Clinical Usefulness of Cell-Free DNA as a Prognostic Marker in Acute Ischemic Stroke.

OBJECTIVE: Stroke has become the second most common cause of death. Several biomarkers have been detected in the peripheral blood from stroke patients, but none has found a place in clinical practice. Cell-free DNA (cf-DNA) liberated into the blood soon after the onset of stroke might be useful for assessing disease severity and prognosis. STUDY DESIGN AND METHODS: A total of 54 patients presenting with ischemic stroke were recruited consecutively with the exclusion of patients having trauma, tumor, infections, and organ failure. The cf-DNA was extracted by circulating nucleic acid kit from Qiagen and measured by real-time quantitative polymerase chain reaction assay for ß-globin gene. The primary outcome measure was poststroke modified Rankin scale Score at 3 months after the onset of symptoms. RESULTS: Higher cf-DNA levels were associated with severity at the time of admission measured by National Institutes of Health Stroke Scale (P=0.003) and poor outcome as measured by modified Rankin scale 3-month scores (P=0.001). Therapeutic intervention in the form of a mechanical thrombectomy or IV thrombolysis was associated with improved outcome in patients with cf-DNA<10,000 kilogenome-equivalents/L (P≤0.01). CONCLUSIONS: cf-DNA level correlates well with the severity of stroke at admission and long-term prognosis. It can be used as an additional marker to predict the outcome of therapeutic intervention.

Cell free DNA: A Novel Predictor of Neurological Outcome after Intravenous Thrombolysis and/or Mechanical Thrombectomy in Acute Ischemic Stroke Patients.

PURPOSE: Several blood markers have been evaluated in stroke patients, but their role remains limited in clinical practice. This study was designed to evaluate the utility of cell free DNA (cf DNA) in stroke patients undergoing therapeutic intervention in the form of mechanical thrombectomy in acute ischemic stroke patients. MATERIALS AND METHODS: Twenty-six patients with ischemic stroke who were managed with interventions like intravenous thrombolysis (IVT) and mechanical thrombectomy were recruited consecutively in this study. The cf DNA was extracted by using circulating nucleic acid kit and measured by real-time quantitative PCR assay for ß-globin gene. The neurological outcome was measured by modified Rankin scale (mRS) score at three months after the onset of symptoms. RESULTS: Cf DNA levels correlated with severity of stroke at the time of admission (r=0.421, P=0.032) and poor outcome at three months (r=0.606, P=0.001). Therapeutic intervention in the form of mechanical thrombectomy or IVT was associated with improved outcome in patients with cf DNA <10,000 kilogenome-equivalents/L (P=<0.05). CONCLUSION: Cf DNA level correlated well with the 3 month outcome in acute ischemic stroke patients. It can be a potential supplementary marker to predict neurological outcome after therapeutic intervention.

Fibrodysplasia ossificans progressiva: three Indian patients with mutation in the ACVR1 gene.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by ectopic bone formation involving the connective tissues leading to severe skeletal manifestations. The genetic defect in this disorder has not been characterized in Indian patients till date. The authors report three cases of FOP along with the molecular defects identified in them. Exon 4 of the ACVR1 gene was amplified and analysed by sequencing. All three cases revealed common heterozygous mutation i.e., c.617(G>A). Identification of this mutation would lead to decrease in misdiagnosis and subsequent iatrogenic harm caused to these children by unnecessary surgical procedures. Also, mutation detection would provide an opportunity for prenatal diagnosis.