Abstract
Objective
Patients with posterior reversible encephalopathy syndrome (PRES) can develop seizures during the acute phase. We sought to determine the long‐term risk of seizure after PRES.
Methods
We performed a retrospective cohort study using statewide all‐payer claims data from 2016–2018 from nonfederal hospitals in 11 US states. Adults admitted with PRES were compared to adults admitted with stroke, an acute cerebrovascular disorder associated with long‐term risk of seizure. The primary outcome was seizure diagnosed during an emergency room visit or hospital admission after the index hospitalization. The secondary outcome was status epilepticus. Diagnoses were determined using previously validated ICD‐10‐CM codes. Patients with seizure diagnoses before or during the index admission were excluded. We used Cox regression to evaluate the association of PRES with seizure, adjusting for demographics and potential confounders.
Results
We identified 2095 patients hospitalized with PRES and 341,809 with stroke. Median follow‐up was 0.9 years (IQR, 0.3–1.7) in the PRES group and 1.0 years (IQR, 0.4–1.8) in the stroke group. Crude seizure incidence per 100 person‐years was 9.5 after PRES and 2.5 after stroke. After adjustment for demographics and comorbidities, patients with PRES had a higher risk of seizure than patients with stroke (HR, 2.9; 95% CI, 2.6–3.4). Results were unchanged in a sensitivity analysis that applied a two‐week washout period to mitigate detection bias. A similar relationship was observed for the secondary outcome of status epilepticus.
Interpretation
PRES was associated with an increased long‐term risk of subsequent acute care utilization for seizure compared to stroke.
Introduction
Posterior reversible encephalopathy syndrome (PRES) is characterized by symptoms such as headache, visual changes, confusion, and seizure, accompanied by cerebral vasogenic edema on imaging. 1 , 2 Seizure is common in the acute phase of PRES, occurring in 22%–81% of patients. 2 , 3 , 4 , 5 , 6 Patients with PRES frequently have residual parenchymal brain changes demonstrated on brain imaging beyond the acute period, which may place them at higher long‐term risk of seizure. However, whether patients with PRES face an increased long‐term risk of seizure after discharge from the initial hospitalization with PRES is not well understood. 7 Retrospective studies have reported low rates of unprovoked seizure after PRES, ranging from 1%–5.3%. 8 , 9 , 10 , 11 These studies were limited by small, single‐center study samples, in addition to lack of controls. Stroke is another acute cerebrovascular condition linked to seizure. Though patients with stroke infrequently present with seizure during the acute phase, stroke is nonetheless associated with an elevated long‐term risk of seizure compared to the general population. 12 , 13 Therefore, we investigated the risk of seizure after PRES in a large, multicenter patient population, and compared the risk of seizure after PRES to the risk of seizure after stroke.
Methods
Study design
We performed a retrospective cohort study using all‐payer claims data on all discharges from all nonfederal emergency departments and acute care hospitals in Arkansas, Florida, Georgia, Iowa, Maryland, Massachusetts, Nebraska, New York, Utah, Vermont, and Wisconsin. Trained analysts at each nonfederal acute care facility in these states used automated online reporting software to provide standardized discharge data to the respective state health department, which then performed a multistep quality assurance check to identify invalid or inconsistent records before making the data publicly available via the Healthcare Cost and Utilization Project. 14 The states included in this analysis have a combined population of ≈83 million residents, comprising 25% of the total US population. 15 Data were available from calendar year 2016 for all 11 states; 2017 for Florida, Georgia, Iowa, Maryland, Utah, and Wisconsin; and 2018 for Iowa. We chose to analyze data from 2016 to 2018 because these are the most recent data available since the introduction of a specific code for PRES in 2015 in the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM), in keeping with a prior large analysis of PRES. 16
We followed the guidelines for analyses of administrative claims data as set forth in the Reporting of studies Conducted using Observational Routinely‐collected Data guidelines. 17 The Institutional Review Board at Weill Cornell Medicine approved the study of Healthcare Cost and Utilization Project data and waived the requirement for informed consent. The Institutional Review Board at the University of Colorado approved the analysis of the validation of the ICD‐10‐CM code for PRES. We will share our analytic code and methods upon reasonable request to the corresponding author. We cannot directly share our data under the terms of our data use agreement, but the data are available from Healthcare Cost and Utilization Project upon application.
