UTMB Neonatology Manual
Neurological Disorders
SUPPORTING NORMAL NEUROLOGIC DEVELOPMENT IN THE ISCU
Asphyxia is the term used to describe an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs. The biochemical definition of asphyxia includes the components of hypoxemia, metabolic acidosis and hypercapnia. Asphyxia is defined as a combination of several findings: Apgar <5 at 5 minutes, PH<7.00, and evidence of seizures or other organ involvement.
Neonatal encephalopathy (NE) is defined clinically on the basis of findings of abnormal consciousness, depressed tone and reflexes, abnormal respiration or seizures in an infant beyond 35 weeks gestational age. Hypoxic-ischemic encephalopathy (HIE) is the term for brain injury associated with asphyxia. HIE is a subset of NE; however, less than 30% of cases of NE meet criteria for intrapartum hypoxia. Cerebral palsy (CP) is a chronic disability of CNS origin characterized by aberrant control of movement and posture which appears early in life and is not due to progressive neurologic disease. Although NE does not always result in permanent neurologic impairment, the pathway from an intrapartum hypoxic-ischemic injury to CP MUST progress through NE.
The following items will determine the likelihood that an acute peripartum or intrapartum event occurred contributing to neonatal encephalopathy in infants > 35 weeks:
I. Neonatal Signs Consistent with Acute Peripartum or Intrapartum Event
II. Type and Timing of Contributing Factors Consistent with Acute Peripartum or Intrapartum Event
III. Developmental Outcome is Spastic Quadriplegia or Dyskinetic Cerebral Palsy
The incidence of moderate or severe HIE has remained essentially unchanged over the past 20 years (1.4-1.8 per 1000 live births). About 15-20% will die and 20-25% of survivors will be disabled.
Infants suspected of having sustained an asphyxial event can generally be identified by the prenatal and perinatal history. Recognition of conditions placing the infant at high risk for asphyxia or depression allows for advanced preparation of a neonatal resuscitation.
Conditions associated with increased risk of fetal asphyxia are: 1) altered placental exchanges (placenta abruptio, placenta previa, prolapsed cord, postmaturity), 2) altered maternal blood flow to the placenta (maternal hypotension, maternal hypertension, abnormal uterine contractions), or 3) reduced maternal arterial oxygen saturation (maternal hypoventilation, maternal hypoxia, maternal cardiopulmonary disease).
A low Apgar score indicates an abnormal condition but not a specific cause. It is important to remember that infants lose their color, respirations, tone, reflexes and heart rate in that order. Effective resuscitation restores functions in a different order: heart rate, reflexes, color, respirations and tone. The amount of time required for restoration of tone and respirations may assist in indicating the severity or duration of the asphyxial insult to the CNS.
The CNS is the organ most frequently affected (72%) by asphyxia, and includes selective neuronal necrosis, status marmorata of basal ganglia and thalamus (more in term infants) and periventricular leukomalacia (more common in prematures)
Associated complications in asphyxiated infants include: hypoglycemia, hypocalcemia, seizures, myocardial ischemia (30%), acute tubular necrosis (42%), renal failure, disseminated intravascular coagulation, hepatic injury (30%), pulmonary hypertension, pulmonary hemorrhage, blood pressure instability with hypotension, subarachnoid hemorrhage, intraventricular hemorrhage, CNS ischemia and infarction.
After the initial steps of neonatal resuscitation, management of an asphyxiated infant includes: assisting the infant to obtain adequate ventilation, oxygenation, pulmonary perfusion, and cardiac output, minimizing body heat loss and maintaining peripheral circulation. The next steps in management would include to:
In the general management of the asphyxiated patient, eliminating the hypoxia, alleviating tissue ischemia, and providing supportive care for anticipated problems in an expeditious manner is imperative. Each infant will respond differently and overall outcomes are difficult to predict.
Apgar score of 0-3 at 20 minutes of age
A staging procedure designed by Sarnat and Sarnat for hypoxic-ischemic encephalopathy may be helpful to determine the severity of the asphyxial event and suspected long term outcome based upon their findings. The stages in this table reflect the clinical state of infants over 36 weeks' gestational age. (Source: H.B. Sarnat and M.S. Sarnat, Neonatal encephalopathy following fetal distress: A clinical and electroencephalographic study. Arch. Neurol. 33:696, 1976.)
Careful assessment of the baby to assign a stage is very useful (see following table).
