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Understanding the Newborn Brain ­ how can I translate this into my clinical practice in 2011

Terrie Inder Washington University in St Louis

What have I heard about?

A lot ­ long days, hard working faculty, engaged participants..... participants How can I integrate this information into my practice?

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The technologies - aEEG g

aEEG is regarded as standard of care for term encephalopathy in many parts of the world p p y yp Bedside technology for continuous brain monitoring Assists in the delineation of the extent of brain injury, injury predicts outcome, identifies who to cool, outcome cool identifies seizures Patterns evolve over time Compliments conventional EEG, examination and neuroimaging Take home message ........very useful technology

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The technologies - CUS g

Bedside technology Acoustic windows Preterm ­ IVH, PHVD, larger cerebellar hemorrhage, white matter injury Term more limited ­ screening for anatomy anatomy, limited in HIE Optimize your use of cranial US

Repeated studies following the brain

Look at all of your own studies Anterior and posterior fontanelle, mastoid views p , Measurements for PHVD

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The technologies ­ CT, MRI g ,

CT

Radiation exposure p Limited in definition of lesion Minimal utility

MRI

The developing brain is different ­ T1,T2 Define anatomy and lesion Timing matters in HIE MRI h s hi h utilit in evaluation of abnormal n ur l ic l has high utility v lu ti n f bn rm l neurological behavior (T1, T2, DWI, MRA, MRV, MRS). Avoid the first 24 hours after the lesion aim 2-3 days or 8-10 days g for ischemic insult. Learn to look at the images ....

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The lesion ­ who and how?

Vulnerability of regions in the brain is related to maturation

Preterm ­ white matter, subplate neurons, hippocampus Term - cortex and DNGM, hippocampus

Mediators of brain injury share common pathways

Oxidative, excitotoxic, inflammatory

Pathway to cell death differs in the immature brain with more apoptosis (longer slower cell death) with brain reorganization and "regeneration" Understanding the common mediators helps to define the selective regional vulnerability ­ where to look, g p y where to target protection and why

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Potential mechanisms of brain injury and repair unique t th newborn b i d i i to the b brain

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Neuroprotection p

Hypotherma

Careful consideration of how to optimize the therapeutic impact of hypothermia (ventilation, sedation etc)

Novel neuroprotectants

Xenon Erythropoietin

Avoid injurious agents j g

Anesthetic, analgesics, stress etc

Support regeneration and plasticity

TMS Inhibition in Stroke, Nutrition, Early Interverntion/Rehabilitation Think about the key mechanism that we should be targeting

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Neurobehavioral evaluation

Assess function at all ages Neurobehavioral evaluation in the NICU

HNNE, NNNS, Premie neuro, APIB

Domains

Cognition g Motor Language Executive Functioning g Behavior

Differences in preterm infants are observable and measurable. Assess at discharge......and with a broad brush at 1 and 2 years

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How to MRI?

You can do it in a bean bag Do not accept that sedation or GA is required. Feed, cuddle and wrap........ , p

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MRI i t interpretation t ti

YOU can d it......... do it Many cases of MRI to look at

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aEEG I t EEG Interpretation t ti

You can do it it................ Background predictive of outcome Seizures detected Continuous evaluation of limited region

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Improving cranial US

You can do it better....... More frequently

<24 hours, 3rd day, weekly till 35 weeks, before discharge

More systematically

Anterior, Posterior Anterior Posterior, Mastoid views Classify IVH, Echogenicity, PVL, measure ventricles

Look at your images

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Neurological examination

You can do it it.......... Systematic approach to examination Consider gestational age, state of the infant, g g , , severity of illness Mental state, cranial nerves, motor and sensory exam

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Hypothermia yp

You can do it better Identify who would benefit early? Consider mechanism in transport p Sedation Ventilation ­ know how your blood gases are measured d Brain monitoring during hypothermia and rewarming

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How do I take all this home?

Recognize Diagnosis Understanding pathway gp y Therapy

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Recognize

Examine neurological behavior acutely and chronically Monitor the infant's neurological status

aEEG Neuroimaging

Think about what could be wrong ­ screen for metabolic insult, sepsis, ischemia

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Diagnosis

Engage in the technologies with multidisciplinary discussion ­ radiology radiology, neurology Electrophysiology

Bedside aEEG monitoring in the term encephalopathic i f t h l thi infant Conventional EEG compliment and more often

Imaging

CUS/ MRI protocols for term and preterm infants f

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Predicting outcome

Term infant

aEEG / EEG MRI ­ deep nuclear gray matter/ PLIC

Preterm infant

CUS IVH/PHVD MRI

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We must start to categorize the patterns of injury and altered development

· Respiratory disease

· R Recognize ­ d i dyspnoea, hypoxia · Diagnosis ­ CXR · Patterns of alteration ­ understanding of diagnostic groups ­ RDS/ P Pneumonia i · Directed research for pathway · Therapy based on the pattern and timing surfactant

· Neurological disease · Recognize ­ altered mental state, aEEG · Di Diagnosis ­ Bl d i Blood, CSF, Imaging · Patterns of injury and altered development · Direct research · Therapy based on pattern

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Barriers to technology

"It is easier not to know " It know.... Who should we monitor/image? Who will do the monitoring/imaging? g/ g g Who will teach us how to interpret this? What will I tell the parents?