Population
We included adult patients admitted to the hospital with a diagnosis of PRES or stroke. Patients who received both diagnoses during a hospitalization were not included. Because we were interested in the risk of incident seizure after PRES, we excluded patients with a diagnosis of seizure before or during the index hospitalization. Patients with PRES were identified using ICD‐10‐CM code I67.83, which was previously validated in academic and community hospital settings. 16 In that validation, the ICD‐10‐CM code for PRES had sensitivity of 100% and specificity of 88% for PRES, as adjudicated by a board‐certified vascular neurologist. Patients with stroke (ischemic stroke, nontraumatic intracerebral hemorrhage, and nontraumatic subarachnoid hemorrhage) were the positive control and were identified using standard, validated ICD‐10‐CM codes. 18 , 19 , 20
Measurements
Any inpatient or emergency department encounter for seizure, defined as having the discharge diagnosis ICD‐10‐CM code G40.x in any diagnostic position, was the primary outcome. However, we excluded diagnosis codes for idiopathic epilepsies (G40.0x and G40.3x), and other conditions that are unlikely a result of PRES (G40.Ax, G40.Bx, G40.42, G40.81x, G40.83x, G40.82x, G40.89x). ICD‐10‐CM code G40.x achieves a positive predictive value >80% for seizure in most studies. 21 , 22 The secondary outcome of status epilepticus was defined using ICD‐10‐CM codes (G40.101, G40.111, G40.201, G40.211, G40.401, G40.411, G40.501, G40.801, G40.803, G40.901, and G49.911). 23 Demographics were age, sex, and race. We tabulated comorbidities that are potential confounders between event type (PRES versus stroke) and seizure: hypertension, diabetes, alcohol abuse, chronic kidney disease, malignancy including central nervous system malignancies, rheumatologic disorders, history of organ transplantation, acute hypertensive disorders of pregnancy (preeclampsia, eclampsia, and Hemolysis Elevated Liver Enzymes Low Platelets syndrome), and HIV/AIDS. 3 , 24 We also tabulated these same potentially confounding comorbidities in patients who had seizures after PRES and patients who did not have seizures after PRES.
Statistical analyses
We reported crude rates using standard descriptive statistics with exact confidence intervals. We used survival statistics to calculate incidence rates per 100‐person years. Cox proportional hazards models were used to evaluate the association between PRES and seizure while comparing to patients with stroke. The proportional hazards assumption was confirmed by visual inspection of the log–log plot. Model 1 was unadjusted. Model 2 was adjusted for demographics (age, sex, race‐ethnicity). Model 3 was additionally adjusted for potential confounders as listed above. We performed two sensitivity analyses, both using Model 3. In the first, to mitigate detection bias related to possible increased vigilance for neurological symptoms after a diagnosis of PRES or stroke, we excluded seizure outcomes within two weeks of index admission. In the second, to mitigate misclassification bias whereby an index episode of PRES may be recorded as a seizure during a subsequent hospital encounter, we restricted our definition of seizure to encounters with seizure only in the primary diagnosis code position. We then evaluated univariate associations of the above covariate with subsequent seizure in people with PRES. Covariates possibly associated with seizure with a p < 0.10 in univariate models were then entered into a multivariable Cox model. The threshold of statistical significance allowed for an α error of 0.05. All analyses were performed using Stata/MP, version 13. 25
Results
We identified 2095 patients with PRES and 341,809 with stroke. This study population was derived after excluding patients with prevalent seizure during or before the time of the index PRES or stroke admission; patients with PRES had a higher prevalence of prior seizure than patients with stroke (8.0% vs 2.3%), and a higher prevalence of concurrent seizure than patients with stroke (23.1% vs 4.0%) (Fig. 1). In 2016, there were 25 cases of PRES per 100,000 hospital admissions (95% CI, 24–26). In 2017, there were 28 cases of PRES per 100,000 hospital admissions (95% CI, 27–29). In 2018, there were 29 cases of PRES per 100,000 hospital admissions (95% CI, 27–31).
