lapkas anak

CHAPTER I

INTRODUCTION

1.1 Background

Neonatal sepsis may be categorized as early-onset or late-onset. Of newborns with

early-onset sepsis, 85% present within 24 hours, 5% present at 24-48 hours, and a smaller

percentage present within 48-72 hours. Onset is most rapid in premature neonates.

Early-onset sepsis is associated with acquisition of microorganisms from the

mother. Transplacental infection or an ascending infection from the cervix may be caused by

organisms that colonize the mother’s genitourinary tract. The neonate acquires the

microorganisms as it passes through the colonized birth canal at delivery. The

microorganisms most commonly associated with early-onset infection include Group B

Streptococcus (GBS), escherichia coli, coagulase-negative Staphylococcus, Haemophilus

influenzae, and Listeria monocytogenes.1

Late-onset sepsis occurs at 4-90 days of life and is acquired from the caregiving

environment. Organisms that have been implicated in causing late-onset sepsis include :

Coagulase-negative Staphylococcus, Staphylococcus aureus, E coli, Klebsiella,

Pseudomonas, Enterobacter, Candida, GBS, Serratia, Acinetobacter, and Anaerobes.2

Pneumonia is more common in early-onset sepsis, whereas meningitis and

bacteremia are more common in late-onset sepsis. Premature and ill infants are more

susceptible to sepsis and subtle nonspecific initial presentations; considerable vigilance is

therefore required in these patients so that sepsis can be effectively identified and treated.

When neonatal sepsis is suspected, treatment should be initiated immediately because of the

neonate’s relative immunosuppression. Begin antibiotics as soon as diagnostic tests are

performed.

On the other hand, seizures are the most distinctive manifestation of neurologic

dysfunction in the newborn infant. Moreover, neonatal seizures often herald potentially

devastating forms of brain injury. Recent advances in diagnostic technology have provided

important insights into neonatal seizures. Techniques such as bedside video-

electroencephalogram (EEG) monitoring and magnetic resonance imaging (MRI) have

1

challenged earlier beliefs and raised fundamental questions regarding the diagnosis, etiology,

and management of seizures in the newborn infant. It is well known that most seizures in the

newborn are symptomatic of a specific etiology; with these diagnostic advances, an etiology

is increasingly identifiable. In addition, these advances have further highlighted the essential

differences between seizures in newborn infants and older patients, including their response

to conventional anticonvulsant agents. Such age-related differences in the manifestations and

treatment response are due in large part to the immature developmental state of the newborn

brain and the different etiologies involved.3

1.2. Objective

The aim of this study is to explore more about the theoritical aspects on neonatal

sepsis and neonatal seizure, also to integrate the theory and application of neonatal sepsis and

neonatal seizure cases in daily life.

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CHAPTER II

LITERATURE REVIEW

2.1. Neonatal Sepsis

2.1.1. Definition

Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection

with or without accompanying bacteremia in the first month of life. It encompasses various

systemic infections of the newborn such as septicemia, meningitis, pneumonia, arthritis,

osteomyelitis, and urinary tract infections. Superficial infections like conjunctivitis and oral

thrush are not usually included under neonatal sepsis.4

2.1.2. Epidemiology

Sepsis is the commonest cause of neonatal mortality; it is responsible for about 30-50%

of the total neonatal deaths in developing countries.4 It is estimated that up to 20% of neonates

develop sepsis and a pproximately 1% die of sepsis related causes.5 Sepsis related mortality is

largely preventable with rational antimicrobial therapy and aggressive supportive care.

The incidence of sepsis in developing countries is high, from 1.8 to 18 per 1,000 live

births, with a mortality rate of 12-68%, while in developed countries, the incidence of sepsis

ranges from 3 per 1,000 live births, with a mortality rate of 10.3%. In Indonesia, the number has

not been recorded. Data obtained from Cipto Mangunkusumo Hospital from January to

September 2005, the incidence of neonatal sepsis was 13.68% with a mortality rate of 14.18%.6

2.1.3. Classification

Neonatal sepsis can be classified into two major categories depending up on the onset of

symptoms.7

Early onset sepsis (EOS): It presents within the first 72 hours of life. In severe cases, the

neonate may be symptomatic at birth. Infants with EOS usually present with respiratory distress

and pneumonia. The source of infection is generally the maternal genital tract. Some maternal /

perinatal conditions have been associated with an increased risk of EOS. Knowledge about these

3

potential risk factors would help in early diagnosis of sepsis. Based on the studies from India, the

following risk factors seem to be associated with an increased risk of early onset sepsis:7,8

1. Low birth weight (<2500 grams) or prematurity

2. Febrile illness in the mother with evidence of bacterial infection within 2 weeks prior

to delivery.

3. Foul smelling and/or meconium stained liquor.

4. Rupture of membranes >24 hours.

5. Single unclean or > 3 sterile vaginal examination(s) during labor

6. Prolonged labor (sum of 1st and 2nd stage of labor > 24 hours)

7. Perinatal asphyxia (Apgar score < 4 at 1 minute)

Presence of foul smelling liquor or three of the above mentioned risk factors warrant

initiation of antibiotic treatment. Infants with two risk factors should be investigated and then

treated accordingly.

Late onset sepsis (LOS): It usually presents after 72 hours of age. The source of infection

in LOS is either nosocomial (hospital-acquired) or community-acquired and neonates usually

present with septicemia, pneumonia or meningitis.9,10 Various factors that predispose to an

increased risk of nosocomial sepsis include low birth weight, prematurity, admission in intensive

care unit, mechanical ventilation, invasive procedures, administration of parenteral fluids, and

use of stock solutions.

Factors that might increase the risk of community-acquired LOS include poor hygiene,

poor cord care, bottle-feeding, and prelacteal feeds. In contrast, breastfeeding helps in prevention

of infections.

2.1.4. Clinical features

1. Non-specific features: The earliest signs of sepsis are often subtle and nonspecific;

indeed, a high index of suspicion is needed for early diagnosis. Neonates with sepsis

may present with one or more of the following symptoms and signs:

a) Hypothermia or fever (former is more common in preterm low birth weight

infants)

b) Lethargy, poor cry, refusal to suck 4

c) Poor perfusion, prolonged capillary refill time

d) Hypotonia, absent neonatal reflexes

e) Brady/tachycardia

f) Respiratory distress, apnea and gasping respiration

g) Hypo/hyperglycemia

h) Metabolic acidosis.

2. Specific features related to various systems:

a) Central nervous system (CNS): Bulging anterior fontanelle, vacant stare, high-

pitched cry, excess irritability, stupor/coma, seizures, neck retraction. Presence of

these features should raise a clinical suspicion of meningitis.

b) Cardiac: Hypotension, poor perfusion, shock.

c) Gastrointestinal: Feed intolerance, vomiting, diarrhea, abdominal distension,

paralytic ileus, necrotizing enterocolitis (NEC).

d) Hepatic: Hepatomegaly, direct hyperbilirubinemia (especially with urinary tract

infections).

e) Renal: Acute renal failure.

f) Hematological: Bleeding, petechiae, purpura.

g) Skin changes: Multiple pustules, abscess, sclerema, mottling, umbilical redness

and discharge.

2.1.5. Investigations

Since treatment should be initiated in a neonate suspected to have sepsis without any

delay, only minimal and rapid investigations should be undertaken.11

1. Blood culture

It is the gold standard for diagnosis of septicemia and should be performed in all

cases of suspected sepsis prior to starting antibiotics. A positive blood culture with

sensitivity of the isolated organism is the best guide to antimicrobial therapy.

Therefore it is very important to follow the proper procedure for collecting a blood

culture. The resident doctor/staff should wear sterile gloves prior to the procedure and

prepare a patch of skin approximate 5 cm in diameter over the proposed veni puncture

site. This area should be cleaned thoroughly with alcohol, followed by povidone 5

iodine, and followed again by alcohol. Povidone iodine should be applied in

concentric circles moving outward from the centre. The skin should be allowed to dry

for at least 1 minute before the sample is collected. One-mL sample of blood should

be adequate for a blood culture bottle containing 5-10 mL of culture media. Since

samples collected from indwelling lines and catheters are likely to be contaminated,

cultures should be collected only from a fresh veni puncture site.

All blood cultures should be observed for at least 72 hours before they are reported as

sterile. It is now possible to detect bacterial growth within 12-24 hours by using

improved bacteriological techniques such as BACTEC and BACT/ALERT blood

culture systems. These advanced techniques can detect bacteria at a concentration of

1-2 colony-forming unit (cfu) per mL.

