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Pathophysiology of Hydrocephalus

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203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 203
CHAPTER 16
Pathophysiology of Hydrocephalus
Giuseppe Cinalli, Pietro Spennato, Maria Consiglio Buonocore, Emilio Cianciulli,
Matthieu Vinchon, Spyros Sgouros
Incidence of Hydrocephalus in Spina Bifida
Patients
The three major clinical manifestations of spina bi-
fida (hydrocephalus, paraplegia and urinary and bow-
el incontinence) are easily observable and have been
described since ancient times, though they were not
described in relationship to spina bifida until the sev-
enteenth century [1].
The first pathologist who came close to recognis-
ing the connection between spina bifida and hydro-
cephalus was Frederick Ruysch (1638-1731), whose
face is familiar from Johan Van Neck’s painting
“Anatomy of Dr Frederick Ruysch” (1683). Howev-
er, only the Italian pathologist Giovanni Battista Mor-
gagni (1672-1771) clearly recognised the connection
and that spina bifida could occur with or without hy-
drocephalus [2]. Gardner theorised that overdistension
of the fetal neural tube caused hydrocephalomyelia and
thereby explained all dysraphic states (which in his
mind included the Chiari I malformation), but this in-
teresting theory has not resisted the evidence gained
from modern imaging and embryology [3].
Hydrocephalus is almost exclusively associated
with the open form of spina bifida, namely
myelomeningocele (MMC). Before the introduction
of shunting in the early 1960s, it was the main cause
of death and poor intellectual outcome in children
born with myelomeningocele [4, 5].
The exact incidence of hydrocephalus in
myelomeningocele is not known; however, in most
surgical series the proportion of patients requiring
shunting reaches 80-90% [5-7]. Correlation between
the level of the spinal defect and the presence of hy-
drocephalus has not been shown in most series [6,
7]; however, some authors have suggested a higher
incidence in thoracic level patients (97%) versus lum-
bar (87%) and sacral-level patients (37%) [8].
The only form of closed spinal dysraphism pos-
sibly associated with hydrocephalus is non-terminal
myelocystoceles [9-11], an epithelised malformation
filled with meninges and cerebrospinal fluid (CSF),
which affects predominantly the cervical and upper
thoracic regions [12]. The common link between
open myelomeningocele and non-terminal myelo-
cystoceles is the association with the Chiari II mal-
formation. The presence of hydrocephalus in spina
bifida patients is, in fact, almost exclusively relat-
ed to the Chiari II malformation [5]. However, the
incidence of such a malformation varies in the dif-
ferent forms of spina bifida: nearly 100% in open
myelomeningocele, 44-62% in non-terminal mye-
locystoceles [5, 10-12]. The severity of the Chiari
II malformation also differs for the two entities, with
patients with open myelomeningocele being more
severely affected.
Time of Onset and Prenatal Diagnosis
In immediate post-natal imaging, hydrocephalus is
seen only in 15-25% of children with myelomeningo-
cele [5, 13], often as the result of aqueductal steno-
sis or occlusion [14]. Thereafter hydrocephalus can
be defined as congenital in only a few cases, while
in a significant proportion of the remaining children
it develops in the first weeks of life, usually following
closure of the back lesion.
The prenatal diagnosis of hydrocephalus is pos-
sible only in the second or third trimester, because
the lateral ventricles are physiologically large in the
early stages of development [15, 16]. During foetal
life, ventricular dilatation, with ultrasound and mag-
netic resonance imaging (MRI), is generally defined
as an atrium larger than 10 mm. The dilatation is con-
sidered to be severe when the atrium is larger than
15 mm and mild when the atrium is between 10 and
15 mm [17].
Intrauterine ventriculomegaly is a common