SARNAT STAGING CRITERIA FOR HIE
|
Stage |
Stage I |
Stage II |
Stage III |
|
Level of consciousness |
Hyperalert |
Lethargic or obtunded |
Stuporous |
|
Neuromuscular control Muscle tone Posture Stretch reflexes Segmental myoclonus |
Normal Mild distal flexion Overactive Present |
Mild hypotonia Strong distal flexion Overactive Present |
Flaccid Intermittent decerebration Decreased or absent Absent |
|
Complex reflexes Suck Moro
Stage Oculovestibular Tonic neck |
Weak Strong, low threshold
Stage I Normal Slight |
Weak or absent Weak, incomplete high threshold
Stage II Overactive Strong |
Absent Absent Weak or absent
Stage III Absent |
|
Autonomic function Pupils Heart rate Bronchial and salivary secretions Gastrointestinal motility |
Generalized sympathetic Mydriasis Tachycardia Sparse Normal or decreased |
Generalized parasympathetic Miosis Bradycardia Profuse Increased diarrhea |
Both systems depressed Variable, often unequal, poor light reflex Variable Variable Variable |
|
Seizures |
None |
Common focal or multifocal |
Uncommon (excluding decerebration) |
|
Electroencephalographic findings |
Normal (awake) |
Early: low-voltage, continuous delta and theta Later: periodic pattern (awake); seizures focal; 1.0-1.5 Hz spike-and-wave |
Early: periodic pattern with isopotential phases Later: totally isopotential |
|
Duration
|
<24 hr |
2-14 days |
Hours to weeks |
ACOG/AAP Task Force on Neonatal Encephalopathy, 2014
Of neonatal seizures approximately 85% begin in the first 15 days of life with about 65% occurring between the second and fifth days of life.
|
0 to 3 Days Hypoxic-ischemic encephalopathy Hypoglycemia Hypocalcemia Intracranial hemorrhage Drug toxicity Drug withdrawal Cerebral malformation Cerebral infarction Pyridoxine dependency
3 to 7 Days Intracranial infection Cerebral malformation Hereditary metabolic disorders Hypocalcemia
>7 Days Cerebral malformation Hereditary metabolic disorders Viral meningoencephalitis |
Only rarely will newborns have well-organized symmetric generalized tonic-clonic seizures.
Neonatal seizures may be clinically expressed in various manners. These include:
Any alteration in the state of the infant that is "on-off" in character and is repetitive or paroxysmal may be a seizure. Clinically, nonepileptic activity can be differentiated by (1) sensitivity to stimulation with spatial and temporal summation, (2) suppression with restraint of movement, and (3) absence of autonomic changes.
Regardless of previous history, each child must be treated as having a potentially treatable disorder. The time of onset may be helpful to determine the etiology. Evaluation of an infant with seizures should include:
1. Laboratory
a. Blood glucose, calcium, magnesium and electrolytes including BUN.
b. Screening for systemic and intracranial infections. (CBC, Blood culture, CSF cultures, analysis of spinal fluid for protein, glucose, cell count and gram stai
c. Urine drug screen if the history suggests prenatal or perinatal drug use.
d. Urine metabolic screen and ammonia level in suspected metabolic disorders.
2. Examination:
a. Complete neurologic examination
b. Complete physical examination making note of any pigmented cutaneous lesions.
3. Neuroimaging and Examination
a. Head ultrasonography is best for IVH while a head CT scan is best for subarachnoid/subdural hemorrhage, intracranial calcifications or lesions.
b. Electroencephalographic study should be obtained whether the patient has been treated for seizures or not. An abnormal EEG can confirm the diagnosis of seizures and provide a means to monitor improvement with anticonvulsant treatment.
A quick determination of the blood glucose level by bedside testing can rule out hypoglycemia.
Treat while awaiting the results.
1. Drugs of choice to treat seizures, in order of administration:
a. Phenobarbital. Loading dose: 20 mg/kg IV over 15-20 minutes (alternative routes IM, PO).
b. Lorazepam. Loading dose: 0.1 mg/kg/dose every 8 hours.
c. Phenytoin
May administer up to a total dose of 40 mg/kg in 10 mg/kg/dose increments.
Maintenance dose: 3-5 mg/kg/day begun no earlier than 12 to 24 hours after the loading dose.
Serum level: 20-40 mcg/ml. Obtain the level on days 3-5 of maintenance.
Used for acute management and desired cessation of seizures refractory to conventional management
When Loading dose: 15-20 mg/kg IV over 20-30 minutes (IV only at a rate of 0.5 -1.0 mg/kg/min)
To be used in seizures refractory to phenobarbital.
Maintenance dose: 4-8 mg/kg/day at rate indicated with loading dose. Serum level: 6-15 mcg/ml. Obtain trough level 48 hours after loading dose.
When these approaches fail in treating refractory neonatal status epilepticus, administration of IV anesthetic agents such as thiopental or pentobarbital may be necessary.
