Evaluating the Clinical Utility of Epstein-Barr Virus Antibodies as Biomarkers in Multiple Sclerosis: A Systematic Review.

BACKGROUND: EBV is a necessary but not sufficient factor in the pathophysiology of multiple sclerosis (MS). EBV antibodies to the nuclear antigen (EBNA1) and viral capsid antigen (VCA) rise rapidly prior to MS disease manifestations, and their absence has clinical utility with a high negative predictive value. It remains unclear whether EBV levels act as prognostic, monitoring, or pharmacodynamic/response biomarkers. Substantial literature on this topic exists but has not been systematically reviewed. We hypothesized that EBV levels against EBNA1 and VCA are potential prognostic and monitoring biomarkers in MS, and that patient population, MS clinical phenotype, and EBV assay method may play important roles in explaining variation among study outcomes. METHODS: We systematically searched PubMed and EMBASE from inception to April 1, 2022. After removal of duplicates, records were screened by abstract. Remaining full-text articles were reviewed. Clinical and MRI data were extracted from full-text articles for comparison and synthesis. RESULTS: Searches yielded 696 unique results; 285 were reviewed in full, and 36 met criteria for data extraction. Heterogeneity in sample population, clinical outcome measures, assay methods and statistical analyses precluded a meta-analysis. EBV levels were not consistently associated with clinical disease markers including conversion from CIS to RRMS, neurological disability, or disease phenotype. Studies using repeated-measures design suggest that EBNA1 levels may temporarily reflect inflammatory disease activity as assessed by gadolinium-enhancing Magnetic Resonance Imaging (MRI) lesions. Limited data also suggest a decrease in EBV levels following initiation of certain disease-modifying therapies. CONCLUSION: Heterogeneous methodology limited generalization and meta-analysis. EBV antibody levels are unlikely to represent prognostic biomarkers in MS. The areas of highest ongoing promise relate to diagnostic exclusion and pharmacodynamic/disease response. Use of EBV antibodies as biomarkers in clinical practice remains additionally limited by lack of methodological precision, reliability, and validation.

Cranial neurolymphomatosis and its oncologic counterparts: Case series on malignant cranial nerve neuropathies.

Neurolymphomatosis occurs due to the infiltration of a nerve by malignant cells. Cranial neurolymphomatosis is a rare disease process associated with non-solid tumors (i.e., lymphoma, leukemia, etc.). Cranial neurolymphomatosis presents with single or multifocal neuropathy. Primary cranial neurolymphomatosis is defined as the initial presenting symptom leading to a new diagnosis of cancer. Secondary cranial neurolymphomatosis is defined as cancer progression with spread to a cranial nerve. While cranial neurolymphomatosis is a recognized cause of cranial nerve neuropathies, a myriad of other malignancies can also lead to similar clinical manifestations. This case series elucidates not only the classical presentations associated with cranial neurolymphomatosis but also introduces other oncologic entities that may compromise cranial nerve functions. A descriptive case series is presented on six patients with malignancy-related cranial neuropathy who came to a tertiary-care center from 2018 to 2022. 5/6 (83.3%) of patients presented with primary cranial neuropathy. Diffuse large B-cell lymphoma was the most prevalent malignancy observed in 3/6 (50.0%) cases. Other malignancies observed include non-Hodgkin lymphoma, monoclonal B-cell lymphocytosis, and peripheral T-cell lymphoma. The most affected cranial nerve was the trigeminal nerve in 4/6 (66.6%) individuals. Multiple cranial neuropathies were seen in 2/6 (33.3%) of patients. The most common neuroradiographic finding was a lesion to Meckel's cave. Other cranial nerves affected include the optic, facial, and vestibulocochlear nerves. Diagnostic modalities utilized included magnetic resonance imaging and 18F-fluoro-2-D-glucose positron emission tomography-computerized tomography. Cerebrospinal fluid analysis for flow cytometry may also have diagnostic value in patients with increased disease burden. Treatment was guided according to individual malignancy and 2/6 (33.3%) patients achieved complete remission, 2/6 (33.3%) died within 1 year, and 1/6 (16.6%) were referred to hospice. Cranial neuropathy may be the first symptom of a neoplastic process; thus, prompt recognition and treatment may improve morbidity and mortality.

Successful Mechanical Thrombectomy of Bilateral Middle Cerebral Artery Occlusions Following Apixaban Discontinuation.

Optimal anticoagulation management in patients with atrial fibrillation (AF) during acute ischemic stroke is complex and often poses a significant clinical challenge. An 82-year-old man with AF presented with left-sided hemiparesis and hypoesthesia due to occlusion of the right middle cerebral artery (MCA) after discontinuing apixaban for 5 days. Successful mechanical thrombectomy (MT) achieved thrombolysis in cerebral infarction (TICI) score of 2C. Anticoagulation was postponed due to a small risk of hemorrhagic conversion. However, the patient developed a rare bilateral M1 segment MCA occlusions on the fifth day with a National Institute of Health Stroke Scale (NIHSS) score of 23, leading to an emergent thrombectomy, resulting in TICI 3 and TICI 2C recanalization in left and right MCAs, respectively. The patient required admission to the intensive care unit and was eventually discharged to an inpatient rehabilitation facility with only residual left hemiparesis and moderate dysarthria. This case underscores the delicate balance between the risk of recurrent ischemic stroke and the potential for hemorrhagic conversion when treating anticoagulation in the acute setting. Close monitoring and an individualized approach are necessary for the treatment of patients with AF who have suffered an acute stroke, especially when anticoagulation must be stopped. We encourage future guidelines to incorporate both imaging and clinical data when determining the continuation of anticoagulation in patients with a recent ischemic stroke. This case also depicts the effectiveness of neuroendovascular interventions such as MT to effectively manage rare simultaneous large multi-vessel occlusions with good outcomes.

