UMEM Educational Pearls - By WanTsu Wendy Chang

Category: Neurology

Title: Gadolinium - To Use or Not Use?

Keywords: MRA, MRV, non-contrast, contrast-enhanced, gadolinium, time-of-flight, TOF (PubMed Search)

Posted: 6/8/2016 by WanTsu Wendy Chang, MD
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Gadolinium - To Use or Not Use?

  • One advantage of MR imaging is the option between non-contrast vs. contrast-enhanced MR angiography (MRA) and venography (MRV)
  • How do they work and when should you use which?

Non-Contrast MRA/MRV Contrast-Enhanced MRA/MRV
How Does It Work?

* Time-of-flight (TOF) is a commonly used sequence

* Relies on flow of blood into imaging plane

* Difference between signal of blood and suppressed background tissue

* Similar to CT angiography/venography

* Higher intravascular signal purely from gadolinium-based contrast, not dependent on flow


* Does not require contrast

* Generally better image quality

* Shorter acquisition time


* Slow, turbulent, or retrograde flow may result in signal loss

* Over-estimates stenosis

* Longer acquisition time

* RIsks associated with contrast use

* Timing of image acquisition important


* Patients with allergy to gadolinium, renal dysfunction, pregnancy

* Evaluation of intracranial vessels and cerebral venous system

* Evaluation of stenoses and occlusions of the neck vessels and their origins at the aortic arch

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Category: Neurology

Title: Shades of Gray Matter - Brain MRI 101

Keywords: magnetic resonance imaging, MRI, T1, T2, FLAIR, DWI, ADC (PubMed Search)

Posted: 5/11/2016 by WanTsu Wendy Chang, MD
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Shades of Gray Matter - Brain MRI 101

Want to learn more about how to read a brain MRI?  Here are the basics:

  • MRIs are described by signal intensity, as compared to CTs where lesions are described by density.
    • A dark lesion on MRI is “hypointense”
    • A bright lesion on MRI is “hyperintense"
  • The most commonly used MRI sequences are T1-weighted, T2-weighted, FLAIR, and Diffusion-weighted.
    • T1-weighted images are good for brain parenchyma.
      • Contrast enhanced T1 with gadolinium helps differentiate pathological tissue (e.g. tumors, inflammation, infection)
    • T2-weighted images are good for CSF spaces and periventricular white matter.
      • Edema from a tumor, subacute stroke or hemorrhage appears bright
      • Periventricular white matter scarring from multiple sclerosis appears bright
    • FLAIR images are T2 images where CSF is dark.  FLAIR is very sensitive to edema and parenchymal lesions.
    • Diffusion-weighted sequences are good for cellular swelling.
      • Acute ischemia appears bright on Diffusion-Weighted Imaging (DWI) and dark on Apparent Diffusion Coefficient (ADC) maps
      • Some neoplasms, abscesses and toxic/metabolic/demyelinating processes can also appear bright on DWI.

Stay tuned for more pearls in this series on brain MRI!

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Category: Neurology

Title: What Do You Mean By Dizzy?

Keywords: dizzy, dizzinesss, acute vestibular syndrome, triggered episodic vestibular syndrome, spontaneous episodic vestibular syndrome, HINTS, Dix-Hallpike (PubMed Search)

Posted: 4/13/2016 by WanTsu Wendy Chang, MD
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What Do You Mean By Dizzy?

  • Patients with dizziness account for 3% of ED visits.
  • The traditional approach based on symptom quality (i.e. “What do you mean by dizzy”) is not reliable.
  • Drs. Edlow and Newman-Toker propose a new paradigm based on the timing and triggers of dizziness.
  • Acute vestibular syndrome begins abruptly or rapidly and continues for days.  Patients’ dizziness may be exacerbated by movement but is not triggered by movement.
  • Triggered episodic vestibular syndrome are repetitive episodes of dizziness triggered by some event.  Patients will be completed asymptomatic at rest and will develop dizziness that is reliably triggered by a specific event or postural shift.
  • Spontaneous episodic vestibular syndrome are multiple episodes of dizziness that occur without any clear identifiable trigger.  Patients are asymptomatic between episodes.


Table 1 shows common benign and serious causes of these vestibular syndromes.


Utilizing the HINTS battery or the Dix-Hallpike maneuver, a “safe to go” algorithm for acute vestibular syndrome and triggered episodic vestibular syndrome is outlined in Figure 2.


