A Newborn Who Has Seizures

Abstract

At 4 days of age, an infant was admitted to the county hospital with an elevated temperature and poor feeding. He was treated for 3 days for presumed sepsis. Two days after discharge, he develops tachypnea and jittery movements and is admitted to the university hospital. Upon arrival, he is having a tonic-clonic seizure that lasts for 5 minutes, followed by a hypotonic phase.The baby is transferred to the neonatal intensive care unit where physical examination reveals hyperirritability, a bulging fontanel, tachypnea, and mild dehydration. Lumbar puncture reveals 400 cells/mm3, and cefotaxime plus amikacin are administered empirically for meningitis.Computed tomography (CT) scan demonstrates ventricular dilatation and gaping of cranial sutures (Fig. 1).An extraventricular catheter is placed for drainage. During the course of therapy, Escherichia coli is isolated from the cerebrospinal fluid and blood cultures. The infant has continuous seizure activity despite anticonvulsant therapy. The head circumference increases significantly secondary to obstructive hydrocephalus.Ultrasonography of the head performed 1 week later reveals bilateral white and gray matter edema without signs of superior sagittal sinus thrombosis. High signal intensity is apparent in the basal ganglia, with dilatation of both ventricles in which septa are detected, presumably due to meningitis. Left middle cerebral artery blood flow is decreased. Magnetic resonance imaging (MRI) performed 1 day later reveals localized areas of infarct in the bilateral thalamic nuclei and left cerebral parietal and frontal lobe gyri. Edema makes it impossible to differentiate white and gray matter. An area of subdural hematoma is evident in the right parietal region (Fig. 2).The patient’s status deteriorates dramatically in the next few days, with disseminated intravascular coagulation and respiratory distress that requires initiation of mechanical ventilation. CT performed 10 days after hospital admission demonstrates diffuse hypodensity within all cerebral and cerebellar hemispheres as well as a centrally hypodense region that has irregular hyperdense borders within the right basal ganglia. Dural surfaces, gyri within the left vertex, and the right basal ganglia are enhanced with contrast material (Fig. 3).One month after the initiation of the therapy, the patient’s neurologic status has not changed. Pupils are not reactive to light, and the infant has hypotonia with absent tendon reflexes. A second MRI shows hyperintensity of all cortical gyri, which is interpreted as subacute hemorrhage (Fig. 4). Regions within the left parietal cortex also show subdural hematoma. The patient dies 2 days later after sudden cardiopulmonary arrest.Stroke associated with heterozygosity for factor V Leiden and meningitis.The true incidence of perinatal stroke is not known, but has been reported as ranging from approximately 1 in 4,000 live births to as high as 17% in autopsy studies of term newborns. The etiologic factors responsible for neonatal cerebral infarction are diverse, as are the clinical presentation and the long-term neurodevelopmental outcomes. Infarction may be due to either thrombotic or embolic causes, and major roles may be played by placental thrombi, congenital heart diseases, sepsis, traumatic vascular damage, consumptive coagulopathy, or metabolic disorders. Blood disorders associated with stroke in neonates include polycythemia, protein-C deficiency, prothrombin 20210A mutation, and the fVL mutation. Multiple factors are associated with a high risk of thrombosis. The fVL mutation, a dominantly inherited coagulation abnormality, has been found in association with cerebral arterial and venous disorders in neonates and children. The fVL mutation is the most common inherited cause of thrombosis in Caucasians. Alone, the fVL mutation does not greatly increase risk, but its presence can interact with other genetic and environmental factors to increase risk. Infants who have stroke associated with the fVL mutation typically develop symptoms within the first postnatal months, but only if additional endogenous or exogenous risk factors for thrombosis are present.Heterozygosity for FV R506Q confers an estimated 5- to 10-fold increased risk of venous thrombosis; homozygosity may be associated with a 50- to 100-fold increased risk. Perinatal stroke has been reported as a complication of meningitis, disseminated intravascular coagulation, and sepsis. Infection leads to a hypercoagulable state. During serious infection, there is a rapid destruction of protein C and antithrombin III, both of which normally inhibit coagulation. Infection also produces endothelial injury and a release of inflammatory cytokines, which lead to the downregulation of thrombomodulin and upregulation of tissue factor. The catastrophic deterioration of the patient in this case was related to the diffuse brain infarction developing within 1 week. Although meningitis can induce stroke by itself, rapid progression of diffuse infarcts is augmented by the fVL mutation.JoDee M. Anderson, MD, Division of Neonatal Medicine, Oregon Health & Science University, Portland, Ore.