A single-center retrospective study of hospitalized COVID-19 patients: demographics, laboratory markers, neurological complications, ICU admission, and mortality.

The coronavirus disease 2019 (COVID-19) pandemic has unveiled a wide array of clinical biomarkers, and neurological manifestations in affected patients, necessitating further exploration. Methods: This single-center retrospective study evaluated clinical and neurological sequelae, demographics, as well as laboratory markers, in hospitalized COVID-19 patients from January to September 2020. Results: Among 1248 inpatients (median age: 68 years; 651 women), 387 (31%) were admitted to the ICU. Central nervous system (CNS) manifestations were present in 521 (41.74%) patients, while peripheral nervous system manifestations were observed in 84 (6.73%). COVID-19-related mortality occurred in 314 (25.16%) cases. ICU-admitted patients were predominantly male (P<0.0001), older (age≥60; P=0.037) and had more comorbidities such as diabetes (P=0.001), hyperlipidemia (P=0.043), and coronary artery disease (P=0.015). ICU patients exhibited more CNS manifestations (P=0.001), including impaired consciousness (P<0.0001) and acute cerebrovascular disease (P=0.023). Biomarkers linked to admission to the ICU included elevated white blood cell count, ferritin, lactate dehydrogenase, creatine kinase, blood urea nitrogen, creatinine, and acute phase reactants (e.g. erythrocyte sedimentation rate and C-reactive protein). ICU patients demonstrated lower lymphocyte and platelet counts compared to non-ICU patients. Those with CNS involvement in the ICU often exhibited elevated blood urea nitrogen, creatinine, and creatine kinase levels. Higher mortality from COVID-19 was observed in ICU patients (P<0.0001). Conclusions: Multiple serum biomarkers, comorbidities, and neurological manifestations in COVID-19 patients have been consistently documented and may be linked to increased morbidity, ICU admission, and mortality. Recognizing and addressing these clinical and laboratory markers is essential for effective COVID-19 management.

COVID-19 in the intensive care unit: Unmasking the critical factors impacting patient survival.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, intensive care units (ICUs) around the world have been pushed to their limits as they grapple with the effects of the severe acute respiratory syndrome coronavirus 2 virus. Identifying prognostic factors that influence mortality in COVID-19 patients admitted to the ICU could offer valuable insights for clinicians seeking to prevent disease progression. A retrospective analysis was conducted on COVID-19 patients admitted to the ICU between January and September 2020. The analysis considered patient demographics, comorbidities, neurological and non-neurological symptoms, as well as laboratory markers. The multivariate logistic regression analysis aims to uncover associations between these factors and patient outcomes. Of the 387 patients included in this study, nearly half (48.5%) of the ICU patients succumbed to COVID-19. Factors that contributed to increased mortality included being 60 years of age or older, impaired consciousness, lung disease, elevated international normalized ratio (INR), and elevated blood urea nitrogen (BUN) levels. Surprisingly, symptoms such as dizziness/lightheadedness, myalgia, and headache were associated with a higher likelihood of survival. In addition, elevated D-dimer and aspartate aminotransferase (AST) levels, as well as lymphopenia, were more commonly observed in deceased patients. The study concluded that those who died in the ICU tended to be older, white, and burdened with more comorbidities and impaired consciousness. With the intriguing link between specific symptoms and survival, further research is essential to uncover the underlying pathophysiological mechanisms that influence ICU patient outcomes in the context of COVID-19.

Predicting mortality in moderate-severe TBI patients without early withdrawal of life-sustaining treatments including ICU complications: The MYSTIC-score.

PURPOSE: To develop and internally validate the MortalitY in Moderate-Severe TBI plus ICU Complications (MYSTIC)-Score to predict in-hospital mortality of msTBI patients without early (<24 h) withdrawal-of-life-sustaining treatments. METHODS: We analyzed data from a Neuro-Trauma Intensive Care Unit prospectively collected between 11/2009-5/2019. Consecutive adult msTBI patients were included if Glasgow Coma Scale≤12, and neither died nor had withdrawal-of-life-sustaining treatments within 24 h of admission (n = 485). Using univariate and multivariable logistic regression in a random-split cohort approach (2/3 derivation;1/3 validation), we identified independent predictors of in-hospital mortality while adjusting for validated predictors of mortality (IMPACT-variables). We constructed the MYSTIC-Score and examined discrimination and calibration. RESULTS: The MYSTIC-Score included the ICU complications brain edema, herniation, systemic inflammatory response syndrome, sepsis, acute kidney injury, cardiac arrest, and urinary tract infection. In the derivation cohort(n = 324), discrimination and calibration were excellent (area-under-the-receiver-operating-curve [AUC-ROC] = 0.95;Hosmer-Lemeshow p-value = 0.09, with p > 0.05 indicating good calibration). Internal validation revealed an AUC-ROC = 0.93 and Hosmer-Lemeshow-p-value = 0.76 (n = 161). CONCLUSIONS: Certain ICU complications are independent predictors of in-hospital mortality and strengthen outcome prediction in msTBI when combined with validated admission predictors of mortality. However, external validation is needed to determine robustness and practical applicability of our model given the high potential for residual confounders.