 6-60 months Generalized seizures accompanying gastroenteritis, in the absence of electrolyte derangements.  Often associated with Shigella and rotavirus infection.20
Benign Familial Neonatal Convulsions First days of life; self-resolves within 1 year. Behavioral arrest, eye deviation, tonic stiffening, myoclonic jerks.  Associated with a positive family history.9
Benign Idiopathic Neonatal Convulsions First days of life; self-resolves within 15 days. “Fifth day fits” – clonic movements, apnea, positive family history.  May represent 5% of all seizures in term infants.21
Infantile Spasms 4-18 months Jerking of extremities, head, neck and trunk; typically in clusters.  Associated with neurologic conditions (95% have developmental delay).  Spontaneously resolve, however the majority develop new seizures.22

Seizure Syndromes Unique to Pediatric Patients1


The emergency physician’s role in addressing seizures in the first year of life is to stabilize the patient and initiate an appropriate evaluation based upon an accurate history and physical examination.  While decision rules exist for simple febrile seizures, the evaluation of a complex febrile seizure and a new onset afebrile seizure must be weighed carefully.  While seizure mimics do exist, the emergency physician must always rule out any life threatening conditions first.

Key Pearls

  • Simple febrile seizure = Fever evaluation.
    • Meningeal symptoms => LP
    • 6-12 months of age with no immunization record/concern for meningitis => LP
    • Received antibiotics and concern that treatment is masking symptoms => LP
  • Complex febrile seizure = No clinical decision rules.
    • Some evidence to suggest that, although rare, we may be missing acute bacterial meningitis (3 of 340 patients in the Kimia, et al.12 study)
    • Further studies required; evaluation should be catered to the clinical scenario.
  • Afebrile seizure = No clinical decision rules, again cater to clinical scenario.
    • Focal seizure < 33 months, prolonged seizure duration, prolonged neuro deficit or co-morbidities => emergent neuroimaging.
    • All patients get an EEG (expedited outpatient if well-appearing and no focal neuro).
      • Up to 54% have recurrent seizures.
    • Seizure treatment = ABCs, benzos => fosphenytoin => sedation with continuous EEG +/- anticonvulsant
    • Seizure mimics exist, but so do seizure syndromes.
      • Your history and physical examination are vital.

References / Further Reading

  1. Agarwal M, and Fox S. Pediatric seizures. Emerg Med Clin N Am 31 (2013):733-754.
  2. Taylor C, Piantino J, Hageman J, Lyons E, Janies K, Leonard D, Kelley K, Fuchs S. Emergency department management of pediatric unprovoked seizures and status epilepticus in the state of Illinois. J Child Neurol. 2015; 30(11):1414-1427.
  3. Carapetian S, Hageman J, Lyons E, Leonard D, Janies K, Kelley K, Fuchs S. Emergency department evaluation and management of children with simple febrile seizures. Clin Pediatr. 2014; 54(10):992-998.
  4. Patel A, and Vidaurre J. Complex febrile seizures: a practical guide to evaluation and treatment. J Child Neurol. 2013; 28(6):762-767.
  5. Sharieff G, Hendry P. Afebrile pediatric seizures. Emerg Med Clin N Am 29 (2011); 95-108.
  6. Granelli S, and McGrath J. Neonatal seizures: diagnosis, pharmacologic interventions, and outcomes. J Perinat Neonat Nurs. 2004; 18(3):275-287.
  7. Learn the Signs. Act Early: Developmental milestones. Centers for Disease Control and Prevention. 2016. Available from: http://www.cdc.gov/ncbddd/actearly/index.html
  8. Graves R, Oehler K, Tingle L. Febrile seizures: risks, evaluation, and prognosis. Am Fam Physician. 2012; 85(2):149-153.
  9. Zupanc M. Neonatal seizures. Pediatr Clin North Am. 2004; 51:961-978.
  10. Clinical practice guideline – febrile seizures: guideline for the neurodiagnostic evaluation of the child with a simple febrile seizure. American Academy of Pediatrics. Pediatrics. 2011; 127(2):389-394.
  11. Colvin J, Jaffe D, Muenzer J. Evaluation of the precision of emergency department diagnoses in young children with fever. Clin Pediatr. 2012; 156:469-472.
  12. Kimia A, Ben-Joseph EP, Rudloe T, et al. Yield of lumbar puncture among children who present with their first complex febrile seizure. Pediatrics. 2010;126(1):62–69.
  13. Sharma S, Riviello J, Harper M, et al. The role of emergent neuroimaging in children with new-onset afebrile seizures. Pediatrics. 2003; 111:1-5.
  14. Warden C, Brownstein E, Del Beccaro M. Predictors of abnormal findings of computed tomography of the head in pediatric patients presenting with seizures. Ann Emerg Med. 1997; 29: 518-523.
  15. Shinnar S, Berg A, Moshe S, et al. The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up. Pediatrics. 1996; 98:216-225.
  16. Abend N, Loddenkemper T. Pediatric status epilepticus management. Curr Opin Pediatr. 2014; 26(6): 668-674.
  17. Stafstrom C. Neonatal seizures. Pediatr Rev. 1995; 16:248-255.
  18. Alam S, Lux A. Epilepsies in infancy. Arch Dis Child. 2012; 97:985-992.
  19. Tibussek D, Karenfort M, Mayatepek E, et al. Clinical reasoning: shuddering attacks in infancy. Neurology. 2008; 70:338-41.
  20. Verrotti A, Nanni G, Agostinelli S, et al. Benign convulsions associated with mild gastroenteritis: a multicenter clinical study. Epilepsy Res. 2011; 93:107-114.
  21. Vining E. Pediatric seizures. Emerg Med Clin North Am 1994; 12:973-988.
  22. Hancock E, Osborne J, Edwards S. Treatment of infantile spasms. Cochrane Database Syst Rev. 2008; (4):CD001770

