DOI:10.2214/AJR.05.0328
AJR 2007; 188:219-221
© American Roentgen Ray Society
Atypical Imaging Findings in a Near-Fatal Case of Posterior Reversible Encephalopathy Syndrome in a Child
Harold F. Keyserling1 and
James M. Provenzale1
1 Both authors: Department of Radiology, Duke University Medical Center, Box
3808, Durham, NC 27710.
Received February 25, 2005;
accepted after revision June 2, 2005.
Address correspondence to H. F. Keyserling.
Keywords: brain • CNS • CT • encephalopathy • hypertension • MRI • posterior reversible encephalopathy syndrome
Introduction
The term "posterior reversible encephalopathy syndrome" (PRES)
refers to a complex of symptoms usually manifested by headache, confusion,
seizures, visual disturbances, or a combination of these symptoms. PRES
usually occurs in the setting of an acute rise in blood pressure, and in
recent years, PRES has been recognized as a complication of immunosuppressive
and chemotherapeutic agents including cyclosporine A and L-asparaginase
[1,
2]. Imaging findings are
characteristic and consist of typically unenhancing lesions that predominate
in the white matter of the posterior brain regions, seen as hypodense regions
on CT and hyperintense areas on T2-weighted MR images. We report an unusual
case in which a child with PRES developed contrast-enhancing lesions with
marked mass effect in the posterior fossa that resulted in cerebellar
tonsillar herniation and cardiac arrest.
Case Report
A 7-year-old boy with B-cell lymphoblastic lymphoma experienced two
5-minute episodes of complex partial seizures on day 20 of outpatient
chemoinduction therapy with L-asparaginase. Brain CT at another institution
was reportedly negative. The patient was admitted to our institution where his
initial blood pressure was 133 over 96 mm Hg and neurologic examination was
normal. Brain MRI on the day of admission showed small areas of hyperintense
T2 signal in the left occipital lobe with facilitated diffusion and mild
contrast enhancement (Figs. 1A
and 1B). The presence of
systemic hypertension was not reported to the interpreting radiologist. A
differential diagnosis including infective cerebritis and lymphomatous
involvement of the CNS was offered. The boy was treated with IV anti-epileptic
medication and empiric broad-spectrum antibiotics.
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Fig. 1A —7-year-old boy with seizures who was being treated with
L-asparaginase chemoinduction therapy for B-cell lymphoblastic lymphoma. Axial
T2-weighted brain image on day of initial seizure shows small area
(asterisk) of cortical and subcortical hyperintense signal
abnormality in posterior left occipital lobe.
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Fig. 1B —7-year-old boy with seizures who was being treated with
L-asparaginase chemoinduction therapy for B-cell lymphoblastic lymphoma.
Contrast-enhanced axial T1-weighted image obtained at same time as A
shows small patchy foci of enhancement (asterisk) in area of T2
signal abnormality.
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On hospital day 4, the patient experienced two seizures followed by
obtundation. At this time, his blood pressure was 177 over 112 mm Hg.
Contrast-enhanced brain CT showed masslike enhancing lesions with vasogenic
edema in the frontal, parietal, and occipital lobes bilaterally and in both
cerebellar hemispheres (Figs.
1C and
1D). Posterior fossa mass
effect, with effacement of the basilar cisterns and fourth ventricle and with
inferior displacement of the cerebellar tonsils, was present. Because of the
rapid development of these imaging findings, a diagnosis of an aggressive
infective process was considered most likely in an immunosuppressed child. The
clinical team was notified of the marked mass effect within a few minutes of
completion of the scan, and a neurosurgical consultation was obtained shortly
thereafter. Later the same day, the patient experienced cardiac arrest and was
immediately resuscitated, at which time a ventriculostomy was placed.
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Fig. 1C —7-year-old boy with seizures who was being treated with
L-asparaginase chemoinduction therapy for B-cell lymphoblastic lymphoma. Axial
unenhanced CT scan of brain obtained 3 days after MRI at time of additional
seizures and obtundation shows hypodensity in cerebellar hemispheres
(asterisks) with mass effect, effacement of fourth ventricle, early
hydrocephalus, and cerebellar tonsillar herniation through foramen magnum (not
shown).
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Fig. 1D —7-year-old boy with seizures who was being treated with
L-asparaginase chemoinduction therapy for B-cell lymphoblastic lymphoma. Axial
contrast-enhanced CT scan of brain obtained at same time as C shows
masslike enhancement in cerebellar hemispheres and, to lesser degree, frontal
lobes.
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IV acyclovir was begun on hospital day 4 after an EEG showed a focus of
abnormal neuronal activity in the left temporal lobe, raising clinical
concerns for herpes encephalitis. Empiric antifungal coverage was begun on
hospital day 5. Serial CSF analyses beginning on the date of admission were
negative for bacterial, viral, and fungal pathogens and for CSF malignancy.
Throughout the first few days of the hospital course, the patient's blood
pressure remained elevated, ranging from 133 over 91 to 177 over 112 mm
Hg.
MRI performed 3 days later (hospital day 7) showed improvement in the
enhancement abnormalities in the cerebral hemispheres with persistent
cerebellar edema and tonsillar herniation. At that time, the patient's blood
pressure was 144 over 95 mm Hg. The patient's history of systemic hypertension
was then brought to the radiologist's attention. Because of the lesion
distribution and negative workup for infectious and malignant causes, PRES
related to the patient's chemoinduction was thought to be the most likely
diagnosis. IV antihypertensive therapy was begun that day, and the patient's
blood pressure normalized to 117 over 57 mm Hg the following day; this
resulted in improvement of his neurologic status over the course of
approximately 2 weeks.
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Fig. 1E —7-year-old boy with seizures who was being treated with
L-asparaginase chemoinduction therapy for B-cell lymphoblastic lymphoma. Axial
contrast-enhanced brain CT scan obtained 13 days after D and after
initiation of antihypertensive therapy shows near resolution of hypodensity
seen in cerebellar hemispheres, normal appearance of fourth ventricle
consistent with resolution of mass effect, and no residual contrast
enhancement.
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Follow-up CT (Fig. 1E) and
MRI examinations showed near resolution of signal and enhancement
abnormalities and mass effect in the posterior fossa. No biopsy was performed.
The negative CSF cytology and cultures and continued clinical and radiologic
improvement after withdrawal of antimicrobial therapy and initiation of
antihypertensive therapy supported PRES as the correct diagnosis. On
discharge, the patient was grossly neurologically intact.
Discussion
PRES is a distinct clinicoradiologic entity characterized by headaches,
altered mental status, visual disturbances, and seizures with imaging findings
of vasogenic edema in a posterior circulation distribution
[1,
2]. Clinical findings are
nonspecific, and imaging plays a major role in suggesting the diagnosis. Our
case shows the importance of early recognition and treatment of PRES. The
myriad causes of PRES—primarily uncontrolled hypertension, preeclampsia
or eclampsia, and immunosuppressive and chemotherapeutic drugs—have been
well documented [2]. The common
feature of these etiologic agents is hypertension, and many cases of PRES were
formerly referred to by the term "hypertensive
encephalopathy."
Our case is atypical for PRES from both its clinical and imaging
standpoints. Clinically, most PRES cases have an indolent course rather than
the catastrophic course seen in our patient. The fact that the patient's
history of systemic hypertension was initially unknown to the interpreting
radiologist may have contributed to the delay in diagnosis in this patient.
Also, primarily posterior fossa involvement is uncommon in PRES syndrome. Most
cases primarily or solely involve the supratentorial white matter. Marked mass
effect is also distinctly unusual; in our patient, cerebellar mass effect led
to effacement of the fourth ventricle, tonsillar herniation, and sudden
deterioration in neurologic status. Furthermore, although contrast enhancement
in a curvilinear or patchy distribution has occasionally been reported
[2,
3], the masslike areas of
contrast enhancement in our patient are distinctly unusual. In fact, the
presence of contrast enhancement and of mass effect led to the initial
assumption that an alternative (i.e., infectious) process was causative.
As mentioned earlier, posterior fossa involvement by PRES is uncommon.
Review of the medical literature shows two main types of posterior fossa
involvement by PRES. Cerebellar involvement typically manifests as focal or
diffuse regions of hyperintense T2 signal on MRI and is not generally
accompanied by the marked mass effect seen in our patient
[4]. The other major type of
posterior fossa involvement is brainstem swelling and signal abnormality alone
or in conjunction with cerebellar signal abnormality. Patients with this
finding typically have only mild neurologic signs and symptoms
[4-6].
In our review of the literature, we did not find a case of death (or, as in
our case, near death) from cerebellar involvement. However, at least one case
of death due to PRES-related brainstem swelling has been reported
[7]. Autopsy findings in that
case revealed extensive brainstem infarction. The marked enhancement seen in
our patient suggests extensive disruption of the blood-brain barrier.
The pathophysiology of PRES is debated. The generally accepted theory is
that elevations in blood pressure lead to autonomic dysfunction of the
posterior circulation, which has less sympathetic innervation than the carotid
intracranial circulation [2].
Hypertension need not be severe in order for PRES to manifest and rapid-onset
or fluctuating hypertension carries a greater risk of developing PRES
[2]. This leads to arteriolar
vasodilation, resulting in hyperperfusion and breakdown of the blood-brain
barrier. Extravasation of fluid into the interstitium causes vasogenic edema
[3]. Proton MR spectroscopy may
reveal reversible elevations in choline and decreases in
N-acetylaspartate throughout the brain, even in areas without signal
abnormality on conventional MR sequences. The pathogenesis of these findings
is uncertain but may be due to microglial proliferation and associated
neuronal dysfunction [8]. In
severe or untreated cases, PRES can lead to irreversible cerebral infarction
[7]. Treatment involves
antihypertensive therapy and discontinuation of the etiologic agent in the
case of drug reaction. Once treatment is initiated, clinical and radiographic
improvement is typically rapid
[2,
9].
PRES may be underrecognized in the pediatric population. This may be due to
the possibility that children may develop PRES at lower blood pressures than
are typically seen in adults because normal mean arterial pressures in
children are lower than in adults
[10]. L-asparaginase has been
linked to cerebrovascular complications in children, usually associated with
thrombosis and hemorrhage, which can be late complications of hypertensive
encephalopathy [11].
In summary, this case illustrates a rare but life-threatening complication
of PRES in a pediatric patient. Recognition of atypical variants of PRES can
be helpful to manage these complications in a timely manner.
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Introduction
Case Report
