INTRACRANIAL HEMORRHAGE AND BRAIN DISORDERSWilliam 2001

Intraventricular hemorrhage

Brain disorders Cerebral palsy Neonatal encephalopathy

INTRAVENTRICULAR HEMORRHAGE

Types of intracranial Hg: Subdural Subarachnoid Intracerebellar Periventricural -

intraventricural: -- In term infants:

½due to trauma/asphyxia ¼due to unknown causes

-- In preterm infants: Due to multifactorial factors:

Hypoxic - ischemic Anatomical causes Coagulopathy

Periventricular – intraventricular Hg:

- Fragile capillaries in germinal matrix rupture Hg

-May extend to the ventricles or brain

parenchyma -Common in neonates < 34 weeks

but may occur in older infants -Starts usually within 72 hours but

may develop 24 days after birth -External perinatal and postnatal

factors may alter it’s % and severity

- Minimal in ½ of the cases no C/P - Mostly small Hg or Hg confined to

the ventricles resolve without neurological impairment

- In large Hg hydrocephalus or periventricular leukomalacia CP

Pathology: -Due to damage of germinal matrix

capillary network -↑in preterm infants due to:

Poor support Venous anatomy in this area stasis Hg Vascular autoregulation is impaired < 32 weeks

Extensive Hg death or handicap due to periventricular leukomalacia:

=Cystic area due to ischemia or HgIncidence and severity:

=4% in term infants =½ infants < 32 weeks are born

with some Hg minimal effect

Very LBW have the: Earliest onset Greatest progression Highest mortality rate

Assessed by: U/S and CT

Grades: I matrix Hg

II intraventricular Hg III dilatation of the ventricles

IV parenchymal HgSurvival:

> 90% in I & II -- 3.2% handicap 50% in III & IV

Very LBW infants: 45% intraventricular Hg

20% of them are III & IV degreeContributing factors:

-Prematurity and it’s complications:

Infection ischemia Acidosis X 3 ↑ risk for grade III & IV if pH < 7.2 RD and mechanical ventilation

Heparin X 4 Hg

-Postnatal factors: RD Ventilation therapy PCO2 ≥ 60 mmHg within 1st 2 hours PO2 < 40 mmHg within 1st 2 hours Pneumothorax

Treatment:1 - Antenatal corticosteroids :

↓ mortality ↓RD

↓intraventricular Hg + benefit in cases of PROM

Betamethasone ↓ leukomalacia compared to dexamethasone

2 – Phenobarbital and vit K = controversial

3 - Vit E ↓ severity and % but does not ↓ mortality

4 - Indomethacin ↑ mortality in infants < 1000 gm

5 - MgSO4 ↓ periventricular Hg

Prevention: Avoid hypoxia CS in preterm cephalic fetus no evidence

Studies: - No significant difference

- ↓early intracranial Hg

Outcome in extreme prematurity:

↑ mortality ↑ neurological injury ↑ ophthalmological injury ↑ pulmonary injury

Age α 1 / severe neurological abnormalities

BRAIN DISORDERS

1862 = abnormal labor spasticity1900 = Sigmund Freud many

abnormalities can spastic rigidityCerebral palsy is caused by a combination of:

Genetic factors Environmental factors Physiological factors Obstetric factors

Still many doctors are afraid of CP from obstetric factors ↑ CS to 1 : 4 births in US

with no ↓ in CP

Asphyxia: Profound metabolic or mixed acidemia <

7 Persistent Apgar score 0 – 3 for > 5 min Neurological sequelae:

- Seizures - Coma

- Hypotonia - Dysfunction of ≥ 1 system : GIT -

Cardiac – Hematologic – respiratory

Causes of low Apgar score alone: PTL Maternal sedation Anesthesia Vigorous suction or intubation Congenital anomalies Newborn diseases as: neurological

musculoskeletal - cardiorespiratory

CEREBRAL PALSY

Definition:Nonprogressive motor disorder of early infant onset in ≥ 1 limbs spasticity orparalysis ± MR / epilepsy ( not associated with perinatal asphyxia in the absence of CP) Categorized by:

Type of neurological dysfunction:

Spastic – dyskinetic - ataxic

Number and distribution of involved limbs:

