Posterior reversible encephalopathy syndrome induced after blood transfusion for severe anemia

doi:10.4236/crcm.2013.25089

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Vol.2, No.5, 332-334 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.25089

Posterior reversible encephalopathy syndrome

induced after blood transfusion for severe anemia

Kei-ichiro Wada1, Masayoshi Kano1, Yutaka Machida1, Nobutaka Hattori2, Hideto Miwa1*

1Department of Neurology, Juntendo University Nerima Hospital, Tokyo, Japan;

*Corresponding Author: [email protected]

2Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan

Received 6 June 2013; revised 30 June 2013; accepted 10 July 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Posterior reversible encephalopathy syndrome

(PRES) is a clinicoradiological syndrome char-

acterized by headache, confusion, seizures, and

cortical visual loss, as well as subcortical ede-

ma without infarction on neuroimaging. We re-

port a 56-year-old woman who developed typi-

cal manifestations of PRES, 6 days after blood

transfusi on for severe anemia. Acu te volume over-

loads by transfusion may exceed the capacity of

autoregulation of perfusion pressure, possibly

resulting in vasogenic edema. We propose that

it is clinically important to recognize that rapid

correction of anemia by blood transfusion may

carry the risk of inducing PRES.

Keyw ords: Posterior Reversibl e Enceph alopathy

Syndrome; Anemia; Blood Transfusion

1. INTRODUCTION

Posterior reversible encephalopathy syndrome (PRES),

or reversible posterior leukoencephalopathy syndrome, is

a clinicoradiological syndrome characterized by head-

ache, confusion, seizures, and cortical visual loss, as well

as subcortical edema without infarction on neuroimaging

[1-3]. It was first described by Hinchey et al. [1] in 1995

based on 15 patients who had subcortical edema without

cerebral infarction. To date, a wide variety of clinical con-

ditions have been reported to cause PRES, such as hy-

pertension, exposure to toxic agents, infection, eclampsia,

autoimmune disease, and other conditions [1-3]. Recently,

we encountered a patient with PRES that was induced

after blood transfusion for severe anemia.

2. CASE REPORT

A 56-year-old Japanese woman was admitted to the

gynecology section in our hospital because of genital

bleeding and abdominal pain. Her past medical and fam-

ily histories were unremarkable, and in particular, she

had no past history of hypertension. After admission, she

was diagnosed with cancer of the corpus uteri. She had

severe anemia with a hemoglobin level of 2 g/dL, and

received blood transfusion with a total of 2 L packed red

blood cells. After transfusion, her hemoglobin level re-

covered to 9.2 g/dL for 4 days. Six days after the last

blood transfusion, she suddenly developed status epilep-

ticus, and was referred to our neurological section.

She was immediately treated with general anesthesia

by intravenous administration of midazolam with pheny-

toin. Two days later, she recovered from anesthesia, but a

drowsy state continued for a few days. On neurological

examination, her pupils were equal, and promptly reac-

tive to light. She could open her eyes if verbal stimuli

were given, but she could not recognize any objects. She

could not maintain her gaze on any objects, and just

stared into space, suggesting that she had cortical blind-

ness. Oculocephalic reflexes, towards either horizontal or

vertical directions, were not disturbed. She was mute. No

obvious motor paresis was noted in both upper and lower

extremities. Deep tendon reflexes were all normal in both

limbs. There were no signs of meningeal irritation. La-

boratory examination revealed mild anemia (9.2 g/dL),

leukocytosis (36,500/L) and elevated C-reactive protein

(4.5 mg/dL). Other routine blood tests, blood coagulation

tests, autoantibodies, and neoplastic markers were within

normal limits. Cerebrospinal fluid examination revealed

a mild increase in protein level (52 mg/dL). Brain mag-

netic resonance imaging (MRI), which included T1-, T2-

and diffusion-weighted images, fluid-attenuated inver-

sion recovery (FLAIR) images, and apparent diffusion

coefficient mapping, were performed. The FLAIR im-

ages demonstrated high-intensity signal areas in bilateral

parietal lobes (Figure 1). Within 10 days, her conscious-

K. Wada et al. / Case Reports in Clinical Medicine 2 (2013) 332-334 333

Figure 1. FLAIR imaging (a), (b) and diffusion-weighted MRI

(c), (d). FLAIR images demonstrate high-intensity signal areas

in bilateral parietal lobes.

ness disturbance fully recovered, as did her visual func-

tions. Abnormal MRI findings also disappeared simulta-

neously. During the course of illness, her blood pressure

generally had been stable within normal ranges (<130

mmHg) except that acute elevation of blood pressure was

transiently noted at the onset of status epileptics, while the

maximum systolic/diastolic blood pressure was 180/70

mmHg.