finding in foetuses with myelomeningocele. When
performing serial sonograms Babcook et al. [18]
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 204
204 G. Cinalli, P. Spennato, M.C. Buonocore, et al.
found that whereas only 44% of foetuses aged 24
gestational weeks or younger had ventriculomegaly,
94% of foetuses older than 24 gestational weeks had
ventriculomegaly. The degree of hydrocephalus cor-
related with the amount of the posterior fossa de-
formity.
Some ultrasonographic signs in the skull, such
as the lemon and banana signs (see Chapters 6, 9),
characteristic of foetuses with spina bifida and the
Chiari II malformation, can be demonstrated at an
early stage, even in the absence of ventricular di-
latation [19].
The natural history of foetal ventricular dilata-
tion is poorly defined even in the context of spina
bifida [17]. Aqueductal stenosis appears to be a fac-
tor that significantly worsens the prognosis, in-
creasing mortality and affecting neurological de-
velopment. For some authors [20], there is a sig-
nificant relationship between the severity of the
dilatation and future developmental delay. The prog-
nosis is considered poor if the dilatation increases
with time and, especially, if the increase in size is
fast [16, 17, 21].
Late Onset Hydrocephalus
Children with a clinical picture of active hydro-
cephalus, with significant ventriculomegaly and, of-
ten, periventricular lucency on computed tomo-
graphic (CT) scan, require treatment early in life.
Otherwise, children with mild or moderate ven-
triculomegaly and head circumferences within the
normal range may not need treatment, but an obser-
vation policy, monitoring head circumference and
a b
neuropsychological development, repeating the ul-
trasound and MR imaging [5].
However, even in the absence of active hydro-
cephalus and progressive macrocrania, the ventric-
ular system often remains dilated and distorted
(colpocephaly). The issue of neuropsychological de-
velopment in these children remains controversial [5].
It is quite common to observe older children or
young adults with dilated ventricles with no clinical
or radiological evidence of active hydrocephalus
(headache, drowsiness, diplopia, periventricular lu-
cency). The clinician should remember that the slow
and insidious progression that characterises the evo-
lution of this specific form of hydrocephalus might
lead to a wrong diagnosis of “arrested” or “com-
pensated” hydrocephalus, not requiring treatment: on-
ly serial IQs and psychometric testing may uncover
the presence of intellectual decline [22]. In a recent
study, a high incidence of intracranial hypertension
has been described following intracranial pressure
monitoring in patients with myelomeningocele and
untreated hydrocephalus [23]. In these cases, the
treatment of hydrocephalus appeared to improve IQ
and overall performance (Fig. 16.1).
Therefore, these patients should be followed up
with serial monitoring of intelligence and psycho-
metric performances. Absence of clinical symptoms
and stability on psychometric testing should dis-
courage shunting. In contrast, if either subtle symp-
toms or evident intellectual decline is diagnosed on
serial psychomotor testing, treatment or revision (in
case of already implanted shunt) should be pro-
posed. In case of doubt, invasive intracranial pres-
sure monitoring should be employed to clarify the
situation [5].
Fig. 16.1 a, b. Seven year-old girl af-
fected by myelomeningocele and
hydrocephalus. Shunted at birth, her
shunt was removed at the age of 2
months because of shunt infection
and never re-implanted because the
hydrocephalus was considered to
be “arrested”. She was admitted at
the age of 7 years for papilledema,
macrocrania and delayed psy-
chomotor development. a CT scan
shows hydrocephalus. b Significant
radiological and clinical improve-
ment was observed after ventriculo-
peritoneal shunt. Reprinted from [5]
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 205

