Deep Medullary Vein White Matter Injury Global Severity Score Predicts Neurodevelopmental Impairment.

AIM: To examine associations between the deep medullary vein white matter injury global severity scoring system and neurodevelopmental impairment. METHODS: This is a prospective observational cohort study of infants born at ≥32 weeks, diagnosed with deep medullary vein thrombosis and infarction on neuroimaging in the first month of life. Developmental testing was performed using validated measures for early, preschool, and school-age follow-up. RESULTS: Nineteen (37%) patients had major neurodevelopmental impairment. Global severity score was higher among patients with neurodevelopmental impairment (21.6 vs 13.4, P = .04). Overall, 78% of patients with epilepsy had neurodevelopmental impairment. A greater degree of asymmetry with right-sided injury predominance was associated with lower Bayley-III cognitive scores and presence of neurodevelopmental impairment (P < .01). CONCLUSIONS: Results suggest a need for targeted clinical surveillance for patients with a high global severity score and/or asymmetric, predominantly right cerebral white matter injury and for those who develop epilepsy.

Possible affective cognitive cerebellar syndrome in a young patient with COVID-19 CNS vasculopathy and stroke.

Early case series suggest that about one-third of patients with COVID-19 present with neurological manifestations, including cerebrovascular disease, reported in 2%-6% of hospitalised patients. These are generally older patients with severe infection and comorbidities. Here we discuss the case of a previously fit and well 39-year-old man who presented with fever and respiratory symptoms, evolving in pneumonia with hypoxia but only requiring continuous positive airway pressure. After resolution of the respiratory disease, the patient developed focal neurology and was found to have bilateral occipital, thalamic and cerebellar infarcts. A diagnosis of COVID-19 central nervous system vasculopathy was made. He developed a florid neuropsychiatric syndrome, including paranoia, irritability, aggression and disinhibition, requiring treatment with antipsychotics and transfer to neurorehabilitation. Neuropsychometry revealed a wide range of cognitive deficits. The rapid evolution of the illness was matched by fast resolution of the neuropsychiatric picture with mild residual cognitive impairment.

miR-22 and cerebral microbleeds in brainstem and deep area are associated with depression one month after ischemic stroke.

In this study, we aimed to explore the relationship among miR-22, deep cerebral microbleeds (CMBs), and post-stroke depression (PSD) 1 month after ischemic stroke. We consecutively recruited 257 patients with first-ever and recurrent acute cerebral infarction and performed PSD diagnosis in accordance with the Diagnostic and Statistical Manual IV criteria for depression. Clinical information, assessments of stroke severity, and imaging data were recorded on admission. We further detected plasma miR-22 using quantitative PCR and analyzed the relationship among miR-22, clinical data, and PSD using SPSS 23.0 software. Logistic regression showed that deep (OR=1.845, 95%CI: 1.006-3.386, P=0.047) and brain stem CMBs (OR=2.652, 95%CI: 1.110-6.921, P=0.040), as well as plasma miR-22 levels (OR=2.094, 95%CI: 1.066-4.115, P=0.032) were independent risk factors for PSD. In addition, there were significant differences in baseline National Institutes of Health Stroke Scale scores (OR=1.881, 95%CI: 1.180-3.011, P=0.007) and Widowhood scores (OR=1.903, 95%CI: 1.182-3.063, P=0.012). Analysis of the receiver operating curve (AUC=0.723, 95%CI: 0.562-0.883, P=0.016) revealed that miR-22 could predict PSD one month after ischemic stroke. Furthermore, plasma miR-22 levels in brainstem and deep CMBs patients showed an upward trend (P=0.028) relative to the others. Patients with acute ischemic stroke, having brainstem and deep cerebral microbleeds, or a higher plasma miR-22 were more likely to develop PSD. These findings indicate that miR-22 might be involved in cerebral microvascular impairment and post-stroke depression.

miR-22 and cerebral microbleeds in brainstem and deep area are associated with depression one month after ischemic stroke

