Matthew Schindler, MD, PhD

"It may be possible that these different mechanisms are causing these different sorts of symptomatology. But we need to do those careful studies while the patient’s acutely ill because a lot of times we’re understandably focused on the clinical case and tried to go back afterwards to look at what happened. Collecting data at that time is going to be the best way for us to answer those questions."

A retrospective chart analysis looking at differences of neurological consultations between COVID-19 and non-COVID-19 respiratory infections showed remarkably similar results in terms of ultimate neurologic diagnosis, with a single exception. Stroke remained the only diagnosis more common in the COVID-19 population as compared with the non-COVID-19 population (14% vs 9%). Furthermore, neurology was consulted significantly later in the hospital course of COVID-19 (3.1 vs 0.96 days), despite a higher mortality in the other population (30% vs 19%).

The associations between stroke and COVID-19 have been documented before, although results are varied. Some research has identified more significant associations, whereas others have shown mixed results, with less meaningful associations. The investigators, including Matthew Schindler, MD, PhD, concluded that the neurological approach to patients with COVID-19 should be similar to that in patients with other respiratory infections.

Schindler, who presented the data at the 

2022 American Academy of Neurology (AAN) Annual Meeting

, April 2-7, in Seattle, Washington, sat down with 

® to discuss the thoughts behind earlier neurological consultation for more severe cases of COVID-19. The assistant professor of neurology at the University of Pennsylvania also provided insight on what clinicians do and do not know regarding the realistic association between COVID-19 and stroke.

Click here for more coverage of AAN 2022.

REFERENCE
1. Emmert B, Gandelman S, Do D, Schindler M. A single center, retrospective analysis of inpatient neurologic consultations of patients infected with SARS-CoV-2. Presented at: 2022 AAN Annual Meeting; April 2-7; Seattle, Washington. Abstract 3171.

Videos

The assistant professor of neurology at the University of Pennsylvania discussed stroke risk among patients with COVID-19 and the need to seek neurological consultation. [WATCH TIME: 3 minutes]

Understanding the Associations of Stroke and COVID-19: Matthew Schindler, MD, PhD

"When you're seeing patients on the inpatient service, you can kind of approach it just like you would in any other virally infected patient. Things such as a encephalopathy, or particularly a toxic metabolic encephalopathy, with more severe infections, we commonly see this, and that independent of whether it was COVID-19, or another infection, another virus. That was sort of the predominant thing that we saw."

, April 2-7, in Seattle, Washington, data were presented from a retrospective chart analysis aimed to determine whether inpatient neurological consultations differ between COVID-19 and non-COVID-19 respiratory infections. Although neurological consultations are common for viral-mediated disease, neurologists are still figuring out whether consultation of patients with COVID-19 should be altered. To do so, investigators compared the reasons for neurologic consultation and final diagnosis of 62 patients with COVID-19 between March 2020 and April 2021 to 56 patients with non-COVID respiratory virus between January 2019 and January 2020.

Non-COVID-19 respiratory viruses included Influenza A and B, respiratory syncytial virus, rhinovirus, and adenovirus. Using a frequency and means analysis, the study investigators concluded that stroke was the only diagnosis more common among patients with COVID-19 compared to the rest of the sample (14% vs 9%). Neurology was consulted significantly later in the hospital course of COVID-19 (3.1 vs 0.96 days), despite a higher mortality in the other population (30% vs 19%).

, believes these results may help guide neurologists when conducting neurological examinations for patients with COVID-19. Schindler, assistant professor of neurology at the University of Pennsylvania, sat down with 

 at AAN 2022 to discuss the reasons behind conducting the study, as well as some of the biggest take-home points clinicians of which should be aware.

The assistant professor of neurology at the University of Pennsylvania discussed the similarities observed between the results of neurological exams in patients with COVID-19 vs other respiratory infections. [WATCH TIME: 3 minutes]

Comparing Neurological Examinations of COVID-19 With Other Viral Infections: Matthew Schindler, MD, PhD

 First, chronic active lesions are an extremely emerging biomarker in multiple sclerosis. There's a lot of research that's been going into them for a number of reasons, so I just like to define it a little bit. So chronic active lesions are based on sort of a histopathological description of having activated microglia macrophages that are at the edge of some MS lesions. So it's a subset of MS lesions. 

We recently, in the last decade or so, have developed MRI markers that have a really good radiological histological correlation with these CALs, as we call them, and we call those PRLs, so paramagnetic rim lesions. A lot of work has gone into showing that MS patients who have the presence of these paramagnetic rim lesions have more aggressive disease phenotypes. So they have, on average, greater disability scores and they reach higher disability levels earlier than patients that do not have any evidence for PRLs on their MRIs. 

We're just really interested in understanding how these lesions affect patient outcomes over time. It also seems to be quite correlated with, or specific to, MS. If we look at other diseases, including other inflammatory diseases and other mimickers of MS, we don't see these lesions on their MRIs. So, it may actually end up being also a very good diagnostic biomarker. So much of the work is really focused on after they occur—after a CRL or a PRL has formed—and their associations, but we really don't know which lesions will actually form into them. That's important because if we're going to start to try to target treatments against this type of lesion for patients, particularly those that have more of these lesions, we want to be able to predict who's going to develop them and then target our treatments to that population. So that way we're avoiding exposing patients to medicines that wouldn't necessarily target their lesions.

The assistant professor of neurology at the University of Pennsylvania discussed how 7T MRI features of newly developed MS lesions can predict the development of chronic active lesions. [WATCH TIME: 3 minutes]

Chronic Active Lesion Evolution in Multiple Sclerosis

"Much of the work is focused on sort of the after of when a CAL or PRL [paramagnetic rim lesion] has formed and the associations. But we don’t know about which lesions will actually form into them. That’s important because, if we’re going to start to try to target treatments against this type of lesion or patient, we want to be able to predict who’s going to develop them."

Chronic active lesions (CALs), a subset of focal multiple sclerosis (MS) lesions, have pathologically been associated with smoldering inflammatory demyelination at the edge, remyelination failure, and axonal degeneration. To better understand which lesions will ultimately become CALs, senior author Matthew Schindler, MD, PhD, and his colleagues developed a predictive model using noncontrast 7T MRI, T2 weighed multiecho gradient echo sequence, quantitative qT1 maps, and thalamic segmentations.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022

, February 24-26, in West Palm Beach, Florida, included 14 patients with 60 incident lesions that were assessed at baseline, 3 months, and 6 months. At the 6-month time point, 12 incident lesions had a hypointense rim on phase contrast and were thus characterized as a CAL. For lesions that evolved into CALs, investigators observed a significantly different baseline qT1 compared to those that did not (

 sat down with Schindler at ACTRIMS Forum 2022 to get his thoughts on the clinical importance of this type of research and the findings he observed. Schindler, assistant professor of neurology, University of Pennsylvania, also provided insight on how he constructed his predictive model and whether this type of approach has potential to be paired with artificial intelligence.

For more coverage of ACTRIMS Forum 2022, 

The assistant professor of neurology at the University of Pennsylvania discussed his abstract at ACTRIMS Forum using 7T MRI features of newly developed MS lesions to predict chronic active lesions. [WATCH TIME: 4 minutes]

Matthew Schindler, MD, PhD

Articles

Understanding the Associations of Stroke and COVID-19: Matthew Schindler, MD, PhD

Comparing Neurological Examinations of COVID-19 With Other Viral Infections: Matthew Schindler, MD, PhD

Chronic Active Lesion Evolution in Multiple Sclerosis

Using Radiologic Markers to Predict Chronic Active Lesion Evolution in MS: Matthew Schindler, MD, PhD

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