Figure 1.
Patient selection flow chart. PRES, posterior reversible encephalopathy syndrome. From among adult patients, we identified patients with posterior reversible encephalopathy syndrome or stroke, excluding patients who had both, and then we excluded patients with prevalent or concurrent seizure.
Patients with PRES (mean age, 56.1; SD, 17.2 years) were younger than those with stroke (mean age, 70.6; SD, 14.8 years), and more often women than patients with stroke. Patients with PRES were more likely to have comorbidities classically associated with PRES including chronic kidney disease, rheumatologic diseases, organ transplantation, or hypertensive disorders of pregnancy, whereas patients with stroke more frequently had diabetes (Table 1).
Table 1.
Baseline characteristics a of study cohort.
| Stroke (n = 341,809) | PRES (n = 2095) | |
|---|---|---|
| Age in years, mean (SD) | 70.6 (14.8) | 56.1 (17.2) |
| Female | 170,198 (49.8) | 1470 (70.2) |
| Race | ||
| White | 233,765 (68.4) | 1432 (68.4) |
| Black | 63,397 (18.6) | 445 (21.2) |
| Other | 44,647 (13.1) | 218 (10.4) |
| Hypertension | 294,829 (86.3) | 1827 (87.2) |
| Diabetes | 144,549 (42.3) | 786 (37.5) |
| Alcohol abuse | 22,700 (6.6) | 200 (9.6) |
| Chronic kidney disease | 73,744 (21.6) | 707 (33.8) |
| Any malignancy | 9438 (2.8) | 150 (7.2) |
| Rheumatologic disease | 3223 (0.9) | 62 (3.0) |
| History of organ transplant | 2452 (0.7) | 88 (4.2) |
| Acute hypertensive disorders of pregnancy b | 176 (0.1) | 136 (6.5) |
| HIV/AIDS | 478 (0.1) | 17 (0.8) |
PRES, posterior reversible encephalopathy syndrome; SD, standard deviation.
Values are expressed as n (%) unless otherwise indicated.
Preeclampsia, eclampsia, superimposed preeclampsia, or Hemolysis Elevated Liver Enzymes Low Platelets syndrome.
The median follow‐up for patients with PRES (0.9 years; IQR, 0.3–1.7) was similar to that for patients with stroke (median, 1.0 years; IQR, 0.4–1.8). The crude incidence of seizure after PRES was 9.5 (95% CI, 8.3–10.9) per 100 person‐years, compared to 2.5 (95% CI, 2.5–2.6) per 100 person‐years after stroke (Fig. 2). The median time to seizure after PRES was 81 days (IQR, 17–204), and the median time to seizure after stroke was 102 days (IQR, 19–265). In unadjusted models, patients with PRES were more likely to have seizure in a subsequent care encounter than patients with stroke (HR, 3.7; 95% CI, 3.2–4.2) after discharge from the index hospitalization with PRES or stroke. After adjustment for demographics and comorbidities, results were similar: patients with PRES were more likely to have seizure after the index hospitalization than patients with stroke (HR, 2.9; 95% CI, 2.6–3.4). Results were similar in sensitivity analyses with a two‐week washout period during which seizure within two weeks was not included among outcomes (HR, 3.0; 95% CI, 2.6–3.4). When applying a stricter definition of seizure that required seizure in the primary diagnosis code position, the effect size was attenuated but remained significant (HR, 1.9; 95% CI, 1.4–2.5) (Table 2).