“Dementia” in the emergency department: can you do anything about it?

Author: Diana Kay Coleman, MD (EM Resident Physician, UTSW / Parkland Memorial Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC)

An elderly patient presents to your emergency department with his adult son who is concerned that his father is acting more and more confused. This is not a new behavior for the patient; the son has noticed it over the past several years. He will repeat questions and not remember significant events from the past few days. Over the past several months he has even become “stubborn” according to the son, often yelling when his family members try to correct him. The only other symptom the patient’s son has noticed is that for the past several months, the patient moves around much more slowly, often needing assistance to walk to the bathroom. He has had many accidents of urinating on himself when he doesn’t get to the bathroom in time. The patient has never been to your hospital before – in fact he moved to the U.S. with his son from Africa 1 year ago, so you have no past medical history, and the patient has not seen a physician in years. The son asks you why his father is acting in this manner and how you can fix it, as he doesn’t think he can take care of his father like this anymore.

Dementia versus Delirium

Differentiating dementia and delirium can be a difficult but important distinction to make in the emergency department, and the best tool to help differentiate the two disease processes is the history. The catch is that both dementia and delirium make for poor patient historians. You will need to rely on family or friends, nursing home staff or home health aids who may have been assisting the patient, and any prior records.

Symptoms of delirium can overlap the symptoms of dementia, but there are some clues that lead more towards a diagnosis of delirium. Patients with delirium will have disturbances in consciousness, memory, cognition, and perception. These patients may develop hallucinations or delusions. Their presentation can vary from hyperactive and agitated to hypoactive and lethargic, or a category of mixed delirium which includes characteristics of both. Studies show that up to 60% of critically ill patients with delirium will present with hypoactive symptoms[i].

 In contrast, patients suffering from dementia are more likely to have predominantly impairments in memory and cognitive function, as opposed to alterations in consciousness and perception. For patients with delirium, their symptoms present much more acutely, over days to weeks, as opposed to the symptoms of dementia, which occur over months and years. Patients with delirium are also much more likely to have a fluctuating course, with symptoms changing abruptly over the course of days, or even hours.

Using laboratory tests and imaging as adjuncts can help delineate between these two disease processes. Delirium will usually be accompanied by some lab or imaging abnormality indicating the cause, such as an electrolyte disturbance, a source of infection, or an intoxicant. Identifying if your patients’ symptoms are caused by dementia or delirium is important because most causes of delirium are reversible. There are many mnemonics to help remember the common causes of delirium. Two different mnemonics are[ii][iii]:

 Screen Shot 2016-08-29 at 4.19.08 PM

Reversible Causes of Dementia

After your initial history has pointed you in the direction of dementia as a cause of your patient’s symptoms, the next step is to determine if your patient has a reversible cause of dementia. The frequency of dementia due to a potentially reversible cause is varied, with reports of anywhere between 0 to 23% of cases being attributed to a reversible cause. The most common reversible causes are alcohol and medication related dementia, depression induced cognitive impairment, surgical brain lesions (normal pressure hydrocephalus, tumors, chronic subdural hematomas), metabolic disorders, vitamin deficiencies, and CNS infections such as neurosyphilis and HIV[iv]. It is important to note that some of those causes, such as drug reactions, metabolic abnormalities, or endocrine derangements can cause either an acute delirium or a gradual progressive dementia[v]. Below is a helpful mnemonic to remember the reversible causes of dementia:

Screen Shot 2016-08-29 at 4.19.27 PM

When evaluating a patient with symptoms of dementia, keep in mind that not all reversible forms of dementia can be diagnosed in the emergency department, let alone treated in the emergency department. For example, a patient in whom you suspect decline in hearing as a cause for dementia will likely require a formal outpatient audiology evaluation. Depending on your facility, an HIV test or RPR or VDRL test to evaluate for syphilis might not result that same day, so the diagnosis might be delayed until the patient has left your emergency department. However, there are some basic labs and imaging that you can order to rule out the common reversible causes of dementia, and you can add other adjunct based on the relevant information from your history and physical exam.

