At the request of all of the authors, the corresponding author of this paper was changed to Dr. Jin Jun Luo.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.
Atherosclerosis ; Dementia ; DNA ; Eclampsia ; Epilepsy ; Female ; Folic Acid ; Homocysteine ; Hyperhomocysteinemia* ; Metabolism ; Methionine ; Methylation ; Methylenetetrahydrofolate Reductase (NADPH2) ; Multiple Sclerosis ; Myocardial Infarction ; Nervous System ; Nervous System Diseases* ; Parkinson Disease ; Plasma ; Pregnancy ; Stroke ; Vitamin B 12 ; Vitamins

Background: and Purpose Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS) hospitalization. Methods: Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines. Results: Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4–6 weeks (P<0.001). In AIS, cancer, obesity, higher National Institutes of Health Stroke Scale (NIHSS) score, longer hospital stay, home or rehabilitation disposition, and absence of atrial fibrillation were associated with VTE readmission. In ICH, longer hospital stay and rehabilitation disposition were associated with VTE readmission. The VTE rate was higher in ICH compared to AIS (adjusted hazard ratio 2.86, 95% confidence interval 1.93–4.25, P<0.001). Conclusions After stroke, VTE readmission risk is highest within the first 4–6 weeks and nearly three-fold higher after ICH vs. AIS. VTE risk is linked to decreased mobility and hypercoagulability. Studies are needed to test short-term VTE prophylaxis beyond hospitalization in high-risk patients.