Neurological Manifestations in COVID-19: An Unrecognized Crisis in Our Elderly?

As of December 2020, there were more than 900,000 COVID-19 hospitalizations in the US with about 414,000 among individuals aged 65 years and older. Recent evidence suggests a growing number of older patients continue to suffer serious neurological comorbidities including polyneuropathy, cerebrovascular disease, central nervous system infection, cognitive deficits, and fatigue following discharge. Studies suggest that complaints manifest late in disease and persist beyond resolution of acute COVID-19 symptoms. Recent research reports that neurocognitive symptoms are correlated with severe disease, older age, male gender, and comorbidities including hypertension, renal failure, and neoplastic disease. The underlying causes are unclear, but current hypotheses include hypoxic-ischemic brain injury, immunopathological mechanisms, and neurotropism of SARS-CoV-2 infection. There is a pressing need for more research into the underlying mechanisms of post-COVID-19 neurological sequela, particularly in the elderly, a population already burdened with neurocognitive disorders.

Chronic Kidney Disease is A Biomarker Rather Than A Risk Factor for Stroke.

BACKGROUND: Over the last approximate 15 years some have suggested that chronic kidney disease (CKD) is a risk factor for stroke in and of itself. The assertion that CKD is a risk factor for stroke requires more scrutiny. It is possible that CKD is a reflection of severity of conditions such as hypertension and diabetes that are themselves among the most treatable risk factors for stroke or it is possible that the effects of CKD change vascular and related physiological functions and therefor directly contribute to increased risk of stroke and it is also possible that treatments for advance CKD such has hemodialysis could contribute to increased risk of stroke as secondary effects of the treatment methods. To addresses these issues as participant in the Brain & Kidney Conference 2020 debate on this issue we were assigned the task of arguing that "Resolved: CKD is not a risk factor for stroke". METHODS: We performed a structured literature review in Pub Med of the currently generally accepted recognized risk factors for stroke as well as publications relating CKD and risk of stroke. RESULTS: We found that CKD and stroke is highly confounded by the cause of CKD such that the highest incidence of stroke happens in persons whose CKD is related to HTN and diabetes mellitus. Non-vascular causes of CKD have a much lower stroke incidence than those with vascular causes of CKD. When the major clinical risk factors are controlled for the relative risk of stroke drops dramatically by more than 35% to an odds ratio of only 1.1. We also found that in large population studies looking at the potential benefits of addressing treatable risk factors for stroke to reduce the incidence of stroke, CKD was either not mentioned or had a low contribution margin for treatment benefit. CONCLUSIONS: In general CKD is not a major risk factor for stroke but we argue that it is a biomarker of severity of vascular injury especially among individuals with hypertension and diabetes mellitus. Techniques for managing CKD such as hemodialysis may be related to increased risk of stroke and the contribution of CKD to intracerebral hemorrhage and brain microhemorrhages deserves more study and these were not addressed in detail in this debate.

Co-occurring Chronic Conditions and Economic Burden among Stroke Survivors in the United States: A Propensity Score-Matched Analysis.

OBJECTIVE: This study examined the impact of co-occurring chronic conditions on healthcare expenditures among noninstitutionalized older adults (age ≥50 years) with stroke in comparison to non-stroke-matched controls. METHODS: This study used a retrospective, cross-sectional, matched case-control design using pooled 2002-2012 Medical Expenditure Panel Survey (MEPS) data. Stroke survivors (N = 2913) were compared with matched controls (N = 8739) based on propensity scores. Healthcare expenditures for co-occurring chronic conditions were compared between stroke survivors and matched controls using ordinary least squares (OLS) regressions. All analyses were conducted in SAS 9.4 (SAS Institute Inc., Cary, NC, USA) using survey procedures adjusting for the complex survey design of the MEPS. RESULTS: The annual mean total healthcare expenditures (expressed in 2012 United States dollars) were significantly higher among stroke survivors compared with matched non-stroke controls ($18,796 versus $14,391, P < .001). OLS regressions revealed that co-occurring chronic conditions partially explained the excess healthcare expenditures among stroke survivors. The annual mean total healthcare expenditures among stroke survivors were significantly higher for most of the co-occurring chronic conditions compared with matched controls (e.g., in presence of hyperlipidemia, stroke survivor expenditures were $18,807 compared to $15,807 among matched controls). Stroke survivors with co-occurring arthritis, diabetes, or hypertension had significantly greater inpatient, emergency room, and prescription expenditures compared with matched controls. CONCLUSIONS: Stroke survivors experience a high economic burden. Interdisciplinary team-based treatment approaches to provide holistic care may help reduce the burden due to co-occurring chronic medical conditions among stroke survivors.