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Category: Neurology

Title: Sunset Eye Sign

Keywords: Up-gaze paresis, ophthalmoparesis, hydrocephalus, shunt malfunction (PubMed Search)

Posted: 3/9/2016 by WanTsu Wendy Chang, MD
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Sunset Eye Sign

  • The "sunset eye sign" can be seen in patients with increased intracranial pressure related to obstructive hydrocephalus or shunt malfunction.
  • It describes an up-gaze paresis caused by compression of the dorsal midbrain.
  • The lower portion of the pupil may be covered by the lower eyelid, appearing like a setting sun.

Category: Neurology

Title: Cerebral Venous Thrombosis - To Scan Or Magnetize?

Keywords: cerebral venous thrombosis, CVT, venography, CTV, MRV (PubMed Search)

Posted: 2/10/2016 by WanTsu Wendy Chang, MD
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Cerebral Venous Thrombosis - To Scan Or Magnetize?
  • Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening disease.
  • Mortality in CVT is largely attributed to herniation.
  • The diagnosis of CVT is made on the basis of clinical presentation and imaging studies.
  • When you are concerned about CVT in a patient, which neuroimaging modality should you obtain?  CT or MRI?
  • Non-contrast CT
    • Often the first neuroimaging obtained as it can evaluate for other processes such as cerebral infarct, intracranial hemorrhage, and cerebral edema.
    • Dense delta sign, dense clot sign and cord sign all refer to hyperattenuation of the clot. 
    • However, these findings are only seen in 20-25% of cases and disappear within 1-2 weeks.
  • MRI
    • Clot appears hyperintense in the subacute phase.
    • In the acute phase, clot can mimic normal venous flow signal and result in potential diagnostic error.
  • CT venography
    • Detailed depiction of cerebral venous system.
    • Timing of contrast bolus affect quality of evaluation.
    • Reconstruction may be difficult to subtract all of the adjacent bone.
  • MR venography (MRV)
    • Unenhanced time-of-flight (TOF) MR venography has excellent sensitivity to slow flow.  It is useful in detection of large occlusions (e.g. jugular venous thrombosis), but susceptible to flow artifacts.
    • Contrast enhanced MR venography improves visualization of small vessels, thus preferred to TOF MR venography.

Bottom Line:  CT venography is good for diagnosing CVT, but MRI/MRV is superior for detection of isolated cortical venous thromboses and assessing parenchymal damage.

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Category: Neurology

Title: Should We Provide Psychiatric Evaluation for Patients After Traumatic Brain Injury?

Keywords: Traumatic brain injury, psychiatric disorders, anxiety, depression (PubMed Search)

Posted: 1/13/2016 by WanTsu Wendy Chang, MD
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Should We Provide Psychiatric Evaluation for Patients After Traumatic Brain Injury?
  • A recent systematic review looked at the prevalence of psychiatric disorders such as anxiety and depressive disorders in patients with traumatic brain injury (TBI).
  • They found a substantial number of patients had a history of anxiety disorders (19%) or depressive disorders (13%) prior to their TBI.
  • In the first year after TBI, pooled prevalence of anxiety and depressive disorders increased to 21% and 17%.
  • Prevalence continued to increase over time, with longterm prevalence of anxiety and depressive disorders of 36% and 43%.
  • Females, those without employment, and those with a history of psychiatric disorders or substance abuse prior to TBI were at higher risk for anxiety or depressive disorders following TBI.


Bottom Line: 

  • Early recognition and treatment of psychiatric disorders in patients after TBI may improve their outcome, psychosocial functioning and health-related quality of life. 
  • Thus we should consider providing appropriate discharge instructions that include psychiatric resources for patients after TBI.

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Should We Use a Modified NIH Stroke Scale?
  • The NIH Stroke Scale (NIHSS) is a widely used scale in assessing neurological deficits in stroke patients.
  • It is a useful communication tool and is accurate in predicting clinical outcomes.
  • However, it has been critiqued for its complexity and potential poor interrater reliability of certain items within the scale.
  • Prior studies have suggested modifying or shortening the scale to 11, 8 or 5 items for use in stroke clinical trials or the prehospital setting.1,2,3


A recent study compared the original NIHSS with the shortened 11, 8, and 5 item versions.4

  • They found the original NIHSS has higher discriminatory value and responsiveness to change as well as improved ability to predict clinical outcomes than shortened versions.