Evaluation of a Patient with Symptoms of Dementia

A focused history in these patients may be all that is needed to point in the direction of a particular etiology of dementia, such as a patient reporting a long history of alcohol abuse prior to symptom onset, or a patient with multiple prior strokes who can be diagnosed with vascular dementia. However, not all cases are straight forward. A thorough history should be obtained regarding the cognitive symptoms, including symptom onset, severity of decline, association with potential emotional stressors, and any other physical complaints that have developed since the symptom onset. Be sure to include a thorough past medical history, including family history of similar symptoms, social history including prior drug or alcohol use, and a complete list of medications, including over-the-counter drugs or vitamins. Asking about prior history of depression or recent changes in mood may provide helpful clues to assess for pseudodementia secondary to depression.

Dementia due to drug toxicity can be a difficult entity to diagnose as well as to treat – particularly in elderly patients – for many reasons. These patients often have multiple prescribed drugs, and it is hard to determine which drug might be the offender. It is rare that dementia is caused solely by a single drug side effect or drug toxicity, but rather many drugs can exacerbate the symptoms of dementia. Many patients require psychoactive drugs to treat the behavioral aspect of dementia, and it is difficult to determine if these drugs are exacerbating the cognitive decline, or if that is just a natural continuation of the disease process. The drugs that are most commonly associated with exacerbating cognitive impairment are psychoactive drugs including anticholinergics, opioids, benzodiazepines, antipsychotics, antidepressants, antiparkinsonian drugs, and anticonvulsants. However, physicians need to be aware that even non-psychoactive drugs can exacerbate symptoms of dementia or even lead to delirium, including histamine antagonists, cardiac drugs – particularly digoxin and other antiarrhythmics – corticosteroids, NSAIDS, and antibiotics.[vi] Therefore, it is important to discuss all medications, either prescription or over-the-counter medications, with the patient or their family members or care-givers during your history.

Your physical exam should focus on a complete neurologic exam as well as a mental status evaluation. There are many different scoring tools to assess mental status, including the Mini Mental Status Examination, or the Six-Item Cognitive Impairment Test, which can be used quickly in the emergency department. The validity for these tests have been best studied in the primary care outpatient setting; however, these tests can be performed quickly and provide a baseline status that will be useful when the patient follows up as an outpatient[vii]. Patients with pseudodementia may present with a chief complaint of memory loss. However, cognitive testing will be less likely to reveal clinical signs of dementia, and instead patients will have poor concentration and impaired motivation and energy when responding to questions[viii].

The neurologic exam could also point towards certain reversible causes of dementia. For example, a patient presenting with cognitive dysfunction and seen to have ataxia on neurologic exam may be suffering from normal pressure hydrocephalus, especially if the history also includes symptoms of urinary incontinence. Alternatively, patients with more focal neurologic findings such as isolated limb weakness or cranial nerve deficits may be suffering from a space-occupying lesion.

The basic labs that you should consider ordering on patients presenting to the emergency department that you suspect have undiagnosed dementia include a complete blood count with peripheral blood smear to assess for anemia, a complete metabolic profile (to evaluate electrolytes, liver function, and renal function), TSH, and urinalysis. If you have clinical suspicion for tertiary syphilis as a cause of the patient’s symptoms, consider adding a VDRL and serum fluorescent treponemal antibody assay. These patients should also undergo CT scan of the head to rule out space-occupying lesions or hydrocephalus. There are additional studies that can be performed as an outpatient, including serum vitamin levels, inflammatory markers, urine corticosteroid levels, and urine screens for drugs or heavy metals. These tests are difficult to run in most emergency departments and may not result for several days, when your patient hopefully is not in your department anymore.

Treatment and Disposition

Treatment for dementia will of course be determined by the cause of dementia. Any space-occupying lesion will require consultation with neurosurgery to determine any possible surgical options. Diagnosis of normal pressure hydrocephalus based on symptoms and CT imaging should prompt a neurology evaluation, as these patients can undergo further evaluation and testing on either an inpatient or outpatient basis, depending on the protocols of your institution.

Disposition can be tricky to manage in patients with dementia, regardless of whether the symptoms are chronic or relatively new. Patients who are not able to ambulate independently or perform their activities of daily living may be safe to discharge home if they have family members who understand the responsibilities of care and are physically able to assist the patient with those activities. Otherwise, the patient may need placement in nursing home or other institution. In rare situations, the patient may be able to get placement from the emergency department, but that depends on the patient’s insurance, their medical conditions, and the available resources of your community. If your emergency department has available social workers, they can help determine what options are available to your patient. If there is not an option for nursing home placement and your patient is not safe for discharge by themselves or with their family, they will require admission for physical therapy and/or occupational therapy evaluation to help better determine eventual disposition.


Your patient from the case turns out to be a very nice gentleman who responds with only one-word answers. Cardiac, pulmonary, and abdominal exam are all normal. The patient has equal weakness in all extremities when tested while supine. When you ask him to walk, he takes a few steps with a wide-based gait, and then requires assistance from his son to make it back to the bed. Labs are all within normal limits, but CT Head shows brain atrophy with dilated ventricles. Neurology is consulted and they agree to take the patient and confirm the diagnosis of normal pressure hydrocephalus with lumbar puncture and begin the discussion with the patient and son about options for possible shunt placement.