In this study, we aimed to explore the relationship among miR-22, deep cerebral microbleeds (CMBs), and post-stroke depression (PSD) 1 month after ischemic stroke. We consecutively recruited 257 patients with first-ever and recurrent acute cerebral infarction and performed PSD diagnosis in accordance with the Diagnostic and Statistical Manual IV criteria for depression. Clinical information, assessments of stroke severity, and imaging data were recorded on admission. We further detected plasma miR-22 using quantitative PCR and analyzed the relationship among miR-22, clinical data, and PSD using SPSS 23.0 software. Logistic regression showed that deep (OR=1.845, 95%CI: 1.006-3.386, P=0.047) and brain stem CMBs (OR=2.652, 95%CI: 1.110-6.921, P=0.040), as well as plasma miR-22 levels (OR=2.094, 95%CI: 1.066-4.115, P=0.032) were independent risk factors for PSD. In addition, there were significant differences in baseline National Institutes of Health Stroke Scale scores (OR=1.881, 95%CI: 1.180-3.011, P=0.007) and Widowhood scores (OR=1.903, 95%CI: 1.182-3.063, P=0.012). Analysis of the receiver operating curve (AUC=0.723, 95%CI: 0.562-0.883, P=0.016) revealed that miR-22 could predict PSD one month after ischemic stroke. Furthermore, plasma miR-22 levels in brainstem and deep CMBs patients showed an upward trend (P=0.028) relative to the others. Patients with acute ischemic stroke, having brainstem and deep cerebral microbleeds, or a higher plasma miR-22 were more likely to develop PSD. These findings indicate that miR-22 might be involved in cerebral microvascular impairment and post-stroke depression.

Association Between Silent Brain Infarcts and Cognitive Function: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Silent brain infarct (SBI), which has traditionally been considered clinically silent, has been proposed as a subclinical risk marker for future cognitive function decline. METHODS: We conducted a systematic review of literature in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure database. RESULTS: In the end, 19 case-control studies, comprising 6712 participants, and 3 prospective cohort studies comprising 4433 participants, met all inclusion criteria and were included in the systematic review. Meta-analysis of 9 studies showed that SBI was an important factor in cognitive function decline (Mini-Mental State score) (standardized mean difference -.47, 95% confidence interval; -.72 to -.22). Another meta-analysis of 4 studies reported the SBI was an independent factor in cognitive dysfunction (Montreal Cognitive Assessment Scale) (standardized mean difference -3.36, 95% confidence interval; -5.90 to -.82). Ten studies further reported that SBI was associated with decreases in specific areas of cognitive function. CONCLUSIONS: These results suggest that rather than being clinically silent, SBI might be a factor inducing cognitive dysfunction.

Prevalence and Risk Factors of Brain Infarcts and Associations With Cognitive Performance in Tenants of Marginal Housing.

Background Homeless and vulnerably housed individuals are at increased risk for multimorbidity compared with the general population. We assessed prevalence of brain infarcts on neuroimaging and associations with vascular risk factors and cognitive performance in a prospective study of residents living in marginal housing. Methods and Results Two hundred twenty-eight participants underwent structured clinical interviews, targeted clinical, laboratory, and neuropsychological assessments, and magnetic resonance imaging with T1, T2-fluid-attenuated inversion recovery and susceptibility-weighted images. Subjects underwent cognitive testing to assess premorbid IQ , verbal learning and memory, inhibition, sustained attention, mental flexibility, and decision making. In this sample (mean age 44.0 years [ SD 9.4], 77% male), prevalence of conventional vascular risk factors was lower than in the general population apart from tobacco use (94%). Ten-year Framingham risk for any cardiovascular event was 11.4%±9.2%. Brain infarcts were present in 25/228 (11%). All were ischemic (40% cortical, 56% lacunar, 4% both). Participants with infarcts were older than those without (48.9±9.4 versus 43.4±9.2, P=0.006). In a multivariable regression analysis, only age remained a significant predictor of brain infarcts (odds ratio 1.08, 95% CI 1.02-1.14, P=0.004). After controlling for age and education, the presence of infarct was a significant predictor of impaired decision making on the Iowa Gambling Task of decision making (ß -28.2, 95% CI -42.7 to -14.1, P<0.001). Conclusions Prevalence of infarcts on neuroimaging in this disadvantaged, community-dwelling cohort was much higher than expected for age and was associated with impaired decision making. Further research is needed to identify individuals at highest risk who may benefit from targeted preventative strategies.

Cingulate infarction: A neuropsychological and neuroimaging study.