Bottom Line: The original 15-item NIHSS should still be used to evaluate patients’ stroke severity.

The reliability of the NIHSS has been found to improve with personal and videotaped training.

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Category: Neurology

Title: Serotonin Syndrome (Part 3) - How to Treat It?

Keywords: serotonin syndrome, SSRI, cyproheptadine (PubMed Search)

Posted: 11/11/2015 by WanTsu Wendy Chang, MD (Emailed: 11/12/2015) (Updated: 11/12/2015)
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Last month we discussed causes of serotonin syndrome including common ED medications such as cyclobenzaprine (Flexeril), tramadol (Ultram), metoclopramide (Reglan), and ondansetron (Zofran).


Let’s conclude this series and discuss how to treat serotonin syndrome:

  • Treatment of serotonin syndrome is mainly supportive.
  • Discontinuation of all serotonergic agents is crucial, and may be all that's needed in mild cases.
  • In moderate to severe cases, use benzodiazepines and titrate to patient sedation and normalization of vital signs.
    • Avoid droperidol and haloperidol due to their anticholinergic properties that inhibit sweating and dissipation of body heat.
    • Caution if using antipsychotics as neuroleptic malignant syndrome can be misdiagnosed as serotonin syndrome.
  • Severely intoxicated patients may exhibit autonomic instability with large and rapid changes in blood pressure and heart rate.
    • This should be managed with short-acting agents, such as esmolol or nicardipine.  
  • Aggressive control of hyperthermia associated with serotonin syndrome can potentially minimize severe complications such as seizures, coma, DIC, and metabolic acidosis.
    • There is a limited role for antipyretics as the mechanism is due to muscle tone rather than central thermoregulation.
    • In cases of uncontrollable hyperthermia, intubation and paralytics may be required.
  • Cyproheptadine is an antihistamine with anti-serotonergic properties that should be used if no significant response to supportive measures.
    • Adult dosing is 12 mg PO followed by 2 mg every 2 hours if symptomatic. Max 32 mg in 24 hours.
  • A case series reported the use of dexmedetomidine for the treatment of refractory serotonin syndrome.

This concludes our 3-part series on serotonin syndrome!

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Category: Neurology

Title: Serotonin Syndrome (Part 2) - What Causes It?

Keywords: serotonin syndrome, SSRI, SNRI, MAOI, TCA (PubMed Search)

Posted: 10/14/2015 by WanTsu Wendy Chang, MD
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Last month we discussed symptoms of serotonin syndrome and its diagnosis by the Hunter Criteria. Let's move on to what causes serotonin syndrome.

Serotonin Syndrome - What Causes It?

  • Serotonin syndrome is not an idiopathic drug reaction, but the result of excess serotonin in the nervous system.
  • It is classically associated with adminstration of two serotonergic agents, but it can occur after initiation of a single agent or increasing the dose of a serotonergic agent in individuals who are particularly sensitive to serotonin.
  • Although selective serotonin reuptake inhibitors (SSRIs) are most commonly implicated, there are other medications encountered in the Emergency Department that can also play a role in serotonin syndrome.


  • There are also reports of serotonin syndrome occuring with methadone, trazodone, and metaxalone (Skelaxin).
  • Serotonin syndrome is often under-recognized if the symptoms are not severe.  Thus a thorough medication history is important in its purely clinical diagnosis.


** Stay tuned for the conclusion on management of serotonin syndrome **

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Category: Neurology

Title: Serotonin Syndrome (Part 1) - What is It?

Keywords: serotonin syndrome, SSRI, autonomic hyperactivity, hyperreflexia, clonus, Hunter Criteria (PubMed Search)

Posted: 9/9/2015 by WanTsu Wendy Chang, MD
Click here to contact WanTsu Wendy Chang, MD


Serotonin Syndrome - What is It?