Quadriplegia 20% Diplegia 35%

Hemiplegia 30% Monoplegia

Major types of CP: Spastic quadriplegia (↑in MR and seizures)

Diplegia ↑ in LBW and preterm Hemiplegia - Choreoathetoid - Mixed

25% of CP + MR ( IQ < 50% )Incidence and epidemiology:

=0.1 - 0.2 % of live birth ( ↑by ↑ survival of LBW)

=0.27 % at age 5 – 7 years =1.5 < % 2500 gm

=1.3 – 9 % from 500 – 1500 gm =50 < % 25 weeks

Risk factors: Genetic - Maternal MR - Microcephaly - Congenital anomalies < 32 weeks < 2000 gm infection

Obstetric complications: Not strongly predictive of CP 20% + perinatal asphyxia 50% + LBW – congenital anomalies – microcephaly and others No single intervention can prevent CP Most cases of CPs unknown causeStudy:

25% of CP is due to NTD or postnatal causes as infection or injury

Strongest predictors for CP: Congenital anomalies LBW Low placental weight Abnormal fetal position as: breech or transverse lie

-No correlation between CS or instrumental delivery with CP

< -1000 gm only early GA

and LBW correlate with neonatal neurological morbidity

Intrapartum events: No special FHR pattern in CP Continuous electronic monitoring equals intermittent monitoring 75% of CP are unavoidable Abnormal FHR = preexisting neurological abnormalities

92% of CP + no intrapartum injury 3% + “”””” is possible 5% + “”””” is likely Since 1965 CS ↑ 1 : 4 in US but % of CP is still the same

Study:Electronic monitoring ↑ CP in preterminfants # intermittent auscultation

Apgar score: - poor predictors of CP except in:

- Complicated birth + 5m Apgar score

= ≥3 ↑ death + ↑ CP - Uncomplicated birth + 5m Apgar

score = ≤ 3 no ↑ risk -Most neurological abnormalities are

due to factors other than perinatal ↓O2

-LBW + 1 m Apgar score ≤ 3 ↑death X 5 + ↑ CP X 3

-Low 5 m Apgar score is predictive of neurological impairment

< -37 weeks completed + 5 m Apgar score ≤ 3 X 75 fold death

-≤38 weeks + 5 m Apgar score ≤ 3 X 1460 fold death within 28 days

-Low 1 & 5 m Apgar score alone are: Excellent predictors for identification of infants who need resuscitation Insufficient evidence that the damage is due to hypoxia

Umbilical cord blood gas: If no metabolic acidosis intrapartum

hypoxia or asphyxia is excluded

Alone U/C pH is not superior to Apgar score in predicting long – term neurological D Most neurological diseases are associated with normal pH + low Apgar score = hypoxia is not a major cause of long – term neurological morbidity Neither pH nor acidemia correlate with long term neurological disease in term infants

The cutoff for clinically significant acidemia is now pH < 7.0 instead of < 7.2 If pH is ≤ 7 only 7% of infants develop mild neurological sequelaeThe use of pH to assess predictability of neonatal death within 28 days:

≤ 7 + Apgar score ≤ 3 3204 relative risk < 6.8 ↑ death X 1400 fold

Nucleated RBCs: ↑ in hypoxia Number of NRBCs α degree of hypoxia and can determine it’s duration

Studies: ↑ NRBCs is associated with asphyxia No relation between hypoxia and NRBCs NRBCs are hematological markers of maternal and neonatal infection as well

placental histological evidence of infection

Neonatal serial lymphocyte and normoblast count may accurately identify the time

before birth when encephalopathy occur: peak 2 hours after injury and normalize in 24 – 36 hoursPeriventricular leukomalacia :

Cyctic areas after hemorrhgic infarction Ischemia necrosis cyst in 2 weeks to 104 days

Severe ICHg and periventricular leukomalacia may CP 40% of LBW develop CP and III or IV degree ICHg Risk of CP ↑ X 16 in III and IV degree ICHg ≤ 34 weeks 11% of transient cysts CP 67% of localized cysts CP 100% of extensive cysts CP Size of the cyst α ↑ CP risk

Symmetrical cysts = highest risk Periventricular leukomalecia is linked more than ICHg to infection as: - Chorioamnionitis - Prolonged PROM - Neonatal hypotension Periventricular leukomalacia is associated with:

1st trimester Hg UTI at labor LBW Smoking PTL Neonatal acidosis Meconium staining >72 hours of ritodrine therapy

Preterm periventricular leukomalacia:Blood supply to the brain < 32 weeks: 1 - Ventriculopedal system: penetrates into the cortex 2 - Ventriculofugal system: reaches down to the ventricles then curves upward

In between the 2 systems the area near the lateral ventricles where the pyramidal tract pass = watershed area because there is no

anastomosis between the 2 systems >32 weeks blood supply shifts away from the brain stem and basal ganglia toward

the cortexEffect of ischemia:

<32 weeks spastic diplegia >32 weeks brain damage

Perinatal infection:Maternal or intrauterine infection

endotoxin ↑ cytokines

↑ PGn PTL

ICHg & PVL CP

↑Cytokines 1, 6, 8, TNF Direct toxic effect on oligodendrocytes and myelin Vessel rupture tissue hypoxia and massive cell death ↑ glutamate - white matter damage - ↑ intracellular Ca toxic - Direct toxic effect on oligodendroglia

Studies: E Coli injection into animal embryo brain damage TNF and IL 6 ↑ in brains of infants with PVL AF culture: 45% of CP microorganisms 85% of CP ↑ IL 6 - 8

PTL after PROM # PTL caused by other causes: ICHg and PVL ↑ after spontaneous labor ↑ after spontaneous ROM Both if + chorioamnionitis ↑ CP Most significant clinical correlates of white matter necrosis in preterm infants:

- Funistis - Purulent AF

- Placental vessel abnormalities

> 2500 gm fetus + maternal fever or chorioamnionitis X 9 CP + neonatal infection X 19 CP

Prevention: Corticosteroid therapy Aggressive treatment or prophylaxis of infection in women delivering preterm infants = neuroprotective

MgSO4:

Stabilizes vascular tone ↓ fluctuations of cerebral blood flow ↓ reperfusion injury ↓ cytokines and bacterial endotoxins ↓ inflammatory effects of infection blocks Ca intracellular toxic effect

Limited to preeclampsia

Neuroradiological imaging:CT:

25% of CP normal CT 70% of preterm infants early insult50% of term infants prenatal insult:

37% periventricular leukomalacia 17% maldevelopment 19% cortical or subcortical injury

MRI: -80% of preterm CP periventricural

white matter damage = hypoxic ischemic -50% of term CP antenatal damage as:

Gyral abnormalities as polymicrogyria = midpregnancy injury Isolated periventricular leukomalacia

In 25% of these cases, MRI + C/P are suggestive of hypoxic ischemic insult

MRI can predict the specific pattern of neurophysiological dysfunction by:

Severity of dilatation Degree and extent of white matter loss Involvement of optic structures Thinning of corpus collosumMRI can determine the most likely time of brain insult in CP

U/S: -1st day U/S diagnose antenatal insult

intraventricular Hg = secondary injury that developed in the nursery

-Results of U/S differ than MRI but complementary to it

NEONATAL ENCEPHALOPATHY

Definition:Disturbed neurological function in the earliest days of life in term infantsClinical picture:

Respiratory depression Hypotonia Subconsciousness Seizures

Due to hypoxic ischemic insult ofunknown time

Mild E: Hyperalertness Irritability Jitteriness Hypo/hypertonia

Moderate E: Lethargy Severe hypotonia Occasional seizures

Severe E: Coma Recurrent apnea Multiple seizures

Normal neurological outcome: Mild E all Moderate E 80% Severe E all

Studies: -High risk term and preterm neonates:

30% neonatal E 17% cognitive and motor deficits:

¼ mild – moderate E ½ severe E

-Respiratory complications are the most common risk factor

-Perinatal hypoxia is associated with: 26% of mild – moderate E 66% of severe E

-Serial head circumflex in E: If ↓ > 3.1% relative to that expected

for age in the 1st 4 months = predicts

microcephaly with 90% specificity

Mental retardation: %0.3

-Isolated MR (=MR without CP or epilepsy)

is associated with perinatal hypoxia in < 5%

Seizure disorders: -Isolated seizure disorders or epilepsy are

not usually caused by perinatal hypoxia

-Major predictors are: Congenital anomalies Family history Neonatal seizures