GERMINAL MATRIX HAEMORRHAGE IN PRE-TERM

GERMINAL MATRIX-INTRAVENTRICULAR HAEMORRHAGE IN PRETERM BABIES : 

GERMINAL MATRIX-INTRAVENTRICULAR HAEMORRHAGE IN PRETERM BABIES Dr Hanumesh KM Clinical Fellow Division of Neonatology Department of pediatrics BVU Medical college, Pune

OVERVIEW : 

OVERVIEW INTRODUCTION INCIDENCE TIMING RISK FACTORS NEUROPATHOLOGY GRADING PATHOGENESIS DIAGNOSIS NEUROPATHOLOGICAL CONSEQUENCES NEUROPATHOLOGICAL ACCOMPANIMENTS PREVENTION MANAGEMENT PROGNOSIS

INTRODUCTION : 

INTRODUCTION

INCIDENCE : 

INCIDENCE Tightly related to gestational age

INCIDENCE : 

INCIDENCE Late 1970s to early 1980s – 35 to 50 % Late 1980s – 20 % Mid 1990s – 15 % In 1990s, IPL alone:8 to 11% 25% are bilateral Australian & New Zealand neonatal network reported IPL rate decreased to 24% in 24-30wks by 1997

TIMING : 

TIMING Occasionally occurs antenatally 1st day – 50 % 2nd day – 25 % 3rd day – 15 % >4th day– 10 % Occur very soon after birth in least mature infants

RISK FACTORS : 

RISK FACTORS PRENATAL: Failure to give antenatal steroids Maternal aspirin therapy Maternal smoking Reason for Prematurity other than PET Male sex Breech vaginal delivery Very preterm delivery

RISK FACTORS (contd) : 

RISK FACTORS (contd) NATAL: Birth depression ; asphyxia Birth trauma ; bruising POSTNATAL : RDS, particularly if complicated by pneumothorax Hypercarbia Acidosis, Hypoxia Hypotension Fluctuating / low cerebral blood flow Coagulation disturbance Increased illness severity PDA Postnatal transfer

NEUROPATHOLOGY GERMINAL MATRIX : 

NEUROPATHOLOGY GERMINAL MATRIX GMH originates in the subependymal germinal matrix The germinal matrix is a source of neuronal precursors The germinal matrix capillary bed is a vascular end zone of arterial supply The principle mechanism underlying GMH-IVH involves rupture of fragile capillaries within germinal matrix

NEUROPATHOLOGY GERMINAL MATRIX : 

NEUROPATHOLOGY GERMINAL MATRIX Arterial supply from: Anterior cerebral A (via Heubner’s A.) Middle cerebral A (via deep lateral striate As & perforating branches from meninges) Internal carotid A (via anterior choroidal A.) Venous drainage by: Medullary, choroidal, and thalamostriate veins drain into terminal v which drains into Vein of Galen

Arterial supply to germinal matrix : 

Arterial supply to germinal matrix Anterior Choroidal Art Striate branches of MCA Heubner’s Art Perforating Arteries

Venous drainage of the germinal matrix : 

Venous drainage of the germinal matrix Thalamostriate V Choroidal V. Medullary Vs Terminal V Internal Cerebral V Vein of Galen

GRADING OF GMH-IVH : 

GRADING OF GMH-IVH PAPILE CLASSIFICATION: Is based on CT scan at 1st week Grade I: confined to subependymal region Grade II:IVH without ventricular distension Grade III:IVH with ventricular distension Grade IV: any parenchymal bleeds Has several disadvantages

GRADING OF SEVERITY HEMORRHAGEBy Volpe,based on Neurosonogram : 

GRADING OF SEVERITY HEMORRHAGEBy Volpe,based on Neurosonogram

Grade I to IV gross HPE findings : 

Grade I to IV gross HPE findings

Neurosonogram findings: IVH-Grade I : 

Neurosonogram findings: IVH-Grade I

Neurosonogram findings: IVH-Grade II : 

Neurosonogram findings: IVH-Grade II

Neurosonogram findings: IVH-Grade II : 

