A machine learning algorithm based on circulating metabolic biomarkers offers improved predictions of neurological diseases.

BACKGROUND AND AIMS: A machine learning algorithm based on circulating metabolic biomarkers for the predictions of neurological diseases (NLDs) is lacking. To develop a machine learning algorithm to compare the performance of a metabolic biomarker-based model with that of a clinical model based on conventional risk factors for predicting three NLDs: dementia, Parkinson's disease (PD), and Alzheimer's disease (AD). MATERIALS AND METHODS: The eXtreme Gradient Boosting (XGBoost) algorithm was used to construct a metabolic biomarker-based model (metabolic model), a clinical risk factor-based model (clinical model), and a combined model for the prediction of the three NLDs. Risk discrimination (c-statistic), net reclassification improvement (NRI) index, and integrated discrimination improvement (IDI) index values were determined for each model. RESULTS: The results indicate that incorporation of metabolic biomarkers into the clinical model afforded a model with improved performance in the prediction of dementia, AD, and PD, as demonstrated by NRI values of 0.159 (0.039-0.279), 0.113 (0.005-0.176), and 0.201 (-0.021-0.423), respectively; and IDI values of 0.098 (0.073-0.122), 0.070 (0.049-0.090), and 0.085 (0.068-0.101), respectively. CONCLUSION: The performance of the model based on circulating NMR spectroscopy-detected metabolic biomarkers was better than that of the clinical model in the prediction of dementia, AD, and PD.

Hook-effect in MAGLUMI immunoassay for serum anti-GAD antibodies in neurological disorders: When "wrong" matrix is the right choice.

Antibodies against glutamic acid decarboxylase (anti-GAD) are a valuable diagnostic tool to detect severe autoimmune conditions as type 1 diabetes mellitus (T1DM) and anti-GAD related neurological disorders, having the latter more often anti-GAD concentrations in serum multiple times higher than in the former. Automated immunoassays, either with ELISA or chemiluminescent technology, are validated for diagnostic use in serum with analytical ranges suitable for T1DM diagnosis. In a patient presenting with a suspected autoimmune ataxia, anti-GAD testing on an automated chemiluminescent immunoassay (CLIA) resulted in slightly abnormal concentrations in serum (39.2 KIU/L) and very high concentrations in CSF (>280 KIU/L), thus prompting to proceed to serum dilutions to exclude a false negative result and a misdiagnosis. Different dilutions of serum resulted in nonlinear concentrations with endpoint result of 276,500 KIU/L at dilution 1:1000. CSF dilution was instead linear with endpoint result of 4050 KIU/L. In this case report we found that anti-GAD testing in CSF was essential to establish the clinical diagnosis and to suspect hook-effect in serum due to the excess of autoantibodies in this severe autoimmune condition.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

COMPARATIVE EVALUATION AND PROGNOSTIC UTILITY OF NEURONAL INJURY BIOMARKERS IN COVID-19 PATIENTS: A PROSPECTIVE STUDY.

ABSTRACT: Background : COVID-19 disease severity markers include mostly molecules related to not only tissue perfusion, inflammation, and thrombosis, but also biomarkers of neural injury. Clinical and basic research has demonstrated that SARS-COV-2 affects the central nervous system. The aims of the present study were to investigate the role of neural injury biomarkers and to compare them with inflammatory markers in their predictive ability of mortality. Methods : We conducted a prospective observational study in critically ill patients with COVID-19 and in a cohort of patients with moderate/severe disease. S100b, neuron-specific enolase (NSE), and inflammatory markers, including soluble urokinase plasminogen activator receptor (suPAR), were measured on intensive care unit or ward admission, respectively. Statistical comparisons between patient groups were performed for all biomarkers under investigation. Correlations between different biomarkers were tested with Spearman correlation coefficient. Receiver operating characteristic curves were plotted using mortality as the classification variable and the biomarker levels on admission as the prognostic variables. Results : A total of 70 patients with COVID-19 were included in the final analysis. Of all studied biomarkers, s100b had the best predictive ability for death in the intensive care unit, with an area under the curve of 0.73 (0.61-0.83), P = 0.0003. S100b levels correlated with NSE, interleukin (IL)-8, and IL-10 (0.27 < rs < 0.37, P < 0.05), and tended to correlate with suPAR ( rs = 0.26, P = 0.05), but not with the vasopressor dose ( P = 0.62). Conclusion : Among the investigated biomarkers, s100b demonstrated the best predictive ability for death in COVID-19 patients. The overall biomarker profile of the patients implies direct involvement of the nervous system by the novel coronavirus.

