Cortical Infarction Research Articles

Prediction of post-stroke cognitive impairment after acute ischemic stroke using machine learning

Background and objectivesPost-stroke cognitive impairment (PSCI) occurs in up to 50% of patients with acute ischemic stroke (AIS). Thus, the prediction of cognitive outcomes in AIS may be useful for treatment decisions. This PSCI cohort study aimed to determine the applicability of a machine learning approach for predicting PSCI after stroke.MethodsThis retrospective study used a prospective PSCI cohort of patients with AIS. Demographic features, clinical characteristics, and brain imaging variables previously known to be associated with PSCI were included in the analysis. The primary outcome was PSCI at 3–6 months, defined as an adjusted z-score of less than − 2.0 standard deviation in at least one of the four cognitive domains (memory, executive/frontal, visuospatial, and language), using the Korean version of the Vascular Cognitive Impairment Harmonization Standards-Neuropsychological Protocol (VCIHS-NP). We developed four machine learning models (logistic regression, support vector machine, extreme gradient boost, and artificial neural network) and compared their accuracies for outcome variables.ResultsA total of 951 patients (mean age 65.7 ± 11.9; male 61.5%) with AIS were included in this study. The area under the curve for the extreme gradient boost and the artificial neural network was the highest (0.7919 and 0.7365, respectively) among the four models for predicting PSCI according to the VCIHS-NP definition. The most important features for predicting PSCI include the presence of cortical infarcts, mesial temporal lobe atrophy, initial stroke severity, stroke history, and strategic lesion infarcts.ConclusionOur findings indicate that machine-learning algorithms, particularly the extreme gradient boost and the artificial neural network models, can best predict cognitive outcomes after ischemic stroke.

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Cryptogenic stroke. Part 4: Antiphospholipid syndrome and cancer

Cryptogenic embolic stroke (embolic strokes of undetermined source, ESUS) is an intermediate diagnosis in patients with unknown etiology of stroke and implies the absence of large sources of cardioembolism and significant extra- and intracranial stenoses and probably embolic pathogenesis of cerebral infarction. In the previous parts of the article, we discussed the issues of diagnosis and secondary prevention of ESUS with underlying potential aortoaortic sources of embolism, paradoxical embolism and atrial cardiopathy. This article discusses the issues of epidemiology, pathogenesis, diagnosis and secondary prevention of ischemic stroke with underlying antiphospholipid syndrome (APS) and cancer-associated stroke (RAI). Both mechanisms of stroke are associated with hypercoagulability, often manifest as multifocal cortical brain lesions, and respond to anticoagulant therapy. While APS should be suspected primarily in young women with pathology of pregnancy, arterial and venous thrombosis, as well as livedo reticularis (racemosa), RAI does not have a specific clinical picture, but can manifest as diffuse cortical infarcts (symptom of three pools) combined with increased D-dimer level. If APS is suspected, appropriate haematological screening is required, followed by the use of the Sydney diagnostic criteria. Possible diagnosis of RAI often requires transesophageal echocardiography (ruling out non-bacterial thromboendocarditis) and oncological screening. Secondary prevention of APS consists in prescribing warfarin with the target international normalized ratio (INR) of 2.0 to 3.0. RAI is treated with anticoagulants, but the choice of a drug and dose is determined by the balance between thrombotic/thromboembolic and hemorrhagic risks.