Chapter 16 • Pathophysiology of Hydrocephalus 205

Associated abnormalities of the surrounding mes-

Chiari II Malformation and Hydrocephalus enchymal structures are responsible for a small poste-
rior fossa, a low-lying tentorium with a much-enlarged
Several mechanisms are implicated in the pathogen- tentorial incisura, a foreshortened clivus, and scallop-
esis of hydrocephalus in patients with myelomeningo- ing of the petrous bone [25]. However, the Chiari II
celes: aqueductal occlusion, fourth ventricular outlet
obstruction, obliteration of the subarachnoid space by
the crowded posterior fossa contents, obstruction at
the level of the tentorial hiatus, and venous abnor-
malities [5, 24, 25]. These mechanisms have a com-
mon origin in the Chiari II malformation.
The Chiari II malformation is present in virtual-
ly all patients with myelomeningoceles and the ma-
jority of patients with non-terminal myelocystoceles.
This malformation, first described by Hans Chiari in
1891 [26], involves the entire brain and the sur-
rounding structures (meninges and bones), but es-
pecially the posterior fossa [25, 27]. The most char-
acteristic finding is the hindbrain herniation; i.e., the
caudal displacement of the cerebellar tonsils and ver-
mis, together with the caudal brainstem (medulla and
occasionally the pons) through an enlarged, funnel
shaped foramen magnum into the cervical spinal
canal (Fig. 16.2). In some instances, the brainstem
becomes kinked (the medullary kink) due to the dor-
sal displacement of the relatively mobile medulla Fig. 16.3. Medullary kink. The ponto-medullary fissure is
combined with the spinal cord being fixed by the den- well below the level of the foramen magnum, medulla is dis-
tate ligament (Fig. 16.3). placed in the upper cervical canal. No CSF space is visible
Often the superior vermis and cerebellar hemi- in the posterior fossa
spheres are displaced cranially through the tentorial in-
cisura, lying within the middle fossa, beaking the col-
licular plate and compressing the aqueduct (Fig. 16.4).