2. Duration of Treatment
Causation of the seizures influences the length of therapy. Discontinuation of drugs may be considered before discharge if the infant shows no demonstrable brain lesions on cranial imaging, demonstrates age-appropriate neurologic examination, and has a normal interictal EEG background. However, most anticonvulsant therapy is continued for the first 3 months.
Apnea is defined as the absence of spontaneous breathing or airflow after 20 seconds, or less if associated with bradycardia or cyanosis. The incidence of apnea increases with decreasing gestational age, and is rare in babies over 35 weeks gestation at birth.
|
Birth Weight |
Incidence (%) |
|---|---|
|
Over 2500 gm |
0.2% |
|
Less than 2500 gm |
2% overall |
|
Less than 1800 gm (34 wks) |
25% |
|
Less than 1500 gm (32 wks) |
54% |
|
Less than 1000 gm (28 wks) |
Nearly 100% |
The classification of apnea is as follows:
Central apnea - respiratory efforts are absent
Obstructive apnea - respiratory efforts are present but airflow is impeded
Mixed apnea - elements of both central and obstructive apnea are present during the same episode.
Understanding the physiologic mechanisms of respiratory control in the neonate allows for a rational approach to the management of apnea in the neonate. These chemical and reflex controls of breathing are principally a maturational process.
1. Chemoreceptor function:
2. Respiratory reflexes:
3. Medullary/Respiratory center depression:
4. Cortical activity:
5. Obstruction:
1. Apnea of prematurity (idiopathic) - Most common form of apnea. Primarily affects premature infants with onset in the first 7-10 days of life but less common in the first 1-2 days. It has been suggested that carbon dioxide response is further decreased in preterm infants who exhibit apnea.
2. Apnea secondary to disease or special procedures
All infants less than 35 weeks at birth or of birth weight < 1800 grams should be monitored for apneic spells for at least 1 week. Electronic monitoring includes heart rate and respiration.
Prevention. To prevent apneic episodes, avoid events to the infant that may be precipitating factors. This would include: mechanical stimulation of the posterior pharynx, rapid changes in oxygen, depressant drugs, airway obstruction from improper positioning, cold stimulation to the face, and oral feedings in small or sick infants.
Evaluation. After the first apneic spell, the infant should be evaluated for a possible underlying cause and treatment initiated if evaluation yields an etiology.
1.Obtain the following:
2. Consider the following if examination and evaluation deem further evaluation is necessary:
Treatment. When apneic spells are repeated or prolonged (> 2-3 times/hr) or require frequent bag and mask ventilation, treatment should be initiated in order of increasing invasiveness and risk.
1. Mild Apnea. Defined as 3 to 4 episodes per day and easily responsive to stimulation. In this situation, close observation and monitoring should be continued with intermittent cutaneous stimulation as necessary. Decreasing the environmental temperature to the low end of the baby's appropriate neutral thermal environmental range should be considered.
2. Severe Apnea. Defined as 3-4 episodes per hour or if bag and mask ventilation is required to terminate an episode. In this situation, once all possible etiologies (sepsis, NEC, electrolyte imbalance) have been evaluated one may begin drug therapy.
a. Caffeine Citrate. Loading dose 20 mg/kg IV. Maintenance dose 5-7.5 mg/kg/1 day. Serum levels are not generally performed.
b. Use of nasal CPAP at 6-8 cm H2O may be initiated before using, or as an adjunct to caffeine.
Use of caffeine has been found to be associated with decreased risk for BPD; therefore, some experts prefer starting caffeine before the onset of apnea in high-risk babies (< 30-31 weeks).
3. Persistent Apnea.
Although most infants resolve their apneic spells by 36 weeks post-conceptional age, some persist until 37-40 weeks post-conceptional age. The infant may require reevaluation to detect an etiology for the apnea (i.e. neurologic problems, feeding problems such as GE reflux and anatomic causes of airway obstruction).
These infants may require restarting caffeine if spells reoccur after discontinuation. Consideration should be made for evaluation for home monitoring. Remember that monitoring may help reduce the risk of undetected apneic spells, but studies have shown NO decrease in the incidence of Sudden Infant Death Syndrome (SIDS) associated with use of home monitors. Infants with BPD on home oxygen and any infant discharged on caffeine should receive home monitoring. Consideration for monitoring may also be given to other high risk populations such as siblings of SIDS victims; these siblings are twice as likely as other babies to have SIDS. More importantly, the family is often very anxious.
Generally, infants should be apnea free for 10 days following discontinuation of caffeine before they are discharged home. If caffeine is not administered, a period of 7 days without apnea is the general rule. However, studies suggest a shorter "apnea countdown" for more mature infants.
Darnall, R.A., Kattwinkel, J., et al. Margin of safety for discharge after apnea in preterm infants. Pediatrics. 100(5):795-801,1997.
