Edited by: Alexander Lerner, University of Southern California, United States
Reviewed by: Bo Gao, Affiliated Hospital of Guizhou Medical University, China; Yunyun Duan, Capital Medical University, China
This article was submitted to Applied Neuroimaging, a section of the journal Frontiers in Neurology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Posterior reversible encephalopathy syndrome (PRES) is a reversible clinico-radiological entity associated with various conditions (e.g., renal failure, blood pressure fluctuations, cytotoxic drugs, autoimmune disorders, and pre-eclampsia or eclampsia), and the diverse clinical manifestations mainly include acute and subacute onset of headache, nausea, vomiting, seizures, altered mental status, visual disturbances, and focal neurological signs (
Previous studies have mostly focused on typical or classical PRES with three primary variations: a dominant parieto-occipital pattern, holohemispheric watershed pattern, and superior frontal sulcus pattern (
This study was approved by the Ethics Committee of our institution. The requirement for informed consent was waived.
We retrospectively collected patient information in two ways. (1) We searched the medical records of patients admitted to our hospital with PRES between April 1, 2015, and May 31, 2019. The diagnostic criteria used for PRES were previously described (
Flowchart of the study population. a, number of articles; n, number of patients.
The clinical information collected and evaluated from the patient records included age, sex, predisposing factors for the development of PRES, presenting blood pressure, related symptoms, current drugs/therapies, follow-up interval and outcome.
The imaging findings were evaluated on T1WI, T2WI, and FLAIR images in all cases. Diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, susceptibility-weighted imaging (SWI) or T2*-weighted gradient-echo imaging (T2*WI), gadolinium-enhanced T1WI, MR angiography (MRA), MR venography (MRV), and other advanced images were evaluated if they were available. DWI and ADC maps were analyzed to determine the vasogenic or cytotoxic edema in the lesions. SWI or T2*WI was used to determine the intracranial hemorrhage and microbleeds.
General demographic, clinical and MRI indicators were expressed as the mean ± SD (normally distributed quantitative variables), median (non-normally distributed quantitative variables), or numbers and percentages (categorical variables) for descriptive analysis.
In total, six patients from our hospital (the clinical and MRI features of six patients are shown in
Demographic, clinical and MRI features of six patients in our hospital.
1 | 52/F | Headache | 200/130 | Hypertension | Brainstem, periventricular | – | – | Antihypertensive |
2 | 23/F | Focal neurological deficits | 163/116 | Preeclampsia | Brainstem, periventricular | – | Pons (+) | Antihypertensive |
3 | 40/M | Focal neurological deficits | 189/110 | Hypertension, psoriasis | Periventricular, basal ganglia, pons, cerebellum | Pons (+) | – | Antihypertensive |
4 | 44/F | Focal neurological deficits | 260/130 | Hypertension, renal dysfunction, renal artery stenosis | Brainstem, periventricular | – | Cerebrum (+) | Antihypertensive |
5 | 45/F | Insomnia | 236/154 | Hypertension, renal dysfunction | Periventricular, basal ganglia, pons | – | – | Antihypertensive |
6 | 22/F | Headache, blurred vision | 224/115 | Hypertension | Periventricular, basal ganglia | – | – | Antihypertensive |
A 52-years-old female with hypertension presented with headache. FLAIR
A total of 305 patients were females, and 248 were males, with a median age of 34 years. The information regarding sex and age of three patients was not available in the descriptions in the literature. The most common symptom was headache (282/556, 50.7%), followed by altered mental status (243/556, 43.7%), seizure (233/556, 41.9%), visual disturbance (194/556, 34.9%), nausea/vomiting (130/556, 23.4%), and focal neurological deficit (104/556, 18.7%) in descending order. Other rare symptoms are shown in
Demographic and clinical characteristic of PRES patients with atypical regions.
