This document summarizes neonatal brain injury from birth asphyxia and hypoxic-ischemic encephalopathy (HIE). It discusses the pattern of brain injury in HIE, clinical presentation and prognosis, and pathophysiology. Current management involves supportive care as well as new therapies like therapeutic hypothermia, chemical therapies targeting glutamate and free radicals, and cellular therapies using stem cells. Hypothermia aims to lower the baby's temperature to reduce neuronal injury from secondary energy failure after birth asphyxia. Chemical therapies block factors contributing to neuronal injury and cell death. Cellular therapies using stem cells may help repair damaged neural tissue. The document reviews evidence for these new therapies and ethical/legal issues surrounding neonatal brain injury.
Management of hypoxic ischemic encephalopathy (HIE) by Sunil Kumar Dahasunil kumar daha
Please find the power point on Management of hypoxic ischemic encephalopathy (HIE) . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Management of hypoxic ischemic encephalopathy (HIE) by Sunil Kumar Dahasunil kumar daha
Please find the power point on Management of hypoxic ischemic encephalopathy (HIE) . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Presentation with extensive details of neonatal seizure. Covering its etiology, diagnosis and treatment . Neonatal seizure is one of the commonest clinical situation faced by any one working in a neonatal unit. Furthermore it is a favourite topic of many examiners in MD/DCH/DNB Pediatrics exams.
Presentation with extensive details of neonatal seizure. Covering its etiology, diagnosis and treatment . Neonatal seizure is one of the commonest clinical situation faced by any one working in a neonatal unit. Furthermore it is a favourite topic of many examiners in MD/DCH/DNB Pediatrics exams.
Hypoxic ischemic insult, by prof Ayman Galhom, ass prof neurosurgery, Suez ca...mohamed osama hussein
A lecture given by dr Ayman Galhom, assistant professor neurosurgery, Suez canal university, during Port said fourth neonatology conference, at 24-25 October, 2013. This lecture was a discussion of the pathophysiology & management of hypoxic ischaemic insult to an infant in PICU
Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathyMCH-org-ua
International conference «Actual approaches to the extremely preterm babies: International experience and Ukrainian realities» (Kyiv, Ukraine, March 5-6, 2013)
Neonatal seizures, dr amit vatkar, pediatric neurologistDr Amit Vatkar
In the presentaion i will give you a brief idea to apprach, diagnosis and management of neonatal seizures.
The most prominent feature of neurologic dysfunction in the neonatal period is the occurrence of seizures. Determining the underlying etiology for neonatal seizures is critical. Etiology determines prognosis and outcome and guides therapeutic strategies.
Neonatal seizures, dr amit vatkar, pediatric neurologist
Definition
A seizure is defined clinically as a paroxysmal alteration in neurologic function (i.e., behavioral, motor, or autonomic function).
Includes phenomena that are associated temporally with seizure activity identifiable on an EEG and, therefore, are clearly epileptic
Also includes paroxysmal clinical phenomena that are not consistently associated temporally with EEG seizure activity
Pathophysiology
Immature brain has many differences from the mature brain that render it more excitable and more likely to develop seizures.
Delay in Na+ , K+ -adenosine triphosphatase maturation and increased NMDA and AMPA receptor density.
Delay in the development of inhibitory GABAergic transmission
GABA in the immature brain has an excitatory function
Causes of Neonatal seizures
The majority of neonatal seizures occur in the context of acute neurologic disorders.
Thus most neonatal seizures may be considered acute symptomatic seizures, which have been defined as seizures occurring at the time of a systemic insult or in close temporal association (often 1 week) with a documented brain insult.
The current IL AE classifies seizure causes as genetic, structural/metabolic, and unknown.
Within that classification scheme, the majority of neonatal seizures are structural/ metabolic in etiology.
The most common underlying etiologies are HIE, stroke, intracranial hemorrhage, intracranial infections, and cerebral dysgenesis.
Less common but important etiologies include
Inborn errors of metabolism and
Neonatal epileptic syndromes, such as benign familial neonatal epilepsy, benign nonfamilial neonatal seizures, early myoclonic epilepsy, early infantile epileptic encephalopathy, and malignant migrating partial seizures of infancy
Types of Neonatal Seizures
Four essential clinically evident seizure types can be recognized: subtle, clonic, tonic, and myoclonic
Subtle seizures do not have a clear position in the most recent ILAES classification report, but they are very common in newborns
A critical fifth seizure type to consider in newborns is a seizure with no observable clinical correlate, which have been referred to as EEG-only seizures
An important initial distinction in classifying a seizure is whether it has a generalized or focal mechanism of onset
Subtle Seizures
Transient eye deviations, nystagmus, blinking, mouthing,
Abnormal extremity movements (rowing, swimming, bicycling, pedalling, and Stepping),
Fluctuations in heart rate, hypertension episodes, and apnea.
