cerebral hemorrhage - hydrocephalus - cerebrospinal fluid
hemorragia cerebral - hidrocefalia - líquido cefalorraquidiano
Intraventricular hemorrhage (IVH) has been a major cause of mortality among premature
neonates for more than 40 years[1],[2] and is associated with neonatal encephalopathy, subsequent subtle apnea, and death[1],[2],[3],[4]. Low birth-weight premature neonates are more vulnerable to IVH and, depending on
the IVH grade, to posthemorrhagic hydrocephalus (PHH). Posthemorrhagic hydrocephalus
can evolve to progressive PHH, and in more severe cases, to periventricular hemorrhagic
infarct, hemorrhagic cerebral injury, and periventricular leukomalacia[1],[4],[5]. Between 15% to 20% of neonates born with a weight less than 1,500 g are estimated
to develop IVH. Further, 75% of those with Papile grade III or IV hemorrhages develop
progressive PHH and need a permanent shunt [4],[6].
The literature does not clearly indicate any standardized protocols for the best PHH
treatment options in this patient group. Rather, a variety of approaches, ranging
from serial lumbar punctures (LP), transcutaneous transfontanellar puncture, external
ventricular drainage, and ventriculosubgaleal shunt (with or without subcutaneous
reservoir) to the endoscopic third ventriculostomy are used[4],[6],[7],[8],[9],[10],[11],[12],[13] Ventriculoperitoneal (VP) shunts are contraindicated as a first option in low birth-weight
(< 1.500g) premature neonates due to the higher risk of complications associated with
the implanted prosthesis and are reserved for selected cases[4],[9],[11],[13]. The scope of this study was describing a case series of premature neonates with
PHH and assessing the outcomes of different approaches used for CSF diversion.
METHODS
Study design and inclusion criteria
This single-center study was approved by the Brazilian Research Ethics Committee (registration
number 38819114.7.0000.5557). This retrospective review and observational study included
all premature neonates admitted with a diagnosis of PHH to the neonatal intensive
care unit at a Reference Public Pediatric Hospital in Salvador da Bahia, Brazil between
December 2009 and December 2014. The diagnosis of PHH identified by a transcranial
ultrasonography, and treated with a CSF drainage procedure, and a minimum follow-up
of three months for the assessment of treatment outcomes.
Definitions of prematurity, IVH and PHH
Premature neonates were defined as those born before 37 weeks of gestation and as
low birth weight when weight-at-birth was less than 1.500g[4]. In all patients, transcranial ultrasonography was performed by a senior radiologist
with more than ten years of experience using a classical transfontanellar approach
with a 1.9–6-MHz curvilinear transducer (Toshiba Aplio™ 100 with color Doppler).
The Papile system was used for grading IVH by transcranial ultrasonography. Briefly,
grade I was defined as hemorrhage restricted to the ventricular subependymal matrix
occupying a maximum of 10% of the ventricles. Grade II and III were defined as hemorrhage
comprising 10–50% and more than 50% of the ventricular system, respectively. If the
hemorrhage extended to the periventricular, i.e., parenchymal, regions, it was considered
as a grade IV IVH[14].
A diagnosis of PHH secondary to IVH was made when the anterior horns width of the
lateral ventricles was ≥ 6 mm as measured in the anterior coronal plane at the level
of the septum pellucidum (median line), with the midpoint in the lateral wall of the
lateral ventricle (at the level of caudate nucleus and the foramen of Monro) ([Figure])[4],[15],[16]. Comorbidities considered as severe were global hypotonia associated to bradycardia,
cardiorespiratory arrest, respiratory failure, cutaneous cyanosis, sepsis and other
infections associated with clinical and laboratory worsening.
Figure Transcranial ultrasonography: the width of the anterior horns of the lateral ventricles
was measured in the anterior coronal plane at the level of the septum pellucidum (median
line), with the midpoint in the lateral wall of the lateral ventricle (at the level
of caudate nucleus and the foramen of Monro).
