Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia
Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia
The purpose of this study is to determine whether the administration of topiramate to
 newborns with hypoxic-ischemic encephalopathy potentiates the neuroprotective effect of
 treatment with hypothermia.
Neonatal hypoxic-ischemic encephalopathy, due to perinatal asphyxia, is one of the leading
 causes of cerebral palsy, whose incidence, despite improvements in perinatal practice and
 neonatal care, has remained essentially unchanged over the recent past decades. It occurs
 approximately in 2-3 newborns every 1000 live births with a mortality rate of 10% for mild
 degrees and 60% for severe degrees. About 30% of survivors with mild hypoxic-ischemic
 encephalopathy and 100% with severe hypoxic-ischemic encephalopathy exhibit variable degrees
 of neurological disability.

 Several studies have demonstrated the therapeutic effects of whole-body or selective head
 cooling to treat neonates with hypoxic-ischemic encephalopathy. Mild hypothermia, (rectal or
 esophageal temperature 33-34°C), started within 6 h after birth and protracted for 48-72 h,
 can significantly improve primary outcome measures such as death or disability at 18 months
 or improve the neurological outcome in survivors. Consequently, mild hypothermia is at
 present recommended for the treatment of moderate degrees of encephalopathy.

 Topiramate an anticonvulsant agent widely used in adults and children, has been demonstrated
 to posses neuroprotective properties against hypoxic ischemic brain damage, both in vitro and
 in animal models and has been included in neuroprotective strategies for ischemic stroke and
 neonatal hypoxic-ischemic cerebral injury. Recently, topiramate treatment in asphyxiated
 newborns has been reported safe.

 Aim of the present study is to confirm the safety and to evaluate whether the association of
 topiramate enhances the neuroprotective properties of hypothermia for the treatment of
 neonatal hypoxic-ischemic encephalopathy.
Inclusion Criteria:

 1. Gestational age > 36 weeks and birth weigh > 1800 g with at least 1 of the following:
 a) Apgar score < 5 at 10 minutes; b) persisting need for resuscitation, including
 endotracheal intubation or mask ventilation 10 minutes after birth; c) acidosis (pH
 <7.0, base deficit >-16 mmol/L in umbilical cord blood or arterial, venous or
 capillary blood) within 60 minutes from birth;

 2. moderate to severe encephalopathy, consisting of altered state of consciousness
 (irritability, lethargy, stupor, or coma) and > 1 of the following sings: a)
 hypotonia, b) abnormal reflexes, including oculomotor or pupil abnormalities, c)
 absent or weak suck, d) clinical seizures.

 3. abnormal aEEG

 Exclusion Criteria:

 congenital abnormalities, congenital viral infections or evidence encephalopathy other than
 HIE.

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