Moving toward elucidating alternative motor pathway structures post-stroke: the value of spinal cord neuroimaging.

Stroke results in varying levels of motor and sensory disability that have been linked to the neurodegeneration and neuroinflammation that occur in the infarct and peri-infarct regions within the brain. Specifically, previous research has identified a key role of the corticospinal tract in motor dysfunction and motor recovery post-stroke. Of note, neuroimaging studies have utilized magnetic resonance imaging (MRI) of the brain to describe the timeline of neurodegeneration of the corticospinal tract in tandem with motor function following a stroke. However, research has suggested that alternate motor pathways may also underlie disease progression and the degree of functional recovery post-stroke. Here, we assert that expanding neuroimaging techniques beyond the brain could expand our knowledge of alternate motor pathway structure post-stroke. In the present work, we will highlight findings that suggest that alternate motor pathways contribute to post-stroke motor dysfunction and recovery, such as the reticulospinal and rubrospinal tract. Then we review imaging and electrophysiological techniques that evaluate alternate motor pathways in populations of stroke and other neurodegenerative disorders. We will then outline and describe spinal cord neuroimaging techniques being used in other neurodegenerative disorders that may provide insight into alternate motor pathways post-stroke.

Hemorrhagic stroke outcomes of KApSR patients with co-morbid diabetes and Alzheimer's disease.

BACKGROUND: Vascular risk factors, such as diabetes mellitus (DM), are associated with poorer outcomes following many neurodegenerative diseases, including hemorrhagic stroke and Alzheimer's disease (AD). Combined AD and DM co-morbidities are associated with an increased risk of hemorrhagic stroke and increased Medicare costs. Therefore, we hypothesized that patients with DM in combination with AD, termed DM/AD, would have increased hemorrhagic stroke severity. METHODS: Kentucky Appalachian Stroke Registry (KApSR) is a database of demographic and clinical data from patients that live in Appalachia, a distinct region with increased health disparities and stroke severity. Inpatients with a primary indication of hemorrhagic stroke were selected from KApSR for retrospective analysis and were separated into four groups: DM only, AD only, neither, or both. RESULTS: Hemorrhagic stroke patients (2,071 total) presented with either intracerebral hemorrhage (ICH), n=1,448, or subarachnoid hemorrhage (SAH), n=623. When examining all four groups, subjects with AD were significantly older (AD+, 80.9±6.6 yrs) (DM+/AD+, 77.4±10.0 yrs) than non AD subjects (DM-/AD-, 61.3±16.5 yrs) and (DM+, 66.0±12.5 yrs). A higher percentage of females were among the AD+ group and a higher percentage of males among the DM+/AD+ group. Interestingly, after adjusting for multiple comparison, DM+/AD+ subjects were ten times as likely to suffer a moderate to severe stroke based on a National Institute of Health Stroke (NIHSS) upon admission [odds ratio (95% CI)] compared to DM-/AD- [0.1 (0.02-0.55)], DM+ [0.11 (0.02-0.59)], and AD+ [0.09(0.01-0.63)]. The odds of DM+/AD+ subjects having an unfavorable discharge destination (death, hospice, long-term care) was significant (P<0.05) from DM-/AD- [0.26 (0.07-0.96)] when adjusting for sex, age, and comorbidities. CONCLUSIONS: In our retrospective analysis utilizing KApSR, regardless of adjusting for age, sex, and comorbidities, DM+/AD+ patients were significantly more likely to have had a moderate or severe stroke leading to an unfavorable outcome following hemorrhagic stroke.

Neurotoxicology: Clinical Approach and Causal Inference.

Clinical neurotoxicology is an unrecognized neurologic subspecialty. Few neurology residency programs offer an organized education or training in the field. Nevertheless, neurotoxic exposures and subsequent injuries are common. This article provides a basic approach to clinical assessment and causal inference. It addresses the knowledge gap for clinical practice and provides a thematic structure to use interdisciplinary resources.

Toxin-Induced Cerebellar Disorders.

