Morning Report

Elisabeth Kaza, MD July 2012

You are in the NICU

39 wk baby boy transferred from OSH via LF with high suspicion of seizure activity At OSH: Jittery movements since birth per mom 13 hrs of life: arching, stiffening of arms Glc wnl, septic r/o initiated, Abx started Head CT was found wnl Loaded with phenobarbital (20mg/kg)

Birth Data
Born to a 29 y/o G2P1001 Delivery:
Repeat C-section at 39 2/7 wks Spinal Anesthesia ROM: Artificial ROM Amniotic fluid: Meconium 2+

Resuscitation:
Dry and stimulation Apgar Score: 7/9

Cord gas: 7.29/33/25.8/15.3/-9

Maternal History
Prenatal Care: uncomplicated pregnancy
Started < 20 wks 17 wk US wnl Mom noted seizure 2 days prior to delivery Prenatal Labs: A-/ Rubella: immune Hepatitis B: neg GBS: neg RPR: neg HIV: undocumented

Family/Social History
FH: not contributory
No seizures or genetic issues No alcohol or tobacco use

SH: lives with parents (married) and 4 year old sister, mom is at home

Physical Exam
Birth data:

Weight: 3.474 kg (60%ile) Length: 50.0 cm (50%ile) OFC: 36.0 cm (60%ile) VS: T 36.5, HR 114, RR 30, BP 72/41, O2 sat: 99% (0.5L)

PE:

Gen: no anomalies noted, asleep initially HEENT: NC, AFOSF, pupils equal/reactive Lungs/CV: CTA BL, no murmur Abdomen: soft, NT/ND Neuro: hypotonic, no DTRs, intermittent rhythmically jerking of both lower extremities GU/back: normal male, no sacral pit/dimple

Laboratory Evaluation at OSH

At 13 hours of life:
CMP: wnl, Mg: 1.8 CBC: WBC 23.2 (5B, 53N, 26L), Hct: 46, Plts: 219 Glc: 62 Lactate: 9.1 CSF studies wnl HSV/Enterovirus not detected

Radiology: Head CT wnl, CXR wnl

Differential Diagnosis ??
39 wk baby boy with high suspicion of seizure activity

AGES 1-4 DAYS HIE IVH Drug withdrawal, maternal narcotic/barbiturate use

AGES 4-14 DAYS Infection

- Meningitis (bacterial) - Encephalitis (enteroviral, HSV)

AGES 2-8 WEEKS Infection - Encephalitis

- Bacterial meningitis

Metabolic disorders - Hypocalcemia

- Hypoglycemia - Galactosemia - Fructosemia - Leucine sensitivity - Beckwith syndrome

Malformations of cortical development

- Lissencephaly - Focal cortical dysplasia

Pyridoxine deficiency

Drug withdrawal

Head injury
-Subdural hematoma -Child abuse

Acute metabolic disorders - Hypocalcemia

- Asphyxia, SGA - Sepsis - Hypoglycemia - Prematurity, SGA - Maternal DM - Sepsis - Hypomagnesemia - Hypo/hypernatremia: SIADH

Benign neonatal convulsions

- Familial - Non-familial

Inherited disorders of metabolism

- Aminoacidurias - Urea cycle defects - Organic acidurias - Neonatal adrenoleukodystrophy

Inborn errors of metabolism - Galactosemia

- Hyperglycinemia - Urea cycle disorder

Kernicterus Hyperbilirubinemia

Tuberous Sclerosis Sturge Weber Syndrome

AGES 1-4 DAYS

AGES 4-14 DAYS Infection

- Meningitis (bacterial) - Encephalitis (enteroviral, HSV)

AGES 2-8 WEEKS Infection - Encephalitis

- Bacterial meningitis

HIE
IVH

Drug withdrawal, maternal narcotic/barbiturate use

Metabolic disorders - Hypocalcemia

- Hypoglycemia - Galactosemia - Fructosemia - Leucine sensitivity - Beckwith syndrome

