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DOI:10.2214/AJR.05.0328
AJR 2007; 188:219-221
© American Roentgen Ray Society

Case Report

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
Top
 Introduction
Case Report
 Discussion
 References
 
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
Top
 Introduction
 Case Report
Discussion
 References
 
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.


Figure 1
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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.

 

Figure 2
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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.

 
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.


Figure 3
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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).

 

Figure 4
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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.

 
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.


Figure 5
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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.

 
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
Top
 Introduction
 Case Report
 Discussion
References
 
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.


References
Top
 Introduction
 Case Report
 Discussion
 References
 

  1. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med1996; 334:494 -500[Abstract/Free Full Text]
  2. Lamy C, Oppenheim C, Meder JF, Mas JL. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging2004; 14:89 -96[CrossRef][Medline]
  3. Schwartz RB, Mulkern RV, Gudbjartsson H, Jolesz F. Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis. Am J Neuroradiol1998; 19:859 -862[Abstract]
  4. Wang MC, Escott EJ, Breeze RE. Posterior fossa swelling and hydrocephalus resulting from hypertensive encephalopathy: case report and review of the literature. Neurosurgery1999; 44:1325 -1327[Medline]
  5. Chang GY, Keane JR. Hypertensive brainstem encephalopathy: three cases presenting with severe brainstem edema. Neurology 1999;53:652 -654[Free Full Text]
  6. Morello F, Marino A, Cigolini M, Cappellari F. Hypertensive brain stem encephalopathy: clinically silent massive edema of the pons. Neurol Sci2001; 22:317 -320[CrossRef][Medline]
  7. Weingarten K, Barbut D, Filippi C, Zimmerman RD. Acute hypertensive encephalopathy: findings on spin-echo and gradient-echo MR imaging. AJR 1994;162:665 -670[Abstract/Free Full Text]
  8. Eichler FS, Wang P, Wityk RJ, Beauchamp NJ Jr, Barker PB. Diffuse metabolic abnormalities in reversible posterior leukoencephalopathy syndrome. Am J Neuroradiol2002; 23:833 -837[Abstract/Free Full Text]
  9. Casali-Rey JI, Davalos EG, Lopez-Amalfara A, Julio-Munoz D, Pagano MA. Posterior reversible encephalopathy syndrome: some case reports. Rev Neurol2003; 37:224 -227[Medline]
  10. Jones BV, Egelhoff JC, Patterson RJ. Hypertensive encephalopathy in children. Am J Neuroradiol1997; 18:101 -106[Abstract]
  11. Feinberg WM, Swenson MR. Cerebrovascular complications of L-asparaginase therapy. Neurology1988; 38:127 -133[Abstract/Free Full Text]

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W.S. Bartynski
Posterior Reversible Encephalopathy Syndrome, Part 1: Fundamental Imaging and Clinical Features
AJNR Am. J. Neuroradiol., June 1, 2008; 29(6): 1036 - 1042.
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