Tissue-Negative Transient Ischemic Attack: Is There a Role for Perfusion MRI?

OBJECTIVE: Approximately 60% of patients with a clinical transient ischemic attack (TIA) do not have DWI evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of perfusion MRI in the evaluation of patients with TIA who have normal DWI findings. MATERIALS AND METHODS: The inclusion criteria for this retrospective study were clinical presentation of TIA at admission with a discharge diagnosis of TIA confirmed by a stroke neurologist, MRI including both DWI and perfusion-weighted imaging within 48 hours of symptom onset, and no DWI lesion. Cerebral blood flow (CBF) and time to maximum of the residue function (Tmax) maps were evaluated independently by two observers. Multivariate analysis was used to assess perfusion findings; clinical variables; age, blood pressure, clinical symptoms, diabetes (ABCD2) score; duration of TIA; and time between MRI and onset and resolution of symptoms. RESULTS: Fifty-two patients (33 women, 19 men; age range, 20-95 years) met the inclusion criteria. A regional perfusion abnormality was identified on either Tmax or CBF maps of 12 of 52 (23%) patients. Seven (58%) of the patients with perfusion abnormalities had hypoperfused lesions best detected on Tmax maps; the other five had hyperperfusion best detected on CBF maps. In 11 of 12 (92%) patients with abnormal perfusion MRI findings, the regional perfusion deficit correlated with the initial neurologic deficits. Multivariable analysis revealed no significant difference in demographics, ABCD2 scores, or presentation characteristics between patients with and those without perfusion abnormalities. CONCLUSION: Perfusion MRI that includes Tmax and CBF parametric maps adds diagnostic value by depicting regions with delayed perfusion or postischemic hyperperfusion in approximately one-fourth of TIA patients who have normal DWI findings.

Objective fall risk detection in stroke survivors using wearable sensor technology: a feasibility study.

BACKGROUND: Stroke survivors often have persistent neural deficits related to motor function and sensation, which increase their risk of falling, most of which occurs at home or in community settings. The use of wearable technology to monitor fall risk and gait in stroke survivors may prove useful in enhancing recovery and/or preventing injuries. OBJECTIVE: Determine the feasibility of using wearable technology (PAMSys™) to objectively monitor fall risk and gait in home and community settings in stroke survivors. METHODS: In this feasibility study, we used the PAMSys to identify fall risk indicators (postural transitions: duration in seconds, and number of unsuccessful attempts), and gait (steps, speed, duration) for 48 hours during usual daily activities in stroke survivors (n = 10) compared to age-matched controls (n = 10). A questionnaire assessed device acceptability. RESULTS: Stroke survivors mean age was 70 ± 8 years old, were mainly Caucasian (60%) women (70%), and not significantly different than the age-matched controls (all P-values >0.20). Stroke survivors (100%) reported that the device was comfortable to wear, didn't interfere with everyday activities, and were willing to wear it for another 48 hours. None reported any difficulty with the device while sleeping, removing/putting back on for showering or changing clothes. When compared to controls, stroke survivors had significantly worse fall risk indicators and walked less (P < 0.05). CONCLUSION: Stroke survivors reported high acceptability of 48 hours of continuous PAMSys monitoring. The use of in-home wearable technology may prove useful in monitoring fall risk and gait in stroke survivors, potentially enhancing recovery.

Six-minute magnetic resonance imaging protocol for evaluation of acute ischemic stroke: pushing the boundaries.

