Posterior reversible encephalopathy syndrome possibly induced by pemetrexed maintenance therapy for lung cancer: a case report and literature review

Abstract

Introduction Advances in systemic chemotherapy, molecular targeted therapy and immunotherapy have extended and improved the quality of life of patients with cancer. However, the central nervous system is very susceptible to complications of systemic cancer and its treatment. Posterior reversible encephalopathy syndrome (PRES) is a rare clinical and neuroradiologic entity which has garnered increasing recognition in the past two decades. Cancer patients are generally treated with cytotoxic agents, immunotherapy, molecular targeted therapies or glucosteroids which are more frequently associated with PRES. Case presentation A 59-year old female, known with a relapse of her lung adenocarcinoma, had been treated with 4 cycles of cisplatin (75 mg/m²) and pemetrexed (500 mg/m²). Six weeks after this combination chemotherapy and within 28 h after the administration of pemetrexed maintenance therapy, she developed a generalised epileptic insult. Magnetic resonance imaging (MRI) of the brain showed bilateral areas of increased signal intensity in the subcortical parietal and frontal white matter. She was treated with a broad spectrum antiseizure drug, levetiracetam 750 mg twice daily and strict control of blood pressure. Discussion Diagnosis of PRES should be considered in all patients with neurologic symptoms who are at risk to develop PRES. It is crucial to establish the diagnosis as soon as possible since there is no specific treatment of PRES other than correction of the underlying risk factors and preventing seizure recurrence. Administration of pemetrexed is a possible risk factor for the development of PRES.

Trastuzumab-associated Posterior Reversible Encephalopathy Syndrome

“…The term posterior reversible encephalopathy syndrome is a misnomer, as this syndrome is not always reversible and is not limited to the posterior portions of the brain [ 2 ]. It is believed that PRES is underdiagnosed, given its variable clinical presentations [ 4 ].…”

“…Two theories explain how PRES develops. The first one is the vasogenic theory, where a rapid increase in blood pressure can cause an abnormality in cerebral autoregulation, leading to hyperperfusion and breakdown of the BBB with increasing permeability [ 3 - 4 ]. The second theory is the endothelial theory where toxic damage to the BBB leads to increased BBB permeability, resulting in edema.…”

“…The second theory is the endothelial theory where toxic damage to the BBB leads to increased BBB permeability, resulting in edema. The endothelial theory provides a better explanation for chemotherapy-associated PRES, including PRES caused by targeted agents [ 4 ]. Moreover, it is believed that some chemotherapeutic agents and targeted agents can increase tumor cell recognition, resulting in an inflammatory reaction and changes in BBB permeability [ 2 ].…”

“…Two theories explain the pathogenesis of PRES: the vasogenic theory and the endothelial theory. Both theories involve an increased permeability of the blood-brain barrier (BBB), which leads to brain edema [ 4 ]. Magnetic resonance imaging (MRI) of the brain is the gold standard to diagnose PRES and exclude important differential diagnoses.…”

Pemetrexed-Induced Pseudotumor Cerebri Syndrome

“…[ 8 ] Posterior reversible encephalopathy syndrome (PRES) with impaired vision occurred with regimens using carboplatin[ 9 ] and pemetrexed. [ 10 ] A patient receiving pemetrexed for adenocarcinoma of the lung developed raised intracranial pressure secondary to communicating hydrocephalus and underwent ventriculoperitoneal shunt. [ 11 ] Our patient did not have features of PRES or hydrocephalus.…”