Cortical Blindness: Clinical and Radiologic
Findings in Reversible Posterior
Leukoencephalopathy Syndrome
Case Report and Review of the Literature
Alon Kahana, MD, PhD,1 Howard A. Rowley, MD,2 Joel M. Weinstein, MD1,3
Purpose: To alert ophthalmologists to the recognition of cortical visual loss as the presenting feature in
patients with reversible posterior leukoencephalopathy syndrome (RPLES). Unique radiologic findings are
paramount to the diagnosis.
Design: Interventional case report.
Methods: A patient was seen with perioperative bilateral cerebral visual loss that was misinterpreted initially
as an irreversible ischemic event. Further detailed analysis of the radiologic findings and clinical history led to the
correct diagnosis.
Main Outcome Measures: Visual acuity and magnetic resonance imaging (MRI) of the brain.
Results: Recognition of the correct diagnosis of RPLES led to the institution of antihypertensive therapy and
recovery of normal vision.
Conclusions: The diagnosis of RPLES should be considered in all patients with acute cerebral visual loss,
especially in the setting of recent surgery, blood transfusion, chemotherapy, immunosuppressant use, hypertension, eclampsia, or seizures. Prompt diagnosis requires close collaboration with a radiologist and an emergent
MRI study, which ideally should include diffusion-weighted imaging with calculation of an apparent diffusion
coefficient map. Differentiation from acute cerebral ischemia is important in order to avoid permanent visual loss
by prompt and vigorous treatment of exacerbating factors such as intermittent hypertension. Prompt diagnosis
will also help to avoid potentially dangerous invasive procedures such as thrombolytic therapy. Ophthalmology
2005;112:e7– e11 © 2005 by the American Academy of Ophthalmology.

Reversible posterior leukoencephalopathy syndrome
(RPLES), also known as posterior reversible encephalopathy syndrome and reversible posterior cerebral edema syndrome, is a clinical entity that includes the acute or subacute
onset of confusion, lethargy, and visual disturbances due to
vasogenic edema of the posterior cerebral white matter.
Reversible posterior leukoencephalopathy syndrome has
been described in various clinical settings, including severe
hypertension, chemotherapy, eclampsia, and seizures.1–12
Less commonly associated findings include a low hematoOriginally received: February 18, 2004.
Accepted: July 15, 2004.
Manuscript no. 240126.
1
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine, Madison, Wisconsin.
2
Department of Radiology, University of Wisconsin School of Medicine,
Madison, Wisconsin.
3
Department of Neurology, University of Wisconsin School of Medicine,
Madison, Wisconsin.
Neither the authors nor their families have a financial interest in any of the
products, drugs, instruments, or equipment discussed in this article.
Correspondence and reprint requests to Joel M. Weinstein, MD, Department of Ophthalmology and Visual Sciences, University of Wisconsin
School of Medicine, 600 Highland Avenue, F4/3, Madison, WI 53705.
© 2005 by the American Academy of Ophthalmology
Published by Elsevier Inc.

crit, blood transfusion, sickle cell complications, acute renal
failure, and liver failure.13–21 Despite the variety of clinical
settings, the etiologic insult is thought to be severe hypertension with dysregulation of the cerebral vasculature, although there is evidence of endothelial damage preceding
the hypertensive episode.22 The reversible neurologic deficits associated with RPLES are felt to result from acute
vasogenic edema, often with little, if any, permanent cellular damage.23,24 The diagnosis of RPLES is often made on
the basis of the clinical setting and neuroradiologic findings
consistent with vasogenic edema, as opposed to cytotoxic
edema, in the parieto-occipital region. These characteristic
parieto-occipital abnormalities are manifested by hypointensity on computed tomography (CT), and hyperintensity
on T2-weighted magnetic resonance imaging (MRI).
More recent advances in MRI technology highlight the
features of vasogenic edema and allow for a more accurate
radiologic diagnosis. Specifically, diffusion-weighted imaging (DWI) shows parieto-occipital signal changes caused by
the entrapment of water in the edematous region.25–29 However, the DWI signal reflects both diffusion weighting and
some underlying T2 effects, such that a bright signal on
DWI could reflect either true ischemic injury or simply T2
ISSN 1549-4713/05/$–see front matter
doi:10.1016/j.ophtha.2004.07.036