The cerebellum plays an important role in motor and nonmotor systems, with damage resulting in clinical manifestations presenting as weakness, ataxia, dysarthria, and nystagmus. There are numerous environmental and industrial agents as well as medications that, through either accidental or intentional use, can result in a range of neurologic presentations. The variability in the presentation is important to recognize promptly so that early cessation in exposure, use, or abuse can be initiated to reduce the severity of symptoms. Recognition of an agent causing the particular pathology is important so that the route of exposure, and subsequent treatment options can be identified.

Neurotoxicity and Chemoreception: A Systematic Review of Neurotoxicity Effects on Smell and Taste.

Several different types of exposure have the potential to produce olfactory and gustatory deficits related to neurotoxicity. Although the literature contains relatively few studies of such chemoreceptive dysfunction in the context of toxic exposure, this review explores the strength of such published associations. Several studies collectively demonstrated moderately strong evidence for an association between manganese dust exposure and olfactory deficits. Evidence of associations between individual chemicals, therapeutics, and composites, such as World Trade Center debris, and olfactory and gustatory deficits remains limited or mixed. Further need for controlled studies for clinical management, exposure limits, and policy development is identified.

High Prevalence of Moyamoya Syndrome in Appalachia.

INTRODUCTION: Moyamoya is a chronic cerebrovascular condition of unclear etiology characterized by progressive occlusion of 1 or both internal carotid arteries with neovascular collateral formation. With both an idiopathic form (moya-moya disease) and congenital condition-associated form (moyamoya syndrome), it can cause ischemic and hemorrhagic stroke. Recent findings in Kentucky have challenged traditional estimates of its incidence in US populations. Using the Kentucky Appalachian Stroke Registry (KApSR), our aim was to further characterize its incidence as a cause of stroke and to understand the patient population in Appalachia. METHODS: A retrospective review of moyamoya patients was performed using the KApSR database. Data collected included demographics, county location, risk factors, comorbidities, and health-care encounters from January 1, 2012, to December 31, 2016. RESULTS: Sixty-seven patients were identified; 36 (53.7%) resided in Appalachian counties. The cohort accounted for 125 of 6,305 stroke admissions, representing an incidence of 1,983 per 100,000 stroke admissions. Patients presented with ischemic strokes rather than hemorrhagic strokes (odds ratio 5.50, 95% CI: 2.74-11.04, p < 0.01). Eleven patients (16.4%) exhibited autoimmune disorders. Compared to the general population with autoimmune disorder prevalence of 4.5%, the presence of autoimmunity within the cohort was significantly higher (p < 0.01). Compared to non-Appalachian patients, Appalachian patients tended to present with lower frequencies of tobacco use (p = 0.08), diabetes mellitus (p = 0.13), and hypertension (p = 0.16). CONCLUSIONS: Moyamoya accounts for a substantial number of stroke admissions in Kentucky; these patients were more likely to develop an ischemic stroke rather than a hemorrhagic stroke. Autoimmune disorders were more prevalent in moyamoya patients than in the general population. The reduced frequency of traditional stroke risk factors within the Appalachian group suggests an etiology distinct to the population.

Evaluation of Patients with High National Institutes of Health Stroke Scale as Thrombectomy Candidates Using the Kentucky Appalachian Stroke Registry.

INTRODUCTION: Mechanical thrombectomy has become standard of care for emergent large vessel occlusive stroke. Estimates of incidence for thrombectomy eligibility vary significantly. National Institutes of Health Stroke Scale (NIHSS) of 10 or greater is highly predictive of large vessel occlusion. Using our Kentucky Appalachian Stroke Registry (KApSR), we evaluated temporal trends in stroke admissions with NIHSS ≥10 to determine patient characteristics among that group along with effects and needs in thrombectomy utilization. METHODS: Using the KApSR database that captures patients throughout the Appalachian region in our stroke network, we evaluated patients admitted with ischemic stroke with NIHSS ≥10. We recorded demographics, comorbidities, treatment (thrombectomy, decompressive craniectomy), and county of origin. Change in NIHSS from admission to discharge was used as an indicator of inpatient outcome. RESULTS: Between 2010 and 2016, 1,510 patients were admitted with NIHSS ≥10. 87.2% had high blood pressure, 69.6% had dyslipidemia, and 41.7% used tobacco. There were significant sex differences in the types of patients presenting with NIHSS ≥10 with females being older on average and having more atrial fibrillation and obesity. There was an increase in thrombectomy utilization from 2010 to 2016, but only 7.5% of the potentially eligible patients underwent the procedure. In comparison to the period 2010-2014, the 2015-2016 period had higher rates of obesity and tobacco abuse. CONCLUSION: Among patients with significant burden of ischemic stroke, the most common coexisting medical condition was high blood pressure. Patients who underwent thrombectomy had significantly better inpatient clinical improvement. These data support the need to maximize utilization of thrombectomy along with need to devote increased resources on modifiable stroke risk factors.