3. DISCUSSION

The present patient exhibited conscious impairment,

status epilepticus, and cortical blindness. Brain MRI de-

monstrated white matter lesions in bilateral parietal re-

gions that could be clearly differentiated from ischemic

lesions. Both clinical and neuroimaging findings were

transient and fully disappeared. Although there are no

established consensual criteria for diagnosis of PRES,

based on clinical characteristics, we consider that the pre-

sent patient did have PRES. The pathophysiology of

PRES is thought to result from abnormalities in the trans-

membrane flow of intravascular fluid and proteins caused

by two phenomena: one is a cerebral autoregulatory fail-

ure, and the other is the loss of integrity of the blood-

brain barrier [2,3]. One important issue is the cause of

PRES in the present patient.

Many conditions are known to be potentially associ-

ated with PRES [2,3]. No medical treatments were given

to her prior to the onset of PRES, except blood transfu-

sion; therefore, it is possible to speculate that blood trans-

fusion and/or rapid correction of severe anemia possibly

contributed to inducing PRES in the present case. The

literature describes seven adult patients with PRES pos-

sibly associated with blood transfusion for anemia (Table

1) [4-9]. It is of particular interest that all the previously

reported patients were female. Mean age at onset was

49.8 ± 13.3 years (mean ± SD). The mean hemoglobin

level before and after blood transfusion was 5.0 ± 2.9 and

11.0 ± 1.7 g/dL, respectively. The mean time interval

between blood transfusion and onset of PRES was 7.3 ±

4.7 days. These clinical data were likely similar to those

of the present patient, supporting the speculation that

rapid correction of anemia by blood transfusion may po-

tentially induce PRES, particularly in women. We think

that such speculation is not unreasonable.

Although the exact pathophysiological mechanisms

underlying PRES remain undetermined, it has been sug-

gested that breakdown of cerebral autoregulation respon-

Table 1. Previously reported cases of PRES associated with blood transfusion.

Patient Age/sex Hb (g/dL) (pre/post)* Intervals** HT*** Causes of anemia Sequelae References

1 45/F 2.0/10.0 2 days + Myoma uteri None [4]

2 48/F 3.0/8.0 6 days + Myuoma uteri None [5]

3 47/F 1.5/10.9 7 days − Aplastic anemia Visual defect [6]

Numbness of extremity

4 58/F 7.7/10.9 8 days + Cancer surgery None [7]

5 77/F 9.2/13.3 17 days + Cancer surgery None [7]

6 32/F 5.7/12.5 5 days − Myoma uteri None [8]

7 42/F 5.7/11.7 6 days − Chronic renal failure None [9]

Alcoholic liver cirrhosis

*Hemoglobin (Hb) levels before and after blood transfusion; **Intervals between blood transfusion and onset of PRES.

K. Wada et al. / Case Reports in Clinical Medicine 2 (2013) 332-334

334

sible for an increase in cerebral blood flow may play a

pivotal role [2,3]. Blood transfusion may result in a rapid

increase in total blood volume, leading to rapid overload

of cerebral blood flow. Cerebral hyperperfusion, if it is

acutely induced and exceeds the capacity for autoregula-

tion of perfusion pressure in cerebral capillaries, could

result in the huge vasogenic edema responsible for PRES.

In addition, the possibility should not be excluded that

severe anemia per se also might be the predisposing fac-

tor contributing to the induction of PRES, because in-

sufficient oxygen supply due to severe anemia might

exert an unfavorable influence on endothelial cell func-

tions, possibly causing a breakdown of the integrity of

the bloodbrain barrier in capillary circulation.

Another issue is whether a rapid increase in blood

pressure, which is frequently associated with PRES [1-3,

10], simultaneously contributed to inducing PRES in the

present study. In this regard, we think that hypertension

might not have played a prominent role in the mecha-

nism underlying PRES in the present case. During the

course of illness, hypertension was only transiently ob-

served, and an extreme increase in blood pressure (>180

mmHg) was not noted. Second, three of the seven previ-

ously reported patients (Table 1) had no hypertension,

suggesting that an acute increase in blood volume, but

not acute hypertension, may play a predominant role in

inducing PRES, if it occurs after blood transfusion for

correction of anemia.

Finally, we propose that it is clinically important to

recognize that rapid correction of anemia by blood trans-

fusion may carry a risk of inducing PRES.

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