Paroxysmal sympathetic hyperactivity in a child with stroke: a case report

BackgroundParoxysmal sympathetic hyperactivity (PSH) is the result of dysregulated autonomic function with sympathetic symptoms characterised by increased heart rate, respiratory rate, blood pressure and temperature with abnormal posture, which predominately occur periodically but can be persistent in severe cases. Common causes that present in similar fashion such as infectious process (bacteremia, meningitis, etc.); non-PSH neurological deterioration (increased intracranial pressure, intracranial haemorrhage, intracranial oedema, seizures, encephalitis); pulmonary embolism; thyrotoxicosis, alcohol or drug withdrawal; neuroleptic malignant syndrome; serotonin syndrome; and malignant hyperthermia need to be excluded before diagnosing PSH. The earlier the diagnosis made, the better the prognosis.Case presentationWe report a case of a 3-year-old male child who was a diagnosed case of Tetralogy of Fallot presented with left focal seizure with secondary generalisation. Child also had respiratory complaints prior to convulsion. He had developed signs of raised intracranial pressure. Blood culture sent to rule out infective endocarditis was negative. CT brain showed bilateral diffuse cortical infarct. Child developed signs and symptoms of PSH such as fever, tachycardia, tachypnoea, hypertension, diaphoresis, dystonia and bilateral completely dilated pupils. Other common causes such as infective endocarditis, increased intracranial pressure, intracranial oedema, intracranial haemorrhage, seizure, encephalitis and infectious processes (bacteremia, meningitis and infective endocarditis) were ruled out. The diagnosis of PSH was made and started on propranolol along with clonidine. Child responded well to the treatment.ConclusionThe complex pathophysiology of PSH warrants extensive work-up to rule out other common causes. The outcome of our patient shows the importance of early diagnosis and multidisciplinary treatment for better outcome.

Brain network analysis reveals convergent and divergent aberrations between mild stroke patients with cortical and subcortical infarcts during cognitive task performing.

Although consistent evidence has revealed that cognitive impairment is a common sequela in patients with mild stroke, few studies have focused on it, nor the impact of lesion location on cognitive function. Evidence on the neural mechanisms underlying the effects of mild stroke and lesion location on cognitive function is limited. This prompted us to conduct a comprehensive and quantitative study of functional brain network properties in mild stroke patients with different lesion locations. Specifically, an empirical approach was introduced in the present work to explore the impact of mild stroke-induced cognitive alterations on functional brain network reorganization during cognitive tasks (i.e., visual and auditory oddball). Electroencephalogram functional connectivity was estimated from three groups (i.e., 40 patients with cortical infarctions, 48 patients with subcortical infarctions, and 50 healthy controls). Using graph theoretical analysis, we quantitatively investigated the topological reorganization of functional brain networks at both global and nodal levels. Results showed that both patient groups had significantly worse behavioral performance on both tasks, with significantly longer reaction times and reduced response accuracy. Furthermore, decreased global and local efficiency were found in both patient groups, indicating a mild stroke-related disruption in information processing efficiency that is independent of lesion location. Regarding the nodal level, both divergent and convergent node strength distribution patterns were revealed between both patient groups, implying that mild stroke with different lesion locations would lead to complex regional alterations during visual and auditory information processing, while certain robust cognitive processes were independent of lesion location. These findings provide some of the first quantitative insights into the complex neural mechanisms of mild stroke-induced cognitive impairment and extend our understanding of underlying alterations in cognition-related brain networks induced by different lesion locations, which may help to promote post-stroke management and rehabilitation.

Transplantation of hESCs-Derived Neural Progenitor Cells Alleviates Secondary Damage of Thalamus After Focal Cerebral Infarction in Rats.

Human embryonic stem cells-derived neural progenitor cells (hESCs-NPCs) transplantation holds great potential to treat stroke. We previously reported that delayed secondary degeneration occurs in the ventroposterior nucleus (VPN) of ipsilateral thalamus after distal branch of middle cerebral artery occlusion (dMCAO) in adult male Sprague-Dawley (SD) rats. In this study, we investigate whether hESCs-NPCs would benefit the neural recovery of the secondary damage in the VPN after focal cerebral infarction. Permanent dMCAO was performed with electrocoagulation. Rats were randomized into Sham, dMCAO groups with or without hESCs-NPCs treatment. HESCs-NPCs were engrafted into the peri-infarct regions of rats at 48 h after dMCAO. The transplanted hESCs-NPCs survive and partially differentiate into mature neurons after dMCAO. Notably, hESCs-NPCs transplantation attenuated secondary damage of ipsilateral VPN and improved neurological functions of rats after dMCAO. Moreover, hESCs-NPCs transplantation significantly enhanced the expression of BDNF and TrkB and their interaction in ipsilateral VPN after dMCAO, which was reversed by the knockdown of TrkB. Transplantated hESCs-NPCs reconstituted thalamocortical connection and promoted the formation of synapses in ipsilateral VPN post-dMCAO. These results suggest that hESCs-NPCs transplantation attenuates secondary damage of ipsilateral thalamus after cortical infarction, possibly through activating BDNF/TrkB pathway, enhancing thalamocortical projection, and promoting synaptic formation. It provides a promising therapeutic strategy for secondary degeneration in the ipsilateral thalamus post-dMCAO.

