Clinico-Epidemiological Profile, Etiology, and Imaging in Neonatal Stroke: An Observational Study from Eastern India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.310081
Source of Support: None, Conflict of Interest: None
Keywords: Arterial ischemic stroke (AIS), encephalopathy, hemorrhagic stroke (HS), magnetic resonance imaging (MRI), neonatal stroke (NS), seizures
Stroke in pediatrics can be classified as perinatal or childhood stroke. Perinatal stroke (PS) can be further subclassified into presumed perinatal and neonatal stroke (NS). PS can occur as a result of vascular insult to the developing fetal brain between 20th week of gestation and 28 days of life. The incidence of PS is 1 in 2300–5000 live births. The onset of stroke between birth and 28 days of life is called as NS.,,, Based on anatomical involvement, NS can be further classified into arterial ischemic stroke (AIS), hemorrhagic stroke (HS), cerebral sinovenous thrombosis (CST), and peri-ventricular venous infarction.This can be differentiated by imaging. NS is a medical emergency and is associated with multiple risk factors. It is associated with long-term morbidity such as hemiplegic cerebral palsy, seizures, and neurodevelopmental delay. Mortality rates are between 1% and 25%. Till date, there are no studies available from India which have looked into the profile of stroke in neonates. This study retrospectively evaluates the clinico-epidemiological profile and imaging findings of neonates admitted with stroke to a tertiary care hospital in eastern India.
This study was carried out in a neonatal intensive care unit (NICU) of a tertiary care hospital in eastern India.
All neonates diagnosed to have a stroke and admitted to NICU between August 2014 and July 2016 were included.
This was a retrospective, observational, descriptive study.
A total of 43 neonates diagnosed to have NS by 28 days of life were included. Neonates with trauma to the head were excluded. Patients were classified under AIS or HS. A registry was maintained to document the clinico-epidemiological profile, clinical symptoms, and signs at presentation. “Hypoxic injury” was considered when there was evidence of fetal distress characterized by absent/reduced fetal movements or inadequate/absence of resuscitation measures following delivery and before referral to a tertiary care unit. “Neonatal encephalopathy” was defined as an abnormal level of consciousness with diminished tone and reflex, with/without seizures. Patients were evaluated for infection (blood, cerebro-spinal fluid study), hypoglycemia, electrolytes, or clotting abnormalities. Electroencephalogram (EEG) was done when there was clinical evidence of seizures. Electrocardiogram (ECG) was performed in all babies admitted with stroke to detect evidence of arrhythmia if any. Echocardiography was done if there was clinical evidence of murmur, difference in pre-ductal and post-ductal saturations, or if femoral pulses were absent. MRI was performed on all babies in our hospital. Ethical clearance was obtained from the hospital ethics committee.
A total of 43 neonates admitted with NS to our NICU were analyzed for this study. Antenatal history of maternal sepsis was present in five neonates (12%). About 88% (n = 38) were born at term (37–40 weeks) and the remaining (n = 5) were pre-term (≥34 to < 37 weeks). Around 70% (n = 30) were male infants with the male-to-female ratio being 2.3:1. There was a male preponderance in both the pre-term and the term populations. APGAR scores were not documented for all patients and hence were not considered for analysis. The median age of presentation in pre-terms was four days. However, term babies presented late and had a median age of presentation of 11 days.
In pre-terms, poor feeding (n = 4), abnormal tone (n = 3), and recurrent apnea (n = 3) were the most common presentation followed by seizures (n = 2) [Table 1]. About 60% (n = 3) had hypoxic injury and 40% (n = 2) had sepsis, of which one baby had Escherichia coli isolated from blood and the other had necrotizing enterocolitis.
In term babies, seizures were documented in 67% (n = 25) and was the most common presentation followed by poor feeding in 32% (n = 12) and abnormal tone in 26% (n = 10) [Table 2]. The remaining presented with recurrent apnea, encephalopathy, hemiparesis, and abnormal tone. A total of 39% (n = 15) remained undiagnosed as financial constraints prevented us from performing thrombophilia or metabolic screen in these babies. Hypoxic injury remained the most commonly diagnosed etiology in 38% (n = 13) babies followed by sepsis in 18%. One baby had hypoglycemia, one had fatty acid oxidation defect, and another had complex cardiac disease [total anomalous pulmonary venous drainage (TAPVD)].