Figure 2.
Cumulative rates of seizure after posterior reversible encephalopathy syndrome and stroke. Cumulative rate of seizure with 95% confidence bands in patients with posterior reversible encephalopathy syndrome (red) and stroke (blue).
Table 2.
Association a between posterior reversible encephalopathy syndrome and seizure.
| Compared to stroke | |
|---|---|
| Model 1: Unadjusted | 3.7 (3.3–4.2) |
| Model 2: Adjusted for demographics | 3.0 (2.6–3.4) |
| Model 3: Adjusted additionally for relevant comorbidities | 2.9 (2.6–3.4) |
| Sensitivity analysis: 2‐week washout b | 3.0 (2.6–3.4) |
| Sensitivity analysis: seizure in primary diagnosis position b | 1.9 (1.4–2.5) |
Results presented as hazard ratio (95% confidence interval) comparing patients with posterior reversible encephalopathy syndrome to stroke.
Sensitivity analyses were run using Model 3.
For the secondary outcome of status epilepticus, there were 26 cases in patients with PRES and 1155 cases in patients with stroke. The incidence of status epilepticus after PRES was 0.9 (95% CI, 0.6–1.4) per 100 person years, whereas it was 0.3 (95% CI, 0.2–0.3) per 100 person years after stroke. In unadjusted models, PRES was associated with a higher risk of status epilepticus than stroke (HR, 3.4; 95% CI, 2.3–5.2), and this was also the case in a model adjusted for demographics and comorbidities (HR, 2.8; 95% CI, 1.9–4.3).
Among patients with PRES, those who had subsequent seizure had greater prevalence of hypertension, diabetes, and chronic kidney disease (Table 3). In univariate models, Black and Other race, hypertension, diabetes, alcohol abuse, and chronic kidney disease were significantly associated with increased risk of seizure after PRES, and greater age and presence of acute hypertensive disorders of pregnancy were associated with a decreased risk of seizure after PRES (Table 4). In the multivariable model, Black race and alcohol abuse remained associated with subsequent seizure, whereas greater age and acute hypertensive disorders of pregnancy remained associated with a lower risk (Table 5).
Table 3.
Characteristics a of patients with posterior reversible encephalopathy syndrome with no seizure versus seizure.
| No Seizure | Seizure | p value | |
|---|---|---|---|
| (N = 1847) | (N = 248) | ||
| Age in years, mean (standard deviation) | 56.3 (17.3) | 54.4 (16.6) | 0.11 |
| Female | 1288 (69.7) | 182 (73.4) | 0.24 |
| Race | 0.20 | ||
| White | 1269 (68.7) | 163 (65.7) | |
| Black | 382 (20.7) | 63 (25.4) | |
| Other | 196 (10.6) | 22 (8.9) | |
| Hypertension | 1598 (86.5) | 229 (92.3) | 0.01 |
| Diabetes | 677 (36.7) | 109 (44.0) | 0.03 |
| Alcohol abuse | 170 (9.2) | 30 (12.1) | 0.15 |
| Chronic kidney disease | 606 (32.8) | 101 (40.7) | 0.01 |
| Any malignancy | 137 (7.4) | 13 (5.2) | 0.21 |
| Rheumatologic disease | 52 (2.8) | c | 0.29 |
| History of organ transplant | 78 (4.2) | c | 0.89 |
| Acute hypertensive disorders of pregnancy b | 132 (7.2) | c | <0.01 |
| HIV/AIDS | 14 (0.8) | c | 0.46 |
Values are expressed as n (%) unless otherwise indicated.
Preeclampsia, eclampsia, superimposed preeclampsia, or Hemolysis Elevated Liver Enzymes Low Platelets syndrome.
