Podcast: Play in new window | Download

Subscribe: RSS

Date: April 7th, 2022

Reference: Wong et al. Sensitivity of diffusion-weighted magnetic resonance imaging in transient global amnesia as a function of time from symptom onset. AEM April 2022

Guest Skeptic: Dr. Chris Bond is an emergency medicine physician and assistant Professor at the University of Calgary.

Case: A 65-year-old man presents to your emergency department with his wife. She tells you that he woke up normally this morning, but after breakfast he began asking the same questions repetitively and was amnestic to the answer, seemingly unable to form new memories. He remained completely awake and alert and otherwise appeared well.  There was no history of recent trauma, infectious symptoms, or any other illness. 

Background: Transient global amnesia (TGA) is an idiopathic acute neurological disorder that presents with sudden onset anterograde memory loss. It was first described as a syndrome in 1956 by Courjon and Guyotat and also by Bender [1,2].  Fisher and Adams formally described as TGA in 1964 [3].

The usual presentation is a patient between 50 and 70 years of age who are cognitively and neurologically intact but asking repetitive questions, unable to form new memory. Symptoms do not last very long and resolve within 24 hours. The incidence has been reported as 23.5 per 100,000 people per year [4] and is more common in people who get migraine headaches [5].

TGA is often precipitated by physical or emotional stressors, pain, the Valsalva maneuver, hot or cold-water immersion or sexual intercourse [6] Diagnosing TGA combines items put forward by Hodges and Warlow and Caplan [7-9]. This results in seven diagnostic criteria for TGA.

Diagnostic Criteria for Transient Global Amnesia

  1. Attack is witnessed
  2. Clear-cut anterograde amnesia during the attack
  3. No neurologic symptoms or signs during the attack other than amnesia (no clouding of consciousness or loss of personal identity)
  4. No neurologic physical examination findings others than anterograde amnesia
  5. Memory loss is transient (resolution within 24 h)
  6. No epileptic features and no active epilepsy (defined as no seizure within 2 years or on antiepileptic medication)
  7. No recent head injury

A diagnostic algorithm has been published for patients with sudden onset of anterograde amnesia [6]. Included in this differential is transient epileptic amnesia, transient ischemic attack, stroke, metabolic disorders, psychogenic disorders, and post traumatic amnesia. The workup can include laboratory testing, EEGs, ECGs, echocardiogram and advanced neuroimaging.

Clinical Question: What is the sensitivity of diffusion-weighted magnetic resonance imaging (DW-MRI) as a function of time from symptom onset compared to clinical diagnosis of TGA?

Reference: Wong et al. Sensitivity of diffusion-weighted magnetic resonance imaging in transient global amnesia as a function of time from symptom onset. AEM April 2022

  • Population: Adult patients 16 years of age and older with a diagnosis of TGA based on the existing clinical criteria
  • Intervention: Evaluation with DW-MRI at varying time intervals post symptom onset
  • Comparison: No comparison as no studies of patients without DW-MRI were included
  • Outcome: Sensitivity of DW-MRI in diagnosis of TGA

Dr. Matt Wong

This is a back-to-back SGEMHOP episode. We did the March episode at the end of last month and the April episode is the first week of this month.

We are pleased to have the lead author on the show. Dr. Matthew Wong is an emergency physician and educator at Beth Israel Deaconess Medical Center, and an Assistant Professor at Harvard Medical School.

Authors’ Conclusions: “DW-MRI lesions are uncommon in patients with TGA early after symptom onset, but the sensitivity (i.e., positivity rate) of DW-MRI increases with time. Despite the limited quality of existing evidence, obtaining an early DW-MRI in patients with clinical diagnosis of TGA in the acute setting is likely a low-yield test.”

Quality Checklist for Systematic Review Diagnostic Studies:

  1. The diagnostic question is clinically relevant with an established criterion standard. Yes
  2. The search for studies was detailed and exhaustive. Yes
  3. The methodological quality of primary studies were assessed for common forms of diagnostic research bias. Yes
  4. The assessment of studies were reproducible. Yes
  5. There was low heterogeneity for estimates of sensitivity or specificity. No
  6. The summary diagnostic accuracy is sufficiently precise to improve upon existing clinical decision-making models. No

Results: They identified 23 studies in their search with a total of 1,688 patients who met inclusion criteria. All studies were case series of adult patients clinically diagnosed with TGA who underwent DW-MRI.

Key Result: The sensitivity of DW-MRI in diagnosing TGA increases with time.

In the first 12 hours from symptom onset, sensitivity of DW-MRI is 15.6%. It improves thereafter to sensitivities between 66 and 83%, with very wide confidence intervals for all point estimates. There is also significant heterogeneity between studies.

Listen to the SGEM podcast to hear Matt answer our ten nerdy questions.

1. Number of Studies: It’s unfortunate that there was a paucity of data to inform our care on TGA. While you identified 23 studies with almost 1,700 patients there were only 2 studies for some time frames with a few dozen patients. The largest time frame only had 10 studies containing 539 patients.