BACKGROUND AND PURPOSE: If magnetic resonance imaging (MRI) is to compete with computed tomography for evaluation of patients with acute ischemic stroke, there is a need for further improvements in acquisition speed. METHODS: Inclusion criteria for this prospective, single institutional study were symptoms of acute ischemic stroke within 24 hours onset, National Institutes of Health Stroke Scale ≥3, and absence of MRI contraindications. A combination of echo-planar imaging (EPI) and a parallel acquisition technique were used on a 3T magnetic resonance (MR) scanner to accelerate the acquisition time. Image analysis was performed independently by 2 neuroradiologists. RESULTS: A total of 62 patients met inclusion criteria. A repeat MRI scan was performed in 22 patients resulting in a total of 84 MRIs available for analysis. Diagnostic image quality was achieved in 100% of diffusion-weighted imaging, 100% EPI-fluid attenuation inversion recovery imaging, 98% EPI-gradient recalled echo, 90% neck MR angiography and 96% of brain MR angiography, and 94% of dynamic susceptibility contrast perfusion scans with interobserver agreements (k) ranging from 0.64 to 0.84. Fifty-nine patients (95%) had acute infarction. There was good interobserver agreement for EPI-fluid attenuation inversion recovery imaging findings (k=0.78; 95% confidence interval, 0.66-0.87) and for detection of mismatch classification using dynamic susceptibility contrast-Tmax (k=0.92; 95% confidence interval, 0.87-0.94). Thirteen acute intracranial hemorrhages were detected on EPI-gradient recalled echo by both observers. A total of 68 and 72 segmental arterial stenoses were detected on contrast-enhanced MR angiography of the neck and brain with k=0.93, 95% confidence interval, 0.84 to 0.96 and 0.87, 95% confidence interval, 0.80 to 0.90, respectively. CONCLUSIONS: A 6-minute multimodal MR protocol with good diagnostic quality is feasible for the evaluation of patients with acute ischemic stroke and can result in significant reduction in scan time rivaling that of the multimodal computed tomographic protocol.

Effect of Tai Chi on physical function, fall rates and quality of life among older stroke survivors.

OBJECTIVE: To examine the effect of a 12-week Tai Chi (TC) intervention on physical function and quality of life. DESIGN: Single-blind, randomized controlled trial. SETTING: General community. PARTICIPANTS: Community-dwelling survivors of stroke (N=145; 47% women; mean age, 70y; time poststroke: 3y; ischemic stroke: 66%; hemiparesis: 73%) who were aged ≥50 years and were ≥3 months poststroke. INTERVENTIONS: Yang style 24-posture short-form TC (n=53), strength and range of movement exercises (SS) (n=44), or usual care (UC) (n=48) for 12 weeks. The TC and SS groups attended a 1-hour class 3 times per week, whereas the UC group had weekly phone calls. MAIN OUTCOME MEASURES: Physical function: Short Physical Performance Battery, fall rates, and 2-minute step test; quality of life: Medical Outcomes Study 36-Item Short-Form Health Survey, Center for Epidemiologic Studies Depression Scale, and Pittsburgh Sleep Quality Index. RESULTS: During the intervention, TC participants had two thirds fewer falls (5 falls) than the SS (14 falls) and UC (15 falls) groups (χ(2)=5.6, P=.06). There was a significant group by time interaction for the 2-minute step test (F2,142=4.69, P<.01). Post hoc tests indicated that the TC (t53=2.45, P=.02) and SS (t44=4.63, P<.01) groups had significantly better aerobic endurance over time, though not in the UC group (t48=1.58, P=.12). Intervention adherence rates were 85%. CONCLUSIONS: TC and SS led to improved aerobic endurance, and both are suitable community-based programs that may aid in stroke recovery and community reintegration. Our data suggest that a 12-week TC intervention was more effective in reducing fall rates than SS or UC interventions. Future studies examining the effectiveness of TC as a fall prevention strategy for community-dwelling survivors of stroke are recommended.

Strategies to improve recruitment and retention of older stroke survivors to a randomized clinical exercise trial.