Hemorrhage into the periventricular subependymal germinal matrix (SEH) with subsequent extension into the ventricles (IVH) is a common cause of death and morbidity in the preterm neonate less than 32 weeks gestation. Most vulnerable is the extremely low birth weight infant of less than 26 weeks gestation. In infants weighing 500-750g, IVH occurs in about 45%.
The incidence of hemorrhage in infants weighing less than 1500 gm was reported to be approximately 40‑50% in the early 1980's and decreased to approximately 20% in the late 1980s. That number has remained relatively unchanged since that time. In 2010, the incidence of SEH/IVH at UTMB was ~20% in infants <1500 gm birth weight.
The primary lesion is bleeding from small vessels, principally capillaries, in the area of the subependymal germinal matrix. In most infants the hemorrhage originates in the matrix at the level of the head of the caudate nucleus and foramen of Monro. In extremely premature infants of less than 28 weeks, the lesion often is at the level of the body of the caudate.
In about 80% of cases, the hemorrhage ruptures through the ependyma and into the ventricular system. Blood spreads through the ventricles, then passes through the medial and lateral apertures of the fourth ventricle (the foramen of Lushka and Magendie) and collects in the basilar cisterns of the posterior fossa. Subsequent to the hemorrhage, an obliterating posterior fossa arachnoiditis may occur and cause obstruction to CSF flow with resultant post-hemorrhagic hydrocephalus.
In particularly severe hemorrhages, the periventricular hemorrhage appears to extend into the cerebral parenchyma and frequently leads to the development of porencephalic cysts. These parenchymal hemorrhages are not extensions of matrix bleeding, but areas of concurrent hemorrhagic infarction in the parenchyma that occur prior to or near the time of the IVH. This extensive infarction may well account for the severe neurological deficits observed on follow‑up.
The factors that must be considered in the pathogenesis of IVH are:
1. Intravascular Factors. This includes the anatomic and physiologic determinants of the distribution and regulation of cerebral blood flow and blood pressure within the germinal matrix area.
a. Distribution of Cerebral Blood Flow to the Periventricular Region. The vascular supply to the germinal matrix area is particularly prominent from 24 to 32 weeks gestation. A rich arterial supply to this region is derived principally from the anterior cerebral artery via Heubner's artery and from the middle cerebral artery via the deep lateral striate arteries. Before 32‑34 weeks gestation a disproportionately larger blood flow goes to the germinal matrix area than to the cerebral cortex. Therefore, any factors that cause increased cerebral blood flow will preferentially tend to overperfuse the periventricular area.
b. Regulation of Cerebral Blood Flow. Cerebral blood flow in the premature infant, particularly the infant who sustains some degree of asphyxia, is pressure‑passive. That is, cerebral blood flow varies directly with arterial pressure, and blood flow to the matrix area will be very sensitive to changes in arterial blood pressure. This pressure‑passive nature of cerebral blood flow is very important because elevations in blood pressure, blood flow, or both have been observed during a number of situations. Blood pressure increase in the first minutes after delivery, with motor activity (either spontaneous or associated with handling), and during seizures, colloid infusions, exchange transfusions, apnea, and asphyxia. Recent studies have shown the importance of fluctuating arterial blood pressure in the pathogenesis of IVH.
Asphyxia is an event that may particularly increase risk of hemorrhage for 3 reasons. First, hypercapnia with increased cerebral blood flow and perivascular acidosis; second, the diving reflex with preferentially increased cerebral blood flow; and third, arterial hypertension with loss of ability to autoregulate cerebral blood flow.
Certain therapeutic maneuvers may also cause marked increase in cerebral blood flow - rapid infusion of volume expanders, use of hyperosmolar solutions (i.e., glucose or bicarbonate), and use of pressor agents.
c. Cerebral Venous Pressure and Flow. Increased venous pressure may cause increase in pressure within the periventricular capillaries. This may occur with hypoxic cardiac failure or with positive pressure ventilation. Elevated venous pressure then may promote rupture of vessels and subsequent hemorrhage.
2. Germinal Matrix Vasculature. The capillary bed in the matrix area is relatively immature and vulnerable to rupture. The endothelial cells are dependent on oxidative metabolism and are readily injured by hypoxia.
3. Extravascular Factors. The germinal matrix area is a gelatinous region that provides poor support for the small vessels that course through it. It also contains an excessive amount of fibrinolytic activity which may explain the frequent extension of the hemorrhage.
The time of onset is most often at some time within the first 2 to 4 days of life, although the occurrence may be much later. In one large series the median age of onset was 38 hours. The occurrence of hemorrhage may be accompanied by two basic clinical syndromes.