Fig. 16.4. Upward herniation of the vermis through the

tentorial hiatus. Note the obliteration of the perimesen-
Fig. 16.2. Note the enlarged occipital foramen and the fun- cephalic cisterns, the compression and deformation of the
nel-shaped upper cervical canal with the low attachment mesencephalon (arrows) and the distortion and occlusion
of the tentorium of the aqueduct
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 206
206 G. Cinalli, P. Spennato, M.C. Buonocore, et al.
malformation also involves the supratentorial com-
partment: enlarged massa intermedia of the thalamus,
dysgenesis of the corpus callosum, beaking of the
quadrigeminal plate, polymicrogyria and cortical het-
erotopias are usually part of the malformation, togeth-
er with characteristic deformities of the skull, such as
lückenschädel or craniolacunia (characterised by ir-
regular patches of thinning or complete erosion of the
cranial vault), scalloping of the petrous pyramid, and
shortening of the clivus [28]. The ventricular system
appearance varies from nearly normal to severely de-
formed and hydrocephalic. The third ventricle is usu-
ally small, secondary to the collapse of the ventricular
system during foetal life. This also results in approxi-
mation of the thalami with a large massa intermedia.
The lateral ventricles, as a consequence of callosal dys-
genesis, cortical heterotopias and polymicrogyria, are
commonly deformed with the occipital horns dispro-
portionately enlarged compared with the frontal horns
(colpocephaly). This finding is often present even in
patients with myelomeningocele who do not have hy-
drocephalus, and frequently persists despite shunting.
In the past it was believed that this complex mal-
formation was part of an overall cerebrospinal dys-
genesis, but there is experimental and clinical evi-
dence that it is acquired in foetal life and progress-
es in severity before and after birth [18, 24].
In his initial theory, Chiari attributed the hindbrain
herniation to hydrocephalus [26]. However, this the-
ory failed to explain many of the features of the
Chiari II malformation. As shown on prenatal imag-
ing and in studies on the aborted foetal brain, hind-
brain herniation is often present prior to the appear-
ance of hydrocephalus [24]; moreover, 10-20% of
children with Chiari II malformation never develop
hydrocephalus [29]. In addition, the small posterior
fossa, low-lying torcular herophili, and upward
“herniation” of the vermis are not explained by this
theory. An alternative hypothesis has been suggest-
ed by Marin-Padilla and Marin-Padilla [30], who pro-
posed a primitive mesodermal disorder that resulted
in a low-volume posterior fossa and its overcrowd-
ing as the cause of hindbrain herniation. Padget pro-
posed a similar theory, in which chronic leaking from
the open spinal defect could be the cause of an “in-
duced” small posterior fossa [31]. However, these
theories fail to explain the widespread central ner-
vous system (CNS) abnormalities present in patients
with myelomeningocele. Also the “traction” theory,
in which the development of Chiari II malformation
could be secondary to pulling the hindbrain caudal-
ly by the open and tethered spinal cord, resulting in
the vermian and brainstem herniation [32], does not
explain all the features of Chiari II malformation.
In 1989 McLone and Knepper proposed their
unifying theory [33], which combined the features
of the abovementioned hypotheses. According to this
theory, the primum movens of the malformation is
the escape of CSF from the ventricular system
through the open neural tube. The absence of the
CSF driving force prevents full development of the
posterior fossa because both neural and calvarial de-
velopment are induced by ventricular distension. At
a later stage of intrauterine development, the growth
of the rhombencephalon becomes more rapid; there-
after the cerebellum and the brainstem are forced in-
to a small posterior fossa and pushed both cephal-
ad and caudad through the tentorial incisura and
foramen magnum.
The result of this disproportionate growth be-
tween the hindbrain and surrounding mesenchyme
is a tightly compacted posterior fossa with little room
[25]. This may also impede the development of the
CSF spaces.
Several interlinked factors may impair the CSF
pathway in Chiari II malformation: the vertical trans-
hiatal translocation of the brain stem and of the cere-
bellum causes increased resistance to CSF flow
through the tentorial incisura; crowding of the fora-
men magnum leads to occlusion of the foramina of
Luschka and Magendie that is often not patent and the
tela choroidea is dysplastic, distended and forms a sac
that can extend down to the thoracic level [3, 34]. The
under-developed subarachnoid space of the posterior
fossa obstructs the CSF flow towards the convexity
(Fig. 16.5); the small volume of the posterior fossa
due to the abnormally low insertion of the tentorium
may impede the egress of CSF and may also lead to
venous hypertension, impeding CSF resorption [5, 25,
27]. Therefore, hydrocephalus is the result and not the
cause of the Chiari II malformation.
To further support this is the observation that in
the small number of children who had intrauterine
repair of myelomeningocele, the incidence of hy-
drocephalus decreases from 91% to 59%. There is
also a suggestion that this technique may prevent or
reduce the severity of the Chiari II malformation [35,
36]. Tulipan et al. [37] theorise that by interrupting
the continuous flow of CSF through the neural pla-
code, the hindbrain can develop normally, and even
reverse abnormal development [37]. The ascent of
the hindbrain structures has been demonstrated us-
ing serial MRIs [38]. This may lead to improved flow
through the aqueduct, improved compliance of CSF
flow around the brain stem and the tentorial hiatus
and lower venous outflow pressure in comparison
with babies born with open myelomeningocele.
These factors may be more important than simple ob-
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 207

Chapter 16 • Pathophysiology of Hydrocephalus 207

Role of Aqueductal Stenosis

Obstruction of the sylvian aqueduct is frequently
found in MMC patients (Fig. 16.6a). It is secondary
to deformation of the midbrain, which is forced both
craniocaudally and ventrodorsally; the tectal plate as-
sumes a beak like configuration, so that the aque-
duct is progressively angulated to the point that, in
more severe cases, it assumes a V-shape pointing dor-
sally (Figs. 16.4, 16.6b). This, combined with the