Surgical intervention
Conditions that were included that required a neurosurgical evaluation were bulging
fontanelles, an increase in the cranial circumference, bradycardia, and other signs
of intracranial hypertension, associated with transcranial ultrasonography showing
ventriculomegaly (anterior horns width showing progressive increase) and IVH grades
III and IV.
The CSF drainage is commonly indicated in cases of progressive increases in cranial
circumference (≥ 2 standard deviations above the patient’s age group during the first
week), bulging fontanelles, or changes in respiratory patterns, associated with progressive
widening of the ventricular system detected by transcranial ultrasonography[13],[17],[18]. In cases of ventriculomegaly from ex vacuo hydrocephalus (i.e. without bulging
fontanelles, increase in the cranial circumference, bradycardia, or other signs of
intracranial hypertension), a nonsurgical treatment was proposed.
The study did not assess the preferred CSF drainage method among transcutaneous transfontanellar
puncture, external ventricular drainage, or ventriculostomy, as our pediatric neurosurgical
team prefers not use them, in cases of neonates with PHH. As described in previous
studies[8],[10],[13],[17],[19],[20],[21],[22],[23], the following techniques were employed for CSF drainage to resolve PHH: Serial LP was performed at the L3-L4 or L4-L5 level, with the anatomical landmark as an imaginary
line traced from the iliac crest to the lumbar column. A valveless ventriculosubgaleal shunt with subcutaneous reservoirs was placed with an incision near the external angle
of the anterior fontanelle, followed by the detachment of subgaleal space and the
introduction of a 3-cm catheter into the anterior ventricular horn; the catheter was
then connected to the reservoir and the scalp. The VP shunt was placed as follows: an incision was made near the lambdoid suture, and a mini-laparotomy
was performed for tunneling of the distal catheter of the VP shunt. A burr-hole was
made for the osseous and dural exposition, the dura was opened, and a 5-cm catheter
was introduced into the posterior ventricular horn. The proximal and distal catheters
were connected and fixed in the periosteum, and the distal catheter was introduced
into the peritoneal cavity under direct vision. Finally, the musculoaponeurotic, subcutaneous,
and cutaneous layers were closed. In this study, the serial LPs and ventriculosubgaleal
shunts were considered to be temporary CSF drainage options, while the VP shunt was
considered as the only permanent CSF drainage approach.
Follow-up and complications
Patients were evaluated for the persistence or enlargement of hydrocephalus, CSF leak,
shunt infection, failure, or mechanical dysfunctions for at least three months after
CSF diversion. Hydrocephalus was assessed by the enlargement of cranial circumference
or bulging fontanelles during follow-up and transcranial ultrasonography showing anterior
horns width ≥ 6 mm measured in the anterior coronal plane.
Statistical analysis
Epi InfoTM version 7, a public domain statistical software for epidemiology developed by the
US Centers for Disease Control and Prevention, was used for database analysis. Some
results were presented as descriptive statistics. Measures of central tendency (mean,
mode, and median) were calculated and presented where relevant. The chi-squared test
was used to compare ratios with a confidence interval of 95%. The differences were
considered statistically significant if the p-value was < 0.05.
RESULTS
Forty-nine preterm neonates with PHH were treated by CSF drainage during the study
period; however, nine patients were excluded because they were lost to follow-up.
Thus, 40 preterm neonates were included in the final analysis. The median gestational
age and birth weight were 28 weeks (range; 24–35 weeks) and 1,105 g (range; 600–2,800
g), respectively. Patient characteristics are shown in [Table 1].