Data for cells with frequency < 11 were suppressed to protect patient privacy as per data use agreement stipulations.
Table 4.
Association of covariates with seizure in patients with posterior reversible encephalopathy syndrome using a univariate Cox model.
| Hazard ratio (confidence interval) | p value | |
|---|---|---|
| Age | 0.99 (0.99–1.00) | 0.05 |
| Female | 1.1 (0.8–1.5) | 0.54 |
| Race | ||
| Black | 1.4 (1.0–1.9) | 0.03 |
| Other | 0.9 (0.5–1.4) | 0.54 |
| Hypertension | 1.9 (1.2–3.2) | 0.01 |
| Diabetes | 1.4 (1.1–1.9) | 0.01 |
| Alcohol abuse | 1.7 (1.1–2.4) | 0.01 |
| Chronic kidney disease | 1.5 (1.1–1.9) | 0.01 |
| Any malignancy | 0.7 (0.4–1.3) | 0.26 |
| Rheumatologic disease | 1.4 (0.7–2.7) | 0.33 |
| History of organ transplant | 1.1 (0.6–2.1) | 0.81 |
| Acute hypertensive disorders of pregnancy a | 0.2 (0.1–0.6) | <0.01 |
| HIV/AIDS | 1.6 (0.5–5.1) | 0.39 |
Preeclampsia, eclampsia, superimposed preeclampsia, or Hemolysis Elevated Liver Enzymes Low Platelets syndrome.
Table 5.
Association of covariates with seizure in patients with posterior reversible encephalopathy syndrome using a multiple Cox model.
| Hazard ratio (confidence interval) | p value | |
|---|---|---|
| Age | 0.98 (0.98–0.99) | <0.01 |
| Race | ||
| Black | 1.4 (1.0–1.9) | 0.03 |
| Other | 0.9 (0.5–1.5) | 0.67 |
| Hypertension | 1.1 (0.7–2.0) | 0.66 |
| Diabetes | 1.3 (1.0–1.7) | 0.11 |
| Alcohol abuse | 1.7 (1.1–2.4) | 0.01 |
| Chronic kidney disease | 1.2 (0.9–1.6) | 0.15 |
| Acute hypertensive disorders of pregnancy a | 0.2 (0.1–0.8) | 0.02 |
Preeclampsia, eclampsia, superimposed preeclampsia, or Hemolysis Elevated Liver Enzymes Low Platelets syndrome.
Discussion
We evaluated the long‐term risk of seizure in 2095 patients after hospitalization for PRES across eleven states and compared their risk to that of patients with stroke. Before and after adjusting for differences in demographics and comorbidities, patients with PRES had a two‐to‐three‐fold elevated risk of seizure compared to patients with stroke, which was preserved in sensitivity analyses. A similar relationship was seen for status epilepticus.
Our paper builds on prior descriptive studies that investigated seizure risk after an initial episode of PRES. Several prior single‐center retrospective cohort studies reported that 1%–5.3% of patients with PRES had an unprovoked seizure after the acute phase of PRES, with study samples ranging from 75–127 patients. 8 , 9 , 10 , 11 One study reported that 14% of patients had a provoked seizure after PRES. 8 Other studies, with smaller sample sizes, found no patients with seizure after PRES, and thus concluded that PRES is a monophasic illness with respect to seizure risk. 26 , 27 , 28 A more recent study found that 1.4% of patients admitted with an episode of PRES were readmitted within 90 days for seizures, and approximately 5% of readmissions within 90 days were for seizure. 5 However, this study included outcomes only from among inpatient admissions, had follow‐up for only up to 90 days, and did not assess status epilepticus. We found a rate of acute care utilization for seizure of 9.5 per 100 person‐years after PRES, and this was notably among people without a prior documented history of seizure or seizure concurrent to PRES. In addition to providing an estimate of seizure risk after PRES from a large cohort, our findings suggest that PRES is followed by a higher rate of seizure than stroke, another acute cerebrovascular condition known to increase seizure risk. Prior studies have not compared patients with PRES to other groups at risk for seizure to contextualize the risk after PRES.
