Journal of Clinical Neuroscience xxx (2017) xxx–xxx

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Journal of Clinical Neuroscience
journal homepage: www.elsevier.com/locate/jocn

Case report

Reversible cerebral vasoconstriction syndrome combined with posterior
reversible encephalopathy syndrome after heart transplantation
Seung Pil Ban a, Gyojun Hwang a, Chang Hyeun Kim b, O-Ki Kwon a,⇑
a
b

Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
Department of Neurosurgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea

a r t i c l e

i n f o

Article history:
Received 9 January 2017
Accepted 13 March 2017
Available online xxxx
Keywords:
Reversible cerebral vasoconstriction
syndrome
Posterior reversible encephalopathy
syndrome
Vasoconstriction
Cerebral infarction
Immunosuppressant

a b s t r a c t
Reversible cerebral vasoconstriction syndrome (RCVS) combined with posterior reversible encephalopathy syndrome (PRES) is a rare complication in patients treated with immunosuppressants. A 52-year-old
male patient presented with seizures after heart transplantation. The patient was suspected of having
PRES on brain images. Despite the strict blood pressure control, the patient presented with altered mentality and the brain images showed a newly developed large acute infarction. Digital subtraction angiography (DSA) revealed the classic ‘‘sausage on a string” appearance of the cerebral arteries – potential
feature of RCVS. To our knowledge, this is the first case report to describe RCVS combined with PRES after
heart transplantation.
Ó 2017 Elsevier Ltd. All rights reserved.

1. Introduction
Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical and radiological condition, characterized by hyperacute onset
of thunderclap headache, evidence of vasoconstriction in angiography and reversibility of these symptoms within weeks to months
after their onset [1–3]. Posterior reversible encephalopathy syndrome (PRES) is another clinical syndrome with similar clinical features that occur mainly in the setting of hypertensive
encephalopathy. RCVS and PRES seem to share clinical features
and can occur together; PRES was reported to occur in 10–38% of
RCVS cases [2,4–6].
In this report, we describe a patient who presented with RCVS
combined with PRES after heart transplantation that resulted in
severe cerebral infarction.
2. Case report
A 52-year-old male patient who had end-stage heart failure due
to dilated cardiomyopathy underwent heart transplantation. At
postoperative day (POD) 8, the patient presented with generalized
⇑ Corresponding author at: Department of Neurosurgery, Seoul National University Bundang Hospital, 82 Gumi-ro 173 beon-gil, Bundang-gu, Seongnam, Gyeonggi
13620, Republic of Korea. Fax: +82 31 787 4097.
E-mail address: meurokwonoki@gmail.com (O-Ki Kwon).

tonic–clonic seizures. There was no abnormality on electroencephalogram (EEG) and laboratory examinations. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA)
of the brain were obtained. The images showed multiple T2 hyperintense lesions in the posterior part of both cerebral hemispheres.
There was no evidence of acute cerebral infarction or abnormalities
of intracranial vessels (Fig. 1). The patient was suspected of having
PRES as a consequence of Tacrolimus (TAC). Considering the risk of
PRES worsening, the TAC dose was reduced to maintain the serum
concentrations in the low-normal range. Additionally, blood pressure was strictly controlled to avoid accelerating brain edema.
The patient was fully recovered a few hours later. At POD 18, the
patient presented with altered mentality and bilateral motor
weakness (strength of 2/5). The brain images showed a newly
developed acute infarction in the fronto-parieto-occipital regions
bilaterally and diffuse stenosis at multiple cerebral arteries
(Fig. 2). Digital subtraction angiography (DSA) was performed
and revealed the classic ‘‘sausage on a string” appearance of the
cerebral arteries; this sign is a potential feature of RCVS (Fig. 3A).
Laboratory examinations showed no evidence of vasculitis. To
reduce stenosis and to prevent further infarction, TAC was stopped
and the patient was treated with intra-arterial (IA) infusion of a
calcium channel blocker (nimodipine). The vessel spasm and flow
to the distal cerebral arteries improved (Fig. 3B). With treatment,
the left upper extremity strength improved to 3/5. At the
3-month follow-up, brain images showed no new infarctions and

http://dx.doi.org/10.1016/j.jocn.2017.03.042
0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Ban SP et al. Reversible cerebral vasoconstriction syndrome combined with posterior reversible encephalopathy syndrome after heart transplantation. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.03.042

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Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx

Fig. 1. (A) Axial T2 image showing multiple hyperintense signals in the cortical-subcortical regions. (B) Matched T2 hyperintense regions were observed on the corresponding
apparent diffusion coefficient image. (C) The corresponding diffusion-weighted images were normal. (D) There was no definite abnormality on magnetic resonance
angiography.

Fig. 2. (A–C) Diffusion-weighted images showing newly developed acute infarctions in both fronto-parieto-occipital regions. (D) Magnetic resonance angiography showed
diffuse stenosis of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery.