More commonly in premature
Clonic Seizures
Focal:
Involve face upper + /- lower extremities on
one site “axial structures (neck / trunk)
Usually associated with neuropathology (i.e. Cerebral infarction and intra cerebral haemorrhage)
Multi focal:
Involve several body parts and often
migrate in a non-jacksonian (random) manner may also involve the face.
Consider the neonatal equivalent of generalized tonic – clonic seizures.
Derived from Greek word “enkephalos”- meaning brain.
“Pathos” meaning is disease.
The term “encephalopathy” is defined as altered mental status as a result of a diffuse disturbance of brain function.
Abstract: Epilepsy is a serious and common chronic neurological disorder characterized by recurrent seizures, which are caused by abnormal synchronized neuronal disorders. It is a relatively common condition (up to 2% of the population) which can affect anyone at any age. Epilepsy can be controlled in a number of ways. The most common way to treat epilepsy is with anti-epileptic drugs. These AEDs can control but not cure epilepsy. Surgery can also be a possible treatment. Curative epilepsy surgery can only be performed in patients in whom the epileptogenic focus can be localized and does not overlap with eloquent brain areas. In the other patients with bilateral or multiple epileptogenic foci, with epilepsy onset in eloquent areas, or with no identifiable epileptogenic focus, treatments such as ketogenic diet, vagus nerve stimulation can be offered. VNS is an available procedure of which the mechanism of action is not understood, but with established efficacy for refractory epilepsy and low incidence of side-effects. The ketogenic diet is a high-fat, moderate protein, low carbohydrate diet used to treat intractable epilepsy, primary in the pediatric population. Hippocampal Deep Brain Stimulation has been used to treat patients with refractory epilepsy. Complementary and Alternative Medicine for epilepsy such as apuncture, aromatherapy, yoga etc may be used for lessening seizures, for alleviating related symptoms and for reducing side effects. Gene therapy aims to utilize viral and non-viral vectors in the delivery of DNA to target areas for the treatment of patients before their disease progresses. Gene therapy has delivered promising results in animal trials and pre-clinical settings and can be used for neurological disorders such as epilepsy.
Similar to Birth asphyxia and Hypoxic-Ischaemic Injury: Prognosis and Management (20)
2. Contents
• Why choose this SSC?
•What is Birth Asphyxia and HIE?
•Prognosis
•Treatment and Management
• Conservative & Supportive
• New therapies:
-Hypothermia
-Chemical Therapy
-Cellular Therapy
• Evidence Based Medicine?
•Disability, Disadvantage and Diversity
•Ethics, Law and Medicine
•References
3. What is Birth
Asphyxia and HIE?
Birth Asphyxia: The result of a critical reduction in O2 delivery
to the fetus either antenatally, during labour and/or delivery
that is sufficient to produce a lactic acidosis and render the
infant in distress at birth.
Hypoxic-Ischaemic Encephalopathy (HIE) describes the
clinical manifestation of brain injury starting immediately or
up to 48hrs post-asphyxia.
4. Pattern of Injury in
HIE
Miller et. al, (2005) Journal of Paediatrics
10. 1. Hypothermia
Reduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
11. 1. Hypothermia
Mechanism
• Modifies cells programmed for apoptosis
• Reduces cerebral metabolic rate, therefore production of toxic NO
and Free Radicals.
Who is treated?
• Neonates with an abnormal aEEG- fairly predictive
What happens?
• Aims to lower basal ganglia temperature 32-34°c
• Whole body or Just head
Disadvantages
• Little benefit if severe brain damage
• Not yet trialled in pre-term infants
14. 2. Chemical Therapy
Reduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
15. 2. Chemical Therapy
Agents that inhibit glutamate release, uptake, or blockage of
glutamate receptors
Blockade of free radical generation or removal- free radical
inhibitor
Blockade of downstream effects and inhibitors of inflammatory
effects
Magnesium Xenon
Deferoxamine Allupurinol
Indomethacin
Erythropoetin
16. 3. Cellular Therapy
Stem cells that may help repair ischaemic neuronal tissue
• Neural Stem cells
• Multi-potent adult progenitor stem cells
• Mesenchymal Stem cells (MSCs)
• Human Umbilical Cord Stem Cells
MSCs can differentiate into neurones and oligodendrocytes,
therefore help repair ischaemic neural tissue.