Fig. 16.5. Note the severe crowding of the posterior fossa

with brainstem compression and deformation with hernia-
tion of the tonsils down to C5. Significant venous abnor-
malities are evident at the level of the quadrigeminal cistern

struction at the foramen magnum, considering that

the incidence of hydrocephalus in patients with Chiari
I malformation is much lower than in patients with
Chiari II malformation [5]. b
The presence of Chiari II malformation in MMC
often makes the clinical manifestations of hydro-
cephalus and of acute intracranial hypertension dur-
ing shunt malfunction quite peculiar. These typical-
ly exacerbate the clinical manifestations of the Chiari
II malformation, such as respiratory distress or up-
per extremity weakness, even in the absence of oth-
er more frequent and typical signs and symptoms of
intracranial hypertension [25, 39]. The treatment of
hydrocephalus usually resolves these symptoms, of-
ten avoiding the more complex (and morbid) cervi- Fig. 16.6 a, b. a Myelomeningocele patient at the time of
cal decompressive procedures [25]. For these reasons, shunt malfunction. Note the aqueductal stenosis. Agenesis
shunt malfunction should be always suspected and of the tentorium allows downward herniation of the later-
ruled out when dealing with any clinical worsening al ventricles with obliteration of the posterior third ventri-
cle, direct compression of the upper vermis, obliteration of
of an MMC patient. the fourth ventricle and creation of a functional aqueduc-
Due to anatomical anomalies of the ventricular tal obliteration. b Following endoscopic third ventricu-
system (enlarged massa intermedia, eccentric bulge lostomy, significant anatomical changes are evident: the
posterior third ventricle has reappeared, the aqueduct has
from the head of the caudate nucleus and anteriorly enlarged assuming the typical V-shape pointing anteriorly,
pointing frontal horns) associated with the Chiari II compression of the vermis has reversed with appearance
malformation, the foramen of Monro is particularly of the quadrigeminal cistern, but the fourth ventricle re-
predisposed to torsion and obstruction if overdrainage mains compressed and obliterated. The real cause of hy-
drocephalus in this case was not aqueductal stenosis but
occurs, possibly resulting in isolated lateral ventri- fourth ventricle and posterior fossa CSF space obliteration
cles after unilateral shunt placement [40, 41]. due to the hindbrain herniation
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 208

208 G. Cinalli, P. Spennato, M.C. Buonocore, et al.

crowding of the tentorial hiatus, creates a function- a

al obstruction (Fig. 16.6) [28]. Histologically, agen-
esis, stenosis or forking of the aqueduct is a classi-
cal feature in MMC, reported in Dandy's pioneering
work [42], which Gilbert found at autopsy in rough-
ly half of MMC patients [43]. The autopsy bias may
have exaggerated this figure, and this author gave no
indication as to whether stenosis was malformative
or secondary to infection, hemorrhage, or shunting
(Fig. 16.7a, b). When live patients studied with ven-
triculography were considered along with autopsy da-
ta, the prevalence of aqueductal stenosis was sub-
stantially lower, around 29% [44]. In live patients
studied with ventriculography at birth, the aqueduct
was often stenosed but never totally occluded [34].
Forking of the aqueduct, along with beaking of the
tectal plate, may be part of the deformation of the
brainstem caused by hydrocephalus, rather than its b
primum movens. The contribution of obstruction of
the aqueduct to the pathogenesis of hydrocephalus
in patients with myelomeningocele is under debate;
in fact, in contrast to typical aqueductal stenosis, the
remaining CSF pathways are also abnormal and de-
formed [5]. Some authors have even postulated that
the obstruction of the aqueduct could be the conse-
quence of long-standing hydrocephalus, which caus-
es axial herniation and entrapment of the midbrain
with secondary compression of the ependymal sur-
faces of the aqueduct, leading to obstruction [45].
As a result, in patients affected by myelomeningo-
cele and hydrocephalus, the finding of an obstruct-
ed or stenosed aqueduct is no guarantee in itself of c
a good outcome after endoscopic treatment.
In neuroimaging obtained early after birth in chil-
dren born with severe hydrocephalus, a large third
and a small fourth ventricle are usually seen, indi-
cating the important role of aqueductal stenosis at
least in congenital cases [5, 14].
While hydrocephalus in children born with
myelomeningocele is always related to Chiari II mal-
formation, in other forms of spina bifida, such as non-
terminal myelocystocele, it may also occur with no ev-
idence of hindbrain herniation. In these rare cases aque-
ductal stenosis has been suspected to play a determinant
role in the pathogenesis of hydrocephalus [12].