Fig. 3. (A) Digital subtraction angiography (DSA) of the right internal carotid artery (ICA) showing vasoconstriction of multiple distal branches prior to treatment with intraarterial nimodipine (arrows). (B) DSA of the right ICA showing improved vasoconstriction after intra-arterial nimodipine administration (arrows).

Please cite this article in press as: Ban SP et al. Reversible cerebral vasoconstriction syndrome combined with posterior reversible encephalopathy syndrome after heart transplantation. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.03.042

Case report / Journal of Clinical Neuroscience xxx (2017) xxx–xxx

no vessel constriction and the patient still had residual difficulties
with bilateral motor weakness with a strength of 2/5 (except for a
strength of 4/5 for the left upper extremity) and decreased visual
acuity.

3

and PRES might be controlled if they are properly detected and
managed. If RCVS had been detected earlier, the patient’s prognosis
might have been better.
4. Conclusion

3. Discussion
PRES and RCVS have been reported in neoplastic, hematologic,
renal and autoimmune diseases. However, there is no report of
RCVS following heart transplantation [4–8]. To our knowledge, this
is the first case report to describe RCVS combined with PRES after
heart transplantation.
The clinical symptoms of PRES and RCVS are similar. They are
characterized by severe headache, seizures and mental changes.
In most patients with PRES and RCVS, the clinical and radiological
abnormalities are resolved within days or weeks [2,9]. Less than 5%
of patients with RCVS develop life-threatening symptoms [1–3].
Transient or persistent focal deficits have been reported in 8–43%
of RCVS cases [2]. Nevertheless, the clinical course of RCVS is generally benign with a low recurrence [10]. PRES also can become
more severe, resulting in cerebral ischemia, infarction, and even
death [11]. Persistent neurological deficits are reported in 10–
20% of patients with PRES, and the mortality was approximately
3–6% [9]. However, the prognosis of PRES is usually favorable. Most
patients recover with low recurrence rates (5–10%) [9].
The pathophysiological mechanisms of PRES and RCVS remain
unknown [3,5], but they are believed to be related to dysregulated
cerebral autoregulation with endothelial dysfunction [11]. The
potential causes of RCVS and PRES are hypertension, eclampsia or
pre-eclampsia, cancer chemotherapy, autoimmune diseases, septic
shock, and immunosuppressive treatment after transplantation,
which are all associated with endothelial damage or activation
[2,3]. In this case, we considered the TAC as a cause of RCVS. When
TAC was suspected as a cause of PRES or RCVS, discontinuation or
marked reduction of TAC is essential [7]. However, abrupt discontinuation of TAC could have exposed this patient to a high risk of
fatal rejection. Alternative drugs, such as Cyclosporine, were suboptimal choices for immunosuppression in the immediate time
frame given the similar risks of PRES or RCVS [4]. In this case, we
decreased the TAC dose first, aiming to maintain serum concentrations in the low-normal range (6–8 ng/ml). However, cerebral
infarction occurred after 10 days. Then, TAC was stopped.
Regarding the management of cerebral arterial spasm, previous
reports have suggested that drugs that can reverse vasoconstriction (e.g., nimodipine, verapamil, and magnesium sulfate) are helpful in symptomatic patients [1–3]. In severe cases, IA infusion of
nimodipine or verapamil has been used, as well as balloon angioplasty [12–14]. Given the importance of an early detection and
management of acute cerebral ischemia for reducing permanent
neurological deficits, early diagnosis and treatment of RCVS and
PRES can be critical, as our present case demonstrates. Although
IA treatment in patients with RCVS is still debatable, we selected
IA nimodipine because the patient’s symptoms were seriously
aggravated.
In the present case, we first diagnosed the patient’s illness as
PRES and treated the patient with only a dose reduction of TAC.
Follow-up studies, including brain MRI and MRA, were not performed. Eventually, cerebral infarction developed due to severe
RCVS and was detected 10 days after the onset of PRES. Both RCVS

This case supports that short-term follow-up with brain vascular imaging is necessary in cases of PRES to identify changes in the
cerebral vascular morphology. Consulting with a neuroendovascular specialist could also be helpful. An appropriate selection of
treatment, such as IA angioplasty, with appropriate timing could
be critical for patients with severe cerebral vasoconstriction and
ischemia.
Source of support
This study was supported by a Grant No. 14-2015-003 from the
SNUBH Research Fund.
Conflict of interest
The authors declare no conflicts of interest.
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Please cite this article in press as: Ban SP et al. Reversible cerebral vasoconstriction syndrome combined with posterior reversible encephalopathy syndrome after heart transplantation. J Clin Neurosci (2017), http://dx.doi.org/10.1016/j.jocn.2017.03.042