Abstract
Background and Objectives
Despite an overall decline in incidence rate, the burden of stroke may be rising in young adults. We aimed to characterize the incidence rates, 30-day case fatality rates (CFR), and the burden of stroke risk factors over time in young adults in a representative population-based study of stroke.
Methods
Using validated methods, hospitalized stroke cases in a 5-county region were ascertained and adjudicated by stroke-trained physicians in 6 study periods: July 1993-June 1994, and calendar years 1999, 2005, 2010, 2015, and 2020. Stroke in the young was defined as those occurring among individuals who were ages 20-54 years old. Incidence rates were generated using U.S. Census data standardized to the 2010 population, and trends were tested with linear regression. Temporal trends in 30-day CFR were evaluated with logistic regression after adjusting for age, race, and sex.
Results
Across all study periods, there were 2,076 first-ever strokes in young adults. Hypertension, diabetes, atrial fibrillation, and substance use were more common over time (P<0.001). The stroke incidence rate increased in young adults over time (33.90 cases/100,000 person-years in 1993/4 to 62.18 cases/100,000 person-years in 2020, trend p=0.04), while declining in older adults (618.78 cases/100,000 person-years in 1993/4 to 453.04 cases/100,000 person-years in 2020, trend p=0.02). The rise in stroke incidence appeared driven by ischemic stroke, with an almost doubled incidence rate of 23.8 cases/100,000 person-years in 1993/4 to 47.3 cases/100,000 person-years in 2020 (trend p=0.02). There was a modest decline in the 30-day CFR in young adults (11.7% in 1993/4 to 9.4% in 2020, trend p=0.002), driven by intracerebral hemorrhage (27.5% in 199/34 to 21.2% in 2020, trend p=0.03) and subarachnoid hemorrhage (27.9% in 1993/4 to 18.6% in 2020, trend p=0.09).
Discussion
The incidence of stroke in young adults is rising over time, while the CFR simultaneously declines. This coincides with a rise in both traditional vascular risk factors and substance use.
Introduction
Stroke in young adults leads to premature death and a high burden of years lived with disability.1,2 This can lead to negative personal and economic impacts to these individuals, their families, and to society overall.2-4 Several recent studies have demonstrated a rise in stroke-related mortality among young adults, with notable geographic-, sex-, and race-based disparities.1,5-7 Stroke-related mortality is a complex measure, and can be affected by changes in either stroke incidence rate or casefatality rates (CFR), which have major implications for population-level interventions.8 Some prior work has suggested that this is largely the result of a rising incidence rate1,9-11, but contemporary data in representative populations of the United States is lacking.
In this study, we aimed to characterize the trends of stroke incidence and 30-day CFR among younger individuals from 1993-2020 in the Greater Cincinnati/Northern Kentucky Stroke Study. We further explored the prevalence of different risk factors among individuals with stroke over the same time periods.
Methods
Standard Protocol Approvals, Registrations, and Patient Consents
The study was approved by the institutional review boards of all participating hospitals with a waiver from informed consent.
Study Population
The Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) is a long-running population-based study in the 5 county-region of Southern Ohio and Northern Kentucky.12 With a population of 1.4 million people, the region is representative of the U.S. population regarding age, percentage of Black race, education, and income.13 The study adhered to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies.14
Case Ascertainment
All instances of hospitalized stroke in the region were ascertained over six study periods: July 1993-June 1994, and the calendar years of 1999, 2005, 2010, 2015, and 2020. Trained study nurses reviewed potential cases based on ICD-9 and ICD-10 codes (ICD9: 430-436; ICD10: G45-46, 160-169). All potential cases were reviewed and abstracted by trained research nurses and adjudicated/subtyped by stroke-trained physicians. Case definitions were consistent across study periods. A case of stroke was defined as sudden-onset, focal neurologic deficits localizing to an anatomical region of the brain, persisting for at least 24 hours. For this analysis, ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) subtypes were included. Transient ischemic attacks, defined as acute focal neurologic symptoms lasting less than 24 hours, were excluded. The stroke mechanism for ischemic stroke was adjudicated by stroke-trained study physicians and recorded, categorized as cardioembolic, large-vessel, small-vessel, other, or undetermined cause.15
Variables
For all cases, demographic, clinical and social information was collected using a standardized data collection instrument. Stroke in the young was defined as stroke occurring in individuals ages 20-54 years old, similar to other literature.1,16-18 Moderate alcohol use was defined as 2 or more servings of alcohol per day. Substance use was defined as cocaine, marijuana, methamphetamine, heroin, other non-prescribed opioids, or other illicit substance use. Information on these variables was collected from the medical record. SAH cases were classified as aneurysmal under two circumstances: (1) if a causal aneurysm was identified on vessel imaging, or (2) in cases where vessel imaging was not obtained due to early death, as long as the volume of SAH was large on initial CT and the clinical story was highly suspicious for aneurysm rupture.19 For the 2020 study period, information on coronavirus-19 (COVID-19) virus positivity, within two weeks (before or after stroke diagnosis), was collected.