The first is catastrophic collapse consisting of neurological deterioration that evolves in minutes or hours and consists of stupor or coma, respiratory abnormalities, seizures, unreactive pupils, flaccid quadraparesis, and absent extraocular movements. This is accompanied by falling hematocrit, bulging fontanelle, systemic hypotension, bradycardia, temperature instability, metabolic acidosis, glucose abnormalities.
The second syndrome is more subtle and follows a somewhat saltatory course. There is a change in level of alertness (either stupor or an irritable, hyperalert state). A clue to the occurrence of IVH may be a falling hematocrit or failure of the hematocrit to rise after transfusion.
At the present time, the most reliable and convenient method of diagnosis is by portable ultrasound scanning using a transducer applied to the skin over the anterior fontanelle. By manipulating the transducer over the fontanelle, various sections of brain can be examined in both coronal and sagittal planes.
CT or MRI scanning are also excellent means of diagnosing hemorrhage but much less convenient because the infant must be transported to the scanner.
CSF examination may be useful as well. Elevated RBC count, xanthochromia and elevated protein content suggest bleeding. Glucose usually becomes very low within 5‑15 days of the hemorrhage (hypoglycorrhacia).
No uniform grading system has been agreed upon. There are at least 3 grading systems in use. This had led to much confusion in terms of categorizing the severity of the hemorrhage in relation to immediate and long term outcome. The grading system we have found most useful is the one originally described by Papile and coworkers.
Grade I ‑ Subependymal germinal matrix hemorrhage only
Grade II ‑ Extension of hemorrhage into the ventricles without ventricular dilatation
Grade III ‑ Intraventricular hemorrhage with ventricular dilatation
Grade IV - Grade III plus parenchymal involvement. Sometimes, only parenchymal involvement is noted initiall .
The outcome of IVH is not uniformly grim. Over the short‑term, there is a distinct relationship between the severity of hemorrhage by CT or US and the prognosis. With mild hemorrhage, most babies survive, and hydrocephalus is relatively uncommon. Even with moderate bleeds, survival is the rule and risk of hydrocephalus is relatively low. Severe lesions carry the worst prognosis for death or hydrocephalus or long-term neurologic impairment.
Grade I and II hemorrhages appear to carry no increased risk for major handicap. Grade III and IV hemorrhages are associated with increased risk of major disability.
1. Prevention
2. Acute Management. Once hemorrhage occurs, initial therapy is primarily supportive. The major aspect is maintenance of cerebral perfusion by maintaining adequate arterial blood pressure. Other important aspects of care include:
a. Maintain adequate ventilation/oxygenation
b. Maintain blood pressure
c. Maintain glucose homeostasis
d. Control seizures
e. Correct acidosis
f. Maintain hematocrit
g. Maintain fluid and electrolyte balance
h. Decrease intracranial pressure
3. Post hemorrhagic hydrocephalus. In surviving infants, the incidence of hydrocephalus has been estimated at 15-22%
a. Prevention ‑ at present no prophylactic intervention for post-hemorrhagic hydrocephalus is known. In one study, serial lumbar punctures instituted at the time of diagnosis of hemorrhage were not found to be effective in prevention of subsequent hydrocephalus.
b. Natural history‑ in a multi-center study in the 1990s of 87 infants of <1500 grams who had severe IVH, 20 developed early rapidly progressive hydrocephalus or death; 47 developed no hydrocephalus; 20 developed ventriculomegaly with normal intracranial pressure. Of the 20 with progressive hydrocephalus, 9 exhibited arrest of the progression within 31 days and 11 of the 20 developed progressive hydrocephalus after a stabile period of up to 12‑84 days. Thus, observation is necessary for many weeks after the hemorrhage, and ventricular size should be serially assessed by ultrasound.
A more recent report from 1999-2008 found that 29% of infants with severe IVH developed symptomatic post hemorrhagic hydrocephalus requiring surgical intervention and 21% required shunt placement. Of note is that not all infants with ventriculomegaly progress to hydrocephalus (Limbrick et al, 2010).
(Source: Limbrick DD Jr, Mathur A, Johnston JM, Munro R, Sagar J, Inder T, et al. Neurosurgical treatment of progressive posthemorrhagic ventricular dilation in preterm infants: a 10-year single-institution study. J Neurosurg Pediatr. 2010; 6:224-230.)
c. Treatment options.
i. Serial ventricular punctures may be effective in management and are often temporary solutions until the CSF protein declines to acceptable levels. At that time, an Omaya reservoir or ventriculostomy is typically placed until the infant is large enough for a VP shunt (~2 kg). Serial lumbar punctures are seldom successful because communication must exist between the lateral ventricles and the lumbar subarachnoid space. It is also necessary that adequate volume of CSF be removed ‑ in the range of 10‑20 cc per LP.
ii. Drugs that decrease CSF production such as isosorbide, glycerol, or acetazolamide are occasionally used.
iii. Placement of a ventriculostomy or ventriculoperitoneal shunt carries a variety of complications, including infection and malfunction. An additional problem with VP shunts in small premies is ulceration of the scalp overlying the shunt.