Role of Venous Hypertension
The driving force for CSF resorption is the difference
between CSF pressure and sagittal sinus pressure. In
the presence of Chiari II malformation, the small pos-
terior fossa volume and the abnormal anatomical dis-
position of the structures within it can lead to the com-
Fig. 16.7 a, b. a Six month-old baby boy with myelo-
meningocele, not shunted at birth, presenting with pro-
gressive macrocrania and hydrocephalus. b Note the defor-
mation of the aqueduct that looks open but is filled by a web-
like material. CSF spaces of the posterior fossa are well
represented except at the level of the occipital foramen. c
Hydrocephalus was successfully treated by endoscopic
third ventriculostomy
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 209
Chapter 16 • Pathophysiology of Hydrocephalus
pression of the sigmoid sinuses, which leads to ve-
nous hypertension [46]. Compression of the internal
cerebral veins, due to deformation of the midbrain,
may also contribute to venous hypertension (Fig. 16.5)
[5]. Usually, collateral venous pathways, through the
foramen magnum and/or through emissary veins and
scalp veins, progressively develop and allow a new
status quo to develop [47]. However, crowding of the
foramen magnum due to cerebellar herniation may pre-
vent the development of collateral venous pathways.
If the venous obstruction is not compensated, the in-
creasing of the sagittal sinus pressure results in a high-
er CSF pressure being required to maintain CSF bal-
ance. The final effect depends also on the degree of
cranial and brain compliance. In children with closed
sutures, intracranial pressure may rise to very high lev-
els, overcoming the high sagittal sinus pressure; this
permits absorption of CSF, with normal-sized or small
ventricles, as seen in some cases of pseudotumor cere-
bri [47]; in infants and children with open sutures, the
rise in CSF pressure may result in progressive hy-
drocephalus and intracranial hypertension [47].
The treatment of hydrocephalus with shunting
does not necessarily improve the venous compression
because the original cause is not removed. Otherwise,
reduction of CSF pressure with shunting may result
in accumulation of interstitial fluid and contribute to
deterioration of aqueductal stenosis due to interstitial
oedema [5, 46]. Intracranial hypertension can thus be-
come a self-aggravating phenomenon, with an ele-
ment of pseudotumor cerebri causing “normal volume
hydrocephalus” with compression of the lateral si-
nuses [48]. When MMC patients grow old, obesity
caused by diminished catabolism often becomes a se-
rious concern, and raised systemic venous pressure
can also interact with intracranial pressure.
Surgical procedures of internal diversion of CSF
(endoscopic third ventriculostomy [ETV]), bypassing
aqueductal occlusion and increasing brain compliance,
may be useful in these situations [5, 49]. As the pa-
tients get older however, a higher proportion can be
treated with endoscopic procedures [50]; this tends
to show that with time intraventricular obstructive fac-
tors become prevalent over extraventricular ones.
Role of Closure of Myelomeningocele
The onset of hydrocephalus is often temporally re-
lated to the surgical closure of the spinal defect. It
is not clear whether this is a causative relationship,
or whether the operation simply precipitates an in-
evitable event [5]. Very rarely, the babies deteriorate
dramatically following closure of the neural sac. The
209
mechanism of this deterioration is multifactorial. Clo-
sure of the myelomeningocele may eliminate the
spinal defect as a drainage pathway [38]. A signifi-
cant role appears to be played by the impaction of
the hindbrain herniation [5]. As already mentioned,
the primary cause of hindbrain herniation is in utero
escape of CSF through the open neural tube. Further
loss of CSF during the first days of life and during
the surgical closure of the defect may result in de-
terioration of the herniation of the hindbrain and the
associated hydrocephalus [5], leading to acute neu-
rological deterioration. This is secondary to in-
tracranial hypertension related to the hydrocephalus
and to brain stem dysfunction related to impaction
of the hindbrain in the foramen magnum. Shunting
