Neuropediatrics 2017; 48(02): 064-065
DOI: 10.1055/s-0037-1600517
Editorial Comment
Georg Thieme Verlag KG Stuttgart · New York

Posterior Reversible Encephalopathy: An Epileptic Syndrome?[*]

Hans Hartmann
1   Clinic for Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, Hannover, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
10 March 2017 (online)

The term “posterior reversible encephalopathy syndrome” (PRES) was first used by Hinchey et al in 1996,[1] which refers to a transient neurologic disorder in patients hospitalized for acute illness. In patients presenting with “altered mental function, visual loss, stupor, and seizures,” the authors described a corresponding pattern of white-matter abnormalities on imaging, mostly affecting the posterior regions of the cerebral hemispheres and typically encompassing more than one vascular territory. When follow-up imaging was available, it showed complete or partial resolution. This description already included clinical, electrophysiologic and imaging characteristics of the syndrome, and the observation that it can occur in patients with a variety of acute illnesses, including renal failure, postpartum eclampsia, and immunosuppressive drug treatment. Raised blood pressure seemed a common feature, and the authors postulated that PRES could be caused by a breakdown of autoregulatory capability of the brain vascularity in the context of sudden elevations in systemic blood pressure, resulting in cerebral edema. The authors emphasized the need to quickly diagnose and treat PRES “by controlling blood pressure and discontinuing the offending immunosuppressive agent or decreasing the dose.”

Over 20 years later, numerous publications have added to our knowledge of frequency and associated conditions in both adults and children. Besides arterial hypertension, PRES has been associated with renal failure, dialysis dependency, organ transplant, malignancies, cytotoxic therapy, autoimmune disorders, and puerperal eclampsia. The pathophysiology remains unraveled. Though PRES is associated with hypertension in the majority of patients, there is no link in approximately 20% of cases.[2] Besides the concept of failed autoregulation leading to hyperperfusion and subsequent vasogenic edema due to endothelial injury, especially in patients receiving cytotoxic drugs, vasoconstriction and hypoperfusion leading to hypoxic-ischemic damage and vasogenic edema have also been postulated.[3] Cytokine activation may also be involved in the pathology.[2] With such different pathologies, it is likely that varied etiologies contribute to the clinical and imaging picture as well as PRES prognosis.

In this issue of Neuropediatrics, Grioni et al[4] shift the focus to the role of seizure activity in the pathogenesis of PRES. The authors present their results from a large cohort of pediatric patients developing PRES in the context of hemato-oncologic diseases, mostly electroencephalogram (EEG) within 1 hour following onset of clinical symptoms (e.g., confusion, headache, or visual disturbance). EEG revealed diffuse slowing and focal unilateral temporo-occipital ictal activity. In all patients, PRES was later ascertained by magnetic resonance imaging (MRI), although emergency cranial computed tomography had only shown features suggestive of PRES in half of the cases. Grioni et al postulate that prompt treatment with antiseizure medication may have helped to avoid a secondary generalized convulsive status epilepticus or generalized tonic-clonic seizures in their patient cohort. Looking at the clinical characteristics of their patients, it is conceivable that seizures might have been missed without concomitant EEG recording. In another cohort of pediatric patients developing PRES after hematopoietic stems cell transplantation, gaze deviation, oculoclonic movements, nystagmus, and altered mental status were also identified as presenting signs of nonconvulsive status epilepticus, followed by convulsive status epilepticus in some patients.[5]

Outcome following PRES is not always favorable. In a recent literature review of 111 pediatric patients presenting with PRES in association with hemato-oncologic diseases,[3] seizures were identified as the presenting symptom in 80.1%. In 19% of the surviving patients, neurologic sequelae were reported, with 12% suffering from epilepsy.

It may be that subtle seizures are not recognized as epileptic in patients with PRES, as is the case for neonates. This may delay adequate treatment with antiseizure medication. PRES is not a homogenous disorder, and the cohort examined by Grioni et al is specific because it only includes pediatric patients with hemato-oncologic diseases. However, irrespective of the underlying etiology, seizures and status epilepticus clearly play an important role in the pathogenesis of PRES. In children with typical risk factors, presenting with acutely impaired mental function, visual loss, and seizures, emergency imaging, preferably MRI, is mandatory for PRES diagnosis and exclusion of differentials such as hypoxic-ischemic injury, intracranial hemorrhages, toxic encephalopathy, or encephalitis.[2] Seizures and especially status epilepticus probably contribute to morbidity and poor outcome. To facilitate adequate treatment, prompt EEG should be attempted in addition to imaging and in patients not responding to first-line antiseizure medication, EEG monitoring should be considered.

* This article is an editorial comment on “Should posterior reversible encephalopathy syndrome be mainly considered an epileptic disorder? Results of a sequential neurophysiological study in a pediatric cohort” by Grioni et al (Neuropediatrics 2017;48(2):72–78).


 
  • References

  • 1 Hinchey J, Chaves C, Appignani B , et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334 (8) 494-500
  • 2 Fugate JE, Rabistein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14: 914-925
  • 3 Tambasco N, Mastrodicasa E, Salvatori C , et al. Prognostic factors in children with PRES and hematologic diseases. Acta Neurol Scand 2016; 134 (6) 474-483
  • 4 Grioni DM, Pavan F, Prunotto G, Canonico F, de Grandi C, Rovelli A. Should posterior reversible encephalopathy syndrome be mainly considered an epileptic disorder? Results of a sequential neurophysiological study in a pediatric cohort.. Neuropediatrics 2017; 48 (2) 72-78
  • 5 Cordelli DM, Masetti R, Bernardi B , et al. Status epilepticus as a main manifestation of posterior reversible encephalopathy syndrome after pediatric hematopoietic stem cell transplantation. Pediatr Blood Cancer 2012; 58 (5) 785-790