Neonatal Encephalopathy

Julie Parsons, M.D

Assistant Professor, Pediatric Neurology

November 19, 2009

Disclosures

PTC Therapeutics PTC 124 Clinical Trial for Duchenne Muscular Dystrophy

Objectives

To promote understanding between legal and medical professionals

To explain the role of a pediatric neurologist To define neonatal encephalopathy To define cerebral palsy To explore the relationship between neonatal

encephalopathy and cerebral palsy

Pediatric Neurologist

A pediatric subspecialist whose expertise is diagnosing and treating disorders in the developing nervous system

This requires completion of a five year residency training program

Board Certification through the American Board of Psychiatry and Neurology Special Qualification in Child Neurology

The Top 10 Neurologic Conditions 1. Attention Deficit Hyperactivity Disorder 2. Seizures and epilepsy 3. Developmental Delay 4. Headache 5. Newborn disorder 6. Mental Retardation 7. Macrocephaly/Microcephaly 8. Motor disturbance 9. Central Nervous system infection 10. Neuromuscular Disturbance

Neonatal Encephalopathy A depression in mental status or alteration of

consciousness Seizures Abnormal muscle tone and reflexes Abnormal respiratory function

Risk Factors for Neonatal Encephalopathy Increased maternal age Family history of neurologic problems Maternal thyroid disease or other autoimmune

disorder Coagulopathy or thrombotic disorders Maternal hypertension Vaginal bleeding Maternal infection Infertility Intrauterine growth restriction

Sarnat StagingStage 1:Mild Stage 2:

ModerateStage 3: Severe

Level of consciousness

Excessively irritable or somnolent, but awakens with light stimulation

Unarousable, but withdraws purposefully

Comatose, minimal if any response to pain

Brainstem and Autonomic function

No brainstem deficits. Sympathetic predominance

Parasympathetic predominance

Depressed or absent brainstem reflexes. Disordered breathing

Motor Function Tone normal to increased

Generalized hypotonia

Flaccid

Sarnat StagingStage 1: Mild Stage 2:

ModerateStage 3: Severe

Reflex abnormality

Exaggerated deep tendon reflexes

Exaggerated deep tendon reflexes: depressed neonatal reflex behaviors

Depressed or absent deep tendon reflexes: absent neonatal reflex behaviors

Paroxysmal Movements

Seizures or myoclonus

Sarnat and Sarnat, 1976

Correlation of Severity of Clinical Abnormalities and OutcomeSeverity of Encephalopathy % with abnormal outcome

MildJittery, increased irritability and DTRs, exaggerated Moro response

0%

ModerateLethargy, hypotonia, suppressed DTRs, + or – seizures

20 % to 40%

SevereComa, hypotonia, seizures, brainstem and autonomic dysfunction, + elevated intracranial pressure

100%

Sarnat and Sarnat 1976; Volpe 1995

Sarnat and Sarnat Staging

Stage 3 More than 7 days at Stage 2 Both associated with poor neurologic prognosis

Hypoxic Ischemic Encephalopathy

Hypoxia= Lack of Oxygen Ischemia= Lack of Perfusion

Hypoxic Ischemic Encephalopathy is caused by a combination resulting in a decreased supply of oxygen to cerebral tissue

Hypoxic Ischemic Encephalopathy Recognizable Pattern of Progression

1st 12 hours—bilateral hemispheric involvement leads to decreased level of consciousness

12 to 24 hours—”apparent improvement” in level of consciousness, but may have seizures which are often refractory

24 to 72 hours—worsening brainstem dysfunction with altered eye movements, abnormal pupillary response, apnea, bulbar dysfunction (may result in death)

Persistent dysfunction may indicate thalamic or basal ganglia involvement which usually predicts poor prognosis

Diagnosis of HIE: History

Complications of pregnancy, labor, delivery Placenta previa, cord prolapse, placental abruption,

maternal shock Presence of meconium Placental condition

chorioamnionitis Apgar scores (<3 at 5 minutes) Acid Base status (cord pH <7, BE -12) Evidence of multiorgan system involvement