  • Delirium is more acute in onset, fluctuates more frequently and drastically, and includes alterations in consciousness and perception; dementia induces a more gradual and steady decline and symptoms are predominantly impairments in memory and cognitive function.
  • Common reversible causes of dementia include drugs (either overdose or poly-pharmacy), depression, metabolic or endocrine disorders, hydrocephalus, space-occupying lesions, decline in hearing or vision, infections, or anemia.
  • Patients presenting with symptoms of dementia should be evaluated with CBC, chemistry, LFTs, TSH, and CT head to help identify reversible causes; not all reversible causes will be identified in the emergency department because they require further outpatient evaluation for diagnosis (such as depression or decline in hearing).
  • Any patient who cannot ambulate or perform their activities of daily living and who does not have family able to care for them at home will require placement in a nursing home or institution; contact your social workers to see if this can be arranged from the emergency department.


References / Further Reading

[i] Pandharipande P, Cotton BA, et al. Motoric subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients. Intensive Care Med. 2007 Oct; 33:726-1731.

[ii] St. Louis University Geriatric Evaluation Mnemonics and Screening Tools. Saint Louis University School of Medicine Division of Geriatric Medicine and the Geriatric Research, Education, and Clinical Center at the St. Louis VA Medical Center. http://aging.slu.edu/uploads/pdf/Saint-Louis-University-Geriatric-Evaluation_2013.pdf

[iii] Smith, JP, Seirafi J: Delirium and Dementia. Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 104: p 1398-1408.

[iv] Tripathi M, Vibha D. Reversible Dementias. Indian J Psychiatry 2009; 51: 52-55

[v] Smith, JP, Seirafi J: Delirium and Dementia. Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 104: p 1398-1408.

[vi] Moore A, O’Keeffe. Drug-Induced Cognitive Impairment in the Elderly. Drugs and Aging 1999; 15: 15-28.

[vii] Upadhyaya A, Rajagopal M, Gale T. The Six Item Cognitive Impairment Test (6-CIT) as a screening test for dementia: comparison with Mini-Mental Status Examination (MMSE). Curr Aging Sci 2010; 3: 138-42.

[viii] Haggerty JJ, Golden RN, et al. Differential diagnosis of pseudodementia in the elderly. Geriatrics 1988; 43: 61-69.

Cerebral Venous Thrombosis: Pearls and Pitfalls

Authors: Brit Long, MD (@long_brit, EM Physician at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) // Edited by: Jennifer Robertson, MD, MSEd

 A 28 year-old female presents to the emergency department (ED) complaining of a left-sided headache with associated nausea and vomiting for the last 24 hours. She went to another ED a few hours prior, where the headache resolved with medications. However, it quickly returned. The patient has no past medical history, including no history of headaches. She is one month postpartum. Her vital signs are normal, including a blood pressure (BP) of 110/62. Her neurologic exam is normal.  You order an intravenous (IV) line and basic medications for headache treatment.  However, you question whether you are missing something important. Besides treating the headache, are any tests necessary?

Emergency physicians evaluate many conditions that are often simple, however, we also train to recognize conditions that can be life-threatening. A patient with neurologic symptoms may have a condition that is benign, while another may be suffering a condition with high morbidity and mortality. Emergency physicians must evaluate for red flags in patients that may signify high risk disorders. Cerebral venous thrombosis (CVT) is one such disorder as it carries significant morbidity and mortality.

CVT is a rare disorder, with an annual incidence of 1.32 cases per 100,000 person-years. It accounts for approximately 1% of strokes.1-4  The disease includes thrombosis of the cerebral veins and major dural sinuses.  CVT is more common in patients with history of thrombophilia, those taking oral contraceptives, and those who are pregnant or in a post-partum state.1-5 The diagnosis is often delayed and most patients are not diagnosed until 4-7 days after symptoms start6-8 Only 10% of patients are over 60 years of age. The majority of patients present under the age of 50 years (80%), with a mean age of 39 years.1-3,6


CVT can be a difficult diagnosis to make due to a wide variety of signs and symptoms. CVT should be suspected in several situations, as shown below in Table 1. The onset may be acute, subacute, or chronic.1-3 This accounts for a high rate of misdiagnosis. ED physicians should keep in mind the risk factors for CVT and specific scenarios shown below in Table 1.

Table 1

Scenarios warranting CVT investigation1-4
– Headache: in a pregnant female patient, in a young female on OCPs, or one that is atypical and persistent

– Stroke with no typical risk factors or in the setting of seizure

– Intracranial hypertension with no explanation

– Multiple hemorrhagic infarcts, or hemorrhagic infarcts not in a specific arterial distribution

– Objective neurologic symptoms in a patient with risk factors for CVT

Symptoms are not always classic, but they can be associated with the thrombus location.3,4

– Cortical vein thrombosis presents with motor and sensory deficits, as well as seizure.

– Sagittal sinus thrombosis may present with motor deficits, bilateral deficits, and seizures.

