J-Shaped Relationship of Serum Uric Acid with Unfavorable Short-Term Outcomes among Patients with Acute Ischemic Stroke.

(1) Background: The role of uric acid in stroke outcomes remains inconclusive. (2) Methods: We retrospectively enrolled 3370 patients with acute ischemic stroke. (3) Results: Uric acid level was higher in men than in women. Univariate analyses revealed that the rates of hyperuricemia were higher in all patients and in women for unfavorable outcomes. For death, the hyperuricemia rates were higher in all patients including men and women, and the uric acid levels were also higher in all patients and in women. A J-shaped curve was observed between uric acid and the discharge-modified Rankin Scale score. Patients within Quartiles 1 (<4.1 mg/dL) and 4 (>6.5 mg/dL) of uric acid had higher rates of unfavorable outcomes and death than patients within Quartiles 2 (4.1−5.1 mg/dL) and 3 (5.1−6.2 mg/dL). Multivariable analyses for unfavorable outcomes revealed that Quartile 1 of uric acid was a significant factor in all patients and in men. In men, a significant factor for death was being in Quartile 1 of uric acid. In women, higher levels of uric acid or hyperuricemia (>6.6 mg/dL) were significant factors for death. (4) Conclusions: Lower uric acid levels are a predictor for unfavorable outcomes and death in men, and higher uric acid levels are a predictor for death in women.

Comparison of Clinical Features, Immune-Inflammatory Markers, and Outcomes Between Patients with Acute In-Hospital and Out-of-Hospital Ischemic Stroke.

PURPOSE: We investigated the differences of clinical features, four immune-inflammatory markers, namely neutrophil counts, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as outcomes between patients with in-hospital ischemic stroke (IHIS) and out-of-hospital ischemic stroke (OHIS). PATIENTS AND METHODS: We retrospectively enrolled 72 patients with IHIS and 3330 patients with OHIS. RESULTS: IHIS accounted for 2% of all patients with ischemic stroke and occurred more often in cardiology and orthopedic surgery wards. Infection, cardiac disease, and pulmonary disorder were the most common causes of hospitalization. Compared with those with OHIS, patients with IHIS had higher levels of immune-inflammatory markers, initial National Institute of Health Stroke Scale (NIHSS) scores, longer hospital stays, higher rates of heart disease, large-artery atherosclerosis or cardioembolism, received more intravenous thrombolysis (IVT) or endovascular thrombectomies (EVTs), more complications, unfavorable outcomes, and mortality. Every immune-inflammatory marker exhibited positive correlations with initial NIHSS scores and discharge modified Rankin Scale scores among patients with OHIS. NLR and SII were higher among patients with a fatal outcome in both groups. Among patients receiving IVT, most of treatment time intervals were shorter for those with IHIS than those with OHIS. Significant factors for mortality were NLR >5.5, atrial fibrillation, and complications, with a C-statistic of 0.897 in those with IHIS; in those with OHIS, these factors were an initial NIHSS score of >10, NLR >6.0, atrial fibrillation, prior stroke, cancer history, and complications with a C-statistic of 0.902. The results were similar after replacing the NLR with SII. CONCLUSION: Patients with IHIS had more complicated clinical features, higher levels of immune-inflammatory markers, and higher rates of mortality than patients with OHIS. The most significant predictor for mortality among those with OHIS was NIHSS score >10, and the predictors among patients with IHIS were NLR >5.5 and SII >2120.

THαß Immunological Pathway as Protective Immune Response against Prion Diseases: An Insight for Prion Infection Therapy.

