Reversible Posterior Leukoencephalopathy Syndrome During Regorafenib Treatment: A Case Report and Literature Review of Reversible Posterior Leukoencephalopathy Syndrome Associated With Multikinase Inhibitors

Myint, Zaw; Sen, Jeremy; Watts, Nicole; Druzgal, T. Jason; Nathan, Barnett R.; Ward, Melanie D.; Boyer, James E.; Fracasso, Paula M.

doi:10.1016/j.clcc.2013.12.003

Cited by 26 publications

(14 citation statements)

References 22 publications

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“…Magnetic resonance imaging (MRI) evidence of hyperintense signal change in the cortical–subcortical areas, typically in posterior circulation distribution, is required to confirm PRES diagnosis . Initially described in hypertensive encephalopathy and eclampsia, subsequent reports have suggested an association with drugs, particularly immune system and vascular endothelial system modulating agents . Outcome of PRES in noncancer patients is usually good, but permanent sequelae and life‐threatening complications have been described .…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] Initially described in hypertensive encephalopathy and eclampsia, subsequent reports have suggested an association with drugs, particularly immune system and vascular endothelial system modulating agents. [3][4][5] Outcome of PRES in noncancer patients is usually good, but permanent sequelae and life-threatening complications have been described. [6,7] Reports on outcomes of PRES in children with cancer have been limited by small number of patients and inadequate follow-up data.…”

Section: Introductionmentioning

confidence: 99%

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Imaging Patterns and Outcome of Posterior Reversible Encephalopathy Syndrome During Childhood Cancer Treatment

Khan

Sadighi

Zabrowski

et al. 2015

Pediatr Blood Cancer

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Background Diagnosis of posterior reversible encephalopathy syndrome (PRES) requires presence of headache, seizures, impaired vision, or altered mentation accompanied by specific imaging findings. We aimed to study long-term clinical and radiologic outcome of PRES in children with cancer to augment limited available data. Procedure Retrospective review of children with cancer who were diagnosed with PRES. Results We identified PRES in 21 males and 16 females amongst the 5,217 children treated during the study period. Median time from cancer diagnosis to PRES was 6.6 months in 25 leukemia (1.6%), 5 brain tumor (0.3%), and 7 other solid tumor (0.4%) patients; p=<0.0001 for leukemia versus all other tumors. Symptoms included seizures (97%), headaches (40%), altered mentation (68%), and vision impairment (27%). Hypertension in 97% and steroids use was seen in 78%. Headaches, visual disturbance, and mental status resolved within a median of <3 days, while epilepsy developed in 19%. T2 hyperintense signal was present in 100% of occipital, 47% of temporal, 75% of parietal, and 55% of frontal lobes, as well as 22% of cerebellum and 5% of basal ganglia. Follow-up MRI in 34 patients showed partial or complete T2 resolution in 79%, development of laminar necrosis in 5, microhemorrhages in 6, and focal atrophy in 3. Conclusion PRES in children is more common in hematological malignancy compared to other tumors and is associated with hypertension and steroid use. Seizure is the most common acute manifestation. Most MRI changes resolve, but persistent imaging abnormality and epilepsy may develop in a significant minority.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imaging Patterns and Outcome of Posterior Reversible Encephalopathy Syndrome During Childhood Cancer Treatment

Khan

Sadighi

Zabrowski

et al. 2015

Pediatr Blood Cancer

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“…Several cases of RPLS have been reported for either regorafenib or other TKIs, [10–12] but – at the best of our knowledge – only 5 cases of HE associated to TKIs have been described in literature. [2,13–15] Among these, only 1 case of regorafenib-induced HE is described, [2] whereas the other have been related to sorafenib (1 case) and sunitinib (3 cases).…”

Section: Discussionmentioning

confidence: 99%

Unexpected side effect in mCRC

et al. 2017

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Rationale:Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable.Patient concerns:A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia.Interventions:Serum ammonia level was 191 mmol/L, liver function tests and complete blood count were normal. Regorafenib was withheld and branched chain amino acids and lactulose were administered.Outcomes:Serum ammonia level returned within the normal range, but when regorafenib was restarted at a lower dose level, a new episode of acute confusion arised.Main lesson:Discontinuation of regorafenib after confirmation of hyperammonemia is strongly recommended; reintroduction of the therapy at lower doses after resolution of symptoms related to hyperammonemic encephalopathy has to be discouraged.

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“…First, oncologic therapies comprise a significant percentage of drugs known to predispose to PRES, which in turn is thought to stem from immune responses unique to malignancy as well as direct endothelial effects from chemotherapeutic agents. 6,13 Second, with the recent proliferation of therapies directed against vascular endothelial growth factor or its receptor and subsequent recognition of a class effect, 22 physicians may be well advised to pay heed to this association.…”

Section: Drugsmentioning

confidence: 98%

“…15 When associated with administration of immunosuppressant medications, reduction in drug dosage or discontinuation of the offending agent is generally advised. 3,5,22,47 Plasmapheresis has been successfully used for RPLE caused by thrombotic thrombocytopenic purpura 48 and cryoglobulinemia. 49 What is the prognosis?…”

Section: What Are the Radiographic Manifestations?mentioning

confidence: 99%