BACKGROUND: Relatively few exercise randomized clinical trials (RCTs) among stroke survivors have reported the effectiveness of recruitment and retention strategies, despite its central importance to study integrity. OBJECTIVE: Our objective is to examine recruitment and retention strategies used among a group of older community-dwelling stroke survivors for an exercise RCT. METHODS: Recruitment strategies were multidimensional using both paid (ie, newspaper, radio and, television) and unpaid advertisements (ie, staff visits, flyers, and brochures placed at outpatient rehabilitation centers, physician offices, and community facilities working with older adults; free media coverage of the study, presentations at stroke support groups, relatives/friends, and study Web site) to obtain referrals. Retention strategies centered on excellent communication, the study participants' needs, and having dedicated study staff. Attrition rates and adherence to the intervention were used to examine the effectiveness of these retention strategies. RESULTS: A total of 393 referrals were received, 233 persons were screened, and 145 stroke survivors enrolled in the study. During 3 years of study recruitment, we achieved 97% of our enrollment target. We enrolled 62% of those screened. Study enrollment from paid advertising was 21.4% (n = 31), whereas unpaid advertisements resulted in 78.6% (n = 114) of our participants. Attrition was 10% (n = 14 dropouts), and adherence to the intervention was 85%. CONCLUSIONS: Recruitment and retention of participants in an exercise RCT are time and labor intensive. Multiple recruitment and retention strategies are required to ensure an adequate sample of community-dwelling stroke survivors. Many of these strategies are also relevant for exercise RCTs among adults with other chronic illnesses.

Healthcare utilization of patients with epilepsy in Yuma County, Arizona: do disparities exist?

The aim of this study was to describe the disparities in healthcare utilization and costs between Hispanic and non-Hispanic patients with seizures or epilepsy. We reviewed the insurance status and healthcare resource utilization data from 2005 to 2008 for all patients with seizures and epilepsy seen at the Yuma Regional Medical Center (YRMC). Charges for medical services provided to Hispanic patients with epilepsy between the ages of 18 and 49 were significantly less than those for non-Hispanic patients with epilepsy (Hispanic: $3167.63 versus non-Hispanic: $5154.36, P<0.001). Taking into account the differences in insurance status, setting of care, and total number of procedures, we still saw a significant difference in charges between the two groups at the outpatient settings. These data differ from currently available data on national and Eastern US Hispanic patients with epilepsy, suggesting that patients in this border community are somehow different from Hispanics elsewhere in the US.

Quantitative analysis of hypoperfusion in acute stroke: arterial spin labeling versus dynamic susceptibility contrast.

BACKGROUND AND PURPOSE: This study compares the concordance between arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) for the identification of regional hypoperfusion and diffusion-perfusion mismatch tissue classification using a quantitative method. METHODS: The inclusion criteria for this retrospective study were as follows: patients with acute ischemic syndrome with symptom onset <24 hours and acquisition of both ASL and DSC MR perfusion. The volumes of infarction and hypoperfused lesions were calculated on ASL and DSC multi-parametric maps. Patients were classified into reperfused, matched, or mismatch groups using time to maximum >6 sec as the reference. In a subset of patients who were successfully recanalized, the identical analysis was performed and the infarction and hypoperfused lesion volumes were used for paired pre- and posttreatment comparisons. RESULTS: Forty-one patients met our inclusion criteria. Twenty patients underwent successful endovascular revascularization (TICI>2a), resulting in a total of 61 ASL-DSC data pairs for comparison. The hypoperfusion volume on ASL-cerebral blood flow best approximated the DSC-time to peak volume (r=0.83) in pretreatment group and time to maximum (r=0.46) after recanalization. Both ASL-cerebral blood flow and DSC-TTP overestimated the hypoperfusion volume compared with time to maximum volume in pretreatment (F=27.41, P<0.0001) and recanalized patients (F=8.78, P<0.0001). CONCLUSIONS: ASL-cerebral blood flow overestimates the DSC time to maximum hypoperfusion volume and mismatch classification in patients with acute ischemic syndrome. Continued overestimation of hypoperfused volume after recanalization suggests flow pattern and velocity changes in addition to arterial transit delay can affects the performance of ASL.

Predictors of depressive symptoms among community-dwelling stroke survivors.