Neurosonogram findings: IVH-Grade II

Neurosonogram findings: IVH-Grade III : 

Neurosonogram findings: IVH-Grade III

Neurosonogram findings: IVH-Grade IV : 

Neurosonogram findings: IVH-Grade IV

Neurosonogram findings: IVH-Grade IV : 

Neurosonogram findings: IVH-Grade IV

PATHOGENESIS : 

PATHOGENESIS Pathogenesis of IVH is multifactorial Divided into - intravascular - vascular & - extra vascular

PATHOGENESIS-INTRAVASCULAR FACTORS : 

PATHOGENESIS-INTRAVASCULAR FACTORS FLUCTUATING CEREBRAL BLOOD FLOW - ventilated PT infant with RDS INCREASE IN CEREBRAL BLOOD FLOW - systemic HT : pressure passive circulation - rapid volume expansion - hypercarbia - decreased Hct - decreased blood glucose

PATHOGENESIS-INTRAVASCULAR FACTORS (contd) : 

PATHOGENESIS-INTRAVASCULAR FACTORS (contd) INCREASE IN CEREBRAL VENOUS PRESSURE - venous anatomy :U turn in direction of venous flow - labour & vaginal delivery - respiratory disturbances DECREASE IN CEREBRAL BLOOD FLOW FOLLOWED BY REPERFUSION - systemic HT : pressure passive circulation PLATELET & COAGULATION DISTURBANCE

PATHOGENESIS-VASCULAR FACTORS : 

PATHOGENESIS-VASCULAR FACTORS TENUOUS CAPILLARY INTEGRITY - involuting , remodelling capillary bed - deficient vascular lining - large vascular & luminal area VULNERABILITYOF MATRIX CAPILLARIES TO HYPOXIC-ISCHEMIC INJURY - vascular border zones - high requirements for oxidative metabolism

PATHOGENESIS-EXTRAVASCULAR FACTORS : 

PATHOGENESIS-EXTRAVASCULAR FACTORS Deficient vascular support Fibrinolytic activity Postnatal decrease in extra vascular tissue pressure

Pathogenesis : 

Pathogenesis Ventilated preterm infant with RDS Decreased CBF Fluctuating CBF Increases in CBF Increases in cerebral venous pressure Capillary rupture INTRAVENTRICULAR HEMORRHAGE Endothelial injury Vulnerable capillaries Platelet & Coag disturbances Fibrinolytic activity

DIAGNOSIS : 

DIAGNOSIS CLINICAL DIAGNOSIS ULTRASOUND DIAGNOSIS MRI DIAGNOSIS

CLINICAL DIAGNOSIS : 

CLINICAL DIAGNOSIS Three basic clinical syndromes: 1 Catastrophic deterioration (least common) 2 Saltatory deterioration 3 Clinically silent

CATASTROPHIC CLINICAL SYNDROME : 

CATASTROPHIC CLINICAL SYNDROME Inexorable evolution in minutes to hrs Neurological features: stupor- coma respiratory disturbance- apnoea generalized tonic seizure decerebrate posturing pupils fixed to light flaccid quadriparesis

SALTATORY SYNDROME : 

SALTATORY SYNDROME Stuttering evolution in hrs to days Neurological features: - altered level of consciousness - decreased spontaneous movement - hypotonia - abnormally tight popliteal angle - abnormal eye position /movement - respiratory disturbance

CLINICALLY SILENT SYNDROME : 

CLINICALLY SILENT SYNDROME Neurological signs are subtle Most valuable sign is unexplained fall in hematocrit/failure of hematocrit to rise after transfusion Recognised on routine ultrasound

NEUROPATHOLOGICAL CONSEQUENCES : 

NEUROPATHOLOGICAL CONSEQUENCES Germinal matrix destruction Periventricular hemorrhagic infarct -15% Post hemorrhagic hydrocephalus- 30%

Slide 34: 

Hydrocephalus

Post hemorrhagic hydrocephalus : 

Post hemorrhagic hydrocephalus

Ventricular index-Normal range : 