Outcomes
The 30-day CFR was assessed for all patients using data from both the medical record and the National Death Index, which captures all deaths (both in-hospital and out-of-hospital) in the territorial United States. All causes of death were included.
Statistical Analysis
Descriptive statistics were generated for demographic, clinical, and social variables with data reported as means with standard deviations or medians with interquartile ranges as appropriate. For analysis of changes over time, standard or multinormal Cochran-Armitage trend tests were used for categorical variables20, and a linear model was used for age with calendar year as an independent variable in the model.
Incidence rates were generated by using the raw case counts as the numerator and data from the United States Census data as the denominator, with direct standardization to the 2010 population. Incidence rates were calculated in terms of 100,000 person-years. We calculated the 95% confidence intervals assuming a Poisson distribution. Incidence rates by stroke subtype (IS, ICH, and SAH) were also performed. Trends over time were assessed using linear regression.
Trends in 30-day CFR were analyzed with logistic regression, after adjustment for age, race, and sex. These rates were analyzed overall and by stroke subtype (IS, ICH, and SAH).
Data Availability
Data not provided in the article may be shared (anonymized) at the request of any qualified investigator for purposes of replicating procedures and results.
Results
Overall Demographics
Across all study periods, there were a total of 2,076 incident strokes among young individuals, with 738 cases occurring in Black individuals (35.6%) and 1,030 cases occurring in females (49.6%). Demographics and risk factors over time are shown in Table 1 for overall stroke, and in the supplement for each subtype (IS, ICH, SAH in eTables 1, 2, and 3 respectively). From 1993 to 2020, individuals with stroke were more likely to have hypertension (from 47.3% in 1993 to 60.3% in 2020, p<0.001), diabetes (from 19.09% in 1993 to 25.5% in 2020, p=0.012), and atrial fibrillation (1.4% in 1993 to 5.9% in 2020, P<0.001). Individuals with stroke also were much more likely to have substance use in later periods (an increase from 4.6% in 1993 to 40.2% in 2020), with much of this increase accounted for by rising marijuana use (from 0.9% in 1993 to 30.6% in 2020). Moderate alcohol use and tobacco use did not significantly change over time. Positivity for COVID-19 was very uncommon in 2020, affecting only 5 individuals (1.65%). In terms of the diagnostic evaluation, MRI was much more commonly performed over time (from 32.7% of cases in 1993 to 79.2% in 2020, p<0.001). There was a significant difference among stroke subtypes over time (IS, ICH, and SAH, omnibus p=0.006), with a rise in IS (69.5% in 1993/4 to 74.3% in 2020). Among IS etiologies, more IS were cardioembolic in later years (16 individuals or 10.46% in 1993/4 to 56 individuals or 18.48% in 2020, trend p=0.005), and there was a nonsignificant decline in IS due to large-vessel disease (25 individuals or 16.34% in 1993/4 to 28 individuals or 9.24% in 2020, trend p=0.064).