Kidney, liver, heart

Differential Diagnosis: Neonatal Encephalopathy

Sepsis Meningitis Sedation Neuromuscular Disease Trauma Metabolic

Sepsis Common antecedent to low Apgar scores and

depression Hypotension Seizures Meconium Aspiration Chorioamnionitis Bacterial Infections—Meningitis or Group B Strep

Sepsis Inflammation

Release of cytokines Widespread endothelial injury

Coagulopathies Germinal matrix injury Intraventricular hemorrhage Stroke

Metabolic Disorders

Biochemical Derangements Hypoglycemia Hypocalcemia Hyponatremia Hyperammonemia Acidosis

Metabolic Disorders

Inborn Errors of Metabolism Symptoms after hours or days of appearing normal Prominent unexplained vomiting Hyperpnea in absence of lung disease Unusual Odor Family history , or excess fetal loss Physical Exam findings: cataracts, hepatosplenomegaly

Diagnosis of HIE: EEG Characteristic Sequence Initially marked suppression of amplitude and

slowing 24 to 48 hours discontinuous pattern of burst

suppression May deteriorate to isoelectric Rapid resolution of abnormalities favors good

prognosis

Burst Suppression EEG

Diagnosis of HIE: Imaging

Cranial Ultrasound—increased echogenicity and effacement of sulci although 50% read as normal

Computerized Tomography (CT) 2 to 5 days maximal extent of parenchymal hypodensities Atrophy or multicystic encephalomalacia develops later

Diagnosis of HIE: MRI

T2 prolongation 12 to 18 hours-transient edema T1 high signal after 3 days T2 shortening after 6 to 7 days denotes permanent

injury DWI (diffusion weighted imaging) more sensitive

especially in signaling injury to the thalami and basal ganglia. Maximum sensitivity at 2 to 4 days

Neuropathology

Parasagittal Injury (>34 wks)– spastic quadriplegia Periventricular White Matter in preterm—spastic

diplegia Basal Ganglia—acute, near total ischemia

associated with poor neurologic outcome chorioathetosis and feeding difficulty

Focal/Multifocal– reflects the area of injury Selective Neuronal Necrosis—HIE

Normal Cranial CT Scan

Cerebral Edema on Cranial CT Scan

Hypoxic Ischemic EncephalopathyBasal Ganglia Injury

Hypoxic Ischemic EncephalopathySevere Global Injury

Cerebral Palsy

A chronic neuromuscular disability of central nervous system origin, characterized by abnormal control of movement or posture appearing early in life and not the result of a progressive disease Intellectual , sensory or behavior problems may

accompany but are not a part of the diagnosis Only 10-15% of children with CP have a history of

severe hypoxic ischemic encephalopathy (NCPP)

Diagnosis of Cerebral Palsy

Delayed Milestones Persistence of developmental reflexes Pathologic Reflexes Failure to develop maturational reflexes No progression or loss of skills by history

Type of Cerebral Palsy

Spastic Choreoathetotic Ataxic Dystonic Ballismic Mixed

Clinical Syndromes

Spastic Quadriplegia is the form of CP most commonly associated with Hypoxic Ischemic Encephalopathy

Spastic Hemiparesis is associated with stroke

Athetosis is associated with kernicterus

About 30% of children with CP have a brain malformation or cortical dysgenesis

Homunculus

Association of Neonatal Encephalopathy and CP In <10% of children with CP or MR was there an

association with intrapartum or perinatal asphyxia 75% of children with CP had normal Apgar scores Apgar < 3 at 15 min 36% with CP at 20 min 57% with CP Persistently low Apgar scores at 10, 15, 20 min are

associated with poor neurologic outcome

Criteria for Exposure Birth Asphyxia

Clinical history Clinical Markers

Abnormal fetal heart rate Meconium

Laboratory Markers Fetal Acidosis (cord pH)

Newborn Status Apgars Encephalopathy

Conclusions ACOG guidelines provide a reasonable framework There is an association between HIE and CP Neonatal Encephalopathy is a non specific clinical

syndrome Neonatal Encephalopathy must be documented to

consider HIE as causation for CP Continued scientific studies are needed to further

understand etiologies of CP