Alberta Stroke Program Early CT Score can Predict Severity of Spasticity and Functional Outcome in Ischemic Stroke Survivors.

Post-stroke spasticity is common and an early predictor of the severity of spasticity can help track recovery trajectory helping to modify rehabilitation plans. We explored the utility of the Alberta Stroke Program Early CT Score (ASPECTS) to predict functional motor capacity in patients after acute ischemic stroke. One hundred and one patients (mean age of 58.6 ± 7.6 years; M:F = 72: 29) with the first documented acute ischemic stroke were followed up for three to twelve months after the stroke. Cerebral lesions within the territory of the middle cerebral artery were evaluated using the ASPECTS. Spasticity was assessed using the Modified Ashworth Score (MAS) and walking with Timed Up and Go test (TUG). The associations between severity of spasticity and size/extent of infarct as derived from ASPECTS and between spasticity and functional walking in post-stroke survivors were analyzed. Among the patients studied, 61.3% (n = 62) had infarct in the region of supply of the left middle cerebral artery (MCA) and 38.7% (n = 39) had infarct in the region supplied by the right MCA. Three percent (n = 3) had a low ASPECTS, 53.6% (n = 54) had an intermediate score and 44.4% (n = 44) had a high score. The majority of patients with no to mild spasticity had high ASPECTS. Worse spasticity was significantly associated with low ASPECTS (P = 0.001). High scores in Timed Up and Go test (TUG) were associated with low ASPECTS (P < 0.001). Patients with high ASPECTS had the propensity to have subcortical infarcts (P < 0.001) when compared to those with moderate ASPECTS, who had a mix of cortical and subcortical infarcts. ASPECTS at admission in patients with acute ischemic stroke is a good predictor of post-stroke spasticity and functional walking. Low ASPECTS is associated with higher spasticity and lower functional walking status on follow-up after stroke.

Pericytes Are Not Associated With Reduced Capillary Perfusion After Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is characterized by an acute reduction of cerebral blood flow and subsequent cortical infarcts, but the underlying mechanisms are not well understood. Since pericytes regulate cerebral perfusion on the capillary level, we hypothesize that pericytes may reduce cerebral perfusion after SAH. Pericytes and vessel diameters of cerebral microvessels were imaged in vivo using NG2 (neuron-glial antigen 2) reporter mice and 2-photon microscopy before and 3 hours after sham surgery or induction of SAH by perforating the middle cerebral artery with an intraluminal filament. Twenty-four hours after, SAH pericyte density was assessed by immunohistochemistry. SAH caused pearl-string-like constrictions of pial arterioles, slowed down blood flow velocity in pial arterioles by 50%, and reduced the volume of intraparenchymal arterioles and capillaries by up to 70% but did not affect pericyte density or induce capillary constriction by pericytes. Our results suggest that perfusion deficits after SAH are not induced by pericyte-mediated capillary constrictions.

Effect of "Tiaoshen Tongluo" acupuncture on nerve function injury, muscle tension and neurotransmitters through Nrf2/ROS pathway in spastic rats after stroke