Table 1:
Characteristics of Younger Individuals (Ages 20 – 54 Years Old) Over Time in the GCNKSS: All Strokes (Ischemic, Hemorrhagic, and Subarachnoid Hemorrhage)
| 1993/4 | 1999 | 2005 | 2010 | 2015 | 2020 | P value |
|
|---|---|---|---|---|---|---|---|
| N | 220 | 294 | 386 | 419 | 349 | 408 | |
|
Age Median, (1st-3rd IQR*) |
46.0 (41.0 – 50.5) |
47.0 (42.0 – 51.0) |
47.0 (42.0 – 51.0) |
49.0 (43.0 – 52.0) |
47.0 (41.0 – 52.0) |
47.0 (41.0 – 51.0) |
0.259 |
| N, (%) | |||||||
| Female Sex | 111 (50.45) | 146 (49.66) | 195 (50.52) | 216 (51.55) | 165 (47.28) | 197 (48.28) | 0.458 |
| Black Race | 75 (34.09) | 102 (34.69) | 129 (33.42) | 139 (33.17) | 138 (39.54) | 155 (37.99) | 0.119 |
| Hypertension | 104 (47.27) | 158 (53.74) | 210 (54.40) | 248 (59.19) | 219 (62.75) | 246 (60.29) | <0.001 |
| Diabetes | 42 (19.09) | 62 (21.09) | 79 (20.47) | 107 (25.54) | 90 (25.79) | 104 (25.49) | 0.012 |
| Atrial Fibrillation | 3 (1.36) | 7 (2.38) | 22 (5.70) | 15 (3.58) | 28 (8.02) | 24 (5.88) | <0.001 |
| Heart Disease | 33 (15.00) | 54 (18.37) | 74 (19.17) | 81 (19.33) | 62 (17.77) | 76 (18.63) | 0.474 |
| MRI performed | 72 (32.73) | 117 (39.80) | 266 (68.91) | 314 (74.94) | 283 (81.09) | 323 (79.17) | <0.001 |
| Current Tobacco Use | 92 (41.82) | 148 (50.34) | 183 (47.41) | 222 (52.98) | 155 (44.41) | 192 (47.06) | 0.762 |
| At least moderate alcohol use † | 20 (9.09) | 30 (10.20) | 29 (7.51) | 44 (10.50) | 40 (11.46) | 51 (12.50) | 0.075 |
| Any substance use ‡ | 10 (4.55) | 28 (9.52) | 54 (13.99) | 74 (17.66) | 86 (24.64) | 164 (40.20) | <0.001 |
| Any marijuana use | 2 (0.91) | 20 (6.80) | 35 (9.07) | 55 (13.13) | 65 (18.62) | 125 (30.64) | <0.001 |
| Only marijuana use | 2 (0.91) | 13 (4.42) | 24 (6.22) | 43 (10.26) | 37 (10.60) | 80 (19.61) | <0.001 |
| Stroke Subtype § | 0.006 | ||||||
| Ischemic Stroke | 153 (69.5) | 189 (64.3) | 276 (71.5) | 311 (74.2) | 263 (75.4) | 303 (74.3) | |
| Intracerebral hemorrhage | 38 (17.3) | 53 (18.0) | 69 (17.9) | 71 (17.0) | 58 (16.6) | 62 (15.2) | |
| Subarachnoid hemorrhage | 29 (13.2) | 52 (17.7) | 40 (10.4) | 37 (8.8) | 28 (8) | 43 (10.5) | |
| Ischemic Stroke Mechanism | |||||||
| Cardioembolic | 16 (10.46) | 19 (10.05) | 33 (11.96) | 28 (9.00) | 36 (13.69) | 56 (18.48) | 0.005 |
| Large Vessel Disease | 25 (16.34) | 22 (11.64) | 31 (11.23) | 40 (12.86) | 29 (11.03) | 28 (9.24) | 0.064 |
| Other-Determined | 14 (9.15) | 19 (10.05) | 33 (11.96) | 45 (14.47) | 35 (13.31) | 38 (12.54) | 0.155 |
| Small Vessel Disease | 28 (18.30) | 35 (18.52) | 57 (20.65) | 61 (19.61) | 43 (16.35) | 54 (17.82) | 0.575 |
| Undetermined | 70 (45.75) | 94 (49.74) | 122 (44.20) | 137 (44.05) | 120 (45.63) | 125 (41.25) | 0.185 |
Inter-quartile range
Moderate alcohol use defined as more than 2 servings of alcohol per day
Substance use defined as marijuana, cocaine, heroin, other illegal opioids, or other substance use
In 2005, there was one unknown subtype (individual was diagnosed with stroke by clinical criteria, but no imaging performed allow for subtyping)
Trends in Incidence Rates
The incidence rate of stroke in young adults increased from 33.90 cases/100,000 person-years in 1993/4 to 62.18 cases/100,000 person-years in 2020 (Figure 1A, trend p=0.04). For older adults, the incidence rate decreased from 618.78 cases/100,000 person-years in 1993/4, to 453.04 cases/100,00 person-years in 2020 (Figure 1B, trend p=0.02). When stratified by subtype for young individuals, only IS had a rising incidence rate over time, from 23.83 cases per 100,000 person-years in 1993/4 to 47.28 cases per 100,000 person years (trend p=0.02, Table 2). No trends in incidence rates were identified in ICH or SAH. Upon stratifying incidence rates further by age subgroups (ages 20-39, and 40-54 years old), the significant trend of increased stroke incidence over time persisted among both groups (ages 20-39 years old: 12.08 cases per 100,000 person-years in 1993/4 to 21.12 per 100,000 person-years in 2020, trend p=0.006; ages 40-54 years old: 72.05 cases per 100,000 person-years in 199/34 to 124.74 per 100,000 person-years in 2020, trend p=0.02; eTable 4).
