Neonatal Seizures occur more commonly during hypothermia or rewarming They rarely occur

Neonatal Seizures occur more commonly during hypothermia or rewarming. They rarely occur after baby returns to normothermia. In new\onates with moderate to severe HIE managed with hypothermia, incidence of seizures was 30% to 65%.(1) Ammerican Academy of Pediatrics recommends availability of conventional EEG or aEEG for identification of seizures while performing therapeutic hypothermia in neonates with HIE.(1)INTRACRANIAL HEMORRHAGE (ICH)Around 15% of neonates have intracranial hemorrhage as the primary cause of their seizure and this incidence is higher in premature neonates.(1)The major clinically important types of neonatal intracranial hemorrhages are(76)Type of hemorrhage Anatomical SiteExtradural Between skull and outside of duraSubdural Between dura and arachnoidSubarachnoid Between arachnoid and piaCerebellar Cerebellar hemispheres or vermisIntraventricular Within ventricles or including periventricular hemorrhageParenchymal Cerebral parenchyma.Various important types of hemorrhages associated with seizures are discussed below.Subarachnoid HemorrhageAlthough this type of hemorrhage is very common but is not of major clinical importance. In full term neonates, subarachnoid hemorrhage can cause seizures. The onset of seizure is usually on 2nd day of life. If this type of hemorrhage occurs in association with HIE then seizures can present on 1st day of life. During the interictal period, neonates usually appear well, and the description “well baby with seizures” often seems appropriate.(76)The diagnosis of primary subarachnoid hemorrhage is usually made by MRI or CT; on rare occasions it is made by ultrasound. Sometimes the possibility of primary subarachnoid hemorrhage is raised initially by the findings of an elevated number of RBCs and an elevated protein content in the CSF, usually obtained for another purpose.In general the prognosis for infants with primary subarachnoid hemorrhage without serious traumatic or hypoxic injury is good. Few full-term neonates with seizures as the primary manifestation of the hemorrhage are normal on follow-up in at least 90% of cases.Intraventricular HemorrhageIVH is a common injury in the preterm brain, originating in the subependymal germinal matrix.(77) Germinal matrix hemorrhage–intraventricular hemorrhage (GMH-IVH) is the most common variety of neonatal intracranial hemorrhage and is characteristic of the premature infant. Overall incidence for all IVH of 25%.(78)The risk period for the occurrence of IVH is highest in the first 3 or 4 days of life. Hemorrhage is rarely seen at birth, although it has been reported as early as the first hour of life.(79) Prenatal hemorrhages can occur, especially in the setting of neonatal alloimmune thrombocytopenia. 25% of hemorrhages occur by the 6th hour of life, and 50% of hemorrhages occur within 1st day of life. Less than 5% of neonates develop IVH after 4th or 5th day of life. Disturbances in cerebral blood flow can lead to extension of the hemorrhage during the first few days.(69)The clinical presentation of IVH in the newborn depends on the extent of the hemorrhage. It may range from asymptomatic to a sudden and catastrophic deterioration that manifests itself with neurologic signs such as stupor or coma, seizures, decerebrate posturing, or apnea. A tense fontanel together with a sudden drop in hematocrit, hyperglycemia, hyperkalemia, hypotension, or bradycardia may herald an IVH. The more common presentation, however, is that of a gradual clinical deterioration with an altered level of consciousness, hypotonia, abnormal extremity, or eye movements. In 25%–50% of cases, clinical signs are lacking.(80)Ultrasound examination is a reliable and sensitive bedside technique for evaluation of the severity of IVH in the newborn nursery.(81) Infants with birth weights of less than 1500 g or a gestational age of less than 32 weeks should undergo a screening ultrasound examination to detect IVH. It was classified into four grades of severity related to the location and extent of the hemorrhage based on Volpe Grading System as:I. Germinal matrix hemorrhage 50%, usually with distention of lateral ventriclePeriventricular echodensity signifying parenchymal lesionIsolated grade I and II hemorrhages generally resolve without evolution. Grade III hemorrhages evolve over a period of 1 to 3 weeks and may produce a fibrotic reaction that obliterates the subarachnoid space with subsequent ventricular dilatation and hydrocephalus. Clinical symptoms of progressive hydrocephalus, such as rapid head growth, a full anterior fontanel, or separation of cranial sutures, often appear days or weeks after the onset of ventricular dilatation. The delayed onset of clinical symptoms is related to the presence of a large subarachnoid space as well as the paucity of myelin in premature infants.(69)Prevention of preterm birth is the most effective method of reducing the incidence of IVH. Prenatal administration of steroids is associated with a decreased risk of IVH and cerebral palsy,(82) but prenatal administration of magnesium sulfate does not reduce the rates of IVH.(83,84) Optimal neurologic intensive care of the preterm infant includes reduced exposure to hyperventilation, hypocarbia, or hypoxia, as well as maintenance of adequate mean arterial pressure (MAP). Abrupt elevations in CBF may be precipitated by excessive handling or tracheal suctioning. Mechanical ventilation may be associated with an increased risk of IVH.(85)Serial cranial ultrasound examinations remain the optimal diagnostic modality to screen neonates for IVH and WMI at the bedside in the perinatal period, when the risk of IVH is the highest.(86) An ultrasound scan on 4th postnatal day detects about 90% of lesions. Because extension of a hemorrhage may occur during the next several days, a repeated ultrasound examination after 5 days is necessary to establish the extent of the IVH. Serial imaging is often necessary, because about half of infants with ventricular enlargement from IVH develop rapidly progressive ventricular dilatation during the next 4 to 8 weeks. MRI is the optimal imaging modality to detect smaller cerebellar hemorrhages and potentially more subtle forms of noncystic white matter injury.(69)Subdural HemorrhageThis is often associated with a traumatic event. 