To observe the effect of "Tiaoshen Tongluo" acupuncture (TTA) at "Dingzhongxian" (MS5) and right "Dingpangxian" (MS8) on neurological injury, muscle tension and neurotransmitters through nuclear transcription factor E2 related factor 2 (Nrf2)/reactive oxygen species (ROS) signaling pathway in spastic rats after stroke, so as to explore its mechanisms underlying relief of post-stroke spasm (PSS). A total of 90 male SD rats were randomly divided into 6 groups, i.e. sham operation, PSS model, medication, non-acupoint acupuncture, TTA, TTA+ML385 groups, with 15 rats in each group. The PSS model was established by middle cerebral artery occlusion. After modeling, rats of the medication group were treated by gavage of baclofen (0.4 mg/kg), once daily for 7 days. For rats of the non-acupoint acupuncture group, the spot about 10 mm above the iliac crest and below the armpit of the affected side was needled, and for those of the TTA group and TTA+ML385 group, EA stimulation (1 mA, 2 Hz/15 Hz) was applied to MS5 and right MS8 for 10 min, once daily for 7 consecutive days. Intraperitoneal injection of ML385 ［ a specific nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg］ was given to rats of the TTA+ML385 group before TTA was performed. The rats' neurological deficit score (0-4 points) was evaluated by referring to Zea Longa's methods and the muscular spasm degree of the quadriceps femoris of the left hindlimb (0-4 points) assessed by using Ashworth scale (MAS). The muscular tension of the left quadriceps femoris was measured by using a tension sensor, and Hoffman (H)-reflex response and M and H waves of electromyogram of the muscle between the metatarsals of the left foot were measured using an electrophysiological recorder. The cerebral infarction volume was measured after 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of γ-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu) and aspartic acid (Asp) of the right cortical infarct area were detected by using high performance capillary electrophoresis, and the contents of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) were detected by fluorescence spectrophoto-metry, as well as the level of ROS in the right cerebral cortical infarction tissues was detected by dihydroethidium staining. The expression levels of Nrf2 and heme oxygenase-1 (HO-1) proteins in the infarcted cerebral area were detected using Western blot. Compared with the sham operation group, the neurological deficit score, MAS score, percentage of cerebral infarction volume, Hmax/Mmax ratio, contents of Glu and Asp and ROS level were significantly increased (P<0.001), whereas the muscle tone, stimulation threshold for inducing H-reflex, GABA, Gly, 5-HT, DA and NE contents, cerebral Nrf2 and HO-1 protein expression levels were apparently decreased (P<0.001) in the model group. In comparison with the model group, the neurological deficit score, MAS score, percentage of cerebral infarction volume, Hmax/Mmax ratio, contents of Glu, Asp and ROS levels were decreased (P<0.001), and the muscle tone, stimulation threshold for inducing H-reflex, GABA, Gly, 5-HT, DA and NE contents, Nrf2 and HO-1 protein expressions were increased (P<0.001, P<0.01) in both the medication and TTA groups. No significant differences were found between the non-acupoint group and model group, and between the medication and TTA groups in all the indexes mentioned above (P>0.05). After administration of ML385, the effects of TTA in reducing neurological deficit score, MAS score, Hmax/Mmax, percentage of cerebral infarct volume, Glu, Asp, ROS, and up-regulating H-reflex threshold, GABA, Gly, 5-HT, DA, NE, Nrf2 and HO-1 levels were eliminated (P<0.001，P<0.05,P<0.01). TTA can improve neurological behavior and muscle spasm in rats with PSS, which may be associated with its functions in regulating the levels of neurotransmitters in the cortical infarcted area by activating the Nrf2/ROS signaling pathway.

Associations of small vessel disease and acute symptomatic seizures in ischemic stroke patients

Background and purposeCerebral microbleeds (CMBs), markers of small vessel disease are frequent in ischemic stroke, yet the association with acute symptomatic seizures (ASS) has not been well characterized. MethodsA retrospective cohort of hospitalized patients with anterior circulation ischemic stroke. The association of CMBs with acute symptomatic seizures was assessed using a logistic regression model and causal mediation analysis. ResultsOf 381 patients, 17 developed seizures. Compared with patients without CMBs, those with CMBs had a three-fold higher unadjusted odds of seizures (unadjusted OR: 3.84, 95% 1.16–12.71, p = 0.027). After adjusting for confounders such as stroke severity, cortical infarct location, and hemorrhagic transformation, the association between CMBs and ASS was attenuated (adjusted OR: 3.11, 95%CI: 0.74–11.03, p = 0.09). The association was not mediated by stroke severity. ConclusionIn this cohort of hospitalized patients with anterior circulation ischemic stroke, CMBs were more likely to be found in patients with ASS than those without ASS, an association that was attenuated when accounting for stroke severity, cortical infarct location, and hemorrhagic transformation. Evaluation of the long-term risk of seizures associated with CMBs and other markers of small vessel disease is warranted.

Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline.

Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits. Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2-3 months) and aged (20 months) male and female mice. Animals were exposed to a variety of gas conditions to assess the contribution of peripheral and central chemoreceptors. A battery of cognitive tests was performed to examine behavioral function. Middle cerebral artery occlusion led to disordered breathing characterized by hypoventilation and apneas. Cognitive decline correlated with the severity of disordered breathing. Distal permanent middle cerebral artery occlusion, which produces a smaller cortical infarct, also produced breathing disorders and cognitive impairment but only in aged mice. Our data suggest that poststroke apnea is associated with cognitive decline and highlights the influence of aging on breathing disorders after stroke. Therefore, the treatment of respiratory instability may be a viable approach to improving cognitive outcomes after stroke.

Subcortical infarcts on admission CTP predict poor outcome despite excellent reperfusion in delayed time windows.

The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows. We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study. Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately. Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts.

Reduced Left Atrial Rotational Flow Is Independently Associated With Embolic Brain Infarcts

BackgroundUp to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms. ObjectivesThis study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF. MethodsThe authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts. ResultsPatients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05). ConclusionsReduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.

The Spectrum of Pediatric Infection-Associated Intracranial Arteriopathies and Acute Ischemic Stroke at 2 Eastern Indian Tertiary Care Centres.

Major and minor pediatric infections may cause intracranial arteriopathies, the long-term outcome of which we investigated and identified the factors influencing the progression/resolution of arteriopathies. We collected the clinical and radiological data of children aged 1 month-15 years who had ischemic stroke with definite arteriopathy following a recent febrile infection. Repeated neuroimaging was done over the next year to ascertain recurrent strokes and the progression and resolution of arteriopathies. The anterior circulation was more frequently affected (83.33%), predominantly involving the middle cerebral artery (41.67%), resolving in 20.84% of cases and progressing in 33.33% of cases. Lesions were commonly unilateral (54.17%) and stenotic (75%), resulting predominantly in cortical infarcts (45.83%), with hemiparesis being the most common neurodeficiency. Apart from tubercular meningitis patients, others had a good functional outcome. Lower age, minor infections, and unilateral arteriopathies had a significantly higher chance of resolution. Postviral arteriopathies had a significantly lower chance of progression compared with those following bacterial infections. Progressive and bilateral arteriopathies were significantly associated with worse outcomes and recurrent strokes.

Prevalence and Prognostic Factors of Cortical Laminar Necrosis in Acute Ischemic Stroke.

Cortical laminar necrosis (CLN) is a specific type of cortical infarction, and little is known about its frequency and outcomes. We aimed to investigate the prevalence and outcomes of CLN caused by brain infarction and its prognostic factors. This retrospective cohort study included patients with acute ischemic stroke (AIS) between 2019 and 2022 and for whom magnetic resonance images obtained at our center showed acute-stage CLN. Their medical records were collected and analyzed. An unfavorable outcome was defined as a modified Rankin Scale score of 3-6 at 90 days. Logistic regression was performed to identify independent predictors of an unfavorable outcome. Among 5548 consecutive patients with AIS, 151 patients (2.7%) were diagnosed with CLN, and 112 had CLN enrolled in the final analysis. At 90 days, 25 patients (22.3%) had an unfavorable outcome. Compared with the favorable group, poor outcome patients had higher rates of previous stroke (p = 0.012), higher National Institutes of Health Stroke Scale (NIHSS) scores at admission (p < 0.001), and were more likely to have early neurologic deterioration (END) (p = 0.014), diffuse ischemic lesions (p = 0.011), and lesions involving multiple lobes (p = 0.030). In multivariable analysis, the initial NIHSS score (OR, 1.258, (95% CI 1.090 - 1.453), p = 0.002) and END (OR, 5.695, [95% CI 1.410 - 23.007], p = 0.015) were independently associated with unfavorable outcome. CLN is a rare ischemic event but has a good prognosis in most cases. A higher initial NIHSS score and END may predict an unfavorable outcome.