Figure 1A and 1B: Incidence Rates in Young and Older Adults Over Time.
Figure 1 depicts the overall stroke incidence rates per study period for young (1A, ages 20-54 years old) and older (1B, ages 55 years old and older) adults.
Table 2:
Stroke Incidence per Subtype
| Study Year | Ages 20 – 54 Years Old | ||
|---|---|---|---|
| Ischemic Stroke | Intracerebral Hemorrhage |
Subarachnoid Hemorrhage |
|
| 1993/4 | 23.83 (20.07 – 27.58) |
6.56 (4.57 – 8.55) |
4.42 (2.81 – 6.03) |
| 1999 | 28.89 (24.80 – 32.98) |
8.65 (6.40 – 10.90) |
7.71 (5.61 – 9.81) |
| 2005 | 43.64 (38.58 – 48.69) |
11.33 (8.76 – 13.90) |
6.14 (4.25 – 8.02) |
| 2010 | 48.33 (43.01 – 53.64) |
11.21 (8.67 – 13.76) |
5.60 (3.81 – 7.38) |
| 2015 | 41.65 (36.69 – 46.62) |
9.65 (7.31 – 11.99) |
4.29 (2.72 – 5.86) |
| 2020 | 47.28 (41.98 – 52.57) |
10.10 (7.64 – 12.55) |
6.66 (4.69 – 8.64) |
| Trend p-value | 0.020 | 0.159 | 0.922 |
Per 100,000 person-years, with 95% confidence intervals
Trends in Case Fatality Rates
After adjustment for age, race, and sex, there was a small decline in the 30-day CFR over time, from 11.7% in 1993/4 to 9.4% in 2020 (Figure 2A, trend p=0.002). No trend was appreciated among older adults, with a 30-day CFR 14.3% in 1993/4 compared with 14.2% in 2020 (Figure 2B, trend p=0.99). Examining this finding by stroke subtype (Table 3), the decline in 30-day CFR in young adults was driven by ICH (trend p=0.030) and a numerical decline in SAH (trend p=0.090). Upon stratifying case fatality rates further by age subgroups (ages 20-39 and 40-54 years old), the significant temporal decline in CFR seen among all young adults with stroke persisted in both age groups (ages 20-39 years old: 18.5% in 1993/4 to 7.6% in 2020, trend p=0.009; ages 40-54 years old: 10% in 1993/4 to 9.5% in 2020, trend p=0.015; eTable 5).
Figure 2A and 2B: 30-Day Case Fatality Rates in Young and Older Adults Over Time.
