Value of clinical neurophysiology in early management of neonatal hypoxic-ischaemic encephalopathy

Neonatal HIE is a complex neurological condition caused by an intrapartum or perinatal event leading to reduced cerebral perfusion. Therapeutic hypothermia (TH), the cornerstone treatment in HIE, should be instigated within six hours of birth and at present remains only indicated for term or near-term neonates with moderate or severe encephalopathy. TH use in mild encephalopathy is increasing internationally driven by concern that these infants are at risk of injury. The balance of risk against potential benefit is unknown and where best to draw that line in the care of mildly encephalopathic neonates is the subject of active debate. In Chapter 1 we review some of the different regional and national eligibility guidelines for treatment and highlight the variability that exists between them. Clinical neurological exams often define the severity of encephalopathy differently, with varying number of domains required for determining eligibility and blurred interpretation of findings assigned to different severity grades in different systems. This reflects in different individual care depending on the location in which infants are born and impacts research data. The role of early electrophysiological assessment is also weighted unequally, and in most jurisdictions the role of clinical assessment predominates over electroencephalography. Nonetheless, recent studies demonstrated that clinical grade may underestimate the severity of the disease as compared with EEG assessment. Existing grading schemes for EEG evaluation in neonatal HIE are focused on background features, while focal abnormalities and recurrent paroxysmal patterns are considered only marginally. In Chapter 2 we characterize the EEG 162 term neonates with HIE within 12 hours of birth to assess severity of encephalopathy and risk for acute provoked seizures. We found that neonates with severe background EEGs had a significantly higher rate of acute provoked seizures. In mildly and moderately altered background EEGs seizure risk was lower, but spikes and/or rhythmic sequences predicted seizures. Early EEG grading combined with analysis of focal features may therefore be more accurate than background evaluation alone in assessing severity of neonatal encephalopathy and need for treatment. In addition to EEG, other neurophysiological methods such as SEPs are known to predict outcome after perinatal asphyxia. In Chapter 3 we report the results of a pilot study, in which we demonstrated the feasibility of simultaneous EEG and SEPs assessment together with neurological examination at admission to the NICU. Standardization of timing of evaluation is crucial to the interpretation of findings in an evolving condition such as HIE. To our knowledge, our study is the first testing SEPs in the earliest 12 hours. The one patient with absent cortical responses also showed the worst Total Sarnat score and the worst EEG grade in the cohort, and developed an early abnormal outcome. We found increased latencies for cortical evoked potentials in neonates with HIE compared to an internal group of healthy controls. Besides refining the care provided in high-income countries, research to support the understanding of the disease in low-income countries should be prioritised to guide appropriate use of available resources. Given the non-availability of TH, prompt detection and adequate treatment of seizures represent the main neuroprotective intervention. In Chapter 4 we performed retrospective characterization of seizure semiology using continuous video-EEG monitoring in neonatal encephalopathy in a Ugandan NE population. Incidence of seizures was high and a relevant proportion of them had a clinical correlate. Clonic, autonomic and automatisms were the more frequently seizure types observed. Respiratory impairment emerged as a prominent concern. Clinical neurophysiology plays a central role in early management of neonatal HIE, providing useful insights in different settings.