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Ophthalmology Volume 112, Number 2, February 2005
shine-through from vasogenic edema. Apparent diffusion
coefficient (ADC) maps (made from the diffusion data)
serve to remove the underlying T2 signal contribution and
highlight free unrestricted water. Therefore, the ADC maps
allow distinction between vasogenic edema and cytotoxic
edema due to brain infarction: ADC maps appear bright in
vasogenic edema but dark in cytotoxic edema and acute
stroke.25,30
As early as 1984, Monteiro et al described a case of
reversible cortical blindness related to hypertension.31 Their
patient showed hypointensities on CT scan. In 1996,
Hinchey et al coined the term reversible posterior leukoencephalopathy syndrome.1,32 Although several cases of
RPLES have been reported in the neurology and neuroradiology literature, exposure in the ophthalmologic literature
has been rather limited.
We describe a patient who developed RPLES in the
setting of intraoperative and postoperative hypertension and
postoperative anemia. The cause of the patient’s cerebral
blindness was not immediately apparent. Radiologic studies
were initially interpreted as consistent with cerebral ischemia. Reinterpretation, taking into consideration the findings on DWI and ADC, led to the diagnosis of RPLES.
Because of this, strict blood pressure (BP) control was
instituted, and the patient recovered fully within 3 days,
consistent with the diagnosis of RPLES, as opposed to a
cerebral ischemic episode.

Case Report
A 42-year-old woman with a history of hypertension, peripheral
arterial occlusive disease, and failed aorto-bifemoral revascularization surgery 6 months earlier was admitted to the vascular
surgery service with complaints of worsening claudication in both
legs, including claudication at rest. Her medications included
aspirin (81 mg daily) and tramadol (Ultram, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ; 50 mg) for pain. She had an allergy
to clopidogrel (Plavix, Sanofi-Synthelabo Inc., New York, NY),
which caused extremity swelling and urticaria, and she had been
diagnosed previously with heparin-induced platelet antibodies, a
contraindication for the use of heparin products. She had a smoking history of 37 packs a year. However, she did not have thrombocytopenia and was negative for lupus anticoagulant factor and
factor V Leiden. Her antithrombin III, protein S, and protein C
levels were normal. Magnetic resonance arteriography showed
clotting of her aorto-bifemoral graft, and a revision of the revascularization graft was performed without complications. Intraoperative records indicate that the highest BP recorded was 180/90,
achieved at the midpoint and at the end of the surgery. Otherwise,
BP intraoperatively was maintained at 120 to 150/60 to 80.
Postoperatively, the patient was admitted to the intensive care
unit (ICU). She was treated with lepirudin and warfarin, and her
partial thromboplastin time and prothrombin time were followed.
Her BP medications were labetalol and furosemide as needed, and
her electrolyte levels, including that of magnesium, were followed
routinely and corrected when necessary. She was oriented to
person and place, but her ICU chart noted disorientation to time
throughout her ICU stay. Beginning on postoperative day 2, BPs
measured by an arterial line were 140 to 183/65 to 86, with one
instance of 196/82. She received a blood transfusion on postoperative day 3 to correct a hematocrit of 21 (from a preoperative level
of 33). Throughout her ICU admission, regular neurologic exam-