2. Septic screen:12,13

All neonates suspected to have sepsis should have a septic screen to collaborate the

diagnosis. However, the decision to start antibiotics need not be conditional to the

sepsis screen result, if there is a strong clinical suspicion of sepsis. The various

components of the septic screen include total leukocyte count, absolute neutrophil

count, immature to total neutrophil ratio, micro-erythrocyte sedimentation rate and C

reactive protein. The absolute neutrophil count varies considerably in the immediate

neonatal period and normal reference ranges are available from Manroe’s charts.14

For very low birth weight infants, the reference ranges are available from Mouzinho’s

charts.12 The ratio of immature to total neutrophils (I/T ratio) is ≤0.16 at birth and

declines to a peak value of 0.12 after 72 hours of age. Presence of two abnormal

parameters in a screen is associated with a sensitivity of 93-100%, specificity of 83%,

positive and negative predictive values of 27% and 100% respectively in detecting

sepsis.

Hence, if two (or more) parameters are abnormal, it should be considered as a

positive screen and the neonate should be started on antibiotics. If the screen is

negative but clinical suspicion persists, it should be repeated within 12 hours. If the

screen is still negative, sepsis can be excluded with reasonable certainty. For early 6

onset sepsis, documentation of polymorphs in the neonatal gastric aspirate at birth

could serve as a marker of chorioamnionitis and it may be taken as one parameter of

sepsis screen.

3. Lumbar puncture (LP)

The incidence of meningitis in neonatal sepsis has varied from 0.3-3% in various

studies.14,15 The clinical features of septicemia and meningitis often overlap; it is quite

possible to have meningitis along with septicemia without any specific

symptomatology. This justifies the extra precaution of performing LP in neonates

suspected to have sepsis. In EOS, lumbar puncture is indicated in the presence of a

positive blood culture or if the clinical picture is consistent with septicemia. It is not

indicated if antibiotics have been started solely due to the presence of risk factors.

In situations of late onset sepsis, LP should be done in all infants prior to starting

antibiotics. Lumbar puncture could be postponed in a critically sick neonate. It should

be performed once the clinical condition stabilizes. The cerebrospinal fluid

characteristics are unique in the newborn period.16

4. Radiology:

Chest x-ray should be considered in the presence of respiratory distress or apnea. An

abdominal x-ray is indicated in the presence of abdominal signs suggestive of

necrotizing enterocolitis (NEC). Neurosonogram and computed tomography (CT

scan) should be performed in all patients diagnosed to have meningitis.

5. Urine culture:

In early onset sepsis, urine cultures have a low yield and are not indicated. Urine

cultures obtained by suprapubic puncture or bladder catheterization have been

recommended in all cases of LOS. Since the procedures are painful and the yield is

often poor, we don’t recommend a routine urine culture in neonates with sepsis.

However, neonates at risk for fungal sepsis and very low birth weight infants with

poor weight gain should have a urine examination done to exclude urinary tract

infection (UTI).

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UTI may be diagnosed in the presence of one of the following: >10 WBC/mm3 in a

10 mL centrifuged sample, >104 organisms /mL in urine obtained by catheterization

and any organism in urine obtained by suprapubic aspiration.

2.1.6. Management

1. Supportive: Adequate and proper supportive care is crucial in a sick neonate with

sepsis. The infant should be nursed in a thermo-neutral environment taking care to

avoid hypo/hyperthermia. Oxygen saturation should be maintained in the normal

range; mechanical ventilation may have to be initiated if necessary. If the infant is

hemodynamically unstable, intravenous fluids should be administered and the infant

is to be monitored for hypo/hyperglycemia. Volume expansion with

crystalloids/colloids and judicious use of inotropes are essential to maintain normal

tissue perfusion and blood pressure. Packed red cells and fresh frozen plasma might

have to be used in the event of anemia or bleeding diathesis.

2. Antimicrobial therapy: There cannot be a single recommendation for the antibiotic

regimen of neonatal sepsis for all settings. The choice of antibiotics depends on the

prevailing flora in the given unit and their antimicrobial sensitivity. This protocol

does not aim to provide a universal recommendation for all settings but lays down

broad guidelines for the providers to make a rational choice of antibiotic combination.

Decision to start antibiotics is based upon clinical features and/ or a positive septic

screen. However duration of antibiotic therapy is dependent upon the presence of a

positive blood culture and meningitis.

The indications for starting antibiotics in neonates at risk of EOS include any one of

the following:

a. presence of >3 risk factors for early onset sepsis

b. presence of foul smelling liquor

c. presence of ≥2 antenatal risk factor(s) and a positive septic screen

d. strong clinical suspicion of sepsis.

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The indications for starting antibiotics in LOS include positive septic screen and/or

strong clinical suspicion of sepsis.

We do not use prophylactic antibiotics in the following circumstances: infants on IV

fluids/TPN, meconium aspiration syndrome, and after exchange transfusion. An

exchange transfusion conducted under strict asepsis does not increase the risk of

sepsis and hence does not merit antibiotics.

However a messy exchange transfusion could be treated with prophylactic antibiotics.

Choice of antibiotics: Empirical antibiotic therapy should be unit-specific and

determined by the prevalent spectrum of etiological agents and their antibiotic

sensitivity pattern. Antibiotics once started should be modified according to the

sensitivity reports.

The empirical choice of antibiotics is dependent upon the probable source of

infection. For infections that are likely to be community-acquired where resistant

strains are unlikely, a combination of ampicillin or penicillin with gentamicin may be

a good choice as a first line therapy. For infections that are acquired during hospital

stay, resistant pathogens are likely and a combination of ampicillin or cloxacillin with

gentamicin or amikacin may be instituted. In nurseries where this combination is

ineffective due to the presence of multiple resistant strains of klebsiella and other

gram-negative bacilli, a combination of a third generation cephalosporin (cefotaxime

or ceftazidime) with amikacin may be appropriate. Third generation cephalosporins

have very good CSF penetration and are traditionally thought to have excellent

antimicrobial activity against gram negative organisms. Hence they were considered

to be a good choice for the treatment of nosocomial infections and meningitis.

However, recent reports suggest that at least 60-70% of the gram negative organisms

are resistant to them.17-19

Moreover, routine use of these antibiotics might increase the risk of infections with

ESBL (extended spectrum beta-lactamase) positive organisms. Therefore it is 9

preferable to use antibiotics such as piperacillin-tazobactam or

methicillin/vancomycin in units with high incidence of resistant strains. A

combination of piperacillin-tazobactam with amikacin should be considered if

pseudomonas sepsis is suspected. Penicillin resistant staphylococcus aureus should be

treated with cloxacillin, nafcillin or methicillin. Addition of an aminoglycoside is

useful in therapy against staphylococcus. Methicillin resistant staphylococcus aureus

(MRSA) should be treated with a combination of ciprofloxacin or vancomycin with

amikacin. Ciprofloxacin has excellent activity against gram negative organisms also;

however, it does not have good CSF penetration. It may be used for the treatment of

resistant gram-negative bacteremia after excluding meningitis. For sepsis due to

enterococcus, a combination of ampicillin and gentamicin is a good choice for initial

therapy. Vancomycin should be used for the treatment of enterococcus resistant to the

first line of therapy. 20,21

Newer antibiotics like aztreonam, meropenem and imipenem are also now available

in the market. Aztreonam has excellent activity against gram-negative organisms

while meropenem is effective against most bacterial pathogens except methicillin

resistant staphylococcus aureus (MRSA) and enterococcus. Imipenem is generally

avoided in neonates because of the reported increase in the incidence of seizures.

Empirical use of these antibiotics should be avoided; they should be reserved for

situations where sensitivity of the isolated organism warrants.22

2.2. Neonatal Seizure

2.2.1. Definition

A seizure is defined as paroxysmal disturbances in neurological function of neurons

which manifested clinically as alteration in motor, behavioral and/or autonomic functions. No

period carry the danger of seizures to the individual person like the first four weeks of life

because of immaturity of brain cell which render it more vulnerable to injury and because of

wide range of problem that might cause seizures operate in this period.

Neonatal seizures tend to be brief, because immature neurons are unable to sustain

repetitive activity for long period of time and to be focal or multifocal. It requires immediate

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evaluation because of the variable conditions that might insult developing and vulnerable

neurons of neonate, some of which might endanger the life of neonate. Sometime seizures might

be the first and probably the only manifestations of underlying significant dysfunction of CNS of

newborn infant. Furthermore, these seizures are sometime difficult to be diagnosed clinically

resulting in delaying treatment and worsening short and long term prognosis.23

2.2.2. Epidemiology

The incidence of neonatal seizure occurs higher in preterm infants (3.9%) especially with

a gestational age <30 weeks. In the United States, the incidence of neonatal seizure has not been

clearly detected, estimated 80-120 per 100,000 newborns per year. The comparison between 1-

5:1000 birth rate. According to the 2002-2003, IDHS neonatal mortality rate in Indonesia was

57% of the infant mortality rate (IMR), while neonatal deaths caused by seizures about 10%.24

2.2.3. Clinical Etiology 3

Using such an orderly and rational approach, most neonatal seizure etiologies should be

identifiable. A list of these seizure etiologies is given in Table 2.1.