Figure 2 depicts the overall 30-day case fatality rates per study period for young (1A, ages 20-54 years old) and older (1B, ages 55 years old and older) adults
Table 3:
Stroke 30-Day Case Fatality Rates per Subtype
| Study Year | Ages 20 – 54 Years Old | ||
|---|---|---|---|
| Ischemic Stroke | Intracerebral Hemorrhage |
Subarachnoid Hemorrhage |
|
| 1993/4 | 4.5 (2.2 – 9.0) |
27.5 (15.4 – 44.2) |
27.9 (14.3 – 47.5) |
| 1999 | 5.5 (3.1 – 9.7) |
31.8 (20.5 – 45.8) |
30.3 (18.5 – 45.4) |
| 2005 | 4.6 (2.7 – 7.8) |
30.9 (21.0 – 42.9) |
14.6 (6.5 – 29.7) |
| 2010 | 2.8 (1.5 – 5.2) |
22.5 (14.2 – 33.8) |
18.1 (8.7 – 33.9) |
| 2015 | 2.3 (1.1 – 4.8) |
10.0 (4.5 – 20.8) |
13.1 (4.9 – 30.8) |
| 2020 | 4.9 (3.0 – 8.0) |
21.2 (12.6 – 33.4) |
18.6 (9.7 – 32.9) |
| Trend p-value | 0.410 | 0.030 | 0.090 |
30-day case fatality rates reported as a percentage, with 95% confidence intervals
Due to the declining CFR among those with ICH and SAH, we explored clinical care management over time in these stroke subtypes. It was more common in recent years for individuals with ICH and SAH to be cared for at institutions with neurological intensive care unit capabilities. There was no change in the frequency of surgical procedures over time (eTable 6).
Discussion
In this representative population-based study of stroke spanning from 1993 to 2020, we found that the stroke incidence rate is rising in younger adults, while declining in older adults. This finding was largely driven by a rise in IS, with an almost doubled incidence rate over the study period. Young adults with stroke have also experienced a small decline in 30-day CFR over time, observed primarily among those with ICH and SAH. Taken together, young adults are suffering more strokes and are more likely to survive, which will result in an increasing burden of long-term stroke-related disability. In response, we must address the underlying reasons for these trends and adapt to the long-term needs of stroke survivors.
Our results expand upon prior studies showing a rising burden of stroke in the young in high-income countries.9,10 The consistency of this trend across populations and study designs suggests it is a truly rising burden, and not just a reflection of increased detection as a result of rising MRI use.21 Further, prior work in our own population has suggested that more widespread MRI use had a minimal effect on stroke incidence, as it helped both rule in and rule out strokes (i.e. stroke mimics) at equal rates.22 We also did not find a decrease in the CFR among patients with IS, which would be expected if milder strokes were increasingly being found with MRI. Additionally, if rising stroke incidence was wholly explained by increased MRI use, we might anticipate a rise in stroke incidence among older adults as well, which was not the case.
Our study cannot definitively identify the mechanisms behind this rising burden, but several potential explanations were observed in our data. The population may be suffering more stroke at a younger age due to a rising burden of traditional stroke risk factors, including hypertension, diabetes, and atrial fibrillation; while we do not have data on comorbidities in the stroke-free individuals in our population, prior work has suggested this to be true as a general trend in the United States.16,23 Importantly, the rise in hypertension and diabetes has not corresponded to a rise in treatment of these conditions, which could plausibly lead to more frequent downstream effects such as stroke.23 Further, while we do not have data on rates of obesity over time in our study, obesity remains highly prevalent in young adults.24 The rates of obesity are rising nationally and likely have similarly risen among individuals in our study as well.25 Obesity is a complex stroke risk factor due to the possibilities of directly adding to stroke risk and mediating other known risk factors.26,27 Increasingly effective treatments for obesity are available28, but it remains uncertain whether their implementation will be sufficiently widespread to have an impact on population-level trends in stroke. Future surveillance on the burden of obesity as it relates to stroke in the young is needed.
As for the rise seen in atrial fibrillation, it is noteworthy that the only ischemic stroke mechanism increasing over time was cardioembolic stroke. This could be due again to a true rise in atrial fibrillation over time in young adults, or enhanced surveillance with cardiac monitoring as part of the diagnostic evaluation for ischemic stroke. This finding does coincidence with a rise in the incidence of atrial fibrillation over time in the general population.29,30 Further surveillance of atrial fibrillation in young adults both with and without stroke, contextualized with current trends in long-term cardiac monitoring, would be beneficial to understand these trends.