  • Potentially life-threatening condition associated with increased serotonergic activity in the CNS.
  • Selective serotonin reuptake inhibitors (SSRIs) are the most commonly implicated class of medications.  However, other medications can also be involved.
  • It is a clinical diagnosis!
  • Classic triad: mental status change, autonomic hyperactivity, and neuromuscular abnormalities
    • Mental status change - anxiety, agitation, restlessness, disorientation
    • Autonomic hyperactivity - diaphoresis, tachycardia, hypertension, hyperthermia, nausea, vomiting, diarrhea
    • Neuromuscular abnormalities - tremor, muscle rigidity, myoclonus, hyperreflexia, clonus, Babinski sign (abnormal plantar reflex)
  • Hunter Criteria is the most accurate diagnostic rule:
    • Serotonergic agent + one of the following:
      • Spontaneous clonus
      • Inducible clonus + agitation or diaphoresis
      • Ocular clonus + agitation or diaphoresis
      • Tremor + hyperreflexia
      • Hypertonia + temperature above 38C + ocular clonus or inducible clonus
  • Majority of cases present within 24 hours, most within 6 hours, of a change in dose or initiation of a medication.


** Stay tuned for part 2 on what causes serotonin syndrome **


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Category: Neurology

Title: Neuroimaging Tip - Loss of the Insular Ribbon Sign

Keywords: insular ribbon sign, MCA stroke, early CT sign of stroke (PubMed Search)

Posted: 8/12/2015 by WanTsu Wendy Chang, MD (Updated: 10/14/2015)
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Neuroimaging Tip - Loss of the Insular Ribbon Sign

  • Loss of the insular ribbon sign refers to loss of the gray-white differentiation of the insular cortex.
  • This is an early sign of middle cerebral artery (MCA) stroke.
  • The insular cortex has less collateral blood supply from the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) than other portions of the MCA territory; thus making it more susceptible to ischemia.



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Category: Neurology

Title: Cerebrospinal Fluid (CSF) Shunts

Keywords: CSF shunts, VP shunt, VA shunt, LP shunt (PubMed Search)

Posted: 7/8/2015 by WanTsu Wendy Chang, MD
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Cerebrospinal Fluid (CSF) Shunts

  • CSF shunts are used to manage hydrocephalus by diverting CSF from either the ventricles within the brain or the subarachnoid space around the spinal cord to another body region. (Figure 1)
  • Several types of CSF shunts exist; common types are:
    • Ventriculoperitoneal shunt
    • Ventriculoatrial shunt
    • Ventriculopleural shunt
    • Lumboperitoneal shunt
  • A CSF shunt consists of 3 parts:
    • An inflow catheter directly draining CSF.
    • A one-way valve mechanism regulating the amount of CSF drainage.
    • An outflow catheter directing CSF to the drainage site.
  • There are 2 types of valve mechanisms:
    • Fixed pressure valves regulate CSF drainage by a predetermined pressure threshold (i.e. low, medium, high).
    • Adjustable pressure valves can be non-invasively adjusted, via specially designed magnetic tools, to set the pressure threshold.
    • Some valves include a reservoir that can be used to test shunt function or to sample CSF for laboratory studies. (Figure 2)
  • Shunt-related complications include:
    • Shunt malfunction (disconnection, migration, breaks, obstruction)
    • Shunt infection / ventriculitis / meningitis
    • Over-drainage
  • A special consideration for adjustable pressure valves is precaution around magnetic devices.  If a patient is undergoing a MRI, it is recommended for the valve setting to be checked and adjusted afterwards if necessary.

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Category: Neurology

Title: What is the ICH Score?

Keywords: Guidelines, intracerebral hemorrhage, ICH score, communication (PubMed Search)

Posted: 6/10/2015 by WanTsu Wendy Chang, MD (Updated: 10/14/2015)
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What is the ICH Score?

  • The most recent AHA/ASA guideline for spontaneous intracerebral hemorrhage (ICH) recommends the use of a clinical severity score for communication.
  • While the NIHSS is used for ischemic stroke, its utility may be limited in ICH due to commonly depressed mental status.
  • The ICH Score is the most widely used and externally validated risk stratification scale:


Take Home Point:  Communicate the severity of your ICH patient by using either the composite ICH Score or by including details such as the patient's GCS, estimated volume of ICH, presence of IVH, and supra- vs. infratentorial origin.

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Category: Neurology

Title: Are We Using the Glasgow Coma Scale Reliably?

Keywords: Glasgow Coma Scale, GCS, traumatic brain injury, TBI, survey (PubMed Search)

Posted: 5/13/2015 by WanTsu Wendy Chang, MD
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Are We Using the Glasgow Coma Scale Reliably?