Etiology Incidence (%)1.Cerebral hypoxia-ischemia —

a. Global (e.g., perinatal asphyxia) 40b. Focal infarction (arterial or venous) 15

2.Intracranial hemorrhage 153.CNS infection 54.Metabolic disease —

a. Transient 5b. Inborn errors of metabolism 1

5.Cerebral dysgenesis 56.Neonatal epileptic syndromes 17.Neonatal abstinence syndrome 18.Unknown 10

TABLE 2.1 Etiologies of Neonatal Seizures.3

1. Hypoxic-ischemic encephalopathy

The leading cause of neonatal seizures is cerebral hypoxia-ischemia, which may

occur in the antenatal, intrapartum, or neonatal periods. Perinatal asphyxia is

implicated in 25% to 40% of neonatal seizures. Postasphyxial seizures occur in

infants with moderate-to-severe grades of encephalopathy, that is, with obtundation,

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stupor, or coma. In addition, these infants tend to have muscle hypotonia, altered

deep tendon reflexes and, in severe cases, brainstem abnormalities. Intrapartum

asphyxia should never be a diagnosis of exclusion, and should satisfy certain criteria,

including evidence of significant fetal distress, immediate postnatal “depression” at

birth, and subsequent altered mental status. Significant fetal distress manifests with

evidence of certain specific abnormal fetal heart rate patterns (e.g., loss of variability

plus late decelerations; sustained bradycardia) and/or evidence of “significant” fetal

metabolic acidosis. Although the absolute criteria for significant metabolic acidosis

remain controversial, most agree that an umbilical artery pH <7.0 with a base deficit

of >12 mEq reflects fetal asphyxia capable of causing neonatal encephalopathy and

seizures. Commonly accepted criteria for immediate neonatal depression include an

Apgar score of <5 at 5 minutes of life. In cases where there is a prolonged latency

between a fetal asphyxial insult (e.g., an antepartum or early intrapartum insult) and

delivery, the criteria in the preceding text may not be satisfied. In these cases,

specialized MRI studies have demonstrated characteristic features of hypoxic-

ischemic brain injury despite the absence of significant acidosis or immediate

neonatal depression.

2. Focal ischemic injury

a. Neonatal arterial stroke occurs in around 1 in 4,000 live births. In most cases, the

etiology of neonatal strokes remains unknown. Seizures are the most common

presentation of stroke in the newborn period, and stroke is the second most

common cause of neonatal seizures, accounting for 15% to 20% of cases. The

onset of clinical seizures is variable and may be missed, because most strokes

occur in otherwise well term infants, without previously known risk factors.

These infants usually appear normal immediately before and after seizures. In

fact, in the absence of identified seizures, the diagnosis of neonatal stroke may be

delayed until the onset of infant hand use around 4 to 5 months when motor

asymmetries become evident. These seizures are typically unifocal, with minimal

spread. Because neonatal arterial stroke most commonly involves the left middle

cerebral artery (MCA), right-sided clonic seizures are the most common clinical

presentation. The clonic activity is generally slower than that in older patients. 12

Poststroke seizures usually have a very good association between clinical and

electrographic manifestations.

b. Cerebral vein thrombosis usually occurs in the large dural sinuses, particularly the

posterior aspects of the superior sagittal sinus. Although the presentation of

cerebral vein thrombosis may be subtle, with lethargy often the only feature,

approximately 60% of cases develop neonatal seizures. Unlike the relatively

normal mental status of infants with arterial stroke and seizures, infants with

cerebral vein thrombosis and seizures are more encephalopathic, with depressed

mental status before and between seizures.

3. Intracranial hemorrhage.

Intracranial hemorrhage is implicated in approximately 10% of neonatal seizures.

The location of hemorrhage and the clinical features of the seizures varies with

gestational age. With term infants, posthemorrhagic seizures are most commonly

associated with primary subarachnoid hemorrhage and less often with subdural

hemorrhage (SDH). Primary subarachnoid hemorrhage occurs more frequently after

difficult prolonged or traumatic labor. However, primary subarachnoid hemorrhage

may occur after apparently uncomplicated labor (i.e., so-called parturitional

hemorrhage). Such primary parturitional subarachnoid hemorrhage results in focal or

multifocal seizures, usually starting on the second day of life, in infants who appear

relatively well between seizures. These seizures often have good clinical and

electrical association. Infants with seizures associated with primary subarachnoid

hemorrhage have a good long-term outcome in 90% of cases.

About half of all subdural hemorrhages (SDH) diagnosed in the newborn are

complicated by seizures, usually presenting in the first days of life. Neonatal SDH

usually occurs in large babies, breech delivery, or difficult instrumented delivery,

because of sheering forces and tears of the tentorium, falx, or cortical bridging veins.

Infratentorial SDH in the limited posterior fossa space demand urgent evaluation

because potentially fatal brainstem dysfunction may evolve rapidly.

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Posthemorrhagic seizures in the preterm infant have different features and a more

ominous prognosis. These seizures are usually associated with severe IVH, or its

parenchymal complication, periventricular hemorrhagic infarction (PVHI). Seizures

following severe IVH usually present within the first 3 days of life in sick, very

premature infants. The seizures are usually generalized tonic seizures with poor

electroclinical association. They form part of a critical illness, which often evolves to

coma and death in the acute phase. Seizures associated with PVHI tend to occur after

the third day of life.

4. Central nervous system infections.

Central nervous system infections from a variety of agents, including viral, bacterial,

or other organisms such as toxoplasmosis, may have neonatal seizures as a

prominent part of their presentation. These infections may originate in the fetus, for

example, congenital encephalitis due to cytomegalovirus (CMV) and toxoplasmosis.

When CMV encephalitis occurs in earlier gestation it may cause cerebral dysgenetic

lesions, which may further increase the risk of seizures. Intrauterine infections with

toxoplasmosis or CMV that are severe enough to cause neonatal seizures usually do

so within the first 3 days of life. Other viral infections of importance are herpes

simplex virus (HSV) infections that may become symptomatic in the first days of

life after intrapartum infection [usually HSV type 2] or have a more delayed

presentation. The development of bacterial meningitis, most commonly Group B

streptococcal meningitis, may also have a biphasic appearance with early and late

forms. The mechanism of seizures in central nervous system infections may be

through direct cerebritis or vaso-occlusive injury with secondary seizures. The onset

of infection-related seizures obviously depends on the various organisms and onset

of infection. Of the bacterial infections, meningitis due to Group B streptococcus and

Escherichia coli are the most common, and in these cases, seizures usually develop

in the latter part of the first week or later.

5. Metabolic disturbances

Two types of metabolic disturbances may result in neonatal seizures:

a. Transient metabolic disturbances include disturbances of blood glucose and

electrolyte disturbances such as hypoglycemia, hypocalcemia and 14

hypomagnesemia. These conditions frequently occur in conjunction with other

potentially epileptogenic conditions such as perinatal asphyxia.

b. Inborn errors of metabolism, are an uncommon cause of neonatal seizures;

nevertheless, neonatal seizures have been described in a long list of such

conditions. The most common diagnostic abnormalities associated with these

conditions include metabolic acidosis, hyperammonemia, hypoglycemia and

ketosis. Most of these conditions are due to permanent enzyme defects, and are

largely incurable. However, their recognition is important for two reasons. First,

some metabolic disturbances have transient forms that resolve over time (e.g.,

nonketotic hyperglycinemia). Second, some of these conditions are treatable (e.g.,

pyridoxine dependency). In both these situations, early diagnosis and treatment

may prevent or limit brain injury.

6. Cerebral dysgenesis.

A number of dysgenetic cerebral lesions may be associated with neonatal seizures. In

many, but not all, cases these lesions can be demonstrated in vivo by computed

tomography (CT) or MRI scan. Conditions most commonly associated with neonatal

seizures are disorders of neuronal migration (e.g., heterotopias, lissencephalies) or

disorders of neuronal organization (e.g., polymicrogyria). These ectopic or

disorganized collections of neurons are abnormally prone to hyperexcitability and

bursts of discharges leading to seizures. The genetic lesions causing these disorders

are being uncovered. Occasionally cerebral dysgenesis may be associated with and

possibly caused by inborn metabolic disturbances, such as 7-dehydrocholesterol

deficiency in certain holoprosencephalies, and carbohydrate-deficient glycoprotein

syndrome and nonketotic hyperglycinemia in some cases of agenesis of the corpus

callosum. Infants with cerebral dysgenesis and fluctuating consciousness, vomiting,

and apparent regression, should be evaluated for metabolic conditions that may cause

ongoing neurodegeneration.