Neurological and psychiatric presentations associated with COVID-19.

The objective is to investigate coronavirus disease 2019 (COVID-19)-associated neurological and psychiatric effects and explore possible pathogenic mechanisms. This study included 77 patients with laboratory-confirmed COVID-19 in Wuhan, China. Neurological manifestations were evaluated by well-trained neurologists, psychologists, psychiatric presentations and biochemical changes were evaluated using the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, Brief Psychiatric Rating Scale, and electronic medical records. Eighteen (23.4%) patients presented with neurological symptoms. Patients with neurological presentations had higher urea nitrogen, cystatin C, and high-sensitivity C-reactive protein levels and lower basophil counts. Among them, patients with muscle involvement had higher urea nitrogen and cystatin C levels but lower basophil counts. In addition, patients with psychiatric presentations were older and had higher interleukin (IL)-6 and IL-10 levels and higher alkaline phosphatase, R-glutamate transferase, and urea nitrogen levels. Moreover, patients with anxiety had higher IL-6 and IL-10 levels than those without, and patients with moderate depression had higher CD8 + T cell counts and lower CD4 + /CD8 + ratios than other patients. This study indicates that the central nervous system may be influenced in patients with COVID-19, and the pathological mechanisms may be related to direct virus invasion of the central nervous system, infection-mediated overreaction of the immune system, and aberrant serum pro-inflammatory factors. In addition, basophils and cystatin C may also play important roles during these pathological processes. Our findings suggest that neurological and psychiatric presentations should be evaluated and managed in patients with COVID-19. Further studies are needed to investigate the underlying mechanisms.

Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

Hyperammonemia during treatment with valproate in critically ill patients.

INTRODUCTION: Hyperammonemia (HA) is a potential side-effect of valproate (VPA) treatment, which has been described during long-term administration. The aim of this study was to evaluate the incidence, the impact and the risk factors of HA in critically ill patients. METHODS: We reviewed the data of all adult patients treated in our mixed 35-bed Department of Intensive Care over a 12-year period (2004-2015) who: a) were treated with VPA for more than 72 h and b) had at least one measurement of ammonium and VPA levels during the ICU stay; patients with Child-Pugh C liver cirrhosis were excluded. HA was defined as ammonium levels above 60 µg/dl. RESULTS: Of a total of 2640 patients treated with VPA, 319 patients met the inclusion criteria (median age 64 years; male gender 55%); 78% of them were admitted for neurological reasons and ICU mortality was 30%. Median ammonium levels were 88 [63-118] µg/dl. HA was found in 245 (77%) patients. For those patients with HA, median time from start of VPA therapy to HA was 3 [2-5] days. In a multivariable analysis, high VPA serum levels, mechanical ventilation and sepsis were independently associated with HA during VPA therapy. In 98/243 (40%) of HA patients, VPA was interrupted; VPA interruption was more frequent in patients with ammonium levels > 100 µg/dl than others (p = 0.001). HA was not an independent predictor of ICU mortality or poor neurological outcome. CONCLUSIONS: In this study, HA was a common finding during treatment with VPA in acutely ill patients. VPA levels, sepsis and mechanical ventilation were risk factors for HA. Hyperammonemia did not influence patients' outcome.

Incidence and clinical spectrum of rhabdomyolysis in general neurology: a retrospective cohort study.

The objective of this retrospective cohort study was to evaluate demographic, clinical and laboratory characteristics of patients with rhabdomyolysis as defined by a serum creatine kinase (sCK) activity > 950 U/L. A total of 248 patients were recruited from the Department of Neurology, Medical University of Vienna, between 01/2000 and 12/2017, with a median sCK activity of 2,160 U/l (IQR 1,342-4,786). Seizures (31.9%), illicit drugs/alcohol (9.7%) and exercise (8.5%) were the most common trigger factors. Rhabdomyolysis incidence rates in specific neurological diseases as estimated by the ratio between rhabdomyolysis cases and the total number of cases with the corresponding disease were highest in myopathies (49.8/1,000 person-years, 95% CI 32.3-67.4), followed by epilepsy (16.4/1,000 person-years, 95% CI 12.8-20.0) and stroke (11.9/1,000 person-years, 95% CI 8.4-15.4). The half-life of sCK activity was 1.5 days in the total cohort. In myopathies, sCK activity was significantly higher as compared to other disease entities 7 days after the peak measurement (p = 0.0023). Acute kidney injury (AKI) developed in 18 patients (7.3%) with no AKI-related deaths during the study period. In conclusion, rhabdomyolysis occurred in a broad range of neurological entities but was associated with a favorable prognosis in most cases rarely resulting in AKI and death.