2. Observational Studies: All the studies were observational in nature. There were no randomized trials allocating patients to any time frame (early or late). This limits conclusions to time being associated with better sensitivity for diagnosis TGA with DW-MRI. There could have been reasons why some patients go an MRI sooner while others receive an MRI later.

3. Heterogeneity: The heterogeneity measured by the I2 test was very high (72%-96%) for all time points besides 36-48 hours and 60-72 hours. Why did you decide to meta-analyze the data rather than just providing a narrative report?

4. Table 3: This has 0-12, 0-24 and 12-24 hour groups for time interval from onset. Why did you use three-time groupings here?

5. Partial Verification Bias (Referral Bias, Work-up Bias) – This happens when only a certain set of patients who underwent the index test is verified by the reference standard. Only those who met the clinical criteria for TGA got a DW-MRI. What about all those patients who did not meet clinical criteria and therefore did not get an MRI? This could increase sensitivity.

Spectrum Bias

6. Spectrum Bias – Sensitivity depends on the spectrum of disease, while specificity depends on the spectrum of non-disease. So, you can falsely raise sensitivity if the clinical practice has lots of people with TGA. Do you know what the prevalence of TGA was in the included studies? Responds

7. Imperfect Gold Standard Bias (Copper Standard Bias): This is what can happen if the “gold’ standard is not that good of a test. False positives and false negatives can really mess up results. What is the diagnostic accuracy of the clinical criteria for diagnosing TGA? Responds

8. Serial MRIs: Some of the studies included in the SRMA used serial MRIs. Can you comment if the results were aligned with the entire group within the meta-analysis?

9. Future Studies: You know this area well after having looked at all these studies. How would you design a study using DW-MRI to evaluate for TGA based upon what you know now?

10. Open Question: Is there anything else you would like the SGEMer to know about TGA in general or your study specifically?

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors conclusions.

SGEM Bottom Line: Urgent DW-MRI for patients meeting standard diagnostic criteria for TGA is a low yield intervention.

Case Resolution: You perform a good history, followed by a directed physical examination. You then observe him over a period of hours in the emergency department and he slowly begins to form new memories. You perform an unenhanced CT head and basic bloodwork which is normal. He is discharged home with his wife and will follow up with a neurologist as an outpatient.

Dr. Chris Bond

Clinical Application: We do not need to request an urgent DW-MRIs in patients who meet clinical diagnostic criteria for TGA.

What Do I Tell the Patient? You have something called transient global amnesia or TGA. This condition is not a stroke or seizure or other dangerous disease and will mostly likely resolve over 24 hours. You should have no long-lasting effects from this. You also explain this to the patient’s caregiver and provide a written handout from the Mayo Clinic explaining the same. Should you develop any other neurologic symptoms such as weakness, sensory changes, speech abnormalities or confusion, or are worried you should return to the emergency department immediately.

Keener Kontest: Last weeks’ winner was Dr. Steven Stelts from NZ. Man is he quick with the answers. He knew Morton Heilig submitted a patent for the first head-mounted virtual reality display in 1957 .

Listen to the SGEM podcast for this weeks’ question.  If you know, then send an email to thesgem@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

SGEMHOP: Now it is your turn SGEMers. What do you think of this episode on the DW-MRI in diagnosing TGA? Tweet your comments using #SGEMHOP.  What questions do you have Matt and his team Ask them on the SGEM blog? The best social media feedback will be published in AEM.

Don’t forget (unless you have TGA) those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References:

  1. Courjon J, Guyotat J. Amnesic strokes [in French]. J Med Lyon. 1956;37(882):697-701.
  2. Bender MB. Single episode of confusion with amnesia. Bull N Y Acad Med. 1960;36:197-207.
  3. Fisher CM, Adams RD. Transient global amnesia. Acta Neurol Scand Suppl. 1964;40(suppl 9):1-83.
  4. Miller JW, Yanagihara T, Petersen RC, Klass DW. Transient global amnesia and epilepsy: electroencephalographic distinction. Arch Neurol. 1987;44(6):629-633.
  5. Zorzon M, Antonutti L, Mase G, Biasutti E, Vitrani B, Cazzato G. Transient global amnesia and transient ischemic attack: natural history, vascular risk factors, and associated conditions. Stroke. 1995;26(9):1536-1542.
  6. Arena JE, Rabinstein AA. Transient global amnesia. Mayo Clin Proc. 2015;90(2):264-272.
  7. Caplan L. Transient global amnesia. In: Vinken P, Bruyn G, Klawans H, Frederisks J, eds. Handbook of Clinical Neurology. 45th ed. Elsevier; 1985:205-218.
  8. Hodges JR, Warlow CP. The aetiology of transient global amnesia: a case-control study of 114 cases with prospective follow-up. Brain. 1990;113(3):639-657.
  9. Hodges JR, Warlow CP. Syndromes of transient amnesia: towards a classification. A study of 153 cases. J Neurol Neurosurg Psychiatry. 1990;53(10):834-843.