50% of neonates with subdural hemorrhage develop seizures appearing mostly within first 48 hours of life.(1)Subdural hemorrhages occur predominantly in vaginal deliveries and are rarely seen in cesarean sections. However, there is no proven association with instrumental deliveries.(76)Clinical features include irritability, bulging fontanelle, lethargy, doll’s eye phenomenon, unequal pupils, nuchal rigidity with retrocollis or opisthotonos posturing, seizures, stupor, coma. Also, skew deviation of eyes, bradycardia, apnea, oculomotor abnormalities, and facial paresis can develop.(76)Although CT is a definitive means of demonstrating the site and extent of neonatal subdural hemorrhage, MRI is superior and currently recommended. When MRI is not available soon enough, CT is particularly useful for a rapid diagnosis and defining the location and extent of the lesions.(76)NEONATAL SEPSISInfections in the neonates are classified into congenital, perinatal, early-onset, and late-onset disease by the timing relative to birth. If the infection is acquired around the time of delivery it is referred as perinatal infection. Organisms acquired perinatally include both bacteria as well as the viruses. Infection occurring usually within 72 hours of postnatal life is known as Early onset neonatal sepsis (EONS).And the ones acquired after 72 hours through 30 days of life are known as Late onset neonatal sepsis (LONS) which may include bacteria, viruses, or other organisms that are typically acquired in the postnatal period. Hospital-acquired infections characteristically occur after the 1st week of life. (87)Approximately 10% of infants develop infections within 1st month of life. The overall incidence of neonatal sepsis ranges from 1 to 5 cases per 1,000 live births. In 2013, neonatal sepsis and other severe infections were responsible for about 430,000 neonatal deaths, comprising of about 15% of all the neonatal deaths.(87)The incidence of meningitis is 0.2-0.4 per 1,000 live births in neonates and is higher in preterm infants. It may be concomitantly with sepsis or may occur as a local meningeal infection. Approximately 1/3rd of VLBW neonates with late-onset meningitis have negative blood culture results . The discordance between results of blood and cerebrospinal fluid (CSF) cultures suggests that meningitis may be underdiagnosed among VLBW infants and emphasizes the need for culture of CSF in VLBW infants when late-onset sepsis is suspected and in all infants who have positive blood culture results.(87)Clinical presentation of sepsis in a neonate includes features like irritability, lethargy, poor feeding, temperature instability, bleeding problems, tachycardia, hypotension, poor perfusion, abdominal distension, emesis, diarrhoea, jaundice, respiratory distress, seizures. Most neonates exhibit respiratory distress in the first 12 hours of life, frequently immediately after birth. In these neonates the progression may be rapid, with cardiovascular instability, shock, and death. Neonates with hypoxia in utero may gasp, inhaling contaminated amniotic fluid and setting the stage for early-onset pneumonia, bacteremia, and sepsis.(88)Microbiologic CulturesBlood CulturesThe gold standard for detection of bacteremia in newborns with suspected sepsis is a positive blood culture result. Most positive blood culture results are detected within 24–48 hours(89,90). However, the use of intrapartum antibiotic prophylaxis in mothers with either GBS colonization or suspected amnionitis originating from any cause can reduce the ability to detect bacteremia in newborns. In a term infant who remains asymptomatic at the initiation of antibiotic therapy, stopping antibiotic administration is recommended if the blood culture results remain negative after 48 hours.(91)Cerebrospinal FluidCerebrospinal Fluis (CSF) analysis should be done in all infants who have positive blood culture results. Most neonates with sepsis presenting in the 1st day of life have a positive blood culture; analysis of CSF is usually deferred until the unstable cardiorespiratory status (shock, respiratory failure) has stabilized. Lumbar punctures are deferred in neonates with uncorrected bleeding disorders.(87)White Blood Cell Count and Neutrophil IndicesNormal white blood cell (WBC) counts range from 9000–32,000 cells per microliter at the time of birth. The absolute neutrophil count (ANC), the ratio of immature neutrophils to total neutrophils (I/T) and the absolute band count of immature neutrophils are regarded as more useful than WBC counts in the diagnosis of neonatal sepsis. The lower limit of total neutrophil count rises to 7200 cells per microliter by 12 hours of age, and then declines to approximately 1720 cells per microliter by 72 hours of age.(92,93) Postnatally, the absolute band count also undergoes similar changes, with peak values of 1400 cells per microliter at 12 hours of age, and then declines. In contrast, the I/T ratio is maximum at birth and then declines to 0.12 beyond 72 hours of age.(92,94). The optimal time to obtain WBC counts is after 4 hours of age, and most recommendations are to obtain the first counts at 6–12 hours of age.(95,96) In VLBW infants there is a greater reference range for the total neutrophil counts.(92,97,98) There are no significant differences in the I/T ratio or absolute immature neutrophil counts in VLBW infants. There is considerable overlap of the cutoff values of the ANC, absolute band count, and I/T ratio between healthy and infected newborns. In approximately two-thirds of infants with sepsis, the total neutrophil count is abnormal. Neutropenia is the best predictor of sepsis, whereas neutrophilia does not correlate well. The absolute neutrophil band count is not a sensitive marker of sepsis but has a relatively good predictive value and specificity. The I/T ratio is considered to have the best sensitivity of all of the neutrophil indices.(99)Platelet CountsApproximately 25%–30% of infants exhibit thrombocytopenia at the time of diagnosis of sepsis, and the frequency increases during the course of infection. Accelerated platelet destruction and possibly depressed production caused by bacterial products on the bone marrow are the underlying mechanisms for thrombocytopenia in infected infants. Disseminated intravascular coagulation may be seen in some infants with severe sepsis.(88)