BACKGROUND AND PURPOSE: Ischemic lesions rarely affect the cingulate cortex (CC) in isolation, restricting human lesion/behavioural change correlational analysis. The aim of this study was to determine clinical, neuropsychological and neuroimaging features of isolated cingulate infarcts. METHODS: We studied, 3800 patients with first-ever ischemic stroke included in our Stroke Registry between 2012 and 2018. Among them we studied 7 patients with an acute isolated cingulate infarct confirmed by MRI. RESULTS: Among all patients, 7 patients (0.01%) showed ischemic lesions in the territory of cingulate cortex territory, allowing us to delineate 2 substantial distributions; (1) Anterior cingulate cortex (ACC) infarction (4 patients [57%]) was presented low vigilance level with apathy, mutism, deficits in executive function, attention, and disturbances of working, episodic and verbal memory; (2) Posterior cingulate cortex (PCC) infarction (3 patients [43%]) developed topographic disorientation, visual memory deficit and affective-emotional behavioural changes. CONCLUSIONS: According rarely seen CC infarction events, we suggest that anterior and posterior CC are functionally separated and differences in clinical presentation are explained by considering; ACC plays a role in executive functions, episodic and working memory, set maintenance, and PCC is focused on spatial and verbal attention, and memory system. We considered that different patterns of cingulate infarcts are the result of variation in cingulate arterial supply or suggest a source of embolism.

DEFENSIVE Stroke Scale: Novel Diagnostic Tool for Predicting Posterior Circulation Infarction in the Emergency Department.

BACKGROUND: Dizziness is the most common posterior circulation symptom; however, diagnosing a posterior circulation infarction is difficult due to a lack of typical symptoms. We aimed to investigate the frequency of misdiagnosis of a posterior circulation infarction in patients who presented with dizziness and to develop a new stroke scale that increased the diagnostic accuracy for stroke among these subjects. METHODS: We retrospectively analyzed consecutive data from subjects hospitalized with ischemic stroke who presented with dizziness (the developmental phase). Based on these results, we created a novel stroke scale, which was used as a diagnostic procedure in the prospective validation phase. We compared the rate of misdiagnosis of ischemic stroke between phases. RESULTS: During the development phase, 115 subjects were hospitalized for ischemic stroke accompanied by dizziness. Six ischemic stroke subjects were not properly diagnosed (6/115, 5.2%). We created the new DisEquilibrium, Floating sEnsation, Non-Specific dizziness, Imbalance, and VErtigo (DEFENSIVE) stroke scale to prevent underdiagnosis of a posterior circulation infarction. During the validation phase, 949 subjects with dizziness were examined with the DEFENSIVE stroke scale; among these subjects, 100 were hospitalized for ischemic stroke accompanied by dizziness. No subject with ischemic stroke was overlooked. The new DEFENSIVE stroke scale had a sensitivity of 100% and decreased the rate of improper diagnosis of stroke (5.2% versus 0%; P = .022). CONCLUSIONS: Our new stroke recognition instrument for a posterior circulation infarction presenting with dizziness and related symptoms (the DEFENSIVE stroke scale) is easy to administer and has good diagnostic accuracy.

Associations of Echocardiography Markers and Vascular Brain Lesions: The ARIC Study.

Background Associations between subtle changes in cardiac and cerebral structure and function are not well understood, with some studies suggesting that subclinical cardiac changes may be associated with markers of vascular brain insult. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) Study (5th ARIC visit; 2011-2013; N=1974) were used to explore relationships between abnormalities of cardiac structure/function and subclinical brain disease and to test specific associations between those cardiac and vascular brain changes that share a common mechanism. In adjusted models white matter hyperintensities were 0.66 cm3 greater (95% confidence interval [CI] 0.08-1.25) for every 1-mm increase in left ventricular LV wall thickness and 0.64 cm3 greater (95% CI 0.19-1.08) for every 10 g/m2 increase in LV mass index, both markers of LV structure. Odds of brain infarction also increased with greater LV wall thickness (odds ratio 1.11, 95% CI 1.01-1.23 per 1 mm) and larger LV mass (odds ratio 1.08, 95% CI 1.00-1.17 per 10 g/m2). Higher ejection fraction (per 5%), a marker of systolic function, was significantly associated with decreased odds of overall infarct (odds ratio 0.85, 95% CI 0.77-0.95), but not with cortical infarction (odds ratio 0.92, 95% CI 0.78-1.08). Conclusions Among elderly participants in a large cohort study, subclinical markers of LV structure and LV systolic dysfunction were associated with increased odds of brain infarction and more white matter hyperintensities, independent of other vascular risk factors. This suggests end-organ dysfunction occurs in the heart and brain in parallel, with further studies needed to determine causality.