usually reverses this neurological status [5, 13].
Role of Associated Cerebral Malformations
Spina bifida is one of the commonest congenital mal-
formations and may be associated with several oth-
er malformations directly or indirectly related to the
neural tube defect [5, 51]. Some of these may fur-
ther impair CSF pathways. Severe forms of dys-
raphism, with the presence of bifid cranium, cervi-
cal myelomeningocele, and encephalocele are asso-
ciated with a high incidence of severe hydrocephalus
and a poor prognosis [5].
A non-random association between neural tube
defects (anencephaly, spina bifida) and holoprosen-
cephaly has been reported [51], indicating a possi-
ble common insult occurring early in embryological
life [52]. Usually such an association is not com-
patible with life and had been described in about 20%
of aborted embryos or foetuses with myeloschisis
[53]. However, viable infants affected by both mal-
formations have been reported [52]. In these cases,
atresia of the aqueduct of Sylvius, secondary to mes-
encephalosynapsis and/or rhomboencephalosynapsis
(fusion on the midline of the colliculi and/or cere-
bellar hemispheres) may be responsible for the se-
vere congenital hydrocephalus [51].
Subependymal grey matter heterotopias are often
part of Chiari II malformation. Occasionally, they
may project into the ventricles, causing narrowing
and, possibly, obstructing crucial areas (foramen of
Monro) [54].
Arachnoid Thickening
Another factor that could explain the lower incidence
of hydrocephalus following uterine reparation of
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 210
210 G. Cinalli, P. Spennato, M.C. Buonocore, et al.
MMC is the possible resolution of subarachnoid
space contamination with amniotic fluid. In fact, the
arachnoid of patients with MMC is frequently thick-
ened, especially at the level of the foramen magnum
[55] and tentorial incisura [56]. In an experiment pub-
lished in 1935 (and not in accordance with present
ethical standards), Russell found that when India ink
was injected into the ventricles of moribund MMC
patients, postmortem study found that its diffusion
was restricted to the spinal meninges, although in
some cases, a faint supratentorial diffusion was
found; she concluded that the degree of obstruction
of the ventricles was variable [57]. The free com-
munication between the arachnoid space and the am-
nion during intrauterine life, illustrated by sponta-
neous pneumocephalus diagnosed at birth [58], has
raised the hypothesis that prenatal meningeal irrita-
tion by amniotic fluid could induce chronic arach-
noiditis, thus adding a potential additional factor to
the complex pathophysiology of hydrocephalus in
MMC (Fig. 16.8).
Among 116 foetuses operated in utero for MMC
and followed at least one year after birth, the shunt-
ing rate was 58%, compared to 93% in a historical
cohort (MMC operated at birth in the same institution)
[59, 60]. As early prenatal closing of the MMC (hence
a shorter duration of exposition to amniotic fluid) ap-
peared to be a decisive factor for the prevention of
hydrocephalus in myelomeningocele (MMH), these
Fig. 16.8. Adolescent affected by MMC presenting with
shunt malfunction. Endoscopic third ventriculostomy was
attempted but resulted in a technical failure. After perfora-
tion of the third ventricular floor, dense arachnoid scarring
completely filling the interpeduncular cistern was found,
making communication with open subarachnoid spaces im-
possible. Retrospectively, dense web-like material is visible
in the interpeduncular cistern on pre-operative MRI
authors considered that these data back the hypothe-
sis that exposition to amniotic fluid plays a role in the
pathogenesis of MMH [59]. However, the two groups
of patients compared (before and after the introduc-
tion of intra-uterine repair) were not contemporary, the
follow-up was short, and several biases restrict the
reach of these figures. In particular, antenatal hydro-
cephalus is considered a contraindication for in utero
repair; and having endured an in utero repair is also
a strong motivation for the child's parents to resist
shunting at birth. Furthermore, as will be discussed
below, the rate of shunting in patients operated after
birth may be as low as 51%, depending on the sur-