Prion diseases, including Creutzfeldt-Jakob disease, are mediated by transmissible proteinaceous pathogens. Pathological changes indicative of neuro-degeneration have been observed in the brains of affected patients. Simultaneously, microglial activation, along with the upregulation of pro-inflammatory cytokines, including IL-1 or TNF-α, have also been observed in brain tissue of these patients. Consequently, pro-inflammatory cytokines are thought to be involved in the pathogenesis of these diseases. Accelerated prion infections have been seen in interleukin-10 knockout mice, and type 1 interferons have been found to be protective against these diseases. Since interleukin-10 and type 1 interferons are key mediators of the antiviral THαß immunological pathway, protective host immunity against prion diseases may be regulated via THαß immunity. Currently no effective treatment strategies exist for prion disease; however, drugs that target the regulation of IL-10, IFN-alpha, or IFN-ß, and consequently modulate the THαß immunological pathway, may prove to be effective therapeutic options.

Association of a High Neutrophil-to-Lymphocyte Ratio with Hyperdense Artery Sign and Unfavorable Short-Term Outcomes in Patients with Acute Ischemic Stroke.

PURPOSE: Immune-inflammatory processes are involved in all the stages of stroke. This study investigated the association of the neutrophil-to-lymphocyte ratio (NLR) with the hyperdense artery sign (HAS) observed on brain computed tomography (CT) and with clinical features in patients with acute ischemic stroke. METHODS: We retrospectively enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data collected included imaging studies, risk factors, laboratory parameters, and clinical features during hospitalization. RESULTS: The HAS was identified in 6% of the 2903 patients and 66% of the 236 patients with acute middle cerebral artery occlusion. Patients with the HAS had a higher NLR. HAS prevalence was higher in men and patients with cardioembolism. The NLR exhibited positive linear correlations with age, glucose and creatinine levels, length of hospital stay, initial National Institutes of Health Stroke Scale (NIHSS) scores, and mRS scores at discharge. The NLR was significantly higher in patients with large-artery atherosclerosis and cardioembolism and was the highest in patients with other determined etiology. Multivariate analysis revealed that an initial NIHSS score of ≥10 and an NLR of >3.5 were significant positive factors, whereas diabetes mellitus and age > 72 years were significant negative factors for the HAS, with a predictive performance of 0.893. An initial NIHSS score of ≥5, positive HAS, age > 75 years, diabetes mellitus, an NLR of >3.5, female sex, a white blood cell count of >8 × 103/mL, and elevated troponin I were significant predictors of unfavorable outcomes, with a predictive performance of 0.886. CONCLUSION: An NLR of >3.5 enabled an efficient prediction of CT HAS. In addition to conventional risk factors and laboratory parameters, both an NLR of >3.5 and CT HAS enabled improved prediction of unfavorable stroke outcomes.

Thrombolysis for atlantoaxial dislocation mimicking acute ischemic stroke.

The frequency of stroke mimics among stroke patients has been reported to be up to 30%, and that in patients who receive thrombolytic therapy ranges between 1% and 16%. Atlantoaxial dislocation with myelopathy mimicking stroke is extremely rare. An 83-year-old man with a history of old cerebellar infarction presented to the emergency department with acute left hemiplegia after a chiropractic manipulation of the neck and back several hours before symptom onset. Mild hypoesthesia was observed on his left limbs. No speech disturbance, facial palsy, or neck or shoulder pain was observed. Intravenous thrombolytic treatment was given 238 min after symptom onset. Brown-Sequard syndrome subsequently developed 6 h after thrombolysis with a hypoesthetic sensory level below the right C5 dermatome. An emergent brain magnetic resonance angiography did not reveal an acute cerebral infarct but rather an atlantoaxial dislocation causing upper cervical spinal cord compression. Clinical symptoms did not deteriorate after thrombolysis. He received successful decompressive surgery 1 week later, and his muscle power gradually improved, with partial dependency when performing daily living activities 2 months later. A literature review revealed that only 15 patients (including the patient mentioned here) with spinal disorder mimicking acute stroke who received thrombolytic therapy have been reported. Atlantoaxial dislocation may present as acute hemiplegia mimicking acute stroke, followed by Brown-Sequard syndrome. Inadvertent thrombolytic therapy is likely not harmful for patients with atlantoaxial dislocation-induced cervical myelopathy. The neurological deficits of patients should be carefully and continuously evaluated to differentiate between stroke and myelopathy.