Ventricular index-Normal range

Post hemorrhagic hydrocephalus : 

Post hemorrhagic hydrocephalus

NEUROPATHOLOGICAL ACCOMPANIMENTS OF IVH : 

NEUROPATHOLOGICAL ACCOMPANIMENTS OF IVH Periventricular leukomalacia : Bilateral, non-haemorrhagic ischemic white matter injury Pontine neuronal necrosis: 46 to 71 % of infants with IVH exhibited pontine neuronal necrosis

Periventricular leukomalacia : 

Periventricular leukomalacia

PREVENTION OF IVH : 

PREVENTION OF IVH Because 25-70% GMH-IVH occurs before 18 hrs of life, antenatal and intrapartum interventions are crucial. ANTENATAL INTERVENTIONS: 1. Prevention of premature delivery 2.Transportation in utero 3.Pharmacological intervention

PREVENTION OF IVH:ANTENATAL INTERVENTIONS: : 

PREVENTION OF IVH:ANTENATAL INTERVENTIONS: Pharmacological intervention : 1.Antenatal corticosteroids: The incidence is two-three folds is lower. Currently most beneficial intervention. 2.Antenatal Phenobarbital and Vit K: a recent comprehensive review for the Cochrane Database of combined data from all clinical trial failed to demonstrate a benefit from either medication 3. Magnesium sulphate: few results found a lower incidence of grade3-4 IVH, most data do not show a beneficial effect on IVH

PREVENTION OF IVH -Intrapartum intervention : 

PREVENTION OF IVH -Intrapartum intervention C. sulfate: Although one Optimal management of labour and delivery: 1.Avoidance of prolonged labour >10-12hrs. 2.Avoidance of vaginal delivery: -deformation of the compliant premature skull and transient increase in cerebral venous pressure. -In multivariate analysis involving VLBW infants, vaginal delivery had more than doubled the risk for IVH compared to relatively low risk of 7% in infants delivered by CS. 3. Antenatal steroids: even incomplete course seems to improve outcome

PREVENTION OF IVH Postnatal intervention : 

PREVENTION OF IVH Postnatal intervention C Avoidance of hemodynamic disturbance: In high risk infants, every efforts should be made to minimize hemodynamic disturbances Thus care must be taken to prevent sharp elevation in BP and CBF with excessive handling, tracheal suctioning, rapid infusion of blood/colloid, pneumothorax, seizures and Hypercarbia.

PREVENTION OF IVH Postnatal intervention : 

PREVENTION OF IVH Postnatal intervention Resuscitation: Establish adequate ventilation Rapid infusion of volume expanders/hypertonic solution to be avoided Ventilated babies are at risk of pneumothorax/GMH Comprehensive analysis of data for the Cochrane Database demonstrated a significant reduction in GMH-IVH after neuromuscular paralysis

PREVENTION OF IVH Postnatal intervention : 

PREVENTION OF IVH Postnatal intervention Because long term pulmonary and neurologic effects are uncertain, the routine use of pancuronium in ventilated newborn is not recommended (Cochrane Database Syst Rev 2000). Other promising possibilities includes use of analgesic e.g fentanyl

PREVENTION OF IVH Postnatal intervention : 

PREVENTION OF IVH Postnatal intervention Pharmacological intervention: 1.Indomethacin: overall data are encouraging, they do not appear to be conclusive to recommend routine administration 2.Phenobarbital: did not reduce GMH-IVH and was associated with an increased need for mechanical ventilation 3.Ethamsylate: There was no difference between treated and control groups in incidence of IVH 4.Vit E: Operates as a free radical scavenger to protect matrix capillary endothelial cell. Vit E administration leads to decrease in incidence and severity of IVH, particularly in smallest infants (future studies are needed).

MANAGEMENT : 

MANAGEMENT ACUTE MANAGEMENT: Maintenance of cerebral perfusion (CPP=MBP-ICP): cautious control of BP, lowering of increase ICP (rarely indicated) Prevention of cerebral haemodynamic disturbances Supportive care: temperature, ventilation ,circulation and metabolic status.

MANAGEMENT : 

MANAGEMENT Serial ultrasound scans: -are necessary to assess ventricular size because, the classic signs of evolving hydrocephalus i.e. rapid head growth, full anterior fontanel and separated cranial sutures do not appear for days to wks after ventricular dilation had already commenced (every 5-10days).

MANAGEMENT : 

MANAGEMENT Other imaging techniques : -diffusion weighted MRI and diffusion tensor MR have potential value for detecting imminent cerebral ischemia, but their routine clinical applications are limited.

MANAGEMENT OF PHH : 

MANAGEMENT OF PHH PREVENTION: Early intervention by repeated LP or ventricular tap :no impact of prophylactic CSF removal and there is some evidence that it may increase risk of CSF infection (Cochrane) Intraventricular Fibrinolytic therapy: with streptokinase for lysis of blood clots to improve CSF circulation and reabsorption does not seem beneficial (adverse effect: bleeding, infection).

NATURAL HISTORY : 

NATURAL HISTORY

Slowly progressive ventricular dilation(<4wks): : 

Slowly progressive ventricular dilation(<4wks): Moderate dilation, appropriate rate of head growth, stable ICP Close surveillance of change in ventricular size, rate of head growth, clinical condition and ICP for 4 wks Outcome: majority spontaneous arrest

Persistent slowly progressive ventricular dilation(>4wks) : 

Persistent slowly progressive ventricular dilation(>4wks) Serial LP: for at least temporary improvement, i.e. arrest of progression and intermittent decrease in ventricular size if adequate quantity of CSF is removed (10-15ml/kg/day for at least 2-3wks). Complications: meningitis, epidural abscess, epidermoid tumour. Drugs: As an alternative to serial LP or perhaps as an additional modality. Acetazolamide: Carbonic anhydrase inhibitor, decrease CSF production by 50% and when combined with Furosemide, completely blocks CSF production

Persistent slowly progressive ventricular dilation(>4wks) : 

Persistent slowly progressive ventricular dilation(>4wks) Acetazolamide: -Adverse reaction: metabolic acidosis, electrolyte disturbance, glial and myelin toxicity, hypercalciuria, nephrocalcinosis. -Comprehensive analysis of data from clinical trial on diuretic therapy for PHH by the Cochrane collaboration conclude that acetazolamide and frusemide are neither effective nor safe as treatment of PHH. -It remains possible, however that acetazolamide alone is safe and useful as a complement to LP.(VOLPE)

Rapidly progressive ventricular dilation : 

Rapidly progressive ventricular dilation Criteria: rising ICP, excessive rate of head growth, moderate to severe dilatation A. Serial LP (do not provide consistent benefit) B. Ventricular drainage : a. direct external ventricular drain b. ventriculosubgaleal shunt c. ventricular access device (reservoir). C. Ventriculoperitoneal shunt:

Rapidly progressive ventricular dilation : 

Rapidly progressive ventricular dilation Absolute indications for CSF drainage: - symptoms such as apnoea, seizure, irritability or vomiting associated with ICP > 10 cm CSF - head circumference crossing 2 centile lines or enlarging at twice the normal rate for >2 wks

Arrested progression : 

Arrested progression Spontaneous arrest, arrest following LP or drugs Approximately 5% develop late progressive dilation so close surveillance for 1 yr Nearly all infants with late onset of progressive hydrocephalus requires VP shunt

PROGNOSIS : 

PROGNOSIS Short term out come : - mortality rate - progressive ventricular dilatation Long term out come : -spastic motor deficit -cognitive deficits

Clinico-pathologic correlation : 

Clinico-pathologic correlation Spastic hemiparesis secondary to PHI involves lower extremities as much as or more than upper limbs MOUTH FACE ARM TRUNK LEG

SHORT TERM OUTCOME : 

SHORT TERM OUTCOME

LONG TERM OUTCOME : 

LONG TERM OUTCOME

THANK YOU ALL : 

THANK YOU ALL