Reversible posterior encephalopathy syndrome due to intravenous immunoglobulin in a child with Guillain-Barré syndrome.

Reversible posterior leukoencephalopathy syndrome is characterized clinically by headache, abnormalities of mental status, and visual perception and seizures. We report a rare case of acute encephalopathy following intravenous immunoglobulin treatment for Guillain-Barré syndrome in whom posterior reversible encephalopathy syndrome developed without severe hypertension.

Introduction

Reversible posterior leucoencephalopathy syndrome (PRES), first described by Hinchey et al., in 1996, is a neurological condition characterized by headache, nausea, vomiting, visual field disturbances, altered mental status, decreased alertness, and seizures.[1]

Several risk factors of PRES are hypertensive encephalopathy, chronic renal insufficiency, blood transfusion, eclampsia, immunosuppressive drugs (such as cyclosporin A, tacrolimus, interferon á, methotrexate), intravenous immunoglobulin (IVIg) treatment, post-transplantation stage in liver disease, and acute phases of autoimmune disorders.[12] The main finding of PRES in magnetic resonance imaging (MRI) is usually bilateral, posterior white matter hyperintensity on T2 weighted images, suggesting vasogenic edema.[13]

In the literature, PRES associated with IVIg treatment has been reported in rare patients.[24] Here, we report a 3-year-old boy with PRES after treatment of Guillain-Barré syndrome (GBS) with IVIg.

Case Report

A previously healthy, 3-year-old boy was admitted to our hospital because of progressive ascending weakness, beginning 5 days before admission. Ten days before admission, he was diagnosed with upper respiratory infection.

On admission, vital signs, and anthropometric measures were in normal limits. He was conscious. Neurological examination revealed reduced muscle strength (2/5) and hypotonia in all extremities especially in distal parts. Deep tendon reflexes were absent. The remainder of the examination was unremarkable.

In laboratory studies, hemogram, serum electrolytes, metabolic screening of urine and blood, lactic acid, pyruvic acid, renal, and liver function tests were normal. Lumbar puncture revealed no white blood cells, 143 mg/dl protein and 61 mg/dl glucose. Cerebrospinal fluid (CSF), urine, and stool culture were negative. Serologic tests for C. jejuni, HIV, HSV, HAV, HBV, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae were negative. The VDRL test for syphylis was also normal. Nerve conduction and electromyographic examination revealed acute motor sensory axonal neuropathy (AMSAN).

Based on the clinical and laboratory findings, the child was diagnosed with GBS. The patient was treated with IVIg at 0.4 g/kg/day for 5 days. Five days after completing IVIg, he became encephalopathic. Initially, he was agitated and then this progressed to somnolence. His blood pressure was within normal limits and he was admitted to our hospital during encephalopathy episode. MRI of the brain [Figure 1] was considered consistent with the vasogenic edema of PRES. Complete recovery of the neurological symptoms occurred spontaneously within 3 days. One week later, the brain MRI [Figure 2] showed significant resolution of lesions.

Figure 1

MRI examination of the brain. Axial FLAIR T2 at day 5 after completing IVIg

Figure 2

One week after first MRI

Discussion

Guillain-Barré syndrome is an acute demyelinating polyneuropathy presumably related to immunological mechanisms. Approximately 75% of all cases of GBS are preceded by an acute infection within 1-3 weeks, usually respiratory or gastrointestinal. After the role of autoimmunity became clear, plasmapheresis and IVIg were used for the treatment.

Intravenous immunoglobulin is commonly used in pediatric GBS treatment. The commonly seen side effects of IVIg are myalgia, headache, nausea, vomiting, fever, anaphylaxis, thromboembolism and aseptic meningitis. PRES is a rare and potentially severe adverse event of IVIg therapy.[23]

In the literature, there have been adult patients who developed PRES after IVIg given for GBS. Mathy et al., reported a 73-year-old man who developed PRES on the first day of IVIg.[5] A similar case was reported by Voltz et al., a 42-year-old woman developed PRES and cerebral arterial vasospasm 3 days after completion of IVIg.[6] Another case has been reported by Doss-Esper et al., the patient has developed acute hypertension, PRES, ischemic, and hemorrhagic strokes and reversible cerebral arterial vasospasm after IVIg treatment for GBS.[7] To our knowledge, only one pediatric patient with GBS has been associated with PRES after IVIg. The case was reported by Koichihara et al. A 14-year-old girl diagnosed as GBS developed PRES 3 days after IVIg.[8] Our patient complained of confusion and somnolence on day 5, after the administration of IVIg. The brain MRI revealed increased signal in the white matter of right parieto-occipital lobe and bilateral basal ganglia on T2-weighted sequences. These findings were considered consistent with PRES, attributable to a manifestation of vasogenic edema. So, we accepted this a complication of IVIg.

The pathophysiology of PRES is not clear yet. Arterial hypertension is frequent in GBS, probably due to autonomic dysfunction. The acute arterial hypertension can be an important provoking factor of PRES, but also that, other GBS-linked factors may play a role in the pathogenesis of PRES. But, in his follow-up, we have not detected hypertension in our patient. Our patients had blood pressure about 90/50, 90/60, 100/50, and 100/60 mmHg.

Vasogenic edema, cerebrovascular endothelial dysfunction, cerebral vasospasm, serum hyperviscosity, intravascular hypercoagulopathy, and platelet hyperactivity have been proposed as probable mechanisms of PRES as caused by IVIg.[7] Another explanation can be the role of cytokines in both syndromes. Takano et al., reported an elevated intrathecal interleukin-6 in a child with hypertensive encephalopathy.[9] GBS is an inflammatory peripheral neuropathy in which serum and CSF levels of cytokines are elevated. Cytokines can also play a role in the pathogenesis of PRES, on the permeability of blood brain barrier.[10]

As a result, we think, we have to suspect PRES in patients that have new neurological signs after IVIg.