Watershed microinfarct pathology and cognition in older persons.

Brain microinfarcts are common in aging and are associated with cognitive impairment. Anterior and posterior watershed border zones lie at the territories of the anterior, middle, and posterior cerebral arteries, and are more vulnerable to hypoperfusion than brain regions outside the watershed areas. However, little is known about microinfarcts in these regions and how they relate to cognition in aging. Participants from the Rush Memory and Aging Project, a community-based clinical-pathologic study of aging, underwent detailed annual cognitive evaluations. We examined 356 consecutive autopsy cases (mean age-at-death, 91 years [SD = 6.16]; 28% men) for microinfarcts from 3 watershed brain regions (2 anterior and 1 posterior) and 8 brain regions outside the watershed regions. Linear regression models were used to examine the association of cortical watershed microinfarcts with cognition, including global cognition and 5 cognitive domains. Microinfarcts in any region were present in 133 (37%) participants, of which 50 had microinfarcts in watershed regions. Persons with multiple microinfarcts in cortical watershed regions had lower global cognition (estimate = -0.56, standard error (SE) = 0.26, p = 0.03) and lower cognitive function in the specific domains of working memory (estimate = -0.58, SE = 0.27, p = 0.03) and visuospatial abilities (estimate = -0.57, SE = 0.27, p = 0.03), even after controlling for microinfarcts in other brain regions, demographics, and age-related pathologies. Neither the presence nor multiplicity of microinfarcts in brain regions outside the cortical watershed regions were related to global cognition or any of the 5 cognitive domains. These findings suggest that multiple microinfarcts in watershed regions contribute to age-related cognitive impairment.

Sonolysis in risk reduction of symptomatic and silent brain infarctions during coronary stenting (SONOREDUCE): Randomized, controlled trial.

BACKGROUND: Silent brain infarcts can be detected on magnetic resonance imaging (MRI) in ~22% of patients after coronary angioplasty and stenting (CS). The effect of periprocedural sonolysis on the risk of new brain infarcts during CS was examined. METHODS: Patients undergoing elective CS were allocated randomly to a bilateral sonolysis group (70 patients, 58 men; mean age, 59.9 years) or a control group (74 patients, 45 men; mean age, 65.5 years). Neurologic examination, cognitive function tests, and brain MRI were performed prior to intervention and at 24 h after CS. Neurologic examination and cognitive function tests were repeated at 30 days after CS. RESULTS: No significant differences were observed in the number of patients with new infarcts (25.7 vs. 18.9%, P = 0.423), the number of lesions (1.3 ±â€¯1.0 vs. 2.9 ±â€¯5.3, P = 0.493), lesion volume (0.16 ±â€¯0.34 vs. 0.28 ±â€¯0.60 mL, P = 0.143), and the number of patients with new ischemic lesions in the insonated MCA territories (18.6vs. 17.6%, P = 0.958) between the sonolysis group and the control group. There were no cases of stroke, transient ischemic attack, myocardial infarction, or death in the two groups. Intracranial bleeding was reported only in 1 patient in the control group (0 vs. 1.4%, P = 0.888). Clock-drawing test scores at 30 days were significantly higher in the sonolysis group than in the control group (median 3.0 vs. 2.5, P = 0.031). CONCLUSIONS: Sonolysis does not reduce the risk of new brain infarcts after CS. The effect of sonolysis on number and volume of ischemic lesions and cognitive function should be assessed in further studies.

Clinical and radiological determinants of transient symptoms associated with infarction (TSI).

