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Posterior Reversible Posterior Reversible Encephalopathy Encephalopathy

Syndrome in Children: Syndrome in Children: Is It Really So Is It Really So Reversible?Reversible?

Ignacio Delgado; Chae B Whang; Angel Sanchez-Montanez; Miquel Raspall; Alfons Macaya; Elida Vazquez

Hospital Universitario Vall dHebron, Barcelona, SpainHospital Universitario Vall dHebron, Barcelona, Spain

Electronic Electronic adressadress: idelgadoalvarez@gmail.com: idelgadoalvarez@gmail.com

o Posterior reversible encephalopathy syndrome (PRES) classically consists on reversible vasogenic edema in the posterior circulation territories accompanied by headache, altered mental status, seizures, and visual disturbance.

o Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure.

o A breakdown in cerebral autoregulation results in the leakage of fluid into the interstitium which is detected as vasogenic edema.

o If promptly recognised and treated, abnormalities can be completely reversed. If not, evolute to ischemia.

o Diffusion-weighted imaging (DWI) can distinguish vasogenic edema in PRES from cytotoxic edema.

o Restricted diffusion have been associated with an adverse outcome.

o Hemorrhage is seen in some patients and prognosis is also worse.

Covarrubias DJ, et al . Posterior reversible encephalopathy syndrome prognostic utility of quantitative diffusion-weighted MR images. AJNR Am J Neuroradiol 2002;23;1038-48

Bartynski WS. Posterior Reversible Encephalopathy Syndrome, Part1: Fundamental Imaging and Clinical Features. AJNR Am J Neuroradiol 2008, 29:1036-42

o PRES is becoming increasingly recognized as a common complication of pediatric cancer therapy.

o Risk factors include hypertension (not necessarily acute), induction chemotherapy, and therapy with immunosuppressive agents (eg, cyclosporine, tacrolimus, and corticosteroids).

o Blood pressure may be normal in some cases of PRES, particularly in the settings of chemotherapy, immunosuppressive therapy, and sepsis

Vazquez E, et al . Side Effects of Oncologic Therapies in the Pediatric Central Nervous System: Update on Neuroimaging Findings . Radiographics 2011, Vol.31: 1123-1139, 10.1148

The purpose of this study is to evaluate which The purpose of this study is to evaluate which clinical and clinical and magneticmagnetic resonanceresonance imagingimaging

(MRI) findings can help to (MRI) findings can help to predict predict the the prognosisprognosis of of PRES PRES and whether or not there is and whether or not there is

differencedifference between PRES in between PRES in childrenchildren and and adults.adults.

RectrospectiveRectrospective analysis

Data of the last last 77 years years (2007(2007--2013)2013)pediatric neuroradiology unit of a reference tertiary centre

Twenty Twenty children with PRES* 9 * 9 : : 1111

* * 2 2 to to 14 years14 years--old old (7,7 yo mean age)(7,7 yo mean age)

* * RecurrenceRecurrence of PRES of PRES in in one one patient patient 3 months after 3 months after complete recovery from first episodecomplete recovery from first episode..

All patients studied by MRI. Follow-up MRI 14/20:

MR imaging MR imaging (T1WI, T2WI, GET2*, FLAIR and DWI)

Clinical Clinical and MRI featuresMRI features and patients outcomepatients outcome

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Most frequent predisposing causes were renal and hemato-oncologic diseases frequently associated with endotheliotoxic cytostatic medication:

* cyclosporine A 10/20

tacrolimus 5/20

mycophenolate 3/20

corticoids 3/20

vincristine 2/20.

Presenting symptoms

seizures in 85% (17/20)

altered mental status in 65% (13/20)

visual disturbance 25% (5/20)

headache 15%

Arterial hypertension present in 16/20 (80%) of patients.

Parieto-occipital regions were the most commonly involved in MRI (19/20 [95%]).

Frontal lobe (40%)

Temporal lobe (15%).

9/20 (45%) showed restriction of diffusion (DWI) in initial MRI

2 patients hemorrhagic changes.

Follow-up MRI performed on 14 patients (range period 4-427 days)

6/14 residual lesions (focal laminar necrosis).