– Patients with thrombus in the lateral sinus may present with intracranial hypertension and headache alone.

– Thrombosis of the left transverse sinus can present as aphasia.

– Thrombosis of the deep venous sinus can cause behavioral symptoms due to lesions in the thalamus.

– Cavernous sinus thrombosis is associated with ocular pain, chemosis, proptosis, and oculomotor palsies.3,4


Figure 1 – Cerebral venous system components2, image from Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. Cerebral venous thrombosis – A primer for the haematologist. Blood Reviews 2015;29:45–50.

Four major syndromes have been described: isolated intracranial hypertension (the most common), focal neurologic abnormality, seizure, and encephalopathy. The patient may present with one or several of these.2-4

  1. The most common syndrome is intracranial hypertension resulting in headache. This is often a localized, persistent headache, seen in up to 90% of patients with acute presentation. This means that 10% of patients will not have a headache during their course, which can delay diagnosis.7-9 Headache may be sudden in onset and severe, mimicking subarachnoid hemorrhage, or it may be persistent and gradually worsening. Visual symptoms may also occur with the headache. It often worsens with valsalva or coughing due to increased ICP.9,10
  2. Focal neurologic deficits are found in 37%-44% of patients, with motor weakness the most common focal symptom.7,9 Sensory deficits are not common.1,2
  3. Seizures (focal, generalized, and status epilepticus) are seen in 30-40% of patients.7,11 CVT should be considered in any patient with a focal neurologic deficit and seizure.1,2
  4. Encephalitis is the final syndrome, which can be found in patients with thrombosis of the straight sinus or with severe cases including extensive hemorrhage, edema, and large venous infarcts leading to herniation.1,2,4 This syndrome is more common in elderly patients, who may present with altered mental status and confusion.12

 Is there a difference between cerebral venous thrombosis and cavernous venous sinus thrombosis?

CVT and CVST have common underlying etiologies including thrombosis. However, CVST includes thrombosis in the cavernous sinuses with infection. Ocular signs and symptoms predominate. Treatment requires anticoagulation and antibiotics.1,2,4,6

Risk factors

At least one risk factor is present in 85% of patients with CVT, however the disease is often multifactorial with several risk factors present.3,4,7  In fact, multiple risk factors are found in 50% of patients with CVT:1,15

Thrombophilia is discovered or is present in 34% of patients with CVT. These disorders include factor V Leiden mutation and deficiencies of antithrombin, protein C, and/or protein S.

– CVT is commonly seen in women who are pregnant. post-partum or who are taking hormonal contraceptives

Infections including osteitis, mastoiditis, sinusitis, and meningitis are associated with CVT

Chronic inflammatory diseases such vasculitis, inflammatory bowel disease, malignancy, nephrotic syndrome, and hematologic disorders such as polycythemia and essential thrombocytosis also contribute to disease development.

– Other risk factors include head trauma, local injury to the cerebral sinuses, and neurosurgical procedures.1,2,4


Two major pathophysiological mechanisms are associated with CVT: (1) Thrombosis of the cerebral drainage system and (2) Decreased cerebrospinal fluid absorption. Both can lead to increased intracranial pressure, cerebral edema, and potentially hemorrhage.3,4

  1. Thrombosis of the cerebral drainage system causes increased venular and capillary pressure. As the local venous pressure rises, cerebral perfusion decreases, and this can cause ischemia and cytotoxic edema. Vasogenic edema can also be a result of blood-brain barrier destruction. This can lead to parenchymal hemorrhage if pressures continue to increase.13,14
  2. The second mechanism includes decreased CSF absorption, leading to increased pressures, cytotoxic and vasogenic edema, and parenchymal hemorrhage.13,14

Your patient denies any known blood disorders and has had no recent infections or trauma. She does have several risk factors for CVT including her age, post-partum status, and a persistent headache. As she has never had headaches before, you consider further testing.


Due to the wide variety of symptoms, delays in diagnosis are common. CVT must be considered in patients under 50 years of age with headaches and atypical features. Atypical features may include focal, objective neurologic deficit(s) (often not fitting a specific anatomical region or with multiple region involvement), seizures, signs of intracranial hypertension, or hemorrhagic infarction present on initial head CT.1-4  Patients may improve with pain medication; however, if focal deficit or seizure is present, CVT must be considered.