4. Screening Ultrasound Examinations
A screening cerebral ultrasound examination should be done on all preterm infants of <1500 gm or of 31 weeks gestation or less who are admitted to the ISCU. The initial examination should be done at 7 days of age, or anytime (earlier or later), if hemorrhage or hydrocephalus is suspected. If periventricular or intraventricular hemorrhage is present, sonography should be repeated in 7‑10 days and at regular intervals thereafter if evidence of ventricular dilatation is present.
Older prematures (over 31 weeks) and term babies should have ultrasonography done as indicated based on their individual clinical histories, problems, and course. Indications in term babies include: abnormally increased or increasing head circumference, clinical signs of major CNS malformation, infection ‑ congenital (calcifications) or ventriculitis, suspected A‑V malformation, and severe trauma.
CT scan should be considered for situations where ultrasound is normal and a peripheral lesion (subdural hemorrhage, etc.) is suspected. Other indications include asphyxia, seizures, tumor, situations where contrast is required, and situations where ultrasound is normal and neurological signs are present.
Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics. 2005; 115 :997-1003.
Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500gm. J Pediatr. 1978; 92: 529-534.
Philip AG, Allan WC, Tito AM, Wheeler LR. Intraventricular hemorrhage in preterm infants: declining incidence in the 1980s. Pediatrics. 1989; 84 :797-801.
Periventricular Leukomalacia (PVL) is an ischemic lesion leading to areas of coagulation necrosis in the periventricular white matter at the external angles of the lateral ventricles in the watershed areas of the deep penetrating arteries of the middle cerebral artery.
The incidence of PVL is reported as approximately 25-75% of very low birth weight infants who die. The incidence among surviving infants is unknown; however, ultrasound findings estimate the incidence at 5-15%. Ultrasonography is typically used to detect cystic PVL, but MRI is more sensitive in detecting noncystic PVL. In recent correlative study of sonographic and neuropathologic studies, only 30-40% of PVL lesions were detected by cranial ultrasound prior to death.
Infants at risk are not just preterm infants but any infant with a maternal history of possible ischemic or hypoxic associated disease (i.e. pregnancy induced hypertension, chronic hypertension, diabetes mellitus, placental insufficiency, severe renal disease). The incidence of PVL is increased with maternal chorioamnionitis, hypocarbia, and hypotension in premature neonates.
PVL may coexist with IVH but likely has a separate pathologic process. Generally, PVL is a focal area of ischemia with coagulation necrosis followed by macrophage and astrocytic proliferation. On occasion secondary hemorrhage occurs. Eventually, there is thinning of the white matter with secondary dilation of the lateral ventricles. This may be followed by cystic or cavitational changes in these areas that can become evident by ultrasound or MRI
Age of Onset. Occurrence may be intrauterine and present at birth. Most commonly, PVL is found at 7-10 days upon routine head ultrasound.
Radiographic Studies. Ultrasonography is most commonly used for diagnosis and has excellent sensitivity at detecting cystic changes >0.5 cm in diameter, but it is not sensitive in detecting decreased myelination. MRI is performed routinely at UTMB to detect PVL in ELBW infants at a corrected gestational age of 40 weeks. MRI has the advantage of detecting noncystic diffuse white matter abnormalities with higher sensitivity.
Neurologic Findings. Spastic paresis of the legs is the most common clinical sequelae. The involved area generally includes white matter through which long descending motor tracts descend from the motor cortex with the leg fibers being closest to the ventricles. With lateral extension of the lesion there may be arm involvement resulting in spastic quadriplegia. Infants with cystic degeneration can develop hydrocephalus ex vacuo or ventricular dilation associated with diffuse cerebral atrophy. In infants showing moderate to severe white matter abnormalities on MRI at corrected age of 40 weeks, there was an increase in cognitive delay, motor delay, neurosensory impairment and cerebral palsy.
Weekly head circumference to monitor for normal head growth.
After initial diagnosis a head ultrasound every 1-3 weeks, depending on the clinical specifics, may be obtained to monitor for hydrocephalus. If the PVL is associated with an IVH event, hydrocephalus may develop as a result of post hemorrhagic hydrocephalus and hydrocephalus ex vacuo.
Good neurodevelopmental follow-up. Early referral (at the time of discharge) for childhood intervention to minimize severity of limb spasticity may be necessary.