BACKGROUND: The definition of transient ischemic attack was traditionally based on clinical features only. The wide use of magnetic resonance imaging (MRI) led to the definition of a new entity - transient symptoms associated with infarction (TSI). It is unclear why patients with similar radiological infarctions may have different clinical manifestation - ranging from complete symptoms resolution to major neurological sequelae. We sought to determine which factors differentiate acute diffuse weighted imaging (DWI) lesion presentation - stroke versus TSI. METHODS: 282 Participants, recruited for the Tel-Aviv Brain Acute Stroke Cohort study (TABASCO), were enrolled consecutively. Participants underwent extensive cognitive evaluation, wide laboratory tests and brain MRI scans evaluated for cerebral small vessel disease (SVD) biomarkers, according to the STRIVE protocol. Demographic and clinical characteristics were also examined. RESULTS: A total of 239 patients had stroke and 43 patients had TSI. TSI patients had smaller average lesion volume (0.77 cm3 versus 2.64 cm3, p = 0.002). Lesion location did not differentiate TSI and stroke. Stroke patients had elevated inflammatory markers, unrelated to lesion size (CRP 4.2 mg/L versus 1.7 mg/L, p = 0.011). TSI patients had better global cognitive score and MoCA score at admission and 24 months following the index event (p < 0.001). TSI patients also had better Berg balance score (p = 0.004). No significant association was found with MRI SVD markers. CONCLUSIONS: Lesion size, but not location, differentiates TSI and stroke, especially at a cutoff value of 10 cm3. Elevated inflammatory response was linked to worse course independently of lesion volume. Cognitive and high function tests are associated to the clinical phenotype of ischemic lesion and may be a marker of brain reserve and compensatory abilities. SVD markers do not differ between TSI and stroke patients and probably do not fully capture the extent of brain vascular pathology and reserve.

Memory Impairment Due to a Small Acute Infarction of the Columns of the Fornix.

BACKGROUND: Clinically infarction of the columns of the fornix is very rare. It is also easy to be overlooked during imaging examination due to the special anatomical localization and features of columns of the fornix. In the meantime, with memory disorder to be its most prominent manifestation, it is very easily false diagnosed as other diseases when the lesion focus is overlooked, causing unnecessary invasive examinations like cerebrospinal fluid tests. METHODS: Case report and Literature review. RESULTS: We presented a 66-year-old woman with memory impairment due to a small acute infarction of the columns of the fornix. Through her diagnosis and treatment, we believed that early diagnosis and treatment were important to these patients who were enduring the disease. In addition, literature review informed us that for those unwilling to undergo cerebral angiography or for small cerebrovascular lesions that cannot be detected by angiography, 7T magnetic resonance imaging (MRI) might be an ideal diagnostic method. CONCLUSION: This case illustrated the significance of MRI in diagnosis for patients with acute memory impairment. When reading MRI results, one needs to pay attention to identify small lesions at special locations. In addition, cerebral apoplexy is still the first consideration of diagnosis when acute memory impairment occurs in patients with cerebrovascular disease risk factors.

Time perception impairment following thalamic stroke: A case study.

Impaired time perception is considered to be a relatively unusual and poorly understood consequence of brain injury. This paper presents a case study of altered time perception in JB, a 50-year-old woman who in 2011 had a small thalamic stroke affecting the right anteromedian region. We report on her subjective experience and present results from studies of retrospective timing (i.e., estimating how much time has passed and the clock time) and prospective timing (i.e., producing and reproducing intervals). The results showed that relative to neurologically healthy and brain-injured controls, JB had impaired retrospective timing and impaired prospective time reproduction. However, her prospective time production did not differ significantly from either of the control groups. We interpret this to mean that JB's essential timing functions are intact, and that rather, her time perception impairment stems from a problem in anterograde memory for time intervals. Further, we argue that unlike other cognitive domains, time perception alteration is neither anticipated nor evaluated in most patients, yet these impairments can have a remarkably serious impact on daily life. We encourage further investigation of this topic.

17ß-estradiol rescues damages following traumatic brain injury from molecule to behavior in mice.

Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom-oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety. Apoptosis in the hippocampus was assayed with Fluoro-Jade B staining and TUNEL staining. Western blot was employed to measure the expression of NMDA receptor subunits and phosphorylation of ERK1/2, and biochemical assays were used to estimate oxidative stress. 17beta-Estradiol (E2) was intraperitoneally administered at 10-80 µg/kg once per day for 7 consecutive days before or after CCI. Chronic administration of E2 both before and immediately after CCI conferred neuroprotection, reducing neurological severity score, brain infarction, and edema in TBI mice. Additionally, E2 improved many aspects of deleterious effects of TBI on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. The present study provides clue for the notion that E2 has therapeutic potential for both prevention and intervention of TBI-induced brain damages.