Labs including a complete blood count (CBC), renal function, and coagulation panel should be obtained. The d-dimer is classically thought to be elevated.4,9,16,17 However, one study found a false negative rate of 24%. In addition, d dimer has been found to be normal in 40% of patients with isolated headache and no other symptoms.9 Therefore, a negative d dimer must not be relied upon to rule out CVT.16,17

A lumbar puncture (LP) should be considered to evaluate for meningitis. Results of the LP are often nonspecific in CVT including increased protein, increased RBCs, and lymphocytosis, findings similar to viral meningitis. The presence of CVT risk factors, objective neurologic deficits, and deficits in multiple arterial distributions should raise suspicion for the disease. Viral studies including polymerase chain reaction (PCR) should be ordered if LP is completed.1,2,4,9 However, CVT is still suspected after a negative or nonspecific LP, further evaluation with

Imaging is required for diagnosis. The American Heart Association/American Stroke Associations (AHA/ASA) recommend imaging of the cerebral venous system for patients with infarction across multiple arterial territories or with lobar intracerebral hemorrhage of unclear origin.4,6 Imaging should also be obtained in patients with idiopathic intracranial hypertension and headache with atypical features.4,6

  1. Head computed tomography (CT) is a first line test in patients with new headache, focal neurologic symptom, seizure, or altered mental status. Any patient with headache and new abnormal neurologic finding(s) (altered mental status, focal neurologic deficit, etc.) warrants emergent head CT per ACEP policy (Level B recommendation).18 Unfortunately, this test has poor sensitivity for CVT and is normal in 30% of cases. The majority of findings on CT are nonspecific, if present.
    1. One third of cases demonstrate direct signs on CT. These signs include a dense triangle sign (hyperdensity with triangular shape in posterior superior sagittal sinus), an empty delta sign (triangular pattern of contrast enhancement surrounding a central area with no enhancement), or a cord sign (curvilinear density over the cerebral cortex).3,4,6,19-21
    2. Indirect signs of CVT are more common and include contrast enhancement over the falx and tentorium, dilated venous structures, small ventricles, and parenchymal abnormalities (seen in 80% including hemorrhagic and nonhemorrhagic lesions).19-21 Multiple infarctions or infarctions in several arterial distributions warrant consideration of the disease.1-3
  2. CT combined with venography is rapid and reliable and will detect a thrombus with heterogeneous density. This test has an overall sensitivity of 95% and is helpful for patients with subacute or chronic presentations.1-4,6,22 Contrast reaction, contrast nephropathy, and radiation exposure can limit its use. Due to availability of CT, this is likely the best test in the ED setting.
  3. Magnetic resonance (MR) imaging with T2 weighted sequence and MR venography (MRV) are the most sensitive imaging modalities. However, disadvantages include the time involved and the anatomical variation of the venous system that may be present.1,3,6,22-28 MRI findings are dependent on the thrombus age. If the diagnosis is based on lack of blood flow only, the test may be false positive.3,4,22,29 Contrast is needed with venography.1,4,6 This test is often unavailable in the ED, thus CT with venography is the usual go-to imaging modality.
  4. Cerebral intra-arterial angiography may be used if CT and MR imaging modalities do not reveal the diagnosis and the diagnosis is still under consideration,.3,6,30,31 This test is best for cortical vein thrombosis.3,4,6

A noncontrast head CT reveals hyperdensities of the left sigmoid sinus. You speak with the radiologist concerning the need for further imaging, and MRV demonstrates thrombosis of the left transverse and sigmoid sinuses. Now that you have the diagnosis, what are your next step


Mortality occurs in approximately 5% of patients, most commonly with lesions leading to increased intracranial pressure (ICP) and herniation.1-3,15 First address life-threatening complications including coma, seizures, or increased ICP. This is followed by specific therapy, supportive care, and treatment of underlying causes and complications.1-4,6 Table 2 outlines treatment goals.

Table 2

Management Goals1-4,6
– Stabilize the immediate condition

– Remove the venous occlusion and stop propagation

– Administration of thrombolytic agents in selected patients

– Use of antiepileptic agents in patients with seizures and supratentorial lesions

– Treat any underlying conditions and risk factors

– Treat long term symptoms such as headache

– Manage complications


  • For patients with signs of increased ICP (posturing, change in breathing, bradycardia/hypertension, decreased mental status), immediate action is needed to reduce ICP.
  • Elevation of the head of the bed, mannitol or hypertonic saline, admission to intensive care unit, and ICP monitoring may be required.3,4,6,32 If these are ineffective, consult neurosurgery for decompressive hemicraniectomy.1,2,32-34

The patient does not show any signs of decompensation, though her pain is unchanged after the first several medications. You consider further, specific treatments for CVT.

After stabilization, the next step is consulting the neurology and hematology teams, along with admission to a stroke unit for monitoring. Specific therapy includes anticoagulation with heparin initially, followed by transition to warfarin.1-3,6,35 Over 50% of patients will experience hemorrhagic transformation, but this is not a contraindication to anticoagulation.2-4,36  The duration of treatment is 3-6 months if the CVT is provoked and 6-12 months if it is unprovoked.3,6 Thrombolysis, either systemic or catheter-directed, can be considered if anticoagulation fails.1,2,34,37,38

Supportive care includes addressing risk factors including cessation of oral contraceptive use, treating infection if present, and seizure prophylaxis.  If the patient seizes with an associated supratentorial lesion such as edema, hemorrhage, or infarction on imaging, then specific seizure treatment and prophylaxis are required.  If a seizure does not occur, seizure prophylaxis is not necessary.1,2,11,39  Further testing for underlying etiology is recommended, including thrombophilia.1,2,3,6 Follow up imaging at 3-6 months is required to assess for recanalization of the affected area.1-4,6

The patient undergoes testing for thrombophilia, which reveals factor V Leiden mutation. She is discharged on warfarin.