Sex/F | 305/553 (55.2%) |
Age (median, range, years) | (34, 0.08–85) |
Dizziness | 38/556 (6.8%) |
Gait disturbances | 27/556 (4.9%) |
Fever | 25/556 (4.5%) |
Disorientation | 23/556 (4.1%) |
Ataxia | 20/556 (3.6%) |
Dyspnea | 16/556 (2.9%) |
Abdominal pain | 13/556 (2.3%) |
Abnormal urine | 12/556 (2.2%) |
Others (each symptom)# | ≤2% |
Autoimmune disorders | 55/556 (9.9%) |
Pre-eclampsia/Eclampsia | 41/556 (7.4%) |
Infection/sepsis/shock | 32/556 (5.8%) |
Steroids | 24/556 (4.3%) |
Metabolic disorders | 15/556 (2.7%) |
Miscellaneous drugs | 13/556 (2.3%) |
Dialysis | 12/556 (2.2%) |
Transfusion | 11/556 (2.0%) |
Endocrine disorders | 7/556 (1.3%) |
Surgery | 6/556 (1.1%) |
Others (each factor)* | ≤1% |
Dehydrating/diuretics | 34/515 (6.6%) |
Intracranial decompression | 24/515 (4.7%) |
Hemodialysis | 23/515 (4.5%) |
Immunosuppressive therapy | 20/515 (3.9%) |
Anti-infective treatment | 16/515 (3.1%) |
Others (each treatment)$ | ≤2% |
All patients showed hyperintensity signals on T2WI and FLAIR images. The atypical regions of the lesions were the cerebellum (331/556, 59.5%), basal ganglia (135/556, 24.3%), periventricular/deep white matter (125/556, 22.5%), pons (124/556, 22.3%), brainstem (115/556, 20.7%), thalamus (114/556, 20.5%), midbrain (48/556, 8.6%), spinal cord (33/556, 5.9%) and medulla (29/556, 5.2%). Additionally, the following typical regions were observed: occipital (278/556, 50.0%), parietal (234/556, 42.1%), frontal (150/556, 27.0%), and temporal (124/556, 22.3%). A total of 148 patients had DWI and ADC maps, and 34 (23.0%) patients showed cytotoxic edema on the background of vasogenic edema. Thirty-three (5.9%) and 35 (6.3%) patients had intracranial hemorrhage and hydrocephalus, respectively. Thirty-one patients had acute infarcts. Ninety-three patients underwent gadolinium-enhanced T1WI, and 29 (31.2%) patients showed lesion enhancements. Twenty-four (4.3%) patients in our study underwent SWI or T2*WI examination, and 79.2% (19/24) of patients were confirmed to have microbleeds based on SWI or T2*WI. The MRI characteristics of PRES with atypical regions are summarized in
MR characteristics of PRES patients with atypical regions.
Cerebellum | 331/556 (59.5%) | T1WI(–)&T2WI(+) | 556/556 (100.0%) |
Occipital lobe | 278/556 (50.0%) | DWI(=)&ADC(+) | 47/148 (31.8%) |
Parietal lobe | 234/556 (42.1%) | DWI(+)&ADC(+) | 43/148 (29.1%) |
Frontal lobe | 150/556 (27.0%) | DWI(+)&ADC(–) | 31/148 (20.9%) |
Basal ganglia | 135/556 (24.3%) | DWI(=)&ADC(=) | 20/148 (13.5%) |
Periventricular/deep white matter | 125/556 (22.5%) | DWI(+)&ADC(=) | 5/148 (3.4%) |
Temporal lobe | 124/556 (22.3%) | DWI(–)&ADC(–) | 3/148 (2.0%) |
Pons | 124/556 (22.3%) | DWI(–)&ADC(+) | 2/148 (1.4%) |
Brainstem | 115/556 (20.7%) | DWI(–)&ADC(=) | 1/148 (0.7%) |
Thalamus | 114/556 (20.5%) | Enhancement | 29/93 (31.2%) |
Midbrain | 48/556 (8.6%) | Hemorrhage | 33/556 (5.9%) |
Spinal cord | 33/556 (5.9%) | Microbleeds | 19/24 (79.2%) |
Medulla | 29/556 (5.2%) | Hydrocephalus | 35/556 (6.3%) |
The details of the treatment were available in 515 cases. The major treatments were antihypertensives (358/515, 69.5%), antiepileptics/sedation (126/515, 24.5%), discontinuation/switching agents (67/515, 13.0%), and steroids (54/515, 10.5%). After appropriate treatments, the neurological symptoms of 244 patients resolved at follow-up [median time, 14 days (range, 0.04–540 days)]. Twenty-five patients died at follow-up; however, most of their deaths (20/25, 80.0%) were not attributable to PRES but to severe infections or malignant tumors. Moreover, the causes of the three patients' deaths were unknown. In 364 patients, data on follow-up time and MR imaging were available. Except for four patients with no significant change, the MRIs of 360 patients at follow-up showed lesion reversal [complete, 273 patients, median time, 21 days (range, 1–720 days); partial, 87 patients, median time, 18 days (0.5–300 days)].