  • The Glasgow Coma Scale (GCS), first described in 1974, has been a tool used worldwide to assess and communicate the consciousness of patients with traumatic brain injury (TBI).
  • There have been reports of variations in which GCS is assessed, such as differences in technique used to elicit pain and how confounding factors such as intubation are reported.
  • Reith et al. conducted an international survey of 613 health care practitioners on their methodology of GCS assessment, reporting of GCS, and attitudes toward its current use in daily practice.
    • Participants included nurses, intensivists, anesthesiologists, emergency physicians, and neurosurgeons
  • Some variations in applications, methodology, and reporting from the survey include:
  Reported by Responders
Patient population in which GCS is used
Traumatic brain injury (96%)
Other neurological disorders (78%)
Intended purpose of GCS
Classification of severity of injury (51%)
Serial evaluation of patient over time (33%)
Clinical decision making (44%)
Prognostication (17%)
Application of stimulus
Both arms and legs (62%)
Only arms (37%)
Type of stimuli used
Nail bed pressure (57%)
Lateral side of finger (22%)
Supra-orbital nerve pressure (52%)
Trapezius or pectoralis pinch (50%)
Sternal rub (53%)
Retromandibular stimulation (24%)
Earlobe stimulation (16%)
Reporting of GCS
Description in words, e.g. no eye opening, no motor (19%)
Numerical report, e.g. E1V1M1 (46%)
Sum score, e.g. EVM=3 (35%)
  • This survey suggests that there is a lack of standardization of GCS assessment and reporting which affects its reliability as an assessment and communication tool
  • A free educational tool has been developed ( to provide a standardized approach to the use of GCS


Bottom line: There are variations in the application, assessment, and reporting of the GCS.  A standardized approach is needed for it to be a reliable assessment and communication tool.


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Category: Neurology

Title: Prognostication in intracerebral hemorrhage - A self-fulfilling prophecy?

Keywords: Intracerebral hemorrhage, ICH score, prognostication, early decisions to limit medical treatment (PubMed Search)

Posted: 4/8/2015 by WanTsu Wendy Chang, MD (Updated: 10/14/2015)
Click here to contact WanTsu Wendy Chang, MD


Prognostication in intracerebral hemorrhage - A self-fulfilling prophecy?


The ICH Score is a validated outcome prediction model for intracerebral hemorrhage (ICH) developed from clinical and neuroimaging characteristics on presentation.


While predictive models are often used in clinical care for prognostication, is it a self-fulfilling prophecy to make early decisions to limit medical treatments based on these models?


Morgenstern et al. conducted an observational study across 5 hospitals looking at 30-day mortality of patients with ICH with initial GCS <12 who received full medical care for at least 5-days following symptom onset.

  • 417/972 (42.9%) of patients had GCS < 12
  • 148/417 (35.5%) of patients were made DNR by family or physician before day 5
  • 109/417 (26.1%) of patients were included in the study
  • Overall observed 30-day mortality was 20.2%, which was 29.8% less than the ICH Score-predicted mortality
  • Each increase in the ICH Score was associated with both an increase in predicted and observed 30-day mortality 


Take Home Point: The ICH Score is a useful tool for stratifying patient severity, but one should be cautious in using the model to provide specific numerical values as outcome predictions.


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Category: Neurology

Title: Neurologic causes of cardiac arrest

Keywords: cardiac arrest, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, seizure (PubMed Search)

Posted: 2/25/2015 by WanTsu Wendy Chang, MD
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Neurologic causes of cardiac arrest have not been well described.  Two recent retrospective studies looked at the epidemiology and clinical features of these patients.

Hubner P. et al.

  • Over 20 years, 154 patients suffered cardiac arrest from neurologic causes.
  • Diagnoses were made by CT in 123 patients (80%), autopsy in 28 patients (18%), and by history and clinical presentation in 4 patients (3%).
  • PEA was the presenting rhythm in 77 patients (50%).  Whereas 61 patients (40%) presented in asystole.
  • Neurologic causes included subarachnoid hemorrhage in 74 patients (48%), intracerebral hemorrhage in 33 patients (21%), seizures in 23 patients (15%), and ischemic stroke in 11 patients (7%).

Arnaout M. et al.