Subarachnoid hemorrhage. Most frequent bleed, between pia matter and arachnoid membrane. This type of bleed is more frequent in preterm babies and is often asymptomatic. In full term babies, it may present as refractory seizures with onset typically within the second day ("well baby" with seizures). Catastrophic deterioration and neuropathologic complications are rare unless associated with asphyxia. Best diagnostic tool: CT scan.
Subdural hemorrhage. The least common, between dura matter and subarachnoid space. This type of hemorrhage is associated with traumatic delivery in full term infant and coagulation/platelet disorder. The symptoms depend on severity and location of bleeding. The prognosis is best for cerebral convexities and worst for posterior fossa bleeds. If signs of brainstem compression suggest infratentorial hematoma, initial neuroimaging should be a CT scna. Al LP should NOT be performed as it may provoke herniation. An MRI may be needed for posterior fossa bleed.
Intracerebellar hemorrhage. Uncommon, more in preterm, found 5-10% of autopsy reports in NICU patients. In term babies, it is associated with traumatic events, difficult breech or forceps. This manifests within 24 hours in term infants, but may be delayed up to 3 weeks in preterm and may progress rapidly. Signs of brainstem compression (apnea, bradycardia, facial paresis, eye deviation) may be present. The outcome is poor in premies; in term babies, half develop hydrocephalus and/or long term neurologic deficits.
section author: Jan Hunter, OTR
At UTMB, we are fortunate to have a team of occupational and physical therapists who are expert in the care of preterm infants. They work with parents, nurses and medical providers to support feeding and developmentally appropriate activities for these fragile babies.
Science, technology, professional dedication and advanced skills have made miracles nearly routine in modern NICU's. When mortality was the primary outcome indicator, any surviving baby was considered a success. Morbidity became another outcome indicator as continually expanding limits of viability placed increasing focus and concern on the functional and developmental outcomes of NICU graduates.
The preterm infant's immature CNS is generally competent for protected intrauterine life, but not sufficiently developed to adapt to the overwhelming stimuli and demands of early birth. This "mismatch" between a neonate's abilities and the high-tech NICU stresses the sensitive infant's vulnerable and disorganized CNS. Excessive sensory stimulation may cause insults to the still-developing brain (from repeated hypoxic episodes related to stress, from reinforcement of atypical neuronal pathways, etc.), and can create maladaptive behaviors that contribute to later poor developmental outcome even in the absence of overt CNS pathology. Neonates with extreme prematurity, critical illness, and major anomalies often have extended hospitalizations with prolonged exposure to potential environmental and caregiving hazards in the NICU.
Developmental support is an evidence-based approach to NICU caregiving intended to improve neurodevelopmental outcome in infants who lack the maturity, health or competence necessary to easily cope with life outside the womb. Incorporating continually evolving scientific knowledge from multiple disciplines, "developmentally supportive care" is an inclusive term applied to animate and inanimate environmental modifications, alterations in caregiving practices, and efforts to increase family involvement.
A prime example of improving developmental outcome that blends medical and developmental care priorities is neuroprotection of the developing brain. Technologies such as continuous EEG and near-infrared spectrospcopy (NIRS) have been advocated to provide real-time data about the impact of environmental factors and caregiving techniques on brain functions such as iatrogenic excessive fluctutations in cerebral perfusion, or duration and quality of sleep for infants in the NICU. The importance of sleep and the relationship to developmental support is elaborated below.
At 23 weeks, the human brain is smooth with undeveloped synaptic connections. These connections will now be formed within the context of the NICU experience, rather than in an orderly sequential process in the womb. The primary ongoing event in brain and sensory-system development during the last trimester is synaptogenesis, occurring at the rate of 1.8 million neural connections formed every second during the last trimester. Synaptogenesis at this stage is endogenous (occurs spontaneously within the brain in the absence of external stimulation), is dampened by external stimuli and sedation, and forms the early brain architecture that is later refined by exogenous (external) stimuli. Endogenous synaptogenesis produces brain complexity and plasticity, only occurs during sleep, and occurs only during REM sleep after 28 weeks " gestation (Graven, 2006; Liu, et al, 2007).
Premature infants during childhood are known to have smaller brains than their full-term counterparts and increased risks for difficulties with sensory processing, learning, abstract thinking, behavior, coping, adaptability, attention, and plasticity. Brain "wiring" can be disturbed even in the absence of structural brain pathology (Bhutta & Anand, 2002; Graven, 2006). Undisturbed sleep is absolutely essential for normal development of the infant brain and sensory systems during the last trimester, but sleep protection remains an elusive goal in the NICU (Laudert, et al, 2007).