The Prevalence of Multiple Comorbidities in Stroke Survivors in Rural Appalachia and the Clinical Care Implications.

BACKGROUND: The majority of studies on multimorbidity have been in aging populations and there is a paucity of data on individuals following stroke. OBJECTIVE: In order to better understand the overall complexity of the stroke population in rural Kentucky, we examined the prevalence of multimorbidity that impact the overall long-term health and health care for these individuals. METHODS: A secondary analysis examined whether there are gender or age differences in this stroke population related to the prevalence of multimorbidity. A total of 5325 individuals, 18 years of age and older, seen at an academic medical center for the primary diagnosis of acute ischemic stroke or transient ischemic attack between the years of 2010-2017 were identified using the Kentucky Appalachian Stroke Registry. Descriptive analysis was used to report the prevalence of each comorbidity in the rural population by age group, gender, and level of multimorbidity by looking at concurrent frequencies. RESULTS: Overall, hypertension, dyslipidemia, tobacco use, diabetes, and obesity were the comorbidities with the highest prevalence in our population irrespective of gender. Over 78% (n = 4153) of the individuals had 3 or more comorbidities while 61% (n = 3285) had at least 3 out of the top 5 comorbidities (hypertension, hyperlipidemia, tobacco, obesity, diabetes). With respect to age, 15% (n = 795) of the sample was under the age of 50, while 32% (n = 1704) were between the age of 50 and 64 and 53% (n = 2826) of the sample were 65 years or older. CONCLUSIONS: The results of this study indicate the majority of individuals affected by stroke in rural Appalachia Kentucky have multimorbidity. In addition, almost half of these individuals are having their strokes at a younger age, which will require a shift in the focus for therapeutic interventions (eg, reintegration into the workforce versus just community reintegration).

Derivation of combined species sensitivity distributions for acute toxicity of pyrethroids to aquatic animals.

The aquatic toxicity profiles of synthetic pyrethroid insecticides are remarkably similar, and results for a large number of species can be combined across compounds in Species Sensitivity Distributions (SSDs). Normalizing acute toxicity values (median lethal concentrations, LC50s) for each species and each pyrethroid to the LC50 of the same pyrethroid to the freshwater amphipod Hyalella azteca (the most sensitive species to all pyrethroids tested) enabled expression of LC50s as Hyalella equivalents that can be pooled across pyrethroids. The resulting normalized LC50s (geometric means for each species across pyrethroids) were analyzed using SSDs. Based on tests with measured exposure concentrations, the fifth percentiles (Hazard Concentrations, HC5s) of the SSDs were 4.8 Hyalella equivalents for arthropods (36 species) and 256 Hyalella equivalents for fish (24 species). HC5 values are useful as effects metrics for screening-level risk assessments, and the full SSDs can be integrated with estimated exposure distributions for higher-level risk characterization. The combined pyrethroid SSDs provide a more taxonomically representative and statistically robust basis for risk characterization than data for the most sensitive single species or SSDs based on data for a single pyrethroid alone, and are especially useful for pyrethroids that have been tested with smaller numbers of species.

The Kentucky Appalachian Stroke Registry (KApSR).