7. Epileptic syndromes in the newborn infant

There are two benign epileptic syndromes presenting with seizures in the newborn

infant.

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a. Benign familial neonatal seizures is an autosomal dominant seizure disorder

presenting in newborn infants without obvious risk factors for seizures. In this

condition, seizures typically have their onset around the second to third day of life

and may recur for days to weeks before gradually resolving. The interictal

neurologic examination is normal, and most cases have a normal long-term

neurodevelopmental outcome. The clinical phenomena are variable but include a

brief initial phase of apnea, tachycardia, and tonic posturing (with abduction or

adduction of the arms, flexion of the hips, and extension of the knees) followed by

a phase of clonic activity.

b. Benign idiopathic neonatal seizures make up approximately 5% of seizures in

term infants. Certain diagnostic criteria have been proposed, including:

i. birth after 39 weeks' gestational age;

ii. normal pregnancy and delivery;

iii. Apgar scores >8;

iv. normal neonatal course before the seizures;

v. seizure onset between days 4 and 6 of life;

vi. normal neurologic state before and between seizures;

vii. clonic and/or apneic (never tonic) seizures;

viii. normal diagnostic testing;

ix. an ictal EEG showing brief (1-3 minute) seizures in the rolandic regions

x. a normal interictal EEG except for theta pointu alternant pattern

The cause for these seizures remains unknown, but may be related to a transient

zinc deficiency, because CSF zinc levels may be decreased. Several features

distinguish these idiopathic seizures from benign familial seizures; these include:

(i) absence of a family history;

(ii) later seizure onset, around day 5 of life;

(iii) convulsions that are clonic and/or apneic, but never tonic;

(iv) multifocal clonic seizures that are never primary generalized;

(v) lack of the initial voltage attenuation on the ictal EEG.

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There are three early epileptic encephalopathies with associated with a poor

prognosis.

a. Neonatal myoclonic encephalopathy (NME) presents with erratic and fragmentary

partial seizures and massive myoclonus. These seizures typically start as focal

motor seizures, and later evolve into typical infantile spasms. The most common

etiologies associated with this condition are metabolic disorders (especially

nonketotic hyperglycinemia). The ictal EEG shows high-amplitude EEG bursts

coinciding with the massive myoclonic seizures. The interictal pattern shows a

burst suppression pattern with complex bursts and sharp waves alternating with

periods of low-amplitude quiescence.

b. Ohtahara syndrome usually presents within the first 10 days of life but may

present as late as 3 months. The seizures are typically numerous brief tonic

spasms (and not clonic or fragmentary myoclonic). In contrast to the metabolic

causes of NME, the causes of Ohtahara syndrome tend to be structural, with most

being dysgenetic or, occasionally, destructive, such as hypoxic-ischemic injury.

The interictal EEG is usually an invariant burst suppression pattern, with no

sleepwake cycling. Unlike the ictal EEG of NME, the tonic spasms tend to occur

with a period of EEG suppression and not with the bursts.

c. Migrating partial seizures of infancy (Coppola syndrome) is an early onset

epileptic encephalopathy starting between birth and 6 months of age, with no

currently identifiable etiology and normal neuroimaging studies at the onset. The

clinical seizures are partial clonic seizures often alternating between the two sides

of the body. The seizures are typically multifocal on EEG and migrate

independently and sequentially over both hemispheres. They are refractory to

conventional antiepileptic medications and in most (but not all) cases develop

marked hypotonia, severe neurodevelopmental retardation and cerebral atrophy

over time.

2.2.4. Classification

There are 2 types of classification of neonatal seizures can be seen in Table 2.2

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Table 2.2. Classification of neonatal seizure24

2.2.5. Pathophysiology23

A clinical seizure results from excessive synchronized depolarization of the neurons

within the central nervous system resulting in excessive synchronous electrical discharge.

Why this excessive depolarization of the neurons might occur remains unknown.

Theories were suggested include the following:

1. Imbalance between excitatory and inhibitory neurotransmitter like excessive

excitatory amino acid or deficient inhibitory neurotransmitter.

2. Failure of energy production due to disruption of ATP dependent resting membrane

potentials resulting in failure of sodium potassium pump which in turn leading to

movement of sodium into the neuron and potassium out of the neuron.

3. Neuronal hyper excitability state in the neonatal period, as evidenced by the

extremely low threshold to seizures in general and that this is the period of highest

incidence of seizures across the life span. Among the factors that cause increase

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excitability are incomplete myelination and neuropeptides particularly corticotrophin

releasing hormone (CRH).

4. Experimental and clinical evidence exists for early microglial activation and

inflammatory cytokine production in the developing brain in both hypoxia/ischemia

and inflammation. Importantly, microglia have been shown to be highly expressed in

immature white matter in rodents and humans during cortical development.

5. Genetic predisposition as most of the cases of Benign Familial Neonatal Seizures

(BFNS) are due to mutations in two genes, KCNQ2 and KCNQ3, which encode

subunits of a type of voltage-gated potassium ion (Kv) channel

6. Idiopathic as in the cases of Benign Non Familial Neonatal Seizures (BNFNS), also

called fifth day disease were the pathophysiology remains unknown.

2.2.6. Clinical manifestations23

Most seizures are subtle, difficult to be recognized and can easily be mistaken for

common normal rhythmic and jerky neonatal behaviors. It might be fragmented,

disorganized with abnormal spread leading to a multi focal appearance. Generalized tonic

clonic seizures are very rare if ever occur in neonatal period because the arborization of

axons and dendritic processes as well as myelination is incomplete in the neonatal brain.

A seizures discharge, therefore, cannot readily be propagated throughout the neonatal

brain to produce a generalized seizure. The five clinical types of neonatal seizures

adopted by Volpe are the most widely accepted classification, these include;

1. Subtle: are the most common type in both term and preterm neonates, constitute about

50% of all neonatal seizures. Usually they manifest as mild paroxysmal alteration in

behavioral, motor or autonomic function that are not clonic, tonic or autonomic and

they are commonly missed or mistaken for normal neonatal behavior. They are often

originated in subcortical area and have no EEG correlate. The most common

manifestations are:

a. Ocular: usually consisting of staring, horizontal or vertical sustained deviation of

the eyes or eye blinking.

b. Oral: can manifest as swallowing movement, tongue thrust, lip smacking or

chewing movement.19

c. Limb: manifest as bicycling of legs, boxing or swimming movement of the arms

or other stereotypic limb movement.

d. Autonomic: include alteration in blood pressure and/or heart rate, excessive

salivation, pupillary dilatation and central apnea associated with tachycardia.

e. Apnea: is a rare manifestation of neonatal seizures, commonly associated with

normal or exaggerated heart rate when evaluated within 20 second after the onset.

It is more common in term infant and usually associated with eye signs. Apnea

alone in preterm neonate should raise the possibility of other underlying problem

than neonatal seizures.

2. Clonic: are more common in term than preterm neonates and usually associated with

electrographic seizures. They involve abnormal slow rhythmic movement of group of

muscles of face, neck, limbs or trunk involving one side of body or both sides

simultaneously in a non synchronous manner.

3. Multifocal clonic: are clonic seizures occurring in several parts of the body. Also they

are seen primarily in term neonates. Clonic and multifocal clonic are easily to be

diagnosed clinically but sometime they may be difficult to be differentiated from non-

epileptic movement’s like jitteriness.

4. Tonic: they involve sustained flexion or extension of axial or appendicular muscles

groups. It could be focal or generalized. The generalized tonic seizures can result in a

posture resemble that of decerbrate (tonic extension of all limbs) or decorticate (tonic

flexion of upper limbs and tonic extension of lower limbs).

5. Myoclonic: these manifests as random single rapid contraction of groups of muscle

the limbs, face, or trunk. It might be generalized, focal or fragmentary. Occurrence at

more rapid speed and predilection for flexor group of muscles can distinguish it from

clonic seizures. EEG might be normal or shows changes including burst suppression

pattern, focal sharp wave and hypsarrhythmia. If the myoclonus is related to sleep or

hypoxic ischemic injury, the EEG shows no abnormal changes. Myoclonic neonatal

seizures carry the worst prognosis regarding the neurodevelopmental out come and

some of it might progress to infantile spasm.

20

Other classification of neonatal seizures depends on correlation between clinical events

and occurrence of electrical seizures activity on EEG trace

1. Electroclinical: when the clinical events overlaps in time with electrographic seizures

activity.