Absolute seizure rates after PRES in our paper are higher than in these prior publications. 8 , 9 , 10 , 11 In these prior studies, up to 77% of the patients had seizures at diagnosis. These patients were often maintained on antiseizure medications after discharge. For example, only a third of patients in the Hinduja et al. 2016 study had their antiseizure medications discontinued during the median follow‐up period of 14.5 months; the group's seizure risk was thus mitigated. 9 By excluding patients who had seizures at onset of diagnosis in our analysis, we believe we excluded many patients discharged on antiseizure medications. This may, in part, explain the higher rate of seizures in our cohort.
Hypertension, diabetes, and chronic kidney disease were more common in people with PRES who had subsequent seizure. In univariate analyses, these comorbidities, and alcohol abuse, were associated with a higher risk of subsequent seizure. While these associations did not persist in a multivariable model, this information is nonetheless clinically pertinent. Perhaps patients with PRES vulnerable to metabolic derangements and alcohol withdrawal are more at risk of subsequent seizure. Conversely, people with the episodic risk factor of hypertensive disorders of pregnancy may lack other long‐lasting seizure risk factors; these people appear to be at a lower risk of future seizure.
There are several potential explanations for our key finding that patients with PRES had a higher risk of seizure than patients with stroke. First, although PRES is typically described as reversible, 27 many patients sustain residual parenchymal brain injury including focal gliosis and vascular changes visible on follow up imaging. 7 Such changes may predispose to seizure by serving as an ictal nidus. Second, increased vigilance for neurologic symptoms after PRES may contribute to increased detection of seizure. However, this also applies to the positive control of patients with stroke, making it an unlikely sole explanation for our findings. Third, patients with PRES and seizure share risk factors, which may explain why patients with PRES in our cohort had a relatively higher prevalence of prior seizure compared to stroke. For example, patients vulnerable to PRES such as those with cancer may have prior seizures from a variety of mechanisms including brain metastases and provoking factors such as infection and metabolic derangement. 29 , 30 Similarly, patients vulnerable to PRES due to hypertension may have had prior seizures resulting from occult cerebrovascular disease. 31 , 32 , 33 Last, organ transplantation may be linked to prior seizures due to provoking factors encountered after organ transplantation such as opportunistic infections of the central nervous system and toxic‐metabolic disturbances. 34 However, our models adjusted for both common (hypertension) and less common (organ transplantation) conditions linked to PRES; so, shared risk factors alone may not completely account for our findings. Fourth, some patients with seizure after the acute phase of PRES may have had recurrent PRES. 8 Whether patients who had seizure after PRES in the present analysis had seizure due to recurrent PRES cannot be reliably determined; however, the rate of recurrent PRES is reported to be low (2%–4%) so should not fully account for our findings. 5 , 35 Last, it is conceivable that some patients with PRES who subsequently presented for other reasons were incorrectly assigned a diagnosis of seizure to reflect their prior PRES. In a sensitivity analysis, we defined seizure based on a primary diagnosis of seizure to mitigate this risk. The association of PRES with seizure after the acute phase of PRES was attenuated in this model but not eliminated, suggesting that this potential diagnostic coding error does not explain our findings. Additionally, PRES was associated with status epilepticus, supporting overall consistency of findings.
Our finding of a substantial rate of acute care utilization for seizure after PRES has potential implications for clinical care. Clinicians caring for patients with PRES may wish to counsel patients about the risk of seizure after the acute phase of PRES and make efforts to identify and mitigate risks as feasible. However, our observational data alone should not be taken as justification to initiate long‐term anti‐seizure medications for all patients after PRES. Further research is necessary to elucidate which patients with PRES are most likely to have recurrent seizure, and whether and when preventive therapy is indicated. Future studies should seek to identify clinical and imaging predictors of seizure after PRES. Future studies should also seek to better understand the etiology of seizure after PRES.
