Posterior reversible encephalopathy syndrome in a patient with metastatic breast cancer:A case report

lNTRODUCTlON

Posterior reversible encephalopathy syndrome(PRES)is a neurotoxic encephalopathic state with clinical features such as headache,vomiting,altered consciousness,visual disturbances,and seizures.The radiologic findings demonstrate vasogenic edema in the posterior occipital and parietal lobes of the brain[1].The pathogenesis of PRES remains unclear,but it is likely related to cerebral autoregulatory failure and end-othelial dysfunction.

Hypertension is the most common cause of PRES.Post-transplantation,immune suppression,infection,or autoimmune disease are also risk factors for PRES.In cancer patients,wide use of chemotherapy and targeted agents can be associated with PRES.Hypercalcemia rarely causes PRES,but there have been few reports on hypercalcemia-induced PRES[2].

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Hypercalcemia is a common finding in patients with advanced stage cancer.Hypercalcemia develops in cancer patientsparathyroid hormone-related peptide(PTHrP)production,osteolytic metastasis,excessive calcium release from the bone,ectopic 1-alpha-hydroxylase activity,and 1,25-dihydroxycholecalciferol formation[3].

We present a case of PRES caused by hypercalcemia and hypertension in a patient with advanced breast cancer with multiple bone metastasis who had never received chemotherapy.

CASE PRESENTATlON

Chief complaints

A 51-year-old woman with unremarkable medical history was admitted to the hospitalthe emergency room for lower back pain.

History of present illness

She complained of worsening back pain after lifting a heavy object two months ago.The numeric rating scale(NRS)score for back pain was seven points.

History of past illness

The patient had an unremarkable medical history.

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Personal and family history

The patient had an unremarkable personal and family history.

Physical examination

Her high BP was controlled using intravenous nicardipine,while the hypercalcemia was treated using normal saline,elcatonin,and zoledronic acid.

Her blood pressure on admission was 150/90 mmHg despite no history of hypertension.When the patient complained of severe pain,the blood pressure elevated to 170-180 mmHg,and when the pain was relieved,it decreased to 150 mmHg.Therefore,we concluded that the increased blood pressure was likely due to the uncontrolled pain,since the patient did not have a history of hypertension.Attempts to alleviate the pain included physical therapy,trigger point injection,and medication(intravenous nefopam and methocarbamol,as well as oral acetaminophen and tramadol).However,the pain and elevated blood pressure persisted(systolic BP,160-180 mmHg).On the 4th day of admission,the patient continued to complain of severe pain(NRS score 8-9),and the patient's blood pressure was measured up to 186/106 mmHg.Therefore,we added oral and intravenous antihypertensive drugs to control her BP,but no improvement was observed.

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Laboratory examinations

In this case,the patient had uncontrolled progressive hypertension after admission.Her systolic BP reached ≥ 180 mmHg.Her elevated BP was one of the leading causes of PRES.

Imaging examinations

Electroencephalography showed repetitive seizures localized in the bilateral posterior region that were more prominent on the left side.Brain magnetic resonance imaging showed bilateral cortical and subcortical edema of the occipital lobes suggesting PRES lesions(Figure 1).

FlNAL DlAGNOSlS

The final diagnosis of the presented case was PRES due to uncontrolled hypertension and hypercalcemia.

TREATMENT

Physical examination revealed paralumbar muscle tenderness,a 5 cm × 8 cm skin ulcer on her right breast,and several mass-like lesions on both breasts.We planned to evaluate the multiple breast masses under the impression of breast cancer while treating her lumbar pain.

OUTCOME AND FOLLOW-UP

After two days of treatment,she had a BP of 130/91 mmHg and a serum cacium level of 10.1 mg/dL.Moreover,her mental status improved.After regaining consciousness,she experienced a partial visual field defect for a few days because of the occipital lobe involvement of PRES.

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After the patient regained consciousness,fluorodeoxyglucose-positron emission tomography(FDGPET)imaging was performed to evaluate the cancer status.FDG-PET imaging suggested right large breast cancer with extensive metastatic lesions,including the left breast,right axillary lymph node,and multiple bones(Figure 2).In addition,a biopsy for histopathological examination of the breast lesion,confirmed invasive ductal carcinoma.

The authors declare that they have no conflict of interest.