Table 1
General characteristics of preterm neonates treated for CSF diversion due to PHH (Salvador,
Brazil, 2009–2014).
|
General characteristics
|
n = 40
|
|
Male sex, n (%)
|
22 (55)
|
|
Median gestational age in weeks
|
28 (24–35)
|
|
Median weight at birth in g
|
1,105 (600–2,800)
|
|
IVH grade, n (%)
|
|
Papile grade III
|
28 (70)
|
|
Papile grade IV
|
12 (30)
|
|
Complications after birth*, n (%)
|
35 (88)
|
CSF: cerebrospinal fluid; IVH: Intraventricular hemorrhage; PHH: posthemorrhagic hydrocephalus.
*hypotonia, bradycardia, cardiac arrest, respiratory failure, skin cyanosis, sepsis
and other infections.
Twenty-five patients (62.5%) were treated with temporary CSF drainage approaches:
10 patients (25%) with serial LP, and 15 cases (37.5%) with a ventriculosubgaleal
shunt as the first option to alleviate PHH. Ventriculoperitoneal shunts were used
in 15 neonates (37.5%) to treat PHH as the first option, generally with low-pressure
valves.
The median age and weight of patients treated with temporary drainage methods were
27 weeks (range; 24–35 weeks) and 867 g (range; 600–1730g), respectively, while the
median age and weight of patients treated with VP shunts were 32 weeks (range; 26–35
weeks) and 2000 g (range; 1500–2800g), respectively ([Table 2]). All of the patients treated with temporary CSF drainage methods were considered
clinically more severely affected, had previous infections, or suffered from severe
comorbidities. In contrast, significantly fewer patients treated with the VP shunt
had severe comorbidities (66%; p = 0.004) ([Table 2]), and none in the latter group had comorbidities related to sepsis or other infections.
Table 2
Characteristics of preterm neonates according to the initial PHH treatment approaches
(Salvador, Brazil, 2009–2014).
|
Criteria
|
Temporary CSF Diversions*
|
Permanent CSF Diversions**
|
p
|
|
|
|
n = 25 (%)
|
n = 15 (%)
|
|
Median
|
|
Age in weeks
|
27 (24–35)
|
32 (26–35)
|
-
|
|
Weight in g
|
867 (600–1730)
|
2000 (1500–2800)
|
|
|
Severe comorbidities***, n (%)
|
25 (100)
|
10 (66)
|
0.004
|
|
IVH Grade, n (%)
|
|
Papile grade III
|
14 (56)
|
14 (93)
|
0.01
|
|
Papile grade IV
|
11 (44)
|
01 (6)
|
|
CSF: cerebrospinal fluid; IVH: intraventricular hemorrhage; PHH: posthemorrhagic hydrocephalus.
*Serial LP and ventriculosubgaleal shunt; **definitive CSF diversion method: VP shunt.
***Global hypotonia associated to bradycardia, cardiorespiratory arrest, respiratory
failure, cutaneous cyanosis, sepsis and other infections associated with clinical
and laboratory worsening.
Regarding the initial method chosen for PHH treatment, 50% (5/10) of those undergoing
serial LP and 46% (7/15) of those undergoing ventriculosubgaleal shunt required VP
shunts during the course of PHH evolution (12/25, 48%) ([Table 3]). During the follow-up period of all enrolled patients, 68% (27/40) were considered
as permanent ventricular drainage dependents and were using VP shunts. The incidence
of progressive PHH was higher in case of IVH grade III (79% vs 42%; p = 0.02).
Table 3
CSF drainage approaches and complications in preterm neonates with PHH (Salvador,
Brazil, 2009–2014).
|
Variable
|
First option for therapeutic relief of hydrocephalus n = 40
|
|
|
LP (n = 10)
|
VSG shunt (n = 15)
|
VP shunt (n = 15)
|
|
Retreatment due to persistence or enlargement of hydrocephalus*, n (%)
|
5 (50)
|
7 (46)
|
-
|
|
CSF leak, n (%)
|
-
|
4 (26)
|
-
|
|
Shunt malfunction or infection, n (%)
|
-
|
-
|
10 (66)
|
CSF: cerebrospinal fluid; PHH: posthemorrhagic hydrocephalus; VSG: ventriculosubgaleal.
