Posterior reversible encephalopathy syndrome and the pediatric population.

Posterior reversible encephalopathy syndrome presents with neurological and imaging features that are reversible, if prompt diagnosis and treatment is undertaken. However, the disease has been more commonly described in adult population, especially in eclampsia. In the background of predisposing factors like renal disease or chemotherapy, the pediatric population is also at equal risk for this condition, as we would like to present through this case and also demonstrate the potential for complete reversal of symptoms and imaging findings if diagnosed without delay.

Introduction

Posterior reversible encephalopathy syndrome (PRES), first described by Hinchey et al. in 1996,[1] is a clinical condition presenting with neurological symptoms including headache, seizures, altered sensorium, and loss of vision, and accompanied by characteristic magnetic resonance imaging (MRI) findings which are potentially reversible. Over the years, this condition has been described by various names including reversible posterior leukoencephalopathy, reversible posterior cerebral oedema, reversible occipitoparietal encephalopathy, and hypertensive encephalopathy.[2] The disease has been more commonly described in adult population,[3] especially in the setting of eclampsia and organ transplantation.[4] Postulated underlying causes include sudden rise in blood pressure, immunosuppression, chemotherapeutic agents for lymphoma and leukemia, severe hypercalcemia, thrombocytopenic syndromes, Henoch–Schönlein purpura, vasculitis, and renal failure,[125] of which sudden rise in blood pressure and renal failure appear to be the most common.[2] At neuroimaging, vasogenic oedema is seen involving the white matter of bilateral cerebral hemispheres posteriorly, most commonly parietal and occipital lobes.[12]

The prevalence of PRES among children is not well established; however, there have been reports of PRES in children following chemotherapy and tumor lysis syndrome, as well as with hypertension.[6]

Case Report

An 11-year-old boy, a known case of chronic kidney disease (stage V) on maintenance hemodialysis, presented with one episode of generalized tonic–clonic seizure approximately 30 minutes prior to presentation to the emergency center. He was in altered sensorium following the episode of seizure. There was history of high-grade fever (upto 103°F) for 3–4 days.

On examination, he was found to be drowsy; however, he was moving all four limbs. His blood pressure in the emergency room was recorded to be 140/100 mmHg. Laboratory tests revealed a serum creatinine of 4.8 mg% and blood urea of 121 mg%. His total leukocyte count was 22,200 per mm3 with Hb of 10.2 gms. Serum calcium, sodium, and potassium were 7.8 mg%, 135 mEq/L, and 5.3 mEq/L, respectively.

MRI brain at admission showed T2W/T2 FLAIR hyperintensities, s/o oedema, involving the subcortical white matter of bilateral frontal, parietal, and occipital lobes, with few areas of cortical involvement [Figure 1]. Similar lesions were also noted involving bilateral basal ganglia, left thalamus, splenium of corpus callosum, as well as brainstem [Figure 2]. Diffusion-weighted imaging (DWI) showed increased signal intensity in the lesions in bilateral occipital lobes and in the splenium of corpus callosum. A diagnosis of PRES was made on the basis of these findings.

Figure 1

MRI Axial T2 FLAIR section showing symmetrical hyperintense lesions involving subcortical and cortical locations of the bilateral frontal and parietal lobes

Figure 2

MRI Axial T2 FLAIR section showing similar lesions involving the basal ganglia and the splenium of corpus callosum

The patient was started on antiepileptics, antihypertensives, and antibiotics, with daily hemodialysis. He had four more episodes of seizures during his hospital stay; however, he slowly improved clinically and was discharged on antiepileptics and antihypertensives on biweekly hemodialysis.

Follow-up MRI brain was done after 2 weeks, which showed near-total resolution of the brain lesions [Figure 3].

Figure 3

Repeat MRI Axial T2 FLAIR sections after 2 weeks show almost complete resolution of the lesions in the brain

Discussion

Although significant elevation of the blood pressure may not always be demonstrated, PRES is considered to be a variant of hypertensive encephalopathy with sudden rise in blood pressure being the most commonly associated feature although other causative factors have also been implicated.[7]

Two theories are considered in the pathophysiology of PRES, the first being sudden increase in blood pressure causing vasospasm and the other being failure of autoregulatory mechanism.[2] With sudden elevation in systolic blood pressure, the autoregulatory capacity of brain vasculature is exceeded which results in a region of vasodilatation and vasoconstriction, especially in the arterial boundary zone. This causes breakdown of the blood–brain barrier with subsequent transudation of fluid along with hemorrhage.[6] The preferential involvement of the posterior circulation has been postulated as being due to the sympathetic innervation protecting the brain from sudden increase in blood pressure being relatively less in the arterioles supplied by the vertebrobasilar system than in the anterior circulation.[5]

In the setting of end-stage renal disease (ESRD), as in our patient, both the rise in pressure beyond the ability of autoregulation of cerebral flow as well as the uremia by itself may serve as triggers for PRES.[2]

Although PRES commonly involves the parietal–occipital region, three different imaging patterns have been described.[4] The first was the holohemispheric watershed pattern with a linear involvement of the frontal, parietal, and occipital lobes predominantly, along a watershed distribution. The second was the superior frontal sulcus pattern with predominant involvement of the frontal lobes, and the third was the dominant parietal–occipital pattern in which the typical predominance for the posterior lobes was maintained. Other than these patterns, asymmetrical and/or partial manifestations of the primary patterns were also described.[4] In our patient, the pattern seen could be best described as holohemispheric watershed pattern. Atypical sites of involvement that have been described include brain stem, cerebellum, basal ganglia, thalami, internal capsule, and splenium of corpus callosum,[246] with uremic encephalopathy sometimes described as having a propensity for central distribution.[8] In our patient, lesions were noted in the brainstem, bilateral basal ganglia, left thalamus, and the splenium of corpus callosum.

DWI and apparent diffusion coefficient (ADC) have been found to be helpful in differentiating atypical presentations of PRES from conditions like central pontine/extrapontine myelinolysis, non-hemorrhagic infarcts, and hypoglycemic or hypoxic encephalopathy. Due to vasogenic oedema in PRES, ADC shows increased values with slightly increased signal intensity on DWI, whereas the other conditions show reduced ADC values due to cytotoxic edema.[9] Our patient demonstrated increased intensity on DWI with increased ADC values in the splenium and occipital lobes.

The symptoms and lesions of PRES may resolve completely if the diagnosis and treatment is prompt, as was seen in our patient; however, failure to diagnose may lead to irreversible infarction and death.[710] Recurrence of PRES is rare and may be associated with infections and rapid rise in blood pressure.[2] The diagnosis may be overlooked, especially in children, unless a high index of suspicion and precise clinical history is maintained.

We maintain that PRES should be kept as a possibility in children presenting with encephalopathy and seizures in the setting of raised blood pressure or renal disease as delay in diagnosis and treatment may result in permanent neurological deficit.