  • Over 13 years, 86 patients suffered out-of-hospital cardiac arrest from neurologic causes (2.3%).
  • PEA was the presenting rhythm in 16 patients (19%).  Whereas 66 patients (77%) presented in asystole.
  • After ROSC, 64% of cases had ECGs with possible ischemic abnormalities.
  • Neurologic causes included subarachnoid hemorrhage in 73 patients (85%), intracerebral hemorrage in 5 patients (6%), ischemic strokes in 5 patients (6%).

Neurologic causes of cardiac arrest are uncommon presentations that may be difficult to distinguish from cardiac etiology of cardiac arrest.  If history and clinical presentation suggests a neurologic cause, obtain a non-contrast head CT for evaluation.

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Category: Neurology

Title: Magnesium, another failed neuroprotectant?

Keywords: acute ischemic stroke, magnesium, neuroprotectant, IMAGES, FAST-MAG (PubMed Search)

Posted: 2/12/2015 by WanTsu Wendy Chang, MD
Click here to contact WanTsu Wendy Chang, MD


Magnesium, another failed neuroprotectant?

Stroke is a leading cause of adult disability and the second leading cause of death worldwide.  Currently available therapies for acute ischemic stroke are based on restoring perfusion to the ischemic penumbra. However, they are only moderately effective.

A series of pathological cascades leading to neuronal death are triggered in acute ischemia.  Thus it may be logical to suggest that if one can interrupt the propagation of these cascades, perhaps part of the brain tissue can be protected and salvaged.

Magnesium has been shown in various animal models to have pluripotent neuroprotective properties.  It is also widely available, simple to administer, and has a favorable risk profile.  A prior study of magnesium in acute ischemic stroke (IMAGES) did not show a benefit when the agent was administered a median 7.4 hours after symptom onset.  However, a subgroup of patients treated within 3 hours of symptom onset showed possible benefit.


The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) trial, funded by the NIH, looked at magnesium administered within 2 hours after symptom onset on the degree of disability at 90 days after stroke as measured by the modified Rankin scale.

  • A total of 1700 patients were included in the study.
  • 73.3% of patients had a final diagnosis of ischemic stroke, compared with 22.8% with intracranial hemorrhage and 3.9% with stroke-mimicking condition.
  • Of the patients with ischemic stroke, 52.4% were treated with tPA.

Magnesium was not found to have any benefit in functional outcome at 90 days.


This study was unique in several ways:

  • It examined the use of a neuroprotective agent in the hyperacute window of 2 hours, as a common criticism of prior neuroprotective studies is that those agents may not have been administered within the optimal therapeutic window
  • Administration of the neuroprotective agent began in the prehospital setting.  Logistically, this was done with a pre-randomized study kit containing the initial bolus dose to be administered by EMS and the maintenance dose to be given to the receiving hospital for administration in the ED.
  • Despite the short window for enrollment and drug administration, patients were screened using a previously validated prehospital stroke scale and 98.7% of patients were enrolled after explicit written informed consent from the patient or a legally authorized representative.

However, despite this study being very well executed, demonstrating the feasibility of conducting a phase 3 trial with targeted intervention within the hyperacute window, it is another neuroprotective agent that failed to translate from the laboratory bench to the clinical realm.

Potential explanations for the discrepancies between preclinical and clinical outcomes of neuroprotective agents thus far include discrepancies on outcome measures, functional assessments, pre-morbid conditions, therapeutic windows, and drug-dosing schedules between animal studies and clinical trials.


Take Home Point: Magnesium does not have any clear benefit in acute ischemic stroke at this time.

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Category: Neurology

Title: Is progesterone yet another disappointing neuroprotectant?

Keywords: traumatic brain injury, progesterone, neuroprotectant, clinical trials, PROTECT III, SYNAPSE (PubMed Search)

Posted: 1/14/2015 by WanTsu Wendy Chang, MD
Click here to contact WanTsu Wendy Chang, MD


Is progesterone yet another disappointing neuroprotectant?

Traumatic brain injury (TBI) affects more than 1.7 million persons in the U.S. annually.  The incidence of TBI is increasing globally, especially in developing countries.  Despite improvement in trauma systems and critical care, the morbidity and mortality associated with severe TBI remain high.

Progesterone has been shown in preclinical and phase 2 randomized clinical trials to have pluripotent neuroprotective properties and improve mortality in TBI.


Two multicenter phase 3 trials were recently completed and published in the December 25th issue of the New England Journal of Medicine.  However, their results were disappointing.