2. Clinical only: when the clinical events occurs in the absence of any EEG seizures

activity. It's significant is not clear.

3. Electrographic only: EEG shows electrical seizures without any coincidental clinical

seizures activity. There is evidence that they have a similar impact on long term

outcome as electroclinical seizures.

2.2.7. Investigations23

Investigations should be guided by history and clinical examination but some

investigations should be obtained in nearly all neonates with seizures. These

investigations include basic biochemistry test, CSF, neuroimaging and EEG. Other tests

might not be needed routinely and are suggested by history and clinical examination such

as screening for TORCH, inborn error of metabolism and intoxications. The goal of

determining the cause of neonatal seizures is to treat and prevent cases and to determine

the prognosis. The investigations can be grouped under the following heading:

1. Septic screen: because infections are common and readily treatable cause of neonatal

seizures, investigations such as blood culture, urine culture and CSF analysis should

urgently obtained when we suspect such cases as meningitis, ventricullitis and brain

abscess. When viral encephalitis is suspected especially herpes simplex virus,

investigations including PCR and viral culture for HSV should be obtained while the

neonate is empirically treated with antiviral agent such as acyclovir.

2. TORCH screening: should be considered in any neonate with seizures and stigmata of

congenital infection as micro or hydrocephaly, hepatosplenomegaly, skin rash, small

for gestational age, thrombocytopenia and chorioretinitis.

3. Metabolic screen: including serum electrolyte (Na, Ca, and Mg), blood sugar, arterial

blood gas, anion gap, urine pH and reducing substances, blood ammonia for urea

cycle abnormalities, urine and serum aminoacidogram, serum and CSF lactate/

21

pyruvate ratio and screening test for various inborn error of metabolism. A persistent

metabolic acidosis suggests an organic acidemia.

4. Neuroimaging: these investigations can detect neonatal strokes, structural

abnormalities, intraventricular hemorrhage and neuronal migration defects. It includes

skull X ray, ultrasound, CT scan and MRI. The choice of neuroimaging is frequently

debated. Skull X ray is of limited value but can shows intracranial classification in

suspected TORCH infection. Cranial ultrasound is the test of choice when the patient

is in critical condition and he or she suspected to have intracranial pathology. The

advantages are that it is readily available in most centers, can be done at bedside and

in most of the time there is no need for anesthesia but it is limited by its low

resolution and its ability to assess cerebral cortex. CT scan is very helpful to exclude

intracranial hemorrhage, infarction, structural abnormalities of the brain and

hydrocephaly. MRI is indicated when other tests not revealed the underlying

pathology and the seizures is refectory to antiepileptic drugs. It can be diagnostic in

Lissencephaly, cerebral dysgenesis, neuronal migration defects and it’s the study of

choice for pattern of hypoxic ischemic brain injury. For symptomatic seizures cause

by HIE, abnormal T2, fluid attenuated inversion recovery, and diffusion signals can

be used to pinpoint regional injury and severity. Some studies revealed that magnetic

resonance spectroscopy can be used to predict the severity and prognosis in those

patients.

5. Electroencephalography: It should be done in all neonates with seizures requiring

anticonvulsant therapy. It has both diagnostic and prognostic value. The EEG

definitions vary, but paroxysms are considered to be seizures if they last more than 10

seconds. The typical duration of the electrographic neonatal seizures is 2-3 minutes

but many seizures is shorter particularly in preterm infants. The background EEG

activity can provide information concerning degree of associated central nervous

system dysfunction, potential risk of seizures and prognosis. The degree of

abnormality of the interictal background activity may suggest the extent and type of

CNS dysfunction associated with seizures. The nature of the interictal background

activity may also indicate the potential risk the individual infants have in

22

experiencing a seizure. Video EEG monitoring has proved to be a powerful tool in

diagnosis and management of neonatal seizures and as well as in clinical research.

2.2.8. Treatment23

The most important factor in determining the treatment in neonatal seizures is the

recognition of underlying cause of the seizure. Some cases require only correction of the

associated metabolic disturbances like hypocalcemia or hypoglycemia without the need

for anticonvulsant drugs. On the other hand, some refractory cases require multiple

anticonvulsant therapy in combination. There is a great debate whether a clinical –

electrographic correlation is necessary to start vigorous treatment with anticonvulsant

medication. Treatment of newborn with seizure involves:

1. General supportive measures: basic medical emergency principles should be applied

to establish airway and breathing and to maintain circulation. Oxygen should be given

if the seizures are prolonged and an intravenous line access should be secured for

administrations of drugs and drawing blood for baseline investigations.

2. Treatment of associated metabolic disturbances:

a. Hypocalcemia: should be treated by slow intravenous infusion of 2ml/kg of 10%

Ca gluconate at a rate of 1 ml/minute under strict monitoring heart rate. The dose

can be repeated in 10 minutes if no response occurs. If ionized calcium level is

suggestive of hypocalcemia, the Ca gluconate should continue for 3 days at a rate

of 8 ml/kg/day. If despite of correction of serum calcium the neonate continue to

have seizures, 0.2 ml/kg of 50% magnesium sulphate (50 mg/kg) should be given

intramuscularly. The dose can be repeated every 12 hours until normalization of

serum magnesium is achieved.

b. Hypoglycemia: Blood glucose should be obtained immediately and if there is

hypoglycemia, 2 ml/kg bolus of 10% glucose in water should be given followed

by continuous infusion of glucose at a rate of 6-8 mg/kg/minute. It is important to

avoid hyperglycemia by frequent checking of blood glucose.

c. Pyridoxine dependency: dramatic response to intravenous 100 mg of pyridoxine

used empirically in refractory seizures is highly suggestive of pyridoxine

dependency this can be confirmed by continuous EEG monitoring.23

d. Anticonvulsant: if the seizures persist or are recurrent, anticonvulsant drugs

should be started. The most widely used drug for neonatal seizures is

phenobarbitone which together with benzodiazepines (diazepam and lorazepam)

and phenytoin (or Fosphenytoin) regarded as first line therapy.

i. Phenobarbitone: is the drug of choice for neonatal seizures by most centers.

It is given as initial intravenous loading dose of 20 mg/ kg. If the seizure is

persist after completions the loading dose, repeated doses of 5-10 mg/ kg

every 20-30 minute until a clinical response or maximum dose of 40 mg / kg

has been given. The highest therapeutic serum level of 180 μmol/L should

not be exceeded. The maintenance dose is 3 – 5 mg/kg/day in 1-2 divided

doses, started 12 hours after the loading dose. Careful monitoring of cardiac

and respiratory function is necessary. The phenobarbitone should be used

for the shortest possible period of time because of the possibility of

phenobarbital induced neurodegeneration, inhibition of brain growth and

impaired cognition and behavior.

ii. Phenytoin: is the second most commonly used drug as first line therapy for

neonatal seizures. It is given as a loading dose of 20 mg/kg by slow

intravenous infusion, not more than 1 mg / kg / minute followed by

maintenance dose of 2-3 mg/kg/day intravenously in 2-4 divided doses. The

drug should not be dissolved in dextrose as it precipitated in it and the

intravenous line should be washed with normal saline before given the

medication if the neonate receiving glucose water. There should be a close

monitoring of the cardiovascular system for arrhythmia and hypotension.

Fosphenytoin is a prodrug of phenytoin has the advantages higher water

solubility and lower pH, which, in addition to the lack of toxic vehicles

required for its formulation, reduce local irritation of skin and blood vessel

at the site of infusion, this will also avoid purple glove syndrome which

represent the soft tissue necrosis and injury which occur with highly alkaline

poorly soluble intravenous phenytoin. Fosphenytoin is converted to

phenytoin by plasma phosphatase enzyme and it does not cause cardiac

arrhythmia and hypotension to the same degree as phenytoin. Dose is 24

calculated as equivalent to phenytoin and 1.5 mg/kg of Fosphenytoin is

equal to 1 mg/ kg of phenytoin.

iii. Benzodiazepines: These drugs are given intravenously ( or rectally in case

of diazepam) and diazepam and midazolam are more effective when given

by continuous intravenous infusion at which time the neonate should be

monitored closely for cardio respiratory and CNS depression. Lorazepam is

preferred over diazepam because of its longer duration of action and wider

therapeutic index. Dose of diazepam is 0.3 mg/kg intravenously and 0.3

mg /kg/hour infusion rate when used by continuous infusion. Rectal rout

might be used in a dose of 0.5 mg/kg. lorazepam is given by intravenous

injection at a dose of 0.05 – 1 mg/kg over 2 – 5 minute while midazolam

given as an initial loading dose of 0.15 mg/kg followed by continuous

intravenous infusion at a rate of 0.1 – 1.4 mg/kg/hour.

iv. Alternative anticonvulsant therapy for refractory seizures: Lidocaine may be

effective in refractory seizures but its use is hampered by potential cardiac

toxicity (101). Lidocaine drip given in an initial loading dose of 2 mg/kg

given over 10 – 20 minutes followed by 4 – 6 mg /kg/hour in continuous

drip. The drug has narrow therapeutic range and adverse effects include

arrhythmia, hypotension and seizures if given in high doses. Levetiracetam

may also be effective in controlling neonatal seizures. Recent study use

mean initial dose is 16 ± 6 mg/kg and the mean maximum dose is 45 ± 19

mg/kg/day. No respiratory or cardiovascular adverse effects were reported

or detected.

