1. 1. Hypoxic Ischemic Encephalopathy Dr Raghavendra . Fellow in neonatology
2. 2. 6/22/2015 Definitions Hypoxia/anoxia : denotes a partial or complete lack of oxygen, respectively, in one or more tissues of the body, including the blood stream. Asphyxia : is the state in which pulmonary or placental gas exchange is affected leading to progressive hypoxemia, which is severe enough to be associated with acidosis. Ischemia : is a reduction in or cessation of blood flow that arises from either systemic hypotension, cardiac arrest, or occlusive vascular disease.
3. 3. APGAR Score
4. 4. Apgar Score Total Score = 10 score 7-10 normal score 5-6 mild birth asphyxia score 3-4 moderate birth asphyxia score 0-2 severe birth asphyxia
5. 5. Hypoxic-Ischemic Encephalopathy Definition : It is the term used to designate the clinical and neuropathological findings of an encephalopathy that occurs in a full term infant who has experienced a significant episode of intrapartum asphyxia.
6. 6. Incidence of HIE Occurs in 1-6 per 1000 live term births in developed countries 25% die or have multiple disabilities. 4% have mild to moderate forms of cerebral palsy. 10% have developmental delay .
7. 7. Etiology of HIE Maternal: Cardiac arrest Asphyxiation Severe anaphylaxis Status epilepticus Hypovolemic shock Uteroplacental: Placental abruption Cord prolapse Uterine rupture Hyper stimulation with oxytocic agents Fetal: Fetomaternal hemorrhage Twin to twin transfusion Severe isoimmune hemolytic disease Cardiac arrhythmia
8. 8. Path physiology Immature brain is more resistant to hypoxic-ischemic events compared to older children & adults This may be due to: Lower cerebral metabolic rate Immaturity in the development of the balance of neurotransmitters & Plasticity of the immature CNS. Gestational age plays an important role in the susceptibility of CNS structures < 20 weeks: Insult leads to neuronal heterotopia or polymicrogyria 26-36 weeks: Insult affects white matter, leading to periventricular leukomalacia Term: Insult affects primarily gray matter
9. 9. Other factors that influence the distribution of CNS injury: Cellular susceptibility (neuron most susceptible) Vascular territories (watershed areas) Regional susceptibility (areas of higher metabolic rates, ie. Thalamus) Degree of asphyxia
10. 10. PATHOPHYSIOLOGY OF BRAIN INJURY Mainly associated with two phases 1. Primary energy failure . 2. secondary energy failure.
11. 11. Primary Energy Failure The impairment of cerebral blood flow leads to decreases in oxygen and glucose, which leads to less energy (ATP)) and increased lactate production. low ATP levels cause failure of many of the mechanisms that maintain cell integrity, particularly the sodium/potassium (Na/K) pumps and mechanisms to maintain low intracellular calcium. This leads to the release of glutamate, a prominent excitatory neurotransmitter. The glutamate binds to glutamate receptors allowing additional influx of intracellular calcium and sodium. Increased intracellular calcium has detrimental effects leading to cerebral edema, ischemia, micro vascular damage with resultant necrosis and/or apoptosis Excitotoxic oxidative cascade get activated. necrosis cell death.
12. 12. Potential pathways for brain injury after hypoxia-ischemia. Perlman J M Pediatrics 2006;117:S28-S33 2006 by American Academy of Pediatrics
13. 13. Secondary Energy Failure Continuation of excitotoxic oxidative cascade . Activation of microglia inflammatory response . Activation of caspase proteins. Reduction in levels of growth factors , protein synthesis. Apoptosis cell death.
14. 14. The interval between primary and secondary energy failure represents an latent phase. That corresponds to a therapeutic window. duration is approximately 6 hrs. Cell death in the brain exposed to HI is delayed over several days to weeks after an injury ,apoptosis and necrosis continue depending on the region and severity of the injury.