Malformations of cortical development

- Lissencephaly - Focal cortical dysplasia

Pyridoxine deficiency

Drug withdrawal

Head injury
-Subdural hematoma -Child abuse

Acute metabolic disorders - Hypocalcemia

- Asphyxia, SGA - Sepsis - Hypoglycemia - Prematurity, SGA - Maternal DM - Sepsis - Hypomagnesemia - Hypo/hypernatremia: SIADH

Benign neonatal convulsions

- Familial - Non-familial

Inherited disorders of metabolism

- Aminoacidurias - Urea cycle defects - Organic acidurias - Neonatal adrenoleukodystrophy

Inborn errors of metabolism - Galactosemia

- Hyperglycinemia - Urea cycle disorder

Kernicterus Hyperbilirubinemia

Tuberous Sclerosis Sturge Weber Syndrome

MRI brain of patient

Hypoxic-Ischemic Encephalopathy
Incidence: 1-6/1000 live term births
25% die in neonatal period 30-50% sustain neuro-developmental abnormalities

Insults damage vulnerable brain regions

Hippocampus Basal ganglia, brainstem Purkinje neurons in cerebellum Periventricular white matter

Perinatal Asphyxia

Profound umbilical artery metabolic acidosis (pH < 7 and BD > 12mmol/L) APGAR score < 3 at 5 min Neonatal neurologic sequelae: sz, hypotonia, coma Multisystem organ dysfunction

Mechanisms of HIE
MATERNAL
Impaired oxygenation Asthma Pulmonary embolism PNA Cardio-respiratory arrest Maternal hypotension Preeclampsia Chronic vascular disease

Inadequate perfusion of placenta

PLACENTAL
Abruptio placenta Tight nuchal cord Cord prolapsed True knot Uterine rupture

FETAL
Impaired fetal oxygenation/perfusion Feto-maternal hemorrhage Fetal thrombosis

Therapeutic Window
INSULT/ASPHYXIA

Redistribution of blood flow (Diving Reflex)

Blood flow to brain, heart, adrenals

PRIMARY ENERGY FAILURE (Minutes) Increased neurotransmitter release

Increased lactate Increased sodium (cerebral edema) Decreased ATP

Reperfusion

IMMEDIATE NECROTIC CELL DEATH

Cerebral metabolism transiently recovers

Calcium overload Increased free radicals, NO

SECONDARY ENERGY FAILURE (Hours to Days: 6-72 hrs)

Mitochondrial dysfunction Caspases Activation DELAYED APOPTOTIC CELL DEATH

HYPOXIC ISCHEMIC BRAIN INJURY

Clinical Manifestations
Seizures:
First noted in first 12-24 hrs Resolve by age 5-7 days (underlying acute encephalopathy resolves) Often resistant to anticonvulsant tx

Hypotonia, possible coma Cardiac: myocardial ischemia, CHF Renal dysfunction, Pulmonary HTN

SARNAT STAGES
Stage 1 Level of consciousness Muscle tone Posture Tendon reflexes Myoclonus
Hyperalert Normal Mild distal flexion Overactive Present

Stage 2
Lethargic Mild hypotonia Strong distal flexion Overactive Present

Stage 3
Stuporous Flaccid Decerebration Depressed Absent

Complex reflexes: Suck Moro Tonic neck Oculocephalic

Autonomic: Pupils Heart rate Secretions Seizures EEG

Weak Strong Slight Normal

Weak or absent Incomplete Strong Overreactive

Absent Absent Absent Weak or absent

Dilated Tachycardia Spars

Absent Normal

Constriced Bradycardia Profuse

Present Low voltage

Variable, unequal Variable Variable

Uncommon Burst suppression

Diagnosis/Treatment
Neuro-imaging:
MRI: deep gray matter lesions (basal ganglia, thalami), PV white matter injury CT: intracranial hemorrhage, calcifications EEG

Hypothermia: neuro-protective within 6hrs

decreases rate of apoptosis suppresses neurotoxic mediators (glutamate, free radicals, NO, lactate)

Control seizures Phenobarbital