Other drugs that have been used orally as an adjunctive anticonvulsant therapy for

controlling seizures in refractory cases include carbamazepine in a dose of 10 mg/kg

initially followed by 15 – 20 mg/kg/day. Also valproic acid can be used per rectally for

acute condition and orally for maintenance therapy. Intravenous preparation of valproic

acid is recently available. The dose is 20 -25 mg/kg/day followed by 5 – 10 mg/kg 12

hourly. Other drugs include primidone, felbamate, lamotrigine and vigabatrin. The

efficacies of the above mention drugs can be difficult to assess since they are seldomly 25

used as sole therapy for neonatal seizures and are usually given in conjunction with other

anticonvulsant drugs.

Maintenance therapy: there are no consensuses guideline exist regarding the duration of

keeping an infant on anticonvulsant therapy after a neonatal seizures. The principle is to

keep the infant for the shortest possible time on anticonvulsant therapy. The duration is

variable according to the underlying etiology, neurological examination and EEG

changes. The most widely accepted drug for maintenance therapy is phenobarbitone in a

dose of 3 – 5 mg/kg/day in one or two divided doses with monitoring serum level.

Phenytoin is an alternative therapy. If the neurological examination is abnormal on

discharge, the neonate kept on anticonvulsant therapy and reassessed at one month age.

At the age of one month, if the neurological examination is normal and the infant has no

further seizures, the phenobarbitone is weaned over two weeks. If the neurological

assessment is abnormal, an EEG is obtained. If the EEG is normal, the drug is tapered

and stopped but if the EEG is abnormal, the infant continue on his anticonvulsant and

reassess every 3 months till the age of one year in the same manner. Another protocol

recommends drug withdrawal 2 weeks after the infant last seizures after doing EEG to

exclude subclinical seizures.

26

Diagram 2.1. Treatment of Neonatal Seizure25

27

2.2.9. Prognosis26

Prognosis is variable and dependent on underlying cause. Some types of neonatal seizure

are associated with high mortality2 and poor long-term neurologic outcome.

The results of neuroimaging and EEG give a better indicator of prognosis than

clinical features alone

Normal interictal EEG is associated with a good outcome

Normal neurological examination and normal / mildly abnormal EEG are associated

with favourable outcome especially if neuroimaging is normal

Cerebral malformations and severe hypoxia-ischaemia are associated with poor

outcome

Babies with burst suppression or a markedly attenuated background pattern that

persists for longer than 12 hours after birth are likely to have an adverse outcome

28

CHAPTER 3

CASE REPORT

A 8 days old girl (DS/MR 55 81 29) was admitted at May 4 th, 2013 to Haji Adam Malik General

Hospital. Her parents complained that their baby was no movement respond since was born.

Short of the breath (-), history of the short of the breath (+) since was born.

History of generalized seizure (+) since was born, with frequency ± 5x/day. Its duration ± 5

minutes. After seizure, the patient conscious.

Micturation (+) Normal. Defecation (+) Normal.

The abnormality of the heart was found when she had thorax X-ray.

History of pregnancy : The patient was second child. G2P2A0. The history illness of her parents:

asthma (+) father, hypertension (-), DM (-), taking medicine (-). No history of bleeding.

History of birth : spontaneous, helped by midwife. Not crying immediately. A patient was post

term (2 weeks). When she was born, she had been drinking meconium. Its colour was green. Her

birth’s weight was 3,3 kg.

She was a patient of Kabanjahe General hospital from April 27th, 2013 until May 3rd , 2013.

Physical Examination

Consciousness: Compos Mentis. Body weight : 3082 gr, Body Length : 42 cm, Head

circumference : 33 cm.

Dyspnea, cyanosis, icteric and oedema were not present

Temperature was 37,0°C

Head Eyes: conjunctiva palpebra’s pale (-). Light reflex: +/+, isocoric

pupil,

Ear/nose/mouth: normal in appearance

Thorax Simetrical fusiform, no retraction

HR: 100 bpm, regular, no murmur, stridor (+), right heart sound >

29

left heart sound.

RR: 44 rpm, regular, no rales, O2 saturation 90 %

Abdomen Soepel, peristaltic (+) normal,

liver/spleen/renal: indeterminate

Extremities Pulse 100bpm, regular, pressure and volume were adequate, CRT

<3”

Laboratory Result:

Complete Blood Count (CBC)

Hemoglobin (HGB) g% 17.8 13.4-19.8

Eritrosit (RBC) 106/mm3 4.99 5.33-5.47

Leucocyte (WBC) 103/mm3 6.05 6.0-17.5

Hematokrit % 52.7 51-65

Trombosit (PLT) 103/mm3 443 217-497

MCV fL 105.6 104-116

MCH Pg 35.7 35-39

MCHC g% 33.80 32-34

RDW % 15.3 14,9-18.7

MPV fL 9.8 7.2-10.0

PCT % 0.43

PDW fL 11.7

Difftel Count

Neutrofil % 58.40 37-80

Limfosit % 21.8 20-40

Monosit % 6.4 2-8

Eosinofil % 13.1 1-6

Basofil % 0.3 0-1

Neutrofil Absolut 103/µL 3.53 5.5-18.3

Limfosit Absolut 103/µL 1.32 2.8-9.3

Monosit Absolut 103/µL 0.39 0.5-1.7

30

Eosinofil Absolut 103/µL 0.79 0.02-0.70

Basofil Absolut 103/µL 0.02 0.1-0.2

Carbohydrate Metabolism

Blood Glucose mg/dL 208 <200

Electrolyte

Natrium (Na) mEq/L 127 135-155

Kalium (K) mEq/L 5.2 3.6-5.5

Chloride (Cl) mEq/L 104 96-106

Working Diagnosis: Postterm neonates- appropriate for gestational age + suspect sepsis +

dextrocardia + neonatal seizure ec DD(HIE/Intracranial hemorrhage)

Management:

Keep in radiant infant warmer

Total fluid requiment : 150 cc/BW/day

o Parenteral : 100 cc/BW/day = 300 cc/day

IVFD D 5% NaCl 0,9 % (430 cc) + D 40% (70cc) +KCl 10 mEq + Ca Gluconas

10 cc = 12 gtt/I (micro)

o Enteral : 50 cc/BW/day = 154 cc/day

Breast milk : 12 cc/ 2 hours/OGT

Inj Phenobarbital 6 mg/IV

Inj Ceftazidine 155 mg/ 12 hours/ IV

Inj Gentamycin 15,5 mg/24 hours/IV

Hiponatremia Correction:

o Deficiency : (135-127)x 0,6x 3 = 14,4 mEq

o Maintance: 2-4 mEq/BW = 6-12 mEq/day

o Total : 25 mEq/day

Fluid correction : D 5% NaCl 0,45% (430 cc) + D 40% (70cc)+ KCl 10 mEq + Ca

Gluconas 10 cc = 13 gtt/I (micro)

31

Follow up

May 5th , 2013

S : faint (+), inactive movement (+)

O: Sens: CM, Temp: 37,1oC. Body weight : 3082 gr. Dyspnea, cyanosis, icteric and oedema were not present

Head Eyes: conjunctiva palpebra’s pale (-). Light reflex: +/+, isocoric pupil,

Ear/nose/mouth: normal in appearance


HR: 124 bpm, regular, no murmur, stridor (+), right heart sound > left heart

sound.