PRES with atypical regions can be easily misdiagnosed, which can lead to a delay or wrong choice of management and subsequent irreversible injury. Thus, it is crucial for clinicians to improve their understanding of the clinical and MRI features of this disease (
Recognition of the clinical features of this disease is important for prompt diagnosis and rational management. In our study, most patients were young females, which is similar to most previous studies, but males were predominant in some other studies (
In addition to the clinical features, neuroimaging, especially MRI, is essential in the evaluation and diagnosis of PRES with atypical regions (
Vasogenic edema, which is an essential pathological feature of PRES, is usually hypointense on T1WI, hyperintense on T2WI and FLAIR, and isointense or hyperintense on DWI and ADC maps. Hyperintensity on DWI and hypointensity on ADC maps, which are called restricted diffusion, can reflect cytotoxic edema. The presence of cytotoxic edema may suggest progression to infarction and eventual irreversible damage, which may be associated with poor outcome (
In addition to the common MRI features, concomitant and coincidental events that occur on neuroimaging, mainly including hemorrhage, microbleeds and hydrocephalus, can occur in PRES. In our study, hemorrhage was found in 33 (5.9%) patients. The incidence rate was lower than that of previous SWI or T2*WI studies, where it ranges from 15 to 65% (
Once PRES has been diagnosed, the treatment, which mainly includes supportive treatment and the elimination of the cause, should be undertaken immediately to prevent poor progression. In our study, 69.5% of patients received antihypertensive treatment, and 24.5% of patients received antiepileptics/sedation. After proper and prompt treatments, the clinical state improved, and abnormal neuroimaging resolved in most patients within 2–3 weeks.
In conclusion, we found that PRES with atypical regions had diverse clinical and MRI features. The common symptoms of this disease include headache, altered mental status, seizure, visual disturbances, nausea or vomiting, and focal neurological deficits; the frequent predisposing factors include hypertension, renal diseases, immunosuppressant drugs, and chemotherapy/chemoradiotherapy; and the MRI features are mainly characterized by vasogenic edema in central zones (such as the basal ganglia, thalami, periventricular or deep white matter, brainstem, and spinal cord) always accompanied by abnormalities in typical regions. Most lesions are reversed in 2–3 weeks when promptly recognized and properly treated. The main limitation of this study is the possible selection bias because only publications in English were searched and included. This aspect needs to be improved in future research.
All datasets generated for this study are included in the article/
The studies involving human participants were reviewed and approved by the Ethics Committee of The Second Affiliated Hospital of Chongqing Medical University. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.
KL, YY, DG, and CL contributed the conception and design of the study. KL and YY organized the database and performed the statistical analysis. KL, YY, and DS wrote the first draft of the manuscript. All authors contributed to the manuscript revision, read, and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The Supplementary Material for this article can be found online at: