|Recurrent posterior reversible encephalopathy syndrome in a hypertensive patient with end-stage renal disease
|Tarkan Ergün1, Hatice Lakadamyalı1, Aynur Yılmaz2
|1From the Departments of Radiology, Başkent University School of Medicine, Antalya, Turkey
2Departments of Neurology, Başkent University School of Medicine, Antalya, Turkey
|Keywords: • kidney failure, chronic • hypertension • recurrence • posterior reversible leukoencephalopathy syndrome
Posterior reversible encephalopathy syndrome (PRES)
is a clinical and radiologic entity characterized by
headache, variable mental status, epilepsy, visual disturbances,
and typical transient changes in the posterior
cerebral perfusion. Recurrence of PRES is not
common, but increasingly in recent years, studies
demonstrate recurrence of this syndrome in populations
with different diseases. In this report, we describe
recurrent PRES in a hypertensive patient with
end-stage renal disease, and discuss recurrence as
the least-characterized feature of PRES. This condition
can cause neurological sequelae such as persistent
brain damage and epilepsy, arising from delays in
diagnosis and therapy. To the best of our knowledge,
this is the first report demonstrating recurrent PRES
in a patient on hemodialysis for end-stage renal disease.
Posterior reversible encephalopathy syndrome (PRES) is a clinical
and radiologic entity characterized by headache, variable mental
status, epilepsy, visual disturbances, and typical transient changes
in the posterior cerebral perfusion[1
]. Although reports of recurrence of
this syndrome in different patient populations have increased recently
in the literature, there is no information about recurrence of this syndrome
in patients with end-stage renal disease undergoing hemodialysis[2
]. Here, we present a case of recurrent PRES in a patient with end-stage
renal disease in a hemodialysis program, who responded well to treatment,
and whose clinical and radiological (conventional magnetic resonance
imaging [MRI]) findings improved.
A 23-year-old woman with end-stage renal disease was brought to our
emergency department with complaints of headache, nausea, vomiting,
loss of conscience, and tonic-clonic seizures involving her arms and legs.
The patient had been undergoing hemodialysis three times per week.
She had multiple congenital anomalies including agenesis of the left
thumb, meningocele, ventricular septal defect, ectopic single kidney,
and defective segmentation of the lumbosacral vertebrae. At the time
of admission, she was in a state of post-ictal confusion, and she experienced
seizures in the emergency department.
Following partial resolution of her confusion, she experienced headache
and loss of vision. She was somnolent, and she showed partial response
to verbal stimulation. She did not have findings of meningeal
irritation. Her visual acuity was decreased, but she could perceive hand
movements. Her pupils were isochoric, and direct and indirect light
reflexes were normal. Ocular examination revealed that the borders of
right disc were not clear. There was no limitation of her gaze. Motor and
sensory examinations were normal. Deep tendon reflexes were equal
and normoactive bilaterally, and Babinski sign was absent bilaterally.
On admission, her blood pressure was 280/160 mmHg, which decreased
gradually to 160/110 mmHg with antihypertensive medication.
The day after admission was the patient's scheduled hemodialysis. Her
laboratory tests on admission were as follows: hemoglobin, 11.2 g/dL;
hematocrit, 33.4%; white blood cells, 8900/mm3, 62% segmented; platelets,
223,000/mm3; blood urea nitrogen, 54 mg/dL; creatinine, 15.1 g/
dL; Na, 141 meq/L; K, 5.3 meq/L; Cl, 107 meq/L; P, 5.7 mg/dL (slightly
elevated). Her liver function tests, total protein, albumin, and calcium
levels were normal.
Computed tomography of the brain was normal, but there were slight
impairment of baseline activity, and paroxysmal lateralizing epileptiform
discharges on her electroencephalogram. MRI revealed edema in
the posterior cerebral region, with preservation of the calcarine fissure and paramedian lobe (Fig. 1). Diffusion
MRI was not performed because this
feature was not available at our hospital.
Additionally, there were lesions
in the subcortical white matter of both
Click to Enlarge
|Figure 1: Axial fluid-attenuated inversion recovery (FLAIR) MR images show symmetrically located, bilateral hyperintense lesions in the parietooccipital
regions affecting the cortex and subcortical white matter.
