Effect of Citicoline on Neurological Severity Score and Cerebral Doppler Resistive Index in Neonatal Hypoxic Ischemic Encephalopathy

Hypoxic‐ischemic encephalopathy (HIE) is a leading cause of neonatal brain injuryworldwide. In the developed world, the incidence is estimated at up to 8 per 1,000 livebirths, while in developing countries, estimates are as high as 26 per 1,000 live births.Approximately 20‐30% of infants with HIE die in the neonatal period, and 33‐50% ofsurvivors are left with permanent neurodevelopmental abnormalities.1 HIE can beclassified into mild (Stage I), moderate (Stage II), and severe (Stage III) based on theSarnat and Sarnat staging system(Table 1), with stage II and III being associated withthe highest morbidity and mortality.Therapeutic hypothermia remains the standard therapy for HIE. However, its availability,high costs, need for specialized equipment and monitoring limit its use in developingcountries like Pakistan, therefore alternative neuroprotective agents are used howeverthere is still no consensus regarding which agent is the most effective. Citicoline(cytidine diphosphate choline) has demonstrated several neuroprotective mechanisms. Ithelps preserve neuronal membrane integrity by maintaining phospholipids while decreasingphospholipase A2 activity and oxidative damage.2 It also enhances phosphatidylcholinesynthesis and promotes glutathione production, thereby decreasing free‐radical‐mediatedneuronal injury. Experimental studies further suggest neuroprotective roles of citicolineas it modulates excitotoxicity by decreasing glutamate levels.3,4 These combined effectsmay contribute to improved neuronal survival and recovery after hypoxic‐ischemic insults.Long term effects have been studied however no study evaluates short term improvementfrom therapy.Resistive Index is a parameter assessed on cranial doppler ultrasonography, it isdifference between peak systolic and end diastolic pressures in the anterior cerebralarteries, normal value is 0.68‐0.72 5it demonstrates cerebral blood flow changes due tohypoxia, lower values have been associated with worse neurological outcome.5 RI has beenstudied in comparison to MRI and also its changes pre and post therapeutic hypothermia,and has been found to be useful tool6,7. American Academy of Neurology and PracticeCommittee of the Child Neurology Society recommends RI and end diastolic flow velocity(EDFV) in the anterior cerebral artery to assess cerebral perfusion and early predictionof outcome.8 This study is therefore designed to assess the effect of citicoline oncerebral resistive index and neurological improvement using Sarnat‐Sarnat scoring after 3days of treatment in neonates with hypoxic‐ischemic encephalopathy. The findings maycontribute to establishing evidence for adjunctive therapeutic strategies aimed atreducing neurological morbidity in affected neonates. Despite its clinical use in somecenters, there is limited published evidence regarding the efficacy of citicoline inneonates with HIE.