The key strengths of this analysis are the use of a large, heterogeneous patient cohort and use of validated diagnosis codes to identify patients with PRES. A key limitation is the risk of misclassification of our primary study outcome. Specifically, patients with PRES later presenting to the hospital with neurological symptoms may be assigned a diagnosis of seizure because of the known association of PRES with seizure during the acute phase. The extent to which such misclassification is more likely after PRES than stroke, which is also associated with long‐term risk of seizure, is not known. If the likelihood of misclassification after PRES is substantially higher than after stroke, then this may have biased our findings toward finding a greater risk of seizure after PRES than stroke. Additionally, using these data, we could not differentiate between provoked and unprovoked seizure, or reliably determine which patients had recurrent PRES. We also lacked granular clinical information, like seizure type and semiology, neuroimaging, electroencephalography, vital signs, use of anti‐seizure medications, and laboratory test data. Last, the median follow‐up time was slightly less than one year; it is possible that a longer study period would find that patients with stroke have seizures years later, thus potentially attenuating the difference between PRES and stroke. Future studies will ideally include detailed clinical data from multicenter cohorts.
In a large retrospective cohort study, we found that PRES was associated with an increased long‐term risk of seizure that was higher than the risk incurred after stroke.
Author Contributions
Alison Seitz, MD, and Sarah C. Parauda, MD, contributed to the conceptualization of the research and wrote the original draft. Setareh Salehi Omran, MD, validated the codes and reviewed and edited the manuscript. Andrew D. Schweitzer, MD, Ava L. Liberman, MD, Santosh B. Murthy, MD, MPH, Alexander E. Merkler, MD, MS, Babak B. Navi, MD, MS, and Costantino Iadecola, MD, reviewed and edited the manuscript. Hooman Kamel MD, MS contributed to the conceptualization, data curation, resources, supervision, and review/editing of the manuscript. Cenai Zhang, MS, completed the formal analysis and contributed to the data curation, software, and visualization in the manuscript. Neal S. Parikh MD, MS contributed to the conceptualization, funding acquisition, investigation, resources, supervision, and review/editing of the manuscript.
Conflict of Interest Statement
Dr. Seitz, Dr. Parauda, Ms. Zhang, and Dr. Salehi Omran report no conflicts. Dr. Schweitzer has received personal compensation for medicolegal consulting on stroke imaging. Dr. Murthy has is supported by NIH (K23NS105948) unrelated to this work and received personal compensation for medicolegal consulting on neurological disorders. Dr. Merkler has received personal compensation for medicolegal consulting on neurological disorders. Dr. Navi has received personal compensation for medicolegal consulting on PRES and stroke. Dr. Iadecola serves on the Scientific Advisory Board of Broadview Ventures. Dr. Kamel serves as a PI for the NIH‐funded ARCADIA trial (NINDS U01NS095869), which receives in‐kind study drug from the BMS‐Pfizer Alliance for Eliquis® and ancillary study support from Roche Diagnostics; as Deputy Editor for JAMA Neurology; on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; and on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim. He has an ownership interest in TETMedical, Inc. Dr. Parikh has received research support from the New York State Empire Clinical Research Investigator Program unrelated to this work, and personal compensation for medicolegal consulting on neurological disorders. Dr. Liberman is supported by NIH/NINDS research grant K23NS10764 unrelated to this work.
Acknowledgment
Dr. Parikh is supported by the NIH/NIA (K23 AG073524), the Leon Levy Neuroscience Fellowship, and the Florence Gould Endowment for Discovery in Stroke. This content is solely the responsibility of the authors and does not represent the official views of the National Institute of Health (NIH).
Funding Statement
This work was funded by National Institute of Health (NIH) ; NIH/NIA grant K23 AG073524.
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