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Term infant

· History, examination and monitoring · Recognize - systematic neurological examination · Diagnosis by blood work, CSF, MRI, · Understand the nature and timing of the insult · Understand the pathway · Monitor seizures ­ bedside EEG, avoid repeated or prolonged seizures · Monitor temperature, glucose, blood pressure

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Who should be monitored/imaged? / g

Any baby who had a hypoxic event around the time of birth.

Flat at birth Low APGARS low ph (acid) in the blood Required resuscitation and artificial ventilation at birth Any baby that is sick enough to be muscle relaxed needs monitoring Abnormal movements Sudden transient changes in vital signs

Any baby that is muscle relaxed. y y

Any baby that is suspected of having seizures Neurologically abnormal

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What will I tell the parents? p

Compliments history, examination, and other technologies For bedside monitoring explain that this is a basic monitor of the brain just as we monitor j the heart and the breathing MR imaging go through the images and the "best" estimate of outcome and direct post discharge therapies Be honest about what we know and what we do not know

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Where does your NICU lie?

Electrophysiology Neuroimaging

Who do you monitor? How? How is the information recorded and interpreted?

Cranial Ultrasound : How often? Is there a regular technician and reader? Do you read/review the images with the radiologist? Do you monitor PHVD by measures Magnetic Resonance Imaging · Do you undertake MRI scans in all term encephalopathic infants? Do you undertake MRI scans in all term encephalopathic infants? · Do you undertake MRI in any preterm infants? · What is the quality of your MRI scans like? · Do you undertake any CT scans in any infants? · Do you use any sedation? o you use any sedation? · Who interprets the MRI scans? · Do you have a regular NICU neuroradiology session

Evaluation of risk Evaluation of risk Follow up

Do you evaluate for maternal depression and/or anxiety; family structure and support? Do you undertake a systematic neurobehavioral examination during NICU stay or at discharge Are all preterm infants being followed up in your NICU for cognitive, motor and behavioral Are all preterm infants being followed up in your NICU for cognitive motor and behavioral outcomes? Do you follow up into school age?

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Preterm infant

Recognition

Complex Obstetric history of risk ­ chronic IUGR, acute y , chorioamnionitis, absence of protection ANS

Diagnosis

White Whit matter injury ­ i f ti /i h tt i j infection/ischemia/inflammation. i /i fl ti Echogenicity on CUS; DWI on MRI; EEG markers: NIRS Subplate injury ­ recognition? Hippocampal & neuronal injury ­ primary /secondary

Timing of white matter injury / Neuroprotection

Window of vulnerability long but potential for neuroprotection long Nature of insult may define the neuroprotective strategy

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Preterm infant

Brain Growth Impact of neonatal therapies on the brain How do we know what we are doing? Drugs, nutrition, stress Monitoring the impact

Anything that you administer or do may have an influence on the brain Continuous bedside monitoring g Intermittent monitoring Impact in RCTs using MRI as a biomarker for later outcome

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Where does your NICU lie?

Electrophysiology Neuroimaging

Who do you monitor? How? How is the information recorded and interpreted?

Cranial Ultrasound : How often? Is there a regular technician and reader? Do you read/review the images with the radiologist? Do you monitor PHVD by measures Magnetic Resonance Imaging · Do you undertake MRI scans in all term encephalopathic infants? Do you undertake MRI scans in all term encephalopathic infants? · Do you undertake MRI in any preterm infants? · What is the quality of your MRI scans like? · Who interprets the MRI scans? · Do you have a regular NICU neuroradiology session o you have a regular NICU neuroradiology

Evaluation of risk Follow up

Do you evaluate for maternal depression and/or anxiety; family structure and support? Do you undertake a systematic neurobehavioral examination during NICU stay or at discharge Are all preterm infants being followed up in your NICU for cognitive, motor and behavioral outcomes? Do you follow up into school age?

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Conclusion

Please go out and be a disciple for the brain

Do not be afraid of the brain and technology Continue to learn - read Preach & convert ­ teach Do so that others may see ­ live Make friends in related fields ­ neurology, radiology, psychology

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My thanks

· · · · · · · · · · Linda de Vries Petra Huppi Frances Jensen Steven Miller Adam Kirton Tyler Reimschisel Nisha Brown Ni h B Bobbi Pineda Chris Smyser Ch i S Russell Lawrence · · · · · · · Jeffrey Neil J ff N il Amit Mathur Eilon Shany Robert McKinstry Karen Lukas Joshua Shimony Catherine Creeley

· And to all of you for coming

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Microsoft PowerPoint - 500 mechanisms of injury preterm brain newborn brain symposium 2011 (2) [Compatibility Mode]

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