  • The Progesterone for the Treatment of Traumatic Brain Injury (PROTECT III) trial, funded by the NIH, looked at progesterone administered within 4 hours after injury in patients with moderate to severe TBI.
  • The Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SYNAPSE) trial, funded by BHR Pharma, looked at progesterone administered within 8 hours after injury in patients with severe TBI.

Both studies used the Glasgow Outcome Scale (GOS) or Extended Glasgow Outcome Scale (GOS-E) at 6 months as their primary outcome.  The GOS and GOS-E capture the degree of recovery from brain injury in terms of disability, stratified into levels by death, vegetative state, severe disability, moderate disability, and good recovery.

Progesterone was not found to have any benefit in functional outcome at 6 months.


Both of these studies were well designed and conducted.  However, they were based on small effect sizes of the phase 2 trials.  In addition, they had very favorable outcome rates in the placebo group, thereby making it hard to demonstrate a benefit by their sample sizes.

There has been a long history of failed neuroprotectant trials likely due to the complex and variable injury mechanisms involved in TBI.  The currently available outcome measures are also insensitive to the targeted mechanistic endpoints.  More research is needed to understand not only potential therapies but also how to select appropriate patients for these therapies.


Take Home Point:  Progesterone does not have any clear benefit in TBI at this time.


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Category: Neurology

Title: Can we decrease CT utilization in mild TBI?

Keywords: clinical decision support, clinical decision rules, head CT, mild traumatic brain injury (PubMed Search)

Posted: 12/10/2014 by WanTsu Wendy Chang, MD
Click here to contact WanTsu Wendy Chang, MD

Does clinical decision support help reduce head CT utilization in mild traumatic brain injury related ED visits?

  • Mild traumatic brain injury (mTBI) account for approximately 1.2 million outpatient visits per year
  • Almost 1 million of these mTBI patients undergo head CT as part of their evaluation
  • Less than 6% have significant intracranial injuries that require neurosurgical intervention

Are we utilizing clinical decision rules adequately to help us appropriately select patients for CT imaging?

Can clinical decision support (CDS) help us reduce head CT utilization in mTBI related ED visits?

  • A recent study by Ip et al. reported on the use of a real-time computerized CDS in an EMR/CPOE system to provide feedback to an ordering provider on "low utility" CT's based on clinical decision rules (New Orleans Criteria, Canadian CT Head Rule, CT in Head Injury Patients Prediction Rule)
  • Over a 2 year period, 1221 of 1988 (64%) of mTBI related ED visits were associated with a head CT being performed
  • A 13.4% decrease in CT utilization was seen in the CDS intervention group (58.1% pre- vs. 50.3% post-, p=0.005)
  • A control cohort using the National Hospital Ambulatory Medical Care Survey (NHAMCS) as a representative of emergency medical care delivered in the U.S. showed no significant change in CT utilization in the same time period (73.3% pre- vs. 76.9% post-, p=0.272)

Take Home Point:

Clinical decision support may be a useful tool to help reduce CT utilization in mild TBI related ED visits.

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Category: Neurology

Title: Evaluation of anisocoria

Keywords: anisocoria, Horner syndrome, third nerve palsy, tonic pupil (PubMed Search)

Posted: 11/12/2014 by WanTsu Wendy Chang, MD
Click here to contact WanTsu Wendy Chang, MD


Anisocoria, or unequal pupil sizes, is a common condition.  Approximately 20% of the normal population have physiologic anisocoria.  However, pathologic anisocoria indicates disease of the iris, parasympathetic pathway or sympathetic pathway.  A systematic approach to the evaluation of anisocoria can help differentiate between etiologies that range from benign to life threatening.


The most important question in the evaluation of anisocoria is whether both pupils are normally reactive to light or is one (or both) poorly reactive.  If both pupils are reactive, the smaller pupil is abnormal and the lesion is likely in the sympathetic pathway because pupillary constriction (parasympathetic pathway) is intact.  If one pupil is poorly or non-reactive (and there is no relative afferent pupillary defect), the larger pupil is abnormal and the lesion is likely in the parasympathetic pathway.



DDx of anisocoria with normally reactive pupils:

  • Physiologic anisocoria
  • Horner syndrome

DDx of anisocoria with poorly or non-reactive pupil:

  • Iris sphincter damage (traumatic mydriasis)
  • Pharmacologic blockade
  • Tonic pupil
  • Cranial nerve III palsy

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