BACKGROUND: The population of rural Kentucky and West Virginia has a disproportionately high incidence of stroke and stroke risk factors. The Kentucky Appalachian Stroke Registry (KApSR) is a novel registry of stroke patients developed to collect demographic and clinical data in real time from these patients' electronic health records. OBJECTIVE: We describe the development of this novel registry and test it for ability to provide the information necessary to identify care gaps and direct clinical management. METHODS: The KApSR was developed as described in this article. To assess utility in patient care, we developed a "Diabetes Quality Assurance Dashboard" by cross-referencing patients in the registry with a diagnosis of ischemic cerebrovascular disease with patients that were tested for hemoglobin A1c (HbA1c) levels, patients with HbA1c levels diagnostic for diabetes mellitus (DM), and patients with an elevated HbA1c that were formally diagnosed with DM. RESULTS: For the 1008 patients treated for ischemic cerebrovascular disease in the year studied, 859 (85%) had their HbA1c tested. Of those, 281 had levels of 6.5 or greater, although only 261 (93%) were discharged with a formal diagnosis of DM. CONCLUSIONS: The KApSR has practical value as a tool to assess a large population of patients quickly for care quality and for research purposes.

Small Rural Hospitals Have a Harder Time Achieving Success in Continuous Quality Improvement: An Example From a Stroke Care Network.

BACKGROUND: University of Kentucky HealthCare established a Stroke Care Network (SCN) in 2008 to address the challenges of rural stroke care and improve care quality. METHODS: The SCN collects quality data from each affiliate that include volumes, mortality, length of stay, turnaround times, rt-PA door-to-needle time, 8 stroke core measures, and dysphagia screen measure. Characteristics of affiliate hospital studies include number of beds, Stroke Disease-Specific Care (DSC) certification by The Joint Commission, Appalachian designated county or not, time dedicated to stroke coordinator, submission of quality data for the calendar year, success of data, and utilization of American Heart Association's Get With the Guidelines. RESULTS: Seventeen of 23 (74%) affiliate hospitals submitted data. Highest scoring quality measures were antithrombotic by discharge (96%), antithrombotic by end of day 2 (93%), and assessed for rehabilitation (92%). Hospitals with DSC certification were more likely to succeed in stroke quality than those without (P = .0357). Hospitals in Appalachian counties were less likely to succeed in quality measures than those in non-Appalachian designated counties (P = .02). CONCLUSIONS: Our results demonstrate successful collection of quality data among hospitals bound only by an affiliation agreement. Areas to improve quality identified are door to computed tomographic interpretation, thrombolytic therapy, and dysphagia screening. We suspect that DSC certification is driving quality success in our network hospitals. That Appalachian affiliate hospitals are less likely to succeed could be due to a number of reasons such as the fewer resources available in Appalachian counties and may reflect the financial plight of rural hospitals more generally.

Evaluations of Neurologists by Their Patients and Residents Are Inversely Correlated.

OBJECTIVE AND BACKGROUND: We hypothesized that evaluation scores for attending neurologists by patients and residents would parallel one another. Additionally, we hypothesized that provider productivity would be also be associated with performance evaluations by patients and residents. METHODS: In a university neurology department, we collected individual Clinician and Group Consumer Assessment of Healthcare Providers and Systems patient satisfaction scores and standardized resident evaluation scores (n = 22 faculty members). We performed bivariate analysis of doctor-patient satisfaction versus resident evaluation scores. RESULTS: Attending neurologists with higher patient satisfaction received lower resident evaluation scores (P < .05). There seem to be disproportionate neurologists with low evaluations not meeting clinical productivity targets. CONCLUSION: Finding a significant inverse correlation was surprising. Perhaps what is valued by patients in their physician is not what residents value in teachers. That deserves further study. Maybe attending physicians who spend their energy on the patient experience do not have sufficient time to devote to teaching and vice versa. That neurologists with low evaluation scores appear more likely to not meet productivity targets supports this idea.

Innovation in Stroke Care Quality: NIH Stroke Scale Change and Shewhart Charts.