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inations, including determining Glasgow coma scores, were conducted, and the patient was neurologically intact except for mild to
moderate confusion, especially related to time. Glasgow coma
scores were normal or near normal; specifically, her Glasgow
coma eye scores were either 3 or 4, implying normal visual
function.* On postoperative day 7, the arterial line was removed,
and the patient was transferred to the regular inpatient unit. Her BP
that day was 151 to 186/75 to 85.
Upon transfer out of the ICU, the receiving nurse noted that the
patient was unable to see out of either eye. She continued to be
confused with respect to time, but was oriented to person and
place. An emergent ophthalmology consultation was requested.
Ophthalmic history was negative except for presbyopia. Bedside
examination revealed a well-nourished woman with significant
confusion and moderate lethargy. Visual acuity (VA) at near
without correction was light perception bilaterally in all quadrants.
Pupils were 6 mm in each eye and were reactive to light, with no
relative afferent pupillary defect. Intraocular pressures were 18 and
19 mmHg. Random conjugate searching eye movements were
present, but amplitude of movements was full in all directions.
Portable slit-lamp and dilated fundus examinations were unremarkable. Disc borders were sharp, with a cup-to-disc ratio of 0.3.
A diagnosis of cerebral visual loss was made.
An emergent head CT scan revealed diffuse hypodensity in
the parieto-occipital area bilaterally, consistent with regional
edema (Fig 1). Magnetic resonance imaging/magnetic resonance angiography studies of the head were obtained. Magnetic
resonance angiography showed patent vasculature, and MRI
showed diffuse hyperintensity of the parieto-occipital regions
bilaterally on T2-weighted images consistent with either ischemia or edema (Fig 1). A neurologic consultation was requested. The original MRI included DWI, which revealed hyperintensity of the same regions (Fig 1). However, at first only
routine T2 images and DWI were reviewed, without ADC maps,
and the initial interpretation was of findings consistent with
acute cerebral ischemia. Reinterpretation later in the day, taking
into consideration the hyperintense signal on ADC maps, led to
the finding of vasogenic edema and the correct diagnosis of
RPLES. In view of this diagnosis, the neurologist recommended
maintaining systolic BP under 140 to 150 mmHg. Blood pressure was maintained in the desired range, and the next day, VAs
at near were 20/400 and 20/200. One day later, the patient was
alert and oriented to person, place, and time. She was no longer
confused, and VA at near was 20/25 bilaterally. The patient
remained hospitalized for 2 more days until her prothrombin
time ratio (international normalized ratio) was 2.1. Lepirudin
was discontinued, and the patient was discharged. On follow-up
in 1 month after surgery, VA was noted as normal and stable,
and she had no neurologic complaints.

Discussion
Reversible posterior leukoencephalopathy syndrome is a
clinical entity that may be unfamiliar to many ophthalmologists. However, the ophthalmologist is often the first consultant to evaluate patients with acute visual loss, and
should therefore be familiar with this diagnosis. The clinical
features that should alert the clinician to RPLES are the
combination of confusion and lethargy, in conjunction with

*Spontaneous eye opening, 4 points; opening to speech, 3; opening to pain, 2;
no opening, 1.

Kahana et al 䡠 Posterior Leukoencephalopathy Presenting as Cortical Blindness

Figure 1. Computed tomography (CT) and magnetic resonance imaging (MRI) in reversible posterior leukoencephalopathy syndrome. CT, T2, Bilateral
occipital lesions with a white matter predominance seen on CT and T2-weighted MRI. DWI, The diffusion-weighted image shows slight hyperintensity,
left more than right. Although the DWI might at first suggest cytotoxic edema due to infarction, this is due to T2 shine-through effects, confirmed by
apparent diffusion coefficient (ADC) maps, which show a vasogenic pattern of edema (see text).

a rather acute episode of visual loss, usually in the setting of
acute hypertension, seizures, or chemotherapy.1 Transplant
patients taking cyclosporine or FK-506 also seem to be at
particular risk for this syndrome. A mini-mental neurologic
examination can assist in determining the extent of confusion and can aid in making the diagnosis of RPLES. Early
diagnosis of RPLES should lead to aggressive medical
control of exacerbating factors, such as hypertension, and
may prevent permanent neurologic damage. Ultimately, the
diagnosis is made by MRI, including DWI.27,28 The diagnosis is subsequently confirmed clinically by a benign outcome, providing that the risk factors mentioned above are
controlled. A case report employing proton magnetic resonance spectroscopy during and after the RPLES event revealed significant metabolic derangement that resolved
completely after successful management.33
The pathophysiology and even the nomenclature of
RPLES (also known as posterior reversible encephalopathy
syndrome) have been somewhat controversial. Earlier studies suggested that cerebral vasospasm, caused primarily by
hypertension but exacerbated by other etiologic factors,
leads to cerebral ischemia with underlying cytotoxic edema.
As several authors have pointed out, the syndrome may not
be completely reversible, is not always limited to the posterior regions, and may involve gray as well as white matter;
hence the call for other names. However, the reversible