Acute and Subacute Neurovascular Impact of Cryptogenic Air Emboli (P12-5.020)

<h3>Objective:</h3> To describe a unique case of severe, delayed ischemia secondary to air embolism. <h3>Background:</h3> Accidental air embolism is a rare cause of ischemic stroke that is becoming increasingly well-described in the literature. However, the mechanism and severity of this type of injury can vary, with significant ischemia typically emerging early in the course of care. To our knowledge, delayed ischemia in this setting has rarely been described. <h3>Design/Methods:</h3> We describe a hospitalized patient who developed cryptogenic air emboli resulting in acute neurologic changes that appeared to improve with emergent care. However, follow up imaging revealed delayed ischemia not identified on initial radiography. <h3>Results:</h3> A stroke code was called for an unresponsive, hospitalized 75-year-old man. On evaluation, he was found to be obtunded with forced left gaze deviation concerning for possible non-convulsive status epilepticus (NCSE). He was treated acutely for seizure and subsequent stat CT head revealed air within the right greater than left hemispheric cortical veins with loss of sulcation, concerning for developing ischemia. On review of his hospitalization, prior TTE showed no PFO. Retrograde movement of air into the cortical veins was the hypothesized etiology,¹ but the source of the air in this case remains cryptogenic. MRI obtained 5.75 hours after the patient’s last known well showed subtle diffusion restriction without definitive cortical infarction and follow up CT head approximately 13 hours afterward showed near complete resolution of the air emboli. However, MRI 4 days later demonstrated diffusion restriction and cerebral edema throughout multiple vascular territories, consistent with venous infarction. <h3>Conclusions:</h3> This case highlights that venous air emboli can cause delayed ischemia that may not be appreciated on initial dedicated brain imaging. As such, affected patients may require intensive neurocritical care irrespective of initial radiographic findings. <b>Disclosure:</b> Dr. Gummerson has nothing to disclose. Dr. Parasram has nothing to disclose. Dr. Peng has nothing to disclose. Dr. Picard has nothing to disclose. Dr. Kahn has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Kahn has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Chronius. Dr. Kahn has stock in Coaptech. Dr. Kahn has stock in Quantum Labs. Dr. Kahn has stock in FVC Health. Dr. Kahn has stock in TEO Science . Dr. Kahn has received intellectual property interests from a discovery or technology relating to health care. Dr. Angelus has nothing to disclose. Dr. Bhatt has nothing to disclose. Dr. De Havenon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Integra. Dr. De Havenon has stock in Certus. The institution of Dr. De Havenon has received research support from NIH/NINDS. The institution of Dr. De Havenon has received research support from Regeneron Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMAG Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMGEN. Dr. De Havenon has received publishing royalties from a publication relating to health care. Dr. Jasne has nothing to disclose. Dr. Magid-Bernstein has nothing to disclose.

The correlation of embolic sources with infarct pattern in patients with embolic stroke (P6-5.015)

<h3>Objective:</h3> To exclusively identify potential embolic sources (PES) applying transesophageal echocardiography (TEE) and correlate them with topographic diffusion-weighted imaging patterns (DWI) in patients with embolic stroke. <h3>Background:</h3> Embolic stroke of undetermined source (ESUS) has been reported to show a relatively high stroke recurrence rate. Thus, early identification of potential embolic source (PES) is critical for acute treatment and/or secondary prevention. If acute topographic diffusion-weighted imaging patterns (DWI) would correlate with specific PES, it may prove very useful. <h3>Design/Methods:</h3> A total of 992 consecutive patients with embolic stroke were studied. Apart from the known embolic group (n=560), we focused on the unknown embolic group (n=366) that was defined as no arrhythmia during the first day from admission and no PES after general examination. DWI were classified based on the arterial supply. Age and sex adjusted odds ratio (OR) of each DWI for the different PESs were calculated. Middle cerebral arteries (MCA) were divided into 4 segments, i.e., M1~M4. Moreover, M2 segments were subdivided into superior and inferior branches. <h3>Results:</h3> 366 patients consisted of 168 with paroxysmal atrial fibrillation (pAf), 82 with paradoxical embolism (PxE), 71 with aorto-embolism (AoE), leaving 39 patients undetermined. The DWIs of internal carotid artery (OR: 15.0, p=0.0027), M1 (4.2, p=0.0003), inferior M2 (3.6, p=0.04) and multiple cortical branches (MCB) (21.6, p&lt;0.0001) were significantly associated with pAf. Striatocapsular infarction (SCI) (15.1, p&lt;0.0001) was significantly associated with PxE and multiple small scattered infarcts (8.6, p&lt;0.0001) with AoE. <h3>Conclusions:</h3> The correlations of DWI with different PESs have their distinctive characteristics. The DWI of inferior M2 as well as large infarcts and multiple cortical infarcts were associated with pAf, that of SCI with PxE and MSS with AoE. The characteristic histopathology and hydrodynamic mechanism of thrombi may determine DWI. <b>Disclosure:</b> Yasumasa Yamamoto has nothing to disclose.