May also help with restoration of functional networks via
axonal sprouting and synaptogenesis.
17. 3. Cellular Therapy
• 9 day old mice
• HIE artificially induced with R common carotid artery
occlusion.
• MSCs injected into mice: 1st dose 3d, 2nd dose 10d.
Velthoven et al. 2010 Journal of Neuroscience
Diagnosis of HIE only made if:
Evidence of hypoxia antenatally eg. Antepartum haemorrhage
- during labour (eg. Cord prolapse)
- Delivery (eg. Shoulder dystocia)
- Resucitation needed
- Fatures of encephalopathy
Hypoxic damage to organs (eg. Liver, kidney, heart)
No other post-natal/antenatal cause identified
Characteristic neuroimigery findings
Neonatal encephalopathy is a clinical syndrome of “disturbed neurological function in the earliest days of life in the term infant, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, subnormal level of consciousness, and often seizures.
Extent of injury is dependent on severity and temporal characteristics of the insult.
Final pattern of injury also depends on the gestational age of the infant when the injury occurs
Severe prolonged hypoxia
Diffuse neuronal injury
Moderate- severe, relatively prolonged
Deep cortical grey matter structures affeted eg. Basal ganglia and thalamus
Severe, abrupt
Deep nuclear brain-stem injuries.
“watershed injury”- another common pattern of injury- parasaggital end artery regions of 3 major cerebral arteries.
MRI scan of brain – term infant
Left normal scan. Grey basal ganglia and white signal fro myelin in posterior limb of internal capsule.
Right- HIE- abnormal signal in basal ganglia and thalami (shown by arrows)- absence of signal in the internal capsule bilaterally
Picture: Brain damage from severe birth asphyxia at term following a sudden, severe antepartum haemorrhage caused this child to become microcephalic, blind and deaf and to have spastic quadriplegia.
Mild: may also have ‘stary eyes’
Moderate: if they make a full clinical neurological recovery and feeding within 7 days, generally excellent prognosis.
- > 10 days persistence, full recovery unlikely
Severe: Poor prognosis: 80% neurodevelopmental problems.
Secondary energy failure:
Hyperaemia
- Cytotoxic oedeme
- Mitochondrial failure
- Accumulatuib if excitotoxins
Apoptosis
No synthesis
Free radical damage
Resucitation: In the delivery room- oxygen- room air rather than 100% o2 due to potential deleteirous effects of oxygen during primary pahse.
Correct any metaboloic acidosis. Avoid hyper or hypo capnia.
RESTORE CONDITIONS THAT DELAY RECOVERY FROM PRIMARY PHASE OF BRAIN INJURY- hypoxia, hypoglycaemia, hypotension.
Respiratory ensure adequate ventilation- changes in PCO2 can affect cerebral blood flow. Hypocapnia- vasoconstriction therefore compromised o2 supply
Seizre: phenobarbital, phosphenytoin, lorazepam
CAI EEG: Cerebral Function Monitoring – confirm early encephalopathy
onitors general neurological status
Monitors and records frequency and intensity of seizures to assist in the management of anticonvulsive therapy
Assists in identifying need for full EEG
Assists in identifying and predicting outcome from hypoxic-ischemic encephalopathy (HIE)
Hypotension: Most commonly related to LV dysfunction following hypoxic-ischaemic injury and endothelial damage therefore give inotropes such as dobutamine. May be hypovolaemic due to placental abruption therefore give fluids.
Fluid restriction: Potential renal injury
U&E- SIADH and cerebral oedema common. Also due to kidney injury may have derranged u&ess
Secondary energy failure:
Hyperaemia
- Cytotoxic oedeme
- Mitochondrial failure
- Accumulatuib if excitotoxins
Apoptosis
No synthesis
Free radical damage
Published by group in New York- Summary of clinical trials on x- axis
Baby receiving hypotherimic treatment via cooling cap.
Target different steps in the cacade and pathways leading to neuronal cell death
Categorised based on mechanism of action/effect
Mag and Xenon- NMDA inhibitors (xenon- also an anaesthetic!)
Free radical inhibitors- block reaction in production of xanthine
Improved sensory motor function, and reduced lesion size- motor: time spent on rotaroad, forepaw initiation differnece- sensory function
VEH- = vehicle ie. placebo.
In the netherlands- applicable in clinical setting treatment in 4years...