Stroke care, admission through discharge, is a process that should lead to symptomatic improvement. Improvement or decline in conditions of patients with acute stroke during hospitalization can be measured by the National Institutes of Health Stroke Scale (NIH Stroke Scale or NIHSS) at both admission and discharge and may indicate the overall quality of acute stroke care for a patient and the stability of care in the system. Shewhart control charts were analyzed for 98 patients with stroke admissions in a random sample at a tertiary care stroke center to determine the feasibility of examining the NIHSS score change to detect statistical control or identify excess variance in outcomes. The study sample showed a mean improvement of 1.33 points from admission to discharge on the NIHSS. Three statistical outliers were found. Excess statistical variation clustered within a specific stroke team's tenure suggested a need for targeted education and examination for process redesign. Using the NIHSS and the Shewhart control charts identified a systematic process flaw that could be targeted to improve stroke outcomes and move the delivery system toward statistical control.

Comparative sensitivity of field and laboratory populations of Hyalella azteca to the pyrethroid insecticides bifenthrin and cypermethrin.

Hyalella azteca are epibenthic invertebrates that are widely used for toxicity studies. They are reported to be more sensitive to pyrethroid insecticides than most other test species, which has prompted considerable use of this species in toxicity testing of ambient surface waters where the presence of pyrethroids is suspected. However, resident H. azteca have been found in some ambient water bodies reported to contain surface water and/or sediment pyrethroid concentrations that are toxic to laboratory reared H. azteca. This observation suggests differences in the sensitivities of laboratory reared and field populations of H. azteca to pyrethroids. The goal of the present study was to determine the sensitivities of laboratory reared and field populations of H. azteca to the pyrethroids bifenthrin and cypermethrin. Specimens of H. azteca were collected from resident populations at field sites that are subject to varied land-use activities as well as from laboratory populations. These organisms were exposed to bifenthrin- or cypermethrin-spiked water in 96-h water-only toxicity tests. The resulting data demonstrated that: 1) field-collected populations in urban and agricultural settings can be >2 orders of magnitude less sensitive to the pyrethroids than laboratory reared organisms; 2) field-collected organisms varied in their sensitivity (possibly based on land-use activities), with organisms collected from undeveloped sites exhibiting sensitivities similar to laboratory reared organisms; and 3) the sensitivity of field-collected "tolerant" organisms increased in subsequent generations reared under laboratory conditions. Potential mechanisms for these differences are discussed.

Understanding history, and not repeating it. Neuroprotection for acute ischemic stroke: from review to preview.

BACKGROUND: Neuroprotection for ischemic stroke is a growing field, built upon the elucidation of the biochemical pathways of ischemia first studied in the 1970s. Beginning in the early 1990s, means by which to pharmacologically intervene and counteract these pathways have been sought, though with little clinical success. Through a comprehensive review of translations from laboratory to clinic, we aim to evaluate individual mechanisms of action, while highlighting potential barriers to success that will guide future research. METHODS: The MEDLINE database and The Internet Stroke Center clinical trials registry were queried for trials involving the use of neuroprotective agents in acute ischemic stroke in human subjects. For the purpose of the review, neuroprotective agents refer to medications used to preserve or protect the potentially ischemic tissue after an acute stroke, excluding treatments designed to re-establish perfusion. This excludes mechanical or pharmacological thrombolytics, anti-thrombic medications, or anti-platelet therapies. RESULTS: This review summarizes previously trialed neuroprotective agents, including but not limited to glutamate neurotransmission blockers, anti-oxidants, GABA agonists, leukocyte migration blockers, various small cation channel modulators, narcotic antagonists, and phospholipid membrane stabilizers. We outline key biochemical steps in ischemic injury that are the proposed areas of intervention. The agents, time to administration of therapeutic agent, follow-up, and trial results are reported. DISCUSSION: Stroke trials in humans are burdened with a marked heterogeneity of the patient population that is not seen in animal studies. Also, trials to date have included patients that are likely treated at a time outside of the window of efficacy for neuroprotective drugs, and have not effectively combined thrombolysis with neuroprotection. Through an evaluation of the accomplishments and failures in neuroprotection research, we propose new methodologies, agents, and techniques that may provide new routes for success.