15. 15. Status of infant at birth Depressed on initial assessment. Generalized hypotonia. Apgars 3 or less @ 1min and 6 or less @ 5min. Major resuscitation required. Large base deficit by blood gas. Poor feeding to deep coma (encephalopathic)
16. 16. Prognosis based on apgars Score at 1, 5 minutes does not give prognosis indicator. The longer the score remains lower, the greater its significance. 0-3 @ 1min has mortality of 5-10%. may be increased to 53% if at 20min apgars score 0-3 0-3 @ 5min , CP risk app. 1%. may be increased to 9% if for 15min. dramatic rise to 57% CP risk if for 20min
17. 17. Newborn neurological assessment Staging system of Sarnat and Sarnat, levene score. Thompson score Means of recording severity of insult to brain, to initiate med management and to predict ultimate prognosis. Infants occasionally sustain insult to brain arising from complication of systemic disease, Seizures in 50-70%
18. 18. Summary of staging Mild(stage1) : Hyper alertness, uninhibited reflexes, sympathetic over activity , duration < 24 hrs Moderate(stage2) : Lethargy-stupor, hypotonia, suppressed primitive reflexes, seizures Severe(stage3) : Coma, flaccid tone, suppressed brainstem function, seizures, increased ICP
19. 19. Assessment Tools in HIE Amplitude-integrated EEG (aEEG) When performed early, it may reflect dysfunction rather than permanent injury Most useful in infants who have moderate to severe encephalopathy. Evoked Potentials Brainstem auditory evoked potentials, visual evoked potentials and somatosensory evoked potentials can be used in full-term infants with HIE More sensitive and specific than aEEG alone However, not as available as aEEG and there is a lack of experience among pediatric neurologists Therefore aEEG is preferred because of easy access, application, and interpretation
20. 20. Standard 16-channel electroencephalogram showing a typically abnormal burst suppression background pattern. (Courtesy AC van Huffelen, PhD, Department of Neurophysiology, University Medical Center, Utrecht, The Netherlands.)
21. 21. Neuroimaging. Cranial ultrasound: Not the best in assessing abnormalities in term infants. Echogenicity develops gradually over days. CT: Less sensitive than MRI for detecting changes in the central gray nuclei. MRI: Most appropriate technique and is able to show different patterns of injury. Presence of signal abnormality in the internal capsule later in the first week has a very high predictive value for neurodevelopmental outcome.
22. 22. Fetal hypoxia The umbilical placental impedance is so high that the diastolic component shows flow in a reverse direction. This finding is an indication of severe intrauterine hypoxia and intrauterine growth restriction . Abnormal Doppler velocimetry. On an umbilical artery Doppler flow velocity waveform
23. 23. Patterns of periodic fetal heart rate (FHR) deceleration Variable deceleration as a result of umbilical cord compression
24. 24. CT BRAIN OF HIE CHILD
25. 25. 6/22/2015 Management Prevention, prevention, prevention Insure physiological oxygen and acid-base balance Maintain environmental temp and humidity Correct caloric, fluid and electrolyte disturbances Maintain blood volume and hemostasis Treat infection Neuro-resus measures to reduce cerebral oedema ineffective Sz treated with PB, dilantin or lorazepam Newer modalities- excitatory amino antagonists, oxygen free radical inhibitors/scavengers, ca channel blockers, nitric oxide synthetase inhibitors Hypothermia
26. 26. References Allan WC. The clinical spectrum and prediction of outcome in hypoxic-ischemic encephalopathy. Neoreviews 2002; 3; e108-e115 Delivoria-Papadopoulos M, et al. Biochemical basis of hypoxic- ischemic encephalopathy. Neoreviews 2010; 11; e184-e193 Fanaroff and Martins Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant, 9th edition. 2011, p 952-976 Marro, PJ, et al. Pharmacology review: Neuroprotective treatments for hypoxic-ischemic injury. Neoreviews 2010; 11; e311-e315. Newborn Infant Nurs Rev. Author manuscript; available in PMC 2012 September 1.