The Vermont Oxford Network is a non-profit voluntary collaborative dedicated to medical care for newborn infants and their families. Five member hospitals of the Neonatal Intensive Care Quality Collaborative 2005 (NIC/Q 2005), formed a physical environment exploratory group (nicknamed "Senses and Sensibilities") with the goal of identifying and implementing care practices that may potentially support newborn brain development (Liu et al. 2007; Laudert, et al, 2007). These articles extensively review relevant literature, and provide a foundational understanding of brain development. Supportive clinical evidence was organized by sensory systems (tactile, chemosensory, auditory and visual), and by the need to develop strategies to preserve newborn sleep.
Sixteen potentially better practices (PBPs) to support neurodevelopment in the NICU were identified. Recognizing the cumulative benefit of addressing multiple rather than solitary needs, these potentially better practices are divided into two clusters. Implementation of the first cluster of interventions is recommended for all NICU admissions, beginning at the youngest age of viability. The second intervention cluster is recommended for all NICU admissions beginning by 31-32 weeks. Of special interest is that 11 of the 16 recommended PBPs have a direct benefit on sleep. Protecting sleep (via therapeutic positioning, inclusion of nonpharmacologic pain management, timing of non-emergent care, noise and light reduction, etc) is a known medical and developmental caregiving priority that is not well implemented in the NICU (Laudert et al, 2007; Hunter, 2010). A summary table of these PBP's (see next page) provides a synopsis of recommended care practices to support neurodevelopment in the NICU; the lead article from VON NIC-Q 2005 is also attached.
Potentially Better Practices (PBPs) to Support Neurodevelopment in the NICU
Adapted from Liu et al. 2007 and Laudert et al. 2007
| Abbreviations:
A = auditory development C = chemosensory development S = preservation of sleep T = somatesthetic/kinesthetic/proprioceptive development V = visual development Note: A potentially better practice may impact multiple developing sensory systems |
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|
Cluster I: Full implementation recommended for all NICU admissions beginning at 23 weeks of age |
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|
System |
Potentially Better Practice |
Benefits |
|
T-1 |
Containment and body flexion |
T, S |
|
T-2 |
Positive oral stimulation; non-nutritive suck |
T |
|
T-3a |
Gentle touch, hand grasping/facial stimulation |
T |
|
T-4 |
Decrease painful/negative stimulation |
T.S |
|
C-1 |
Exposure to mother's scent |
C,S |
|
C-2 |
Minimize exposure to noxious odors |
C,S |
|
A-1 |
Noise abatement |
A,S |
|
V-1 |
Minimize ambient light exposure |
V,S |
|
V-2 |
Avoid direct light exposure |
V,S |
|
S-1 |
Develop strategies that preserve normal infant sleep cycles. Support family involvement in care practices that promote sleep. Non-emergent care provided at appropriate times to minimize the disruption of sleep (with diurnal implementation, as possible, after 30 weeks gestation) |
S |
|
S-2 |
Minimize exposure to narcotics and other medications that may disrupt or disturb sleep cycles |
S |
|
Cluster II: Full implementation recommended for all NICU admissions beginning by 31 - 32 weeks |
||
|
T-3b |
Infant massage/diurnal implementation |
T |
|
T-3c |
Skin-to-skin care |
T, C, S |
|
A-2 |
Exposure to audible maternal voice/diurnal implementation |
A |
|
V-3 |
Cycled lighting: minimum of 1-2 hours |
A, V, S |
|
V-4 |
Provide more complex visual stimulation: after 37 weeks |
V |
Bhutta, A. T., & Anand K. J. (2002). Vulnerability of the developing brain: Neuronal mechanisms. Clinics in Perinatology, 29(3), 357-372.
Graven, S. (2006). Sleep and brain development. Clinics in Perinatology. 33(3), 693-706.
Hunter, J. (2010). Therapeutic Positioning: Neuromotor, Physiologic, and Sleep Implications. In C. Kenner & J. M. McGrath (Eds), Developmental Care of Newborns & Infants: A Guide for Health Professionals, 2nd ed. National Association of Neonatal Nurses (NANN). (note: UTMB Occupational Therapist)
Laudert, S., Liu, W. F., Blackington, S., Perkins, B., Martin, S. MacMillan-York, E., Graven, S., & Handyside, J. (on behalf of the NIC/Q 2005 Physical Environment Exploratory Group). (2007). Implementing potentially better practices to support the neurodevelopment of infants in the NICU. Journal of Perinatology, 27, S75-S93.
Liu, W. F., Laudert, S., Perkins, B., MacMillan-York, E., Martin, S., & Graven, S. (for the NIC/Q 2005 Physical Environment Exploratory Group). (2007). The development of potentially better practices to support the neurodevelopment of infants in the NICU. Journal of Perinatology, 27, S48-S74. (note: Extensive references are listed in this article; not duplicated here)