Mortality can reach up to 5.6% during an acute CVT, commonly due to herniation.1-3,6 Approximately 88% of patients experience complete recovery or experience only mild deficits.1-4,40 Headaches continue in up to half of patients.1,2,10,40 Recurrence is rare and occurs in only 3% of patients.40,41 Two thirds of patients achieve recanalization of the vasculature with treatment.3,6,42,43 Markers for poor long-term prognosis include malignancy or infection as the instigating event, associated intracranial hemorrhage, altered mental status on admission (particularly GCS < 9), male gender, age greater than 37 years, and deep venous system involvement.1-3,7,44

The patient undergoes repeat imaging at her six month visit, which reveals complete recanalization of the affected sinus. Her headaches are gone, and her warfarin is discontinued.


– CVT is a rare and difficult diagnosis to make due to a wide variety of signs and symptoms.

– Patients are commonly under 50 years of age.

– Scenarios warranting CVT investigation include headache that is atypical and persistent, stroke with no typical risk factors or in the setting of seizure, intracranial hypertension with no explanation, multiple hemorrhagic infarcts, hemorrhagic infarcts not in a specific arterial distribution, or objective neurologic symptoms in a patient with risk factors for CVT.

– Patients can present with four major syndromes, the most common of which is headache from intracranial hypertension.

– Do not rely on labs such as D-dimer for ruling out or ruling in. Imaging is required, including CT with venography or MRI/MRV.

– Treatment includes stabilizing immediate condition, anticoagulation, and managing underlying condition.

References/Further Reading:

  1. Piazza G. Cerebral venous thrombosis. Circulation 2012;125:1704-1709.
  2. Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. Cerebral venous thrombosis – A primer for the haematologist. Blood Reviews 2015;29:45–50.
  3. Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol 2007; 6:162-70.
  4. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791–8.
  5. Coutinho JM, Ferro JM, Canhao P, Barinagarrementeria F, Cantu C, Bousser MG, Stam J. Cerebral venous and sinus thrombosis in women. Stroke 2009;40:2356 –2361.
  6. Saposnik G, Barinagarrementeria F, Brown Jr RD, Bushnell CD, Cucchiara B, Cushman M, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:1158–92.
  7. Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F, Investigators I. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664–70.
  8. Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F, Massaro A, et al. Delay in the diagnosis of cerebral vein and dural sinus thrombosis: influence on outcome. Stroke 2009;40:3133–8.
  9. Tanislav C, Siekmann R, Sieweke N, Allendorfer J, Pabst W, Kaps M, Stolz E. Cerebral vein thrombosis: clinical manifestation and diagnosis. BMC Neurol 2011;11:69.
  10. Agostoni E. Headache in cerebral venous thrombosis. Neurol Sci 2004;25(Suppl 3):S206 –S210.
  11. Ferro JM, Canhao P, Bousser MG, Stam J, Barinagarrementeria F. Early seizures in cerebral vein and dural sinus thrombosis: risk factors and role of antiepileptics. Stroke 2008;39:1152–1158.
  12. Ferro JM, Canhao P, Bousser MG, Stam J, Barinagarrementeria F. Cerebral vein and dural sinus thrombosis in elderly patients. Stroke 2005;36:1927–1932.
  13. Schaller B, Graf R. Cerebral venous infarction: the pathophysiological concept. Cerebrovasc Dis 2004;18:179.
  14. Gotoh M, Ohmoto T, Kuyama H. Experimental study of venous circulatory disturbance by dural sinus occlusion. Acta Neurochir (Wien) 1993;124:120.
  15. Canhao P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F, et al. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005;36:1720–5.
  16. Crassard I, Soria C, Tzourio C, Woimant F, Drouet L, Ducros A, Bousser MG. A negative D-dimer assay does not rule out cerebral venous thrombosis: a series of seventy-three patients. Stroke 2005;36:1716 –1719.
  17. Kosinski CM, Mull M, Schwarz M, Koch B, Biniek R, Schlafer J, Milkereit E, Willmes K, Schiefer J. Do normal D-dimer levels reliably exclude cerebral sinus thrombosis? Stroke 2004;35:2820–2825.
  18. Edlow JA, Panagos PD, Godwin SA, Thomas TL, Decker WW. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Headache. Ann Emerg Med 2008 Oct;52(4):407-430.
  19. Virapongse C, Cazenave C, Quisling R, et al. The empty delta sign: frequency and significance in 76 cases of dural sinus thrombosis. Radiology 1987;162:779.
  20. Lee EJ. The empty delta sign. Radiology 2002;224:788.
  21. Boukobza M, Crassard I, Bousser MG. When the “dense triangle” in dural sinus thrombosis is round. Neurology 2007; 69:808.
  22. Khandelwal N, Agarwal A, Kochhar R, Bapuraj JR, Singh P, Prabhakar S, Suri S. Comparison of CT venography with MR venography in cerebral sinovenous thrombosis. AJR Am J Roentgenol 2006;187:1637–1643.
  23. Chu K, Kang DW, Yoon BW, Roh JK. Diffusion-weighted magnetic resonance in cerebral venous thrombosis. Arch Neurol 2001;58:1569–76.
  24. Dormont D, Anxionnat R, Evrard S, Louaille C, Chiras J,    Marsault C. MRI in cerebral venous thrombosis. J Neuroradiol 1994;21:81–99.
  25. Lafitte F, Boukobza M, Guichard JP, Hoeffel C, Reizine D, Ille O, et al. MRI and MRA for diagnosis and follow-up of cerebral venous thrombosis (CVT). Clin Radiol 1997;52:672–9.
  26. Selim M, Fink J, Linfante I, Kumar S, Schlaug G, Caplan LR. Diagnosis of cerebral venous thrombosis with echo-planar T2-weighted magnetic resonance imaging. Arch Neurol 2002;59:1021–6.
  27. Leach JL, Fortuna RB, Jones BV, Gaskill-Shipley MF. Imaging of cerebral venous thrombosis: current techniques, spectrum of findings, and diagnostic pitfalls. Radiographics 2006;26(Suppl. 1):S19–41 [discussion S42-13].
  28. Meckel S, Reisinger C, Bremerich J, Damm D, Wolbers M, Engelter S, et al. Cerebral venous thrombosis: diagnostic accuracy of combined, dynamic and static, contrast-enhanced 4D MR venography. AJNR Am J Neuroradiol 2010;31:527–35.
  29. Linn J, Ertl-Wagner B, Seelos KC, Strupp M, Reiser M, Bruckmann H, Bruning R. Diagnostic value of multidetector-row CT angiography in the evaluation of thrombosis of the cerebral venous sinuses. AJNR Am J Neuroradiol. 2007;28:946 –952.
  30. Ayanzen RH, Bird CR, Keller PJ, McCully FJ, Theobald MR, Heiserman JE. Cerebral MR 
venography: normal anatomy and potential diagnostic pitfalls. AJNR Am J Neuroradiol 2000;21:74–8.
  31. Zouaoui A, Hidden G. Cerebral venous sinuses: anatomical variants or thrombosis? Acta Anat 1988;133:318–24.
  32. Bullock, R, Clifton G. Guidelines for the Management of Severe Brain Injury, Brain trauma foundation/American Association of Neurologic Surgeons, New York 1995.
  33. Stefini R, Latronico N, Cornali C, Rasulo F, Bollati A. Emergent decompressive craniectomy in patients with fixed dilated pupils due to cerebral venous and dural sinus thrombosis: report of three cases. Neurosurgery 1999;45(3):626–9.
  34. Ferro JM, Crassard I, Coutinho JM, Canhao P, Barinagarrementeria F, Cucchiara B, Derex L, Lichy C, Masjuan J, Massaro A, Matamala G, Poli S, Saadatnia M, Stolz E, Viana-Baptista M, Stam J, Bousser MG. Decompressive surgery in cerebrovenous thrombosis: a multicenter registry and a systematic review of individual patient data. Stroke. 2011;42:2825–2831.
  35. Stam J, De Bruijn SF, DeVeber G. Anticoagulation for cerebral sinus thrombosis. Cochrane Database Syst Rev. 2002: CD002005.
  36. Tait C, Baglin T, Watson H, Laffan M, Makris M, Perry D, et al. Guidelines on the investigation and management of venous thrombosis at unusual sites. Br J Haematol 2012;159:28–38.
  37. Canhao P, Falcao F, Ferro JM. Thrombolytics for cerebral sinus thrombosis: a systematic review. Cerebrovasc Dis 2003;15:159 –166.
  38. Dentali F, Squizzato A, Gianni M, De Lodovici ML, Venco A, Paciaroni M, Crowther M, Ageno W. Safety of thrombolysis in cerebral venous thrombosis: a systematic review of the literature. Thromb Haemost 2010;104:1055–1062.
  39. Masuhr F, Busch M, Amberger N, Ortwein H, Weih M, Neumann K, et al. Risk and predictors of early epileptic seizures in acute cerebral venous and sinus thrombosis. Eur J Neurol 2006;13:852–6.
  40. Dentali F, Gianni M, Crowther MA, Ageno W. Natural history of cerebral vein thrombosis: a systematic review. Blood 2006;108:1129 –1134.
  41. Martinelli I, Bucciarelli P, et al. Long-term evaluation of the risk of recurrence after cerebral ainu-venous thrombosis. Circulation 2010;121:2740.
  42. Baumgartner RW, et al. Recanalisation of cerebral venous thrombosis. J Neurol Neurosurg Psychiatry 2003;74:459.
  43. Arauz A, et al. Time to recanalisation in patients with cerebral venous thrombosis under anticoagulation therapy. J Neurol Neursurg Psychiatry 2016;87:247.
  44. Ferro J, et al. External validation of a prognostic model of cerebral vein and dural sinus thrombosis. Cerebrovasc Dis 2005;19(Suppl 2):154.