Refractory anti-NMDA Receptor Encephalitis During Pregnancy: Treatment and Neonatal Outcome with Review of Literature (P5-5.001)

<h3>Objective:</h3> To report a case of refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with multiple relapses during pregnancy and peripartum with successful use of rituximab during pregnancy and resultant healthy neonatal outcome. <h3>Background:</h3> Anti-NMDAR encephalitis is a severe but treatable autoimmune encephalitis which often affects women of childbearing age. The clinical presentation in pregnancy is usually characterized by progressive neuropsychiatric manifestations, seizures and dysautonomia posing a danger to the fetus and a challenge to the treating neurologist. Refractory presentations often need escalation to second-line immunotherapies which have limited safety data in pregnancy. <h3>Design/Methods:</h3> Case report and literature review. <h3>Results:</h3> A 25-year-old primiparous Caucasian woman, 24 weeks pregnant presented with a 3-week history of worsening behavioral/personality changes, confusion, dysarthria, emotional lability and a single generalized tonic-clonic seizure. Brain MRI showed T2/FLAIR hyperintensity in the right frontal lobe suggestive of remote cortical infarct vs cortical dysplasia. CSF showed pleocytosis (WBC 19; 75% lymphocytes) with &gt;10 CSF-restricted oligoclonal bands. Due to high clinical suspicion for an immune-mediated process, she was started on IV methylprednisolone and IVIG. Subsequently, NMDAR antibody returned positive in serum (1:10) and CSF (1:128). Abdominal/pelvic ultrasound and MRI showed no ovarian teratoma. She clinically improved and was discharged, but subsequently relapsed 10 days later at 27 weeks needing treatment with plasma exchange and rituximab, and her symptoms improved. She delivered a healthy baby at 37 weeks but had another relapse immediately post-partum necessitating further immunotherapy. Since then, she has remained stable on maintenance rituximab with no further relapses. At one-year follow up, the baby remains healthy. <h3>Conclusions:</h3> This case illustrates the successful use of rituximab during pregnancy for anti-NMDAR encephalitis. Our literature review showed only a handful of such patients treated with rituximab and one patient with cyclophosphamide. Further studies are needed to assess the safety and long-term outcomes of using rituximab for anti-NMDAR encephalitis during pregnancy. <b>Disclosure:</b> The institution of Mr. Lew has received research support from NIH. Dr. Shirani has nothing to disclose. Dr. Arcot Jayagopal has nothing to disclose.

Biological Mechanism of Sex Difference in Stroke Manifestation and Outcomes.

Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location. This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations. The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001). Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients.

A composite hydrogel improves the survival and differentiation of human iPSC-derived neural stem cells after ischemic stroke

Stem cell transplantation can replace lost and damaged neurons after ischemic stroke and has been proposed as a potential treatment for stroke. However, stem cell therapy is challenged by poor cell retention, survival, and differentiation following transplantation. In this study, we developed a composite hydrogel incorporating brain decellularized extracellular matrix (dECM) and a matrix metallopeptidase (MMP)-responsive host–guest (HG) hydrogel that acts as a platform for human induced pluripotent stem cell-derived neural stem cells (iPSC-NSCs) delivery to improve transplant stem cell survival and differentiation. The optimized composite hydrogel ratio was screened by rheology analysis and neurite outgrowth assessment. We then examined the effects of HG/dECM composite hydrogels on iPSC-NSCs survival and differentiation on two-dimensional surfaces modified with hydrogel and in a three-dimensional hydrogel network. Moreover, iPSC-NSCs-laden composite hydrogels were injected into the infarct cavity in an ischemic stroke model to replace lost and damaged nerve cells. As expected, the HG/dECM composite hydrogels better facilitated the survival and differentiation of iPSC-NSC in vivo than the control. Likewise, the iPSC-NSCs loaded in HG/dECM composite hydrogels showed superior retention and survival in the cortical infarct cavity, and the composite hydrogels promoted the differentiation of iPSC-NSCs into neurons. Overall, HG/dECM composite hydrogels are a promising platform to regulate stem cell survival and differentiation.