Sequelae

Six patients developed epilepsy

Two patients remained with ataxia

One patient had a persistent mydriasis

One hypotonia

One learning disability

Two patients died after the initial MR examination but PRES did not play a role in these patients outcome.

Six of the patients with sequelae had hemorrhage or DWI lesions in the initial MRI.

Classical PRES in a transplanted 14yo girl underantirejection therapy with seizures and headache . (a) Axial FLAIR MR images demonstrate subcorticalhyperintensities in the posterior circulation territories(blue arrow) . (b)Axial diffusion-weighted MR image shows facilitated diffusion consistent with vasogenic edema.

(a)

(b)

Classical PRES in a transplanted14yo girl under antirejection therapywith seizures and headache . (a) Axial FLAIR MR imagesdemonstrate subcorticalhypersignals in the posterior circulation territories (blue arrow) . (b) Follow-up Axial FLAIR MR images show resolution of vasogenicedema after 25 days. Patient is now asypmptomatic.

(a)

(b) 7yo boy with medulloblastomatreated with vincristine. (a) Axial MR images (FLAIR) demonstrateextensive vasogenic edema in frontal lobes, parietal and occipital regions (black arrows) consistent with PRES. Axial diffusion-weighted MR image shows restricted diffusion in the left lesion (red). Follow-up Axial FLAIR MR image shows gliosis involving the left occipital lobe (yellow). Patient remained with epilepsy.

(a) (b)

(c)

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6yo girl with leukemia . (a) Axial MR images (FLAIR) demonstrate vasogenic edema in posterior parietal area (bluearrow) . (b)Axial diffusion-weighted MR image shows restricted diffusion in the lesion (red). (c)Follow-up Axial FLAIR MR image shows gliosis and atrophy (yellow) .

(a) (c) (b)

4yo boy with leukemia treatedwith cyclosporine. (a) Axial FLAIR MR images show vasogenic edema in parietal lobes (blue arrows) consistent with PRES. (b) Axial GET2* MR image shows hemorrhagic changes in the left parietal lesion (red). (c) Follow-up Axial FLAIR MR image shows gliosis involving the left posterior parietal lobe (yellow) and hemosiderin deposition (blackblack) Patient remained with seizures.

(a)

(b)

(c)

(d)

Recurrent PRES in a 3yo boy after renal transplantation.(a) Axial FLAIR MR imagesshow focal hyperintensities in right frontal and parietal lobes(blue arrow) . (b) 4 day follow-up MR image shows partial recovery. (c) Axial FLAIR MR images 3 months later with new similar lesions in contralateralparietal lobe (red) (d) 1 year follow-up with total resolution.

(a) (b)

(c) (d)

7yo boy with PRES. (a) Vasogenicedema involving frontal an parietal lobes in axial FLAIR MR images (bluearrow). (b) Follow-up MRI shows total recovering . (c) Initial coronal DWIwith restriction in right hypoccampusand thalamus (red). (d) Patientdeveloped messial sclerosis (yellow)

6yo girl with PRES . (a) Axial FLAIR MR images shows edema in occipitotemporal lobe (blue arrow) . (b)Axial diffusion-weighted MR image shows restricted diffusion (red). ASL perfusion in acute (c) and follow-up (d). Note the focal hyperperfusion during the acute phase and hypoperfusion 3 months later.(a)

(b) (c) (d)

Posterior reversible encephalopathy may develop in patients who have renal insufficiency or hypertensionor who are immunosuppressed. This syndrome should be recognized immediately and trigger agents must be discontinued to prevent long-term sequelae. Recurrence of PRES is infrequent.

PRES has not a so good long-term prognosis in children. Epilepsy is the most frequent sequela.

Diffusion-weighted imaging restriction is a sign of cytotoxic non reversible edema and indicate poor prognosis. The presence of hemorrhagic changes in the initial MRI is also linked with a worse patients outcome.

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MRI may help predicting the prognosis of PRES.

PRES in children is not only linked with hypertension like in adult population but also with chemotherapy, immunosupressors and other endotheliotoxic medication, which play and important role in the its pathophysiology .

Early recognition of PRES, discontinuation of trigger chemoterapy agent and hypertension control is crucial to avoid sequelae.