Hemodialysis International 2011; 15:S64–S67

Medulloblastoma presenting as dialysis
disequilibrium syndrome
Robertino DILENA,1 Fabio PAGLIALONGA,2 Sergio BARBIERI,1 Alberto EDEFONTI2
1

Department of Neurological Sciences, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
Milan, Italy; 2Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore
Policlinico, Milan, Italy

Abstract
Dialysis disequilibrium syndrome (DDS) is a central nervous system disorder that occurs during or
after hemodialysis. This is caused by brain edema that manifests as neurological symptoms that
include headache, emesis, nausea, blurring of vision, disturbed consciousness, tremors and seizures, and in severe cases, death. The incidence of DDS is very high among patients with
preexisting neurological diseases. There has been much debate about the origin of DDS. We report
a case of DDS, as presenting syndrome of a medulloblastoma in a child aged 5 years, and discuss
the pathogenesis and the possible role of DDS for an earlier detection of occult brain lesions in
dialyzed patients.
Key words: Headache,
medulloblastoma

renal

dialysis,

dialysis

INTRODUCTION
Dialysis disequilibrium syndrome (DDS) is the clinical
manifestation of an acute neurological dysfunction, attributed to cerebral edema occurring during hemodialysis
treatment. It is necessary to keep in mind that preexisting
neurological conditions can reduce the intracranial compliance and consequently increase the probability of the
hemodialysis-associated brain edema to become symptomatic, causing the so-called DDS.

CASE REPORT
A 5-year-old boy with end-stage renal disease, due to
congenital anomalies of kidneys and urinary tract, was
shifted from peritoneal dialysis, performed since the age of
6 months, to hemodialysis, because of recurrent peritoniCorrespondence to: R. Dilena, MD, Department of
Neurological Sciences Fondazione IRCCS Ca’ Granda
Ospedale Maggiore Policlinico, via Francesco Sforza 35,
20122 Milan, Italy. E-mail:
robertino.dilena@policlinico.mi.it

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disequilibrium

syndrome,

hydrocephalus,

tis. During the previous year, two renal transplants had
been performed and failed due to renal thrombosis. After
his third hemodialysis treatment, the boy complained of
headache during the session. The headache had frontal
location and throbbing quality, onset 1 hour after the
beginning of hemodialysis, of increasing intensity (the
child often cried desperately), and ended with the end of
treatment. Nausea and vomiting were sometimes associated with the headache.
Dialysis prescription (as regards small solutes removal)
was adequate and predialysis blood urea nitrogen (BUN)
was 140 mg/dL. Intradialytic mannitol infusion, sodium
profiling, and reduction of blood flow rate proved unsuccessful in improving the symptoms.
One month after the first hemodialysis-related headache, short episodes of mild headache started to appear
occasionally in between the hemodialysis sessions. Family
history was positive for migraine (father and maternal
grandmother). The neurological examination was normal.
A diagnosis of dialysis headache, supported by familiar
susceptibility to migraine, was at first considered
(Table 1), but unusual headache intensity, occurrence of
vomiting, and then initial signs of bilateral papilledema

© 2011 The Authors
Hemodialysis International © 2011 International Society for Hemodialysis
DOI:10.1111/j.1542-4758.2011.00604.x

Medulloblastoma presenting as DDS

Table 1 Diagnostic criteria for dialysis headache according
to the second edition of the International Classification of
Headache Disorders3
Diagnostic criteria of dialysis headache
A.

At least three attacks of acute headache, fulfilling
criteria C and D
B. Patient is on hemodialysis
C. Headache develops during at least half of hemodialysis
sessions
D. Headache resolves within 72 h after each hemodialysis
session and/or ceases altogether after successful
transplantation

suggested intracranial hypertension. Brain computed
tomography (CT) scan revealed a triventricular dilatation
related to an isodense mass in the posterior fossa. Brain
magnetic resonance imaging (MRI) confirmed the presence of ventricular dilatation, showed transependymal
absorption and a median large cerebellar mass,
hypointense in T1, hyperintense in T2, having dishomogeneous gadolinium enhancement (Figure 1). A radical
surgical resection of the mass was performed: the pathological diagnosis was “desmoplastic medulloblastoma
with extensive nodularity.” After surgery, no more headache or other symptoms of DDS occurred.