nature of the clinical and radiologic findings casts doubt on
the role of cytotoxicity associated with this process. The
alternative and currently favored hypothesis holds that
RPLES is manifest as vasogenic rather than cytotoxic edema,28,34,35 although vasogenic and cytotoxic edema have
been reported to coexist in some cases (Fig 2).36 The posterior circulation may be predisposed to RPLES because
perivascular sympathetic activity is reduced in the posterior
relative to the anterior cerebral region, leading to loss of
protective vasoconstriction and, therefore, breakthrough vasodilation in the face of hemodynamic challenge.35 This, in
turn, leads to an increase in local hydrostatic pressure,
resulting in extravasation of fluid into the surrounding brain
tissue. Therefore, vasogenic edema develops preferentially
in the posterior cerebral territories and appears hyperintense
on T2, diffusion, and ADC maps.37,38
Interestingly, in vasogenic edema associated with preeclampsia/eclampsia,36 elevated levels of lactic dehydrogenase and abnormal erythrocyte morphology preceded the
development of radiologic and neurologic abnormalities.22
Schwartz et al speculated that endothelial cell damage may
participate in the dysregulation of the cerebral vasculature,
leading to vasogenic edema.
Performance of MRI with diffusion-weighted images is
central to the evaluation of patients with suspected RPLES
and has helped advance our understanding of the pathophys-

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Ophthalmology Volume 112, Number 2, February 2005

Figure 2. Acute occipital infarction. Left, T2-weighted images show hyperintensity along the right calcarine cortex. Top right, Diffusion-weighted images
show the typical marked hyperintensity (lightbulb sign) characteristic of acute infarction. Bottom right, Hypointensity on apparent diffusion coefficient
maps confirms that this is restricted diffusion related to cytotoxic edema.

iology. Diffusion-weighted imaging creates images based
on the molecular movement of water, and has been used to
document the abrupt slowdown of water movement in cytotoxic edema due to acute ischemic stroke. Ischemic stroke
has a pattern opposite the accentuated water motion seen
with vasogenic edema, the dominant pattern seen with
RPLES. However, DWI has signal contributions from both
underlying T2 weighting as well as diffusion weighting.
Therefore, hyperintensity on DWI can result from true diffusion restriction or strong T2 effects—so-called T2 shinethrough. Fortunately, a simple postprocessing step—
namely, the construction of an ADC map— can remove the
T2 contribution and allow the reader to see pure diffusion
characteristics. As noted earlier, ADC maps allow distinction between vasogenic edema and cytotoxic edema due to
brain infarction: ADC maps appear bright in vasogenic
edema, but dark in cytotoxic edema and acute stroke.30 In
this case, as in others of RPLES, the ADC maps confirm a
predominantly vasogenic (and therefore reversible) pattern
of edema.
In the evaluation of cerebral blindness, diffusionweighted MRI is invaluable in differentiating RPLES from
an ischemic stroke. The important features of cranial imaging studies in the context of RPLES include diffuse posterior white-matter abnormalities manifested as hypointensity
on CT, hyperintensity on T2-weighted MRI, and hyperintensity on both DWI and ADC maps.
The diagnosis of RPLES should be considered in all
patients with acute cerebral visual loss. This diagnosis is
especially relevant in patients with some degree of lethargy and confusion, often in the setting of recent surgery,
blood transfusion, chemotherapy, immunosuppressant
use, intermittent hypertension, or seizures. Prompt diag-

e10

nosis requires close collaboration with a radiologist and
an emergent MRI study, which ideally should include
diffusion-weighted images and ADC maps. Differentiation from acute cerebral ischemia is important to avoid
permanent visual loss by prompt and vigorous treatment
of exacerbating factors such as intermittent hypertension.
Prompt diagnosis will also help to avoid potentially dangerous invasive procedures such as thrombolytic therapy.

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