There was also a dramatic rise in substance use over time among young individuals with stroke, with almost one-third of the study population with documented marijuana use in 2020. Depending on the specific exposure and frequency of use, substance use can cause stroke, enhance known stroke risk factors such as hypertension, or simply be comorbid.31-34 While some of this rising burden could be explained by more detailed documentation or screening practices in later years, our results are concordant with national survey data also suggesting a true rise in substance use in the United States due to a variety of factors.35-37 Stimulants such as cocaine and methamphetamine are widely accepted as stroke risk factors.31,33,38 There is a growing body of evidence pointing towards marijuana as at least a modest stroke risk factor, though additional study is needed.32,39 Whether or not substance use is playing a causal role in the rising burden of stroke in the young, it is important to identify it as a highly common comorbidity in this population with potential negative health consequences. Due to the very minimal burden of endocarditis-related strokes in our study over time40, we do not suspect that endocarditis related to substance use is the sole driver of substance-use related stroke. Future studies should identify the best ways to integrate identification and treatment of substance use-related disorders into the care for individuals with stroke.
We also report a small decline in CFR among young individuals with stroke over time, driven by intracerebral hemorrhage and subarachnoid hemorrhage. The declining CFR in subarachnoid hemorrhage has previously been reported in our population.19 This may be multifactorial, due to improvements in diagnostic neuroimaging and endovascular treatment for aneurysmal subarachnoid hemorrhages, and a higher utilization of neurologic intensive care units. The reason for the decline seen in intracerebral hemorrhage CFR over time is less certain. Our focus on young individuals limits the generalizability of this finding to ICH overall. Evaluating individuals with ICH of all ages, CFR have remained fairly stable over time41-43; however, it is possible that younger patients disproportionately benefit from the more widespread availability of neurologic intensive care.44
There are several strengths to our study. It was performed in a large population that is representative of the United States in terms of percentage of Black race, age, educational attainment, and socioeconomic status.45 In addition, we conducted this work with consistent case definitions of stroke over time. We also report limitations to this study. First, we rely on utilization of the electronic health record for ascertainment of medical comorbidities and social history. Second, as the primary goal of our study is stroke surveillance, we do not have comparative data of individuals without stroke to evaluate for any causal mediators of the observed trends. Third, our study population is not representative of other individuals other than those of white or Black race, such as individuals of Hispanic, Asian, and American Indian heritage. Fourth, though we do report a very minimal burden of identified COVID-19 cases in our study, the potential impact of the pandemic in the 2020 data is unknown. Lastly, the data from our study was most recently collected in 2020. We hope to repeat the study in the future to further our knowledge of stroke epidemiological trends.
In conclusion, we report a worrisome trend of a rise in stroke incidence in young adults and a promising but modest decline in 30-day CFR. Contextualizing our findings, the recent rise in United States stroke mortality rates in young adults is likely attributable to a rise of stroke incidence in this group, without a contribution of higher CFR.1 The rise in stroke in young adults highlights the ongoing importance of primary prevention, even among well-appearing young adults, and the importance for primary care providers to identify and treat vascular risk factors aggressively in this group to reduce the risk of stroke. These findings have great individual and societal impacts and should prompt additional study to identify the causes of these trends.
Supplementary Material
Acknowledgements
This work was supported by the National Institutes of Health under award number NINDS, R01NS030678. This manuscript is the result of funding in whole or in part by the National Institutes of Health (NIH). It is subject to the NIH Public Access Policy. Through acceptance of this federal funding, NIH has been given a right to make this manuscript publicly available in PubMed Central upon the Official Date of Publication, as defined by NIH.
Funding
This work is supported by the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS; NINDS, R01NS030678).
Disclosures
E.R. Fisher reports no disclosures relevant to the manuscript. L. Ding receives relevant funding from NINDS, R01NS03067. R.J. Stanton receives relevant funding from NINDS, R01NS03067. Y.N. Aziz, S. Demel, S. Ferioli, M.L. Flaherty, J. LaPorta, L.E. Menzies, E.M. Mistry, P. Wechsler, K.B. Walsh, O. Adeoye, E. Coleman, F.D.L.R. La Rosa, A.S. Jasne, P. Khatri, J. Mackey, S.R. Martini, L. Nobel, and S. Slavin report no disclosures relevant to the manuscript. B. Stamm receives support from NINDS, K23NS146645. M. Star, D. Woo, S. Wright, and J.P. Broderick report no disclosures relevant to the manuscript. B. Kissela and D. Kleindorfer receives relevant funding from NINDS, R01NS03067. D. Robinson receives support from NINDS, K23NS121633 and relevant funding from NINDS, R01NS03067.
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Data Availability Statement
Data not provided in the article may be shared (anonymized) at the request of any qualified investigator for purposes of replicating procedures and results.