The New Indication for an MRI in the ED

I was working in one of our satellite EDs talking with an elderly patient and her daughter about some recent headaches and increased confusion. She was in her early 70s, with a history of Alzheimer’s Dementia (AD). After my initial evaluation and exam, I went back to my computer to place some orders. Looking over her chart, I noticed something odd; the patient had been getting MRIs of her brain every month.

While thinking to myself how odd that was, I remembered a previous ERcast segment about an emerging therapy for AD: a new type of treatment called amyloid-targeting therapy (ATT) delivered as an IV infusion. I went back into the room to ask the patient about her MRIs and confirmed that she had recently started ATT infusions a few months prior.

A promising therapy with serious risks

Studies evaluating the efficacy of ATT treatment have found up to a 30% slowing of disease progression over an 18-month period. For patients with AD, this can mean a substantial impact on quality of life. For patients with a diagnosis of AD who watched their own family members succumb to the disease, ATT may hold the key to precious time and priceless memories with their loved ones. But like many things in medicine, there is a tradeoff. In the case of ATT, this comes with the very real risk of serious and life-threatening complications.

Amyloid-related imaging abnormality (ARIA) is a very serious complication that can occur as a result of ATT treatment. As antibodies act directly on the amyloid beta in the brain, damage to microvascular blood vessels can occur, resulting in either cerebral edema (ARIA-E) or hemorrhage (ARIA-H). The incidence of ARIA ranges between 12.6-31%, depending on the specific ATT therapy that the patient is on.

Symptoms can be anything from headache or confusion to dizziness, visual disturbances, nausea and vomiting, gait changes or even seizures. In short, any patient on ATT presenting with a symptom with a potential neurological pathology needs to be evaluated for possible ARIA.

While the relative risk of developing ARIA while on ATT is significant, the majority of cases will be mild to moderate in terms of symptoms. Approximately 1% of patients on ATT therapy will develop severe ARIA symptoms. Because of the high incidence of ARIA, all patients on ATT therapy have to undergo a baseline MRI, and then will undergo routine monthly MRIs so that their new images can constantly be compared to their baseline and previous scan to evaluate for any evidence of ARIA. The reason for this is that the edema or bleeding can occur on such a microvascular level that CT just isn’t sensitive enough to pick up early cases of ARIA. Patients with a contraindication for MRIs cannot be considered candidates to start ATT therapy.

A very scary mimic

With the constant push for ED clinicians to be faster and faster with their stroke evaluations, the risk of accidentally treating a stroke mimic with thrombolytics in the name of metrics is very real. We are expected to make critical decisions in short periods of time with limited information, whereas the critique of our decisions is made slowly and methodically with the full clinical picture in retrospect.

Patients presenting with ARIA symptoms can easily mimic an acute stroke, especially given the poor sensitivity of CT for detecting early edema or hemorrhage. A case study published in 2023 unfortunately documents this exact situation, where a patient with a “clean” CT and stroke-like symptoms was given tPA, resulting in massive cerebral hemorrhages and eventual withdrawal of care by the family.

Risk and reward

The risks are very real, and as ED clinicians, this needs to be on our radar. For AD patients, ATT therapy is a chance for more of the precious gift of time, stealing back from a terrible disease that robs patients of it.

Patients with ARIA will likely present with very vague, mild symptoms that can mimic a litany of common conditions. The key clinical takeaway here is to add one question to your H&P when evaluating patients with a history of AD: “Do you take an IV infusion for your Alzheimer's?" If the patient is a poor historian or no family is around, scour the chart for any notes from a neurologist or a history of frequent MRIs.

If the answer is yes, go ahead and get a head CT while waiting on MRI, in case the edema or bleeding is severe enough to be evident on CT. If you are unable to obtain an MRI at your facility, ATT therapy is an absolute indication for transferring the patient to a higher level of care. For facilities that do have on-call MRI access, do not push this off as a routine inpatient scan; the tech needs to be paged to come in for an emergent MRI.

Lastly, be wary of clinging to an alternative diagnosis in lieu of getting the MRI. ATT patients with a UTI still need to have ARIA ruled out.

Have you encountered any patients on ATT therapy? We would love to hear your feedback on how the encounter went, and any safety measures your institution has in place to alert providers about this new and very serious therapy. You can email the Hippo EM team at emvertical@hippoeducation.com.