MRI brain revealed 53% (n = 23) to be having AIS and 47% with HS [Table 3]. There was an increase in male preponderance in both the groups with median presentation being seven days in both AIS and HS. Around 70% (n = 16) had involvement of the middle cerebral artery (MCA) which was the most common area of distribution in AIS [Table 4]; [Figure 1]. Among 20 babies with HS, 11 had intra ventricular hemorrhage (IVH), 4 had intra parenchymal hemorrhage (IPH), and the remaining five had both IPH and IVH. There was one baby with sepsis and extensive hemorrhage involving the brain stem who died.
The etiology of NS is still not well-explained in literature. In about 25%–50% of cases, the etiology may remain unexplained., The acute presentation is usually as neonatal encephalopathy. Neurodevelopmental delay, sensori-motor deficits, poor cognition, epilepsy, and behavioural problems have been noted in infants having an early insult to the developing brain., However, studies have shown a more favorable outcome in neonates compared with other population group due to the increased plasticity of the developing brain. Imaging techniques especially MRI remains the investigation of choice as focal neurological signs are often difficult to elicit in neonates.
NS especially HS is quite common in less than 32 weeks of gestation, mainly due to germinal matrix hemorrhage. However, they have been documented in late pre-term and term infants as we found in our study. NS was more common in males in our study, although no such prevalence has been noted in previous studies.
NS has been associated with sepsis/meningitis, fetal hypoxia, embolism, trauma, arteriopathy, vascular malformations, prothrombotic conditions, and idiopathic reasons.,,, In our population, we found an increasing association with hypoxia (37%) and sepsis (21%). About 35% remained undiagnosed similar to previous studies. The significant large number of patients with hypoxia is possible because of limited resuscitation facilities and inadequate airway support during transport. National neonatal perinatal database has documented perinatal asphyxia contributing to 20% of neonatal deaths and a third of still births in 2000.We were also not able to perform thrombophilia screen because of financial constraints. Several studies have documented prothrombotic conditions to be the etiology behind 30% of NS. Hence, a considerable number of neonates remained undiagnosed.
Seizures were the most common symptom in our study similar to other studies and usually were noted within the first 24 h. Apnea, altered tone, hemiparesis, encephalopathy, poor feeding, and irritability were also noted. Apnea along with bradycardia or change in tone was considered as a manifestation of seizure.
Although AIS remains the most common subtype of NS, we found an almost equal distribution of AIS and HS., This might be because of the small population size of our study. MCA territory was the most common site of involvement in AIS similar to other studies., IVH was the most common form of involvement in HS. Subdural and subarachnoid hemorrhage was also noted along with IPH. MRI is the most sensitive tool for diagnosis and prognostication of outcome in NS. Diffusion-weighted imaging along with T1- and T2-weighted sequence help in early delineation of AIS within the first week of life.
Congenital heart disease has been documented to cause HS in several studies., Because our hospital is not a cardiac referral center, we had only one baby with TAPVD with HS. Babies should undergo ECG and echocardiography whenever there is suspicion of cardiac involvement.
Limitations of the study
We did a retrospective collection of data on a small population referred to our hospital for diagnosis and management. Antenatal risk factors for stroke were therefore difficult to document for all the patients. Placental biopsy and thrombophilia screen were also not possible due to various constraints. Thrombophilia remains one of the common causes of NS.Metabolic panel was done in only four babies due to financial constraints.
NS remains an acute emergency with high morbidity and mortality. Seizures remain the most common presenting symptom. MRI helps in delineating and prognostication of infants with NS. Improvement in resuscitation facilities and better antenatal monitoring will help in improving the outcome in neonates and reduce the incidence of NS in India.
Source of support
Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4]