Lesion location and cognitive impact of cerebral small vessel disease.

Cerebral small vessel disease (SVD) is an important cause of cognitive impairment. Important MRI manifestations of SVD include white matter hyperintensities (WMH) and lacunes. This narrative review addresses the role of anatomical lesion location in the impact of SVD on cognition, integrating findings from early autopsy studies with emerging findings from recent studies with advanced image analysis techniques. Early autopsy and imaging studies of small case series indicate that single lacunar infarcts in, for example the thalamus, caudate nucleus or internal capsule can cause marked cognitive impairment. However, the findings of such case studies may not be generalizable. Emerging location-based image analysis approaches are now being applied to large cohorts. Recent studies show that WMH burden in strategic white matter tracts, such as the forceps minor or anterior thalamic radiation (ATR), is more relevant in explaining variance in cognitive functioning than global WMH volume. These findings suggest that the future diagnostic work-up of memory clinic patients could potentially be improved by shifting from a global assessment of WMH and lacune burden towards a quantitative assessment of lesion volumes within strategic brain regions. In this review, a summary of currently known strategic regions for SVD-related cognitive impairment is provided, highlighting recent technical developments in SVD research. The potential and challenges of location-based approaches for diagnostic purposes in clinical practice are discussed, along with their potential prognostic and therapeutic applications.

Isolated punctuate hippocampal infarction and transient global amnesia are indistinguishable by means of MRI.

Background Small punctuate lesions in the hippocampus on diffusion-weighted images are a typical finding in transient global amnesia. Consequently, it has been suggested that diffusion-weighted images findings might corroborate the diagnosis of transient global amnesia. However, isolated punctuate hippocampal infarction might be a differential diagnosis of transient global amnesia. Aim Evaluation of isolated punctuate hippocampal infarction frequency and comparison of its clinical presentation and MRI findings to transient global amnesia. Methods From an MRI database, we identified 10 patients with isolated punctuate hippocampal infarction and compared these to 12 patients with transient global amnesia with diffusion-weighted images lesion with regard to clinical symptoms and MRI findings. Results Disorientation and memory deficits were more common in transient global amnesia patients, whereas dysphasia/aphasia and vertigo were more common in hippocampal infarction patients. MRI findings in isolated punctuate hippocampal infarction and transient global amnesia did not differ significantly, neither regarding the affected hemisphere, lesion distribution, size, nor relative ADC values. Conclusions Differentiation of isolated punctuate hippocampal infarction and transient global amnesia based on neuroimaging findings is not possible. Thus, in the case of isolated punctuate hippocampal diffusion-weighted images lesions the final diagnosis of hippocampal infarction or transient global amnesia should be based on the clinical presentation.

Lipopolysaccharide exacerbates infarct size and results in worsened post-stroke behavioral outcomes.

BACKGROUND: A third of ischemic stroke cases have no traditional underlying causes such as hypertension, diabetes, atherosclerosis, obesity, or age. Moreover, thirty to forty percent of strokes occur during or acutely after an active infection and the incidence of stroke increases during flu season. We and others have shown that the combination of a minor bacterial infection mimic, 100 µg/kg of lipopolysaccharide (LPS) prior to a minor stroke-30 min transient middle cerebral artery occlusion (tMCAO)-exacerbates infarct volume in a mouse model. Thus, experimental and epidemiological data strongly suggest that infection and/or inflammation play a role in stroke occurrence and severity. However, to date, long-term outcomes of stroke during an active infection has not been studied. METHODS: 3-4 month old C57Bl6/J mice were treated with saline or LPS 30 min prior to a 30 min tMCAO or sham surgery. A behavioral battery was administered to assess health status/sickness behavior, neurological deficits, motor, cognitive, and affective behaviors. RESULTS: We show for the first time that exposure to a low dose of LPS prior to a mild stroke significantly worsens neurological deficits and sickness scores. Motor, cognitive, and affective behaviors were assessed post-stroke and while stroke significantly affected motor behavior on rotarod, LPS did not increase the motor deficits. We did not observe any effects of stroke or LPS on cognitive and affective behaviors. CONCLUSIONS: Our observations of the association between infection, stroke, and worse sickness and neurological outcomes identify (1) a clinical need to aggressively treat infections in people with risk factors for stroke and (2) the need to understand the mechanism(s) of the association between infections and stroke.