Complete blood cell count-derived ratios can be useful biomarkers for neurological diseases.

Complete blood cell count-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have recently shown to be highly sensitive biomarkers. Their usefulness has been proven as prognostic factors in several cancers, in the stratification of mortality in major cardiac events, as predictors and markers of infectious or inflammatory pathologies, and in many other conditions. Surprisingly, the study of these biomarkers in neurological diseases is somewhat limited. This paper aims to take stock of the data present in the literature regarding the complete blood cell count-derived ratios in this group of pathologies and to formulate a hypothesis, based on the most recent data concerning innate and acquired immunity, on which diseases of the nervous system could benefit in diagnostic and prognostic terms from the in-depth study of these new biomarkers.

Extra cellular vesicles in blood circulation as biomarkers and messengers of patho-hysiological activity and alterations.

There is an increasing interest in Extracellular Vesicles released by many cells through membrane shedding. In addition to cell signaling, these particles are true messenger cargos, which can carry cell surface proteins, miRNAs and non-coding RNAs to other and distant cells. They are part of the inter-cellular crosstalk and they contribute to transferring biological messages far away from the triggering event. EVs are biomarkers of many diseases, including thrombo-embolic pathology, infections, neurological or metabolic disorders, and malignancy. Their role and significance are presented and discussed in this short review, as consequences of disease and causes of its progression. But they can also be beneficial for tissue healing or repair, and they can be prepared in vitro to be used for cell- targeted treatments. Many identification and measurement methods for EV's are sophisticated, which restricts their use to research studies, but they have, nevertheless, a high laboratory potential for diagnosis, prognosis and evolution as follow-up of many pathologies. New emerging laboratory tools offer more friendly and easy applications for characterizing EVs and testing their associated activity, especially for the procoagulant ones.

Neurological complications in COVID-19 - a diagnostic challenge.

With the exponential growth of COVID-19 cases, the neurological complications reported during or after the infection became more common. There is limited knowledge regarding the pathophysiological mechanisms that are responsible for these complications. Recent data provides compelling evidence for the neurotropic nature of SARS-CoV-2, based on neurological manifestations reported during the current pandemic, as well as on previous experience with other coronaviruses. We present the case of a patient who developed headaches, motor deficit and dysphasia after respiratory COVID-19. Imaging tests showed heterogeneous central nervous system lesions (multiple subarachnoid hemorrhages and two ischemic strokes). Given the plethora of atypical neurological complications of COVID-19 described in the current literature, establishing a positive diagnosis and deciding on a treatment plan proved to be particularly challenging. We set to discuss some of the possible pathologies, hypothesized to be associated with COVID-19, that could lead to concomitant neurological lesions, similar to those noticed in our patient.

Prehospital troponin as a predictor of early clinical deterioration.

BACKGROUND AND OBJECTIVES: Elevated troponin T (cTnT) values are associated with comorbidities and early mortality, in both cardiovascular and noncardiovascular diseases. The objective of this study is to evaluate the prognostic accuracy of the sole utilization of prehospital point-of-care cardiac troponin T to identify the risk of early in-hospital deterioration, including mortality within 28 days. METHODS: We conducted a prospective, multicentric, controlled, ambulance-based, observational study in adults with acute diseases transferred with high priority by ambulance to emergency departments, between 1 January and 30 September 2020. Patients with hospital diagnosis of acute coronary syndrome were excluded. The discriminative power of the predictive cTnT was assessed through a discrimination model trained using a derivation cohort and evaluated by the area under the curve of the receiver operating characteristic on a validation cohort. RESULTS: A total of 848 patients were included in our study. The median age was 68 years (25th-75th percentiles: 50-81 years), and 385 (45.4%) were women. The mortality rate within 28 days was 12.4% (156 cases). The predictive ability of cTnT to predict mortality presented an area under the curve of 0.903 (95% CI: 0.85-0.954; P < .001). Risk stratification was performed, resulting in three categories with the following optimal cTnT cut-off points: high risk greater than or equal to 100, intermediate risk 40-100 and low risk less than 40 ng/L. In the high-risk group, the mortality rate was 61.7%, and on the contrary, the low-risk group presented a mortality of 2.3%. CONCLUSIONS: The implementation of a routine determination of cTnT on the ambulance in patients transferred with high priority to the emergency department can help to stratify the risk of these patients and to detect unknown early clinical deterioration.