The patient was hospitalized in the
intensive care unit, and her blood
pressure was carefully monitored and
controlled. With treatment for edema,
anticonvulsive medication, hemodialysis
every other day, and supportive
care, her mean blood pressure was
120/80 mmHg, blood urea nitrogen
35 mg/dL, and creatinine 10.1 mg/dL
(after hemodialysis). There was no
electrolyte imbalance. Her vision had
been restored completely by approximately
one week after admission. Reevaluation
with MRI three weeks later
showed complete resolution of previously
described abnormalities (Fig. 2).
She did not experience any further seizures
during her hospitalization.
Click to Enlarge
|Figure 2: Axial fluid-attenuated inversion recovery (FLAIR) MR images reveal that the lesions
have disappeared completely following treatment.
The patient presented to the emergency
department again six weeks after
her previous admission, with the
complaint of loss of vision. Her blood
pressure was 240/130 mmHg, and her
physical findings were normal other
than a decrease in visual acuity. Her
blood urea nitrogen was 54 mg/dL, and
creatinine was 10.1 mg/dL. Her electrolytes
and liver enzymes were normal.
Cranial MRI revealed a new edematous
lesion 2 cm in diameter at the right
centrum semiovale (Fig. 3). The patient's
visual disturbance improved in
a short time with intravenous antihypertensive
and supportive treatment. This lesion
had resolved at follow-up MRI three months later. Cortical and subcortical
changes attributable to chronic hemodialysis
and end-stage renal disease
were found on MRI two years later. Two
additional years later, the patient died
from a cardiovascular complication.
Click to Enlarge
|Figure 3: Axial fluid-attenuated inversion
recovery (FLAIR) MR image shows a 2-cm
edematous lesion at the right centrum
semiovale at the time of posterior reversible
encephalopathy syndrome (PRES) recurrence.
Lesions observed during the patient's initial
hospitalization for PRES had resolved.
PRES is characterized by mental impairment,
headache, epilepsy, and
visual disturbances, and is frequently
seen in patients receiving chemotherapy.
The lesions generally disappear
with appropriate treatment, although
reversibility of the lesions depends on
the underlying disease and location of
the lesions. In addition, different signal
characteristics on MRI may affect
the degree to which lesions appear to
]. Although there are
reports in the literature concerning
the development of new PRES lesions following complete disappearance of
lesions from a previous episode, there
is no information about this condition
in patients with end-stage renal disease
on chronic hemodialysis[2
Hypertensive encephalopathy, eclampsia,
immunosuppressive and cytotoxic
medications, renal failure with
hypertension, collagen vascular disease,
purpura, human immunodeficiency
virus (HIV) infection, acute intermittent
porphyria, and organ transplantation
are among the known conditions
associated with PRES. Of the
limited cases of recurrent PRES in the
literature, the underlying diseases were
rheumatologic diseases in two cases[2,5], bone marrow transplantation
in one case, and sickle cell anemia in
one case. Among patients undergoing
chronic hemodialysis for end-stage
renal disease, our patient is the first to
have developed recurrent PRES.
In PRES, factors that trigger the development
of new lesions following
complete disappearance of the edematous
lesions of an acute episode are not
fully understood. Sweany et al. suggest
that infections might trigger the development
of new lesions in patients with
recurrent PRES unrelated to inflammation; however, there was no infection
in our patient at the time of development
of the recurrent lesion.
Information about recurrent PRES is
limited; however, the time period for
the development of a new lesion is reported
to be at least 30 days, and at
most, two years. The time to recurrence
was six weeks in our case.
Two possible mechanisms have been
proposed in the pathophysiology of
PRES. The first is vasospasm due to
acutely increased blood pressure, and
the second is loss of autoregulation.
In the first hypothesis, it has been suggested
that vasospasm contributes to
ischemia and cytotoxic edema at regions
of the arterial border zone.
The second, more recent hypothesis is
supported by diffusion images suggesting
that dilation develops in cerebral
arterioles due to autoregulatory failure.
The objective of cerebral autoregulation
is to keep blood flow constant, and
to protect the brain during changes in
blood pressure; however, sudden and
severe increases in blood pressure can
impair autoregulation, and such impairment
can, in turn, lead to arteriolar
vasodilation and endothelial dysfunction. In this condition, plasma and red
blood cells migrate to the extravascular
space from the intravascular space,
and vasogenic edema occurs. Thus,
it is reasonable to infer that the lesions
of PRES would have a predilection for
the parieto-occipital region, because
the posterior cerebral arterial circulation
has a lower level of sympathetic
Despite the fact that cases of PRES
have been reported with only slight
increases in blood pressure in patients
with preeclampsia or eclampsia, or
in patients receiving immunosuppressive
therapy, many authors have
accepted that PRES was caused by an
acute increase in blood pressure.
