Cakmak, Ozden Yener

Can, Ufuk

Guler, Tulay

Kibaroglu, Seda

Toprak, Selami Kocak

Turkish Journal of Hematology

English

Baskent Universtiy

Figure 1a. MRI FLAIR images show bilateral multiple 
subcortical and cortical hyperintense lesions.
Figure 1b. MRI images 3 weeks after developing PRES 
revealed significant improvement.
109
MRI in Hematology DOI: 10.4274/Tjh.2012.0191
Posterior reversible encephalopathy syndrome (PRES) is an 
acute neuroradiological diagnosis presenting with headache, 
vomiting, seizure, abnormalities of the mental status, and 
visual disturbances associated with a breakdown in cerebral 
vasculature regulation. It has a unique neuroradiological 
pattern of symmetrical parietooccipital vasogenic edema 
[1]. The most common causes of this syndrome are sudden 
arterial hypertension, preeclampsia, eclampsia, uremia, 
immunosuppressive drugs, and cancer chemotherapies such 
as cyclosporine, tacrolimus, L-asparaginase, vincristine, 
gemcitabine, cytarabine, and cisplatin, typically used in cases 
of hematopoietic malignancies [2,3,4,5,6,7]. Intrathecal 
methotrexate-induced PRES in an adult is exceedingly rare 
[8].
A 43-year-old woman was admitted to gynecology with 
metrorrhagia. Cervical cancer was diagnosed and radical 
hysterectomy with lymph node dissection was performed. 
Final pathology and immunohistochemical analyses revealed 
B-cell phenotype malign lymphoma, which is consistent with 
Burkitt lymphoma. A chemotherapy treatment protocol with 
R-Hyper CVAD, consisting of rituximab, cyclophosphamide, 
vincristine, adriamycin, and dexamethasone plus 12 mg of 
intrathecal methotrexate without preservative, was then 
started. Twelve days after chemotherapy she had severe 
analgesic-irresponsive headache, nausea, motor agitation, 
and cooperation failure. Her vital signs and laboratory 
findings were normal. Cranial computed tomography 
revealed hypodense areas due to edema in the bilateral 
cerebral hemispheres, predominantly in the posterior regions. 
Magnetic resonance imaging (MRI) of the brain showed 
Intrathecal Methotrexate-
Induced Posterior 
Reversible Encephalopathy 
Syndrome (PRES)  
İntratekal Metotreksat İlişkili 
Posterior Reversible Ensefalopati 
Sendromu (PRES)
Address for Correspondence: Tülay Güler, M.D., 
Başkent University School of Medicine, Department of Neurology, Ankara, Turkey 
Phone: +90 312 212 68 68 E-mail: drtulis@yahoo.com
Received/Geliş tarihi    :  December 04, 2012 
Accepted/Kabul tarihi   :  February 18, 2013
Tülay Güler1, Özden Yener Çakmak1,  
Selami koçak Toprak2, Seda kibaroğlu1, Ufuk Can1
1Başkent University School of Medicine, Department of 
Neurology, Ankara, Turkey 
2Başkent University School of Medicine, Department of 
Hematology, Ankara, Turkey
Image-2.MRI in Hematology
110
Turk J Hematol 2014;31:109-110
multiple confluent hyperintense lesions in T2-weighted and 
fluid-attenuated inverse recovery (FLAIR) sequences (Figure 
1a), with no contrast enhancement in T1-weighted sequences. 
PRES was diagnosed and she was admitted to the intensive 
care unit (ICU) because of decreased alertness and agitation. 
Intrathecal methotrexate treatment was discontinued. On the 
second day in the ICU her blood pressure rose and was then 
normalized by diltiazem infusion. On the third day in the ICU, 
myoclonic jerks were seen in all extremities. Levetiracetam was 
started. Myoclonic symptoms were no longer observed. After 
treatment she had no neurological symptoms. Three weeks later, 
cranial MRI showed significantly improved brain lesions (Figure 
1b). The 6-month follow-up was uneventful. Informed consent 
was obtained.
During chemotherapy for hematopoietic malignancies, 
possible causes of neurological symptoms (cerebrovascular 
disease, metabolic disturbances, neoplasia, and infections) 
must be excluded by clinical, biological, and imaging findings. 
During chemotherapy, various types of anticancer drugs are 
administered, and it is difficult to identify which drug induces 
PRES. In our case, intrathecal methotrexate treatment was 
stopped, and the patient’s symptoms were relieved and did 
not reoccur while her treatment was continued with other 
anticancer drugs. 
In treatment, the causal factor must be discontinued. The 
treatment of overdose of intrathecal methotrexate is dilution 
and removal from the cerebrospinal fluid with specific antidotal 
therapy. Leucovorin and anti-inflammatory agents are useful 
[9]. Although PRES is usually reversible with patient recovery 
and resolution of the imaging findings, it might be recurrent or 
result in permanent damage [10,11].  
key words: Posterior reversible encephalopathy syndrome 
(PRES), Methotrexate, Magnetic resonance imaging, Fluid-
attenuated inversion recovery
Anahtar kelimeler: Arka geri dönüşümlü ensefalopati 
sendromu (PRES), Ensefalopati, Metotreksat, Manyetik 
rezonans görüntüleme, Sıvı zayıflatılmış dönüşüm kazanımı 
(FLAIR)
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Güler T, et al: MRI in Hematology 


Intrathecal Methotrexate-Induced Posterior Reversible Encephalopathy Syndrome (PRES)

http://acikerisim.baskent.edu.tr/xmlui/bitstream/11727/4429/1/TJH_31_1_109_110.pdf

Intrathecal Methotrexate-Induced Posterior Reversible Encephalopathy Syndrome (PRES)

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