RR: 40 rpm, regular, no rales, O2 saturation 98 %



Extremities Pulse 124bpm, regular, pressure and volume were adequate, CRT <3”,

muscle tone ↓

A : Postterm neonates- appropriate for gestational age + suspect sepsis + dextrocardia + neonatal seizure ec DD(HIE/Intracranial hemorrhage)

P :


Total fluid requiment : 150 cc/BW/day


IVFD D 5% NaCl 0,9 % (430 cc) + D 40% (70cc) +KCl 10 mEq + Ca Gluconas 10 cc = 12 gtt/I (micro)


Breast milk : 12cc/ 2 hours/OGT

Inj Phenobarbital 6 mg/12 hours/IV



32

Laboratorium Finding :

Electrolyte

Natrium (Na) mEq/L 138 135-155

Kalium (K) mEq/L 4.9 3.6-5.5

Chloride (Cl) mEq/L 109 96-106

Chest X-ray : infiltrate(-) & the patient’s right sided heart

May 6th , 2013

S : crying weakly (+), inactive movement (+)

O: Sens: CM, Temp: 37oC. Body weight : 3030 gr. Dyspnea, cyanosis, icteric and oedema were not present


Ear: normal in appearance. Nose : O2 nasal canule (+). Mouth : OGT (+)



sound.

RR: 44 rpm, regular, no rales, no stridor, O2 saturation : 98 %



Extremities pressure and volume were adequate, CRT <3” & warm extremities


P :


Total fluid requiment : 150 cc/BW/day = 454,5 cc/day

o Parenteral : 90 cc/BW/day = 272,7 cc/day

IVFD D 5% NaCl 0,9 % (430 cc) + D 40% (70cc) +KCl 10 mEq + Ca



33





Plan :

septic work up

Cardiology consult

Neurology consult

Laboratory Result:



Eritrosit (RBC) 106/mm3 4.89 5.33-5.47

Leucocyte (WBC) 103/mm3 5.64 6.0-17.5



MCV fL 104.1 104-116

MCH Pg 36 35-39

MCHC g% 34.60 32-34

RDW % 15.10 14,9-18.7

MPV fL 10.80 7.2-10.0

PCT % 0.30

PDW fL 13.5

LED mm/jam 7 <15

Difftel Count

Neutrofil % 17.3 37-80

Limfosit % 45.9 20-40

Monosit % 29.10 2-8

Eosinofil % 7.3 1-6

Basofil % 0.4 0-1

34






IT Ratio 0.01 <0.2

Liver

Total Bilirubin mg/dl 0.27 <1

Direct Bilirubin mg/dl 0.11 0-0.2

Fosfatase alkali U/L 105 <449

AST/SGOT U/L 131 <38

ALT/SGPT U/L 138 <41

May 7th , 2013


O: Sens: CM, Temp: 36,6 oC. Body weight : 3030 gr. Dyspnea, cyanosis, icteric and oedema were not present





sound.

RR: 44 rpm, regular, no rales, no stridor





P :

35


Total fluid requiment : 150 cc/BW/day = 462 cc/day









Plan :

EEG

Echocardiography

Laboratory finding :

Electrolyte

Calcium (Ca) mg/dl 9.3 8.4-10.8

Magnesium (Mg) mEq/L 1.87 1.4-1.8

Echocardiography result : Mesocardia

May 8th , 2013







36

sound.





A : Postterm neonates- appropriate for gestational age + suspect sepsis + mesocardia + neonatal seizure ec DD(HIE/Intracranial hemorrhage)

P :











Plan :

EEG

Laboratory Result :

Electrolyte

Calcium (Ca) mg/dl 9.3 8.4-10.8

May 9th , 2013




37




sound.




Extremities Pols 102 bpm, pressure and volume were adequate, CRT <3” & warm

extremities


P :











May 10th , 2013


O: Sens: CM, Temp: 37 oC. Body weight : 3100 gr. Dyspnea, cyanosis, icteric and oedema were not present



38



sound.





extremities


P :








Inj Phenobarbital 7,5 mg/12 hours/IV


Inj Gentamycin 16 mg/24 hours/IV

Plan :


Folllow Culture result

EEG

May 11th , 2013


O: Sens: CM, Temp: 37 oC. Body weight : 3100 gr. Dyspnea, cyanosis, icteric and oedema were

39

not present


Ear: normal in appearance. Nose : normal in appearance. Mouth : OGT (+)



sound.





extremities


P :











Plan :

Follow blood culture

EEG

Laboratory Result:

EEG Result : General Convulsions disease with multifocal irritative focus.

40

May 12th , 2013







sound.





extremities


P :











May 13th , 2013


41



Ear: normal in appearance. Nose : 02 nasal kanul. Mouth : OGT (+)



sound.





extremities


P :











Nystatin 4 x 1 cc

Plan :

Follow blood culture (13/5/2013)

Follow EEG result (13/5/2013)

42

May 14th , 2013







sound.





extremities


P :










Inj Amikasin 25 mg/8 hours/IV

Nystatin 4 x 1 cc

Ezera Gel 4 x 1 Applic

43

Nebule Nacl 0,9 2,5 cc % /8 jam

Plan :

CBC

Elektrolit ( Na, K, Cl, Ca, Mg )

Laboratory Result:



Eritrosit (RBC) 106/mm3 3.82 5.33-5.47

Leucocyte (WBC) 103/mm3 10.69 6.0-17.5



MCV fL 104.50 104-116

MCH Pg 34.60 35-39

MCHC g% 33.10 32-34

RDW % 15.80 14,9-18.7

Difftel Count

Neutrofil % 55.60 37-80

Limfosit % 22.40 20-40

Monosit % 18.40 2-8


Basofil % 0.300 0-1






Elektrolit

Kalsium (Ca) mg/dl 8.6 8.4 – 10.8

Natrium (Na) mEq/L 136 135 - 155

44

Kalium (K) mEq/L 4.8 3.6 – 5.5

Klorida (Cl) mEq/L 108 96 - 106

Magnesium (Mg) mEq/L 2.25 1,4 – 1,8

Carbohydrate metabolism

Blood Glucose mg/dl 9.3 < 200

Faal Hemostasis

PT + INR

Protrombin Time

Control sekon 14.50

Patient sekon 15,7

INR 1.09

APTT

Control sekon 29.9

Patient Sekon 38.2

Trombin Time

Control sekon 15.5

Patient sekon 19.5

May 15th , 2013







sound.

45





extremities


P :











Nystatin 4 x 1 cc


Nebule Nacl 0,9 2,5 cc % /8 jam

May 16th , 2013







46

sound.





extremities

A : Postterm neonates- appropriate for gestational age + unproven sepsis + mesocardia + neonatal seizure ec DD(HIE/Intracranial hemorrhage)

P :











Nystatin 4 x 1 cc


Nebule Nacl 0,9 % 2,5 cc /8 jam

May 17th , 2013

S : crying weakly (+), active movement (+)





47


sound.





extremities


P :











Nystatin 4 x 1 cc


Nebule Nacl 0,9 % 2,5 cc /8 jam

May 18th , 2013





48



sound.





extremities


P :











Nystatin 4 x 1 cc


Nebule Nacl 0,9 % 2,5 cc/8 jam

May 19th , 2013




49




sound.





extremities


P :











Nystatin 4 x 1 cc



May 20th , 2013



50





sound.





extremities


P :











Nystatin 4 x 1 cc



51

May 23th , 2013







sound.





extremities


P :











Nystatin 4 x 1 cc


52


May 24th , 2013







sound.





extremities


P :











53

Nystatin 4 x 1 cc



Plan :

Inj Phenobarbital is given until june 5th 2013 then tapering off

CBC and electrolyte

Laboratory Result:



Eritrosit (RBC) 106/mm3 3.82 5.33-5.47

Leucocyte (WBC) 103/mm3 10.69 6.0-17.5



MCV fL 104.50 104-116

MCH Pg 34.60 35-39

MCHC g% 33.10 32-34

RDW % 15.80 14,9-18.7

Difftel Count

Neutrofil % 55.60 37-80

Limfosit % 22.40 20-40

Monosit % 18.40 2-8


Basofil % 0.300 0-1






Elektrolit

54

Kalsium (Ca) mg/dl 8.6 8.4 – 10.8

Natrium (Na) mEq/L 136 135 - 155

Kalium (K) mEq/L 4.8 3.6 – 5.5

Klorida (Cl) mEq/L 108 96 - 106

Magnesium (Mg) mEq/L 2.25 1,4 – 1,8

Carbohydrate metabolism

Glukosa Darah (Sewaktu) mg/dl 9.3 < 200

Faal Hemostasis

PT + INR

Protrombin Time

control sekon 14.50

Patient sekon 15,7

INR 1.09

APTT

Control sekon 29.9

Patient sekon 38.2

Trombin Time

Control sekon 15.5

Patient sekon 19.5

May 25th , 2013







sound.

55





extremities


P :











Nystatin 4 x 1 cc



56

CHAPTER 4

DISCUSSION AND SUMMARIES

4.1. Discussion

A 8 days old girl (DS/MR 55 81 29) was admitted at May 4 th, 2013 to Haji Adam Malik

General Hospital. Her parents complained that their baby was no movement respond since was

born and has generalized seizure since was born. The abnormality of the heart was found when

she had thorax X-ray. Clinical examination and laboratory diagnose was established and she

was been diagnosed with postterm neonates-appropriate for gestational age with unproven

sepsis plus mesocardia and neonatal seizure ec DD(HIE/Intracranial hemorrhage).