There is a risk of development of hypertensive
encephalopathy in patients
who experience a sudden increase in
blood pressure to a level 30% greater
than that of the normal blood pressure
for persons of that age. There is no association
between the severity of hypertension
and the prognosis in PRES;
leukoencephalopathy findings are
found to improve in most cases within
Areas of low attenuation are seen in
posterior white matter in computed
brain tomography of patients with
PRES. On MRI, bilateral symmetrical
edema in the parieto-occipital region,
supplied by the posterior cerebral
circulation, is hyperintense on T2-
weighted and fluid-attenuated inversion
recovery (FLAIR) sequences, and
hypointense on T1-weighted sequences.
The calcarine fissure and paramedian
lobe generally are not affected.
This is helpful in the differential diagnosis
of bilateral posterior cerebral
artery infarcts (embolus at the basilar
tip). In basilar tip embolism, thalamic
and mid-cerebral infarcts generally accompany
involvement of the calcarine
region. Although PRES typically affects
the parietal and occipital lobes, lesions might develop in locations other than
the parieto-occipital region in atypical
PRES, as in our recurrent case. The
diagnosis is difficult in such cases; history
of previous occurrence of PRES,
and the presence of diagnostic criteria
) are helpful[12
There is high signal intensity in apparent
diffusion coefficient (ADC)
maps in PRES. Signal intensity of the
lesion is normal or decreased in diffusion-
weighted MR images. Vasogenic
edema of PRES (low signal in diffusion
weighted MR images) is differentiated
from cytotoxic edema, which indicates
acute cerebral infarct (high signal in
diffusion-weighted images) by such
characteristics. We did not perform diffusion
MRI, which might have provided
valuable information in this case,
because this feature was not present at
our hospital. The bright signal that is
seen on diffusion-weighted MR images
of some cases might be related to high
T2 signal due to increased fluid content
in the area of vasogenic edema.
ADC maps that remove the underlying
T2-signal effect differentiate vasogenic
edema (increased ADC) from cytotoxic
edema (decreased ADC). A few cases in
which vasogenic and cytotoxic edema
were reported together had complete
resolution of the vasogenic edema
associated with PRES.
Click to Enlarge
|Table 1: Diagnostic criteria for posterior reversible encephalopathy syndrome (PRES) \(12\)
Magnetic resonance spectroscopy
evaluations have revealed high lactate,
and normal N-acetylaspartate/creatine
and N-acetylaspartate/choline levels in
Early diagnosis and treatment of
PRES is particularly important. Without
prompt treatment, the syndrome
may lead to permanent brain injury or
neurological sequelae such as chronic
epilepsy. Despite the absence of neurological
sequelae attributable to PRES in
our patient, corticomedullary malacia
was seen due to hemodialysis and endstage
renal failure. Cerebral and cerebellar atrophy are seen frequently in
patients with uremia, and may manifest
as cortical or subcortical atrophy,
or a combination of both. Histopathologic
evaluation shows loss of neurons
and nerve fibers. Cerebral atrophy in
patients with uremia may be related to
chronic anemia and a decrease in tissue
oxygenation due to hypertensive
heart failure. Vascular calcification due
to hyperparathyroidism and/or dyslipidemia
and systemic hypertension may
also contribute to the development of
atrophy via compromise of the vasculature
of the brain.
Moreover, sudden pressure changes
due to hemodialysis in hypertensive
patients with volume overload may
lead to brain injury. Although
Al(OH)3 is no longer a component of
dialysate solution, previous intoxication
from this compound remains one
of the major causes of cerebral atrophy
in patients undergoing hemodialysis.
First-line treatment of PRES is to
regulate blood pressure. Mean arterial
pressure should be reduced 20–25%, or
diastolic pressure should be lowered to
100 mmHg within the first 1–2 hours.
Rapid decrease in blood pressure should
be avoided due to the risk of hypoperfusion and consequent cerebral infarction
or impairment of organ function.
In this report, we presented the first
case of recurrent PRES in a patient undergoing
chronic hemodialysis for endstage
renal disease. Although PRES is a
rare condition, in light of new clinical
and radiological findings, the possibility
of recurrence should be considered in
various patient groups with a history of
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