*Enlargement of cranial circumference or bulging fontanelles during follow-up.
Among the 27 patients considered as permanent ventricular drainage dependents, 44%
(12/27) had infectious complications or mechanical dysfunction (obstruction or overdrainage).
Ten of these patients had received a VP shunt as the first option for PHH treatment
([Table 3]). This group that received a VP shunt as the first option for PHH treatment (n =
15) had a higher incidence of complications than those treated for progressive PHH
with a VP shunt during the follow-up period (n = 12) (66% vs 16%, p = 0.01). There
was a total of five deaths (5/40; 13%). The average and median time of follow-up was
11.8 months (DP +/- 16.2 months) and three months (range; 3–60 months).
DISCUSSION
Intraventricular hemorrhage is the leading cause of hydrocephalus in premature neonates,
especially those with low birth-weight, and generally occurs within the first four
days of life[11]. Low gestational age and low birth-weight increase the risk for developing IVH[4],[6],[11],[17], a finding consistent with the median age (28 weeks) and weight (1,105g) of the
patients enrolled in this study. There is a minor male predominance reported in previous
studies[17].
Most of the patients included in the current study were diagnosed with Papile grade
III IVH. This finding is in agreement with previously reported risk of PHH in this
patient population[6],[13],[23]. These patients are commonly referred to pediatric neurosurgery for either temporary
or permanent CSF diversion to relieve PHH-induced intracranial hypertension[6],[13],[17],[22],[23], while grade I and II patients are usually not referred for neurosurgical evaluation
due to the lower incidence of PHH and intracranial hypertension. The high number of
patients with clinical complications such as hypotonia, bradycardia, cardiac arrest,
respiratory failure, skin cyanosis, sepsis, and other infections, highlight the susceptibility
of these patients as well as the challenges in their management[4],[17], both of which are clinically considered in deciding the appropriate treatment options
for CSF diversion in PHH cases[23].
The method chosen for CSF drainage in PHH cases does not follow a specific protocol,
and varies with the neurosurgeon’s experience, the age and weight of the premature
neonate, the presence of associated comorbidities, the characteristics of the ventricular
system assessed by imaging studies, and the clinical presentation. In this study,
none of the patients received an initial treatment with transcutaneous transfontanellar
puncture, external ventricular drainage, or ventriculostomy. Transcutaneous transfontanellar
puncture is not used as a first choice at our hospital due to the associated risks,
which include CSF leak, porencephalic cysts, and multiloculated hydrocephalus[4]. External ventricular drainage is not used for temporary relief of hydrocephalus
as a first option in premature neonates due to the risks associated with infection
and accidental removal of the external ventricular drainage, which have been observed
in other reference centers as well[4],[6],[10],[13],[17],[19],[22],[23]. While still considered as a controversial method in neonates with IVH, several
groups have recommended the irrigation of ventricles for the removal of blood clots,
the coagulation of choroid plexus, and the opening of the third ventricle floor by
ventricular endoscopy, with the aim of reducing progressive PHH rates or, at a minimum,
of delaying the use of permanent shunts in select cases[20],[21]. At our hospital, we do not have experience in the use of ventriculostomy in premature
neonates; rather, this technique is reserved for use in children over two years of
age who are diagnosed with obstructive and noncommunicating hydrocephalus, or congenital
cerebral cysts (arachnoid cysts).
In this study, we found a tendency to use temporary drainage methods in infants with
lower gestational age and birth weight, while the VP shunt was reserved for older,
heavier and healthier children, a finding that corroborates previously published data
regarding CSF diversion options[23]. The serial LP was chosen in low birth-weight premature neonates with more severe
and clinically unstable comorbidities, as it is the fastest method that does not require
general anesthesia or transportation to the operating room; the procedure can be performed
in the neonatal intensive care unit. In cases of more stable clinical conditions,
the ventriculosubgaleal shunt as an alternative temporary drainage approach is considered,
especially in infants with grade III IVH. As seen in [Table 2], in addition to age and weight, additional factors including associated morbidities
and the IVH grade, aid the neurosurgeon in deciding between a temporary and a permanent
CSF drainage.