DISCUSSION
To our knowledge, this is the first report of a medulloblastoma presenting with DDS. DDS, first described in
1962 by Kennedy et al.,1 is a clinical manifestation of an

acute neurological dysfunction attributed to cerebral
edema occurring during hemodialysis treatment or within
24 hours following hemodialysis. DDS manifests as variable combination of symptoms of different severity that
include headache, nausea, vomiting, disorientation,
blurred vision, tremors, muscle twitching, hypertension,
seizures, coma.2 When DDS is mild and characterized by
headache, it needs to be distinguished by dialysis headache (as defined by the diagnostic criteria of the International Classification of Headache Disorders,3 Table 1).
When severe, it can lead to death, due to massive cerebral
edema. New patients, just being started on hemodialysis,
are at higher risk to develop DDS, particularly if the BUN
is markedly elevated (above 175 mg).4 Also, young age is
a risk factor for DDS. Important predisposing factors2 are
the preexisting neurological conditions, particularly
intracranial lesions (subdural hematoma, head trauma,
recent stroke, hydrocephalus, brain tumors) or conditions
associated with cerebral edema (hyponatremia, hepatic
encephalopathy, malignant hypertension, rapid elevation
of pCO2, severe metabolic acidosis, severe sepsis). Several
cases of DDS in patients with intracranial lesions, such as
head injury,5 intracerebral hemorrhage6 and hydrocephalus,7 have been reported and the direct measurement of
intracranial pressure (ICP) in these patients has shown
that ICP increases significantly during hemodialysis.
Animal experimental studies8,9 have shown that DDS is
caused by brain edema, as a result of rapid hemodialysis,
which determines an osmotic gradient between brain and
plasma. Data from neuroimaging in humans support this
finding. Brain CT scans in uremic patients undergoing
intermittent hemodialysis have shown a decreased density,

Figure 1 Brain magnetic resonance imaging: (a) FLAIR sequence, ventricular dilatation with transependimal absorption; (b) T2
sequence, hyperintense cerebellar mass sized 4.5 ¥ 3.5 ¥ 3 cm; (c) T1 sequence, dishomogeneous gadolinium enhancement.

Hemodialysis International 2011; 15:S64–S67

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Dilena et al.

Figure 2 The pressure (P)–volume (V) curve of the intracranial compartment is exponential. If intracranial pressure
(ICP) is within the normal range (point a), small volume
increases leave the ICP substantially unchanged. If basal ICP
is high (point b), similar small volume increases determine a
steep rise of ICP (point c).

which gives evidence of an increased brain water content.10 Diffusion-weighted MRI in nephrectomized
animals and humans after an initial hemodialysis treatment has shown the presence of interstitial brain
edema.10,11 Regarding the pathogenesis, the current evidence12 suggests that urea disequilibrium (according to
the so-called “reverse urea effect theory”) and perhaps (to
a minor degree) organic osmolytes contribute to cerebral
edema. According to the first theory (“the reverse urea
effect”), during hemodialysis the clearance of urea is
slower across blood–brain barrier than across dialytic
membrane (from plasma to dialysate), generating an
osmotic gradient that produces water movement into
brain tissue, finally causing brain edema.13 This theory has
been demonstrated in experimental animals.8,9 In peritoneal dialysis, where the clearance of urea is more gradual,
DDS never happens. The second proposed mechanism for
brain edema related to hemodialysis, the so-called “idiogenic osmoles theory”, states that an osmotic gradient
between brain and plasma develops during rapid dialysis
because of newly formed brain organic osmolytes.13
However, according to some more recent evidence,14 it is
unlikely that organic osmolytes (like glutamine,
glutamate, taurine, and myoinositol) can have an important contribution to cerebral edema in DDS, because they
do not significantly rise after hemodialysis.
In our patient, the DDS was caused by the combined
effects of an occult brain tumor and the added brain
edema caused by hemodialysis. Pathogenesis is easily
understood looking at the exponential pressure–volume
relationship of the intracranial compartment (Figure 2).
The raising of ICP reflects the relationship between alterations of the craniospinal content volume and the compliance, which is the ability of craniospinal axis to
accommodate added volume.15 Considering that the brain
is enclosed in a nonexpandable case of bone and that the
brain parenchyma is nearly incompressible, a new slowly

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growing intracranial volume (like a tumor) displaces
venous blood and cerebrospinal fluid (CSF), initially producing a little change in ICP and no symptoms. However,
in doing so, the ability to accept other volumes and even
the cerebral blood flow component of the cardiac cycle is
decreased and becomes clear where other volume is
added.15
In other words, compared with normal intracranial
system (Figure 1, point a) in patients with a pathological
intracranial mass, like our patient, the compensatory
reserve of intracranial system is low (Figure 2, point b).
Consequently, while in normal intracranial systems the
modest parenchymal swelling added by hemodialysis
treatment is compensated and asymptomatic, in pathological intracranial systems (Figure 2, point c) it is sufficient to cause a steep rise of ICP, producing acute
symptoms of DDS.
In conclusion, when evaluating patients who develop
neurological symptoms during hemodialysis, DDS must
be differentiated from dialysis headache, the former presenting with symptoms of intracranial hypertension. DDS
suggests a reduced compliance of intracranial compartment, especially when it persists despite optimal hemodialysis prescription: in these cases, a neuroimaging study
needs to be urgently performed. Therefore, hemodialysis
can paradoxically allow an earlier diagnosis of unknown
and potentially treatable intracranial lesions.

Manuscript received March 2011; revised August 2011.

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