DlSCUSSlON

PRES has been reported in cancer patients who have undergone chemotherapy of targeted agents[6,7].However,herein we focused on the pathophysiology found in advanced cancer in a case of PRES in an untreated breast cancer patient.

Her serum calcium level was 15.8 mg/dL.

Another consideration was her high calcium level,associated with her advanced breast cancer and multiple bone metastasis.Hypercalcemia is common in breast cancer patients,especially those with advanced-stage and multiple skeletal metastases[3].The intervention of osteoclasts is the main mechanism of hypercalcemia in patients with extensive osteolytic bone metastases[4].Excessive osteoclast activation,resulting from RANKL/RANK interaction and malignancy-secreted cytokines,leads to enhanced bone resorption and hypercalcemia.

Although the precise mechanism remains unclear,the pathophysiology of PRES can be correlated with increased calcium levels.Hypercalcemic conditions impair endothelial function by inhibiting the activation of nitric oxide released from endothelial cells.This has a vasodilating effect and increases systolic blood pressure[5].In this case,the patient's high blood pressure was not controlled by antihypertensive drugs but was controlled after hypercalcemia was corrected.Another hypothesis is that hypercalcemia-induced hypomagnesemia results in hypertension.Based on the antagonism between calcium and magnesium,and the vasodilating properties of magnesium elevated calcium levels lower magnesium concentration.Thus,a magnesium deficit contributes to the development of vasoconstriction.The patient had slight hypomagnesemia(0.72 mmol/L,reference value 0.77-1.03 mmol/L).Based on this,the excessive calcium level of the patient made her vulnerable to developing PRES.

On the 7day of hospitalization,the patient had an altered mental status with generalized tonicclonic seizures lasting for 1 min.

The pathophysiology of PRES remains unclear,but there are two leading theories.First,when the blood pressure exceeds the upper limit of cerebral blood flow autoregulation,cerebral hyperperfusion occurs,and the blood-brain barrier breaks,allowing interstitial extravasation,which may cause vascular leakage and vasogenic edema[1].The posterior brain areas are particularly susceptible to hyperperfusion due to the lack of sympathetic innervation.The second theory suggests that the syndrome is triggered by endothelial dysfunction,caused by circulating endogenous or exogenous toxins.The excessive release of pro-inflammatory cytokines results in endothelial activation,enhancing the release of vasoactive agents,and increasing vascular permeability and edema formation,which can also cause hypertension[1].

CONCLUSlON

This was a rare case of PRES caused by hypertension and hypercalcemia.Although hypercalcemia is a rare cause of PRES,it can,directly and indirectly,result in uncontrolled hypertension,which can lead to PRES.Thus,it is essential to recognize diseases that induce hypercalcemia because PRES has been associated with severe consciousness disturbances and can be fatal.A prompt diagnosis is essential for adequate treatment.

FOOTNOTES

Jeon HR,and Song CH designed the research study;Jeon HR,Song CH,and Lee SJ wrote the manuscript;all authors have read and approve the final manuscript.

Meat and drink for the seven years were carried into the tower, and then she and her waiting-woman were led into it and walled up, and thus cut off from the sky and from the earth

This report is a retrospective study based on medical records,and written consent was obtained from the Ethics Committee.

I remember seeing Harry that first evening. He wasn t much more than a thin, anxious kid then. He was all dressed up and I knew he was meeting his girl and that they would be married twenty minutes after she arrived.

The authors have read the CARE Checklist(2016),and the manuscript was prepared and revised according to the CARE Checklist(2016)

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South Korea

The Prince s next idea for Potentilla s amusement was to cause a fleet of boats exactly like those of Cleopatra, of which you have doubtless read in history, to come up the little river, and upon the most gorgeously decorated of these reclined the great Queen herself, who, as soon as she reached the place where Potentilla sat in rapt attention, stepped majestically37 on shore and presented the Princess with that celebrated38 pearl of which you have heard so much, saying: You are more beautiful than I ever was

Chae Hyun Song 0000-0002-0689-1524;Seung Jun Lee 0000-0002-7152-2880;Ha Ra Jeon 0000-0001-9446-9552.

Liu JH

Very soon they recognized the large town where they lived, and the tall steeples of the churches, in which the sweet bells were ringing a merry peal18 as they entered it, and found their way to their grandmother’s door

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Liu JH