Ventriculoperitoneal shunt was chosen as the first option for relief in 37.5% of patients,
similar to that found in previous studies (34%)[17]. In several reference centers, the VP shunt is often chosen as a first-line treatment
modality for IVH-associated PHH (range; 53–72%)[13],[23]. This divergence in published studies on the subject shows the lack of a standardized
protocol across different institutions. Our findings corroborate earlier studies suggesting
that the VP shunt should be chosen as the initial therapy in select cases, specifically
in older preterm neonates who are heavier, healthier, and are without infections[4],[17],[23].
As previous studies[6], among the temporary ventricular drainage options, we found that serial LP in up
to 50% of the cases resolved PHH. The ventriculosubgaleal shunt achieved resolution
in 54% of the cases, comparable to the serial LP. The advantages of the ventriculosubgaleal
shunt over the serial LP include the likelihood and the ease of serial punctures in
the reservoir if intracranial hypertension develops[10],[13],[23].
In this study, 48% of the patients were initially treated with temporary methods for
PHH resolution and were subsequently treated by the VP shunt based on monitoring for
the clinical signs of intracranial hypertension, such as bulging fontanelles and increased
head circumference. The predictive factors that can aid in the replacement of a temporary
ventricular drainage method with a permanent one are not yet established[4],[13],[17]. In general, depending on the study sample, the percentage of patients depending
on a permanent shunt in the follow-up period ranges from 30% to 75% [4],[6],[15], in agreement with our findings that show 68% of our patients needing the permanent
shunt.
Ventriculoperitoneal shunt complications in these patients are often higher than those
observed in the general pediatric population. In certain series, more than 50% of
VP shunt recipients need further VP shunt exchanges and revisions[6],[23]. Our data corroborate these earlier findings; the patients treated with a VP shunt
for initial PHH management had higher complication rates than those treated with a
VP shunt as a second option during the follow-up period. In a series of children with
congenital hydrocephalus described previously by our team[24], we observed a much lower incidence of VP shunt-related complications than those
observed in the current series, which confirms the need for extreme care in the selection
of PHH patients for a VP shunt as a first CSF drainage option.
The overall mortality rates of IVH in preterm neonates may vary from 30% to 58%, and
are higher in those with Papile grade IV IVH[4],[6],[25]. The mortality rate in this study refers to only those patients undergoing neurosurgical
evaluation. Moreover, nine patients were excluded from the final analysis due to the
lack of the minimum stipulated follow-up period of three months. The mortality rate
in our cohort (13%) is similar to the previously-published studies that included only
the IVH patients with PHH undergoing neurosurgical treatment[23].
Only the CSF drainage methods used for PHH treatment at the hospital where the study
was conducted were analyzed, and do not necessarily reflect the reality of other reference
centers. Finally, we would also like to indicate that only those patients assessed
by a pediatric neurosurgeon were included in this study, while those determined by
the neonatologist not to qualify for neurosurgical evaluation were excluded.
In conclusion, temporary CSF diversion methods should be the first option for PHH
treatment in premature neonates, especially in those small for gestational age and
those with low birth-weight. A serial LP should be considered in more severe cases
as general anesthesia, transportation, or excessive handling of the patients are not
required. The ventriculosubgaleal shunt is another option, especially in those with
more stable clinical conditions and controlled comorbidities. Only in the older, heavier,
and healthier newborns, especially in those with Papile IVH grade III, should the
VP shunt be considered as the first option for PHH treatment. As reflected in our
findings, which showed complications in patients who were treated with the VP shunt
as the first option, ventricular endoscopy should be considered and evaluated as an
alternative option in PHH treatment to delay the implantation of a permanent shunt.