geon's tolerance to ventriculomegaly [61]. These da-
ta are not sufficient to ascertain the role of meningeal
fibrosis as a causative factor in MMH.
Moreover, intrauterine surgery appears to increase
the risk of several obstetrical complications, such as
oligohydramnios, premature rupture of membranes,
premature uterine contractions, premature delivery,
uterine ruptures, placental abruption and maternal
bowel obstruction [62, 63]. Finally, the apparent ben-
efit may be due to selection bias; in fact, only a small
number of mothers and foetuses in very good con-
dition are considered for intrauterine repair. Only a
prospective, randomised trial will be able to answer
these concerns.
Communicating or Obstructive Hydrocephalus?
This issue is not without importance, due to the wide-
spread use of ETV in the treatment of obstructive hy-
drocephalus in the last decade. ETV has been pro-
posed in the management of hydrocephalus with
myelomeningocele since the mid 90s, but its role re-
mains controversial. The results, especially in the cas-
es where ETV has been performed as first line of
treatment in younger babies, are not encouraging,
with a success rate rarely exceeding 30% [64-66],
indicating that, in these patients, the form of hydro-
cephalus is mainly of the communicating type. Bet-
ter results were achieved in older patients who un-
derwent ETV as a secondary procedure at the time
of shunt malfunction, in whom the reported success
rate is above 70% in most series [64-66]. These da-
ta indicate a mainly obstructive hydrocephalus in old-
er children. However, some authors failed to observe
significant differences in relation to age and previ-
ous shunting [67, 68].
Recently, specific CSF biomarkers (transforming
growth factor α1 [TGFα1] and aminoterminal
propeptide of type 1 collagen [PC1NP]) have been
found to be indicative of growth factor- and fibro-
203_000_16_Cinalli:Cinalli 22-04-2008 15:16 Pagina 211
Chapter 16 • Pathophysiology of Hydrocephalus
sis-related CSF malabsorption in hydrocephalic pa-
tients [69, 70]. Thereafter, finding of such biomark-
ers in CSF samples could discriminate between the
presence and the absence of CSF malabsorption,
which should indicate communicating hydro-
cephalus. Heep et al. [71], assessing CSF samples
during interventions performed in hydrocephalic in-
fants, found relative low TGFα1 and PC1NP CSF
concentrations in spina bifida patients and aqueduc-
tal stenosis patients, compared with high values in
case of post-haemorrhagic hydrocephalus. These da-
ta indicate that, in spina bifida and non-haemorrhagic
triventricular hydrocephalus, CSF obstruction, rather
than malabsorption, may play a pivotal role in the
pathogenesis of hydrocephalus [71].
The recent views on the pathophysiology of hy-
drocephalus enhance the importance of intracranial
compliance that is widely dependent on the free move-
ment of the CSF between the cranial and the spinal
subarachnoid spaces. According to Greitz [49], any
processes that interfere with the expansion of the ar-
teries in the subarachnoid space and with the pulsatile
CSF flow may cause communicating hydrocephalus.
In Chiari I and II malformations, the impairment to
the pulsatile flow at the level of the foramen magnum
may be the main cause of hydrocephalus. In these cas-
es intracranial compliance may be restored by poste-
rior fossa decompression, which simply recreates com-
munication with the compliant spinal canal [49]. The
diversion of CSF following shunting also increases
brain compliance because it causes a forced dilation
of the compressed cortical veins. This increases ve-
nous compliance, decreases vascular resistance and in-
creases cerebral blood flow [49]. Greitz also consid-
ers third ventriculostomy potentially successful in
these forms of hydrocephalus [49]. The surgically cre-
ated opening into the subarachnoid space ultimately
should reduce the intraventricular pulse pressure, due
to increased expulsion of ventricular CSF during sys-
tole. This in turn will reduce the transmantle pulsatile
stress, reduce ventricular size and expand the sub-
arachnoid spaces including the compressed cortical
veins, thus again restoring intracranial compliance and
cerebral blood flow.
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