Pro- and anti-inflammatory response in neurological disorders associated to anti-glutamate decarboxylase antibodies.

Rare conditions showing psychiatric symptoms and movement disorders have been linked with the presence of anti-glutamate decarboxylase antibodies. Proinflammatory and antiinflammatory immune responses were assessed in patients with neurological disorders associated to anti-glutamic acid decarboxylase antibodies (NDGAD). Immunoregulatory and proinflammatory cell populations were quantified by flow cytometry. No polarization toward Th1, Th2, or Th17 phenotypes was observed in NDGAD patients. Immunoregulatory responses were significantly reduced for Breg, activated Treg, Tr1, and Th3 cells, suggesting a deficient regulatory response, while intermediate monocyte levels were increased. The reduced levels of regulatory T and B cells suggest an impairment in regulatory immune response, while intermediate monocytes could be playing a role in the increased proinflammatory response.

Circulating 4-F4t-Neuroprostane and 10-F4t-Neuroprostane Are Related to MECP2 Gene Mutation and Natural History in Rett Syndrome.

Neuroprostanes, a family of non-enzymatic metabolites of the docosahexaenoic acid, have been suggested as potential biomarkers for neurological diseases. Objective biological markers are strongly needed in Rett syndrome (RTT), which is a progressive X-linked neurodevelopmental disorder that is mainly caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene with a predominant multisystemic phenotype. The aim of the study is to assess a possible association between MECP2 mutations or RTT disease progression and plasma levels of 4(RS)-4-F4t-neuroprostane (4-F4t-NeuroP) and 10(RS)-10-F4t-neuroprostane (10-F4t-NeuroP) in typical RTT patients with proven MECP2 gene mutation. Clinical severity and disease progression were assessed using the Rett clinical severity scale (RCSS) in n = 77 RTT patients. The 4-F4t-NeuroP and 10-F4t-NeuroP molecules were totally synthesized and used to identify the contents of the plasma of the patients. Neuroprostane levels were related to MECP2 mutation category (i.e., early truncating, gene deletion, late truncating, and missense), specific hotspot mutations (i.e., R106W, R133C, R168X, R255X, R270X, R294X, R306C, and T158M), and disease stage (II through IV). Circulating 4-F4t-NeuroP and 10-F4t-NeuroP were significantly related to (i) the type of MECP2 mutations where higher levels were associated to gene deletions (p ≤ 0.001); (ii) severity of common hotspot MECP2 mutation (large deletions, R168X, R255X, and R270X); (iii) disease stage, where higher concentrations were observed at stage II (p ≤ 0.002); and (iv) deficiency in walking (p ≤ 0.0003). This study indicates the biological significance of 4-F4t-NeuroP and 10-F4t-NeuroP as promising molecules to mark the disease progression and potentially gauge genotype-phenotype associations in RTT.

Development of delayed neurologic sequelae in acute carbon monoxide poisoning cases caused by briquette-based kotatsu: A case-control study.

ABSTRACT: Briquette-based kotatsu, a traditional Japanese heating system, is still used in rural areas and has been linked to the development of acute carbon monoxide (CO) poisoning. This study aimed to investigate the occurrence of delayed neurologic sequelae (DNS) in patients with acute CO poisoning caused by briquette-based kotatsu.This retrospective study included 17 patients treated for acute CO poisoning due to briquette-based kotatsu, between April 2017 and March 2020. Patients were divided into either a sequelae group (3 patients) or a non-sequelae group (14 patients) based on the presence or absence, respectively, of DNS. Demographic data, kotatsu characteristics, clinical findings, and therapies were compared between the 2 groups.Significant differences were noted in patient posture during their initial discovery. Specifically, all non-sequelae patients only had their legs under the kotatsu quilt and all sequelae patients had their entire bodies under the kotatsu quilt (P = .001). There were no statistically significant differences in carbon monoxide levels in hemoglobin (CO-Hb) or the creatine-kinase myocardial band (CK-MB), between the 2 groups; however, troponin-I levels were significantly higher in the sequelae group (P = .026). Abnormal head imaging findings were noted in 2 sequelae-group patients, with a significant difference between the groups (P = .025).We speculate that acute CO poisoning, caused by briquette-based kotatsu, may lead to DNS more frequently in patients in who cover their entire body with the kotatsu quilt and are found in this position. Patients should be warned about the dangers of acute CO poisoning when using briquette-based kotatsu.