The patient hasn’t had clinical presentation of repetitive seizure for long period of time. It’s

related to theory that neonatal seizures tend to be brief, because immature neurons are unable to

sustain repetitive activity for long period of time and to be focal or multifocal. After that, in this

patient, we found her no immediate cry when was born. This can make the baby asphyxia.

Consequently, patients may experience seizure. It's related with the theory that the leading cause

of neonatal seizures is cerebral hypoxia-ischemia

We can also found in this patients with clinical symptoms are staring, sustained vertical or

horizontal deviation of the eyes and sustained flexion upper limbs. It’s related with the theory

that the most common manifestations in neonatal seizure are from ocular, they are usually

consisting of staring, horizontal or vertical sustained deviation of the eyes or eye blinking. From

oral, it can manifested as swallowing movement, tongue thrust, lip smacking or chewing

movement. From limb, we can found bicycling of legs, boxing or swimming movement of the

arms or other stereotypic limb movement. From autonomic system, we can found alteration in

blood pressure and/or heart rate, excessive salivation, pupillary dilatation and central apnea

associated with tachycardia. Apnea is a rare manifestation of neonatal seizures, but it is more

common in term infant and usually associated with eye signs.

At the first suspicion of neonatal seizure, the immediate focus should be the exclusion of

rapidly correctable and potentially injurious processes, including hypoglycemia, hypocalcemia,

and hypomagnesemia, among others. More over, the doctor must do septic screen and EEG if he

57

suspect neonatal seizure. In this patient, we check CBC and electrolyte. After that, we also

check septic screen and EEG in this patient.

In this patient, we also found that she has mesocardia. From Kabanjahe Hospital, the doctor

diagnosed her with dextrocardia. We can see it from chest x-ray. So, when she was admitted to

Haji Adam Malik General Hospital, the doctor diagnosed it with dextrocardia at first, but

diagnose changed with mesocardia when echocardiography was performed at May 7th 2013.

In this patient, we also found that she was a postterm baby because her birth was more than

2 weeks later from prediction. After that, the baby’s data was plotted in the graph so that she

was diagnosed postterm neonates-appropriate for gestational age.

Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection

with or without accompanying bacteremia in the first month of life. In this patient, we found she

was 8 days old. After that, neonates with sepsis may present with one or more of the following

symptoms and signs, that is hypothermia or fever, lethargy, poor cry, refusal to suck, poor

perfusion, prolonged capillary refill time, hypotonia, absent neonatal reflexes,

brady/tachycardia, respiratory distress, apnea and gasping respiration, hypo/hyperglycemia, and

metabolic acidosis.in this patient, she was found no movement respond since was born.

In theory, neonatal seizure was also one of the clinical feature of neonatal sepsis besides

gastrointerstinal, cardiac, hepatic, renal, hematological, and skin problem. We can found Central

Nervous System (CNS) problem in this patient.

4.2. Summary

This paper reports a case of a 8 days old female baby diagnosed with Postterm neonates-

appropriate for gestational age, unproven sepsis, mesocardia, and neonatal seizure ec

DD(HIE/Intracranial hemorrhage). A comprehensive workup had been done to confirm the

diagnosis. Nevertheless, treatment include antibiotic, anticonvulsant, ad rehydration have been

given to this patient. This patient is in this hospital until now.

58

References

1. Klinger G., Levy I., Sirota L., Boyko V., Reichman B., Lerner-Geva L.. Epidemiology And Risk Factors For Early Onset Sepsis Among Very-Low-Birthweight Infants. Am. J. Obstet. Gynecol. 2009;201(1):38-46.

2. Hoogen, A.v.d., Gerards, L.J., Verboon-Maciolek, M.A., Fleer, A., Krediet, T.G. Long-Term Trends in the Epidemiology of Neonatal Sepsis and Antibiotic Susceptibility of Causative Agents. Neonatology. 2009;97(1):22-28.

3. Cloherty, J.P., Eichenwald, E.C., Stark, A.R. Neonatal seizure. Manual of Neonatal Care, 6 th

ed. 2008 Lippincott:Williams & Wilkins; 483-498.

4. Bang, A.T., Bang, R.A., Bactule, S.B., Reddy, H.M., Deshmukh M.D. Effect Of Home-Based Neonatal Care And Management Of Sepsis On Neonatal Mortality: Field Trial In Rural India. Lancet 1999;354:1955-61.

5. Stoll, B.J. The Global Impact Of Neonatal Infection. Clin. Perinatol. 1997;24:1-21

6. Aminullah, A. et al. Penatalaksanaan Sepsis Neonatorum. Departemen Kesehatan. 2007. 1-70.

7. Singh, M., Narang, A., Bhakoo, O.N. Predictive Perinatal Score In The Diagnosis Of Neonatal Sepsis. J. Trop. Pediatr. 1994. Dec;40(6):365-8.

8. Takkar, V.P., Bhakoo, O.N., Narang, A. Scoring System For The Prediction Of Early Neonatal Infections. Indian. Pediatr. 1974;11:597-600.

9. Baltimore, R.S. Neonatal Nosocomial Infections. Semin. Perinatol. 1998;22:25-32

10. Wolach, B. Neonatal Sepsis: Pathogenesis and Supportive Therapy. Semin Perinatol. 1997;21:28-38

11. Gerdes, J.S, Polin, R. Early Diagnosis And Treatment Of Neonatal Sepsis. Indian J. Pediatr. 1998;65:63-78.

12. Polinski, C. The Value Of White Blood Cell Count And Differential In The Prediction Of Neonatal Sepsis. Neonatal. Netw. 1996;15:13-23

13. Da Silva, O., Ohlsson, A, Kenyon, C. Accuracy Of Leukocyte Indices And C-Reactive Protein For Diagnosis Of Neonatal Sepsis: A Critical Review. Pediatr. Infect. Dis. J. 1995;14:362-6

14. Manroe, B.L., Weinberg, A.G., Rosenfeld, C.R., Brown, R. The Neonatal Blood Count In Health And Disease: Reference Values For Neutrophilic Cells. J. Pediatr. 1979;95:89-98

15. Mouzinho, A., Rosenfeld, C.R., Sanchez, P.J., Risser, R. Revised Reference Ranges For Circulating Neutrophils In Very-Low-Birth-Weight Neonates. Pediatrics 1994;94:76-82.

16. Sarff, L.D., Platt, L.H., McCracken, G.H.Jr. Cerebrospinal Fluid Evaluation In Neonates: Comparison Of High-Risk Neonates With And Without Meningitis. J Pediatr. 1976;88:473-7

17. Upadhyay, A., Aggarwal, R., Kapil, A., Singh, S., Paul, V.K., Deorari, A.K. Profile Of Neonatal Sepsis In A Tertiary Care Neonatal Unit From India: A Retrospective Study. Journal of Neonatology 2006;20:50-57.

59

18. Deorari, A. K. For the Investigators of the National Neonatal Perinatal Database (NNPD). Changing Pattern Of Bacteriologic Profile In Neonatal Sepsis Among Intramural Babies. Journal of Neonatology 2006;20:8-15.

19. Zaidi, A.K., Huskins, W.C., Thaver, D., Bhutta, Z.A., Abbas, Z, Goldmann, D.A. Hospital-Acquired Neonatal Infections In Developing Countries. Lancet 2005;365:1175-88.

20. Sadana, S., Mathur, N.B., Thakur, A. Exchange Transfusion In Septic Neonates With Sclerema: Effect On Immunoglobulin And Complement Levels. Indian Pediatr. 1997;34:20-5

21. Jenson, H.B., Pollock, H.B. The Role Of Intravenous Immunoglobulin For The Prevention And Treatment Of Neonatal Sepsis. Semin. Perinatol. 1998;22:50-63.

22. Goldman, S., Ellis, R., Dhar, V., Cairo, M.S. Rationale And Potential Use Of Cytokines In The Prevention And Treatment Of Neonatal Sepsis. Clin. Perinatol. 1998;25:699-710

23. Zwaini, I.A. Neonatal Seizures In Epilepsy in Children-Clinical and Social Aspects. Zeljka Petelin Gadze (Ed.). InTech 2011. 1-21.

24. Sankar, J., Agarwal, R. Seizures In The Newborn. Department of Pediatrics. All India Institute of Medical Sciences.

25. Pressler, R.M. Neonatal Seizures. London: Department of Clinical Neurophysiology, Great Ormond Street Hospital. 2011.1-15

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