BACKGROUND: Depression is a common yet often unrecognized consequence of stroke, affecting between 25% and 70% of all survivors. Untreated depression post-stroke leads to a poorer prognosis and increased mortality. However, the pattern and profile of post-stroke depression in chronic stroke are poorly understood. OBJECTIVE: The aim of this study was to examine the independent predictors of depressive symptoms in chronic stroke. METHODS: Community-dwelling stroke survivors (n = 100) completed the Center for Epidemiological Studies-Depression (CES-D) scale, Multidimensional Scale of Perceived Social Support, Medical Outcomes Study Short Form-36, and the Pittsburgh Sleep Quality Index. Functional disability and cognitive impairment were assessed using standardized procedures. Multiple linear regression was conducted to explore potential independent predictors of depressive symptoms. RESULTS: Subjects were, on average, 70 ± 10 years old and 39 ± 49 months post-stroke. The majority were white/European-American (78%), college educated (79%), and retirees (77%). Annual income was $50 000 or greater for 32%. Hemiparesis was common (right side, 39%; left side, 42%); 35% had a Center for Epidemiological Studies-Depression scale score of 16 or higher, and 21% had a history of major depression. Approximately 64% of the variance in depressive symptoms could be explained by the independent variables in the model: quality of life, sleep quality, social support, cognitive impairment, functional disability, months post-stroke, age, gender, history of major depression, and lesion location (R = 0.64, F12,87 = 12.97, P < .01). Only poor quality of life (t1,87 = -6.99, P < .01) and low social support (t1,87 = -2.14, P = .04) contributed uniquely and significantly to the severity of depressive symptoms among these stroke survivors. CONCLUSION: Depressive symptoms are prevalent in chronic stroke survivors, even among an educated and economically advantaged population. Our findings are similar to reports by others that poor quality of life and low social support are major contributors to depressive symptoms in chronic stroke and should be routinely assessed and monitored to improve long-term rehabilitation efforts and promote wellness and community reintegration.

Community-based Yang-style Tai Chi is safe and feasible in chronic stroke: a pilot study.

OBJECTIVE: Examine the safety and feasibility of a 12-week Tai Chi intervention among stroke survivors. DESIGN: Two-group, prospective pilot study with random allocation. SETTING: Outpatient rehabilitation facility. SUBJECTS: Stroke survivors ≥50 years and at ≥three months post-stroke. INTERVENTIONS: Tai Chi subjects attended group-based Yang Style classes three times/week for 12-weeks, while Usual Care subjects received weekly phone calls along with written materials/resources for participating in community-based physical activity. MAIN OUTCOME MEASURES: Indicators of study safety and feasibility included recruitment rates, intervention adherence, falls or adverse events, study satisfaction, drop-outs, and adequacy of the outcomes measures. RESULTS: Interested persons pre-screened by phone (n = 69) were on average 68 years old, (SD = 13) years old, 48% (n = 33) women, 94% (n = 65) were at least three months post-stroke. A total of 28 subjects aged 69 (SD = 11) years enrolled in this pilot study. Intervention adherence rates were very high (≥92%). There were no falls or other adverse events. The dose of Tai Chi exercise (≥150 minutes/week) was well tolerated. Overall study satisfaction was high (8.3 (SD = 1.9); 1 = not satisfied, 10 = most satisfied), while drop-outs (n = 3, 11%) were unrelated to study intervention. Score distributions for the outcome measures were approximately normal, sensitive to change, and seemed to favor the Tai Chi intervention. CONCLUSIONS: Tai Chi is a safe, community-based exercise program for stroke survivors. Our data suggest that recruitment and retention of an adequate sample is feasible, and that in a full-scale study 52 subjects/group are needed to detect statistically significant between group differences (alpha = 0.05, power = 0.80).

Predictors of gait velocity among community-dwelling stroke survivors.

INTRODUCTION: Gait velocity is an objective, fundamental indicator of post-stroke walking ability. Most stroke survivors have diminished aerobic endurance or paretic leg strength affecting their walking ability. Other reported underlying factors affecting gait velocity include functional disability, balance, cognitive impairment, or the distance they are required to walk. OBJECTIVE: To examine the relationship between gait velocity and measures of physical and cognitive functioning in chronic stroke. METHODS: Cross-sectional design using baseline data from community-dwelling stroke survivors enrolled in an exercise intervention study. Functional disability (modified Rankin Scale), aerobic endurance (2-min step-test), leg strength (timed 5-chair stand test), balance (single-leg stance) and cognitive impairment (Mini-Mental Status Exam) were assessed. Gait velocity was assessed using a timed 4-m walk test. Multiple linear regression was used to explore potential independent predictors of gait velocity. RESULTS: Subjects had an average gait velocity of 0.75±0.23m/s, categorized as limited community walkers. Approximately 37% of the variance in gait velocity, could be explained by the 5 independent variables, functional disability, aerobic endurance, leg strength, balance, and cognitive impairment (R(2)=0.37, F(5,74)=8.64, p<0.01). Aerobic endurance (t(1,74)=3.41, p<0.01) and leg strength (t(1,74)=-2.23, p=0.03) contributed significantly to gait velocity. CONCLUSION: Diminished aerobic endurance and leg strength are major contributors to slow gait velocity in chronic stroke. Long term rehabilitation efforts are needed to improve gait velocity in chronic stroke, and may need to incorporate multifaceted strategies concurrently, focusing on aerobic endurance and leg strength, to maximize community ambulation and reintegration.

Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial.

BACKGROUND AND PURPOSE: Hyperglycemia may worsen brain injury during acute cerebral infarction. We tested the feasibility and tolerability of aggressive hyperglycemia correction with intravenous insulin compared with usual care during acute cerebral infarction. METHODS: We conducted a randomized, multicenter, blinded pilot trial for patients with cerebral infarction within 12 hours after onset, a baseline glucose value >or=8.3 mmol/L (>or=150 mg/dL), and a National Institutes of Health Stroke Scale score of 3 to 22. Patients were randomized 2:1 to aggressive treatment with continuous intravenous insulin or subcutaneous insulin QID as needed (usual care). Target glucose levels were <7.2 mmol/L (<130 mg/dL) in the aggressive-treatment group and <11.1 mmol/L (<200 mg/dL) in the usual-care group. Glucose was monitored every 1 to 2 hours, and the protocol treatments continued for up to 72 hours. Final clinical outcomes were assessed at 3 months. RESULTS: We randomized 46 patients (31 to aggressive treatment and 15 to usual care). All patients in the aggressive-treatment group and 11 (73%) in the usual-care group had diabetes (P=0.008). Glucose levels were significantly lower in the aggressive-treatment group throughout protocol treatment (7.4 vs 10.5 mmol/L [133 vs 190 mg/dL], P<0.001). Hypoglycemia <3.3 mmol/L (<60 mg/dL) occurred only in the aggressive-treatment group (11 patients, 35%), 4 (13%) of whom had brief symptoms, including only 1 (3%) neurologic. Final clinical outcomes were nonsignificantly better in the aggressive-treatment group. CONCLUSIONS: The intravenous insulin protocol corrected hyperglycemia during acute cerebral infarction significantly better than usual care without major adverse events and should be investigated in a clinical efficacy trial.

Leukocyte-platelet aggregates in rat peripheral blood after ischemic stroke and reperfusion.

Ischemic stroke and reperfusion (ISR) is associated with an inflammatory response characterized, in part, by the formation of leukocyte-platelet aggregates (LPA). Aggregate formation may amplify the immunologic and hemostatic functions of both cell types and thus exacerbate reperfusion injury after ischemic stroke. LPA formation in peripheral blood may also serve as a biomarker of the severity of injury. However, it is not fully known whether ISR causes LPA formation that can be detected in the peripheral blood. Therefore, the purpose of this study was to measure LPA in the peripheral blood after ISR using a rat model. The filament method was used to perform ISR. Blood was collected from the jugular vein before ischemia, after 4 hours of ischemia, and after 1 hour of reperfusion. Flow cytometry was used to quantify LPA in peripheral blood. Separate ISR groups were treated with tirofiban, a platelet GPIIb/IIIa inhibitor, and fucoidan, a selectin adhesion molecule inhibitor, and analyzed for LPA. Leukocyte CD11b expression and reactive oxygen species production were also analyzed to note the role of polymorphonuclear neutrophilic (PMN) activation on LPA formation. After ISR, LPA levels in peripheral blood were twice as large as preischemic levels. Both GPIIb/IIIa and selectin adhesion molecule inhibition (p < .05) decreased LPA to preischemic values. PMN CD11b expression was increased above baseline but did not differ between groups. Reactive oxygen species production did not differ between groups during reperfusion. These data suggest that ischemic stroke and reperfusion results in an increase in LPA that can be consistently measured in peripheral blood. LPA formation may be a useful biomarker and potential therapeutic target after ischemic stroke and reperfusion.