Characterization and Biomarker Analyses of Post-COVID-19 Complications and Neurological Manifestations.

As the SARS-CoV-2 pandemic continues, reports have demonstrated neurologic sequelae following COVID-19 recovery. Mechanisms to explain long-term neurological sequelae are unknown and need to be identified. Plasma from 24 individuals recovering from COVID-19 at 1 to 3 months after initial infection were collected for cytokine and antibody levels and neuronal-enriched extracellular vesicle (nEV) protein cargo analyses. Plasma cytokine IL-4 was increased in all COVID-19 participants. Volunteers with self-reported neurological problems (nCoV, n = 8) had a positive correlation of IL6 with age or severity of the sequalae, at least one co-morbidity and increased SARS-CoV-2 antibody compared to those COVID-19 individuals without neurological issues (CoV, n = 16). Protein markers of neuronal dysfunction including amyloid beta, neurofilament light, neurogranin, total tau, and p-T181-tau were all significantly increased in the nEVs of all participants recovering from COVID-19 compared to historic controls. This study suggests ongoing peripheral and neuroinflammation after COVID-19 infection that may influence neurological sequelae by altering nEV proteins. Individuals recovering from COVID-19 may have occult neural damage while those with demonstrative neurological symptoms additionally had more severe infection. Longitudinal studies to monitor plasma biomarkers and nEV cargo are warranted to assess persistent neurodegeneration and systemic effects.

Neurological symptoms and blood neurofilament light levels.

Neurofilament light chain (NfL) is an incredibly specific marker of neuronal injury that is not specific for cause or location of the neuronal damage. NfL is increasingly considered as possible biomarker of disease activity in neurological conditions. Several works reviewed the utility of NfL in the different diseases. Nonetheless, NfL is a universal marker of neuronal damage, which interpretation spaces beyond the single disease. Because of this, the interpretation of NfL may benefit by also considering how neurological symptoms relate to its blood concentration. Here, we review how different neurological symptoms can be associated with blood NfL levels with a practical interpretation of it.

Neurological Involvement in Patients With Primary Sjögren's Syndrome.

BACKGROUND/OBJECTIVE: The neurological involvement associated with primary Sjögren's syndrome (pSS) can be life threatening. However, the specific characteristics of pSS-related neurological involvement remain obscure. This study aimed at determining the clinical characteristics of this neurological involvement in patients with pSS. METHODS: The clinical data of 205 patients with pSS who were admitted to our department between January 2015 and June 2017 were studied. Characteristics and laboratory findings of pSS patients with neurological abnormalities were compared with pSS patients without. RESULTS: Forty of the 205 patients with pSS exhibited neurological abnormalities (19.51%); of these, 13 patients exhibited central nervous system (CNS) involvement only, 20 patients exhibited peripheral nervous system (PNS) involvement only, and 7 patients exhibited both, yielding a total of 20 (9.76%) patients with CNS involvement and 27 (13.17%) patients with PNS involvement. The titers of anti-Sjögren's syndrome type A (SSA) antibodies were significant higher while the presence of anti-Sjögren's syndrome type B (SSB) antibodies was significant lower in patients with vs. without neurological involvement. Similar results were found in patients with CNS involvement. No significant differences between patients with and without neurological involvement were found for the other clinical parameters examined. CONCLUSIONS: Neurological involvement in patients with pSS is common and needs to be carefully evaluated. Patients with pSS with a high titer of anti-SSA and low presence of anti-SSB antibodies might have a relatively high risk of developing neurological involvement. Future studies should focus on identifying biomarkers that may aid in the early diagnosis of neurological involvement in patients with pSS.

The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. RESULTS: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. CONCLUSIONS: NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.